Ye Penghui, Wu Xingqian, Gu Rifang, Zhu Huan, Chen Jitao, Dai Yuhe, Zhang Qianbo, Tang Ming, Nie Xuqiang
College of Pharmacy, Zunyi Medical University, Zunyi 563006, China; Key Lab of the Basic Pharmacology of the Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, China.
School Medical Office, Zunyi Medical University, Zunyi 563006, China.
Int Immunopharmacol. 2025 Feb 6;147:113997. doi: 10.1016/j.intimp.2024.113997. Epub 2025 Jan 8.
Centella asiatica (L.) Urban, one of the authentic medicinal materials from Guizhou Province in China, has been traditionally applied for the treatment of contusions and fractures, as well as for promoting wound healing. Preliminary research suggests that asiaticoside-nitric oxide hydrogel (ACNO) exhibits the potential to enhance the healing of diabetic wounds (DWs); however, the underlying molecular mechanisms require further elucidation. Here, we aim to identify ACNO's anti-apoptotic targets and its mode of action in DWs treatment. ACNO was applied topically on db/db and db/m mice with DWs. Wound healing was evaluated through photography, histology, and molecular analyses including molecular docking, RT-qPCR, and western blotting. The impact of ACNO on cell migration and apoptosis was assessed in hyperglycosylated HFF-1 cells using CCK-8, scratch, and cloning assays, with molecular mechanisms confirmed using a Bcl-2 inhibitor. ACNO hydrogel promotes wound epithelialization and angiogenesis in diabetic mice, and also regulates abnormal apoptosis of wound cells. In vitro studies showed that ACNO promoted the proliferation and migration of hyperglycosylated HFF-1 cells and enhanced their anti-apoptotic capacity in vitro. Further experimental studies showed that ACNO hydrogel enhances the healing process of DWs by modulating the Bcl-2/Bax/Caspase-3/PARP signaling cascade, which stimulates cell growth and movement, encourages the formation of new blood vessels, and diminishes cell death. This discovery presents a pioneering approach to harnessing the potential of traditional chinese medicine for the management of persistent and challenging injuries, including DWs.
积雪草是中国贵州省的地道药材之一，传统上用于治疗挫伤和骨折，以及促进伤口愈合。初步研究表明，积雪草苷 - 一氧化氮水凝胶（ACNO）具有促进糖尿病伤口（DWs）愈合的潜力；然而，其潜在的分子机制尚需进一步阐明。在此，我们旨在确定ACNO在DWs治疗中的抗凋亡靶点及其作用模式。将ACNO局部应用于患有DWs的db/db和db/m小鼠。通过摄影、组织学以及包括分子对接、RT-qPCR和蛋白质印迹在内的分子分析来评估伤口愈合情况。使用CCK-8、划痕和克隆实验评估ACNO对高糖基化HFF-1细胞迁移和凋亡的影响，并使用Bcl-2抑制剂确认分子机制。ACNO水凝胶可促进糖尿病小鼠伤口的上皮化和血管生成，并调节伤口细胞的异常凋亡。体外研究表明，ACNO可促进高糖基化HFF-1细胞的增殖和迁移，并增强其体外抗凋亡能力。进一步的实验研究表明，ACNO水凝胶通过调节Bcl-2/Bax/Caspase-3/PARP信号级联反应来增强DWs的愈合过程，该信号级联反应可刺激细胞生长和移动，促进新血管形成，并减少细胞死亡。这一发现为利用传统中药治疗包括DWs在内的持续性和挑战性损伤提供了一种开创性的方法。
