Amelioration of adjuvant induced arthritis in Sprague Dawley rats through modulation of inflammatory mediators by Ribes alpestre Decne.
Ribes alpestre Decne has been commonly used in the treatment of joint complaints.
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.
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-1β, IL-6, NF-Kβ, 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.
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-1β, TNF-α, IL-6, COX-2, PGE2 and NF-Kβ 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.
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.
Hassan UH
，Alamgeer
，Shahzad M
，Shabbir A
，Jahan S
，Saleem M
，Bukhari IA
，Assiri AM
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Launaea fragilis extract attenuated arthritis in rats through modulation of IL-1β, TNF-α, IL-6, NF-κB, COX-2, IL-4, and IL-10.
Launaea fragilis (Asso) Pau is a Cholistan desert medicinal plant. Launaea species are used as traditional remedies against various inflammatory conditions. The current research was designed to evaluate the anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of L. fragilis (Et-LF). The plant extract was prepared by triple maceration. GC-MS screening explored the presence of various bioactive phytoconstituents including n-tetracosanol-1, 1-heptacosanol, and n-hexadecanoic acid. DPPH assay demonstrated the antioxidant potential of Et-LF. Safety profile data indicated that Et-LF was safe up to the oral dose of 5000 mg/kg in female rats. Anti-nociceptive activity of Et-LF was assessed in hot plate method and acetic acid-induced writhing model and the results suggested that Et-LF had significant analgesic effects in both animal models. Carrageenan, histamine, and serotonin-induced edema models were used to estimate the anti-inflammatory effects of Et-LF and were found to prevent paw edema development dose dependently. The anti-arthritic effect of Et-LF was estimated in CFA-induced arthritic rat model. Treatment with Et-LF 125, 250, 500 and flurbiprofen (FP) 10 mg/kg/day significantly attenuated the paw edema, reversed the reduced body weight, and restored the altered hematological parameters in arthritic rats. Gene expression studies revealed the significant downregulation of IL-1β, TNF-α, IL-6, NF‑κB, and COX-2, and upregulation of IL-4 and IL-10 in arthritic rats treated with various doses of plant extract. Histological evaluation of ankle joints showed that Et-LF mitigated pannus formation, infiltration of inflammatory cells, and fibrous connective tissue formation in the diseased rats. Thereof, it may be concluded that the recent study demonstrated the anti-nociceptive, anti-inflammatory, and anti-arthritic effects ascribed to the signifying presence of phytoconstituents in L. fragilis.
Fiaz M
，Asif M
，Khan KUR
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Ephedra gerardiana aqueous ethanolic extract and fractions attenuate Freund Complete Adjuvant induced arthritis in Sprague Dawley rats by downregulating PGE2, COX2, IL-1β, IL-6, TNF-α, NF-kB and upregulating IL-4 and IL-10.
The whole plant, roots and stems of Ephedra gerardiana (Family Ephedraceae) have long been used as a folk remedy to treat rheumatism and painful joints in Northern Areas of Pakistan.
The purpose of study was to observe the preventive efficacy of Ephedra gerardiana (EG) aerial parts in treating rheumatoid arthritis using Freund's complete adjuvant (FCA) induced arthritis in rat model and to determine its possible mechanism of action.
Arthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. EG aqueous ethanolic extract (30:70) and its aqueous, n-butanol and ethyl acetate fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1β, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) while, PGE2 and TNF-α levels in serum samples were measured by Enzyme linked immunosorbent assay (ELISA). Moreover, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. In addition, anti-oxidant activity of plant extract and fractions was also evaluated using DPPH and reducing power assays. Also, preliminary phytochemistry and total phenolic and flavonoid contents were investigated in most active fraction (aqueous fraction).
EG extract and fractions (notably aqueous fraction) significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, the overproduction of PGE2, COX-2, IL-1β, IL-6, NF-kB and TNF-α were remarkably attenuated in all EG treated rats, however, IL-4 and 10 were markedly increased. The radiographic and histopathologic improvement in joint architecture was also observed in EG treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols, tannins, saponins and glycosides.
These results indicate that EG extract and fractions significantly attenuated adjuvant arthritis in rats by decreasing the levels of aforementioned pro-inflammatory and increasing the levels of anti-inflammatory mediators. This suggests that Ephedra gerardiana aerial parts might be used as a therapeutic agent for treating human arthritis.
Uttra AM
，Alamgeer
，Shahzad M
，Shabbir A
，Jahan S
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