A new dammarane saponin and other triterpenoids from Siolmatra brasiliensis and evaluation of the antidiabetic activity of its extract

Context Siolmatra brasiliensis (Cogn.) Baill (Cucurbitaceae) is a climbing plant widely used for the treatment of diabetes mellitus symptoms.

Objective This work evaluates the antidiabetic activity of an extract of S. brasiliensis in streptozotocin-diabetic rats and promotes the phytochemical investigation to isolate the major compounds of the same extract.

Materials and methods Male Wistar rats were divided into normal (N) and diabetic rats (DC) treated with water; diabetic rats treated with 3U insulin (DI) or with 250 (DSb₂₅₀) or 500?mg/kg (DSb₅₀₀) of hydroalcoholic extract of the stalks of S. brasiliensis, via oral gavage, for 21 days. Physiological and biochemical parameters classically altered in diabetes were monitored. The triterpenoids were isolated from the ethyl acetate fraction under silica gel column chromatography and Sephadex-LH20 methods and their structures were determined by NMR, HR-ESI-MS and DC analysis.

Results When compared with DC, DSb₂₅₀ rats showed a reduction in the hyperglycemia (DC: 26.46?±?0.69 versus DSb₂₅₀: 19.67?±?1.06?mmol/L) and glycosuria (DC: 43.02?±?3.19 versus DSb₂₅₀: 28.46?±?2.14?mmol/24?h) and increase in hepatic glycogen (DC: 14.44?±?1.26 versus DSb₂₅₀: 22.08?±?4.26?mg/g). Three known cucurbitacins were isolated from a hydroalcoholic extract of S. brasiliensis, i.e., cayaponosides A1, B4, D, and a new dammarane saponin 3-O-β-d-gentiobiosyl-26-O-β-d-glucopyranosyl-20-hydroxydammar-24-ene. The structures of these compounds were elucidated by spectral data analysis of the natural products and their acetyl derivatives.

Discussion and conclusion The known cucurbitacins and/or the new identified saponin may be related with the antidiabetic activity of S. brasiliensis.     

Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats

Abstract

Context: In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored.

Objective: The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats.

Material and methods: The aqueous suspension of P. dactylifera seeds (aqPDS) (1?g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase.

Results: Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248?±?42 versus 508?±?60?mg/dl), urea (32?±?3.3 versus 48.3?±?5.6?mg/dl), creatinine (2.2?±?0.35 versus 3.8?±?0.37?mg/dl), ALT (29.6?±?3.9 versus 46.4?±?5.9?IU/l), and AST (73.3?±?13 versus 127.8?±?18.7?IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats.

Discussion and conclusion: The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.     

Antidiabetic effects of Mukia maderaspatana and its phenolics: An in vitro study on gluconeogenesis and glucose uptake in rat tissues

Context: Traditional medicine is used by over 60% of the world’s population for health care. Mukia maderaspatana (L.) M. Roem. (Cucurbitaceae) (Mukia) is extensively used in folklore medicine as an antidiabetic plant. It is rich in phenolics that contribute to its medicinal properties.

Objective: Mukia extract and phenolics such as quercetin and phloroglucinol are investigated for their in vitro antidiabetic activity.

Materials and methods: Quercetin, phloroglucinol, and methanol extract of the dried whole plant (0.25 and 0.5?mg/ml) were studied for the inhibition of gluconeogenesis in rat liver slices and glucose uptake in isolated rat hemi-diaphragm (50 and 100?µg/ml). Phenolics of Mukia were analyzed by HPLC.

Results and discussion: Glucose (1.2?mg/g/h) was synthesized from pyruvate and the synthesis was completely inhibited by insulin (1?U/ml). Quercetin at 0.25 and 0.5?mg/ml caused 65% and 89% inhibition (0.42?mg/g/h and 0.13?mg/g/h glucose). Addition of insulin did not increase inhibition. Phloroglucinol inhibited 100% glucose production with or without insulin. Mukia (0.25?mg/ml) inhibited gluconeogenesis (0.65?mg/g/h) by 45%, and with insulin, inhibition increased to 50% (0.59?mg/g/h). At 0.5?mg/ml, glucose production was stimulated by1.2-fold, but with insulin it was inhibited by 89% (0.13?mg/g/h glucose). Mukia had no effect on glucose uptake, but potentiated the action of insulin mediated glucose uptake (152.82?±?13.30?mg/dl/g/30?min) compared with insulin control (112.41?±?9.14?mg/dl/g/30?min) (p?0.05). HPLC analysis revealed the presence of phenolics.

