The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Irmgard Wiesenberg - One of the best experts on this subject based on the ideXlab platform.
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Specific Activation of the Nuclear Receptors PPARγ and RORA by the Antidiabetic Thiazolidinedione BRL 49653 and the Antiarthritic Thiazolidinedione Derivative CGP 52608
Molecular Pharmacology, 1998Co-Authors: Irmgard Wiesenberg, Martin Missbach, Michele Chiesi, Carsten Spanka, Werner Pignat, Carsten CarlbergAbstract:The thiazolidinedione BRL 49653 and the thiazolidinedione derivative CGP 52608 are lead compounds of two pharmacologically different classes of compounds. BRL 49653 is a high affinity ligand of peroxisome proliferator-activated receptor γ (PPARγ) and a prototype of novel antidiabetic agents, whereas CGP 52608 activates retinoic acid receptor-related orphan receptor α (RORA) and exhibits potent Antiarthritic Activity. Both receptors belong to the superfamily of nuclear receptors and are structurally related transcription factors. We tested BRL 49653 and CGP 52608 for receptor specificity on PPARγ, RORA, and retinoic acid receptor α, a closely related receptor to RORA, and compared their pharmacological properties in in vitro and in vivo models in which these compounds have shown typical effects. BRL 49653 specifically induced PPARγ-mediated gene activation, whereas CGP 52608 specifically activated RORA in transiently transfected cells. Both compounds were active in nanomolar concentrations. Leptin production in differentiated adipocytes was inhibited by nanomolar concentrations of BRL 49653 but not by CGP 52608. BRL 49653 antagonized weight loss, elevated blood glucose levels, and elevated plasma triglyceride levels in an in vivo model of glucocorticoid-induced insulin resistance in rats, whereas CGP 52608 exhibited steroid-like effects on triglyceride levels and body weight in this model. In contrast, potent Antiarthritic Activity in rat adjuvant arthritis was shown for CGP 52608, whereas BRL 49653 was nearly inactive. Our results support the concept that transcriptional control mechanisms via the nuclear receptors PPARγ and RORA are responsible at least in part for the different pharmacological properties of BRL 49653 and CGP 52608. Both compounds are prototypes of interesting novel therapeutic agents for the treatment of non-insulin-dependent diabetes mellitus and rheumatoid arthritis.
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thiazolidine diones specific ligands of the nuclear receptor retinoid z receptor retinoid acid receptor related orphan receptor α with potent Antiarthritic Activity
Journal of Biological Chemistry, 1996Co-Authors: Martin Missbach, Bruno Jagher, Ivo Sigg, Sepideh Nayeri, Carsten Carlberg, Irmgard WiesenbergAbstract:Abstract Rat adjuvant arthritis is a chronic T cell-dependent autoimmune disease with many similarities to rheumatoid arthritis. We have identified a class of thiazolidine diones with high potency in suppressing chronic inflammation and joint destruction in this experimental model. The lead compound CGP 52608 (1-(3-allyl-4-oxothiazolidine-2-ylidene)-4-methylthiosemicarbazone) exhibits Antiarthritic Activity at daily oral doses between 0.01 and 1 mg/kg and was shown to specifically activate the retinoid Z receptor/retinoid acid receptor-related orphan receptor α (RZR/RORα) in low nanomolar concentrations. This receptor is a novel member of the superfamily of ligand-inducible transcription factors, and we have recently identified the pineal gland hormone melatonin as a natural ligand. Structure-Activity relationship studies with 13 closely related analogues of CGP 52608 revealed a striking correlation between RZR/RORα activation and Antiarthritic Activity. We therefore suggest that nuclear signaling via RZR/RORα is a key mechanism in mediating the Antiarthritic effects of these thiazolidine diones and may open a novel therapeutic approach for the treatment of rheumatoid arthritis and other autoimmune diseases. The existence of a nuclear melatonin receptor may lead to a better understanding of the immunomodulatory actions of melatonin.
