Free Radical-Induced Inflammatory Responses Activate PPAR-? and TNF-a Feedback Loops, Driving HIF-a Mediated Metastasis in HCC: Insilico Approach of Natural Compounds Inhibitory Effect on Proposed Pathway

Hemanth Kumar Manikyam, Sunil K Joshi, Sandeep Balvant Patil, Abhinandan Ravsaheb Patil, Venkata Suresh Ponnuru

Citation: Hemanth Kumar Manikyam, Sunil K Joshi, Sandeep Balvant Patil, Abhinandan Ravsaheb Patil, Venkata Suresh Ponnuru, "Free Radical-Induced Inflammatory Responses Activate PPAR-? and TNF-a Feedback Loops, Driving HIF-a Mediated Metastasis in HCC: Insilico Approach of Natural Compounds Inhibitory Effect on Proposed Pathway", Universal Library of Biological Sciences, Volume 02, Issue 01.

Copyright: This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths, arises from complex interactions between hypoxia, chronic inflammation, and metabolic dysregulation within the tumor microenvironment. Key drivers of these processes include hypoxia-inducible factor 1-alpha (HIF-1a), tumor necrosis factor-alpha (TNF-a), and peroxisome proliferator-activated receptor gamma (PPAR?). This study evaluates the therapeutic potential of several natural compounds, including curcumin, resveratrol, epigallocatechin gallate (EGCG), berberine, gingerol, andrographolide, luteolin, apigenin, sulforaphane, omega-3 fatty acids, and ginseng, using CB-Dock2 for computational docking analysis. Results reveal high-affinity interactions between these compounds and their respective targets, indicating their potential to inhibit HIF-1a stabilization, suppress TNF-a-mediated inflammation, and activate PPAR? to restore metabolic homeostasis.Curcumin and EGCG demonstrated robust inhibition of HIF-1a, reducing angiogenesis and tumor progression. Resveratrol, luteolin, and andrographolide effectively modulated TNF-a signalling, attenuating inflammation and epithelial-mesenchymal transition (EMT). Compounds such as omega-3 fatty acids and ginseng activated PPAR?, regulating lipid metabolism and immune responses. The multi-targeted actions of these natural agents disrupt angiogenesis, inflammation, and metastasis, offering a holistic approach to combating HCC. This study highlights the promise of natural compounds as complementary therapies, emphasizing their bioavailability, safety, and potential synergy with conventional treatments in addressing the complexity of HCC progression.


Keywords: Hepatocellular Carcinoma (HCC), PPAR?, HIF-1a, TNF-a, Feedback Loops, Natural Compounds.

Download doi https://doi.org/10.70315/uloap.ulbsc.2025.0201001