Evaluation of hypoglycemic activity of total lignans from Fructus Arctii in the spontaneously diabetic Goto-Kakizaki rats

Ethnopharmacological relevance

Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese Materia Medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions. Meanwhile it has been utilized extensively in a number of classical drug formulas as a major component for the treatment of noninsulin-dependent diabetes mellitus. It has also been reported recently that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. The aim of this study was to investigate hypoglycemic activity of total lignans from Fructus Arctii (TLFA) in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and the mechanism of its hypoglycemic activity.

Materials and methods

Male GK rats and normal Wistar rats were used in this study, GK rats fed twice daily were given TLFA (300 mg/kg) or nateglinide (50 mg/kg) orally before each meal for 12 weeks. Besides common evaluation indexes of hypoglycemic activity such as blood glucose level, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters such as cholesterol (CHOL), triglycerides (TG), et al., in rat serum. The effects of TLFA on insulin secretion and pancreas tissue sections, the levels of serum glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the α-glucosidase inhibitory activity of TLFA in vitro were investigated.

Results

TLFA demonstrated stable and long-lasting hypoglycemic activity in GK rats and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. Both TLFA and nateglinide controlled the glycosylated hemoglobin levels of the experimental animals very well. Stimulation of insulin secretion was proved to be one of the hypoglycemic mechanism of TLFA, promoting the release of GLP-1 should be another one, and ɑ-glucosidase inhibitory activity of TLFA also contributes to its hypoglycemic activity. In this study, we didn't found that TLFA could effect the body weight of GK rats, which was also verified by the changes of biochemical parameters of blood in experimental rats.

Conclusion

The results of this study indicates that TLFA has significant hypoglycemic potential in GK rats, and it may be acting through stimulating insulin secretion, promoting the release of GLP-1, and decreasing intestinal absorption of glucose.     

Astragalus polysaccharide improves insulin sensitivity in KKAy mice: Regulation of PKB/GLUT4 signaling in skeletal muscle

Ethnopharmacological relevance

Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus Bunge (Leguminosae) that has been used in traditional Chinese medicine for treating diabetes.

Aim of the study

To study the mechanisms by which APS ameliorates diabetes, we examined whether treatment with APS improves insulin sensitivity in insulin-resistant mice and whether this is associated with an improvement of dysregulated protein kinase B and glucose transporter 4 expressions in skeletal muscle.

Methods

APS (700 mg kg⁻¹ day⁻¹) or vehicle was administered to 12-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Changes in body weight, blood glucose level, insulin resistance index, and oral glucose tolerance were routinely evaluated. The expressions of protein kinase B and glucose transporter 4 in skeletal muscle tissues were determined with Western blot.

Results

KKAy mice developed persistent hyperglycemia, impaired glucose tolerance and insulin resistance. Insulin-stimulated protein kinase B phosphorylation and glucose transporter 4 translocation were significantly decreased in KKAy compared to age-matched C57BL/6J mice. APS treatment ameliorated hyperglycemia and insulin resistance. Although the content of protein kinase B and glucose transporter 4 in KKAy skeletal muscle were not affected by APS, insulin-induced protein kinase B Ser-473 phosphorylation and glucose transporter 4 translocation in skeletal muscle were partially restored by APS treatment. In contrast, APS did not have any effect on C57BL/6J mice.

Conclusions

These results indicate that APS can regulate part of the insulin signaling in insulin-resistant skeletal muscle, and that APS could be a potential insulin sensitizer for the treatment of type 2 diabetes.     

