Article

Effect of Withania somnifera on Insulin Sensitivity in Non-Insulin-Dependent Diabetes Mellitus Rats

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

We investigated the effect of an aqueous extract of Withania somnifera (WS) on insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA(1)c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA(1)c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index (K(ITT)) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Animal models resembling human T2DM play a key role for the biological screening of anti-diabetic drugs. In current study, T2DM was induced with a single dose injection of STZ (100 mg/ kg; i.p.) given to 2-day old rat pups [8]. However, repeated multiple low dose of STZ provokes a condition with clinical, histological, and immunopathogenic characteristics resembling human T1DM, including the development of hyperglycaemia associated with infiltration of pancreatic islets by T lymphocytes and macrophage [9]. ...
... 2.6. Determination of levels of HbA1c, blood glucose, insulin, lipid profile and pro-inflammatory cytokines Glycosylated hemoglobin (HbA1c) and blood glucose level in serum were estimated using a previous reported method using manufacturers guidelines [8]. Plasma insulin level was estimated using Enzyme-linked Immunosorbent assay (ELISA) kit from Mercodia, (Uppsala, Sweden). ...
... OGTT has been determined following the earlier documented method [8]. Glucose solution (2 g/kg) was given to overnight fasted rats and blood samples were taken at 0, 15, 30, 60 and 120 min after glucose administration. ...
... 8 Additionally, it has also been well documented that blood glucose and insulin level significantly increases after administration of single dose of STZ in 2-day-old pups. 9 Previous finding suggests that oxidative stress actively involved in the etiology of diabetic complications that arise from chronic hyperglycemia and increased lipogenesis. 10 Cytotoxic action of STZ leads to the generation of reactive oxygen species (ROS), which is responsible for oxidative damage in pancreatic tissues. ...
... Severe NIDDM was induced by a single intraperitoneal injection of STZ (100 mg/kg body weight) that was freshly dissolved in 0.01 M sodium citrate buffer (pH 4.5) after overnight fasting. 9 The animals were awake during the administration of saline or STZ. Rats with blood glucose level !250 mg/dl were considered diabetic and used in this study. ...
... Previously, it has been well reported that chronic hyperglycemia develops in neonatal rats after STZ injection on the second day. 9 It has been also documented that STZ administration causes oxidative stress and free radical generation which damages the pancreatic -cells and results in hyperglycemia and glycosylation of various proteins including hemoglobin. 33 In Figure 4. Effect of BAC on HOMA-IR level in STZ-induced NIDDM rats. ...
Article
4-Methyl-2-[(2-methylbenzyl) amino]-1,3-thiazole-5-carboxylic acid (bioactive compound (BAC)), a novel thiazole derivative, is a xanthine oxidase inhibitor and free radical scavenging agent. Effects of BAC on hyperglycemia, insulin sensitivity, oxidative stress, and inflammation mediators were evaluated in streptozotocin (STZ)-induced neonatal models of non-insulin-dependent diabetes mellitus (NIDDM) rats where NIDDM was induced in neonatal pups with single intraperitoneal injection of STZ (100 mg/kg). The effect of BAC (10 and 20 mg/kg, p.o.) for 3 weeks was evaluated by the determination of blood glucose, oral glucose tolerance test (OGTT), HbA1c level, insulin level, insulin sensitivity, and insulin resistance (IR). Furthermore, inflammatory mediators (tumor necrosis factor-alpha and interleukin-6) and oxidative stress were estimated in serum and pancreatic tissue, respectively. Significant alteration in the level of blood glucose, OGTT, HbA1c, insulin level, insulin sensitivity, in addition variation in the antioxidant status and inflammatory mediators, and alteration in histoarchitecture of pancreatic tissue confirmed the potential of BAC in STZ-induced neonatal models of NIDDM rats. Pretreatment with BAC restored the level of glucose by decreasing the IR and increasing the insulin sensitivity. Furthermore, BAC balanced the antioxidant status and preserved the inflammatory mediators. Histological studies of pancreatic tissues showed normal architecture after BAC administration to diabetic rats. Altogether, our results suggest that BAC successfully reduces the blood glucose level and possesses antioxidant as well as anti-inflammatory activities. This leads to decreased histological damage in diabetic pancreatic tissues, suggesting the possibility of future diabetes treatments.
... It has been reported that STZ-induced diabetes in neonatal rats is a better tool for elucidating the importance of the beta-cell dysfunction in the development of IR or NIDDM [6]. Additionally, it has also been well established that blood glucose and insulin level significantly increases after administration of single dose of STZ in two-day-old pups [7]. Hyperglycemia due to STZ administration causes overproduction of reactive oxygen species (ROS), which in turn leads to oxidative stress in various tissues [8,9]. ...
... DM is a chronic disease in which pancreatic beta-cells damage leads to insufficient release of insulin and/or due to IR [32]. IR is the major risk factor for the impairment of glucose tolerance [7]. The method of NIDDM induction was first described by Portha et al. [33]. ...
... This experimental study was designed to analyze IR, oxidative stress, and inflammation both in serum and pancreas tissues of STZ-induced NIDDM rats and to investigate the effects of BAC supplementation on hyperglycemia, insulin sensitivity, and oxidative stress-induced inflammatory responses and beta-cells damage in pancreas of STZ induced NIDDM rats.Several body of evidence suggested that chronic hyperglycemia develops in neonatal rats after STZ injection on the second day [7] and HbA1c is a very important parameter for the manifestation of DM in clinical setting [37]. Previously, it has been documented that STZ administration causes oxidative stress and free radical generation which damages the pancreatic beta-cells and results in hyperglycemia and glycosylation of various proteins including haemoglobin [38]. ...
... Amongst all currently available antidiabetic drugs, metformin is the only one highly recommended for prevention and cure of type-2 diabetes, which is the most prevalent type (ca. 90%) encountered amongst all diabetic patients (Liu et al. 2010;Anwer et al. 2008). The development of type-2 diabetes begins with an impairment of glucose tolerance and insulin resistance, i.e. a condition when the cells in the body are unable to use insulin secreted from the β-pancreatic and other cells, and which eventually leads to hyperglycemia and hyperinsulinemia (Anwer et al. 2008;Zimmet and Thomas 2003;Robertson and Harmon 2006). ...
... 90%) encountered amongst all diabetic patients (Liu et al. 2010;Anwer et al. 2008). The development of type-2 diabetes begins with an impairment of glucose tolerance and insulin resistance, i.e. a condition when the cells in the body are unable to use insulin secreted from the β-pancreatic and other cells, and which eventually leads to hyperglycemia and hyperinsulinemia (Anwer et al. 2008;Zimmet and Thomas 2003;Robertson and Harmon 2006). The symptoms of diabetes include high blood sugar, polydypsia, polyuria, unusual thirst, polyphagia, weakness and tiredness, intense hunger and sudden weight loss. ...
... Anti-oxidant action and increased insulin sensitivity Bhattacharya et al. (1997a) Extra-pancreatic insulin production and secretion have been observed in streptozotocin-induced diabetic rats (Cunha et al. 2007), and antidiabetic activity of repeated daily treatments with W. somnifera extracts have also been reported in such animals as well (Sarangi et al. 2013;Safhi and Anwer, 2011). In one of the reports dealing with anti-diabetic activity of W. somnifera (Anwer et al. 2008), no effects of even 400 mg/kg daily oral doses of an extract on blood glucose and glycosylated haemoglobin (HbA1C) levels, or in glucose and insulin tolerance tests, or on hepatic insulin resistance, were observed, whereas 200 mg/kg daily doses of the same extract was effective in affording protections against all these altered parameters in diabetic rats. Others using other animal models for hyperglycemia and in nondiabetic animals have also reported analogous observations. ...
Chapter
Full-text available
Ashwagandha (Withania somnifera) extracts and several pharmaceutical formulations containing them are currently often used as tonics useful for prevention and cure of mental health problems, including sleep disturbances, accompanying or caused by diverse slowly progressing chronic diseases. The possibility that W. somnifera could be used for treatments of diabetes and associated metabolic disturbances were first suggested by the results of an exploratory clinical study conducted with its root powdered in diabetic patients and published in 2000. Since then, numerous preclinical and a randomized, double blind and placebo controlled clinical study with extracts of the plant have continued to add experimental evidences in favor of the convictions of the scholars and practitioners of Ayurvedic and other traditionally known systems of medicine that the plant could also be used for prevention and cure of diabetes and other metabolic disorders associated physical and mental health problems. Currently available information suggesting such possibilities are summarized and critically analyzed in this chapter. Potential uses of our current knowledge on phytopharmaclogy and medicinal phytochemistry of the plant and its bioactive constituents for obtaining more sustainable and reproducible health benefits from the plant in patients suffering from, or at risk to, metabolic disorders associated mental health problems, or for discovering novel therapeutic lead against such health problems of the twenty-first century are also discussed.
... In all analyses, a p-value <.05 (two-tailed test) was considered statistically significant. Huerta, Mihalik, Becket, Maitin, & Vattem, 2010;Jonathan, Rivka, Avinoam, Lumír, & Nirit, 2015;Khan, Khan, & Ali, 2014;Nirupama, Devaki, Nirupama, & Yajurvedi, 2014;Shah, Khan, Vakil, & Qureshi, 2017;Singh, Joshi, & Jatwa, 2013); pre-clinical (n = 13 [mice model, n = 2; rat model, n = 11]; Anwer et al., 2017;Anwer, Sharma, Pillai, & Iqbal, 2008;Anwer, Sharma, Pillai, & Khan, 2012;Jain, Pandhi, Singh, & Malhotra, 2006;Kiasalari, Khalili, & Aghaei, 2009;Kyathanahalli, Manjunath, & Muralidhara, 2014; M. S. Parihar, Chaudhary, Shetty, & Hemnani, 2004;P. Parihar, Shetty, Ghafourifar, & Parihar, 2016;Sarangi, Jena, Sarangi, & Swain, 2013; Tekula, Khurana, Anchi, & Godugu, 2018; Thakur, Dey, Shyam Chatterjee, & Kumar, 2015;Udayakumar et al., 2009Udayakumar et al., , 2010; clinical (n = 5; Agnihotri, Sontakke, Thawani, Saoji, & Goswami, 2013;Andallu & Radhika, 2000;Nayak, Nayak, Panda, & Das, 2015;. ...
... STZ injection resulted in hyperinsulinemia and treatment with W. somnifera (200 and 400 mg/ kg) statistically (p < .001) reduced (17.71 and 30.21%) the elevated levels of insulin (Anwer et al., 2008). On the contrary, Thakur et al. ...
... 61.37 and 73.87%) and K ITT (p < .001; 33.34 and 75.56%) levels in diabetic rats (Anwer et al., 2008). ...
Article
Withania somnifera Dunal, also known as Indian ginseng, has been in use since ancient times in the management of diabetes mellitus (DM). This systematic review and meta‐analysis evaluated the efficacy/effectiveness, safety and tolerability of W. somnifera in managing DM. Literature search (published/unpublished) was performed from inception to April 2019 in guidelines recommended databases. A total of 6 in‐vitro, 13 pre‐clinical and 5 clinical studies were included for systematic evaluation. W. somnifera treatment in DM significantly restored the altered levels of blood glucose (experimental data; mean difference, −196.27; 95% confidence interval [−220.96, −171.58]; p < .00001) glycosylated haemoglobin (HbA1c), insulin, lipid profile, serum and oxidative stress markers with no safety concerns. The results suggest the potential role of W. somnifera in managing DM. However, the available clinical data are not considerably enough to provide novel and sufficiently robust evidence for the use of W. somnifera in managing DM. To further strength the anti‐diabetic profile of W. somnifera, well‐designed randomized‐controlled trial(s) with a larger sample size and longer duration is warranted with evaluation of its effect primarily on blood glucose, HbA1c and insulin. Future research also needs to elucidate the molecular mechanism(s) of W. somnifera including its active principles in DM.
... Asgand-Indian ginseng (Withania somnifera Linn.) Hypoglycemic, antiinflammatory, Immuno modulatory, antitumour, antioxidant, hepatoprotective antiageing, anticonvulsant [19] Alkaloids (withanine, withananine, pseudo-withanine, somnine, somniferine, somniferinine [17,20] -decreases blood glucose level, prevent hyperinsulinemia & improves glucose tolerance in NIDDM rats by improving insulin sensitivity [21] Anwer T et al (2007) [21] 3. ...
