Baicalin Attenuates H2O2-Induced Oxidative Stress by Regulating the AMPK/Nrf2 Signaling Pathway in IPEC-J2 Cells

Abstract

Oxidative stress can adversely affect the health status of the body, more specifically by causing intestinal damage by disrupting the permeability of the intestinal barrier. This is closely related to intestinal epithelial cell apoptosis caused by the mass production of reactive oxygen species (ROS). Baicalin (Bai) is a major active ingredient in Chinese traditional herbal medicine that has antioxidant, anti-inflammatory, and anti-cancer properties. The purpose of this study was to explore the underlying mechanisms by which Bai protects against hydrogen peroxide (H2O2)-induced intestinal injury in vitro. Our results indicated that H2O2 treatment caused injury to IPEC-J2 cells, resulting in their apoptosis. However, Bai treatment attenuated H2O2-induced IPEC-J2 cell damage by up-regulating the mRNA and protein expression of ZO-1, Occludin, and Claudin1. Besides, Bai treatment prevented H2O2-induced ROS and MDA production and increased the activities of antioxidant enzymes (SOD, CAT, and GSH-PX). Moreover, Bai treatment also attenuated H2O2-induced apoptosis in IPEC-J2 cells by down-regulating the mRNA expression of Caspase-3 and Caspase-9 and up-regulating the mRNA expression of FAS and Bax, which are involved in the inhibition of mitochondrial pathways. The expression of Nrf2 increased after treatment with H2O2, and Bai can alleviate this phenomenon. Meanwhile, Bai down-regulated the ratio of phosphorylated AMPK to unphosphorylated AMPK, which is indicative of the mRNA abundance of antioxidant-related genes. In addition, knockdown of AMPK by short-hairpin RNA (shRNA) significantly reduced the protein levels of AMPK and Nrf2, increased the percentage of apoptotic cells, and abrogated Bai-mediated protection against oxidative stress. Collectively, our results indicated that Bai attenuated H2O2-induced cell injury and apoptosis in IPEC-J2 cells through improving the antioxidant capacity through the inhibition of the oxidative stress-mediated AMPK/Nrf2 signaling pathway.

A Comprehensive Review of Ethnomedicinal Uses, Phytochemistry, Pharmacology, and Toxicity of Prunus africana (Hook. F.) Kalkman from Africa

“…Furthermore, research shows lauric acid inhibits the 5- α -reductase enzyme, which blocks the conversion of testosterone to dihydrotestosterone, in turn, preventing prostate cancer [ 60 , 81 ]. Moreover, these phytochemicals exert their antitumor activity by activating the 5′-AMP-activated protein kinase (AMPK) enzyme, disrupting key metabolic pathways in prostate cancer cells [ 55 , 56 ].…”

“…Additionally, P. africana-derived phytochemicals such as tannins and terpenoids have exhibited antimicrobial and antiviral activities, suggesting their potential in combating infectious diseases [23,46,[53][54][55][56]. Te elucidation of these biological activities not only underscores the therapeutic potential of P. africana but also highlights the importance of further research to explore their mechanisms of action and clinical applications.…”

“…Furthermore, research shows lauric acid inhibits the 5-α-reductase enzyme, which blocks the conversion of testosterone to dihydrotestosterone, in turn, preventing prostate cancer [60,81]. Moreover, these phytochemicals exert their antitumor activity by activating the 5′-AMP-activated protein kinase (AMPK) enzyme, disrupting key metabolic pathways in prostate cancer cells [55,56]. Te synergistic efects of the phytochemical compounds of P. africana lead to a reduction in cancer cell proliferation, early senescence, and senescence-associated betagalactosidase activity [47,82].…”

Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase

“…This extends lifespans and reduces metabolic disorders [24,25]. The AMPK's responses to oxidative stress are as follows: (1) to facilitate an increase in antioxidant enzymes by nuclear factor erythroid 2-related factor 2 (Nrf2); (2) to facilitate an increase in autophagy activity, including mitophagy and mitochondrial biogenesis; and (3) to facilitate a reduction in energy surplus through the inhibition of ROS production [26,27]. Ultimately, oxidative stress activates AMPK, as a stress response process.…”