Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model

BMC Veterinary Research

Original Research

Jianhua Guo¹  Kuohai Fan²  Xiaozhong Zheng³  Hongquan Li⁴  Panpan Sun⁴  Yaogui Sun⁴  Na Sun⁴  Wei Yin⁴  Ajab Khan⁵  Shuangxiu Wan⁶  Yinlan Xu⁷ 

[1] Department of Veterinary Pathobiology, Schubot Exotic Bird Health Center, Texas A&M University, College Station, 77843, Texas, TX, USA;Laboratory Animal Center, Shanxi Agricultural University, 030801, Taigu, Shanxi, China;Medical Research Council (MRC) Centre for Inflammation Research, Queen’s Medical Research Institute, The University of Edinburgh, EH16 4TJ, Edinburgh, UK;Shanxi Key Lab. for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, 030801, Taigu, Shanxi, China;Shanxi Key Lab. for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, 030801, Taigu, Shanxi, China;Department of Veterinary Pathology, Faculty of Veterinary and Animal Sciences, the University of Agriculture, Dera Ismail Khan 29050, Khyber Pakhtunkhwa, Pakistan;Shanxi Key Lab. for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, 030801, Taigu, Shanxi, China;School of Pharmacy, Heze University, 274000, Heze, Shandong, China;Shanxi Key Lab. for Modernization of TCVM, College of Veterinary Medicine, Shanxi Agricultural University, 030801, Taigu, Shanxi, China;School of Public Health, Xinxiang Medical University, 453003, Xinxiang, Henan, China;

关键词: Matrine;    Osthole;    PCV2;    GRP78;    Apoptosis;    PERK;   

DOI  :  10.1186/s12917-023-03581-9

 received in 2021-02-08, accepted in 2023-01-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPorcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days.ResultsThe synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils.ConclusionsThe synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

【 授权许可】

CC BY   
© The Author(s) 2023

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