Pharmacological effect of Heritiera fomes on Long Evans rats against Postprandial Hyperglycemia and adsorption in vitro.

Background: Natural restoratives from traditional medicinal plants are considered to be a convenient, potent, and risk-free substitute treatment for hyperglycaemia. Our objective was to explore the activity of the crude extract of Heritiera fomes on postprandial hyperglycaemia by assessing relative measurements in a laboratory animal model. Methods: The Streptozotocin induced diabetic rat (n = 88, twenty-two per group) was used for the glucose tolerance test as an initial support for the study. BaSO4 was administered orally as a marker to measure gut motility after one hour of methanolic extract (500 mg/kg body weight) administration where, only purified water (10 ml/kg) was used to treat the control group (n = 12) and a dose (500 mg/kg) of H. fomes extract was used for the test group (n = 12 in each group). After 60 min of incubation of the mixture of extract and glucose with 10% (v/v) yeast cell suspension, the absorbance was measured to determine the capacity of glucose absorption by yeast cells. Sixty Long Evans rats (n = 12 in each group) were used to assess disaccharidase enzyme activity as µmol/mg protein per hour by Lowry's protein estimation method. The carbohydrate absorption investigation was executed to evaluate the leftover sucrose content in the gastrointestinal system (n = 64). Results: After oral administration of MHFL (71.84%), MHFB (71.41%), and MHFR (72.55%), GI motility (%) increased significantly (p < 0.001) compared to the control group (59.06%). A significant increase in glucose uptake and adsorption capacity measured by different concentrations of glucose ensures the decrease of glucose bound rate and a significant drop in blood glucose concentration. The significant (p < 0.001) decrease in intestinal disaccharidase activity of MHFL (1.40), MHFB (1.36), and MHFR (1.20) in comparison to the control group (1.50) indicates that the presence of H. fomes may reduce glucose absorption in the small bowel. Significant (p < 0.001 & p < 0.05) accumulation of sucrose content in the six different parts of the GI tract suggests the absorption of sucrose was decreased. Conclusions: The findings of this study provide evidence on probable mechanisms for the anti-diabetic characteristics of H. fomes, and it is predicted that this plant will be studied further for the development of strong anti-hyperglycemic medicines.

Association of household fuel use with hypertension and blood pressure among adult women in rural Bangladesh: A cross-sectional study.

OBJECTIVES: This study aimed to determine the association of household fuel use with hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) among adult women. METHODS: A cross-sectional survey through face-to-face interviews and blood pressure (BP) measurement were conducted among 2182 randomly selected women (1236 solid fuel users and 946 clean fuel users) in rural areas of Bangladesh. RESULTS: Overall, 21% of women were hypertensive. Mean SBP and DBP for the study population were 121.27 mmHg (SD ± 15.43) and 76.18 mmHg (SD ± 12.00), respectively. Hypertension was found significantly (p = .006) higher among solid fuel users (23%) compared to clean fuel users (18%). Women using solid fuels have a 35% higher chance (AOR: 1.35, CI: 1.10-1.80) of having hypertension and have more than twice the risk of developing elevated SBP (AOR: 2.01, CI: 1.55-2.95) relative to women using clean fuels for their daily cooking. The probability of hypertension (AOR: 1.39, CI: 1.17-1.60) and elevated SBP (AOR: 1.35, CI: 1.10-1.61) increased significantly for every hour of fuel use. CONCLUSIONS: Using clean fuel, reducing the duration of daily cooking time, and improved cooking facilities may help minimizing hypertension and ultimately cardiovascular disease risk among women.

Antidiabetic Actions of Ethanol Extract of Camellia sinensis Leaf Ameliorates Insulin Secretion, Inhibits the DPP-IV Enzyme, Improves Glucose Tolerance, and Increases Active GLP-1 (7-36) Levels in High-Fat-Diet-Fed Rats.

