Metalloproteinase is one of the key components of
Russell viper
venom and it is the root cause of edema, blood coagulation, local tissue damage, hemorrhage, and inflammation during snakebite ...envenoming. Hence, finding a suitable metalloproteinase inhibitor from natural source will be of great biological importance in mitigating pathological effects. In this current study, we employed computational analysis to examine the inhibition of metalloproteinase by phytochemicals present in
Andrographis paniculata
. Molecular docking studies revealed interaction of
A. paniculata
phytochemicals with the catalytic M domain’s active site amino acid residues, namely ASN203, ARG293, PHE203, LEU206, LYS199, and ALA122, similar to that of the reference compound Batimastat. 14-acetylandrographolide, 14-deoxy-11,12 didehydroandrographolide, Andrograpanin, Isoandrographolide, and 14-deoxy-11-oxoandrographolide displayed high binding energy and inhibition against the metalloproteinase. Molecular dynamic simulation analysis revealed less root mean square fluctuation of amino acid residues of metalloproteinase-14-acetylandrographolide complex than metalloproteinase-Batimastat complex indicating the high stability for metalloproteinase with the phytochemical. In silico analysis of parameters like ADME properties and drug-likeness of the phytochemicals exhibited good pharmacokinetic properties. Ligand-based virtual screening of phytochemicals to identify similarity to FDA-approved drugs and identification of their possible targets were also performed. The outcome of the current study strengthens the significance of these phytochemicals as promising lead candidates for the treatment of snakebite envenomation. Moreover, the study also encourages the in vivo and in vitro evaluation of the phytochemicals to validate the computational findings.
MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs ...influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.
We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a
mice.
This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.
Staphylococcus aureus a pathogenic bacterium responsible for hospital and community-acquired infections. Trimethoprim is generally administrated for treating S.aureus infection in combination with ...sulfamethoxazole. But increasing antimicrobial resistance towards antibiotics is a major concern. Trimethoprim targets Dihydrofolate reductase (DHFR), a crucial enzyme involved in nucleic acid and amino acid biosynthesis pathways. DHFR catalyzes the conversion of dihydrofolate to tetrahydrofolate using NADH as a cofactor. Andrographis paniculata is a traditionally used medicinal plant for treating various ailments, including microbial infections. More than 25 bioactive phytochemicals have been reported to exhibit various activities. The aim of the present study is to identify the lead phytochemical(s) mediating antimicrobial property of A. paniculata by using computational analysis. Molecular docking of A.paniculata phytochemicals with wild and mutated DHFR were performed. Results reveal phytochemicals interact and exhibit strong binding affinity with active site residues of wild and mutated strains. 14-deoxy-11-oxoandrographolide showed binding energy greater than 10 kCal/mol with both strains. Further analysis of A. paniculata phytochemicals for their efficacy would lead to the development of potential drugs for the treatment of microbial infections.
Diabetes is a chronic metabolic disorder affecting a vast number of people worldwide. Oxidative stress is the causative agent amplifying diabetic complications in various organs by generating noxious ...amount of free radicals. A huge interest always exists in exploring nutraceuticals from plant materials to replace synthetic drugs in order to overcome their adverse effects and also for economic reasons. The anti-diabetic efficiency of a medicinal plant,
Tinospora cordifolia
(TC) was studied in experimentally induced type 2 diabetes in Sprague–Dawley rats. Diabetes was induced by a combination of high fat diet (HFD) for a period of 10 weeks followed by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg of body weight). Oral treatment of TC (100 and 200 mg/kg body weight) for 14 days regulated blood glucose, provoked insulin secretion and also suppressed oxidative stress marker, thiobarbituric acid reactive substances (TBARS), formation and restored cellular defence anti-oxidant markers including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH), in liver. Treatment with TC (100 and 200 mg/kg) also inhibited glucose 6-phosphatase and fructose 1,6-diphosphatase (
p
< 0.001); and restored glycogen content in liver (
p
< 0.005), which was also studied by histopathological staining with periodic acid–Schiff stain. In conclusion, the traditional plant
Tinospora cordifolia
mediates its anti-diabetic potential through mitigating oxidative stress, promoting insulin secretion and also by inhibiting gluconeogenesis and glycogenolysis, thereby regulating blood glucose.
Abstract only
Palmatine a naturally existing alkaloid isolated from a medicinal plant
Tinospora cordifolia
commonly used in Indian System of Medicine for various ailments has been tested for its ...biological activities. Palmatine in 3T3‐L1 (murine pre‐adipocytes) cells effectively inhibited adipocyte differentiation and promoted glucose consumption. Quantification of genes (Glut‐4, PPARα, PPARγ, LPL, FAS and Adiponectin) involved in diabetes and obesity using Real Time PCR and comparing the activity of Palmatine with specific inhibitors of insulin pathway (IRTK, PI3K, Glut 4) reveals that Palmatine is a novel anti‐adipogenic and anti‐diabetic molecule. It is also evidenced by the up regulation of Glut‐4 and PPARα; and down regulation of PPARγ, LPL and FAS. Oxidative stress is the common pathway linking and intensifying in all metabolic disorders. However, the anti‐oxidant property of Palmatine studied by hydrogen peroxide induced cytotoxicity study in 3T3 L1 cells was found to be mild as compared to the proven antioxidant flavonoid Quercitin. In conclusion, the results strongly support the anti‐diabetic, anti‐adipogenic and mild antioxidant activity of the naturally occurring Palmatine in
Tinospora cordifolia
an antidiabetic‐medicinal plant used in India which could serve as a lead pharmaceutical agent to benefit the growing diabetic/obese population. The work was sponsored by the Department of Science & Technology, Govt. of India
Nerium oleander Linn. (NO), an evergreen shrub, is used in folklore medicine as a cardiotonic and exhibits a wide spectrum of bioactivities. Herein, the hypolipidemic potential of the ethanolic ...extract of flowers of Nerium oleander (ENO) in a minimal dose was assessed. A high fat diet (HFD) resulted in a significant increase in cardiac lipids and lipoproteins and an increase in body weight gain. Simultaneous treatment with ENO significantly lowered the increase in body weight gain, lipid and lipoprotein levels, with a concomitant increase in HDL in the plasma and heart when compared to HFD-fed rats. Likewise, the activities of lipolytic enzymes were also upheld by the ENO treatment in the heart compared to HFD-fed rats. The above findings highlight the possible mechanism of N. oleander as a hypolipidemic agent in its use in folklore medicine as a cardiotonic.
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