Hypoglycemic effect of aqueous extract of seabuckthorn (Hippophae rhamnoides L.) seed residues in streptozotocin‐induced diabetic rats

An extract of seabuckthorn (Hippophae rhamnoides L.) seed residues has been shown to possess hypoglycemic and hypolipidemic properties in normal mice. The present study investigated the effects of an aqueous extract of seabuckthorn seed residues (ASSR) on serum glucose, lipid profiles and antioxidant parameters in streptozotocin‐induced diabetic rats. Male Sprague‐Dawley rats were divided into four groups: a normal control group; diabetic control group; diabetic groups supplemented with 5 mg/kg body weight glibenclamide (reference drug) and 400 mg/kg body weight ASSR. Diabetes in rats was induced by intraperitoneal injection of streptozotocin (45 mg/kg body weight). Vehicle (distilled water), glibenclamide and ASSR were administered orally to normal and diabetic rats once a day lasting for 4 weeks. The data showed that administration of ASSR significantly lowered the serum glucose, triglyceride and nitric oxide levels in diabetic rats. Moreover, ASSR treatment also increased serum superoxide dismutase activity and glutathione level markedly. These results show that ASSR has hypoglycemic, hypotriglyceridemic and antioxidant effects in streptozotocin‐induced diabetic rats, suggesting that ASSR supplementation can be useful in preventing diabetic complications associated with hyperlipidemia and oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd.     

Inhibitory effect of total lignan from Fructus Arctii on aldose reductase

The potent inhibitory effect of the total lignan from the plant Fructus Arctii on aldose reductase was observed, suggesting its preventive potential on diabetic complications upon long term administration. Copyright © 2009 John Wiley & Sons, Ltd.     

Extracts of Scutellaria baicalensis Reduced Body Weight and Blood Triglyceride in db/db Mice

Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia, atherosclerosis, hypertension, dysentery, inflammatory diseases, and the common cold. The present study was performed to investigate the anti‐obesity and anti‐dyslipidemia effect of Scutellaria baicalensis extracts (SBE) in type 2 diabetic db/db mice. Male db/db mice were divided into three groups (n = 5) and orally administrated vehicle (control), SBE 10, and 100 mg/kg body weight/day for 4 weeks everyday. Administration of SBE improves weight gain, hypertriglyceridemia, and hyperinsulinemia in db/db mice. In obese db/db mice, SBE treatment also reduced plasma alanine aminotransferase levels. In the livers of db/db mice, SBE promoted 5' AMP‐activated protein kinase activity and restored metabolic process and insulin signaling pathways. Our data demonstrate that SBE exerts potent anti‐obesity and anti‐hypertriglyceride effects suggesting its useful potential function as adjuvant therapeutic agent for the treatment of weight gain and hypertriglyceridemia. Copyright © 2012 John Wiley & Sons, Ltd.     

Mixture of five herbal extracts ameliorates pioglitazone-induced aggravation of hepatic steatosis via activating the adiponectin receptor 2/AMP-activated protein kinase signal pathway in diabetic KKAy mice

OBJECTIVE: To assess the effect of a mixture of five herbal extracts(FT-5) on insulin resistance, glucose/lipid metabolism, hepatic steatosis, and to investigate whether the combination of FT-5 and pioglitazone would provide a robust effect on diabetes treatment, while may minimize undesirable side-effects of pioglitazone in diabetic Ay gene(KKAy)mice.METHODS: Seven-week-old KKAy mice were randomly divided into five groups: control(CON)group, FT-5(2.0 g/kg) group, pioglitazone(20 mg/kg)(PIO) group, pioglitazone(20 mg/kg) + FT-5(2.0 g/kg)(P + F) group. Age-matched C57 BL/6 J micewere used as the control group. After seven weeks of continuous intragastric administration of medication, the glucose metabolism, insulin sensitivity and lipid metabolism of KKAy mice were evaluated by assessing the fasting blood glucose(FBG), oral glucose tolerance test(OGTT), fasting serum insulin(FINS), insulin tolerance test(ITT), homeostasis model of assessment-insulin resistance index(HOMA-IR), total cholesterol(TC), total triglycerides(TG), and free fatty acids(FFA) in plasma and liver.Plasma and hepatic adiponectin were measured via enzyme-linked immunosorbent assays. Genes related to adipogenesis and lipolysis in white adipose tissues(WAT) and liver were examined by real-time polymerase chain reaction. Lipid metabolism-related protein expression in the liver of KKAy mice were detected by Western blotting.RESULTS: PIO treatment remarkably improved insulin resistance. However, it also showed substantial side effects. FT-5 group exhibited no significant decrease in serum glucose. However, it reduced fasting plasma TG levels and improved hepatic steatosis of KKAy mice. P + F group showed improved insulin resistance and similar body weight gain, as compared with control group. The m RNA expression of genes related to fatty acid oxidation was markedly up-regulated in the liver of P + F group.Pioglitazone administration markedly decreased the phosphorylation levels of AMPK, as compared with all other groups. Besides, even though plasma adiponectin increased in PIO, FT-5, P + F group, adipo R2 gene expression significantly decreased in the liver of PIO group.CONCLUSION: FT-5 decreased plasma TG and alleviated aggravating hepatic steatosis induced by pioglitazone in KKAy mice. FT-5's mechanism might be associated with its ability to activate the Adipo R2/AMPK pathway.     

