Synergistic interaction between Astragali Radix and Rehmanniae Radix in a Chinese herbal formula to promote diabetic wound healing
Synergistic interaction between Astragali Radix and Rehmanniae Radix in a Chinese herbal formula to promote diabetic wound healing
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DOI：
10.1016/j.jep.2012.02.025
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发表时间：
2012-05-07
影响因子：
5.4
通讯作者：
Lau, Clara Bik-San
中科院分区：
文献类型：
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作者：
Lau, Kit-Man;Lai, Kwok-Kin;Lau, Clara Bik-San
民族药理学相关性：研究目的：在我们以前的研究中，发现由AR和RR以2：1的比例组成的草药配方NF 3通过组织再生、促进血管生成和抑制炎症的作用而有效地促进大鼠糖尿病伤口愈合。本研究的目的是探讨中药与中药的相互作用研究NF 3中AR和RR之间的协同作用（或可能的协同作用）以促进糖尿病伤口愈合，并通过评估不同机制研究中单个AR和RR的效力来鉴定配方中的主要草药。采用化学诱导的糖尿病足溃疡大鼠模型，检测NF 3及其单味中药AR和RR的伤口愈合作用。对于机制研究，小鼠巨噬细胞（RAW 264.7）炎症、人成纤维细胞（Hs 27）增殖和人内皮细胞（HMEC-1）迁移试验分别用于研究草药提取物的抗炎、肉芽形成和促进血管生成活性。在足溃疡动物模型中，临床相关剂量（0.98 g/kg）的AR和RR均未促进糖尿病伤口愈合。然而，当它们作为NF 3组合使用时，显示出协同相互作用，其中NF 3与水组相比可显著减少大鼠的伤口面积（p < 0.01）。在抗炎和肉芽形成方面，AR在抑制脂多糖（LPS）诱导的RAW 264.7细胞产生一氧化氮和促进Hs 27成纤维细胞增殖方面比RR更有效。在促血管生成方面，只有NF 3能促进HMEC-1细胞的迁移。结论：AR在NF 3的抗炎和促成纤维细胞增殖活性中起着突出的作用。然而，包含RR对于NF 3发挥其整体伤口愈合以及潜在的血管生成促进作用至关重要。本研究结果证明了AR和RR以2：1的比例联合使用作为NF 3治疗糖尿病足溃疡，并说明AR是该草药配方中的主要药物。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Ethnopharmacological relevance: Astragali Radix (AR) and Rehmanniae Radix (RR) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic foot ulcer.Aim of study: In our previous study, a herbal formula NF3 comprising AR and RR in the ratio of 2:1 was found effective in enhancing diabetic wound healing in rats through the actions of tissue regeneration, angiogenesis promotion and inflammation inhibition. The aims of the present study were to investigate the herb-herb interaction (or the possible synergistic effect) between AR and RR in NF3 to promote diabetic wound healing and to identify the principal herb in the formula by evaluating the potencies of individual AR and RR in different mechanistic studies.Materials and methods: A chemically induced diabetic foot ulcer rat model was used to examine the wound healing effect of NF3 and its individual herbs AR and RR. For mechanistic studies, murine macrophage cell (RAW 264.7) inflammation, human fibroblast (Hs27) proliferation and human endothelial cell (HMEC-1) migration assays were adopted to investigate the anti-inflammatory, granulation formation and angiogenesis-promoting activities of the herbal extracts, respectively.Results: In the foot ulcer animal model, neither AR nor RR at clinical relevant dose (0.98 g/kg) promoted diabetic wound healing. However, when they were used in combination as NF3, synergistic interaction was demonstrated, of which NF3 could significantly reduce the wound area of rats when compared to water group (p < 0.01). For anti-inflammation and granulation formation, AR was more effective than RR in inhibiting lipopolysaccharide (LPS)-induced nitric oxide production from RAW 264.7 cells and promoting Hs27 fibroblast proliferation. In the aspect of angiogenesis promotion, only NF3 promoted cell migration of HMEC-1 cells.Conclusions: AR plays a preeminent role in the anti-inflammatory and fibroblast-proliferating activities of NF3. The inclusion of RR, however, is crucial for NF3 to exert its overall wound-healing as well as the underlying angiogenesis-promoting effects. The results of present study justified the combined usage of AR and RR in the ratio of 2:1 as NF3 to treat diabetic foot ulcer and illustrated that AR is the principal herb in this herbal formula. (c) 2012 Elsevier Ireland Ltd. All rights reserved.