... Asgand-Indian ginseng (Withania somnifera Linn.) Hypoglycemic, antiinflammatory, Immuno modulatory, antitumour, antioxidant, hepatoprotective antiageing, anticonvulsant [19] Alkaloids (withanine, withananine, pseudo-withanine, somnine, somniferine, somniferinine [17,20] -decreases blood glucose level, prevent hyperinsulinemia & improves glucose tolerance in NIDDM rats by improving insulin sensitivity [21] Anwer T et al (2007) [21] 3. ...
Article
Full-text available
Insulin resistance recognized recently as a strong predictor of diseases in adults, and has become the leading element of the metabolic syndrome and renewed as a focus of research. It affects about one-fourth of the population. Obesity and diabetes reach epidemic proportions in the developed world; hence the role of insulin resistance and its consequences are gaining prominence. Insulin resistance pathologically grows through many interactions of genotype, lifestyle change mainly sedentary life and over eating. Physiologically, many circulating factors regulate insulin sensitivity in target tissue such as adipokines, plasma lipid, circulating hormones and their signaling pathways. Insulin resistance is a powerful independent analyst of wide range of serious illnesses, including stroke, type II diabetes, cardiovascular diseases, hypertension and even cancer. The complications associated with insulin resistance, includes particularly the development of diabetes, atherosclerosis, polycystic ovarian syndrome (PCOS) etc, which are potentially fatal in patient care; consequently, the detection and treatment of insulin resistance is rising appropriately. In last decade, many trials has been carried out on herbal drugs which act as insulin sensitizers, effective in improving the insulin resistance in PCOS and other metabolic diseases. KEYWORDS: Insulin Resistance, Metabolic Diseases, Insulin Sensitizer, Herbal drugs, Unani Medicine
... The root and leave W. somnifera produces hypoglycaemic and hypolipidaemic effects in diabetic rats. [132,133] It is also used in Ayurvedic and Unani systems for treatment of tumors and tubercular glands. An aqueous extract of this plant (200 and 400 mg/kg bwt) produdes hypoglycemic activity in streptozocine induced diabetic rats. ...
... The pharmacological effects of W. somnifera are attributed to the presence of withanolides. [132] CONCLUSION The prevalence of diabetes mellitus continues to rise worldwide. It is associated with decreased insulin production or resistance towards its action. ...
Article
Full-text available
Diabetes mellitus is a common and serious metabolic disorder of the endocrine system throughout the world. This frightful disease is found in every part of the world and is becoming a serious threat to healthcare providers and leads to major cause of death. The number of person suffering from diabetes is increasing due to growth population, aging, urbanization, pollution, and increasing prevalence of obesity and lack of physical activity. It is a group of metabolic disorder characterized by high blood sugar levels that result from the deficiency or ineffective production of insulin by pancreas or action or both. There are lots of chemical agents available to control and treat diabetic patients. It may cause unwanted side effects, if these agents will be used for longer duration. Thus, the need arises to cure this disease with potent drug causing fewer side effects. Alternative to these agents, many of the herbal plants are available across the world having anti-diabetic activity and show their action by different mechanism like stimulating or regenerating the β cell or extra pancreatic effect for hypoglycemic. It may delay the development of diabetic complications or correct the metabolic abnormalities. Numerous herbal plants have been investigated for their potential to treat different types of diabetes. This systemic review article focused on some reported anti-diabetic medicinal plants with their botanical name, common name, constituent, and mechanism of action.
... This test measures insulin sensitivity using the constant disappearance of glucose (Kitt) and glucose metabolism mediated by insulin index. Kitt corresponds to the decrease in percentage of glucose per minute, so the higher is the Kitt; the greater is the insulin sensitivity [16]. To achieve the ITT, rats were anesthetized with pentobarbital (50 mg/kg body weight, IP), and then regular insulin Novolin V R was injected into the tail vein 1 U/kg body weight. ...
... Blood glucose was measured at 0, 5, 10, 15, and 20 min using a glucometer with strips for blood glucose (Accu Check ACTIVE Roche V R ). Kitt was calculated using the following formula: Kitt ¼ 0.693 Â 100/t 1 = 2 where, t 1 = 2 represents the half-life of glucose decay and it was determined from the decrease of linear regression of the natural logarithm of glucose versus time [16]. ...
Article
Full-text available
The objective of this study was to evaluate the action of soy isoflavones and 17 beta estradiol on the extracellular matrix in the uterus and mammary gland of diabetic rats. Sixty adult female rats underwent ovariectomy, then randomized into seven groups of ten animals each: Non-diabetic: GI Sham control animals ovariectomized; and GII control ovariectomized that received propylene glycol vehicle. Diabetic: GIII Sham control diabetic animals ovariectomized; GIV ovariectomized diabetic animals receiving propylene glycol vehicle; GV diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI ovariectomized diabetic rats treated with estrogen (17b-estradiol, 10 mg/kg, subcutaneously); GVII diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage), and with estrogen (17b-estradiol, 10 mg/kg combination therapy). Treatments occurred during 30 consecutive days. After animals euthanasia, a portion of the uterus was immersed in liquid nitrogen for molecular biology analysis, the other portion of uterus and mammary glands were removed and processed for paraffin embedding. Soy isoflavones (GV) and 17b estradiol improved the production of compounds of extracellular matrix, such as small leucine-rich proteoglycans (SLRPs). The combination of both therapies had an additive effect in SLRPs expression. Soy isoflavones contribute to the uterine integrity of SLRPs of diabetic rats.
... The aqueous extract of W. somnifera significantly improved insulin sensitivity index in streptozocin diabetic rats [402]. The leaf and root extracts of W. somnifera increased glucose uptake in myotubes and adipocytes in a dose-dependent manner, and increased insulin secretion. ...
... The extract also decreased blood glucose levels in alloxan and streptozocin diabetic rats [402,404]. The antidiabetic activity may be due to an increase in hepatic metabolism, increased insulin release from pancreatic β-cells, or the insulin-sparing effect [405] (Tables 20, 21 and 22). ...
Article
Full-text available
Diabetes is a global health problem, and the number of diabetic patients is in continuous rise. Conventional antidiabetic therapies are associated with high costs and limited efficiency. The use of traditional medicine and plant extracts to treat diabetes is gaining high popularity in many countries. Countries in the Middle East region have a long history of using herbal medicine to treat different diseases, including diabetes. In this review, we compiled and summarized all the in vivo and in vitro studies conducted for plants with potential antidiabetic activity in the Middle East region. Plants of the Asteraceae and Lamiaceae families are the most investigated. It is hoped that this review will contribute scientifically to evidence the ethnobotanical use of medicinal plants as antidiabetic agents. Work has to be done to define tagetes, mechanism of action and the compound responsible for activity. In addition, safety and pharmacokinetic parameters should be investigated.
... The Ayurvedic herb, Ashwagandha, (Withania somnifera), also known as Indian ginseng, has been used for millennia with numerous beneficial health effects having been reported; it helps fight infections, deters oil plugs from being formed on the skin, and is a natural and healthy way to treat acne scars [6,7]. A newer usage of Ashwagandha root is as an insulin sensitizer [8]. Hyperinsulinemia may exert its redirection of adrenal steroidogenesis to androgens and away from cortisol, via its effects on the synthesis and expression of steroidogenic factor-1 (SF-1) and the nuclear transcription factor Nur77 [9]. ...
... It has been prescribed for a multiplicity of indications over several millennia and is considered by some as an adaptogen (an herb, molecule, or substance that promotes homeostasis). The first report of Ashwagandha root acting as an insulin sensitizer was by Anwer et al. [8]. As mentioned previously, we have reported amelioration of CAH through treatment with a number of insulin-sensitizing interventions including metformin, lifestyle changes, bariatric surgery, thiazolidinediones, and vitamin D repletion [10][11][12][13]15]. ...
Article
Full-text available
An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3- β -ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.
... T2DM is a serious metabolic disorder which is displayed as hyperglycemia, that is elevated blood glucose level. The hyperglycemia in DM is due to inadequate insulin secretion or its reduced responsiveness in target cells followed by development of insulin resistance (American Diabetes Association (ADA), 2017 ;Anwer et al., 2008). Despite increasing awareness of diabetes, around 415 million population is effected worldwide and approximately 193 million remains undiagnosed with this pandemic (Chatterjee et al., 2017;Makinde et al., 2020). ...
... Previous research studies have reported that obesity and T2DM is associated with IR, which results in progression of hyperglycemia (Taylor, 2012;Wu et al., 2020). Similarly, in our previous studies (Anwer et al., 2008;, it was reported that T2DC group exhibited significant hyperinsulinemia, which is clearly evident from increased level of insulin. The administration of TQ (10 & 20 mg/kg) dose dependently decreased insulin levels F I G U R E 7 Superposition of the docked TQ with known ligand of PPARγ, VSP-51, co-crystallized with the target protein (shown in grey colour in the background). ...
Article
Full-text available
The aim was to investigate whether thymoquinone (TQ) attenuates hyperglycemia-induced insulin resistance in experimental type 2 diabetes. Type 2 diabetes mellitus (T2DM) was induced by injection of streptozotocin (STZ, 40 mg/kg) in high fat diet (HFD) rats. The levels of glucose, insulin, area under curve (AUC) of glucose, lipid profile parameters, homeostasis model assessment of insulin resistance (HOMA-IR), peroxisome proliferator-activated receptor-γ (PPARγ), and dipeptidyl peptidase peptidase-IV (DPP-IV) were evaluated in HFD + STZ-induced type 2 diabetic rats. TQ treatment significantly reduced elevated levels of glucose, AUC of glucose, insulin, and DPP-IV in diabetic-treated groups. In addition, TQ treatment significantly reduced high levels of triglycerides (TG) and cholesterols (total, low-density and very low-density lipoprotein) accompanied by significant augmentation in high-density lipoprotein (HDL) levels in diabetic-treated groups. However, TQ treatment significantly improved insulin sensitivity in diabetic-treated groups, which was confirmedby increased level of PPARγ and decreased level of HOMA-IR. Molecular docking of TQ exhibited substantial binding affinity with PPARγ and DPP-IV target proteins, which is supported by in vivo results. These results demonstrate that TQ attenuates hyperglycemia-induced insulin resistance by counteracting hyperinsulinemia, improving lipid profile, insulin sensitivity, and inhibiting DPP-IV.
... Type 2 diabetes mellitus (T2DM) or non-insulin-dependent diabetes mellitus (NIDDM) is possibly the world's foremost metabolic disorder that results from defects in insulin secretion on one side and insulin resistance on the other side of the β-cell (Tripathy et al., 2010). Hyperglycemia is mainly observed in people with increased concentration of carbohydrates and fats in their body; assisted with low physical activities (Anwer et al., 2008). Recently, considerable interest has been generated by a novel class of antihyperglycemic agents that act at distinct levels of the incretin therapies. ...
... Several studies have been carried out in the last few decades by using the various extract/chemical constituents of WS for its biological activity, mostly by using the non-standardized extract derived from the roots of wild plants. Several specific reports have evidenced the antistress, cardioprotective, antiosteoarthritis, immunomodulatory, anticancer, antitumour and antiageing (Mirjalili et al., 2009;Sharma et al., 2011;Anwer et al., 2008) of this botonical. The current study aims on the incretin based anti-diabetic approach of WS extract and its purified component by assessing the inhibition DPP-4 activity. ...
Article
Full-text available
Background: Pharmacologic treatments for type 2 diabetes are based upon increasing insulin availability and improving sensitivity to insulin. Nowadays, glucagon like peptide-1 (GLP-1) based therapies aims at glucose control through DPP-4 inhibitors. DPP-4 is a transmembrane glycoprotein belongs to prolyl oligopeptidase family, with the specificity of removing X-Pro or X-Ala dipeptides from the N-terminus of polypeptides. GLP-1 effect by stimulating glucose-dependent insulin release from the pancreatic islets, inhibit inappropriate post-meal glucagon release and slow gastric emptying promoting leaky gut. The current study investigated DPP-4 inhibitory activity of catechin, isolated from Withania somnifera (WS), for ethnopharmacological treatment of type 2 diabetes and aimed to increase availability of GLP-1and sensitivity to insulin. Materials and Methods: Young and matured fresh roots, leaves, and fruits of WS plant extract were considered and were systematically evaluated for DPP-4 inhibitory activity using in vitro method, enzyme kinetics, phytochemical analysis, RP-HPLC, LCMS and 1H and 13C NMR method and structure-activity relationship (SAR) studies. Results: In this study, methanol (100% and 80%) extracts of WS matured root exhibited maximum DPP-4 inhibitory activity when compared to other extracts. The maximum DPP-4 inhibitory activity was found in 100% methanol extract of matured root. Phytobioactive was purified by RP-HPLC. The compound purified was found to be flavonoid and was characterized (LCMS, 1H and 13C NMR studies), identified as catechin. Auxiliary, molecular docking was performed using Ligand Fit method using PatchDock package. The study revealed the binding affinity of catechin with DPP-4 to be -6.601 kcal/mol with 13 hydrogen interactions with the receptor and was very similar to the standard potent blockers withaferin A and others (cuscohygrine, scopoletin, sitoindoside IV, tropine), further confirming its hyperglycemic potency. Conclusion: The study reveals that, 100% methanol extract of WS matured roots contains the compound- catechin, which exhibits DPP-4 inhibitory activity resulting in increased level of bioactive GLP-1 and GIP. In this background, we concluded that the WS will be a better source for further development as new antidiabetic drugs.
