Microsoft Word jsfa 6111 Pharmacological potentials of Syzygium cumini A review Shalini Srivastava and Deepak Chandra Department of Biochemistry, University of Lucknow, Lucknow, India Address for corr[.]
Pharmacological potentials of Syzygium cumini: A review Shalini Srivastava and Deepak Chandra Department of Biochemistry, University of Lucknow, Lucknow, India Address for correspondence – Dr Deepak Chandra Associate Professor Department of Biochemistry, University of Lucknow, Lucknow, India e-mail – deepakvns@yahoo.com Phone: 91-9415164388 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record Please cite this article as doi: 10.1002/jsfa.6111 © 2013 Society of Chemical Industry Abstract In the last few years there has been an exponential growth in the field of herbal medicine and these drugs are gaining popularity both in developing and developed countries because of their natural origin and lesser side effects Syzygium cumini (syn Eugenia jambolana, Syzygium jambolana, Eugenia cumini, Syzygium jambos) commonly known as “Jamun” in India, is an evergreen tree distributed in the Indian sub-continent, south-east Asian countries and eastern Africa It is mainly utilised as a fruit producer and for its timber Medicinally, the fruit is stated to have anti-diabetic, anti-hyperlipidemic, anti-oxidant, anti-ulcer, hepatoprotective, anti- allergic, anti-arthritic, anti-microbial, anti-inflammatory, anti-fertility, anti-pyretic, anti-plaque, radioprotective, neuropsychopharmacological, nephroprotective and anti-diarrhoeal activities Among these beneficial physiological effects, the anti- diabetic property of S cumini has the most promising nutraceutical value These health beneficial effects of S.cumini are mainly attributed to the various phytoconstituents such as tannins, alkaloids, steroids, flavonoids, terpenoids, fatty acids, phenols, minerals, carbohydrates and vitamins present in the fruit This review presents an overview of experimental evidences for the pharmacological potential of S cumini Keywords anti-oxidant Syzygium cumini, phytochemistry, pharmacological, anti-diabetic, anti-hyperlipidemic, Introduction S cumini (syn.Eugenia jambolana), a member of family Myrtaceae is commonly known as Jamun or Jambul in Hindi and Black Plum or Indian Blackberry in English S cumini is an evergreen tree distributed in the Indian sub-continent, south-east Asian countries and eastern Africa S cumini, is widely used in different countries including India for the treatment of many disorders including diabetes.1 Various parts of this plant have been recognized to posses several medicinal properties in the traditional system of medicine The bark of the plant is carminative, digestive, anti-hyperglycemic, anti-helminthic and antibacterial The fruits and seeds are used to treat diabetes, pharyngitis, spleenopathy, urethrorrhea and ringworm infection The leaves possess antibacterial property and are used to strengthen teeth and gums The leaves have also been extensively used to treat diabetes, constipation, leucorrhoea, fever, gastropathy, dermopathy and to inhibit blood discharges in the feces.2-5 Phytochemistry 2.1 Fruit The major acid present in the fruit of S cumini is malic acid with traces of oxalic acid, gallic acid and tannins which account for astringency of the fruit The purple colour of the fruit is due to presence of cyanidin diglycosides.6 Glucose, fructose, mannose and galactose are the principal sugars.7 The fruit is a rich source of minerals and vitamins.6,8 2.2 Seed S cumini seeds contain a glucoside jamboline, chlorophyll, fat, resin, albumen, tannins and phenolics such as ellagic acid, gallic acid, caffeic and ferulic acids and their derivatives The seeds are fairly rich in protein, calcium and also contain monoterpenoids, flavonoids such as rutin, quercetin,6-9 β-sitosterol and oil containing saturated and unsaturated fatty acids.10,11 2.3 Stem Bark Stem bark of S cumini contains betulinic acid, β-sitosterol, friedelin, epi-friedelanol6 and an ester of epi-friedelanol (eugenin).12 It also contains β-sitosterol-D-glucoside, kaempferol-3glucoside, quercetin,13 myricetin, astragalin and gallic acid.7 2.4 Leaves The presence of different flavonoids, terpenoids and phenolics viz sitosterol, betulinic acid, crategolic acid, quercetin, myricetin, methylgallate, kaempferol etc have been reported to be present in the leaves of S cumini.14-16 Pharmacology S cumini is known to have various pharmacological activities like anti-diabetic, antioxidative, anti-hyperlipidemic, anti-ulcer, hepatoprotective, anti-allergic, anti-inflammatory, anti-arthritic, anti-bacterial