Ebook Medicinal plants in asia for metabolic syndrome - Natural products and molecular basis: Part 2

Part 2 book “Medicinal plants in asia for metabolic syndrome - Natural products and molecular basis” has contents: Inhibiting insulin resistance and accumulation of triglycerides and cholesterol in the liver, increasing the sensitivity of adipocytes and skeletal muscle cells to insulin, inhibiting low-density lipoproteins intimal deposition and preserving nitric oxide function in the vascular system.

3 Inhibiting Insulin Resistance and Accumulation of Triglycerides and Cholesterol in the Liver Visceral obesity favors the generation of reactive oxygen species, plasmatic nonesterified fatty acids, tumor necrosis factor-α, and interleukin-6 that act synergistically to bring about hepatic insulin resistance.1 Insulin resistance evokes a subnormal hepatic storage of glucose into glycogen and increases glucose production by the liver from glycogen, as well as de novo synthesis of glucose (gluconeogenesis) accounting for a fasting glycaemia, above 6.1 mmol/L (110 mg/dL) and below 6.9 mmol/L (125 mg/dL).2 In a state of insulin resistance, insulin is unable to suppress lipolysis in adipocytes and to activate adipose tissues endothelial lipoprotein lipase resulting in increased plasma nonesterified fatty acid supply to the liver that translates into increased hepatic production of very low-density lipoprotein levels and atherogenic hyperlipidemia.3–5 According to the National Cholesterol Education Program Adult Treatment Panel (ATP) III definition, metabolic syndrome will be present if at least three of the following criteria are met: waist circumference more than 40 inches (men) or 35 inches (women), blood pressure more than 130/85 mmHg, fasting triglyceride level superior to 150 mg/dl, fasting high-density lipoprotein–cholesterol below 40 mg/dL (men) or 50 mg/dL (women), and fasting blood sugar above 100 mg/dL.6 Excess of plasma glucose and triglycerides in metabolic syndrome result is fatty acid accumulation in the liver disrupting hepatocytes function leading to nonalcoholic steatohepatitis.7 Thus, inhibiting insulin resistance and accumulation of triglycerides and cholesterol in the liver with natural products constitute one therapeutic strategy to prevent or manage insulin resistance in metabolic syndrome 3.1 Myristica fragrans Hout Synonyms: Myristica aromatica Lam.; Myristica moschata Thunb.; Myristica officinalis L.f Common names: buah pala (Malay); ru du ku (Chinese); nutmeg Subclass Magnoliidae, Superorder Magnolianae, Order Myristicales, Family Myristicaceae Medicinal use: facilitate digestion (Malaysia) Pharmacological targets: atherogenic hyperlipidemia; insulin resistance Macelignan from Myristica fragrans Hout at a concentration of μM protected HepG2 cells against tert-butyl hydroperoxide increasing their viability by 91.2% as evidenced by a decrease in reactive oxygen species and malondialdehyde, which is a marker of lipid peroxidation.8 Insulin binding to its hepatic receptor stimulates the expression of the transcription factor sterol regulatory element-binding protein-1c in the liver mediating most of insulin effects on fatty acid synthesis.9 Meso-dihydroguaiaretic acid (Figure 3.1) from this plant at a concentration of 10 μM repressed the transcription factor sterol regulatory element-binding protein-1c and consequently fatty acid synthetase and acetyl-CoA carboxylase in HepG2 cells.10 Furthermore, this lignan reduced by more than 50% of triglyceride accumulation in HepG2 cells pretreated with insulin.10 Simultaneously, this lignan induced the expression of peroxisome proliferator-activated receptor-α and downstream carnitine palmitoyltransferase-1 and uncoupling protein-2,10 which catalyze fatty acids oxidation in 177 178 Medicinal Plants in Asia for Metabolic Syndrome O HO O OH FIGURE 3.1 Meso-dihydroguaiaretic acid the liver.11 In hepatocytes, protein tyrosine phosphatase 1B is a negative regulator in insulin signal transduction by dephosphorylating the activated insulin receptor or insulin receptor substrates.12 Meso-dihydroguaiaretic acid and otobaphenol inhibited the enzymatic activity of this enzyme with IC50 values equal to 19.6 and 48.9 mM, respectively,13 implying increased insulin sensitivity In 32D cells, meso-dihydroguaiaretic acid at a concentration of 10 μM enhanced the phosphorylation of insulin receptor tyrosine resulting from insulin binding and increased insulin sensitivity.13 For every 30 mg/dL, reduction in plasmatic low-density lipoprotein, the relative risk of developing cardiovascular diseases is lowered by approximately 30%.14 Myristica fragrans tetrahydrofuran lignans mixture given orally to C57BL/6 at a dose of 200 mg/kg/day poisoned with a high-fat diet for weeks resulted in a 30% reduction of epididymis fat compared with untreated animals, a mild reduction in food intake, low-density lipoprotein–cholesterol, cholesterol, and glyceamia.15 Adenosine monophosphate-activated protein kinase is a heterotrimeric protein consisting of a catalytic subunit (α) and noncatalytic subunits (β and γ) In response to elevated AMP/ATP (State of energy deprivation) ratios, adenosine monophosphate-activated protein kinase is phosphorylated in the α-subunit.16 Activated adenosine monophosphate-activated protein kinase phosphorylates and inhibit acetyl-CoA carboxylase, which is the rate-limiting enzyme in fatty acid synthesis.17 Fatty acid synthetase is the rate-limiting enzyme in fatty acid synthesis by catalyzing the final step.18 Adenosine monophosphate-activated protein kinase promotes fatty acid oxidation by upregulating the expression of peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1.19 Activated adenosine monophosphate-activated protein kinase inhibits the synthesis of cholesterol, via the suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.20 The lignans tetrahydrofuroguaiacin B, nectandrin B, and nectandrin A isolated from this plant at a concentration of μM induced the activation of adenosine monophosphate-activated protein kinase and downstream inhibition of acetyl-CoA carboxylase.14 Lipid peroxidation in the liver is linked with insulin resistance.21 3.2 Cinnamomum burmannii (Nees & T Nees) Blume Synonyms: Cinnamomum chinense Blume; Cinnamomum dulce (Roxb.) Sweet; Laurus burmannii Nees & T Nees; Laurus dulcis Roxb Common names: yin ziang (Chinese); kayu manis (Malay); Indonesian cassia Subclass Magnoliidae, Superorder Lauranae, Order Laurales, Family Lauraceae Medicinal use: hypertension (Indonesia) Pharmacological target: insulin resistance 179 Liver O FIGURE 3.2 Cinnamaldehyde In the postprandial state, insulin inhibits phosphoenolpyruvate carboxykinase and glucose6-phosphatase to block the production of glucose also termed gluconeogenesis.22 Cinnamomum burmannii (Nees & T Nees) Blume contains cinnamaldehyde (Figure 3.2), which given orally at a dose of 20 mg/kg/days for 60 days to streptozotocin-induced diabetic Wistar rats decreased glycaemia from 396 to 152 mg/dL, decreased weight loss and polydipsia and an increased plasma insulin.23 At the hepatic level, a normalization of phosphoenolpyruvate carboxykinase was observed as a possible consequence of insulin stimulation.23 Phosphoenolpyruvate carboxykinase is the ratelimiting enzyme of gluconeogenesis leading to the release of glucose from the liver, and the expression of this enzyme is used as an indicator of liver glucose secretion.24 Ethanol extract of bark given at a single oral dose of 500 mg/kg to hyperglycemic C57Bl/6J mice lowered fasting glycaemia by 18.9% after hours.25 Decrease of glycaemia in fasting rodents by natural products, if not owed to increased insulin secretion, can be explained by stimulation of glucose uptake by peripheral tissues, correction of insulin resistance, inhibition of liver glucose production, or stimulation of glycogen synthesis by stimulating glycogen synthetase activity The extract at a dose of 25 μg/mL inhibited glucose production by H4IIE rat hepatoma cells with concomitant repression phosphoenolpyruvate carboxykinase and glucose-6-phosphatase.25 Aqueous extracts of bark of Cinnamomum burmanii inhibited the enzymatic activity of protein tyrosine phosphatase 1B with IC50 values 6.2 μg/mL respectively implying increased insulin sensitivity.26 From this extract, 5ʹ-hydroxy-5hydroxymethyl-4”,5”-methylenedioxy-1,2,3,4-dibenzo-1,2,5-cycloheptatriene and cinnamaldehyde inhibited the enzymatic activity of protein tyrosine phosphatase B with IC50 values of 29.7 and 57.6 μM, respectively.26 Protein tyrosine phosphatase B decreases the sensitivity of insulin to its receptor and contributed to insulin resistance.27 3.3 Cinnamomum zeylanicum Blume Synonym: Cinnamomum verum J S Presl Common names: cocam (India); true cinnamon Subclass Magnoliidae, Superorder Lauranae, Order Laurales, Family Lauraceae Medicinal use: indigestion (India) History: the plant was known of Hippocrates, Greek physician (circa 460–370 BC) Pharmacological targets: atherogenic hyperlipidemia; insulin resistance In hepatocytes, excess of fatty acids brought by the plasmatic circulation from adipose tissues activate peroxisome proliferator-activated receptor-α that binds to the peroxisome proliferators response element of DNA and induce the transcription of genes encoding hepatic fatty acid β-oxidation.11 Spontaneous type diabetic obese db/db mice receiving orally bark powder of Cinnamomum zeylanicum Blume at a daily dose of 200 mg/kg for 12 weeks had fasting glucose levels reduced by more than 50% and insulinaemia increased by 74%.28 This regimen decreased triglyceridaemia, plasma cholesterol, fatty acids, and increased in high-density lipoprotein–cholesterol.28 Furthermore, the hepatic contents in fatty acids was reduced by 65.6% compared with untreated rodents and histological observation livers evidenced a reduction in lipid droplets.28 Of note, Cinnamon-treated rodents had increased expression of peroxisome proliferator-activated receptor-α by 11.4%,28 and this is interesting because activators of peroxisome proliferator-activated receptor-α by induce fatty acid 180 Medicinal Plants in Asia for Metabolic Syndrome β-oxidation in the liver whence lipid-lowering activity.29 In a subsequent study, Ranasinghe et al provided evidence that aqueous extract of Cinnamomum zeylanicum Blume given to streptozotocininduced Sprague–Dawley rats orally at a dose of 600 mg/kg/day for month decreased fasting glycaemia from 320 to 247 mg/dL, lowered plasma cholesterol from 72 to 50 mg/dL, low-density cholesterol from 12.9 to 3.1 mg/dL, elevated high-density lipoprotein–cholesterol from 19.5 to 26.9 mg/dL, and lowered triglycerides from 198.2 to 131 mg/dL.30 In hepatocytes, fatty acids contribute to insulin resistance by via metabolic competition or through an effect on the insulin-signaling pathway, possibly by activating atypical protein kinase C.31 Activation of peroxisome proliferatoractivated receptor-α increase the oxidation of fatty acids by decreasing liver content of fatty acids and triglycerides to reduce lipotoxicity and increase insulin sensitivity.32 Spontaneous type diabetic obese db/db mice receiving orally cinnamaldehyde at a dose of 20 mg/kg/day for 4 weeks evoked a mild reduction of body weight, fasting blood glucose, insulinaemia, free fatty acids, and increase in high-density lipoprotein–cholesterol, a protective factor against coronary heart disease.33,34 Furthermore, an increase in phosphorylated Akt and glucose transporter-4 expression in peripheral tissues were observed.33 The consumption of Cinnamomum zeylanicum Blume could be beneficial in metabolic syndrome Clinical trails are warranted 3.4 Lindera strychnifolia (Siebold & Zucc.) Fern.