Inhibition of Experimental Systemic Inflammation (Septic Inflammation) and Chronic Bronchitis by New Phytoformula BL Containing Broussonetia papyrifera and Lonicera japonica.

Broussonetia papyrifera and Lonicera japonica have long been used in the treatment of inflammatory disorders in Chinese medicine, especially respiratory inflammation. Previously, a new phytoformula (BL) containing B. papyrifera and L. japonica was found to exert strong anti-inflammatory activity against several animal models of inflammation, especially against an animal model of acute bronchitis. In the present investigation, the effects of BL on animal models of septic inflammation and chronic bronchitis are examined. Against lipopolysaccharide (LPS)-induced septic inflammation in mice, BL (200-400 mg/kg) reduced the induction of some important proinflammatory cytokines. At 1 h after LPS treatment, BL was found to considerably inhibit TNF-α production when measured by cytokine array. At 3 h after LPS treatment, BL inhibited the induction of several proinflammatory cytokines, including IFN-γ and IL-1ß, although dexamethasone, which was used as a reference, showed a higher inhibitory action on these biomarkers. Against chronic bronchitis induced by LPS/elastase instillation in rats for 4 weeks, BL (200-400 mg/kg/day) significantly inhibited cell recruitment in bronchoalveolar lavage fluid. Furthermore, BL considerably reduced lung injury, as revealed by histological observation. Taken together, these results indicate that BL may have a potential to treat systemic septic inflammation as well as chronic bronchitis.

New synthetic anti-inflammatory chrysin analog, 5,7-dihydroxy-8-(pyridine-4yl)flavone.

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.

Inhibition of experimental atopic dermatitis by rhubarb (rhizomes of Rheum tanguticum) and 5-lipoxygenase inhibition of its major constituent, emodin.

The antiallergic activity of rhubarb and its constituents, anthraquinones, has been reported previously. For further evaluation of the antiallergic activity, a 70% ethanol extract of the rhizomes of Rheum tanguticum (RTE) was prepared and its inhibitory activity on an animal model of atopic dermatitis (AD) was examined for the first time. Oral administration of RTE (30-300 mg/kg/day) for 5 weeks significantly inhibited hapten-induced dermatitis in NC/Nga mice based on the skin severity score. In addition, treatment with RTE at 100 mg/kg/day also reduced the numbers of white blood cells, neutrophils and eosinophils in the blood, and led to a significant reduction in the IgE concentration in the serum. In rat basophilic leukemia (RBL)-1 cells, RTE inhibited 5-lipoxygenase (5-LOX)-catalysed leukotriene production (IC(50) = 43.6 µg/mL). Among the anthraquinone derivatives isolated, emodin strongly inhibited this parameter (IC(50) = 4.3 µM). Taken together, these findings suggest that rhubarb exerts inhibitory activity against AD, and that the 5-LOX inhibitory activity of its major constituent, emodin, may contribute to this inhibitory action.

Anti-allergic activity of sesquiterpenes from the rhizomes of Cyperus rotundus.

From the 70% ethanol extract of the rhizomes of Cyperus rotundus (CRE), several major constituents including the sesquiterpene derivatives (valencene, nootkatone, and caryophyllene α-oxide), monoterpenes (ß-pinene, 1,8-cineole, and limonene) and 4-cymene were isolated and examined for their anti-allergic activity in vitro and in vivo. In rat basophilic leukemia (RBL)-1 cells, the sesquiterpenes strongly inhibited 5-lipoxygenase-catalyzed leukotrienes production. In addition, they inhibited ß-hexosaminidase release by antigen-stimulated RBL-2H3 cells, with valencene having the highest inhibitory effect. CRE inhibited leukotrienes production and ß-hexosaminidase release at 300 µg/mL. It was also found that the most active sesquiterpene (valencene) and CRE inhibited ß-hexosaminidase degranulation by inhibiting the initial activation reaction, Lyn phosphorylation, in IgE-stimulated RBL-2H3 cells. Moreover, CRE, valencene and nootkatone significantly inhibited the delayed-type hypersensitivity reaction in mice when administered orally at 50-300 mg/kg. In conclusion, C. rotundus and its constituents, valencene, nootkatone, and caryophyllene α-oxide, exert anti-allergic activity in vitro and in vivo. These sesquiterpenes, but not monoterpenes, certainly contribute to the anti-allergic activity of the rhizomes of C. rotundus.

Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Sophora flavescens have long been used in Chinese medicine for the treatment of fever, inflammatory disorders, ulcers and skin burns. Sophora flavescens contains flavonoids and alkaloids. AIM OF THE STUDY: This study was conducted to develop a plant-based anti-inflammatory agent focused on chronic inflammatory disorders. To accomplish this, the alkaloid-free prenylated flavonoid-enriched fraction (PFS) of rhizomes of Sophora flavescens was prepared and its in vitro and in vivo anti-inflammatory activities were then evaluated for the first time. MATERIALS AND METHODS: The inhibitory activity of PFS on PGE(2), NO, IL-6 and TNF-alpha production of lipopolysaccharide (LPS)-treated RAW 264.7 cells was measured. Additionally, adjuvant-induced arthritis in rats was used as an animal model of chronic inflammation to establish the in vivo anti-inflammatory effects of PFS. RESULT: PFS inhibited cyclooxygenase-2 (COX-2)-catalyzed PGE(2) and inducible nitric oxide synthase (iNOS)-catalyzed NO production by lipopolysaccharide (LPS)-treated RAW 264.7 cells at 10-50 microg/ml, and these effects primarily occurred via COX-2 inhibition and iNOS down-regulation, respectively. PFS also inhibited IL-6 and TNF-alpha production. When tested against adjuvant-induced arthritis in rats (chronic inflammation), PFS strongly inhibited arthritic inflammation when administered orally at doses of 10-100mg/kg/day. In addition, PFS administered orally potently inhibited acetic acid-induced writhing in mice. CONCLUSIONS: Our results suggest that PFS inhibits chronic inflammatory response and the inhibition of proinflammatory molecules such as COX-2, iNOS and IL-6 may contribute, at least in part, to the anti-inflammatory activity in vivo. Overall, these results indicate that PFS from Sophora flavescens may have the potential for treatment of chronic inflammatory disorders such as rheumatoid arthritis.