HiPSC-Derived Hepatocyte-like Cells Can Be Used as a Model for Transcriptomics-Based Study of Chemical Toxicity

Traditional toxicity risk assessment approaches have until recently focussed mainly on histochemical readouts for cell death. Modern toxicology methods attempt to deduce a mechanistic understanding of pathways involved in the development of toxicity, by using transcriptomics and other big data-driven methods such as high-content screening. Here, we used a recently described optimised method to differentiate human induced pluripotent stem cells (hiPSCs) to hepatocyte-like cells (HLCs), to assess their potential to classify hepatotoxic and non-hepatotoxic chemicals and their use in mechanistic toxicity studies. The iPSC-HLCs could accurately classify chemicals causing acute hepatocellular injury, and the transcriptomics data on treated HLCs obtained by TempO-Seq technology linked the cytotoxicity to cellular stress pathways, including oxidative stress and unfolded protein response (UPR). Induction of these stress pathways in response to amiodarone, diclofenac, and ibuprofen, was demonstrated to be concentration and time dependent. The transcriptomics data on diclofenac-treated HLCs were found to be more sensitive in detecting differentially expressed genes in response to treatment, as compared to existing datasets of other diclofenac-treated in vitro hepatocyte models. Hence iPSC-HLCs generated by transcription factor overexpression and in metabolically optimised medium appear suitable for chemical toxicity detection as well as mechanistic toxicity studies.

Oral Toxicity Studies, Histopathology and Anti-Diabetic activity of Polyherbal Extract in STZ induced diabetes in Rats

Background: Diabetes mellitus is a disease and endocrine disorder and it's a growing health problem in various countries. The prevalence of diabetes rises worldwide including South Africa 5.4% in 2025 increases as expected. The World Health Organization (WHO) estimated the diabetes mellitus problem in adults 173 million in developing counties. In this research observation of glucose levels indicated the diabetic state in Wistar rats by resulting from Streptozotocin administration and using a Metformin as a standard dose. This study demonstrated the acute oral toxicity and subacute oral toxicity of ethanolic extract of Saraca asoca leaves and Asparagus racemosus roots and showed the antidiabetic activity. Objective: To perform acute toxicity studies and sub-acute toxicity of the polyherbal ethanolic extract on the vital organ and isolated organ and record and noticed the visible changes on organs of each group of Wistar rats. Explore the hypoglycaemic action of the polyherbal extract of Saraca asoca and Asparagus racemosus. Methods: Wistar rats were divided into required groups for toxicity study first is acute oral toxicity 5,50, 300,2000 mg/kg body weight. Subacute oral toxicity studies were performed by administering a 250, 500, 1000mg/kg body weight. For demonstrating the antidiabetic activity the animals divided into 5 groups 1 normal control given saline group 2 standard dose Metformin compulsory dose groups 3 Streptozotocin-Induced diabetic 150mg/kg body weight body weight, groups 4 ethanolic extracts at a 100mg/kg groups 5 ethanolic extract 200mg/kg. On the last day of all the dosing period examined the Blood glucose levels and body weights of rat and histopathology studied were done by animal sacrifice and cut organs such as tissue pancreas, spleen, heart, lungs, liver, and kidney, placed on the slide and done a microscopic examination. Data selection has been complete by research papers from many databases such as NCBI, Web of science and Science direct and PubMed from year 1989 to 2020 by utilize research. skeywords such as “Antidiabetic”, “Saraca indica”, “Asparagus racemosus”, “ethanolic polyherbal extract”, “oral toxicity study”, “histopathology”, “Streptozotocin. Results : The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus at a dose of 100mg/kg and 200mg/kg was showed better effects against Streptozotocin-Induced diabetic 150mg/kg body weight body weight. All the extracts showed significantly (P <0.05) and it is safe and non-toxic nature by performed a toxicity study acute and subacute oral toxicity and the bodyweight are also improved, no inflammation and erosion are seen on any organs of Wistar rat by demonstrated a histopathology analysis. Conclusions: The polyherbal ethanolic extract of Saraca asoca and Asparagus racemosus showed hypoglycaemic activity against STZ-induced diabetes in experimental Wistar rats in Wistar rats. The results are shown beneficial effects of these ethanolic extract it helps in improving the changes in lipid metabolism, and protect the organs of Wistar rat liver, kidney, spleen, pancreas, lungs, heart against due to impairment of blood glucose and also in body weight. All organs were weighted and cut the tissue of organs and stained from eosin dye and changes observed by microscopy photos. no signs of inflammation and erosion.

