The induction of cyclooxygenase-2 in IL-1beta-treated endothelial cells is inhibited by prostaglandin E2 through cAMP.

Prostaglandins (PGs) have numerous cardiovascular and inflammatory effects. Cyclooxygenase (COX), which exists as COX-1 and COX-2 isoforms, is the first enzyme in the pathway in which arachidonic acid is converted to PGs. Prostaglandin E2 (PGE2) exerts a variety of biological activities for the maintenance of local homeostasis in the body. Elucidation of PGE2 involvement in the signalling molecules such as COX could lead to potential therapeutic interventions. Here, we have investigated the effects of PGE2 on the induction of COX-2 in human umbilical vein endothelial cells (HUVEC) treated with interleukin-1beta (IL-1beta 1 ng/ml). COX activity was measured by the production of 6-keto-PGF1alpha, PGE2, PGF2alpha and thromboxane B2 (TXB2) in the presence of exogenous arachidonic acids (10 microM for 10 min) using enzyme immunoassay (EIA). COX-1 and COX-2 protein was measured by immunoblotting using specific antibody. Untreated HUVEC contained only COX-1 protein while IL-1beta treated HUVEC contained COX-1 and COX-2 protein. PGE2 (3 microM for 24h) did not affect on COX activity and protein in untreated HUVEC. Interestingly, PGE2 (3 microM for 24h) can inhibit COX-2 protein, but not COX-1 protein, expressed in HUVEC treated with IL-1beta. This inhibition was reversed by coincubation with forskolin (100 microM). The increased COX activity in HUVEC treated with IL-1beta was also inhibited by PGE2 (0.03, 0.3 and 3 microM for 24h) in a dose-dependent manner. Similarly, forskolin (10, 50 or 100 microM) can also reverse the inhibition of PGE2 on increased COX activity in IL-1beta treated HUVEC. The results suggested that (i) PGE2 can initiate negative feedback regulation in the induction of COX-2 elicited by IL-1beta in endothelial cells, (ii) the inhibition of PGE2 on COX-2 protein and activity in IL-1beta treated HUVEC is mediated by cAMP and (iii) the therapeutic use of PGE2 in the condition which COX-2 has been involved may have different roles

In vitro protective effects of plants frequently used traditionally in cancer prevention in Thai traditional medicine: An ethnopharmacological study

ETHNOPHARMACOLOGICAL RELEVANCE: Thai traditional medicine (TTM) has been used widely in cancer management in Thailand. Although several Thai medicinal plants were screened for pharmacological activities related to cancer treatment, such evidence still suffers from the lack of linking with TTM knowledge. AIM OF THE STUDY: To document knowledge and species used in cancer prevention in TTM and to preliminary investigate pharmacological activities related to the documented knowledge of twenty-six herbal drugs used in cancer/mareng prevention. METHODS: Fieldwork gathering data on TTM concept and herbal medicines used in cancer prevention was performed with TTM practitioners across Thailand. Later, water and ethanol extracts from twenty-six herbal drugs mentioned as being used in cancer prevention were screened for their protective effect against tert-butyl hydroperoxide-induced cell death in HepG2 cells. Then active extracts were investigated for their effects on NQO1 activity, glutathione level, and safety in normal rat hepatocytes. RESULTS: The fieldwork helped in the development of TTM cancer prevention strategy and possible experimental models to test the pharmacological activities of selected medicinal plants. Fifteen plant extracts showed significant protective effect by restoring the cell viability to 40-59.3%, which were comparable or better than the positive control EGCG. Among them, ethanol extracts from S. rugata and T. laurifolia showed the most promising chemopreventive properties by significantly increased NQO1 activity, restored GSH level from oxidative damage, as well as showed non-toxic effect in normal rat hepatocytes. CONCLUSION: TTM knowledge in cancer prevention was documented and used in the planning of pharmacological experiment to study herbal medicines, especially in cancer, inflammation, and other chronic diseases. The proposed strategy should be applied to in vivo and clinical studies in order to further confirm the validity of such a strategy. Other traditional medical systems that use integrated approaches could also apply our strategy to develop evidence that supports a more rational uses in traditional medicine

