RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a relapsing inflammatory disease that still demands for effective remedies due to various adverse effects of the current principal treatments. Centella asiatica is a traditional medical herb with long application history in anti-inflammation. AIM OF THE STUDY: To explore the anti-inflammatory effect and possible mechanism of C. asiatica ethanol extract (CA) in a murine colitis model induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: CA was analyzed by high performance liquid chromatograph (HPLC). The colitis model was induced by free access to 3% DSS in distilled water for 7 days. CA (100, 200, and 400â¯mg/kg) and 5-aminosalicylic acid (5-ASA, 400 mg/kg) were administrated by gavage during the 7-day DSS challenge. At the end of experiment, mice were sacrificed and the brain, colon and cecum contents were harvested for analysis. Colitis was evaluated by disease activity index (DAI), colon length and colon lesion macroscopic score with hematoxylin-eosin staining. Myeloperoxidase (MPO) activity in colon and 5-hydroxytryptamine (5-HT) in brain were determined by ELISA. Tight junction protein expressions (ZO-1, E-Cadherin, Claudin-1) and c-Kit in colon were assessed by western blot and immunohistochemistry, respectively. Microbiota of cecum content was analyzed by 16S rRNA sequencing. RESULTS: Data showed that with recovery on the colon length and histological structure, CA prominently decreased DAI and macroscopic score for lesion in the suffering mice. CA relieved the colitis by suppressing inflammatory cell infiltration with decreased MPO activity in the colon, and up-regulated the expression of tight junction protein (ZO-1, E-cadherin) to enhance the permeability of intestinal mucosa. Moreover, CA restored intestinal motility by promoting c-Kit expression in the colon and 5-HT in the brain. Moreover, CA was able to reshape the gut microbiota in the suffering mice. It increased the α-diversity and shifted the community by depleting the colitis-associated genera, Helicobacter, Jeotgalicoccus and Staphylococcus, with impact on several metabolism signaling pathways, which possibly contributes to the renovation on the impaired intestinal mucosal barrier. CONCLUSIONS: CA displayed the anti-inflammatory activity against the DSS-induced colitis, which would possibly rely on the restoration on mucosa barrier and gut microbiota homeostasis, highlights a promising application of C. asiatica in the clinical treatment of UC.
Asunto(s)
Antiinflamatorios/farmacología , Bacterias/efectos de los fármacos , Colitis Ulcerosa/prevención & control , Colon/efectos de los fármacos , Fármacos Gastrointestinales/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Extractos Vegetales/farmacología , Triterpenos/farmacología , Animales , Bacterias/crecimiento & desarrollo , Centella , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/microbiología , Colon/metabolismo , Colon/microbiología , Colon/patología , Sulfato de Dextran , Modelos Animales de Enfermedad , Etanol/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones Endogámicos BALB C , Permeabilidad , Serotonina/metabolismo , Solventes/química , Proteínas de Uniones Estrechas/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Pogostemon cablin has been widely used in traditional Chinese medicine for the treatment of many diseases, including skin disorders. In the skin beauty and care prescriptions, Pogostemon cablin is one of the top ten frequently used traditional Chinese medicines. AIM OF THE STUDY: The present study was aimed to investigate the protective effects of the essential oil of Pogostemon cablin (patchouli oil, PO) against UV-induced skin photoaging in mice. MATERIALS AND METHODS: To ensure the quality of PO, the chemical compositions of PO were identified, and the content of its chemical marker patchouli alcohol was determined, which was around 28.2% (g/g) in PO. During the experiment period, the dorsal depilated skin of mice was treated with PO for two hours prior to UV irradiation. Then the protective effects of PO on UV-induced skin photoaging were determined by macroscopic and histological evaluations, skin elastic test, collagen content determination and biochemical assays of malondiaidehyde (MDA) content, activities of anti-oxidative indicators including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). RESULTS: Compared to UV exposure groups, present results showed that topical administration of PO, especially at dose of 6mg/mouse and 9mg/mouse, significantly inhibited the increase in skin wrinkle formation, alleviated the reduction in skin elasticity and increased the collagen content by about 21.9% and 26.3%, respectively. We also found that application of 6-9mg/mouse PO could not only decrease the epidermal thickness by about 32.6%, but also prevent the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, the content of MDA was decreased by almost 26.5% and activities of SOD, GSH-Px and CAT were significantly up-regulated after the treatment of PO. CONCLUSION: Results of present study revealed that PO was capable of maintaining skin structural integrity caused by UV irradiation and it was useful in preventing photoaging. These protective effects of PO were possibly due to its anti-oxidative property. Therefore, we suggested that PO should be viewed as a potential therapeutic agent for preventing photoaging.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Lamiaceae/química , Aceites de Plantas/uso terapéutico , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Administración Cutánea , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Etnofarmacología , Femenino , Medicina Tradicional China , Ratones Endogámicos , Aceites de Plantas/administración & dosificación , Aceites de Plantas/químicaRESUMEN
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.