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Thiazolidine Diones, Specific Ligands of the Nuclear Receptor Retinoid Z Receptor/Retinoid Acid Receptor-related Orphan Receptor α with Potent Antiarthritic Activity
Journal of Biological Chemistry, 1996Co-Authors: Martin Missbach, Bruno Jagher, Ivo Sigg, Sepideh Nayeri, Carsten Carlberg, Irmgard WiesenbergAbstract:Abstract Rat adjuvant arthritis is a chronic T cell-dependent autoimmune disease with many similarities to rheumatoid arthritis. We have identified a class of thiazolidine diones with high potency in suppressing chronic inflammation and joint destruction in this experimental model. The lead compound CGP 52608 (1-(3-allyl-4-oxothiazolidine-2-ylidene)-4-methylthiosemicarbazone) exhibits Antiarthritic Activity at daily oral doses between 0.01 and 1 mg/kg and was shown to specifically activate the retinoid Z receptor/retinoid acid receptor-related orphan receptor α (RZR/RORα) in low nanomolar concentrations. This receptor is a novel member of the superfamily of ligand-inducible transcription factors, and we have recently identified the pineal gland hormone melatonin as a natural ligand. Structure-Activity relationship studies with 13 closely related analogues of CGP 52608 revealed a striking correlation between RZR/RORα activation and Antiarthritic Activity. We therefore suggest that nuclear signaling via RZR/RORα is a key mechanism in mediating the Antiarthritic effects of these thiazolidine diones and may open a novel therapeutic approach for the treatment of rheumatoid arthritis and other autoimmune diseases. The existence of a nuclear melatonin receptor may lead to a better understanding of the immunomodulatory actions of melatonin.
Martin Missbach - One of the best experts on this subject based on the ideXlab platform.
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Specific Activation of the Nuclear Receptors PPARγ and RORA by the Antidiabetic Thiazolidinedione BRL 49653 and the Antiarthritic Thiazolidinedione Derivative CGP 52608
Molecular Pharmacology, 1998Co-Authors: Irmgard Wiesenberg, Martin Missbach, Michele Chiesi, Carsten Spanka, Werner Pignat, Carsten CarlbergAbstract:The thiazolidinedione BRL 49653 and the thiazolidinedione derivative CGP 52608 are lead compounds of two pharmacologically different classes of compounds. BRL 49653 is a high affinity ligand of peroxisome proliferator-activated receptor γ (PPARγ) and a prototype of novel antidiabetic agents, whereas CGP 52608 activates retinoic acid receptor-related orphan receptor α (RORA) and exhibits potent Antiarthritic Activity. Both receptors belong to the superfamily of nuclear receptors and are structurally related transcription factors. We tested BRL 49653 and CGP 52608 for receptor specificity on PPARγ, RORA, and retinoic acid receptor α, a closely related receptor to RORA, and compared their pharmacological properties in in vitro and in vivo models in which these compounds have shown typical effects. BRL 49653 specifically induced PPARγ-mediated gene activation, whereas CGP 52608 specifically activated RORA in transiently transfected cells. Both compounds were active in nanomolar concentrations. Leptin production in differentiated adipocytes was inhibited by nanomolar concentrations of BRL 49653 but not by CGP 52608. BRL 49653 antagonized weight loss, elevated blood glucose levels, and elevated plasma triglyceride levels in an in vivo model of glucocorticoid-induced insulin resistance in rats, whereas CGP 52608 exhibited steroid-like effects on triglyceride levels and body weight in this model. In contrast, potent Antiarthritic Activity in rat adjuvant arthritis was shown for CGP 52608, whereas BRL 49653 was nearly inactive. Our results support the concept that transcriptional control mechanisms via the nuclear receptors PPARγ and RORA are responsible at least in part for the different pharmacological properties of BRL 49653 and CGP 52608. Both compounds are prototypes of interesting novel therapeutic agents for the treatment of non-insulin-dependent diabetes mellitus and rheumatoid arthritis.
