Anti-Inflammatory, Antinociceptive, Antipyretic, and Gastroprotective Effects of Eurycoma longifolia Jack Ethanolic Extract.

Tongkat ali (Eurycoma longifolia Jack) (ELJ) is a plant in the Simaroubaceae family. Its roots are used in traditional Thai medicine to treat inflammation, pain, and fever; however, the antiulcer abilities of its ethanolic extract have not been studied. This study examined the anti-inflammatory, antinociceptive, antipyretic, and gastroprotective effects of ethanolic ELJ extract in animal models and found that ELJ effectively reduced EPP-induced ear edema in a dose-dependent manner and that a high dose of ELJ inhibited carrageenan-induced hind paw edema formation. In cotton-pellet-induced granuloma formation, a high dose of ELJ suppressed the increases in wet granuloma weight but not dry or transudative weight. In the formalin-induced nociception study, ELJ had a significant dose-dependent inhibitory impact. Additionally, the study found that yeast-induced hyperthermia could be significantly reduced by antipyretic action at the highest dose of ELJ. In all the gastric ulcer models induced by chemical substances or physical activity, ELJ extracts at 150, 300, and 600 mg/kg also effectively prevented gastric ulcer formation. In the pyloric ligation model, however, the effects of ELJ extract on gastric volume, gastric pH, and total acidity were statistically insignificant. These findings support the current widespread use of Eurycoma longifolia Jack in traditional medicine, suggest the plant's medicinal potential for development of phytomedicines with anti-inflammatory, antinociceptive, and antipyretic properties, and support its use in the treatment of gastric ulcers due to its gastroprotective properties.

Speed of action and stage specificity of Bencha-loga-wichian, a Thai traditional antipyretic formulation, against Plasmodium falciparum and the chloroquine-potentiating activity of its active compounds, tiliacorinine and yanangcorinine.

ETHNOPHARMACOLOGICAL RELEVANCE: Bencha-loga-wichian (BLW), a Thai traditional antipyretic formulation, has been reported to have promising antiplasmodial activity, and it was previously revealed that tiliacorinine and yanangcorinine, isolated from Tiliacora triandra, were the active compounds. However, the mechanisms of action of BLW have not been investigated. In addition, these active compounds are bisbenzylisoquinoline alkaloids, many compounds of which have been reported to potentiate the efficacy of chloroquine. AIMS OF THE STUDY: To investigate the antiplasmodial mechanisms of action of BLW and evaluate the effects of chloroquine combined with tiliacorinine or yanangcorinine. MATERIALS AND METHODS: Chloroquine-resistant Plasmodium falciparum (PfW2) strains at the ring, trophozoite, and schizont stages were exposed to the extracts or compounds for 2, 4, 6, 8, 10, 12, 24 or 48 h. The percentages of parasitemia were determined by flow cytometry, and their morphologies were examined by Giemsa-stained smear to evaluate the speed of action and stage specificity. For the drug combination assay, a modified fixed-ratio isobologram method was used. RESULTS: The antiplasmodial activity of BLW possessed a slow onset of action and was the most effective against ring-stage parasites. After 48 h of extracts or compounds exposure, most of the treated parasites, at all stages, turned to the pyknotic form and could not recover even after extracts or compounds removal. The results suggested that these extracts and compounds could kill the parasites or possess parasiticidal effects. In addition, the combination of chloroquine with tiliacorinine or yanangcorinine demonstrated a synergistic effect, indicating that these compounds could potentiate chloroquine efficacy against chloroquine-resistant parasites. CONCLUSION: The antiplasmodial mechanisms of action of BLW appeared to differ from that of chloroquine and other current antimalarial drugs. In addition, tiliacorinine and yanangcorinine, the active compounds of BLW, could potentiate the efficacy of chloroquine. Accordingly, BLW was shown to be a good candidate for development as a new antimalarial and useful for drug combination therapy.

Salacia chinensis L. Stem Extract Exerts Antifibrotic Effects on Human Hepatic Stellate Cells Through the Inhibition of the TGF-ß1-Induced SMAD2/3 Signaling Pathway.

