Therapeutic potential of Thai herbal formula for cognitive impairment: A metabolomics approach for Comprehensive Insights.

Chronic cerebral ischemia hypoperfusion plays a role in the initiation and progression of vascular dementia, which causes changes in metabolites. Currently, there is no standard treatment to treat, prevent and reduce the severity of this condition. Thai herbal Yahom no.20 (YHF20) is indicated for fatigue and dizziness. The components of YHF20 have been found to have pharmacological effects related to the pathology of chronic cerebral ischemia hypoperfusion. This study aimed to investigate metabolomic changes after YHF20 administration in a rat model of permanent bilateral common carotid artery occlusion (2-VO) induced chronic cerebral ischemia hypoperfusion, and to explore its impact on spatial learning and memory. Albino Wistar rats were randomly allocated to 5 groups; sham, 2-VO, 2-VO+ 100 mg/kg YHF20, 2-VO+300 mg/kg YHF20, and 2-VO+1000 mg/kg YHF20. The rats were administered YHF20 daily by oral gavage for 56 days after 2-VO induction. Plasma was collected weekly for metabolome change analysis using LC-MS/QTof and toxicity study. The rats were evaluated for spatial learning and memory using the Morris water maze. The results showed that 78 known metabolites and 10 tentative pathways altered after chronic cerebral hypoperfusion, although it was not able to determine the effect on memory and learning behaviors of rats. Glutathione and glutathione metabolism might be metabolite-pathway that were the affect after YHF20 administration in cerebral ischemic condition. The 4 known metabolites may be the metabolites from the constituents of YHF20 could be considered and confirmed for quality control purpose. In conclusion, YHF20 administration might contribute to metabolic changes related to cerebral ischemia condition without the effect on spatial learning and memory, including hepatotoxicity and nephrotoxicity after 56 days of treatment. Alterations in the potential metabolites may provide data support for elucidating dementia pathogenesis and selecting pathways for intervention.

Metabolomics of Personalized Body Elements in Thai Traditional Medicine Response to Herbal Medicine for Body Elements Balancing in Healthy Volunteers.

Background: In Thai traditional medicine (TTM), the dominant body element called "Dhat Chao Ruean" (DCR) is an integral part in the diagnostic process of Thai traditional medicine. TTM practitioners usually use Thai herbal Benjakul formula (BKF) for adjusting and balancing the body elements. However, the effects of BKF on metabolism and individual response to it have not been studied yet. Methods: This study proposed to investigate the metabolic profiling in 24 volunteers categorized by their types of birth month DCR (bDCR) after the administration of BKF (450 mg, three tablets three times a day before meals) for seven days. Differences in metabolic profiling between bDCR groups were investigated by using liquid chromatography coupled with mass spectrometry for untargeted analysis, and in addition, the safety was assessed by testing the plasma biochemical level. Results: This study identified 57 biomarkers in positive ESI and 12 in negative ESI. Piperine was found in varying amount among the participants but it was the highest in the earth group. In addition, this study found that elemicin, phenylpropionic acid, ricinoleic acid, and ß-sitosterol are important substances in a single herb of BKF. Regarding biochemical tests, the results indicated that BKF can decrease the lipid profile and it has no toxic effects on liver and kidney functions. Conclusion: The findings indicated that it is safe to use BKF which can help to improve health in chronic diseases by adjusting abnormality of the elements of the body. In addition, the information gathered from this study is valuable for further study in the field of Thai traditional medicine.

Metabolomic analysis of Thai Herbal Analgesic Formula based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Sahatsatara formula (STF), a Thai herbal medicine formula which has been commonly used as analgesic drugs to relieve musculoskeletal pain and numbness in Thai traditional medicine. The pharmacological studies of its ingredients have represented that have anti-inflammatory and antioxidant properties. However, the quality markers (Q-markers) for STF are still unknown and require further investigation. The primary goal of this study was to establish the chemical profile of STF though metabolomic analysis. Untargeted metabolomics were used to analyze global components and accurately qualify compounds. Multivariate analysis (MVA) was used to classify STF extract at three different concentrations and a quality control sample. Furthermore, samples' characteristics and identification-related markers were observed and compounds matched to the Traditional Chinese medicine library in UNIFI software. According to the results, chemical analysis revealed 63 compounds in positive mode and 33 compounds in negative mode within STF. Notably, 19 potential Q-markers were tentative identified in all three concentrations of STF, including alkaloids, terpenes, phenols, organic acids, disaccharides, fatty acids, glycosides, quinonoids, and steroids. The compounds exhibited pharmacological effects such as anti-inflammatory activity, anti-oxidant activity, and analgesic properties, which correlated to traditional properties of STF. Consequently, this study provides insights into the chemical profiles of the STF and identifies potential markers that can be utilized for qualitative and quantitative quality control of STF. Additionally, the findings can also be useful for further research into STF's anti-inflammatory properties through in vitro assays, as well as exploring its clinical efficacy to support evidence-based medicine for STF.