-Vill Common name: wu yao (Chinese) Subclass Magnoliidae, Superorder Lauranae, Order Laurales, Family Lauraceae Medicinal use: blood stasis (China) Pharmacological targets: atherogenic hyperlipidemia; insulin resistance Bile acids in the liver activate a nuclear receptor termed farnesoid X receptor that controls triglyceride and cholesterol metabolism With regard to cholesterol metabolism, this nuclear receptor induces the expression of small heterodimer partner (SHP) that inhibits CYP7A1, an enzyme also known as cholesterol-7α-hydroxylase, which catalyze the synthesis of bile acids from cholesterol.35 Besides, activation of farnesoid X receptor prompts the secretion of bile acids and cholesterol into bile duct via the activation of hepatic ATP-binding cassette (ABC) transporters ABCB11 and ABCG5/8, respectively.36 Natural products with the ability to activate farnesoid X receptor promote biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol.37 The roots of Lindera strychnifolia (Sieb et Zucc.) Fern.-Vill contain isoquinoline alkaloids including boldine (Figure 3.3).38 Boldine given orally at a dose of 100 mg/kg/day for weeks reduced the glycaemia of rodents poisoned with streptozotocin from 538.4 to 311.4 mg/dL, increased body weight, reduced HO N O H O OH FIGURE 3.3 Boldine 181 Liver hepatic lipid peroxidation, and increased hepatic glutathione peroxidase activity.39 Boldine is antioxidant as at a concentration of 100 μM prevented in vitro the generation of superoxide and hydrogen peroxide production from hepatic mitochondria challenged with antimycin.39 In a subsequent study, boldine given to hereditary hypertriglyceridemic rats on as part of 0.2% of high-sucrose diet for weeks induced a decrease of glycaemia from 15 to 14 mmol/L, increased high-density lipoprotein–cholesterol from 0.8 to 0.9 mmol/L, triglycerides from 2.7 to 1.5 mmol/L, and bile acids from 5.5 to 2.7 μmol/L, whereas plasma cholesterol was unchanged.40 This alkaloid reduced hepatic triglyceride contents in high-sucrose diet rats from 4.9 to 4.2 μmol/L and improved hepatic cytoarchitecture.40 Boldine increased bile flow and bile acid secretion toward levels seen in control animals, increased hepatic glutathione contents, and increased the expression of transporters for bile acids, ATP-dependent human bile salt export pump (Bsep/ABCB11) and sodium-taurocholate cotransporting polypeptide (Ntcp).40 Boldine at a concentration of μM evoked the activation of farnesoid X receptor in transfected HepG2 cells.41 Other hepatoprotective constituents in the roots of Lindera strychnifolia (Sieb et Zucc.) Fern.-Vill are sesquiterpenes of which bi-linderone and lindestrene.38 Lindestrene given orally at a dose of 100 mg/kg, twice daily for days, and hour before galactosamine-induced hepatic insults evoked a decrease of plasmatic aspartate aminotransferase and GPT I Wistar rats.42 Bi-linderone at a concentration of μg/mL protected HepG2 cells against glucosamine-induced inhibition of insulin receptor sensitivity as evidenced by increased expression of phosphorylated insulin receptor and phosphorylated Akt.43 3.5 Persea americana Mill Synonyms: Laurus persea L.; Persea edulis Raf.; Persea gratissima C.F Gaertn Common name: e li (Chinese); avocado Subclass Magnoliidae, Superorder Lauranae, Order Laurales, Family Lauraceae Medicinal use: diarrhea (Philippines) Pharmacological targets: atherogenic hyperlipidemia; insulin resistance Hashimura et  al provided evidence that persin also known as (2R,12Z,15Z)-12-hydroxy-4-oxoheneicosa-12,15-dienyl acetate as well as 5E, 12Z, 15Z-2-hydroxy-4-oxo-heneicosa-5,12,15-trienyl actetate or persenone A from the fruits of Persea americana Mill inhibited in vitro acetyl-CoA carboxylase with IC50 values of 4.9 × 10 −6 M and × 10 −6 M, respectively.44 In the liver, the synthesis of fatty acid starts with the building of malonyl-CoA from acetyl-CoA by acetyl-CoA carboxylase.45 Inhibition of acetyl-CoA carboxylase may account for the fact that aqueous extract of leaves given orally to high-cholesterol diet albino rats at a dose of 10 mg/kg/day for weeks lowered plasma cholesterol by 8%, increased high-density lipoprotein by 85%, and decreased low-density lipoprotein–cholesterol by 19%.46 In the liver, fatty acids are used for the building of triglycerides, which are packed into very low-density lipoproteins.47 Besides, the fruits given at 5% of diet to rats for 14 days prevented hepatic damages evoked by d-galactosamine as evidence by a drastic reduction of plasmatic aspartate aminotransferase compared with untreated animals.48 From the fruits, persenone A, (2E,5E,12Z,15Z)-1-hydroxyheneicosa-2,5,12,15-tetraen-4-one, (2E,12Z,15Z)1-hydroxyheneicosa-2,12,15-trien-4-one, and (5E,12Z)-2-hydroxy-4-oxoheneicosa-5,12-dien-1-yl acetate given orally at a single dose of 100 mg/kg prevented by d-galactosamine-induced liver injuries with a reduction of markers of liver insults plasma serum aspartate transaminase and alanine transaminase by about 50%.48 The hepatoprotective mechanism involved here is unknown but it must be recalled that in hepatocytes, insults induce the transcription of lipogenic genes and accumulation of triglycerides in intracellular lipid droplets.49 In hepatocytes, accumulation of fatty acids forsters the formation of reactive oxygen promoting hepatic insulin resistance,49 and inhibition of acetyl-CoA carboxylase improve hepatic insulin sentitivity.50 Hydroalcoholic extract of leaves of Persea americana Mill given at a dose of 0.3 g/kg/day for 28 days to streptozotocin-diabetic rats 182 Medicinal Plants in Asia for Metabolic Syndrome reduced fasting glucose levels by 71%, improved glucose tolerance, lowered daily water intake, and increased body mass gain compared with untreated diabetic animals.51 Further, hepatocytes and soleus muscles of treated diabetic rats exhibited an increased expression of phosphorylated Akt by more than 75% suggesting increased glucose intake from skeletal muscles in treated animals.51 Of note, hours after consumption of a test beef burger, the peripheral arterial tone score of healthy male volunteers was decreased by 27.4% and this was prevented by adding 68 g of avocado into a test beef burger.52 Peripheral blood mononuclear cells isolated after test burger consumptions evidenced a slight elevation of IkB-α suggesting a decrease in nuclear factor-κB activity and therefore peripheral inflammation.52 A decrease in serum interleukin-6 was observed hours after burgers consumption.52 The consumption of avocado could be of benefit in metabolic syndrome 3.6 Piper longum L Synonym: Chavica roxburghii Miq Common names: bi ba (Chinese); long pepper Subclass Magnoliidae, Superorder Piperanae, Order Piperales, Family Piperaceae Medicinal use: facilitates digestion (China) History: the plant was known of the plant was known of Hippocrates Pharmacological targets: atherogenic hyperlipidemia; insulin resistance In the liver, the synthesis of triglycerides from fatty acids and glycerol-3-phosphate is catalyzed by glycerol-3-phosphate-acyltransferase and acyl CoA:diacylglycerol acyltransferase and synthetized triglycerides are either stored in cytosolic lipid droplets or packed into very low-density lipoproteins by conjugation to apoB-100 and exported in the blood stream.47 (2E,4Z,8E)-N-[9-(3,4Methylenedioxyphenyl)-,4,8-nonatrienoyl]-piperidine and pipernonaline from Piper longum L inhibited acyl CoA:diacylglycerol acyltransferase with IC50 values of 29.8 and 37.2 μM.53 Ethanol extract of fruits of Piper longum L given orally to rats at a dose of 20 mg/kg/day for 15 days lowered plasma cholesterol from 7.5 to 5.8 mmol/L and triglycerides from 0.7 to 0.6 mmol/L.54 From this extract, piperlonguminine, piperine, and pipernonaline given orally at a dose of 5.6 mg/kg/day for 15 days reduced plasma cholesterol and triglycerides and elevated high-density lipoprotein–cholesterol more potently that simvastatin at 5.6 mg/kg/day for 15 days.54 In this experiment, piperlonguminine, piperine, and pipernonaline given orally at a dose of 5.6 mg/kg/day for 15 days had no effect of low-density lipoprotein–cholesterol.54 Piperine given to C57BL/6N mice as part of 0.05% high-fat diet for 10 weeks had no effect on food intake, lowered body weight gain by 67%, significantly reduced plasma triglycerides by 83%, free fatty acids by 81%, cholesterol by 58%, high-density lipoprotein–cholesterol by 38%, and very low-density lipoprotein–cholesterol + low-density lipoprotein–cholesterol by 82%.55 This regimen decreased lipid deposition in the livers of mice fed a high-fat diet.55 Piperine administration decreased insulin receptor substrate-1 serine phosphorylation, increased Akt phosphorylation, and elevated glucose transporter-2 membrane translocation.55 Improved insulin sensitivity was also evidenced by a decreased activity gluconeogenic enzymes namely, glucose 6-phosphatase and phosphoenolpyruvate carboxykinase that are physiologically inhibited by insulin.55 In hepatocytes, liver X receptor-α is activated by metabolites of cholesterol also known as oxysterols Activation of this nuclear receptor induce the expression of sterol regulatory element binding protein-1c and subsequent expression of fatty acid synthase and stearoyl coenzyme A desaturase (SCD-1) leading to fatty acid synthesis and increased triglyceridemia.56 In transfected HEK293 cells, piperine at a concentration of 100 μM inhibited the transcriptional activity of liver X receptor-α.55 Physiologically, adenosine monophosphate-activated protein kinase is activated by adiponectin via LKB1.57 Phosphorylated adenosine monophosphate-activated protein kinase inhibits mTORC1, S6 protein kinase and downregulates the expression of liver X receptor-α At the same time, phosphorylated adenosine monophosphate-activated protein kinase inhibits acetyl-CoA carboxylase lifting malonyl-CoA inhibition Liver 183 on carnitine palmitoyltransferase-1 and promoting thus the entry of fatty acyl-CoA in mitochondria for β oxidation.58 S6 protein kinase inhibition results in insulin receptor substrate-1 activation and Akt phosphorylation and thereby increased sensitivity to insulin.59 Piperine given at a dose of 50 mg/ kg/day to C57BL/6N mice feeding a high-fat diet for 13 weeks evoked in the liver of treated animals increased expression of adiponectin receptors, phosphorylated adenosine monophosphate-activated protein kinase, and reduction in expression of liver X receptor-α, sterol regulatory element binding protein-1c, and fatty acid translocase as well as decreased phosphorylation of S6K1 implying adenosine monophosphate-activated protein kinase activation.59 In line, administration of piperine to mice resulted in an increase in glucose transporter-2 found in the membrane, decreased phosphorylation of insulin receptor substrate-1 and