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thiazolidine diones specific ligands of the nuclear receptor retinoid z receptor retinoid acid receptor related orphan receptor α with potent Antiarthritic Activity
Journal of Biological Chemistry, 1996Co-Authors: Martin Missbach, Bruno Jagher, Ivo Sigg, Sepideh Nayeri, Carsten Carlberg, Irmgard WiesenbergAbstract:Abstract Rat adjuvant arthritis is a chronic T cell-dependent autoimmune disease with many similarities to rheumatoid arthritis. We have identified a class of thiazolidine diones with high potency in suppressing chronic inflammation and joint destruction in this experimental model. The lead compound CGP 52608 (1-(3-allyl-4-oxothiazolidine-2-ylidene)-4-methylthiosemicarbazone) exhibits Antiarthritic Activity at daily oral doses between 0.01 and 1 mg/kg and was shown to specifically activate the retinoid Z receptor/retinoid acid receptor-related orphan receptor α (RZR/RORα) in low nanomolar concentrations. This receptor is a novel member of the superfamily of ligand-inducible transcription factors, and we have recently identified the pineal gland hormone melatonin as a natural ligand. Structure-Activity relationship studies with 13 closely related analogues of CGP 52608 revealed a striking correlation between RZR/RORα activation and Antiarthritic Activity. We therefore suggest that nuclear signaling via RZR/RORα is a key mechanism in mediating the Antiarthritic effects of these thiazolidine diones and may open a novel therapeutic approach for the treatment of rheumatoid arthritis and other autoimmune diseases. The existence of a nuclear melatonin receptor may lead to a better understanding of the immunomodulatory actions of melatonin.
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Thiazolidine Diones, Specific Ligands of the Nuclear Receptor Retinoid Z Receptor/Retinoid Acid Receptor-related Orphan Receptor α with Potent Antiarthritic Activity
Journal of Biological Chemistry, 1996Co-Authors: Martin Missbach, Bruno Jagher, Ivo Sigg, Sepideh Nayeri, Carsten Carlberg, Irmgard WiesenbergAbstract:Abstract Rat adjuvant arthritis is a chronic T cell-dependent autoimmune disease with many similarities to rheumatoid arthritis. We have identified a class of thiazolidine diones with high potency in suppressing chronic inflammation and joint destruction in this experimental model. The lead compound CGP 52608 (1-(3-allyl-4-oxothiazolidine-2-ylidene)-4-methylthiosemicarbazone) exhibits Antiarthritic Activity at daily oral doses between 0.01 and 1 mg/kg and was shown to specifically activate the retinoid Z receptor/retinoid acid receptor-related orphan receptor α (RZR/RORα) in low nanomolar concentrations. This receptor is a novel member of the superfamily of ligand-inducible transcription factors, and we have recently identified the pineal gland hormone melatonin as a natural ligand. Structure-Activity relationship studies with 13 closely related analogues of CGP 52608 revealed a striking correlation between RZR/RORα activation and Antiarthritic Activity. We therefore suggest that nuclear signaling via RZR/RORα is a key mechanism in mediating the Antiarthritic effects of these thiazolidine diones and may open a novel therapeutic approach for the treatment of rheumatoid arthritis and other autoimmune diseases. The existence of a nuclear melatonin receptor may lead to a better understanding of the immunomodulatory actions of melatonin.
Shashi Bhushan - One of the best experts on this subject based on the ideXlab platform.
