Ginseng is a very famous Chinese
herbal medicine with various pharmacological
effects. Ginsenosides, the main effective compounds of ginseng, show
favorable biological activities in the central nervous system (CNS),
but the protein targets of ginsenosides in brain tissues have not
been clarified clearly. First, we screened proteins that interact
with ginsenosides by mass spectrometry-based drug affinity responsive
target stability (DARTS) and cellular thermal shift assay (CETSA).
Then, we identified and confirmed adenylate kinase 5 (AK5) as a target
protein of ginsenosides by biolayer interferometry (BLI), isothermal
titration calorimetry (ITC), and molecular docking. Finally, an enzyme
activity kit was used to determine the effect of 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, on AK5 activities in vivo and in vitro. We screened out seven
overlapping target proteins by proteomics of DARTS and CETSA. The
BLI direct action assays showed that the direct interaction of PPD
with AK5 was higher compared to the parental ginsenosides. Subsequently,
BLI kinetic analysis and ITC assay showed that PPD specifically bound
to AK5. Furthermore, key amino acid mutations predicted by molecular
docking decreased the affinity between PPD and AK5. Enzyme activity
assays showed that PPD increased AK5 activities in vivo and in vitro. The above-mentioned findings indicated
that AK5 is a protein target of ginsenoside in the brain and PPD is
considered to be a small-molecular activator of AK5, which can improve
comprehension of the molecular mechanisms of ginseng pharmacological
effects in the CNS and further develop AK5 activators based on the
dammarane-type triterpenoid structure.
Introduction
Hypertension (HTN) is a significant risk factor for cardiovascular disease. Identifying new risk factors for hypertension is crucial. This study aims to determine the predictive value of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) in the development of hypertension.
Methods
In this study, we examined 16,026 individuals without diabetes and other cardiovascular risk factors who were underwent annual screening at the People’s Hospital of Yuxi, Yunnan, China from 2013 to 2016. The participants were divided into two groups: normoglycemic and prediabetic. Normoglycemia was defined as having an HbA1c level of less than 5.7% and an FPG level of less than 5.6 mmol/ L. Prediabetes was defined according to the ADA criteria, which includes having an HbA1c level between 5.7% and 6.5%, or an impaired fasting glucose level between 5.6 mmol/L and 7.0 mmol/L. The participants were further divided into four subgroups based on their FPG and HbA1c levels: normoglycemia, impaired HbA1c only, FPG only, and both parameters impaired.
Results
The cohort study was conducted on 16,026 participants from Yunnan, China, consisting of 60.6% males and 39.4% females, with a mean age of 44.6 ± 12.5 years. The study revealed that prediabetes was independently associated with an increased risk for HTN (OR 1.53, 95% CI 1.41~1.67, P < 0.001). The analysis of different subgroups of HbA1c and FPG showed that FPG was a better predictor of HTN than HbA1c, regardless of the group.
Conclusion
FPG and HbA1c were significantly associated with the future development of HTN in individuals with prediabetes.
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