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.

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.

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.

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.

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.

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 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.