Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification / 中国中药杂志

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

Effect of Chaenomelis Fructus Alcohol Extract on Arthritis Inflammation and Apoptosis of Synovial Cells in Rheumatoid Arthritis Model / 中国实验方剂学杂志

Objective:To study the protective effect and mechanism of Chaenomelis Fructus alcohol extract (CFE) on the synovium of rheumatoid arthritis (RA). Method:Sixty male SD rats were randomly divided into normal group and model group. RA model was made by injection of complete Freund's adjuvant， and then was randomly divided into model group， CFE low， medium and high dose group and Tripterygium glycoside group according to the inflammatory score. The CFE groups (0.15，0.30，0.60 g·kg-1·d-1) had intragastric administration once a day for 30 d after the model establishment. The blank control group and the model group were given the same volume saline water by gavage. After all the drugs were given， the blood， joint tissues and synovium tissue of rats were collected. The levels of interleukin-1β (IL-1β)， interleukin-6 (IL-6)， interleukin-10 (IL-10) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA)， the pathological changes of synovium were observed by hematoxylin eosin (HE) staining， and the expressions of B-cell lymphoma-2 (Bcl-2)，Bcl-2 associated X protein (Bax) and death factor (Fas) in joints were detected by Western blot. Result:Compared with normal group， the swelling degree and inflammation index of rats' feet in model group increased significantly， the levels of inflammatory factors IL-1β， IL-6， TNF-α in serum increased (P<0.01)， anti-inflammatory factor IL-10 decreased (P<0.01)， the protein expression of Bax， Fas and Bcl-2 increased， and the statistical results of Bcl-2 showed significant difference (P<0.05). Compared with model group， the swelling degree and inflammatory index of the plantar of RA rats were improved in the middle and high dose groups of CFE (P<0.01)， the pathological changes such as synovial tissue hyperplasia and inflammatory cell infiltration were reduced in each dose group， and the levels of IL-1β， IL-6 and TNF-α in serum were reduced (P<0.05)， anti inflammatory factor IL-10 increased (P<0.05)， the disorder of inflammatory cytokine in the model was corrected， Bax， Fas expression increased， Bcl-2 protein expression decreased (P<0.01). Conclusion:CFE can reduce the degree of inflammation in RA joint and has obvious anti RA effects， which may be related to the apoptosis of synoviocytes induced by CFE.

Chemical constituents and pharmacological activities of the traditional Chinese medicine Chaenomelis Fructus: research advances / 国际药学研究杂志

Chaenomelis Fructus contains triterpenoids,phenylpropanoids,flavonoids,organic acids,esters, amino acids,lipids,steroids and other chemical constituents and possesses various pharmacological properties,includ- ing the analgesic,inflammatory,immune-enhancing and hepatoprotective effects as well as the anti-gastric ulcer,anti- intestinal injury and anticancer activities. This paper reviews the chemical constituents and pharmacological activities of Chaenomelis Fructus,and also addresses some ideas and Methods: for the research on Chaenomelis Fructus.

Discussion on the Non-pollution Cultivation Technology of Chaenomelis Fructus / 世界科学技术-中医药现代化

Chaenomelis Fructus is a traditional medicinal material derived from dry near-mature fruit of Chaenomeles speciosa (Sweet) Nakai. Chaenomelis Fructus has efficacy of leveling liver and relaxing tendons, harmonizing the stomach and resolving dampness. As the limit of the usage of available forest land, cultivated ginseng in the farmland would become the mainly Chaenomelis Fructus planting mode, meanwhile the non-polluted production technology would be the mainly development direction in the future. In this study, the non-polluted cultivation technology system of Chaenomelis Fructus was established based on the research results of field investigation in the cultivated regions. The system includes suitable planting regions selecting, planting method, field management, pest control and quality control. In order to promote the healthy and sustainable development of the cropland industry of Chaenomelis Fructus, the new varieties of good quality cultivated in farmland and the comprehensive prevention and control platform of disease and insect pest are put forward in this paper.

Simultaneous determination of eight organic acids in Chaenomelis Fructus by UFLC-MS / 中草药

Objective: To establish an UFLC-MS method for simultaneous determination of eight active components (shikimic acid, citric acid, protocatechuate, chlorogenic acid, caffeic acid, cinnamic acid, oleanolic acid, and ursolic acid). Methods: Shimadzu LC-20A system was used, equipped with AB Sciex Qtrap 5500. The analysis was performed on a Poroshell 120 column (100 mm× 4.6 mm, 2.7 μm). The eight components were separated in 25 min with gradient mobile phase consisting of 0.5% CH3COOH-H2O (A) and 0.5% CH3COOH-CH3OH (B): 0-5 min, 10% A; 5-13 min, 10%-30% A; 13-15 min, 30%-95% A; 15-25 min, 95% A. The temperature of column was 30℃, and the injection volume was 2 μL. The multiple-reaction monitoring scanning (MRM) was employed for the quantification with switching electrospray ion source polarity in negative mode. The ion spray voltage was set at -4 500 V and the turbo spray temperature was maintained at 550℃. Results: The eight components had a good linearity (r ≥ 0.999 2) within the linear ranges. The average recoveries were 96.14%-101.20%. The contents of the eight components in Chaenomelis Fructus varied from the different habitats. The contents of shikimic acid, citric acid, and chlorogenic acid were high while the content of caffeic acid was low. Conclusion: The developed UFLC-MS method is simple, sensitive, and accurate and has the good repeatability in separation, which is available for the quality control of Chaenomelis Fructus.