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 (dhatu 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.

The Effects of Thai Herbal Ha-Rak Formula on COX Isoform Expression in Human Umbilical Vein Endothelial Cells Induced by IL-1ß.

OBJECTIVE: To investigate the modulated effects of HRF on cyclooxygenase isoform expression and its activity, using the human umbilical vein endothelial cell (HUVEC) model induced by interleukin-1 beta (IL-1ß). METHODS: Cells were treated with indomethacin (positive control), HRF, and its components at various concentrations prior to treatment with IL-1ß at 24 h. Cell viability was determined by MTT assay. Moreover, the anti-inflammatory effects of HRF and its components through mRNA and protein expression were established using real-time quantitative PCR and Western blot, respectively. COX activity was identified via exogenous and endogenous PGE2 productions using the EIA. RESULT: There was no cytotoxicity in HUVECs treated with HRF. None of the experimental conditions used in the study affected the expression of COX-1, but COX-2 protein expression was inhibited at concentrations under 10 µg/mL. Despite the significantly increased levels of exogenous PGE2, HRF had no effect on COX-2 mRNA expression. However, the production of PGE2 was lower at a concentration of 100 µg/mL HRF than at a concentration below 10 µg/mL. Interestingly, each component of HRF revealed different effects of the Ha-Rak formula. CONCLUSION: Our preliminary findings suggest that HRF and its components provide diverse modulation of COX-2 and PGE2 at the in vitro level.

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.

The anatomical study of the major signal points of the court-type Thai traditional massage on legs and their effects on blood flow and skin temperature.

OBJECTIVE: This study aims to investigate the relationship between major signal points (MaSPs) of the lower extremities used in court-type Thai traditional massage (CTTM) and the corresponding underlying anatomical structures, as well as to determine the short-term changes in blood flow and skin temperature of volunteers experiencing CTTM. METHODS: MaSPs were identified and marked on cadavers before acrylic color was injected. The underlying structures marked with acrylic colors were observed and the anatomical structures were determined. Then, pressure was applied to each MaSP in human volunteers (lateral side of leg and medial side of leg) and blood flow on right dorsalis pedis artery was measured using duplex ultrasound while skin temperature changes were monitored using an infrared themographic camera. RESULTS: Short-term changes in the blood flow parameters, volume flow and average velocity, compared to baseline (P < 0.05), were observed on MaSP of the lower extremity, ML4. Changes in the peak systolic velocity of the area ML5 were also observed relative to baseline. The skin temperature of two different MaSPs on the lateral side of leg (LL4 and LL5) and four on the medial side of leg (ML2, ML3, ML4 and ML5) was significantly increased (P < 0.05) at 1 min after pressure application. CONCLUSION: This study established the clear correlation between the location of MaSP, as defined in CTTM, and the underlying anatomical structures. The effect of massage can stimulate skin blood flow because results showed increased skin temperature and blood flow characteristics. While these results were statistically significant, they may not be clinically relevant, as the present study focused on the immediate physiological effect of manipulation, rather than treatment effects. Thus, this study will serve as baseline data for further clinical studies in CTTM.

Vasculoprotective and vasodilatation effects of herbal formula (Sahatsatara) and piperine in spontaneously hypertensive rats.

