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      Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

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          Abstract

          Background

          Chemotherapy 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/Design

          The 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.

          Results

          Promising 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.

          Conclusion

          Plants 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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          Most cited references36

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          Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs.

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            Pharmacological and toxicological properties of Nigella sativa.

            The seeds of Nigella sativa Linn. (Ranunculaceae), commonly known as black seed or black cumin, are used in folk (herbal) medicine all over the world for the treatment and prevention of a number of diseases and conditions that include asthma, diarrhoea and dyslipidaemia. This article reviews the main reports of the pharmacological and toxicological properties of N. sativa and its constituents. The seeds contain both fixed and essential oils, proteins, alkaloids and saponin. Much of the biological activity of the seeds has been shown to be due to thymoquinone, the major component of the essential oil, but which is also present in the fi ed oil. The pharmacological actions of the crude extracts of the seeds (and some of its active constituents, e.g. volatile oil and thymoquinone) that have been reported include protection against nephrotoxicity and hepatotoxicity induced by either disease or chemicals. The seeds/oil have antiinflammatory, analgesic, antipyretic, antimicrobial and antineoplastic activity. The oil decreases blood pressure and increases respiration. Treatment of rats with the seed extract for up to 12 weeks has been reported to induce changes in the haemogram that include an increase in both the packed cell volume (PCV) and haemoglobin (Hb), and a decrease in plasma concentrations of cholesterol, triglycerides and glucose. The seeds are characterized by a very low degree of toxicity. Two cases of contact dermatitis in two individuals have been reported following topical use. Administration of either the seed extract or its oil has been shown not to induce significant adverse effects on liver or kidney functions. It would appear that the beneficial effects of the use of the seeds and thymoquinone might be related to their cytoprotective and antioxidant actions, and to their effect on some mediators of inflammation. Copyright 2003 John Wiley & Sons, Ltd.
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              Cancer preventive properties of ginger: a brief review.

              Ginger, the rhizome of Zingiber officinalis, one of the most widely used species of the ginger family, is a common condiment for various foods and beverages. Ginger has a long history of medicinal use dating back 2500 years. Ginger has been traditionally used from time immemorial for varied human ailments in different parts of the globe, to aid digestion and treat stomach upset, diarrhoea, and nausea. Some pungent constituents present in ginger and other zingiberaceous plants have potent antioxidant and anti-inflammatory activities, and some of them exhibit cancer preventive activity in experimental carcinogenesis. The anticancer properties of ginger are attributed to the presence of certain pungent vallinoids, viz. [6]-gingerol and [6]-paradol, as well as some other constituents like shogaols, zingerone etc. A number of mechanisms that may be involved in the chemopreventive effects of ginger and its components have been reported from the laboratory studies in a wide range of experimental models.
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                Author and article information

                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central
                1472-6882
                2012
                27 March 2012
                : 12
                : 23
                Affiliations
                [1 ]Thailand Center of Excellence for Drug Discovery and Development (TCEDDD), Thammasat University, Pathumthani, Thailand
                [2 ]Department of Research, National Cancer Institute, Ministry of Public Health, Bangkok, Thailand
                [3 ]Applied Thai Traditional Medicine Center, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
                [4 ]Thailand Center of Excellence for Drug Discovery and Development (TCEDDD), Thammasat University, 99 Moo 18 Paholyothin Rd., Klongluang, Pathumthani 12121, Thailand
                Article
                1472-6882-12-23
                10.1186/1472-6882-12-23
                3353211
                22448640
                6fc87a8b-a6b3-4761-b168-511950213a70
                Copyright ©2012 Plengsuriyakarn et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 January 2012
                : 27 March 2012
                Categories
                Research Article

                Complementary & Alternative medicine
                anticancer,cholangiocarcinoma,thai medicinal plants,nude mouse xenograft model

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