Total triterpenes of Euphorbium alleviates rheumatoid arthritis via Nrf2/HO-1/GPX4 pathway / 中国中药杂志

This study aims to investigate the effect and mechanism of total triterpenes of Euphorbium in treating rheumatoid arthritis(RA). The rat model of RA was established with Freund's complete adjuvant(FCA). Male rats were randomly assigned into control, model, Tripterygium glycosides(7.5 mg·kg~(-1)), and low-, medium-, and high-dose total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1), respectively) groups, with 10 rats in each group. In other groups except the control group, 0.2 mL FCA was injected into the right hind toe. Rats in the intervention groups were administrated with corresponding drugs by gavage, and the control group and the model group with the same volume of 0.5% CMC-Na solution once a day. During the treatment period, the swelling degree of the hind paw was measured and the arthritis was scored until day 30. At the end of drug administration, the pathological changes of the joint tissue were observed by hematoxylin-eosin staining. The content of malondialdehyde(MDA), glutathione(GSH), and Fe~(2+) and the activity of superoxide dismutase(SOD) in the joint tissue were measured by biochemical colorimetry. RT-PCR was performed to determine the mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), and acyl-CoA synthetase long chain family member 4(ACSL4) in the joint tissue. Western blot was employed to determine the protein levels of Nrf2, Kelch-like ECH-associated protein 1(Keap1), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), SOD2, GPX4, and ACSL4 in the joint tissue. The results showed that the treatment with Tripterygium glycosides(7.5 mg·kg~(-1)) and total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1)) alleviated the swelling degree of bilateral hind limbs, decreased the arthritis score, reduced joint tissue lesions and the content of MDA and Fe~(2+) in the joint tissue, and increased GSH content and SOD activity. Furthermore, the interventions up-regulated the protein and mRNA levels of Nrf2 and GPX4, down-regulated the protein and mRNA levels of ACSL4, and up-regulated the protein levels of Keap1, NQO1, HO-1, and SOD2 in the Nrf2/HO-1/GPX4. In summary, the total triterpenes of Euphorbium can treat RA by inhibiting lipid peroxidation and abnormal ferroptosis, which may involve the Nrf2/HO-1/GPX4 signaling pathway.

Chemical constituents from Clausena excavata and their inhibitory activities against proliferation of synoviocytes / 中国中药杂志

The chemical constituents from the stems and leaves of Clausena excavata were isolated and purified by column chromatography with silica gel, ODS, Sephadex LH-20 and RP-HPLC. The chemical structures of the isolated compounds were identified on the basis of physicochemical properties, spectroscopic analysis, as well as the comparisons with the data reported in literature. Nineteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. excavata, which were identified as methyl orsellinate(1), syringaresinol(2), lenisin A(3), scopoletin(4), osthenol(5), N-benzoyltyrarnine methyl ether(6), N-p-coumaroyltyramine(7), aurantiamide acetate(8), 1H-indole-3-carboxaldehyde(9), furostifoline(10), clausenalansine E(11), 3-formylcarbazole(12), clausine L(13), clausine E(14), methyl carbazole-3-carboxylate(15), glycosinin(16), murrayafoline A(17), clausine H(18) and 2,7-dihydroxy-3-formyl-1-(3'-methyl-2'-butenyl)carbazole(19). Among these isolated compounds, compounds 1-11 were isolated from C. excavata for the first time, and compounds 1, 2 and 10 were isolated from the genus Clausena for the first time. In addition, this study evaluated the anti-rheumatoid arthritis activities of compounds 1-19 by measuring their anti-proliferative effects on synoviocytes in vitro according to MTS method. Compounds 10-19 displayed remarkable anti-rheumatoid arthritis activities, which exhibited the inhibitory effects on the proliferation of MH7 A synovial fibroblast cells with the IC_(50) values ranging from(27.63±0.18) to(235.67±2.16) μmol·L~(-1).

Anti-rheumatoid arthritis potential of diterpenoid fraction derived from Rhododendron molle fruits / 中国天然药物

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 mollefruits 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

Evaluating the quality of Miao medicine Periploca forrestii Schltr based on 6 caffeoylquinic acid components combined with stoichiometry / 中草药

Objective: To investigate the effects of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C in effective parts of rhizoma arthritis against rhizoma arthritis from different sources of Miao medicine Periploca forrestii Schltr. The determination of 6 kinds of caffeoacylquinic acid chemical components and comprehensive analysis of their quality combined with chemometrics provide a basis for a reasonable and effective evaluation of the efficacy of Miao Medicine Periploca forrestii Schltr against rheumatoid arthritis. Methods: Simultaneous determination was performed by HPLC-UV method. The column was Xtimate C18 (250 mm×4.6 mm, 5 μm), the mobile phase was 0.1% formic acid-acetonitrile, gradient elution, the injection volume was 10 μL, and the flow rate was 1 mL/min. The column temperature is 25 ℃ and the detection wavelength is 327 nm. SPSS24.0 and SIMCA14.1 software are used for comprehensive analysis and evaluation of the quality of medicinal materials. Results: The content of 21 batches of Periploca forrestii Schltr samples from different sources was determined. Through the cluster analysis, the 21 batches of samples were classified into type III, of which the quality of types II and III was better; principal component analysis and partial least squares discriminant analysis The results were consistent with the clustering results. The chlorogenic acid and isochlorogenic acid C were screened to be the markers that caused the differences in the quality of Periploca forrestii Schltr from different sources. Conclusion The determination of the contents of six caffeoacylquinic acid components combined with stoichiometry can further evaluate the efficacy and quality of the anti-rheumatoid arthritis effect of Periploca forrestii Schltr, and provide a reference basis for the quality control of Periploca forrestii Schltr.

Isolation of endophytic fungi from Zanthoxylum simulans and screening of its active strain / 中国中药杂志

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.