Qingre Xiaoyanning inhibits emotional stress-induced reactivation of latent herpes simplex virus type 1 in mice
10.16438/j.0513-4870.2022-0249
- VernacularTitle:清热消炎宁抑制潜伏Ⅰ型单纯疱疹病毒激活的作用研究
- Author:
Shan JIANG
1
,
2
;
Jie NIU
1
,
2
;
Shu-hua OUYANG
1
,
2
,
3
;
Tao JIANG
4
;
Hong-ying PENG
4
;
Zhuo LUO
1
,
2
;
Kurihara HIROSHI
1
,
2
;
Yi-fang LI
1
,
2
;
Rong-rong HE
1
,
2
,
3
Author Information
1. Guangdong Engineering Research Center of Chinese Medicine and Disease Susceptibility, Jinan University, Guangzhou 510632, China
2. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China
3. School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China
4. Guangzhou Baiyunshan Jingxiutang Pharmaceutical Co., Ltd., Guangzhou 510130, China
- Publication Type:Research Article
- Keywords:
emotional stress;
Qingre Xiaoyanning;
italic>Sarcandra glabra (Thunb.) Nakai;
liver qi stagnation forming fire;
herpes simplex virus type 1 reactivation;
ferroptosis
- From:
Acta Pharmaceutica Sinica
2022;57(6):1641-1648
- CountryChina
- Language:Chinese
-
Abstract:
In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.