Effect and mechanism of Dahuang Zhechong Pills in improving liver aging in rats by regulating ROS-mediated PI3K/Akt/FoxO4 signaling pathway.
10.19540/j.cnki.cjcmm.20230403.401
- Author:
Yan FU
1
;
Wei WU
2
;
Yi-Gang WAN
2
;
Hai-Ming YANG
3
;
Yue TU
4
;
Si-Yi LIU
4
;
Qi-Jun FANG
2
;
Ying-Lu LIU
2
;
Mei-Zi WANG
5
;
Huang HUANG
6
Author Information
1. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing 210008,China Institute of Chinese Medicine,Nanjing University Nanjing 210008,China Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School,Nanjing University Nanjing 210008,China.
2. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School,Nanjing University Nanjing 210008,China.
3. Department of Health Management Centre,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University Nanjing 210008,China.
4. Acupuncture,Moxibustion and Massage College,Health Preservation and Rehabilitation College,Nanjing University of Chinese Medicine Nanjing 210023,China.
5. Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing 210008,China.
6. International Jingfang Insititute,Nanjing University of Chinese Medicine Nanjing 210023, China.
- Publication Type:Journal Article
- Keywords:
Dahuang Zhechong Pills;
PI3K/Akt/FoxO4 signaling pathway;
liver aging;
oxidative stress
- MeSH:
Animals;
Rats;
Proto-Oncogene Proteins c-akt/genetics*;
Phosphatidylinositol 3-Kinases/genetics*;
Reactive Oxygen Species;
Tumor Suppressor Protein p53/genetics*;
Signal Transduction;
Liver;
Aging;
Cell Cycle Proteins;
Interleukin-6
- From:
China Journal of Chinese Materia Medica
2023;48(11):3014-3021
- CountryChina
- Language:Chinese
-
Abstract:
Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
