RESUMO
BACKGROUND: Zingiber cassumunar Roxb., commonly known as Phlai in Thai, has been used as a traditional medicine in Thailand for the treatment of various diseases, including inflammation and chronic airway disease. OBJECTIVE: The purpose of this study was to assess the antihistaminic effect of Phlai on skin testing. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a randomized, open-label, three-way crossover study. Twenty allergic rhinitis (AR) patients were enrolled. In randomized sequence, patients received a single dose of Phlai capsules (100 or 200 mg) or loratadine (10 mg) with a washout period of 1 week between each treatment. MAIN OUTCOME MEASURES: Skin prick testing for histamine and common aeroallergen (house dust mite) were performed before treatment and after 1, 2, 3, 4, 6, 8, 12 and 24 hours of treatment. The main treatment outcomes were the mean wheal and flare responses to the skin prick test after treatment. RESULTS: Both 100 mg and 200 mg Phlai doses suppressed wheal and flare responses to house dust mite allergen, but only 200 mg of Phlai capsules significantly suppressed wheal and flare responses to histamine. Repeated measures analysis of variance showed that loratadine caused more wheal and flare suppression than Phlai capsules in responses to the histamine skin prick test. However, there were no significant differences among the effects of 100 mg Phlai capsules, 200 mg Phlai capsules and loratadine in suppression of wheal and flare induced by the mite skin prick test. Both doses of Phlai were well-tolerated with no adverse events. CONCLUSION: Both 100 mg (compound D 4 mg) and 200 mg (compound D 8 mg) Phlai capsules, when taken as a single therapeutic dose, inhibited skin reactivity to histamine and mite skin prick tests in AR patients. TRIAL REGISTRATION: Thai clinical trial registry (TCTR20160510001).
Assuntos
Alérgenos , Antagonistas dos Receptores Histamínicos/farmacologia , Histamina , Extratos Vegetais/farmacologia , Rinite Alérgica , Pele/efeitos dos fármacos , Zingiberaceae , Adulto , Alérgenos/farmacologia , Animais , Antialérgicos/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Histamina/farmacologia , Humanos , Loratadina/farmacologia , Ácaros , Fitoterapia , Rinite Alérgica/tratamento farmacológico , Testes CutâneosRESUMO
Rhizomes of Zingiber cassumunar have been used for many years in traditional Thai medicine as an anti-inflammatory agent. The major bioactive component of this plant is Compound D [E-4-(3', 4'-dimethoxyphenyl)but-3-en-1-ol], which is a strong smooth muscle relaxant, and has antihistamine and anti-inflammatory actions. There is, however, incomplete information available for the pharmacokinetics of Compound D in mammals. In this study, we examined the pharmacokinetic profiles of Compound D in male Wistar rats. A standardized extract of Z. cassumunar containing 4â% w/w Compound D was administered intravenously at 25 mg/kg or by oral gavage at 25, 75, or 250 mg/kg to Wistar rats. Blood, tissues, urine, and feces were collected from 0 to 48 h after dosing and the level of Compound D was determined by liquid chromatography-tandem mass spectrometry. The concentration of Compound D ranged from 10-100 µg/L, reached a maximum approximately 0.15 h after oral dosing. Compound D exhibited an excellent tissue to plasma ratio, ranging from 1- to 1000 in several organs at 1-4 h after oral dosing. Less than 1â% of unchanged Compound D was excreted in the urine and feces. Further studies on tissue uptake and metabolite identification are required to obtain complete pharmacokinetic information and to develop appropriate dosing strategies of Compound D and the standardized extract of Z. cassumunar.
