Jianpi Lishi Jiedu Decoction (JLJD) Inhibit Th17 Cell Differentiation via the Jak/Stat3/RORγt Pathway in Colorectal Adenomas.

BACKGROUND

Jianpi Lishi Jiedu Decoction (JLJD) are used in China to prevent colorectal adenoma recurrence, but their molecular mechanism is unclear.

OBJECTIVE

Evaluate JLJD's preventive and therapeutic effects on colorectal adenomas and elucidate its molecular mechanisms.

METHODS

JLJD components were identified via HPLC. The Apc Min/+ 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).

RESULTS

JLJD significantly reduced adenoma number and progression in Apc Min/+ 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.

CONCLUSION

JLJD inhibits the differentiation of Th17 cells by suppressing the Jak2/Stat3/RORγ pathway, thereby exerting an inhibitory effect on colorectal adenomas.