Prolonged Egg Supplement Advances Growing Child's Growth and Gut Microbiota.

Protein-energy malnutrition still impacts children's growth and development. We investigated the prolonged effects of egg supplementation on growth and microbiota in primary school children. For this study, 8-14-year-old students (51.5% F) in six rural schools in Thailand were randomly assigned into three groups: (1) whole egg (WE), consuming 10 additional eggs/week (n = 238) (n = 238); (2) protein substitute (PS), consuming yolk-free egg substitutes equivalent to 10 eggs/week (n = 200); and (3) control group (C, (n = 197)). The outcomes were measured at week 0, 14, and 35. At the baseline, 17% of the students were underweight, 18% were stunted, and 13% were wasted. At week 35, compared to the C group the weight and height difference increased significantly in the WE group (3.6 ± 23.5 kg, p < 0.001; 5.1 ± 23.2 cm, p < 0.001). No significant differences in weight or height were observed between the PS and C groups. Significant decreases in atherogenic lipoproteins were observed in the WE, but not in PS group. HDL-cholesterol tended to increase in the WE group (0.02 ± 0.59 mmol/L, ns). The bacterial diversity was similar among the groups. The relative abundance of Bifidobacterium increased by 1.28-fold in the WE group compared to the baseline and differential abundance analysis which indicated that Lachnospira increased and Varibaculum decreased significantly. In conclusion, prolonged whole egg supplementation is an effective intervention to improve growth, nutritional biomarkers, and gut microbiota with unaltered adverse effects on blood lipoproteins.

A double-blinded, randomized, split-side, vehicle-controlled study of the efficacy of cleanser containing Acanthus ebracteatus Vahl., Suregada multiflora, and Acacia concinna in patients with atopic dermatitis: A pilot study.

BACKGROUND: Barrier repair therapy is the key management approach for both eczematous and non-lesional skin of atopic dermatitis. The use of appropriate cleansers to enhance skin hydration is an adjunctive treatment that increases topical drug penetration. Anti-inflammatory properties of various medicinal plants in tropical Asia have been reported. OBJECTIVE: Investigate the efficacy of herbal cleanser containing a combination of herbal extracts from Acanthus ebracteatus Vahl., Suregada multiflora, and Acacia concinna on seemingly intact skin in patients with atopic dermatitis by measuring improvements in the skin barrier function. METHODS: This 2-week pilot study was a split-side, randomized, double-blinded, vehicle-controlled trial. All patients (n = 30) were asked to use both a cleanser with an active formulation containing the herbal extracts and a vehicle- controlled cleanser on each side of mid-volar forearm. Biophysical assessments including transepidermal water loss (TEWL), skin hydration, skin pH, and skin roughness were performed at baseline and upon study completion. RESULTS: Compared to baseline, the median percentage change in TEWL at the end of the study was significantly greater for the active side 10.4 (-19, 20.7) g/m2h than the control side -13.2 (-28.7, 9.1) g/m2h; p = 0.01. The median percentage change of skin hydration, skin pH, and skin roughness of the active side compared to the control side had no a statistical significance. CONCLUSIONS: This cleanser is beneficial when used as adjunctive therapy. Further studies should evaluate its anti- sinflammatory properties in the remedy or active phase of atopic dermatitis or other inflammatory skin diseases.

A comparative study of chemical constituents and safety of Thai herbal medicated oil formula and traditional medicated oil.

