Annona squamosa is generally referred to as a ‘custard apple’. Antidiabetic actions of hot water extract of Annona squamosa (HWAS) leaves together with isolation of active insulinotropic compounds were studied. Insulin release, membrane potential and intracellular Ca2+ were determined using BRIN-BD11 cells and isolated mouse islets. 3T3L1 adipocytes and in vitro models were used to determine cellular glucose uptake, insulin action, starch digestion, glucose diffusion, DPP-IV activity and glycation. Glucose intolerant high-fat fed rats were used for in vivo studies. Active compounds were isolated and characterized by HPLC, LCMS and NMR. HWAS stimulated insulin release from clonal β-cells and mouse islets. Using fluorescent indicator dyes and modulators of insulin secretion, effects could be attributed to depolarization of β-cells and influx of Ca2+. Secretion was stimulated by isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, indicating additional non-KATP dependent pathways. Extract stimulated cellular glucose uptake and insulin action and inhibited starch digestion, protein glycation, DPP-IV enzyme activity and glucose diffusion. Oral HWAS improved glucose tolerance and plasma insulin in high-fat fed obese rats. Treatment for 9 days with HWAS (250 mg/5 mL/kg), partially normalised energy intake, body weight, pancreatic insulin content, and both islet size and beta cell mass. This was associated with improved oral glucose tolerance, increased plasma insulin and inhibition of plasma DPP-IV activity. Isolated insulinotropic compounds, including rutin (C27H30O16), recapitulated the positive actions of HWAS on beta cells and in vivo glucose tolerance and plasma insulin responses. Annona squamosa is attractive as a dietary adjunct in treatment of T2DM and as a source of potential antidiabetic agents including rutin.

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Correspondence: Prawej Ansari (chemist89ansari@gmail.com) Moringa oleifera has potential anti-hyperglycaemic effects that have been reported earlier by different scientific groups using animal models of diabetes. We aimed to explore the possible mechanisms of action of M. oleifera extract through different methods. Primarily, we measured fasting blood glucose and performed glucose tolerance test, in Type 2 diabetic rats. Further, we studied the effects of extracts on pancreatic insulin concentration. Extracts' effect on carbohydrate breakdown was assayed using α-amylase inhibition assays and assay of six different segments of gastrointestinal (GI) tracts. An in situ intestinal perfusion model and a glucose fibre assay were performed to see the potentiality of M. oleifera on glucose absorption. M. oleifera showed no significant change in insulin secretion in vivo. Additionally, substantial effect of the extract was seen on retarded glucose absorption and in the in situ perfusion study of rat intestinal model. α-amylase action was inhibited by the extract, yet again, these findings were further confirmed via the Six Segment assay, where sucrose digestion was found to be inhibited throughout the length of the GI tract. A combined in vitro, in vivo and in situ tests justified the potential of anti-hyperglycaemic activity of M. oleifera and its tissue level mechanism is also justified. IntroductionFor the last few decades, diabetes has held its position as one of the world's predominant endocrine disorder [1]. By nature, it cannot be completely cured but it should be kept under tight control. Usually modified lifestyle, medications, diet or a combination of all these are prescribed to diabetic patients to control diabetes. Complementary and alternative medicines (CAMs) have become popular among people from developing countries for managing a multitude of disorders including diabetes. However, unclear mechanism of action and lack of scientific evidence of efficacy of these therapies keeps them far behind from important use. Another drawback of these plants used in various ailments is that they have no established safety profile; although it is thought that they are safe besides being economical, effective and their easy availability. Traditional practitioners globally emphasize these advantages of medicinal plants in their day-to-day practice. Traditional use of medicines is recognized as a way to learn about potential future medicines. In 2001, researchers identified 122 compounds used in mainstream medicine that were derived from 'ethnomedical' plant sources; 80% of these compounds were used in the same or related manner as the traditional ethnomedical use [2].Moringa oleifera is also known as Moringa pterygosperma Gaertn, is a member of the Moringaceae family of perennial angiosperm plants, which includes 12 other species. This plant is commonly named in English as Moringa and drumstick tree [3]. M. oleifera is one of the most useful tropical trees [4], it has the following characteristics: high protein, vitamin...

