Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice

Min Guo; Liwei Gu; Heping Hui; Xiaodong Li; Ling Jin

doi:10.3389/fphar.2022.830532

Extracts of Dracocephalum tanguticum Maxim Ameliorate Acute Alcoholic Liver Disease via Regulating Transcription Factors in Mice

Front Pharmacol. 2022 Mar 16:13:830532. doi: 10.3389/fphar.2022.830532. eCollection 2022.

Authors

Min Guo^{1

2

3}, Liwei Gu⁴, Heping Hui⁵, Xiaodong Li^{2

3}, Ling Jin¹

Affiliations

¹ College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China.
² Institute of Chinese Materia Medica, Gansu Academy of Traditional Chinese Medicine, Lanzhou, China.
³ Laboratory of Chinese Medicine, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, China.
⁴ Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
⁵ Gansu Agriculture Technology College, Lanzhou, China.

Abstract

Alcoholic liver disease (ALD) caused by excessive drinking is a health and economic concern worldwide. Given the high morbidity, mortality, and the progressive nature of ALD, finding effective interventions is essential. Previous studies have confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. Dracocephalum tanguticum Maxim (DTM) is one of the important traditional Tibetan medicines in China with the effect of clearing away liver heat, used for the treatment of hepatitis. In this study, the DTM chloroform extract (DtM-C), ethyl acetate extract (DtM-E), and n-butanol extract (DtM-B) were obtained by ethanol extraction combined with fractional extraction. Acute ALD was induced in mice given intragastric ethanol. Serum and liver biochemical markers were detected by ELISA. Liver histological observation, Oil Red O, and Masson's trichrome staining were performed. Liver injury cells were induced by ethanol. The cell vitality was detected by using MTT colorimetry. The expressions of Nrf2, NF-κB, STAT3, AP-1, CREB, HIF-1α, HO-1, NQO-1, GSTA1, IKB2, and Keap1 were detected by real-time polymerase chain reaction (PCR) to elucidate the mechanism of hepatoprotective effect, and the results were verified by using Western blot. The results of serum liver function indicators (ALT, AST, and ADH), serum hepatic lipid indicators (TC, TG, HDL-C, and LDL-C), and lipid peroxidation indicators (ADH, MDA, SOD, CAT, and GSH-Px) in liver tissue and liver histological observation showed that DtM-E could improve liver function, alleviate fatty degeneration, edema, cell necrosis, and liver fibrosis caused by alcohol. DtM-E also increased the vitality of EtOH-induced liver injury cells, upregulated the mRNA expression of Nrf2, HO-1, NQO-1, and GSTA1, while downregulated the expression of Keap-1, p65, and NF-κB. Western blot results were consistent with PCR. The results suggest that DtM-E has a protective effect against ALD in vitro and in vivo, and its mechanism of action may be related to the activation of Nrf2/Keap-1 and inhibition of the P65/NF-κB signaling pathways.

Keywords: Dracocephalum tanguticum Maxim; Tibetan medicine; acute alcoholic liver disease; extract; transcription factors.