Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhein, an active metabolite of diacerein, down-regulates the gene-expression and production of pro-matrix metalloproteinases and up-regulates the tissue inhibitors of metalloproteinase-1 production. The therapeutic effects of diacerein on osteoarthritis are, at least in part, due to the chondroprotective effect of rhein. Boswellic acid is a specific, non-redox inhibitor of leukotriene synthesis. It is claimed to possess good anti-inflammatory, anti-arthritic, analgesic, and anti-ulcer activities. It prevents the destruction of articular cartilage by decreasing degradation of glycosaminoglycans. Therefore, rhein and boswellic acid were linked chemically through a bioreversible ester linkage to synthesize their mutual prodrug by reported procedure. In vitro release profile of this prodrug was extensively studied in aqueous buffers of varied pH, upper GIT homogenates and 80% human plasma. In vivo release studies were undertaken in blood, urine and feces of rats. The prodrug was stable in HCl buffer (pH 1.2) and stomach homogenates of rats. However; in phosphate buffer (pH 7.4) and in intestinal homogenates the prodrug exhibited 91% and 96% release of rhein and 27.5% and 38% release of boswellic acid respectively over a period of 6h following first order kinetics. In 80% human plasma (in vitro) and rat blood (in vivo) also 96.35% and 91% release of rhein and 78% and 86.41% release of boswellic acid respectively was observed. The 24 h pooled samples of rat urine revealed presence of 6.2% intact prodrug, 7.1% of rhein and 8.9% of boswellic acid indicating their renal excretion. Samples of rat feces pooled over a period of 24 h showed absence of rhein and presence of 3.1% of intact boswellic acid and 4.6% of boswellic acid emphasizing their intestinal excretion. The in vivo release kinetics of prodrug in rat clearly indicated activation of prodrug to be occurring in blood, being catalyzed by the weak alkaline pH of blood (7.4) in combination with esterases present therein.
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PMID:Synthesis and pharmacokinetic profile of rhein- boswellic acid conjugate. 2310 83

Diacerein and its active metabolite rhein are promising disease modifying agents for osteoarthritis (OA). Boswellic acid is an active ingredient of Gugglu; a herbal medicine commonly administered in osteoarthritis. Both of them possess excellent anti-inflammatory and anti-arthritic activities. It was thought interesting to conjugate rhein and boswellic acid into a mutual prodrug (DSRB) and evaluate its efficacy on collagenase-induced osteoarthritis in rats wherein the conjugate, rhein, boswellic acid and their physical mixture, were tested based on various parameters. Oral administration of 3.85 mg of rhein, 12.36 mg of boswellic acid and 15.73 mg of DSRB which would release equimolar amounts of rhein and boswellic acid, exhibited significant restoration in rat body weight as compared to the untreated arthritic control group. Increase in knee diameter (mm), due to edema was observed in group injected with collagenase, which reduced significantly with the treatment of conjugate. The hematological parameters (Hb, RBC, WBC and ESR) and biochemical parameters (CRP, SALP, SGOT and SGPT) in the osteoarthritic rats were significantly brought back to normal values on treatment with conjugate. It also showed better anti-ulcer activity than rhein. Further the histopathological studies revealed significant anti-arthritic activity of conjugate when compared with the arthritic control group. In conclusion, the conjugate at the specified dose level of 15.73 mg/kg, p. o. (BID) showed reduction in knee diameter and it could significantly normalize the hematological and biochemical abnormalities in collagenase-induced osteoarthritis in rats. Further the histopathological studies confirmed the additive anti-arthritic effect of DSRB as compared to plain rhein.
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PMID:Disease-modifying effect of anthraquinone prodrug with boswellic acid on collagenase-induced osteoarthritis in Wistar rats. 2370 Nov 73