Camellia sinensis (green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of Camellia sinensis (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 ß cells, and mouse islets. In vitro models examined the additional glucose-lowering properties of EECS, and 3T3L1 adipocytes were used to assess glucose uptake and insulin action. Non-toxic doses of EECS increased insulin secretion in a concentration-dependent manner, and this regulatory effect was similar to that of glucagon-like peptide 1 (GLP-1). The insulin release was further enhanced when combined with isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, but was decreased in the presence of verapamil, diazoxide and Ca2+ chelation. EECS also depolarized the ß-cell membrane and elevated intracellular Ca2+, suggesting the involvement of a KATP-dependent pathway. Furthermore, EECS increased glucose uptake and insulin action in 3T3-L1 cells and inhibited dipeptidyl peptidase IV (DPP-IV) enzyme activity, starch digestion and protein glycation in vitro. Oral administration of EECS improved glucose tolerance and plasma insulin as well as inhibited plasma DPP-IV and increased active GLP-1 (7-36) levels in high-fat-diet-fed rats. Flavonoids and other phytochemicals present in EECS could be responsible for these effects. Further research on the mechanism of action of EECS compounds could lead to the development of cost-effective treatments for type 2 diabetes.

Polyphenol-Rich Leaf of Annona squamosa Stimulates Insulin Release from BRIN-BD11 Cells and Isolated Mouse Islets, Reduces (CH2O)n Digestion and Absorption, and Improves Glucose Tolerance and GLP-1 (7-36) Levels in High-Fat-Fed Rats.

Annona squamosa, commonly known as custard apple, is traditionally used for the treatment of various diseases including diabetes, cardiovascular disease (CVD), and gastritis. This study was undertaken to investigate the effects of an ethanolic (80% v/v) extract of A. squamosa (EEAS) leaves in vitro on insulin secretion from clonal pancreatic BRIN BD11 ß-cells and mouse islets, including mechanistic studies on the effect of EEAS on membrane potential and intracellular calcium ion concentration. Additional in vitro glucose-lowering actions were assessed. For in vivo studies, high-fat-fed (HFF) obese/normal rats were selected. EEAS increased insulin secretion in vitro in a dose-dependent manner. This effect was linked to ß-cell membrane depolarisation and cytoplasmic Ca2+ influx. In the presence of isobutyl methylxanthine (IBMX), tolbutamide, or KCl, the insulin-releasing effect of EEAS was increased, suggesting its effect was also mediated via a KATP-independent pathways. EEAS inhibited insulin glycation, glucose absorption, and DPP-IV enzyme activity in vitro and enhanced glucose uptake and insulin action in 3T3L1 cells. In vivo, gut motility, food intake, glucose tolerance, plasma insulin, and active GLP-1 (7-36) levels were improved, whereas plasma DPP-IV levels were reduced in HFF rats. EEAS attenuated the absorption of sucrose and glucose as well as decreased serum glucose levels after sucrose loading and in situ intestinal perfusion in non-diabetic rats. Rutin, proanthocyanidin, and squafosacin G were putatively identified as the anti-hyperglycaemic phytomolecules in EEAS using HPLC followed by LC-MS analysis. This study illustrates the potential of A. squamosa and its phytoconstituents as a source of potential antidiabetic agents.

Therapeutic Potential of Quercetin in the Management of Type-2 Diabetes Mellitus.

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 ß-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-1ß, 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.

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.

Pharmacologically Active Phytomolecules Isolated from Traditional Antidiabetic Plants and Their Therapeutic Role for the Management of Diabetes Mellitus.

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.

Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of Acacia arabica Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents.

Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal ß 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 isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of A. arabica (HWAA) increased insulin release from clonal ß cells and mouse islets by 1.3-6.8-fold and 1.6-3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30-42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca2+ together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and ß-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol.

Effects of Spirulina platensis on insulin secretion, dipeptidyl peptidase IV activity and both carbohydrate digestion and absorption indicate potential as an adjunctive therapy for diabetes.

