Department of Laboratory Medicine The First Affiliated Hospital of Yangtze University, Jingzhou, China.
Department of Immunology School of Medicine Yangtze University, Jingzhou, China.
Mediators Inflamm. 2024 Oct 1;2024:3938136. doi: 10.1155/2024/3938136. eCollection 2024.
Aloperine (ALO), an alkaloid isolated from L., possesses multiple pharmacological activities and holds a promise potential for the treatment of various clinical conditions, including skin hypersensitivity, cancer, and inflammatory disorders. The purpose of this study was to investigate the role of ALO in acetaminophen (N-acetyl-para-aminophenol (APAP))-induced acute liver injury and its underlying mechanisms.
An animal model of acute liver injury was induced by intraperitoneal injection of APAP (150 mg/kg). Prior to APAP injection, ALO (40 mg/kg) was administered daily for 7 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were then measured using an automated chemical analyzer. Histopathological changes were evaluated using hematoxylin and eosin staining. Oxidative stress levels were measured by detecting superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). Pro-inflammatory cytokines were detected in serum and liver tissues using ELISA and quantitative real-time polymerase chain reaction (q-PCR). The expression of members of the HMGB1/TLR4/NF-B signaling pathway and NLRP3 inflammasome were determined by Western blot and/or q-PCR. In addition, the expression and location of NLRP3, cleaved caspase-1, high-mobility group box 1 (HMGB1), and phosphorylated p65 (p-p65) were detected by immunofluorescence.
Pretreatment with ALO significantly protected mice from APAP-induced acute liver injury, with decreased MDA content, and significantly increased GSH and SOD activities. Furthermore, ALO pretreatment reduced the release of pro-inflammatory cytokines (IL-1 and TNF-) and decreased the expression of caspase-1, cleaved caspase-1, and NLRP3. In addition, ALO pretreatment also inhibited the activation of the HMGB1/TLR4/NF-B signaling pathway.
Taken together, ALO can ameliorate APAP-induced acute liver injury by inhibiting oxidative stress, inflammation by inhibiting the HMGB1/TLR4/NF-B, and NLRP3/inflammasome pathway.
从 中分离得到的生物碱阿罗品（ALO）具有多种药理活性，有望用于治疗多种临床疾病，包括皮肤过敏、癌症和炎症性疾病。本研究旨在探讨 ALO 在对乙酰氨基酚（N-乙酰-对氨基酚（APAP））诱导的急性肝损伤中的作用及其机制。
采用腹腔注射 APAP（150mg/kg）建立急性肝损伤动物模型。APAP 注射前，每天给予 ALO（40mg/kg）连续 7 天。采用自动化学分析仪测定血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和乳酸脱氢酶水平。采用苏木精-伊红染色评估组织学变化。通过检测超氧化物歧化酶（SOD）、谷胱甘肽（GSH）和丙二醛（MDA）来测定氧化应激水平。采用 ELISA 和实时定量聚合酶链反应（q-PCR）检测血清和肝组织中促炎细胞因子的表达。采用 Western blot 和/或 q-PCR 检测 HMGB1/TLR4/NF-B 信号通路和 NLRP3 炎性小体成员的表达。此外，通过免疫荧光检测 NLRP3、裂解的 caspase-1、高迁移率族蛋白 B1（HMGB1）和磷酸化 p65（p-p65）的表达和定位。
ALO 预处理可显著减轻 APAP 诱导的急性肝损伤，降低 MDA 含量，显著增加 GSH 和 SOD 活性。此外，ALO 预处理可减少促炎细胞因子（IL-1 和 TNF-）的释放，并降低 caspase-1、裂解的 caspase-1 和 NLRP3 的表达。此外，ALO 预处理还抑制了 HMGB1/TLR4/NF-B 信号通路的激活。
综上所述，ALO 通过抑制 HMGB1/TLR4/NF-B 和 NLRP3/炎性小体通路抑制氧化应激和炎症，可改善 APAP 诱导的急性肝损伤。