Conclusion: Results provide scientific rationale for the use of Mukia in folk medicine as an antidiabetic nutraceutical.     

Effects of exenatide versus sitagliptin on postprandial glucose,insulin and glucagon secretion,gastric emptying,and caloric intake: a randomized,cross-over study

ABSTRACT

Background: This study evaluated the effects of exenatide, a GLP-1 receptor agonist, and sitagliptin, a DPP-4 inhibitor, on 2-h postprandial glucose (PPG), insulin and glucagon secretion, gastric emptying, and caloric intake in T2D patients.

Methods: This double-blind, randomized cross-over, multi-center study was conducted in metformin-treated T2D patients: 54% female; BMI: 33?±?5?kg/m²; HbA_1c: 8.5?±?1.2%; 2-h PPG: 245?±?65?mg/dL. Patients received exenatide (5?µg BID for 1 week, then 10?µg BID for 1 week) or sitagliptin (100?mg QAM) for 2 weeks. After 2 weeks, patients crossed-over to the alternate therapy. Postprandial glycemic measures were assessed via standard meal test; caloric intake assessed by ad libitum dinner (subset of patients). Gastric emptying was assessed by acetaminophen absorption (Clinicaltrials.gov Registry Number: NCT00477581).

Results: After 2 weeks of therapy, 2-h PPG was lower with exenatide versus sitagliptin: 133?±?6?mg/dL versus 208?±?6?mg/dL, p?<?0.0001 (evaluable, N?=?61). Switching from exenatide to sitagliptin increased 2-h PPG by +73?±?11?mg/dL, while switching from sitagliptin to exenatide further reduced 2-h PPG by ?76?±?10?mg/dL. Postprandial glucose parameters (AUC, C_ave, C_max) were lower with exenatide than sitagliptin (p?<?0.0001). Reduction in fasting glucose was similar with exenatide and sitagliptin (?15?±?4?mg/dL vs. ?19?±?4?mg/dL, p?=?0.3234). Compared to sitagliptin, exenatide improved the insulinogenic index of insulin secretion (ratio exenatide to sitagliptin: 1.50?±?0.26, p?=?0.0239), reduced postprandial glucagon (AUC ratio exenatide to sitagliptin: 0.88?±?0.03, p?=?0.0011), reduced postprandial triglycerides (AUC ratio exenatide to sitagliptin: 0.90?±?0.04, p?=?0.0118), and slowed gastric emptying (acetaminophen AUC ratio exenatide to sitagliptin: 0.56?±?0.05, p?<?0.0001). Exenatide reduced total caloric intake compared to sitagliptin (?134?±?97?kcal vs. +130?±?97?kcal, p?=?0.0227, N?=?25). Common adverse events with both treatments were mild to moderate in intensity and gastrointestinal in nature.

Conclusions: Although this study was limited by a 2-week duration of exposure, these data demonstrate that, exenatide had: (i) a greater effect than sitagliptin to lower postprandial glucose and (ii) a more potent effect to increase insulin secretion and reduce postprandial glucagon secretion in T2D patients. In contrast to sitagliptin, exenatide slowed gastric emptying and reduced caloric intake. These key findings differentiate the therapeutic actions of the two incretin-based approaches, and may have meaningful clinical implications.     

Selenium and rutin alone or in combination do not have stronger protective effects than their separate effects against cadmium-induced renal damage

Context: Selenium (Se) and rutin (RUT) are antioxidants that protect against tissue damage.

Objective: In this study, the separate and combine protective effects of RUT and Se against cadmium (Cd)-induced renal damage were evaluated in rats.

Materials and methods: Wistar rats were treated by gavage to RUT (30?mg/kg) or Se (0.15?ppm) or Cd (200?ppm) in drinking water alone or in combination (30?mg/kg RUT?+0.15?ppm Se?+?200?ppm Cd). Corn oil was used as vehicle (2?mL/kg). After a 5-week treatment period, rat kidneys were removed for biochemical assays and histopathological examination. Se and Cd levels were evaluated by flame atomic absorption spectrophotometry.