BACKGROUND: The herbal formula (Sahatsatara, STF), the Thai traditional poly-herbal recipe, has been used for treatment of muscle pain, anti-flatulence and numbness on hands and feet, with the caution when used in hypertensive patients. However, there is no scientific evidence to prove its effects on cardiovascular system. Piperine is the proposed major active compound in STF. It is shown to have antihypertensive effect in the L-NAME-induced endothelial dysfunction rats. PURPOSE: This study investigated the pharmacokinetics, mechanism of action, as well as the hemodynamic and vasoactive effect and toxicity of STF and piperine using spontaneously hypertensive rats (SHR) and normal Wistar rats (NWR). METHODS: The amount of piperine in STF was measured by ultra performance liquid chromatography (UPLC). SHR and NWR were gavaged with piperine (50mg/kg/day) or STF (100, 300, or 1000mg/kg/day) alone or together with L-NAME (in drinking water) for 28 days. Hemodynamic effects were monitored by noninvasive tail cuff every 7 days. Vasorelaxation effect on the thoracic aorta in organ chamber was observed through force transducer at the end of the experiment. Biochemical parameters for kidney and liver toxicity were measured. In addition, pharmacokinetic study was performed using non-compartment analysis. RESULTS: The amount of piperine in STF was 1.29%w/w. Both STF and piperine did not affect blood pressure and heart rate in both SHR and NWR. Interestingly, STF and piperine increased acetylcholine-induced vasorelaxation of isolated thoracic aorta and have vascoluprotective effect in nitric oxide (NO) impaired rats. No liver or kidney toxicity was found in this study. Non-compartment pharmacokinetic analysis showed that the time to reach maximum concentration (Tmax) of plasma piperine after administration of piperine and STF were 3.9 and 1.7h, respectively. This result suggested that piperine in the recipe had better absorption than the pure standard piperine. CONCLUSIONS: STF had no effect on blood pressure in both SHR and NWR. However, it was able to relax isolated thoracic aorta and had the potential for vasculoprotective effect in hypertensive and NO impaired condition. The effects of STF were comparable to those of piperine.

IL-1ß-induced modulation of gene expression profile in human dermal fibroblasts: the effects of Thai herbal Sahatsatara formula, piperine and gallic acid possessing antioxidant properties.

BACKGROUND: Pain is the main symptom of most musculoskeletal disorders and can be caused by inflammation in association with oxidative stress. Thai herbal Sahatsatara formula (STF), a polyherbal formula, has been traditionally used for relieving muscle pain and limb numbness. This study aimed to investigate biologically active compounds of STF and its pharmacological effects related to antioxidant and anti-inflammatory activities. METHODS: The identification of possibly active compounds of STF was performed by high performance liquid chromatography (HPLC). Moreover, this study also assessed the free radical scavenging activities of STF and its components using DPPH radical scavenging assay and their inhibitory effects on IL-1ß-induced intracellular reactive oxygen species (ROS) formation in primary human dermal fibroblasts (NHDFs) using DCFDA-flow cytometry analysis. Modulation of human gene expression by STF and its active compounds was investigated by microarray analyzed through Gene Ontology (GO) classification and pathway enrichment analysis. RESULTS: HPLC analysis has revealed the presence of gallic acid (GA) and piperine (PP) as the major compounds in STF extracts. Our finding discovered that STF and its active compounds (GA and PP) yielded free radical scavenging activities and abilities to inhibit IL-1ß-induced cellular ROS formation in NHDFs. Furthermore, microarray analysis demonstrated that a total of 84 genes (54 upregulated and 30 downregulated) were significantly affected by IL-1ß involved in inflammatory cytokines, chemokines, transcription factors, cell adhesion molecules and other immunomodulators participating in NF-κB signaling. The significantly upregulated genes in IL-1ß-treated in NHDFs participate in interleukin and cholecystokinin (CCRK) signaling pathways. The GO analysis of the target genes showed that all test compounds including indomethacin, STF and its active compounds, can downregulate the genes involved in NF-кB signaling pathway in IL-1ß-treated NHDFs compared to the cells treated with IL-1ß alone. CONCLUSIONS: STF and its active compounds possessing antioxidant actions can modulate the effects of IL-1ß-mediated alteration of gene expression profiles associated with inflammatory signaling in NHDFs.

The Efficacy of Thai Herbal Prasaplai Formula for Treatment of Primary Dysmenorrhea: A Short-Term Randomized Controlled Trial.

This study aims to compare the efficacy of pain relief between a specific Thai herbal Prasaplai formula (PPF) and placebo in patients with primary dysmenorrhea. Forty women with primary dysmenorrhea symptoms were randomized into two groups. The experimental group received PPF capsules 1000 mg orally three times per day before meals for three days starting from the first day of menstruation. The placebo group received placebo as the same dose and time. Average pain intensity from the first day to the third day of cycle significantly decreased in both groups (p < 0.001), but with no statistically significant difference between groups. Using a pre- and posttreatment difference in NRS of at least 2, a greater proportion of patients in PPF group experienced pain relief compared to placebo during the first and second day of period. A greater proportion of PPF group also experienced no pain compared to the placebo group on day 1 and day 3 by using multidimensional scoring. The PPF demonstrates pain relief activity when used during menstruation in primary dysmenorrhea patients, with no adverse effects. However, further studies are needed in order to assess the value of PPF as a long-term prophylaxis for primary dysmenorrhea.

