Toxicological Profiling of Potential Shikimate Kinase Inhibitors Against Mycobacterium tuberculosis.

Over the last decade, Mycobacterium tuberculosis has mutated into a putative 'superbug', as treatments against it have failed due to increasing antimicrobial resistance. As a result, the rising incidence of multidrug-resistant tuberculosis (MDR-TB) is posing a significant public health threat, thus, the need to develop effective drugs for MDR-TB has become an urgent priority. To identify new drug candidates for the treatment of MDR-TB, the present study was based on mycobacterial shikimate kinase (MtSK) as the pharmacological target. One hundred potential MtSK inhibitors were identified from literature and database searches to identify compounds that were designed to specifically function as MtSK antagonists. The ADME properties of these compounds were evaluated by using the SwissADME web tool. ProTox-II software was also used to investigate any potential endocrine disrupting effects, mediated through their interaction with oestrogenic and/or androgenic receptors. This study also aimed to predict LD50 values of potential drug candidates that would be active against the standard H37Rv strain of M. tuberculosis, by using the ProTox-II in silico tool. The molecules for which no structural hazard alerts were identified with these software tools were further subjected to molecular docking analyses and molecular dynamic simulations to estimate their ability to interact with the MtSK enzyme. Preliminary results from SwissADME indicated that 30 molecules were drug-like, due to their physicochemical and pharmacokinetic properties. However, subsequent analysis with ToxTree and ProTox-II indicated that only three of these 30 drug-like molecules were suitable for taking forward into further in vitro experiments. This study, which is based on the use of commonly used open-source in silico tools, identified new MtSK ligands for potential use in the development of new drugs for the therapeutic management of tuberculosis. An initial prediction of their safety profile was also generated.

Comparative clinical evaluation of a local drug delivery of cranberry and garcinia fruit gel with tetracycline fibers for amelioration of periodontitis: A split mouth study.

Background: The present study formulates and evaluates a polyberry gel comprising extracts of cranberry (Vaccinium macrocarpon) and brindle berry (Garcinia cambogia) in patients suffering from chronic periodontitis. Materials and Methods: The polyberry gel was evaluated for various physicochemical parameters, in vitro permeability and stability, and the active phytoconstituents were quantified by High-performance thin layer chromatography (HPTLC). Total phenolic content, total antioxidants, and ascorbic acid were estimated in the two extracts by in vitro assays. Patients suffering from chronic periodontitis with probing pocket depth (PPD) up to 5 mm were divided into 3 groups of 21 patients each and treated with scaling and root planing (SRP) or SRP followed by subgingival placement of polyberry gel or tetracycline fibers (standard). Plaque Index (PI), Gingival Index (GI), PPD, Clinical Attachment Level (CAL), and the salivary aspartate aminotransferase (AST) and C-reactive protein (CRP) levels were recorded at baseline and after 1 month. Results: A significant (P < 0.01) reduction in the periodontic disease parameters was observed in the standard and gel-treated groups between their baseline and 1-month time-interval readings. The polyberry gel treatment significantly (P < 0.05 for AST and P < 0.01 for the rest) attenuated the periodontitis-elevated PI, GI PPD, CAL, AST and CRP levels when compared with SRP at the end of the study and was comparable with tetracycline. Conclusion: The amelioration of periodontitis and gingival inflammation may be attributed to the potent antioxidant activity of the polyphenolic phytoconstituents of the gel. The polyberry gel may thus be used as a safe adjunct to SRP/tetracycline in chronic periodontitis.

Cardioprotective potential of Spinacia oleracea (Spinach) against isoproterenol-induced myocardial infarction in rats.