: Salacia chinensis L. (SC) stems have been used as an ingredient in Thai traditional medicine for treating patients with hepatic fibrosis and liver cirrhosis. However, there is no scientific evidence supporting the antifibrotic effects of SC extract. Therefore, this study aimed to determine the antifibrotic activity of SC stem extract in human hepatic stellate cell-line called LX-2. We found that upon TGF-ß1 stimulation, LX-2 cells transformed to a myofibroblast-like phenotype with a noticeable increase in α-SMA and collagen type I production. Interestingly, cells treated with SC extract significantly suppressed α-SMA and collagen type I production and reversed the myofibroblast-like characteristics back to normal. Additionally, TGF-ß1 also influenced the development of fibrogenesis by upregulation of MMP-2, TIMP-1, and TIMP-2 and related cellular signaling, such as pSmad2/3, pErk1/2, and pJNK. Surprisingly, SC possesses antifibrotic activity through the suppression of TGF-ß1-mediated production of collagen type 1, α-SMA, and the phosphorylation status of Smad2/3, Erk1/2, and JNK. Taken together, the present study provides accumulated information demonstrating the antifibrotic effects of SC stem extract and revealing its potential for development for hepatic fibrosis patients.

Antipsoriatic Effects of Wannachawee Recipe on Imiquimod-Induced Psoriasis-Like Dermatitis in BALB/c Mice.

Psoriasis is a common immune-mediated chronic inflammatory skin disease characterized by thick and erythema raised plaques with adherent silvery scales. T-cells are activated via the IL-23/Th17 axis which is involved in psoriasis pathogenesis. Conventional treatments of psoriasis have adverse events that influence patients' adherence. Wannachawee Recipe (WCR) is Thai traditional medicine that is known to be effective for psoriasis patients; however, preclinical evidence is still lacking. This study investigated the therapeutic potential of WCR on antiproliferant activity using imiquimod- (IMQ-) induced psoriasis-like dermatitis in a mouse model. Psoriasis-like dermatitis was induced on the shaved dorsal skin and right ear pinna of BALB/c mice by topical application of IMQ for 15 consecutive days after which WCR was administered to the mice by oral gavage for 10 days. Phenotypical observations, histopathological examinations, and ELISA of skin and blood samples were conducted. WCR significantly ameliorated development of IMQ-induced psoriasis-like dermatitis and reduced levels of Th17 cytokines (IL-17A, IL-22, and IL-23) in both serum and dorsal skin. Histopathological findings showed a decrease in epidermal thickness and inflammatory T-cell infiltration in the WCR-treated groups. The WCR has pharmacological actions which regulate Th17 related cytokines suggesting that it is a potential alternative therapeutic strategy for psoriasis.

Marcanine G, a new cytotoxic 1-azaanthraquinone from the stem bark of Goniothalamus marcanii Craib.

The ethanolic extract from the stem bark of Goniothalamus marcanii Craib was shown in preliminary brine shrimp lethality data having good cytotoxic activity. Further bioassay guided isolation was done by means of solvent partition, chromatography and precipitation to provide four isolated compounds: a novel compound 1 with the core structure of 1-azaanthraquinone moiety referred as marcanine G; as well as compounds 2-4 with known aristolactam structures namely, piperolactam C, cepharanone B and taliscanine. These compounds were characterised by spectroscopic techniques. The assessment of cytotoxicity was established on an SRB assay using doxorubicin as a positive control. Marcanine G (1) was considered the most active compound indicating the IC50 values of 14.87 and 15.18 µM against human lung cancer cells (A549) and human breast cancer cells (MCF7), respectively. However, 2 showed mild activity with the IC50 values of 83.72 and 82.32 µM against A549 and MCF7 cells, respectively.

Effects of Wannachawee Recipe with Antipsoriatic Activity on Suppressing Inflammatory Cytokine Production in HaCaT Human Keratinocytes.

