Natthakarn Chiranthanut

Toxicity evaluation of standardized extract of Gynostemma pentaphyllum Makino

ETHNOPHARMACOLOGICAL RELEVANCE To evaluate the safety of standardized extract of Gynostemma pentaphyllum in rats. MATERIALS AND METHODS The water extract of Gynostemma pentaphyllum was prepared and standardized, the dry powder yielded 6% gypenosides. In the acute oral toxicity test, the single oral dose of 5000 mg/kg of Gynostemma pentaphyllum extract was given to female Sprague-Dawley rats. In subchronic toxicity test, the oral dose of 1000 mg/kg/day of the extract was given to rats in treatment and satellite groups for 90 days. Satellite groups of both sexes were kept for additional 28 days after 90-day treatment. Control rats received distilled water. RESULTS Standardized extract of Gynostemma pentaphyllum did not cause death or any toxic signs in rats. The daily administration of the extract for 90 days did not produce lethal or harmful effects. Although certain hematological and blood chemistry values (i.e., neutrophil, monocyte, glucose, and serum alkaline phosphatase levels) were found to be statistically different from the control group, however; these values were within the ranges of normal rats. CONCLUSION Standardized extract of Gynostemma pentaphyllum did not produce mortality or any abnormality in rats.

Investigation of anti-inflammatory, antinociceptive and antipyretic activities of Stahlianthus involucratus rhizome ethanol extract

ETHNOPHARMACOLOGICAL RELEVANCE Stahlianthus involucratus (Zingiberaceae) has long been used in traditional medicine to treat inflammation, pain, and fever. However, no pharmacological study of this plant has been reported to confirm these activities. The aim of this study was to investigate the anti-inflammatory, antinociceptive and antipyretic activities of Stahlianthus involucratus rhizome ethanol extract (SiE) in animal models. MATERIALS AND METHODS Anti-inflammatory activity of SiE was investigated in rats using ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema, and cotton pellet-induced granuloma formation models. Acetic acid-induced writhing response in mice and tail-flick test in rats as well as yeast-induced hyperthermia in rats were used to investigate the antinociceptive and antipyretic activities, respectively. RESULTS SiE significantly inhibited EPP-induced ear edema, carrageenan- and AA-induced hind paw edema. Its inhibitory effect in carrageenan-induced hind paw edema seemed to be in a dose-dependent manner. In cotton pellet-induced granuloma formation, SiE showed suppressive effects on granuloma formation but not on body weight gain and dry thymus weight. It could normalize serum alkaline phosphatase activity to nearly normal level. SiE also possessed a significant inhibitory effect, which seemed to be dose-dependent, on acetic acid-induced writhing response, whereas only at the highest dose of SiE could significantly increase test reaction time at all time-points in tail-flick test. However, no antipyretic activity was observed. CONCLUSIONS These results suggest that SiE possesses anti-inflammatory and antinociceptive, but not antipyretic, activities. This study therefore rationalizes the traditional use of SiE for the treatment of inflammation and pain.

Pharmacokinetics of Ganoderic Acids A and F after Oral Administration of Ling Zhi Preparation in Healthy Male Volunteers

The objectives of this paper were to evaluate the pharmacokinetics of ganoderic acids A and F after a single oral dose of the water extract of MG2-strain Ling Zhi (MG2FB-WE) and to assess the influence of food on the pharmacokinetics in 12 healthy male volunteers. This study was a single-dose, open-label, randomized, two-phase crossover study with at least 2 wk washout period. Each subject was randomly assigned to receive a single oral dose of 3,000 mg of MG2FB-WE in granular formulation dissolved in 200 mL of warm water, either under a fasting condition, or immediately after a standard breakfast (fed condition). Blood samples were collected immediately before and at specific time points until 8 h after MG2FB-WE administration. Plasma ganoderic acids A and F concentrations were determined by using liquid chromatography-mass spectrometry (LC-MS) technique. In conclusion, the pharmacokinetic profile of both ganoderic acids under a fasting condition was characterized by rapid absorption from the gastrointestinal tract (T max at approximately 30 min) and a short elimination half-life (<40 min). Food significantly decreased C max and delayed T max, but did not affect the extent of ganoderic acid A absorption. However, concomitant food intake markedly impeded both rate and extent of ganoderic acid F absorption.

