Andrographolide inhibits porcine epidemic diarrhea virus by inhibiting the JAK2-STAT3 pathway and promoting apoptosis

IF 2.4 2区农林科学 Q3 MICROBIOLOGY Veterinary microbiology Pub Date : 2024-08-24 DOI:10.1016/j.vetmic.2024.110235

Cong He , Rongjie Zhang , Liangyu Yang , Bin Xiang

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Abstract

Porcine epidemic diarrhea (PED) is an acute, virulent, and highly contagious disease caused by the porcine epidemic diarrhea virus (PEDV). The high mutation rate of PEDV makes it difficult to effectively control using traditional vaccines, emphasizing the need for novel anti-PEDV-specific drugs. Therefore, this study aimed to investigate the activity and mechanism of action of andrographolide (AND) against PEDV in vitro and in vivo. In vitro experiments showed that AND treatment significantly inhibited PEDV replication in a cell model. The mechanism is that AND treatment significantly suppressed PEDV-induced activation of the JAK2-STAT3 pathway, which promoted apoptosis and inhibited the proliferation of the virus. Moreover, PEDV-infected 3-day-old piglets were treated with AND, and clinical symptoms, intestinal morphology, and viral load were examined. In vivo experiments showed that AND treatment reduced clinical symptoms, ameliorated intestinal damage, and increased the survival rate of infected piglets by 16.7 %. Conclusively, this study contributes to the field of PEDV antiviral drug development and provides new directions for PED prevention and treatment.

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穿心莲内酯通过抑制 JAK2-STAT3 通路和促进细胞凋亡抑制猪流行性腹泻病毒

猪流行性腹泻（PED）是由猪流行性腹泻病毒（PEDV）引起的一种急性、烈性和高度传染性疾病。PEDV 变异率高，传统疫苗难以有效控制，因此需要新型抗 PEDV 特异性药物。因此，本研究旨在研究穿心莲内酯（AND）在体外和体内对 PEDV 的活性和作用机制。体外实验表明，穿心莲内酯能显著抑制 PEDV 在细胞模型中的复制。其机制是穿心莲内酯能明显抑制 PEDV 诱导的 JAK2-STAT3 通路激活，从而促进细胞凋亡并抑制病毒增殖。此外，用 AND 治疗感染 PEDV 的 3 日龄仔猪，并检测其临床症状、肠道形态和病毒载量。体内实验表明，AND 治疗可减轻临床症状，改善肠道损伤，并使感染仔猪的存活率提高 16.7%。总之，这项研究有助于 PEDV 抗病毒药物的开发，并为 PED 的预防和治疗提供了新的方向。

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来源期刊

Veterinary microbiology 农林科学-兽医学

CiteScore

5.90

自引率

6.10%

发文量

221

审稿时长

52 days

期刊介绍： Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.