Emerging role of selenium in treatment of rheumatoid arthritis: An insight on its antioxidant properties.

Rheumatoid Arthritis is an inflammatory disease primarily involves the inflamed synovium, affecting about 0.5-1 % population worldwide. It is the assumption from many years that oxidative stress is involved in the pathophysiology of inflammatory disorders like RA and many others. The significance of micronutrients in arthritis is linked to their role as a cofactor for the activation of selenoenzymes. Dietary interventions can manage the clinical symptoms of RA like pain, swelling and tenderness of joints and their associated disability along the progression of disease. This review highlights the antioxidant potential of selenium in treatment of RA along with the scientific evidence that Se supplementation can reduce disease progression by managing its clinical symptoms.

Toxicological and Anti-Rheumatic Potential of Trachyspermum ammi Derived Biogenic Selenium Nanoparticles in Arthritic Balb/c Mice.

PURPOSE: The existing treatment modalities for rheumatoid arthritis are less effective and safe, therefore it is essential to develop new treatments that particularly target the inflamed joints with decreased off-target side-effects. The current study proposes a nanoparticle-based therapeutic approach to target the anti-oxidant defense system of arthritic Balb/c mice. METHODS: Biogenic selenium nanoparticles (SeNPs) were synthesized by using Trachyspermum ammi seed extract and were evaluated for their toxicological, as well as their therapeutic potential in collagen-induced arthritic mice. RESULTS: The tested doses of SeNPs had no significant toxic effects on liver, kidney, spleen, and serum biochemical parameters in comparison to healthy mice. The SeNPs treatment reduced the disease severity, as demonstrated by decreased paw edema along with reduced lymphocytic cellular infiltration in the histopathological findings. SeNPs also revealed dose-independent improvement in the redox state of inflamed synovium by significantly improving the activity of antioxidant enzymes in comparison to the arthritic controls. CONCLUSION: It is therefore concluded that nano-selenium in combination with TAE extract showed enhanced therapeutic efficacy as compared to their individual effects.

Therapeutic Potential Of Foeniculum vulgare Mill. Derived Selenium Nanoparticles In Arthritic Balb/c Mice.

PURPOSE: Rheumatoid arthritis is an inflammatory autoimmune multifactorial disorder that primarily affects the joints. Currently available treatment options, although effective, still present some side effects. This study proposes an alternative treatment option for rheumatoid arthritis through elucidation of therapeutic potential of Foeniculum vulgare Mill.-derived selenium nanoparticles in arthritic Balb/c mice. METHODS: Synthesis and characterization of selenium nanoparticles were followed by their toxicity analysis on healthy mice. Subsequently, anti-arthritic efficacy of two doses (5 mg/kg and 10 mg/kg) of synthesized selenium nanoparticles was checked on arthritic mice using multiple parameters. RESULTS: Selenium nanoparticles in 10 mg/kg dose turned out to be more effective in treatment of rheumatoid arthritis as evident by significant reduction in paw volume and normal clinical chemistry parameters of treated arthritic mice. This dose also showed significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. CONCLUSION: Foeniculum vulgare Mill.-derived selenium nanoparticles retain significant anti-arthritic and antioxidant potential and consequently can further be explored as an alternative treatment option for rheumatoid arthritis.

Tomorou attenuates progression of rheumatoid arthritis through alteration in ULK-1 independent autophagy pathway in collagen induced arthritis mice model.

Rheumatoid arthritis (RA) is a multifactorial disease which is complicated by apoptosis resistance. Autophagy is one of the key mechanisms which are involved in the development of resistance to apoptosis as well as to the standard therapies against RA. Aberration in autophagy and apoptosis homeostasis results in the development of oxidative stress thus complicates the pathogenesis of RA. In the given study, tomorou, an indigenous herb of Hunza-Nagar Valley, has been evaluated for its pro-apoptotic, anti-inflammatory, and anti-rheumatic activity. Several major classes of bioactive phytochemicals including steroids, terpenoids, phenols, flavonoids, and essential oils have been detected in the aqueous and ethyl acetate extracts of tomorou through phytochemical analysis. Plant extracts depicted enhanced free radical scavenging activity through di-phenyl-2-picryl hydrazyl hydrate (DPPH) assay and ameliorated the symptoms of arthritis in collagen induced arthritic (CIA) mice model. Moreover, the 6 week extract treatment resulted in the reduction of IL-6 serum levels thus making it an effective anti-inflammatory agent. Upregulation of microtubule-associated proteins light chain 3b (LC3b) and downregulation of UNC51-like kinase 1 (ULK-1) in arthritic mice proposed a ULK-1 independent non-canonical autophagy pathway. Treatment with extracts upregulated the expression of caspase 3 which in turn inhibited the activity of LC3b thus altering the autophagy pathway. However, ULK-1 expression was restored to normal in aqueous extract treated group whereas it was upregulated in ethyl acetate extract treated group. On the other hand, a novel LC3b-independent autophagy pathway was observed in mice treated with ethyl acetate extract due to ULK-1 upregulation. Despite of significantly high IL-6 levels, the arthritic symptoms waned off which suggested the participation of IL-6 in LC3b-independent autophagy pathway in the extract prepared in ethyl acetate. Conclusively, the study established pro-apoptotic, antioxidant, anti-inflammatory and anti-rheumatic activity of tomorou and suggested an intricate autophagy pathway shift.

Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen-induced arthritic BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum verum (CV), also known as 'Dalchini', is the dry bark of the Cinnamomum verum (L.) plant, and has been used as a traditional Pakistani medicine to alleviate pain and inflammation in patients suffering from arthritic rheumatism. It contains alkaloids, triterpenes, Cinnamaldehyde and other volatile oils. The aim of the present study was to investigate the underlying biological effect of ethyl alcohol (EtOH) and methyl alcohol (MeOH) extracts from CV on collagen type-II induced arthritic (CIA) mice. MATERIALS AND METHODS: Gas chromatography mass spectrophotometry was used to perform fingerprinting identification of the EtOH and MeOH extracts. CIA mice model was established by subdermal injections of type-II bovine collagen (CII) on the 1st, 8th and 14th day of the experiment. Ethyl alcohol extract and methyl alcohol extract (1 mg/KgBW, 2 mg/KgBW and 4 mg/KgBW), was orally administered from the 15th day onwards for 2 weeks. Progression of oedema and joint inflammation was measured in the paws using a digital Vernier calliper every 3 days from day 1 till the end of the experiment. The oxidative scavenging ability of cinnamaldehyde was evaluated using a DPPH assay. Similarly, the nitrogen free radical (NOS) production of isolated lymphocytes was evaluated using Greiss's method. The spleen index was calculated and knee joint changes were observed by histopathological sectioning. Western blot analysis was performed on peripheral blood derived serum for CII, CAPN1, TNFα and NFATc3. RESULTS: Extracts were shown to be enriched in trans-cinnamaldehyde and its analogues. Extracts showed good ameliorative effects (p < 0.05) after day 2 of treatment. A greater therapeutic role was observed for the 4 mg/kgBW dosage of the methanolic extract (p < 0.01). Swelling in the spleen was greatly reduced along with the generation of free radicals by lymphocytes, post treatment. There was also an inhibitory role by the extracts on NFATc3 (p < 0.05), TNF-Alpha (p < 0.05), CAII (p < 0.05) and mCalpain (p < 0.05) all proteins involved in RA. CONCLUSION: In this study, it has been demonstrated that administration of CV has a therapeutic potential on CIA. The data suggest that CV could have a potential role in the treatment of RA patients.