and radioprotective activity These effects have been attributed to the presence of different phenolics and flavonoids in S cumini tree The medicinal benefits of S cumini seeds, leaves, stem bark and whole fruit were mentioned in Ayurveda and other traditional therapeutic systems in India.17 3.1 Anti-diabetic activity S cumini is a widely used medicinal plant for the management of diabetes in animal models The anti-diabetic effect of E jambolana (EJ) seed powder, at 0.5 and g/kg body weight doses for 15 days, was observed with increase in body weight and improvement in peak blood glucose levels in diabetic treated rats.18 The effect of oral administration of ethanolic extract of S cumini seed powder was studied on body weight, fasting blood glucose (FBG) levels and pancreatic islets in alloxan induced diabetic rats Three different doses, 0.25 g, 0.5 g and 0.75 g/kg body weight of alcoholic extract of S cumini administered orally increased the body weight of rats by 21, 24 and 18%, respectively after 30 days of extract feeding The blood glucose level was lowered in a dose dependent and duration dependent manner by all three doses mentioned above 10%, 23% and 33% decrease in blood glucose level was observed with above mentioned three doses after days of treatment These three doses resulted in 33-52% decrease and 40-82% decrease in blood glucose levels on day 15th and 30th respectively Alloxan monohydrate intravenous treatment caused clumping and degranulation of β cells initially, followed by hyperplasia and hydropic degeneration of some cells and finally islets are replaced by fibroblasts only After 30 days treatment, all the β cells showed recovery and blood glucose became normal in almost all the animals treated with 0.5 and 0.75 g doses The normalized blood glucose levels and improved histopathology of β cells did not change even after the discontinuation of extract feeding for next 15 days.19 Anti-diabetic effect of ethanolic extract of dried seed kernel of E jambolana (EJE) was evaluated An optimal dose of 0.2 g/kg body weight showed anti-hyperglycemic effect from the tenth day onwards, while the anti-diabetic drug, glibenclamide (0.6 x 10-3 g/kg body weight) showed the above effect after four days of administration to mild diabetic rats (FBG level between 120-250mg/dL) Further, EJE caused a significant reduction in triglyceride, total cholesterol and decrease in glycosylated hemoglobin after 30 days treatment.20 In another study, administration of alcoholic extract of S cumini seed at a dose of 0.1 g/kg body weight restored the FBG and urine sugar to normal levels in alloxan induced diabetic rats Significant improvement in total hemoglobin, body weight, cholesterol, phospholipids and free fatty acids were also observed.21 The anti-hyperglycemic activity of aqueous extract of S cumini seeds was reported in male albino Wistar rats Three different doses of S cumini seed extract, 2.5g/kg, 5.0g/kg, 7.5g/kg body weight, and glibenclamide (0.6 x 10-3 g/kg body weight), were administered orally to the diabetic rats for weeks The elevated levels of FBG, urine sugar and decrease in body weight and total hemoglobin were observed in diabetic rats The altered values of the above mentioned parameters were brought close to normal values with 2.5 g/kg body weight dose of S cumini seed extract and 0.6 x 10-3 g/kg body weight glibenclamide dose The other two doses of S cumini seed extract did not show any better effect The possible mechanism by which S cumini seed extract brings about its anti-hyperglycemic action was explained by stimulation of pancreatic insulin secretion Decrease in total hemoglobin during diabetes may be due to the formation of glycosylated haemoglobin The increased hemoglobin in animals given S cumini seed extract was explained due to decreased glycosylated haemoglobin when normoglycemic condition was achieved.22 Few attempts have been made to purify/isolate different active constituents from S cumini seed extract and their anti-diabetic potential has been evaluated.23,24 The anti-diabetic activity of mycaminose, an active compound isolated from methanol extract of S cumini seed was reported Administration of mycaminose at a dose of 0.05 g/kg body weight resulted in 28% decrease in elevated FBG levels in 15 days Administration of 0.2 g/kg and 0.4 g/kg body weight of crude methanolic S cumini seed extract resulted in 27% and 39% decrease in FBG levels, respectively after 15 days The possible mechanism by which S cumini seeds bring about a decrease in blood sugar