Spirulina platensis has been found to be useful in the treatment of type 2 diabetes. The present study aims to elucidate the effects of ethanol extract and butanol fraction of S. platensis on insulin release and glucose homoeostasis in type 2 diabetic rats, together with their mechanism of actions. In vitro and in vivo methods were used including cellular studies to determine potential role of ion channels and cAMP in the insulinotropic actions of the extracts. The ethanol extract and butanol fraction stimulated insulin release from mouse islets and pancreatic ß-cells in a concentration-dependent manner. The butanol fraction also similarly stimulated insulin release from perfused rat pancreas. The insulin-releasing action was augmented by glucose, isobutylmethylxanthine, tolbutamide and a depolarising concentration of KCl. The insulin secretory effect was attenuated with diazoxide and verapamil and by omission of extracellular Ca2+. Butanol fraction was found to significantly inhibit dipeptidyl peptidase IV enzyme activity. Moreover, butanol fraction improved glucose tolerance following oral glucose administration (2·5 g/kg body weight (b.w.)). The butanol fraction was tested on 24 h starved rats given an oral sucrose load (2·5 g/kg b.w.) to examine possible effects on carbohydrate digestion and absorption. S. platensis substantially decreased postprandial hyperglycaemia after oral sucrose load and increased unabsorbed sucrose content throughout the gut. During in situ intestinal perfusion with glucose, the butanol fraction reduced glucose absorption and promoted gut motility. Finally, chronic oral administration of butanol fraction for 28 d significantly decreased blood glucose, increased plasma insulin, pancreatic insulin stores, liver glycogen and improved lipid profile. The characterisation of active compounds from butanol fraction revealed the presence of p-coumaric acid, ß-carotene, catechin and other antioxidant polyphenols. In conclusion, S. platensis could be an adjunctive therapy for the management of type 2 diabetes.

Anti-hyperglycaemic activity of H. rosa-sinensis leaves is partly mediated by inhibition of carbohydrate digestion and absorption, and enhancement of insulin secretion.

ETHNOPHARMACOLOGICAL RELEVANCE: Hibiscus rosa-sinensis (HRS) is a tropical flowery plant, widely distributed in Asian region and an important traditional medicine used in many diseases including cough, diarrhoea and diabetes. AIM OF THIS STUDY: Hibiscus rosa-sinensis (HRS) leaves have been reported to possess anti-hyperglycaemic activity, but little is known concerning the underlying mechanism. This study investigated effects of ethanol extract of HRS on insulin release and glucose homeostasis in a type 2 diabetic rat model. MATERIALS & METHODS: Effects of ethanol extract of grinded H. rosa-sinensis (HRS) leaves on insulin release, membrane potential and intracellular calcium were determined using rat clonal ß-cells (BRIN-BD11 cells) and isolated mouse pancreatic islets. Effects on DPP-IV enzyme activity were investigated in vitro. Acute effects of HRS on glucose tolerance, gut perfusion in situ, sucrose content, intestinal disaccharidase activity and gut motility were measured. Streptozotocin induced type 2 diabetic rats treated for 28 days with ethanol extract of HRS leaf (250 and 500 mg/kg) were used to assess glucose homeostasis. RESULTS: HRS, significantly increased insulin release from clonal rat BRIN-BD11 cells and this action was confirmed using isolated mouse pancreas islets with stimulatory effects equivalent to GLP-1. HRS induced membrane depolarization and increased intracellular Ca2+ in BRIN BD11 cells and significantly inhibited DPP-IV enzyme activity in vitro. HRS administration in vivo improved glucose tolerance in type 2 diabetic rats, inhibited both glucose absorption during gut perfusion and postprandial hyperglycaemia and it reversibly increased unabsorbed sucrose passage through the gut following sucrose ingestion. HRS decreased intestinal disaccharidase activity and increased gastrointestinal motility in non-diabetic rats. In a chronic 28-day study with type 2 diabetic rats, HRS, at 250 or 500 mg/kg, significantly decreased serum glucose, cholesterol, triglycerides and increased circulating insulin, HDL cholesterol and hepatic glycogen without increasing body weight. CONCLUSION: These data suggest the antihyperglycaemic activity of HRS is mediated by inhibiting carbohydrate digestion and absorption, while significantly enhancing insulin secretion in a dose dependent manner. This suggests that HRS has potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes.

