Arctigenic acid,the key substance responsible for the hypoglycemic activity of Fructus Arctii

We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively.GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice.This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.     

Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice

Human acatalasemia may be a risk factor for the development of diabetes mellitus. However, the mechanism by which diabetes is induced is still poorly understood. The impact of catalase deficiency on the onset of diabetes has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of diabetogenic alloxan. The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan. A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic β cell apoptosis in acatalasemic mice in comparison to wild-type mice. Catalase activity remained low in the acatalasemic pancreas without the significant compensatory up-regulation of glutathione peroxidase or superoxide dismutase. Furthermore, daily intraperitoneal injection of angiotensin II type 1 (AT1) receptor antagonist telmisartan (0.1 mg/kg body weight) prevented the development of alloxan-induced hyperglycemia in acatalasemic mice. This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic β cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.     

Total phenolic,flavonoid contents,and biological activities of stem extracts of Astragalus spinosus (Forssk.) Muschl. grown in Northern Border Province,Saudi Arabia

Background and objectiveGenus Astragalus belongs to the family Fabaceae and is one among the largest genera consisting of around 3000 species. The plants have been used traditionally in treatment of various ailments in folklore. The study was planned to assess the analgesic and inflammatory activity of Astragulus spinosus (Forssk.) Muschl extract of the stem.Materials and methodsCourse powder of stems of Astragulus spinosus was extracted using chloroform and methanol as solvents. Folin ciocalteu method was employed for determination of the phenolic acid content. Aluminum chloride colorimetric procedure was followed for estimating the flavonoid content. Both chloroform and methanolic extracts at 250 and 500 mg/kg, were tested for the analgesic activity, however, only methanolic extract was selected for anti-inflammatory property based on the results of analgesic activity. The analgesic effect was executed on male rats by the hot plate model. The anti-inflammatory effect was studied in the carrageenan rat paw edema model. The experimental information was interpreted statistically using one-way ANOVA and p < 0.05 was used to express importance of the results.ResultsThe total phenolics of the methanol extract was 420 µg and that of chloroform extract was 265 µgwhile total flavonoid content in terms of quercetin was found to be 68 µg and 17.5 µg for methanol and chloroform extract respectively. Only methanolic extract exhibited significant (p < 0.001) analgesic activity by elevating the pain threshold starting from 15 min. The methanolic extract inhibited (p < 0.001) the edema in carrageenan induced model. The performance of higher dose (500 mg/kg) was better with reference to lower dose (250 mg/kg).ConclusionOutcome of the results show that the methanolic stem extracts exhibited significant analgesic and anti-inflammatory-like activity with reference to chloroform extract. Credit of which is given to flavonoids and phenolic content present in the methanolic extract. However, more research is suggested to establish the safety and effectiveness of the herbal drug to manage diseased states including pain and inflammation.     

In vitro alpha-amylase inhibition and in vivo antioxidant potential of Amaranthus spinosus in alloxan-induced oxidative stress in diabetic rats

Amaranthus spinosus Linn. (Amaranthaceae), commonly known as “Mulluharivesoppu” in Kannada, is used in the Indian traditional system of medicine for the treatment of diabetes. The present study deals with the scientific evaluation of alpha amylase and the antioxidant potential of methanol extract of A. spinosus (MEAS). The aim of this study was to investigate in vitro alpha-amylase enzyme inhibition by CNPG3 (2-chloro-4-nitrophenol α-d-maltotrioside) and in vivo antioxidant potential of malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and total thiols (TT) in alloxan-induced diabetic rats of a methanolic extract of A. spinosus. Blood sugar was also determined in MEAS-treated alloxan-induced diabetic rats. MEAS showed significant inhibition of alpha-amylase activity and IC₅₀ 46.02 μg/ml. Oral administration of MEAS (200 and 400 mg/kg) for 15 days showed significant reduction in the elevated blood glucose, MDA and restores GSH, CAT and TT levels as compared with a diabetic control. The present study provides evidence that the methanolic extract of A. spinosus has potent alpha amylase, anti-diabetic and antioxidant activities.     

