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In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from the aerial parts of Zanthoxylum dimorphophyllum var. spinifolium (ZDS), a plant revered in traditional Chinese medicine, particularly for treating rheumatoid arthritis (RA). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy, complemented by ECD, [Rh2(OCOCF3)4]-induced ECD, Mo2(OAc)4 induced ECD, IR, and HR-ESI-MS mass spectrometry. A network pharmacology approach allowed for predicting their anti-RA mechanisms and identifying the MAPK and PI3K-Akt signaling pathways, with EGFR as a critical gene target. A CCK-8 method was used to evaluate the inhibition activities on HFLS-RA cells of these compounds. The results demonstrated that Spinifoliumin A, B, and D-H are effective at preventing the abnormal proliferation of LPS-induced HFLS-RA cells. The results showed that compounds Spinifoliumin A, D, and G can significantly suppress the levels of IL-1β, IL-6, and TNF-α. Moreover, molecular docking methods were utilized to confirm the high affinity between Spinifoliumin A, D, and G and EGFR, SRC, and JUN, which were consistent with the results of network pharmacology. This study provides basic scientific evidence to support ZDS's traditional use and potential clinical application. [ABSTRACT FROM AUTHOR]

Carboxyamidotriazole (CAI) was previously recognized as a well‐tolerated anticancer drug. It has also demonstrated significant anti‐inflammatory effects in various cell and animal model experiments, prompting its investigation as a potential treatment for rheumatoid arthritis. In this study, the potential biotransformation metabolites of CAI were identified both in vitro and in vivo. A sensitive, specific, and accurate LC–MS method was developed for the quantitative analysis of CAI and its major metabolite, CAI‐OH, in rat plasma. CAI, CAI‐OH, and telmisartan (used as an internal standard) were separated using a Zorbax SB C18 column. The mobile phase consisted of water (phase A, containing 0.1% formic acid) and acetonitrile (phase B, containing 0.1% formic acid) at a flow rate of 0.2 mL/min. The analytes were examined using a high‐resolution mass spectrometer, with detected mass‐to‐charge ratios of m/z 424.01293 for CAI, m/z 440.00785 for CAI‐OH, and m/z 515.24415 for telmisartan. Good linearity was observed within the range of 10–5000 ng/mL. Both inter‐ and intra‐batch precision (relative standard deviation, %) were below 6%, and the accuracy ranged from 94.9% to 106.1%. The analytes remained stable throughout the entire experimental period. This method was successfully applied in a pharmacokinetic study of CAI following oral administration in rats. [ABSTRACT FROM AUTHOR]

AbstractOrthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,β-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1β, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.

In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from the aerial parts of Zanthoxylum dimorphophyllum var. spinifolium (ZDS), a plant revered in traditional Chinese medicine, particularly for treating rheumatoid arthritis (RA). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy, complemented by ECD, [Rh2(OCOCF3)4]-induced ECD, Mo2(OAc)4 induced ECD, IR, and HR-ESI-MS mass spectrometry. A network pharmacology approach allowed for predicting their anti-RA mechanisms and identifying the MAPK and PI3K-Akt signaling pathways, with EGFR as a critical gene target. A CCK-8 method was used to evaluate the inhibition activities on HFLS-RA cells of these compounds. The results demonstrated that Spinifoliumin A, B, and D-H are effective at preventing the abnormal proliferation of LPS-induced HFLS-RA cells. The results showed that compounds Spinifoliumin A, D, and G can significantly suppress the levels of IL-1β, IL-6, and TNF-α. Moreover, molecular docking methods were utilized to confirm the high affinity between Spinifoliumin A, D, and G and EGFR, SRC, and JUN, which were consistent with the results of network pharmacology. This study provides basic scientific evidence to support ZDS’s traditional use and potential clinical application.

