Acute and sub-chronic toxicity of Liberin, an anti-diabetic polyherbal formulation in rats.

BACKGROUND: The polyherbal formulation (PHF) liberin, is known to exert anti-hyperglycemic effects in type 2 diabetes mellitus. Hence, it is important to study the safety profile of PHF in the current study through acute and chronic toxicity evaluation. OBJECTIVES: This research aims to assess the acute and sub-chronic toxicity of PHF in rats. MATERIALS AND METHODS: PHF was administered once orally (1000 mg/kg body weight), and the rats (male and female) were monitored for toxicity signs for a 14-day period. For a 28-day chronic toxicity study, rats were daily administered with PHF dose of 500 mg/kg and 1000 mg/kg body weight. Rats were followed up for mortality, weight changes, and other morbidities. Further haematological, biochemical, and histopathological changes were assessed. RESULTS: No death related to treatment or toxicity signs were recorded in the acute single-dose administration group. The results showed that the PHF was tolerated well up to a dose of 1000 mg/kg body weight. Even at the high dose of 1000 mg/kg body weight, sub-chronic tests did not show any significant difference between the dosed and normal groups. No significant changes were seen in the histopathological analysis of the liver, spleen, and kidney as well as haematological and biochemical parameters in acute, sub-chronic and satellite groups following the administration of PHF. CONCLUSION: The results confirmed that there was no adverse effect of this PHF at the maximum dose of 1000 mg/kg body weight in Wistar rats. Further, no adverse delayed effects related to PHF were observed in the satellite group. Therefore, this PHF appears safe for therapeutic purposes in the Ayurvedic medicinal system.

Anti-hyperglycemic, anti-hyperlipidemic, and anti-inflammatory effect of the drug Guggulutiktaka ghrita on high-fat diet-induced obese rats.

BACKGROUND: Ayurveda is a holistic system of medicine and describes a vast array of herbs and herbal mixtures that are been demonstrated to possess efficacy in research investigations. Guggulutikthaka gritha (GTG) is one such drug evaluated for its role in skin and bone diseases. OBJECTIVE: In the current study, the hypoglycemic, hypolipidemic, and anti-inflammatory effect of the drug GTG was studied with the scope to treat dyslipidemia and thereby reduce the risk of cardiovascular disease. MATERIALS AND METHOD: The animals (Wistar rats) were fed a high-fat diet and dyslipidemia was induced. The control group was provided with a normal chow diet and had free access to water. The treatment with the drug GTG was given for 21 days after confirming dyslipidemia. The blood glucose was measured immediately using a glucometer. The serum was analyzed for lipid profile and Vascular Cell Adhesion Molecule - 1(VCAM 1) by ELISA method before and after treatment. The histopathology of the heart and liver was also performed. RESULTS: The abnormal change in lipid profile, blood glucose, and inflammatory marker along with the accumulation of intracellular fats in the arteries of the heart and liver confirmed dyslipidemia. A significant reduction in serum lipid profile (p < 0.05), blood glucose (p < 0.05), and VCAM 1 (p < 0.05) was noted after the treatment with significant histopathological changes in arteries of the heart and liver. CONCLUSION: The study provides scientific validation on the drug GTG being effective in hyperglycemia, hyperlipidemia, and inflammation in dyslipidemia.

Purification of Bhallathaka (Semecarpus anacardium L.f.) enhanced anti-cancer activity.

Semecarpus anacardium L. F. commonly known as Bhallathaka, is an important Ayurvedic medicinal plant of the family Anacardiaceae. Mature fruit of this plant is used as an Ayurvedic drug for treating various ailments including cancer. The drug has been reported to cause irritation, blisters, toxicity and contact dermatitis if used in raw form. In Ayurvedic texts, various methods have been described for purification process of Bhallathaka in order to minimize the toxic effects as well as to potentiate the drug. This study was carried out to evaluate chemical profiles and anti-cancer activity of raw and purified samples of Bhallathaka. Chemical characterization was done by Liquid chromatography mass spectroscopic (LC/MS) analysis and anticancer activity was evaluated using Ehrlich Ascites Carcinoma (EAC) model in mice with 5-fluorouracil as standard. The result indicated that purification of Bhallathaka imparted chemical changes to certain active compounds and enhanced its anti-cancer activity when compared to raw sample. The present study concluded that traditional purification process can impact the chemical and pharmacological profile of herbal drugs and thus beneficial in increasing its safety and efficacy.

Acute Kidney Injury and Progressive Diabetic Kidney Disease: An Epidemiological Perspective.

PURPOSE: Diabetic kidney disease (DKD) represents a unique subset of patients with chronic kidney disease (CKD). Acute kidney injury (AKI) is implicated in DKD progression; however, their interplay is not studied well. We studied risk factors for AKI and the effect of AKI on disease progression in a homogeneous group of patients with DKD. PATIENTS AND METHODS: We conducted a retrospective open cohort study of patients with DKD at a single tertiary care centre between August 2016 - August 2019. Patients with a minimum follow-up of 2 years were included in the study. The incidence, etiology and risk factors for AKI were studied. The primary outcome studied was the effect of AKI on reduction in estimated glomerular filtration rate (eGFR) in DKD. Loss in eGFR by 50% and need for renal replacement therapy or reaching CKD stage V were studied as secondary outcomes. RESULTS: Two hundred and ninety-two DKD patients meeting the study criteria with a follow-up of 29.57 (±4.3) months were included. The incidence of AKI was 31.1%. Sepsis was the most common etiology (61%). Proteinuria was an independent risk factor for AKI after adjusting for covariates (adjusted OR - 1.158; 95% CI (1.018-1.316); p=0.025). In patients with AKI, median decline in eGFR was 10.29 mL/min/1.73m2/year (IQR-5.58-13.84) which was significantly higher compared to patients with no AKI [eGFR 7.25 (IQR 5.06-11.38); p-0.014]. On subgroup analysis, sepsis-induced AKI (versus non-sepsis AKI; p<0.001) and higher AKI stage (stage 2/3 versus stage 1; p=0.019) were associated with a faster decline in eGFR. CONCLUSION: AKI is common in patients with DKD with sepsis being the most common etiology. AKI in diabetic kidney disease is associated with a faster decline in eGFR. Baseline proteinuria is an independent risk factor for AKI.

