Jiawei Yanghe Decoction alleviates pulmonary sarcoidosis by upregulating NR1D1/2 and suppressing Th17 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD) is a modified version traditional Chinese medicine formula Yanghe Decoction which has been used to treat various autoimmune diseases. However, the effect of JWYHD on pulmonary sarcoidosis remains unclear.

AIM OF THE STUDY: This study aimed to determine the therapeutic efficacy and potential mechanism of action of JWYHD in pulmonary sarcoidosis.

MATERIALS AND

METHODS

A murine model of sarcoidosis was established by intravenous injection of inactivated Propionibacterium acnes and mature dendritic cells to assess the efficacy of JWYHD. Lung tissue mRNA sequencing was conducted to identify the targets of JWYHD's action. Molecular docking verified of the interaction between identified compounds and key targets.

RESULTS

JWYHD treatment alleviated the formation of granulomas in the lung tissue of sarcoidosis model mice. JWYHD significantly attenuated the pulmonary accumulation of macrophages and CD4+T lymphocytes in sarcoidosis mice, and effectively suppressed the proportion of Th17 cells and the levels of IL-17A and TNF-α in BALF, which are pivotal in the pathogenesis of granuloma formation and progression. The therapeutic efficacy of JWYHD was found to be equivalent to that of prednisone. RNA-seq revealed that JWYHD upregulated Nr1d1/2 expression in the lung tissue. Nr1d1/2 is highly expressed in Th17 cells and regulates their differentiation. The NR1D1/2 agonist SR9009 could inhibit Th17 cell proportion and reduce the formation of pulmonary granuloma, exhibiting effects similar to those of JWYHD. Molecular docking result showed that Cyclocephaloside II, Epimedin B, Glycyrrhetic acid, Glycyrrhizic acid, Uralsaponin B, and Uralsaponin U may be key compounds in JWYHD for the treatment of pulmonary sarcoidosis, which had a strong binding ability for NR1D1/2.

CONCLUSIONS

JWYHD might exert a therapeutic benefit in pulmonary sarcoidosis through upregulating NR1D1/2 and suppressing Th17 cells. NR1D1/2 might serve as a therapeutic target for the treatment of pulmonary sarcoidosis.