Background and purpose: Plantago major has been applied as a herbal remedy for centuries. However, studies on anti-inflammatory activities and their chemical ingredients are limited. The objective of this study was to investigate the anti-inflammatory properties of P. major in three animal models and its phytochemical contents. Experimental approach: Dichloromethane extract (DCM) of P. major was fractionated with n-hexane to yield the soluble (SHF) and insoluble (IHF) fractions. The anti-inflammatory activities of DCM, SHF, and IHF were evaluated using rat’s paw edema induced by carrageenan, thioglycolate-induced leukocyte emigration in the mice, and rheumatoid arthritis (RA) induced by complete Freund’s adjuvants in rats. The chemical constituents were analyzed using a high-resolution mass spectrometer (HRMS). Findings / Results: The DCM, SHF, and IHF inhibited paw edema in the rats and reduced the leukocyte migration in the mice. At dose 560 mg/kg, the percentage of inhibitory was 47.33%, 55.51%, and 46.61% for the DCM, IHF, and SHF, respectively. In the RA animal model, IHF at 280 and 560 mg/kg reduced osteoclast formation and COX-2 expression compared to diclofenac. Some compounds namely oleic acid, linoleic acid, palmitic acid, and oleamide identified in the DCM, IHF, and SHF may be responsible for these activities. Conclusion and implications: This study showed that P. major has several in-vivo anti-inflammatory activities.

Context Cinnamomi ramulus, the dry twig of Cinnamomum cassia Presl. (Lauraceae), has been reported to exert several activities such as antitumor, anti-inflammatory, and analgesic effects. Objective This study investigates the effects of an aqueous extract of Cinnamomi ramulus (ACR) on rheumatoid arthritis (RA). Materials and methods TNF-α-induced RA-derived fibroblast-like synoviocyte MH7A cells were incubated with ACR (0.1–2 mg/mL) for 24 h. The proliferation was tested using CCK-8 and colony formation assays. The migration and invasion abilities were measured using transwell tests and wound healing assays. Apoptosis and cell cycle were examined by flow cytometry. The potential mechanisms were determined by western blotting and quantitative real-time PCR. UPLC-QE-MS/MS was used for chromatographic analysis of ACR and its compounds were identified. Molecular docking strategy was used to screen the potential anti-RA active compounds of ACR. Results We found that ACR induced apoptosis in MH7A cells at concentrations of 0.4, 0.8, and 1.2 mg/mL. The proliferation of MH7A cells was reduced and the cell cycle was blocked in the G2/M phase at concentrations of 0.2, 0.4, 0.6 mg/mL. Migration and invasion of MH7A cells were reduced through inhibiting the expression of MMP-1, MMP-2, and MMP-3. The molecular docking strategy results showed that 9 compounds in ACR have good affinity with protein crystal, and benzyl cinnamate (10–100 µg/mL) could inhibit cell migration and induce apoptosis. Conclusions The anti-RA effect of ACR may be attributed to its anti-proliferative and anti-migration effects on synovial fibroblasts. These data suggest that Cinnamomi ramulus may have therapeutic value for the treatment of RA.

Qintengtongbi Decoction (QTTBD) is a traditional prescription for rheumatoid arthritis (RA) treatment in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, southern China’s Guangxi Zhuang Autonomous Region. However, there is not yet any analysis on its active compounds or action mechanism for treating RA. Moreover, the prescription has not been investigated from the perspective of network pharmacology. Therefore, this study aimed to analyze the compounds QTTBD and their potential pharmacological effects and the mechanism by which they treat RA via an integrated network pharmacology approach. With the aid of the relevant database tools and research indices, 188 compounds and 272 related drug targets genes/proteins were collected from QTTBD through the compound-target network, and 175 common gene targets between the QTTBD and RA were obtained by Venn 2.1. Finally, the top 10 gene targets and pathways were identified through the protein– protein interaction network, gene ontology, and KEGG pathway analysis: the gene targets include AKT1, IL6, TP53, VEGFA, MAPK3, TNF, CASP3, JUN, EGF, and EGFR; the pathways include oxytocin signaling pathway, amphetamine addiction, graftversus-host disease, ovarian steroidogenesis, cGMP-PKG signaling pathway, Rap1 signaling pathway, allograft rejection, cytokine–cytokine receptor interaction, regulation of lipolysis in adipocytes and inflammatory mediator regulation of transient receptor potential channels. Therefore, it is concluded that a network pharmacology-based approach can help reveal and clarify the anti-RA role of QTTBD, and provide a scientific basis for further research into the mechanism. [ABSTRACT FROM AUTHOR]