CONTEXT: Spinacia oleracea is rich in antioxidant phyto-constituents, termed as the natural antioxidant mixture (NAO). OBJECTIVE: This study investigates the cardioprotective effect of an antioxidant-rich extract of Spinacia oleracea (NAOE) and its phytoconstituent rutin in isoproterenol (ISO)-induced myocardial infarction in rats. METHODS: Rats were treated with NAOE (400 and 800 mg/kg), rutin (50 mg/kg) and the reference drug gemfibrozil (50 mg/kg) daily for 30 days and were administered ISO (85 mg/kg, s.c) on the last 2 days. RESULTS: NAOE treatment attenuated the ISO-elevated levels of serum marker enzymes (AST, LDH and CPK), troponin I, total cholesterol, triglycerides, uric acid, CRP, TNF-α, IL-6 and malondialdehyde. It also restored the ISO-skewed ECG and systolic blood pressure, and the ISO-depleted marker enzymes and endogenous antioxidants in all treated rats. CONCLUSION: It may be concluded that NAOE treatment to ISO-challenged rats exhibited significant cardioprotective effect probably due to the potent antioxidant activity of its NAO.

Effect of Withania somnifera hydroalcoholic extract and other dietary interventions in improving muscle strength in aging rats.

BACKGROUND: Aging leads to loss of skeletal muscle, diminished muscle strength, and decline in physical functions. OBJECTIVE: This study evaluates Withania somnifera and some dietary interventions to combat muscle weakness in aging rats. MATERIALS AND METHODS: Rats (12-13 months old) corresponding to a human age of 60-65 years were assigned to various groups and given orally a standardized W. somnifera extract (WSE, 500 mg/kg) or a protein cocktail comprising soybean (1.5 g/kg) and quinoa (1 g/kg) or a combination of WSE and the protein cocktail or whey protein (1 g/kg) as a reference standard or only resistance exercise for 60 days. Grip strength and blood glucose levels were monitored weekly. At the end of the treatment, total protein, inflammatory markers (CRP, IL-6 and TNF-α), AMPK, malondialdehyde, glutathione, antioxidant enzymes and apoptotic regulator genes (Bax and Bcl-2) were assayed. The biceps brachii muscle of all animals was subjected to histomorphological study. RESULTS: All treatments successfully attenuated aging-elevated glucose, CRP, IL-6, TNF-α, AMPK, malondialdehyde, and Bax levels. A significant restoration of the aging-depleted total protein levels, glutathione, superoxide dismutase, catalase, and Bcl-2 was noted in the treatment groups. An increase in grip strength and greater biceps mass with all treatments indicated regaining of the frail aging muscle's strength and functionality. The WSE + protein treatment elicited the best results among all treatment groups to optimize muscle strength. CONCLUSION: All the interventions curbed muscle loss and strengthened the skeletal muscle by reducing inflammation, oxidative stress and apoptosis, and increasing ATP availability to the muscle.

An Ayurvedic formulation of Emblica officinalis and Curcuma longa alleviates insulin resistance in diabetic rats: Involvement of curcuminoids and polyphenolics.

BACKGROUND: Nishamalaki is an Ayurvedic herbal formulation used to treat type 2 diabetes mellitus (T2DM), comprises Emblica officinalis and Curcuma longa. OBJECTIVE(S): One of the main cause of T2DM is Insulin Resistance (IR) hence, this study was planned to evaluate IR lowering effect of a standardized Nishamalaki extract "EmbliQur" in high-fat diet (HFD) and streptozotocin (STZ) induced T2DM rats. MATERIALS AND METHODS: Curcuminoids (23.89% w/w), gallic acid (5.27% w/w) and tannins (25.44% w/w) were quantified from EmbliQur. Rats were fed HFD throughout the study of 45 days and received STZ (40 mg/kg, i.p) on the 15th day of the study. Rats with more than 250 mg/dl of fasting blood glucose level (FBGL) were considered diabetic and selected for administration of EmbliQur (500 mg and 1000 mg/kg) or the standard drug metformin (120 mg/kg, p.o) from the 18th day of the study for the next 27 days. FBGL and insulin levels of all rats were measured weekly and an oral glucose tolerance test (OGTT) was done at the end of the study. The values of FBGL and insulin were used to calculate IR by the HOMA-IR, QUICKI and Matsuda methods. RESULTS: Rats treated with STZ/HFD had significantly higher than normal FBGL and insulin levels throughout the study and exhibited skewed IR indices in the above three methods of IR assessment. EmbliQur treatment successfully lowered the HFD/STZ-elevated BGL and insulin levels, and ameliorated IR in all models of IR evaluation. CONCLUSION: EmbliQur 1000 mg/kg was noted to be more effective than EmbliQur 500 mg/kg in alleviating IR.

