Coptidis alkaloids extracted from Coptis chinensis Franch attenuate IFN-γ-induced destruction of bone marrow cells

Abstract

Coptidis alkaloids are the primary active components of Coptis chinensis Franch. Clinical and pharmacodynamic studies have confirmed that Coptidis alkaloids have multiple therapeutic effects including anti-inflammatory, antioxidant and antitumor effects, and they are usually used to treat various inflammatory disorders and related diseases. Mouse bone marrow cells (BMCs) were isolated from BALB/c mice. Immune-mediated destruction of BMCs was induced by interferon (IFN)-γ. High-performance liquid chromatography-electrospray ionization/ mass spectrometry was used to analyze the ingredients of the aqueous extract from Coptis chinensis Franch. The results confirmed that Coptidis alkaloids were the predominant ingredients in the aqueous extract from Coptis chinensis. The functional mechanism of Coptidis alkaloids in inhibiting immune-mediated destruction of BMCs was studied in vitro. After Coptidis alkaloid treatment, the percentages of apoptotic BMCs and the proliferation and differentiation of helper T (Th) cells and regulatory T (Treg) cells were measured by flow cytometry. The expression and distribution of T-bet in BMCs were observed by immunofluorescence. Western blotting analysis was used to assay the expression of key molecules in the Fas apoptosis and Jak/Stats signaling pathways in BMCs. We identified five alkaloids in the aqueous extract of Coptis chinensis. The apoptotic ratios of BMCs induced by IFN-γ were decreased significantly after Coptidis alkaloid treatment. The levels of key molecules (Fas, Caspase-3, cleaved Caspase-3, Caspase-8 and Caspase-8) in Fas apoptosis signaling pathways also decreased significantly after treatment with low concentrations of Coptidis alkaloids. Coptidis alkaloids were also found to inhibit the proliferation of Th1 and Th17 cells and induce the differentiation of Th2 and Treg cells; further, the distribution of T-bet in BMCs was decreased significantly. In addition, the levels of Stat-1, phospho-Stat-1 and phospho-Stat-3 were also reduced after Coptidis alkaloid treatment. These results indicate that Coptidis alkaloids extracted by water decoction from Coptis chinensis Franch could inhibit the proliferation and differentiation of T lymphocytes, attenuate the apoptosis of BMCs, and suppress the immunemediated destruction of the BMCs induced by pro-inflammatory cytokines.

Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases

“…With the integration of traditional and modern medicine, an increasing number of studies have found that traditional Chinese monomers have the dual advantages of traditional Chinese medicine and chemical medicine ( 205 ), which can optimise their functions. Therefore, to maximise the curative effect, adequacy of theory, and achieve better integration of traditional Chinese and Western medicines, we will pay more attention to the treatments of diseases using traditional Chinese medicine monomers should be further investigated ( 206 ).…”

Coptisine Alleviates Imiquimod-Induced Psoriasis-like Skin Lesions and Anxiety-like Behavior in Mice

“…In the psoriasis model, further studies are needed to determine whether coptisine suppresses the proportion of Th1 and Th17 cells and regulates associated transcription factors. Coptidis alkaloids, which are present in the aqueous extract of Coptidis Rhizoma, have been demonstrated to inhibit the proliferation of Th1/Th17 and regulatory T (Treg) cells in mouse bone marrow cells by suppressing T-bet (the transcription factor of Th1) and Foxp3 (the transcription factor of Treg) [74]. Furthermore, it has been revealed that herbal formulas containing coptisine also affect Th cell-specific transcription factors such as T-bet and RORγt (the transcription factor of Th17) [75].…”