Hepatoprotective Effect of the Penthorum Chinense Pursh Extract against the CCl4-Induced Acute Liver Injury via NF-κB and p38-MAPK PATHWAYS in Dogs.

Weilai Tao,Bhutto Zohaib Ahmed,Fazul Nabi,Ruiling Ye,Xin Yue,Zhaorong Zhu,Juan Liu,Yangfei Shang

doi:10.3390/ani12050569

Abstract

Simple SummaryTraditional 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 CCl4. 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.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 (CCl4) induced ALI in dogs via mitogen-activated protein kinase (MAPK) and Nuclear factor κB (NF-κB) signaling pathway. Healthy dogs were induced by CCl4 and treated with different dosage regimes of PCPE for 7 days. CCl4 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.

Highlights

The liver is a vital organ involved in the metabolism and detoxification of xenobiotics, chemicals, drugs, and foreign particles from the body
It is well established after reported studies that mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways play an important role in controlling the Acute liver injury (ALI) via protective mechanisms which include inflammatory response and oxidative stress [6]
Oxidative stress has been reported to activate Nuclear factor κB (NF-κB), an important transcriptional regulator in cells, and induces NF-κB nuclear translocation to promote the expression of pro-inflammatory genes, including tumor necrosis factor α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) [9,10]

Summary

Introduction

The liver is a vital organ involved in the metabolism and detoxification of xenobiotics, chemicals, drugs, and foreign particles from the body. Acute liver injuries or failure caused by CCl4 -induction are associated with oxidative stress and inflammatory responses [5]. It is well established after reported studies that mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways play an important role in controlling the ALI via protective mechanisms which include inflammatory response and oxidative stress [6]. The oxidative stress involved in the pathogenesis of liver injury as an intracellular serine or threonine protein kinase, MAPK can be activated by stress factors and inflammatory stimulation and plays an important role in cell proliferation, differentiation, and apoptosis [7,8]. Oxidative stress has been reported to activate NF-κB, an important transcriptional regulator in cells, and induces NF-κB nuclear translocation to promote the expression of pro-inflammatory genes, including tumor necrosis factor α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6

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