Rhododendron molle G. Don is first recorded in Shengnong's Herbal Classic, and its fruits, which are termed as Liuzhouzi , are often used to treat rheumatoid arthritis in Chinese folk. During our ongoing investigation to develop a safer and potential new arthritis therapy, a process for the preparation of diterpenoid fraction from Rhododendron molle fruits was established. In order to evaluate the main components and the anti-rheumatoid arthritis effect of the diterpenoid fraction, phytochemical and pharmacological experiments were used. As the result, the main components of diterpenoid fraction were identified as rhodojaponin III (1), rhodojaponin VI (2), 2- O -methylrhodojaponin (3), and 5′- β -D-glucopyranosy-loxyjasmonic acid (4). These four components constitute greater than 95% of diterpenoid fraction using area normalization method of HPLC-ELSD. The results of CIA rat experiment showed that high dose of diterpenoid fraction (0.6 mg·kg–1·d–1) significantly alleviated the symptoms of rheumatoid arthritis, similar to tripterygium polyglycosides, an effective RA therapy. Preliminary mechanism studies indicated that diterpenoid fraction significantly inhibited the abnormal proliferation of T and B lymphocytes, and remarkably reduced the levels of pro-inflammatory cytokines IL-6, IL-1 β and TNF- α. Overall, our findings may provide a more effective and safe alternative treatment for RA using common clinical Chinese medicines like tripterygium polyglycosides. [ABSTRACT FROM AUTHOR]

Cinnamomi ramulus, the dry twig of Cinnamomum cassia Presl. (Lauraceae), has been reported to exert several activities such as antitumor, anti-inflammatory, and analgesic effects. This study investigates the effects of an aqueous extract of Cinnamomi ramulus (ACR) on rheumatoid arthritis (RA). TNF-α-induced RA-derived fibroblast-like synoviocyte MH7A cells were incubated with ACR (0.1–2 mg/mL) for 24 h. The proliferation was tested using CCK-8 and colony formation assays. The migration and invasion abilities were measured using transwell tests and wound healing assays. Apoptosis and cell cycle were examined by flow cytometry. The potential mechanisms were determined by western blotting and quantitative real-time PCR. UPLC-QE-MS/MS was used for chromatographic analysis of ACR and its compounds were identified. Molecular docking strategy was used to screen the potential anti-RA active compounds of ACR. We found that ACR induced apoptosis in MH7A cells at concentrations of 0.4, 0.8, and 1.2 mg/mL. The proliferation of MH7A cells was reduced and the cell cycle was blocked in the G2/M phase at concentrations of 0.2, 0.4, 0.6 mg/mL. Migration and invasion of MH7A cells were reduced through inhibiting the expression of MMP-1, MMP-2, and MMP-3. The molecular docking strategy results showed that 9 compounds in ACR have good affinity with protein crystal, and benzyl cinnamate (10–100 µg/mL) could inhibit cell migration and induce apoptosis. The anti-RA effect of ACR may be attributed to its anti-proliferative and anti-migration effects on synovial fibroblasts. These data suggest that Cinnamomi ramulus may have therapeutic value for the treatment of RA. [ABSTRACT FROM AUTHOR]

Purpose: To propose an improved chemical skeleton whose scaffolds could be used for the design of future thymidylate synthase (TS)-inhibitors against rheumatoid arthritis. Methods: The drug discovery platform, ‘MCULE’, was employed for inhibitor-screening. The ‘methotrexate-interaction site’ in the crystal (PDB ID 5X66) was used as a target. One ‘RO5 violation’ was permitted. A maximum of ‘10 rotatable bonds’ and ‘100 diverse molecules’ were also allowed in the protocol. The ‘threshold similarity cut off’ was 0.7. The input values describing the remaining parameters were kept as ‘default’. The ‘Open Babel Linear Fingerprint’ was used for the analyses of molecular descriptors, followed by ADME-check. Results: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidine corresponding to the MCULE ID-7590816301-0-93 exhibited the overall best binding with TS. The free energy of binding was -8.6 kcal/mol. A total of 17 amino acid residues were significant for the binding interactions. Importantly, 9 residues were common to methotrexate binding. It satisfied pertinent ADME conditions. Conclusion: 4-(4-Methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d]pyrimidinemay emerge as a potent seed molecule for TS-inhibitor design in the context of rheumatoid arthritis. It has satisfied pertinent ADME features. However, there is need for further wet laboratory validation. [ABSTRACT FROM AUTHOR]