In vitro alpha-amylase and alpha-glucosidase inhibitory activity and in vivo antidiabetic activity of Quercus coccifera (Oak tree) leaves extracts

Quercus species are group of plants known as oak which represent important genus of Fagaceae family. These species are widely distributed in Mediterranean countries. Many of those species used in traditional medicine to treat and prevent various human disorders such as diabetes. Exhausted extraction for Quercus coccifera leaves were carried out using n-hexane, chloroform, methanol, boiled water and microwaved water. Extracts were subjected to phytochemical screening, acute toxicity study, and in vitro and in vivo animal model to evaluate antidiabetic activity of the produced extracts. The highest in vitro activity against α-amylase and α-glucosidase activity was obtained from methanolic extract with an IC₅₀ of 0.17 and 0.38 µg/ml respectively and better than the positive control acarbose. While the rest of the extract was either with moderate or low activity. Similarly, in the in vivo study, methanolic extract with a concentration of 200 mg/kg/day was able to reduce the blood glucose level for the diabetic mice to 146.8 mg/dL with normal bodyweight and biochemical signs when compared to the normal mice group. While the rest of the extracts were either with moderate or low ability to maintain blood glucose level for diabetic mice with few signs of hepatic and renal toxicity and weight loss. All data were statistically significantly different with p-value of less than 0.001 at confidence interval of 95% with high variance homogeneity. In conclusion, methanolic plant leaves extract of Q. coccifera can possibly be used alone to control the elevation of blood glucose level with a renal and hepatic protective property.     

Cytoprotective and anti-diabetic effects of Derris reticulata aqueous extract

The current study was aimed to investigate pancreatic protective and anti-diabetic activities of the aqueous extract of Derris reticulata stem. First, we evaluated a cytoprotective potential of D. reticulata extract on alloxan-induced damage in vitro. Treatment with D. reticulata extract at the doses of 250 and 500 μg/ml significantly increased cell viability of the pancreatic β-cell line RINm5F after exposure of alloxan. The anti-hyperglycemic activity of D. reticulata extract was further studied in alloxan-induced diabetic rats. A significant reduction in blood glucose level along with an increase in body weight was observed in diabetic rats treated with D. reticulata extract at 250 mg/kg body weight for 15 days. Serum aspartate transaminase and alanine transaminase levels were also significantly decreased compared to diabetic control rats. In accordance with in vitro cytoprotective effect, histopathological examination revealed that pancreatic islet cells of the extract-treated diabetic rat were less damage than those of the untreated diabetic group. In order to find another possible mechanism of action underling hypoglycemic activity, the effect on glucose absorption was examined using everted sac jejunum. The results showed that D. reticulata extract suppressed glucose absorption from small intestine. To corroborate safety use of D. reticulata extract, acute oral toxicity was also conducted in rats. Our results showed that none of the tested doses (250, 500, 1,000, and 2,000 mg/kg) induced signs of toxicity or mortality after administration of the extract. The results suggested that D. reticulata extract possess anti-diabetic activity, which resulting from its pancreatic cytoprotective effect and inhibition of intestinal glucose absorption.     

Consequence of the antioxidant activities and tyrosinase inhibitory effects of various extracts from the fruiting bodies of Pleurotus ferulae

