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

Abstract

\n Background\n\nPCV2 (Porcine circovirus type 2) is one of the major pathogens commonly in pigs, which can cause immunosuppression and apoptosis. Vaccinations and single drugs are not totally prevent and treat PCV2 diseases. We have previously reported that the synergistic anti-PCV2 effects of Matrine and Osthole were better than Matrine or Osthole alone in vitro, Matrine and Osthole were purchased with a clear content, chemical structure and plant origin. This study aimes to evaluate theirs synergistic anti-PCV2 effect and mechanism in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups, namly: normal control group, PCV2 infected group, Matrine combined with Osthole high dose treatment group (40 mg/kg\u2009+\u200912 mg/kg), medium dose treatment group (20 mg/kg\u2009+\u20096 mg/kg), low dose treatment group (10 mg/kg\u2009+\u20093 mg/kg), Matrine treatment group (40 mg/kg), Osthole treatment group (12 mg/kg) and Ribavirin positive control group (40 mg/kg). PCV2 was intraperitoneally (i.p.) injected in all mice except the normal control group. At 5 days post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for 5 consecutive days.\nResults\n\nThe synergistic inhibition effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly stronger than that of Matrine and Osthole alone. The protein expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax were significantly reduced, but the protein expression of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological change caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils.\nConclusions\n\nThe synergistic effect of anti-apoptosis was better than that of Matrine and Osthole alone, although both of Matrine and Osthole could also directly inhibited the expression of PCV2 Cap and then inhibited the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provide a new insight into controlling PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.