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Protective Effects of Sepia Ink Melanin on Hepatic Tissue in Streptozotocin-Induced Diabetic Mice

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Abstract

Diabetes mellitus (DM) has emerged as a serious public health concern, due to the high morbidity and mortality resulted from its complications, such as diabetic nephropathy, diabetic cardiovascular complication, and diabetic neuropathy, etc. In this study, we investigated the beneficial effects of sepia ink melanin (SIM) on hyperglycaemia and the restoration of diabetic symptoms in streptozotocin (STZ)-induced diabetic model mice. At first, the normal experimental mice were performed with intraperitoneal injection of STZ (40 mg (kg BW)−1) (BW, body weight) to attain diabetes and then were treated with different concentrations of SIM (120, 240 and 480 mg (kg BW)−1) for four weeks. After treatment, significant decrease in gluconeogenesis were determined, accompanied by a notable increase in both glycolysis and oxidative enzyme activities in SIM-treated groups, such as liver marker enzymes in the serum and key antioxidant enzymes in liver. qPCR results revealed the transcriptional alterations in SIM-treated groups. SIM exposure increased the expression levels of several genes related to insulin transduction and PI3K/Akt pathway, including PI3K, Akt, Irs-2, and InsR. Meanwhile, expression levels of Dicarbonyl/l-xylulose reductase (Dcxr) and UDP-glucose dehydrogenase (Ugdh), which are involved in pentose-glucuronate interconversion pathway, were also elevated in SIM-treated groups. Furthermore, histological observation results indicated that nuclear deformation and organelle dissolution were improved, thus could enhance the liver function. These results demonstrated that SIM can be effective in ameliorating diabetic symptoms and improving disease management for diabetic patients.

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Abbreviations

SIM:

sepia ink melanin

Dcxr:

dicarbonyl/l-xylulose reductase

Ugdh:

UDP-glucose dehydrogenase

DHI:

5,6-di-hydroxyindole

DHICA:

5,6-dihydroxyindole-2 carboxylic acid

ROS:

reactive oxygen species

STZ:

streptozotocin

ALT:

alanine aminotransaminase

AST:

aspartate aminotransferase

ALP:

alkaline phosphatase

LD:

lactate dehydrogenase

SOD:

superoxide dismutase

GSH-Px:

glutathione peroxidase

CAT:

catalase

MDA:

malondialdehyde

TEM:

transmission electron microscopy

FBG:

fasting blood glucose

OGTT:

oral glucose tolerance test

cAMP:

cyclic adenosine monophosphate

DCs:

dicarbonyl compounds

AGEs:

advanced glycation end-products.

References

  • Abdelhalim, M. A. K., Moussa, S. A. A., Qaid, H. A., and Al-Ayed, M. S., 2018. Effect of melanin on gold nanoparticle-induced hepatotoxicity and lipid peroxidation in rats. International Journal of Nanomedicine, 13: 5207–5213.

    Article  Google Scholar 

  • Abolfathi, A. A., Mohajeri, D., Rezaie, A., and Nazeri, M., 2012. Protective effects of green tea extract against hepatic tissue injury in streptozotocin-induced diabetic rats. Evidence-Based Complementary and Alternative Medicine, 2012: 740671.

    Article  Google Scholar 

  • Balamurugan, R., Duraipandiyan, V., and Ignacimuthu, S., 2014. Antidiabetic activity of γ-sitosterol isolated from Lippia nodiflora L. in streptozotocin induced diabetic rats. European Journal of Pharmacology, 30: 410–418.

    Google Scholar 

  • Bohlender, J. M., Franke, S., Stein, G., and Wolf, G., 2005. Advanced glycation end products and the kidney. European Journal of Clinical Investigation, 40: 742–755.

    Google Scholar 

  • Borges, C. R., Roberts, J. C., Wilkins, D. G., and Rollins, D. E., 2001. Relationship of melanin degradation products to actual melanin content: Application to human hair. Analytical Biochemistry, 290: 116–125.

    Article  Google Scholar 

  • Burns, N., and Gold, B., 2007. The effect of 3-methyladenine DNA glycosylase-mediated DNA repair on the induction of toxicity and diabetes by the beta-cell toxicant streptozotocin. Toxicological Science, 95: 391–400.

    Article  Google Scholar 

  • Chen, S. G., Xue, C. H., Xue, Y., Li, Z. J., and Ma, Q., 2007. Studies on the free radical scavenging activities of melanin from squid ink. Chinese Journal of Marine Drugs, 26: 24–27.

    Google Scholar 

  • Chen, T. S., Lai, C. H., Shen, C. Y., Pai, P. Y., Chen, R. J., PadmaViswanadha, V., et al., 2020. Orally administered resveratrol enhances the therapeutic effect of autologous transplanted adipose-derived stem cells on rats with diabetic hepatopathy. Biotechnic & Histochemistry, 95: 37–45.

