Astaxanthin: Unveiling biochemical mysteries, expanding horizons, and therapeutic opportunities in health science and biomedical research

Abstract

This systemic study surveys the multifaceted nature of Astaxanthin (AXT), a member of carotenoid pigments broadly used in nutraceuticals and pharmaceuticals. Starting with an insight into its biological origin, the review proceeds to detail the complex chemical structure of AXT followed by considerations on its bioavailability, pharmacokinetics and safety as a dietary supplement. Foremost among these is the biological activities of AXT, especially its strong antioxidant activity which plays an important role in reducing oxidative stress (OS) damage to cells. The description of AXT as an anti-apoptotic and anti-inflammatory cytokine indicates its important role in cell protection and chronic inflammation improvement. Additional studies emphasize positive anti-obesity and anti-diabetic activities that could be exploited as therapy for metabolic disease. The review goes on to describe the immunomodulatory and neuroprotective effects of AXT, its role in cardiovascular protection, as well as hepatic health. The discussion of the anti-cancer activity of AXT is important, since it is related with its mechanisms for preventing and treating cancer. The broad perspective ends with an overview of the diverse biological activities of AXT, suggesting future research directions and its ability to be a multi-target ameliorator. Data compiled here aims to significantly help to improve knowledge on AXT, thus facilitating health and biomedical research progression.

Keywords

• Astaxanthin
• Anticancer activity
• Anti-inflammatory activity
• Neuroprotective activity
• Cardioprotective activity

Supporting Institution

The authors declared that this study has received no financial support.

Ethical Statement

Since the article does not contain any studies with human or animal subject, its approval to the ethics committee was not required.

Abstract

Bu sistematik çalışma, geniş çapta nutrasötiklerde ve farmasötiklerde kullanılan karotenoid pigmentlerinin bir üyesi olan Astaksantinin (AXT) çok yönlü doğasını incelemektedir. İncelemede, öncelikle AXT'nin biyolojik kökenine dair bilgiler sunulmakta, ardından karmaşık kimyasal yapısı detaylandırılmakta ve diyet takviyesi olarak biyoyararlanımı, farmakokinetiği ve güvenliği ele alınmaktadır. Bunların başında AXT'nin biyolojik aktiviteleri, özellikle oksidatif stresin hücrelere verdiği hasarı azaltmada önemli rol oynayan güçlü antioksidan aktivitesi gelmektedir. AXT'nin anti-apoptoz ve anti-enflamatuvar sitokin olarak tanımlanması, hücre koruma ve kronik iltihaplanmanın iyileştirilmesindeki önemli rolünü göstermektedir. Ek çalışmalar, AXT'nin metabolik hastalıkların tedavisinde kullanılabilecek olumlu anti-obezite ve anti-diyabetik aktivitelerini vurgulamaktadır. Çalışma ayrıca AXT'nin immünomodülatör ve nöroprotektif etkilerini, kardiyovasküler korumadaki rolünü ve karaciğer sağlığı üzerindeki etkilerini ele almaktadır. AXT'nin anti-kanser aktivitesinin tartışılması önemlidir, çünkü bu, kanseri önleme ve tedavi etme mekanizmaları ile ilgilidir. Geniş kapsamlı perspektif, AXT'nin çeşitli biyolojik aktivitelerine genel bir bakış sunarak gelecekteki araştırma yönlerini ve çok hedefli bir iyileştirici olarak potansiyelini önermektedir. Bu derleme, AXT hakkındaki bilgileri önemli ölçüde geliştirmeyi, böylece sağlık ve biyomedikal araştırmaların ilerlemesine katkıda bulunmayı amaçlamaktadır.