OBJECTIVES: Medicated oil has been traditionally used as an analgesic medicine to relieve pain by applying to the skin over painful muscles, and has been established in The National List of Essential Medicines (2556 B.E.). Traditional Medicated oil (TMO) consists of cassumunar ginger, Wan En Lueang, and Wan Ron Thong. It is prepared by frying herbs in coconut oil which is a traditional method. Thai Herbal Medicated oil formula (MOF) comprises cassumunar ginger, sweet flag, lesser galangal, wild turmeric, Wan En Lueang, and Wan Ron Thong. Its preparation by maceration with methyl salicylate is modified method to avoid the heat in the traditional preparation. Since both recipes have different methods of extraction and compositions, it is necessary to determine the chemical constituents and acute skin irritation potential of MOF and TMO. METHODS: This study applied Gas Chromatography-Mass Spectrometry (GC-MS) for quality assessment of MOF extract and TMO extract. The mass spectra of the compounds matched with authentic standards from the NIST library. The compounds were identified by comparing their retention time and peak area, and the percentage of matched factor was more than 80%. The safety assessment on acute skin irritation used the 4 h human patch test (4 h HPT) in 36 healthy subjects. RESULTS: The 37 compounds were found in MOF extract. The most common chemical constituents were terpene derivatives; monoterpenes and sesquiterpenes, and others, namely benzene derivatives, ester, phenylpropanoid, and other compounds. The 33 compounds were found in TMO extract and the chemical groups were similar to MOF extract. The 4 h HPT demonstrated that the MOF extract, TMO extract, methyl salicylate solvent, and coconut oil solvent, did not induce skin irritation. However, the vehicle of the formulae and the whole formulae as MOF and TMO clinically induced skin irritation and accorded with rubefacient. The characteristic as mild erythema or dryness, but not erythema with edema, could appear after the use of rubbing skin products. CONCLUSIONS: The chemical constituents found in MOF and TMO extracts were partially different and their acute skin irritation reactions were not significantly different. A study on the efficacy of both remedies should be performed in the future, as well as a study on active chemical constituents. This study provides scientific evidences of quality and safety, including GC-MS condition for poly-herbal medicated oil standardization.

Utilization of UPLC-PDA and GC-MS/MS coupled with metabolomics analysis to identify bioactive metabolites in medicinal turmeric at different ages for the quality assurance.

BACKGROUND: Available monographs often suggest measurement of curcumin or curcuminoids for quality control of turmeric-based medicines/products. However, one compound is not enough to indicate the quality of traditional herbal medicines due to the holistic approach. Furthermore, to ensure high quality of such products, good harvesting practice plays an important role in the quality control of turmeric raw materials. PURPOSE: This study aimed to indicate quality markers of turmeric and to suggest optimum harvesting times for turmeric used for medicinal purposes by integration of Thai traditional medicine knowledge. METHODS: Turmeric rhizomes at 4, 6, 8, 9, 10, and 11 months old were analyzed. UPLC-PDA was used for quantitation of curcumin. GC-MS/MS was used to obtain chemical profiles of turmeric volatile oil. PCA, Volcano plot, and HCA were performed to identify similarities or differences of the data. RESULTS: Turmeric aged between 6 and 10 months old contained > 5%w/w of curcumin, which complied with Thai Herbal Pharmacopoeia 2021. GC-MS/MS analysis suggested suitable chemical markers, namely Ar-turmerone, turmerone, curlone, and zingiberene, because they exhibited pharmacological activities related to the traditional uses of turmeric. Eucalyptol, santalene, ß-caryophyllene, cis-ß-farnesene, α-caryophyllene, curcumene, ß-bisabolene, ß-sesquiphellandrene, and cis-sesquisabinene hydrate were also tentatively identified. Later, the multivariate analysis revealed that turmeric aged between 6 and 10 months old showed similar metabolite profiles. CONCLUSION: Based on curcumin content and chemical profiles, turmeric aged between 6 and 10 months old are appropriate for uses in Thai traditional medicine. Our study suggests additional information in the quality control of turmeric to assure its efficacy, especially for uses in traditional medicines.

The Protective Effect of Polyherbal Formulation, Harak Formula, on UVA-Induced Photoaging of Human Dermal Fibroblasts and Mouse Skin via Promoting Nrf2-Regulated Antioxidant Defense.

Polyherbal formulation combining multiple herbs is suggested to achieve enhanced therapeutic effects and reduce toxicity. Harak herbal formula (HRF) extracts were proposed to regulate skin responses to UVR through their ability to suppress UVA-induced matrix metalloproteinase-1 (MMP-1) and pigmentation via promoting antioxidant defenses in in vitro models. Therefore, natural products targeting Nrf2 (nuclear factor erythroid 2-related factor 2)-regulated antioxidant response might represent promising anti-photoaging candidates. Hesperetin (HSP) was suggested as a putative bioactive compound of the HRF, as previously shown by its chemical profiling using the liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). In this study, we explored the anti-photoaging effects of HRF extracts and HSP on normal human dermal fibroblasts (NHDFs) and mouse skin exposed to UVA irradiation. Pretreatment of NHDFs with HRF extracts and HSP protected against UVA (8 J/cm2)-mediated cytotoxicity and reactive oxygen species (ROS) formation. The HRF and HSP pretreatment also attenuated the UVA-induced MMP-1 activity and collagen depletion concomitant with an upregulation of Nrf2 activity and its downstream genes (GST and NQO-1). Moreover, our findings provided the in vivo relevance to the in vitro anti-photoaging effects of HRF as topical application of the extracts (10, 30 and 100 mg/cm2) and HSP (0.3, 1, and 3 mg/cm2) 1 h before UVA exposure 3 times per week for 2 weeks (a total dose of 60 J/cm2) mitigated MMP-1 upregulation, collagen loss in correlation with enhanced Nrf2 nuclear accumulation and its target protein GST and NQO-1 as well as reduced 8-hydroxy-2'-deoxyguanosine (8-OHdG) in irradiated mouse skin. Thus, our findings revealed that HRF extracts and HSP attenuated UVA-induced photoaging via upregulating Nrf2, together with their abilities to reduce ROS formation and oxidative damage. Our study concluded that the HRF and its bioactive ingredient HSP may represent potential candidates for preventing UVA-induced photoaging via restoration of redox balance.