Cognitive Ameliorating Effect of Acanthopanax koreanum Against Scopolamine‐Induced Memory Impairment in Mice

Acanthopanax koreanum Nakai (Araliaceae) is one of the most widely cultivated medicinal plants in Jeju Island, Korea, and the roots and stem bark of A. koreanum have been traditionally used as a tonic agent for general weakness. However, the use of A. koreanum for general weakness observed in the elderly, including those with declined cognitive function, has not been intensively investigated. This study was performed to investigate the effect of the ethanol extract of A. koreanum (EEAK) on cholinergic blockade‐induced memory impairment in mice. To evaluate the ameliorating effects of EEAK against scopolamine‐induced memory impairment, mice were orally administered EEAK (25, 50, 100, or 200 mg/kg), and several behavioral tasks, including a passive avoidance task, the Y‐maze, and a novel object recognition task, were employed. Besides, western blot analysis was conducted to examine whether EEAK affected memory‐associated signaling molecules, such as protein kinase B (Akt), Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII), and cAMP response element‐binding protein (CREB). The administration of EEAK (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine‐induced cognitive impairment in the passive avoidance task, the Y‐maze, and the novel object recognition task. The phosphorylation levels of both Akt and CaMKII were significantly increased by approximately two‐fold compared with the control group because of the administration of EEAK (100 or 200 mg/kg) (p < 0.05). Moreover, the phosphorylation level of CREB was also significantly increased compared with the control group by the administration of EEAK (200 mg/kg) (p < 0.05). The present study suggests that EEAK ameliorates the cognitive dysfunction induced by the cholinergic blockade, in part, via several memory‐associated signaling molecules and may hold therapeutic potential against cognitive dysfunction, such as that presented in neurodegenerative diseases, for example, Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.     

Hypoglycemic effects of malonyl‐ginsenosides extracted from roots of Panax ginseng on streptozotocin‐induced diabetic mice

Hypoglycemic effects of malonyl‐ginsenosides (MGR), extracted from roots of Panax ginseng, were examined in streptozotocin‐ (STZ‐) induced diabetic mice. Animals received daily intravenous injections of MGR in doses of 30, 60, 120 mg/kg. At a dose of 120 mg/kg, MGR reduced the fasting blood glucose level of diabetic mice by 77.8% (76.7 ± 8.5 mg/dl versus 345.2 ± 35.8 mg/dl, P < 0.01). The same dose also showed a marked improvement in glucose tolerance of 80% (75.3 ± 10.8 mg/dl versus 375.6 ± 43.3 mg/dl, P < 0.01) in diabetic mice after four days. The alkali hydrolysis productions of MGR, ginseng panaxadiol (PDS), malonic acid and a mixture of malonic acid with PDS, showed no effects on fasting blood glucose levels indicated the hypoglycemic effect of MGR relied on their unique esterified chemical structures. The findings from this study suggest that MGR extracted from Panax ginseng may be prescribed as adjunct to drug treatment for controlling diabetes mellitus. Copyright © 2009 John Wiley & Sons, Ltd.     

