PMID- 37715565 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20231216 IS - 1097-0010 (Electronic) IS - 0022-5142 (Linking) VI - 104 IP - 2 DP - 2024 Jan 30 TI - Therapeutic potential of enzymatically extracted eumelanin from squid ink in type 2 diabetes mellitus ICR mice: Multifaceted intervention against hyperglycemia, oxidative stress and depression. PG - 993-1007 LID - 10.1002/jsfa.12986 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that poses significant health risks due to its numerous complications. However, the effects of eumelanin on oxidative stress, hyperglycemia and depression in diabetic mice have not been extensively studied. RESULTS: Our study employed an enzymatic approach to extract eumelanin from squid ink and characterized it using spectroscopic techniques. Remarkably, eumelanin extracted with alkaline-neutral-flavor protease (ANF) displayed superior inhibitory activity against alpha-glucosidase and alpha-amylase, while enhancing glucose utilization and hepatic glycogen synthesis in human hepatocellular carcinoma cell line (HepG2) insulin resistance model. Further evaluation of ANF in a T2DM ICR mouse model demonstrated its significant potential in alleviating hyperglycemia, reducing glycosylated serum protein levels, improving glucose tolerance and modulating total cholesterol and low-density lipoprotein levels, as well as antioxidant indices at a dosage of 0.04 g kg(-1) . Additionally, ANF exhibited positive effects on energy levels and reduced immobility time in antidepressant behavioral experiments. Moreover, ANF positively influenced the density and infiltration state of renal cells, while mitigating inflammatory enlargement and deformation of liver cells, without inducing any adverse effects in mice. CONCLUSION: Overall, these findings underscore the significant therapeutic potential of ANF in the treatment of T2DM and its associated complications. By augmenting lipid and glucose metabolism, mitigating oxidative stress and alleviating depression, ANF emerges as a promising candidate for multifaceted intervention. (c) 2023 Society of Chemical Industry. CI - (c) 2023 Society of Chemical Industry. FAU - Song, Wen AU - Song W AD - CAS and Shandong Province Key laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China. AD - University of Chinese Academy of Sciences, Beijing, China. FAU - Xing, Ronge AU - Xing R AUID- ORCID: 0000-0001-9745-8808 AD - CAS and Shandong Province Key laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China. FAU - Yang, Haoyue AU - Yang H AD - CAS and Shandong Province Key laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China. FAU - Liu, Song AU - Liu S AD - CAS and Shandong Province Key laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China. FAU - Yu, Huahua AU - Yu H AD - CAS and Shandong Province Key laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China. FAU - Li, Pengcheng AU - Li P AD - CAS and Shandong Province Key laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China. LA - eng GR - 2022QNLM030003-2/the 14th Five-Year Plan of Qingdao Pilot National Laboratory of Marine Science and Technology/ GR - 2021T3013/Fujian Science and Technology Planning Project-STS Program/ GR - 2022CXGC020413/Shandong Key R&D Plan, Major Scientific and Technological Innovation Project/ PT - Journal Article DEP - 20230929 PL - England TA - J Sci Food Agric JT - Journal of the science of food and agriculture JID - 0376334 RN - 0 (Hypoglycemic Agents) RN - 12627-86-0 (eumelanin) RN - 0 (Insulin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Mice MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - Mice, Inbred ICR MH - Hypoglycemic Agents/metabolism MH - Insulin MH - *Diabetes Mellitus, Experimental/metabolism MH - Depression MH - Ink MH - Blood Glucose/metabolism MH - *Hyperglycemia/drug therapy/metabolism MH - Oxidative Stress MH - Liver/metabolism OTO - NOTNLM OT - antidepressant activity OT - antioxidant activity OT - eumelanin OT - hypoglycemic activity OT - type 2 diabetes mellitus (T2DM) EDAT- 2023/09/16 10:43 MHDA- 2023/12/17 09:44 CRDT- 2023/09/16 04:33 PHST- 2023/08/03 00:00 [revised] PHST- 2023/05/20 00:00 [received] PHST- 2023/09/13 00:00 [accepted] PHST- 2023/12/17 09:44 [medline] PHST- 2023/09/16 10:43 [pubmed] PHST- 2023/09/16 04:33 [entrez] AID - 10.1002/jsfa.12986 [doi] PST - ppublish SO - J Sci Food Agric. 2024 Jan 30;104(2):993-1007. doi: 10.1002/jsfa.12986. Epub 2023 Sep 29.