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pyrano isochromanones as il 6 inhibitors synthesis in vitro and in vivo Antiarthritic Activity
Journal of Medicinal Chemistry, 2014Co-Authors: Shreyans K. Jain, Janhavi R. Nadkarni, Amarinder Singh, Prashant Joshi, Anamika Khajuria, Surjeet Singh, Sonali S. Bharate, Santosh Kumar Guru, Samdarshi Meena, Shashi BhushanAbstract:Bergenin (1), a unique fused C-glycoside isolated from Bergenia species, possesses interesting anti-inflammatory and antipain activities. To study SAR of this scaffold, first-generation derivatives were synthesized and evaluated for inhibition of lymphocyte proliferation and production of pro-inflammatory cytokines. The C-7 substituted derivatives showed inhibition of IL-6 as well as TNF-α production. Bergenin and its most potent IL-6 inhibitor derivatives 4e and 4f were then investigated in a panel of in vitro and in vivo inflammation/arthritis models. These compounds significantly decreased the expression of NF-kB and IKK-β in THP-1 cells. In in vivo study in BALB/c mice, a dose-dependent inhibition of SRBC-induced cytokines, reduction in humoral/cell-mediated immunity, and antibody titer was observed. The CIA study in DBA/1J mice indicated that compounds led to reduction in swelling of paws, cytokine levels, and anticollagen IgG1/IgG2a levels. The significant in vivo immunosuppressive efficacy of pyran...
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Pyrano-isochromanones as IL-6 inhibitors: Synthesis, in vitro and in vivo Antiarthritic Activity
Journal of Medicinal Chemistry, 2014Co-Authors: Shreyans K. Jain, Janhavi R. Nadkarni, Amarinder Singh, Prashant Joshi, Anamika Khajuria, Surjeet Singh, Sonali S. Bharate, Santosh Kumar Guru, Samdarshi Meena, Shashi BhushanAbstract:Bergenin (1), a unique fused C-glycoside isolated from Bergenia species, possesses interesting anti-inflammatory and antipain activities. To study SAR of this scaffold, first-generation derivatives were synthesized and evaluated for inhibition of lymphocyte proliferation and production of proinflammatory cytokines. The C-7 substituted derivatives showed inhibition of IL-6 as well as TNF-alpha production. Bergenin and its most potent IL-6 inhibitor derivatives 4e and 4f were then investigated in a panel of in vitro and in vivo inflammation/arthritis models. These compounds significantly decreased the expression of NF-kB and IKK-beta in THP-1 cells. In in vivo study in BALB/c mice, a dose-dependent inhibition of SRBC-induced cytokines, reduction in humoral/cell-mediated immunity, and antibody titer was observed. The CIA study in DBA/1J mice indicated that compounds led to reduction in swelling of paws, cytokine levels, and anticollagen IgG1/IgG2a levels. The significant in vivo immunosuppressive efficacy of pyrano-isochromanones demonstrates the promise of this scaffold for development of next-generation Antiarthritic drugs.
Carsten Carlberg - One of the best experts on this subject based on the ideXlab platform.
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Specific Activation of the Nuclear Receptors PPARγ and RORA by the Antidiabetic Thiazolidinedione BRL 49653 and the Antiarthritic Thiazolidinedione Derivative CGP 52608
Molecular Pharmacology, 1998Co-Authors: Irmgard Wiesenberg, Martin Missbach, Michele Chiesi, Carsten Spanka, Werner Pignat, Carsten CarlbergAbstract:The thiazolidinedione BRL 49653 and the thiazolidinedione derivative CGP 52608 are lead compounds of two pharmacologically different classes of compounds. BRL 49653 is a high affinity ligand of peroxisome proliferator-activated receptor γ (PPARγ) and a prototype of novel antidiabetic agents, whereas CGP 52608 activates retinoic acid receptor-related orphan receptor α (RORA) and exhibits potent Antiarthritic Activity. Both receptors belong to the superfamily of nuclear receptors and are structurally related transcription factors. We tested BRL 49653 and CGP 52608 for receptor specificity on PPARγ, RORA, and retinoic acid receptor α, a closely related receptor to RORA, and compared their pharmacological properties in in vitro and in vivo models in which these compounds have shown typical effects. BRL 49653 specifically induced PPARγ-mediated gene activation, whereas CGP 52608 specifically activated RORA in transiently transfected cells. Both compounds were active in nanomolar concentrations. Leptin production in differentiated adipocytes was inhibited by nanomolar concentrations of BRL 49653 but not by CGP 52608. BRL 49653 antagonized weight loss, elevated blood glucose levels, and elevated plasma triglyceride levels in an in vivo model of glucocorticoid-induced insulin resistance in rats, whereas CGP 52608 exhibited steroid-like effects on triglyceride levels and body weight in this model. In contrast, potent Antiarthritic Activity in rat adjuvant arthritis was shown for CGP 52608, whereas BRL 49653 was nearly inactive. Our results support the concept that transcriptional control mechanisms via the nuclear receptors PPARγ and RORA are responsible at least in part for the different pharmacological properties of BRL 49653 and CGP 52608. Both compounds are prototypes of interesting novel therapeutic agents for the treatment of non-insulin-dependent diabetes mellitus and rheumatoid arthritis.