Chemoprotective effects of Ulva lactuca (green seaweed) aqueous‐ethanolic extract against subchronic exposure to benzo(a)pyrene by CYP1A1 inhibition in mice

The protective effect of the supplementation with an aqueous‐ethanolic extract obtained from Ulva lactuca (Delile) green seaweed on benzo[a] pyrene‐induced damage in mice was evaluated. Animals were treated with oral doses of U. lactuca extract (100 and 400 mg/kg) for 9 weeks. They were exposed to 50 mg/kg of oral doses of benzo(a)pyrene starting from the second week and up to the fifth week. Groups treated with benzo(a)pyrene only (second to fifth weeks), sunflower oil (vehicle, 9 weeks), or U. lactuca extract (100 and 400 mg/kg, 9 weeks) were also included in the study. The treatment with 400 mg/kg of the extract ameliorated the oxidative damage, decreased IL‐1β and TNF‐α levels, and favorably regulated the antioxidant defenses compared with benzo(a)pyrene‐exposed group. The benzo(a)pyrene‐induced DNA damage was also reduced, as it was evidenced by the lower micronucleus formation in U. lactuca extract‐supplemented animals. The extract protected the hepatic tissue, and it reduced the liver activity/expression of CYP1A1. These results altogether suggested a chemoprotective effect of U. lactuca extract against benzo(a)pyrene‐induced‐toxicity in mice, probably associated with an inhibitory effect of carcinogen bioactivation.     

Inhibition of UDP‐Glucuronosyltransferase (UGT) Isoforms by Arctiin and Arctigenin

Arctiin is the major pharmacological ingredient of Fructus Arctii, and arctigenin is the metabolite of arctiin formed via the catalysis of human intestinal bacteria. The present study aims to investigate the inhibition profile of arctiin and arctigenin on important phase II drug‐metabolizing enzymes UDP‐glucuronosyltransferases (UGTs), indicating the possible herb–drug interaction. In vitro screening experiment showed that 100 μM of arctiin and arctigenin inhibited the activity of UGT1A3, 1A9, 2B7, and 2B15. Homology modeling‐based in silico docking of arctiin and arctigenin into the activity cavity of UGT2B15 showed that hydrogen bonds and hydrophobic interactions contributed to the strong binding free energy of arctiin (?8.14 kcal/mol) and arctigenin (?8.43 kcal/mol) with UGT2B15. Inhibition kinetics study showed that arctiin and arctigenin exerted competitive and noncompetitive inhibition toward UGT2B15, respectively. The inhibition kinetic parameters (K_i) were calculated to be 16.0 and 76.7 μM for the inhibition of UGT2B15 by arctiin and arctigenin, respectively. Based on the plasma concentration of arctiin and arctigenin after administration of 100 mg/kg of arctiin, the [I]/K_i values were calculated to be 0.3 and 0.007 for arctiin and arctigenin, respectively. Based on the inhibition evaluation standard ([I]/K_i < 0.1, low possibility; 0.1 < [I]/K_i < 1, medium possibility; [I]/K_i > 1, high possibility), arctiin might induce drug–drug interaction with medium possibility. Based on these results, clinical monitoring the utilization of Fructus Arctii is very important and necessary. Copyright © 2016 John Wiley & Sons, Ltd.     

Protective Effects of Lepidium meyenii (Maca) Aqueous Extract and Lycopene on Testosterone Propionate‐Induced Prostatic Hyperplasia in Mice