Nigella sativa stimulates insulin secretion from isolated rat islets and inhibits the digestion and absorption of (CH2O)n in the gut.

Nigella sativa seeds are traditionally reputed as possessing anti-diabetic properties. As a result, we aim to explore the mechanism of its anti-hyperglycemic activity. The present study uses various experimental designs including gastrointestinal (GI) motility, intestinal disaccharidase activity and inhibition of carbohydrate digestion and absorption in the gut. The animals used as type 2 diabetic models were induced with streptozotocin to make them as such. Oral glucose tolerance test was performed to confirm that the animals were indeed diabetic. The extract reduced postprandial glucose, suggesting it interfered with glucose absorption in the gut. It also improved glucose (2.5g/kg, b/w) tolerance in rats. Furthermore, treatment with N. sativa produced a significant improvement in GI motility, while reduced disaccharidase enzyme activity in fasted rats. The extract produced a similar effect within an acute oral sucrose (2.5g/kg, b/w) load assay. Following sucrose administration, a substantial amount of unabsorbed sucrose was found in six different parts of the GI tract. This indicates that N. sativa has the potentiality to liberate GI content and reduce or delay glucose absorption. A potential hypoglycemic activity of the extract found in insulin release assay, where the extract significantly improved insulin secretion from isolated rat islets. These concluded present findings give rise to the implication that N. sativa seeds are generating postprandial anti-hyperglycemic activity within type 2 diabetic animal models via reducing or delaying carbohydrate digestion and absorption in the gut as well as improving insulin secretion in response to the plasma glucose.

PEG modification of Amorfrutin B from Amorpha fructicosa increases gastric absorption, circulation half-life and glucose uptake by T3T-L1 adipocytes.

Through a simple PEG-conjugation of the natural product Amorfrutin B, we enhanced its pharmacokinetic profile. The PEGylated molecule displayed significantly improved gastrointestinal absorption (p<0.05) and had a longer systemic circulation life (p<0.05). Oral glucose tolerance study showed PEGylated Amorfrutin B displayed longer protection against oral glucose load compared to Amorfrutin B (p<0.05). It also showed significant improvement in glucose uptake in-vitro by T3T-L1 adipocytes (p<0.05). The PEGylated molecule also showed reduced propensity of crossing the blood brain barrier and accumulating in the brain (p<0.05). It also showed reduced accumulation in the adipose tissue. Preliminary liver and kidney toxicity screening showed no significant alteration in liver or kidney function of Amorfrutin B or its PEGylated form. In conclusion, PEG modification can be an attractive strategy to reduce lipophilicity and enhance pharmacokinetic properties of natural products, derived from traditional medicine.

[6]-Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated insulin secretion pathway in pancreatic ß-cells and increases RAB8/RAB10-regulated membrane presentation of GLUT4 transporters in skeletal muscle to improve hyperglycemia in Leprdb/db type 2 diabetic mice.