Psoriasis is a chronic inflammatory and immune-mediated skin disease. The pathogenesis involves T cells activation via the IL-23/Th17 axis. Conventional treatments of psoriasis have adverse events influencing patients' adherence. Wannachawee Recipe (WCR) has been effectively used as Thai folk remedy for psoriasis patients; however, preclinical evidence defining how WCR works is still lacking. This study defined mechanisms for its antiproliferation and anti-inflammatory effects in HaCaT cells. The cytotoxicity and antiproliferation results from SRB and CCK-8 assays showed that WCR inhibited the growth and viability of HaCaT cells in a concentration-dependent manner. The distribution of cell cycle phases determined by flow cytometry showed that WCR did not interrupt cell cycle progression. Interestingly, RT-qPCR revealed that WCR significantly decreased the mRNA expression of IL-1ß, IL-6, IL-8, IL-17A, IL-22, IL-23, and TNF-α but induced IL-10 expression in TNF-α- and IFN-γ-induced HaCaT cells. At the protein level determined by ELISA, WCR significantly reduced the secretion of IL-17A, IL-22, and IL-23. The WCR at low concentrations was proved to possess anti-inflammatory effect without cytotoxicity and it did not interfere with cell cycle of keratinocytes. This is the first study to provide convincing evidence that WCR is a potential candidate for development of effective psoriasis therapies.

Efficacy and safety of "Yahom" as a traditional Thai herbal therapy: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Yahom is a traditional Thai medicine used to treat syncope and abdominal discomfort. AIM OF THE STUDY: This study aimed to systematically review all available evidence which purports to support these claims. MATERIAL AND METHODS: The systematic review accorded with the Cochrane Collaboration framework and PRISMA reporting. Databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane library database, and Google Scholar were searched by keywords, Yahom and Ya-hom. Pharmacological and toxicity data from non-animal and animal studies were included. RESULTS: Twenty-four articles: 2 on in vitro cell lines or bacteria, 3 in vitro cell-free, 5 in vitro animal, 13 in vivo and 1 human mainly reported (A) Cardiovascular effects (i) transient hypotension (0.2-0.8g/kg, intravenous injection (i.v.)), increased cerebral blood flow (2g/kg, single oral) and vascular dilatation/relaxation (ii) elevated blood pressure (BP) (0.2-0.8g/kg, i.v. or 2-4g/kg oral) and vasocontraction. Single Yahom doses (3g) given to healthy volunteers had no effect on cutaneous blood flow, ECG or systolic BP although marginally increased diastolic BP was claimed. (B) Yahom (2-4g/kg) completely inhibited gastric acid secretion evoked by gastric secretagogues. (C) Toxicity: Chronic oral doses of selected Yahoms to rodents (0.001-1g/kg) supports its status as generally regarded as safe. CONCLUSIONS: Most studies supported declared objectives relating to perceived Yahom actions, but lacked background demonstrating clinical efficacy, and mechanistic data that would validate conclusions. Our study suggests that research into traditional medicinal herbs needs underpinning by appropriate clinical interventions and pharmacovigilance, thereby optimising efficacy and minimizing toxicity by combining traditional wisdom and modern testing.

Antiplasmodial activities of a Thai traditional antipyretic formulation, Bencha-Loga-Wichian: A comparative study between the roots and their substitutes, the stems.

ETHNOPHARMACOLOGICAL RELEVANCE: Bencha-Loga-Wichian (BLW) is a polyherbal antipyretic formulation that is comprised of Capparis micracantha, Clerodendrum indicum, Ficus racemosa, Harrisonia perforata, and Tiliacora triandra. A traditional medical textbook has documented the use of this formulation for the treatment of many types of fever, including malaria-like fever. Traditionally, BLW is composed of the root parts of those plants. However, in current practice, the stem parts are frequently substituted. Thus, this study aimed to evaluate the antiplasmodial activities of BLW and compare the efficacy between the stem and root parts. MATERIALS AND METHODS: BLW formulations produced from either the stem or root parts of the various constituent plants as well as the stems or roots of the individual plants were separately extracted and tested against the chloroquine-sensitive (Pf3D7) and -resistant (PfW2) strains Plasmodium falciparum using flow cytometry. The cytotoxicity against peripheral blood mononuclear cells was evaluated using the WST-8 assay to determine the selectivity index (SI). The active compounds of BLW were isolated using antiplasmodial-guided isolation and quantified using Ultra-Performance Liquid Chromatography (UPLC). RESULTS: The stem and root parts of BLW and the individual plants exhibited antiplasmodial activities at the same levels with good SI values in the range of 3.55-19.74. The extracts of BLW exhibited promising antiplasmodial activity against both Pf3D7 (IC50<5µg/mL) and PfW2 (IC50=6-10µg/mL). Among the five component plants, T. triandra was the most active and exhibited an IC50<5µg/mL against both strains of parasites with SI values >10. We isolated tiliacorinine and yanangcorinine as the major active compounds (IC50<2µg/mL). However, these two compounds demonstrated cytotoxic effects (SI<1). The UPLC analysis identified these compounds in both the stem and root parts of BLW in the range of 0.57-7.66%, which correlated with the antiplasmodial activity. The concentrations of these compounds in BLW, at comparable efficacy, were much less than those at the IC50s for the single compounds alone. It suggested that synergistic interactions increased the antiplasmodial effects as well as alleviated the toxicity of the active compounds in BLW. CONCLUSION: This study described a promising antiplasmodial activity of BLW that had good selectivity and a toxicity-alleviating effect. The results provided scientific support for the use of this formulation for the treatment of malaria. In addition, the stem and root parts of the plants in BLW exhibited equivalent activities, which indicates the potential for the substitution of the stem parts in the formulation. Thus, we recommend additional study of the stem parts of these plants for further development on the basis of the availability and sustainability.