The inhibitory effect of maca extractant, lycopene, and their combination was evaluated in benign prostatic hyperplasia (BPH) mice induced by testosterone propionate. Mice were divided into a saline group, solvent control group and testosterone propionate‐induced BPH mice [BPH model group, solvent BPH model group, benzyl glucosinolate group (1.44 mg/kg), maca group (60 mg/kg), lycopene treated (15, 5, and 2.5 mg/kg), maca (30 mg/kg) combine lycopene treated (7.5, 2.5, and 1.25 mg/kg), and finasteride treated]. Benzyl glucosinolate was used in order to evaluate its pharmacological activity on BPH to find out whether it is the major active component of maca aqueous extract. Finasteride was used as positive control. The compounds were administered once for 30 successive days. Compared with solvent BPH model group, BPH mice fed with maca (30 mg/kg) and lycopene (7.5 mg/kg) combination exhibited significant reductions in the prostatic index, prostatic acid phospatase, estradiol, testosterone, and dihydrotestosterone levels in serum. They also had similar histological compared with those aspects observed in the mice in the solvent control group. The results indicated that combination of maca and lycopene synergistically inhibits BPH in mice. Copyright © 2017 John Wiley & Sons, Ltd.     

Effects of Hypericum perforatum extract on diabetes‐induced learning and memory impairment in rats

Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin‐induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients. Copyright © 2010 John Wiley & Sons, Ltd.     

桑叶多糖降血糖作用及其机制研究

目的探讨桑叶多糖降血糖的作用机制。方法以四氧嘧啶诱导小鼠糖尿病模型,桑叶多糖以0.25、0.50、1.00 g/kg ig给药,连续6周,每周称体质量;在实验2、4、6周末各测空腹血糖;实验末期进行糖耐量试验,测定糖化血清蛋白、血清胰岛素水平;测定肝组织肝糖元、肝匀浆蛋白水平及己糖激酶(HK)、丙酮酸激酶(PK)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)水平。结果桑叶多糖能明显缓解糖尿病小鼠症状;具有明显控制糖尿病小鼠空腹血糖值升高,降低糖化血清蛋白和血糖曲线下面积的作用;具有促进血清胰岛素、肝HK的分泌和肝糖元的合成,提高肝SOD活性,降低肝MDA水平,促进体质量恢复的作用;桑叶多糖中剂量还具有促进肝PK分泌的作用,而对肝GSH-Px活性影响不明显;糖尿病小鼠肝脏、肾脏和脾脏指数均增高,桑叶多糖具有降低脏器指数的作用。结论桑叶多糖通过提高四氧嘧啶糖尿病小鼠抗氧化能力,使胰岛素分泌增加,同时提高肝HK、PK活性等综合作用,促使血糖进入肝细胞,使肝糖元合成增加,葡萄糖氧化分解加快,从而达到调节糖代谢、降低血糖、改善糖尿病症状的作用。     

Scopoletin Supplementation Ameliorates Steatosis and Inflammation in Diabetic Mice

Scopoletin is a bioactive component in many edible plants and fruits. This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high‐fat diet fed type 1 diabetic mice by comparison with metformin. Scopoletin (0.01%, w/w) or metformin (0.5%, w/w) was provided with a high‐fat diet to streptozotocin‐induced diabetic mice for 11 weeks. Both scopoletin and metformin lowered blood glucose and HbA_1c, serum ALT, TNF‐α and IL‐6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group. Scopoletin or metformin down‐regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up‐regulated Cyp7a1 gene. Hepatic PPARγ and DGAT2 protein levels were also down‐regulated in scopoletin or metformin group compared with the control group. Scopoletin or metformin also inhibited hepatic fatty acid synthase and phosphatidate phosphohydrolase activities. These results suggest that scopoletin protects against diabetes‐induced steatosis and inflammation by inhibiting lipid biosynthesis and TLR4‐MyD88 pathways. Copyright © 2017 John Wiley & Sons, Ltd.     