References

1. 1. Abdelazim, K., Ghit, A., Assal, D., Dorra, N., Noby, N., Khattab, S.N., El Feky, S.E. & Hussein, A. 2023. Production and therapeutic use of astaxanthin in the nanotechnology era. Pharmacological Reports, 75(4): 771-790.
2. 2. Aburai, N., Sumida, D. & Abe, K. 2015. Effect of light level and salinity on the composition and accumulation of free and ester-type carotenoids in the aerial microalga Scenedesmus sp. (Chlorophyceae). Algal Research, 8: 30-36. https://doi.org/10.1016/j.algal.2015.01.005
3. 3. Adam Lauver, D., Lockwood, S.F. & Lucchesi, B.R. 2005. Disodium disuccinate astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion. Journal of Pharmacology and Experimental Therapeutics, 314(2): 686-692. https://doi.org/10.1124/jpet.105.087114
4. 4. Agostoni, C., Berni Canani, R., Fairweather-Tait, S., Heinonen, M., Korhonen, H., La Vieille, S., Marchelli, R., Martin, A., Naska, A., Neuhäuser-Berthold, M., Nowicka, G., Sanz, Y., Siani, A., Sjödin, A., Stern, M., Strain, S., Tetens, I., Tomé, D., Turck, D., Brantom, P., Engel, K.-H., Pöting, A., Poulsen, M., Salminen, S., Schlatter, J., Van Loveren, H. & Verhagen, H. 2014. Scientific Opinion on the safety of astaxanthin-rich ingredients (AstaREAL A1010 and AstaREAL L10) as novel food ingredients. EFSA Journal, 12(7): 3757-3757. https://doi.org/10.2903/j.efsa.2014.3757
5. 5. Aijaz, M., Keserwani, N., Yusuf, M., Ansari, N.H., Ushal, R. & Kalia, P. 2023. Chemical, Biological, and Pharmacological Prospects of Caffeic Acid. Biointerface Research in Applied Chemistry, 13(4): 324. https://doi.org/10.33263/BRIAC134.324
6. 6. Aijaz, M., Kumar, A., Ahmad, M. & Ansari, M.A. 2024. Plant-Based Therapies in Parkinson’s Disease Management: Mechanisms, Clinical Evidence, and Future Perspectives. Letters in Applied NanoBioScience, 13(3): 1-23. https://doi.org/10.33263/LIANBS133.148
7. 7. Ambati, R.R., Moi, P.S., Ravi, S. & Aswathanarayana, R.G. 2014. Astaxanthin: Sources, extraction, stability, biological activities and its commercial applications - A review. Marine Drugs, 12(1): 128-152. https://doi.org/10.3390/md12010128
8. 8. An, J., Gao, F., Ma, Q., Xiang, Y., Ren, D. & Lu, J. 2017. Screening for enhanced astaxanthin accumulation among Spirulina platensis mutants generated by atmospheric and room temperature plasmas. Algal Research, 25: 464-472. https://doi.org/10.1016/j.algal.2017.06.006