increased the phosphorylation of Akt and increased expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, key enzymes involved in hepatic gluconeogenesis implying improved insulin sensitivity.59 All of these suggest that intake of Piper longum L could be of value in metabolic syndrome to lower hepatic insulin resistance as well as lowdensity lipoprotein–cholesterol, the elevation of which is a strong indicator of a coronary heart disease in diabetic patients.60 Clinical trails are warranted 3.7 Piper retrofractum Vahl Synonyms: Chavica officinarum Miq.; Piper chaba Hunter; Piper officinarum (Miq.) C DC Common names: jia bi ba (Chinese); litlit (Philippines) Subclass Magnoliidae, Superorder Piperanae, Order Piperales, Family Piperaceae Medicinal use: indigestion (Philippines) Hypercholesterolemia is the critical step in the initiation of atherosclerosis, placing hypercholesterolemic individuals at a greater risk of cardiovascular diseases.61 Total plasma cholesterol depends on the absorption of cholesterol by the intestine, the synthesis of cholesterol in the liver and the catabolism of cholesterol In C57BL/6J mice fed with high-fat diet, piperidine alkaloids of which piperidine, dehydropipernonaline, and pipernonaline given at a dose of 300 mg/kg/day for weeks reduced plasma cholesterol by 44.3% and low-density lipoprotein–cholesterol by 57.6%.62 In the liver of high-fat diet fed C57BL/6J mice piperidine alkaloids evoked the phosphorylation of adenosine monophosphate-activated protein kinase and target acetyl-CoA carboxylase.62 This regimen also inhibited the expression of sterol regulatory element-binding protein-1c and subsequently fatty acid synthetase and acetyl-CoA carboxylase.62 In parallel, this regimen increased carnitine palmitoyltransferase-1 and uncoupling protein 2, which are targets of peroxisome proliferator-activated receptor-α hence hepatic lipolysis.62 Activation of adenosine monophosphate-activated protein kinase in the liver evokes the activation of peroxisome proliferator-activated receptor-γ coactivator 1-α that coactivates peroxisome proliferator-activated receptor-α leading to β-oxidation of fatty acids.63 3.8 Nelumbo nucifera Gaertn Synonyms: Nelumbium nuciferum Gaertn.; Nelumbo speciosa Willd.; Nymphaea nelumbo L Common names: lian (Chinese); sacred lotus Subclass Ranunculidae, Superorder Proteanae, Order Nelumbonales, Family Nelumbonaceae Medicinal use: anxiety (China) Visceral adiposity is associated with elevated triglycerides and reduced high-density lipoprotein– cholesterol concentrations in the plasma.64 Nuciferine given orally at a dose of 15 mg/kg/day to golden Syrian hamsters on high-fat diet for weeks protected rodents against high-fat diet induced obesity for weeks attenuated body weight gain and liver weight gain without decreasing food intake.65 This regimen decreased toward normal values plasma and liver cholesterol, triglycerides and fatty acids, and decreased plasma low-density lipoprotein–cholesterol without affecting high-density 184 Medicinal Plants in Asia for Metabolic Syndrome lipoprotein–cholesterol.65 In the same experiment, nuciferine defended hepatocytes against fatinduced hepatosteatosis and hepatic necroinflammation as evidenced by a decrease in plasma alanine transaminase.65 In hepatocytes, nuciferine decreased the expression of liver X receptor-α, sterol regulatory element binding protein-1c and subsequently acetyl-CoA carboxylase, fatty acid synthetase, stearoyl coenzyme A desaturase 1.65 Simultaneously, nuciferine treatment increased the expression of peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase implying increased fatty acid β-oxidation.65 This alkaloid repressed the expression of peroxisome proliferator-activated receptor-γ, lipoprotein lipase, and fatty acid translocase suggesting reduced infiltration of plasmatic fatty acids.65 The isoqunoline enhanced the expression of apolipoprotein-B and microsomal triglyceride transfer protein that account for very low-density lipoprotein secretion.65 Nuciferine itself may not be responsible for the aforementioned effect as, after oral administration, nuciferine undergoes phase I and phase II metabolism to afford about 10 metabolites, with phase I demethylation being the principal route.66 It must be recalled that oral LD50 of nuciferine in mice and rat is 240 and 280 mg/kg, respectively,67 and that it evokes decreased motor activity, ptosis, hind-leg spread, and hypotonia in rodents.68 Having a relatively low LD50 and psychopharmacological effect, nuciferine itself may be of limited use in therapeutic Instead, intake of leaves as a form of tea, if not toxic, could be possibly envisaged in metabolic syndrome The current tendency to look for pure compounds and to impose the standardization of extract could be a mistake 3.9 Coptis chinensis Franch Common name: huang lian (Chinese) Superorder Ranunculanae, Order Ranunculales, Family Ranunculaceae Medicinal use: fever (China) Evidence has been provided to demonstrate that berberine, coptisine, columbamine, and jatrorrhizine present in the rhizome of Coptis chinensis Franch inhibit the synthesis of triglycerides and cholesterol in hepatocytes in vitro Berberine inhibited the synthesis of cholesterol and triglycerides in HepG2 cells with an IC50 value equal to approximately 15 μg/mL in vitro,69 and this effect was later confirmed by Fan et al.70 and Cao et al.71 with increased expression of carnitine palmitoyltransferase and medium-chain acyl-CoA dehydrogenase, which are associated with fatty acid oxidation Berberine induced the expression of low-density lipoprotein receptor in HepG2 cells at dose of 20 μg/mL via with phosphorylation of extracellular signal-regulated kinase-1/2.72 From this plant columbamine at a concentration of 15 μM reduced triglyceride contents in Hep G2 cells by 35% with concomitant phosphorylation of adenosine monophosphate-activated protein kinase as potently as berberine, and consequently both alkaloids repressed the expression fatty acid synthetase, acetyl-CoA carboxylase, and glycerol-3-phosphate-acyltransferase, which are associated with triglyceride synthesis and of 3-hydroxy-3-methyl-glutaryl-CoA reductase, which catalyzes the synthesis of cholesterol.71 Columbamine also increased the gene expression of and medium-chain acyl-CoA dehydrogenase, but had no effects on carnitine palmitoyltransferase 1.71 Coptisine for this plant at concentration of 0.2 μg/mL reduced the accumulation of triglycerides in HepG2 cells cultured in the presence of fatty acids by 48.9%.70 Jatrorrhizine at a concentration of 15 μM reduced triglyceride contents in HepG2 cells challenged with fatty acids by 30% with modest effects on adenosine monophosphate-activated protein kinase phosphorylation.71 As for in vivo studies, Brusq et  al administered orally to rodent on high-fat diet berberine given at a dose of 100 mg/kg/day for 10 days and noted a decrease in plasma low-density lipoprotein–cholesterol by 39% and at the hepatic level a reduction of triglycerides, cholesterol, and cholesteryl ester by 23%, 27%, and 41%, respectively.69 In a subsequent study, Cao et al provided evidence that an alkaloidal extract of rhizomes of a member of the genus Coptis Salisb given orally to Sprague–Dawley rats 185 Liver on high-fat diet for 14 days at a dose of 100 mg/kg/day reduced plasma cholesterol and low-density lipoprotein–cholesterol and normalized triglycerides and high-density lipoprotein–cholesterol.73 Furthermore, this regimen doubled the production of bile in the liver and tripled the presence of bile acids in the feces.73 The extract at a dose of 100 mg/kg/day for 14 days increased the expression of peroxisome proliferator-activated receptor-α and decreased the expression of farnesoid X receptor and therefore increased the expression of cholesterol 7α-hydroxylase also known as CYP7A1, a key enzyme in bile acids synthesis from cholesterol.73 Jatrorrhizine from Coptis chinensis Franch at a dose of 100 mg/kg to mice induced a reduction of glycaemia from 5.9 to 4.6 mmol/L and a decrease in liver glycogen from 17.4 to 8.4 mg/.74 In alloxan-induced diabetic mice the glycaemia was reduced by daily administration of jatrorrhizine oral at a dose 100 mg/kg/day for days from 21.6 to 16.4 mmol.74 The enzymatic activity of succinate dehydrogenase was increased from 6.8 to 11.2 U/mg protein suggesting an increase in aerobic utilization of glucose in hepatocytes.74 In a subsequent study, this protoberberine given orally to Syrian golden hamsters at a dose of 70 mg/kg/day for 90 days lowered plasma cholesterol, triglycerides, and low-density lipoprotein–cholesterol by 20%, 43%, and 19%, respectively, and increased high-density lipoprotein–cholesterol and bile acids content in feces.75 Besides, jatrorrhizine upregulated the expression of low-density lipoprotein– cholesterol receptor and cholesterol 7α-hydroxylase but exhibited no effect on the expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase and sodium-dependent bile acid transporter in hamsters.75 In  human, a direct effect of berberine is improbable because oral administration of decoction of rhizomes of a member of the genus Coptis Salisb in healthy volunteers is followed by the presence of jatrorrhizine 3-O-β-d-glucuronide, columbamine 2-O-β-d-glucuronide, jatrorrhizine 3-O-sulfate, and traces of berberine.76 3.10 Agrostemma githago L Synonyms: Lychnis githago (L.) Scop Common names: mai xian weng (Chinese); katir cicegi (Turkey); corn-rose (English) Subclass Caryophyllidae, Superorder Caryophyllanae, Order Caryophyllales, Family Caryophyllaceae Medicinal use: cough (Turkey) Agrostemma githago given orally at a dose of 100 mg/kg/day for 30 days to Swiss albino mice feeding on diet containing 1% cholesterol, reduced cholesterolaemia from 218.4 to 98.2 mg/dL.77 Serum high-density lipoprotein–cholesterol was increased by Agrostemma githago L from 25.8 to 36.8 mg/dL.77 Agrostemma githago reduced low-density lipoprotein–cholesterol from 143.0 to 42.0 mg/L77 triglyceridemia from 194.2 to 117.8 mg/dL and glycaemia from 79.8 to 61 mg/dL.77 The use of the plant for cough suggests the presence of saponins, which have the tendency to inhibit dietary cholesterol absorption as discussed in chapter 3.11 Nigella sativa L Common names: Krishna jiraka (India); habbatus sauda (Malay); fennel flower seeds Subclass Caryophyllidae, Superorder Ranunculanae, Order Menispermales, Family Ranunculaceae Medicinal use: tonic (Malaysia) History: known of Hippocrates Ethanol extract of seeds of Nigella sativa L at a concentration of 200 μg/mL increased in vitro the phosphorylation of Akt in H4IIE hepatocytes with increased contents of phosphorylated adenosine monophosphate-activated protein kinase and its downstream substrate acetyl-CoA carboxylase.78 In addition, the extract evoked uncoupling of oxidative phosphorylation in isolated liver 186 Medicinal Plants in Asia for Metabolic Syndrome mitochondria.78 In vitro, ethanol extract of seeds of Nigella sativa L reduced the triglycerides levels in high glucose-pretreated HepG2 cells by about 15% at a dose of 10 μg/mL.79 In vivo, this extract given to streptozotocin-induced diabetic Wistar rats at a dose of 300 mg/kg/day for 30 days lowered plasma cholesterol from 283.5 to 171.2 mg/dL, low-density lipoprotein–cholesterol from 186.1 to 85 mg/dL, increased high-density lipoprotein–cholesterol from 59.8 to 63.5 mg/dL, and lowered plasma triglycerides from 185.1 to 113.8 mg/dL.80 This regimen increased plasma insulin from 4.2 to 11.3 μU/mL.80 Methanol extract of seeds given orally at a doses of 500 mg/kg/day for 3 days mildly increased food intake, body and liver weights, and reduced liver triglycerides in ddY male mice.79 One of the major constituent of the seeds is thymoquinone (Figure 3.4), which given to Sprague–Dawley rats on high-cholesterol diet orally at a dose of 100 mg/kg/day for weeks plasma cholesterol from 2.1 to 0.9, low-density lipoprotein–cholesterol from 1.6 to 0.4 and plasma triglycerides from 0.6 to 0.4.81 At the hepatic level, this regimen increased the expression of low-density lipoprotein–cholesterol receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase.81 Thymoquinone given orally at a dose of 20 mg/kg/day for weeks to Wistar rats on high-fat diet lowered glycaemia and plasma insulin, insulin resistance by 53%, decreased triglyceride from 89 to 61.5 mg/dL, cholesterol from 205.9 to 151.3 mg/dL, and increased highdensity lipoprotein–cholesterol from 30.2 to 47.2 mg/dL.82 High-fat diet elevated the expression of peroxisome proliferator-activated receptor-γ, which was reduced by 167% upon thymoquinone treatment.82 Male volunteers aged 35–50 years with mild hypertension receiving 200 mg of an aqueous extract of seeds of Nigella sativa twice a day for weeks had lower systolic blood pressure and diastolic blood pressure compared to untreated individuals as well as reduced low-density lipoprotein–cholesterol.82 3.12 Corydalis saxicola Bunting Synonym: Corydalis thalictrifolia Franch Common name: yan huang lian (Chinese) Subclass Ranunculidae, Superorder Ranunculanae, Order Papaverales, Family Fumariaceae Medicinal use: hepatitis (China) Koruk et  al observed increased plasmatic malondialdehyde, nitric oxide, and lower activity of superoxide dismutase in patients with nonalcoholic steatohepatitis and suggested an impairment of hepatic antioxidant enzymatic defense system.83,84 In hepatocytes, superoxide dismutase converts superoxide into hydrogen peroxide, oxygen, and water.85 Glutathione peroxidase catalyzes reductive destruction of hydrogen peroxide and lipid hydroperoxide using glutathione.85 Increased intrahepatic levels of fatty acids are a source of oxidative stress, which interferes with insulin sensitivity Corydalis saxicola Bunt elaborates series of hepatoprotective alkaloids of which tetrahydropalmatine,86 palmatine,87 protopine,88 berberine, coptisine, and dehydroapocavidine.89 Dehydrocavidine given at a dose of mg/kg before or after carbon tetrachloride poisoning, prevented the increase O O FIGURE 3.4 Thymoquinone 474 AMPK See Adenosine monophosphate-activated protein kinase (AMPK) Andrographis paniculata (Burm f.) Wall ex Nees, 250–251, 437 Andrographolide, 250, 251f Anemarrhena asphodeloides Bunge, 352, 444–445 Anethum graveolens L., 229 Angelica acutiloba (Siebold & Zucc.) Kitag., 230, 422–423, 422f Angelica dahurica (Fisch.) Benth & Hook f., 113, 114f, 423 Angelica gigas (Miq.) Franch & Sav., 325 Angelica japonica A Gray, 114–115 Angelica keiskei Koidz., 230, 325–326 Angiotensin, 426–427 Anisodamine, 131, 132f Anisodus tanguticus (Maxim.) Pascher, 131 Annona squamosa L., 75 Anoectochilus roxburghii (Wall.) Lindl ex Wall., 146, 446 Anthocyanin-rich fraction, 226 Anthocyanins, 435 extract of fruits, Cornus mas L., 109 fraction, 435 fruits, 19, 30 Ipomoea batatas (L.) Lam., 435–436 Anthraquinone, 190–191, 299, 396 Aphadilactone C, 319, 319f Aphanamixis grandifolia Bl., 319 Apigenin-7,4′-dimethyl ether, 2f Apigenin 7-O-glucoside, 239 ApoE –/– C57BL6J mice, 433 ApoE knock-out mice piperlongumine, 387 Polygonum aviculare L., 396 Apolipoprotein A-I, 217 Apolipoprotein B, 189 Apoliproptein-E gene (ApoE –/–) mice, 226 anthocyanins, 435 berberine, 390 Dioscorea batatas Decne., 451 Hippophae rhamnoides L., 420 Juglans regia L., 395 salvianolic acid A, 440 Aporosa lindleyana (Wight) Baill., 90 Aqueous extract aerial part Achillea santolina L., 116 Desmodium gangeticum (L.) DC., 99–100 Teucrium polium L., 144 Anoectochilus roxburghii (Wall.) Lindl., 446 Arbutus unedo L., 300 bark Ficus religiosa L., 89–90 Garuga pinnata Roxb., 97 Octomeles sumatrana Miq., 202 Benincasa hispida (Thunb.) Cogn., 399–400 Calamintha officinalis Moench, 346–347 Camellia sinensis (L.) Kuntze, 397 Caralluma fimbriata Wall., 246 Centaurium erythraea Rafn, 123 Chromolaena odorata (L.) R.M King & H Rob., 119 Chrysanthemum morifolium, 333 Cinnamomum zeylanicum Blume, 180 Enicostemma littorale Blume, 244, 337 Index Euodia rutaecarpa (Juss.) Hook f & Thoms., 413 flowers Inula japonica Thunb., 120 Spilanthes acmella (L.) L., 431 fruits Aegle marmelos (L.) Corrêa, 311–312 Carum carvi L., 115, 424 Cornus officinalis Siebold & Zucc., 110 Cucumis trigonus Roxb., 84 Cucurbita ficifolia Bouché, 83, 302 Diospyros peregrina Gürke, 197 Embelia ribes Burm.f., 82 Lycium barbatum L., 247 Momordica charantia L., 85 Momordica cymbalaria Fenzl ex Naudin, 86 Phyllanthus emblica L., 402 Siraitia grosvenori Swingle, 86 Solanum muricatum Aiton, 434 Solanum xanthocarpum Schrad & Wendl., 340 Terminalia catappa L., 93 Withania coagulans (Stocks) Dunal, 340–341, 435 Gmelina arborea Roxb ex Sm., stem bark, 138 Gmelina asiatica L., 138 Hippophae rhamnoides L., deffated seeds of, 224 Ipomoea aquatica Forssk., leafy stem, 44 leaves Aegle marmelos (L.) Corrêa, 311–312 Arbutus unedo L., 398 Carica papaya L., 86 Combretum micranthum G., 93 Cosmos caudatus Kunth, 428 Cynara scolymus L., 239 Dendropanax morbiferum H Lév., 111 Eclipta prostrata (L.) L., 240 Gynura procumbens (Lour.) Merr., 429 Lagerstroemia speciosa, 94 Ocimum canum Sims, 141 Orthosiphon stamineus Benth., 143 Perilla frutescens (L.) Britton, 442 Persea americana Mill., 181 Phyllanthus acidus (L.) Skeels, 306 Rosmarinus officinalis L., 143 Rubus fruticosus L., 307 Smallanthus sonchifolius (Poeppig) H Robinson, 430 Tecoma stans (L) Juss ex Kunth, 343 Tephrosia purpurea (L.) Pers., 217 Tetracera scandens (L.) Merr., 299 Toona sinensis (A Juss.) M Roem., 318 Lycopersicon esculentum Mill., unripe fruits, 338–339 Marrubium vulgare L., 141 Morus alba L., 401 Ocimum basilicum L., 440 Ocimum canum Sims, 141 Ocimum sanctum L., 441 Orthosiphon stamineus Benth., 143, 441 Panax ginseng C.A Meyer, 421 Phyllanthus amarus Schumach & Thonn., 208 Phyllanthus simplex Retz., 91 Pinellia ternata (Thunb.) Makino, 350 Pterocarpus marsupium Roxb., 100, 310 rhizomes Asparagus adscendens Roxb., 147 Atractylodes macrocephala Koidz., 331–332 Curcuma longa, 259 475 Index roots Acanthopanax senticosus (Rupr ex Maxim.) Harms, 323–324 Achyranthes japonica (Miq.) Nakai, 79 Aporosa lindleyana (Wight) Baill., 90 Arbutus unedo L., 398 Casearia esculenta Roxb., 82 Codonopsis lanceolata (Siebold & Zucc.) Trautv., 236 Desmodium gangeticum (L.) DC., 406 Ficus benghalensis L., 89 Hygrophila auriculata Heine, 251 Rhodiola rosea L., 403 Salacia oblonga Wall., 28, 322, 419 Salvia miltiorrhiza Bunge, 438 Withania somnifera (L.) Dunal, 134–135, 341 Saururus chinensis (Lour.) Baill., Scutellaria baicalensis Georgi, 253 seeds Amomum xanthioides Wall ex Baker, 148, 357 Carum carvi L., 115 Cuminum cymimun L., 112 Lepidium sativum L., 400 Nigella sativa L., 186 Swietenia humilis Zucc., 317 Arachidonic acid, 382, 393–394 Aralia cachemirica Decne., 110 Aralia cordata Thunb., 227 Aralia, root bark, 81 Aralia taibaiensis Z.Z Wang & H.C Zheng, 110–111 Arbutin, 398, 398f Arbutus unedo L., 300, 398 Arctigenin, 116, 117f Ardisia japonica (Thunb.) Blume, 300 Areca catechu L., 354 Arecoline, 354, 354f Argyreia nervosa (Burm f.) Bojer, 135 Arjunolic acid, 341, 341f Artemetin, 426, 426f Artemisia capillaris Thunb., 329 Artemisia dracunculus L., 117, 330 Artemisia herba-alba Asso, 35 Artemisia indica Willd., 330 Artemisia princeps Pamp., 331 Artemisia sacrorum Ledeb, 238 Artemisia scoparia Maxim., 237, 329 AS160 See Akt substrate of 160 kDa (TBC1D) Asiatic acid, 231, 231f Asparagus adscendens Roxb., 147 Asparagus officinalis L., 148, 255 Asparagus racemosus Willd., 147–148, 448 Aster koraiensis Nakai, 427 Atherogenesis, 452f ATP-binding cassette (ABC), 180 Atractylodes macrocephala Koidz., 331–332 Aurapten, 411 Azadirachta indica A Juss, 107–108 B Bacopa monnieri (L.) Wettst., 436–437 Balb/c mice, 41, 124, 432 Barleria lupulina L., 345 Barringtonia racemosa (L.) Spreng., 9–10 Belamcanda chinensis (L.) Redouté, 147, 447 Benincasa hispida (Thunb.) Cogn., 399–400 Benzoquinone, 301 Berberine, 184–185, 295–296, 389, 390f Berberis wallichiana DC, 389–390 β-Amyrin acetate, 247 β-Amyrin palmitate, 129, 129f, 247 β-Asarone, 349–350, 349f β-Elemene, 227 Betulin, 251–252 Betulinic acid, 9f, 126 Bidens pilosa L., 117–118, 428 Biguanides, 107 Bile acids, 90, 180, 191, 226 Bile acid-sequestrating agents, 191 Bi-linderone, 181 Boesenbergia pandurata (Roxb.) Schltr., 357–358 Boldine, 180–181, 180f, 385 Borago officinalis L., 343–344 Boswellia serrata Roxb ex Colebr., 95–97, 96f, 417 Brassica juncea (L.) Coss., 87, 88f Brassica napus L., 204–205 Brassica oleracea L., 12–13, 12f, 203–204 Brassica rapa L., 204 Broussonetia kazinoki Siebold & Zucc., 14, 305 Broussonone A, 14f Brucea javanica (L.) Merr., 106 Bupleurum falcatum L., 423 Bupleurumin, 423 Butanol extract Momordica charantia L., fruits, 303–304 Polygonum cuspidatum Siebold & Zucc., rhizomes, 298 Butein, 98f Butylidenephthalide, 230 C C2C12 myocytes, 296 C2C12 myotubes, 318 C56BL6 mice, 113 C57BL/6J mice, 8, 63, 68 Adenophora tetraphylla (Thunberg) Fischer, 235 Alpinia officinarum Hance, 356 Angelica gigas (Miq.) Franch & Sav., 325 Artemisia scoparia Maxim., 237 betulin, 251 Boesenbergia pandurata (Roxb.) Schltr., 357–358 Catalpa bignonioides Walter, 342 Celastrus orbiculatus Thunb., 223 Centaurium erythraea Rafn, 123 citrulline, 198 Citrus maxima (Burm.) Merr., 218 Citrus reticulata Blanco, 312–313 Clerodendrum colebrookianum Walp., 345 Dioscorea batatas Decne., 354 geniposide, 241 Geranium thunbergii Siebold ex Lindl & Paxton, 321–322 Hippophae rhamnoides L., 224 Melissa officinalis L., 347–348 Momordica charantia L., 201 Panax ginseng C A Meyer, 227 Piper retrofractum Vahl., 183, 294–295 Platycodon grandiflorus (Jacq.) A DC., 328 476 C57BL/6J mice (Continued) Trigonella foenum-graecum L., 310–311 Vigna nakashimae (Ohwi) Ohwi & H Ohashi, 311 Zingiber mioga (Thunb.) Roscoe, 260 Zingiber officinale Roscoe, 358–359 C57BL/6 mice, 334, 422 acanthoic acid, 226 Adenophora tetraphylla (Thunberg) Fischer, 235 Aegle marmelos (L.) Corrêa, 311–312 alkylphenol, 262 Amorpha fruticosa L., 308–309 andrographolide, 250 Artemisia princeps Pamp., 331 asiatic acid, 231 Citrus iyo Tanaka, 411 Citrus japonica Thunb., 219 Citrus reticulata Blanco, 312–313 Codonopsis lanceolata (Siebold & Zucc.) Trautv., 236 Cornus mas L., 109 Euodia rutaecarpa (Juss.) Hook f & Thoms., 313–314 Fagopyrum tataricum (L.) Gaertn., 189 fisetin, 418 Garcinia dulcis (Roxb.) Kurz, 194 Graptopetalum paraguayense (N.E Br.) E Walther, 93 Leonorus sibiricus L., 442 Lindera erythrocarpa Makino, 293–294 Lithospermum erythrorhizon Siebold & Zucc., 344 Lonicera coerulea L., 30 Lycopersicon esculentum Mill., 338–339 