ABSTRACT
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.
ABSTRACT
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.
