Ginsenoside Rb1-engineered nanocomposite hydrogel promotes pressure injury repair through SIRT1-AMPK-mediated ferroptosis inhibition and angiogenesis activation

IF 7.5 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2026-05-01 Epub Date: 2026-01-30 DOI:10.1016/j.jgr.2026.100987

Hongbo Zhu , Hang Li , Yinong Shi , Jinhui Liu , Hua Zhi , Xuelu Zhao , Zhiwen Wang , Fumin Ping

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引用次数: 0

Abstract

Background

Pressure injuries (PIs) remain a therapeutic challenge due to persistent inflammation and ferroptosis-driven tissue damage. Ginsenoside Rb1, a key bioactive component of Panax ginseng, demonstrates anti-inflammatory and anti-ferroptotic properties, but its clinical application is limited by poor bioavailability and rapid degradation in wound environments.

Purpose

This study aimed to develop a chitosan/alginate nanocomposite hydrogel loaded with ginsenoside Rb1 (Rb1@CS@ALG) to enhance Rb1 delivery and investigate its therapeutic mechanisms in PI repair, focusing on SIRT1-AMPK-mediated ferroptosis inhibition and angiogenesis promotion.

Methods

The pH-responsive Rb1@CS@ALG hydrogel was synthesized and characterized (TEM/DLS/HPLC). In vitro studies evaluated ferroptosis markers (GPX4, SLC7A11), ROS levels, and cell migration in HaCaT cells under ischemia-reperfusion. A rat PI model (n = 6/group) assessed wound closure rates, histopathology (H&E/Masson's), and protein expression (CD31/Col I). RNA-seq analyzed differential gene expression.

Results

The hydrogel showed sustained Rb1 release (82.3 % at 24 h) and pH-dependent drug delivery. Treatment upregulated GPX4/SLC7A11 (2.3-fold) while reducing ROS (58 %) and ACSL4 (45 %) via SIRT1-AMPK activation (p-AMPK↑2.9-fold). In vivo, it accelerated wound closure by 75 % (vs. controls, p < 0.001), increased angiogenesis (CD31↑3.1-fold), and improved collagen organization (Col I/III ratio↑2.7-fold). RNA-seq confirmed enrichment in ferroptosis and extracellular matrix pathways.

Conclusion

This study establishes ginsenoside Rb1 as a potent therapeutic agent for PIs when delivered via nanocomposite hydrogel, with dual mechanisms of ferroptosis inhibition and angiogenesis activation. The findings provide a scientific foundation for applying ginseng-derived compounds in chronic wound management.

Abstract Image

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人参皂苷rb1工程纳米复合水凝胶通过sirt1 - ampk介导的铁凋亡抑制和血管生成激活促进压力损伤修复

背景：压力性损伤（PIs）仍然是一个治疗挑战，由于持续的炎症和铁中毒驱动的组织损伤。人参皂苷Rb1是人参的一种重要生物活性成分，具有抗炎和抗铁腐蚀的特性，但其生物利用度差，在伤口环境中降解快，限制了其临床应用。目的制备一种壳聚糖/海藻酸盐纳米复合水凝胶，负载人参皂苷Rb1 (Rb1@CS@ALG)，增强Rb1的递送，并研究其在PI修复中的治疗机制，重点研究sirt1 - ampk介导的铁上吊抑制和血管生成。方法合成ph响应性Rb1@CS@ALG水凝胶，并用TEM/DLS/HPLC对其进行表征。体外研究评估了缺血再灌注下HaCaT细胞中的铁下垂标志物（GPX4、SLC7A11）、ROS水平和细胞迁移。大鼠PI模型（n = 6/组）评估伤口愈合率、组织病理学（H&E/Masson’s）和蛋白表达（CD31/Col I）。RNA-seq分析差异基因表达。结果制备的水凝胶在24 h时Rb1释放率为82.3%，并具有ph依赖性。处理上调GPX4/SLC7A11（2.3倍），同时通过SIRT1-AMPK激活（p-AMPK↑2.9倍）降低ROS（58%）和ACSL4（45%）。在体内，它加速了75%的伤口愈合（与对照组相比，p < 0.001），增加了血管生成（CD31↑3.1倍），并改善了胶原组织（Col I/III比值↑2.7倍）。RNA-seq证实在铁下垂和细胞外基质途径中富集。结论人参皂苷Rb1通过纳米复合水凝胶给药，具有抑制铁下沉和激活血管生成的双重机制，是一种有效的PIs治疗药物。研究结果为人参类化合物在慢性伤口治疗中的应用提供了科学依据。

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来源期刊

Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE

CiteScore

11.40

自引率

9.50%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.