Effect of Tri-sa-maw recipe on gastrointestinal regulation and motility. .

BACKGROUND: Tri-sa-maw recipe is comprised ofequal proportions of three herbal fruits, including Terminalia chebula Retz., Terminalia sp. and Terminalia bellirica Roxb. The traditional use of this recipe has been reported as a medication for fever; expectorant, relief of tightness in the stomach, laxative and antidiarrheal agent. OBJECTIVE: To study the effects of Tri-sa-maw recipe extract on gastrointestinal tract in both in vitro and in vivo. MATERIAL AND METHOD: Gastrointestinal effect of Tri-sa-maw recipe was studied by using two in vivo models (gastric emptying, gastrointestinal transit) and in vitro isolated guinea pig ileum experiment. RESULTS: Tri-sa-maw recipe showed both stimulatory and inhibitory effects on the stomach function. Not only did the extract at the dose of 1,000 mg/kg inhibit the gastric emptying time, but also stimulate the movement of the digestive tract by increasing the mobility of charcoal. In the isolated guinea pig ileum experiment, the extract at low concentration (0.1 ng/mL) induced the contraction of isolated guinea pig ileum. However the stimulation effect on contractions of isolated guineapig ileum was very much decreased at the high concentration (0.2-1 ng/mL) of the extract. CONCLUSION: The findings of this study support to traditional uses of Tri-sa-maw recipe as a laxative and antidiarrheal agent.

Acute and sub-chronic toxicity of Tri-sa-maw recipe in rats.

BACKGROUND: Tri-sa-maw recipe is a botanical preparation comprised of equal proportions ofthe three herbalfruits, namely Terminalia chebula Retz., Tenninalia sp. and Terminalia bellirica Roxb. This recipe is used for antipyretic, expectorant, periodic maintenance, and relieving stomach tight. OBJECTIVE: To evaluate the acute and sub-chronic toxicities of Tri-sa-maw recipe extract in rats. MATERIAL AND METHOD: In the present study of acute toxicity, a single oral dose 5,000 mg/kg of Tri-sa-maw recipe extract was administered to rats. Sub-chronic toxicity was studied by the daily oral administration ofthe extract at the doses of 600, 1,200 and 2,400 mg/kg body weight for consecutive 90 days. RESULTS: Tri-sa-maw recipe extract at the dose of 5,000 mg/kg showed no signs of differences as compared to the control rat. No abnormalities were found in the sub-chronic toxicity study; none of the parametersfor body and organ weights, hematol- ogy, blood chemistry, necropsy, and histopathology showed any differences between the control and all treatment groups. CONCLUSION: Tri-sa-maw recipe extract did not significantly cause acute toxicity or sub-chronic toxicity in rats.

Analgesic and antipyretic activity of Tri-sa-maw recipe.