Alangium chinense has been used as traditional folk medicine for centuries to treat rheumatoid arthritis (RA) by Guizhou Miao nationality with remarkable clinical effect. But the mechanism of its anti-RA is not fully clarified. To explore the effect and underlying mechanism of A. chinense against RA. RA rats were induced by CII/IFA, and oral administrated with or without ethyl acetate extracts of Alangium chinense (ACEE) and tripterygium glycosides (GTW). Then arthritis scores, inflammatory factors in serum and histological evaluation were evaluated to assess the degree of joints disease. Proteomics were conducted via LC-MS/MS to clarify the mechanism of ACEE preliminarily, and further examined by immunohistochemistry, immunofluorescence, western botting, and molecular docking. ACEE decreased joints swelling, cell abscission and necrosis of joint tissues arthropathy of RA rats, and attenuated expression of TNF-α, IL-1β, IL-6, PGE2, TGF-β. Meanwhile, differentially expressed proteins in the ACEE treated groups were observed, which were involved in RA, spliceosome, cell adhesion molecules, phagosome and lysosome signaling pathways. Moreover, ACEE significantly ameliorated arthropathy, suppressed JAK-STAT pathway (JAK3, p-JAK3, STAT3, iNOS, RANKL), COX-2 pathway (COX-2, TNF-α, IL-6I, L-1β, 5-LOX), and autophagic signaling pathway (LC3-Ⅰ, LC3-Ⅱ, p62, mTOR). But it showed little effect on the expression of COX-1, JAK1, JAK2, TyK2. It is the first evidence that A. chinense significantly ameliorates RA, and the underlying immune mechanism involves reducing autophagy with targeting regulate JAK3-STAT3 and COX-2 pathways. [Display omitted] • DEPs were reversed in the ACEE groups with proteomic analyse in CII/IFA-induced RA rats. • ACEE decreased inflammatory cytokines production and inflammatory pathology in RA rats. • ACEE regulated the expression of COX-2, JAK3 LC3 and p62 of ankle joint tissues in RA rats. • ACEE ameliorated RA by reducing autophagy with targeting regulate JAK3-STAT3 and COX-2 pathways. • Alangium chinense can serve as a candidate drug for anti-RA by inhibiting JAK-STAT and COX-2 pathways. [ABSTRACT FROM AUTHOR]

The 29 plant species in the Kadsura genus of the Schisandraceae family are mainly distributed in eastern and southeas-tern Asia. Ten species of plants in this genus are distributed in China, some of which are folk medicinal plants with activating blood circulation, relieving pain, dispelling wind, and dehumidifying effects. Their main constituents are lignans and triterpenes. The current pharmacology and clinical studies have shown that their extracts and constituents have anti-rheumatoid arthritis, liver protection, antioxidation, anti-inflammatory, and other biological activities. The rheumatologic and liver diseases can also be treated with the plants in the clinic. The new chemical constituents reported in the last decade(2012 to date) from the plants of Kadsura genus in China, as well as their pharmacological effects and clinical applications in recent years were reviewed, so as to provide a theoretical basis for further research on the genus.

A new morphinandienone alkaloid, fissistigmine A (1), together with three known alkaloids (2−4), were isolated and identified from the stems of Fissistigma tungfangense. Among them, fissistigmine A (1) represents the first example of a novel naturally occurring morphinandienone alkaloid with a unique cleavage of the C-9−N-17 bond. All isolated compounds were evaluated for their anti-rheumatoid arthritis activities via examining their anti-proliferative effects on synoviocytes in vitro. Compound 1 exhibited inhibitory effect on the proliferation of synoviocytes with an IC50 value of 114.6 ± 2.2 μM. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The objective of this present study was to develop and evaluate the triptolide-loaded nanostructured lipid carriers (TPL-NLCs) for transdermal drug delivery system (TDDS). TPL-NLCs was prepared with emulsification technique and optimized by central composite design of a response surface methodology (CCD-RSM). The optimized TPL-NLCs were spherical and physically stable with the average size of 139.6.0 ± 2.53 nm and Zeta potential of −36.03 ± 2.41 mV. The encapsulation efficiency and drug loading were 97.15% ± 9.46 and 10.35% ± 1.12, respectively. Moreover, the in vitro release study showed that TPL-NLCs had a sustained release profiles and the in vitro penetration study indicated that TPL-NLCs could effectively penetrate into skin. Besides, the methodology of skin-blood synchronous microdialysis was established to evaluate the pharmacokinetics of TPL-NLCs in vivo and the results displayed that the TPL concentration in skin was higher than that in blood. And TPL-NLCs presented a remarkable effect of decreasing knee edema, inhibiting inflammation by regulating the levels of TNF-α, IL-1β and IL-6, which indicated that TPL-NLCs was a promising topical administration in treatment of edema and inflammation associated with rheumatoid arthritis (RA). [ABSTRACT FROM AUTHOR]

