| Reference | 1. BMB Rep. 2018 May;51(5):249-254.
<br>
Medicarpin induces lipolysis via activation of Protein Kinase A in brown
adipocytes.
<br>
Imran KM(1), Yoon D(1), Lee TJ(2), Kim YS(1).
<br>
Author information: <br>
(1)Institute of tissue regeneration, College of Medicine, Soonchunhyang
University, and Department of Microbiology, College of Medicine, Soonchunhyang
University, Cheonan 31151, Korea.
(2)Department of Anatomy, College of Medicine, Yeungnam University, Daegu 42415,
Korea.
<br>
Natural pterocarpan Medicarpin (Med) has been shown to have various beneficial
biological roles, including inhibition of osteoclastogenesis, stimulation of bone
regeneration and induction of apoptosis. However, the effect of the Med on
lipolysis in adipocytes has not been reported. Here, we show the effect of Med on
lipolysis in different mouse adipocytes and elucidate the underlying mechanism.
We observed that Med treatment promoted release of glycerol in the media.
Differentiated mouse brown adipose tissue cells were treated with Med. RNA-Seq
analysis was performed to elucidate the effect of med and subsequently was
confirmed by qRT-PCR and western blotting analyses. Med treatment increased both
protein and gene expression levels of hormone-sensitive lipase (Hsl) and adipose
triglyceride lipase (Atgl), which are two critical enzymes necessary for
lipolysis. Mechanistic study showed that Med activates Protein Kinase A (PKA) and
phosphorylates Hsl at PKA target position at Serine660. Silencing of PKA gene by
short interfering RNA attenuated the Med-induced increase in glycerol release and
Hsl phosphorylation. The results unveil that Med boosts lipolysis via a
PKA-dependent pathway in adipocytes and may provide a possible avenue of further
research of Med mediated reduction of body fat. [BMB Reports 2018; 51(5):
249-254].
<br><br>
2. Biofactors. 2018 Mar;44(2):168-179. doi: 10.1002/biof.1392. Epub 2017 Oct 24.
<br>
A pivotal role of AMPK signaling in medicarpin-mediated formation of brown and
beige.
<br>
Imran KM(1)(2), Yoon D(1)(2), Kim YS(1)(2).
<br>
Author information: <br>
(1)Institute of Tissue Regeneration, College of Medicine, Soonchunhyang
University, Cheonan, Chung-nam, 330-090, Korea.
(2)Department of Microbiology, College of Medicine, Soonchunhyang University,
Cheonan, Chung-nam, 330-090, Korea.
<br>
Obesity poses a substantial threat of a worldwide epidemic and requires better
understanding of adipose-tissue biology as well as necessitates research into the
etiology and therapeutic interventions. In this study, Medicarpin (Med), a
natural pterocarpan, was selected (by screening) as a small-molecule inducer of
adipocyte differentiation among 854 candidates by using C3H10T1/2 mesenchymal
stem cell; a cellular model of adipogenesis. Med induced the expression of
brown-adipocyte commitment marker Bmp7 as well as the early regulators of brown
fat fate Pparγ, Prdm16, and Pgc-1α during differentiation of C3H10T1/2
mesenchymal stem cells. Med also induced the expression of a key thermogenic
marker-uncoupling protein 1 (UCP1)-along with expression of other
brown-fat-specific markers and beige-fat-specific markers. Of note, Med
significantly reduced the expression of white fat markers too. Furthermore, Med
treatment promoted formation of multilocular lipid droplets (LDs), expression of
mitochondrial-biogenesis-related genes, and increased oxygen consumption. Gene
silencing study revealed that Med promotes the development of brown- and
beige-adipocyte characteristics in C3H10T1/2 mesenchymal stem cells through
activation of the AMPK pathway, and our data allow us to propose Med as a
candidate for therapeutics against obesity or related metabolic disorders. © 2017
BioFactors, 44(2):168-179, 2018.
<br><br>
3. J Nat Prod. 2017 Dec 22;80(12):3284-3288. doi: 10.1021/acs.jnatprod.7b00741. Epub
2017 Nov 22.
<br>
Total Synthesis of (+)-Medicarpin.
<br>
Yang X(1), Zhao Y(1), Hsieh MT(1)(2)(3), Xin G(1), Wu RT(4), Hsu PL(4), Horng
LY(4), Sung HC(4), Cheng CH(5), Lee KH(1)(2).
<br>
Author information: <br>
(1)Natural Products Research Laboratories, UNC Eshelman School of Pharmacy,
University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599,
United States.
(2)Chinese Medicine Research and Development Center, China Medical University and
Hospital , Taichung 40402, Taiwan.
(3)School of Pharmacy, China Medical University , Taichung 404, Taiwan.
(4)Research Center for Drug Discovery, National Yang-Ming University , Taipei
112, Taiwan.
(5)PhytoHealth Corporation, Maywafa Biopharma Group, Taipei 105, Taiwan.
<br>
(+)-Medicarpin has been synthesized asymmetrically for the first time in a linear
scalable process with an overall yield of 11%. The two chiral centers were
constructed in one step via condensation using a chiral oxazolidinone auxiliary.
This method will likely accelerate research on medicarpin as an erythropoietin
inducer for erythropoietin-deficient diseases.
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