Bakuchiol Contributes to the Hepatotoxicity of Psoralea corylifolia in Rats

Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has antiinflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG‐CoA reductase, BSEP, PPARα, SREBP‐2, and MRP3 were measured. Many abnormalities were observed in the bakuchiol‐treated groups including suppression of weight gain and food intake, change of some parameters in serum biochemistry, and increased weight of liver. The mRNA expression of CYP7A1, HMG‐CoA reductase, PPARα, and SREBP‐2 decreased in bakuchiol‐treated group, the expression of BSEP increased in bakuchiol‐treated low dosage, and the expression of BSEP decreased in bakuchiol‐treated high dosage. In conclusion, we provide evidence for the first time that bakuchiol can induce cholestatic hepatotoxicity, suggesting potential hepatotoxicity. The mechanism may be related to effects on liver lipid metabolism, but further investigation is necessary. Copyright © 2017 John Wiley & Sons, Ltd.     

A Novel Extract of Gymnema sylvestre Improves Glucose Tolerance In Vivo and Stimulates Insulin Secretion and Synthesis In Vitro

Herbal medicines, especially plant‐derived extracts, have been used to treat Type 2 diabetes mellitus (T2DM) for many centuries, and offer the potential of cheap and readily available alternatives to conventional pharmaceuticals in developing countries. Extracts of Gymnema sylvestre (GS) have anti‐diabetic activities and have been used as a folk medicine in India for centuries. We have investigated the effects of a novel high molecular weight GS extract termed OSA® on glucose tolerance in insulin‐resistant ob/ob mice, and on insulin secretion and synthesis by isolated mouse islets. Single administration of OSA® (500 mg/kg) to ob/ob mice 30 min before an intraperitoneal glucose load improved their abnormal glucose tolerance. In vitro studies indicated that OSA® (0.25 mg/ml) initiated rapid and reversible increases in insulin secretion from isolated mouse islets at substimulatory (2 mM) and stimulatory (20 mM) glucose concentrations. In addition, prolonged treatment (24–48 h) of mouse islets with OSA® elevated the expression of preproinsulin mRNA and maintained the total insulin content of mouse islets in the presence of stimulated insulin secretion. These effects of OSA® are consistent with its potential use as a therapy for the hyperglycemia associated with obesity‐related T2DM. Copyright © 2012 John Wiley & Sons, Ltd.     

Antihyperglycemic effects of total flavonoids from Polygonatum odoratum in STZ and alloxan-induced diabetic rats

Aim of the study

Total flavonids of Polygonatum(P) odoratum (TFP) were tested for anti-diabetic activity in streptozotocin (STZ)-induced diabetic mice and alloxan-induced diabetic rats.

Materials and methods

Rhizoma Polygonati Odorati, well-known Chinese traditional medicine, is widely used for treatment of diverse diseases for example diabetes. In our study, TFP was extracted by 70% ethanol and purified by macroreticular resin. The experiments were designed to detect the anti-diabetic activity of TFP by determination of blood glucose (BG) using one touch gluco-meter and insulin levels by using a radioimmunoassay kit in streptozotocin (STZ)-induced diabetic mice and alloxan-induced diabetic rats and alpha-amylase inhibitory activity by alpha-amylase inhibition assay in vitro.

Results

TFP had beneficial effects on regulation of blood glucose. Daily administration with 50–200 mg/kg body weight of TFP for 9 days can reduce significantly hyperglycemia in STZ-induced diabetic mice. Thirtieth day administration with TFP (50–200 mg/kg body weight) also decreased significantly fasting blood glucose in alloxan-induced diabetic rats. The hypoglycemic effect of TFP at 50 and 100 mg/kg is less than that of acarbose 20 mg/kg and gliclazide 15 mg/kg. The hypoglycemic effects of TFP at 200 mg/kg is similar to that of acarbose 20 mg/kg and gliclazide 15 mg/kg. TFP also could increase significantly the insulin level in alloxan-induced type 2 diabetic rats (P < 0.05) compared with control. Alpha-amylase inhibition assay in vitro showed that TFP inhibited significantly alpha-amylase activity in a dose-dependent manner.

Conclusions

TFP possess significant dose-dependent anti-diabetic activity. TFP is one of the primary hypoglycemic active compounds of Polygonatum odoratum which would worth further study and development.     

