Triterpenoid esters from Capparis erythrocarpos (Isert), Capparaceae, root bark ameliorates CFA-induced arthritis.

The root bark of Capparis erythrocarpos (CERB) is employed to treat rheumatoid arthritis (RA) in Africa, particularly in Ghana. However, there was no isolation and characterization of the bioactive constituents responsible for the pharmacological actions of this plant. The aim of this study is to isolate, characterize and evaluate the anti-arthritic activity of the constituents of CERB. CERB was soxhleted and partitioned into various fractions. The constituents were isolated using column chromatography and characterized by 1D and 2D NMR spectroscopy. The precise carboxylic acid residues of the esters were determined using saponification, derivatization and GC-MS analysis. Anti-arthritic activity was evaluated in the CFA-induced arthritic model. Two triterpenoid esters namely, sitosterol 3-hexadecanoate or sitosterol 3-palmatate (1) and sitosterol 3-tetradecanoate or sitosterol 3-myristate (2) in addition to beta sitosterol (3) were isolated and characterized. Compounds 1 and 2 administered at 3 µmol/kg (p.o.) produced anti-inflammatory activity (P < 0.0001) of 31.02 and 39.14% respectively, in addition to arthritic score index (P < 0.0001) of 1.600 ± 0.2449 and 1.400 ± 0.2449 against CFA-induced arthritis which are equivalent to those of the standard drug, diclofenac sodium (DS), 3 µmol/kg (p.o.), (30.79% anti-inflammatory activity and 1.800 ± 0.3742 arthritic score index). The compounds produced similar anti-inflammatory effects as DS. Also, radiographical and histopathological studies showed that, the compounds and DS protected against bone destruction, inflammatory cells invasion into interstitial spaces and synovial liner hyperplasia of the joints. This is the first study to report the characterization of the constituents of C. erythrocarpos in addition to anti-arthritic activity of sitosterol 3-palmatate and sitosterol 3-myristate. These results provide the missing link between the chemistry and the pharmacological activities of C. erythrocarpos. The isolates also offer a different class of molecule which could provide alternative treatment for RA.

Biosynthesis of Silver Nanoparticles Using Commiphora mukul Extract: Evaluation of Anti-Arthritic Activity in Adjuvant-Induced Arthritis Rat Model.

Rheumatoid arthritis (RA) is a major global public health challenge, and novel therapies are required to combat it. Silver nanoparticles (AgNPs) have been employed as delivery vehicles of anti-inflammatory drugs for RA therapy, and it has been recently realized that AgNPs have anti-inflammatory action on their own. However, their conventional synthesis processes might result in cytotoxicity and environmental hazards. Instead, the use of natural products as a reducing and stabilizing agent in the biosynthesis of silver nanoparticles has arisen as an option to decrease the cytotoxic and environmental concerns associated with chemical synthesis of AgNPs. In this study, we challenged the efficacy of Commiphora mukul (guggul) aqueous extract as a reducing and/or capping agent for the biosynthesis of AgNPs. Guggul-mediated biosynthesized silver nanoparticles (G-AgNPs) were characterized via UV-vis spectroscopy, dynamic light scattering, and scanning electron microscopy. In addition, their anti-arthritic potential was evaluated in an adjuvant-induced arthritis (AIA) model. The fabricated NPs showed an absorption peak at 412 nm, corresponding to the typical surface plasmon resonance band of AgNPs. The synthesized G-AgNPs were nearly spherical, with a particle size of 337.6 ± 12.1 nm and a negative surface charge (−18.9 ± 1.8 mV). In AIA rat model, synthesized G-AgNPs exerted a potent anti-inflammatory action, as manifested by a remarkable reduction in paw volume (>40%) along with elicitation of a minimal arthritic score, compared to control rats. In addition, when compared to arthritic rats, treatment with G-AgNPs efficiently restored the activity of antioxidant enzyme, superoxide dismutase, and catalase, indicating the efficiency of synthesized G-AgNPs in alleviating the oxidative stress associated with RA. Finally, histological examination revealed comparatively lower inflammatory cells infiltration in ankle joint tissue upon treatment with G-AgNPs. Collectively, biosynthesized G-AgNPs might represent a plausible therapeutic option for the management of RA.

Interferon gamma/interleukin-4 modulation, anti-inflammatory and antioxidant effects of hesperidin in complete Freund's adjuvant (CFA)-induced arthritis model of rats.