The effects of the court-type Thai traditional massage on anatomical relations, blood flow, and skin temperature of the neck, shoulder, and arm.

BACKGROUND: Court-type Thai traditional massage (CTTM) has specific major signal points (MaSP) for treating musculoskeletal conditions. The objectives of this study are to investigate the anatomical surfaces and structures of MaSPs, and to examine blood flow (BF) and skin temperature (ST) changes after applying pressure on the MaSPs on neck, shoulder, and arm areas. METHODS: In the anatomical study, 83 cadavers were dissected and the anatomical surfaces and structures of the 15 MaSPs recorded. In human volunteers, BF, peak systolic velocity (PS), diameter of artery (DA), and ST changes were measured at baseline and after pressure application at 0, 30, 60, 180, and 300 s. RESULTS: There was no statistical difference in anatomical surfaces and structures of MaSP between the left and right side of the body. The 3 MaSPs on the neck were shown to be anatomically separated from the location of the common carotid arteries. The BF of MaSPs of the neck significantly and immediately increased after pressure application for 30 s and for 60 s in the arm (p < 0.001). ST increased significantly and immediately after pressure application for 300 s (p < 0.001). There was no significant correlation between BF and ST at any of the MaSPs. CONCLUSIONS: This study showed that MaSP massages were mainly directed towards muscles. MaSPs can cause significant, but brief, increases in BF and ST. Further studies are suggested to identify changes in BF and ST for all of the MaSPs after actual massage treatment sessions as well as other physiological effects of massage.

Physical effects and cognitive function after exercising "Rue-si-dad-ton" (exercise using the posture of the hermit doing body contortion): a randomized controlled pilot trial.

BACKGROUND: This study aims to preliminarily evaluate effect on physical properties of shoulder joints and cognitive function after practicing Rue-si-dad-ton, a Thai traditional exercise using the postures of the hermit doing body contortion which still lacks systematically conducted evidence-based regarding its benefits. MATERIAL AND METHOD: Thirty-seven participants who have routinely worked on computer at least 3 hours per day were recruited and randomized into intervention (n = 19) or control group (n = 18). Physical effect on shoulder joints was evaluated by measuring shoulder range of motion (ROM) and evaluating shoulder function with the American Shoulder & Elbow Surgeons Standardized Shoulder Assessment Form. Cognitive function was determined by Verbal Fluency Test, Trail Maker B Test, and Digit Span Test. Both study groups were assessed by all tests at the beginning and at the end of study by blinded assessors. The intervention group performed 3 postures of Rue-si-dad-ton exercise (an hour per day for 4 days by a well-trained instructor) before thefinal measurement. RESULTS: Only left and right shoulder flexion of the intervention group (p-value = 0.006 and 0.010 respectively) showed significant increment compared with the control group using ANCOVA test with baseline adjusted as covariate. Other variables, including joint and cognitive function, indicated no significant changes between groups. No complications from exercise were found during the study CONCLUSION: Rue-si-dad-ton may safely help improve range of joint motion with potential benefit for joint and cognitive function. Additional extensive studies with adequate number of participants and longer period of exercise are warranted.

Redox Mechanisms of AVS022, an Oriental Polyherbal Formula, and Its Component Herbs in Protection against Induction of Matrix Metalloproteinase-1 in UVA-Irradiated Keratinocyte HaCaT Cells.

Ayurved Siriraj HaRak (AVS022) formula has been used for topical remedy of dermatologic disorders. Oxidative stress induced by ultraviolet (UV) A irradiation could be implicated in photoaged skin through triggering matrix metalloproteinase-1 (MMP-1). We, therefore, explored the antioxidant mechanisms by which AVS022 formulation and its individual components protected against UVA-dependent MMP-1 upregulation in keratinocyte HaCaT cells. TLC analysis revealed the presence of multiple phenolics including gallic acid (GA) in the AVS022 extracts. We demonstrated that pretreatment with the whole formula and individual herbal components except T. triandra protected against increased MMP-1 activity in irradiated HaCaT cells. Moreover, all herbal extracts and GA, used as the reference compound, were able to reverse cytotoxicity, oxidant production, glutathione (GSH) loss, and inactivation of catalase and glutathione peroxidase (GPx). F. racemosa was observed to yield the strongest abilities to abolish UVA-mediated induction of MMP-1 and impairment of antioxidant defenses including GSH and catalase. Our observations suggest that upregulation of endogenous antioxidants could be the mechanisms by which AVS022 and its herbal components suppressed UVA-stimulated MMP-1 in HaCaT cells. In addition, pharmacological actions of AVS022 formula may be attributed to the antioxidant potential of its components, in particular F. racemosa, and several phenolics including GA.

