Salomon1, 2, E. Fudim1, O. Picard1, M. Yavzori1, U. Kopylov1,D. Gamus2, R. Elyakim1, S. Ben-Horin1
(1) Integrative Medicine Clinic & IBD Service, Gastroenterology Department, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel
(2) Department of Complementary & Alternative Medicine, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel
BACKGROUND AND AIMS
Purine analogues such as 6-mercaptopurine (6MP) and biologics such as infliximab (INF) are used to treat inflammatory bowel disease (IBD). However, these therapies are not universally effective. Berberine, an isoquinoline alkaloid, has been used to treat bacteria-associated diarrhea and intestinal parasitic infections in China for thousands of years. This study aimed to investigate the immunological effects of berberine alone and in conjunction with 6MP or INF in-vitro.
METHODS
Graded concentrations of berberine were added to cultures of human peripheral blood lymphocytes (PBL), alone and in combination with different doses of 6MP or INF. Following T-cell stimulation by OKT3, apoptosis induction of CD4+T-cells was investigated by annexin-V/PI while effect on proliferation was measured by fluorescence-activated cell sorting (FACS) analysis. LPS-induced cytokine secretion was measured by both intracellular staining and enzyme-linked immunosorbent assay (ELISA), and multiple cytokine arrays were measured by Quansis™.
RESULTS
Berberine alone down-regulated tumour necrosis factor (TNF)-α secretion, suppressed proliferation and induced apoptosis of CD4+T-cells in a dose-dependent fashion. Also, berberine inhibited secretion of multiple cytokines including interleukin (IL)-1, IL-6 and interferon (IFN)-y. Berberine combined with 6MP reduced TNF secretion (P=0.05) and inhibited proliferation (p=0.001) compared to 6MP alone, and similarly berberine combined with infliximab reduced TNF secretion and CD4+T-cells proliferation compared to infliximab alone (P<0.01 for both comparisons).
CONCLUSION
In this in-vitro study, berberine alone and in conjunction with thiopurine or anti-TNF showed a marked inhibitory effect on activated CD4+ T-cell function. Berberine enhanced the immune-modulating effects conferred by infliximab or 6MP in vitro, suggesting a possible beneficial role for combing these agents in the treatment of IBD. The role of berberine as a therapeutic agent for IBD should be further explored.