Glycosides Based Standardized Fenugreek Seed Extract Ameliorates Bleomycin-induced Liver Fibrosis in Rats Via Modulation of Endogenous Enzymes.

BACKGROUND: Liver fibrosis a complex process of excess collagen deposition resulted in disturbance of hepatic cellar function. Glycosides based standardized fenugreek seed extract (SFSE-G) has potent anti-inflammatory, antioxidant, and anti-fibrotic properties. OBJECTIVE: The aim of this study is to evaluate the hepatoprotective potential of SFSE-G against bleomycin (BLM)-induced liver fibrosis in laboratory animals. MATERIALS AND METHODS: Sprague-Dawley rats (180-220 g) were assigned to various groups, namely, normal, sham, BLM control, SFSE-G (5, 10, 20, and 40 mg/kg, p.o.), methylprednisolone (10 mg/kg, p.o.), and sildenafil (25 mg/kg, p.o.). Liver fibrosis was induced in various groups (except normal and sham) by single intratracheal BLM (6 IU/kg) injection. Various biochemical, molecular (reverse transcription polymerase chain reaction) and histological parameters were evaluated. RESULTS: Intratracheal BLM administration caused significant induction (P < 0.001) of hepatotoxicity and liver fibrosis reflected by elevated levels of serum aspartate transaminase (AST), alanine transaminase (ALT), total as well as direct bilirubin, and gamma-glutamyl transferase (GGT). Administration of SFSE-G (20 and 40 mg/kg, p.o.) significantly reduced (P < 0.001) levels of AST, ALT, and GGT and significantly increased (P < 0.001) the level of serum albumin. BLM-induced elevated liver oxidative stress and decreased total antioxidant capacity was significantly restored (P < 0.001) by SFSE-G (20 and 40 mg/kg) treatment. It also significantly inhibited BLM-induced alteration in liver Farnesoid X receptor (FXR) mRNA expression. SFSE-G treatment reduced histopathological alteration induced by BLM in liver. CONCLUSION: SFSE-G exerts its hepatoprotective potential via inhibition of oxido-nitrosative stress and modulation of FXR mRNA expression thus ameliorates BLM-induced liver fibrosis.

Isolation and Structure Determination of 24-Methylenecycloartanyl Ferulate from Indian Rice Bran and Its Quantitative Analysis.

BACKGROUND: γ-oryzanol is a major bioactive constituent in rice. Most of the literature reports isolation of 24-methylenecycloartanyl ferulate (24-mCAF) from rice bran oil (RBO) of other than Indian variety. Current research has successfully applied high-performance thin layer chromatography (HPTLC) method for isolation of 24-mCAF from Indian variety (Indrayani) of RBO. MATERIALS AND METHODS: HPTLC method was developed for standard γ-oryzanol using tinidazole as an internal standard. The proposed HPTLC method was optimized and validated as per the guidelines stated by the International Conference on Harmonization Q2 R1 recommendations. The mobile phase composed of toluene:ethyl acetate:methanol (15.0:1.7:3.3, (v/v/v) was selected because well-resolved peaks were obtained. The optimum wavelength chosen for detection and quantitation was 317 nm. RESULTS: The retention factors for tinidazole, 24-mCAF, and CAF were found to be 0.27 ± 0.02, 0.72 ± 0.02, and 0.79 ± 0.02, respectively. The percent content of 24-mCAF in ethanol fraction was found to be 1.02%. The 24-mCAF was isolated from RBO using HPTLC method. CONCLUSION: The characterization data of 1D, 2D spectral analysis confirm that the isolated compound 1 is 24-mCAF. SUMMARY: HPTLC method was developed for standard γ-oryzanol using tinidazole as an internal standardThe proposed HPTLC method was optimized and validated as per the guidelines stated by the ICH Q2 R1 recommendationsThe characterization data of 1D, 2D spectral analysis confirms that the isolated compound is 24-methylenecycloartanyl ferulateIn this work, high purity 24-mCAF was successfully isolated from crude RBO using HPTLC with a solvent system composed toluene: ethyl acetate: methanol (15.0:1.7:3.3, v/v/v) Abbreviations used: RBO: Rice Bran Oil, CAF: Cycloartenol ferulic acid, 24-mCAF: 24-Methylcycloartenol ferulic acid, HPLC: High-Performance Liquid Chromatography, HPTLC: High-Performance Thin Layer Chromatography, 1H: Proton nuclear magnetic resonance spectroscopy, 13C: Carbon-13 nuclear magnetic resonance spectroscopy, COSY: Correlation spectroscopy, NOESY: Nuclear overhauser effect spectroscopy, HMBC: Heteronuclear multiple bond correlation nuclear magnetic resonance spectroscopy, HSQC: heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy.

