Integrated Metabolomic, Proteomic, and Transcriptomic Analyses Reveal the Production of Bioactive Metabolites and Antidiabetic Effects in Mature Solanum lasiocarpum Fruit

Fangbo Li¹Zixiao Jiang^2,3,4Arunrat Chaveerach⁵Frédéric Anderson KONKOBO⁶Mohd Kafeel Ahmad Ansari⁷Gwendolyn Felocity Ban⁸Mamadou Abdoulaye Konare⁹Lamin Manjang¹⁰Zachary Rochelin¹¹Yang Yang¹²NURUL SYAMEERA ADUKA^13,4Runglawan Sudmoon^14*Yangyang Liu^15,3*Shiou Yih Lee^13,4*

• ¹Faculty of Health and Life Sciences, INTI International University, Nilai, Malaysia
• ²Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine; International Joint Research Center for Quality of Traditional Chinese Medicine;, Haikou 570311, China
• ³Hainan Branch of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences; Peking Union Medical College, Haikou 570311, China, Haikou, China
• ⁴Faculty of Health and Life Sciences, INTI International University, 71800 Nilai, Negeri Sembilan, Malaysia, Nilai, Malaysia
• ⁵Khon Kaen University Faculty of Science, Khon Kaen, Thailand
• ⁶Laboratory of Biochemistry, Biotechnology, Food Technology and Nutrition (LABIOTAN), Department of Biochemistry, and Microbiology, University Joseph Ki-Zerbo, Ouagadougou, 03 BP 7021, Burkina Faso, Ouagadougou, Burkina Faso
• ⁷University of Guyana, Georgetown, Guyana
• ⁸Papua New Guinea University of Technology, Lae, Papua New Guinea
• ⁹Universite des Sciences des Techniques et des Technologies de Bamako, Bamako, Mali
• ¹⁰Catholic Relief Services, 40 Atlantic Road, Fajara, P.O.Box 2361 Serekunda, The Gambia, Serrekunda, Gambia
• ¹¹College of Agriculture and Environmental Science, American University of the Caribbean, Les Cayes, Haïti, Les Cayes, Haiti
• ¹²Faculty of Liberal Arts, Shinawatra University, Pathum Thani 12160, Thailand, Pathum Thani, Thailand
• ¹³Center of Health, Well-Being, and Environmental Sustainability, INTI International University, 71800, Nilai, Negeri Sembilan, Malaysia, Nilai, Malaysia
• ¹⁴Faculty of Law, Khon Kaen University, Khon Kaen 40002, Thailand, Khon Kaen, Thailand
• ¹⁵Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine; International Joint Research Center for Quality of Traditional Chinese Medicine;, Haikou, China

Diabetes mellitus is a chronic metabolic disorder that affects millions of people globally. Among three types of diabetes, Type 2 diabetes mellitus (T2DM) is a rapidly growing global health challenge. Despite available modern antidiabetic drugs, patients still struggle with side effects and treatment failure, as an alternative to this, there is a crucial requirement to develop a potential and traditional plant-based medicine which could be a safer sources and multi-target therapies to treat chronic disease like diabetes. Solanum lasiocarpum (S. lasiocarpum) is a sour fruit-vegetable being widely used in Southeast Asia as both food and traditional medicine, including for the management of diabetes. However, its active components and antidiabetic mechanisms have not been systematically explored. In this study, we combined metabolomics, proteomics, and transcriptomics to investigate the bioactive pathways and potential molecular targets of S. lasiocarpum. Untargeted UHPLC–QTOF–MS profiling identified 45 candidate bioactive compounds with good predicted gastrointestinal absorption, and the network pharmacology analysis linked these compounds to 43 diabetes-related human targets. Protein–protein interaction analysis highlighted several core nodes, including TNF, PPARG, IL6, AKT1, and STAT3, and functional enrichment suggested roles in hormone regulation, inflammation, glucose and lipid metabolism, and vascular function. De novo transcriptome assembly and data-independent acquisition-based proteomics of mature S. lasiocarpum fruit showed that central carbon metabolism is highly active and that the shikimate, phenylpropanoid, and flavonoid pathways are strongly expressed at both gene and protein levels. Key enzymes such as EPSPS, PAL, C4H, 4CL, CHS, CHI, F3H, and FLS formed a coherent biosynthetic network supporting sustained production of phenolic and flavonoid metabolites. Integrating these omics layers with target prediction suggests that S. lasiocarpum may exert antidiabetic effects by modulating a TNF–PPARG axis, reducing pro-inflammatory signaling while supporting insulin-sensitizing pathways. Overall, these results support the traditional use of S. lasiocarpum and provide a multi-omics resource to prioritise candidate metabolites, enzymes and targets for follow-up studies. As the pathway links were inferred computationally, the proposed TNF–PPARG-centred mechanism should be regarded as hypothesis-generating and will require validation in experimental models and, ultimately, well-designed human intervention trials.