Gastroprotective activity of the rhizome ethanol extract of Zingiber simaoense Y. Y. Qian in rats.

ETHNOPHARMACOLOGICAL RELEVANCE Zingiber simaoense Y. Y. Qian belongs to the Zingiberaceae family. Its rhizome has been used in Thai folk medicine to relieve gastric disorders; however, scientific evidence of its pharmacological activities has not yet been revealed. AIM OF THE STUDY This study was designed to validate the gastroprotective activity and to identify possible mechanisms of gastroprotection of Z. simaoense rhizome ethanol extract (ZSE) in rats. MATERIALS AND METHODS The gastroprotective effect of ZSE was tested using models of gastric ulcers induced by acidified ethanol, indomethacin, and restraint water immersion stress. Models for determination of gastric wall mucus secretion and plasma malondialdehyde levels as well as pylorus ligation were used to explore the mechanisms of action. RESULTS After oral administration by intragastric gavage, ZSE 7.5, 15, and 30mg/kg or cimetidine 100mg/kg significantly inhibited the formation of gastric ulcer in all gastric ulcer models. The gastric wall mucus amount was significantly higher than that of the ulcer control group, plasma malondialdehyde levels were normalized, and gastric secretion was partly inhibited by pretreatment with ZSE. CONCLUSIONS This study demonstrates the gastroprotective activity of ZSE in rats. The mechanisms of action of ZSE may depend on its ability to maintain the integrity of gastric wall mucus through the protection of gastric mucus, and/or by increasing the gastric mucus synthesis and secretion through prostaglandin synthesis. Moreover, the antioxidant activity of ZSE may also contribute to its mechanism of gastroprotection.

Thai Massage, and Thai Herbal Compress versus Oral Ibuprofen in Symptomatic Treatment of Osteoarthritis of the Knee: A Randomized Controlled Trial

The aim of this study was to verify the clinical responses to Thai massage (TM) and Thai herbal compression (THC) for treating osteoarthritis (OA) of the knee in comparison to oral ibuprofen. This study was a randomized, evaluator-blind, controlled trial. Sixty patients with OA of the knee were randomly assigned to receive either a one-hour session of TM or THC (three times weekly) or oral ibuprofen (three times daily). The duration of treatment was three weeks. The clinical assessments included visual analog scale assessing pain and stiffness, Lequesnes functional index, time for climbing up ten steps, and physicians and patients overall opinions on improvement. In a within-group comparison, each treatment modality caused a significant improvement of all variables determined for outcome assessments. In an among group comparison, all modalities provided nearly comparable clinical efficacy after a three-week symptomatic treatment of OA of the knee, in which a trend toward greatest improvement was likely to be found in THC group. In conclusion, TM and THC generally provided comparable clinical efficacy to oral ibuprofen after three weeks of treatment and could be considered as complementary and alternative treatments for OA of the knee.

Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study.

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (C max), time to reach peak concentration (T max), area under the plasma concentration-time curve (AUC), and half-life (t 1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects.

Cytotoxic Effect of Coscinium fenestratum on Human Head and Neck Cancer Cell Line (HN31)

Coscinium fenestratum is widely used as a medicinal plant in many Asian countries. This study aimed to investigate the cytotoxic effect of a crude water extract of C. fenestratum (CF extract) compared to 5-fluorouracil (5-FU) on human HN31 cell line, a metastatic squamous cell carcinoma of the pharynx. The results revealed that cell morphology visualized under inverted light microscopy was changed from flat with a polygonal appearance to round appearance after CF extract application. The cell viability assay (MTT test) showed that the concentration producing 50% growth inhibition (IC50) at 48-hour incubation of CF extract on HN31 was 0.12 mg/mL, while the IC50 of 5-FU was 6.6 mg/mL, indicating that CF extract has a higher potency. However, combining various concentrations of 5-FU and CF extract at IC50 did not show synergistic effect. The CF extract dose dependently increased cell apoptosis determined by Annexin-V and propidium iodide staining. It decreased the phosphorylation of p38 MAPK and pAkt, while it increased the tumor suppressor protein p53. In conclusion, the cytotoxicity of CF extract was associated with the modulation of p38 MAPK, pAkt, and p53 signal molecules, leading to inhibiting cell survival and increasing apoptosis. No synergistic effects of CF extract and 5-FU were observed.