Graphical abstract Three complexes containing the dipyrimidine-2-thiolategold(I) anion have been synthesized and characterized by spectroscopy (1H NMR, IR, and ESI –MS) and by X-ray crystallography. All three monomeric complexes are missing Au Au interactions, and all have different 3D arrangements based on the identity of the countercation. Abstract Three complexes containing the dipyrimidine-2-thiolategold(I) anion, [Au(2-pymS) 2 ]-, (2-pymSH = pyrimidine-2-thione), Na[Au(2-pymS) 2 ] (1), N(C 2 H 5) 4 [Au(2-pymS) 2 ] (2), and H[Au(2-pymS) 2 ] (3), have been synthesized and characterized by spectroscopy (1H NMR, IR, and ESI –MS) and by X-ray crystallography. The monomeric compounds are easily solubilized in water and in various polar organic solvents. The complex anion shows a linear S Au S geometry in all three compounds, but the counter cations create a different space group for each compound and also deter Au Au interactions. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Smilax glabra Roxb. (Tufuling) and Bolbostemma paniculatum (Maxim.) Franquet (Tubeimu) are used as couplet medicine in traditional Chinese medicine for the treatment of arthritis. This study is conducted to provide evidence on their therapeutic effects on rheumatoid arthritis (RA) and to explore its possible mechanisms of action. The identification and quantification of representative components (Astilbin and Tubeimoside I) in the n-butyl alcohol fraction of this couplet medicine (BFCM) were carried out by HPLC-UV assays. The contents of Astilbin and Tubeimoside I in BFCM were 13.13% (15.434 min) and 3.4% (18.619 min) respectively. For the assessment of anti-RA and anti-inflammatory activities, a carrageenan-induced paw edema model in rats was used. The swelling rates of paws and levels of IL-1β, IL-6 and TNF-α in the swelling tissue were determined. We observed that the BFCM exhibited significant inhibitory activity on carrageenan-induced paw edema model (p <0.01). The down regulated levels of IL-1β, IL-6 and TNF-α (all p <0.05) were reported. The results indicate that BFCM possesses significant anti-RA and anti-inflammatory effects, and it has a potential to be developed as a new therapeutic agent against RA. [ABSTRACT FROM AUTHOR]

In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by 1H, 13C, and 11B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.

A new polyoxygenated abietane diterpenoid, bauchampine A (1), together with seven known compounds (2-8), were isolated from the rattans of Bauhinia championii (Benth.) Benth. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with the data reported in the literature. New compound 1 was evaluated for its anti-rheumatoid arthritis activity via examining its anti-proliferative effect on synoviocytes in vitro. Compound 1 exhibited inhibitory effect on the proliferation of synoviocytes with IC50 value comparable to that of methotrexate. [ABSTRACT FROM AUTHOR]

Three new aporphine alkaloids, fissitungfines C–E ( 1–3 ), together with five known analogues ( 4 – 8 ) were isolated from the stems of Fissistigma tungfangense . Their structures were elucidated by extensive spectroscopic methods Among them, fissitungfines C ( 1 ) and D ( 2 ) are two unusual aporphine alkaloids with a carboxyl group as a substituent at N-6. All isolated compounds were evaluated for their anti-rheumatoid arthritis activities via examining their anti-proliferative effects on synoviocytes in vitro . Fissitungfine E ( 3 ) exhibited a significant inhibitory effect on the proliferation of synoviocytes comparable to that of methotrexate. [ABSTRACT FROM AUTHOR]

Two new dibenzofurans, bauhichamines A ( 1 ) and B ( 2 ), along with six known compounds ( 3 - 8 ), were isolated from the rattans of Bauhinia championii (Benth.) Benth. (Fabaceae). The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparison of their data with those reported in the literatures. All new compounds were evaluated for their anti-rheumatoid arthritis activities via examining their anti-proliferative effects on synoviocytes in vitro . Compounds 1 and 2 exhibited significant inhibitory effects on the proliferation of synoviocytes with the IC 50 values of 103.1 ± 1.8 and 146.4 ± 1.2 μM, respectively. [ABSTRACT FROM AUTHOR]