... These include anti-cancerous [4], antioxidant [5], antiepileptic [6], antidepressant, anti-anxiety [7], anti-inflammatory, antiarthritic [8], and antimicrobial [9]. It also has neuroprotective [5]), spermatogenic [11], hepatoprotective [10], hypoglycemic and hypolipidemic [11,12] properties. ...
... These include anti-cancerous [4], antioxidant [5], antiepileptic [6], antidepressant, anti-anxiety [7], anti-inflammatory, antiarthritic [8], and antimicrobial [9]. It also has neuroprotective [5]), spermatogenic [11], hepatoprotective [10], hypoglycemic and hypolipidemic [11,12] properties. ...
Article
Withania somnifera (L) Dunal, a wonder herb of family Solanaceae, has multiple medicinal properties. Here, we reported the chloroplast genome sequence of Withania somnifera (154,386 bp) which comprises of a large single copy region (85,688 bp), and a small single copy region (18,464 bp), separated by a pair of large inverted repeats (25,117 bp). The chloroplast genome has 132 genes including 86 protein-coding, 37 tRNAs and 8 rRNAs. Comparison of chloroplast genomes of Withania somnifera with four other Solanaceae species revealed similarities in genomic features, including structure, nucleotide content, codon usage, RNA editing sites, simple sequence repeats (SSRs), oligonucleotide repeats, and tandem repeats. We identified 147 simple sequence repeats in protein-coding, and 229 in non-protein-coding regions. We observed numerous post-transcriptional substitutions of Serine to Leucine, specifically at the second nucleotide position of the codon. Maximum likelihood and maximum parsimony tree reconstructed displayed Withania somnifera a sister taxon of Physalis peruviana.
... In humans with type-2 diabetes, glucose challenge induces a rise in blood glucose which is markedly higher than in healthy people and is comparable with that observed in rats with STZ-NA-induced diabetes. However, in type-2 diabetic humans, hyperglycemia observed after glucose load usually results from both insulin resistance and impaired function of β-cells [28]. Hence, in addition to glycemic control, management of impaired function of β-cells is also essential for controlling insulin resistance and limiting the complications of non-insulin-dependent diabetes mellitus (NIDDM). ...
... Mol Cell Biochem (2017) 432:[25][26][27][28][29][30][31][32] ...
Article
Full-text available
Dietary measures and plant–based therapies as prescribed by native systems of medicine have gained attraction among diabetics with claims of efficacy. The present study investigated the effects of S-Allylcysteine (SAC) on body weight gain, glucose, insulin, insulin resistance, and nitric oxide synthase in plasma and argininosuccinate synthase (AS) and argininosuccinate lyase (ASL), lipid peroxides and antioxidant enzymes in aorta of control and streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Changes in body weight, glucose, insulin, insulin resistance, and antioxidant profiles of aorta and mRNA expressions of nitric oxide synthase, AS, and ASL were observed in experimental rats. SAC (150 mg/kg b.w) showed its therapeutic effects similar to gliclazide in decreasing glucose, insulin resistance, lipid peroxidation, and increasing body weight; insulin, antioxidant enzymes, and mRNA levels of nitric oxide synthase, argininosuccinate synthase, and argininosuccinate lyase genes in STZ-NA rats. Histopathologic studies also revealed the protective nature of SAC on aorta. In conclusion, garlic and its constituents mediate the anti-diabetic potential through mitigating hyperglycemic status, changing insulin resistance by alleviating endothelial dysregulation in both plasma and tissues.
... Forty eight hours after STZ and vehicle injection, hyperglycemia was confirmed by measuring tail vein blood glucose levels using a glucose monitoring kit (Accu-Chek Active; Roche V R ). Only animals with mean plasma glucose levels >250 mg/dl were accepted as having DM [29][30][31] . ...
... Using a glucometer (Accu Chek V R Active Kit; Roche), blood glucose was measured at 0.5, 10, 15, and 20 min. K ITT was calculated using the following formula: K ITT ¼ (0.693 Â 100) / t 1/2 (where t 1/2 represents the half-life of glucose decay, determined from the decrease of linear regression of the natural logarithm of glucose versus time 30 ). ...
Article
Full-text available
Objective: The objective of this study was to evaluate the action of soy isoflavones (ISO) and 17β-estradiol on collagen I (CollI) and sulfated glycosaminoglycans (GAGs) in the bone matrix of diabetic rats. Methods: Sixty adult female rats (Rattus norvegicus albinus) underwent ovariectomy, and then were randomized into six groups of 10 animals each: GI, sham control ovariectomized animals; GII, sham control diabetic (DM) ovariectomized animals; GIII, control ovariectomized animals receiving propylene glycol vehicle; GIV, control ovariectomized DM animals receiving propylene glycol vehicle; GV, ovariectomized DM animals treated with ISO (150 mg/kg by gavage); and GVI, ovariectomized DM animals treated with estrogen (17β-estradiol, 10 mg/kg, subcutaneously). 17β-Estradiol was used as a positive control when compared with ISO. To obtain significant depletion of the estrogen levels and subsequent bone loss, a postsurgical period of 90 days was observed. Treatments occurred during 30 consecutive days. After euthanasia, shafts of the animals’ femurs were immersed in liquid nitrogen for molecular biology analysis, and the distal femurs were removed and processed for paraffin embedding. Results: ISO (GV) and 17β-estradiol (GVI) improved bone formation, increasing GAGs and CollI formation when compared to the control group (GIV) (p < 0.05). Conclusions: ISO and 17β-estradiol contribute to the decrease of bone loss in diabetic rats.
... Type 2 diabetes mellitus (T2DM) or non-insulin-dependent diabetes mellitus (NIDDM) is possibly the world's foremost metabolic disorder that results from defects in insulin secretion on one side and insulin resistance on the other side of the β-cell (Tripathy et al., 2010). Hyperglycemia is mainly observed in people with increased concentration of carbohydrates and fats in their body; assisted with low physical activities (Anwer et al., 2008). Recently, considerable interest has been generated by a novel class of antihyperglycemic agents that act at distinct levels of the incretin therapies. ...
... Several studies have been carried out in the last few decades by using the various extract/chemical constituents of WS for its biological activity, mostly by using the non-standardized extract derived from the roots of wild plants. Several specific reports have evidenced the antistress, cardioprotective, antiosteoarthritis, immunomodulatory, anticancer, antitumour and antiageing (Mirjalili et al., 2009;Sharma et al., 2011;Anwer et al., 2008) of this botonical. The current study aims on the incretin based anti-diabetic approach of WS extract and its purified component by assessing the inhibition DPP-4 activity. ...
... Oral administration of W. somnifera to streptozotocin-diabetic two-day-old rat pups caused significant normalcy in blood glucose, HbA1c and serum insulin levels. Oral glucose tolerance test was also found significantly improved [44]. ...
Article
Full-text available
Diabetes is a metabolic syndrome increasing rapidly due to occupational stress, lack of physical activity, sedentary lifestyle and increasing occurrence of obesity, associated with rapidly growing urbanization and industrialization. Due to erroneous carbohydrate metabolism, diabetics are more prone to chronic complications like nephropathy, neuropathy, retinopathy, coronary artery disease and peripheral arterial disease resulting in tissue damage. Current treatment protocols to these problems produce more serious adverse effects and are costly too. Medicinal plants provide an alternative of safe, reliable and cost-effective pharmacological source to all these ailments. This review provides the compiled data of isolated active phytoconstituents of 22 potent antidiabetic plants with their plant-part used, which might be useful for drug development.
... Diabetes mellitus (DM) is one of the serious growing health problems worldwide and is characterised by long-term hyperglycaemia due to diminished insulin secretion and/or insulin resistance (Anwer et al. 2008). The World Health Organisation (WHO 2016) has reported that approximately 422 million people are suffering from diabetes and this will increase to 622 million by 2040. ...
Article
The study was designed to find out the effect of thymoquinone (TQ) alone and combination of TQ + fluoxetine in depression of type-2 diabetic rats. Glucose level was significantly decreased in TQ alone treated group, whereas no significant change was recorded when TQ was combined with fluoxetine. Administration of TQ alone and combination of TQ and fluoxetine significantly decreased immobility time, increased latency to immobility and increased locomotor activity. Treatment with TQ alone significantly decreased level of TBARS, increased GSH and restored the activities of antioxidant enzymes (GPx, GR & CAT). However, TQ and fluoxetine combination reduced TBARS level, increased GSH content but no change in the antioxidant enzymes activities. Inflammatory markers (IL-1β, IL-6 & TNF-α) levels were significantly reduced after the administration of TQ alone and TQ + fluoxetine. The study suggests that combination of TQ and fluoxetine can be used to control depression in type-2 diabetes mellitus.
... Several studies on this plant indicated that it possesses anti-inflammatory, anti-tumour, anti-stress, antioxidant, immunemodulatory, hemopoetic and rejuvenating properties besides its positive influence on the endocrine, cardiopulmonary and central nervous system (Singh, et al., 2011). Ashwagandha has a reputation as a general energy-promoting, disease preventing tonic may be its effect on the immune system and regulate blood sugar which aids in suppressing sugar cravings (Anwer, et al., 2008). Thus, the present study was taken up to investigate the effect of low GI products based on W. somnifera root powder on blood glucose in healthy subjects. ...
Article
Full-text available
The glycemic index (GI) provides an indication of carbohydrate quality whereas glycemic load (GL) provides carbohydrates quantity in a food and the insulin demand. Diet with low glycemic index and glycemic load have been shown to improve glucose tolerance on normal healthy subjects so there is a need for a more diversified range of foods with a low glycemic response. The objective of present work was to formulate ashwagandha based food products by utilizing their root powder as an ingredient and their glycemic responses on normal healthy subjects. The products (Chappati, Naan and Thepla) were developed by incorporation of 2%, 4%, 6% and 8% aswagandha root. The result showed that the products with 2% root powder were most acceptable by semi trained panels. Further, study was conducted on randomly selected 30 healthy subjects were fed most acceptable test recipe i.e. thepla and their glycemic response was anticipated. GI and GL values were 37.30 and 11.36 found to be lower 2% root incorporated in thepla while comparing with standard thepla. The data demonstrated that the test thepla belongs to low glycemic index and medium glycemic load. Thus, the inclusion of ashwagandha powder as a constituent can be used to achieve a wider range of low glycemic functional foods possessing sensory attributes that could be valuable for managing the diabetes mellitus.
... Glycowithanoide [29] [48]. In another study by Anwer et al., aqueous WSREt reduced levels of blood glucose, improved hyperinsulinemic condition, and promoted glucose tolerance in non-insulin-dependent diabetes mellitus rats [49]. These results highlighted the fact that W. somnifera can improve insulin sensitivity. ...
... Withania somnifera (L.) Dunal (Aswagandha) [116,117] ▪ Root ▪ Leaf ▪ Flavonoids ▪ Improve insulin sensitivity ▪ Reduce the activity of glucose-6-phosphatase Xylocarpus moluccensis (Lam.) M. Roem. ...
Article
Full-text available
Diabetes mellitus is a degenerative disease being responsible for about 1.5 million deaths globally. In Bangladesh, the stress of diabetes is on rising and resulting in serious health implications along with significant economic crisis. Due to undesirable and inherent side effects, researchers are now shifting from the conventional therapy and trying to prevent and manage diabetes through traditional medicine. World Health Organization (WHO) also recommends the practice of customary herbal medicine for diabetes management, and support and encourage the augmentation of research to evaluate the hypoglycemic properties of the diverse medicinal plant species. Consequently, in the current review, the antihyperglycemic potency of some Bangladeshi medicinal plants has been evaluated and verified utilizing human as well as experimental animals. The results elucidate the glucose-lowering effects of the plants via different cellular mechanisms, including restoration of pancreatic β-cell, controlling the action of carbohydrate metabolizing enzymes, enhancing peripheral glucose utilization, increase in muscle glycogen store as well as activation of the insulin signaling cascade. In summary, this work may invigorate the researchers for more specific and focused research to provide a better and broad understanding of the antihyperglycemic mechanism and can act as an effective tool for choosing the plants with robust potential for unbolting of novel antidiabetic agents.