Results: The malondialdehyde and glutathione levels as well as superoxide dismutase and catalase activities in the Cd-treated animals were increased compared with control values (0.056?±?0.0003 versus 0.011?±?0.0005?μmol/mg; 0.005?±?0.0006 versus 0.00085?±?0.0002?μg/mg; 1.62?±?0.09 versus 0.48?±?0.12 units/mg; 650?±?25 versus 361.89?±?31?μmol H₂O₂/mg, respectively). Cd treatment was also associated with decreased renal Se concentration (4.19?±?0.92 versus 7.73?±?0.7?μg/g dry weight), increased alkaline phosphatase (0.07?±?0.0015 versus 0.033?±?0.0019 unit/mg), acid phosphatase (0.029?±?0.0021 versus 0.015?±?0.0016 unit/mg), and lactate dehydrogenase (0.032?±?0.004 versus 0.014?±?0.0027 unit/mg) activities, respectively, and with evidence of severe renal damage. The combination of RUT and Se or their separate effects prevented the Cd-induced oxidative renal damage. However, their combine effects do not have stronger effects than their separate effect against Cd-induced renal damage.

Discussion and conclusion: RUT and Se function as potent antioxidant in the protection of renal damage induced by Cd.     

Myrtenal alleviates hyperglycaemia,hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Context: Myrtenal is monoterpene a constituent of essential oils found mainly in herbs such as mint, pepper, cumin, etc. It exerts admirable pharmacological activities against many diseases including diabetes. Hyperlipidaemia is a secondary complication of diabetes and also a major risk factor for cardiovascular diseases.

Objective: The present study investigated the possible antihyperlipidaemic efficacy of myrtenal on plasma glucose, pancreatic insulin, plasma and tissue lipid levels in streptozotocin (STZ) induced diabetic rats.

Materials and methods: Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40?mg/kg b.w.). Myrtenal (80?mg/kg) was administered orally to diabetic rats for a period of 28 d. Plasma glucose, pancreatic insulin, TC, TGs, FFAs, PLs, LDL-C, HDL-C, VLDL, atherogenic index, (HMG-CoA) reductase, LPL, LCAT and liver histology were analyzed.

Results: Diabetic rats showed significantly (p?<?0.05) increased plasma glucose (273.18?mg/dL), total cholesterol (142?mg/dL), triglycerides (126?mg/dL), free fatty acids (118?mg/dL), phospholipids (153?mg/dL), low-density lipoprotein (88.07?mg/dL), very low-density lipoprotein (25.2?mg/dL), atherogenic index, whereas a decrease in the levels of pancreatic insulin (97.48?ng/mg) and high-density lipoprotein (29.12?mg/dL). In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase (0.94 HMG-CoA ratio/(mevalonate) increased significantly in contrast to the activities of lipoprotein lipase (4.87 μmoles of glycerol liberated/h/L) and lecithin cholesterol acyltransferase (54.61 μmoles of cholesterol esterified/h/L) in diabetic rats. Treatment with myrtenal significantly (p?<?0.05) improved the levels of plasma glucose, pancreatic insulin and lipid profiles. Moreover, the histopathological analysis of liver was also in agreement with the biochemical findings.

Discussion and conclusions: The present study indicates that myrtenal possess antihyperglycaemic and antihyperlipidemic properties, and could potentially be a useful phytochemical in treating diabetes.     

Hesperidin,a citrus flavonoid,protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress,endothelial dysfunction and neurotoxicity in Wistar rats

Context: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties.

Objective: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats.

Materials and methods: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100?mg/kg), HSP-per se (100?mg/kg) and donepezil (0.1?mg/kg). HHcy was induced by oral administration of l-methionine (1.7?g/kg) for 32 days. From the 14^th day of study HSP (25, 50 and 100?mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28^th–32^nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done.

Results: HSP (100?mg/kg) treatment in l-methionine-treated rats exhibited significant (p?p?l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations.

Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.     

Amelioration of hyperglycaemia and modulation of antioxidant status by Alcea rosea seeds in alloxan-induced diabetic rats

Context: Alcea rosea L. (Malvaceae) has various medicinal uses including anticancer, anti-inflammatory and analgesic properties. However, there is no report on its antidiabetic activity.

