Potential in vitro antioxidant and protective effects of Gymnema montanum H. on alloxan-induced oxidative damage in pancreatic β-cells, HIT-T15

The present study describes the antioxidant activities of ethanol extract from Gymnema montanum (GLEt) which is an endemic plant of India. Antioxidant activity of the GLEt was studied in vitro based on scavenging of hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide, peroxynitrite, reducing power and inhibition of lipid peroxidation estimated in terms of thiobarbituric acid reactive substances (TBARS). Further, we examined its protective effect against alloxan-induced oxidative stress in pancreatic β-cells, HIT-T15 by measuring the free radical generation, malonaldehyde formation and antioxidant levels such as CAT, GPx and GSH. Results showed that G. montanum leaves exhibited significant antioxidant activities measured by various in vitro model systems. The HIT-T15 cell line studies showed the tendency of GLEt to increase antioxidant levels meanwhile decrease the free radical formation and inhibit the lipid peroxidation. The antioxidant activity was found to be well correlated with the phenolic phytochemicals present in the extract. GC–MS analyses revealed the presence of few phenolic compounds in the extract. As this plant has already been demonstrated for a variety of medicinal properties from our laboratory, results of this study suggest that G. montanum is an interesting source for antioxidant compounds and useful for various therapeutic applications.     

Antidiabetic activity of alcoholic stem extract of Gymnema montanum in streptozotocin-induced diabetic rats

In the present study, the effect of alcoholic stem extract of Gymnema montanum (GMSt) on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in experimental diabetes. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg bw). Five days after STZ induction, diabetic rats received GMSt orally at the doses of 25, 50, 100 and 200 mg/kg daily for 3 weeks. Graded doses of stem extract showed a significant reduction in blood glucose levels and improvement in plasma insulin levels. The effect was more pronounced in 100 and 200 mg/kg than 50 mg/kg. GMSt showed significant increase in hexokinase, Glucose-6-phosphate dehydrogenase and glycogen content in liver of diabetic rats while there was significant reduction in the levels of glucose-6-phosphatase and fructose-1,6-bisphosphatase. The present study clearly indicated significant antidiabetic effect with the stem extract of G. montanum and lends support for its traditional usage.     

Antidiabetic effect of Gymnema montanum leaves: effect on lipid peroxidation induced oxidative stress in experimental diabetes

Gymnema montanum is widely used in ancient medicine for the ailment of various diseases. Oral administration of 200 mg kg(-1) (body weight) BW of the alcoholic extract of the leaf for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin, whereas the effect of 50 and 100 mg kg(-1) BW was not significant. The alcoholic extract also resulted in decreased free radical formation in plasma of diabetic rats. Thus, this study shows that Gymnema montanum leaf extract (GLEt) possess antihyperglycemic and antiperoxidative effect. The decrease in lipid peroxides and increase in reduced glutathione (GSH), ascorbic acid (Vitamin C) and alpha-tocopherol (Vitamin E) clearly show the antioxidant properties of GLEt. The effect of GLEt was most prominently seen in the case of animals given 200 mg kg(-1) BW. In addition, the results suggest that GLEt was highly effective than the reference drug glibenclamide.     

Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats

The present study was designed to evaluate the radioprotective effect of N- acetylcysteine (NAC) on gamma-radiation induced toxicity in hepatic tissue in rat. The cellular changes were estimated using malondialdehyde (MDA, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), reduced glutathione (GSH), and total nitrate/nitrite (NO(x)) as markers of hepatic oxidative stress in rats following gamma-irradiation. The DNA damage was determined by agarose gel electrophoresis. To achieve the ultimate goal of this study, 40 adult rats were randomly divided into 4 groups of 10 animals each. Group I was injected intraperitoneally with saline solution for 7 consecutive days and served as control group. Group II was irradiated with a single dose of 6Gy gamma-radiation. Group III was daily injected with NAC (1g/kg, i.p.) for 7 consecutive days. Group IV received a daily i.p. injection of NAC (1g/kg, i.p.) for 7 consecutive days and 1h after the last dose, rats were irradiated with a single dose (6Gy) gamma-radiation. The animals were sacrificed after 24h. DNA damage was observed in tissue after total body irradiation with a single dose of 6Gy. Malondialdehyde and total nitrate/nitrite were increased significantly whereas the levels of GSH and antioxidant enzymes were significantly decreased in gamma-irradiated group. Pretreatment with NAC showed a significant decrease in the levels of MDA, NO(x) and DNA damage. The antioxidant enzymes increased significantly along with the levels of GSH. Moreover, histopathological examination of liver tissues confirmed the biochemical data. Thus, our results show that pretreatment with N-acetylcysteine offers protection against gamma-radiation induced cellular damage.     

