Network Pharmacology and Experimental Validation Explore the Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid Arthritis.

OBJECTIVE: This study aimed to elucidate the multitarget mechanism of the Mori Ramulus - Taxilli Herba (MT) herb pair in treating rheumatoid arthritis (RA). METHODS: The targets of the herb pair and RA were predicted from databases and screened through cross-analysis. The core targets were obtained using protein-protein interaction (PPI) network analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Finally, animal experiments were conducted to validate the anti-RA effect and mechanism of this herb pair. RESULTS: This approach successfully identified 9 active compounds of MT that interacted with 6 core targets (AKT1, TNF, IL6, TP53, VEGFA, and IL1ß). Pathway and functional enrichment analyses revealed that MT had significant effects on the TNF and IL-17 signaling pathways. The consistency of interactions between active components and targets in these pathways was confirmed through molecular docking. Moreover, the potential therapeutic effect of MT was verified in vivo, demonstrating its ability to effectively relieve inflammation by regulating these targeted genes and pathways. CONCLUSION: The present work suggests that the therapeutic effect of MT herb pair on RA may be attributed to its ability to regulate the TNF signaling pathway and IL-17 signaling pathway.

Ultrafine Pt nanoparticles anchored on core-shell structured zeolite-carbon for efficient catalysis of hydrogen generation.

Ammonia borane (AB) is a potential hydrogen storage material with high-efficiency hydrolytic dehydrogenation under a suitable catalyst. Noble metal catalysts have drawn a lot of attention. In this study, a carbon-coated zeolite was obtained by calcination at high temperatures using glucose as a carbon source. Pt nanoparticles were fixed on a core-shell composite support by a simple chemical reduction method. A series of catalysts were prepared with different synthesis parameters. The results show that PSC-2 has excellent catalytic performance for hydrolytic dehydrogenation of AB in alkaline solution at room temperature, and the turnover frequency (TOF) is 593 min-1. The excellent catalytic performance is attributed to the carbon layer on the zeolite surface which inhibits the aggregation or deformation of metals in the catalytic reaction. The metal-support interaction activates the water and accelerates the rate-limiting step of hydrolysis. The activation energy (E a = 44 kJ mol-1) was calculated based on the reaction temperature. In addition, the kinetics of AB hydrolysis was studied, and the effects of catalyst concentration, AB concentration and NaOH concentration on AB hydrolysis rate were further investigated. The high-efficiency catalyst prepared in this work provides a new strategy for the development of chemical hydrogen production in the field of catalysis.

The multi-omics and analysis to reveal thermal processing enhanced anti-rheumatoid arthritis efficacy of Radix Clematidis in rats.

Radix Clematidis (RC) is the roots and rhizomes of Clematis chinensis Osbeck, which has potent effects for expelling wind and dispelling dampness. Processing RC with yellow wine is a traditional processing method. This study aimed to investigate thermal and yellow wine processing influences on potential effective components of RC and its anti-rheumatoid arthritis enhancement mechanisms. Different thermal and wine processing were adopted to get different RC samples. Scanning electron microscope and mercury intrusion porosimetry were used to measure fractal parameters of pore structure. Based on ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), main constituents were identified and quantified. Besides, the correlation between fractal parameters and main constituents was investigated. The anti-rheumatoid arthritis effect was researched in adjuvant-induced arthritis (AIA) rats. The levels of inflammatory cytokine were determined with ELISA kits. Non-targeted serum metabolomics was performed with UPLC-QTOF/MS. 35 compounds were identified in RC, mainly triterpenoid saponins, also including organic acids and lignanoids. The extraction yield of four active triterpenoid saponins significantly increased because looser tissue and wider pore size distribution. Fractal dimension and total surface area significantly increased while total porosity and total volume decreased. In AIA rats, thermal and wine processed RC could markedly inhibit inflammatory cytokines IL-6, IL-1ß, TNF-α, and VEGF. Besides, tryptophan and lipid metabolism disorders were ameliorated. Thermal and yellow wine treatments engendered complex pore structure to increase the contents of four active triterpenoid saponins of RC, leading to greater anti-rheumatoid arthritis efficacy.