level was explained by increase in either the pancreatic secretion of insulin from β-cells of the islets of Langerhans or its release from the bound form.23 Petroleum ether, chloroform, acetone, methanol, and water extracts of S cumini seed (0.1 g/kg body weight), when administered orally for 20 days, reduced FBG levels in diabetic rats Solvents of different polarity were used to extract active constituents from S cumini seed These different extracts were tested for their anti-diabetic activity in diabetic rats The phytochemical analysis of these different extracts was done and the petroleum ether extract showed presence of steroids, chloroform and acetone extracts were rich in carbohydrates and alkaloids Water extract showed presence of gums and methanolic extract contained saponins The methanolic extract, which showed the most significant, 56% reduction in FBG, was subjected to column chromatography and an active principle, cuminoside, was isolated Administration of cuminoside, a phenolic glycoside isolated from methanolic extract of S cumini seed, at a dose of 0.05 g/kg body weight to diabetic rats, exhibited 61% reduction in FBG, where as glibenclamide showed 67% reduction Cuminoside also caused significant increase in the levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase in diabetic rats The anti-hyperglycemic effect of Cuminoside may be due to increase in peripheral glucose utilization and secretion of insulin from the pancreatic β cells.24 LH II fraction purified from ethanolic seed extract of E.jambolana using a combination of silica gel (60-120 mesh) and sephadex LH 20 column chromatography showed significant anti-hyperglycemic effect in alloxan induced diabetic rabbits 0.01 g/kg body weight dose of LH II fraction showed decreased glycosylated hemoglobin, elevated plasma insulin levels and decreased total lipid content.25 The aqueous and alcoholic seed extracts of S cumini, as well as the different active constituents isolated from them have been found to exhibit effect on various enzymes of carbohydrate metabolism Oral administration of glibenclamide (0.6 x 10-3 g/kg body weight), S cumini aqueous seed extract (2.5 g/kg body weight), and insulin (6 U/kg body weight) for one month, resulted in increased hexokinase activity by 64.7%, 72.7%, and 79.5%, respectively and decreased glucose-6-phosphatase activity by 64.7%, 73.5%, and 88.4%, respectively which suggested an increased utilization of glucose for energy production and decreased gluconeogenesis Oral administration of S cumini seed extract resulted in decreased serum levels of enzymes of hepato-cellular toxicity namely, alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH) in comparison to diabetic control.26 The LH II fraction purified from the ethanolic seed extract of S cumini, restored the decreased activities of glycolytic enzymes (glucokinase and phosphofructokinase) and increased activities of enzymes of gluconeogenesis (glucose-6-phosphatase and fructose-1,6bis phosphatase) to their normal levels in alloxan induced diabetic rabbits Thus LH II induced activation of glycolysis resulted in increased consumption of glucose by restoring insulin secretion in the treated rabbits Insulin is also a suppressor of gluconeogenic enzymes which could be a reason for LH II mediated reduction in the activities of gluconeogenic enzymes.25 The mechanism of action of LH II was observed to be both pancreatic27 and extrapancreatic as E jambolana is reported to inhibit insulinase activity in both liver and kidney.28 Treatment of diabetic rats with E jambolana (EJ) aq lyophilized seed powder extract led to increase in hepatic and skeletal muscle glycogen content and no significant change in renal glycogen content in comparison to diabetic controls It also led to a significant rise in levels of enzymes namely, hexokinase, glucokinase and phosphofructokinase, and substrate, Glucose-6-phosphate as compared to diabetic controls.29 Anti-hyperglycemic activity of EJ and its prevention of depletion of glycogen in the liver and muscle was also explained possibly due to either stimulation of insulin release from β cells or due to insulin mimetic activity of some components of the fruit resulting in direct peripheral glucose uptake or due to a combination of the two.30 Inhibition of pancreatic α-amylase activity by aqueous S cumini seed extract has been reported to be a possible mechanism for its anti-diabetic action.31 Oral administration of aqueous S cumini bark extract (SBEt) significantly lowered the blood glucose and urine sugar levels of diabetic rats SBEt