Effect and mechanism of Dahuang Zhechong Pills against testicular aging in rats by inhibiting necroptosis signaling pathway.
10.19540/j.cnki.cjcmm.20220425.401
- Author:
Huan LI
1
;
Yue TU
2
;
Yi-Gang WAN
3
;
Geng-Lin MU
4
;
Wei WU
3
;
Jia-Xin CHEN
1
;
Mei-Zi WANG
1
;
Jie WANG
1
;
Yan FU
1
;
Yu-Feng CAI
1
;
Yu WANG
1
;
Zi-Yue WAN
5
Author Information
1. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of ChineseMedicine Nanjing 210008,China.
2. Acupuncture and Moxibustion and Massage College & Health Preservation and Rehabilitation College,Nanjing University of Chinese Medicine Nanjing 210023,China Jiangsu Provincial TCM Technology Engineering Research Center of Health and Health Preservation,Nanjing University of Chinese Medicine Nanjing 210023,China.
3. Department of Traditional Chinese Medicine,Nanjing DrumTower Hospital,The Affiliated Hospital of Nanjing University Medical School Nanjing 210008,China.
4. Institute of Chinese Medicine ,Nanjing University Nanjing 210008,China.
5. Graduate Schoolof Social Sciences,Faculty of Social Sciences,Hitotsubashi University Tokyo 186-8601,Japan.
- Publication Type:Randomized Controlled Trial, Veterinary
- Keywords:
Dahuang Zhechong Pills;
RIPK1/RIPK3/MLKL signaling pathway;
necroptosis;
testicular aging
- MeSH:
Aging;
Animals;
Drugs, Chinese Herbal;
Male;
Necroptosis;
Protein Kinases/genetics*;
Rats;
Reactive Oxygen Species/metabolism*;
Receptor-Interacting Protein Serine-Threonine Kinases/pharmacology*;
Serine/pharmacology*;
Signal Transduction;
Testis;
Threonine/pharmacology*
- From:
China Journal of Chinese Materia Medica
2022;47(15):4119-4127
- CountryChina
- Language:Chinese
-
Abstract:
To explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a classical prescription, in improving testicular aging(TA) in vivo, the authors randomly divided 24 male rats into four groups: the normal, model, DHZCP and vitamin E(VE) groups. The TA rat model was established by continuous gavage of D-galactose(D-gal). During the experiment, the rats in the DHZCP and VE groups were given DHZCP suspension and VE suspension, respectively by gavage, while those in the normal and model groups were gavaged saline separately every day. After the co-administration of D-gal and various drugs for 60 days, all rats were sacrificed, and their blood and testis were collected. Further, various indexes related to TA and necroptosis of testicular cells in the model rats were examined and investigated, which included the aging phenotype, total testicular weight, testicular index, histopathological features of testis, number of spermatogenic cells, sex hormone level, expression characteristics of reactive oxygen species(ROS) in testis, expression levels and characteristics of cyclins in testis, and protein expression levels of the key molecules in receptor-interacting serine/threonine-protein kinase 1(RIPK1)/receptor-interacting serine/threonine-protein kinase 3(RIPK3)/mixed lineage kinase domain like pseudokinase(MLKL) signaling pathway in each group. The results showed that, for the TA model rats, both DHZCP and VE improved their aging phenotype, total testicular weight, testicular index, pathological features of testis, number of spermatogenic cells, serum testosterone and follicle stimulating hormone levels, expression characteristics of ROS and protein expression levels and characteristics of P21 and P53 in testis. In addition, DHZCP and VE improved the protein expression levels of the key molecules in RIPK1/RIPK3/MLKL signaling pathway in testis of the model rats. Specifically, DHZCP was better than VE in the improvement of RIPK3. In conclusion, in this study, the authors found that DHZCP, similar to VE, ameliorated D-gal-induced TA in model rats in vivo, and its mechanism was related to reducing necroptosis of testicular cells by inhibiting the activation of RIPK1/RIPK3/MLKL signaling pathway. This study provided preliminary pharmacological evidence for the development and application of classical prescriptions in the field of men's health.
