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整合网络药理学与药理学研究阐明加味葛根芩连汤治疗猪流行性腹泻的作用机制。

Integrating network pharmacology with pharmacological research to elucidate the mechanism of modified Gegen Qinlian Decoction in treating porcine epidemic diarrhea.

机构信息

College of Veterinary Medicine, Shanxi Agricultural University, Mingxian South Road 1, Jinzhong, 030801, Shanxi, China.

School of Medicine, Xinxiang University, Xinxiang, 453003, China.

出版信息

Sci Rep. 2024 Aug 15;14(1):18929. doi: 10.1038/s41598-024-70059-5.

DOI:10.1038/s41598-024-70059-5
PMID:39147857
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11327325/
Abstract

Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug's efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-β, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections.

摘要

猪流行性腹泻病毒(PEDV)对仔猪具有重大威胁,特别是由于现有疫苗的效果有限,以及有效的治疗药物稀缺。葛根芩连汤(GQD)在治疗感染性腹泻方面已经使用了两千多年。然而,为了提高药物的疗效并阐明其作用机制,仍需要进一步研究。在这项研究中,开发了改良的葛根芩连汤(MGQD),并证明其能够抑制 PEDV 的复制。动物试验表明,MGQD 有效缓解了免疫组织的病理损伤,并调节了 T 淋巴细胞亚群。网络分析与 UHPLC-MS/MS 的结合有助于鉴定 MGQD 中的活性成分,并阐明其对 PEDV 感染的治疗作用的分子机制。体外研究表明,MGQD 显著抑制了 IPEC-J2 细胞中的 PEDV 增殖,通过病毒杀灭活性、抑制病毒附着和破坏病毒生物合成来促进细胞生长。此外,MGQD 处理导致 IFN-α、IFN-β 和 IFN-λ3 的表达水平增加,同时降低 TNF-α 的表达,从而增强了 IPEC-J2 细胞对 PEDV 感染的抵抗力。总之,我们的研究结果表明,MGQD 有望成为治疗 PEDV 感染的新型抗病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/7acc61214e7e/41598_2024_70059_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/775465dd4c8d/41598_2024_70059_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/0fa0ceaf5bfc/41598_2024_70059_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/28c04bc1f7ca/41598_2024_70059_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/7acc61214e7e/41598_2024_70059_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/050d8d3d216e/41598_2024_70059_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/fdc166a86118/41598_2024_70059_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/813e47cb58f2/41598_2024_70059_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/e2697cee88d9/41598_2024_70059_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/775465dd4c8d/41598_2024_70059_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/0fa0ceaf5bfc/41598_2024_70059_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/28c04bc1f7ca/41598_2024_70059_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d25b/11327325/7acc61214e7e/41598_2024_70059_Fig8_HTML.jpg

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