9. 9. Aoi, W., Naito, Y., Takanami, Y., Ishii, T., Kawai, Y., Akagiri, S., Kato, Y., Osawa, T. & Yoshikawa, T. 2008. Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification. Biochemical and Biophysical Research Communications, 366(4): 892-897. https://doi.org/10.1016/j.bbrc.2007.12.019
10. 10. Aquilina, G., Bampidis, V., De, M., Bastos, L., Guido Costa, L., Flachowsky, G., Gralak, A., Hogstrand, C., Leng, L., López-Puente, S., Martelli, G., Mayo, B., Ramos, F., Renshaw, D., Rychen, G., Saarela, M., Sejrsen, K., Van Beelen, P., Wallace, R.J. & Westendorf, J. 2014. Scientific Opinion on the safety and efficacy of synthetic astaxanthin as feed additive for salmon and trout, other fish, ornamental fish, crustaceans and ornamental birds. EFSA Journal, 12(6): 35-35. https://doi.org/10.2903/j.efsa.2014.3724
11. 11. Augusti, P.R., Quatrin, A., Somacal, S., Conterato, G.M.M., Sobieski, R., Ruviaro, A.R., Maurer, L.H., Duarte, M.M.F., Roehrs, M. & Emanuelli, T. 2012. Astaxanthin prevents changes in the activities of thioredoxin reductase and paraoxonase in hypercholesterolemic rabbits. Journal of Clinical Biochemistry and Nutrition, 51(1): 42-49. https://doi.org/10.3164/jcbn.11-74
12. 12. Azadian, R., Mohammadalipour, A., Memarzadeh, M.R., Hashemnia, M. & Aarabi, M.H. 2024. Examining hepatoprotective effects of astaxanthin against methotrexate-induced hepatotoxicity in rats through modulation of Nrf2/HO-1 pathway genes. Naunyn-Schmiedeberg's Archives of Pharmacology, 397(1): 371-380. https://doi.org/10.1007/s00210-023-02581-8
13. 13. Bahbah, E.I., Ghozy, S., Attia, M.S., Negida, A., Emran, T.B., Mitra, S., Albadrani, G.M., Abdel-Daim, M.M., Uddin, M.S. & Simal-Gandara, J. 2021. Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent. Marine Drugs, 19(4): 201-201. https://doi.org/10.3390/md19040201
14. 14. Bennedsen, M., Wang, X., Willén, R., Wadström, T. & Andersen, L.P. 2000. Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Immunology Letters, 70(3): 185-189. https://doi.org/10.1016/S0165-2478(99)00145-5
15. 15. Bernabeu, M., Gharibzahedi, S.M.T., Ganaie, A.A., Macha, M.A., Dar, B.N., Castagnini, J.M., Garcia-Bonillo, C., Meléndez-Martínez, A.J., Altintas, Z. & Barba, F.J. 2023. The potential modulation of gut microbiota and oxidative stress by dietary carotenoid pigments. Critical Reviews in Food Science and Nutrition. 64(33): 12555-12573. https://doi.org/10.1080/10408398.2023.2254383
16. 16. Binti Ibnu Rasid, E.N., Mohamad, S.E., Jamaluddin, H. & Salleh, M.M. 2014. Screening factors influencing the production of astaxanthin from freshwater and marine microalgae. Applied Biochemistry and Biotechnology, 172(4): 2160-2174. https://doi.org/10.1007/s12010-013-0644-x
17. 17. Bjerkeng, B., Hatlen, B. & Wathne, E. 1999. Deposition of astaxanthin in fillets of Atlantic salmon (Salmo salar) fed diets with herring, capelin, sandeel, or Peruvian high PUFA oils. Aquaculture, 180(3-4): 307-319. https://doi.org/10.1016/S0044-8486(99)00206-9
18. 18. Boussiba, S. & Vonshak, A. 1991. Astaxanthin accumulation in the green alga Haematococcus pluvialis. Plant and Cell Physiology, 32(7): 1077-1082. https://doi.org/10.1093/oxfordjournals.pcp.a078171
19. 19. Brotosudarmo, T.H.P., Limantara, L., Setiyono, E. & Heriyanto. 2020. Structures of Astaxanthin and Their Consequences for Therapeutic Application. International Journal of Food Science, 2020: 2156582. https://doi.org/10.1155/2020/2156582
20. 20. Capelli, B., Talbott, S. & Ding, L. 2019. Astaxanthin sources: Suitability for human health and nutrition. Functional Foods in Health and Disease, 9(6): 430-445. https://doi.org/10.31989/ffhd.v9i6.584
