Morus mesozygia leaf extract ameliorates behavioral deficits, oxidative stress and inflammation in Complete Freund’s adjuvant-induced arthritis in rats

Ariyo, Oluwakemi O.; Ajayi, Abayomi Mayowa; Ben‐Azu, Benneth; Aderibigbe, Adegbuyi Oladele

doi:10.1016/j.jep.2022.115202

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…In the present study, FCA-induced inflammation resulted in a notable upregulation of the pro-inflammatory factor NFkB, accompanied by a notable downregulation of its inhibitor, IkB. These findings are consistent with a previous investigation conducted on the same model that similarly reported a significant increase in NFkB levels and a concurrent decrease in IKB ( Saleem et al, 2020 ; Ariyo et al, 2022 ). We also showed that the administration of TMZ or MTX significantly decreased the level of NFkB together with a considerable increase in IkB levels, with the best results produced by the combination of both drugs ( Figure 9 ).…”

Section: Discussionsupporting

confidence: 93%

“…We also showed that the administration of TMZ or MTX significantly decreased the level of NFkB together with a considerable increase in IkB levels, with the best results produced by the combination of both drugs ( Figure 9 ). These results are consistent with previously reported studies that showed that the antiarthritic effects of various plant extracts, including Morus mesozygia leaf, Moringa leaf, difengpienol, plumbagin, Chinese herbal Huayu Qiangshen-Tongbi and Kashayams, are associated with their ability to reduce NFκB levels while increasing IκB expression in an RA rat model ( Saleem et al, 2020 ; Aswathy et al, 2021 ; Ariyo et al, 2022 ; Chen et al, 2022 ; Martin et al, 2022 ; Shu et al, 2022 ).…”

Section: Discussionsupporting

confidence: 93%

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Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study

Omran,

Alzahrani,

Ezzat

et al. 2024

Front. Pharmacol.

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Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund’s complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study

Omran,

Alzahrani,

Ezzat

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…In the present study, FCA-induced inflammation resulted in a notable upregulation of the proinflammatory factor NFkB, accompanied by a notable downregulation of its inhibitor, IkB. These findings are consistent with a previous investigation conducted on the same model that similarly reported a significant increase in NFkB levels and a concurrent decrease in IKB (Saleem et al, 2020;Ariyo et al, 2022). We also showed that the administration of TMZ or MTX significantly decreased the level of NFkB together with a considerable increase in IkB levels, with the best results produced by the combination of both drugs (Figure 9).…”

Section: Discussionsupporting

confidence: 93%

“…We also showed that the administration of TMZ or MTX significantly decreased the level of NFkB together with a considerable increase in IkB levels, with the best results produced by the combination of both drugs (Figure 9). These results are consistent with previously reported studies that showed that the antiarthritic effects of various plant extracts, including Morus mesozygia leaf, Moringa leaf, difengpienol, plumbagin, Chinese herbal Huayu Qiangshen-Tongbi and Kashayams, are associated with their ability to reduce NFκB levels while increasing IκB expression in an RA rat model (Saleem et al, 2020;Aswathy et al, 2021;Ariyo et al, 2022;Chen et al, 2022;Martin et al, 2022;Shu et al, 2022).…”

Section: Discussionsupporting

confidence: 92%