Objective: Alcea rosea seed extracts were evaluated for antihyperglycaemic and antioxidative potential in diabetic rats.

Materials and methods: Single intra-peritoneal injection of alloxan (130?mg/kg b.w.) was used for induction of diabetes in Albino Wistar rats. Antihyperglycaemic and antioxidant activities of methanol and aqueous extracts of Alcea rosea seed (100 and 300?mg/kg b.w.), administered orally on daily basis for 15 days, were assessed in vivo for fasting blood glucose level and antioxidant status of liver and pancreas. Metformin was used as a positive control.

Results: Aqueous and methanol extracts (300?mg/kg b.w.) decreased blood glucose level in diabetic rats by 24% and 46%, respectively. Administration of aqueous and methanol extracts at 300?mg/kg b.w. significantly (p?2O₂ decomposed/min/mg of protein), respectively. Similar results were observed for pancreas.

Discussion and conclusions: Antihyperglycaemic and antioxidative potentials of Alcea rosea seeds suggest its usefulness in management of diabetes and its complications. This is the first report on antidiabetic activity of this plant.     

Mineral pitch stimulates humoral,cellular and innate immune responses in mice

Abstract

Context: Mineral pitch (MP), a traditional medicine, is proposed to boost immunity in conditions that suppress Th1 cytokines such as AIDS/HIV, tuberculosis, leishmaniasis and cancer.

Objective: This study investigates the immunoregulatory mechanisms of MP in innate, humoral and cell-mediated immunity.

Materials and methods: Mice given MP (100, 200, 300 or 400?mg/kg, orally) for 10 consecutive days were immunized intravenously with goat RBC or ovalbumin, and investigated for plaque-forming cells (PFC), hemagglutination titer, hypersensitivity response, lymphocyte proliferation and macrophage function.

Results: MP increased PFC (330.2 versus 182.2/10⁶ splenocytes) in mice immunized with goat RBC and elicited ovalbumin-specific IgG titer at 400?mg/kg. Increase in Th1 immunity was correlated with the increased level of IFN-γ (724 versus 470?pg/ml) and decreased IL-4 (96 versus 178?pg/ml). CD4⁺/CD3⁺ ratio and delayed-type hypersensitivity response also increased to, respectively, 20.62?±?0.59 (versus 16.47?±?0.72) and 1.59?±?0.12 (versus 0.87?±?0.10?mm) in MP-treated mice. MP increased lymphocyte proliferation (11.14?±?0.60 versus 5.81?±?0.40 SI) and macrophage phagocyte response (0.24?±?0.02 versus 0.15?±?0.009), expressed as absorbance at 570?nm, but decreased nitrite production (17.4?±?1.10 versus 24.3?±?1.30?µM/10⁶ cells). We also observed an increased bone marrow cellularity (24.5?±?1.10 versus 17.10?±?0.70 cells/femur) and WBC count (12?667?±?377 versus 9178?±?213 cells/mm³) following MP treatment. There was no sign of toxicity at 400?mg/kg, 1/12th of reported LD₅₀.

Conclusion: MP elicits a dose-dependent Th1 immune response.     

Galangin,a dietary flavonoid,ameliorates hyperglycaemia and lipid abnormalities in rats with streptozotocin-induced hyperglycaemia

Context: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known.

Objective: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia.

Materials and methods: Diabetes was induced in adult Wistar rats by administering 40?mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320?mg/kg. Therefore three doses of galangin (4, 8 or 16?mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days.

Results: Diabetic rats showed a significant (p?p?p?Discussion and conclusions: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed.     

Therapeutic potential of octyl gallate isolated from fruits of Terminalia bellerica in streptozotocin-induced diabetic rats

Abstract

Context: Medicinal plants are a potential source of antidiabetic drugs. Terminalia bellerica Roxb. (Combretaceae) is used in Indian traditional systems of medicine to treat diabetes mellitus.

Objective: The aim of this study was to isolate and identify antihyperglycemic principle(s) from the fruits of T. bellerica and assess the bioactivity in streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Bioassay-guided fractionation was followed to isolate the active compound(s), structure was elucidated using ¹H and ¹³C NMR, IR and mass spectrometry and administered intragastrically to diabetic Wistar rats at different doses (5, 10 and 20?mg/kg, body weight) for 28?d. Plasma glucose, insulin, C-peptide and other biochemical parameters were studied.