This study was initiated to screen the antioxidant activities, tyrosinase inhibitory effects on the fruiting bodies of Pleurotus ferulae extracted with acetone, methanol and hot water. The antioxidant activities were performed on β-carotene–linoleic acid, reducing power, DPPH, ferrous ions chelating abilities, and xanthine oxidase. In addition to this, phenolic compounds were also analyzed. The methanolic extract showed the strongest β-carotene–linoleic acid inhibition and high reducing power as compared to other extracts. The scavenging effects on DPPH radicals, the acetonic and methanolic extracts were more effective than hot water extracts. The strongest chelating effect was obtained from the methanolic extract as compared to the tested synthetic antioxidant. Gallic acid, protocatechuic acid, caffeic acid, vanillin, ferulic acid, naringin, resveratrol, naringenin, hesperetin, formononetin and biochanin-A were detected from acetonitrile and hydrochloric acid (5:1) solvent extract. Xanthine oxidase and tyrosinase inhibitory activities of acetonic, methanolic, and hot water extracts of P. ferulae increased with increasing concentration. The results suggested that consumption of P. ferulae might be beneficial to the antioxidant, xanthine oxidase, and tyrosinase protection system of the human body against oxidative damage and others complications.     

Pharmacological evidence for the use of Cissus assamica as a medicinal plant in the management of pain and pyrexia

The existing therapeutic agents for the management of pain and pyrexia are not very efficient and accompanied by numerous side effects. Thus, new effective agents are the most needed. The present study investigates bioactivities and phytochemical screening of different parts of Cissus assamica (Vitaceae), a Bangladeshi tribal medicinal plant. Three plant parts stems, leaves and roots were collected, washed, dried, powdered and then prepared for cold extraction. The methanolic stems and leaves extracts were fractioned with four and two solvents respectively. Different plant extracts were then investigated for in vivo antinociceptive activity and only methanolic leaves extract was investigated for in vivo antipyretic activity. In Swiss-albino mice, 200 and 400 mg/kg body weight doses were used for all extracts. In the peripheral antinociceptive activity, the methanolic stem extract and its dichloromethane, chloroform, pet ether fractions and methanolic roots extract at their both doses showed significant antinociceptive responses when compared to standard diclofenac sodium (60.49% inhibition). In the central antinociceptive activity, the response was found significant for methanolic stem and methanolic roots extract in their both doses compared to standard morphine. In antipyretic activity, methanolic leaves extract significantly reduced pyrexia level at 400 and 200 mg/kg body weight doses after two, three and 4 h of administration when compared to standard. So our findings indicate that this plant possesses noteworthy pharmacological activities which may be a basis for further researches to establish a possible mode of action of its different parts.     

Effect of the Zinc Oxide Nanoparticles and Thiamine for the Management of Diabetes in Alloxan-Induced Mice: a Stereological and Biochemical Study

This research was carried out to evaluate the antidiabetic effects of zinc oxide nanoparticles (ZnO NPs) and thiamine following experimental diabetes. Fifty-six 6-week-old female mice were used and divided into seven groups of eight animals. Diabetes was induced in fasted mice by using intraperitoneal (IP) injection of alloxan (180 mg/kg). Groups included (I) non-diabetic control, (II) thiamine (30 mg/l, IP), (III) alloxan-induced diabetic mice, (IV) diabetes + ZnO NPs (0.1 mg/kg IP), (V) diabetes + ZnO NPs (0.5 mg/kg IP), (VI) diabetes + ZnO NPs (0.1 mg/kg IP) + thiamine (30 mg/l, IP), and (VII) diabetes + ZnO NPs (0.5 mg/kg IP) + thiamine (30 mg/l, IP). Coincident with pancreas recovery, in diabetic treated mice (groups IV to VII), the mean islet volume, islets per square micrometer, and volume density of the pancreas had increased than in alloxan-induced diabetic mice. ZnO NPs and thiamine induced a decreasing blood glucose, lower serum triglyceride (TG), LDL, and total cholesterol (TC) levels in alloxan-induced diabetic mice treated with ZnO NPs and thiamine, simultaneously increasing HDL as well. In conclusion, ZnO NPs and thiamine are potent antidiabetic factors, and that, these compound supplementation possesses hypoglycemic properties and have effect on serum lipid parameters in diabetes mice.     

