Therapeutic potential of alkaloid extract from Codonopsis Radix in alleviating hepatic lipid accumulation: insights into mitochondrial energy metabolism and endoplasmic reticulum stress regulation in NAFLD mice.
10.1016/S1875-5364(23)60403-0
- Author:
Cailian FAN
1
;
Guan WANG
2
;
Miao CHEN
3
;
Yao LI
4
;
Xiyang TANG
5
;
Yi DAI
6
Author Information
1. College of Medicine, Henan Engineering Research Center of Funiu Mountain's Medicinal Resources Utilization and Molecular Medicine, Pingdingshan University, Pingdingshan 467000, China. Electronic address: fan20094569@163.com.
2. Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu 610041, China. Electronic address: guan8079@163.com.
3. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: chenmiaoo1998@163.com.
4. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: 1809940539@qq.com.
5. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: tangxiyangjnu@163.com.
6. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: daiyi1004@163.com.
- Publication Type:Journal Article
- Keywords:
Alkaloids;
Codonopsis Radix;
Endoplasmic Reticulum stress;
Mitochondrial energy metabolism;
NAFLD
- MeSH:
Mice;
Animals;
Non-alcoholic Fatty Liver Disease/metabolism*;
Codonopsis;
Liver;
Lipid Metabolism;
Antineoplastic Agents/pharmacology*;
Alkaloids/pharmacology*;
Endoplasmic Reticulum Stress;
Energy Metabolism;
Lipids;
Diet, High-Fat/adverse effects*;
Mice, Inbred C57BL
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(6):411-422
- CountryChina
- Language:English
-
Abstract:
Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine. This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix (ACR) in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD). The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD. Furthermore, ACR ameliorated the dysregulated lipid metabolism in NAFLD mice, as evidenced by reductions in serum triglyceride, total cholesterol, and low-density lipoprotein levels, accompanied by a concomitant increase in the high-density lipoprotein level. ACR treatment also demonstrated a profound anti-oxidative effect, effectively alleviating HFD-induced oxidative stress and promoting ATP production. These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes I, II, IV, and V, in addition to the activation of the AMPK/PGC-1α pathway, suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism. Moreover, ACR administration mitigated HFD-induced endoplasmic reticulum (ER) stress and suppressed the overexpression of ubiquitin-specific protease 14 (USP14) in NAFLD mice. In summary, the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress. These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.
