BackgroundChemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed.Methods/DesignThe study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification.ResultsPromising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities.ConclusionPlants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA.

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Abstract. The aim of this study was to evaluate the estrogenic activity of tuberous samples of wild, phytoestrogen-rich Pueraria mirifica collected from 28 out of 76 provinces of Thailand by MCF-7 proliferation assay. The plant extracts were administered to MCF-7, ERα positive human mammary adenocarcinoma cell cultures, for 3 days at dosages of 0.1, 1, 10, 100 and 1,000 µg/ml and were compared with 17β-estradiol at concentrations of 10 -12 -10 -6 M. The mean P. mirifica population at 1 µg/ml exhibited significant proliferation. Two plant samples exhibited levels of proliferation in MCF-7 that were similar to 17β-estradiol. The mean P. mirifica populations at 100 and 1,000 µg/ml exhibited significant cytotoxicity in MCF-7. Analysis of the estrogenic activity of puerarin, representative of major isoflavonoids in P. mirifica tubers, revealed proliferation in MCF-7 only at the highest dose (10 -6 M) that was 10 2 -10 5 times less active than 17β-estradiol. Puerarin and 17β-estradiol at concentration of 10 -12 -10 -6 M exhibited no cytotoxicity in MCF-7. Key words: Isoflavonoid, MCF-7 proliferation assay, Phytoestrogen, Pueraria mirifica, Puerarin (J. Reprod. Dev. 54: [63][64][65][66][67] 2008) he plants in genus Pueraria are largely distributed in Asia and have a long history of ethnopharmacological applications [1]. Pueraria mirifica Airy Shaw et Suvatabhandu, family Leguminosae, is an indigenous Thai herb. The potent estrogenic activity of the plant has been proven in a 1-year human clinical trial of 4 menopausal volunteers at Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand. An average dose of 100 mg of tuberous powder per day was effective for long-term treatment of menopausal symptoms [2], and toxicological tests showed that it did not have significant adverse effects in animals and human volunteers. An acute toxicity test of P. mirifica treatment at a dose of 16 g/kg BW using rats did not reveal any adverse effects [3]. However, P. mirifica did initiate adverse effects such as anemia, during subchronic treatment for 3 months at doses of 100 and 1,000 mg/kg BW [4]. Haemotological adverse effects were confirmed in a 6-month chronic toxicity test at a dose of 250 mg/kg BW [5]. Treatment with the plant extract at high doses 600 and 800 mg/kg BW, for 30 days induces micronucleus formation in male rats [6]. However, pretreatment of weanling rats with P. mirifica powder at a dose of 10, 100 and 1,000 mg/kg BW for 28 days resulted in a dose-dependent prevention of mammary tumors induced by 7, 12-dimethylbenz (a) anthracene (7, 12-DMBA) [7].The phytoestrogens of P. mirifica exhibit the following responses: dose-dependent estrogenic effects on the reproductive system, initiated vaginal cornification, increased uterine weight with decreased follicle stimulating hormone (FSH) and luteinizing hormone (LH) serum levels in ovariectomized rats [8], increased length of the follicular phase and total menstruation cycle [9], decreased estrogen, progesterone, FSH, and LH concentrations at the do...

Paramichelia baillonii has been used by the natives of Northern Thailand for medicinal purposes. Four components have been isolated from the bark of this plant and their structures determined by spectroscopic means. Three of the components had been reported previously: the germacranolide epoxides (--)-dihydroparthenolide [1] and (--)-parthenolide [2] and the oxoaporphinoid alkaloid liriodenine [4]. The fourth component is an unusual new germacranolide alkaloid which has been named (--)-bisparthenolidine [3] because it was presumably formed in the plant from ammonia and two molecules of parthenolide. Parthenolide was reported previously to possess anti-tumor activity, and in the present study we report on the significant activity of the new alkaloid 3 in the KB cell culture assay.

The volatile oil from fresh leaves of Streblus asper Lour. was isolated by hydrodistillation and analysed through a combination of gas chromatography with FID (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The essential oil was obtained in 0.005% yield as a brown liquid. The major constituents of the volatile oil of S. asper were phytol (45.1%), α α α α α-farnesene (6.4%), trans-farnesyl acetate (5.8%), caryophyllene (4.9%) and trans-trans-α α α α α-farnesene (2.0%). In addition, the volatile oil showed significant anticancer activity (ED 50 < < < < << < < < < 30 µ µ µ µ µg/ml) from cytotoxicity primary screening tests with P388 (mouse lymphocytic leukaemia) cells but no significant antioxidant activity (IC 50 values of Analysis of the Volatile OilFresh leaves were homogenized and hydrodistilled for 5 h, to obtain a volatile brown oil in 0.005% yield based on the fresh weight of the sample. The sample was stored at low temperature (−30°C) prior to analysis. GC-FID analysis was performed on a Varian 3700 gas chromatograph coupled to a Shimadzu C-R3A integrator and fitted with a fused silica capillary column (25QC/ BP5) obtained from SGE, Australia (25 m × 0.25 mm i.d., 0.25 µm film thickness). The analytical conditions were: carrier gas hydrogen (ca. 1 ml/min) injector temperature 260°C, detector (FID) temperature 280°C, oven temperature 40°C (2 min hold) to 280°C (5 min hold) at 4°C/min. Programmed-temperature Kováts retention indices (RI) were obtained by GC-FID analysis of an aliquot of the essential oil spiked with an n-alkane mixture containing each homologue from n-C 8 to n-C 30 . GC-MS analysis was performed in electron impact mode (EI, 70 eV) using a VG AutoSpec system interfaced with a Hewlett-Packard 5890 Series II gas chromatograph, fitted with a capillary column (BPX5) supplied by SGE, Australia (2 m × 0.25 mm i.d., 0.25 µm film thickness). Oven temperature settings were the same as those described for the GC-FID analysis, with helium (ca. 1.4 ml/min) used as carrier gas.

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The interactive effects of combined treatment with heat and CDDP (0.5 micrograms/ml) or CBDCA (10 micrograms/ml) were examined on the surviving fractions of V-79 cells. Both CDDP and CBDCA treatment induced a slight enhancement in thermosensitivity of thermotolerant cells. The development of thermotolerance during step-up heating was partially inhibited by simultaneous treatment with CDDP or CBDCA throughout the heating process. Simultaneous heat treatment at 42 degrees C with either drug showed marked interactive effect and inhibited the thermotolerance developed during 42 degrees C heating.