Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activation

Zanthoxylum schinifolium (ZS), which is widely used as a seasoning and traditional medicine in East Asia, has demonstrated pharmacological potential. This study investigated the effects of the leaf and twig extracts of ZS (LZSE and TZSE, respectively), which are native to the Honam region of Korea,...

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Main Authors: Jiseok Lee, Bo-Ram Kim, Kyeoungtae Park, Eunbin Kim, Jin-Woo Jeong, Jung Jin Kim, Sung-Suk Suh, Jong Bae Seo
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Animal Cells and Systems
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Online Access:https://www.tandfonline.com/doi/10.1080/19768354.2025.2536022
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author Jiseok Lee
Bo-Ram Kim
Kyeoungtae Park
Eunbin Kim
Jin-Woo Jeong
Jung Jin Kim
Sung-Suk Suh
Jong Bae Seo
author_facet Jiseok Lee
Bo-Ram Kim
Kyeoungtae Park
Eunbin Kim
Jin-Woo Jeong
Jung Jin Kim
Sung-Suk Suh
Jong Bae Seo
author_sort Jiseok Lee
collection DOAJ
description Zanthoxylum schinifolium (ZS), which is widely used as a seasoning and traditional medicine in East Asia, has demonstrated pharmacological potential. This study investigated the effects of the leaf and twig extracts of ZS (LZSE and TZSE, respectively), which are native to the Honam region of Korea, on adipocyte differentiation and assessed the ligand-binding energy score of their components to bind peroxisome proliferator-activated receptor gamma (PPARγ), a critical regulator of adipogenesis and metabolic health. LZSE and TZSE were prepared using 70% ethanol, and their molecular effects on adipocyte differentiation were evaluated in 3T3-L1 preadipocytes. Single compounds from the extracts were identified using UPLC-ESI-Q-TOF-MS, and their ligand-binding energy scores were calculated via in silico molecular docking studies. PPARγ activity was further confirmed through reporter assays. LZSE and TZSE significantly promoted adipocyte differentiation, as demonstrated by morphological changes and the increased mRNA and protein levels of key adipogenic and lipogenic genes, such as PPARγ and CCAAT-enhancer-binding protein alpha (C/EBPα). LZSE specifically enhanced adipogenesis without inducing cytotoxicity, attributed to the inhibition of C/EBP homologous protein (CHOP) and stimulation of mitotic expansion. Additionally, UPLC-ESI-Q-TOF-MS identified several active compounds in LZSE and TZSE, and in silico docking revealed the high binding affinity of these compounds for the full-agonist ligand-binding domain of PPARγ. LZSE and TZSE could emerge as novel antidiabetic drug candidates based on their effects on adipocyte differentiation and PPARγ activation. Furthermore, the active compounds identified in these extracts hold promise as tentative PPARγ agonists, highlighting their therapeutic potential in the treatment of metabolic disorders.
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spelling doaj-art-0da2c7a795874976a55ad5018e585a4a2025-08-20T03:13:55ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852025-12-0129146948710.1080/19768354.2025.2536022Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activationJiseok Lee0Bo-Ram Kim1Kyeoungtae Park2Eunbin Kim3Jin-Woo Jeong4Jung Jin Kim5Sung-Suk Suh6Jong Bae Seo7Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDivision of Natural Products Research, Honam National Institute of Biological Resource, Mokpo, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDivision of Natural Products Research, Honam National Institute of Biological Resource, Mokpo, Republic of KoreaDepartment of Biosciences, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaDepartment of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University, Jeonnam, Republic of KoreaZanthoxylum schinifolium (ZS), which is widely used as a seasoning and traditional medicine in East Asia, has demonstrated pharmacological potential. This study investigated the effects of the leaf and twig extracts of ZS (LZSE and TZSE, respectively), which are native to the Honam region of Korea, on adipocyte differentiation and assessed the ligand-binding energy score of their components to bind peroxisome proliferator-activated receptor gamma (PPARγ), a critical regulator of adipogenesis and metabolic health. LZSE and TZSE were prepared using 70% ethanol, and their molecular effects on adipocyte differentiation were evaluated in 3T3-L1 preadipocytes. Single compounds from the extracts were identified using UPLC-ESI-Q-TOF-MS, and their ligand-binding energy scores were calculated via in silico molecular docking studies. PPARγ activity was further confirmed through reporter assays. LZSE and TZSE significantly promoted adipocyte differentiation, as demonstrated by morphological changes and the increased mRNA and protein levels of key adipogenic and lipogenic genes, such as PPARγ and CCAAT-enhancer-binding protein alpha (C/EBPα). LZSE specifically enhanced adipogenesis without inducing cytotoxicity, attributed to the inhibition of C/EBP homologous protein (CHOP) and stimulation of mitotic expansion. Additionally, UPLC-ESI-Q-TOF-MS identified several active compounds in LZSE and TZSE, and in silico docking revealed the high binding affinity of these compounds for the full-agonist ligand-binding domain of PPARγ. LZSE and TZSE could emerge as novel antidiabetic drug candidates based on their effects on adipocyte differentiation and PPARγ activation. Furthermore, the active compounds identified in these extracts hold promise as tentative PPARγ agonists, highlighting their therapeutic potential in the treatment of metabolic disorders.https://www.tandfonline.com/doi/10.1080/19768354.2025.2536022AdipocytesdifferentiationadipogenesisZanthoxylum schinifoliummolecular docking
spellingShingle Jiseok Lee
Bo-Ram Kim
Kyeoungtae Park
Eunbin Kim
Jin-Woo Jeong
Jung Jin Kim
Sung-Suk Suh
Jong Bae Seo
Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activation
Animal Cells and Systems
Adipocytes
differentiation
adipogenesis
Zanthoxylum schinifolium
molecular docking
title Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activation
title_full Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activation
title_fullStr Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activation
title_full_unstemmed Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activation
title_short Zanthoxylum schinifolium extracts enhance 3T3-L1 adipocyte differentiation via CHOP inhibition and PPARγ activation
title_sort zanthoxylum schinifolium extracts enhance 3t3 l1 adipocyte differentiation via chop inhibition and pparγ activation
topic Adipocytes
differentiation
adipogenesis
Zanthoxylum schinifolium
molecular docking
url https://www.tandfonline.com/doi/10.1080/19768354.2025.2536022
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