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J Ethnopharmacol. 2018 May 10;217:118-125. doi: 10.1016/j.jep.2018.02.003. Epub 2018 Feb 5.

Protective effects of a traditional Chinese herbal formula Jiang-Xian HuGan on Concanavalin A-induced mouse hepatitis via NF-κB and Nrf2 signaling pathways.

Author information

1
Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China; Department of Pharmacology, School of Pharmacy, Guilin Medical University, No. 109 Huanchengbei Road Two, Guilin 541004, China.
2
Infinitus R&D Center, Infinitus (China) Company Ltd, No.19, Sicheng Road, The First Floor of HongTai Zhihui Valley, Tianhe Area, Guangzhou 510663, China.
3
Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China.
4
Infinitus R&D Center, Infinitus (China) Company Ltd, No.19, Sicheng Road, The First Floor of HongTai Zhihui Valley, Tianhe Area, Guangzhou 510663, China. Electronic address: Ken.Zhou@infinitus-int.com.
5
Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China. Electronic address: shxiaoy@fudan.edu.cn.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea), Curcuma longa L., Ligustrum lucidum, Eclipta prostrata (L.) L. and Paeonia lactiflora Pall., has exhibited a great hepatoprotective effect.

AIM OF THIS STUDY:

We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms.

MATERIALS AND METHODS:

Jiangkanling Capsule (900 mg/kg), low-dose JXHG (LJXHG, 700 mg/kg), high-dose JXHG (HJXHG, 1400 mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20 mg/kg). Liver injury was evaluated by measuring the serum levels of enzymes and cytokines as well as liver histological analysis. We also measured the hepatic expression of cytokines at mRNA levels and the proteins related to NF-κB and Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways.

RESULT:

Our results showed that JXHG pretreatment significantly alleviated ConA-induced live injury as evidenced by decreased serum levels of glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST), and reduced hepatocyte apoptosis and mortality. Furthermore, JXHG was able to significantly reduce the serum levels of proinflammatory cytokines, down-regulate the mRNA expression of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and up-regulate IL-10 as well as superoxide-dimutase-1 (SOD1), glutathione reductase (GSR) and Glutathione peroxidase 2 (GPX2) mRNA in the liver tissues after Con A injection. In addition, JXHG pretreatment dramatically suppressed the phosphorylation of NF-κB p65 (p65), increased Nrf2 expression, and decreased the expression ratio of cleaved caspase-3/caspase-3 in liver tissues.

CONCLUSION:

These results suggest that JXHG protects against ConA-induced acute live injury through inhibiting NF-κB mediated inflammatory pathway and promoting Nrf2 mediated anti-oxidative stress signaling pathway.

KEYWORDS:

Autoimmune hepatitis; Concanavalin A; JXHG; NF-κB; Nrf2

PMID:
29421593
DOI:
10.1016/j.jep.2018.02.003
[Indexed for MEDLINE]

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