... Additionally, W. somnifera root powder normalized blood glucose levels over a period of 30 days, and these effects were comparable to that of an oral hypoglycemic drug, Daonil. Aqueous extract of W. somnifera normalizes hyperglycemia in noninsulin-dependent diabetes mellitus in rats by improving insulin sensitivity (Anwer et al., 2008). Consistent with these studies, W. somnifera leaf and root extracts showed antidiabetic activity by normalizing glucose uptake in skeletal myotubes and adipocytes in a dose-dependent manner, the leaf extract being more effective than root extract in this activity (Gorelick et al., 2015). ...
Chapter
Withania somnifera, also known as ashwagandha, is one of the prominent medicinal plants in Indian systems of medicine. Since antiquity, it is used against myriad of clinical conditions and, in fact, its history of use as a medicine dates back to AD 6000. The plant contains a range of different classes of chemical constituents such as alkaloids, steroidal lactones, and flavonoids. These chemical moieties are responsible for various biological activities of the plant. Laboratory studies demonstrated the plant to be antiinflammatory, antitumor, neuroprotective, antimicrobial, antistress, antidiabetic, and cardioprotective. These pharmacologic activities are in part due to the capability of W. somnifera to reduce reactive oxygen species, modulate mitochondrial function, regulate apoptosis, reduce inflammation, and enhance endothelial function. Additionally, it has been used singly or in combination against various diseases of humans. Here, we recapitulate ethnobotanical and pharmacologic characteristics and therapeutic applications of the plant and its active constituents.
... In Sikkim and Darjeeling Himalayas decoction of young leaves and shoots (50–100 ml) taken as curry one or two times daily with meals for 4–8 weeks to cure diabetes (Chhetri et al., 2005).Leaf powder in one cup of water is taken once a day for the treatment of diabetes and its allied complications (Thirumalai et al., 2012). It decreases blood glucose level, prevents hyperinsulinemia and improved glucose tolerance in NIDDM rats and it can improve insulin sensitivity (Anwer et al., 2008). ...
... The homeostasis model assessment of IR (HOMA-IR) was calculated using fasting serum glucose (FSG) and fasting serum insulin (FSI) concentrations according to the following formula: HOMA-IR ϭ insulin (U/ml) ϫ FSG (mg/dl)/405 (1). ...
Article
This study was performed to examine the effects of long-term caffeine-intake, with and without exercise, on the progression of diabetic nephropathy (DN) in an obese diabetic rat model. Thirty-two male Otsuka Long Evans Tokushima Fatty (OLETF) rats were assigned to sedentary (OLETF-Sed), exercise (OLETF-Ex), caffeine-intake (OLETF-Caf), and combined (OLETF-Caf & Ex) groups. Caffeine-intake groups were fed rat chow containing caffeine (90.7 ± 4.7 mg/kg/day). The OLETF-Ex and OLETF-Caf & Ex groups were able to run voluntarily at any time using a rotatory wheel. Body weight (BW) and blood pressure (BP) were measured weekly from 24 to 29 weeks of age. Pre- and post-treatment serum glucose, insulin, and creatinine concentrations were measured, and a 24 h urine sample was collected for measurement of creatinine clearance (Ccr) and albumin excretion (UEAlb). After treatment, the kidneys were removed for morphological analysis. The OLETF-Caf and OLETF-Caf & Ex groups exhibited no BP increase during the study. Both the caffeine-intake groups exhibited a significant increase in urine volume (UV), electrolyte excretion, and Ccr, and decreased UEAlb, following treatment. Furthermore, no structural damage was observed in the kidneys of rats from either caffeine-intake group, whereas the OLETF-Sed and OLETF-Ex groups exhibited DN progression. This study demonstrates that caffeine-intake alone and/or combined with exercise significantly decreases BW and improves glucose intolerance, without the progression of DN. Further research should be performed to examine whether the quantities of caffeine contained in a normal human daily intake also have a protective effect against kidney damage.
... Likewise, W. coagulans demonstrated hypoglycemic effect and modulating glucose tolerance test in normal, mild, moderate and severe diabetic rats (Jaiswal et al., 2009). Five week administration of aqueous extract from W. somnifera significantly attenuates hyperglycemia, hyperinsulinemia and accumulation of glycosylated hemoglobin, as well as prevention of the rise of homeostasis model assessment of insulin resistance in rats with non-insulin-dependent diabetes mellitus (Anwer et al., 2008). Enhancement of liver and muscle glycogen as well as improvement of enzymes involved in glucose homeostasis, including glucokinase, phosphofructokinase and glucose-6-phosphatase are among the main antidiabetic mechanisms of W. coagulans in preclinical study of STZ/nicotinamide-induced diabetes (Shukla et al., 2012a). ...
Article
Full-text available
Diabetes mellitus is the most common endocrine disorder and a major cause of morbidity and mortality. Traditional medicines worldwide suggest a wide range of natural remedies for the prevention and treatment of chronic disorders, including diabetes mellitus. This mechanistic review aims to highlight the significance of medicinal plants traditionally used as dietary supplements in Persian medicine in adjunct with restricted conventional drugs for the prevention and treatment of diabetes mellitus. Mounting evidence suggests that these natural agents perform their protective and therapeutic effect on diabetes mellitus via several cellular mechanisms, including regeneration of pancreatic β cell, limitation of glycogen degradation and gluconeogenesis, anti-inflammatory, immunoregulatory, antiapoptosis, antioxidative stress, as well as modulation of intracellular signaling transduction pathways. In conclusion, traditional medicinal plants used in Persian medicine can be considered as dietary supplements with therapeutic potential for diabetes mellitus and maybe potential sources of new orally active agent(s).
... The traditional uses and anti-diabetic activity of W. somnifera have been reviewed [12]. Hypoglycemic effects [13] and the effects of W. somnifera on insulin sensitivity in NIDDM rats [14] have been reported. The chemistry and nutritional properties of phenolic compounds, including flavonoids, have been extensively reviewed [15]. ...
Article
Full-text available
p> Objective: The present investigation explores the possibilities of using the in vitro and in vivo root and leaf extracts of Withania somnifera for anti-diabetic and anti-hyperlipidaemic effects on streptozotocin-induced diabetic rats. Methods: In vitro shoot cultures of Withania somnifera were raised by the axillary proliferation in nodal explants from a garden grown plant using Murashige and Skoog medium then in vitro raised roots and shoots were used for the anti-hyperglycemic and anti-hyperlipidaemic experiment. After 72 h of STZ administration, the fasting blood glucose levels were measured and the rats showing FBG level>220 mg/dl were considered to be diabetic and were used for the hyperglycemic study. In vitro and in vivo methanolic root and leaf extracts were orally administered daily to diabetic rats for eight weeks. After the treatment period, blood glucose and serum enzymes like aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total cholesterol, triglycerides, HDL-c high density lipoprotein-bound cholesterol, LDL-c low density lipoprotein-bound cholesterol, LDH, serum protein level, total phenolics and anti-oxidative analysis (DPPH and FRAP) were determined. Results: The levels of blood glucose, AST, ALT, ALP, LDH, HDL-c significantly increased by the use of in vitro methanolic root extracts compared to normal control rats. However, remarkable loss of total protein, albumin, albumin: globulin (A: G) ratio was reported in streptozotocin-induced diabetic rats by using in vitro root extracts. Methanolic in vitro root extract at the dose levels of 300 mg/kg body weight produced a significant decrease in fasting blood glucose (FBG) level by 102.65 with respect to initial fasting blood glucose level after 30 d of the treatment. In vitro root extract demonstrated highest DPPH and FRAP free radical scavenging activity, i.e. 86.55±1.77 and 48.87±2.55 than other extracts. Conclusion: It may be concluded that methanolic in vitro root extract W. somnifera at the dose (300 mg/kg) has more potent anti-hyperglycaemic activity than the other in vitro and in vivo extracts of leaf and root on streptozotocin induced diabetic rats and was also found to be similar in effect to that of the standard drug ‘Glibenclamide’.</p
... The blood glucose was measured at 0.5, 10, 15 and 20 min using a glucometer (Accu Chek V R Active Kit Roche). Kitt was calculated using the following formula: Kitt ¼ 0.693 Â 100/t1 =2 , where t1 =2 represents the half-life of glucose decay, determined from the decrease of linear regression of the natural logarithm of glucose versus time 13 . ...
Article
Full-text available
Objective: To assess the effects of isoflavones and 17β-estradiol on the vaginal epithelium extracellular matrix and hyaluronic acid (HA) in the diabetic rat model. Methods: Sixty adult, virgin, female rats underwent ovariectomy, then randomization into six groups of ten animals each: GI, sham ovariectomized control animals; GII, sham ovariectomized control diabetic animals; GIII, control ovariectomized rats receiving propylene glycol vehicle; GIV, control ovariectomized diabetic animals receiving propylene glycol vehicle; GV, diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI, ovariectomized diabetic rats treated with estrogen (17β-estradiol, 10 mg/kg, subcutaneously). Treatment took place over 30 consecutive days. After euthanasia, a portion of the vagina was immersed in liquid nitrogen for RT-qPCR and Western blotting. Another portion was processed for paraffin embedding. Sections were stained with hematoxylin & eosin for histomorphometry and Picro Sirius Red for collagen quantification. Results: Vaginal epithelium histomorphometry in GIII (15.3 ± 1.1 µm) and GIV (14.5 ± 1.8 µm) was thinner than in GV (41.3 ± 1.5 µm) and GVI (74.3 ± 1.6 µm). There was an increase in collagen content in GV (84.1 ± 1.2 µm) and GVI (88.2 ± 1.7 µm). HA quantification was higher in GV (0.38 ± 1.1 μg/mg) and GVI (0.49 ± 1.4 μg/mg) when compared with GIII (0.12 ± 1.1 μg/mg) and GIV (0.10 ± 1.2 μg/mg), p < 0.05. Conclusions: Soy isoflavones increase hyaluronic acid concentration in the vagina of diabetic ovariectomized rats. Such findings might help to attenuate the effects of vulvovaginal atrophy in women.
... Thus streptozotocin (STZ) induced rat model is one of the most frequently used for T2D-like models [16][17][18] which mimics human diabetes [19]. Previous studies on this model were found to have characteristics of pancreatic beta-cell destruction followed by beta-cell regeneration and glucose intolerance [20,21]. ...
... Ashwagandha has become the most popular ayurveda herb in western world. It has anti-cancer properties (Khan et al. 2009), and also reduces blood sugar level (Anwer et al. 2008), cortisol levels, cholesterol (Shubashree and Sadashiva 2003) stress and anxiety, symptoms of depression. It is found to boost testosterone (Santos et al. 2019) and improve fertility in men, increase muscle mass and strength. ...
Article
Natural products, especially plants and herbs, have always been a common medicament source, either as pure active principles or traditional preparations. Traditional medicine has been used in developing and developed countries for centuries, and still, 80% of the population uses plant-based medicines for their health care needs. The present review discusses all the possible pharmacological activity reported in various literature and active chemical constituents of herbs. A list of various herbs/plants used by Ayurvedacharya Ratiram Sharma (93-year-old and practicing since 1952) and mentioned in Ayurvedic texts. The curated list was prepared by their general availability in the household and local market. This study comprehensively documented the medicinal value of sixty-six dominant plant species used in Ayurveda and local people. In the present review, each herb is discussed with its scientific and common names, geographical distribution, traditional medicinal uses, beneficial plant parts, and active chemical constituents. For each plant, pharmacological activities of different parts of plants are displayed with their chemical constituents and structure. Toxicologists, phytologists, medicinal chemists, and other researchers who are interested in the various therapeutic and related applications of plant materials will be benefited from present review. This information will open new horizons of application for the many novel drugs and drug candidates.
... In a study with W. somnifera by Anwer et al 33 , animal models have shown significant reductions in blood glucose and HbA1c levels and Insulin resistance. In another study with a polyherbal formulation (Cardipro) in which Withania somnifera is an active constituent done by us, we concluded that there was a significant increase in the level of NO and decrease in RI thereby reflecting an improvement of endothelial function in patients with type II diabetes mellitus 34 . ...