The antidiabetic activity of total lignan from Fructus Arctii against alloxan-induced diabetes in mice and rats

The antidiabetic activity of the total lignan from the plant Fructus Arctii, used in China for the control of diabetes, was investigated in models of alloxan-induced diabetic mice and hyperglycemic-hyperlipidemic diabetic rats. The biochemical parameters studied were: blood glucose, glucose tolerance, serum insulin, serum triglycerides, total cholesterol and high density lipoprotein (HDL). Total lignan was given to mice and rats daily for 10 days at doses of 2.0, 1.0, 0.5 g/kg and 1.38, 0.69, 0.35 g/kg respectively. The alloxan-diabetic animals showed significant reductions in plasma glucose, triglycerides and total cholesterol after treatment with the total lignan from the plant Fructus Arctii and glibenclamide (used as standard) compared with the diabetic controls, while the glucose tolerance, serum insulin level and HDL-cholesterol were elevated without the risk of hypoglycemia. In conclusion, the total lignan from the plant Fructus Arctii has been proven to be a safer antidiabetic agent and might help to prevent diabetic complications. It can serve as a good adjuvant in the present armamentarium of antidiabetic drugs.     

Momordica charantia Ameliorates Insulin Resistance and Dyslipidemia with Altered Hepatic Glucose Production and Fatty Acid Synthesis and AMPK Phosphorylation in High‐fat‐fed Mice

Momordica charantia Linn. (Cucurbitaceae) fruit is commonly known as bitter melon. C57BL/6J mice were firstly divided randomly into two groups: the control (CON) group was fed with a low‐fat diet, whereas the experimental group was fed a 45% high‐fat (HF) diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and still on HF diet and was given orally M. charantia extract (MCE) or rosiglitazone (Rosi) or not for 4 weeks. M. charantia decreased the weights of visceral fat and caused glucose lowering. AMP‐activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. MCE significantly increases the hepatic protein contents of AMPK phosphorylation by 126.2–297.3% and reduces expression of phosphenolpyruvate carboxykinase (PEPCK) and glucose production. Most importantly, MCE decreased expression of hepatic 11beta hydroxysteroid dehydroxygenase (11beta‐HSD1) gene, which contributed in attenuating diabetic state. Furthermore, MCE lowered serum triglycerides (TGs) by inhibition of hepatic fatty acid synthesis by dampening sterol response element binding protein 1c and fatty acid synthase mRNA leading to reduction in TGs synthesis. This study demonstrates M. charantia ameliorates diabetic and hyperlipidemic state in HF‐fed mice occurred by regulation of hepatic PEPCK, 11beta‐HSD1 and AMPK phosphorylation. Copyright © 2013 John Wiley & Sons, Ltd.     

Antidiabetic activity of Passiflora incarnata Linn. in streptozotocin-induced diabetes in mice

Ethnopharmacological relevance

The present study was designed to investigate the hypoglycemic and hypolipidemic properties of Passiflora incarnata Linn. leaves which are widely used as traditional treatment for diabetes mellitus.

Materials and methods

The methanolic extracts of leaves of Passiflora incarnata were administered orally (100 and 200 mg/kg, for 15 days) to streptozotocin-induced diabetic mice. Hypoglycemic effects, oral glucose tolerance test, change in body weight and lipid profile of diabetic mice treated with methanolic extracts were assessed and compared with normal, diabetic control and standard drug treated mice. Histological examination during 15 days of treatment was also carried out.

Results

Methanolic extract (200 mg/kg) produced a significant reduction in fasting blood glucose level in streptozotocin-induced diabetic mice. Significant differences were also observed in urine glucose level, oral glucose tolerance test, serum lipid profile and body weight of methanolic extract treated diabetic mice, when compared with diabetic, normal and standard drug treated mice. Histopathological studies of the pancreas showed comparable regeneration of the cells by extract which were earlier necrosed by streptozotocin.

Conclusion

Methanolic extract of Passiflora incarnata exhibit significant anti-hyperglycemic and hypolipidemic activities in streptozotocin-induced diabetes in mice.