Abbreviations & AcronymsObjectives: To evaluate the anti-oxidant activity of the flavonoid compound, kaempferol, and to examine its role in the suppression of oxidative stress and attenuation of bladder hyperactivity in a rat model of bladder injury. Methods: The anti-oxidative activity of kaempferol was examined in lipopolysaccharidetreated RAW264.7 macrophages by using flow cytometry. For in vivo studies, rats were pretreated with kaempferol or vehicle for 24 h. The rat urothelium was injured by the administration of protamine sulfate for 1.5 h and irritated by the subsequent infusion of potassium chloride for 4 h. Oxidative stress in the bladder tissue was assessed using chemiluminescence assay, and the bladder pressure was determination by cystomertrogram. Results: Kaempferol significantly suppressed lipopolysaccharide-induced reactive oxygen species production in RAW264.7 rat macrophages. Exposure of the rat bladder to sequential infusion of protamine sulfate and potassium chloride induced bladder hyperactivity. Pretreatment with kaempferol, prevented the formation of reactive oxygen species and prolonged the intercontraction interval. Conclusion: Kaempferol suppresses oxidative stress and attenuates bladder hyperactivity caused by potassium chloride after protamine sulfate-induced bladder injury.

In this study, submicron emulsions have been employed as a carrier for the topical application of kaempferol. The effect of components of submicron emulsions on the physicochemical properties and permeation capability of drug were evaluated. In case of drug-loaded submicron emulsions, the cumulative amount over 12 h (Q 12 h ), lag time and deposition in skin amount ranged from 13.0 3.4 to 236.1 21.2 µg/cm 2 , 1.7 to 5.3 h, and 1.10 to 7.76 µg/cm 2 , respectively, which indicated that the permeation parameters of kaempferol were markedly influenced by the component ratio. Kaempferol dispensed in isopropyl myristate was used as the control. The Q 12 h , lag time and deposition amount in skin were 4.2 1.8 µg/cm 2 , 6.0 h and 2.25 0.60 µg/cm 2 , respectively. The data showed that used appropriate submicron emulsions as vehicle could significantly increase the Q 12 h and deposition amount in skin and shorten the lag time, demonstrating that submicron emulsions have a potent enhancement effect for kaempferol transdermal delivery.Key words kaempferol; submicron emulsion; in vitro permeation study; permeation parameter; skin deposition amount Kaempferol (C 15 H 10 O 6 , molecular weight 286.24, mp 276°C) is one of the phytoestrogens, and it is found in berries and Brassica and Allium species. It has been recognized to have antioxidative, anti-inflammatory, antiallergic, and anticancer properties.1-10) Regarding its anti-inflammatory properties, Wang et al. 1) reported that kaempferol dose-dependently inhibited inducible nitric oxide synthase (iNOS) mRNA expression and prostaglandin E2 production, in part through a reducing nuclear factor-kappaB (NF-kappaB) signaling pathway. Park et al. 4) reported that kaempferol could inhibit the activation of inflammatory NF-kappaB transcription factor through nuclear factor-inducing kinase (NIK)/IkappaB kinase (IKK) and mitogen-activated protein kinases (MAPKs) in aged rat kidney. Moreover, under daily treatment with 100 µL kaempferol in ethanol 100 µM for 10-30 d, the inflammatory cell infiltrates in the dermis and thickening of the epidermis in the burned area of skin were clearly ameliorated.11) These results demonstrated the efficacy of kaempferol in thermal burn-induced skin injuries. Oral administration of kaempferol results in very low bioavailability (2%) because it exhibits an extensive first-pass metabolism.12) Hence, kaempferol is a good candidate for topical application.Submicron emulsion systems are fine oil-in-water or waterin-oil dispersions with small droplet sizes in the range of 100-600 nm. 13) They offer many advantages over other traditional vehicles including ease of manufacturing, thermodynamic stability, enhanced drug solubilization and increased drug permeation rate.14) Submicron emulsions are typically composed of large amounts of surfactants and oil, which are irritants for skin. However, previous studies [14][15][16][17] reported that submicron emulsion did not cause barrier perturbation of the skin, and that they can even decrease the skin irritation caus...

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