No abstract

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 (β-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 β-hexosaminidase release by antigen-stimulated RBL-2H3 cells, with valencene having the highest inhibitory effect. CRE inhibited leukotrienes production and β-hexosaminidase release at 300 μg/mL. It was also found that the most active sesquiterpene (valencene) and CRE inhibited β-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.

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-1β, 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.

-To establish the anti-inflammatory activity of the total flavonoid fraction of the root barks of Broussonetia papyrifera (EBP) and a new formula, the ethanol extract of the root barks of B. papyrifera was fractionated with ethylacetate, yielding the hydrophobic prenylated flavonoid-enriched fraction. EBP and the ethanol extract of the whole Lonicera japonica (ELJ) plant were then mixed at a ratio of 1:1 (w/w) to give a new preparation (BL) in the hope of obtaining an optimal formula with a higher anti-inflammatory activity. Evaluation of the effects of these preparations on A23187-treated rat basophilic leukemia (RBL-1) cells revealed that EBP potently inhibited 5-lipoxygenase (5-LOX), while ELJ showed weak inhibition. Additionally, the mixture (BL) clearly showed stronger inhibitory effects against 5-LOX than either preparation alone. These preparations also inhibited cyclooxygenase-2-catalyzed PGE2 and inducible nitric oxide (NO) synthase-catalyzed NO production by lipopolysaccharide-treated RAW 264.7 cells. When tested against arachidonic acid-induced mouse ear edema, EBP showed strong inhibitory activity at doses of 5-200 mg/kg when administered orally, but BL had obviously stronger inhibitory effects. When tested against λ-carrageenaninduced paw edema in mice, BL showed a potent and synergistic anti-inflammatory effect. In addition, in the acetic acid-induced writhing test, BL was found to have strong analgesic activity at 50-400 mg/kg. Taken together, these results indicate that each of these preparations exert anti-inflammatory activity in vitro and in vivo. In particular, BL showed stronger anti-inflammatory activity than EBP, and these anti-inflammatory effects were partially related to the inhibition of eicosanoid and NO production. BL may be useful for the treatment of human inflammatory disorders.

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.