摘要：
Background: Betulinic acid (BA) is a plant-derived pentacyclic triterpenoid with a variety of biological activities. The purpose of this study was to assess the potential protective role of BA against intestinal mucosal injury induced by cyclophosphamide (CYP) treatment. Methods: Mice were pretreated with BA daily (0.05, 0.5, and 5.0 mg/kg) for 14 days, then injected intraperitoneally with CYP (50 mg/kg) for 2 days. Results: BA pretreatment reduced the contents of malondialdehyde (MDA) and glutathione (GSH), decreased the activity of superoxide dismutase (SOD) in small intestine, increased villus hight/crypt depth ratio and restored the morphology of intestinal villi in CYP-induced mice. Moreover, BA pretreatment could significantly down-regulate the levels of pro-inflammatory cytokines interleukin-5 (IL-5), IL-17, IL-12 (P70) and tumor necrosis factor alpha (TNF-alpha), reduced production of chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha), macrophage inflammatory protein-1 beta (MIP-1 beta) and regulated upon activation, normal T-cell expressed and secreted (RANTES), and enhanced the levels of anti-inflammatory such as IL-2 and IL-10 in serum, and decreased the mRNA expressions of IL-1 beta and TNF-alpha in intestine of CYP-induced mice. Furthermore, RT-PCR demonstrated that BA improved intestinal physical and immunological barrier in CYP-stimulated mice by enhancing the mRNA expressions of zonula occluden 1 (ZO-1) and Claudin-1. Conclusions: BA might be considered as an effective agent in the amelioration of the intestinal mucosal resulting from CYP treatment. (C) 2019 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.
摘要：
Ganoderma lucidum polysaccharide (GLP) extracted from Ganoderma lucidum (Leyss. ex Fr.) Karst, a traditional Chinese medicine, is a biologically active substance reported to possess anti-oxidative, anti-apoptotic, and neurological protection. However, it is unknown whether GLP have any protective effect against high-fat constituents-induced epithelial cell injury. The aim of this study was to investigate the protection and molecular mechanism of GLP on injury induced by palmitic acid (PA) in the intestinal porcine epithelial cell line (IPEC-J2). First, we tested whether the treatment of GLP attenuate PA-induced IPEC-J2 cell death. GLP markedly blocked PA-caused cytotoxicity and apoptosis in IPEC-J2 cells. Moreover, GLP recovered the decreased mitochondrial function and inhibited activation of caspase-dependent apoptotic pathway. Interestingly, PA promoted cell apoptosis and autophagy through stimulation of phosphorylation of mitogen-activated protein kinases (MAPKs), AMP-activated protein kinase (AMPK), and inhibition of phosphorylation of Akt and mammalian target of rapamycin (mTOR), which was reversed by GLP. Taken together, this study revealed a protective effect of GLP against PA-evoked IPEC-J2 cell death through anti-apoptotic and anti-autophagic properties.
摘要：
lambda-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, anti-tumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE(2) signal pathway. BA pretreatment significantly reduced the in-flammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1 alpha, IL-1 beta, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE(2) in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE(2) signaling pathway activation.
作者机构：
[Wu, Jing; Wang, Naidong; Wang, ND; Tian, Yanan; Zhou, Yu; Yi, Jine; Yuan, Zhihang] Hunan Agr Univ, Coll Vet Med, Changsha 410128, Hunan, Peoples R China.;[Wu, Jing; Yuan, Zhihang] Hunan Agr Univ, Hunan Collaborat Innovat Utilizat Bot Funct Ingre, Changsha 410128, Hunan, Peoples R China.;[Wu, Jing; Yuan, Zhihang] Hunan Agr Univ, Hunan Engn Res Ctr Vet Drug, Changsha 410128, Hunan, Peoples R China.;[Chen, Jingshu; Tian, Yanan] Texas A&M Univ, Coll Vet Med, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA.
通讯机构：
[Wang, ND; Tian, YA] H;[Tian, Yanan] T;Hunan Agr Univ, Coll Vet Med, Changsha 410128, Hunan, Peoples R China.;Texas A&M Univ, Coll Vet Med, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA.
关键词：
T-2 toxin;toxicity;autophagy;apoptosis
摘要：
T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin.
通讯机构：
[Wu, J; Sun, ZL] H;Hunan Agr Univ, Coll Vet Med, Dept Clin Vet Med, Changsha 410128, Hunan, Peoples R China.;Hunan Coinnovat Ctr Utilizat Bot Funct Ingredient, Changsha 410128, Hunan, Peoples R China.
关键词：
H2O2;IPEC-J2 cells;apoptosis;koumine
摘要：
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 (H(2)O(2))-induced oxidative stress and apoptosis in porcine intestinal epithelial cell line (IPEC-J2 cells). MTT assays showed that koumine significantly increased cell viability in H(2)O(2)-mediated IPEC-J2 cells. Preincubation with koumine ameliorated H(2)O(2)-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 H(2)O(2)-induced IPEC-J2 cells upon koumine exposure. Furthermore, pretreatment with koumine suppressed H(2)O(2)-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 H(2)O(2) 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 H(2)O(2)-induced apoptosis.
摘要：
Gamma-oryzanol (Orz), a mixture of ferulic acid esters of plant sterols and triterpene alcohols, has been proven to possess multiple activities. The purpose of this study was to explore the hepatoprotective effects and potential mechanisms of Orz against ethanol-induced liver injury in mice. Orz pretreatment significantly reduced the serum levels of ALP, ALT, AST and CYP2E1, and increased the TP and GLB levels in the ethanol-challenged mice. Orz increased the activities of CAT, SOD, GSH-PX and the GSH content in the liver, while decreased hepatic steatosis in ethanol-induced liver injure. Furthermore, Orz significantly decreased the protein expression of ASK1, JNK, P38, active-caspase-9 and active-caspase-3, and the protein ratio of Bax/Bcl-2 in livers of ethanol-challenged mice. These results suggest that Orz provides protection against ethanol-induced liver injury which might be due to its alleviation of oxidative stress and inhibition of apoptosis, possibly inhibiting MAPK signaling pathways mediated mitochondrial signaling pathway activation.
摘要：
Although mTOR (the mammalian target of rapamycin) can regulate intracellular free Ca2+concentration in normal cultured podocytes, it remains elusive as to how mTORC2/AKT-mediated Ca2+participates in the process of T-2 toxin-induced apoptosis. The potential signaling responsible for intracellular Ca2+ concentration changes was investigated using immunoblot assays in an in vitro model of TM3 cell injury induced by T-2 toxin. Changes in Ca2+ were assessed using the Ca2+-sensitive fluorescent indictor dye Fura 2-AM. The cytotoxicity of TM3 cells was assessed with an MTT bioassay, and apoptosis was measured using Annexin V-FITC staining. Following T-2 toxin treatment, the growth of cells, phospho-mTORSer2481, phospho-mTORSer2448, and phospho-AktSer473 were significantly decreased in a time-dependent manner, whereas Ca2+ and apoptosis were increased. T-2 toxin-induced apoptosis was prevented by BAPTA-AM (a Ca2+chelator) and MHY1485 (an mTOR activator), and the application of mTOR activator MHY1485 also prevented the increase of intracellular free Ca2+concentration in TM3 cells. Our results strongly suggest that T-2 toxin exposure induces apoptosis in TM3 cells by inhibiting mTORC2/AKT to promote Ca2+ production.