Protective effect of a polyherbal bioactive fraction in propylthiouracil-induced thyroid toxicity in ratsby modulation of the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes.

Hypothyroidism is the most frequent consequence of the interaction of a large variety of drugs, environmental pollutants and industrial chemicals with the thyroid gland. It is associated with diminished endocrine function which may lead to hyperlipidemia, diabetes, Alzheimer's disease, weight gain, and other metabolic disorders. The present study evaluates the pro-thyroid activity of a bioactive fraction from a polyherbal teabag in rats with hypothyroidism induced by propylthiouracil. The teabag was formulated to stimulate synthesis and/or release of T4 and affectthe conversion of T4 to T3. Phytoconstituents of the polyherbal teabag are potent antioxidants that may be responsible for the pro-thyroid activity. The tea-extract (1000 mg) was found to contain 1076 µg of gallic acid and 1131 µg of rutin from HPTLC analysis. Rats received propylthiouracil (8 mg/kg) for the first 15days followed by the polyherbal tea-extract (500, 1000 and 1500 mg/kg), the standard drug levothyroxine (0.1 mg/kg), aerobic exercise, and a combination of tea-extract (1000 mg/kg) and aerobic exercise daily along with propylthiouracil for the next 30 days. Finally, rats received their respective treatments alone without propylthiouracil for 15 more days. Lipid profile and levels of glucose, insulin, T3, T4, TSH, cortisol, homocysteine, creatinine, uric acid, malondialdehyde, glucose-6 phosphatase, and endogenous antioxidants were determined. All treatments attenuated significantly the propylthiouracil-elevated TSH, homocysteine, creatinine, uric acid, glucose-6-phosphatase, insulin, and malondialdehyde levels, and restored favorably the propylthiouracil-altered lipid profile, T3, T4, and endogenous antioxidant levels. The polyherbal tea-extract (1000 and 1500 mg/kg) treatment and thecombination treatment of tea-extract (1000 mg/kg) with aerobic exercise displayed significant restoration of the suboptimalthyroid function. This may be due to a favorablemodulation ofthe hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal axes.

Comparative distribution of somatostatin and somatostatin receptors in PTU-induced hypothyroidism.

PURPOSE: Propylthiouracil (PTU)-induced hypothyroidism is a well-established model for assessing hormonal and morphological changes in thyroid as well as other central and peripheral tissues. Somatostatin (SST) is known to regulate hormonal secretion and synthesis in endocrine tissues; however, nothing is currently known about the distribution of SST and its receptor in hypothyroidism. METHOD: In the present study, the comparative immunohistochemical distribution of SST and somatostatin receptors (SSTRs) were analyzed in PTU-induced hypothyroid rats. Rats were treated with PTU for 15 days followed by a co-administration of levothyroxine (LVT) for 15 days. After PTU and LVT treatments (day 30), rats were further administered LVT alone for 15 more days (day 45). The subcellular distribution of SST and SSTR subtypes was determined by peroxidase immunohistochemistry in the thyroid gland collected from control and treated rats. RESULTS: SST and SSTR subtypes were found to be moderately expressed in control thyroid tissues. SST and SSTR subtypes like immunoreactivity increased significantly in follicular and parafollicular epithelial cells in the thyroid of PTU-treated rats. The PTU-induced changes in the expression of SST and SSTR subtypes were suppressed by the administration of the LVT. In addition to thyroid tissues, SST and SSTRs expression was also changed in non-follicular tissues including blood vessels, smooth muscle cells, and connective tissue following treatments. CONCLUSION: The present study revealed a distinct subcellular distribution of SST and SSTR subtypes in the thyroid and provides a new insight for the role of SST and SSTR subtypes in hypothyroidism in addition to its well-established role in negative regulation of hormonal secretion.