treatment also elevated plasma insulin levels and C-peptide in diabetic groups Insulin and C-peptide are the products of the enzymatic cleavage of proinsulin and secreted into the circulation in equimolar concentrations The measurement of both C-peptide and insulin levels have been reported to be valuable indices of insulin secretion than insulin alone.32, 33 There was a significant gain in body weight of the treated rats as compared to the diabetic control, which might be due to the protective effect of SBEt in controlling muscle wasting (i.e reversal of gluconeogenesis and glycogenolysis) and also due to the improvement in insulin secretion and glycemic control.34 Immunohistochemical staining study revealed positive staining for insulin in epithelia of pancreatic duct and cells around the duct in diabetic rats treated with aqueous extract of S.cumini bark at a dose of 1g/kg body weight for 30 days This effect was not seen in control groups, suggesting the possibility that S cumini can stimulate β-cell regeneration by the proliferation of its precursor cells in the pancreatic duct, since practically all of its β-cells were destroyed by alloxan.35 The methanolic leaf extract of S cumini was assessed for its lipogenic, anti-lipolytic and glucose uptake activities It did induce lipogenesis, inhibit epinephrine induced lipolysis and enhance insulin mediated glucose uptake in primary adipocytes at a dose range of 0.1-10 x 10-3 g/L, suggesting insulin like activity in S cumini leaves.36 Aqueous extract of S cumini pulp also showed hypoglycemic activity and prevented decrease in body weight at doses of 0.1 and 0.2 g/kg body weight.37 Therefore it is concluded that S cumini (bark, seed and pulp) is effective in controlling glucose levels in chemically induced mild to severe animal models (rat and rabbit) of diabetes mellitus The anti-diabetic potential of constituents in different parts of S cumini seem to work by stimulating enzymes involved in peripheral utilization of glucose38, potentiating damaged β-cells of pancreas,25 summarized in Table 39 and 3.2 Anti-hyperlipidemic activity One of the most common complications in diabetes mellitus is abnormal lipid profile The anti-hyperlipidemic effect of alcoholic E.jambolana seed extract (0.1 g/kg body weight) was reported in plasma, kidney and liver tissues of streptozotocin induced diabetic rats The increased levels of plasma lipids observed in diabetic rats were restored to near normal by treatment with E.jambolana seed extract and glibenclamide (0.6 x 10-3 g/kg) Oral administration of E.jambolana seed extract reduced the levels of serum LDL and VLDL cholesterol and increased HDL cholesterol in diabetic rats by controlling the hydrolysis of lipoproteins and their selective uptake and metabolism in liver and kidney.40 Insulin sensitive lipases are found in fat depots, in the absence of insulin these are active or uninhibited and cause lipolysis and mobilization of fatty acids from fat depots to plasma causing hyperlipidemia.41 Undersecretion of insulin and elevated levels of glucagon and catecholamines in diabetics also enhance lipolysis Diabetes-induced hyperlipidemia may be attributed to excess mobilization of fat from the adipose tissues due to the under utilization of glucose.42 E jambolana seed administration increases the peripheral utilization of glucose, by affecting the metabolisms described above The effect of aqueous extract of S cumini pulp on serum lipids was observed in streptozotocin induced diabetic rats The total-cholesterol, LDL-cholesterol and triacylglycerol significantly increased and HDL-cholesterol, phospholipids significantly decreased in streptozotocin induced diabetic rats when compared with the normal rats The aqueous extract of S cumini pulp at a dose of 0.1 g/kg and 0.2 g/kg body weight resulted in a dose dependent decrease in the levels of total cholesterol, LDL cholesterol, triglycerides and increase in the levels of HDL cholesterol and phospholipids.37 ... treated rats showed a significant increase in the levels of serum marker enzymes, aspartate aminotransferase (ALT), alanine aminotransferase (AST) and ALP, and decrease in total protein and albumin... 3.8 Anti-bacterial Activity Syzygium jambos is a widespread medicinal plant traditionally used in sub-Saharan Africa to treat infectious diseases The anti-microbial activity of acetone and aqueous... induced by paracetamol, which was brought about by the antioxidant activity of EPEJ The flavonoids, gallic acid and anthocyanins present in the pulp of E.jambolana, acted as natural antioxidants.69