chrysin and Edema

This study was intended to appraise the anti-inflammatory and anti-arthritic potential of Chrysin (CR), a natural dietary flavone found in several plant genera, including Passiflora and Propalis, and honey. The in vitro anti-arthritic potential was assessed by protein denaturation and membrane stabilization assays. The acute anti-inflammatory action was assessed by Carrageenan and Xylene induced oedema models in Wistar rats. For determining anti-arthritic potential, 0.1 ml Complete Freund's adjuvant was injected into the left hind paw of rats to induce adjuvant-induced arthritis, followed by initiation of treatment with individual CR at 25, 50, 100 mg/kg and in combination with methotrexate (MTX) by oral gavage for 21 days. The standard treatment group was given MTX (1 mg/kg). Treatment with MTX, chrysin and their combination exhibited a notable inhibition of paw oedema and pain, restoration of body weight and immune organ weight as evident by the histology of ankle joints. Treatment with chrysin alone and in combination significantly (p < 0.0001) restored altered blood parameters (CRP, RF, Hb, WBC, and platelets) with notable (p < 0.0001) down-regulation of interleukin (IL)-6,-1β, tumor necrosis factor-α, NF-κβ, and cyclooxygenase-2 and up-regulation (p < 0.0001) of IL-4, 10, and I-κβ in contrast to disease control rats. The treatment with the combination noticeably improved the superoxide dismutase, and catalase activities while reduced the peroxidation level in liver homogenate. It can be concluded from the findings that chrysin especially in combination with MTX ameliorated CFA-induced arthritis owing to its profound anti-oxidant, analgesic and anti-inflammatory actions.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Biomarkers; Cytokines; Edema; Interleukin-6; Methotrexate; Oxidative Stress; Rats; Rats, Wistar

Docetaxel (DTX) is an effective commercial anticancer agent for chemotherapy in non-small cell lung cancer (NSCLC), breast cancer, gastric cancer, and prostate cancer, but its adverse effects including edema, neurotoxicity, and hair loss limit its application. To improve the chemotherapeutic efficacy of DTX and reduce adverse effects, combination therapy is one of the alternative methods. So chrysin, which has various biological activities including anticancer effects, was considered. In vitro, the combination of chrysin and DTX was investigated in A549 cells. Increased cytotoxicity, suppressed cellular proliferation, and induced apoptosis were observed with posttreatment of chrysin following DTX treatment. In vivo, chrysin enhanced the tumor growth delay of DTX and increased DTX-induced apoptosis in the A549-derived xenograft model. Furthermore, chrysin prevented DTX-induced edema in ICR mouse. These results indicated that chrysin strengthened the therapeutic efficacy of DTX and diminished the adverse effect of DTX, suggesting chrysin could be exploited as an adjuvant therapy for NSCLC.

Topics: A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Docetaxel; Edema; Female; Flavonoids; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Taxoids; Xenograft Model Antitumor Assays

To identify anti-inflammatory flavonoid derivatives with optimal chemical structures, various 8-heterocyclic-substituted chrysin derivatives were previously synthesized and their effects on prostaglandin E₂ (PGE₂) production from the lipopolysaccharide (LPS)-treated mouse macrophage cell line, RAW 264.7, were evaluated. Through this screening procedure, 5,7-dihydroxy-8-(pyridine-4yl)flavone (C-721) among the derivatives was selected for further pharmacological study. Contrary to the parent molecule, chrysin, C-721 was found to potently inhibit PGE₂ and NO production by LPS-treated RAW cells. The IC₅₀ values of C-721 were 6.2 and 22.6μM, respectively, for cyclooxygenase-2 (COX-2) mediated PGE₂ and inducible nitric oxide (iNOS)-mediated NO production. Western blotting and reverse transcriptase-polymerase chain reaction analysis demonstrated that this compound inhibited PGE₂ production, at least in part, via COX-2 down-regulation and COX-2 inhibition, while C-721 primarily inhibited NO via down-regulation of iNOS expression. In addition, C-721 inhibited TNF-α and IL-6 production at 10-50 μM. An in vivo study revealed that oral and intraperitoneal administration of C-721 showed 25.2%-44.3% inhibition against λ-carrageenan-induced paw edema in mice at 10-100mg/kg. Furthermore, this compound significantly inhibited collagen-induced arthritis in mice when administered by intraperitoneal injection at 50mg/kg three times/week. Taken together, these results suggest that C-721 has the potential for use as a synthetic lead compound for development of a new anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Flavones; Flavonoids; Male; Mice; Mice, Inbred ICR; Pyridines

We previously reported that oral administration of luteolin can inhibit serum tumor necrosis factor (TNF)-alpha production and several inflammatory and allergic models. We investigated here the effect of various flavonoids which resemble luteolin in structure. Lipopolysaccharide (LPS)-induced TNF-alpha production from macrophages was inhibited by treatment with flavone (luteolin, apigenin, and chrysin), flavonol (quercetin and myricetin), flavanonol (taxifolin), and anthocyanidin (cyanidin chloride) in vitro. Most of these, however, did not affect mice when administered orally. Serum TNF-alpha production was inhibited only by luteolin or apigenin, and only luteolin or quercetin inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema. These results suggest that the structure of luteolin: 3',4',5,7-tetrahydroxyflavone, is most suitable for the oral anti-inflammatory activity and that existence or disappearance of a hydroxy group may cause a loss of efficiency.

Topics: Administration, Oral; Animals; Anthocyanins; Anti-Inflammatory Agents; Apigenin; Cells, Cultured; Ear, External; Edema; Flavonoids; Flavonols; Lipopolysaccharides; Luteolin; Macrophages, Peritoneal; Male; Mice; Mice, Inbred ICR; Quercetin; Structure-Activity Relationship; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha