Cel-CS1K: A Celastrol-Chitosan Conjugate for Treating Diet-Induced Obesity.
Chem Res Toxicol
; 37(6): 944-956, 2024 Jun 17.
Article
in En
| MEDLINE
| ID: mdl-38771988
ABSTRACT
Celastrol (Cel), extracted from Tripterygium wilfordii Hook, is a potential antiobesity drug, except for its adverse reactions in clinic. In the present study, we synthesized a promising celastrol-chitosan conjugate (Cel-CS1K) and evaluated its antiobesity effect and biological safety in diet-induced obese mice. Cel-CS1K showed higher drug loading (over 10 wt %), good solubility (18-19 mg/mL) in water, slower peak time (Tmax = 4 h), and clearance (T1/2 = 8.97 h) in rats. Cel-CS1K effectively attenuated the cytotoxicity, celastrol-induced apoptosis, and fat accumulation of hepatocytes. Cel-CS1K reduced body weight and dietary amount same as the free Cel but with lower toxicity in blood, liver, and testis. Cel-CS1K improved the glucose homeostasis, HDL-C level, insulin sensitivity, and leptin sensitivity, while it significantly reduced the gene expression levels of LDL-C, TG, and TC in obese mice. Furthermore, the adipose-related gene expression levels provided evidence in support of a role for Cel-CS1K in losing weight by the multimode regulation. Overall, Cel-CS1K provides a translatable therapeutic strategy for the treatment of diet-induced obese humans.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triterpenes
/
Anti-Obesity Agents
/
Chitosan
/
Pentacyclic Triterpenes
/
Obesity
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Chem Res Toxicol
Journal subject:
TOXICOLOGIA
Year:
2024
Type:
Article
Affiliation country:
China