Si Min, Wang Yan, Wu Hao, Huang Yuzhen, Ma Mengqing, Su Kunhan, Qiao Dan, Tao Weiwei, Liu Wanli
Department of Gastroenterology, Nanjing First Hospital, Nanjing University of Chinese Medicine, Nanjing, 210014, People's Republic of China.
Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People's Republic of China.
J Inflamm Res. 2025 Aug 21;18:11479-11492. doi: 10.2147/JIR.S522927. eCollection 2025.
Jianpi Lishi Jiedu Decoction (JLJD) are used in China to prevent colorectal adenoma recurrence, but their molecular mechanism is unclear.
Evaluate JLJD's preventive and therapeutic effects on colorectal adenomas and elucidate its molecular mechanisms.
JLJD components were identified via HPLC. The mouse model assessed therapeutic efficacy. Effects on colorectal tissue proliferation/apoptosis were analyzed. Flow cytometry evaluated Th17 cells; ELISA quantified inflammatory cytokines (IL-17, IL-6, IL-1β, IL-18). Jak2/Stat3/RORγt pathway proteins were detected by Western blot (WB) and immunohistochemistry (IHC). A Jak2 activator (RO8191) validated functional targets. Key components (chlorogenic acid, atractylenolide I) were tested in vitro for: (1) non-toxic concentrations (MTT), (2) IL-17A levels, (3) Th17 differentiation, (4) p-Stat3/RORγt expression (WB).
JLJD significantly reduced adenoma number and progression in mice. Anti-Ki67 IHC showed suppressed proliferation; TUNEL assay confirmed induced apoptosis. ELISA indicated JLJD significantly decreased pro-inflammatory cytokine levels. WB/IHC demonstrated JLJD inhibited Th17 cell differentiation by downregulating Jak2/Stat3/RORγt pathway proteins in colon tissues and mesenteric lymph nodes. RO8191 abrogated JLJD's anti-adenoma effects, reversed Th17 suppression, and nullified pathway inhibition. In vitro, chlorogenic acid and atractylenolide I significantly reduced IL-17A, reversed Th17 expansion, and decreased p-Stat3/RORγt expression.
JLJD inhibits the differentiation of Th17 cells by suppressing the Jak2/Stat3/RORγ pathway, thereby exerting an inhibitory effect on colorectal adenomas.
在中国，健脾利湿解毒汤（JLJD）被用于预防大肠腺瘤复发，但其分子机制尚不清楚。
评估JLJD对大肠腺瘤的防治作用并阐明其分子机制。
通过高效液相色谱法鉴定JLJD的成分。采用小鼠模型评估治疗效果。分析对大肠组织增殖/凋亡的影响。流式细胞术评估Th17细胞；酶联免疫吸附测定法量化炎性细胞因子（IL-17、IL-6、IL-1β、IL-18）。通过蛋白质免疫印迹法（WB）和免疫组织化学法（IHC）检测Jak2/Stat3/RORγt信号通路蛋白。使用Jak2激活剂（RO8191）验证功能靶点。对关键成分（绿原酸、白术内酯I）进行体外试验，检测：（1）无毒浓度（MTT），（2）IL-17A水平，（3）Th17分化，（4）p-Stat3/RORγt表达（WB）。
JLJD显著减少小鼠腺瘤数量并抑制其进展。抗Ki67免疫组化显示增殖受到抑制；TUNEL检测证实诱导了细胞凋亡。酶联免疫吸附测定法表明JLJD显著降低促炎细胞因子水平。蛋白质免疫印迹法/免疫组织化学法显示，JLJD通过下调结肠组织和肠系膜淋巴结中的Jak2/Stat3/RORγt信号通路蛋白抑制Th17细胞分化。RO8191消除了JLJD的抗腺瘤作用，逆转了对Th17细胞的抑制，并消除了对信号通路的抑制。在体外，绿原酸和白术内酯I显著降低IL-17A水平，逆转Th17细胞扩增，并降低p-Stat3/RORγt表达。
JLJD通过抑制Jak2/Stat3/RORγ信号通路抑制Th17细胞分化，从而对大肠腺瘤发挥抑制作用。
