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An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.
- Source :
- Chinese Medicine; 7/2/2024, Vol. 19 Issue 1, p1-12, 12p
- Publication Year :
- 2024
-
Abstract
- Background: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. Objective: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. Methods: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. Results: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. Conclusion: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified. [ABSTRACT FROM AUTHOR]
- Subjects :
- GASTROINTESTINAL disease prevention
IRINOTECAN
CHINESE medicine
IN vitro studies
WOUND healing
RESEARCH funding
HERBAL medicine
ANTINEOPLASTIC agents
APOPTOSIS
HYDROCARBONS
COLORECTAL cancer
IN vivo studies
CELL cycle
XENOGRAFTS
MICE
PLANT extracts
ANIMAL experimentation
CELL survival
GENETIC techniques
METABOLOMICS
DRUG synergism
GASTROINTESTINAL diseases
Subjects
Details
- Language :
- English
- ISSN :
- 17498546
- Volume :
- 19
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Chinese Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 178230227
- Full Text :
- https://doi.org/10.1186/s13020-024-00967-1