Protective Effect of Koumine, an Alkaloid from Gelsemium Sempervirens, on Injury Induced by H2O2 in IPEC-J2 Cells

Abstract

Medicinal herbal plants have been commonly used for intervention in different diseases and improvement of health worldwide. Koumine, an alkaloid monomer found abundantly in Gelsemium plants, can be effectively used as an antioxidant. The purpose of this study was to evaluate the potential protective effect of koumine against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in porcine intestinal epithelial cell line (IPEC-J2 cells). MTT assays showed that koumine significantly increased cell viability in H2O2-mediated IPEC-J2 cells. Preincubation with koumine ameliorated H2O2-medicated apoptosis by decreasing reactive oxygen species (ROS) production, and efficiently suppressed the lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production. Moreover, a loss of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) activities was restored to normal level in H2O2-induced IPEC-J2 cells upon koumine exposure. Furthermore, pretreatment with koumine suppressed H2O2-mediated loss of mitochondrial membrane potential, caspase-9 and caspase-3 activation, decrease of Bcl-2 expression and elevation of Bax expressions. Collectively, the results of this study indicated that koumine possesses the cytoprotective effects in IPEC-J2 cells during exposure to H2O2 by suppressing production of ROS, inhibiting the caspase-3 activity and influencing the expression of Bax and Bcl-2. Koumine could potentially serve as a protective effect against H2O2-induced apoptosis.

Koumine Suppresses IL-1β Secretion and Attenuates Inflammation Associated With Blocking ROS/NF-κB/NLRP3 Axis in Macrophages

“…Although many studies have attempted to explore the therapeutic effect and mechanism of KM in diseases ( Qiu et al, 2015 ; Yang et al, 2016 ; Yuan et al, 2016b ; Chen et al, 2017 ; Jin et al, 2018a ; Jin et al, 2018b ; Jin et al, 2019 ; Yuan et al, 2019a ; Yuan et al, 2019b ; Yue et al, 2019 ), its effect on NLRP3 inflammasome activation and the underlying mechanism remain unknown. In this study, we identified KM as a broad-spectrum inhibitor of NLRP3 inflammasome activation that inhibited NLRP3 inflammasome activation both in vitro and in vivo .…”

“…Under LPS challenge, TLR4 binds to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 and further promotes the production of ROS-induced NF-κB activation ( Park et al, 2004 ). KM is an antioxidant agent that maintains the mitochondrial membrane potential in porcine intestinal epithelial cells ( Yuan et al, 2019b ). We confirmed that KM can exert NLRP3 inhibitory activity by eliminating ROS generation in response to stimulation with LPS plus ATP.…”

“…Koumine (KM) is a type of alkaloid derived from Gelsemium elegans, which is used as a traditional medicinal plant in China and other Asian countries ( Jin et al, 2014 ). Recent studies have demonstrated that KM has diverse pharmacological activities, including anti-psoriatic, anti-inflammatory, anti-tumor, analgesic, antioxidant and anxiolytic activities ( Xu et al, 2012 ; Chen et al, 2017 ; Jin et al, 2018b ; Jin et al, 2019 ; Yuan et al, 2019a ; Yuan et al, 2019b ; Wu et al, 2020 ). Numerous studies have shown that KM exerts anti-inflammatory effects by inhibiting the production of reactive oxygen species (ROS), regulating the Nrf2/NF-κB signaling pathway and decreasing the production of IL-1β, IL-6, TNF-α and nitric oxide ( Yuan et al, 2016a ; Wu et al, 2020 ).…”

Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

“…Koumine (KM), the most abundant alkaloid in Gelsemium elegans Benth. ( G. elegans ) has various pharmacological properties and is known to be effective in the treatment of numerous age-associated conditions including postoperative pain ( Xiong et al., 2017 ; Shoaib et al., 2019 ), inflammation ( Yuan et al., 2016 ; Wu et al., 2020 ), rheumatoid arthritis ( Yang et al., 2016 ), malignant tumors ( Yuan et al., 2019a ), nonalcoholic fatty liver disease ( Yue et al., 2019 ), oxidative stress ( Yuan et al., 2019b ), and neuropathic pain ( Jin et al., 2018a ; Jin et al., 2018b ). However, the pharmacokinetic profile of KM in the elderly or aged animals remains to be fully evaluated.…”

Astilbin ameliorates deoxynivalenol‐induced oxidative stress and apoptosis in intestinal porcine epithelial cells (IPEC‐J2)

“…The small intestine is particularly vulnerable to be damaged by DON. Exposure to DON can give rise to augment intestinal permeability (Pinton et al, 2010), the irritation or necrosis of intestinal mucosa (Pestka, 2007), cell apoptosis (Pestka, 2008), low antioxidative capacity and mitochondrial dysfunction (Yuan et al, 2019), resulting in intestinal damage in pigs. Tight junctions are the junctional multiprotein complexes, which mainly sustain the intestinal epithelial barrier (Ashida, Ogawa, Kim, Mimuro, & Sasakawa, 2011).…”