Biology subjects

Chethala N, V.

Publications and source records attributed to Chethala N, V..

3 recordsLinked to original sources

bioRxiv2024

Anti-diabetic and anti-adipogenic effects of polyherbal formulation Varanadi kashayam with a focus on incretin modulation

BackgroundFrontiers of health science increasingly emphasizes systems and network medicine approaches for managing complex lifestyle diseases such as diabetes. In this context, systemic targets like incretin hormones and their modulators - particularly DPP4 inhibitors - have gained prominence. Ayurveda, the Indian System of Medicine (ISM), with its clinically validated multicomponent formulations offers a valuable resource for integrative therapeutic strategies with systemic mode of action. PurposeThe study investigates the incretin modulatory effect of Varanadi Kashayam (VA), an Ayurveda polyherbal formulation used in the clinical management of diabetes and its comorbidities. Experimental approachA high-fat diet induced Sprague-Dawley (SD) rat model was used to study the anti-diabetic, GLP-1 secretory, and anti-obesity effects of VA. In vitro studies using GLUTag cells assessed the GLP-1 secretion and DPP4 gene expression modulation; and studies using 3T3-L1 fibroblasts examined the anti-adipogenic effects. Computational methods including molecular docking and molecular dynamic simulations were used to identify the phytochemicals responsible for DPP4 inhibition. ResultsVA administration significantly improved fasting blood glucose and oral glucose tolerance in experimental animals, along with enhanced GLP-1 secretion. The in vitro results showed inhibition of DPP4 enzyme activity, increase in GLP-1 secretion and downregulation of DPP4 gene expression in GLUTag cells, and suppression of adipogenesis in 3T3-L1 fibroblast cells. Computational analyses ascertained Chebulinic acid, Chebulagic acid and Terchebin as top ranked phytochemicals responsible for DPP4 inhibition effect. ConclusionCombining in vitro, in vivo and in silico findings, this study provides valuable insight into the incretin modulatory effect of VA in treating diabetes and associated metabolic diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/601306v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1d424fcorg.highwire.dtl.DTLVardef@c84555org.highwire.dtl.DTLVardef@40094borg.highwire.dtl.DTLVardef@225272_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIVaranadi Kashayam (VA) improved blood glucose and GLP-1 levels in diabetic rats. C_LIO_LIInhibited DPP4 activity and gene expression in GLUTag cells. C_LIO_LISuppressed adipogenesis and adipogenic markers in 3T3-L1 cells. C_LIO_LIChebulinic acid, Chebulagic acid, and Terchebin identified as key DPP4 inhibitors. C_LI

cell biology↗

bioRxiv2023

Multicomponent Ayurveda formulation Lodhrasavam ameliorates steatosis and lipotoxicity in HepG2 cell model of NAFLD

BackgroundMetabolic-dysfunction associated steatotic liver disease (MASLD) is a complex, multifactorial condition and a leading cause of liver-related morbidity worldwide. Due to its heterogeneous pathogenesis, conventional single-target therapies often show limited efficacy. Multicomponent ayurveda formulations offer a promising alternative through their multitargeted actions. This study explores the therapeutic potential and underlying mechanisms of Lodhrasavam (LS), a classical, polyherbal ayurveda formulation, in both in vitro and in vivo models of MASLD. MethodsLS was evaluated for its anti-steatotic and anti-obesogenic potential using in vitro (HepG2, 3T3-L1) and in vivo (HF-HFD-induced rat) models. Antioxidant, lipase inhibition, cytotoxicity, anti-steatotic, and anti-adipogenic activities were assessed via DPPH, MTT, ORO/BODIPY staining, triglyceride quantification, ROS assay, and qPCR. Lipidomic profiling was done in HepG2 cells. Biochemical analyses (GLP-1, insulin, lipid panel), histopathology and OGTT further validated efficacy. Data were statistically analyzed by one-way ANOVA (p<0.05). Results/discussion: In HepG2 cells, LS reduced PA-induced lipid accumulation, ROS, triglycerides, and restored viability, while downregulating lipogenic genes (PPAR{gamma}, SREBP-1c, FASN). Lipidomics confirmed lipid modulation. In 3T3-L1 cells, LS suppressed adipogenesis and key adipogenic genes. In HFD-fed rats, LS reduced weight gain, hepatic steatosis, serum lipids, and improved liver histology. LS enhanced insulin and GLP-1 secretion, improved glucose tolerance, and restored pancreatic islet structure. These findings highlight the multitargeted potential of LS in ameliorating MASLD by modulating lipid metabolism, oxidative stress, inflammation, and glucose homeostasis. ConclusionLodhrasavam ameliorates MASLD by modulating the liver-adipose-pancreas axis, improving lipid metabolism, reducing inflammation, and enhancing insulin and GLP-1 secretion through multitargeted mechanisms.

pharmacology and toxicology↗

bioRxiv2022

In vitro and in silico analysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation - Nisakathakadi Kashaya.

Frontiers of disease biology started recognizing the importance of systems and network medicine approach for managing chronic disease like diabetes. Dipeptidyl-peptidase IV (DPP4) inhibitors are one such class of anti-diabetic drugs recognized for their systemic biological actions. Polyherbal preparations like Ayurveda formulations are ideal for identifying novel DPP4 inhibitors having greater efficacy and safety profile. Additionally, expanding the research on the multitargeted mode of action of these polyherbal formulations can render novel insights into the complex biology of disease manifestations. The current study aims at identifying DPP4 inhibitory potential of a clinically established Ayurveda anti-diabetic formulation Nisakathakadi Kashaya (NK) using in vitro and in silico methods as well as the modulation of diabetes associated gene network by NK. a. Standard enzyme inhibition assay was used to study the DPP4 inhibitory potential of NK, followed by bioinformatics and computational biology tools for identifying the potential bioactives and their molecular interactions involved in DPP4 inhibition. STITCH, CHEMBL and BindingDB databases were used for target mapping and depicting the multi-targeted network pharmacology interaction of NK and the formulation. EnrichR was used to depict a sub-network of diabetes proteins and their relationship with diabetes associated comorbidities. NK demonstrated a dose dependent DPP4 inhibition with an IC50 of 2.06 g GAE/mL. Molecular docking identified three compounds namely Terchebin, Locaracemoside B and 1,2,4,6 Tetra o Galloyl Beta D Glucose showing stable interactions with DPP4 similar to the standard drug Vildagliptin. The network pharmacology analysis of NK identified a number of targets like TNF, TGF{beta}1, SOD1, SOD2, AKT1, DPP4 and GLP1R in its protein-protein interaction network which are vital to diabetic progression and complications. The present work demonstrated that the polyherbal formulation NK has DPP4 inhibition potential and modulates a large number of diabetes related proteins and pathways. The approach adopted in the current study by combining in vitro and in silico methods allowed us to understand the mechanism of DPP4 inhibition by the formulation and also the possible pharmacological networking through which the formulation exert its systemic effect in diabetes management.

systems biology↗