Phytochemical profiling and antioxidant potential of Daphne mucronata Royle and action against paracetamol-induced hepatotoxicity and nephrotoxicity in rabbits

The paracetamol-induced injuries of liver and kidneys in animals are mostly used to screen out the hepato and nephroprotective effect of extract or other therapeutic agents. In the present study total phenolic and flavonoid contents, in vitro antioxidant, and in vivo hepato/nephroprotective (on paracetamol-induced intoxication in experimental rabbits) potentials of the Daphne mucronata leaves methanolic extract were determined. For the identification of possible phytochemicals, HPLC (high performance liquid chromatography) analysis was carried out and a total of eight phenolic compounds; malic acid, gallic acid, chlorogenic acid, epigallocatechin gallate, quercetin, morin, ellagic acid, and rutin were identified. D. mucronata extract at doses of 250 and 500 mg/kg body weight were given for eight days to paracetamol intoxicated rabbits and the observed results were compared with standard Silymarin. The level of liver enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum triglyceride, serum cholesterol, serum bilirubin, and kidneys biomarkers like serum urea, uric acid, and creatinine, as well as lipid peroxidation malondialdehyde contents were increased while the antioxidant enzymes like reduced glutathione and total antioxidant capacity were decreased. Furthermore, histopathological analysis of the liver and kidney tissues of control and treated groups also confirmed the hepatoprotective and nephroprotective effect of the D. mucronata which was most probably due to its high antioxidant phenolic and flavonoid phytoconstituents.     

Antioxidant activities of the volatile oils and methanol extracts from olive stems

This study was designed to examine the chemical composition and antioxidant activities of the volatile oils and methanol extracts of Olea europaea L. (cvs) chemlali and neb jmel stems. GC and GC–MS analyses of the volatile oils resulted in the identification of 38 and 35 compounds, representing 91.1 and 87.4 % of the volatile oils. Phenylethyl alcohol was found in the volatile oil of each cultivar, which was also the major volatile component of cv. chemlali and cv. neb jmel stems. Besides benzyl alcohol, methyl salicylate and 3-ethenylpyridine were the main volatile compounds of cv. chemlali, while nonanal, 3-ethenylpyridine and benzyl alcohol of cv. neb jmel stems were also the main constituents. Significant differences were also found in total tannin contents among two cultivars, representing 8.10 mg CEQ/g DW in cv. chemlali and 20.47 mg CEQ/g DW in cv. neb jmel. The highest contents of total phenols and o-diphenols were observed in stems extracts of cv. neb jmel (78.26, and 9.56 mg/100 g, respectively). The HPLC profiles for methanol extracts from stems of cv. chemlali and cv. neb jmel showed that oleuropein, vanillic acid and gallic acid were the predominant free phenolic compounds. Antioxidant activities of the volatile oils and the methanolic extract from stems parts were evaluated by DPPH and ABTS⁺ radical-scavenging activity assays. In all tests, methanolic extracts obtained from stems parts showed better antioxidant activity than volatile oils. Principal components analysis of the phenolics content and antioxidant activities showed discrimination between methanol extracts of the two cultivars.     

Assessment of pharmacological activities of two medicinal plant of Bangladesh: Launaea sarmentosa and Aegialitis rotundifolia roxb in the management of pain,pyrexia and inflammation

Background

The current study aims at evaluating the analgesic, anti-pyretic and anti-inflammatory properties of methanolic extract of the stem, bark and leaves of Launaea sarmentosa and Aegialitis rotundifolia roxb.