BACKGROUND: [6]-Gingerol, a major component of Zingiber officinale, was previously reported to ameliorate hyperglycemia in type 2 diabetic mice. Endocrine signaling is involved in insulin secretion and is perturbed in db/db Type-2 diabetic mice. [6]-Gingerol was reported to restore the disrupted endocrine signaling in rodents. In this current study on Leprdb/db diabetic mice, we investigated the involvement of endocrine pathway in the insulin secretagogue activity of [6]-Gingerol and the mechanism(s) through which [6]-Gingerol ameliorates hyperglycemia. METHODS: Leprdb/db type 2 diabetic mice were orally administered a daily dose of [6]-Gingerol (200 mg/kg) for 28 days. We measured the plasma levels of different endocrine hormones in fasting and fed conditions. GLP-1 levels were modulated using pharmacological approaches, and cAMP/PKA pathway for insulin secretion was assessed by qRT-PCR and ELISA in isolated pancreatic islets. Total skeletal muscle and its membrane fractions were used to measure glycogen synthase 1 level and Glut4 expression and protein levels. RESULTS: 4-weeks treatment of [6]-Gingerol dramatically increased glucose-stimulated insulin secretion and improved glucose tolerance. Plasma GLP-1 was found to be significantly elevated in the treated mice. Pharmacological intervention of GLP-1 levels regulated the effect of [6]-Gingerol on insulin secretion. Mechanistically, [6]-Gingerol treatment upregulated and activated cAMP, PKA, and CREB in the pancreatic islets, which are critical components of GLP-1-mediated insulin secretion pathway. [6]-Gingerol upregulated both Rab27a GTPase and its effector protein Slp4-a expression in isolated islets, which regulates the exocytosis of insulin-containing dense-core granules. [6]-Gingerol treatment improved skeletal glycogen storage by increased glycogen synthase 1 activity. Additionally, GLUT4 transporters were highly abundant in the membrane of the skeletal myocytes, which could be explained by the increased expression of Rab8 and Rab10 GTPases that are responsible for GLUT4 vesicle fusion to the membrane. CONCLUSIONS: Collectively, our study reports that GLP-1 mediates the insulinotropic activity of [6]-Gingerol, and [6]-Gingerol treatment facilitates glucose disposal in skeletal muscles through increased activity of glycogen synthase 1 and enhanced cell surface presentation of GLUT4 transporters.

Anti-hyperglycaemic activity of Moringa oleifera is partly mediated by carbohydrase inhibition and glucose-fibre binding.

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.

Investigation of antinociceptive activity of methanolic extract of Persicaria orientalis leaves in rodents.

BACKGROUND: This study aims to evaluate the scientific basis of traditional application of Persicaria orientalis for reducing pain and inflammation. METHODS: An in vitro method was performed to investigate the presence of the anti-inflammatory activity of methanolic crude extract of P. orientalis. In addition, an in vivo study was conducted in which the hot-plate and tail immersion methods were applied to explore the acute effect of P. orientalis on analgesia. The potency to inhibit chronic inflammation in mice was justified by the carrageenan-induced paw edema and formalin-induced edema methods. For all in vivo testing in animal models (albino mice and rats), plant extract was given via the oral route at doses of 250 mg/kg and 500 mg/kg. RESULTS: The methanolic extract of P. orientalis produced a significant (p<0.001) inhibition of analgesia with a prolongation of pain response time by 61.80% at 500 mg/kg. The extract also exhibited a potential anti-inflammatory (56.99%) effect, which was also statistically significant (p<0.001). The present study suggests that the methanolic extract of P. orientalis has potential anti-inflammatory as well as analgesic activity and this extract is effective in the treatment of both acute and chronic pain. CONCLUSIONS: Our current study revealed pharmacological properties of the methanolic extract of P. orientalis and also gave a solid scientific platform against its traditional use. The protecting ability of P. orientalis against inflammatory stimuli may be due to phenolic or flavonoid compounds which we have found through phytochemical analysis.

Anti-hyperglycemic activity of Aegle marmelos (L.) corr. is partly mediated by increased insulin secretion, α-amylase inhibition, and retardation of glucose absorption.