Results: Octyl gallate (OG) isolated first time from the fruit rind of T. bellerica significantly (p?<?0.05) reduced plasma glucose to near normal values (108.47?±?6.9?mg/dl) after 14?d at the dose of 20?mg/kg. In addition, OG significantly increased plasma insulin, C-peptide, total protein, albumin, tissue glycogen, body weight and markedly decreased serum total cholesterol, triglyceride, LDL-cholesterol, urea, uric acid and creatinine in diabetic rats. Also OG restored the altered regulatory enzymes of carbohydrate metabolism.

Discussion and conclusion: OG might have augmented the secretion of insulin by the modulation of cAMP and intracellular calcium levels in the β cells of the pancreas. Our findings indicate that OG isolated first time from the fruit rind of T. bellerica has potential antidiabetic effect as it augments insulin secretion and normalizes the altered biochemical parameters in experimental diabetic rat models.     

HL301 versus Umckamin in the treatment of acute bronchitis: a phase III,randomized, controlled,double-blind,multicenter study

Abstract

Objective: HL301 is a combination product of seven medicinal plants that has been proven effective in acute bronchitis by two phase II studies. In the present study, its efficacy and safety compared with those of Umckamin in the treatment of acute bronchitis were evaluated in phase III, randomized, controlled, double-blind, multicenter trial design.

Methods: A total of 246 acute bronchitis patients were randomized to receive either HL301 (600?mg/day) or Umckamin (333?mg/day) for seven days. The primary outcome was the difference in their baseline (visit 2) and end of treatment (visit 3) bronchitis severity score (BSS). Other efficacy variables included the change in each BSS component (cough, sputum, dyspnea, chest pain, and crackle), response rate, improvement rate, and satisfaction rate with treatment.

Results: A full analysis set and per protocol set analysis of both groups revealed that the difference of BSS between visit 2 and visit 3 in the HL301 and Umckamin group was not significantly different (4.58?±?1.79 versus 4.29?±?1.88, p?=?.37 and 4.60?±?1.81 versus 4.33?±?1.88, p?=?.42, respectively). The change in five BSS components (cough, sputum, dyspnea, chest pain, and crackle) of the HL301 and Umckamin groups did not differ after treatment. HL301 or Umckamin treated participants showed an equal level of response, improvement, and satisfaction rates with treatment. Both the HL301 group and Umckamin group showed the same safety profile.

Conclusions: HL301 (600?mg/day) was as effective and safe as Umckamin (333?mg/day) in treating acute bronchitis.     

Evaluation of turmeric (Curcuma longa) effect on biochemical and pathological parameters of liver and kidney in chicken aflatoxicosis

Context: Aflatoxins as potent mycotoxins can influence vital parameters in chickens. Turmeric was used in decreasing toxic effect of mycotoxins on vital organs, traditionally.

Objective: The study compared the protective effect of turmeric and Mycoad^TR in broilers exposed to aflatoxin.

Materials and methods: Chickens (270) were divided into six groups. The chickens were fed a basal diet, turmeric extract (5?mg/kg diet), Mycoad^TR (25?mg/kg diet), productive aflatoxin (3?mg/kg diet), aflatoxin plus turmeric extract (3 versus 5?mg/kg diet), and aflatoxin plus Mycoad^TR (3 versus 25?mg/kg diet) in basal diet. At 28?d old, we determined plasma concentration of total protein, albumin, triglyceride, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), calcium, potassium, phosphorous, uric acid, aspartate transferase (AST), and alanine aminotransferase (ALT). Furthermore, liver and kidney were sampled for pathological examination.

Results: Chickens fed turmeric with aflatoxin had significant lower ALT, AST, and uric acid than chickens fed aflatoxin (11.4?±?0.79, 228?±?9, and 6?±?0.4 versus 17.2?±?1.7, 283?±?5, and 7.7?±?0.1) whereas, total protein, calcium, and HDL values in chickens fed aflatoxin plus turmeric increased significantly (2.66?±?0.16, 8.4?±?0.2, and 920?±?4.1 versus 1.7?±?0.17, 7?±?0.2, and 690?±?4.8). Pathological examination revealed severe congestion, degeneration, and necrosis in liver and kidney in chickens that received aflatoxin.

