The aim of the present study was to investigate the anti-rheumatoid activity of secondary metabolites produced by endophytic mycobiota in Egypt. A total of 27 endophytic fungi were isolated from 10 dominant medicinal plant host species in Wadi Tala, Saint Katherine Protectorate, arid Sinai, Egypt. Of those taxa, seven isolates of Chaetomium globosum (CG1–CG7), being the most frequent taxon, were recovered from seven different host plants and screened for production of active anti-inflammatory metabolites. Isolates were cultivated on half – strength potato dextrose broth for 21 days at 28°C on a rotatory shaker at 180 rpm, and extracted in ethyl acetate and methanol, respectively. The probable inhibitory effects of both extracts against an adjuvant induced arthritis (AIA) rat model were examined and compared with the effects of methotrexate (MTX) as a standard disease-modifying anti-rheumatoid drug. Disease activity and mobility scoring of AIA, histopathology and transmission electron microscopy (TEM) were used to evaluate probable inhibitory roles. A significant reduction (P < 0.05) in the severity of arthritis was observed in both the methanolic extract of CG6 (MCG6) and MTX treatment groups 6 days after treatment commenced. The average arthritis score of the MCG6 treatment group was (10.7 ± 0.82) compared to (13.8 ± 0.98) in the positive control group. The mobility score of the MCG6 treatment group (1.50 ± 0.55) was significantly lower than that of the positive control group (3.33 ± 0.82). In contrast, the ethyl acetate extract of CG6 (EACG6) treatment group showed no improvements in arthritis and mobility scores in AIA model rats. Histopathology and TEM findings confirmed the observation. Isolate CG6 was subjected to sequencing for confirmation of phenotypic identification. The internal transcribed spacer (ITS) 1–5.8 s – ITS2 rDNA sequences obtained were compared with those deposited in the GenBank Database and registered with accession number KC811080 in the NCBI Database. The present study revealed that the methanol extract of endophytic fungus C. globosum (KC811080) recovered from maidenhair fern has an inhibitory effect on inflammation, histopathology and morphological features of rheumatoid arthritis in an AIA rat model.
BackgroundRheumatoid arthritis (RA) is an autoimmune disease that leads to chronic inflammation in the joints with subsequent cartilage and bone destruction. RA induces a massive burden on health services worldwide. Aim of the work This study was designed to evaluate the possible therapeutic effect of 'Chaetomium globosum' extract in the treatment of RA in a rat model.
Materials and methodsForty male Wistar albino rats aged 8-10 weeks were divided into four groups of 10 rats each. The control group (group I) was injected subcutaneously with 0.1 ml of saline. RA was induced in the other three groups (groups II, III, and IV) by single subcutaneous injection of 0.1 ml of complete Freund's adjuvant in the footpad of the right hind paw. Group II was induced with arthritis and left untreated. Rats in groups III and IV were treated by administering either C. globosum 10 µg/kg or methotrexate (MTX) 0.3 mg/kg subcutaneously twice weekly for 2 weeks from day 12 after induction of arthritis. Animals of all groups were sacrificed on day 28 from the start of the experiment. The ankle joints were processed and stained with H&E, Masson's trichrome, and immunohistochemical stain for inducible nitric oxide synthase. Specimens were also processed for transmission electron microscopic study.
ResultsUntreated arthritic rats revealed paw swelling, synovial hyperplasia, inflammatory infiltration, collagen accumulation, cartilage degradation, bone destruction, and significant increase in inducible nitric oxide synthase-positive chondrocytes. Transmission electron microscopic examination confirmed these results. The present study demonstrated for the first time that C. globosum significantly reduced all the clinical and histopathological changes of arthritis similar to MTX. Conclusion C. globosum extract had therapeutic effects similar to the well-established drug MTX and could be devoid of its serious side effects.
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