Mangifera indica L., 321 Matricaria chamomilla L., 334–335 Melissa officinalis L., 347–348 Momordica charantia L., 201 Myristica fragrans Hout., 178 Perilla frutescens (L.) Britton, 348 Peucedanum japonicum Thunb., 34, 234, 327–328 Phyllanthus urinaria L., 209 Polygonatum odoratum (Mill.) Druce, 353 Raphanus sativus L., 206 Rheum rhabarbarum L., 298–299 sinomenine, 389 Sophora japonica L., 217 Toona sinensis (A Juss.) M Roem., 318 Zanthoxylum piperitum (L.) DC., 316 C57BL/6N mice Brassica rapa L., 204 carvacrol, 254 piperine, 182–183 Caesalpinia bonduc (L.) Roxb., 211–212, 211f Caffeic acid, 50, 248–249, 248f, 346, 428 Calamintha officinalis Moench, 50, 346–347 Calcium/calmodulin-dependent protein-kinase kinase (CaMKK), 202, 237, 249 Calluna vulgaris (L.) Hull, 397–398 Calotropis gigantea (L.) W.T Aiton, 125 Calotropis procera (Aiton) W.T Aiton, 125 Camellia assamica (J.W Mast.) H.T Chang, 192–193 Camellia japonica L., 299–300 Camellia sinensis (L.) Kuntze, 7–8, 81, 397 CaMKK (calcium/calmodulin-dependent protein-kinase kinase), 202, 237, 249 Campsis grandiflora (Thunb.) K Schum., 341, 436 Canarium odontophyllum Miq., 320 Capparis decidua (Forssk.) Edgew., 304 Index Capparis moonii Wight, 304 Capparis spinosa L., 304–305 Capsaicin, 249, 338 Capsicum annuum L., 249 Capsicum frutescens L., 132–133, 132f Capsicum minimum Mill., 338 Caralluma attenuata Wight, 127 Caralluma fimbriata Wall., 246 Caralluma tuberculata N.E Br., 127 Carbazole alkaloids, 24 Carbon tetrachloride, metabolism, 187 Cardamonin, 355, 355f Cardiovascular diseases, 183, 235 Carica papaya L., 86–87 Carissa carandas L., 42, 126 Carnosol, 144, 144f CART (cocaine- and amphetamine-regulated transcript), 314 Carthamus tinctorius L., 35 Carum carvi L., 115–116, 423–424 Carvacrol, 51f, 254 Carvone, 115f Casearia esculenta Roxb., 82 Cassia auriculata L., 21 Cassia fistula L., 405, 406f Catalpa bignonioides Walter, 342 Catalpol, 342, 342f, 437 Catharanthus roseus (L.) G Don, 126–127 Caulophine, 391 Caulophyllum robustum Maxim., 390–391 Cedrela odorata L., 26 Ceiba pentandra (L.) Gaertn., 88–89 Celastrol, 419 Celastrus orbiculatus Thunb., 223–224 Celosia argentea L., 6, 80–81 Centaurium erythraea Rafn, 123 Centella asiatica (L.) Urb., 33, 231 Centratherum anthelminticum (L.) Gamble, 118 Charles Foster rats Amoora rohituka (Roxb.) W & A., 219 Brassica oleracea L., 12–13 Enicostemma littorale Blume, 244 Neolamarckia cadamba (Roxb.) Bosser, 242 Ocimum sanctum L., 142 Phyllanthus simplex Retz., 91 Quassia amara L., 319 Chelerythrine, 393 Chlorogenic acid, 242, 332 Chlorophytum borivilianum Santapau & R.R Fern., 53–54 CHO/IR cells, 253 Cholesterol metabolism, 180 synthesis, 202 Cholesterol 7α-hydroxylase (CYP7A1), 180, 185, 190–191, 226, 261 Cholesteryl ester, 217 transfer protein, 261 Choline deficient diet, 209 Chromolaena odorata (L.) R.M King & H Rob., 35, 118–119, 332–333 Chronic inflammatory disease, 313 Chrysanthemum coronarium L., 238 Chrysanthemum morifolium, 36, 333 Chrysophanol, 299 Cichorium intybus L., 36, 332 477 Index Cinnamaldehyde, 179, 179f Cinnamomum burmannii (Nees & T Nees) Blume, 178–179 Cinnamomum cassia (L.) J Presl, 383 Cinnamomum zeylanicum Blume, 179–180 Cirsium japonicum DC., 238–239, 333–334 Citrulline, 198 Citrullus colocynthis (L.) Schrad., 83–84 Citrullus lanatus (Thunb.) Matsum & Nakai, 197–198, 198f Citrus grandis (L.) Osbeck, 410–411 Citrus iyo Tanaka, 411 Citrus japonica Thunb., 219 Citrus limon (L.) Osbeck, 23, 24f, 103 Citrus maxima (Burm.) Merr., 217–219 Citrus reticulata Blanco, 312–313, 411 Clausena anisata (Willd.) Hook f ex Benth., 104 Clerodendrum bungei Steud., 49, 437–438 Clerodendrum colebrookianum Walp., 345 Cnidium monnieri (L.) Cusson, 232, 326–327 Cnidium officinale Makino, 33 Coagulin L, 340 Cocaine- and amphetamine-regulated transcript (CART), 314 Coccinia grandis (L.) Voigt., 302 Cocculus hirsutus (L.) Diels, 389 Codonopsis lanceolata (Siebold & Zucc.) Trautv., 236 Colocacia esculenta (L.) Schott, 444 Columbamine, 184 Combretum micranthum G Don, 93 Commelina communis L., 58 Commipheric acid, 320 Commiphora mukul (Hook ex Stocks) Engl., 97, 320, 417 Conophylline, 131 Coptis chinensis Franch., 4–5, 4f, 184–185, 295–296, 391–392 Coptisine, 184 Coriandrum sativum L., 232–233 Cornus mas L., 109 Cornus officinalis Siebold & Zucc., 109–110, 225, 420 Corosolic acid, 20f Corydalis saxicola Bunting, 186–187 Corydalis turtschaninovii Besser, 392–393 COS-7 cells, 320 Cosmos caudatus Kunth, 428 Cotylelobium melanoxylon (Hook f.) Pierre, 13 Coumarin, 229, 232 Crateva nurvala Buch.-Ham, 400 Crocetin, 432 Crocus sativus L., 146, 351–352 Croton klotzschianus (Wight) Twaites, 92 Cryptotanshinone, 349 Cucumis trigonus Roxb., 84 Cucurbitacin B, 200 Cucurbita ficifolia Bouché, 82–83, 302 Cucurbita moschata Duschesne, 302–303 Cucurbita pepo L., 198–200, 199f Cudraflavanone A, 402f Cudrania tricuspidata (Carrière) Bureau ex Lavalle, 402 Cuminaldehyde, 113f Cuminum cyminum L., 112–113, 424 Curcuma comosa Roxb., 258–259 Curcuma longa L., 56–57, 259, 358 Curcuma wenyujin Y.H Chen & C Ling, 448, 449f Curcumin, 56f Curdione, 448, 449f Cuscuta japonica Choisy, 436 Cyamopsis tetragonoloba (L.) Taub., 308 Cyanidin-3, 19f Cylindrene, 149 Cynanchum acutum L., 127–128 Cynanchum wilfordii Franch & A Sav., 433 Cynara scolymus L., 36–37, 239 Cynarin, 239 Cynaropicrin, 37f, 239 CYP7A1 (cholesterol 7α-hydroxylase), 180, 185, 190–191, 226, 261 Cyperus rotundus L., 359 Cytosol, 190 D Datura metel L., 133 Db/db mice, 35 Bidens pilosa L., 117–118 Brassica rapa L., 204 Catalpa bignonioides Walter, 342 Catharanthus roseus (L.) G Don, 126 Cinnamomum zeylanicum Blume, 179–180 Citrus maxima (Burm.) Merr., 218 Cornus officinalis Siebold & Zucc., 110 iridoid glycoside, 225 Physalis peruviana L., 339 vindoline, 126 ddY mice (−)-balanocarpol, 13 carnosic acid, 53 carvacrol, 51 Helichrysum arenarium, 120 Origanum majorana L., 51 Salacia reticulata Wight, 29 Terminalia bellirica (Gaertn.) Roxb., 18 vaticanol A, 13 vaticanol G, 13 Decursin, 325, 325f Dehydrodiconifery-l alcohol, 302, 303f Dendrobium chrysotoxum Lindl., 447 Dendrobium loddigesii Rolfe, 54 Dendropanax morbiferum H Lév., 111–112, 227 Dendropanoxide, 111f, 114f Desmodium gangeticum (L.) DC., 99–100, 406, 407f Desoxyrhaponticin, 190 Dexamethasone, 315 d-galactosamine, 181 Diabetic ddY mice, 336 Diaboline, 122 Dicentrine, 382 Dichloromethane-methanol extract, 126 Dietary fats emulsification, 60f Dietary triglycerides hydrolysis, Diethyl ether fraction, 254 Diet-streptozotocin-induced diabetic Balb/c mice, 41 Dihydrotanshinone, 438 Dimeric carbazole alkaloids, 24 Dioscorea batatas Decne., 354, 451 Dioscorea bulbifera L., 54 Dioscorea nipponica Makino, 256–257 Dioscorea oppositifolia L., 257–258, 353 Diosgenin, 54, 54f Diospyros kaki Thunb., 196–197, 399 478 Diospyros peregrina Gürke, 197 Dolichandrone falcata Seem., 47 Dracaena cochinchinensis (Lour.) S.C Chen, 256 Ducrosia anethifolia DC., 33–34 Duranta repens L., 49 E (E)-8β,17-epoxylabd-12-ene-15,16-dial, 259 East Indian kino, 22 Echium vulgare L., 44–45 Eclipta prostrata (L.) L., 239–240 Elephantopus mollis Kunth, 37, 119 Elettaria cardamomum (L.) Matton, 259 Ellagic acid, 91, 91f Ellagitannins, 16, 21, 94, 188, 210 Embelia ribes Burm.f., 10, 81–82, 301, 399 Embelin, 301, 301f, 399 Emblica officinalis Gaertn., 91 Emodin, 299 Endocrine pancreas, 75 Endothelial cells, 394 Endothelial dysfunction, 394–395 Enicostemma littorale Blume, 244, 337 Ent-16β H,17-isobutyryloxy-kauran-19-oic acid, 335 Entada phaseoloides (L.) Merr., 212–213, 213f Enterocytes, 18–19 glucose, fatty acids and cholesterol absorption by, 61f Enterohepatic cycle, 191 Ent-Kaur-16-en-19-oic acid, 323, 323f (−)-Epicatechin, 23f, 310, 322 Epididymal adipose tissues, 338 (−)-Epigallocatechin-3-gallate, 8, 8f Episesamin, 294, 294f Erigeron annuus (L.) Pers., 428–429 Eruca sativa Mill., 88 Ethanol-enriched diet, 189 Ethanol extract aerial part Achillea santolina L., 116 Angelica keiskei Koidz., 230 Artemisia princeps Pamp., 331 Aster koraiensis Nakai, 427 Cassia auriculata L., 21 Centaurium erythrea Rafn, 123 Croton klozchianus (Wight) Twaites, 92 Desmodium gangeticum (L.) DC., 99 Ducrosia anethifolia DC., 34 Lindera obtusiloba Bl., 384 Melothria heterophylla (Lour.) Cogn., 85 Nasturtium officinale R Br., 206 Teucrium polium L., 144 Aerva lanata (L.) Juss ex Schult., 297–298 Alpinia officinarum Hance, 356 Althernanthera paronychioides A St.-Hil., 79 Artemisia dracunculus L., 117, 330 Artemisia scoparia Maxim., 237 Bacopa monnieri (L.) Wettst., 436 bark Ceiba pentandra (L.) Gaertn., 88–89 Cinnamomum burmannii (Nees & T Nees) Blume, 179 Symplocos racemosa Roxb., 195 Index Tectona grandis L.f., 346 Terminalia arjuna (Roxb ex DC.) Wight & Arn., 404 Terminalia paniculata Roth, 210 Boesenbergia pandurata (Roxb.) Schltr., 357–358 Caesalpinia bonduc (L.) Roxb., defatted seeds, 211 Camellia japonica L., 299–300 Canarium odontophyllum Miq., deffated fruits, 320 Caralluma fimbriata Wall., 246 Cedrela odorata L., inner stembark, 26 Celosia argentea L., defatted seeds, 80 Centella asiatica (L.) Urb., 33 Cichorium intybus L., 332 Citrus reticulata Blanco, peel, 312–313 Commiphora mukul (Hook ex Stocks) Engl., gum resin, 320 Cynachum wilfordii Franch & A Sav., tubers, 433 Cynara scolymus L., 239 Dendrobium chrysotoxum Lindl., 447 Dioscorea opposita L., 353 Echium vulgare L., 44 fruits Capparis decidua (Forssk.) Edgew., 304 Capparis spinosa L., 304–305 Citrus japonica Thunb., 219 Neolamarckia cadamba (Roxb.) Bosser, 242 Piper longum L., 182 Solanum torvum Swartz, 248 Terminalia pallida Brandis, 307 Zanthoxylum piperitum (L.) DC., 316 Garcinia mangostana L., pericarps, 194 Geranium thunbergii Siebold ex Lindl & Paxton, 321–322 Juglans regia L., pellicles, 188 leaves Annona squamosa L., 75 Calotropis procera (Aiton) W.T Aiton, 125 Chromolaena odorata (L.) R.M King & H Rob., 119, 332–333 Cocculus hirsutus (L.) Diels, 389 Euphorbia hirta L., 403 Graptopetalum paraguayense (N.E Br.) E Walther, 93 Gymnema montanum (Roxb.) Hook f., 128, 434 Hippophae rhamnoides L., 224 Ipomoea batatas (L.) Lam., 135 Juglans regia L., 297 Leptadenia reticulata (Retz.) Wight & Arn., 130 Mangifera indica L., 321 Murraya koenigii (L.) Spreng., 314–315 Ocimum sanctum L., 142 Peucedanum japonicum Thunb., 34, 234, 327–328 Phyllanthus reticulatus Poir., 15 Pseuderanthemum palatiferum (Wall.) Radlk., 137 Tabernaemontana divaricata (L.) R Br ex Roem. & Schult., 131 Vernonia amygdalina Delile, 121 Leonorus sibiricus L, 442 Lonicera japonica Thunb., flowering parts, 421 Lycium barbarum L, root bark, 247 Matricaria chamomilla L., chamomile flowers, 334–335 Melissa officinalis L., 347–348 479 Index Nelumbo nucifera Gaertn., 295 Ocimum sanctum L., inflorescence, 142 Panax ginseng C A Meyer, 227 Perilla frutescens (L.) Britton, 348 Platycodon grandiflorus (Jacq.) A DC., 328 rhizome(s) Alpinia pricei Hayata, 258 Anemarrhena asphodeloides Bunge, 445 Curcuma longa L., 358 Cyperus rotundus L., 359 Dioscorea batatas Decne., 354 Polygonatum odoratum (Mill.) Druce, 352–353 Rheum rhabarbarum L., 298–299 Smilax glabra Roxb., 445 Zingiber officinale Roscoe, 358–359 Zingiber zerumbet (L.) Roscoe ex Sm., 262 roots Angelica acutiloba (Siebold & Zucc.) Kitag., 230, 422 Aralia cachemirica Decne., 110 Asparagus racemosus Willd., 147, 448 Brassica rapa L., 204 Capparis spinosa L., 304–305 Coccinia grandis (L.) Voigt., 302 Coptis chinensis Franch., 295–296 Inula racemosa Hook f., 429 Lithospermum erythrorhizon Siebold & Zucc., 344 Morus alba L., 305–306 Panax ginseng C A Meyer, 106, 421 Polygonum aviculare L., 396 Salvia miltiorrhiza Bunge, 440 Sphaeranthus indicus L., 120 Tamarindus indica L., 408 Taraxacum officinale F.H Wigg., 39 Trianthema decandra L., 78 seeds Alpinia katsumadai Hayata, 258 Ammi majus L., 229 Arctium lappa L., 427 Cichorium intybus L., 332 Fagopyrum tataricum (L.) Gaertn., 189 Macrotyloma uniflorum (Lam.) Verdc., 309–310 Nigella sativa L., 185–186 Strychnos potatorum L.f., 122 Trigonella foenum-graecum L., 310–311 Vigna nakashimae (Ohwi) Ohwi & H Ohashi, 311 Solanum lyratum Thunb ex Murray, 435 sprout Brassica oleracea L., 203 Raphanus sativus L., 206 stems Celastrus orbiculatus Thunb., 223 Nervilia plicata (Andrews), 447 Peucedanum japonicum Thunb., 34, 234, 327–328 Taxillus chinensis (DC) Danser, 323 Swertia kouitchensis, 41 Swertia macrosperma (C.B Clarke) C.B Clarke, 124 Taraxacum mongolicum Hand.