    Article  Google Scholar 

  • Choudhary, S. K., Chhabra, G., Sharma, D., Vashishta, A., Ohri, S., and Dixit, A., 2012. Comprehensive evaluation of anti-hyperglycemic activity of fractionated Momordica charantia seed extract in alloxan-induced diabetic rats. Evidence-Based Complementary and Alternative Medicine, 2012: 293650.

    Article  Google Scholar 

  • Dong, H., Wang, L. D., Wang, C. L., Song, W. W., Mu, C. K., and Li, R. H., 2016. Immunomodulatory effects of melanin from Sepiella maindroni ink on hypoimmune mice. Journal of Biology, 33: 27–30.

    Google Scholar 

  • Edhager, A. V., Povlsen, J. A., Løfgren, B., Bøtker, H. E., and Palmfeldt, J., 2018. Proteomics of the rat myocardium during development of type 2 diabetes mellitus reveals progressive alterations in major metabolic pathways. Journal of Proteome Research, 17: 2521–2532.

    Article  Google Scholar 

  • Ferre, T., Riu, E., Franckhauser, S., Agudo, J., and Bosch, F., 2003. Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance. Diabetologia, 46: 1662–1668.

    Article  Google Scholar 

  • Fiorino, P., Evangelista, F. S., Santos, F., Motter Magri, F. M., Delorenzi, J. C., Ginoza, M., et al., 2012. The effects of green tea consumption on cardiometabolic alterations induced by experimental diabetes. Experimental Diabetes Research, 2012: 309231.

    Article  Google Scholar 

  • Gomis, R. R., Favre, C., García-Rocha, M., Fernández-Novell, J. M., Ferrer, J. C., and Guinovart, J. J., 2003. Glucose 6-phosphate produced by gluconeogenesis and by glucokinase is equally effective in activating hepatic glycogen synthase. Journal of Biological Chemistry, 278: 9740–9746.

    Article  Google Scholar 

  • Grover, J. K., Vats, V., and Rathi, S. S., 2000. Anti-hyperglycemic effect of Eugenia jambolana and Tinospora cordifolia in experimental diabetes and their effects on key metabolic enzymes involved in carbohydrate metabolism. Journal of Ethnopharmacology, 73: 461–470.

    Article  Google Scholar 

  • Hamed, A. E., Elsahar, M., Elwan, N. M., El-Nakeep, S., Naguib, M., Soliman, H. H., et al., 2018. Managing diabetes and liver disease association. Arab Journal of Gastroenterology, 19: 166–179.

    Article  Google Scholar 

  • Hossain, M. P., Rabeta, M. S., and Husnal, A. T., 2018. Medicinal and therapeutic properties of cephalopod ink: A short review. Food Research, 3: 188–198.

    Article  Google Scholar 

  • Ito, S., and Jimbow, K., 1983. Quantitative analysis of eumelanin and pheomelanin in hair and melanomas. Journal of Investigative Dermatology, 80: 268–272.

    Article  Google Scholar 

  • Jiang, S., Liu, X. M., Dai, X., Zhou, Q., Lei, T. C., Beermann, F., et al., 2010. Regulation of DHICA-mediated antioxidation by dopachrome tautomerase: Implication for skin photoprotection against UVA radiation. Free Radical Biology & Medicine, 48: 1144–1151.

    Article  Google Scholar 

  • Johansen, J. S., Harris, A. K., Rychly, D. J., and Ergul, A., 2005. Oxidative stress and the use of antioxidants in diabetes: Linking basic science to clinical practice. Cardiovascular Diabetology, 4: 5.

    Article  Google Scholar 

  • Kurosaki, E., Nakano, R., Momose, K., Shimaya, A., Suzuki, T., Shibasaki, M., et al., 2003. Hypoglycemic agent YM440 suppresses hepatic glucose output via gluconeogenesis by reducing glucose-6-phosphatase activity in obese Zucker rats. European Journal of Pharmacology, 468: 151–158.

    Article  Google Scholar 

  • Lee, S. K., Le, T. S., Choi, H. J., and Ahnn, J., 2013. Dicarbonyl/L-xylulose dehydrogenase (DCXR): The multifunctional pentosuria enzyme. International Journal of Biochemistry & Cell Biology, 45: 2563–2567.

    Article  Google Scholar 

  • Lei, M., Zhao, M., and Liu, Q., 2012. Immunomodulatory effects of sepia melanin on hypoimmune mice. Science and Technology of Food Industry, 33: 397–400.

    Google Scholar 

  • Li, F., Luo, P., and Liu, H., 2018. A potential adjuvant agent of chemotherapy: Sepia ink polysaccharides. Marine Drugs, 16: 106.

    Article  Google Scholar 

  • Meng, J. M., Cao, S. Y., Wei, X. L., Gan, R. Y., Wang, Y. F., Cai, S. X., et al., 2019. Effects and mechanisms of tea for the prevention and management of diabetes mellitus and diabetic complications: An updated review. Antioxidants (Basel), 8: 170.

    Article  Google Scholar 

  • Meyer, C., Woerle, H. J., Dostou, J. M., Welle, S. L., and Gerich, J. E., 2004. Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes. American Journal of Physiology Endocrinology and Metabolism, 287: E1049–1056.

