Chemical constituents from <i>Morus alba</i> with proprotein convertase subtilisin/kexin type 9 expression and secretion inhibitory activity

Won, Hongic; Son, Min-Gyung; Pel, Pisey; Nhoek, Piseth; An, Chae-Yeong; Kim, Youngmi; Chae, Hee‐Sung; Chin, Young‐Won

doi:10.1039/d3ob00225j

Cited by 6 publications

(2 citation statements)

References 49 publications

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

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.

Wei,

Wen,

Yang

et al. 2024

Nat. Prod. Bioprospect.

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Four new isoquinoline alkaloids, hypecotumines A-D (1–4), were isolated and identified from the whole herbs of Hypecoum erectum L. Their structures were determined by a combination of HRESIMS, NMR, and X-ray diffraction analysis methods. Compounds 1–4 were characterized by a terminal double bond at C-9 and their plausible biosynthetic pathway was hypothesized. Since PCSK9 plays a key role in the development of cardiovascular disease (CVD), exploration of PCSK inhibitors from natural products are beneficial for drug discovery of CVD treatment. SPR and Western blot assays showed compound 4 had PCSK9 inhibition activity with KD value of 59.9 µM and thus elevated the LDLR level. Further molecular docking studies demonstrated that 4 and PCSK9 could form stable interactions via key hydrogen bonds. Graphical Abstract

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A promising therapy for fatty liver disease: PCSK9 inhibitors

Han,

Wu,

Yin

et al. 2024

Phytomedicine

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Chemical constituents from Morus alba with proprotein convertase subtilisin/kexin type 9 expression and secretion inhibitory activity

Abstract: Six new flavanones, including sanggenol W (1), morusalnol D–F (2–4) and neovanone A–B (5–6), and fourteen known compounds were isolated from methanol extract of dried root bark of Morus alba...

Cited by 6 publications

References 49 publications

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

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

Hypecotumines A-D, new isoquinoline alkaloids with potential PCSK9 inhibition activity from Hypecoum erectum L.

A promising therapy for fatty liver disease: PCSK9 inhibitors

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