ISOLATION OF CUCURBITACIN-B FROM CUCUMIS CALLOSUS AND ITS HYPOGLYCEMIC EFFECT IN ISOLATED RAT ENTEROCYTES

Objective: The pericarp of fruits of Cucumis callous (Rottl.) Cogn. (Cucurbitaceae) is traditionally used for curing diabetes, epilepsy, and diarrhea. It has an active compound include Cucurbitacin-B (CuB), which acts as a potent inducer of CYP450 of rat enterocytes. This study was conducted with the aim of elaborating and reconciling our previous finding on the glucose-lowering effect of Cucumis callosus (Rottl.) Cogn. fruits.Methods: In vivo hypoglycemic potential for methanolic pericarp extracts from C callosus (MPCC, 350 mg/kg b.w. p. o), methanolic seed extract of C callosus (MSCC, 250 mg/kg b.w. p. o) and CuB (80 µg/kg b.w. p. o) were studied in streptozotocin (STZ, 55 mg/kg b.w. i. p) induced diabetic rats. Metformin (25 mg/kg b.w. p. o) served as reference drug. Ex vivo model of intestinal tissue preparation of Swiss albino rats named Single Pass Intestinal Perfusion (SPIP) technique was performed for ex vivo hypoglycemic study. The glucose levels in the serosal fluid were determined by commercially available glucose oxidase kit and compared with the standard drug metformin (0.1 mg/kg).Results: In vivo results showed that administration of MPCC (350 mg/kg b.w. p. o) and Cucurbitacin-B (80 µg/kg b.w. p. o) produced the hypoglycemic effect. The MPCC (1.4 mg/kg) and CuB (0.4 µg/kg) produced hypoglycemic effect in ex vivo technique. These effects are due to induction of 0.53 mµmoles of CYP450 proteins with maximum absorption at 454 mµ in rat enterocytes.Conclusion: The present investigation gave evidence that bitter pericarp of C callosus fruit has a hypoglycemic effect due to the presence of Cucurbitacin B as phytoconstituent but seeds did not have such effects

EVALUATION OF ANTICANCER ACTIVITY OF CUCUMIS CALLOSUS AGAINST EHRLICH'S ASCITES CARCINOMA BEARING MICE

Objective: Our previous research isolated Cucurbitacin B (CuB) and ebenone leucopentaacetate (ELP) from methanolic fruit extract of Cucumis callosus (MFCC). The fruits of C. callosus (Rottl.) Cogn. (Family: Cucurbitaceae) plant have been traditionally used for antioxidant, anti-inflammatory, and antidiabetic actions. The objective of this research was to evaluate in vitro and in vivo anticancer effect of MFCC on Ehrlich Ascites Carcinoma (EAC) cell lines.Methods: In vitro anticancer assay of MFCC and standard drug, 5-fluorouracil (5-FU) was evaluated using Trypan blue and 3-(4, 5-dimethylthiazol-yl)-2, 5-diphenyl tetrazolium bromide methods. In vivo anticancer activity of MFCC and 5-FU was also performed after 24h of EAC cells (2×106cells/ mouse) inoculation based on toxicity study for 9 consecutive days. The activity of the extract was assessed by the study of tumor volume, tumor weight, viable and non-viable cell count, hematological parameters, and biochemical estimations.Results: The MFCC showed the direct antitumor effect on EAC cells in a dose-dependent manner with an IG50 value of 0.61 mg/ml. Furthermore, MFCC (350 mg/kg) exhibited significant (p<0.01) decrease in tumor volume, tumor weight, and viable cell count of EAC-treated mice. Hematological profile, biochemical estimation assay significantly (p<0.01) reverted to normal level in MFCC, and 5-FU treated mice.Conclusion: The anticancer activity of fruits of C callosus is may be either due to the presence of CuB or/and ELP as phytoconstituent and the activity is comparable to standard drug 5-FU

EFFECTIVE STRATEGIES FOR MEDICATIONS TO TREAT SUBSTANCE USE DISORDERS

The authors of this paper briefly review the pharmacotherapeutic experts who are currently available for the treatment of substance use disorders. The best tobacco cessation treatments use nicotine. The usage of naltrexone, acamprosate, and disulfiram can reduce alcohol consumption. Agonist medications, such as methadone and buprenorphine, are the most effective pharmacotherapies for sedative use disorders. The authors also review recent improvements in medicine for treating illnesses caused by other substances, such as energizer dependency. The job of prescription adherence and social medicines and the joining of conduct and pharmacotherapeutic intercessions are likewise examined. Patients were shown to employ feelings-based stress coping techniques more frequently than other methods in the Stress Coping Ways Scale assessment, which is consistent with other local studies. After rundown and assessment of Socrates study information when the treatment, such inclinations were seen - before the treatment not exactly 50% of the patients evaluated their compulsion as extremely serious, yet after the treatment the greater part of the patients thought that it is exceptionally serious