... In vitro studies on Ashwagandha root extracts have demonstrated its neuroprotective, anti-inflammatory and chondroprotective effects [10,11]. Experiments using animal models indicated cardioprotective, immunomodulatory, anti-diabetic and neuroprotective effects of Ashwagandha root extracts [12][13][14][15]. Clinical studies conducted in various conditions suggest that Ashwagandha root extract improves sexual performances in both males and females, aids in reducing and managing stress and anxiety, improves memory and cognition in healthy adults and patients with bipolar disorder [16][17][18][19][20]. ...
Article
Full-text available
Introduction Insomnia is a prevalent sleep disorder that can profoundly impact a person's physical health and mental wellbeing. Most of the currently available drugs for insomnia exert adverse effects. Hence, alternative herbal therapies could be effective in treating insomnia. Ashwagandha, a proven "Rasayana" from ancient Ayurveda is having the required potential to treat insomnia. Objective To determine the efficacy and safety of Ashwagandha root extract in patients with insomnia and anxiety. Methods This was a randomized, double-blind, placebo-controlled study conducted at Prakruti Hospital, Kalwa, Maharashtra, India. A total of 60 patients were randomly divided into two groups: test (n = 40) and placebo (n = 20) in a randomization ratio of 2:1. Test product was a capsule containing highest concentration full-spectrum Ashwagandha root extract 300 mg, and the placebo was an identical capsule containing starch. Both treatments were given twice daily with milk or water for 10 weeks. Sleep actigraphy (Respironics Philips) was used for assessment of sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE) and wake after sleep onset (WASO). Other assessments were total time in bed (sleep log), mental alertness on rising, sleep quality, Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAM-A) scales. Results Two patients, one from each group, did not complete study and the per-protocol dataset (n = 58) included 29 and 19 patients from test and placebo, respectively. The baseline parameters were similar in the two groups at baseline. The sleep onset latency was improved in both test and placebo at five and 10 weeks. However, the SOL was significantly shorter (p, 0.019) after 10 weeks with test [29.00 (7.14)] compared to placebo [33.94 (7.65)]. Also, significant improvement in SE scores was observed with Ashwagandha which was 75.63 (2.70) for test at the baseline and increased to 83.48 (2.83) after 10 weeks, whereas for placebo the SE scores changed from 75.14 (3.73) at baseline to 79.68 (3.59) after 10 weeks. Similarly, significant improvement in sleep quality was observed with test compared to placebo (p, 0.002). Significant improvement was observed in all other sleep parameters, i.e., SOL, SE, PSQI and anxiety (HAM-A scores) with Ashwagandha root extract treatment for 10 weeks. Conclusion Ashwagandha root extract is a natural compound with sleep-inducing potential, well tolerated and improves sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. It could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but need further large-scale studies.
... Thus streptozotocin (STZ) induced rat model is one of the most frequently used for T2D-like models which mimics human diabetes [19][20][21][22]. Previous studies on this model were found to have characteristics of pancreatic beta-cell destruction followed by beta-cell regeneration and glucose intolerance [23,24]. ...
... All interventions ↓: PPG; ↑serum insulin; ↓HbA1c% ↓: HbA1c, serum insulin, PPG in 1 and 2 h; ↑ insulin sensitivity index Anwer et al. (2008) Alloxan (150 mg/kg, i.p); male Wistar albino rats (n = 6) (Udayakumar et al, 2009(Udayakumar et al, , 2010 (continued on next page) E.L. Peter et al. ...
Article
Abstract Ethnopharmacological relevance The increasing national prevalence of diabetes mellitus (DM) and its complications have overstretched the health care system in Tanzania and influenced patients to use herbal medicines as alternative therapeutic strategies. Therefore, an urgent need exists to validate the safety and efficacy of plants used locally. Aim of the study To identify plants used for the management of DM in Tanzania and analyses their pharmacological, phytochemistry, and safety evidence with a special focus on the mechanism of action. Methods Researchers searched Medline, web of science, and Scopus for published articles. Also, specialized herbarium documents of Muhimbili Institute of traditional medicine were reviewed. Articles were assessed for relevance, quality, and taxonomical accuracy before being critically reviewed. Results We identified 62 plant species used locally for DM management. Moringa oleifera Lam. and Cymbopogon citratus (D.C) stapf were the most mentioned. Fifty-four phytochemicals from 13 species had DM activities. These were mainly; polyphenolics, phytosterols, and triterpenoids. Extracts, fractions, and pure compounds from 18 species had in vitro antidiabetic activities of which 14 had α-glucosidase and α-amylase inhibition effects. The most studied -Momordica charantia L. increased; glucose uptake and adiponectin release in 3T3-L1 adipocytes, insulin secretion, insulin receptor substrate-1 (IRS-1), GLUT-4 translocation, and GLP-1 secretion; and inhibited protein tyrosine phosphatase 1 B (PTP1B). Preclinical studies reported 30 species that lower plasma glucose with molecular targets in the liver, skeletal muscles, adipose tissues, pancreases, and stomach. While three species; Aspilia mossambiscensis (Oliv.) Willd, Caesalpinia bonduc (L.) Roxb, and Phyllanthus amarus Schumach. & Thonn. had mild toxicity in animals, 33 had no report of their efficacy in DM management or toxicity. Conclusion Local communities in Tanzania use herbal medicine for the management of DM. However, only a fraction of such species has scientific evidence. A. mossambiscensis, C. bonduc., and P. amarus had mild toxicity in animals. Together, our findings call for future researches to focus on in vitro, in vivo, and phytochemical investigation of plant species for which their use in DM among the local communities in Tanzania have not been validated.
... W. somnifera possesses broad dimensions of pharmacological activities such as antioxidant, antibacterial (Bisht and Rawat, 2014;Singh and Kumar, 2011), antifungal (Girish et al., 2006), anticarcinogenic (Vaishnavi et al., 2012;Mayola et al., 2011), anti-inflammatory (Pawar et al., 2011), anti-stress (Kaur et al., 2001, anti-parkinson (Ahmad et al., 2005), anti-alzheimer (Pingali et al., 2014;Sehgal et al., 2012), cardio protective (Ojha and Arya, 2009), neural and physical health enhancer, sedative, neurodefensive (Konar et al., 2011;Kumar et al., 2014), anti-diabetic (Anwer et al., 2008;Gorelick et al., 2015), astringent, liver tonic, emaciation, asthma, bronchitis, ulcers, aphrodisiac and memory boosting potential have been well documented in literature (Dar et al., 2015;Lee and Choi, 2016;Verma and Kumar, 2011;Mishra et al., 2000;Owais et al., 2005). Its high antioxidant potential may be due to the presence of phenolics and flavonoids (Razdan et al., 2013) but its therapeutic activity is mainly conferred by withanolides (Verma and Kumar, 2011). ...
Article
Ethnopharmacological relevance. Withania somnifera, commonly known as Ashwagandha, is an important medicinal herb belonging to family Solanaceae. It is widely used in folkloric and Ayurvedic medicines since antiquity. Traditionally, the plant is highly practiced throughout the globe as immunomodulator, anti-inflammatory, anti-stress, anti-parkinson, anti-alzheimer, cardio protective, neural and physical health enhancer, neurodefensive, anti-diabetic, aphrodisiac, memory boosting etc. The plant is also effective in combating various cancer and related problems of colon, mammary, lung, prostate, skin, blood, liver and kidney. Aim of this review. The present review represents the critical assessment of the literature available on the anticancerous role of W. somnifera. The present study throws light on its diverse chemical compounds and the possible mechanisms of action involved. This review also suggests further research strategies to harness the therapeutic potential of this plant. Materials and methods. The present review is the outcome of a systematic search of scientific literature about ‘Withania somnifera and its role in cancer prevention’. The scientific databases viz. Google Scholar, Science Direct, Pubmed and Web of Science were searched from 2001 to 2019. Textbooks, magazines and newspapers were also consulted. This review summarizes all the published literature about its therapeutic potential for the treatment of different types of cancers. Results. W. somnifera has been widely used in traditional and ayurvedic medicines for treatment of numerous problems related to health and vitality. The plant is a reservoir of diverse phytoconstituents like alkaloids, steroids, flavonoids, phenolics, nitrogen containing compounds and trace elements. Withanolides are the major alkaloids which renders its anticancer potential due to its highly oxygenated nature. The plant is highly effective in combating various types of cancers viz. colon, mammary, lung, prostate, skin, blood, liver and kidney. Previous studies depict that this plant is more effective against breast cancer followed by colon, lung, prostate and blood cancer. Furthermore, from different clinical studies it has been observed that the active constituents of the plant like withaferin-A, withanolide-D have least toxic effects. Conclusion. The present review confirms the various medicinal values of W. somnifera without any significant side effects. Withaferin-A (WA) and Withanolides are its most promising anticancer compounds that play a major role in apoptosis induction. Keeping in mind the anticancerous potential of this plant, it is suggested that this plant may further be investigated and more clinical studies can be performed.
... [29], antiepileptic [30][31][32], antidepressant, [33] and anti-anxiety [34]. Its other restorative properties include hepatoprotective [34], hypoglycaemic and hypolipidemic [35][36][37], sexual vitality as an adaptogen [38]. W. somnifera seeds also possess unique medicinal benefits includes antihelminthic, eliminate white corneal spots, increase the count of sperm, and increase the development of the testicles [39]. ...
... If left untreated, sustained hyperglycemia may lead to impairment of glucose tolerance (IGT) which eventually results in type 2 DM. It has been suggested that impairment of glucose tolerance is due to decreased utilisation of glucose by peripheral tissues [19]. An investigation of OGTT is usually carried out to determine whether the patient has IGT, especially when the fasting blood glucose level is within the normal range. ...
Article
Full-text available
Purpose: To explore the antidiabetic potential of Moringa oleifera leaf extract in type 2 diabetic rats, and the underlying mechanisms. Methods: Streptozotocin (STZ) at a dose of 40 mg/kg was given to high fat diet (HFD)-fed rats to induce type 2 diabetes. M. oleifera leaf extract at doses 100, 200 and 400 mg/kg were given to 3 groups of type 2 diabetic rats. The area under curve (AUC) of glucose and homeostasis model assessment of insulin resistance (HOMA-R) were calculated using appropriate formulas, whereas levels of glucose, insulin, peroxisome proliferator activated receptor-γ (PPARγ, dipeptidyl peptidase-IV (DPP-IV) and inflammatory cytokines (IL-6, IL-1β and TNFα) were assayed using ELISA kits. Results: The leaf extract of M. oleifera significantly reduced the levels of glucose, insulin and cytokines in treated type 2 diabetic groups (p < 0.05). DC group had significantly increased AUC for glucose, whereas the extract-treated groups showed significant decrease in glucose AUC. There was significant decrease in insulin sensitivity parameters, as indicated by increase in HOMA-R and decrease in PPARγ levels in the DC group (p < 0.05). However, treatment with the M. oleifera extract reversed this trend via marked decrease in HOMA-R level and significant rise in PPARγ level. In contrast, the extract had no effect on DPP-IV concentration in diabetic treated groups (p < 0.05). Conclusion: These results indicate that M. oleifera leaf extract mitigates hyperglycemia in type 2 DM by modulating hyperinsulinemia, PPARγ and inflammatory cytokines. Thus, the extract is a potential source of drug for the management of type 2 DM. This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest
... Root powder of W. somnifera was reported to have profound effect in reducing sugar levels in humans when administered orally that was comparable to antidiabetic drug [88]. W. somnifera was reported to possess the ability to enhance the insulin sensitivity index in rat models [89]. Extracts were reported to influence the glucose uptake potential in skeletal myotubes and adipocytes with leaf extract possessing more profound effects when compared with root extract [87]. ...
Article
Plants have always been an indispensable part of human life since the beginning of human civilisation. Withania somnifera (L.) DUNAL, popularly known as Wintercherry or Indian Ginseng, is widely considered as Ashwagandha. In Ayurveda, it is classified as a Rasayana (rejuvenation) and projected to promote mental and physical health, rejuvenate the body in debilitated conditions and increase longevity. Due to its beneficial chemical constituents, the herb possesses a broad spectrum of biological activities and is used to treat a variety of diseases affecting human health. These include Cardioprotective activity, Anti-cancer activity, Immunomodulatory activity, Neuroprotective activity, Antimicrobial activity, Anti-stress activity,Anti-diabetic activity and Anti-inflammatory activity. The present review discusses the pharmacological importance of Withania somnifera and its important constituents.
