Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Faculty of Health Sciences, University of Macau, Macao, China.
J Ethnopharmacol. 2020 Mar 25;250:112519. doi: 10.1016/j.jep.2019.112519. Epub 2019 Dec 25.
Pogostemon cablin, commonly named "Guang-Huo-Xiang" in China, has long been renowned for its ability to dispel dampness and regulate gastrointestinal functions. Patchouli oil (P.oil), the major active fraction of Pogostemon cablin, has been traditionally used as the principal component of Chinese medicinal formulae to treat exterior syndrome and diarrhea. However, the effects of P.oil in treating 5-fluorouracil (5-FU)-induced intestinal mucositis have not yet been reported.
To investigate the protective effects of P.oil against 5-FU-induced intestinal mucositis and the mechanisms underlying these effects.
Sprague-Dawley rats were intraperitoneally injected with 5-FU (30 mg/kg) to establish an intestinal mucositis model. Meanwhile, rats with intestinal mucositis were orally administered with P.oil (25, 50, and 100 mg/kg). Histological analysis, ELISA (for detecting inflammatory cytokines and aquaporins), immunohistochemistry analysis (for examining caspases), qRT-PCR analysis (for assessment tight junctions), and western blotting analysis (for the assessment of TLR2/TLR4-MyD88 and VIP-cAMP-PKA signaling pathway-related proteins) were performed to estimate the protective effects of P.oil against intestinal mucositis and the mechanisms underlying these effects.
The histopathological assessment preliminarily exhibited that P.oil alleviated the 5-FU-induced damage to the intestinal structure. After P.oil administration, the elevation of the expression of cytokines (TNF-α, IFN-γ, and IL-13) decreased markedly and the activation of NF-κB and MAPK signaling was significantly inhibited. P.oil also increased the mRNA expression of ZO-1 and Occludin, thereby stabilizing intestinal barrier. In addition, P.oil decreased the expressions of caspase-8, caspase-3, and Bax, and increased the expression of Bcl-2, thereby reducing the apoptosis of the intestinal mucosa. These results were closely related to the regulation of the TLR2/TLR4-MyD88 signaling pathway. It has been indicated that P.oil possibly protected the intestinal barrier by reducing inflammation and apoptosis. Furthermore, this study showed that P.oil inhibited the abnormal expression of AQP3, AQP7, and AQP11 by regulating the VIP-cAMP-PKA signaling pathway. Furthermore, it restored the intestinal water absorption, thereby alleviating diarrhea.
P.oil ameliorated 5-FU-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport.
广藿香，在中国俗称“广藿香”，长期以来因其祛湿和调节胃肠功能的能力而闻名。广藿香油（P.oil）是广藿香的主要活性成分，传统上被用作中药方剂的主要成分，用于治疗表证和腹泻。然而，广藿香油治疗 5-氟尿嘧啶（5-FU）诱导的肠道粘膜炎的效果尚未得到报道。
研究广藿香油对 5-FU 诱导的肠道粘膜炎的保护作用及其作用机制。
采用腹腔注射 5-FU（30mg/kg）建立大鼠肠道粘膜炎模型。同时，给予肠道粘膜炎大鼠口服广藿香油（25、50 和 100mg/kg）。采用组织学分析、ELISA（检测炎症细胞因子和水通道蛋白）、免疫组织化学分析（检测半胱天冬酶）、qRT-PCR 分析（检测紧密连接）和 Western blot 分析（检测 TLR2/TLR4-MyD88 和 VIP-cAMP-PKA 信号通路相关蛋白）来评估广藿香油对肠道粘膜炎的保护作用及其作用机制。
组织病理学评估初步表明，广藿香油减轻了 5-FU 诱导的肠道结构损伤。给予广藿香油后，细胞因子（TNF-α、IFN-γ 和 IL-1β）的表达升高明显降低，NF-κB 和 MAPK 信号通路的激活明显受到抑制。广藿香油还增加了 ZO-1 和 Occludin 的 mRNA 表达，从而稳定了肠道屏障。此外，广藿香油降低了半胱天冬酶-8、半胱天冬酶-3 和 Bax 的表达，增加了 Bcl-2 的表达，从而减少了肠道黏膜的凋亡。这些结果与 TLR2/TLR4-MyD88 信号通路的调节密切相关。表明广藿香油可能通过减轻炎症和凋亡来保护肠道屏障。此外，本研究表明，广藿香油通过调节 VIP-cAMP-PKA 信号通路抑制 AQP3、AQP7 和 AQP11 的异常表达。此外，它恢复了肠道水吸收，从而缓解了腹泻。
广藿香油通过保护肠道屏障和调节水转运改善了 5-FU 诱导的大鼠肠道粘膜炎。