Consumption of Spinacia Oleracea (spinach) and aerobic exercise controls obesity in rats by an inhibitory action on pancreatic lipase.

Context: Spinaciaoleracea (spinach) is abundant in antioxidant phytoconstituents, termed as the natural antioxidant mixture (NAO).Objective: This study evaluates the anti-hyperlipidemicand anti-obesity effects of an antioxidant-rich extract of Spinaciaoleracea (NAOE) and aerobic exercise (AE) in rats fed with high fat diet (HFD).Methods: Rats received NAOE (200 and 400 mg/kg), the standard drug orlistat (10 mg/kg), AE and NAOEAE (NAOE 400 mg/kg + AE) daily with HFD for 21 d.Results: Orlistat, NAOE and NAOEAE treatments to HFD-fed rats significantly reduced the HFD-elevated food intake, weight gain, pancreatic lipase activity and lipid peroxidation, and successfully restored the HFD-skewed lipid profile and antioxidant levels.Conclusions: It may be concluded that NAOE exhibited a promising anti-hyperlipidemic effect by its inhibitory action on pancreatic lipase. The combination treatment NAOEAE produced the best results indicating the essential role of exercise along with consumption of antioxidant-rich foods in maintaining a normal lipid profile and controlling obesity.

A herbal premix containing Macrotyloma uniflorum, ginger, and whey curtails obesity in rats fed a high-fat diet by a novel mechanism.

The present study designed and evaluated a polyherbal premix comprising Macrotyloma uniflorum, whey protein, Zingiber officinale, and Mentha piperita. Animals were fed a high-fat diet (HFD) for 30 days and were daily administered the premix (1.5 g/kg) in milk (PM) and water (PW), aerobic exercise (AE), premix in milk and water along with AE (PMAE and PWAE), ferulic acid (100 mg/kg), and the reference drug fluoxetine (6 mg/kg). All treatments showed significant reduction in food intake, weight gain, abdominal circumference, and body mass index compared with their initial values. All treatments generated a faster peak of the satiety marker cholecystokinin compared with the HFD group and control groups; PMAE and PWAE exhibited sustained satiety. The HFD-elevated blood glucose levels were significantly attenuated on the 30th day by all treatments when compared with their 15th day and basal values; PMAE exhibited the best results. All treatments significantly attenuated the HFD-elevated serum insulin, homeostasis model assessment of insulin resistance, C-reactive protein, triglycerides, total cholesterol, very-low-density lipoprotein, and low-density lipoprotein levels and significantly restored the HFD-depleted high-density lipoprotein and adiponectin levels. HFD-elevated thiobarbituric acid reactive substances values were attenuated successfully and the HFD-depleted reduced glutathione, superoxide dismutase, and catalase levels were significantly restored by all treatments. The histological findings corroborated the biochemical results. Novelty The polyherbal premix brought about appetite regulation and induction of satiety to control obesity in HFD-fed rats through homeostasis of energy metabolism. The premix along with exercise is a complete way to combat obesity.

A comparative study of the antacid effect of some commonly consumed foods for hyperacidity in an artificial stomach model.

