Plant-derived natural products, recognized for their bioactive properties and minimal side effects, have been widely explored for their potential in obesity management. Identifying plant-based agents that can modulate adipocyte function with low cytotoxicity is essential for developing safe and effective anti-obesity interventions. In this study, Philadelphus schrenkii (Korean mock orange) was identified as a promising candidate following an initial screening for agents that exhibit minimal cytotoxicity and reduced adipocyte differentiation, as assessed by Oil Red O staining. The anti-obesity effects of P. schrenkii methanol extract (PSE) were evaluated by using in vitro and in vivo models. PSE treatment significantly reduced C3H10T1/2 preadipocyte differentiation and upregulated thermogenic markers, including Ucp1 and Dio2, in differentiated cells. Although PSE did not induce weight loss, alter food intake, or improve the serum metabolic profiles in a diet-induced obesity mouse model, it notably enhanced the thermogenic Ucp1 expression in inguinal white adipose tissue (iWAT) and brown adipose tissue. It also mitigated high-fat diet-induced adiposity in iWAT, accompanied by Protein Kinase A signaling activation. These findings suggest that PSE modulates adipose tissue function by suppressing adipogenesis and promoting thermogenic gene expression without weight reduction or metabolic improvement. Based on these effects, PSE may contribute as a supportive agent to plant-based therapeutic strategies against obesity

Abstract
INTRODUCTION
MATERIALS AND METHODS
    Preparation of plant extracts
    Cell viability and Oil Red O staining
    Animal experiments
    Glucose tolerance test
    Western blot analysis
    Histological analysis
    Serum analysis
    mRNA quantification and analysis
    Statistical analysis
RESULTS
    In vitro screening of plant extracts
    Effects of Philadelphus schrenkii extract on cultured adipocytes
    Philadelphus schrenkii methanol extract stimulates thermogenic gene expressionin chow diet-fed mice
    Philadelphus schrenkii methanol extract promotes the expression of thermogenicand mitochondrial markers in high-fat diet-fed mice
DISCUSSION
SUPPLEMENTARY MATERIALS
REFERENCES

• Min-Jung Park(Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea) Corresponding author
• Merc Emil Matienzo(Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea)
• Dong-il Kim(Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea) Corresponding author
• Ba-Wool Lee(College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea, Department of Veterinary Pharmacology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea)
• Chang-Min Lee(College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea, Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea)
• Keon Kim(College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea, Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea)
• Ji-Hye Ha(Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Korea)
• Da-Hye Yi(Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Korea)
• In-Chul Lee(Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Korea, Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Korea)
• Hyung-Jun Kwon(Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Korea, Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup 53212, Korea)