Background: Geranium wilfordii is one of the major species used as Herba Geranii (lao-guan-cao) in China, it is commonly used solely or in polyherbal formulations for treatment of joint pain resulted from rheumatoid arthritis (RA) and gout. This herb is used to validate a target-based drug screening platform called Herbochip® and evaluate anti-inflammatory effects of Geranium wilfordii ethanolic extract (GWE) using tumor necrosis factor-alpha (TNF-α) as a drug target together with subsequent in vitro and in vivo assays. Methods: A microarray-based drug screening platform was constructed by arraying HPLC fractions of herbal extracts onto a surface-activated polystyrene slide (Herbochip®). Using TNF-α as a molecular probe, fractions of 82 selected herbal extracts, including GWE, were then screened to identify plant extracts containing TNF-α-binding agents. Cytotoxicity of GWE and modulatory effects of GWE on TNF-α expression were evaluated by cell-based assays using TNF-α sensitive murine fibrosarcoma L929 cells as an in vitro model. Results: The in vivo anti-inflammatory effects of GWE were further assessed by animal models including carrageenan-induced hind paw edema in rats and xylene-induced ear edema in mice, in comparison with aspirin. The hybridization data obtained by Herbochip® analysis showed unambiguous signals which confirmed TNF-α binding activity in 46 herbal extracts including GWE. In L929 cells GWE showed significant inhibitory effect on TNF-α expression with negligible cytotoxicity. GWE also significantly inhibited formation of carrageenan-induced hind paw edema and xylene-induced ear edema in animal models, indicating that it indeed possessed anti-inflammatory activity. Conclusion: We have thus validated effectiveness of the Herbochip® drug screening platform using TNF-α as a molecular target. Subsequent experiments on GWE lead us to conclude that the anti-RA activity of GWE can be attributed to inhibitory effect of GWE on the key inflammatory factor, TNF-α. Our results contribute towards validation of the traditional use of GWE in the treatment of RA and other inflammatory joint disorders. [ABSTRACT FROM AUTHOR]

Background and Purpose: Plantago major has been applied as a herbal remedy for centuries. However, studies on anti-inflammatory activities and their chemical ingredients are limited. The objective of this study was to investigate the anti-inflammatory properties of P. major in three animal models and its phytochemical contents., Experimental Approach: Dichloromethane extract (DCM) of P. major was fractionated with n -hexane to yield the soluble (SHF) and insoluble (IHF) fractions. The anti-inflammatory activities of DCM, SHF, and IHF were evaluated using rat's paw edema induced by carrageenan, thioglycolate-induced leukocyte emigration in the mice, and rheumatoid arthritis (RA) induced by complete Freund's adjuvants in rats. The chemical constituents were analyzed using a high-resolution mass spectrometer (HRMS)., Findings / Results: The DCM, SHF, and IHF inhibited paw edema in the rats and reduced the leukocyte migration in the mice. At dose 560 mg/kg, the percentage of inhibitory was 47.33%, 55.51%, and 46.61% for the DCM, IHF, and SHF, respectively. In the RA animal model, IHF at 280 and 560 mg/kg reduced osteoclast formation and COX-2 expression compared to diclofenac. Some compounds namely oleic acid, linoleic acid, palmitic acid, and oleamide identified in the DCM, IHF, and SHF may be responsible for these activities., Conclusion and Implications: This study showed that P. major has several in-vivo anti-inflammatory activities., (Copyright: © 2022 Research in Pharmaceutical Sciences.)