OBJECTIVES: The incorporation of certain alkalinizing vegetables, fruits, milk and its products in the diet has been known to alleviate hyperacidity. These foods help to restore the natural gastric balance and function, curb acid reflux, aid digestion, reduce the burning sensation due to hyperacidity and soothe the inflamed mucosa of the stomach. The present study evaluates and compares the antacid effect of broccoli, kale, radish, cucumber, lemon juice, cold milk and curd in an artificial stomach model. DESIGN: The pH of the test samples and their neutralizing effect on artificial gastric acid was determined and compared with that of water, the active control sodium bicarbonate and a marketed antacid preparation ENO. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization of artificial gastric acid by the test samples. The neutralizing capacity of the test samples was determined in vitro using the classical titration method of Fordtran. RESULTS: All test samples except lemon showed significantly higher (p<0.05 for cucumber and p<0.001 for the rest) acid neutralizing effect than water. All test samples also exhibited a significantly (p<0.001) higher duration of consistent neutralization and higher antacid capacity than water. Highest antacid activity was demonstrated by cold milk and broccoli which was comparable with ENO and sodium bicarbonate. CONCLUSION: It may be concluded that the natural food ingredients used in this study exhibited significant antacid activity, justifying their use as essential dietary components to counter hyperacidity.

Amelioration of Abnormalities Associated with the Metabolic Syndrome by Spinacia oleracea (Spinach) Consumption and Aerobic Exercise in Rats.

The present study evaluates the protective effects of an antioxidant-rich extract of Spinacea oleracea (NAOE) in abnormalities associated with the metabolic syndrome (MetS) in rats. HPTLC of NAOE revealed the presence of 13 total antioxidants, 14 flavonoids, and 10 phenolic acids. Rats administered with fructose (20% w/v) in drinking water for 45 days to induce abnormalities of MetS received NAOE (200 and 400 mg/kg, po), the standard drug gemfibrozil (60 mg/kg, po), aerobic exercise (AE), and a combination of NAOE 400 mg/kg and AE (NAOEAE) daily for 45 days. All treatments significantly altered the lipid profile and attenuated the fructose-elevated levels of uric acid, C-reactive protein, homocysteine, and marker enzymes (AST, LDH, and CK-MB) in serum and malondialdehyde in the heart and restored the fructose-depleted levels of glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). A significant decrease in blood glucose and insulin levels decreased insulin resistance, and improved glucose tolerance was observed in the treatment animals when compared with the fructose-fed animals. The best mitigation of MetS was shown by the NAOEAE treatment indicating that regular exercise along with adequate consumption of antioxidant-rich foods such as spinach in diet can help control MetS.

Appetite suppressing effect of Spinacia oleracea in rats: Involvement of the short term satiety signal cholecystokinin.

Spinacia oleracea (spinach) is a green leafy vegetable rich in antioxidant phyto-constituents such as flavonoids, polyphenols, carotenoids and vitamins. Fruits and vegetables rich in flavonoids are known to prevent weight gain by inducing satiety. The present study evaluates the appetite suppressing effect of a flavonoid rich extract of the spinach leaf (SOE) in rats. HPTLC of SOE was performed for detecting flavonoids. Rats were administered SOE (200 mg/kg and 400 mg/kg, p. o) and fluoxetine (6 mg/kg i. p) as a pre-meal for 14 days. Food intake and weight gain was observed daily during the treatment period. Serum levels of the short term satiety signals cholecystokinin (CCK) and glucose were measured on the 7th and 14thdays at different time points after start of meal to study the satiety inducing effect of SOE. HPTLC showed the presence of 14 flavonoids in SOE. SOE and fluoxetine treated rats showed a significant reduction in food intake and weight gain when compared with the normal control rats. On the 7th day of treatment, peak CCK levels were reached in 30 min after start of meal in fluoxetine treated rats and in 60 min in the remaining rats. On the 14th day, CCK peaking was observed in 30 min after start of meal in the fluoxetine as well as SOE 400 mg/kg treated rats. Peak glucose levels in all treatment groups were obtained in 60 min after start of feeding on both days of the study. It maybe concluded that SOE exhibited a promising appetite suppressing effect by inducing a quicker than normal release of CCK, thus eliciting an early onset of satiety in rats. This effect may be due to its high flavonoid content.

A comparative study of the antacid effect of raw spinach juice and spinach extract in an artificial stomach model.

