Pengzong Zhang, Yuanmin Li, Xiaoming Xiong, Shang Deng, Wei Xiong, Zhigang Lang, Dongzhou Du, Wenjing Yu, Jianbiao Yue, Yang Xiang, Xia Li
Medical Quality Control Office, Sichuan Provincial Orthopedic Hospital, Chengdu, P. R. China.
Key Laboratory of Transplant Engineering and Immunology, NHFPC, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, P. R. China.
Planta Med. 2019 May;85(8):657-669. doi: 10.1055/a-0881-3000. Epub 2019 Mar 25.
The aim of the present study was to evaluate the wound healing potential and possible mechanism of action of the standardized extract of against the experimental model of diabetic foot ulcer. -Boswellic acid was isolated from the standardized extract of and characterized (HPLC, H-NMR, C-NMR, ESI-MS). Diabetes was induced in Sprague-Dawley rats by streptozotocin (55 mg/kg, i. p.), and wounds were created on the dorsal surface of the hind paw. (100, 200, and 400 mg/kg, p. o.) was administered to the rats for 16 days. The HPLC analysis showed a single peak with a retention time of 12.51 min. The compound was identified with ESI-MS [M + Na] = 455.37 as -boswellic acid. Treatment with (200 and 400 mg/kg) significantly increased the rate of wound contraction via modulation of oxido-nitrosative stress and elevated the hydroxyproline level at the wound area. reverse transcription-PCR analysis revealed that streptozotocin-induced increases in TNF-, interleukin-1, interleukin-6, nuclear factor-kappa-light-chain-enhancer of activated B cells, and Bcl-2-associated X protein, and decreases in angiopoietin-1, Tie2, transforming growth factor beta 1, vascular endothelial growth factor, and collagen-1 mRNA expression were significantly inhibited by . It also significantly reduced wound cellular necrosis as evaluated by flow cytometry using propidium iodide fluorescence intensity. Streptozotocin-induced histopathological alterations were also significantly ameliorated by . In conclusion, standardized extracts of exert its wound healing potential via orchestrating mechanisms, which include the inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells), increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2), promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor), and inhibition of apoptosis (Bcl-2-associated X protein) to accelerate wound healing in experimental delayed diabetic foot ulcer.
本研究的目的是评估[提取物名称]标准化提取物对糖尿病足溃疡实验模型的伤口愈合潜力及其可能的作用机制。从[提取物名称]标准化提取物中分离出β-乳香酸并进行表征（高效液相色谱法、氢核磁共振、碳核磁共振、电喷雾电离质谱）。通过链脲佐菌素（55mg/kg，腹腔注射）诱导Sprague-Dawley大鼠患糖尿病，并在后爪背侧制造伤口。将[提取物名称]（100、200和400mg/kg，口服）给予大鼠，持续16天。高效液相色谱分析显示一个保留时间为12.51分钟的单峰。该化合物经电喷雾电离质谱鉴定为β-乳香酸，[M + Na]=455.37。用[提取物名称]（200和400mg/kg）治疗可通过调节氧化亚硝化应激显著提高伤口收缩率，并提高伤口区域的羟脯氨酸水平。逆转录聚合酶链反应分析显示，链脲佐菌素诱导的肿瘤坏死因子-α、白细胞介素-1、白细胞介素-6、活化B细胞核因子κB轻链增强子以及Bcl-2相关X蛋白增加，血管生成素-1、Tie2、转化生长因子β1、血管内皮生长因子和胶原蛋白-1信使核糖核酸表达降低，均被[提取物名称]显著抑制。通过使用碘化丙啶荧光强度的流式细胞术评估，它还显著减少了伤口细胞坏死。链脲佐菌素诱导的组织病理学改变也被[提取物名称]显著改善。总之，[提取物名称]标准化提取物通过协调多种机制发挥其伤口愈合潜力，这些机制包括抑制氧化炎症标志物（氧化亚硝化应激、肿瘤坏死因子-α、白细胞介素和活化B细胞核因子κB轻链增强子）、增加胶原蛋白合成（羟脯氨酸和胶原蛋白-1）和血管生成（血管生成素-1/Tie2）、促进生长因子（转化生长因子β1和血管内皮生长因子）以及抑制细胞凋亡（Bcl-2相关X蛋白），以加速实验性延迟糖尿病足溃疡的伤口愈合。