Discussion and conclusion: The study showed that turmeric may provide protection against the toxic effects of aflatoxin on liver and kidney.     

Momordica charantia extracts ameliorate insulin resistance by regulating the expression of SOCS-3 and JNK in type 2 diabetes mellitus rats

Context: Momordica charantia L. (Cucurbitaceae) has long been widely used as a traditional remedy for diabetes mellitus in some countries. However, detailed antidiabetic mechanisms are largely unknown.

Objectives: This study clarified the ameliorating effects of M. charantia ethanol extracts (MCE) on the insulin resistance in type 2 diabetes mellitus (T2DM) rats.

Materials and methods: T2DM rat model was established by high-fat diet and streptozotocin (STZ) injection. Diabetic rats were randomized into five groups: the model control group (n?=?8) (common diet), the high-fat diet metformin (50?mg/kg/d), and the three-dose MCE (100, 200, and 400?mg/kg/d) groups (n?=?8 each). After 8 weeks, the fasting serum glucose, insulin, TNF-α, and IL-6 were measured, and the relevant factors of glucose and insulin were monitored by glycogen dyeing, RT-PCR, and western blot, respectively.

Results: The 8-week treatment of 400?mg/kg MCE significantly lowered body weight (330.1 versus 365.9?g), serum glucose (7.41 versus 16.63?mmol/L), insulin (12.06 versus 15.89 mIU/L), TNF-α (52.72 versus 81.83?ng/L), and IL-6 (104.81 versus 135.74?ng/L) in comparison with those of the diabetic control group (p?p?Conclusions: MCE can ameliorate insulin resistance in T2DM rats. This effect may be related to the regulation of mRNA and protein levels of SOCS-3 and JNK.     

Prunus mume leaf extract lowers blood glucose level in diabetic mice

Context Diabetes is a common metabolic disease with long-term complications. Prunus mume Sieb. et Zucc. (Rosaceae) fruits have shown to ameliorate glucose intolerance. However, the antidiabetic effects of P. mume leaves have not been investigated.

Objective This study evaluated the effects of P. mume leaf 70% ethanol extract (PMLE) on alleviating diabetes in vivo and in vitro.

Materials and methods PMLE was fractionated into n-hexane, dichloromethane (CH₂Cl₂), ethyl acetate (EtOAc), n-butanol (BuOH) and water. Polyphenol and flavonoid contents in PMLE fractions were determined using Folin–Ciocalteu reagent and the aluminium chloride colorimetric method, respectively. We evaluated α-glucosidase inhibition using a microplate reader at 400?nm. Adipocyte differentiation by lipid accumulation was measured using Nile Red staining. Male imprinting control region (ICR) mice were injected with streptozotocin (STZ, 100?mg/kg, i.p.). High-fat diets were provided for three weeks prior to PMLE treatments to induce type 2 diabetes. PMLE (0, 5, 25 or 50?mg/kg) was administrated for four weeks with high-fat diets.

Results The EtOAc fraction of PMLE inhibited α-glucosidase activity (IC₅₀?=?68.2?μg/mL) and contained 883.5?±?14.9?mg/g of polyphenols and 820.1?±?7.7?mg/g of flavonoids. The 50?mg/kg PMLE supplement reduced 40% of blood glucose level compared to obese/diabetes mice. Obese/diabetic mice treated with 50?mg/kg PMLE showed a lower level of triacylglycerol (320.7?±?20.73?mg/dL) compared to obese/diabetes mice (494.9?±?14.80?mg/dL).

Conclusion The data demonstrate that P. mume leaves exert antidiabetic effects that may be attributable to high concentrations of polyphenols and flavonoids.     

Crataegus Aronia protects and reverses vascular inflammation in a high fat diet rat model by an antioxidant mechanism and modulating serum levels of oxidized low-density lipoprotein

Context: Crataegus aronia (Willd.) Bosc (Rosaceae) (syn. Azarolus L) is traditionally used to treat cardiovascular disorders.

Objectives: To investigate C. aronia protection against a high-fat diet (HFD)-induced vascular inflammation in rats.