BackgroundSpinacia oleracea known as spinach is a green-leafy vegetable consumed by people across the globe. It is reported to possess potent medicinal properties by virtue of its numerous antioxidant phytoconstituents, together termed as the natural antioxidant mixture (NAO). The present study compares the antacid effect of raw spinach juice with an antioxidant-rich methanolic extract of spinach (NAOE) in an artificial stomach model. MethodsThe pH of NAOE at various concentrations (50, 100 and 200 mg/mL) and its neutralizing effect on artificial gastric acid was determined and compared with that of raw spinach juice, water, the active control sodium bicarbonate (SB) and a marketed antacid preparation ENO. A modified model of Vatier's artificial stomach was used to determine the duration of consistent neutralization of artificial gastric acid for the test compounds. The neutralizing capacity of test compounds was determined in vitro using the classical titration method of Fordtran. Results NAOE (50, 100 and 200 mg/mL), spinach juice, SB and ENO showed significantly better acid-neutralizing effect, consistent duration of neutralization and higher antacid capacity when compared with water. Highest antacid activity was demonstrated by ENO and SB followed by spinach juice and NAOE200. Spinach juice exhibited an effect comparable to NAOE (200 mg/mL). ConclusionsThus, it may be concluded that spinach displays significant antacid activity be it in the raw juice form or as an extract in methanol.

Dietary Phenolic Acids of Macrotyloma uniflorum (Horse Gram) Protect the Rat Heart Against Isoproterenol-Induced Myocardial Infarction.

The present study investigates the cardioprotective activity of the Macrotyloma uniflorum seed extract (MUSE) and its phenolic acids (p-coumaric acid and ferulic acid) in isoproterenol (ISO)-induced myocardial infarction in rats. The previously mentioned phenolic acids were isolated and quantified from MUSE by HPLC. Pretreatment of gemfibrozil (reference standard), MUSE (250 and 500 mg/kg) and the phenolic acids for 30 days to rats treated with ISO (85 mg/kg) on the last 2 days resulted in a significant attenuation of the ISO-elevated levels of serum marker enzymes (aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase MB), total cholesterol, triglycerides, uric acid, C-reactive protein and malondialdehyde and a restoration of the levels of the ISO-depleted marker enzymes, reduced glutathione and the antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in heart. Restoration of the ISO-altered electrocardiogram pattern and haemodynamic parameters (left ventricular end diastolic pressure, heart rate, systolic, diastolic and mean arterial pressure) was also brought about by treatment with MUSE and the phenolic acids. It may be concluded that MUSE treatment to ISO-challenged rats exhibits a significant cardioprotective effect probably because of the potent antioxidant activity of its phenolic acids that salvage the myocardium from the deleterious effects of ISO. Copyright © 2016 John Wiley & Sons, Ltd.

Wound healing activity of the inflorescence of Typha elephantina (Cattail).

Methanolic extracts of Typha elephantina inflorescence (TE) and its bandage were screened for wound healing by incision and excision wound models in Wistar rats. In the incision wound model, incision wounds were topically treated with TE gel (2.0% [w/w], 3.0% [w/w], and 5.0% [w/w]), Typha elephantina inflorescence bandage, and the reference standard 5.0% w/w povidone iodine for a period of 10 days. When the wounds healed thoroughly, sutures were removed on the 8th postwounding day, and the tensile strength of the skin was measured on the 10th day. In the excision wound model, excision wounds were treated with TE gel (3.0% [w/w] and 5.0% [w/w]), inflorescence bandage, and 5.0% w/w povidone iodine till the wounds completely healed. Epithelization time, wound contraction, hydroxyproline and hexosamine content of the scab, and ascorbic acid and malondialdehyde content of the plasma were determined in this model. In the incision wound model, high tensile strength of the skin of the healed wound was observed in rats treated with the TE gels and the inflorescence bandage when compared with wounded control rats. The increase in tensile strength indicates a promotion of collagen fibers and a firm knitting of the disrupted wound surfaces by collagen. In the excision wound model, higher rate of wound contraction, decreased period of epithelization, elevated hydroxyproline, hexosamine, and ascorbic acid levels, and a significant decrease in malondialdehyde content was observed in treated groups when compared with the wounded control animals. It may be concluded that the inflorescence of Typha elephantina possesses a potent wound healing activity, which may be due to an underlying antioxidant mechanism.