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thiazolidine diones specific ligands of the nuclear receptor retinoid z receptor retinoid acid receptor related orphan receptor α with potent Antiarthritic Activity
Journal of Biological Chemistry, 1996Co-Authors: Martin Missbach, Bruno Jagher, Ivo Sigg, Sepideh Nayeri, Carsten Carlberg, Irmgard WiesenbergAbstract:Abstract Rat adjuvant arthritis is a chronic T cell-dependent autoimmune disease with many similarities to rheumatoid arthritis. We have identified a class of thiazolidine diones with high potency in suppressing chronic inflammation and joint destruction in this experimental model. The lead compound CGP 52608 (1-(3-allyl-4-oxothiazolidine-2-ylidene)-4-methylthiosemicarbazone) exhibits Antiarthritic Activity at daily oral doses between 0.01 and 1 mg/kg and was shown to specifically activate the retinoid Z receptor/retinoid acid receptor-related orphan receptor α (RZR/RORα) in low nanomolar concentrations. This receptor is a novel member of the superfamily of ligand-inducible transcription factors, and we have recently identified the pineal gland hormone melatonin as a natural ligand. Structure-Activity relationship studies with 13 closely related analogues of CGP 52608 revealed a striking correlation between RZR/RORα activation and Antiarthritic Activity. We therefore suggest that nuclear signaling via RZR/RORα is a key mechanism in mediating the Antiarthritic effects of these thiazolidine diones and may open a novel therapeutic approach for the treatment of rheumatoid arthritis and other autoimmune diseases. The existence of a nuclear melatonin receptor may lead to a better understanding of the immunomodulatory actions of melatonin.
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Thiazolidine Diones, Specific Ligands of the Nuclear Receptor Retinoid Z Receptor/Retinoid Acid Receptor-related Orphan Receptor α with Potent Antiarthritic Activity
Journal of Biological Chemistry, 1996Co-Authors: Martin Missbach, Bruno Jagher, Ivo Sigg, Sepideh Nayeri, Carsten Carlberg, Irmgard WiesenbergAbstract:Abstract Rat adjuvant arthritis is a chronic T cell-dependent autoimmune disease with many similarities to rheumatoid arthritis. We have identified a class of thiazolidine diones with high potency in suppressing chronic inflammation and joint destruction in this experimental model. The lead compound CGP 52608 (1-(3-allyl-4-oxothiazolidine-2-ylidene)-4-methylthiosemicarbazone) exhibits Antiarthritic Activity at daily oral doses between 0.01 and 1 mg/kg and was shown to specifically activate the retinoid Z receptor/retinoid acid receptor-related orphan receptor α (RZR/RORα) in low nanomolar concentrations. This receptor is a novel member of the superfamily of ligand-inducible transcription factors, and we have recently identified the pineal gland hormone melatonin as a natural ligand. Structure-Activity relationship studies with 13 closely related analogues of CGP 52608 revealed a striking correlation between RZR/RORα activation and Antiarthritic Activity. We therefore suggest that nuclear signaling via RZR/RORα is a key mechanism in mediating the Antiarthritic effects of these thiazolidine diones and may open a novel therapeutic approach for the treatment of rheumatoid arthritis and other autoimmune diseases. The existence of a nuclear melatonin receptor may lead to a better understanding of the immunomodulatory actions of melatonin.
