Targeting Some Key Metalloproteinases by Nano-Naringenin and <i>Amphora coffeaeformis</i> as a Novel Strategy for Treatment of Osteoarthritis in Rats

Osteoarthritis (OA) represents the highest degenerative disorder. Because cartilage erosion is a common pathological alteration in OA, targeting some key metalloproteinases such as MMP-3, ADAMTS-5 besides their inhibitor TIMP-3 by natural products, could be an effective strategy to protect against osteoarthritis. Forty female Wister rats were categorized into five equal groups. Control, osteoarthritic (OA) (monosodium iodoacetate (MIA) 2 mg/50 µL saline, single intra-articular injection), OA+ indomethacin (2 mg/kg/daily/orally), OA+ nano-naringenin (25 mg/kg/daily/orally), and OA+ Amphora coffeaeformis (772 mg/kg/daily/orally). Treatments were initiated on the 8th day after osteoarthritis induction and continued for 28 days thereafter. Finally, blood and knee joint samples were collected from all rats for biochemical and histopathological evaluations. The current study showed that MIA induced oxidative stress, which resulted in changes in the inflammatory joint markers associated with increased right knee diameter and higher clinical scores for lameness. Amphora coffeaeformis followed by nano-naringenin exhibited a potential anti-arthritic activity by reducing the concentrations of serum MMP-3, ADAMTS-5, and joint MDA and increasing the levels of serum TIMP-3 and joint GSH, similar to indomethacin. The histopathological results confirmed these outcomes. In conclusion, Amphora coffeaeformis and nano-naringenin can be considered as natural therapeutic agents for osteoarthritis owing to their antioxidant and anti-inflammatory activities

Therapeutic Potential of Zeolites/Vitamin B12 Nanocomposite on Complete Freunds Adjuvant-Induced Arthritis as a Bone Disorder: In Vivo Study and Bio-Molecular Investigations

Rheumatoid arthritis (RA) is a long-term autoimmune disease. As nanotechnology has advanced, a growing number of nanodrugs have been used in the treatment of RA due to their unique physical and chemical properties. The purpose of this study was to assess the therapeutic potential of a novel zeolite/vitamin B12 nanocomposite (Nano ZT/Vit B12) formulation in complete Freunds adjuvant (CFA)-induced arthritis. The newly synthesized Nano ZT/Vit B12 was fully characterized using various techniques such as XRD, FT-IR, BET analysis, HERTEM, SEM, practical size, zeta potential, XRF, and EDX. The anti-arthritic, anti-inflammatory, and antioxidant activities as well as the immunomodulation effect of Nano ZT/Vit B12 on the CFA rat model of arthritis were examined. Histopathologic ankle joint injuries caused by CFA intrapedal injection included synovium hyperplasia, inflammatory cell infiltration, and extensive cartilage deterioration. The arthritic rats Nano ZT/Vit B12 supplementation significantly improved these effects. Furthermore, in arthritic rats, Nano ZT/Vit B12 significantly reduced serum levels of RF and CRP, as well as the levels of IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, while increasing IL-4 and TIMP-3 levels. Nano-ZT/Vit B12 significantly declined the LPO level and increased antioxidant activities, such as GSH content and GST activity, in the arthritic rats. In arthritic rats, Nano ZT/Vit B12 also reduced TGF-beta mRNA gene expression and MMP-13 protein levels. Collectively, Nano ZT/Vit B12 seems to have anti-arthritic, anti-inflammatory, and antioxidant properties, making it a promising option for RA in the future.Funding Agencies|King Salman Center for Disability Research [KSRG-2022-047]</p

Targeting Some Key Metalloproteinases by Nano-Naringenin and Amphora coffeaeformis as a Novel Strategy for Treatment of Osteoarthritis in Rats