BACKGROUND: Tri-sa-maw recipe is composed of equal proportions of the three fruits including Terminalia chebula Retz., Terminalia sp. and Terminalia bellirica Roxb. In Southeast Asia, these fruits are used as both food and medicine. In Thai traditional medicine, Tri-sa-maw recipe is well known for treating fever, expectorant, periodic maintenance, and tight stomach relief OBJECTIVE: To study anti-inflammatory, analgesic and antipyretic activities of Tri-sa-maw recipe in experimental animals. MATERIAL AND METHOD: The anti-inflammatory study was conducted by two experimental models; ethyl phenylpropiolate- induced ear edema and carrageenin-induced paw edema. For analgesic activity, the pain was induced by acetic acid or heat. In addition, yeast-induced hyperthermia was performedfor the study of antipyretic activity. RESULTS: The results showed that Tri-sa-maw recipe extract reduced ear edema ofrat induced by EPP but did not inhibit acute inflammation in the carrageenin-inducedpaw edema. However the extract at the doses of 300-1,200 mg/kg was able to inhibit the acetic acid-induced writhing response, but not the heat-induced pain. This result suggests the peripheral effect of its analgesic activity, which inhibits the biosynthesis, and/or release of some pain mediators. Finally, oral administration ofthe extract at the dose of 1,200 mg/kg body weight effectively reduced the hyperthermia, which possibly is due to the inhibition of prostaglandins. CONCLUSION: The present study has clearly demonstrated both analgesic and antipyretic activities of Tri-sa-maw recipe.

Alkaline phosphatase activity-guided isolation of active compounds and new dammarane-type triterpenes from Cissus quadrangularis hexane extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem of Cissus quadrangularis L. (CQ) is used in traditional medicine to treat bone fractures and swelling. Anti-osteoporotic activity of CQ hexane extract has been reported, but the active compounds in this extract remain unknown. Thus, we aimed to identify the active compounds in CQ hexane extract using bioassay-guided isolation. MATERIALS AND METHODS: The CQ hexane extract was fractionated sequentially with benzene, dichloromethane, ethyl acetate, and methanol. The examination of CQ extract and its fractions was guided by bioassays for alkaline phosphatase (ALP) activity during the differentiation of MC3T3-E1 osteoblastic cells. The cells were treated with or without the CQ extract and its fractions for a period of time, and then the stimulatory effect of the alkaline phosphatase enzyme, a bone differentiation marker, was investigated. The compounds obtained were structurally elucidated using spectroscopic techniques and re-evaluated for activity during bone differentiation. RESULTS: A total of 29 compounds were isolated, viz., triterpenes, fatty acid methyl esters, glycerolipids, steroids, phytols, and cerebrosides. Four new dammarane-type triterpenes were isolated for the first time from nature, and this report is the first to identify this group of compounds from the Vitaceae family. Seven compounds, viz., glycerolipids and squalene, stimulated ALP activity at a dose of 10µg/mL. Moreover, the synergistic effect of these compounds on bone formation was demonstrated. CONCLUSION: This report describes, for the first time, the isolation of active compounds from CQ hexane extract; these active compounds will be useful for the quality control of extracts from this plant used to treat osteoporosis.

A preliminary study of the acaricidal activity of clove oil, Eugenia caryophyllus.

BACKGROUND: The search for more eco-friendly acaricides has prompted testing of medicinal plants from botanical sources. OBJECTIVE: To evaluate the eradication of house dust mites (HDM), Dermatophagoides pteronyssinus, by direct contact using the essential clove oil (Eugenia caryophyllus). METHODS: A pilot study was initiated to determine the killing power of clove oil. Synthetic fibers were immersed in 2% clove oil for 30 min, dried in a hot air oven at 60°C for 2 hrs after which 0.5 gm of HDMs were exposed to these coated fibers placed in the Siriraj Chamber (SC). Two additional long-term methods were employed. Ten mites were placed in the SC and 10 µl of clove oil was pipetted or sprayed onto them. These latter two procedures were each carried out for 3 consecutive days at 0, 1, 3 and 6 months. The solutions antimicrobial and antifungal properties were evaluated by exposing common bacteria and fungi to sterile filter disks impregnated with the mixture, and after overnight incubation, the disc diffusion method on nutrient agar was used. Ethyl alcohol served as the placebo. 99% and 81%, respectively, while the placebo mortality was <5%. The zone of inhibition indicated significant clearance for all the bacteria and fungi indicating greater biocidal activity when compared to the controls. RESULTS: SEMs revealed dead mites on the fibers. The effectiveness of pipetting and spraying was 99% and 81%, respectively, while the placebo mortality was <5%. The zone of inhibition indicated significant clearance for all the bacteria and fungi indicating greater biocidal activity when compared to the controls. CONCLUSIONS: Clove oil is a promising agent for killing dust mites with a potential use in dust-mite laden mattresses. Spraying diminishes in efficiency after 3 months.