Yashdeep Gupta - One of the best experts on this subject based on the ideXlab platform.
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anti inflammatory and Antiarthritic Activity of unim 301 a polyherbal unani formulation in wistar rats
Pharmacognosy Research, 2015Co-Authors: Surender Singh, Rohit Kumar, Hitesh Jain, Yashdeep GuptaAbstract:Background: UNIM-301 is a polyherbal formulation used in the Unani system of medicine for the treatment of joint pain and rheumatoid arthritis (RA). Objective: The objective was to evaluate the anti-inflammatory and Antiarthritic Activity of UNIM-301 in carrageenan-induced paw edema and complete Freund's Adjuvant (CFA) induced arthritis. Materials and Methods: The anti-inflammatory and Antiarthritic Activity of UNIM-301 was evaluated using carrageenan-induced paw edema and CFA induced animal arthritis models, respectively, in doses of 250, 500, and 1000 mg/kg body weight. Anti-inflammatory Activity of UNIM-301 was evaluated using carrageenan-induced paw edema model using a digital plethysmometer. Anti-arthritic Activity was evaluated using CFA induced arthritis, and joint sizes were measured at regular intervals using a micrometer screw gauge. Serum was collected and subjected to estimation of pro-inflammatory cytokine. Indomethacin 3 mg/kg body weight) was used as a standard drug in both the models. The acute and chronic toxicity study was carried out to evaluate the safety of the test drug. Results: UNIM-301 treatment produced a dose-dependent reduction in paw edema and paw thickness in carrageenan-induced paw edema and CFA-induced arthritis, respectively, as compared to control. UNIM 301 also reduced the expression of pro-inflammatory mediator in a dose-dependent manner as compared to control. Conclusion: The result of the present study suggests that anti-inflammatory and anti-arthritic Activity of UNIM-301, which might be accredited to inhibitory Activity on pro-inflammatory cytokines to its various individual constituents.
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Evaluation of disease modifying Activity of Coriandrum sativum in experimental models
Indian Journal of Medical Research, 2012Co-Authors: Vinod Nair, Surender Singh, Yashdeep GuptaAbstract:Background & objectives: Coriandrum sativum (CS), has been widely used in traditional systems of medicine for treatment of rheumatoid arthritis. However, the mechanism of action for its Antiarthritic effects is not clearly known. Therefore, the present study was carried out to evaluate the Antiarthritic Activity of CS in rats in two experimental models. Methods: The Antiarthritic Activity of CS seed hydroalcoholic extract (CSHE) was evaluated in adult Wistar rats by using two experimental models, viz . formaldehyde and Complete Freund's adjuvant (CFA) induced arthritis. The expression of pro-inflammatory cytokines (predominantly contributed by macrophages) was also evaluated. TNF- α level was estimated in serum by ELISA method. TNF-R1, IL-1 β and IL-6 expression in the synovium was analysed by immunohistochemistry. Results: CSHE produced a dose dependent inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA induced arthritis. Although there was a dose dependent increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control. Interpretation & conclusions: Our results demonstrate that the Antiarthritic Activity of CSHE may be attributed to the modulation of pro-inflammatory cytokines in the synovium. In further studies CSHE could be explored to be developed as a disease modifying agent in the treatment of RA.