-Mazz., 241 Tithonia diversifolia (Hemsl.) A Gray, 336 Woodfordia fruticosa (L.) Kurz, flowers, 94 Ethylacetate extract Oenanthe javanica (Blume) DC., 233 Toddalia asiatica (L.) Lam, leaves, 105 fraction barks, 214 fruits, 201 roots, 145, 235, 349 Eugenol, 142, 142f Euodia rutaecarpa (Juss.) Hook f & Thoms., 313–314, 412–413 Euonymus alatus (Thunb.) Siebold, 418–419 Eupatilin, 331, 331f Euphorbia hirta L., 403 Euphorbia lathyris L., 306–307 Euphorbia thymifolia L., 16 Evodiamine, 313–314, 412 F Fagopyrum esculentum Moench, 188–189 Fagopyrum tataricum (L.) Gaertn., 189 FAS (fatty acid synthetase), 178, 265 FATP4 (fatty acid transporter protein 4), 233 Fatty acid(s) hepatic contents in, 179 in liver, 181 polyunsaturated, 187, 198 unesterified, 187 unsaturated, 201–202 Fatty acid synthetase (FAS), 178, 265 Fatty acid transporter protein (FATP4), 233 Fenofibrate, 252, 311 Ficus benghalensis L., 89 Ficus carica L., 305 Ficus deltoidea Jack, 14, 15f Ficus religiosa L., 89–90 Fisetin, 418 Flavones C-glycosides, 15f Flavonoids, 219, 355 fraction, 256 Hippophae rhamnoides L., 224 Tephrosia purpurea (L.) Pers., 217 Foam cells, formation, 390, 429 Fumaria parviflora Lam., 187, 393–394 Furosemide, 389 G Galega officinalis L., 307 Gallic acid, 18f, 308, 321 Gallotannin(s), 304, 321 γ-mangostin, 9f, 194–195 Garcinia atroviridis Griff ex T Anderson, 193 Garcinia dulcis (Roxb.) Kurz, 194 Garcinia mangostana L., 8–9, 194–195 Gardenia jasminoides J Ellis, 40–41, 40f, 122, 241, 432 Garuga pinnata Roxb., 97–98 Gastrodia elata Blume, 351 Gemfibrozil, 250 Geniposide, 122, 122f, 241, 432 Gentiana olivieri Griseb., 245 Geraniin, 322 Geranium thunbergii Siebold ex Lindl & Paxton, 321–322 Ginsenoside Rg3, 107f Glibenclamide, 91 Glucokinase, 197 480 Gluconeogenesis, 179, 214 Glucotoxicity, 4, 50, 75 Glutathione (GSH), 186, 434 Glycaemia, 179 Glycosmis parviflora (Sims) Little, 409–410 Glycyrrhiza glabra L., 213–214, 214f Gmelina arborea Roxb ex Sm., 138 Gmelina asiatica L., 138–139 Goto–Kakizaki rats, 199 Arctium lappa L., 116 Oenanthe javanica (Blume) DC., 233 oleanolic acid, 46 Siraitia grosvenorii (Swingle) C Jeffrey ex A.M Lu & Z.Y Zhang, 86 Trigonella foenum-graecum L., 310 G-protein-coupled receptor (GPR40), 111 G-protein-coupled receptor 119 (GPR119), 113 Graptopetalum paraguayense (N.E Br.) E Walther, 93 GSH (glutathione), 186, 434 Guggulsterone, 97, 320 Gymnema montanum (Roxb.) Hook f., 128, 434 Gymnema sylvestre (Retz.) R Br ex Schult., 42, 128–129 Gynostemma pentaphyllum (Thunb.) Makino, 10–11, 84–85 Gynura divaricata (L.) DC., 334 Gynura japonica (Thunb.) Juel, 429 Gynura procumbens (Lour.) Merr., 429 Gypenosides, 10 H Hedychium spicatum Buch.-Ham ex Sm., 56–57, 57f Helichrysum arenarium (L.) Moench, 119–120 Heliotropium zeylanicum Lam., 45 Hemidesmus indicus (L.) R Br ex Schult., 129–130 Hepatocyte(s), 178–179, 182 cholsterol and fatty acids metabolism, 265f glucose metabolism, 264f Hepatoprotective mechanism, 181 HepG2 cells, 177, 181, 190, 195, 227, 233 Hesperetin, 218, 218f Heterotrimeric protein, 178, 309 Hexane fraction, 229, 234 Hexokinase, 197 Hippophae rhamnoides L., 224–225, 419–420 Holarrhena antidysenterica (L.) Wall ex A DC., 42–43 Hormone-sensitive lipase, 356 Human embryonic kidney (HEK) 293 cells, 142 Hydroalcoholic extract of leaves Morus alba L., 306 Persea americana Mill., 181–182 Hydroxycarboxylic acid receptor-2 (HCAR2/GPR109A), 200 (−)-Hydroxycitric acid, 193 Hygrophila auriculata Heine, 251–252 Hypaphorine, 305 Hypercholesterolemia, 183 Hyperglycemia, 381 Hypericum perforatum L, 195 Hyperlipidemia, 381 Hypertension, 389 Hypoglycemia, 345 Hypolipidemic effect, 221 Hypothalamus arcuate nucleus, 314 Hyssopus officinalis L., 50 Index I ICAM-1 (intercellular adhesion molecule 1), 109, 399 ICR mice Acorus calamus L., 145 Alpinia katsumadai Hayata, 258 Alpinia officinarum Hance, 56 Asparagus officinale L., 255 crocin and crocetin, 40 Dioscorea oppositifolia L., 257 Hippophae rhamnoides L., 224 Lupinus albus L., 100 Salicornia herbacea (L.) L., 192 saponin, 107 starch, 115 Taraxacum officinale F.H Wigg., 39 Trapa japonica Flerow, 21 Ilex cornuta Lindl & Paxton, 31 Illigera luzonensis (C Presl) Merr., 382–383 Imperata cylindrica (L.) P Beauv., 149 Imperatonin, 34f, 423 Indole-3-carbinol, 205 Inositol-3 phosphate (IP3), 90 INS-1 rat insulinoma cell, 122 Marrubium vulgare L., 141 Insulin binding, 177, 197 receptor, peripheral cell, 151f resistance, 1, 177, 257, 293 secretion by β-cells, 150f Insulinotropic gut hormone, 136 Insulin-signaling pathway, 180 Intercellular adhesion molecule (ICAM-1), 109, 399 Interleukin-6, 200, 212, 330 Intraperitoneal glucose tolerance test, 204, 331 Inula japonica Thunb., 120 Inula racemosa Hook f., 429–430 IP3 (inositol-3 phosphate), 90 Ipolamiide, 140f Ipomoea aquatica Forssk., 44 Ipomoea batatas (L.) Lam., 43–44, 43f, 135–136, 435–436 Iridoid glucoside, 140 Iridoid glycoside, 225, 241 Isoorientin, 245, 245f Isooxymaistemonine, 263 Isoprenoid-substituted benzoic acid, 309 Isoquercitrin, 298, 298f Isoquinoline alkaloids, 4, 75, 184 Isorhamnetin, 329, 329f, 419, 420f Isothiocyanate, 206 sulforaphane, 204 J Jatrorrhizine, 77, 184–185 Juglans regia L., 187–188, 297, 395 Jussiaea suffruticosa L., 95 K Kaempferia parviflora Wall ex Baker, 57–58, 358, 449–450 Kaempferol, 262–263, 262f Kaempferol-3-O-rutinoside, 22f, 335 Khaya grandifoliola C DC., 108 481 Index Khaya senegalensis (Desr.) A Juss., 108–109 Kigelia pinnata (Jacq.) DC., 342 Kinsenoside, 146, 146f, 446 KK-Ay mice, 314 Chrysanthemum morifolium, 333 Curcuma longa L., 358 ellagitannins, 188 Ipomoea batatas (L.) Lam., 135–136 safranal, 352 spontaneous type diabetic obese, 321 unsaturated fatty acid, 201 Knoxia valerianoides Thorel ex Pit., 432 Kochia scoparia (L.) Schrad., 6, 7f Kunming mice Anoectochilus roxburghii (Wall.) Lindl., 446 C-glycosylflavones, 245 Cnidium monnieri (L.) Cusson, 232 Erigeron annuus (L.) Pers., 429 germacrane sesquiterpene, 448 Inula japonica Thunb., 120 Polygonatum odoratum (Mill.) Druce, 256 Reinioside C, 23 Tinospora cordifolia Miers ex Hook f & Thomson, 77 L L6-GLUT4myc myotubes, 315 L6 myocytes, 294 L6 myotubes, 296, 318, 322–323, 327 L6 rat myoblast cells, 359 Lagenaria siceraria (Mol.) Standl., 11, 200, 303 Lagerstroemia speciosa (L.) Pers., 19, 20f, 94, 405 Lantana camara L., 139 Leonorus sibiricus L., 442–444, 443f Leonurine, 443f, 444 Lepidium sativum L., 400 Leptadenia reticulata (Retz.) Wight & Arn., 130 Leukotriene B4, 412 Ligusticum wallichii Franch., 424 Ligustilide, 230 Linalool, 142, 233, 233f Lindera erythrocarpa Makino, 293–294 Lindera obtusiloba Blume, 294, 384 Lindera strychnifolia (Siebold & Zucc.) Fern.-Vill., 180–181 Lindestrene, 181 Linoleic acid, 344 Lipid peroxidation, 178, 225 Lipotoxicity, 75, 85 Liriodenine, 383 Liriope platyphylla F.T Wang & T Tang, 351, 445 Litebamine, 384 Lithospermic acid B, 439 Lithospermum erythrorhizon Siebold & Zucc., 45, 344 Litsea cubeba (Lour.) Pers., 384 Liver X receptor-α, 182 Loganin, 420, 420f Long–Evans rat Asparagus racemosus Willd., 147 Caesalpinia bonduc (L.) Roxb., 211–212 Citrus maxima (Burm.) Merr., 218 Lonicera coerulea L., 30 Lonicera japonica Thunb., 420–421 Low-density lipoprotein, 221–222, 228 Lupanine, 101f Lupenone, 235, 236f Lupeol, 31f, 251 Lupinus albus L., 100–101 Lycium barbarum L., 247 Lycopene treatment, 133 Lycopersicon esculentum Mill., 338–339 M Macelignan, 177 Macrotyloma uniflorum (Lam.) Verdc., 309–310 Magnoflorine, 5, 391, 391f Mahanimbine, 25f, 314 Malondialdehyde, 383 Malonyl-CoA, 309–310 Malonyldialdehyde, 385 Mangifera indica L., 26–27, 27f, 321, 418 Marrubium vulgare L., 141, 347, 444 Matricaria chamomilla L., 334–335 Matrine, 215, 216f MCF-7 cells, 190 Melicope triphylla (Lam.) Merr., 413 Melissa officinalis L., 50–51, 347–348 Melothria heterophylla (Lour.) Cogn., 85 Melothria maderaspatana (L.) Cogn., 400 Meso-dihydroguaiaretic acid, 177–178, 178f Metabolic syndrome, 177 Methanol extract aerial part Barleria lupulina L., 345 Centaurium erythrea Rafn, 123 Gentiana oliveri Griseb., 245 Hygrophila auriculata Heine, 251 Marrubium vulgare L., 444 Thymus linearis Benth., 442 Amaranthus viridis L., 80, 395 Argyreia nervosa (Burm f.) Bojer, stems, 135 bark Aegle marmelos (L.) Corrêa, 102 Syzygium cumini (L.) Skeels, 95 Bidens pilosa L., 428 Caralluma tuberculate N.E Br., 127 Citrullus colocynthis (L.) Schrad., defatted seeds, 83–84 Corydalis turtschaninovii Besser, tubers, 392 Crocus sativus L., stigma, 146 Euphorbia thymifolia L., 16 flowers Helichrysum arenarium, 120 Tectona grandis L.f., 139 fruits Cucurbita ficifolia Bouché, 83 Lagenaria siceraria (Mol.) Standl., 200 Ocimum sanctum L., 441 Sphaeranthus indicus L., 431 Fumaria parviflora Lam., shoots, 187 Jussiaea suffruticosa L., 95 leaves Ailanthus excelsa Roxb., 105 Aleurites moluccana (L.) Willd., 92 Clerodendrum colebrookianum Walp., 345 Cynara scolymus L., 36 Juglans regia L., 297 482 Methanol extract (Continued) Moringa oleifera Lam., 87 Olea europaea L., 46 Phyllanthus emblica L., 402 Withania somnifera (L.) Dunal, 134 oleogum resin, 417 Orthosiphon stamineus Benth., 441 Quassia amara L., stem wood, 319 Rheum rhabarbarum L., rhizome, 396 rhizome(s) Alpinia galanga (L.) Willd., 355 Rheum rhabarbarum L., 396 Zingiber officinale Roscoe, 262 roots Aporosa lindleyana (Wight) Baill., 90 Aralia cordata Thunb., 227 Calotropis procera (Aiton) W.T Aiton, 125 Clausena anisata (Willd.) Hook f ex Benth., 104 Imperata cylindrical (L.) P Beauv., 149 Orchis mascula L., 402 Rubia yunnanensis Diels, 243 Ruta angustifolia Pers., 413 seeds Asparagus officinalis L., 148 Cuminum cymimun L., 112 Nigella sativa L., 186 Rhus coriaria L., 321 Sinocrassula indica (Decne.) A Berger, 16 Swietenia mahagoni (L.) Jacq., stem bark, 318 Viscum articulatum Burm f., 419 Methyl caffeate, 134, 134f Methyl gallate, 15, 16f, 18 Methyl-protodioscin, 257 MIN6 mouse β-cell, 129, 142 Miogadial, 259, 260f Mitochondria, 230 Mitragyna speciosa (Korth.) Havil., 242 Mogroside V., 12f Mollugin, 337, 337f Momordica charantia L., 85, 201–202, 303–304 Momordica cymbalaria Fenzl ex Naudin, 85–86 Monoacyl glycerol, 356 Morinda citrifolia L., 336 Moringa oleifera Lam., 87 Morolic and moronic acid, 222, 222f, 223f