Butanolides and clerodane diterpenes from the twigs of Casearia grewiifolia and their effects on adiponectin secretion

Piseth Nhoek; Seokyoung Hwang; Jungmoo Huh; Pisey Pel; Chan-Woong Park; Piseth Khiev; Hyun Woo Kim; Minsoo Noh; Young-Won Chin

doi:10.1016/j.bioorg.2024.107890

Butanolides and clerodane diterpenes from the twigs of Casearia grewiifolia and their effects on adiponectin secretion

Bioorg Chem. 2024 Oct 16:153:107890. doi: 10.1016/j.bioorg.2024.107890. Online ahead of print.

Authors

Piseth Nhoek¹, Seokyoung Hwang¹, Jungmoo Huh¹, Pisey Pel¹, Chan-Woong Park¹, Piseth Khiev², Hyun Woo Kim³, Minsoo Noh⁴, Young-Won Chin⁵

Affiliations

¹ Natural Product Research Institute and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
² Royal University of Phnom Penh, Department of Biology, Russian Federation Boulevard, Khan Toul Kork, Phnom Penh 12156, Cambodia.
³ College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Gyeonggi-do 04620, Republic of Korea.
⁴ Natural Product Research Institute and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: [email protected].
⁵ Natural Product Research Institute and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: [email protected].

PMID: 39427630
DOI: 10.1016/j.bioorg.2024.107890

Abstract

Three butanolides derivatives, grewiifolides A-C, and nine clerodane diterpenes, grewiifolins M-U, as well as a known sterol were isolated from the twigs of Casearia grewiifolia. The chemical structures and configurations of all isolates were established by various spectroscopic means and chemical derivatization. In a cell-based phenotypic assay using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs), grewiifolide B significantly promoted adiponectin-secretion with EC₅₀ value of 24.8 µM. In target identification studies, butanolide derivatives were selectively bound to PPARγ with K_i values of 4.65, 0.55, and 17.8 µM, respectively. Further functional analysis and molecular modeling revealed that grewiifolide B promotes adiponectin-secretion through PPARγ full agonism.

Keywords: Adiponectin-secretion; Butanolide; Casearia grewiifolia; Clerodane-type diterpene; PPARγ; hBM-MSC.