21. 21. Chang, M.X. & Xiong, F. 2020. Astaxanthin and its Effects in Inflammatory Responses and Inflammation-Associated Diseases: Recent Advances and Future Directions. Molecules, 25(22): 5342. https://doi.org/10.3390/molecules25225342
22. 22. Chen, J., Hendriks, M., Chatzis, A., Ramasamy, S.K. & Kusumbe, A.P. 2020. Bone Vasculature and Bone Marrow Vascular Niches in Health and Disease. Journal of Bone and Mineral Research, 35(11): 2103-2120. https://doi.org/10.1002/jbmr.4171
23. 23. Chieco, C., Morrone, L., Bertazza, G., Cappellozza, S., Saviane, A., Gai, F., Di Virgilio, N. & Rossi, F. 2019. The Effect of Strain and Rearing Medium on the Chemical Composition, Fatty Acid Profile and Carotenoid Content in Silkworm (Bombyx mori) Pupae. Animals (Basel), 9(3): 103. https://doi.org/10.3390/ani9030103
24. 24. Childs, C.E., Calder, P.C. & Miles, E.A. 2019. Diet and Immune Function. Nutrients, 11(8): 1933. https://doi.org/10.3390/nu11081933
25. 25. Choi, H.D., Kim, J.H., Chang, M.J., Kyu‐Youn, Y. & Shin, W.G. 2011. Effects of astaxanthin on oxidative stress in overweight and obese adults. Phytotherapy Research, 25(12): 1813-1818. https://doi.org/10.1002/ptr.3494
26. 26. Choudhari, S.M., Ananthanarayan, L. & Singhal, R.S. 2008. Use of metabolic stimulators and inhibitors for enhanced production of β-carotene and lycopene by Blakeslea trispora NRRL 2895 and 2896. Bioresource Technology, 99(8): 3166-3173. https://doi.org/10.1016/j.biortech.2007.05.051
27. 27. Ciaraldi, T.P., Boeder, S.C., Mudaliar, S.R., Giovannetti, E.R., Henry, R.R. & Pettus, J.H. 2023. Astaxanthin, a natural antioxidant, lowers cholesterol and markers of cardiovascular risk in individuals with prediabetes and dyslipidaemia. Diabetes, Obesity and Metabolism, 25(7): 1985-1994.
28. 28. Crupi, P., Toci, A.T., Mangini, S., Wrubl, F., Rodolfi, L., Tredici, M.R., Coletta, A. & Antonacci, D. 2013. Determination of fucoxanthin isomers in microalgae (Isochrysis sp.) by high-performance liquid chromatography coupled with diode-array detector multistage mass spectrometry coupled with positive electrospray ionization. Rapid Communications in Mass Spectrometry, 27(9): 1027-1035. https://doi.org/10.1002/rcm.6531
29. 29. Dansou, D.M., Wang, H., Nugroho, R.D., He, W., Zhao, Q., Tang, C., Zhang, H. & Zhang, J. 2021. Effects of duration and supplementation dose with astaxanthin on egg fortification. Poultry Science, 100(9): 101304.
30. 30. Das, U.N. 2011. Essential fatty acids enhance free radical generation and lipid peroxidation to induce apoptosis of tumor cells. Clinical Lipidology, 6(4): 463.
31. 31. Demirel, P.B. & Tuna, B.G. 2021. Anticancer properties of astaxanthin: A molecule of great promise. pp. 427-445. In: Ravishankar, G.A. & Rao, A.R (eds). Global Perspectives on Astaxanthin. Academic Press, 824 pp. https://doi.org/10.1016/B978-0-12-823304-7.00003-9
32. 32. Deng, X., Wang, M., Hu, S., Feng, Y., Shao, Y., Xie, Y., Wu, M., Chen, Y. & Shi, X. 2019. The neuroprotective effect of astaxanthin on pilocarpine-induced status epilepticus in rats. Frontiers in Cellular Neuroscience, 13: 123.
33. 33. Derias, M.S.M., Sabaa, A.E.R.F.A., Osman, A.E.M.M.A., Mohamed, A.E.-H.A. & Abou-bakr Darwish, D.A. 2021. The Potential protective role of astaxanthin on doxorubicin-induced cardiac toxicity in rats. QJM: An International Journal of Medicine, 114(Supplement_1): hcab117.003. https://doi.org/10.1093/qjmed/hcab117.003
34. 34. Donoso, A., González-Durán, J., Muñoz, A.A., González, P.A. & Agurto-Muñoz, C. 2021. Therapeutic uses of natural astaxanthin: An evidence-based review focused on human clinical trials. Pharmacological Research, 166: 105479. https://doi.org/10.1016/j.phrs.2021.105479
