Wang Canhong, Wu Yulan, Gong Bao, Mou Junyu, Cheng Xiaoling, Zhang Ling, Wei Jianhe
Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine, Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China.
Guangdong Key Laboratory of Green Agricultural Products Processing and Intelligent Equipment, Guangdong University of Petrochemical Technology, Maoming 525099, China.
Pharmaceuticals (Basel). 2025 Mar 31;18(4):514. doi: 10.3390/ph18040514.
Agarwood has been widely used for the treatment of gastrointestinal diseases. Our research group has suggested that agarwood alcohol extracts (AAEs) provide good gastric mucosal protection. However, the exact mechanisms underlying this effect remain unclear. This study aimed to investigate the ameliorative effect of agarwood chromone on gastric ulcers and its mechanism. Network pharmacology was used to predict the disease spectrum and key therapeutic targets of 2-(2-phenylethyl)chromone (CHR1) and 2-(2-(4-methoxyphenyI)ethyl)chromone (CHR2). Mice were orally administered CHR1 (20 and 40 mg/kg) and CHR2 (20 and 40 mg/kg) and the positive drug omeprazole as an enteric-coated capsule (OEC, 40 mg/kg) orally. After 7 days of pretreatment with the CHRs, gastric ulcers were induced using absolute ethanol (0.15 mL/10 g). The ulcer index, gastric histopathology, biochemical parameters, and inflammatory and apoptotic proteins were evaluated. Finally, binding of the core compounds to the key targets was verified via molecular docking and visualized. The pharmacological results show that the CHRs reduced the gastric occurrence and ulcer inhibition rates by up to more than 70% in a dose-dependent manner. The CHRs decreased the levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interleukin 18 (IL-18), and tumor necrosis factor α (TNF-α), and improved the severity of the pathological lesions in the gastric tissue. The expression of ATP-binding box transporter B1 (ABCB1), arachidonic acid-5-lipoxygenase (ALOX5), nuclear factor kappa B (NF-κB), cysteinyl aspartate specific proteinase 3 3 (Caspase3), and cysteinyl aspartate specific proteinase 9 (Caspase9) was inhibited, but the expression of B-cell lymphoma-2 (Bcl-2) was enhanced. The CHRs bound stably to the key targets via hydrogen bonding, van der Waals forces, etc. These results demonstrate that agarwood chromone compounds exert alleviative effects against the occurrence and development of gastric ulcers by inhibiting the NF-κB and caspase pathways. The CHRs have a therapeutic effect on gastric ulcers through anti-inflammation and anti-apoptosis mechanisms. This study suggests that agarwood may have a potential role in drug development and the prevention and treatment of gastrointestinal inflammation, and tumors.
沉香已被广泛用于治疗胃肠道疾病。我们的研究小组表明，沉香醇提取物（AAEs）具有良好的胃黏膜保护作用。然而，这种作用的确切机制尚不清楚。本研究旨在探讨沉香色酮对胃溃疡的改善作用及其机制。采用网络药理学预测2-(2-苯乙基)色酮（CHR1）和2-(2-(4-甲氧基苯基)乙基)色酮（CHR2）的疾病谱和关键治疗靶点。将CHR1（20和40mg/kg）和CHR2（20和40mg/kg）以及阳性药物奥美拉唑作为肠溶胶囊（OEC，40mg/kg）口服给予小鼠。在用CHRs预处理7天后，用无水乙醇（0.15mL/10g）诱导胃溃疡。评估溃疡指数、胃组织病理学、生化参数以及炎症和凋亡蛋白。最后，通过分子对接验证核心化合物与关键靶点的结合并进行可视化。药理学结果表明，CHRs以剂量依赖性方式使胃溃疡发生率和溃疡抑制率降低高达70%以上。CHRs降低了白细胞介素6（IL-6）、白细胞介素12（IL-12）、白细胞介素18（IL-18）和肿瘤坏死因子α（TNF-α）的水平，并改善了胃组织病理损伤的严重程度。ATP结合盒转运蛋白B1（ABCB1）、花生四烯酸-5-脂氧合酶（ALOX5）、核因子κB（NF-κB）、半胱天冬酶3（Caspase3）和半胱天冬酶9（Caspase9）的表达受到抑制，但B细胞淋巴瘤-2（Bcl-2）的表达增强。CHRs通过氢键、范德华力等与关键靶点稳定结合。这些结果表明，沉香色酮化合物通过抑制NF-κB和半胱天冬酶途径对胃溃疡的发生和发展发挥缓解作用。CHRs通过抗炎和抗凋亡机制对胃溃疡具有治疗作用。本研究表明，沉香在药物开发以及胃肠道炎症和肿瘤的预防与治疗中可能具有潜在作用。