Protective effect of AVS073, a polyherbal formula, against UVA-induced melanogenesis through a redox mechanism involving glutathione-related antioxidant defense.

BACKGROUND: Ayurved Siriraj Brand Wattana formula (AVS073), a Thai herbal formula, has traditionally been used for health promotion and prevention of age-related problems. Ultraviolet A (UVA) is recognized to play a vital role in stimulation of melanin synthesis responsible for abnormal skin pigmentation possibly mediated by photooxidative stress. We thus aimed to study the inhibitory effect of AVS073 extracts on UVA-induced melanogenesis via a redox mechanism involving glutathione (GSH) synthesis and glutathione S-transferase (GST) using human melanoma (G361) cell culture. METHODS: The standardization of AVS073 extracts was carried out by TLC and UHPLC to obtain fingerprinting profiles of the formula, which identified several phenolic compounds including gallic acid (GA) in the formula. Antimelanogenic actions of AVS073 (up to 60 µg/ml) and GA (up to 10 µg/ml) were investigated by measuring tyrosinase activity and mRNA as well as melanin level in G361 cells irradiated with UVA. Moreover, antioxidant actions of the herbal formula and GA were determined by evaluating oxidant formation and modulation of GSH-related antioxidant defenses including GSH content, GST activity and mRNA level of γ-glutamate cysteine ligase catalytic (γ-GCLC) and modifier (γ-GCLM) subunit and GST. RESULTS: AVS073 extracts and GA, used as a reference compound, suppressed UVA-augmented tyrosinase activity and mRNA and melanin formation. In addition, pretreatment with AVS073 and GA was able to inhibit cellular oxidative stress, GSH depletion, GST inactivation and downregulation of γ-GCLC, γ-GCLM and GST mRNA in G361 cells exposed to UVA radiation. CONCLUSIONS: AVS073 formula exerted antimelanogenic effects possibly through improving the redox state by upregulation of GSH and GST. Moreover, pharmacological activity of the polyherbal formula would be attributed to combined action of different phenolic compounds present in the formula.

The safety of Homnawakod herbal formula containing Aristolochia tagala Cham. in Wistar rats.

BACKGROUND: A dried root of Aristolochia tagala Cham. (ATC) is often used in Thai traditional medicine as an antipyretic, anti-inflammatory agent, muscle relaxant, appetite-enhancing agent, and analeptic. Homnawakod, an important herbal recipe, originally contains ATC in its formula, however, some Aristolochia species have been reported to cause nephrotoxicity due to aristolochic acid (AA) and its derivatives, resulting in ATC removal from all formulae. Therefore, this study investigates the chemical profiles of ATC, the original (HNK+ATC) and the present Homnawakod Ayurved Siriraj Herbal Formulary™ (HNK), and investigates whether they could cause nephrotoxicity or aggravate LPS-induced organ injuries in vivo. METHODS: HPLC and LC/MS were used for chemical profile study. Male Wistar rats were randomly divided into groups in which the rats were intragastrically administered distilled water (2 groups), ATC (10 or 30 mg/kg), HNK+ATC (540 or 1,620 mg/kg), or HNK (1,590 mg/kg) for 21 days. A positive control group was administered with single dose 100 mg/kg standard AA-I intragastrically at day 1. Serum creatinine and urea were measured at baseline and at 7, 14 and 21 days of the treatment. On day 22, a model of lipopolysaccharide (LPS)-induced endotoxemia was used. One-way and two-way analyses of variance were performed and a P value of less than 0.05 was considered to be significant. RESULTS: The similarity of the HPLC chromatograms of HNK+ATC and HNK could suggest that the qualities of both formulae are nearly the same in terms of chemical profile. The amount of AA-I found in ATC is 0.24%w/w. All experimental groups exhibited similar levels of serum urea at baseline and 7 and 14 days of the treatment. At 21 days, rats received AA exhibited a significant increase in serum urea, whereas the others did not exhibit such toxicity. On day 22, there were no significant changes in LPS-induced renal and liver dysfunction, or LPS-induced mean arterial pressure (MAP) reduction upon administration of ATC, HNK+ATC, HNK or AA-I. CONCLUSIONS: These results suggest that ATC, HNK+ATC or HNK, at the animal dose equivalent to that used in human, do not cause the acute nephrotoxicity in rats and do not aggravate LPS-induced organ injuries even further.

