Cymbaria daurica L.: A Mongolian herbal medicine for treating eczema via natural killer cell-mediated cytotoxicity pathway.

Ethnopharmacological Relevance: Cymbaria daurica L. (C. daurica) is a perennial herb known commonly as "Xinba" (Chinese) and "Kanba-Arong" (Mongolian). In Mongolia, it is used as a traditional medicine to treat eczema and other skin diseases due to its anti-swelling, anti-inflammatory, anti-hemorrhagic, and anti-itching properties. However, the potential mechanism of action for eczema treatment has not been reported.

Aim Of The Study: To investigate the effect of C. daurica on 1-chloro-2,4-dinitrobenzene (DNCB)-induced eczema in rats and the associated action mechanism.

Materials And Methods: Qualitative analysis of C. daurica was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on information obtained from compound identification and relevant literature, the possible targets of C. daurica against eczema were analyzed using network pharmacology and molecular docking methods. The DNCB-induced eczema rat models were treated with different dosages of C. daurica extract (10, 50, and 250 mg/mL per day), and the therapeutic effects subsequently evaluated based on the degree of skin inflammation, spleen index, and hematoxylin and eosin staining (H&E staining). Enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting were used to analyze the relevant target effects. The C. daurica mechanism of action on eczema was verified by animal experiments. High-performance liquid chromatography (HPLC) was carried out to determine the content of active ingredients in C. daurica. In addition, the physicochemical properties of the extract were evaluated.

Results: Our analysis of the 173 targets included in the protein-protein interaction (PPI) network identified tumor necrosis factor (TNF) and interleukin 2 (IL-2) as key targets involved in the treatment of eczema with C. daurica extract. Furthermore, the 173 targets were associated with the natural killer cell-mediated cytotoxicity pathway. Our results showed that C. daurica significantly reduced IL-2 and TNF-α serum levels in eczema rat models (P < 0.0001); thus, playing an important role in the anti-inflammatory response. Furthermore, according to the p-value, RT-qPCR and western blotting showed that the expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Vav guanine nucleotide exchange factor (Vav), and growth factor receptor-bound protein 2 (Grb2) changed in the skin of the eczema model rats after treatment with the C. daurica extract.

Conclusion: Our study confirms that C. daurica can inhibit SHP-1, Vav, and Grb2 expression; thereby, inhibiting the natural killer cell-mediated cytotoxicity pathway. These results provide insight into the mechanism of C. daurica in treating eczema.