    Article  Google Scholar 

  • Novellino, L., d’Ischia, M., and Prota, G., 1998. Nitric oxide-induced oxidation of 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid under aerobic conditions: Non-enzymatic route to melanin pigments of potential relevance to skin (photo)protection. Biochimica et Biophysica Acta—General Subjects, 1425: 27–35.

    Article  Google Scholar 

  • Ohaeri, O. C., 2001. Effect of garlic oil on the levels of various enzymes in the serum and tissue of streptozotocin diabetic rats. Bioence Reports, 21: 19–24.

    Google Scholar 

  • Prabakaran, D., and Ashokkumar, N., 2012. Antihyperglycemic effect of esculetin modulated carbohydrate metabolic enzymes activities in streptozotocin induced diabetic rats. Journal of Functional Foods, 4: 776–783.

    Article  Google Scholar 

  • Roman, E., Roberts, I., Lidholt, K., and Kusche-Gullberg, M., 2003. Overexpression of UDP-glucose dehydrogenase in Escherichia coli results in decreased biosynthesis of K5 polysaccharide. Biochemical Journal, 374: 767–772.

    Article  Google Scholar 

  • Sha, L., Wu, W. H., Wu, H. B., Hou, Y. Y., and Xu, J. F., 2014. Anti-inflammatory effect of the extract from Sepiella maindroni visceral organs. Journal of Shanghai Ocean University, 23: 629–633.

    Google Scholar 

  • Soty, M., Chilloux, J., Delalande, F., Zitoun, C., Bertile, F., Mithieux, G., et al., 2016. Post-translational regulation of the glucose-6-phosphatase complex by cyclic adenosine monophosphate is a crucial determinant of endogenous glucose production and is controlled by the glucose-6-phosphate transporter. Journal of Proteome Research, 15: 1342–1349.

    Article  Google Scholar 

  • Wang, C. C., Shi, H. H., Xu, J., Yanagita, T., Xue, C. H., Zhang, T. T., et al., 2020. Docosahexaenoic acid-acylated astaxanthin ester exhibits superior performance over non-esterified astaxanthin in preventing behavioral deficits coupled with apoptosis in MPTP-induced mice with Parkinson’s disease. Food & Function, 11: 8038–8050.

    Article  Google Scholar 

  • Wang, X., Wang, Z., and Chen, Y., 2013. The functions of PI3K/AKT signaling pathway in glucose homeostasis. Chinese Bulletin of Life Sciences, 25: 133–139.

    Google Scholar 

  • Wei, M., Ong, L., Smith, M. T., Ross, F. B., Schmid, K., Hoey, A. J., et al., 2003. The streptozotocin-diabetic rat as a model of the chronic complications of human diabetes. Heart Lung and Circulation, 12: 44–50.

    Article  Google Scholar 

  • Xia, X., Yan, J., Shen, Y., Tang, K., Yin, J., Zhang, Y., et al., 2011. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS One, 6: e16556.

    Article  Google Scholar 

  • Xie, J. W., Li, H. Y., Che, H. X., Dong, X. F., Yang, X. H., and Xie, W. C., 2021. Extraction, physicochemical characterisation, and bioactive properties of ink melanin from cuttlefish (Sepia esculenta). International Journal of Food Science and Technology, 56: 3627–3640.

    Article  Google Scholar 

  • Yu, X., Shen, N., Zhang, M. L., and Pan, F. Y., 2011. Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice. Embo Journal, 30: 3754–3765.

    Article  Google Scholar 

  • Zhang, H. J., Chen, C., Ding, L., Shi, H. H., Wang, C. C., Xue, C. H., et al., 2020. Sea cucumbers-derived sterol sulfate alleviates insulin resistance and inflammation in high-fat-high-fructose diet-induced obese mice. Pharmacological Research, 160: 105191.

    Article  Google Scholar 

  • Zhou, Y. Y., Wang, C. L., Mu, C. K., Li, R. H., and Song, W. W., 2015. Research on the extraction method of the melanin from Sepiella maindroni ink. Journal of Biology, 2: 28–32.

    Google Scholar 

  • Zhou, Y. Y., Wang, L. D., Du, M. F., Wang, C. L., Mu, C. K., Li, R. H., et al., 2015. Antioxidant effects of melanin from Sepiella maindroni on subacute aged model mice. Natural Product Research and Development, 27: 1664–1667.

    Google Scholar 

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Acknowledgements

This research was supported by the Natural Science Foundation of Zhejiang Province (No. LY18C190006) and sponsored by K. C. Wong Magna Fund in Ningbo University.

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Correspondence to Weiwei Song or Chunlin Wang.

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Wang, X., Han, M., Dong, H. et al. Protective Effects of Sepia Ink Melanin on Hepatic Tissue in Streptozotocin-Induced Diabetic Mice. J. Ocean Univ. China 21, 1362–1372 (2022). https://doi.org/10.1007/s11802-022-5018-y

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