Chemical profiling of selected Ayurveda formulations recommended for COVID-19.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is the global health concern since December 2019. It has become a big challenge for the researchers to find a solution for this newly evolved pandemic. In Ayurveda point of view, COVID-19 is a Janapadodhwamsa vikara (epidemic disease), a situation where the environment-air, water, land, and seasons-is vitiated, causing a simultaneous manifestation of a disease among large populations. The aim of this study is to identify the active compounds of selected Ayurveda medicines recommended for COVID-19. RESULTS: The selected preparations are traditionally recommended for the management of various kinds of fever including the infectious ones and to enhance the immunity. HPTLC analysis of the same showed presence of many active molecules like umbelliferone, scopoletin, caffeic acid, ferulic acid, gallic acid, piperine, curcumin, berberine, and palmatine. CONCLUSION: The study provided valuable scientific data regarding the active ingredients of the selected medicines with proven therapeutic potentials like anti-viral, immunomodulatory, and anti-inflammatory activities.

Role of UHRF1 in malignancy and its function as a therapeutic target for molecular docking towards the SRA domain.

The figure describes the location of UHRF1 (Ubiquitin-like with containing PHD and RING Finger domains 1) gene, mRNA and protein synthesis in the tumor cell and its structural domains with a focus on the docking of Naphthazarin on the SRA domain of UHRF1, resulting in reduction of tumor size.

Glucose 6 phosphate dehydrogenase deficiency unmasked by diabetic ketoacidosis: an underrated phenomenon.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disease responsible for moderate to severe hemolytic anaemia. Despite being the most common erythrocyte enzyme disorder, it is often overlooked in the regular diagnostic parlance. A 40-year-old male patient admitted to the casualty with an acutely exacerbated diabetic ketoacidosis, showed features of hemolytic anaemia on peripheral smear examination. Crucially, the spherocytes and bite cells suggested a possibility of G6PD deficiency. This was substantiated by an increased reticulocyte count (6.8%) and a reduced quantitative G6PD enzyme assay (7.2%). There was no significant family or prior medical/ drug history. Interestingly, the hemolytic features were evidenced when blood glucose levels were returning to normal values. The insulin mediated NADPH loss may have resulted in an increased erythrocyte oxidant sensitivity and a loss of sulfhydryl group availability; causing hemolysis to manifest. G6PD deficiency is conventionally affiliated with drug induced oxidative stress. But an association with a diabetes mellitus is seldom reported. This case is being presented as it highlights the lesser known complication of diabetic crisis such as hemolysis secondary to a G6PD deficiency.

In vitro safety evaluation and anticlastogenic effect of BacoMind on human lymphocytes / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>BacoMind (BM) is a standardized extract of Bacopa monnieri, which belongs to the family Scrophulariaceae and is a creeping annual plant found throughout the Indian subcontinent. It has been used by Ayurvedic medicinal practitioners in India for almost 3000 years and is classified as a medharasayana, a substance which improves memory and intellect. With the widespread traditional use as well as scientific validation of Bacopa monnieri for nootropic activity, a bioactive-rich unique phytochemical composition-BacoMind was developed from B. monnieri for use as a cognition and memory enhancing agent. The present study aimed to investigate the in vitro toxicity of this formulation of BacoMind on human lymphocytes and to rule out its possible contribution to mutagenicity.</p><p><b>METHODS</b>In the present investigation the active ingredients present in BM were identified and quantified by high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC). Antioxidant and anticlastogenic properties of BM were studied in vitro with and without metabolic activation. Doses of BM were chosen on the basis of mitotic index (MI) and cytokinesis-block proliferation index (CBPI). Clastogenicity assays were performed at 31.2 microg/mL, 62.5 microg/mL, and 125 microg/mL, while the Salmonella reverse mutation assay (Ames test) was performed at doses of 61.72, 185.18, 555.55, 1666.67, and 5000.00 microg/plate.</p><p><b>RESULTS</b>HPLC and HPTLC analysis of BM revealed the presence of bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopasaponin C, bacosine, luteolin, apigenin, bacosine, and beta-sitosterol D glucoside. BM demonstrated significant antioxidant activity. The number of chromosomal aberrations and the frequency of micronuclei induced by BM were not statistically significant up to a dose of 62.5 microg/mL. A subsequent dose of 125 microg/mL prior to metabolic activation induced mild clastogenicity, but it was found to be biologically insignificant as this effect was not seen post metabolic activation. BM also demonstrated a dose-dependent protection against the clastogens used in this study using the above tests for clastogenicity. Maximum protection was observed in presence of metabolic activation. Moreover, BM demonstrated no mutagenic effect on the tested strains, as observed in the Ames test.</p><p><b>CONCLUSION</b>BM protected human lymphocytes against various clastogens. BM also exhibited high antioxidant activity which might be responsible for the observed protective effects against the clastogens since the used clastogens are known to induce their clastogenic effects via production of oxidative radicals.</p>