Protective effects of Pimpinella diversifolia DC. root essential oil against lipopolysaccharide/D-galactosamine-induced acute liver injury in mice through inhibiting inflammation and reducing oxidative stress

Abstract

Acute liver injury (ALI) is a life-threatening syndrome with few therapeutic drugs are available. Excessive inflammatory response and imbalance of the antioxidant system are the hallmark of ALI. Therefore, anti-inflammatory and anti-oxidant treatment would be beneficial for ALI. Pimpinella diversifolia DC. is a perennial aromatic herb of the Umbelliferae family. The whole herb has been used as a medicine for thousands of years by the She ethnic minority of China, and is claimed to have beneficial health effects on liver disease. Its roots are rich in essential oil, but there are few reports on its pharmacological study. Therefore, the aim of the current work was to reveal the hepatoprotective effects of P. diversifolia root essential oil (PDREO). PDREO was prepared by a simultaneous distillation–extraction method and characterized by gas chromatography–mass spectroscopy (GC–MS). The potential application of PDREO in detoxification of liver injury was evaluated using a lipopolysaccharide (LPS)- and D-galactosamine (D-GalN)-induced acute liver injury mouse model. The results showed that the major constituents of PDREO were isodaucene (29.97%), 4-methoxy-2-(3-methyloxiranyl)-phenyl isobutyrate (19.53%), geijerene isomer (12.33%), and 2-methyl-4-methoxy-2-(3-methyl-2-oxiranyl) phenyl butyrate (6.88%). Isodaucene was identified in the essential oil of the Pimpinella species for the first time. Pre-treatment with PDREO (50 mg/kg) and (150 mg/kg) can effectively reduce the serum levels of alanine aminotransferase and aspartate aminotransferase, and dramatically alleviate liver edema, hemorrhage, hepatocyte apoptosis, and necrosis, which may be attributed to the significant anti-inflammatory activity (inhibiting the secretion of inflammatory cytokines and chemokines and reducing the infiltration of monocyte-derived macrophages and neutrophils) and the regulatory effects on oxidative stress (upregulating the expression of antioxidant enzymes such as GPX4, SOD1, and CAT) of PDREO. In addition, PDREO (150 mg/kg) can completely block the death of mice induced by LPS/D-GalN, while the survival rate of mice treated with the clinical first-line drug N-acetylcysteine (300 mg/kg) was only 10%. In light of the results obtained, PDREO is a promising natural detoxification agent, with potential applications in the food and pharmaceutical industries.