Srinivas Nammi

The juice of fresh leaves of Catharanthus roseus Linn. reduces blood glucose in normal and alloxan diabetic rabbits

BackgroundThe leaf juice or water decoction of Catharanthus roseus L. (Apocyanaceae) is used as a folk medicine for the treatment of diabetes all over the world. In the present investigation, the leaf juice of C. roseus has been evaluated for its hypoglycemic activity in normal and alloxan-induced diabetic rabbits.MethodsThe blood glucose lowering activity of the leaf juice was studied in normal and alloxan-induced (100 mg/kg, i.v.) diabetic rabbits, after oral administration at doses of 0.5, 0.75 and 1.0 ml/kg body weight. Blood samples were collected from the marginal ear vein before and also at 4, 6, 8, 10, 12, 16, 18, 20 & 24 h after drug administration and blood glucose was analyzed by Nelson-Somogyis method using a visible spectrophotometer. The data was compared statistically by using Students t-test.ResultsThe leaf juice of C. roseus produced dose-dependent reduction in blood glucose of both normal and diabetic rabbits and comparable with that of the standard drug, glibenclamide. The results indicate a prolonged action in reduction of blood glucose by C. roseus and the mode of action of the active compound(s) of C. roseus is probably mediated through enhance secretion of insulin from the β-cells of Langerhans or through extrapancreatic mechanism.ConclusionsThe present study clearly indicated a significant antidiabetic activity with the leaf juice of Catharanthus roseus and supports the traditional usage of the fresh leaves by Ayurvedic physicians for the control of diabetes.

Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats

BackgroundTerminalia chebula (Combretaceae) has been widely used in Ayurveda for the treatment of diabetes. In the present investigation, the chloroform extract of T. chebula seed powder was investigated for its antidiabetic activity in streptozotocin-induced diabetic rats using short term and long term study protocols. The efficacy of the extract was also evaluated for protection of renal functions in diabetic rats.MethodsThe blood glucose lowering activity of the chloroform extract was determined in streptozotocin-induced (75 mg/kg, i.p.; dissolved in 0.1 M acetate buffer; pH 4.5) diabetic rats, after oral administration at the doses of 100, 200 and 300 mg/kg in short term study. Blood samples were collected from the eye retro-orbital plexus of rats before and also at 0.5, 1, 2, 4, 6, 8 and 12 h after drug administration and the samples were analyzed for blood glucose by using glucose-oxidase/peroxidase method using a visible spectrophotometer. In long term study, the extract (300 mg/kg) was administered to streptozotocin-induced diabetic rats, daily for 8 weeks. Blood glucose was measured at weekly intervals for 4 weeks. Urine samples were collected before the induction of diabetes and at the end of 8 weeks of treatments and analyzed for urinary protein, albumin and creatinine levels. The data was compared statistically using one-way ANOVA with post-hoc Dunnets t-test.ResultsThe chloroform extract of T. chebula seeds produced dose-dependent reduction in blood glucose of diabetic rats and comparable with that of standard drug, glibenclamide in short term study. It also produced significant reduction in blood glucose in long term study. Significant renoprotective activity is observed in T. chebula treated rats. The results indicate a prolonged action in reduction of blood glucose by T. chebula and is probably mediated through enhanced secretion of insulin from the β-cells of Langerhans or through extra pancreatic mechanism. The probable mechanism of potent renoprotective actions of T. chebula has to be evaluated.ConclusionThe present studies clearly indicated a significant antidiabetic and renoprotective effects with the chloroform extract of T. chebula and lend support for its traditional usage. Further investigations on identification of the active principles and their mode of action are needed to unravel the molecular mechanisms involved in the observed effects.

Obesity: An overview on its current perspectives and treatment options

Obesity is a multi-factorial disorder, which is often associated with many other significant diseases such as diabetes, hypertension and other cardiovascular diseases, osteoarthritis and certain cancers. The management of obesity will therefore require a comprehensive range of strategies focussing on those with existing weight problems and also on those at high risk of developing obesity. Hence, prevention of obesity during childhood should be considered a priority, as there is a risk of persistence to adulthood. This article highlights various preventive aspects and treatment procedures of obesity with special emphasis on the latest research manifolds.

Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model

BackgroundThe aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity.MethodsFor the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cooks pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals.ResultsDaily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner.ConclusionThe present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders.

Protective effects of ethanolic extract of Zingiber officinale rhizome on the development of metabolic syndrome in high-fat diet-fed rats

Metabolic syndrome, including obesity, dyslipidaemia, hyperglycaemia and insulin resistance that predisposes type 2 diabetes is a major disease problem around the world and a plethora of herbal medicines are claimed to be effective in controlling these disorders. The rhizome of Zingiber officinale (Zingiberaceae) is commonly used as a spice in various foods and beverages. Apart from its other traditional medical uses, Z. officinale has been used to control diabetes and dyslipidaemia. In the present study, the protective effects of an ethanolic extract of Z. officinale on the development of metabolic syndrome were investigated in a high-fat diet-fed rat model at doses of 100, 200 and 400 mg/kg body weight. The marked rise in body weights, glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, free fatty acids and phospholipids in serum of the rats that followed 6 weeks of high-fat diet treatment were significantly reduced by Z. officinale treatment. However, no significant change in serum HDL cholesterol was observed either with high-fat diet or Z. officinale compared to both control groups. The present results provide scientific evidence to substantiate the traditional use of Z. officinale in preventing metabolic disorders.

