4β-Hydroxywithanolide E and withanolide E from Physalis peruviana L. inhibit adipocyte differentiation of 3T3-L1 cells through modulation of mitotic clonal expansion

Obesity is a risk factor for many diseases, including type 2 diabetes and cardiovascular disease, and is related to the rising morbidity and mortality. Discovery of agents targeting adipogenesis, especially from natural sources, is important for the treatment of obesity. Here, we aimed to identify a...

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Bibliographic Details
Published in:Journal of natural medicines 2021, Vol.75 (1), p.232-239
Main Authors: Kumagai, Momochika, Yoshida, Izumi, Mishima, Takashi, Ide, Masahiro, Fujita, Kazuhiro, Doe, Matsumi, Nishikawa, Keisuke, Morimoto, Yoshiki
Format: Article
Language:English
Subjects:
3T3-L1 Cells - metabolism
Adipocytes
Adipocytes - metabolism
Adipogenesis
Animals
Biomedical and Life Sciences
Biomedicine
Cardiovascular diseases
CCAAT/enhancer-binding protein
Cell Differentiation
Clonal Hematopoiesis - drug effects
Complementary & Alternative Medicine
Diabetes mellitus (non-insulin dependent)
G1 phase
Gene expression
Humans
Medicinal Chemistry
Mice
Mitosis
Morbidity
Obesity
Pharmacology/Toxicology
Pharmacy
Physalis - chemistry
Physalis peruviana
Phytochemicals
Plant Extracts - chemistry
Plant Sciences
Preadipocytes
Ribes - chemistry
Risk factors
Transcription factors
Withanolides - metabolism
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Summary:Obesity is a risk factor for many diseases, including type 2 diabetes and cardiovascular disease, and is related to the rising morbidity and mortality. Discovery of agents targeting adipogenesis, especially from natural sources, is important for the treatment of obesity. Here, we aimed to identify anti-adipogenic substances in methanol extracts of Physalis peruviana and to investigate their effect, along with underlying mechanisms. Activity-guided fractionation of the extract revealed 4β-hydroxywithanolide E (HWE) and withanolide E (WE) as the adipogenesis inhibitors. Both compounds suppressed mRNA expression of central adipogenic transcription factors, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer-binding protein α in the early stage of adipocyte differentiation. The inhibitory action of these two withanolides on adipogenesis was largely limited to this stage. The proliferation of preadipocytes was markedly suppressed by treatment with HWE and WE for 24 and 48 h in the differentiation medium, and cell-cycle arrest in the G 0 /G 1 phase was observed. Therefore, our results suggested that withanolides from P. peruviana to be novel anti-adipogenic compounds that modulate mitotic clonal expansion. Graphic abstract
ISSN:1340-3443
1861-0293
DOI:10.1007/s11418-020-01458-x