Comparative comprehension on the anti-rheumatic Chinese herbal medicine Siegesbeckiae Herba: Combined computational predictions and experimental investigations.

ETHNOPHARMACOLOGICAL RELEVANCE: Siegesbeckiae Herba (SH) is a traditional anti-rheumatic herbal medicine in China. The SH-derived product is the first licensed traditional herbal medicinal product for the management of rheumatism-induced joint and muscle pain in United Kingdom. The authenticated plant origins listed in the official Chinese Pharmacopeia for SH include Siegesbeckia orientalis L. (SO), S. pubescens Markino (SP) and S. glabrescens Markino (SG). Although the therapeutic effects of these SH species in treating rheumatoid arthritis (RA) are similar, their difference in chemical profiles suggested their anti-rheumatisms mechanisms and effects may be different. AIM OF THE STUDY: This study was designed to comparatively comprehend the chemical and biological similarity and difference of SO, SP and SG for treating rheumatoid arthritis based on the combination of computational predictions and biological experiment investigations. MATERIALS AND METHODS: The reported compounds for SO, SP and SG were obtained from four chemical databases (SciFinder, Combined Chemical Dictionary v2009, Dictionary of Natural Products and Chinese academy of sciences Chemistry Database). The RA-relevant proteins involved in nuclear factor-kappa B (NF-κB), oxidative stress and autophagy signaling pathways were collected from the databases of Kyoto Encyclopedia of Genes and Genomes and Biocarta. The comparative comprehension of SH plants was performed using similarity analysis, molecular docking and compounds-protein network analysis. The chemical characterization of different SH extracts were qualitatively and quantitatively analyzed, and their effects on specific RA-relevant protein expressions were investigated using Western blotting analysis. RESULTS: Chemical analysis revealed that SO contains mainly sequiterpenes and pimarenoids; SP contains mainly pimarenoids, sequiterpenes, and kaurenoids; and SG contains mainly pimarenoids, flavonoids and alkaloids. Moreover, coincided with the predicted results from computational analysis, different SH species were observed to present different chemical constituents, and diverse effects on RA-relevant proteins at the biological level. CONCLUSIONS: The chemical and biological properties of SO, SP and SG were different and distinctive. The systematic comparison between these three confusing Chinese herbs provides reliable characterization profiles to clarify the pharmacological substances in SH for the precise management of rheumatism/-related diseases in clinics.

Discrimination of three Siegesbeckiae Herba species using UPLC-QTOF/MS-based metabolomics approach.

The plant origin is one of the most important factors for the quality control of traditional Chinese medicines (TCMs) and highly affected on their safety and effectiveness in clinical applications. Multi-origin has been widely observed for many TCMs. Siegesbeckiae Herba (SH) is a traditional anti-rheumatic TCM which is originated from the plants of Siegesbeckia pubescens Makino (SP), S. orientalis L. (SO), and S. glabrescens Makino (SG). In the present study, an UPLC-QTOF/MS method were validated and successfully applied for the determination of the chemical profiles in the three SH species. The data were statistical analyzed with the OPLS-DA analysis and One-Way ANOVA F-test. Obvious differences in chemistry were observed in different SH species and 40 components were identified. Finally, 6 components were selected as potential chemical markers for the discrimination of SP, SO and SG based on the characteristic distribution in individual SH species.