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linseed oil an investigation of its Antiarthritic Activity in experimental models
Phytotherapy Research, 2012Co-Authors: Surender Singh, Vinod Nair, Yashdeep GuptaAbstract:Food sources rich in omega-3 fatty acids have been valued for their beneficial effect in the management of inflammatory disorders. The present study evaluates the Antiarthritic and immunomodulatory Activity of Linum usitatissimum fixed oil (LUFO) in experimental models. The LUFO produced a dose-dependent reduction in joint swelling and circulating TNF-α levels in both preventive and curative protocols of arthritis induced by complete Freund's adjuvant (CFA). Expression of TNF-R1 and Interleukin (IL) 6 proteins in the arthritic paw was also significantly reduced in the LUFO-treated animals. In the cotton pellet induced granuloma model, LUFO treatment significantly reduced the dry granuloma weight as compared with the control group. Results of our present study thus demonstrate the Antiarthritic and disease modifying Activity of LUFO. We believe that dietary incorporation of LUFO may be beneficial in the prevention and management of rheumatoid arthritis and other chronic inflammatory disorders. Copyright © 2011 John Wiley & Sons, Ltd.
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Antiarthritic Activity of majoon suranjan a polyherbal unani formulation in rat
Indian Journal of Medical Research, 2011Co-Authors: Surender Singh, Vinod Nair, Yashdeep GuptaAbstract:Background & objectives: Majoon Suranjan (MS) is a polyherbal formulation used in Unani system of medicine for the treatment of rheumatoid arthritis (RA). The present study evaluates the Antiarthritic efficacy of this formulation in three different experimental models. Methods: The anti-inflammatory Activity of MS (in doses of 450, 900 and 1800 mg/kg body wt) was evaluated using the turpentine oil induced paw oedema model and the Antiarthritic efficacy was evaluated using the formaldehyde and complete Freund's adjuvant (CFA) induced arthritis models. Aspirin (100 mg/kg body wt) was used as the standard drug in all the models. In order to assess the safety of the test drug, oral acute and 28 day toxicity studies were also carried out. Results: MS produced a dose dependent protective effect in all the experimental models. Its Antiarthritic efficacy was comparable to aspirin in formaldehyde induced arthritis and was superior to aspirin in turpentine oil induced paw oedema and CFA induced arthritis. MS also inhibited the delayed increase in joint diameter as seen in control and aspirin treated animals in CFA induced arthritis. Oral LD 50 of MS was found to be >5000 mg/kg in rats. Chronic administration did not produce any significant physiological changes in the tested animals. Interpretation & conclusions : Results of the present study suggest that the Antiarthritic Activity of MS was due to the interplay between its anti-inflammatory and disease modifying activities, thus supporting its use in traditional medicine for the treatment of RA.
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Evaluation of the disease modifying Activity of Colchicum luteum Baker in experimental arthritis
Journal of Ethnopharmacology, 2010Co-Authors: Vinod Nair, Surender Singh, Yashdeep GuptaAbstract:Abstract Ethnopharmacological relevance Colchicum luteum (CL) has been traditionally used in the Unani system of medicine as a chief ingredient of many polyherbal formulations for the treatment of joint pain and rheumatoid arthritis (RA). Aim of the study To evaluate the Antiarthritic Activity of CL hydroalcoholic extract (CLHE) in formaldehyde and complete Freund's adjuvant (CFA) induced arthritis. Materials and methods Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. Joint swelling was measured on days 8, 9 and 10 in formaldehyde induced arthritis and days 3, 7, 14 and 21 in CFA induced arthritis. In order to evaluate the effect of CLHE on disease progression, serum TNF-α level and synovial expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was determined in CFA induced arthritis. Results CLHE produced a significant and dose dependent inhibition of joint swelling during the entire duration of the study in both, formaldehyde and CFA induced arthritis. Serum TNF-α level was also reduced significantly in a dose dependent manner in all the CLHE treated groups. The expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1β) was also found to be less in the CLHE treated group as compared to control. Conclusion We believe that the Antiarthritic Activity of CLHE was due to its modulatory effect on the expression of proinflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of CL in the treatment of RA and other inflammatory joint disorders.
