摘要：
Viola yedoensis Makino (Vy) is a well-known traditional Chinese medicine widely used to treat inflammatory diseases. However, the regulatory effects of dietary Vy supplementation on lipopolysaccharide (LPS)-induced intestinal damage in broilers and the underlying molecular mechanisms remain unclear. In this study, broilers were intraperitoneally injected with 1 mg/kg LPS on days 17, 19 and 21 to induce intestinal damage. Vy supplementation at 0.5, 1.5 and 4.5 % in the diet was administered separately for 21 days to investigate the potential protective effects of Vy supplementation against LPS-induced intestinal impairment in broilers. Vy supplementation improved intestinal morphology and restored growth performance. Vy supplementation attenuated intestinal inflammation by regulating the nuclear factor kappa B (NF-κB) / NLR family pyrin domain-containing 3 (NLRP3) signaling pathway and inhibited its downstream pro-inflammatory factor levels. In addition, Vy supplementation relieved intestinal oxidative impairment by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) / mitogen-activated protein kinase (MAPK) signaling pathway and downstream antioxidant enzyme activity. Vy supplementation reduced LPS-induced mitochondrial damage and apoptosis. Furthermore, Vy supplementation alleviated LPS-induced intestinal inflammation and oxidative damage in chickens by increasing the abundance of protective bacteria (Lactobacillus and Romboutsia) and reducing the number of pathogenic bacteria (unclassified_f_Ruminococcaceae, unclassified_f_Oscillospiraceae and norank_f_norank_o_Clostridia_vadinBB60_group). Overall, Vy supplementation effectively ameliorated LPS-induced intestinal damage by regulating the NF-κB-NLRP3/Nrf2-MAPK signaling pathway and maintaining intestinal microbiota balance. Vy supplementation can be used as a dietary supplement to protect broilers against intestinal inflammation and oxidative damage.
摘要：
三萜类化合物是一类富含多种异戊二烯单元的天然产物,其具有抗炎、抗氧化等生物活性,并在缓解肠道炎症方面具有潜在的治疗效果。首先,三萜类化合物可通过抑制炎性介质(白细胞介素、前列腺素、肿瘤坏死因子)及其相关信号通路来减少炎性...展开更多 三萜类化合物是一类富含多种异戊二烯单元的天然产物,其具有抗炎、抗氧化等生物活性,并在缓解肠道炎症方面具有潜在的治疗效果。首先,三萜类化合物可通过抑制炎性介质(白细胞介素、前列腺素、肿瘤坏死因子)及其相关信号通路来减少炎性因子的分泌,起到抗肠道炎症的作用;其次,三萜类化合物通过改善活性氧的产生,平衡氧化还原系统,降低氧化应激损伤,达到抗炎的作用;再次,三萜类化合物也能通过调节NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体、多条信号通路(NF-κB/MAPK/Nrf2信号通路)来改善免疫球蛋白和补体水平含量达到免疫平衡作用;第四,三萜类化合物还可通过促进紧密连接蛋白表达,修复损伤的肠道黏膜上皮,提高肠道屏障功能,减少刺激性物质的渗透来抑制肠道炎症;另外,三萜类化合物与肠道菌群间具有紧密联系,能维持肠道微生物稳定,保持肠道上皮屏障的完整性,减少肠道炎症的发生。综上,三萜类化合物通过调控炎症、氧化应激、免疫平衡、黏膜屏障、肠道微生物5个途径,发挥对肠道炎症的保护作用。目前对于三萜类化合物的研究还存在一些限制和挑战,本综述为进一步探索、开发和利用三萜类化合物提供了重要参考,为其在肠道炎症治疗领域的应用提供了新的思路。收起
期刊：
Ecotoxicology and Environmental Safety,2022年246:114150 ISSN：0147-6513
通讯作者：
Jiang, Weiwei;Yi, Jine
作者机构：
[Luo, Chenxi; Huang, You; Zhu, Lijuan; Huang, Chunlin; Yi, Jine; Ma, Chaoyang; Kong, Li; Yang, Wenjiang] Hunan Agr Univ, Coll Vet Med, Hunan Engn Res Ctr Livestock & Poultry Hlth Care, Changsha 410128, Peoples R China.;[Jiang, Weiwei] Hunan Polytech Environm & Biol, Coll Med Technol, Hengyang 421005, Peoples R China.