Assuntos
Butanóis/farmacocinética , Parassimpatolíticos/farmacocinética , Extratos Vegetais/farmacocinética , Zingiberaceae/química , Animais , Butanóis/química , Butanóis/isolamento & purificação , Masculino , Estrutura Molecular , Parassimpatolíticos/isolamento & purificação , Parassimpatolíticos/urina , Extratos Vegetais/química , Ratos , Ratos Wistar , TailândiaRESUMO
BACKGROUND/PURPOSE: The 3Mix-MP formulation (a mixture of metronidazole, ciprofloxacin, and minocycline; macrogol and propylene glycol) has been used to kill residual bacteria in dentin caries. This study aimed to investigate the dentin disinfection and cytotoxicity of a novel zinc oxide (ZnO) based medicament, Z-Mix. MATERIALS AND METHODS: Z-Mix was prepared as a prefilled syringe of materials containing mainly ZnO, incorporated with amoxicillin, ciprofloxacin, and metronidazole (1 g% of each antibiotic). Drug penetration was measured at 24 hours and 72 hours. Streptococcus mutans, Lactobacillus acidophilus, or Enterococcus faecalis were inoculated into dentinal tubules for 30 days and were then subjected to Z-Mix or 0.2% chlorhexidine (CHX) for 48 hours. Viable bacteria in the dentin were determined using fluorescence staining. Their cytotoxicity against human dental pulp cells was assessed using an MTT assay. RESULTS: Z-Mix obviously diffused into dentinal tubules and the root apex, compared to the 3Mix-MP (P < 0.05). Fluorescence staining demonstrated a reduction of viable bacteria at 100 µm and 500 µm below infected cavities after treatment with Z-mix or CHX for 48 hours. Live and dead bacteria ratios indicated that Z-Mix exhibited markedly antimicrobial effects on inoculated bacteria in dentin samples (P < 0.05). There was no significant difference in the antimicrobial property between Z-Mix and CHX (P > 0.05). An acceptable level of cytotoxicity was observed in Z-Mix and its ingredients. CONCLUSION: Z-Mix, a soft shapeable paste containing a mixture of three antibiotics, is successfully. It can penetrate to the root apex and exhibits antimicrobial properties.
RESUMO
BACKGROUND: House dust mite (HDM) induced matrix metalloproteinase (MMP)-9 plays a role in asthma. Zingiber cassumunar Roxb. (Phlai in Thai) has been used in folk medicine for asthma treatment. OBJECTIVE: We investigated effects of Phlai and its constituent (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol (compound D) on the cleavage of pro- MMP-9 by HDM. The effects of these compounds on phorbol 12-myristate 13-acetate (PMA)- induced MMP-9 gene and protein expression in airway epithelial cells (NCI-H292) were also investigated. METHODS: Pro-MMP-9 was directly activated in vitro with HDM in the presence or absence of the ethanolic extracts of Phlai or compound D for 1 hour. The amount of activated MMP-9 was determined using gelatin zymography. To study the cellular response of Phlai, NCI-H292 cells were pretreated with crude Phlai extracts or compound D for 2 hours, and then the cells were stimulated with PMA for 48 hours. The mRNA RT-PCR and Western blotting, respectively. MMP-9 activity was determined by gelatin zymography. RESULTS: Crude Phlai extracts (0.25 - 2.0 mg/ml) and compound D (0.5 - 4.0 mg/ml) inhibited pro- MMP-9 cleavage by HDM. Furthermore, crude Phlai extracts (100 mg/ml) and compound D, at concentrations of 50 and 100 mg/ml, attenuated the PMA-induced MMP-9 gene and expression in NCI-H292 cells. These compound also suppressed MMP-9 release from PMA-induced NCI-H292 cells. CONCLUSION: The crude ethanolic extract of Z. cassumunar and its active constituent compound D inhibited the cleavage of pro-MMP-9 by HDM. They also inhibited PMA-induced MMP-9 gene and protein synthesis in human airway epithelial cells.
Assuntos
Antígenos de Dermatophagoides/farmacologia , Proteínas de Artrópodes/farmacologia , Butanóis/farmacologia , Cisteína Endopeptidases/farmacologia , Células Epiteliais/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Extratos Vegetais/farmacologia , Pyroglyphidae/química , Zingiberaceae/química , Animais , Antígenos de Dermatophagoides/isolamento & purificação , Proteínas de Artrópodes/isolamento & purificação , Butanóis/isolamento & purificação , Linhagem Celular Tumoral , Cisteína Endopeptidases/isolamento & purificação , Ativação Enzimática/efeitos dos fármacos , Precursores Enzimáticos/genética , Precursores Enzimáticos/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Expressão Gênica , Humanos , Metaloproteinase 9 da Matriz/genética , Ésteres de Forbol/farmacologia , Preparações de Plantas/química , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismoRESUMO
Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P < 0.05). The weights of lung and kidney of treated females were increased (P < 0.05). Treated males were increased in spleen and epididymis weights (P < 0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.