The Phyllanthus emblica L. infusion carries immunostimulatory activity in a mouse model.

BACKGROUND: Phyllanthus emblica L. (Indian gooseberry, Ma khaam pom) has been an herbal component of Thai traditional recipes proposed to slow down the aging process. A number of methodologies have been employed to investigate the immunological aspects of the so called "anti-aging effects" of P. emblica in a BALB/c mice model. OBJECTIVE: 1) To investigate the immunological efficacy of the anti-aging effects of P. emblica infusion in a BALB/c mice model. 2) To verify the safety for the consumption of P. emblica infusion in BALB/c mice. MATERIAL AND METHOD: For in vitro studies, splenocytes were isolated from mice and examined in comparison with the human umbilical endothelial cells, fibroblasts and YAC-1 (mouse lymphoma) cells for proliferative activity upon the exposure to P. emblica infusion. For in vivo studies, mice were orally administered with P. emblica infusion at a dose range of 0, 50, 100, 200 mg/kg BW for 14 days. After the treatments, splenocytes isolated from these mice examined for proliferative and NK cell activities. RESULTS: For in vitro studies, the infusion of P. emblica could directly drive the proliferation of mouse splenocytes in a dose-dependent manner. The P. emblica infusion itself was already cytotoxic to YAC-1 in the studied dose, while sparing the human umbilical endothelial cells and fibroblasts. For in vivo studies, splenocytes isolated from these mice exhibited dose-dependent proliferative activities. Only the isolated splenocytes from mice ingesting 100 mg/kg BW exhibited an enhancement in NK cell activity. CONCLUSION: P. emblica infusion could drive proliferative activity of splenocyte in vitro and in vivo, with an enhancement in the NK cell-induced cytotoxic activity. The infusion in the aforementioned dose was safe throughout the study.

Effect of Ayurved Siriraj herbal recipe Chantaleela on platelet aggregation.

INTRODUCTION: Ayurved Siriraj Chantaleela recipe is a traditional Thai remedy consisting of eight medicinal plants, which is employed for the treatment of fever. OBJECTIVE: To investigate the effects of Ayurved Siriraj Herbal recipe Chantaleela on platelet aggregation. STUDY DESIGN: Clinical research; ex vivo with before and after study design. MATERIAL AND METHOD: Twelve healthy male and female volunteers participated in the present study. Platelet aggregation test before Chantaleela ingestion was done as a control. After administration of 750 mg Chantaleela (3 x 250 mg tablets) every 8 hours for 3 doses, platelet aggregation was measured 8 hours following the first dose using an aggregometer and microplate reader. Adrenaline (Adr) and adenosine diphosphate (ADP) were used as platelet stimulants. Platelet aggregation was measured again at 32 hours and 8-10 days after the first dose. RESULTS: All of the participants completed the present study without any adverse event. Ayurved Siriraj Chantaleela did not affect platelet aggregation; neither Adr nor ADP were used as platelet agonists in both aggregometer and microplate reader Subgroup analysis revealed no significant change in platelet aggregation after Chantaleela administration according to the control for both male and female groups. The same results were also obtained in other subgroup analysis including hyperaggregation group, hypo-normal aggregation group. CONCLUSION: From the present study, normal dose of Chantaleela for alleviation of fever does not have an effect on either platelet aggregation or platelet numbers. It may conclude that the present study supports the safety use of Chantaleela for relieving fever as platelet status does not need to be taken into consideration.