35. 35. Fakhri, S., Abbaszadeh, F., Dargahi, L. & Jorjani, M. 2018. Astaxanthin: A mechanistic review on its biological activities and health benefits. Pharmacological Research, 136: 1-20. https://doi.org/10.1016/j.phrs.2018.08.012
36. 36. Fakhri, S., Aneva, I.Y., Farzaei, M.H. & Sobarzo-Sánchez, E. 2019. The neuroprotective effects of astaxanthin: Therapeutic targets and clinical perspective. Molecules, 24(14): 2640. https://doi.org/10.3390/molecules24142640
37. 37. Fan, Q., Chen, Z., Wu, Y., Zhu, J. & Yu, Z. 2021. Study on the Enhancement of Immune Function of Astaxanthin from Haematococcus pluvialis. Foods, 10(8): 1847. https://doi.org/10.3390/foods10081847
38. 38. Fang, J., Bai, W. & Yang, L. 2023. Astaxanthin inhibits oxidative stress and apoptosis in diabetic retinopathy. Acta Histochemica, 125(6): 152069-152069. https://doi.org/10.1016/j.acthis.2023.152069
39. 39. Faraone, I., Sinisgalli, C., Ostuni, A., Armentano, M.F., Carmosino, M., Milella, L., Russo, D., Labanca, F. & Khan, H. 2020. Astaxanthin anticancer effects are mediated through multiple molecular mechanisms: A systematic review. Pharmacological Research, 155: 104689. https://doi.org/10.1016/j.phrs.2020.104689
40. 40. Faraone, I., Sinisgalli, C., Ostuni, A., Armentano, M.F., Carmosino, M., Milella, L., Russo, D., Labanca, F. & Khan, H. 2020. Astaxanthin anticancer effects are mediated through multiple molecular mechanisms: A systematic review. Pharmacological Research, 155: 104689-104689. https://doi.org/10.1016/j.phrs.2020.104689
41. 41. Fithriani, D., Ambarwaty, D. & Nurhayati. 2019. Identification of bioactive compounds from Nannochloropsis sp. IOP Conference Series: Earth and Environmental Science, 404(1): 012064-012064. https://doi.org/10.1088/1755-1315/404/1/012064
42. 42. Foss, P., Storebakken, T., Austreng, E. & Liaaenjensen, S. 1987. Carotenoids in diets for salmonids. V. Pigmentation of rainbow trout and sea trout with astaxanthin and astaxanthin dipalmitate in comparison with canthaxanthin. Aquaculture, 65(3-4): 293-305. https://doi.org/10.1016/0044-8486(87)90242-0
43. 43. Gmoser, R., Ferreira, J.A., Lennartsson, P.R. & Taherzadeh, M.J. 2017a. Filamentous ascomycetes fungi as a source of natural pigments. Fungal Biology and Biotechnology, 4: 1-25. https://doi.org/10.1186/s40694-017-0033-2
44. 44. Gao, H.L., Yu, X.J., Liu, K.L., Zuo, Y.Y., Fu, L.Y., Chen, Y.M., Zhang, D.D., Shi, X.L., Qi, J., Li, Y., Yi, Q.Y., Tian, H., Wang, X.M., Yu, J.Y., Zhu, G.Q., Liu, J.J., Kang, K.B. & Kang, Y.M. 2021. Chronic Infusion of Astaxanthin into Hypothalamic Paraventricular Nucleus Modulates Cytokines and Attenuates the Renin-Angiotensin System in Spontaneously Hypertensive Rats. Journal of Cardiovascular Pharmacology, 77(2): 170-181. https://doi.org/10.1097/FJC.0000000000000953
45. 45. Gutteridge, J.M.C. & Halliwell, B. 2010. Antioxidants: Molecules, medicines, and myths. Biochemical and Biophysical Research Communications, 393(4): 561-564. https://doi.org/10.1016/j.bbrc.2010.02.071
46. 46. Haines, D.D., Varga, B., Bak, I., Juhasz, B., Mahmoud, F.F., Kalantari, H., Gesztelyi, R., Lekli, I., Czompa, A. & Tosaki, A. 2011. Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: A comparison with ibuprofen. Phytotherapy Research, 25(1): 128-136. https://doi.org/10.1002/ptr.3160
47. 47. Harada, F., Morikawa, T., Lennikov, A., Mukwaya, A., Schaupper, M., Uehara, O., Takai, R., Yoshida, K., Sato, J., Horie, Y., Sakaguchi, H., Wu, C.Z., Abiko, Y., Lagali, N. & Kitaichi, N. 2017. Protective Effects of Oral Astaxanthin Nanopowder against Ultraviolet-Induced Photokeratitis in Mice. Oxidative Medicine and Cellular Longevity, 2017: 1956104. https://doi.org/10.1155/2017/1956104
48. 48. Hayashi, M., Ishibashi, T., Kuwahara, D. & Hirasawa, K. 2021. Commercial Production of Astaxanthin with Paracoccus carotinifaciens. Advances in Experimental Medicine and Biology, 1261: 11-20. https://doi.org/10.1007/978-981-15-7360-6_2
