Astragaloside IV Alleviates Ammonia-Induced Apoptosis and Oxidative Stress in Bovine Mammary Epithelial Cells

Abstract

Ammonia is one of the major toxic components of metabolites in blood and tissues of high-producing dairy cows and could affect the health of bovine mammary glands. Bovine mammary epithelial cells are sensitive to oxidative stress induced by intensive cell metabolism. In our previous study, we found that ammonia could induce oxidative stress, apoptosis and inflammatory responses in bovine mammary epithelial cells. In the present study, the cytoprotective effects of astragaloside IV against ammonia in vitro were explored. The results demonstrated that pretreatment of MAC-T cells with astragaloside IV could potently suppress the increase in the level of intracellular reactive oxygen species (ROS) and the rate of cell apoptosis, inhibit the ammonia-induced inflammatory responses, and rescue the decrease of cell viability. Astragaloside IV prevented ammonia-induced endoplasmic reticulum stress. Astragaloside IV also significantly suppressed the levels of BAX, caspase 3 and p53 phosphorylation in ammonia-induced MAC-T cells. Nuclear factor erythroid 2-related factor 2(Nrf2) was essential for cytoprotective effects of astragaloside IV in MAC-T cells, as knockdown of Nrf2 dramatically abolished the prosurvival effects of astragaloside IV on treated cells. Furthermore, the PI3K/AKT and ERK/MAPK pathways were responsible for the induction of Nrf2 by astragaloside IV. In conclusion, astragaloside IV played a beneficial role against ammonia-induced damage of MAC-T cells. This provides a cue for future study to use astragaloside IV as a protective and curative agent against ammonia exposure of mammary glands in dairy cows.

PDE9 Inhibitor PF-04447943 Attenuates DSS-Induced Colitis by Suppressing Oxidative Stress, Inflammation, and Regulating T-Cell Polarization

“…Our results suggested the Nrf2 pathway was also activated by PF-04447943 in a dose-dependent manner. In the oxidative stress condition, the upregulation of ERK and AKT show the protective role to induce the expression of cytoprotective gene, such as Nrf2 and HO-1 (Wang et al, 2019). Nevertheless, ERK and AKT are profound for their inflammatory role in UC (Gao et al, 2019;Li et al, 2019).…”

Sanqi Oral Solution Ameliorates Renal Ischemia/Reperfusion Injury via Reducing Apoptosis and Enhancing Autophagy: Involvement of ERK/mTOR Pathways

“…Calycosin, one of the major components in Astragalus membranaceus, has been verified to inhibit oxidative stress-induced cardiomyocyte apoptosis via activating estrogen receptor-α/β ( Liu B. et al., 2016 ). Another active component Astragaloside IV can not only suppress apoptosis in mammary epithelial cells ( Wang F. et al., 2019 ) or cerebral I/R Injury ( Zhang et al., 2019 ), but also enhance autophagy via mTORC1 signalling ( Lin et al., 2020 ) or SIRT-NF-κB p65 axis ( Wang X. et al., 2019 ), and can reduce complement membranous attack complex induced podocyte injury through decreasing ERK expression ( Zheng et al., 2012 ). Ginsenoside Rg1, the main component in Panax notoginseng, was capable of protecting pheochromocytoma (PC12) cells against dopamine-induced apoptosis ( Chen et al., 2001 ).…”

Jianpiyifei II Granules Suppress Apoptosis of Bronchial Epithelial Cells in Chronic Obstructive Pulmonary Disease via Inhibition of the Reactive Oxygen Species-Endoplasmic Reticulum Stress-Ca2+ Signaling Pathway

“…Interestingly, compounds isolated from these eight medical herbs have been reported to display similar apoptosis inhibitory effect. Astragaloside IV, one of the main and active ingredients of A. membranaceus, has been demonstrated to possess anti-oxidative and anti-apoptotic effects (Shang et al, 2011;Liu et al, 2017;Zhao et al, 2018;Wang F. et al, 2019), as well as inhibitory effect on ER stress (Ju et al, 2019). Furthermore, atractylodesin III from C. pilosula (Cao et al, 2019), atractylenolide I and atractylenolide III from A. macrocephala (More and Choi, 2017;Zhu et al, 2018), saikosaponin C and saikosaponin D from B. chinense (Lee et al, 2014;Wang et al, 2015;Lin et al, 2016), and vitegnoside and vitexilactone from V. negundo (Wang Q. et al,…”