The Therapeutic Effect Of Essential Oil Of Ligusticm Chuanxiong Hort.on Human Hypertrophic Scar And Its Safety Evaluation

Hypertrophic scar is a pathological phenomenon, which results from skin wound healing. It's characterized by proliferative disorder of dermal fibroblasts and overproduction of collagen and excessive deposition of extracellular matrix.Patients with hypertrophic scars often report itching and pain, and experience serious functional and cosmetic problems. The pathogenesis is still unclear, so there is no effective treatment without side effects. Our previous study showed that essential oil of Ligusticum chuanxiong Hort.(LEO) can inhibited fibroblasts proliferation and induced apoptosis, and had a good preventive effect in rabbit ear model with hypertrophic scars. But the good preventive effect of a drug does not mean its favorable therapeutic action.Therefore we investigate the therapeutic effect on hypertrophic scar.Hypertrophic fibroblasts (FB) were cultured from HS tissue. Chuanxiong rhizome collecting from Xindu, Pengshan, Aoping and Du jiangyan were extracted by petroleum ether and hydrodistillation respectively. We picked up the best habit and extract way by comparing their inhibitory effect on FB proliferation. Then extract essential oil through the best extract way from Chuanxiong rhizome which is collected from the best habit. The LEO would be used in the next study. The results showed that the best habit is Xindu, best way of extraction is hydrodistillation, and the best concentration is200μg/ml when the best inhibitory effect. So we extract LEO from Chuanxiong rhizome produced in Xindu through hydrodistillation.EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with hypertrophic scars was established. On postoperative day29and afterwards, LEO (2.5,5, and10%), contractubex and liposomes without EO were applied once daily to the scars for28days. One further unwounded rabbit with full-thickness skin on its ears received neither liposomes (with or without EO) nor contractubex. On postoperative day56, the scar tissue was excised for HE and masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1(MMP-1), caspase-3and-9, and transforming growth factor P1(TGF-β1). In addition, the scar elevation index (SEI) was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of caspase-3and-9levels and apoptosis cells were markedly increased, and TGF-β1, MMP-1, collagen Ⅰ, and collagen Ⅲ were evidently decreased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars.The essential oil was extracted by hydrodistillation and analyzed by GC-MS;100mice were divided into10groups, the first five groups were intragastric administrated EO, the last five groups were intraperitoneal EO;20rabbits were divided into2groups, normal skin group and injured skin group. There are six subgroups, normal group,12.5%EO,25%EO,50%EO and100%EO group. Observe the irritative reaction after using EO by external application;60guinea pigs were divided into6groups,12.5%EO,25%EO,50%EO and100%EO group, positive and negative group. Observe the allergic reaction of EO. Fingerprint was established and74common peaks were found, of which12components were listed. LD50of EO by intragastric administration and intraperitoneal to mice is7.23g/kg and2.52g/kg, which is respectively equal to14606times and5091times of60kg people's daily dried medicinal herb expenses; rabbits skin test shows that there were slight erythema and edema response after the intact skin and the damaged skin had contact with25%EO,50%EO and100%EO, but the stimulus index were all below2.0and the doses is equal to101,202and404times of60kg people's daily dried medicinal herb expenses; EO and basic ointment did not cause anaphylaxis such as erythema and edema etc. on the guinea pigs skin. The findings above showed that EO belongs to the safe preparation.In conclusion, EO had a good therapeutic effect on hypertrophic scar, and the dose is safe in clinic. It has the potential to be a new therapeutic medicine on hypertrophic scar.