Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells.

Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox's cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox's effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.

Barium Chloride-Induced Cardiac Arrhythmia Mouse Model Exerts an Experimental Arrhythmia for Pharmacological Investigations.

AIM: Cardiac arrhythmias are among the most important pathologies that cause sudden death. The exploration of new therapeutic options against arrhythmias with low undesirable effects is of paramount importance. METHODS: However, the convenient and typical animal model for screening the potential lead compound becomes a very critical modality, particularly in anti-arrhythmia. In this study, mice were intraperitoneally (i.p.) injected with BaCl2, CaCl2, and adrenaline to induce arrhythmia, and simultaneously compared with BaCl2-induced rats. RESULTS: Electrocardiogram (ECG) showed that the majority of mice repeatedly developed ventricular bigeminy, ventricular tachycardia (VT), and ventricular fibrillation (VF) after BaCl2-injection as seen in rats. The ECG of mice developed ventricular bigeminy and VT after CaCl2 and AT after adrenaline i.p. injection. Additionally, acute cardiac arrhythmia after BaCl2 i.p. injection could be reverted by drugs (lidocaine and amiodarone) administration. Additionally, the different routes of administration for various chemical-induced arrhythmia in both mice and rats were also retrieved from PubMed and summarized. Comparing this approach with previous studies after the literature review reveals that arrhythmia of BaCl2-induced i.p. mice is compatible with the induction of other routes. CONCLUSIONS: This study brings an alternative experimental model to investigate antiarrhythmic theories and provides a promising approach to discovering new interventions for acute arrhythmias.

Pharmacological properties and underlying mechanisms of curcumin and prospects in medicinal potential.

Curcumin, isolated from Curcuma longa L., is a fat-soluble natural compound that can be obtained from ginger plant tuber roots, which accumulative evidences have demonstrated that it can resist viral and microbial infection and has anti-tumor, reduction of blood lipid and blood glucose, antioxidant and removal of free radicals, and is active against numerous disorders various chronic diseases including cardiovascular, pulmonary, neurological and autoimmune diseases. In this article is highlighted the recent evidence of curcuminoids applied in sevral aspects of medical problem particular in COVID-19 pandemics. We have searched several literature databases including MEDLINE (PubMed), EMBASE, the Web of Science, Cochrane Library, Google Scholar, and the ClinicalTrials.gov website via using curcumin and medicinal properties as a keyword. All studies published from the time when the database was established to May 2021 was retrieved. This review article summarizes the growing confirmation for the mechanisms related to curcumin's physiological and pharmacological effects with related target proteins interaction via molecular docking. The purpose is to provide deeper insight and understandings of curcumin's medicinal value in the discovery and development of new drugs. Curcumin could be used in the prevention or therapy of cardiovascular disease, respiratory diseases, cancer, neurodegeneration, infection, and inflammation based on cellular biochemical, physiological regulation, infection suppression and immunomodulation.

Syringaldehyde promoting intestinal motility with suppressing α-amylase hinders starch digestion in diabetic mice.

The antihyperglycemic potential of syringaldehyde has been previously investigated; however, the underlying mechanism remains unclear. In this study, we performed a postprandial glucose test (in vivo) including oral glucose tolerance test (OGTT) and oral starch tolerance test (OSTT) in fructose-induced diabetic mice on a high-fat diet for mimicking type 2 diabetes to explore the hypoglycemic efficacy of syringaldehyde and the underlined molecular involvement of syringaldehyde in a glucose-lowering effect. The results revealed that syringaldehyde dose-dependently suppressed blood glucose in both the OSTT and OGTT when referenced to acarbose and metformin, respectively. Surprisingly, syringaldehyde triggered jejunum motility (ex vivo) via activation of the muscarinic-type acetylcholine receptor. By performing virtual screening with molecular docking, the data showed that syringaldehyde nicely interacted with glucagon-like peptide 1 receptor (GLP-1R), peroxisome proliferator-activated receptor (PPAR), dipeptidyl peptidase-IV (DPP-4), acetylcholine M2 receptor, and acetylcholinesterase. These results showed that syringaldehyde can potentiate intestinal contractility to abolish the α-amylase reaction when concurrently reducing retention time and glucose absorption to achieve a glucose-lowering effect in diabetic mice, suggesting its potential therapeutic benefits with improvement for use as a prophylactic and treatment.