BACKGROUND: This study sought to assess the effect of hesperidin on serum inflammatory cytokines and oxidative damage in liver of complete Freund's adjuvant (CFA)-induced arthritic rats. METHOD: Fifty-six adult female Wistar rats (220-250 g) were acclimatized for two weeks. Intraplantar injection of CFA was done for the induction of arthritis and confirmed on the 14th day prior to oral administration of 40 and 80 mg/kg of hesperidin or dexamethasone for 45 days. RESULT: The result showed that treatment with both doses of hesperidin and dexamethasone in the joint of arthritic rats significantly (p < .05) diminished paw swelling/edema and arthritis score as well as enhanced latency in thermal hyperalgesia test. In addition, hesperidin treatment in arthritis rats showed significant (p < .01) improvement in red blood cells and platelets counts as well as hemoglobin and hematocrit compared to the arthritis control rat group. Furthermore, hesperidin treatment significantly (p < .05) reduced serum interferon gamma (IFN-γ) and interleukin-4 (IL-4) levels in arthritic rat. In addition, treatment with hesperidin significantly (p < .05) decreased the liver of thiobarbituric acid reactive species and reactive oxygen species levels but raised the levels of total and non-protein thiols of rat induced with CFA. The reduced activities of liver δ-aminolevulinate dehydratase, catalase, glutathione-S transferase in arthritic rats were significantly (p < .05) increased with hesperidin treatment in arthritic rats. This study suggests that hesperidin demonstrated an anti-arthritic effect via modulation of serum IFN-γ and IL-4 levels as well as protection against oxidative damage. CONCLUSION: Hence, hesperidin could be a potential immune-modulatory, anti-inflammatory and anti-oxidant agent.

Anti-inflammatory effects of the root, stem and leaf extracts of Chloranthus serratus on adjuvant-induced arthritis in rats.

Context: Chloranthus serratus [(Thunb.) Roem. et Schult, (Chloranthaceae)] is a folk medicine used for the treatment of rheumatoid arthritis.Objective: The aim of this study was to investigate anti-arthritic effects of the ethanol extracts of the roots (ER), stems (ES) and leaves (EL) of C. serratus on adjuvant arthritis rats and related mechanisms.Materials and methods: The rats were immunized by intradermal injection of complete Freund's adjuvant (CFA, 0.18 mL) into the right hind feet, and received intragastric administrations of the ER, ES and EL (2.07, 1.61 and 0.58 g/kg/d, respectively) for 14 days. The anti-arthritic activity was assessed by swelling rates, serum indicators, antioxidant capacity, histopathological and immunohistochemical analyses.Results: The LD50 of the ER, ES and EL was higher than 10.35, 8.05 and 2.90 g/kg/p.o., respectively. Extract treatments decreased swelling rates, tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), interleukin 1 beta (IL-1ß), migration inhibitory factor 1 (MIF-1), immunoglobulin G (IgG) and immunoglobulin M (IgM) levels and positive expression of VEGF in the arthritic rats (p < 0.01 or p < 0.05). The ER significantly decreased NO (3.91 ± 0.61 µmol/L), IL-6 (75.67 ± 16.83 pg/mL) and malondialdehyde (MDA) (2.28 ± 0.32 nmol/mL) contents and clearly increased IFN-γ (2082 ± 220.93 pg/mL) and superoxide dismutase (SOD) (601.98 ± 38.40 U/mL) levels. The ES and EL did not reverse the changes in some indicators. All the extracts alleviated inflammatory cell infiltration and synovial cell proliferation. Among them, the ER was the most pronounced.Discussion and conclusions: ER exerts the most promising effects, as shown by inhibiting the releases of inflammatory cytokines and enhancing antioxidant capacity, which provides a scientific basis for further research on C. serratus and its clinical applications.

Polystichum braunii extracts inhibit Complete Freund's adjuvant-induced arthritis via upregulation of I-κB, IL-4, and IL-10, downregulation of COX-2, PGE2, IL-1ß, IL-6, NF-κB, and TNF-α, and subsiding oxidative stress.

Polystichum braunii (Spenn.) Fée is a traditional remedy for rheumatoid arthritis, a chronic inflammatory disorder of polygenetic origin. The current project was intended to demonstrate the role of inflammatory and oxidative stress biomarkers in the anti-arthritic activity of the P. braunii extracts. Methanolic and aqueous extracts of the plant roots were prepared by triple maceration. The phytochemical evaluation of the plant extracts was carried out by high-performance liquid chromatography (HPLC). The plant extracts at 150, 300, and 600 mg/kg/day and piroxicam (10 mg/kg/day) were orally administered to Wistar rats for 21 days that were previously immunized with Complete Freund's adjuvant (150 µl on right hind paw) except normal and arthritic control rats. Both plant extracts mitigated the paw oedema, restored the immune organ and body weights, and ameliorated the level of blood parameters such as haemoglobin, red blood cells, platelets, white blood cells, alkaline phosphatase (ALP), C-reactive proteins, and rheumatoid factor. The evaluation of gene expression using quantitative-real-time polymerase chain reaction (qRT-PCR) revealed the substantial downregulation of tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-1ß, cyclo-oxygenase (COX)-2, nuclear factor (NF)-κB, and upregulation of IL-4, IL-10 and I-κB in polyarthritic rats treated with the plant extracts. Methanolic plant extract exhibited the maximum effect on upregulation of IL-4 (79 ± 3%), IL-10 (62.66 ± 4.93%), and I-κB (73.66 ± 3.05%) at 600 mg/kg/day. Treatment with the plant extracts also reduced the level of prostaglandin E2 and TNF-α in the serum of arthritic rats' dose dependently. It was also found that the plant extracts and piroxicam increased (p < 0.05) the activities of superoxide dismutase and catalase in the liver tissue while reduced the level of malondialdehyde in arthritic rats. Histological examination of ankle joints revealed that the plant extracts decreased the pannus formation, inflammation, and synovial hyperplasia in arthritic animals. HPLC analysis depicted that the plant extracts had contained kaempferol, quercetin, gallic acid, and other phenolic acids. It can be elucidated from the results that the extracts of P. braunii roots exhibited anti-arthritic activity in Wistar rats through modulation of inflammatory cytokines and boosting the antioxidant defense mechanism.

