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Original Article

Korean J Physiol Pharmacol 2019; 23(6): 501-508

Published online November 1, 2019 https://doi.org/10.4196/kjpp.2019.23.6.501

Copyright © The Korean Journal of Physiology & Pharmacology.

Effects of rosmarinic acid on immunoregulatory activity and hepatocellular carcinoma cell apoptosis in H22 tumor-bearing mice

Wen Cao1,#,*, Kai Mo2,#, Sijun Wei1, Xiaobu Lan2, Wenjuan Zhang1, and Weizhe Jiang3,*

1Department of Pharmacy, Guangxi International Zhuang Medicine Hospital, Guangxi 530200, 2Department of Pharmacy, Nanning First People's Hospital, Guangxi 530022, 3Department of Pharmacology, Guangxi Medical University, Guangxi 530021, China

Correspondence to:Wen Cao
E-mail: mosquito1106@foxmail.com
Weizhe Jiang
E-mail: jiangweizhe6812@163.com

#These authors contributed equally to this work.

Received: July 26, 2019; Revised: September 24, 2019; Accepted: September 27, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and NF-κB p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of CD4+/CD8+ and the secretion of interleukin (IL)-2 and interferon-γ, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

Keywords: Apoptosis, Hepatocellular carcinoma, Immunoregulation, Rosmarinic acid