Cinnamtannin D1 is an orally active polyphenolic compound that modulates the Th17/Treg cell balance by inhibiting AHR expression. It reduces apoptosis and ROS in INS-1 cells and primary cultured mouse islets induced by Palmitic acid (PA). Cinnamtannin D1 mitigates Th17 cell differentiation by downregulating p-STAT3/RORγt and enhances Treg cell differentiation by upregulating p-STAT5/Foxp3. In a collagen-induced arthritis (CIA) mouse model, it demonstrates excellent anti-arthritic efficacy. Cinnamtannin D1 is applicable for rheumatoid arthritis (RA) research.

Cinnamtannin D1 at 40 μM for 72 hours significantly inhibits the differentiation of Th17 cells while promoting Treg cell differentiation under Th17 or Treg polarizing conditions in initial CD4+ T cells derived from BALB/c mice. It also reduces IL-17A levels and increases IL-10 levels in respective Th17 and Treg cell supernatants. Under stimulation with 6-formylindolo[3,2-b]carbazole (FICZ), Cinnamtannin D1 suppresses Th17 cell differentiation in BALB/c mouse splenocytes. At concentrations of 20-40 μM over 96 hours, it dose-dependently inhibits Th17 cell differentiation and decreases AHR protein expression. Additionally, Cinnamtannin D1 enhances cell viability in PA-treated INS-1 cells in a dose-dependent manner over 48 hours. At doses of 25-50 μM for 48 hours, it reduces apoptosis rates, as well as ROS and NO production in PA-induced INS-1 cells and primary cultured mouse islets. Phosphorylation of NF-κB and c-Jun N-terminal kinase (JNK) is also decreased in INS-1 cells.

Cinnamtannin D1 (administered orally at 50 mg/kg daily for 4 weeks) demonstrates significant anti-arthritis effects in the collagen-induced arthritis (CIA) model in DBA/1 mice.