Zhang Yuefeng, Yu Fei, Hao Jingyou, Nsabimana Eliphaz, Wei Yanru, Chang Xiaohan, Liu Chang, Wang Xiaozhen, Li Yanhua
Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Harbin Lvda Sheng Animal Medicine Manufacture Co., Ltd., Harbin, China.
Front Vet Sci. 2021 Oct 4;8:724491. doi: 10.3389/fvets.2021.724491. eCollection 2021.
Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Schischkin (HQ), Roscoe (SJ), and L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K-Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of and , inhibited the expression of (), and activated the PI3K-Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of and and inhibiting the expression levels of .
应激性腹泻是断奶仔猪面临的一大挑战,它限制了养猪生产效率,并造成巨大经济损失。我们实验室研发了一种由诃子(HQ)、石菖蒲(SJ)和黄连(CQC)组成的中药方剂(QJC),该方剂显示出显著的抗应激性腹泻效果。然而,这种效果的活性成分、潜在靶点和作用机制仍不清楚,值得进一步研究。在我们的研究中,我们通过网络药理学和实验研究验证了QJC的生物活性成分以及抗应激性腹泻作用的相关机制。在成功建立应激性腹泻模型后,研究了肠黏膜的组织形态学,并使用定量实时聚合酶链反应(RT-qPCR)探针检测磷脂酰肌醇3-激酶(PI3K)-Akt信号通路,以验证QJC对腹泻的治疗效果。首先,使用网络药理学方法,我们在QJC中鉴定出35种活性成分和130条京都基因与基因组百科全书(KEGG)通路。从中,我们推测槲皮素、木犀草素、山奈酚、黄芩素和豆甾醇是主要的生物活性成分,并认为QJC的止泻作用与PI3K-Akt信号通路有关。RT-qPCR表明,QJC及其生物活性成分增加了 和 的表达水平,抑制了 ()的表达,并激活PI3K-Akt信号通路以缓解应激性腹泻。此外,我们发现QJC减轻了小肠组织的病理状况,改善了肠道屏障的完整性。综上所述,我们的研究表明,中药QJC、槲皮素、木犀草素、山奈酚、黄芩素和豆甾醇通过增加 和 的表达水平以及抑制 的表达水平,减轻了小肠组织的病理状况,缓解了应激性腹泻。