Materials and methods: Wistar Male rats (180–220?g) were divided (n?=?10/group) as control fed a standard diet (STD), STD + C. aronia (200?mg/kg, orally), HFD, HFD + C. aronia and HFD post-treated with C. aronia. Simvastatin (20?mg/kg) was co- or post-administered as a positive control drug. HFD was given for 8?weeks, and all other treatments were administered for 4?weeks.

Results: Most significantly, co-administration of C. aronia to HFD-fed rats reduced the thickness of aorta tunica media (90?±?5 vs. 160?±?11.3?µm) and adventitia (54.3?±?3.8 vs. 93.6?±?9.4?µm). It also lowered protein levels of TNF-α (0.51?±?0.15 and 0.15?±?0.16 vs. 0.1?±?0.09%) and IL-6 (0.52?±?0.19 vs. 1.0?±?0.2%) in their aorta or serum (5.9?±?0.91 vs. 12.98?±?1.3?ng/mL and 78.1?±?6.7 vs. 439?±?78?pg/mL, respectively). It also lowered all serum lipids and increased aorta levels of GSH levels (70.4?±?4.0 vs. 40.7?µM) and activity of SOD (5.7?±?0.7 vs. 2.9?±?0.6?U/mg) and decreased serum levels of ox-LDL-c (566.7?±?46 vs. 1817?±?147?ng/mL). Such effects were more profound than all other treatments.

Conclusions: C. aronia inhibits the HFD-induced vascular inflammation and its use in clinical trials is recommended.     

Studies on the antidiabetic activities of Momordica charantia fruit juice in streptozotocin-induced diabetic rats

Context: Momordica charantia Linn (Cucurbitaceae) (MC) is used in folk medicine to treat various diseases including diabetes mellitus.

Objective: This study investigates the antidiabetic activities of Momordica charantia (bitter gourd) on streptozotocin-induced type 2 diabetes mellitus in rats.

Materials and methods: Male Wister rats were randomly assigned to 4 groups. Group I, Normal control; Group II, STZ diabetic; Group III and IV, Momordica charantia fruit juice was orally administered to diabetic rats (10?mL/kg/day either as prophylaxis for 14 days before induction of diabetes then 21 days treatment, or as treatment given for 21 days after induction of diabetes). The effects of MC juice were studied both in vivo and in vitro by studying the glucose uptake of isolated rat diaphragm muscles in the presence and absence of insulin. Histopathological examination of pancreas was also performed.

Results: This study showed that MC caused a significant reduction of serum glucose (135.99?±?6.27 and 149.79?±?1.90 vs. 253.40*?±?8.18) for prophylaxis and treatment respectively, fructosamine (0.99?±?0.01 and 1.01?±?0.04 vs. 3.04?±?0.07), total cholesterol, triglycerides levels, insulin resistance index (1.13?±?0.08 and 1.19?±?0.05 vs. 1.48?±?1.47) and pancreatic malondialdehyde content (p?p?p?Conclusions: Momordica charantia presents excellent antidiabetic and antioxidant activities and thus has great potential as a new source for diabetes treatment whether it is used for prophylaxis or treatment.     

Antidiabetic,antilipidemic, and antioxidant activities of Gouania longipetala methanol leaf extract in alloxan-induced diabetic rats

Abstract

Context: Gouania longipetala Hemsl. (Rhamnaceae) is used in folkloric medicine for treating diabetes mellitus and its associated symptoms.

Objective: This study evaluated the antidiabetic antilipidemic and antioxidant activities of the plant methanol leaf extract.

Materials and methods: Diabetes was induced in rats by intraperitoneal injection of alloxan monohydrate (160?mg/kg). Three test doses (50, 100, and 150?mg/kg) of G. longipetala extract (GLE) were administered orally and the effects were compared with glibenclamide (2?mg/kg). The effect of GLE on hyperglycemia and sub-acute study for 21?d were carried out using its effect on fasting blood sugar (FBS) level. Serum biochemistry and antioxidant activity were evaluated. Histopathological evaluation of the pancreas was also done.