Results

The AELS and AEAR extract presented a significant (***p < 0.001) dose dependent increase in reaction time in writhing method and showed inhibition of 63.1% and 57.1% respectively at the doses of 400 mg/kg body weight while standard drug showed (P < 0.001) inhibition of 69.23%. In tail immersion method, AELS and AEAR showed maximum time of tail retention at 30 min in hot water i.e. 6.93 sec and 6.54 sec respectively at highest doses of 400 mg/kg body weight than lower dose while standard pentazocine showed reaction time of 7.62 sec. The AELS and AEAR extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant inhibition of paw volume by 32.48% and 26.75% respectively at the dose of 400 mg/kg body weight while the value at the dose of 200 mg/kg body weight were linear to higher dose at the 3^rd hour of study. On the other hand, Standard indomethacin inhibited 40.13% of inflammation (***P < 0.001). In Cotton-pellet granuloma method, AELS and AEAR extract at the dose of 400 mg/kg body weight exhibited inhibition of inflammation of 34.7% and 29.1% respectively while standard drug showed (P < 0.001) inhibition of 63.22%. Intraperitoneal administration of AELS and AEAR showed dose dependent decrease in body temperature in brewer’s yeast induced hyperthermia in rats at both doses. However, AELS significantly decreased body temperature (***p < 0.001) at 400 mg/kg compared to control.

Conclusions

Present work propose that the methanolic extract of Launaea sarmentosa and Aegialitis rotundifolia roxb possesses dose dependent pharmacological action which supports its therapeutic use in folk medicine possibly mediated through the inhibition or blocking of release of prostaglandin and/or actions of vasoactive substances such as histamine, serotonin and kinins.     

Assessment of Toxic Effects of the Methanol Extract of Citrus macroptera Montr. Fruit via Biochemical and Hematological Evaluation in Female Sprague-Dawley Rats

Citrus macroptera Montr. (C. macroptera) is locally known as Satkara. The fruit of this plant is used as appetite stimulant and in the treatment of fever. This study therefore aimed to evaluate the toxic effects of the fruit extract using some biochemical and hematological parameters in rat model. The effects of methanol extract of Citrus macroptera Montr. fruit administered at 250, 500 and 1000 mg/kg body weight were investigated on hematological and biochemical parameters in Sprague-Dawley female rats. Moreover, histopathological study was performed to observe the presence of pathological lesions in primary body organs. The extract presented no significant effect on body weight, percent water content, relative organ weight and hematological parameters in rat. Significant decrease from control group was observed in the levels of triglyceride, total cholesterol, low density lipoprotein and very low density lipoprotein; thus leading to significant decrease of cardiac risk ratio, castelli''s risk index-2, atherogenic coefficient and atherogenic index of plasma at all doses. 500 mg/kg dose significantly decreased alkaline phosphatase (P<0.05), 1000 mg/kg dose significantly increased high density lipoprotein cholesterol (P<0.05) and 250 mg/kg dose significantly decreased the level of glycated hemoglobin (P<0.05) from the control group. There were no significant alterations observed with other serum biochemical parameters. Histopathological study confirmed the absence of inflammatory and necrotic features in the primary body organs. Study results indicate that methanolic fruit extract is unlikely to have significant toxicity. Moreover, these findings justified the cardio-protective, moderate hepato-protective and glucose controlling activities of the fruit extract.     

Comparative lipid and uric acid suppressing properties of four common herbs in high fat-induced obese mice with their total phenolic and flavonoid index

Our present study was designed to investigate the comparative anti-obesity efficacy of ethanolic extract of Azadirachta indica A. Juss., Trigonella foenum-graecum L., Allium sativum L. and Zingiber officinale Roscoe in high fat-induced mice with their total phenolic and flavonoid profile. Total phenolic and flavonoid content were determined by Folin–Ciocalteu's and Aluminium chloride UV method respectively. In our study, 55 healthy mice were separated into 11 groups to take their respective treatments. Lipid and uric acid profile were estimated by using the enzymatic colourimetric method. Ethanolic extract of A. indica contained the highest phenolic and flavonoid content. A. indica normal and high fat diet group showed reduced weight gaining tendency than other extract groups. A. indica at a dose of 400 mg/kg body weight significantly (p < 0.001) reduced serum cholesterol (SC), triglyceride (TG), and uric acid (UA) level than other three extracts when compared with the control group. Thus, a considerable correlation was found between serum uric acid reducing potentials of the present experimental extracts with a lipid-lowering profile. Pathological examination revealed that the average weight of liver and kidney were significantly decreased in A. indica normal. Results obtained from the present study it can be concluded that ethanolic extract of A. indica possesses better lipid-lowering efficacy than the other three herbs.     