Field evaluation of in vitro-induced tetraploid and diploid Centella asiatica (L.) Urban.

Centella asiatica-a medicinal plant that produces high-value active triterpenoids-is in increasing demand by the pharmaceutical and cosmetic industries. The aim of this study was to field-test one induced tetraploid and three diploid C. asiatica lines for the selection of high-quality plants with high phytomass and triterpenoid content and to determine their optimal harvesting time. All tested C. asiatica were micropropagated using an established protocol. One-month-old plantlets were acclimatized for the field experiment. The plants were grown in a randomized complete block design (RCBD) with three replications, ten plantlets per replication, and the experimental bed site was 0.6 × 1.0 m. Growth parameters, phytomass and the amounts of four active triterpenoids were evaluated. All lines exhibited the highest growth, yields and triterpenoids at 4 months after cultivation. The tetraploid line showed significantly better characteristics, i.e., larger leaf area, leaf width, petiole length, and greater yields, than diploid lines. Dry weight per cultivated area (77.53 ± 3.07 g/m(2)) and total triterpenoids (15.38 ± 0.76 % dry weight) were increased significantly in tetraploid plants of C. asiatica. Furthermore, the harvesting time had an effect on the yield and triterpenoid content (P < 0.001). In all tetraploid and diploid lines, the yields and triterpenoid content per cultivated area reached their maximum at 4 months after planting. Our results demonstrated that polyploidy induction is a beneficial tool that can be used to improve the medicinal value of C. asiatica.

Acute and chronic toxicity studies of the water extract from dried fruits of Terminalia bellerica (Gaertn.) Roxb. In Spargue-Dawley rats.

Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results showed no signs of toxicity such as general behavior changes, morbidity, mortality, changes on gross appearance or histopathological changes of the internal organs of rats. The study of chronic toxicity was determined by oral feeding both female and male rats (10 female, 10 male) daily with the test substance at the dose of 300, 600 and 1,200 mg/kg body weight continuously for 270 days. The examinations of signs of toxicity showed no abnormalities in the test groups compared to the controls. In addition, these rats were analyzed for final body and organ weights, necropsy, as well as hematological, blood chemical and histopathological parameters. Taken together, the water extract from the dried fruits of T. bellerica did not cause acute or chronic toxicities in either female or male rats.

Evaluation of anti-inflammatory and antinociceptive activity of Triphala recipe.

The anti-inflammatory and antinociceptive activities of Triphala recipe were studied in animal models. Triphala recipe (4 mg/ear) significantly exhibited an inhibitory effect on the ear edema formation induced by ethyl phenylpropiolate-induced, but not on the arachidonic acid-induced ear edema in rats. Furthermore, Triphala recipe at the doses of 300, 600 and 1,200 mg/kg significantly reduced carrageenan-induced hind paw edema. Next, the anti-inflammatory action in chronic inflammation was measured using the cotton pellet-induced granuloma formation assay in rats. Triphala recipe (1,200 mg/kg) reduced neither transudative weight nor granuloma formation. It also did not affect on body weight gain and thymus weight indicating that Triphala recipe does not have a steroid-like effect. In antinociceptive study, Triphala recipe (300, 600, 1,200 mg/kg), elicited significant inhibitory effect on both phases, especially in late phase, of the formalin test in mice suggesting that the antinociceptive action of Triphala recipe may be via both peripheral and at least partly centrally acting.

Anti-inflammatory and anti-ulcerogenic activities of Chantaleela recipe.