Osteoarthritis (OA) represents the highest degenerative disorder. Because cartilage erosion is a common pathological alteration in OA, targeting some key metalloproteinases such as MMP-3, ADAMTS-5 besides their inhibitor TIMP-3 by natural products, could be an effective strategy to protect against osteoarthritis. Forty female Wister rats were categorized into five equal groups. Control, osteoarthritic (OA) (monosodium iodoacetate (MIA) 2 mg/50 µL saline, single intra-articular injection), OA+ indomethacin (2 mg/kg/daily/orally), OA+ nano-naringenin (25 mg/kg/daily/orally), and OA+ Amphora coffeaeformis (772 mg/kg/daily/orally). Treatments were initiated on the 8th day after osteoarthritis induction and continued for 28 days thereafter. Finally, blood and knee joint samples were collected from all rats for biochemical and histopathological evaluations. The current study showed that MIA induced oxidative stress, which resulted in changes in the inflammatory joint markers associated with increased right knee diameter and higher clinical scores for lameness. Amphora coffeaeformis followed by nano-naringenin exhibited a potential anti-arthritic activity by reducing the concentrations of serum MMP-3, ADAMTS-5, and joint MDA and increasing the levels of serum TIMP-3 and joint GSH, similar to indomethacin. The histopathological results confirmed these outcomes. In conclusion, Amphora coffeaeformis and nano-naringenin can be considered as natural therapeutic agents for osteoarthritis owing to their antioxidant and anti-inflammatory activities

A Novel Hydroxyapatite/Vitamin B-12 Nanoformula for Treatment of Bone Damage: Preparation, Characterization, and Anti-Arthritic, Anti-Inflammatory, and Antioxidant Activities in Chemically Induced Arthritic Rats

The usage of nanomaterials for rheumatoid arthritis (RA) treatment can improve bioavailability and enable selective targeting. The current study prepares and evaluates the in vivo biological effects of a novel hydroxyapatite/vitamin B-12 nanoformula in Complete Freunds adjuvant-induced arthritis in rats. The synthesized nanoformula was characterized using XRD, FTIR, BET analysis, HERTEM, SEM, particle size, and zeta potential. We synthesized pure HAP NPs with 71.01% loading weight percentages of Vit B12 and 49 mg/g loading capacity. Loading of vitamin B-12 on hydroxyapatite was modeled by Monte Carlo simulation. Anti-arthritic, anti-inflammatory, and antioxidant effects of the prepared nanoformula were assessed. Treated arthritic rats showed lower levels of RF and CRP, IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, but higher IL-4 and TIMP-3 levels. In addition, the prepared nanoformula increased GSH content and GST antioxidant activity while decreasing LPO levels. Furthermore, it reduced the expression of TGF-beta mRNA. Histopathological examinations revealed an improvement in joint injuries through the reduction of inflammatory cell infiltration, cartilage deterioration, and bone damage caused by Complete Freunds adjuvant. These findings indicate that the anti-arthritic, antioxidant, and anti-inflammatory properties of the prepared nanoformula could be useful for the development of new anti-arthritic treatments.Funding Agencies|King Salman Center for Disability Research [KSRG-2022-047]</p

A Novel Hydroxyapatite/Vitamin B₁₂ Nanoformula for Treatment of Bone Damage: Preparation, Characterization, and Anti-Arthritic, Anti-Inflammatory, and Antioxidant Activities in Chemically Induced Arthritic Rats

The usage of nanomaterials for rheumatoid arthritis (RA) treatment can improve bioavailability and enable selective targeting. The current study prepares and evaluates the in vivo biological effects of a novel hydroxyapatite/vitamin B12 nanoformula in Complete Freund’s adjuvant-induced arthritis in rats. The synthesized nanoformula was characterized using XRD, FTIR, BET analysis, HERTEM, SEM, particle size, and zeta potential. We synthesized pure HAP NPs with 71.01% loading weight percentages of Vit B12 and 49 mg/g loading capacity. Loading of vitamin B12 on hydroxyapatite was modeled by Monte Carlo simulation. Anti-arthritic, anti-inflammatory, and antioxidant effects of the prepared nanoformula were assessed. Treated arthritic rats showed lower levels of RF and CRP, IL-1β, TNF-α, IL-17, and ADAMTS-5, but higher IL-4 and TIMP-3 levels. In addition, the prepared nanoformula increased GSH content and GST antioxidant activity while decreasing LPO levels. Furthermore, it reduced the expression of TGF-β mRNA. Histopathological examinations revealed an improvement in joint injuries through the reduction of inflammatory cell infiltration, cartilage deterioration, and bone damage caused by Complete Freund’s adjuvant. These findings indicate that the anti-arthritic, antioxidant, and anti-inflammatory properties of the prepared nanoformula could be useful for the development of new anti-arthritic treatments