49. 49. Heinzelmann, M., Scott, M. & Lam, T. 2002. Factors predisposing to bacterial invasion and infection. American Journal of Surgery, 183(2): 179-190. https://doi.org/10.1016/S0002-9610(01)00866-2
50. 50. Hormozi, M., Ghoreishi, S. & Baharvand, P. 2019. Astaxanthin induces apoptosis and increases activity of antioxidant enzymes in LS-180 cells. Artificial Cells, Nanomedicine and Biotechnology, 47(1): 891-895. https://doi.org/10.1080/21691401.2019.1580286
51. 51. Hussein, G., Nakagawa, T., Goto, H., Shimada, Y., Matsumoto, K., Sankawa, U. & Watanabe, H. 2007. Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp. Life Sciences, 80(6): 522-529.
52. 52. Ibrahim, A., Shimizu, C. & Kono, M. 1984. Pigmentation of cultured red sea bream, Chrysophrys major, using astaxanthin from Antarctic krill, Euphausia superba, and a mysid, Neomysis sp. Aquaculture, 38(1): 45-57. https://doi.org/10.1016/0044-8486(84)90136-4
53. 53. Indrayani, I., Egeland, E.S., Moheimani, N.R. & Borowitzka, M.A. 2022. Carotenoid production of Botryococcus braunii CCAP 807/2 under different growth conditions. Journal of Applied Phycology, 34(3): 1177-1188. https://doi.org/10.1007/s10811-022-02682-6
54. 54. Ip, P.F. & Chen, F. 2005. Production of astaxanthin by the green microalga Chlorella zofingiensis in the dark. Process Biochemistry, 40(2): 733-738. https://doi.org/10.1016/j.procbio.2004.01.039
55. 55. Jannel, S., Caro, Y., Bermudes, M. & Petit, T. 2020. Novel insights into the biotechnological production of haematococcus pluvialis-derived astaxanthin: Advances and key challenges to allow its industrial use as novel food ingredient. Journal of Marine Science and Engineering, 8(10): 1-48. https://doi.org/10.3390/jmse8100789
56. 56. Jyonouchi, H., Sun, S., Iijima, K. & Gross, M.D. 2000. Antitumor activity of astaxanthin and its mode of action. Nutrition and Cancer, 36(1): 59-65. https://doi.org/10.1207/S15327914NC3601_9
57. 57. Jyonouchi, H., Zhang, L., Gross, M. & Tomita, Y. 1994. Immunomodulating Actions of Carotenoids: Enhancement of In Vivo and In Vitro Antibody Production to T-Dependent Antigens. Nutrition and Cancer, 21(1): 47-58. https://doi.org/10.1080/01635589409514303
58. 58. Kandy, S.K., Nimonkar, M.M., Dash, S.S., Mehta, B. & Markandeya, Y.S. 2022. Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function. Mar Drugs, 20(10): 645. https://doi.org/10.3390/md20100645
59. 59. Kanwugu, O.N., Glukhareva, T.V., Danilova, I.G. & Kovaleva, E.G. 2022. Natural antioxidants in diabetes treatment and management: prospects of astaxanthin. Critical Reviews in Food Science and Nutrition, 62(18): 5005-5028. https://doi.org/10.1080/10408398.2021.1881434
60. 60. Kara, Ö. & Kilitçi, A. 2023. The effect of astaxanthin on amiodarone induced cardiac tissue damage in rat. Cukurova Medical Journal, 48(1): 194-199. https://doi.org/10.17826/cumj.1224847
61. 61. Kavitha, K., Kowshik, J., Kishore, T.K.K., Baba, A.B. & Nagini, S. 2013. Astaxanthin inhibits NF-κB and Wnt/β-catenin signaling pathways via inactivation of Erk/MAPK and PI3K/Akt to induce intrinsic apoptosis in a hamster model of oral cancer. Biochimica et Biophysica Acta - General Subjects, 1830(10): 4433-4444. https://doi.org/10.1016/j.bbagen.2013.05.032
62. 62. Kim, S.H. & Kim, H. 2019. Astaxanthin Modulation of Signaling Pathways That Regulate Autophagy. Mar Drugs, 17(10): 546. https://doi.org/10.3390/md17100546
63. 63. Kim, Y.J., Kim, Y.A.E. & Yokozawa, T. 2009. Protection against oxidative stress, inflammation, and apoptosis of high-glucose-exposed proximal tubular epithelial cells by astaxanthin. Journal of Agricultural and Food Chemistry, 57(19): 8793-8797. https://doi.org/10.1021/jf9019745