... The antidiabetic and antioxidant effects of Euphorbiaceae family have been described previously in different animal models [28]. The rise in insulin and C-peptide levels in the untreated diabetic rats of the PC group is in contrast to type 2 diabetic animals, where elevated blood glucose is followed by increased insulin synthesis and insulin resistance resulting in hyperglycemia [29]. In humans with type 2 diabetes, the glucose challenge causes a substantially higher increase in blood glucose than in healthy individuals and is similar to that found in rats with diabetes caused by STZ-NA. ...
Article
Full-text available
Background Traditional plant-based remedies prescribed to treat diabetes have shown promise in research-based setting. Current research was conducted to examine the antidiabetic and antioxidant effects of methanolic extract of a folk herbal plant Euphorbia helioscopia in a rat model of type 2 diabetes. Methods Diabetes was induced in male Wistar rats by administering 5% sucrose in drinking water and cafeteria diet for 8 weeks with subsequent nicotinamide and streptozotocin administration. Diabetic rats were then distributed into four individual groups ( n = 8); Positive control (PC; no treatment), standard control (SC; Metformin @ 10 mg/kg bw), treatment 1 (EH1, E. helioscopia methanolic extract @200 mg/kg bw) and treatment 2 (EH2, E. helioscopia methanolic extract @400 mg/kg bw). After 21 days of treatments, the rats were decapitated for blood collection. Serum was evaluated for antidiabetic potential, antioxidant and lipid profile, thyroid hormone, amylin, leptin, and carbohydrate metabolic enzymes. Data were analyzed statistically by one-way analysis of variance (ANOVA). Results Serum levels of glucagon, glucose and C-peptide were significantly ( P ≤ 0.05) decreased in EH1 (1915.33 ± 98.26 a pg/ml, 122.59 ± 2.99 a mg/dl, 277.59 ± 28.41 a pg/ml respectively) and EH2 (1575.28 ± 56.46 a pg/ml, 106.04 ± 5.21 a mg/dl, 395.06 ± 42.55 a pg/ml respectively) as compared to the PC (3135.78 ± 189.46 b pg/ml, 191.24 ± 17.75 b mg/dl, 671.70 ± 109.75 b pg/ml respectively) group. A similar trend was observed in serum insulin levels in EH1 and EH2 groups. The plant’s methanolic extract effectively reduced the total oxidant status (TOS) and MDA levels in the diabetic rats and increased the total antioxidant capacity (TAC) along with an increased level of SOD, Catalase, Paraoxonase, and arylesterase. The plant extract also induced antihyperlipidemic activity and recovered the thyroid hormones, amylin, and leptin levels to normal. The activity of different carbohydrate metabolic enzymes like Pyruvate Kinase, Glucose 6 phosphate dehydrogenase, phosphofructokinase, and glucokinase has also been restored by the extract treatment. Conclusion Current study indicates the antioxidant and antidiabetic potential of E. helioscopia methanolic extract in normalizing the lipid profile, thyroid hormones, amylin, leptin, and carbohydrate metabolism in type 2 diabetic rat model.
... Vishal Shivalingappa Patil, V.B. Hupparage, A.P. Malgi et al. Chinese Herbal Medicines xxx (xxxx) xxx antioxidant, immunomodulatory potency, and many researchers demonstrated that the therapeutic effect of W. somnifera roots is due to the presence of withanolides (Subbaraju et al., 2006;Anwer et al., 2008;Kushwaha et al., 2012). In the current study, Withanone formed two hydrogen bond interactions with active site 1 region amino acid of spike glycoprotein i.e. ...
Article
Full-text available
Objective: To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell lines. Methods: First, compounds were retrieved from the PubChem database and predicted for their druggability using the MolSoft web server, and compounds having drug-like property were predicted for major adverse drug reactions like cardiotoxicity, hepatotoxicity, arrhythmia, myocardial infarction, and nephrotoxicity using ADVERpred. Docking of nontoxic antiviral compounds with spike glycoprotein and main protease 3CLpro was performed using AutoDock vina by PyRx 0.8 version. The stability of compound-protein interactions was checked by molecular dynamic (MD) simulation using Schrodinger Desmond software. Results: Based on the druggable and nontoxic profile, nine compounds were selected. Among them, Withanone from Withania somnifera showed the highest binding affinity and best fit at active sites 1 of spike glycoprotein (glycosylation site) and main protease 3CLpro via interacting with active site amino acid residues before and after MD simulation at 50 ns. Withanone, which may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication. Conclusion: The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation.
... e most common heavy metals implicated in human toxicity include lead, mercury, arsenic, and cadmium, although aluminum and cobalt may also cause W. somnifera extract oral administration at two doses (200 and 400 mg/kg) reduced the blood glucose level significantly (P < 0.001) in a dosedependent manner in streptozotocin-induced diabetes rats. Only WS treatment did not register any significant change in the blood glucose level when compared to citrate control rats [119]. Another study also confirmed similar results in alloxan-induced diabetic rats [120] 47 ...
Article
Full-text available
The purpose of this review is to summarize the available antidiabetic medicinal plants in the Kingdom of Saudi Arabia with its phytoconstituents and toxicological findings supporting by the latest literature. Required data about medicinal plants having antidiabetic activities and growing in the Kingdom of Saudi Arabia were searched/collected from the online databases including Wiley, Google, PubMed, Google Scholar, ScienceDirect, and Scopus. Keywords used in search are in vivo antidiabetic activities, flora of Saudi Arabia, active ingredients, toxicological evaluations, and medicinal plants. A total of 50 plant species belonging to 27 families were found in the flora of Saudi Arabia. Dominant family was found Lamiaceae with 5 species (highest) followed by Moraceae with 4 species. β-Amyrin, β-sitosterol, stigmasterol, oleanolic acid, ursolic acid, rutin, chlorogenic acid, quercetin, and kaempferol are the very common bioactive constituents of these selected plant species. This paper has presented a list of antidiabetic plants used in the treatment of diabetes mellitus. Bioactive antidiabetic phytoconstituents which showed that these plants have hypoglycemic effects and highly recommended for further pharmacological purposes and to isolate/identify antidiabetes mellitus (anti-DM) active agents also need to investigate the side effects of active ingredients.
... Patients administered with root powder of WS (3 g/day to each human subject for 30 days) were observed to have a stabilized blood glucose concentration that could be compared to the effect of an oral hypoglycemic drug Daonil [24] with no adverse effects. In addition to that, WS treatment could significantly improve the insulin sensitivity index in non-insulin-dependent diabetes mellitus (NIDDM) rats [27]. Aqueous extracts of WS (200, 400 mg/kg for 5 days) were found to be effective in decreasing blood glucose, HbA1c, and insulin levels. ...
Article
Full-text available
Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.
... In this study, WSE decreased blood glucose levels and improved glucose tolerance in aging rats. These results are in concurrence with other reports and suggest that WSE can improve insulin sensitivity and thus, reduce IR [30]. ...
Article
Full-text available
Background Aging leads to loss of skeletal muscle, diminished muscle strength, and decline in physical functions. Objective This study evaluates Withania somnifera and some dietary interventions to combat muscle weakness in aging rats. Materials and methods Rats (12–13 months old) corresponding to a human age of 60–65 years were assigned to various groups and given orally a standardized W. somnifera extract (WSE, 500 mg/kg) or a protein cocktail comprising soybean (1.5 g/kg) and quinoa (1 g/kg) or a combination of WSE and the protein cocktail or whey protein (1 g/kg) as a reference standard or only resistance exercise for 60 days. Grip strength and blood glucose levels were monitored weekly. At the end of the treatment, total protein, inflammatory markers (CRP, IL-6 and TNF-α), AMPK, malondialdehyde, glutathione, antioxidant enzymes and apoptotic regulator genes (Bax and Bcl-2) were assayed. The biceps brachii muscle of all animals was subjected to histomorphological study. Results All treatments successfully attenuated aging-elevated glucose, CRP, IL-6, TNF-α, AMPK, malondialdehyde, and Bax levels. A significant restoration of the aging-depleted total protein levels, glutathione, superoxide dismutase, catalase, and Bcl-2 was noted in the treatment groups. An increase in grip strength and greater biceps mass with all treatments indicated regaining of the frail aging muscle's strength and functionality. The WSE + protein treatment elicited the best results among all treatment groups to optimize muscle strength. Conclusion All the interventions curbed muscle loss and strengthened the skeletal muscle by reducing inflammation, oxidative stress and apoptosis, and increasing ATP availability to the muscle.
Article
Full-text available
Aswagandha (Withania somnifera) is an ornamental and medicinal plant. It is used as a medicinal plant from the ancestor era. Parts of this plant used as a medicine for curing different diseases. Aurveda describes its medicinal use for human beings. The Sanskrit name "ashva" meaning horse and "gandha" meaning smelling was given to this plant due to the smell of the roots resembling a sweating horse. [1] Currently around 200 traditional medicinal formulae are prepared in Ayurveda, Sid-dha and Unani systems using this plant. All the plant parts are credited with medicinal properties. [2] Parts of plant used for curing different types of diseases. Property of curing a disease is depending upon the phytochemical/active compound composition of plant part. Different plant parts contain different types of active compounds. As a medicine all parts of this plant are used. Withanaloid is major active compound of Withania somnifera. This active compound show different types of pharmacological effect. Withanaloid is a lipid compound and show maximum medicinal activity against different types of diseases and disorders. This plant used for diuretic, anti-inflammatory, immunomodulatory, anti-stress agent. It is also used for increasing body energy, so it is now days used in food supplements for increasing body energy. Ashwagandha is taken for treating cold and coughs,
Article
Full-text available
Medicinal plants are a source of naturally active compounds used extensively by tribal people worldwide for many ailments. Withania somnifera (WS) is one such plant used to treat many ailments from the time of Ayurveda. The dried roots of Withania somnifera are widely used in the treatment of many disorders, the current investigation aimed at extraction and detection or screening of active phytochemical compounds from different extracts of Withania somnifera root. From chemistry point of view, the drug contains group of biologically active constituents known as withanolides. The chemical structures of withanolides have been studied and they are widely distributed in family Solanacae. Phytochemical screening of different extractions revealed the presence of phenols, flavonoids, tannins, saponins, alkaloids, steroids, terpenoids, and glycosides which could account for its varied medicinal properties like anti-inflammatory, anti-oxidant, anti-analgesic. The root samples of Withania somnifera are used to examine the anti-bacterial activity against some pathogenic bacteria such as Escherichia coli and Bacillus subtilis. The anti-bacterial activity of the powder extract was done with Chloroform, methanol and petroleum ether. Petroleum ether extract showed minimum anti-bacterial activity followed by aqueous, chloroform and methanolic extract. In the present study, the free radical scavenging potential of three extracts of the root of Withania somnifera was assessed by measuring its capability for scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH). Our study demonstrated that the three different extracts of Withania somnifera root showed different level of antioxidant activity and is a potential source of antioxidants and thus could prevent many radical related diseases. In the present study, withaferin A (active component of Withania somnifera), a steroid lactone was examined for its analgesic and anti-inflammatory properties employing different experimental models in mice. The study was done to evaluate the analgesic and anti-inflammatory activity of the aqueous, methanolic, choloroform and petroleum ether extract of the roots of Withania somnifera . The analgesic activity was studied using Eddy’s Hot Plate method in swiss albino mice and for anti-inflammatory investigation Carrageenan-Induced Paw Edema method was applied.