Chantaleela recipe is indicated for relieving fever in Thai traditional folk medicine. In the present study, Chantaleela recipe was investigated for anti-inflammatory, analgesic, antipyretic and anti-ulcerogenic activities. In preliminary investigation Chantaleela recipe was found to exert an inhibitory activity on the acute phase of inflammation as seen in ethyl phenylpropiolate-induced ear edema as well as in carrageenan-induced hind paw edema in rats. The results suggest that the anti-inflammatory activity of Chantaleela recipe may be due to an inhibition via cyclooxygenase pathway. In the analgesic test, Chantaleela recipe showed a significant analgesic activity in both the early and late phases of formalin test, but exerted the most pronounced effect in the late phase. The analgesic activity of Chantaleela recipe may act via mechanism at peripheral and partly central nervous system. In antipyretic test, Chantaleela recipe significantly decreased rectal temperature of brewer's yeast-induced hyperthermia rats, probably by inhibiting synthesis and/or release of prostaglandin E2 in the hypothalamus. Therefore, the key mechanism of anti-inflammatory, analgesic, and antipyretic activity of the Chantaleela recipe likely involves the inhibition of the synthesis and/or release of inflammatory or pain mediators, especially prostaglandins. The oral administration of the Chantaleela recipe reduced ulcer formation in acute gastric ulcer models (EtOH/HCl-, indomethacin-, and stress-induced gastric lesions). In contrast, this recipe did not reduce the secretory rate, total acidity, and increase pH in rat stomach. These results indicated that Chantaleela seem to possess anti-ulcerogenic effect. This activity may be due to the increase of gastric mucosal resistance or potentiation of defensive factors and/or the decrease of aggressive factors but did not associate the anti-secretory activity. Moreover, the high oral doses treated did not cause acute toxicity in rats and the long term oral administration did not produce gastric and ileum lesions.

Anti-diarrheal activity and toxicity of Learng Pid Samud recipe.

Learng Pid Samud (LPS) recipe is a traditional remedy in Thai folk medicine to ease the common diarrhea. The anti-diarrheal potential of LPS recipe was herein examined in vitro using a guinea-pig ileum model. The LPS exerted an inhibitory effect on acetylcholine-induced smooth muscle contraction in the guinea pig ileum. Significantly, not only did the LPS reduce the total amount of feces in the induced diarrhea rats, but also the intestinal transit in the charcoal meal test. A single oral administration with the recipe at 5,000 mg/kg did not cause acute toxicity and the daily oral administration (1,000, 2,000 and 4,000 mg/kg) for 90 days in rats did not produce any toxic signs and symptoms. In conclusion, the Learng Pid Samud recipe remedy is evidently safe and effective for the anti-diarrheal treatment which supports its therapeutic uses in the alternative medicine.

Acute and subchronic toxicity of Chantaleela recipe in rats.

Acute and subchronic toxicities of Chantaleela recipe were studied in both male and female rats. Oral administration of the extract at a single dose of 5,000 mg/kg body weight (5 females, 5 males) did not produce signs of toxicity, behavioral changes, mortality or differences on gross appearance of internal organs. The subchronic toxicity was determined by oral feeding the test substance at the doses of 600, 1,200 and 2,400 mg/kg body weight for 90 days (10 females, 10 males). No signs of abnormalities were observed in the test groups as compared to the controls. The test and control groups (on the 90(th) day) and the satellite group (on the 118(th) day) were analyzed by measuring their final body and organ weights, taking necropsy, and examining hematological parameters, blood clinical chemistry and histopathology features. The results suggest that Chantaleela recipe did not cause acute or subchronic oral toxicities to female and male rats.

Effect of Thai plant extracts on P-glycoprotein function and viability in paclitaxel-resistant HepG2 cells.

The effects of ethanol extracts from Thai plants on P-glycoprotein (P-gp) function and cell viability were examined using paclitaxel-resistant HepG2 (PR-HepG2) cells. KP018 from Ellipeiopsis cherrevensis and AT80 from Ancistrocladus tectorius increased both rhodamine 123, a typical P-gp substrate, and [(3)H]paclitaxel uptake in PR-HepG2 cells. However, some extracts such as MT80 from Microcos tomentosa increased rhodamine 123, but not [(3)H]paclitaxel, uptake, while MM80 from Micromelum minutum increased only [(3)H]paclitaxel uptake. Thus, the effects of extracts of Thai plants on rhodamine 123 uptake were not necessarily the same as those on [(3)H]paclitaxel uptake. Purified compounds such as bergapten did not affect the uptake of either substrate. KP018, AT80, and MM80 increased [(3)H]paclitaxel uptake and decreased the cell viability in a concentration-dependent manner. Among these extracts, KP018 showed the most potent cytotoxicity. The cytotoxic potency of KP018 on PR-HepG2 cells was similar to that on wild-type HepG2 cells, and was not potentiated by verapamil. At concentrations resulting in no cytotoxicity, AT80 and MM80 potentiated paclitaxel-induced cytotoxicity in PR-HepG2 cells. These results indicate that K018 may be a useful source to search for a new anticancer drug, while AT80 and MM80 may be useful as modulators of P-gp-mediated multidrug resistance in cancer cells.