RESUMO
The present work was designed to evaluate the in vitro and in vivo anti-Candida activity of pogostone (PO), a natural product isolated from Pogostemon cablin (Blanco) Benth. PO showed potent in vitro activity against clinical Candida spp. isolates tested in this study. PO and the reference drug voriconazole (VRC) were equally effective against all the fluconazole-resistant Candida albicans strains, with MIC ranging from 3.1 µg/ml to 50 µg/ml. Besides, PO was fungicidal against all Candida isolates with MFC ranging from 50 µg/ml to 400 µg/ml. By contrast, VRC was fungistatic as it failed to elicit a fungicidal effect against the Candida spp. isolates at the highest tested concentration (400 µg/ml). Furthermore, oral and topical PO administration effectively reduced the fungal load in vagina of vulvovaginal candidiasis mouse models. Topical PO administration (1.0-4.0 mg/kg) demonstrated higher activity against the vulvovaginal candidiasis than VRC (4.0 mg/kg). The pharmacokinetics and safety profile of PO were also investigated. The pharmacokinetics assay revealed that PO was easily absorbed after oral administration in mice, which might account for its in vivo anti-Candida effect. The acute toxicity test showed that the median lethal dose of PO in mice was 355 mg/kg, which was much higher than the daily dose used for the therapeutic experiments. This study demonstrated the potential of PO as a promising candidate for the treatment of Candida infections, particularly for vulvovaginal candidiasis.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Lamiaceae/química , Óleos Voláteis/farmacologia , Fitoterapia , Vagina/efeitos dos fármacos , Animais , Antifúngicos/isolamento & purificação , Antifúngicos/farmacocinética , Modelos Animais de Doenças , Feminino , Absorção Intestinal , Camundongos , Camundongos Endogâmicos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacocinética , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/farmacologia , Vagina/microbiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemum indicum (Compositae) Linné, Pogostemon cablin (Blanco) Benth and Curcuma wenyujin (Zingiberaceae) Y. H. Chen et C. Ling are three of the extensively used herbal remedies among traditional Chinese medicines for the purpose of anti-inflammation. A traditional Chinese medicine (TCM) recipe named CPZ consisting extracts of the above three herbs, has shown noteworthy anti-influenza activity, which is closely related to its anti-inflammatory feature. AIM OF THIS STUDY: To investigated the anti-inflammtory activity of CPZ in vivo for a further exploration of the recipe's anti-inflammatory properties. MATERIALS AND METHODS: The anti-inflammatory property of CPZ on acute inflammation was evaluated by inflammatory models of dimethylbenzene (DMB)-induced ear vasodilatation and acetic acid-induced capillary permeability enhancement in mice, as well as the carrageenan-induced paw edema rat model, in which inflammation-related cytokine including prostaglandin E(2) (PGE(2)), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) in the edematous paw tissue were determined by enzyme linked immunosorbent assay (ELISA). Moreover, effect of CPZ on chronic inflammation was observed through granuloma formation in rats subjected to cotton pellet implantation. RESULTS: CPZ (340, 170, and 85 mg/kg for mice, p.o.) not only decreased the DMB-induced ear vasodilatation but also attenuated capillary permeability under acetic acid challenge in mice. And the significant inhibition on carrageenan-induced paw edema was observed. Further more, the ELISA results showed that CPZ (170, 85, and 42.5 mg/kg for rats, p.o.) could up-regulate the level of IL-1ß in the edema paw tissue of rats significantly while down-regulate that of PGE(2), but no apparent effect on TNF-α or NO was observed in the test. Besides, CPZ had a certain degree of restraining effect on the cotton pellet-induced granuloma formation in rats and the highest dose of 170 mg/kg even showed a significant suppression on it. CONCLUSION: The above results indicated that CPZ possessed a potent anti-inflammatory activity, which is indicated to be closely associated with its regulation on IL-1ß and PGE(2) thereby mediating the inflammatory response acting at an appropriate level.