A nutraceutical combination of cinnamon, purple onion, and tea linked with key enzymes on treatment of type 2 diabetes.

Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause adverse effects. This study was to explore the efficacy of polyherbal dietary supplement cinnamon, purple onion, and tea on the mediation of postprandial hyperglycemia in the search of combinations with a maximal response. A starch solution (3 g/kg Bwt) of oral starch tolerance test (OSTT) and glucose solution (4 g/kg Bwt) of oral glucose tolerance test (OGTT) with and without cinnamon, purple onion, tea extract (15 mg/kg Bwt), and mixture (each 5 mg/kg Bwt, 1:1:1), metformin (14 mg/kg Bwt), or acarbose (50 mg/kg Bwt) was administered to high fat plus high fructose-induced diabetic mice after an overnight fast. Postprandial plasma glucose levels were measured and changed areas under the response curve were calculated to find out the maximal efficacy of optimal polyherbal combinations. Compared with acarbose, the mixture of extracts (purple onion, cinnamon, and tea) indicated the decreasing blood glucose in OSTT. In OGTT, the mixture of extracts showed greater efficacy for hypoglycemia when compared with metformin. The molecular docking of α-amylase, α-glucosidase, and AMPK was further confirmed the putatively acting molecules from the extracts of purple onion, cinnamon, and tea. Overall, this investigation evidenced a beneficial mediation for the progression of lowering blood glucose with a combinatory extract of cinnamon, dietary onion, and tea, implicating their prospective as nutraceuticals that might ameliorate hyperglycemia in diabetes. PRACTICAL APPLICATIONS: Diabetes mellitus (DM), one of metabolic syndrome, attributes to risk factors like obesity, physical inactivity, ageing, life style, and genetic predisposition even with significant morbidity and mortality. DM is increasing and accounts for an estimated annual medical expenditure of US$ 827 billion worldwide. Therefore, maintaining blood glucose levels within the normal range is critical for preventing diabetes and its co-morbidities. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; nevertheless, they may also cause adverse or side effects. In an effort to design novel and well-tolerated solutions to halt the progression of DM, however evidence-base is extremely limited regarding the efficacy of polyherbal dietary supplement individual herbs for the management of glycemia. In this investigation evidenced a beneficial mediation for the progression of lowering blood glucose with a combinatory extract of cinnamon, dietary onion, and tea, implicating their prospective as nutraceuticals that might ameliorate hyperglycemia in diabetes.

RGD-modified injectable hydrogel maintains islet beta-cell survival and function.

OBJECTIVE: A potential solution for islet transplantation and drug discovery vis-à-vis treating diabetes is the production of functional islets in a three-dimensional extracellular matrix. Although several scaffold materials have been reported as viable candidates, a clinically applicable one that is injectable and can maintain long-term functionality and survival of islet pancreatic beta-cells (ß-cells) is far from being established. RESULTS: In the current study, we evaluated a ready-to-use and injectable hydrogel's impact on ß-cells' function and viability, both in vitro and in vivo. We found that ß-cells in high concentration with hydrogels functionalized via Arg-Gly-Asp (RGD) demonstrated better viability and insulin secretory capacity in vitro. Moreover, it is a biocompatible hydrogel that can maintain ß-cell proliferation and vascularization without stimulating inflammation after subcutaneous injection. Meanwhile, modifying the hydrogel with RGD can maintain ß-cells' secretion of insulin, regulating the blood glucose levels of mice with streptozotocin-induced diabetes. CONCLUSIONS: Thus, these preliminary results indicate that this RGD-modified hydrogel is a potential extracellular matrix for islet transplantation at extrahepatic sites, and they also provide a reference for future tissue engineering study.