Synthesis, beta-adrenergic blocking activity and beta-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates.

The compounds 1-isopropylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate (5) and 1-tert-butylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate (6) were synthesized from thymol (1), a naturally occurring agent in Thymus vulgaris L. Pharmacological evaluation of 5 and 6 were carried out using mouse ECG and isolated rat uterus models. Pretreatment of 5 (100 microg/kg, i.v.) and 6 (50 microg/kg, i.v.) antagonized isoprenaline (2 microg/kg, i.v.) induced tachycardia, similar to that of atenolol (CAS 29122-68-7, 20 microg/kg, i.v.) pretreatment in mouse ECG experiments as measured by R-R interval. Pretreatment of 5 and 6 blocked isoprenaline and adrenaline induced relaxation of isolated rat uterus (unprimed). Also the compounds 5 and 6 were subjected to in vitro beta1- and beta2-adrenergic receptor binding assay using turkey erythrocyte membrane (beta1) and lung homogenate of rats (beta2). Both 5 and 6 showed beta-adrenergic receptor affinity comparable with that of propranolol (propranolol hydrochloride, CAS 318-98-9) with out selectivity to any one beta-adrenergic receptor. These results suggest that both the compounds possess non-selective beta-adrenergic blocking activity, with the tert-butyl derivative 6 being more active than the isopropyl derivative 5.

Association of smoking, alcohol and NSAIDs use with expression of cag A and cag T genes of Helicobacter pylori in salivary samples of asymptomatic subjects.

OBJECTIVE: To determine the association of smoking, alcohol and nonsteroidal anti-inflammatory drugs (NSAIDs) use with presence and virulence of Helicobacter pylori (H. pylori) infection in a representative sample of a random adult population of asymptomatic subjects. METHODS: Non virulent 16S rRNA and virulent cag A and T genes from salivary samples of 854 asymptomatic subjects were determined using polymerase chain reaction. The presence and absence of virulent and non virulent infection was statistically compared with consumption of smoking, alcohol and NSAIDs. RESULTS: The prevalence of infection in male and female subjects was found to be 69.25% and 66.90%, respectively. The prevalence of infection in the population of asymptomatic subjects with respect to consumption of alcohol was as follows: current (31.22%), former (52.20%) and never (43.58%). The prevalence of infection in the population of asymptomatic subjects with respect to smoking of cigarettes was as follows: current (88.80%), former (57.14%) and never (33.33%). The prevalence of infection in the subject population consuming NSAIDs and not consuming NSAIDs frequently was found to be 82.75% and 21.16%, respectively. Virulence in male and female subjects was found to be 60.00% and 50.00%, respectively. The presence of virulent infection in the population of asymptomatic subjects with respect to consumption of alcohol was as follows: current (28.57%), former (40.15%) and never (50.00%). The prevalence of virulent infection in the population of asymptomatic subjects with respect to smoking of cigarettes was as follows: current (79.32%), former (75.00%) and never (50.00%). The prevalence of virulent infection in the subject population consuming NSAIDs and not consuming NSAIDs frequently was found to be 88.23% and 66.66%, respectively. CONCLUSIONS: It can be concluded that smoking and NSAIDs consumption are aggravating factors for virulence of H. pylori and alcohol can inhibit H. pylori infection in asymptomatic subjects.

Hepatorenal repercussions of alcoholic exposure in a rat model: a dose-dependent study of metformin intervention.

BACKGROUND: Diabetes mellitus is an alarming life style disease in the modern world. Exploitation of the anti-diabetic drugs for the amelioration of diabetes and associated life style diseases has become an imperative concern. In this milieu, this study was designed to explore the plausible effects of metformin intervention on hepatic and renal functions in a rat model of alcoholic liver disease. METHODS: Thirty rats were divided into five groups (n = 6): ethanol control, ethanol water and also low, moderate and high doses of metformin. Ethanol 20% v/v (1 ml/100 g) was administered by oral gavage to all five groups for 21 days. Blood and tissue samples were collected for the assessment of lipid profile, hepatic and renal functions. RESULTS: After 21 days, the levels of hepatic function and lipid parameters were maintained at normalcy, especially in the high-dose metformin treated alcoholic rats as compared to the levels at day 1. Despite this, the renal biomarkers did not display any significant variation due to ethanolic exposure in any group. The histopathological score portrayed that the noxious effect of ethanol is prevented in the liver of moderate- and high-dose metformin, whereas the renal histological scores were unchanged in all the groups including ethanol control. CONCLUSION: These results suggest that the dose of ethanol required to induce hepatic dysfunction does not influence renal functions. In addition, high-dose metformin offers maximal hepatoprotection and spares kidney from per se toxicity, thereby advocating the beneficial intervention of the anti-diabetic drug, metformin, in alcoholic liver dysfunction.