System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from herb couple on rheumatoid arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herb couple Angelicae pubescentis radix (APR) and Notopterygii rhizoma et radix (NRR), composition of two traditional Chinese medicinal herbs, has been used clinically in China for the treatment of rheumatoid arthritis (RA) over years. APR and NRR contain coumarins and phenolic acids, which have been reported to have analgesic and anti-inflammatory activities. AIM OF THE STUDY: The active ingredients combination (AIC) and potential therapeutic mechanism of APR and NRR (AN) herb couple remain unclear. Therefore, the present study aimed to identify the AIC and elucidate the underlying mechanism of AIC on RA. MATERIALS AND METHODS: Firstly, a novel strategy of in vitro experiments, computational analysis, UPLC-QTOF-MS and UPLC-QQQ-MS was established to confirm the optimum ratio of AN herb couple samples and identified the AIC. Then, the anti-arthritis effects of the optimal herb couple and AIC were studied with Collagen II induced rheumatoid arthritis (CIA) rats in vivo. Finally, an integrated model of network pharmacology, metabolomics, gut microbiota analysis and biological techniques were applied to clarify the underlying mechanism through a comprehensive perspective. RESULTS: AN7:3 herb couple was regarded as the optimal ratio of AN herbal samples, and AIC was screened as osthole, columbianadin, notopterol, isoimperatorin, psoralen, xanthotoxin, bergapten, nodakenin and bergaptol respectively. Additionally, AIC exerted similar therapeutic effects as AN 7:3 in CIA rats. Moreover, AIC ameliorated RA might via regulating MAPK signaling pathway, altering metabolic disorders and gut microbiome involved autoimmunity. CONCLUSIONS: our findings provided scientific evidence to support that AIC of AN herb couple could be used as a prebiotic agent for RA. Importantly, this research provided a systematic and feasible strategy to optimize the proportion of medicinal materials and screen AIC from multi-component traditional Chinese herb couples or Chinese medicine formulae. Moreover, it provided a comprehensive perspective to discover AIC, clarify the overall effects and understand the mechanisms for natural products through the perspective of database and multi-omics integration.

A network pharmacology approach to determine the synergetic mechanisms of herb couple for treating rheumatic arthritis.

PURPOSE: The purpose of this study was to investigate the therapeutic mechanism(s) of Clematis chinensis Osbeck/Notopterygium incisum K.C. Ting ex H.T (CN). METHODS: A network pharmacology approach integrating prediction of ingredients, target exploration, network construction, module partition and pathway analysis was used. RESULTS: This approach successfully helped to identify 12 active ingredients of CN, interacting with 13 key targets (Akt1, STAT3, TNFsf13, TP53, EPHB2, IL-10, IL-6, TNF, MAPK8, IL-8, RELA, ROS1 and STAT4). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that CN-regulated pathways were mainly classified into signal transduction and immune system. CONCLUSION: The present work may help to illustrate the mechanism(s) of action of CN, and it may provide a better understanding of antirheumatic effects.

Anti-rheumatoid arthritic effect of volatile components in notopterygium incisum in rats via anti-inflammatory and anti-angiogenic activities.

Notopterygium incisum (QH) has been used for the treatment of rheumatoid arthritis (RA), and volatile oils may be its mainly bioactive constituents. The present study was designed to analyze the volatile compounds in QH and to determine the anti-arthritic capacity of Notopterygium volatile oils and the potential mechanism of action. The volatile compounds analysis was conducted by GC-MS. The anti-arthritic capacity test of the volatile oils was conducted on adjuvant-induced arthritis (AIA) rats. The anti-inflammatory property was tested in NO release model in RAW 264.7 cells. Endothelial cells were used to evaluate the anti-proliferative and anti-tube formative effects. 70 compounds were analyzed by GC-MS in the volatile oils. Notopterygium volatile oils weakened the rat AIA in a dose-dependent manner (2, 4, and 8 g crude drug/kg). The NO production by RAW 264.7 was decreased by more than 50% in Notopterygium volatile oils (5, 15, and 45 µg·mL-1) pretreated groups. Notopterygium volatile oils also inhibited EAhy926 cell proliferation and further delayed EAhy926 cell capillary tube formation in a concentration-dependent manner. The anti-NO productive, anti-proliferative, and anti-tube formative effects of Notopterygium volatile oils strongly suggested that the therapeutic effect of QH in AIA might be related to the potent anti-inflammatory and anti-angiogenic capacities of the volatile oils.

[The protective effects of gangliosides on LPS-induced PC12 cells injury].

OBJECTIVE: To investigate the protective effects of endogenous gangliosides on LPS-induced PC12 cells injury and its possible mechanism. METHODS: PC12 cells were cultured, and lipopolysaccharide(LPS) injury model was established. We detected the changes in sur-vival rate of different concentrations of LPS on PC12 cells, and the changes in survival rate of LPS when endogenous gangliosides were exhaust-ed by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol(D-PDMP), and the protective effects of monosialoganglioside (GM1) on LPS-induced PC12 cells injury. Meanwhile, we observed the morphological changes of GM1 on PC12 cells induced after LPS injury by inverted microscope and fluorescence microscope, and then we detected the relative expression of NF-κB. RESULTS: LPS could decrease the survival rate of cells in a concentration-dependent manner, and GM1 could significantly protect the cells against the changes in survival rate and morphologi-cal damages induced by LPS; After depletion of endogenous gangliosides by D-PDMP, LPS had more injury to PC12 cells, which could be im-proved by adding GM1; RT-PCR results showed that the relative expression of NF-κB in PC12 cells was increased in LPS group, while relative expression of NF-κB increased much higher when endogenous gangliosides were exhausted by D-PDMP, and the relative expression of NF-κB was decreased after GM1 being added. CONCLUSIONS: The endogenous gangliosides might through NF-κB signal pathway to protect PC12 cells a-gainst LPS-induced injury.