Antioxidant and hepatoprotective effect of Garcinia indica fruit rind in ethanol-induced hepatic damage in rodents.

The protective effects of aqueous extracts of the fruit rind of Garcinia indica (GIE) on ethanol-induced hepatotoxicity and the probable mechanisms involved in this protection were investigated in rats. Liver damage was induced in rats by administering ethanol (5 g/kg, 20% w/v p.o.) once daily for 21 days. GIE at 400 mg/kg and 800 mg/kg and the reference drug silymarin (200 mg/kg) were administered orally for 28 days to ethanol treated rats, this treatment beginning 7 days prior to the commencement of ethanol administration. Levels of marker enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), triglyceride (sTG), albumin (Alb) and total protein (TP) were evaluated in serum. Antioxidant parameters (reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)), hepatic triglycerides (hTG) and the lipid peroxidation marker malondialdehyde (MDA) were determined in liver. GIE and silymarin elicited significant hepatoprotective activity by attenuating the ethanol-elevated levels of AST, ALT, ALP, sTG, hTG and MDA and restored the ethanol-depleted levels of GSH, SOD, CAT, GPx, GR, Alb and TP. GIE 800 mg/kg demonstrated greater hepatoprotection than GIE 400 mg/kg. The present findings indicate that hepatoprotective effects of GIE in ethanol-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation in liver.

Evaluation of cardioprotective activity of Ginkgo biloba and Ocimum sanctum in rodents.

This study investigates the cardioprotective activity of a combined treatment of Ginkgo biloba phytosomes (GBP) and Ocimum sanctum extract (Os) in isoproterenol (ISO)-induced myocardial necrosis in rats. Significant myocardial necrosis, depletion of the endogenous antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH), and increases in the serum marker enzymes aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were observed in ISO-treated rats compared with normal rats. Co-administration of GBP (100 mg per kg) with Os at two doses (50 and 75 mg per kg) for 30 days to rats treated with ISO (85 mg per kg, sc) on the 29th and 30th days demonstrated a significant decrease in ISO-induced serum marker enzyme elevations and a significant attenuation of the ISO-elevated myocardial lipid peroxidation marker malondialdehyde (MDA). A significant restoration of ISO-depleted activities and levels of AST, LDH, CPK, GSH, SOD, CAT, GPx, and GR in the hearts of the treatment groups was observed. The combination of Os 75 mg per kg and GBP 100 mg/kg elicited greater protection than the combination of Os 50 mg per kg and GBP 100 mg per kg. It may be concluded that GBP-Os oral treatment to ISO-challenged rats demonstrates significant cardiac protection, decreases lipid peroxidation, and restores antioxidant activities. However, the combined treatment failed to enhance cardioprotective activity of either herb when used alone.

Cardioprotective activity of Ginkgo biloba Phytosomes in isoproterenol-induced myocardial necrosis in rats: a biochemical and histoarchitectural evaluation.

The protective effects of Ginkgo biloba Phytosomes (GBP) in isoproterenol (ISO)-induced cardiotoxicity and the antioxidant activity involved in this protection were investigated in rats. Myocardial infarction was produced in rats with 65, 85, 120 and 200mg/kg of ISO administered subcutaneously (sc) twice at an interval of 24h. An ISO dose of 85mg/kg was selected for the present study as this dose offered significant alteration in biochemical parameters and moderate necrosis in heart. Effect of GBP oral treatment for 21 days at two doses (100mg and 200mg/kg body weight) was evaluated against ISO (85mg/kg, sc)-induced cardiac necrosis. Levels of marker enzymes (AST, LDH and CPK) were assessed in serum and heart, antioxidant parameters viz., reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) and malondialdehde (MDA) were assayed in heart homogenate. Significant myocardial necrosis, depletion of endogenous antioxidants and increase in serum levels of marker enzymes were observed in ISO-treated animals when compared with the normal animals. GBP elicited a significant cardioprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPx and GR. The present findings have demonstrated that the cardioprotective effects of GBP in ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of membrane.