Effect of Thunbergia laurifolia Herbal Tea on Glucose Homeostasis in Healthy Volunteers: A Single-Arm Phase I Study.

BACKGROUND: Thunbergia laurifolia (TL) is a commonly used herbal medicine in Thailand and in other Asian countries. TL has been approved as a Thai traditional medicine for detoxifying poisons, and the list of possible adverse effects includes hypoglycemia. TL showed hypoglycemic effect in animals possibly due to antioxidant effect and beta-cell preservation. However, the safety of TL herbal tea and its effects on glucose homeostasis have never been investigated in humans. METHODS: Twenty healthy volunteers (10 men and 10 women) drank TL herbal tea 3 times/day for 2 weeks. Ten subjects took TL herbal tea 9 grams daily. After the safety of TL herbal tea was established, 10 more subjects took TL 12 grams daily. Clinical and biochemical tests were assessed at baseline and at 2 weeks. RESULTS: Mean age was 34.9 ± 10.2 years, and mean body mass index was 27.5 ± 5.8 kg/m2. Baseline and posttreatment plasma concentrations were as follows: fasting plasma glucose (89 ± 6 vs. 89 ± 7 mg/dL), fructosamine (213 ± 32 vs. 212 ± 33 µmol/L), fasting insulin (8.8 [IQR: 5.9-18.4] vs. 10.4 [IQR: 7.4-15.2] µU/mL), HOMA-B (101.6 [IQR: 82.3-189.8] vs. 120.4 [IQR: 93.2-153.2]), and HOMA-IR (1.1 [IQR: 0.8-2.3] vs. 1.4 [IQR: 0.9-2.0]), all respectively. There were no significant changes in these parameters, including body weight, blood pressure, lipid profile, and C-reactive protein. No serious adverse events were observed during the study period. CONCLUSIONS: TL herbal tea at doses of 9 and 12 grams daily had good tolerability without any significant adverse effects on fasting plasma glucose level or other glucose homeostasis parameters measured.

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.

The Effects of Andrographis paniculata on Platelet Activity in Healthy Thai Volunteers.

Background. Andrographis paniculata (AP) has been used in Thai traditional medicine to treat various infections, including the common cold and fever. Its bioactive compound, andrographolide, has shown antiplatelet activities in an in vitro study model. Since clinical studies of the effects of AP on the human platelet function have never been reported, we investigated its effect on platelet activity in ten healthy volunteers. Methods. Two grams of AP was taken 3 times within one day. The blood was withdrawn by venipuncture before and 2 and 24 hours after the AP administration to analyze the effects of AP on platelet aggregation, the expression of enzyme cyclooxygenase (COX) mRNA and protein, and TXB2, including P-selectin. Result. Even though there was no significant change in the studied parameters, this study exhibited patient-to-patient variability in platelet function. It was found that ADP-induced platelet aggregation tended to decrease after AP administration, while epinephrine-induced platelet aggregation in females tended to be higher than that in males for the entire study period. Moreover, COX-1 mRNA levels tended to decrease while P-selectin levels tended to rise after AP administration. Conclusion. These controversial results are possibly due to the multifactorial mechanisms of platelet aggregation as well as the multichemical composition of AP. Further study, probably at the molecular level, is needed to unveil the underlying mechanisms of action of AP.

Thai herbal antipyretic 22 formula (APF22) inhibits UVA-mediated melanogenesis through activation of Nrf2-regulated antioxidant defense.

