Effects and Mechanisms of Total Flavonoids from Blumea balsamifera (L.) DC. on Skin Wound in Rats.

Chinese herbalmedicine (CHM) evolved through thousands of years of practice and was popular not only among the Chinese population, but also most countries in the world. Blumea balsamifera (L.) DC. as a traditional treatment for wound healing in Li NationalityMedicine has a long history of nearly 2000 years. This study was to evaluate the effects of total flavonoids fromBlumea balsamifera (L.) DC. on skin excisional wound on the back of Sprague-Dawley rats, reveal its chemical constitution, and postulate its action mechanism. The rats were divided into five groups and the model groups were treated with 30% glycerol, the positive control groups with JingWanHong (JWH) ointment, and three treatment groups with high dose (2.52 g·kg-1), medium dose (1.26 g·kg-1), and low dose (0.63 g·kg-1) of total flavonoids fromB. balsamifera. During 10 consecutive days of treatment, the therapeutic effects of rateswere evaluated. On day 1, day 3, day 5, day 7, and day 10 after treatment, skin sampleswere taken fromall the rats for further study. Significant increases of granulation tissue, fibroblast, and capillary vessel proliferationwere observed at day 7 in the high dose and positive control groups, comparedwith themodel group, with themethod of 4% paraformaldehyde for histopathological examination and immunofluorescence staining. To reveal the action mechanisms of total flavonoids on wound healing, the levels of CD68, vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and hydroxyproline were measured at different days. Results showed that total flavonoids had significant effects on rat skin excisional wound healing compared with controls, especially high dose ones (p < 0.05). Furthermore, the total flavonoid extract was investigated phytochemically, and twenty-seven compounds were identified from the total flavonoid sample by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry/diode array detector (UPLC-Q-TOF-MS/DAD), including 16 flavonoid aglucons, five flavonoid glycosides (main peaks in chromatogram), five chlorogenic acid analogs, and 1 coumarin. Reports showthat flavonoid glycoside possesses therapeutic effects of curingwounds by inducing neovascularization, and chlorogenic acid also has anti-inflammatory and wound healing activities; we postulated that all the ingredients in total flavonoids samplemaybe exert a synergetic effect onwound curing. Accompaniedwith detection of four growth factors, the upregulation of these key growth factors may be the mechanism of therapeutic activities of total flavonoids. The present study confirmed undoubtedly that flavonoids were the main active constituents that contribute to excisional wound healing, and suggested its actionmechanismof improving expression levels of growth factors at different healing phases. [ABSTRACT FROM AUTHOR]