Inhibition of Protein Kinase C Restores Na+, K+-ATPase Activity in Sciatic Nerve of Diabetic Mice

We have tested if inhibition of protein kinase C is able to prevent and/or to restore the decrease of Na+,K(+)-ATPase activity in the sciatic nerve of alloxan-induced diabetic mice. Mice were made diabetic by subcutaneous injection of 200 mg of alloxan/kg of body weight. The activity of Na+,K(+)-ATPase decreased rapidly (43% after 3 days) and slightly thereafter (58% at 11 days). We show that intraperitoneal injection of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C, prevents completely the loss of Na+,K(+)-ATPase activity produced by alloxan. Also, H7 injected into diabetic mice, 4-9 days after the injection of alloxan, restores the activity of the enzyme. The amount of activity recovered depends on the dose of H7 administered; complete recovery was reached with injection of 15 mg of H7/kg of body weight. The effect of H7 is transient, with a half-life of approximately 1 h.     

Effects of Se-enriched polysaccharides produced by Enterobacter cloacae Z0206 on alloxan-induced diabetic mice

In this study, the water-soluble selenium-enriched exopolysaccharides (Se-ECZ-EPS) were isolated from submerged culture broth of Enterobacter cloacae Z0206 through fermentation, ethanol precipitation and deproteinization. The protective effects of Se-ECZ-EPS on alloxan-induced diabetic mice were investigated. Diabetes was induced in ICR (Institute of Cancer Research) mice by administration of single doses of alloxan intraperitoneally (190 mg/kg body weight). Se-ECZ-EPS at a dose of 200 mg/kg body weight were administered per os (p.o.) as single dose per day to diabetes-induced mice for a period of 42 days. The decrease in body weight, serum insulin level, and the increase in blood glucose level, glycosylated serum protein (GSP), total cholesterol (TC) and triglycerides (TG) in liver were observed in diabetic mice. On the other hand, oral administration of Se-ECZ-EPS resulted in a significant reduction in fasting blood glucose levels, GSP, TC and TG contents in liver coupled with improvement of body weight and serum insulin level in comparison with diabetic control group. These results suggest that Se-ECZ-EPS possess significant protective and anti-diabetic effects in alloxan-induced diabetic mice.     

Effect of Gymnema montanum Leaves on Serum and Tissue Lipids in Alloxan Diabetic Rats

The effect of Gymnema montanum leaves on alloxaninduced hyperlipidemia was studied in male Wistar rats. Ethanolic extract of G. montanum leaves was administered orally and different doses of the extract on blood glucose, serum and tissue lipids, hexokinase, glucose-6-phosphatase, thiobarbituric acid–reactive substances (TBARS), hydroperoxides, and glutathione in alloxan-induced diabetic rats were studied. G. montanum leaf extract (GLEt) at doses of 50, 100, 200 mg/kg body weight for 3 weeks suppressed the elevated blood glucose and lipid levels in diabetic rats. GLEt at 200 mg/kg body weight was found to be comparable to glibenclamide, a reference drug. These data indicate that G. montanum represents an effective antihyperglycemic and antihyperlipidemic adjunct for the treatment of diabetes and a potential source of discovery of new orally active agent for future therapy.     