Protective effect of yacon leaves decoction against early nephropathy in experimental diabetic rats

Nephropathy is the most common cause of morbidity and mortality in diabetic patients. Prevention of this complication has a major relevance. Smallanthus sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon leaves decoction on diabetic nephropathy and explored the possible underlying action mechanism.     

Mutagenicity of Mouriri pusa Gardner and Mouriri elliptica Martius

Mouriri pusa Gardner and Mouriri elliptica Martius are fruit-bearing plants of the Melastomataceae family, popularly known in Brazil as puçá-preto or jaboticaba-do-cerrado, and they are used in folk medicine for the treatment of gastric ulcers. In this study, we employ the Ames test to assess the mutagenicity of compounds obtained from the leaves of these species. The methanol extract of the M. pusa was mutagenic to the Salmonella typhimurium strains TA98, TA97a and TA100, with or without metabolic activation. The methanol extract of M. elliptica induced mutagenic activity in TA98 when metabolized with S9 fraction and TA97a with and without S9, but with lower mutagenicity index (MI) and potencies values than those for M. pusa. Enriched fractions of flavonoids and tannins of M. pusa were also evaluated and they demonstrated positive mutagenicity. The highest values of MI and potency were obtained with the flavonoid fraction, which contains large amounts of quercetin, quercetin glycosides and myricetin. These compounds are probably related to the mutagenicity observed in the Ames test. The dichloromethane extract was not mutagenic in any of the test conditions employed.     

Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats

Sedentary lifestyle, consumption of energy-rich diet, obesity and longer lifespan are some of the major reasons for the rise of metabolic disorders like type II diabetes, obesity, hypertension and dyslipidemia among people of various age groups. High fat diet induced diabetic rodent models resembling type II diabetic condition in human population were used to assess the anti-diabetic and hypolipidemic activity of guggulsterone (isolated from Commiphora mukul resin). Four groups of rats were fed high fat diet, for 16 weeks. On feeding the normal rats with fat rich diet they showed increased serum glucose, cholesterol and triglyceride levels along with increase in insulin resistance significantly (p < 0.05) in comparison to control animals. Different biochemical parameters like GTT, glycogen content, glucose homeostatic enzymes (like glucose-6-phosphatase, hexokinase), insulin release in vivo and expression profiles of various genes involved in carbohydrate and lipid metabolism clearly demonstrated the hypoglycemic effect of this extract. Guggulsterone demonstrated a differential effect with a significantly improved PPARγ expression and activity in in vivo and in vitro conditions, respectively. However, it inhibited 3T3-L1 preadipocytes differentiation in vitro. The results presented here suggest that the guggulsterone has both hypoglycemic and hypolipidemic effect which can help to cure type II diabetes.     

蓍草总倍半萜内酯对类风湿性关节炎模型大鼠保护作用的实验研究

目的 探讨蓍草总倍半萜内酯对类风湿性关节炎（RA）模型大鼠的抗炎作用,并初步探讨其作用机制。方法 大鼠右后足跖皮下注射弗氏完全佐剂建立佐剂性关节炎大鼠模型,给予不同剂量蓍草总倍半萜内酯和雷公藤多苷药物干预21 d。通过检测大鼠关节肿胀度、关节炎指数和血清白介素（IL）-6、IL-1β、肿瘤坏死因子（TNF）-α水平等指标,观察蓍草总倍半萜内酯片对佐剂性RA大鼠的影响。结果 与模型组比较,蓍草总倍半萜内酯中、高剂量组在14、21、28 d大鼠足跖肿胀度显著低于模型组（P<0.05,P<0.01）,明显抑制了RA大鼠足关节肿胀度。蓍草总倍半萜内酯中、高剂量组在14、21、28 d大鼠关节指数显著低于模型组（P<0.05,P<0.01）。与模型组比较,蓍草总倍半萜内酯低、中、高剂量组均能够显著降低IL-6、IL-1β、TNF-α水平（P<0.05,P<0.01）,各剂量组的抑制作用呈剂量依赖性。结论 蓍草总倍半萜内酯具有较好的治疗大鼠RA作用,其作用机制可能与下调炎症因子IL-6、IL-1β、TNF-α水平有关。     

Protective properties of tanshinone I against oxidative DNA damage and cytotoxicity