Natural Products for the Treatment of Obesity, Metabolic Syndrome, and Type 2 Diabetes

Globally, the incidence of obesity, metabolic syndrome, and diabetes (OMD) are continuously on the rise because of rapid changes in human life-style and dietary habits. Herbal extracts are of special interest in treating combination of these diseases because of their multipronged mode of action. The list of potential herbals to control metabolic diseases is ever-expanding. However, because of poor characterization and safety issues, these herbs face limitations for their clinical usage. This special issue is a collection of research and review articles on preclinical and clinical benefits of herbals in controlling OMD. This special issue contains 24 articles accepted from a total of 37 submissions consisting of 20 research articles, 3 review articles, and 1 clinical study. The research articles in this issue can be broadly divided into three disease categories—nonalcoholic steatohepatitis (NASH), obesity, and diabetic complications. Four articles of this special issue focus on evaluating the protective role of herbal extracts on NASH. The studies by X. R. Yang et al. “Effect of dietary cocoa tea (Camellia ptilophylla) supplementation on high-fat diet-induced obesity, hepatic Steatosis, and hyperlipidemia in mice” and H.-Y. Jung et al. “The Korean mistletoe (Viscum album coloratum) extract has an antiobesity effect and protects against hepatic steatosis in mice with high-fat diet-induced obesity” report the potential benefits of Camellia ptilophylla and Viscum album coloratum extracts against HFD-induced NASH. Another two articles evaluated protective effects of biherbal combination (S. miltiorrhiza, G. jasminoides and Grape Pomace, Omija Fruit) in ameliorating experimental NASH. This special issue also contains five articles that focus on antiobesity potential of herbal extracts. These detailed studies evaluated the benefits of 10 herbs and their potential mechanisms responsible in controlling obesity using experimental HFD-fed mice/rat in vivo and 3T3L1 preadipocyte in vitro models. Modulation of PPARγ was a key antiobesity mechanism of Artemisia iwayomogi, Codonopsis lanceolata, Populus balsamifera and its active component (salicortin), and beta-glucan-rich extract from Pleurotus sajor-caju (Fr.) Singer. H.-Y. Shin et al. reported an activation of AMP-activated protein kinase by extract of six herbal medicines (OB-1). In this special issue, 11 articles focus on the potential benefits of various herbal extracts/phytocompounds on diabetes-induced insulin resistance, nephropathy, retinopathy, cardiomyopathy, and inflammation. A. l. Al-Malki showed oat extract to be beneficial for diabetic nephropathy and retinopathy by modulating nuclear factor kappa B (NF-kB). Inhibition of aldose reductase activity by scopoletin ameliorated cataractogenesis in galactose-fed rats (J. Kim et al.). Boehmeria nivea extract (S. H. Kim et al.) and swertiamarin (T. P. Patel et al.) regulated experimental insulin resistance by modulating PPARγ. In another report, S. Kadan et al. evaluated effect of eight antidiabetic medicinal plants extracts on GLUT 4 translocation. The benefits of fisetin and an ayurvedic herbal formulation (Kal-1) on diabetes-induced inflammation was also reported. Further, quercetin was shown to preserve β-cell mass and function in fructose-fed hyperinsulinemic rats via modulating pancreatic akt/foxo1 activation. Berberine ameliorated glucose- and insulin-induced cardiomyocyte hypertrophy by modulating PPARα/NO. In an interesting article by S. E. Martinez et al. pharmacometrics of an antidiabetic compound, 3-methoxypterostilbene was reported. 3-Methoxypterostilbene inhibited α-glucosidase and α-amylase activity and exhibited approximately 50% bioavailability. Three review articles were also incorporated in this special issue. A review by Y. Liu et al. (recent updates on beneficial role of berberine in controlling NASH) provides detailed account on molecular regulation of lipid metabolism and NASH by berberine. In another review by C. D. Lorenzo et al. the use of in vitro and clinical approaches to assess the benefits of plant food supplements is critically discussed. The potential benefits of Kampo, a Japanese traditional medicine, in treating obesity was reviewed by J.-i Yamakawa et al. based on basic and clinical evidence. The only clinical study as a part of this special issue focuses on evaluating body weight lowering effects of herbal extract-THI (target herbal ingredient) on exercising healthy overweight humans following a two-month randomized double-blind, placebo-controlled trial. The study reports a significant reduction in body weight indicating its potential antiobesity effect. We envisage that this special issue will attract broad interest in the fields of obesity, metabolic syndrome, and type 2 diabetes and encourage the perusal of in-depth molecular and cellular mechanistic investigations into the use of natural products, in particular the herbal therapies for metabolic disorders and their complications.

