Effect of Compatibility of Effective Monomer Components of Fujin Shengjisan on Angiogenesis of HUVEC Based on Uniform Design
10.13422/j.cnki.syfjx.20241815
- VernacularTitle:基于均匀设计的腐尽生肌散有效单体成分配伍对HUVEC血管新生的影响
- Author:
Xianying LU
1
;
Jing GAO
1
;
Dingxi BAI
1
;
Chaoming HOU
1
;
Wenting JI
1
;
Huan CHEN
1
;
Chenxi WU
1
Author Information
1. School of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu 610075,China
- Publication Type:Journal Article
- Keywords:
Fujin Shengjisan;
diabetic ulcer;
angiogenesis;
uniform design
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(8):9-20
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo determine the optimal combination of the effective monomer components "quercetin-kaempferol-abietic acid-boswellic acid" in Fujin Shengjisan for promoting diabetic ulcer (DU) wound healing through uniform design, thereby achieving the modern application of the ancient formula. MethodsFollowing the principle of "uniform design-pharmacodynamic experiment-mathematical modeling and model verification", the U14(145) uniform design table was adopted.The four monomer components of Chinese medicine were considered as the independent variables, and the proliferation rate of human umbilical vein endothelial cells (HUVECs) induced by glucose was used as the pharmacodynamic indicator. A mathematical model was constructed using DPS software to correlate the effective monomer components with the pharmacodynamic indicator. The results of uniform design were verified through CCK-8 assay, cell scratch healing, tube formation, Western blot, and Real-time PCR. ResultsAmong the 14 compatibility groups, compared with the high-glucose model group, compound compatibility group 6 showed the strongest proliferation effect and statistical significance (P<0.05). Four quadratic polynomial regression equations (Y1-Y4) were obtained through DPS modeling. Considering the model's fit, stability, and practical application, equations Y1-Y3 were selected for the follow-up verification. To ensure experiment reproducibility, group 6 was used for validation. Group 6 and equations Y1-Y3 were renamed as compound prescription ① to compound prescription④, respectively, to represent the modern application of the ancient FJSJ Powder through compatibility of monomer components. Verification experiments showed that in the CCK-8, scratch healing, and tube formation assays, the cell viability, wound healing rate, and tube formation number of HUVECs stimulated with 50 mmol·L-1 glucose were significantly reduced compared with the blank group. Moreover, the expression levels of angiogenesis-related cytokines, vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2), and CD31 secretion were significantly down-regulated. However, after intervention with compound prescriptions ① to ④, compound prescriptions ① and ③ significantly improved the biological functions of HUVECs induced by 50 mmol·L-1 glucose. Further analysis of the regression coefficients of compound prescriptions ① and ③, and the relative dose ratios of each monomer component, indicated that abietic acid, quercetin, and boswellic acid promoted angiogenesis of HUVECs in the high glucose environment, with a major effect (positive partial correlation coefficients, all > 0.9). Abietic acid and boswellic acid, as well as kaempferol and boswellic acid, promoted angiogenesis in HUVECs through interaction (positive partial correlation coefficients). ConclusionCompound prescriptions ① and ③ are the optimal combinations. They can reverse the inhibitory effects of high glucose, stimulate the proliferation, migration, and tube formation abilities of HUVECs in a high glucose environment, and promote the expression of vascular endothelial growth factorA(VEGFA), FGF2, and CD31, thereby promoting angiogenesis and facilitating DU wound healing. This finding not only confirms the good reproducibility and feasibility of compound prescriptions ① and ③ but also provides new insights and methods for the rational construction of mathematical models to further study the compatibility theory of Chinese medicine.