BACKGROUND: Aegle marmelos (commonly known as Bael, golden apple) was formerly described to have anti-hyperglycemic activity. The present study aimed to explore the possible effects, in depth, of A. marmelos extracts on carbohydrate absorption, glucose utilization, and α-amylase inhibition and insulin content in pancreases of type 2 diabetic rats. METHODS: This research begins with fasting blood glucose and oral glucose tolerance test (OGTT) to evaluate the primary anti-hyperglycemic effect in chemically induced type 2 diabetic rats. Furthermore, the plasma insulin concentration and serum glucose level were studied, which include measuring the sucrose content in six different segments of the gastrointestinal (GI) tract of the rats following oral sucrose feeding. An in situ, perfused, intestinal model in rats and glucose-fiber binding assay were conducted to find the effects of A. marmelos extracts on glucose absorption. Extract effects on carbohydrate breakdown, intestinal disaccharidase enzyme activity, and α-amylase inhibition were assessed. Effect on GI motility was evaluated using BaSO4 milk traverse test. RESULTS: Treatment of extracts suppressed blood glucose elevation after oral sucrose (2.5 g/kg) administration and significantly (p<0.05) improved oral glucose tolerance in type 2 diabetic rats. Aegle marmelos extracts showed remarkable (p<0.05) changes in plasma insulin secretion at 30 min and 60 min, respectively. A noticeable reduction in glucose absorption was observed in the in situ perfused rat intestinal model at two different doses (250 and 500 mg/kg). The extract was also found to inhibit the action of both α-amylase and intestinal disaccharidase enzyme, and this study was affirmed again by the sucrose malabsorption test, where sucrose digestion was inhibited throughout the length of the GI tract. During this chronic study, body mass of rats became normal and their polydipsic and polyphagic conditions were ameliorated also. CONCLUSIONS: The findings demonstrate that anti-hyperglycemic activity of A. marmelos is mediated by the inhibition of carbohydrate digestion and absorption, and improvement of insulin action to uptake glucose in peripheral tissue. Additional study is required to correlate A. marmelos extracts' specific mechanism of glucose-fiber binding capacity and glucose transporters.

Evaluation of antinociceptive and anti-inflammatory properties of methanolic crude extract of Lophopetalum javanicum (bark).

BACKGROUND: The aim of the current study was to investigate the scientific basis of the traditional application of Lophopetalum javanicum for measuring anti-inflammatory and analgesic activity and phytochemical screening. METHODS: Present study includes the preliminary screening of the phytochemical composition and in vivo analgesic and anti-inflammatory activity of methanolic extract of L. javanicum (MELJ). Hot-plate test and tail immersion method were used to investigate acute analgesic effects of L. javanicum, and the potency in inhibition of chronic inflammation in mice was tested by carrageenan-induced paw edema and formalin-induced edema method. RESULTS: One hour after the administration of carrageenan, rat's paw was inflamed, and after treating it with 500 mg/kg dose, increase in the significant inhibitory effect on paw was observed. At the third hour after carrageenan injection, extreme inhibition (55.61%±0.015%; p<0.001) resulted by methanolic extract. By using hot plate method, it was found that L. javanicum increases pain tolerance time up to 17.89±0.079 min, whereas the compared standard's interval was 21.48±0.397 min. In tail immersion method, the pain threshold was 3.02±0.074 (p<0.001) at 400 mg/kg by L. javanicum at 90 min of experiment. CONCLUSIONS: This study manifested that the methanolic extract of L. javanicum is efficient in inhibiting pain mediators to release, and conceivably, this report should get priority while searching for a new analgesic and anti-inflammatory agent.

Aqueous fraction of Beta vulgaris ameliorates hyperglycemia in diabetic mice due to enhanced glucose stimulated insulin secretion, mediated by acetylcholine and GLP-1, and elevated glucose uptake via increased membrane bound GLUT4 transporters.

