目的 探討山茱萸主要成分莫諾苷（morroniside，MO）的炮制轉(zhuǎn)化成分脫水莫諾苷元（sarracenin，SA）的抗炎及肝保護(hù)作用。方法 采用超高效液相色譜法對(duì)MO及SA進(jìn)行鑒定；將對(duì)數(shù)生長(zhǎng)期的人單核細(xì)胞白血病THP-1細(xì)胞隨機(jī)分為對(duì)照組、模型組及MO低、高劑量（25、100 μmol/L）組和SA低、高劑量（25、100 μmol/L）組，采用脂多糖（lipopolysaccharide，LPS）聯(lián)合腺嘌呤核苷三磷酸（adenosine triphosphate，ATP）刺激THP-1細(xì)胞構(gòu)建炎癥細(xì)胞模型，各給藥組分別給予不同濃度的MO及SA，Western blotting法檢測(cè)細(xì)胞總蛋白中含NLR家族PYRIN域蛋白3（NOD-like receptor family pyrin domain containing 3，NLRP3）、白細(xì)胞介素-1β（interleukin-1β，IL-1β）、絲氨酸/蘇氨酸激酶（protein kinase B，Akt）及磷酸化絲氨酸/蘇氨酸激酶（phosphorylation protein kinase B，p-Akt）的表達(dá)以及細(xì)胞培養(yǎng)液中IL-1β的蛋白表達(dá)；將雄性Balb/c小鼠隨機(jī)為對(duì)照組、SA組（50 mg/kg）、對(duì)乙酰氨基酚（acetaminophen，APAP，300 mg/kg）組和APAP（300 mg/kg）＋SA低、中、高劑量（5、25、50 mg/kg）組，各給藥組小鼠ig相應(yīng)質(zhì)量濃度SA 2 h后，除對(duì)照組及SA組小鼠外，其余各組小鼠ig APAP，24 h后麻醉處死小鼠，檢測(cè)血清中丙氨酸氨基轉(zhuǎn)移酶（alanine aminotransferase，ALT）、天冬氨酸氨基轉(zhuǎn)移酶（aspartate aminotransferase，AST）及肝臟組織中丙二醛（malonic dialdehyde，MDA）水平，檢測(cè)組織病理學(xué)變化情況，檢測(cè)小鼠含生長(zhǎng)因子樣模體黏液樣激素樣受體1（mouse EGF-like module-containing mucin-like hormone receptor-like 1，EMR1，又稱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的蛋白表達(dá)情況。結(jié)果 體外實(shí)驗(yàn)表明SA與MO均能抑制巨噬細(xì)胞中NLRP3及IL-1β的蛋白表達(dá)（P＜0.05、0.01、0.001），且SA的藥效要優(yōu)于MO；體內(nèi)實(shí)驗(yàn)進(jìn)一步發(fā)現(xiàn)SA能夠抑制APAP誘導(dǎo)的小鼠血清中ALT、AST及肝臟組織中MDA的蛋白表達(dá)（P＜0.05、0.01、0.001），改善肝臟病理?yè)p傷，網(wǎng)絡(luò)藥理學(xué)揭示SA的抗炎及肝保護(hù)作用與Akt通路有關(guān)。結(jié)論SA是山茱萸炮制增效成分，能夠通過調(diào)控Akt通路發(fā)揮抗炎及肝保護(hù)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

國(guó)家自然科學(xué)基金青年科學(xué)基金項(xiàng)目(82104394);浙江省基礎(chǔ)公益研究項(xiàng)目(LY23H280008);浙江中醫(yī)藥大學(xué)校級(jí)科研項(xiàng)目(2024JKZKTS09);浙江省中醫(yī)藥科技項(xiàng)目(2025ZR104)