Results: The LD₅₀ of G. longipetala was found to be >4000?mg/kg. The extract significantly (p?<?0.0001) decreased the FBS levels of treated rats from 16.2?±?2.03 to 6.5?±?1.52?mM/L at 150?mg/kg within 24?h. The extract decreased FBS levels of rats by 62.0, 74.8, and 75.0% on day 21 at 50, 100, and 150?mg/kg, respectively. GLE reduced the level of malondiadehyde from 23.0?±?1.34?to 10.3?±?0.43?mg/dL, increased superoxide dismutase activities from 2.97?±?0.34 to 5.80?±?0.53?IU/L at 150?mg/kg, and improved the serum lipid profile of treated rats. GLE also caused restoration of the altered histopathological changes of the pancreas.

Discussion and conclusion: Gouania longipetala demonstrated significant antidiabetic, antilipidemic, and antioxidant activities that may be due to its multiple effects involving both pancreatic and extra-pancreatic mechanisms.     

Protective potential of Tamarindus indica against gentamicin-induced nephrotoxicity

Context: Gentamicin is an antibiotic that is effective against Gram-negative microorganisms. However, its clinical applications are often limited due to nephrotoxic effects.

Objective: This study investigated the protective effects of aqueous-ethanol extract of Tamarindus indica L. (Leguminosae) fruits against gentamicin-induced renal toxicity.

Materials and methods: A daily dose of 200?mg/kg of 70% aqueous-ethanol extract derived from T. indica was employed in male rabbits as a co-therapy with gentamicin (80?mg/kg) for a period of three weeks. Serum and urinary renal function parameters and histological assessments were carried out and compared with one way analysis of variance (Graphpad prism version 5.00, Graphpad Software, San Diego, CA).

Results: The results showed that gentamicin-treated animals had significantly elevated blood urea nitrogen (54.1?±?2.6?mg/dl), serum creatinine (4.0?±?0.1?mg/dl), serum uric acid (2.3?±?0.1?mg/dl) and urinary protein excretion (3.8?±?0.3?mg/dl) with a fall in body weight (10?±?1%), creatinine clearance (0.7?±?0.09?ml/min), serum potassium (3.4?±?0.1?mEq/l), serum calcium (7.6?±?0.2?mg/dl), urinary volume (126?±?9?ml/24?h) and urinary lactate dehydrogenase secretion (103.1?±?4.2?U/l). However, animals treated by co-therapy with gentamicin and T. indica had significantly improved renal structure and function.

Discussion and conclusion: Co-therapy of 200?mg/kg/d of T. indica for a period of three weeks successfully prevented functional and morphological derangements caused by gentamicin as assessed by different renal function parameters and histological examinations.     

Effects of rosmarinic acid on an experimental model of painful diabetic neuropathy in rats

Context: Diabetic neuropathic (DN) pain is one of the diabetes complications. Rosmarinic acid (RA), a natural phenol antioxidant, shows some biological activities, including anti-inflammatory, analgesic, and anti-diabetic effects.

Objectives: We investigated the efficacy of RA administration (10 and 30?mg/kg) on streptozotocin (STZ)-induced neuropathy in rats.

Material and methods: The animals received saline or RA (10 and 30?mg/kg, p.o.; once daily) for 8 weeks. DN was evaluated by the tail flick (TF) method, formalin test, and tactile allodynia. At the end, all rats were weighed and underwent plasma glucose measurement.

Results: There was an increase in licking time during both formalin test phases in diabetic animals (138.5?±?10.7 and 448.7?±?2.6?s) that was decreased by RA10?mg/kg (103.5?±?7.5 and 284.4?±?19?s) and RA 30?mg/kg (81.8?±?11 and 192.7?±?14?s). RA 30?mg/kg caused anti-nociception during the early phase in treated controls (52.1?±?6?s) than untreated controls (99.4?±?5.9?s). The TF latency in diabetics (2.9?±?0.1?s) was increased in RA10 and 30?mg/kg treated diabetics (5.3?±?0.4 and 6?±?0.86?s). The paw withdrawal threshold (PWT) of the diabetics (3.6?±?0.7?g) was increased after RA 10 and 30?mg/kg (13.8?±?0.3 and 14?±?0.4?g) treatment. RA did not induce a significant change in body weight and plasma glucose of rats.

Conclusion: RA showed efficacy in amelioration of some aspects of DN. Therefore, RA makes a good candidate for DN treatment in clinical studies.