Amelioration of adjuvant induced arthritis in Sprague Dawley rats through modulation of inflammatory mediators by Ribes alpestre Decne.

ETHNOPHARMACOLOGICAL RELEVANCE: Ribes alpestre Decne has been commonly used in the treatment of joint complaints. AIM OF STUDY: The present study was undertaken to evaluate the antiarthritic potential of ethanolic extract and fractions of Ribes alpestre and to explore its probable mechanism of action. MATERIAL AND METHODS: Complete Freunds adjuvant induced arthritis in Sprague Dawley rats was used to assess antiarthritic activity of aqueous ethanol extract, butanol and aqueous fractions at 200 mg/kg oral dose for 28 days. Paw volume and diameter, arthritic index, body weight, hematological and biochemical parameters, radiographic and histological analysis of ankle joints were carried out. An array of pro-inflammatory mediators (IL-1ß, IL-6, NF-Kß, TNF-α, COX-2, IL-4, IL-10 and PGE2) were estimated by RT-PCR and enzyme linked immunosorbent assay. Antioxidant capacity was assessed using DPPH and reducing power assays. Qualitative phytochemical screening, total phenolic and flavonoid content and HPLC analysis of aqueous fraction of Ribes alpestre were also carried out. RESULTS: Significant (p < 0.001) reduction in paw volume and thickness and arthritic score by aqueous ethanolic extract and its fractions has been found. Aqueous ethanolic extract and fractions in particular aqueous fraction considerably prevented decrease in body weight, alterations in hematological parameters. Radiographic and histological examination revealed no significant architectural changes in joints of treated rats. Significant (p < 0.05-0.001) down regulation of pro-inflammatory genes IL-1ß, TNF-α, IL-6, COX-2, PGE2 and NF-Kß alongwith noteworthy increase in levels of IL-4 and IL-10 was recorded among treated animals. Aqueous ethanol extract and its fractions demonstrated notable and concentration dependent (50-6400 µg/ml) antioxidant potential. Qualitative phytochemical analysis of active fraction (aqueous) displayed presence of flavonoids, alkaloids, tannins and glycosides. Besides total phenolic and flavonoid contents has been found to be 179.3 mg GAE/ml and 389.40 µg QE/ml in aqueous fraction of Ribes alpestre respectively. HPLC profile demonstrated presence of quercitin, chlorogenic acid, vanillic acid and cinamic acid in aqueous fraction. CONCLUSION: Present communication suggests Ribes alpestre a potent antiarthritic therapy by ameliorating adjuvant arthritis in rats by downregulating proinflammatory mediators with up regulation of anti-inflammatory cytokines.

Rutin and rutin-conjugated gold nanoparticles ameliorate collagen-induced arthritis in rats through inhibition of NF-κB and iNOS activation.

Numerous studies have suggested that nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) are important mediators of inflammatory response in human and animal models of arthritis. Besides, oxidative stress markers, nitric oxide (NO) and peroxide (PO) are also major contributors in the pathogenesis of rheumatoid arthritis (RA). Over expression of these inflammatory mediators leads to the extracellular matrix degradation, and excessive cartilage and bone resorption, ultimately leading to the irreversible damage to joints. The aim of the present study was to investigate the anti-arthritic mechanism of bioflavonoids, rutin and rutin-conjugated gold nanoparticles (R-AuNPs) by determining their role in the modulation of NF-κB and iNOS expression in collagen-induced arthritis (CIA) model of rats. Arthritis was induced by the subcutaneous administration of bovine type II collagen. Treatment was started with rutin, indomethacin + rutin (I + R) and R-AuNPs on the day of CIA induction. The severity of arthritis was determined by measuring the arthritic score on alternate days until mean arthritic score of 4 was observed. The NO and PO levels were also analyzed in serum samples. NF-κB and iNOS expression levels were determined in spleen tissue samples by real time RT-PCR and immunohistochemistry. Marked reduction in the arthritic score as well as in the NO and PO levels was observed in the treated groups. A significant downregulation in the NF-κB and iNOS expression levels was also observed in the treatment groups compared to the arthritic control group. Collectively, the findings suggest potential clinical role of rutin and R-AuNPs in the treatment of rheumatoid arthritis.