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							| Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007



	

				
						
 
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																Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007
										

				


				
				
					
					
						
																					
				
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					Vol. 15 No. 12 (2025): December 2025
				
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									Research Articles
							
		



	
		  	 

		
	
		Anti-type 2 diabetes mellitus activity of Citrus reticulata-derived materials: Mechanistic insights from integrated network pharmacology, molecular docking, and in vitro assays
	


	
	
		

							
					Authors

						
							
								Hanhua Wang
							
																																		
	
							
								Mingyue Li
							
																																		
	
							
								Yanyue Wang
							
																																		


				
			
																	
					
												DOI:
					

					
						
							https://doi.org/10.31989/ffhd.v15i12.1802
						
					
				
			

						
										
					Abstract

					Background: Citrus reticulata-derived materials (CRDMM) are representative medicinal and edible resources, yet their systematic evaluation for anti-type 2 diabetes mellitus (T2DM) potential remains to be fully elucidated. Objective: This study aimed to investigate the anti-T2DM potential of CRDMM and explore the underlying mechanisms of action using an integrated experimental and computational approach. 

Results: In vitro assays demonstrated significant α-glucosidase inhibitory activity across 16 CRDMM extracts, with Guangchenpi exhibiting the strongest potency (IC₅₀: 2.5–3.8 mg/mL). Network pharmacology analysis identified 10 active compounds and 74 potential targets, among which AKT1, TP53, PPARG, and PTGS2 were highlighted as core targets via protein-protein interaction analysis. Pathway enrichment suggested involvement in lipid metabolism and inflammatory pathways. Molecular docking confirmed strong binding affinities (< –7.0 kcal/mol) between key flavonoids (e.g., neohesperidin_qt and nobiletin) and the core targets. ADMET predictions indicated favorable drug-likeness, despite potential nephrotoxicity risks. 

Novelty: This study is the first to integrate multi-approach validation—combining in vitro bioactivity, network pharmacology, molecular docking, and ADMET profiling—to systematically reveal that CRDMM exerts anti-T2DM effects via a multi-component, multi-target mechanism. 

Conclusion: The results provide a scientific basis for developing CRDMM as functional food ingredients or dietary supplements for blood glucose management in T2DM.

Keywords: Citrus reticulata, type 2 diabetes mellitus, α-glucosidase inhibition, network pharmacology, molecular docking, functional food, medicinal-food homology, nobiletin

				
			
			

						
																																	
						
		


		

						
										
					
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																			2025-12-10
																	

				
							

			
						
										

											
							
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									Vol. 15 No. 12 (2025): December 2025
								
							

						
					
											
							
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								Research Articles
							

						
					
									

			
						
										
					
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																										Copyright (c) 2025 Hanhua Wang, Mingyue Li, Yanyue Wang

														This work is licensed under a Creative Commons Attribution 4.0 International License.

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This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged.

By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained.

				

			
			

		

	




	




	


							



	

	

					
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