通讯机构：
[Yi, Jine] H;[Jiang, Weiwei] C;College of Medical Technology, Hunan Polytechnic of Environment and Biology, Hengyang 421005, China. Electronic address:;Hunan Engineering Research Center of Livestock and Poultry Health Care, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China. Electronic address:
摘要：
Betulinic acid (BA), an occurring pentacyclic triterpenoid, has various biological activities, such as anti-inflammation and antioxidation. Previous studies found that BA attenuated cyclophosphamide (CYP)-induced intestinal mucosal damage by inhibiting intestinal mucosal barrier dysfunctions and cell apoptosis. However, the effects and regulation mechanisms of BA on CYP-induced renal damage has not been reported in literature. Here, we found that BA pretreatment alleviated the elevation of serum urea level and inhibited the increase in serum neutrophil gelatinase-associated lipocalin level induced by CYP. Meanwhile, BA ameliorated renal tubular epithelial cell edema, and vacuolization of renal cortical tubular and renal glomerulus. Moreover, pretreatment with BA inhibited the mRNA expressions of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, and increased mRNA expressions of anti-inflammatory cytokines such as IL-10 and transforming growth factor-β by inactivation nuclear factor kappa-B. Simultaneously, BA decreased the accumulation of reactive oxygen species and malondialdehyde, and lowered the levels of superoxide dismutase and glutathione, while increased the activity of glutathione peroxidase in CYP-induced kidney damage mice. Besides, BA reduced the phosphorylation of extracellular signal-regulated kinases (ERK), inhibited the ratio of Bcl-2/Bax and cell apoptosis in CYP-triggered kidney damage. Furthermore, BA and/or PD98059 (an inhibitor of ERK) regulated mitigation of CYP-elicited renal injury and deactivation of the ERK pathway and mitochondrial apoptotic pathway, indicating that the protective effect of BA on CYP-induced renal damage may be associated with the down-regulation of ERK-mediated mitochondrial apoptotic pathway. Thus, BA could be a candidate agent against chemotherapy drug-induced nephrotoxicity by reducing inflammation and oxidative stress through suppression of ERK-mediated mitochondrial apoptotic pathway.
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.
摘要：
Phenethyl isothiocyanate (PEITC) is one of the glucosinolates (GLs) present in cruciferous vegetables. Although there are many reports of livestock and poultry poisoning caused by plants containing GLs, the actual dosage that causes poisoning and the characteristics of GLs and their metabolites are unclear. Herein, we investigated the inhibitory effects of PEITC on IPEC-J2 cells and examined the mechanisms of PEITC-induced apoptosis via the mitochondrial pathway. Cell viability was determined by the MTT assay, and the levels of reactive oxygen species, mitochondrial membrane potential (Psi), intracellular Ca(2+) concentration, and cell apoptosis were detected by flow cytometry. IPEC-J2 cells were collected to assess the activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as the contents of glutathione, malondialdehyde, H2O2, ATP, and lactate dehydrogenase, using biochemical methods. The levels of cytochrome c, Bax, Bcl-2, caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP)-1, p53, CDC25C, and cyclin A2 were analyzed by western blotting. We found that PEITC effectively inhibited the growth of IPEC-J2 cells, causing apoptosis. PEITC suppressed the level of mitochondrial membrane potential; released cytochrome c from the mitochondria to the cytoplasm; reduced ATP levels; inhibited Bcl-2 expression; increased Bax expression; and activated caspase-9, caspase-3, and PARP-1, leading to apoptosis. PEITC also induced G2/M and S phase arrest by affecting cell cycle-associated proteins such as p53, CDC25C, and cyclin A2. We conclude that PEITC causes oxidative stress, cell cycle arrest, and apoptosis in IPEC-J2 cells via a mitochondrial-dependent Bax/Bcl-2 pathway.
摘要：
T-2 toxin is one of the most toxic type A trichothecene mycotoxins in nature, and it exhibits reproductive toxicity. Betulinic acid (BA) is a natural pentacyclic triterpene compound found in species of Betula, and it has been reported to have antioxidant activity. The aim of the present study was to investigate the protective effect of BA on T-2-toxin-induced testicular injury in mice and explore its molecular mechanism. Sixty adult male mice were randomly divided into groups. The mice were pretreated orally with BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and the T-2 toxin (4 mg/kg body weight) was administered via intraperitoneal injection to induce oxidative stress after the last administration of BA. BA pretreatment significantly increased the secreted levels of testosterone and sperm motility. Moreover, BA pretreatment significantly increased the total antioxidant capacity (T-AOC), the activity of SOD and CAT, and the content of GSH, and it reduced the content of MDA. Furthermore, BA relieved testicular injury and reduced the number of apoptotic cells, and it significantly decreased the protein expression of Janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), caspsae-3, and Bcl-2-associated X protein (Bax). BA also increased the expression of B-cell lymphoma-2 (Bcl-2). We suggest that BA reduced the oxidative damage induced by T-2 toxin, and that these protective effects may be partially mediated by the JAK2/STAT3 signaling pathway.
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.