沙棘籽渣水提物对正常和糖尿病小鼠血糖的影响

本文研究了沙棘籽渣水提物(Aqueous extract of seabuckthorn seed residues,ASSR)对正常及糖尿病小鼠血糖、血脂代谢的影响。首先采用ASSR灌胃昆明种小鼠的急性毒性试验评价了ASSR的安全性;继而以250mg/kg和500 mg/kg剂量的ASSR连续灌胃正常小鼠3周;以250、500和800 mg/kg剂量的ASSR连续灌胃Al-loxan诱导的糖尿病小鼠3周,监测血糖,测定体重、血清胰岛素、总胆固醇和甘油三酯水平。结果显示:ASSR的LD50大于9.8 g/kg体重;连续给药3周,ASSR对正常小鼠的血糖和血脂代谢没有明显影响,但能明显降低糖尿病小鼠的血清葡萄糖和甘油三酯水平。上述结果表明:ASSR的LD50大于5 g/kg体重,按WHO急性毒性分级标准属于实际无毒级,其在实验性1型糖尿病小鼠模型上具有降血糖和降甘油三酯活性。     

Effect of <Emphasis Type="Italic">Gymnema montanum</Emphasis> leaves on red blood cell resistance to oxidative stress in experimental diabetes

The aim of the present study was to evaluate the protective effect of Gymnema montanum on red blood cell (RBC) membrane in diabetic rats during lipid peroxidation. Ethanol extract of G. montanum leaves (GLEt) was administered orally to alloxan-induced diabetic rats for 3 weeks, and the effects on blood glucose, insulin, lipid peroxidation markers, thiobarbituric acid reactive substances, hydroperoxides in plasma and antioxidant enzymes including superoxide dismutase, catalase and glutathione peroxidase activities in erythrocytes were studied. Administration of GLEt to diabetic animals at doses of 50, 100, and 200 mg/kg body weight lowered elevated blood glucose levels by 24, 35, and 66%, respectively, relative to untreated diabetic rats. In comparison, treatment with the known antidiabetic drug, glibenclamide (600 μg/kg body weight) decreased blood glucose concentrations by 51%. Plasma insulin concentrations were increased in the diabetic rat by 73% with GLEt (200 mg/kg body weight) and 45% with glibenclamide (600 μg/kg body weight). Although a significant decrease in the lipid peroxidation markers was observed in plasma on treatment with GLEt and glibenclamide, the RBC antioxidant levels were increased significantly in diabetic rats. Furthermore, erythrocytes from the GLEt-treated animals were found to be more resistant to H₂O₂-induced peroxidation than that of untreated diabetic animals. The chemical characterization of the polyphenolics of the extract showed the presence of gallic acid (5.29% w/w), resveratrol (2.2% w/w), and quercetin (16.6% w/w). The results of this study suggest that G. montanum may be useful for the control, management, and prevention of oxidative stress associated with diabetes.     

Hypoglycemic effects of MDG-1, a polysaccharide derived from Ophiopogon japonicas, in the ob/ob mouse model of type 2 diabetes mellitus

Ophiopogon japonicus is a traditional Chinese medicine used to treat diabetes mellitus. We investigate the anti-ischemic properties of a water-soluble β-d-fructan (MDG-1) from O. japonicus, and assess the antidiabetic effects of MDG-1. In the study, ob/ob mice were treated with 150 mg/kg or 300 mg/kg MDG-1 by gavage for 23 d. Blood glucose levels were measured regularly. An oral glucose tolerance test (OGTT) was preformed on day 21. The levels of insulin, total cholesterol and triglyceride in the serum were measured at the end of administration. The liver triglyceride content and tissue weights were also determined. Results show that MDG-1 (300 mg/kg) was demonstrated to exert acute and long-term hypoglycemic effects on fed blood glucose in ob/ob mice. However, only a marginal hypoglycemic effect on fasting blood glucose levels was observed. MDG-1 (300 mg/kg) improved oral glucose tolerance and reduced serum insulin levels and triglyceride content in the liver in ob/ob mice. Furthermore, a reduction in body weight gain and the weight of subcutaneous fat were observed following treatment with MDG-1 (150 mg/kg) compared with the control group. MDG-1 had no significant effects on the total cholesterol and triglyceride levels, food intake and other adipose and organ tissues. These data suggest that MDG-1 exhibits hypoglycemic activity and reduces insulin resistance.