Cancer is one of the leading causes of death for the Thai people. Cancer chemotherapy has developed rapidly, but some chemotherapies cause unacceptable side effects. This has led to the search for more natural biological products, especially those derived from plant products. Additionally, substitution or combination of conventional chemotherapeutic compounds with herbal medicine might improve efficacy and decrease side effects. Medicinal plants are recognized as being important sources of materials for developing novel drugs. Many Thai plants have been reported to possess anti-cancer efficacy, but the molecular mechanisms of these natural products are not well understood.

     Currently, the Laboratory of Pharmacology is exploring the molecular mechanisms for the anti-proliferative effects of Thai medicinal plants, as well as their ability to induce apoptosis, in order to evaluate their potential as candidates for further development as anti-cancer agents. Medicinal plants that are presently being studied include Terminalia chebula, Andrographis paniculata, Gynostemma pentaphyllum, and Euphoria longana. Since chemopreventive and chemotherapeutic agents can exhibit tissue specificity, the first phase of the study is to evaluate anti-cancer activity on a wide variety of cancers by utilizing different human cancer cell lines including hepatocarcinoma, leukemia, breast adenocarcinoma, and lung cancer. Our studies focus on the modulatory effects of the medicinal plant extracts and pure compounds on the cell cycle machinery, as well as study of the molecular mechanisms and signaling pathways responsible for anti-proliferation activity and induction of apoptosis. A better understanding of the mechanisms of action of these anti-cancer candidates will facilitate development of novel anti-cancer drugs derived from these potentially valuable medicinal plants.

     Traditional medicine has been an integral part of Thai society for centuries, but its popularity has gradually declined. However, interest in medicinal plants was revived in 1980, when the Ministry of Public Health included medicinal plants in its list of essential drugs for the primary health care system of the nation. It is generally accepted that therapeutic efficacy and safety must be proven, not only for modern drugs, but also for herbal medicines. With herbal medicines, variations in the levels of active ingredients have been well documented and can account for lack of therapeutic effectiveness and occurrence of side effects. At present, we focus on four selected medicinal plants namely, Terminalia chebula, Andrographis paniculata, Gynostemma pentaphyllum, and Euphoria longana.

     Andrographis paniculata has been selected for study in our laboratory since 1999, because it is widely used to treat common cold and was included in “the National List of Essential Drugs: List of Herbal Medicinal Products” in 1999. The scientific literature also shows that A. paniculata has a wide spectrum of pharmacological activities, including anti-diarrhoeal, anti-hepatotoxic, anti-malarial and anti-viral (including anti-HIV) activities. It is also active against the common cold, and has immunostimulatory and cardiovascular activities. To make the most effective and safe use of this plant, it is necessary to isolate the pure active compounds and use them for standardization of the active compounds in plant extracts. With the close collaboration of various laboratories in the institute, as well as with the Office of Special Activities, we have been able to isolate three major bioactive triterpenoids, and to develop a HPLC fingerprint, using the isolated compounds as markers. We are able to show that 14-deoxy-11, 12-didehydroandrographolide (AP3) is responsible for the lowering of blood pressure observed in some patients taking this medicinal plant. The content of AP3 increases to nearly double, if it is stored more than 1 year. Furthermore, AP3 content varies from one preparation to another, which may be due to different sites of cultivation, time of harvesting, and the parts of the plant used for extraction, as well as to differences in storage time. Therefore, the first step should be to develop appropriate HPLC fingerprints, which can be used for the optimization and standardization of the bioactive compounds in the plant extracts. (click here to download AP brochure in Thai)

      Currently, the research activities of the Laboratory of Pharmacology on natural products involve the development of rapid analytical methods for extraction, identification, and quantification of the phytochemicals from selected Thai medicinal plants. This includes the assessment of variation among plant materials and the standardization of the plant extracts. We have developed HPLC techniques for simultaneous determination of these phytochemicals from many plants. High quality concentrated plant extracts will be produced by different techniques, e.g. by freeze drying, spray drying, and supercritical fluid extraction. Fingerprints of all phytochemicals present in the plants will be used for the quality control of these plant extracts. In addition, as these medicinal plants are normally produced in dried-leaf form or whole plant, they can be easily contaminated with heavy metals and microorganisms from the environment (soil, water, or air) during growing and/or the manufacturing processes when the ready-made products are produced. Additional sources of heavy metal contamination are rainfall, atmospheric dust, plant protective agents, and fertilizers. Therefore, determination of some toxic metals such as cadmium, lead, arsenic, and mercury in medicinal plant products should be part of the quality control process to ensure the purity, safety and efficacy of these products. Furthermore, pharmacological and toxicological studies of the pure active compounds are also being carried out. The pharmacological studies focus on the cardiovascular system, respiratory system, neuronal and immune systems, as well as anti-malarial, anti-oxidant, and anti-cancer activities of the plants. These studies have the potential to lead to major discoveries in the development of modern drugs and nutraceutical products. In addition, these standardized plant extracts may be used as value-added ingredients in various food products such as fruit drinks, cooked or canned foods, to enhance their nutritional values and promote good health. (click here to download GP brochure in Thai)

     As Thailand becomes more industrialized, varieties of chemicals are being used and are inevitably being emitted to the environment. Thus, with technological advancements, humans are increasingly being exposed to environmental toxicants. Moreover, many chronic diseases such as, Alzheimer’s disease, and Parkinson’s disease are found to be associated with exposure to environmental toxicants. The Laboratory of Pharmacology is particularly interested in the neurotoxicological aspect of environmental toxicants, especially those that affect cholinergic functions. Our study will focus on the toxic effects of metals (i.e. arsenic, cadmium, and mercury), acrylonitrile, benzene, and pesticides (synthetic pyrethroids such as cypermethrin). The key processes affecting cell proliferation, apoptotic cell death, oxidative-induced DNA damage, as well as signal transduction will be investigated. Special attention will be given to alterations of neuronal muscarinic cholinergic and non-neuronal cholinergic receptors and their signaling pathways leading to the altered physiological responses. Understanding the underlying molecular mechanisms may potentially lead to treatment and prevention of the harmful effects of these toxicants.

     At present, we also focus our attention to environmental chemical-induced susceptibility to malarial infection, metal-induced cardiovascular disorders i.e. hypertention, platelet aggregation and contamination of toxic metals in agricultural products and medicinal plants. Attenuation of environmental chemical-induced cardiovascular disorders by standardized extracts and pure compounds from selected medicinal plants are currently being investigated.

     In addition to cholinergic function, physiological homeostasis of several systems such as reproductive, immune, cognitive, and circulatory systems are under regulation of the endocrine system. Emerging evidence has indicated that many environmental contaminants possess ability to modulate this system. Likewise, an increasing amount of evidence indicates correlation of incidences of many diseases induced by chemicals via the mechanism of disrupting the homeostasis of the endocrine system. Due to the uppertone of this, Laboratory of Pharmacology aims to study the effects of environmental pollutants on the endocrine system, specifically on the estrogenic effect. Environmental contaminants especially the group of heavy metal such as arsenite, cadmium, and mercury which have been termed metalloestrogens will be particularly investigated for the molecular mechanisms on estrogen signaling pathway. Moreover, a project is also underway to investigate the application of selected compounds from Thai medicinal plant as chemoprevention agents for toxicity of environmental contaminants.