Tanshinone I, a naturally occurring diterpene from Danshen, has been shown to possess hepatocyte protective, anticancer, and memory enhancing properties. However, there are few stringent pharmacological tests for neuroprotection of tanshinone I thus far. Since peroxynitrite is involved in the pathogenesis of neurodegenerative disorders, this study was undertaken to investigate whether the neuroprotective effect of tanshinone I is associated with inhibition of peroxynitrite-caused DNA damage, a critical event leading to peroxynitrite-induced cytotoxicity. Our results show that tanshinone I can significantly inhibit peroxynitrite-induced DNA damage both in φX-174 plasmid DNA and rat primary astrocytes. EPR spectroscopy indicates that tanshinone I potently diminished the DMPO-hydroxyl radical adduct signal from peroxynitrite. Taken together, these results demonstrate for the first time that tanshinone I can protect against peroxynitrite-induced DNA damage, hydroxyl radical formation and cytotoxicity, which might have implications for tanshinone I-mediated neuroprotection.     

In ovo exposure of a Fusarium mycotoxin butenolide induces hepatic and renal oxidative damage in chick embryos, and antioxidants provide protections

Butenolide is a mycotoxin produced by several toxigenic Fusarium species. It frequently invades many important grains, and evokes a broad spectrum of toxic effects. For these reasons, butenolide poses a health risk to both humans and animals. However, many toxicology issues of butenolide including targets and mechanisms of toxicity remain to be elucidated so far. The present study therefore attempts to reveal the toxic profile of butenolide from a viewpoint of oxidative damage, using chick embryos as an in vitro model. A single in ovo injection of butenolide resulted in significant oxidative injuries in embryonic livers and kidneys, as manifested by a dose-dependent depletion of sulfhydryl groups, reduction of glutathione peroxidase activity, and increase of thiobarbituric acid reactive substances production, an indicator of lipid peroxidation. In contrast, co-injections of butenolide with antioxidants sodium selenite, vitamin C and a representative antioxidative enzyme superoxide dismutase markedly abated these oxidative toxicities. In conclusion, the present study suggests that oxidative damage may serve as a mediator in the toxicity of butenolide, and amelioration of antioxidant defense capacity by exogenous supplementation may play a role in the prevention and treatment of butenolide intoxication.     

Protective effect of Corchorus olitorius leaves on sodium arsenite-induced toxicity in experimental rats

The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves (AECO) against sodium arsenite-induced toxicity in experimental rats. The animals exposed to sodium arsenite at a dose of 10 mg/kg body weight p.o. for 10 days exhibited a significant inhibition (p < 0.01) of hepatic and renal antioxidant enzymes namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase. In addition, arsenic intoxication significantly decreased (p < 0.01) the level of reduced glutathione and increased (p < 0.01) the levels of oxidized glutathione and thiobarbituric acid reactive substances in selected tissues. Treatment with AECO at doses of 50 and 100 mg/kg body weight p.o. for 15 days prior to arsenic intoxication significantly improved hepatic and renal antioxidant markers in a dose dependant manner. AECO treatment also significantly reduced the arsenic-induced DNA fragmentation of hepatic and renal tissues. Histological studies on the ultrastructural changes of liver and kidney supported the protective activity of the AECO. The results concluded that the treatment with AECO prior to arsenic intoxication has significant role in protecting animals from arsenic-induced hepatic and renal toxicity.     

Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin -induced diabetic rats

Aim and Objectives:

In the present study, we have evaluated the antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of Phyllanthus amarus (PAAEt) in streptozotocin (STZ)-induced diabetic rats.

Materials and Methods:

PAAEt was administered at 200 mg/kg body weight/day to normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by gavage for eight weeks. During the experimental period, blood was collected from fasted rats at 10 days intervals and plasma glucose level was estimated. The plasma lipid profile was estimated at the end of experimental period. After the treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were also assayed.

Results:

The significant decrease in the body weight, hyperglycemia and hyperlipidemia observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt treatment in diabetic treated group (DT-group). D-group rats showed increased renal oxidative stress with increased LPO and protein oxidation. DT-group showed a significant decrease in renal LPO, protein oxidation and a significant increase in GSH content and GR, GPx and GST activities when compared with D-group. The activities of SOD and CAT decreased significantly in D-group, but were normalized in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant decrease in lipid profile, renal LPO and protein oxidation, with significant increase in renal GSH and activities of antioxidant enzymes compared to normal rats (N-group).

Conclusion:

Our results demonstrated that PAAEt with its antidiabetic, hypolipidemic and antioxidant properties could be a potential herbal medicine in treating diabetes and renal problems.     