BACKGROUND: The study was designed to investigate the probable mechanisms of anti-hyperglycemic activity of B. Vulgaris. METHODOLOGY/PRINCIPAL FINDINGS: Aqueous fraction of B. Vulgaris extract was the only active fraction (50mg/kg). Plasma insulin level was found to be the highest at 30 mins after B. Vulgaris administration at a dose of 200mg/kg. B. Vulgaris treated mice were also assayed for plasma Acetylcholine, Glucagon Like Peptide-1 (GLP-1), Gastric Inhibitory Peptide (GIP), Vasoactive Intestinal Peptide, Pituitary Adenylate Cyclase-Activating Peptide (PACAP), Insulin Like Growth Factor-1 (IGF-1), Pancreatic Polypeptides (PP), and Somatostatin, along with the corresponding insulin levels. Plasma Acetylcholine and GLP-1 significantly increased in B. Vulgaris treated animals and were further studied. Pharmacological enhancers, inhibitors, and antagonists of Acetylcholine and GLP-1 were also administered to the test animals, and corresponding insulin levels were measured. These studies confirmed the role of acetylcholine and GLP-1 in enhanced insulin secretion (p<0.05). Principal signaling molecules were quantified in isolated mice islets for the respective pathways to elucidate their activities. Elevated concentrations of Acetylcholine and GLP-1 in B. Vulgaris treated mice were found to be sufficient to activate the respective pathways for insulin secretion (p<0.05). The amount of membrane bound GLUT1 and GLUT4 transporters were quantified and the subsequent glucose uptake and glycogen synthesis were assayed. We showed that levels of membrane bound GLUT4 transporters, glucose-6-phosphate in skeletal myocytes, activity of glycogen synthase, and level of glycogen deposited in the skeletal muscles all increased (p<0.05). CONCLUSION: Findings of the present study clearly prove the role of Acetylcholine and GLP-1 in the Insulin secreting activity of B. Vulgaris. Increased glucose uptake in the skeletal muscles and subsequent glycogen synthesis may also play a part in the anti-hyperglycemic activity of B. Vulgaris.

Ethanolic Extract of Butea monosperma Leaves Elevate Blood Insulin Level in Type 2 Diabetic Rats, Stimulate Insulin Secretion in Isolated Rat Islets, and Enhance Hepatic Glycogen Formation.

We measured a vast range of parameters, in an attempt to further elucidate previously claimed antihyperglycemic activity of Butea monosperma. Our study clearly negates the possibility of antidiabetic activity by inhibited gastrointestinal enzyme action or by reduced glucose absorption. Reduction of fasting and postprandial glucose level was reconfirmed (P < 0.05). Improved serum lipid profile via reduced low density lipoprotein (LDL), cholesterol, triglycerides (TG), and increased high density lipoprotein (HDL) was also reestablished (P < 0.05). Significant insulin secretagogue activity of B. monosperma was found in serum insulin assay of B. monosperma treated type 2 diabetic rats (P < 0.01). This was further ascertained by our study on insulin secretion on isolated rat islets (P < 0.05). Improved sensitivity of glucose was shown by the significant increase in hepatic glycogen deposition (P < 0.05). Hence, we concluded that antihyperglycemic activity of B. monosperma was mediated by enhanced insulin secretion and enhanced glycogen formation in the liver.

Analgesic, anti-inflammatory, and antipyretic effects of Ixora coccinea.

Abstract Background: The present study was carried out to explore the potential of the ethanol extract of Ixora coccinea L. (IC) leaves as analgesic, anti-inflammatory and antipyretic agents using the hot-plate, acetic acid-induced writhing, carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests in rodents. Methods: The extract was prepared by soaking the dried powdered leaves of IC in ethanol for 2 days. The filtrate thus obtained by filtration and evaporation was considered as a stock solution and was used in all experimental models. Results: Oral administration of IC (250 and 500 mg/kg) significantly (p<0.05) increased the reaction time in the hot-plate test. Ixora coccinea (250 and 500 mg/kg) produced 56.14% and 63.16% inhibition (p<0.05) in acetic acid-induced writhing. It also (250 and 500 mg/kg) produced significant (p<0.05) inhibition of paw edema pronounced at 6 h after carrageenan injection. Intraperitoneal administration of IC (250 and 500 mg/kg) lowered the body temperature in brewer's yeast-induced hyperthermia. Conclusions: Based on the findings, it may be concluded that the IC leaves possessed analgesic, anti-inflammatory, and antipyretic activities. Phytochemical constituents of IC leaves such as flavonoids, tannins, and triterpenes in ethanol extract could be correlated with its observed biological activities.