Discovery of Flavonoids from Scutellaria baicalensis with Inhibitory Activity Against PCSK 9 Expression: Isolation, Synthesis and Their Biological Evaluation

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Piseth NhoekYoung-Won Chin

Abstract

Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of Scutellaria baicalensis through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cells. All structures were established by interpreting the corresponding spectroscopic data and comparing measured values from those in the literature. All compounds were assessed for their ability to inhibit PCSK9 mRNA expression; compounds 1 (3,7,2'-trihydroxy-5-methoxy-flavanone) and 4 (skullcapflavone II) were found to suppress PCSK9 mRNA via SREBP-1. Furthermore, compound 1 was found to increase low-density lipoprotein receptor protein expression. Also, synthesis of compound 1 as a racemic mixture form (1a) was completed for the first time. Natural compound 1 and synthetic racemic 1a were evaluated for their inhibitory activities against PCSK9 mRNA expression and the results confirmed the stereochemistry of 1 was important.

References

Jun 1, 1979·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·M Iinuma, S Matsuura
Oct 25, 2001·The Journal of Organic Chemistry·Karsten WoydowskiJürgen Liebscher
Apr 24, 2002·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Takahiko IsobeKumiko Nagata
Sep 27, 2003·Journal of Natural Products·Tian-Shung WuHsien-Chang Chang
Apr 6, 2006·Chemical & Pharmaceutical Bulletin·Yukinori MiyaichiTsuyoshi Tomimori
Oct 13, 2006·Bioscience, Biotechnology, and Biochemistry·Wen-Hsin HuangChing-Huey Yang
Nov 3, 2006·The Journal of Clinical Investigation·Thomas A LagaceJay D Horton
Jun 6, 2007·Magnetic Resonance in Chemistry : MRC·Younghee ParkYoongho Lim
Jul 5, 2007·The Biochemical Journal·Jun LiJennifer L Harris
Jul 13, 2007·Journal of Natural Products·Karel SmejkalVáclav Suchý
Sep 19, 2008·Journal of Medicinal Chemistry·José C AponteGerald B Hammond
Nov 13, 2008·BMJ : British Medical Journal·Jorie VersmissenEric J G Sijbrands
Dec 31, 2008·Journal of Natural Products·Xiang Hua HanBang Yeon Hwang
Jun 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daniel Steinberg, Joseph L Witztum
Jun 10, 2010·The Journal of Organic Chemistry·Jean-Charles MariéJohn A Porco
May 21, 2011·Fitoterapia·Ren-yi YanBin Yang
Nov 9, 2011·The Journal of Pharmacy and Pharmacology·Yoshiyuki Kimura, Maho Sumiyoshi
Mar 8, 2012·Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica·Jinlan WangShujun Zhang
Mar 16, 2016·Archives of Biochemistry and Biophysics·Cristobal L MirandaJan F Stevens
Jun 30, 2016·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·K YadavK C Ferdinand
Oct 1, 2016·European Journal of Medicinal Chemistry·Yuou TengPeng Yu
Oct 30, 2016·Australian Prescriber·Michael M Page, Gerald F Watts
Apr 2, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Amir Abbas MomtaziAmirhossein Sahebkar
Jan 31, 2018·Journal of the American Chemical Society·Jaru TaechalertpaisarnKevin Burgess

❮ Previous
Next ❯

Citations

Mar 21, 2019·Future Medicinal Chemistry·Antonio Lavecchia, Carmen Cerchia
Jun 7, 2019·International Journal of Molecular Sciences·Young Hun LeeSeung-Taek Lee
Sep 22, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li LiJi-Hua Liu
Sep 24, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xinyu JiYongyan Wang
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jagadeesh Nagarajappa MasagalliWon Jun Choi
Jul 9, 2021·Journal of Natural Products·Jae Sung ParkJongheon Shin

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
circular dichroism
Nuclear magnetic resonance
size exclusion chromatography
column chromatography

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.