Morroniside, 225 Morus alba L., 207–208, 207f, 305–306, 401 Morusinol, 401f Morus notabilis C.K Schneid., 306 Mucuna pruriens (L.) DC., 22 Multiflorine, 100, 100f Murraya euchrestifolia Hayata, 414–415 Murrayafoline A, 414f Murraya koenigii (L.) Spreng., 24–25, 314–315, 315f Murraya paniculata (L.) Jack., 410 Myocardial infarction, 390 Myricetin, 3f Myristica fragrans Hout., 177–178, 381–382 N NADPH oxidase, 229 Naringenin, 410 chalcone, 338 Index Nasturtium officinale W.T Aiton, 205–206, 205f Nectandrin B, 382f Nelumbo nucifera Gaertn., 3–4, 75–76, 183–184, 295, 385–386 Neolamarckia cadamba (Roxb.) Bosser, 242–243, 243f Nervilia plicata (Andrews) Schltr., 447 Neuropeptide Y (NPY), 314 Nicotinic acid (niacin), 199–200 Nigella sativa L., 5–6, 185–186 Nomilin, 103f Normoglycemics rats, 319 NPY (neuropeptide Y), 314 Nuciferine, 76, 76f, 183–184 Nω -nitro-l-arginine methyl ester (L-NAME), 396, 398–399 O Ob/ob mice, 314 Ocimum basilicum L., 51, 252, 440–441 Ocimum canum Sims, 141–142 Ocimum sanctum L., 142, 441 Octomeles sumatrana Miq., 202–203, 203f Odoratin, 333, 333f Oenanthe javanica (Blume) DC., 233–234, 234f Olea europaea L., 46–47 Oleanolic acid, 46f, 419 Oleic acid, 205, 221–222 Oligostilbene, 13 Opuntia ficus-indica (L.) Mill., 78–79 Oral glucose tolerance test, 202, 318, 326, 334–335, 342, 352 Orchis mascula L., 446 Origanum majorana L., 51 Orlistat, 10, 40 Oroxylin A, 342, 343f Oroxylum indicum (L.) Kurz., 342–343 Orthosiphon stamineus Benth., 52, 143, 441 Osthol, 232, 232f Otobaphenol, 178 Otsuka Long-Evans Tokushima Fatty rats, 324, 439 Oxymatrine, 215, 407 Oxysterols, 182, 190 P Paeonia suffruticosa Andrews, 394 Paeonol, 394, 394f PAF (Platelet-activating factor), 388 Palmitic acid, 343 Panax ginseng C.A Meyer, 106–107, 227–228, 324–325, 421 Panax japonicus (Nees) C.A Meyer, 32 Panax notoginseng (Burkill) F.H Chen ex C.H Chow, 228, 422 Pancreatic α-amylase, Parvisoflavone B, 22f PDGF (Platelet-derived growth factor), 452f Peganum harmala L., 418 Pelargonium graveolens L’Hér ex Aiton, 322 Pentacyclic triterpenes, 128, 130, 223, 300 Perilla frutescens (L.) Britton, 348, 442 Peroxisome proliferator-activated receptor-α, 179–180 activators, 188 endothelial cell, 109 483 Index gemfibrozil, 250 white adipose tissue, 342 zerumbone, 263 Peroxisome proliferator-activated receptor-γ, 293, 301–303, 312–313 amorfrutin-1, 309 induction, 313 linoleic acid, 344 Persea americana Mill., 181–182, 384 Persicaria hydropiper (L.) Delarbre, 298 Persimmon kaki Thunb., 399 Petasites japonicus (Siebold & Zucc.) Maxim., 335 Petroleum ether fraction, 112, 238 Peucedanum japonicum Thunb., 34, 234–235, 327–328, 424–425 Phenolic acids, 308–309, 332 Phenolic reactive substances, 394 Phosphoenolpyruvate carboxykinase, 179 Phospholipase C (PLC), 387 Phospholipase C epsilon (PLCε), 90 Phosphorylated adenosine monophosphate-activated protein kinase, 182, 208 Phyllanthus acidus (L.) Skeels, 306 Phyllanthus amarus Schumach & Thonn., 208–209 Phyllanthus emblica L., 91, 402 Phyllanthus reticulatus Poir., 15 Phyllanthus simplex Retz., 91 Phyllanthus urinaria L., 209 Physalis peruviana L., 339–340 Phytosterols, 11 Picrasma quassiodes (D Don) Benn., 417 (−)-pimara-9(11),15-dien-19-oic acid, 226 Pinellia ternata (Thunb.) Makino, 350 Piperine, 182–183, 294–295, 387 Piper kadsura (Choisy) Ohwi, 386, 386f Piperlongumine, 387 Piper longum L., 2–3, 182–183, 387 Piper retrofractum Vahl., 183, 294–295 Piper taiwanense Lin & Lu, 385 Pistacia chinensis Bunge, 27–28 Pistacia vera L., 221–222 Pistagremic acid, 27, 28f Plantago asiatica L., 136–137, 137f Plasma lipoproteins, 266f Plasmatic oxidative stress, 384 Platelet-activating factor (PAF), 388 Platelet aggregation, 382, 454f Platelet-derived growth factor (PDGF), 452f Platycodin D, 328 Platycodon grandiflorus (Jacq.) A DC., 34–35, 236–237, 328, 425, 426f PLC (phospholipase C), 387 Pluchea indica (L.) Less., 38f Polygala aureocauda Dunn, 23 Polygonatum falcatum A Gray, 352 Polygonatum odoratum (Mill.) Druce, 255–256, 352–353 Polygonum aviculare L., 396–397 Polygonum cuspidatum Siebold & Zucc., 298 Polysaccharide fraction, 247 Polyunsaturated fatty acids, 187, 198 Polyunsaturated linoleic acid, 205 POMC (pro-opiomelanocortin), 314 Poncirus trifoliata (L.) Raf., 104–105 Postprandial state, 179, 212, 241, 253, 306 Potentilla reptans L., 209–210 Premna tomentosa Kurz, 49 Proanthocyanidins, 210, 399 Pro-opiomelanocortin (POMC), 314 Protodioscin, 257 Protopine, 187, 393–394, 394f Prunella vulgaris L., 348 Pseuderanthemum palatiferum (Wall.) Radlk., 137 Psoralen, 305 Pterocarpus marsupium Roxb., 22–23, 100, 310 Pterocarpus santalinus Buch.-Ham ex Wall., 214 Pterostilbene, 100 Puchea indica (L.) Less, 37, 430 Punica granatum L., 21, 307–308, 404 Pyranocoumarin pteryxin, 234,235f Q Quassia amara L., 319 Quercetin, 208, 224 Quercetin-3-O-β-d-glucuronide, 3f Quinolizidines, 101 R Rapeseed oil, 204 Raphanus sativus L., 206–207, 206f Rauvolfia serpentina (L.) Benth ex Kurz, 131, 246 Reactive oxygen species, 177, 313, 423 Reactive phenolics species, 439 Rehmannia glutinosa (Gaertn.) Libosch ex Fisch & C.A Mey., 437 Reserpine, 246 Resveratrol, 396, 396f Rhaponticin, 190, 190f Rhapontigenin, 191 Rheum officinale Baill., Rheum palmatum L., 190–191 Rheum rhabarbarum L., 191, 298–299, 395–396 Rheum ribes L., Rheum tanguticum Maxim ex Balf., 189–190 Rhodiola rosea L., 403 Rhododendron brachycarpum G Don, 300 Rhus chinensis Mill., 222–223 Rhus coriaria L., 321 Rhus verniciflua Stokes, 98, 418 Rodents, 101, 193, 412 Rohitukine, 219–220, 220f Rosmarinic acid, 50, 50f, 438 Rosmarinus officinalis L., 52, 143–144, 438 Rubia cordifolia L., 337 Rubia tinctorum L., 243–244 Rubia yunnanensis Diels, 243 Rubus alceifolius Poir., 210 Rubus fruticosus L., 307 Ruellia tuberosa L., 138, 346 Ruta angustifolia Pers., 413, 414f Rutaecarpine, 314, 412–413 Rutin, 33, 33f, 145, 237, 318 S Safranal, 146f, 352 Saikosaponin, 423 484 Salacia oblonga Wall., 28, 322, 419 Salacia reticulata Wight., 28–29, 322 Salicornia herbacea (L.) L., 192 Salidroside, 403 Salvia miltiorrhiza Bunge, 52–53, 252, 349, 438–440 Salvianolic acid B, 439, 439f Salvia officinalis L., 53 Salvia plebeia R Br., 253 Sambucus nigra L., 225–226 Sanguinarine, 393, 393f Saponin, 6, 236–237, 255 Dioscorea nipponica Makino, 257 Gymnema sylvestre (Retz.) R.Br ex Schult., 42 Momordica cymbalaria Hook., 86 Platycodon grandiflorus (Jacq.) A DC., 34, 236, 425 Saururus chinensis (Lour.) Baill., 1, 2f Scutellaria baicalensis Georgi, 53, 253 Scutellarin, 428–429 Sechium edule (Jacq.) Sw., 202 Secoiridoid glycoside, 225 Serum adiponectin, 230 triglycerides, 188 Sesamum indicum L., 48 Shorea roxburghii G Don, 13 SHP (small heterodimer partner), 180, 238 Sida cordifolia L., 305 Siegesbeckia pubescens (Makino) Makino, 335, 430 Silent information regulator T1 (SIRT1), 194, 309 Silybum marianum (L.) Gaertn., 38, 121, 240–241 Silymarin, 121, 241 Sinocrassula indica (Decne.) A Berger, 16–17 Sinomenine, 388–389 Sinomenium acutum (Thunb.) Rehder & E.H Wilson, 388–389 Siraitia grosvenorii (Swingle) C Jeffrey ex A.M Lu & Z.Y Zhang, 11–12, 86 Sirtuin (SIRT1), 328 Skeletal muscles, 134, 309, 315 cell, 324 metabolism, 360f Smallanthus sonchifolius (Poeppig) H Robinson, 240, 430–431 Small heterodimer partner (SHP), 180, 238 Smilax glabra Roxb., 445–446 Sodium-dependent glucose transporter-1 (SGLT-1), 5, 16 Solanum lyratum Thunb ex Murray, 435 Solanum muricatum Aiton, 434 Solanum surattense Burm.f., 133 Solanum torvum Sw., 134, 247–249, 248f Solanum xanthocarpum Schrad & Wendl., 340 Soleus muscles, 182, 262 Solidago virgaurea L., 335 Sophocarpine, 216, 216f Sophora flavescens Aiton, 214–216, 215f, 308, 407–408 Sophora japonica L., 217 Sphaeranthus indicus L., 120–121, 431 Spilanthes acmella (L.) L., 38–39, 431–432 Spirodela polyrhiza (L.) Schleid., 350 Spondias pinnata (L.f.) Kurz., 99 Spontaneously hypertensive rats Angelica dahurica (Fisch.) Benth & Hook f., 423 Caffeic acid, 248–249 Cnidium monnieri (L.) Cusson, 232 Index Diospyros kaki Thunb., 399 Gardenia jasminoides J Ellis, 432 Gynura procumbens (Lour.) Merr., 429 Ipomoea batatas (L.) Lam., 435 Lepidium sativum L., 400 Orchis mascula L., 446 Orthosiphon stamineus Benth., 441 Panax ginseng C.A Meyer, 421 Persimmon kaki Thunb., 399 Picrasma quassiodes (D Don) Benn., 417 Vaccinium myrtillus L., 398 Sprague–Dawley rats 2-methoxycinnamaldehyde, 383 Abelmoschus manihot (L.) Medik, 401 Aegle marmelos (L.) Corrêa, 101 Amaranthus esculentus Besser ex Moq., 79 Ammi majus L., 229 aporphine alkaloid, 383 Arctium lappa L., 427 Argyreia nervosa (Burm f.) Bojer, 135 Artemisia indica Willd., 330 Atractylodes macrocephala Koidz., 331–332 Belamcanda chinensis (L.) Redouté, 447 Berberis vulgaris L., 390 Brassica oleracea L., 203 Calluna vulgaris (L) Hull, 397 Camellia sinensis (L.) Kuntze, 81 capsaicin, 249 Capsicum frutescens L., 132–133 Carissa carandas L., 126 catalpol, 437 Catharanthus roseus (L.) G Don, 126 Chlorogenic acid, 242 Cichorium intybus L., 332 Cirsium japonicum DC., 238 Citrullus lanatus (Thunb.) Matsum & Nakai, 197 Clerodendrum colebrookianum Walp., 345 Cnidium monnieri (L.) Cusson, 326–327 Coptis chinensis Franch., 184–185 coptisine, 391 Coriandrum sativum L., 232 Cornus officinalis Siebold & Zucc., 420 Croton klozchianus (Wight) Twaites, 92 Cucurbita ficifolia Bouch, 83 Curcuma longa, 259 Cyperus rotundus L., 359 Dendrobium chrysotoxum Lindl., 447 Desmodium gangeticum (L.) DC., 99, 406 Dioscorea nipponica Makino, 256 Dioscorea opposita L., 353 diosgenin, 148 Diospyros kaki Thunb., 196 Dracaena cochinchinensis, 256 Enicostemma littorale Blume, 244, 337 Entada phaseoloides (L.) Merr., 212 Euodia rutaecarpa (Juss.) Hook f & Thoms., 313–314 evodiamine, 412 Fagopyrum esculentum Moench, 188–189 fluorenone alkaloid, 391 Gastrodia elata Blume, 351 Gentiana oliveri Griseb., 245 Hippophae rhamnoides L., 224, 419 Hygrophila auriculata Heine, 251 Ipomoea batatas (L.) Lam., 44 485 Index Khaya senegalensis (Desr.) A Juss., 108 leonurine, 442, 444 Ligusticum wallichii Franch., 424 Lindera obtusiloba Bl., 384 loganin, 420 Lycium barbarum L., 247 Macrotyloma uniflorum (Lam.) Verdc., 309–310 Momordica charantia L., 85, 303–304 morphinan, 389 Morus alba L., 207 myocardial ischemia, 388 naringenin, 410 Nigella sativa L., Ocimum sanctum L., 441 Octomeles sumatrana Miq., 202 Orthosiphon stamineus Benth., 441 Panax ginseng C.A Meyer, 324–325 Panax notoginseng (Burkill) F.H Chen ex C.H. Chow, 228 Pistacia chinensis Bunge, 27–28 Polygonatum odoratum (Mill.) Druce, 255 protodioscin, 257 Raphanus sativus L., 206 Rheum rhabarbarum L., 191 Rheum ribes L., Rhodiola rosea L., 403 Ruta angustifolia Pers., 413 Salacia reticulata Wight, 28 Salvia miltiorrhiza Bunge, 252, 440 Sida cordifolia L., 305 streptozotocin-induced, 8, 180 streptozotocin-nicotinamide induced type diabetic, 118 Swietenia humilis Zucc., 317 Symplocos racemosa Roxb., 195 Tabernamontana divaricata (L.) R Br ex Roem & Schult., 131 Taraxacum mongolicum Hand.-Mazz., 241 Terminalia paniculata Roth, 210 Teucrium polium L., 144–145 thaliporphine, 392 thymoquinone, 186 Thymus linearis Benth., 442 trigonelline acid, 199 Viburnum dilatatum Thunb., 29 Withania coagulans (Stocks) Dunal, 340–341 Zingiber officinale Roscoe, 358–359 Stachytarpheta indica (L.) Vahl, 139 Stearoyl coenzyme A desaturase (SCD-1), 182 Stemona sessilifolia (Miq.) Miq., 263 Stephania cephalantha Hayata, 387–388 Stephania tetrandra S Moore, 76–77, 77f, 388 Stereospermum colais (Buch.