ANTI-INFLAMMATORY AND ORAL TOXICITY ASSESSMENT OF R-38TM: A TRADITIONAL HERBAL SUPPLEMENT FOR ARTHRITIS

R-38TM is a traditional herbal supplement for treating arthritis-related conditions. High-performance liquid chromatography (HPLC) analysis was performed for identification and quantification of rosmarinic acid in the R-38TM water extract. The anti-arthritic potential of the R-38TM water extract was investigated by measuring the production of IL-6 and TNF-α in inflamed cells. Xanthine oxidase (XO) and cyclooxygenase-2 (COX-2) inhibition assays were also conducted. The cytotoxic effect of R-38TM water extract was investigated on HSF1184 cell line. Acute and subacute oral toxicity studies were conducted on female Sprague-Dawley (SD) rats. The rosmarinic acid was identified at 1.208 min (3.61 %w/w). The inflamed cells showed a decrease in the production of IL-6 (55.9%) and TNF-α (52.13%). The COX-2 and XO enzymes were moderately inhibited by R-38TM water extract. The cytotoxicity analysis showed no cytotoxic effect on the cell. The acute and subacute oral toxicity studies revealed no mortality and normal body weight at all doses. There were no significant differences (p > 0.05) in organ weight, hematological and biochemical parameters, and histology of liver and kidneys with the control group. In conclusion, R-38TM water extract exhibited no toxic effect orally and may possess potential therapeutic properties against pro-inflammatory diseases including arthritis.

Toxicity Studies of Centella asiatica for Drug Development: Mini Review

Toxicity studies' quality control of drug plant-based products is an important aspect of pharmacological research. The purpose of this literature review is to extract about toxicity test on Centella asiatica. The plant component utilized, the test animals used, the type of toxicity test, evaluation, the findings, and conclusions of each test are all included in this review—the database used in PubMed. Most of the literature results obtained from this review indicate high safety in C. asiatica plants. The acute toxicity test is that the most frequently used toxicity test. The use varies from plant parts to whole plants, with minimal side effects reported and high in safety, so it can be concluded that C. asiatica is very prospective to be developed as a medicine.

An Updated Review on Phyto-Pharmacological and Pharmacognostical Profile Of Buchanania Lanzan : A Pharmacognostic Miracle Herb

Buchanania lanzan (Anacardiaceae) is a miracle herb widely used by Indian tribes for treating various diseases. Aim of the current review is to search literature for the pharmacological properties, pharmacognostic studies and phytochemical investigation of Buchanania lanzan. The compiled data may be helpful for the researchers to focus on the priority areas of research yet to be discovered. Complete information about the plant has been collected from various books and journals. Particulars of pharmacological activities, phytochemical isolation, toxicity studies etc. ongoing and emerging areas of research of this plant, especially in the field of phytomedicnes and pharmaceuticals was concluded in the review.

Monitoring of Cardiorespiratory Parameters in Rats—Validation Based on Pharmacological Stimulation

The methods used in preclinical studies should minimize the suffering and the number of animals but still provide precise and consistent results enabling the introduction of drug candidates into the phase of clinical trials. Thus, we aimed to develop a method allowing us to perform preliminary safety and toxicity studies of candidates for human medicines, while reducing the number of animals. We have devised a method based on a combination of two devices: Plugsys (Transonics System Inc., Ithaca, NY, USA) and PhysioSuite (Kent Scientific Corporation, Torrington, CT, USA), which allow simultaneous registration of nine circulatory and respiratory parameters, and body temperature. Vehicle and adrenaline, or nitroglycerin, as reference substances were administered into the right femoral vein of Wistar rats. Physiological conditions were registered over 60 min after drug administration by measuring systolic, diastolic and mean blood pressure, heart rate (HR), blood perfusion of paw vessels, blood oxygen saturation, respiratory rate, average and peak exhaled CO2, and body temperature. Blood pressure was measured by cannula placed in the left common carotid artery and connected to the pressure transducer (Plugsys). The other parameters were measured by the PhysioSuite. Adrenaline-induced immediate dose-related hypertension and nitroglycerin hypotension were correlated with the change in blood perfusion. They both increased HR. Adrenaline decreased blood oxygen saturation and slightly affected respiratory parameters, while nitroglycerin caused a progressive increase in respiratory rate and a decrease in the peak of exhaled CO2. Our method may become an inseparable part of the preliminary safety and toxicity studies of tested drugs, while being an important step towards improving animal welfare.

Critical Analysis of Snuhi - Euphorbia Neriifolia (Upavisha- Poisonous Plant) and its Application as a Therapeutic Aid

Traditional system of medicines has vast applications of poisonous plants; hence the knowledge about poisonous plant and its therapeutic effects becomes very essential to develop a new drug for the new diseases like Covid 19 and other diseases. Many research studies have showed that the poisonous medicinal plants are endowed with properties like Antidiabetic, Anticancer, Antibacterial, Antifungal, and Cytogenetic effect. This study focused on one such drug called Snuhi - Euphorbia Neriifolia, a Upavisha or a poisonous plant to evaluate its therapeutic effects, which would be helpful for the mankind after the proper Shodhana (purification), by conducting experimental studies, toxicity studies and thereby applied in various diseases for its therapeutic benefits and to relieve the sufferings of the patients.