Inhibitory effect of Phlai capsules on skin test responses among allergic rhinitis patients: a randomized, three-way crossover study.

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).

Pharmacokinetics of Compound D, the Major Bioactive Component of Zingiber cassumunar, in Rats.

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 4 % 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 1 % 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.

Safety Evaluation of Zingiber cassumunar Roxb. Rhizome Extract: Acute and Chronic Toxicity Studies in Rats.

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.