Protective effect of medicinal plants used in cancer prevention by traditional healers in Thailand

Based on a field work focusing on cancer prevention by traditional healers in Thailand suggested that prevention of oxidative stress is one of the key aims. Oxidative stress is involved with degenerative diseases, as well as cancer initiation and progression [1]. Therefore, protective effect against oxidative stress-induced cell death was used to investigate cancer chemopreventive properties of plant extracts. HepG2 cells were incubated with plant extracts or (-)-Epigallocatechin gallate (EGCG) (positive control) at their non-toxic concentrations for 24 hours before an induction of the cell deaths using tert-butyl hydroperoxide (t-BHP). The Alamar Blue assay was used to determine the cell viability. After 0.5 mM t-BHP treatment for 3 hours, the viability of non-pre-treated cells was around 30%. EGCG at 50µM increased the viability to 48%. Nineteen extracts increased the viability while twelve extracts decreased the viability and six of them had no effect. Water extracts from Terminalia bellirica (Gaertn.) Roxb. and Aucklandia lappa DC. gave the highest protection by increasing the viability to 59% and 54%, respectively. In conclusion, half of the extracts from plants used traditionally in cancer prevention possess protective effect against oxidative stress-induced cell death. Further pharmacological investigation based on the key strategy will provide more detailed scientific evidence for assessing these traditional medical methods in cancer prevention

Understanding cancer and its treatment in Thai traditional medicine: An ethnopharmacological-anthropological investigation

ETHNOPHARMACOLOGICAL RELEVANCE: Thai traditional medicine (TTM) is widely practiced in Thailand and continues to gain importance in cancer management, but little is known about the TTM practitioners' emic concepts and practice. AIM OF THE STUDY: With this study we firstly aim to document the practice of cancer treatment and prevention by TTM practitioners and, secondly, to evaluate how such traditional concepts and practices are correlated with biomedical ones. This in turn can form the basis for developing novel strategies for designing pharmacological experiments and longer term strategies to develop TTM practice. METHODS: Semi-structured interviews with 33 TTM practitioners were performed in five provinces in different regions of Thailand. The following information were recorded; basic information of informants, descriptions of cancer (mareng in Thai), causes, diagnosis, treatment, and prevention. Plants used in the treatment and prevention of mareng were also collected. RESULTS: Using an in depth ethnographic approach four representative case studies to assist in a better understanding of the characteristics of mareng, its diagnosis, treatment, and prevention are reported here. Five characteristics of mareng - waste accumulation (khong sia), chronic illnesses (krasai), inflammation (kan aksep), bad blood (luead) and lymph (namlueang), and the imbalance of four basic elements (dhātu si) - have been identified. Explanatory models of cancer in TTM were linked with biomedical concepts and relevant pharmacological actions. Traditional uses and available scientific evidence of medicinal plants mentioned in the case studies for the treatment or prevention of mareng are presented and discussed. CONCLUSION: Here for the first time five main characteristics of cancer based on Thai traditional medical concepts are analysed. Our findings are relevant not only for the planning of clinical studies or pharmacological experiment in the search for novel compounds for cancer treatment and prevention, but also for the integration of Thai traditional medicine in cancer care

Regulation and pharmacology of the inducible isoform of cylco-oxygenase (COX-2)

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN002279 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Metabolomics and Integrative Omics for the Development of Thai Traditional Medicine

In recent years, interest in studies of traditional medicine in Asian and African countries has gradually increased due to its potential to complement modern medicine. In this review, we provide an overview of Thai traditional medicine (TTM) current development, and ongoing research activities of TTM related to metabolomics. This review will also focus on three important elements of systems biology analysis of TTM including analytical techniques, statistical approaches and bioinformatics tools for handling and analyzing untargeted metabolomics data. The main objective of this data analysis is to gain a comprehensive understanding of the system wide effects that TTM has on individuals. Furthermore, potential applications of metabolomics and systems medicine in TTM will also be discussed