Hepatoprotective effect of Ginkgoselect Phytosome in rifampicin induced liver injury in rats: evidence of antioxidant activity.

The protective effects of Ginkgoselect Phytosome (GBP) on Rifampicin (RMP) induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. Liver damage was induced in Wistar rats by administering rifampicin (500 mg/kg, p.o.) daily for 30 days. Simultaneously, GBP at 25 mg/kg and 50 mg/kg, and the reference drug silymarin (100 mg/kg) were administered orally for 30 days/daily to RMP treated rats. Levels of marker enzymes (SGOT, SGPT and SALP), albaumin (Alb) and total proteins (TP) were assessed in serum. The effects of GBP on lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were assayed in liver homogenates to evaluate antioxidant activity. GBP (25 and 50 mg/kg) and silymarin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPX, GR, Alb and TP in a dose dependant manner. The present findings suggest that the hepatoprotective effect of GBP in RMP induced oxidative damage may be related to its antioxidant and free radical scavenging activity.

An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract.

BACKGROUND: The MCE, Momordica charantia fruit extract Linn. (Cucurbitaceae) have been documented to elicit hypoglycemic activity on various occasions. However, due to lack of standardization of these extracts, their efficacy remains questionable. The present study was undertaken by selecting a well standardised MCE. This study reports hypoglycemic and antilipidemic activities of MCE employing relevant animal models and in vitro methods. METHODS: Diabetes was induced in Wistar rats by a s.c., subcutaneous injection of alloxan monohydrate (100 mg/kg) in acetate buffer (pH 4.5). MCE and glibenclamide were administered orally to alloxan diabetic rats at doses of 150 mg/kg, 300 mg/kg & 600 mg/kg, and 4 mg/kg respectively for 30 days, blood was withdrawn for glucose determination on 0, 7, 14, 21 and 30th days. On the 31st day, overnight fasted rats were sacrificed and blood was collected for various biochemical estimations including glycosylated haemoglobin, mean blood glucose, serum insulin, cholesterol, triglcerides, protein and glycogen content of liver. The hemidiaphragms and livers were also isolated, carefully excised and placed immediately in ice cooled perfusion solution and processed to study the glucose uptake/transfer processes. Hypolipidemic activity in old obese rats was evaluated by treating two groups with MCE (150 mg/kg & 300 mg/kg) orally for 30 days and determining total cholesterol, triglyceride and HDL-CH, LDL-CH and VLDL-CH levels from serum samples. RESULTS: Subchronic study of MCE in alloxan induced diabetic rats showed significant antihyperglycemic activity by lowering blood glucose and GHb%, percent glycosylated haemoglobin. Pattern of glucose tolerance curve was also altered significantly. MCE treatment enhanced uptake of glucose by hemidiaphragm and inhibited glycogenolysis in liver slices in vitro. A significant reduction in the serum cholesterol and glyceride levels of obese rats following MCE treatment was also observed. CONCLUSION: Our experimental findings with respect to the mechanism of action of MCE in alloxan diabetic rats suggest that it enhances insulin secretion by the islets of Langerhans, reduces glycogenesis in liver tissue, enhances peripheral glucose utilisation and increases serum protein levels. Furthermore, MCE treatment restores the altered histological architecture of the islets of Langerhans. Hence, the biochemical, pharmacological and histopathological profiles of MCE clearly indicate its potential antidiabetic activity and other beneficial effects in amelioration of diabetes associated complications. Further, an evaluation of its antilipidemic activity in old obese rats demonstrated significant lowering of cholesterol and triglyceride levels while elevating HDL-cholesterol levels. Also, the extract lowered serum lipids in alloxan diabetic rats, suggesting its usefulness in controlling metabolic alterations associated with diabetes.