PREDICTING THE VULNERABILITY AND RESILIENCE TO CARDIOVASCULAR AND NEUROENDOCRINE EFFECTS OF STRESS IN ADULT RATS THROUGH A NOVEL MACHINE LEARNING APPROACH

Chronic stress has been risk of cardiovascular disease and neuroendocrine illness in humans and animals. However, not all individuals are equally vulnerable to the negative effects of stress, and some may even exhibit resilience. Identifying biomarkers or other predictors of vulnerability and resilience could help to develop personalized prevention and treatment strategies. In this study, we aimed to predict vulnerability and resilience to stress-related health effects in adult rats using a novel machine learning approach. We exposed male rats to chronic stress or control conditions for six weeks and measured their cardiovascular and neuroendocrine responses at baseline and at the end of the stress exposure. Rats were considered vulnerable if they exhibited large growth in heart rate and reaction of blood pressure to stress, and resilient if they did not show significant changes in these parameters. We then applied a novel machine learning algorithm to identify patterns in the data that could predict vulnerability or resilience. In this case, we employed a combination methods for selecting features using Support Vector Machine and classification algorithm Principal component Analysis to identify the most important predictors of vulnerability and resilience. We also compared the performance of the machine learning approach with traditional statistical methods, such as logistic regression and discriminant analysis. Our results suggest that heart rate variability were among the most important predictor of vulnerability and resilience to stress-related health effects in rats. Specifically, rats with lower heart rate variability and higher cortisol levels at baseline were more likely to be vulnerable to stress. Conversely, rats with greater concentrations of anti-inflammatory cytokines increased risk of becoming resilient to stress. The machine learning approach was more accurate in predicting vulnerability and resilience than traditional statistical methods, with an overall accuracy of 89%, respectively. Our study provides new insights into the complex interplay between stress and health, and highlights the potential of machine learning to improve our understanding of this relationship. The identification of biomarkers and predictors of vulnerability and resilience could lead to the development of personalized approaches to stress management and prevention of stress-related health conditions

Optimization and Hepatoprotective Activity of Herbal Formulation of Methanolic Extracts of Ruta Graveolens and Angelica Sinensis

The goal of this study was to evaluate the antioxidant and hepatoprotective effects of RAAS, a specially created herbal mixture that contains methanol extracts of Ruta graveolens and Angelica sinensis. A range of in vitro tests were performed as part of the study to assess any potential health advantages of RAAS. The laboratory assays employed to assess the antioxidant capacity of RAAS included the total antioxidant activity assay, the reducing power assay, and the DPPH radical scavenging assay. These evaluations showed that RAAS has strong antioxidant characteristics, demonstrating its capacity to counteract oxidative stress and disarm dangerous free radicals. Additionally, the study examined the hepatoprotective effects of RAAS utilizing a cellular model that included HepG2 cells and carbon tetrachloride-induced liver injury (CCl4). According to the findings, RAAS significantly protected HepG2 cells from the negative effects of CCl4-induced liver damage. In conclusion, this study highlights the prospective antioxidant and hepatoprotective properties of RAAS, an herbal formula made from methanol extracts of Ruta graveolens and Angelica sinensis. Strong in vitro antioxidant activity and the capacity to prevent CCl4-induced damage to liver cells show the potential therapeutic utility of RAAS in reducing oxidative stress and liver-related diseases. Deeper understanding of its uses in boosting liver health and general wellbeing may come from additional studies in the clinical setting and other fields of stud

STABILITY INDICATING METHOD DEVELOPMENT AND VALIDATION OF FIMASARTAN BY REVERSE-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY IN BULK AND PHARMACEUTICAL DOSAGE FORM

Objective: A rapid, sensitive and specific reverse phase High performance liquid Chromatography (RP-HPLC) method was developed for the estimation of Fimasartan in bulk and pharmaceutical dosage form. Method: The RP-HPLC analysis was performed isocratically on a Primacel C18 column (150 mm × 4.6 mm internal diameter, 5 μm particle size) using mobile phase of composition Acetonitrile and 0.1% orthophosphoric Acid in 80:20, v/v proportions with a flow rate of 0.8 ml/min. Results: The analyte was monitered with UV-detector at 265 nm. In the developed method Fimasartan elutes at a typical retention time of 2.4 min. The proposed method is having linearity in the concentration ranging from 5-30 μg/ml of Fimasartan. Conclusion: : The method was statistically validated and had been applied to analysis of the drug in bulk and pharmaceutical dosage form