Diabetes mellitus is a chronic complication that affects people of all ages. The increased prevalence of diabetes worldwide has led to the development of several synthetic drugs to tackle this health problem. Such drugs, although effective as antihyperglycemic agents, are accompanied by various side effects, costly, and inaccessible to the majority of people living in underdeveloped countries. Medicinal plants have been used traditionally throughout the ages to treat various ailments due to their availability and safe nature. Medicinal plants are a rich source of phytochemicals that possess several health benefits. As diabetes continues to become prevalent, health care practitioners are considering plant-based medicines as a potential source of antidiabetic drugs due to their high potency and fewer side effects. To better understand the mechanism of action of medicinal plants, their active phytoconstituents are being isolated and investigated thoroughly. In this review article, we have focused on pharmacologically active phytomolecules isolated from medicinal plants presenting antidiabetic activity and the role they play in the treatment and management of diabetes. These natural compounds may represent as good candidates for a novel therapeutic approach and/or effective and alternative therapies for diabetes.

These findings suggest that Po-MeOH has significant anti-inflammatory and anti-diarrheal effects along with moderate thrombolytic and lower cytotoxic properties that may warrant the further exploration.

Diabetes Mellitus (DM) is a metabolic disorder that is spreading alarmingly around the globe. Type-2 DM (T2DM) is characterized by low-grade inflammation and insulin resistance and is closely linked to obesity. T2DM is mainly controlled by lifestyle/dietary changes and oral antidiabetic drugs but requires insulin in severe cases. Many of the drugs that are currently used to treat DM are costly and present adverse side effects. Several cellular, animal, and clinical studies have provided compelling evidence that flavonoids have therapeutic potential in the management of diabetes and its complications. Quercetin is a flavonoid, present in various natural sources, which has demonstrated in vitro and in vivo antidiabetic properties. It improves oral glucose tolerance, as well as pancreatic β-cell function to secrete insulin. It inhibits the α-glucosidase and DPP-IV enzymes, which prolong the half-life of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Quercetin also suppresses the release of pro-inflammatory markers such as IL-1β, IL-4, IL-6, and TNF-α. Further studies are warranted to elucidate the mode(s) of action of quercetin at the molecular level. This review demonstrates the therapeutic potential of quercetin in the management of T2DM.

Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.

Objective The aim of this study was to delineate the mechanisms of action of the plant Eucalyptus citriodora used traditionally for the treatment of type 2 diabetes. Methods Insulin secretion and signal transduction were measured using clonal pancreatic β-cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation and phytoconstituents were identified by RP-HPLC followed by LC-MS. Key findings Eucalyptus citriodora stimulated 1.2–4.6-fold insulin release that was inhibited by the Ca2+-channel blocker, verapamil, KATP-channel opener, diazoxide and Ca2+ free conditions. The effect was potentiated by IBMX and preserved in presence of tolbutamide or 30 mM KCl. The action mechanism involved membrane depolarization and elevation of intracellular Ca2+. Eucalyptus citriodora also significantly increased glucose uptake by 3T3-L1 cells and inhibited digestion of starch, glucose absorption, DPP-IV enzyme and glycation of protein. Administration of E. citriodora (250 mg/5 ml/kg) for 9 days to HFF obese-diabetic rats improved glycaemic control and β-cell function. The isolated phytoconstituents responsible for the β-cell actions included quercitrin, isoquercitrin and rhodomyrtosone E. Conclusions Eucalyptus citriodora improves glycaemic control via multiple mechanisms. Further studies are required to assess the utility of the plant or active constituents in the therapy of type 2 diabetes.