Book
Plants are a fascinating group of plants that have been dominating the earth for 400 million years. During evolution, they have undergone series of evolutionary changes to suit themselves with the surrounding environment. These evolutionary changes not only included morphological changes to suit varied climatic conditions but also armed with intricate physiological changes to synchronize with the former and fortify better adaptability. These physiological changes of the plant later proved to be of immense help to the humans who evolved much later somewhere between 6 million to 2 million years ago. The physiological and biochemical evolution of the plants with the synchronous origin of various taxa resulted in the formation of numerous biochemical pathways producing a large number of secondary metabolites whose one primary aim is to protect the plants from herbivores and insect which in the due course of evolution became an integral part of the food chain. However, the secondary metabolites also proved to be of immense use to humans since antiquity who unknowingly since prehistoric times used plants for their food and medicine. It is only in the past hundred years or so, people became aware of the chemical constituent of the plants and started exploring their various beneficial properties. The agricultural activities also coevolved with human civilization and with the increase in population, higher yield along with protection of crops from pathogen attack became a necessity. This lead to the formulation of fertilizers which consequently paved the way for biofertilizers with a fewer side effects on humans and animals but with a more green approach towards fertility enhancement. With the advent of industrialization the menace of pollution cropped up and presently this pollution is encroaching soil water and air. This is having a deleterious effect on the ecosystem concerning human and animal health and also agricultural productivity. Thus keeping this in mind the scientific community was determined to remediate the polluted sites with the help of biological agents in which the plants and microbes played an important role. This provided major protection to agriculture from contamination thereby sustaining productivity. Thus, an attempt is made to highlight the progress and advances in the field of agriculture and plant science. Thus A handbook of Agricultural and Plant Sciences is an attempt to compile information related to the field of agriculture and plant science. The main purpose of the book is to provide relevant information to the readers on aspects largely cantered on plants. The book is divided into three sections namely agriculture and sustainable development, plants and microbes as nutraceutical agents, and medicinal potential of plants. Selected chapters in relevance to the sections have been accommodated to provide an overview. The first section deals with various aspects through which crops can be fortified through bio fertilization and also decontamination of polluted lands. The world population is presently stressing upon consumption of foods from natural sources as consumption of fast food with artificial agents is leading to the onset of several diseases. This has led to a group of foods that confers nutrition as well as a medicinal benefit at the same time. They are presently termed and considered nutraceuticals. The second section of the book deals with the nutraceutical potential of plants and microbes which are symbiotically associated with plants. The third section is also related to the second one concerning the medicinal importance. This section encompasses the medicinal importance of plants. Plants as antiviral agents have been accommodated because of the current pandemic situation. The section also contains a chapter on the ant diabetic potential of plants and also the medicinal importance of gymnosperms and bioactive potentials of bryophytes which adds up to the variation in chapters focusing on the medicinal aspect. The book is also accompanied by several tables within each chapter which gives a clear and systematic description of the theme that is discussed upon. The book is an academic venture and would benefit the scientific community and readers who are interested in the field of plant sciences.
Chapter
Full-text available
In conventional Ayurveda and Unani frameworks of medication, the foundations of Indian Ginseng or Ashwagandha have a long history of utilization as an adaptogen. Ashwagandha (Withania somnifera (L.) Dunal) is an individual from the Solanaceae group of plants. Keeping up with general prosperity and improvement of essentialness has been the essential significance of this "Rasayana". In spite of the fact that the idea to be valuable as a restorative spice in Ayurveda and sold in numerous nations as a dietary enhancement, there is lacking logical proof that it is protected or successful for treating any infection.
Article
Withania somnifera, commonly known as "Ashwagandha" or "Indian ginseng" is an essential therapeutic plant of Indian subcontinent regions. It is regularly used, alone or in combination with other plants for the treatment of various illnesses in Indian Systems of Medicine over the period of 3,000 years. Ashwagandha (W. somnifera) belongs to the genus Withania and family Solanaceae. It comprises a broad spectrum of phytochemicals having wide range of biological effects. W. somnifera has demonstrated various biological actions such as anti-cancer, anti-inflammatory, anti-diabetic, anti-microbial, anti-arthritic, anti-stress/adaptogenic, neuro-protective, cardio-protective, hepato-protective, immunomodulatory properties. Furthermore, W. somnifera has revealed the capability to decrease reactive oxygen species and inflammation, modulation of mitochondrial function, apoptosis regulation and improve endothelial function. Withaferin-A is an important phytoconstituents of W. somnifera belonging to the category of withanolides been used in the traditional system of medicine for the treatment of various disorders. In this review, we have summarized the active phytoconstituents, pharmacologic activities (preclinical and clinical), mechanisms of action, potential beneficial applications, marketed formulations and safety and toxicity profile of W. somnifera.
Article
Full-text available
In view of the increasing demand by patients to use herbal preparations with antidiabetic effects in the management of diabetes mellitus worldwide especially in developing countries. Also considering the economic resource constraints of diabetics in developing countries and given the cheapness of these herbal products which are readily available to rural dwellers, this present review was undertaken to search for some of the herbs used around the world with antidiabetic effects which may be pursued for their clinical usefulness in the management of diabetes mellitus and other associated complications. The search used keywords such as herbal medicine, hypoglycaemic and hypolipidaemic herbs each crossed with the term diabetes mellitus with particular emphasis on experimental animal models, effective dosage and hypoglycaemic/or hypolipidaemic effects of these herbs. The search result revealed fifteen of some of the antidiabetic herbs which are Vernonia amygdalina, Tapinanthus butungii, Nauclea latifolia, Sarcocephalus latifolus, Benincasa hispida, Azadirachta indica, Momordica charantia, Aloe vera, Ocimum gratissimum, Gongronema latifolium, Gymnema sylvestre, Trigonella foenum graecum, Allium cepa, Zingiber officinale, Allium sativum. Further research may be necessary to elucidate the pharmacological principle of these herbs which will stimulate future pharmaceutical development of therapeutically beneficial antidiabetic herbal drugs.
Article
Full-text available
The Maillard reaction has been implicated in cross-linking and fluorescence formation of collagen exposed to high glucose in vitro. However, several pharmacologic agents, whose action seems unrelated to pathways of nonenzymatic glycation, have been demonstrated to prevent cross-linking in diabetes. To clarify this discrepancy, kinetic changes in glycation, glycoxidation (carboxymethyllysine, CML), and cross-linking (measured as tendon breaking time, TBT) were evaluated in rat tail tendons incubated in 5 and 30 mM glucose in vitro and in tendons implanted in vivo into diabetic rat peritoneal cavity. In vitro, rates were found to be both O2- and glucose-dependent. Tendon preglycation and presence of added 2 mM glycosylamine and Amadori compounds (Amadori product of glucose and propylamine) catalyzed these changes in a primarily O2-dependent manner. In the presence of Amadori compounds, kinetic changes were dramatically increased and were preventable by addition of catalase to the medium. Tendons implanted into diabetic rat peritoneum became more rapidly glycoxidized and cross-linked when implanted at day 30 from diabetes onset (high tissue glycation) compared to day 3 (low tissue glycation) in spite of similar glycation kinetics, suggesting a mechanistic dissociation between glycation, glycoxidation, and cross-linking in diabetes. Indeed, intraperitoneal injection of catalase and other antioxidants dramatically suppressed cross-linking, fluorescence formation, and, to some extent, glycoxidation, without affecting glycation. This study confirms the role of oxidative stress in protein cross-linking by the Maillard reaction in vitro and provides the first evidence for a role of H2O2 in cross-linking in diabetes. Whereas Amadori products are a potent source of H2O2 formation in vitro, their precise contribution to H2O2 generation and the actual role of Maillard reaction products in collagen cross-linking in diabetes requires further investigation.
Article
Full-text available
To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans. In the present study, we compared insulin sensitivity as assessed by a 4-h euglycemic (approximately 5 mmol/l) hyperinsulinemic (approximately 300 pmol/l) clamp with HOMA in 115 subjects with various degrees of glucose tolerance and insulin sensitivity. We found a strong correlation between clamp-measured total glucose disposal and HOMA-estimated insulin sensitivity (r = -0.820, P<0.0001), with no substantial differences between men (r = -0.800) and women (r = -0.796), younger (aged <50 years, r = -0.832) and older (r = -0.800) subjects, nonobese (BMI <27 kg/m2, r = -0.800) and obese (r = -0.765) subjects, nondiabetic (r = -0.754) and diabetic (r = -0.695) subjects, and normotensive ( r = -0.786) and hypertensive (r = -0.762) subjects. Also, we found good agreement between the two methods in the categorization of subjects according to insulin sensitivity (weighted k = 0.63). We conclude that the HOMA can be reliably used in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity
Article
Full-text available
The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity. This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study. Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound. Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.
Article
Full-text available
Metabolic syndrome, insulin resistance, prediabetes, and overt type 2 diabetes mellitus are associated with an accelerated atherosclerosis (atheroscleropathy). This quartet is also associated with multiple metabolic toxicities resulting in the production of reactive oxygen species. The redox stress associated with these reactive oxygen species contribute to the development, progression, and the final fate of the arterial vessel wall in prediabetic and diabetic atheroscleropathy. The prevention of morbidity and mortality of these intersecting metabolic diseases can be approached through comprehensive global risk reduction.
Article
Full-text available
Streptozotocin (Streptozocin, STZ, CAS No. 18883-66-4) is a monofunctional nitrosourea derivative isolated from Streptomyces achromogenes. It has broad spectrum antibiotic activity and antineoplastic properties and is often used to induce diabetes mellitus in experimental animals through its toxic effects on pancreatic beta cells. STZ is a potent alkylating agent known to directly methylate DNA and is highly genotoxic, producing DNA strand breaks, alkali-labile sites, unscheduled DNA synthesis, DNA adducts, chromosomal aberrations, micronuclei, sister chromatid exchanges, and cell death. This antibiotic was found to be mutagenic in bacterial assays and eukaryotic cells. STZ is also carcinogenic; a single administration induces tumors in rat kidney, liver, and pancreas. Several lines of evidence indicate that free radicals are involved in the production of DNA and chromosome damage by this compound. Because of the use of STZ as an antineoplastic agent, the study of its genotoxicity has considerable practical significance. The purpose of this review is to present our current knowledge regarding the genotoxicity of STZ.
Article
Full-text available
The metabolic syndrome is a highly prevalent clinical entity. The recent Adult Treatment Panel (ATP III) guidelines have called specific attention to the importance of targeting the cardiovascular risk factors of the metabolic syndrome as a method of risk reduction therapy. The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states. An insulin resistance following nuclear peroxisome proliferator activated receptors (PPAR) deactivation (mainly obesity-related) is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) with preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. We suggest that a PPAR-based appraisal of metabolic syndrome and type 2 diabetes may improve our understanding of these diseases and set a basis for a comprehensive approach in their treatment.
Article
Full-text available
Compensatory hyperinsulinemia stemming from peripheral insulin resistance is a well-recognized metabolic disturbance that is at the root cause of diseases and maladies of Syndrome X (hypertension, type 2 diabetes, dyslipidemia, coronary artery disease, obesity, abnormal glucose tolerance). Abnormalities of fibrinolysis and hyperuricemia also appear to be members of the cluster of illnesses comprising Syndrome X. Insulin is a well-established growth-promoting hormone, and recent evidence indicates that hyperinsulinemia causes a shift in a number of endocrine pathways that may favor unregulated tissue growth leading to additional illnesses. Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG). Since IGFBP-3 is a ligand for the nuclear retinoid X receptor alpha, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body's endogenous retinoids. These endocrine shifts alter cellular proliferation and growth in a variety of tissues, the clinical course of which may promote acne, early menarche, certain epithelial cell carcinomas, increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding. Consequently, these illnesses and conditions may, in part, have hyperinsulinemia at their root cause and therefore should be classified among the diseases of Syndrome X.
Article
Though India has a rich tradition in the use of medicinal plants, the effort to develop drugs from plants has had limited success. The global market for herbal drugs however claims US $20 billion and promises to grow even further. Herbal drugs are prescribed widely even when their biologically active compounds are unknown because of their effectiveness, minimal side effects in clinical experience and relatively low cost. It is imperative that India launches a programme on drugs from plants, based on clues from traditional knowledge and harnessing modern technologies for the development of new chemical entities.
Article
Effects of glycowithanolides (Ws, 10–150 mg/kg, i.p.), consisting of sitoindosides VII-X, in combination with withaferin-A, from Withania somnifera, in Swiss mice were evaluated on (i) morphine-induced inhibition of gastrointestinal tract (GIT) transit and (ii) development of tolerance to morphine-induced analgesia. Pretreatment with Ws significantly reversed the morphine (5 mg/kg, s.c.)-induced inhibition of GIT transit at all doses. Ws (100 mg/kg, i.p., o.d., for 10 days) significantly inhibited the development of tolerance to morphine-induced analgesia. Ws per se did not influence the intestinal motility nor did it produce any perceptible analgesic effect. The present and earlier findings with Ws suggest its potential in alleviating the adverse effects of morphine and the attendant immunodepression.
Article
Two new glycowithanolides, sitoindoside IX (1) and sitoindoside X (2), isolated from Withania somnifera Dun., were evaluated for their immunomodulatory and CNS effects (anti-stress, memory and learning) in laboratory animals, because the plant extract is used by practitioners of the Indian systems of medicine for similar purposes. The two compounds, in doses of 100–400 μg/mouse, produced statistically significant mobilization and activation of peritoneal macrophages, phagocytosis and increased activity of the lysosomal enzymes secreted by the activated macrophages. Both these compounds (50–200 mg/kg p.o.) also produced significant anti-stress activity in albino mice and rats and augmented learning acquisition and memory retention in both young and old rats. These findings are consistent with the use of W. somnifera, in Ayurveda, to attenuate cerebral function deficits in the geriatric population and to provide non-specific host defence.