Therapeutic potential of 20(S)-ginsenoside Rg(3) against streptozotocin-induced diabetic renal damage in rats

The inhibitors of advanced glycation endproduct and oxidative stress, as well as N-methyl-d-aspartate (NMDA) receptor antagonists have received considerable interest because of their close association with renoprotective effects. The therapeutic potential of 20(S)-ginsenoside Rg(3) (20(S)-Rg(3)), isolated from Panax ginseng, against streptozotocin-induced diabetic renal damage, was investigated in this study. The diabetic rats received 5, 10, and 20 mg/kg body weight/day of 20(S)-Rg(3) orally via gavage for fifteen consecutive days. The physiological abnormalities such as increases in water intake and urine volume of diabetic rats were significantly decreased by the 20 mg/kg body weight of 20(S)-Rg(3) administration. The elevated serum glucose, glycosylated protein, and thiobarbituric acid-reactive substance levels in diabetic rats were also significantly reduced by the 20(S)-Rg(3) administrations. Moreover, the renal dysfunction of diabetic rats was significantly ameliorated by the 20(S)-Rg(3) administrations in a dose-dependent manner. These beneficial effects on diabetic renal damage were related to the inhibitory effect of 20(S)-Rg(3) against NMDA receptor-mediated nitrosative stress.     

Hepatoprotective potentials of Phyllanthus amarus against ethanol-induced oxidative stress in rats

The hepatoprotective effect of methanolic extract of the leaf of Phyllanthus amarus (P. amarus) against ethanol-induced oxidative damage was investigated in adult male Wistar albino rats. P. amarus (250 and 500 mg/kg/day) and ethanol (5 g/kg/day, 20% w/v) were administered orally to animals for 4 weeks and 3 weeks, respectively. Ethanol treatment markedly decreased the level of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in the liver, which were significantly enhanced by P. amarus treatment. Glutathione-S transferase (GST), which was increased after chronic ethanol administration, was significantly reduced by P. amarus treatment in the liver. Also, P. amarus significantly increased the activities of hepatic alanine transaminase (ALT) and aspartate transaminase (AST) as well as alkaline phosphatase (ALP), with a concomitant marked reduction in the plasma activity of the transaminases in the ethanol-challenged rats. Lipid peroxidation level, which was increased after chronic ethanol administration, was significantly reduced in the liver by P. amarus co-treatment. Results show that P. amarus leaf extract could protect the liver against ethanol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and increasing the antioxidant defence mechanism in rats.     

Protective effect of embelin against acetic acid induced ulcerative colitis in rats

The aim of the present study is to evaluate the effect of embelin isolated from Embelia ribes on acetic acid induced colitis in rats. Experimental animals received embelin (25 and 50 mg/kg, p.o.) and sulfasalazine (100 mg/kg, p.o.) for five consecutive days before induction of colitis by intra-rectal acetic acid (3% v/v) administration and the treatment continued up to 7 days. The colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. Embelin treatment significantly decreased clinical activity score, gross lesion score, percent affected area and wet colon weight when compared to acetic acid induced controls. The treatment also reduced significantly the colonic myeloperoxidase activity, lipid peroxides and serum lactate dehydrogenase and significantly increased the reduced glutathione. The histopathological studies also confirmed the foregoing findings. The protective effect may be due to its antioxidant and anti-inflammatory activities.     

Protective effect of a novel antioxidative peptide purified from a marine Chlorella ellipsoidea protein against free radical-induced oxidative stress

Protein derived the marine Chlorella ellipsoidea was hydrolyzed using different proteases (papain, trypsin, pepsin and α-chymotrypsin) for production of antioxidative peptide, and the antioxidant activities of their hydrolysates were investigated using free radical scavenging assay by electron spin resonance spin-trapping technique. Among the hydrolysates, the peptic hydrolysate exhibited the highest antioxidant activity compared to other hydrolysates. To identify antioxidant peptide, the peptic hydrolysate was purified using consecutive chromatographic methods, and the antioxidant peptide was identified to be Leu-Asn-Gly-Asp-Val-Trp (702.2 Da) by Q-TOF ESI mass spectroscopy. The antioxidant peptide scavenged peroxyl, DPPH and hydroxyl radicals at the IC₅₀ values of 0.02, 0.92 and 1.42 mM, respectively. The purified peptide enhanced cell viability against AAPH-induced cytotoxicity on normal cells. Furthermore, the purified peptide reduced the proportion of apoptotic and necrotic cells induced by AAPH, as demonstrated by decreased sub-G₁ hypodiploid cells and decreased apoptotic body formation by flow cytometry.     