Flax lignan concentrate attenuate hypertension and abnormal left ventricular contractility via modulation of endogenous biomarkers in two-kidney-one-clip (2K1C) hypertensive rats

ABSTRACT The present investigation was designed to study the effect of flax lignan concentrate obtained from Linum usitatissimum L., Linaceae, in two-kidney, one clip (2K1C) hypertension model in Wistar rats. 2K1C Goldblatt model rats were divided randomly into six groups: sham, 2K1C control, captopril (30 mg/kg), flax lignan concentrate (200, 400 and 800 mg/kg). Flax lignan concentrate and captopril were administered daily for eight consecutive weeks. Sham-operated, and 2K1C control rats received the vehicle. Treatment with flax lignan concentrate (400 and 800 mg/kg) significantly and dose-dependently restored the hemodynamic parameters systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and left ventricular functions. The flax lignan concentrate significantly restored the elevated hepatic, renal and cardiac marker enzymes in the serum. It also restored the organs weights (kidney and heart), serum electrolyte level and histological abnormalities. Furthermore, flax lignan concentrate significantly elevated the level of biochemical markers that is enzymatic antioxidants superoxide dismutase, glutathione and decreased malondialdehyde in the heart and kidney tissues. Meanwhile, we found that plasma nitric oxide and plasma nitric oxide synthase contents were significantly increased in the flax lignan concentrate-treated group, and plasma endothelin-1 and renal angiotensin-II levels were significantly lower than 2K1C hypertensive group. In conclusion, the antihypertensive and antioxidant effect of flax lignan concentrate were dose-dependent and at the highest dose (i.e. 800 mg/kg) similar to those of captopril (30 mg/kg). It is suggested that flax lignan concentrate reduced blood pressure by reduction of renal angiotensin-II level, inhibition of plasma endothelin-1 production, induction of the nitric oxide, nitric oxide synthase and in vivo antioxidant defense system.

Protective effect of Etoricoxib against middle cerebral artery occlusion induced transient focal cerebral ischemia in rats.

Stroke is the third leading cause of global death and disability. Cyclooxygenase-2 mRNA has been shown to be up-regulated after stroke and also the time window of its expression extends from 4 to 12 h. The objective of this study was to elucidate the protective effect of Etoricoxib (a selective Cyclooxygenase-2 inhibitor) against transient middle cerebral artery occlusion induced behavioral, biochemical and histological alterations. Transient ischemia reperfusion significantly caused behavioral (neurological deficits, decreased locomotor activity and rotarod performance), biochemical (increased lipid peroxidation and nitrite concentration, while decreased superoxide dismutase and catalase activity) and histological (increased infarct volume) changes. Etoricoxib (3 and 10 mg/kg, i.p.) significantly reversed the alterations caused by cerebral ischemia however, 1 mg/kg dose was not found effective in any of the parameters. Finally, we can conclude that Etoricoxib has beneficial effects against transient middle cerebral artery occlusion model in rats. The present study indicates that Etoricoxib may be considered as a potential candidate in the treatment of stroke, clinically.

Synthesis and local anaesthetic activity of 2-substituted-N-(2-diethylaminoethyl)-acetamides.

The synthesis of 2-substituted-N-(2-diethylaminoethyl)acetamide oxalates (6a, 6b) and the evaluation of their in vivo local anaesthetic activities are described. The compounds 6a and 6b were obtained starting from 4-acetamidophenol and 1-naphthol, respectively. The in vivo local anesthetic activity was evaluated by infiltration anaesthesia, sciatic nerve block and corneal anaesthesia models. N-(2-Diethylaminoethyl)-2-(naphthalen-1-yloxy)acetamide oxalate (6b) was found to have potency, onset and duration of action comparable to that of lidocaine (2) (lidocaine hydrochloride, CAS 6108-05-0). Procaine (1) (procaine hydrochloride, CAS 51-05-8) was also used for comparison. Dissociation constants (pKa) of compounds 5a and 5b (2-substituted-N-(2-diethylaminoethyl)acetamide) have been determined to be 8.9 and 8.6, respectively.