Thai herbal antipyretic 22 formula (APF22), a polyherbal formula, has been traditionally used to treat dermatologic problems including hyperpigmentation. Exposure of the skin to ultraviolet A (UVA) causes abnormal melanin production induced by photooxidative stress. This study thus aimed to investigate the protective effects of APF22 extracts and phenolic compounds, ferulic acid (FA), and gallic acid (GA; used as positive control and reference compounds), on melanogenesis through modulation of nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in mouse melanoma (B16F10) cells exposed to UVA. Our results revealed that the APF22 extracts, FA, and GA reduced melanin synthesis as well as activity and protein levels of tyrosinase in UVA-irradiated B16F10 cells. Moreover, APF22 extracts and both FA and GA were able to activate Nrf2-antioxidant response element signaling and promote antioxidant defenses including glutathione, catalase, glutathione peroxidase, and the glutathione-S-transferase at both mRNA and enzyme activity levels in irradiated cells. In conclusion, APF22 extracts suppressed UVA-mediated melanogenesis in B16F10 cells possibly via redox mechanisms involving activation of Nrf2 signaling and upregulation of antioxidant defenses. Moreover, pharmacological action of the APF22 extracts may be attributed to the phenolic compounds, FA, and GA, probably serving as the APF22's active compounds.

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.

13C-Acetic Acid Breath Test Monitoring of Gastric Emptying during Disease Progression in Diabetic Rats.

Gastric motility disturbance is commonly found in long-standing hyperglycemia. Both delayed and rapid gastric emptying has been reported in diabetes. However, very few studies have followed the changes in gastric emptying during disease progression in diabetes because of technical limitations. 13C-Acetic acid breath test is a validated method which is non-invasive and can be used repeatedly or serially to evaluate gastric emptying changes in animal. We investigated the gastric emptying changes in different stages of diabetes using 13C-acetic acid breath test, as well as its related mechanisms involving interstitial cells of Cajal (ICCs), and stem cell factor (SCF) in streptozotocin-induced diabetic rats. The results showed that gastric emptying was accelerated at the early stage (12 weeks of diabetes) whereas intramuscular ICCs (ICC-IM) networks were not different from normal group. At long-term stage (28 weeks of diabetes), gastric emptying had returned to normal pattern with no delayed. ICC-IM networks were decreased in the diabetic group compared to 12th weeks, and were lower than in the normal group at the same time point. SCF levels were constantly high in the diabetic group than in the normal group. This result indicated that 13C-acetic acid breath test is useful to track the alteration in gastric emptying during disease progression. The change of gastric emptying was not found to be significantly associated with ICC-IM. Elevated SCF may help to preserve ICC-IM, especially in the early phase of diabetes.

Bacopa monnieri extract enhances learning-dependent hippocampal long-term synaptic potentiation.

Bacopa monnieri has been used in Ayurvedic medicine as a memory enhancer for a long time; however, its direct effect on synaptic plasticity has not been investigated. To the best of our knowledge, this study is the first to report the effect of B. monnieri on long-term synaptic potentiation in acute hippocampal slices. Adult male Wistar rats were orally administered either sterile water or the ethanolic extract of B. monnieri for 60 days. The extracellular recording was performed to measure the field excitatory postsynaptic potential in the acute hippocampal slices of these rats. Our results showed that B. monnieri extract significantly increased long-term potentiation magnitude compared with the control group, whereas there was no change in basal synaptic transmission. The data support the beneficial mnemonic effect of B. monnieri, and suggest that this effect might be because of the increase of learning-associated synaptic machinery, resulting in the long-term potentiation enhancement and strengthening of hippocampal synapses, which plays a critical role in learning and memory formation.

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.

The Polyherbal Wattana Formula Displays Anti-Amyloidogenic Properties by Increasing α-Secretase Activities.

Alzheimer's disease is characterized by the deposition of insoluble amyloid-ß peptides produced from the ß-amyloid precursor protein (ßAPP). Because α-secretase cleavage by ADAM10 and ADAM17 takes place in the middle of Aß, its activation is considered as a promising anti-AD therapeutic track. Here we establish that the polyherbal Wattana formula (WNF) stimulates sAPPα production in cells of neuronal and non-neuronal origins through an increase of both ADAM10 and ADAM17 catalytic activities with no modification of BACE1 activity and expression. This effect is blocked by specific inhibition or genetic depletion of these disintegrins and we show that WNF up-regulates ADAM10 transcription and ADAM17 maturation. In addition, WNF reduces Aß40 and Aß42 generation in human cell lines. Altogether, WNF presents all the characteristics of a potent preventive anti-Alzheimer formula. Importantly, this natural recipe, currently prescribed to patients for the treatment of other symptoms without any secondary effect, can be tested immediately for further clinical studies.