Characterization of bioactive compounds and ameliorative effects of Ceratonia siliqua leaf extract against CCl4 induced hepatic oxidative damage and renal failure in rats

Ceratonia siliqua is a typical Mediterranean plant, mainly used in food and Tunisian traditional folk medicine. Among the tested extracts, the ethyl acetate fraction (EACs) exhibited the highest total phenolic and flavonoids content. The antioxidant activity in vitro systems showed a more significant potent free radical scavenging activity of this extract than other analysis fractions. The HPLC finger print of EACs active extract showed the presence of six phenolic compounds. The in vivo results showed that oral administration of CCl₄ enhanced levels of hepatic and renal markers (ALT, AST, ALP, LDH, γ-GT, urea and creatinine) in the serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a concomitant decrease in the levels of enzymatic antioxidants (SOD, CAT, GPx) in both liver and kidney. The pre-treatment of experimental rats with 250 mg/kg (BW) of the EACs, by intraperitoneal injection for 8 days, prevented CCl₄ induced disorders in the levels of hepatic and kidney markers. The biochemical changes were in accordance with histopathological observations suggesting a marked hepatoprotective and nephroprotective effect of the EACs extract.     

In vitro antimicrobial activity of a chitooligosaccharide mixture against Actinobacillus actinomycetemcomitans and Streptococcus mutans

The purpose of this study was to evaluate the in vitro antibacterial activity of a chitooligosaccharide mixture (MW 2000–30 000 Da) with a deacetylation degree of 91.5% against two representative oral pathogens, Actinobacillus actinomycetemcomitans and Streptococcus mutans. A 0.1% concentration of the chitooligosaccharides (derived from the exoskeletons of marine crustaceans) was used to estimate antibacterial activity. Approximately 2 log colony forming units (CFU)/ml of A. actinomycetemcomitans were inactivated by 0.1% chitosan after 30 min, while 120 min exposure inactivated about 4.5 log CFU/ml of this organism. In contrast, the level of inactivation against S. mutans was less than 0.5 log CFU/ml after an exposure of up to 120 min. Electron microscopy showed that the exposure of A. actinomycetemcomitans to the chitooligosaccharides resulted in the disruption of cell membranes and that it could be considered for the treatment of periodontal diseases associated with A. actinomycetemcomitans.     

Protective effect of cactus (Opuntia ficus indica) cladode extract upon nickel-induced toxicity in rats

The purpose of this study carried out on male Wistar rats, was to evaluate the protective effects of regular ingestion of juice from the prickly pear cactus (Opuntia ficus indica) cladodes against nickel chloride toxicity. Rats were given either normal tap water or water containing 25% of cactus juice for one month. Then, rats of each group were injected daily, for 10 days, with either NiCl₂ solution (4 mg (30 μmol)/kg body weight) or with the same volume of saline solution (300 mM NaCl).Significant increases of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase activities and of cholesterol, triglycerides and glucose levels were observed in blood of nickel-treated rats. In the liver, nickel chloride was found to induce an oxidative stress evidenced by an increase in lipid peroxidation and changes in antioxidant enzymes activities. Superoxide-dismutase (SOD) activity was found to be increased whereas glutathione peroxidase and catalase activities were decreased. These changes did not occur in animals previously given cactus juice, demonstrating a protective effect of this vegetal extract.     

Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats

The present study was designed to investigate the protective effects of L-carnitine (LC) on changes in the levels of lipid peroxidation and endogenous antioxidants induced by cisplatin (cis-diamminedichloroplatinum II, CDDP) in the liver and kidney tissues of rats. Twenty-four Sprague Dawley rats were equally divided into four groups of six rats each: control, cisplatin, L-carnitine, and L-carnitine plus cisplatin. The degree of protection produced by L-carnitine was evaluated by determining the level of malondialdehyde (MDA). The activity of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), and superoxide dismutase (SOD) were estimated from liver and kidney homogenates, and the liver and kidney were histologically examined as well. L-carnitine elicited significant liver and kidney protective activity by decreasing the level of lipid peroxidation (MDA) and elevating the activity of GSH, GSHPx, GST, and SOD. Furthermore, these biochemical observations were supported by histological findings. In conclusion, the present study indicates a significant role for reactive oxygen species (ROS) and their relation to liver and kidney dysfunction, and points to the therapeutic potential of LC in CDDP-induced liver and kidney toxicity.