Herbal Medicines and Nutraceuticals for Diabetic Vascular Complications: Mechanisms of Action and Bioactive Phytochemicals

Diabetes is one of the most prevalent chronic diseases throughout the world. The majority of its complications arise from vascular-related inflammation apparently initiated by endothelial cell injury. One cause of this injury has been attributed to hyperglycaemia-induced reactive oxygen species. Consequently, current drug developmental strategy has targeted specific inflammatory and oxidative stress pathways for the prevention of diabetic vascular complications. Herbal medicines have traditionally been used for the treatment of diabetes and its complications. In fact, current pre-clinical and clinical studies have demonstrated that many of them exhibit potent anti-inflammatory and anti-oxidative properties, and have also identified the active phytochemicals responsible for their activities. The present review summarises the latest research on the molecular mechanisms of diabetic vascular complications, and evaluates the level of scientific evidence for common herbal medicines and their bioactive phytochemicals. These agents have been shown to be effective through various mechanisms, particularly the NF-κB signalling pathways. Overall, herbal medicines and nutraceuticals, as well as their bioactive components, which exhibit anti-inflammatory and anti-oxidative properties, provide a promising approach for the prevention and treatment of diabetic complications.

Regulation of Low-Density Lipoprotein Receptor and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Expression by Zingiber officinale in the Liver of High-Fat Diet-Fed Rats

Zingiber officinale has been used to control lipid disorders and reported to possess remarkable cholesterol-lowering activity in experimental hyperlipidaemia. In the present study, the effect of a characterized and standardized extract of Zingiber officinale on the hepatic lipid levels as well as on the hepatic mRNA and protein expression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated in a high-fat diet-fed rat model. Rats were treated with an ethanol extract of Zingiber officinale (400 mg/kg) extract along with a high-fat diet for 6 weeks. The extract of Zingiber officinale significantly decreased hepatic triglyceride and tended to decrease hepatic cholesterol levels when administered over 6 weeks to the rats fed a high-fat diet. We found that in parallel, the extract up-regulated both LDL receptor mRNA and protein level and down-regulated HMG-CoA reductase protein expression in the liver of these rats. The metabolic control of body lipid homeostasis is in part due to enhanced cholesterol biosynthesis and reduced expression of LDL receptor sites following long-term consumption of high-fat diets. The present results show restoration of transcriptional and post-transcriptional changes in low-density lipoprotein and HMG CoA reductase by Zingiber officinale administration with a high-fat diet and provide a rational explanation for the effect of ginger in the treatment of hyperlipidaemia.

A Comparative Study on the Inhibitory Effects of Different Parts and Chemical Constituents of Pomegranate on α-Amylase and α-Glucosidase

Pomegranate has been documented for the management of diabetes in Unani and Chinese medicine. This study compared the effects of the extracts of different pomegranate parts, including juice, peels, seeds and flowers, on carbohydrate digestive enzymes (α‐amylase and α‐glucosidase) in vitro. The methanolic flower extract inhibited α‐amylase and α‐glucosidase, while the methanolic peel extract inhibited α‐glucosidase selectively. The most active flower extract was subjected to water‐ethyl acetate partition. The ethyl acetate fraction was more potent than the water fraction in inhibiting both enzymes. Gallic acid and ellagic acid also showed selective inhibition against α‐glucosidase, and their presence in the ethyl acetate fraction was confirmed by HPLC‐DAD and HPLC‐HESI‐MS. Our findings suggest that the inhibition of carbohydrate digestive enzymes and their phenolic content may contribute to the anti‐hyperglycaemic effects of pomegranate flower and peel, and support their claims in diabetes. Copyright

Attenuation of Liver Pro‐Inflammatory Responses by Zingiber officinale via Inhibition of NF‐kappa B Activation in High‐Fat Diet‐Fed Rats

The aim of this study was to investigate whether treatment with a ginger (Zingiber officinale) extract of high-fat diet (HFD)-fed rats suppresses Nuclear factor-kappa B (NF-κB)-driven hepatic inflammation and to subsequently explore the molecular mechanisms in vitro. Adult male Sprague-Dawley rats were treated with an ethanolic extract of Zingiber officinale (400 mg/kg) along with a HFD for 6 weeks. Hepatic cytokine mRNA levels, cytokine protein levels and NF-κB activation were measured by real-time PCR, Western blot and an NF-κB nuclear translocation assay, respectively. In vitro, cell culture studies were carried out in human hepatocyte (HuH-7) cells by treatment with Zingiber officinale (100 μg/mL) for 24 hr prior to interleukin-1β (IL-1β, 8 ng/mL)-induced inflammation. We showed that Zingiber officinale treatment decreased cytokine gene TNFα and IL-6 expression in HFD-fed rats, which was associated with suppression of NF-κB activation. In vitro, Zingiber officinale treatment decreased NF-κB-target inflammatory gene expression of IL-6, IL-8 and serum amyloid A1 (SAA1), while it suppressed NF-κB activity, IκBα degradation and IκB kinase (IKK) activity. In conclusion, Zingiber officinale suppressed markers of hepatic inflammation in HFD-fed rats, as demonstrated by decreased hepatic cytokine gene expression and decreased NF-κB activation. The study demonstrates that the anti-inflammatory effect of Zingiber officinale occurs at least in part through the NF-κB signalling pathway.