The Effects of Gyejibokryeong-hwan (桂枝茯苓丸) for Wound Healing after Skin Suture

계지복령환(桂枝茯苓丸)이 피부봉합 후 상처 치유에 미치는 영향

Objectives There is few Korean medicinal studies about post-operation wound healing despite much effort for minimizing wound or post-op scar. The aim of this study is to evaluate the wound healing effect of Gyejibokryeong-hwan (Guizhifuling-wan, GBH) after skin suture. Methods < In vitro > We observed anti-oxidative and anti-inflammatory effect by using lipopolysaccharide (LPS)-treated RAW 264.7 cells. For anti-oxidation, we mesured the total amount of polyphenol, flavonoid, DPPH scavenging ability, ABTS scavenging ability and the value of ROS production, and for anti-inflammation, we mesured the amount of NO and pro-inflammatory cytokines ($TNF-{\alpha}$, $IL-1{\beta}$, IL-6). < In vivo > Thirty SD rats were divided into five equal groups (n=6, one normal, two controls and two experimentals). All groups except normal group were made a scar (around $1{\times}4cm^2$) in the back by the depth of the fascia and then sutured by a thread and needle. Normal group rats received no treatment at all. Control group rats were fed distilled water, and positive control group rats were percutaneously applied terramycin once in 2 days. GBH 200 group rats were orally medicated GBH 200 mg/kg, and GBH 400 group rats were orally medicated GBH 400 mg/kg per day for two weeks. We analyzed the blood samples (WBC, neutrophil, lymphocyte, monocyte, eosinophil), and the serums (TIMP-1, MMP-2, MMP-2. $PGE_2$, $TGF-{\beta}$, VEGF), and examined the wounded skin tissue histopathologically. Results < in vitro > 1. DPPH and ABTS scavenging activity was increased concentration-dependantly, and ROS production was significantly increased in GBH treated cells ($100{\mu}g/ml$). Therefore in this study, Gyejibokryeong-hwan appears to have the anti-oxidative. 2. NO production was significantly reduced in GBH treated cells ($100{\mu}g/ml$), and $IL-1{\beta}$ production was significantly reduced in GBH treated cells ($1{\mu}g/ml$). But, $TNF-{\alpha}$ and IL-6 did not show uneffective action. Therefore in this study, Gyejibokryeong-hwan did not show any significant effect on anti-inflammatory process. < in vivo > 1. Monocyte and neutrophil was significantly increased in GBH (200, 400) groups. WBC, lymphocyte and eosinophil did not show significant change. 2. TIMP-1, MMP-2, VEGF were significantly increased in GBH 400 group, $PGE_2$ was significantly reduced in GBH 400 group. $TGF-{\beta}$ was significantly increased in GBH (200, 400) groups, and MMP-9 was increased concentration-dependantly in GBH groups, but there was no significance. 3. In histopathological examinations, collagen was significantly increased and keratin was significantly decreased in GBH (200, 400) groups. Conclusions According to in vitro experiment, GBH appears to have the anti-oxidative effect and in vivo experiment, GBH stimulate the wound healing process hematologically and histopathologically. In conclusion, the results suggest that GBH promotes wound healing after skin suture.