Hepatoprotective Effect of the Penthorum Chinense Pursh Extract against the CCl(4)-Induced Acute Liver Injury via NF-κB and p38-MAPK PATHWAYS in Dogs

SIMPLE SUMMARY: Traditional Chinese herbal medicines have been used to treat animal diseases and play an important role in the treatment of liver injury. The current study used Penthorum Chinense Pursh extract (PCPE) to treat acute liver injury of dogs caused by CCl(4). Our study found that PCPE reduced the pathological symptoms and liver tissue lesions caused by ALI, improved serum biochemical indicators, and alleviated the inflammatory response and oxidative stress. Our results clarified that the NF-κB and MAPK signaling pathways in dogs are related to the antioxidant and anti-inflammatory effects of PCPE. PCPE may be used as a safe and effective medicine for the treatment of acute liver injury in dogs. ABSTRACT: Acute liver injury (ALI), manifested by acute hepatocellular damages and necrosis, is a life-threatening clinical syndrome and Penthorum Chinense Pursh (PCP) is a well-known folk medicine practiced for liver-related diseases. This study aimed to investigate the ameliorative effects of PCP extract (PCPE) on carbon tetrachloride (CCl(4)) induced ALI in dogs via mitogen-activated protein kinase (MAPK) and Nuclear factor κB (NF-κB) signaling pathway. Healthy dogs were induced by CCl(4) and treated with different dosage regimes of PCPE for 7 days. CCl(4) produced acute liver injury and induced both oxidative stress and an inflammatory response in dogs. The PCPE significantly ameliorated and improved vacuolar inflammatory lesions in liver tissues during ALI, enhanced activity of superoxide dismutase, and restored glutathione peroxidase, further significantly reducing the indices of malondialdehyde and nitric oxide in serum. Inflammatory factors (IL-1β, IL-6, and TNF-α) were declined and anti-inflammatory factors (IL-10) were increased by the application of PCPE. PCPE treatment, down-regulated the MEKK4, MKK3, p38MAPK, MSK1, and NF-κB, and upregulated the IkB mRNA levels (p < 0.01) in ALI affected dogs. In conclusion, PCPE repaired acute liver injury by improving antioxidant enzymes and by reducing oxidation products. Furthermore, the PCPE inhibited the MAPK/NF-κB signaling pathway, which resulted in anti-inflammatory and antioxidant effects on ALI-induced dogs. In the future, PCPE could be a useful ethnomedicine in veterinary clinical practices for the treatment of liver injuries or failures.