Article
The active principles of Withania somnifera (WS, 20–50 mg/kg, p.o.), consisting of equimolar amounts of sitoindosides. VII–X and withaferin A, were investigated for putative nootropic activity in an experimentally validated Alzheimer's disease (AD) model. The syndrome was induced by ibotenic acid (IA) lesioning of the nucleus basalis magnocellularis (NBM) in rats. Cognitive deficits induced in NMB-lesioned rats were assessed by attenuation of a learned active avoidance task and a decrease in frontal cortical and hippocampal acetylcholine (ACh) concentrations, choline acetyltransferase (ChAT) activity and muscarinic cholinergic receptor (MCR) binding. IA-induced NBM lesioning in rats caused a marked cognitive deficit, as evidenced by severe reduction of the learned task, and was accompanied by a significant decrease in frontal cortex and hippocampal ACh levels, ChAT activity and MCR binding. WS (50 mg/kg) significantly reversed both IA-induced cognitive deficit and the reduction in cholinergic markers after 2 weeks of treatment. The findings validate the medharasayan (promoter of learning and memory) effect of W. somnifera, as has been reported in Ayurveda.
Article
Injection of streptozotocin in newborn rats induced a severe diabetic syndrome on day 4 after birth, with acute hyperglycaemia and glycosuria. Over the next 3 weeks spontaneous recovery occurred as attested by normal basal blood glucose and plasma insulin levels. Recovery was, however, incomplete in the adult since a definite impairment in insulin release and glucose disposal was observed. This state was characterized by the following features: 1) a 72% decrease in pancreatic insulin stores without change in pancreatic glucagon stores; 2) a slight but consistent elevation of blood glucose in the fasted and fed basal states and especially of blood glucose 90 min after an IV glucose load (2 g/kg) performed under pentobarbitone anaesthesia; 3) a considerable decline in the glucose-induced insulin release with a decrease in the maximal response. Both early and late phases of insulin release were impaired, as indicated by in vivo glucose infusion experiments. Basal plasma glucagon levels were normal. Over a period of 12 months with a normal laboratory diet no aggravation of the chemical diabetic state was observed. This new experimental syndrome is a potentially interesting model for the study of the influence of environmental factors on the development of overt diabetes.
Article
The ability of insulin to stimulate glucose uptake can vary substantially in non-obese individuals with no apparent disease (10). In addition, differences in either degree of obesity or level of habitual physical activity can also modulate in vivo insulin action (18,24). In an apparent attempt to maintain glucose homeostasis, the compensatory response to a decrease in insulin-stimulated glucose up take is an increase in plasma insulin concentration. A defect in the ability of insulin-stimulated glucose uptake has also been demonstrated (21) in patients with either impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). It has been suggested that the degree to which glucose tolerance deteriorates in these individuals is a function of the level of compensatory hyperinsulinemia that they can maintain, and the appearance of severe fasting hyperglycemia marks the failure of the pancreatic beta cell to sustain the necessary increase in insulin secretory response (21).
Article
High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.
Article
Insulin resistance is a characteristic feature of non-insulin dependent diabetes mellitus (NIDDM) due to target tissue defects in insulin action. Abnormalities of cellular insulin action can be divided into receptor and post-receptor defects. Patients with impaired glucose tolerance are insulin resistant due to decreased insulin receptors resulting in decreased insulin sensitivity and rightward shifted in vivo dose response curves. Patients with NIDDM are insulin resistant due to a combination of receptor and post-receptor defects. The greater the severity of the diabetes (greater fasting hyperglycemia) the greater the post-receptor defect, and in those patients with more significant fasting hyperglycemia the post-receptor defect is the predominant abnormality leading to the insulin resistant state. At least one of the abnormalities underlying this post-receptor defect involves a decrease in glucose transport system activity in freshly isolated adipocytes. This defect in glucose transport, is not expressed in cultured fibro-blasts, indicating that the abnormality in glucose disposal seen in vivo and in glucose transport seen in freshly isolated cells is an acquired phenomenon. Consistent with this, the post-receptor defect is partially reversible by insulin therapy, which leads to a 50–70% reversal of the reduced rates of in vivo glucose disposal and in vitro glucose transport. Insulin resistance also exists in poorly controlled IDDM patients, due to a postreceptor defect in insulin action. This insulin resistance is not present in well controlled IDDM patients, and is completely reversible when poorly controlled patients are treated with intensive insulin therapy.
Article
The diabetogenic effect of streptozotocin was investigated in the rat during fetal and neonatal life. Streptozotocin was directly injected in the vitellin vein of the fetus or in the saphenous vein of the neonate. In the 21.5 day old fetus, diabetogenic activity was demonstrated with a single dose of 100 μg/g administered the day before, and this was indicated by a fall in the pancreatic insulin content to 20% and a lowering of the plasma insulin to 60% of the controls. A single dose (100 μg/g) of streptozotocin administered on the day of birth produced an overt diabetes in the neonate: the maximal fall in the pancreatic insulin content (7% of the controls) was observed 4 days after the streptozotocin injection, during the highest blood glucose level (300% of the controls). A significant increase in the pancreatic glucagon content was observed 24 hr after the maximal insulin depletion. Liver glycogen content was occasionally decreased. More severe diabetes was obtained by 2 streptozotocin injections (50 μg/g), with lowest pancreatic and highest blood glucose levels at 1% and 60%, respectively. A clearcut drop of the plasma insulin/glucose ratio was observed in the drug treated animals. 3 wk after injection(s), basal blood glucose and plasma insulin levels were normal, although impairment of insulin secretion still appeared after glucose load and insulin pancreatic content was still slightly lower. A rapid and spontaneous, if not quite complete recovery, is a characteristic pattern of the streptozotocin diabetes in the neonate as compared with that in the adult.
Article
A method involving the use of 4-aminophenazone as a colour coupler with sulphonated 2,4-dichlorophenol is described for determining the hydrogen peroxide produced from glucose with glucose oxidase.
Article
In the Whitehall Study of 18,403 male civil servants aged 40--64 years, 7 1/2 year coronary-heart-disease (CHD) mortality has been examined in relation to blood-sugar concentration 2 h after a 50 g oral glucose load. CHD mortality was approximately doubled for subjects with inpaired glucose tolerance (IGT), defined as a blood-sugar above the 95th centile (greater than or equal to 96 mg/dl). There was no trend of CHD mortality with blood-sugar below the 95th centile. Within the IGT group, age, systolic blood-pressure, and ECG abnormality (Whitehall criteria) were significantly predictive of subsequent CHD mortality. These findings are relevant to discussions on the criteria for diabetes which include the definition of an IGT category with increased risk of large-vessel disease, but without the high risk of small-vessel disease as occurs in diabetes mellitus.
Article
Non-insulin-dependent diabetes (NIDDM) was obtained in adult rats following a neonatal streptozotocin injection. Rats with NIDDM exhibited slightly lowered plasma insulin, slightly elevated basal plasma glucose values (less than 200 mg/dl), and low pancreatic insulin stores (50% of the controls). Insulin secretion was studied in this model using the isolated perfused pancreas technique. Insulin response to glucose stimulation over the range 5.5-22 mM was lacking, thus indicating complete loss of B-cell sensitivity to glucose. Even in presence of theophylline, the B-cells remained insensitive to glucose. In contrast, glyceraldehyde elicited an insulin release as important as that obtained in the control pancreata. This could possibly suggest that the B-cell dysfunction in rats with NIDDM involves a block in glucose metabolism in the early steps of glycolysis prior to the triose-phosphate. Mannose stimulated insulin secretion less in the diabetics than in the controls. The insulin secretion obtained in response to isoproterenol indicated that the ability of the adenylcyclase to generate cAMP in the B-cells of the diabetics was not decreased. The insulinotropic actions of acetylcholine and tolbutamide were normal and increased, respectively, as compared with the controls. In the absence of glucose, the B-cells of the diabetics were unexpectedly hypersensitive to arginine and leucine. The alpha-ketoisocaproate effect in the diabetics was not significantly different from that obtained in the controls. The possibility that enhancement of insulin response to leucine in the diabetics might be related to a more active conversion of leucine to ketoisocaproate along the first steps of intraislet leucine metabolism is proposed.
Article
The fact that hyperinsulinemia occurs in simple obesity and mild glucose intolerance has been well established. Altered hepatic insulin extraction may influence the levels of circulating hormone. The simultaneous measurement of insulin and C-peptide concentrations in peripheral blood enables an in vivo estimation of hepatic insulin removal. To evaluate hepatic insulin extraction, insulin and C-peptide responses to oral glucose were studied in 176 obese and nonobese subjects with normal, impaired, or diabetic glucose tolerance. Insulin levels as well as insulin incremental areas in glucose intolerant subjects were significantly higher than in weight-matched controls. The levels of C-peptide as well as C-peptide incremental areas were only slightly enhanced in subjects with impaired glucose tolerance, whereas they were reduced in subjects with diabetic tolerance. The molar ratios of C-peptide to insulin, both in the fasting state and after ingestion of glucose, as well as the relationship between the incremental areas of the two peptides were used as measures of hepatic insulin extraction. They were significantly reduced in glucose intolerant subjects and, to a lesser extent, in nondiabetic obese subjects. These results indicate that peripheral hyperinsulinemia in subjects with simple obesity or impaired glucose tolerance is a result of both pancreatic hypersecretion and diminished hepatic insulin extraction. In subjects with a more severe degree of glucose intolerance, decreased hepatic insulin removal is the primary cause of hyperinsulinemia.
Article
Streptozotocin, an antibiotic widely used for induction of diabetes in experimental animals and for the treatment of pancreatic neoplasms, was shown to be a potent methylating agent reacting with DNA in vitro to form methylated purines. The reaction was similar in extent and relative proportions of methylation products to that produced by N-methyl-N-nitrosourea, the aglycone of streptozotocin. When streptozotocin was administered to rats by i.v. injection, DNA was methylated with the formation of 7-methylguanine, O6-methylguanine, 3-methyladenine, and 7-methyladenine in liver, kidney, intestine, and pancreas. In contrast to N-methyl-N-nitrosourea which produced approximately equal amounts of methylation in DNA of liver, brain, and kidney, streptozotocin caused virtually no methylation in brain DNA; but, both liver and kidney DNA were alkylated to a greater extent than with N-methyl-N-nitrosourea. This methylation of renal DNA may account for the ability of streptozotocin to induce renal tumors. Streptozotocin produced significant methylation of pancreatic DNA which, if concentrated in the beta-cells, may account for their destruction. Pretreatment with nicotinamide reduced the extent of methylation of pancreatic DNA but did not affect the methylation in the liver or kidney. Methylation of beta-cell DNA in the pancreas may lead to the initiation of tumors if the extent of alkylation is not so great that cell death occurs.
Article
Production of hydroxyl radicals was examined in the diabetic rats induced by streptozotocin to prove its involvement to the pathogenesis of diabetes. Hydroxyl radicals generated in plasma, heart muscle, liver and brain of the hyperglycemic rats were quantitatively assayed by trapping hydroxyl radicals with salicylic acid as 2,3- and 2,5-dihydroxybenzoic acid. The concentrations of 2,3- and 2,5-dihydroxybenzoic acid were significantly increased in all the tissues of the diabetic rats. In the brain and heart muscle of the diabetic rats, the increase of 2,3-dihydroxybenzoic acid was more manifest than that of 2,5-dihydroxybenzoic acid, while in liver 2,5-dihydroxybenzoic acid increased markedly. All the values of 2,3-dihydroxybenzoic acid detected in the tissues of the diabetic rats were quite higher than those in control. Hydroxyl radical production and blood glucose concentration were depended almost linearly on the amount of streptozotocin injected to rats up to 60 mg/kg body weight. It was suggested that 2,3-dihydroxybenzoic acid was produced from hydroxyl radicals themselves, while 2,5-dihydroxybenzoic acid was produced by hydroxylation of salicylic acid not only with hydroxyl radicals, but also by enzymatic reaction of microsomal cytochrome-P450. Hydroxyl radical formation may account for some pathological process especially in the heart muscle and brain.
Article
Non-insulin-dependent diabetes mellitus (NIDDM), the commonest form of diabetes, affects approximately 5 percent of the population of the United States. Although the pathophysiology of this condition has not been fully characterized and the nature of the primary defect is controversial, the results of recent studies provide insights into its basic causes. Here, we review these studies and suggest how insulin resistance and genetically programmed pancreatic beta-cell dysfunction may interact in susceptible persons to cause diabetes. Insulin Resistance Insulin resistance is a diminished ability of insulin to exert its biologic action across a broad range of concentrations. Unless persons with insulin . . .