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用于骨折治疗的局部应用草药配方的体外和体内评估。

In vitro & in vivo assessment of a herbal formula used topically for bone fracture treatment.

机构信息

College of Pharmaceutical Sciences, ZheJiang University, Hangzhou City, ZheJiang Province, PR China.

出版信息

J Ethnopharmacol. 2010 Sep 15;131(2):282-9. doi: 10.1016/j.jep.2010.06.039. Epub 2010 Jun 30.

DOI:10.1016/j.jep.2010.06.039
PMID:20600749
Abstract

AIM OF THE STUDY

A novel topical paste used for fracture healing (FH), consisting of the extracts of six herbs, Radix Dipsaci, Ramulus Sambucus Williamsii, Rhizoma Notoginseng, Flos Carthami, Rhizoma Rhei and Fructus Gardeniae, was developed according to the classical theory of traditional Chinese medicine. This study aimed to determine the effectiveness of this formula, and some of its important chemical components in the promotion of fracture healing. The transdermal transport of FH was also examined.

MATERIALS AND METHODS

The osteogenic, angiogenic and nitric oxide suppressing effects of FH and its important chemical marker components were assessed by using osteoblastosacroma UMR-106 cells, human umbilical vein endothelial cells (HUVEC) and murine macrophage RAW264.7 cells, respectively. The bone healing effects of the FH paste and its transdermal absorption were determined using a rabbit fracture model. The callus sizes, bone specific alkaline phosphatase levels and biomechanical properties of the healed bone were assessed.

RESULTS

FH significantly increased the cell proliferation in UMR-106 and HUVEC cells and inhibited the nitric oxide production in murine macrophage in dose-dependent manner. Its important chemical components asperosaponin VI, ginsenoside Rg1 and emodin were shown to be acting positively in the respective in vitro studies. FH paste significantly improved the bone healing in the rabbit fracture model, as was indicated by the increases in callus size at weeks 2-5, and the elevations in bone specific alkaline phosphatase activities at weeks 5-6. The analysis using LC/MS/MS also showed the presence of important chemical marker components of the FH formula in the plasma after 8 weeks of topical treatment.

CONCLUSION

This study presents the first scientific evidence of the efficacy of a herbal paste in the promotion of fracture healing. There were evidences of transdermal transport of the chemical components, control the inflammation through nitric oxide inhibition, promotion of angiogenesis, and bone healing in the in vitro tests, as well as in the experimental animal.

摘要

研究目的

根据传统中医的经典理论,开发了一种用于骨折愈合(FH)的新型局部贴剂,由六种草药的提取物组成,包括续断、桑枝、三七、红花、大黄和栀子。本研究旨在确定该配方及其一些重要化学成分在促进骨折愈合方面的有效性。还研究了 FH 的经皮转运。

材料和方法

分别使用成骨肉瘤 UMR-106 细胞、人脐静脉内皮细胞(HUVEC)和鼠巨噬细胞 RAW264.7 细胞评估 FH 及其重要化学标记成分的成骨、血管生成和抑制一氧化氮的作用。使用兔骨折模型评估 FH 贴剂的骨愈合效果及其经皮吸收。评估了愈合骨的骨痂大小、骨特异性碱性磷酸酶水平和生物力学特性。

结果

FH 以剂量依赖的方式显著增加 UMR-106 和 HUVEC 细胞的细胞增殖,并抑制鼠巨噬细胞中的一氧化氮产生。其重要的化学成分asperosaponin VI、ginsenoside Rg1 和大黄素在各自的体外研究中表现出积极作用。FH 贴剂显著改善了兔骨折模型中的骨愈合,从第 2-5 周的骨痂大小增加以及第 5-6 周的骨特异性碱性磷酸酶活性升高可以看出。LC/MS/MS 分析还显示,在 8 周的局部治疗后,血浆中存在 FH 配方的重要化学标记成分。

结论

本研究首次提供了一种草药贴剂促进骨折愈合的疗效的科学证据。在体外试验和实验动物中,有证据表明化学成分的经皮转运、通过抑制一氧化氮控制炎症、促进血管生成和骨愈合。

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