Health Sciences (International Program), College of Graduate Studies, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
Inflammopharmacology. 2022 Aug;30(4):1369-1382. doi: 10.1007/s10787-022-01021-y. Epub 2022 Jul 13.
Plant-derived medicinal compounds are increasingly being used to treat acute and chronic inflammatory diseases, which are generally caused by aberrant inflammatory responses. Stephania pierrei Diels, also known as Sabu-lueat in Thai, is a traditional medicinal plant that is used as a remedy for several inflammatory disorders. Since aporphine alkaloids isolated from S. pierrei tubers exhibit diverse pharmacological characteristics, we aimed to determine the anti-inflammatory effects of crude extracts and alkaloids isolated from S. pierrei tubers against lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Notably, the n-hexane extract strongly suppressed nitric oxide (NO) while exhibiting reduced cytotoxicity. Among the five alkaloids isolated from the n-hexane extract, the aporphine alkaloid oxocrebanine exerted considerable anti-inflammatory effects by inhibiting NO secretion. Oxocrebanine also significantly suppressed prostaglandin E, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, inducible nitric oxide synthase, and cyclooxygenase (COX)-2 protein expression by inactivating the nuclear factor κB, c-Jun NH-terminal kinase, extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3-kinase/Akt inflammatory signalling pathways. Molecular docking analysis further revealed that oxocrebanine has a higher affinity for toll-like receptor 4/myeloid differentiation primary response 88 signalling targets and the COX-2 protein than native ligands. Thus, our findings highlight the potential anti-inflammatory effects of oxocrebanine and suggest that certain alkaloids of S. pierrei could be used to treat inflammatory diseases.
植物来源的药用化合物越来越多地被用于治疗急性和慢性炎症性疾病，这些疾病通常是由异常的炎症反应引起的。Stephania pierrei Diels，也被称为泰语中的 Sabu-lueat，是一种传统的药用植物，用于治疗几种炎症性疾病。由于从Stephania pierrei 块茎中分离出的阿朴啡生物碱具有多种药理学特性，我们旨在确定Stephania pierrei 块茎的粗提取物和生物碱对脂多糖（LPS）激活的 RAW264.7 巨噬细胞的抗炎作用。值得注意的是，正己烷提取物强烈抑制一氧化氮（NO），同时表现出较低的细胞毒性。从正己烷提取物中分离出的 5 种生物碱中，阿朴啡生物碱氧化阿朴啡碱通过抑制 NO 分泌表现出相当大的抗炎作用。氧化阿朴啡碱还通过抑制核因子 κB、c-Jun NH-末端激酶、细胞外信号调节激酶 1/2 和磷酸肌醇 3-激酶/蛋白激酶 B 炎症信号通路，显著抑制前列腺素 E、肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6、诱导型一氧化氮合酶和环氧化酶（COX）-2 蛋白的表达。分子对接分析进一步表明，氧化阿朴啡碱对 Toll 样受体 4/髓样分化初级反应 88 信号靶点和 COX-2 蛋白的亲和力高于天然配体。因此，我们的研究结果强调了氧化阿朴啡碱的潜在抗炎作用，并表明Stephania pierrei 的某些生物碱可用于治疗炎症性疾病。
