Batri-7 attenuates established inflammation-associated colorectal adenoma via PI3K/AKT inhibition and BAX-associated apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Batri-7 (BT-7) is a classic Mongolian herbal formula traditionally valued for its anti-inflammatory properties. It has been utilized within Mongolian medicine for gastrointestinal disorders and inflammatory conditions, suggesting its potential therapeutic value in inflammation-associated colorectal carcinogenesis. However, its efficacy against inflammation-associated colorectal adenoma (IACA)-the primary precursor lesion of colitis-associated colorectal cancer (CAC)-and the underlying molecular mechanisms remain poorly understood.

AIM OF THE STUDY: This study aims to systematically evaluate the efficacy and mechanism of BT-7 in suppressing progression of established IACA by integrating network pharmacology, in vivo models, and patient-derived organoids.

METHODS

The chemical profile of BT-7 was characterized by Liquid chromatography-mass spectrometry (LC-MS). Network pharmacology was employed to predict potential targets and pathways. An AOM/DSS-induced CAC mouse model was used to assess in vivo efficacy, with therapeutic dosing initiated after adenoma formation. Patient-derived IACA organoids were established and treated with BT-7 to evaluate its anti-adenoma effects in vitro. Transcriptomic analyses and functional rescue experiments were conducted to elucidate the underlying mechanisms.

RESULTS

BT-7 treatment significantly reduced adenoma burden and curtailed the progression of pre-existing lesions in AOM/DSS mice, alleviated colitis symptoms, and reduced proliferative activity. In patient-derived adenoma organoids, BT-7 inhibited growth and induced apoptosis in a dose- and time-dependent manner. Transcriptomic analyses consistently identified the PI3K/AKT pathway as a key target of BT-7. Functional studies confirmed that BT-7 downregulated PI3K/AKT signaling and specifically upregulated the pro-apoptotic protein BAX. Rescue experiments using PI3K and AKT activators (740Y-P and SC-79) reversed BT-7-induced growth inhibition and apoptosis, whereas an AKT inhibitor (MK-2206) phenocopied the pro-apoptotic effects of BT-7.

CONCLUSION

BT-7 effectively suppresses progression of established IACA in the inflammatory context by inhibiting the PI3K/AKT signaling pathway and activating BAX-associated apoptosis. These preclinical findings demonstrate that BT-7 exerts therapeutic efficacy against established inflammation-associated colorectal adenoma, providing a mechanistic foundation for its further translational investigation.