Abstract: Impatiens pritzellii Hook. f. var. hupehensis Hook. f. (Balsaminaceae) has been well-known and widely used in China as an anti-rheumatoid arthritis (anti-RA) herb. In this present study, mice with collagen-induced arthritis (CIA) have been treated with the methanol (MeOH) extract (0.56, 1.12, 1.68 and 2.24g/kg body weight) and the n-butanol (BuOH) fraction (0.13, 0.27, 0.40 and 0.53g/kg body weight) of the rhizomes of Impatiens pritzellii orally for 3 weeks. The progression of CIA was evaluated by macroscopic scoring. Administration of the MeOH extract at dose of 1.12g/kg and the BuOH fraction at 0.53g/kg suppressed the development of CIA in mice significantly. The spleen and thymus indexes were measured and the levels of IgG, IL-10, INF-γ and IL-18 in the serum of CIA mice were examined after the treatment of the MeOH extract (1.12 and 1.68g/kg body weight) and the BuOH fraction (0.40 and 0.53g/kg body weight). Administration of the MeOH extract and the BuOH fraction of Impatiens pritzellii decreased the spleen and thymus indexes, down-regulated the levels of IgG, INF-γ, IL-18, and up-regulated the concentration of IL-10 in the serum of mice with CIA. From the results, it was concluded that administration of Impatiens pritzellii had obviously therapeutic effects on RA including immunomodulatory activity. Moreover, the BuOH fraction exerted the activity of anti-RA of Impatiens pritzellii. [Copyright &y& Elsevier]

Genkwa flos , as a traditional herb, is the dried flower buds of Daphne genkwa Sieb.et Zucc. It is used in traditional medicine for the treatment of cough, sore throats, edema. The study aimed to explore a new mathematical method for multivariate evaluation, investigate the anti-inflammatory and anti-angiogenic activities of flavonoids in Daphne Genkwa under ex vivo conditions. The flavonoids monomers in Daphne Genkwa were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS. An in vitro inflammatory model of macrophage RAW264.7 induced by LPS and an angiogenesis model of human umbilical vein endothelial cells induced by TNF-α were established. Flavonoids were extracted and prepared for intervention to detect the amount of secretion after drug intervention to reflect the anti-inflammatory and anti-angiogenic activities of each component. In addition, a new mathematical method, which combined principal component analysis and efficacy coefficient method, was adopted in pharmacodynamic evaluation. Fourteen flavonoids monomers were separated by preparative liquid chromatography and identified by HPLC-ESI-ITMS including H1 (hydroxygenkwanin-5-O-β-D-glucoside), H2 (apigenin-7-O-β-D-glucoside), H3 (kaempferol-3-O-β-D-glucoside), H4 (hydroxygenkwanin-5-O-β-D-primeveroside), H5 (apigenin-5-O-β-D-primeveroside), H6 (apigenin-7-O-β-D-glucuronide), H7 (luteolin-5-O-β-D-glucopyranoside), H8 (genkwain-5-O-β-D- glucoside), H9 (luteolin), H10 (Daphnodorin G), H11 (tiliroside), H12 (apigenin), H13 (3′- hydroxygenkwain) and H14 (genkwanin). We found that most of flavonoids down-regulated VCAM and MMP-3, while H1, H8, H9, H14 reduced VEGF and ICAM was only decreased by H14. Genkwanin may be the most active anti-rheumatoid arthritis flavonoids in Daphne genkwa. Meanwhile, the new mathematical method used in the study provided a new direction for solving the problem of multi-index pharmacodynamic evaluation. Image 1 [ABSTRACT FROM AUTHOR]

In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by 1H, 13C, and 11B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively. [ABSTRACT FROM AUTHOR]

This study aims at making full use of microbial resources, and screening the active endophytic fungi of anti-rheumatoid arthritis from Zanthoxylum simulans. The endophytic fungi were cultured and isolated by tissue culture and scribing method, and the active strain of inhibiting the proliferation of human rheumatoid arthritis synovial fibroblasts (HFLS-RA) was screened by MTT method. Morphological characteristics and rDNA ITS1-5.8S-ITS2 sequences were applied for the taxonomy of endophytic fungi. Strains were isolated from Z. simulans. Among them, MK-05, MK-17, MK-19, MK-23 having inhibiting activity to HFLS-RA, the IC₅₀ were 0.367, 0.775, 0.689, 0.757 g·L⁻¹, respectively. By classic morphologic classification and sequencing the PCR-amplified rDNA ITS1-5.8S-ITS2 regions, four effective strains were identified as Botryosphaeria dothidea, Phomopsis sp., P. liquidambari and Diaporthe perseae. The active endophyic fungi that inhibited the proliferation of HFLS-RA were screened from Z. simulans for the first time, and the results lay the foundation for the development and utilization of the Z. simulans resources., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)