目的 探讨山茱萸主要成分莫诺苷（morroniside，MO）的炮制转化成分脱水莫诺苷元（sarracenin，SA）的抗炎及肝保护作用。方法 采用超高效液相色谱法对MO及SA进行鉴定；将对数生长期的人单核细胞白血病THP-1细胞随机分为对照组、模型组及MO低、高剂量（25、100 μmol/L）组和SA低、高剂量（25、100 μmol/L）组，采用脂多糖（lipopolysaccharide，LPS）联合腺嘌呤核苷三磷酸（adenosine triphosphate，ATP）刺激THP-1细胞构建炎症细胞模型，各给药组分别给予不同浓度的MO及SA，Western blotting法检测细胞总蛋白中含NLR家族PYRIN域蛋白3（NOD-like receptor family pyrin domain containing 3，NLRP3）、白细胞介素-1β（interleukin-1β，IL-1β）、丝氨酸/苏氨酸激酶（protein kinase B，Akt）及磷酸化丝氨酸/苏氨酸激酶（phosphorylation protein kinase B，p-Akt）的表达以及细胞培养液中IL-1β的蛋白表达；将雄性Balb/c小鼠随机为对照组、SA组（50 mg/kg）、对乙酰氨基酚（acetaminophen，APAP，300 mg/kg）组和APAP（300 mg/kg）＋SA低、中、高剂量（5、25、50 mg/kg）组，各给药组小鼠ig相应质量浓度SA 2 h后，除对照组及SA组小鼠外，其余各组小鼠ig APAP，24 h后麻醉处死小鼠，检测血清中丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）及肝脏组织中丙二醛（malonic dialdehyde，MDA）水平，检测组织病理学变化情况，检测小鼠含生长因子样模体黏液样激素样受体1（mouse EGF-like module-containing mucin-like hormone receptor-like 1，EMR1，又称F4/80）、NLRP3、半胱氨酸天冬氨酸蛋白水解酶-1（cysteinyl aspartate specific proteinase-1，Caspase-1）、IL-1β、p-Akt及Akt的蛋白表达情况。结果 体外实验表明SA与MO均能抑制巨噬细胞中NLRP3及IL-1β的蛋白表达（P＜0.05、0.01、0.001），且SA的药效要优于MO；体内实验进一步发现SA能够抑制APAP诱导的小鼠血清中ALT、AST及肝脏组织中MDA的蛋白表达（P＜0.05、0.01、0.001），改善肝脏病理损伤，网络药理学揭示SA的抗炎及肝保护作用与Akt通路有关。结论SA是山茱萸炮制增效成分，能够通过调控Akt通路发挥抗炎及肝保护作用。

Objective To investigate the anti-inflammatory and hepatoprotective effects of sarracenin (SA), a processed and transformed component of morroniside (MO) from Shanzhuyu (Corni Fructus). Methods Ultra performance liquid chromatography was used for the identification of MO and SA. In vitro, firstly, THP-1 cells were randomly divided into control group, model group, MO (25, 100 μmol/L) groups and SA (25, 100 μmol/L) groups. Among these, model groups, including MO and SA groups were established by lipopolysaccharide (LPS) combined with adenosine triphosphate (ATP), while MO and SA groups were treatment with doses of MO as well as SA, Western blotting was used to detect the expressions of NOD-like receptor family pyrin domain containing 3 (NLRP3), interleukin-1β (IL-1β), protein Kinase B (Akt), and phosphorylation protein kinase B (p-Akt) in cells as well as the expression of IL-1β in the supernatants. In vivo, male Balb/c mice were randomly divided into control group, SA alone group (50 mg/kg), acetaminophen (APAP) group, APAP + SA group (5, 25, 50 mg/kg), among these, SA groups were intragastric administration with different doses of SA, 2 h later, except control group and SA alone group, the mice in other groups were given a single APAP (300 mg/kg) by gavage, and mice were executed under anesthesia after 24 h. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum, the level of malonic dialdehyde (MDA) in liver tissue and histopathological changes were detected. Moreover, Western blotting and immunofluorescence were performed to detect the expression of mouse EGF-like module-containing mucin-like hormone receptor-like 1 (EMR1, F4/80) and NLRP3, the protein expressions of NLRP3, cysteinyl aspartate specific proteinase (Caspase-1), IL-1β, p-Akt and Akt were also evaluated by Western blotting. Results In vitro, both SA and MO could inhibit the expressions of NLRP3 and IL-1β proteins in macrophages (P < 0.05, 0.01, 0.001), and the efficacy of SA was superior to that of MO. In vivo further revealed that SA could inhibit the increase of serum ALT, AST, and liver MDA levels induced by APAP in mice (P < 0.05, 0.01, 0.001) and improved liver pathological injury, and network pharmacology revealed that the anti-inflammatory and hepatoprotective effects of SA were related to the Akt pathway. Conclusion SA is a synergistic ingredient of Corni Fructus, which can play anti-inflammatory and liver protective effects by regulating Akt pathway.

R285.5

国家自然科学基金青年科学基金项目(82104394);浙江省基础公益研究项目(LY23H280008);浙江中医药大学校级科研项目(2024JKZKTS09);浙江省中医药科技项目(2025ZR104)