Chemical Constituents from the Roots and Rhizomes of <i>Sophora tonkinensis</i> and Their Effects on Proprotein Convertase Substilisin/Kexin Type 9 Expression

Pel, Pisey; Chae, Hee‐Sung; Nhoek, Piseth; Kim, Young-Mi; An, Chae-Yeong; Yoo, Han‐Ill; Kang, Minseok; Kim, Hyun Woo; Choi, Young Hee; Chin, Young‐Won

doi:10.1021/acsomega.2c01676

Cited by 1 publication

(3 citation statements)

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“…F12−2 (20.8 Structural analysis of all isolated compounds was conducted according to the procedures outlined in our previous study for structural elucidation. 15,16 (3R,20S) 3,6,10,15,19,10,14,18, ECD Calculation. Compounds 1 and 2 were subjected to conformational searches using the GMMX program in Gaussian 16 software after their minimized structures were generated in ChemBio3D Ultra 13.03.…”

Section: Methodsmentioning

confidence: 99%

“…Structural analysis of all isolated compounds was conducted according to the procedures outlined in our previous study for structural elucidation. , …”

Section: Methodsmentioning

confidence: 99%

“…katsumadai extracts including diarylheptanoids, kavalactones, flavonoids, stilbenes, monoterpenes, sesquiterpenes, and triterpenes. Among these compounds, chalcones were found to prevent lipid accumulation, and acyclic triterpenoids were found to inhibit cholesterol acyl transferase activity. , As part of our ongoing study, , we conducted bioassay-guided isolation to identify compounds that have PCSK9 mRNA expression inhibitory activities. Based on in vitro experiments, it was found that the hexane-soluble fraction exhibited the highest activity.…”

Section: Introductionmentioning

confidence: 99%

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Acyclic Triterpenoids from Alpinia katsumadai Seeds with Proprotein Convertase Subtilisin/Kexin Type 9 Expression and Secretion Inhibitory Activity

An,

Son,

Chin

2023

ACS Omega

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Cholesterol is one of the primary causes of cardiovascular disease. Investigating and developing potential drugs to effectively treat hypercholesterolemia are therefore of critical importance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been developed to lower the levels of low-density lipoprotein cholesterol in patients with hypercholesterolemia. In this study, we aimed to identify compounds that inhibit the PCSK9 mRNA expression and secretion. The bioassay-guided investigation of Alpinia katsumadai seeds utilizing a PCSK9 mRNA expression monitoring assay yielded the isolation and identification of seven new compounds. Among these were three acyclic triterpenoids (1−3), an acyclic sesquiterpenoid (5), one arylpentanoid (6), and two diarylheptanoids (7 and 8), alongside 10 known compounds. The structures of these compounds were determined using nuclear magnetic resonance (NMR) spectroscopy, vibrational circular dichroism (VCD), and electronic circular dichroism (ECD). The absolute configurations of compounds 1 and 2 were identified by comparing the calculated and experimental VCD data as the ECD method was unable to distinguish the diastereomers. All the isolated compounds were evaluated for their regulatory effects on the low-density lipoprotein receptor (LDLR) and PCSK9 mRNA expression, as well as PCSK9 secretion. Of the tested compounds, two of the acyclic triterpenoids (1 and 2) demonstrated potent effects in downregulating PCSK9 at both the mRNA and protein levels, compared with the positive control (berberine chloride). Additionally, compound 1 inhibited PCSK9 secretion to a level comparable to that of berberine chloride. This study identifies compounds that inhibit PCSK9 mRNA expression and secretion, offering significant contributions to the development of novel drugs for the effective treatment of hypercholesterolemia..

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Section: Methodsmentioning

confidence: 99%

“…Structural analysis of all isolated compounds was conducted according to the procedures outlined in our previous study for structural elucidation. , …”

Section: Methodsmentioning

confidence: 99%