-Ham ex Dillwyn) Mabb., 47 Sterol regulatory element-binding protein-1c (SERBP-1c), 216 Streptomyces toxytricini, 10 Streptozotocin, 79, 113 Streptozotocin-induced diabetic mice albino mice, 403 Artemisia dracunculus L., 330 Balb/cA mice, 434 BALB/c mice, 124, 432 Cnidium monnieri (L.) Cusson, 327 Gynura divaricata (L.) DC., 334 kinsenoside, 446 Lagerstroemia speciosa (L.) Pers., 19 Salacia reticulata Wight., 29 rats Aster koraiensis Nakai, 427 Ducrosia anethifolia DC., 34 Lepidium sativum L., 400 Lonicera japonica Thunb., 421 Rhodiola rosea L., 403 Stephania tetrandra S Moore, 388 Terminalia L., 404 tetrandrine, 388 Streptozotocin-nicotinamide-induced type diabetic mice, 317 Strychnos potatorum L.f., 121–122 Styrax japonicus Siebold & Zucc., 300 Sucrase, 5, Sulfonylureas, 93, 124, 355 Sulforaphane, 204 Sulphonylurea, 81 Swertia corymbosa (Griseb.) Wight ex Clarke, 123–124 Swertia kouitchensis Franch., 41, 124 Swertia macrosperma (C.B Clarke) C.B Clarke, 124–125 Swertiamarin, 41f, 244, 337 Swertia punicea Hemsl., 432 Swietenia humilis Zucc., 317 Swietenia macrophylla King., 317–318 Swietenia mahagoni (L.) Jacq., 318 Swiss albino mice, 293, 315 Aerva lanata (L.) Juss ex Schult., 297 Agrostemma githago L., 185 Celosia argentea L., 80 Euphorbia thymifolia L., 16 Neolamarckia cadamba (Roxb.) Bosser, 242 oleanolic acid, 348 Phyllanthus reticulatus Poir., 15 Phyllantin, 209 Potentilla reptans L., 209 Thymbra spicata L., 254 ursolic acid, 195 Urtica dioica L., 208 Viscum album L., 29 rat, 85 Swiss Webster mice Cynanchum acutum L., 128 Imperata cylindrical (L.) P Beauv., 149 Syzygium cumini (L.) Skeels, 95 Symplocos racemosa Roxb., 195–196 Syzygium cumini (L.) Skeels, 95, 405 T Tabernaemontana divaricata (L.) R Br ex Roem & Schult., 131 Tamarindus indica L., 408–409, 408f Tangeretin, 104–105, 104f Tanshinone IIA, 438–439 Taraxacum mongolicum Hand.-Mazz., 241 Taraxacum officinale F.H Wigg., 39 Taxillus chinensis (DC) Danser, 323 Tecoma stans (L) Juss ex Kunth, 249–250, 343 Tecomine, 250, 250f Tectona grandis L.f., 49, 139, 346 486 Tectoridin, 447, 448f Tephrosia purpurea (L.) Pers., 217 Terminalia arjuna (Roxb ex DC.) Wight & Arn., 403–404 Terminalia bellirica (Gaertn.) Roxb., 17–18, 17f Terminalia catappa L., 93–94 Terminalia pallida Brandis, 307 Terminalia paniculata Roth, 210–211 Tetracera scandens (L.) Merr., 299 Tetrahydropalmatine, 392–393 Tetrandrine, 76, 388 Teucrium polium L., 144–145 Thalictrum minus L., 392 Thaliporphine, 392, 392f Theacrine, 193 Theophylline, 192, 299, 397 Thrombin, 398 Thromboxane B2 (TXB2), 389 Thymbra spicata L., 253–254 Thymol, 425, 425f Thymoquinone, 186, 186f Thymus linearis Benth., 442 Tinospora cordifolia (Willd.) Miers ex Hook f & Thomson, 77–78, 296–297 Tinospora crispa (L.) Hook f & Thomson, Tirotundin, 336, 336f Tithonia diversifolia (Hemsl.) A Gray, 336 TN-α(tumor necrosis factor-α), 330, 343 Toddalia asiatica (L.) Lam, 105, 315–316, 316f, 415 Toona sinensis (A Juss.) M Roem., 318 Tournefortia sarmentosa Lam., 136 Trachyspermum ammi (L.) Sprague, 425 Transfected HEK293 cells, 182 Transient receptor potential vanilloid subfamily (TRPV-1), 115–116, 133 Trapa japonica Flerow, 21 Trianthema decandra L., 78 Trigonella foenum-graecum L., 310–311, 409 Trigonelline, 83, 83f, 199, 310–311 Triterpene(s), 31 betulinic acid, glycyrrhizin, 213 oleanane, 348 pistagremic acid, 27 saponins, 23, 80 Tsumara Suzuki Obese Diabetes (TSOD) mice, 18, 57, 241 Tumor necrosis factor-α (TN-α), 330, 343 Tussilago farfara L., 39 TXB2 (thromboxane B2), 389 Type diabetes, 200, 220, 225, 314 features, 383, 421 obese db/db mice, 396 pathophysiology, 98 U Uncaria laevigata Wall ex G Don, 41 Uncaria rhynchophylla (Miq.) Miq ex Havil., 433 Unesterified cholesterol, 251 Unesterified fatty acids, 187, 356 Unsaturated fatty acid, 201–202, 343 Ursolic acid, 47, 47f, 109, 195–196, 253, 436 Urtica dioica L., 208 Index V Vaccinium myrtillus L., 18–19, 398 Vagal activation, 101 Vanillic acid, 36, 36f Vanilloid receptor (VR1), 115, 133, 142 Vascular ageing, 411 Vascular endothelial dysfunction, 381 Vascular endothelium and smooth muscle cell, 453f Veratrum dahuricum (Turcz.) Loes., 444 Vernonia amygdalina Delile, 121 Viburnum dilatatum Thunb., 29, 30f Vigna nakashimae (Ohwi) Ohwi & H Ohashi, 311 Vinca minor L., 433–434 Vindoline, 126–127 Vinpocetine, 433–434 Visceral adiposity, 183, 293, 313, 411 Viscum album L., 29 Viscum articulatum Burm f., 419 Vitex negundo L., 140–141, 140f W Walsura pinnata Hassk., 220–221, 221f Weigela subsessilis L.H Bailey, 323 Wistar rats 6-gingerol, 261–262 Acanthopanax senticosus (Rupr ex Maxim.) Harms, 323–324 Achillea santolina L., 116 Ailanthus excelsa Roxb., 105 Aleurites moluccana (L.) Willd., 92 allantoin, 136 alloxan-induced, 78 Alpinia galanga (L.) Willd., 355 Amaranthus viridis L., 80, 395 Andrographis paniculata (Burm f.) Wall ex Nees, 437 Anemarrhena asphodeloides Bunge, 445 Anethum graveolens L., 229 Angelica acutiloba (Siebold & Zucc.) Kitag., 230, 422 Angelica keiskei Koidz., 230 Anoectochilus roxburghii (Wall.) Lindl., 146 Aporosa lindleyana (Wight) Baill., 90 Aralia cachemirica Decne., 110 Aralia taibaiensis Z.Z Wang & H.C Zheng, 110 Arbutus unedo L., 300, 398 Asparagus officinalis L., 148 Asparagus racemosus Willd., 147, 448 Bacopa monnieri (L.) Wettst., 436 Barleria lupulina L., 345 Belamcanda chinensis (L.) Redouté, 147 Bidens pilosa L., 428 Caesalpinia bonduc (L.) Roxb., 211 Calamintha officinalis Moench, 50, 346–347 Calotropis procera (Aiton) W.T Aiton, 125 Camellia sinensis (L.) Kuntze, 397 Capparis spinosa L., 304–305 Caralluma attenuata Wight, 127 Caralluma fimbriata Wall., 246 Carica papaya L., 86 Carum carvi L., 115, 424 Casearia esculenta Roxb., 82 Cassia auriculata L., 21 Index Cassia fistula L., 405 Cedrela odorata L., 26 Ceiba pentandra (L.) Gaertn., 88 Centaurium erythraea Rafn, 123 Centella asiatica (L.) Urb., 33, 231 Chlorophytum borivilianum Santapau & R.R Fern., 53 Chromolaena odorata (L.) R.M King & H Rob., 119, 332–333 Chrysanthemum coronarium L., 238 Cichorium intybus L., 332 Cinnamomum burmannii (Nees & T Nees) Blume, 179 Citrullus colocynthis (L.) Schrad., 83–84 Citrus reticulata Blanco, 411 Clausena anisata (Willd.) Hook f ex Benth., 104 Cocculus hirsutus (L.), 389 Combretum micranthum G Don, 93 Commiphora mukul (Hook ex Stocks) Engl., 320, 417 Cosmos caudatus Kunth, 428 Crateva nurvala Buch.-Ham, 400 Cucurbita pepo L., 198 Cuminum cymimun L., 112 Cyamopsis tetragonoloba (L.) Taub., 308 Cynara scolymus L., 239 Datura metel L., 133 Dendropanax morbiferum H Lév., 111, 227 Dioscorea nipponica Makino, 257 Diospyros peregrina Gürke, 197 diterpene, 430 Eclipta prostrata (L.) L., 240 Elephantopus mollis Kunth, 119 ellagic acid, 404 Embelia ribes Burm.f., 301 embelin, 399 emodin, 396 Enicostemma littorale Blume, 244 Eruca sativa Mill., 88 eugenol, 142 Fagopyrum tataricum (L.) Gaertn., 189 fenugreek seeds, 409 Ficus benghalensis L., 89 galactose, 405 Garuga pinnata Roxb., 97 glycoside, 403 Gmelina arborea Roxb ex Sm., 138 Gymnema montanum (Roxb.) Hook f., 128, 434 Gymnema sylvestre (Retz.) R.Br ex Schult., 42, 128 Gynostemma pentaphyllum Makino, 11 Heliotropium zeylanicum, 45 Hemidesmus indicus (L.) R Br ex Schult., 129–130 (−)-hydroxycitric acid, 193 Hypericum perforatum L., 195 Ipomoea aquatica Forssk., 44 Jussiaea suffruticosa L., 95 Kaempferia parviflora Wall ex Baker, 449 kaempferol, 262 Khaya grandifolia C DC., 108 Lagenaria siceraria (Molina) Standl., 11, 200 Lepidium sativum L., 400 Leptadenia reticulata (Retz.) Wight & Arn., 130 linalool, 142 lupanin, 101 Marrubium vulgare L., 141, 444 487 Melissa officinalis L., 347–348 Melothria maderaspatana (L.) Cogn., 400 Momordica cymbalaria Fenzl ex Naudin, 86 Murraya paniculata (L.) Jack., 410 neferine, 386 Nelumbo nucifera Gaertn., Nervilia plicata (Andrews) Schltr., 447 Nigella sativa L., 186 Ocimum basilicum L., 440 Ocimum sanctum L., 441 Opuntia ficus-indica (L.) Mill., 78 Orthosiphon stamineus Benth., 143 oxymatrine, 407 Pelargonium graveolens L’Hér ex Aiton, 322 Phyllanthus acidus (L.) Skeels, 306 Phyllanthus amarus Schumach & Thonn., 208 Poncirus trifoliata (L.) Raf., 104 prenylated flavonoid, 401 Pterocarpus santalinus Buch.-Ham ex Wall., 214 Punica granatum L., 404 Raphanus sativus L., 206 Rheum rhabarbarum L., 298–299 Rhus chinensis Mill., 222 Rhus coriaria L., 321 Rosmarinus officinalis L., 438 Rubus fruticosus L., 307 Silybum marianum (L.) Gaertn., 121 Siraitia grosvenorii (Swingle) C Jeffrey ex A.M Lu & Z.Y Zhang, 11 Smallanthus sonchifolius (Poeppig) H Robinson, 430 Solanum surattense Burm.f, 133 Solanum torvum Swartz, 248 Solanum xanthocarpum Schrad & Wendl., 340 Sphaeranthus indicus L., 120 Spondias pinnata (L.f.) Kurz., 99 streptozotocin, 424 streptozotocin-induced diabetic, 248, 318, 409 Swertia macrosperma (C.B Clarke) C.B Clarke, 124 Swietenia macrophylla King., 317–318 Tectona grandis L.f., 49, 139, 346 Tephrosia purpurea (L.) Pers., 217 Terminalia arjuna (Roxb ex DC.), 404 Terminalia bellirica (Gaertn.) Roxb., 17 Terminalia catappa L., 93 Terminalia pallida Brandis, 307 Tetracera scandens (L.) Merr., 299 thymoquinone, 186 Tinospora cordifolia Miers ex Hook f & Thomson, 77–78 Toddalia asiatica (L.) Lam, 105 Trachyspermum ammi (L.) Sprague, 425 Trigonella foenum-graecum L., 409 trigonelline, 83, 409 Uncaria rhynchophylla (Miq.) Miq ex Havil., 433 ursolic acid and luteolin-7-O-glucoside, 253 Urtica dioica L., 208 Vernonia amygdalina Delile, 121 Viscum articulatum Burm f., 419 Vitex negundo L., 140 Withania coagulans (Stocks) Dunal, 435 Withania somnifera (L.) Dunal, 341 Woodfordia fruticosa (L.) Kurz, 94 Zingiber zerumbet (L.) Roscoe ex Sm., 262, 451 488 Withania coagulans (Stocks) Dunal, 340–341, 434–435 Withania somnifera (L.) Dunal, 134–135, 341 WNT/β-catenin, 328 Woodfordia fruticosa (L.) Kurz, 94 Wrightia tomentosa (Roxb.) Roem & Schult., 246–247 X Xanthoangelol, 325–326 Xanthomicrol, 440–441, 440f Z Zanthoxylum bungeanum Maxim., 415 Zanthoxylum piperitum (L.) DC., 25, 26f, 316 Zanthoxylum schinifolium Siebold & Zucc., 416 Index Zanthoxylum simulans Hance, 416–417, 416f Zerumbone, 263, 263f Zingiber mioga (Thunb.) Roscoe, 259–261, 260f, 450 Zingiber officinale Roscoe, 261–262, 358–359, 450 Zingiber zerumbet (L.) Roscoe ex Sm., 262–263, 450–451, 451f Zucker rats Cyperus rotundus L., 359 fa/fa rats, 240 fatty rats Gynostemma pentaphyllum Makino, 10, 11 Ipomoea batatas (L.) Lam., 43 Rosmarinus officinalis L., 52 Salacia reticulata Wight., 29 obese rats, 239 Pinellia ternata (Thunb.) Makino, 350 Salacia oblonga Wall., 419 ... apigenin, 3,6-di-C-glucosyl acacetin, 2? ?-O-α-l-rhamnosyl4ʹ-O-methylvitexin, 2? ?-O-α-l-rhamnosyl-4ʹ-O-methylisovitexin, 2? ?-O-α-l-rhamnosyl orientin and ponicilin .28 8 Flavonoids from members of the genus... hyperin, and isoquercitrin ,23 4 kaempferol 3-O-glucoside, kaempferol 3-O-rutinoside, isorhamnetin 3-O-rutinoside ,23 5 as well as chlorogenic acid and 2- O-caffeoyl-malic acid .23 6 Quercetin inhibited... Liver catechin-(4? ?-8 )-catechin, and catechin-(4? ?-8 )-epicatechin as well as flavan-3-ols.319, 320 The leaves of this plant contain catechin, rutin, kaempferol, quercetin, and isorhamnetin. 321 3.63