64. 64. Kitahara, T. 1983. Behavior of carotenoids in the chum salmon (Oncorhynchus keta) during anadromous migration. Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 76(1): 97-101. https://doi.org/10.1016/0305-0491(83)90177-3
65. 65. Kogure, K. 2019. Novel antioxidative activity of astaxanthin and its synergistic effect with vitamin E. Journal of Nutritional Science and Vitaminology, 65(Supplement): S109-S112. https://doi.org/10.3177/jnsv.65.S109
66. 66. Krestinina, O., Baburina, Y., Krestinin, R., Odinokova, I., Fadeeva, I. & Sotnikova, L. 2020. Astaxanthin prevents mitochondrial impairment induced by isoproterenol in isolated rat heart mitochondria. Antioxidants, 9(3): 262. https://doi.org/10.3390/antiox9030262
67. 67. Kupcinskas, L., Lafolie, P., Lignell, Å., Kiudelis, G., Jonaitis, L., Adamonis, K., Andersen, L.P. & Wadström, T. 2008. Efficacy of the natural antioxidant astaxanthin in the treatment of functional dyspepsia in patients with or without Helicobacter pylori infection: A prospective, randomized, double blind, and placebo-controlled study. Phytomedicine, 15(6-7): 391-399. https://doi.org/10.1016/j.phymed.2008.04.004
68. 68. Lee, J., Kim, M.H. & Kim, H. 2022. Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases. International Journal of Molecular Sciences, 23(24): 15471-15471. https://doi.org/10.3390/ijms232415471
69. 69. Li, J., Guo, C. & Wu, J. 2020. Astaxanthin in liver health and disease: A potential therapeutic agent. Drug Design, Development and Therapy, 14: 2275-2285. https://doi.org/10.2147/DDDT.S230749
70. 70. Li, S., Tan, H.Y., Wang, N., Zhang, Z.J., Lao, L., Wong, C.W. & Feng, Y. 2015. The role of oxidative stress and antioxidants in liver diseases. International Journal of Molecular Sciences, 16(11): 26087-26124. https://doi.org/10.3390/ijms161125942
71. 71. Lim, J.Y. & Wang, X.D. 2020. Mechanistic understanding of β-cryptoxanthin and lycopene in cancer prevention in animal models. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1865(11): 158652-158652. https://doi.org/10.1016/j.bbalip.2020.158652
72. 72. Lima, S.G.M., Freire, M.C.L.C., Oliveira, V.d.S., Solisio, C., Converti, A. & de Lima, Á.A.N. 2021. Astaxanthin delivery systems for skin application: A review. Marine Drugs, 19(9): 511-511. https://doi.org/10.3390/MD19090511
73. 73. Lin, K.H., Lin, K.C., Lu, W.J., Thomas, P.A., Jayakumar, T. & Sheu, J.R. 2016. Astaxanthin, a carotenoid, stimulates immune responses by enhancing IFN-γ and Il-2 secretion in primary cultured lymphocytes in Vitro and ex Vivo. International Journal of Molecular Sciences, 17(1): 44. https://doi.org/10.3390/ijms17010044
74. 74. Liu, B.H. & Lee, Y.K. 1999. Composition and biosynthetic pathways of carotenoids in the astaxanthin- producing green alga Chlorococcum sp. Biotechnology Letters, 21(11): 1007-1010. https://doi.org/10.1023/A:1005660313289
75. 75. Liu, F.T., Yang, R.Y. & Hsu, D.K. 2012. Galectins in acute and chronic inflammation. Annals of the New York Academy of Sciences, 1253(1): 80-91. https://doi.org/10.1111/j.1749-6632.2011.06386.x
76. 76. Liu, X., Xie, J., Zhou, L., Zhang, J., Chen, Z., Xiao, J., Cao, Y. & Xiao, H. 2023. Recent advances in health benefits and bioavailability of dietary astaxanthin and its isomers. Food Chemistry, 404: 134605-134605. https://doi.org/10.1016/j.foodchem.2022.134605
77. 77. Madhavi, D., Kagan, D. & Seshadri, S. 2018. A study on the bioavailability of a proprietary, sustained-release formulation of astaxanthin. Integrative Medicine (Boulder), 17(3): 38-42.
78. 78. Martemucci, G., Costagliola, C., Mariano, M., D’andrea, L., Napolitano, P. & D’Alessandro, A.G. 2022. Free Radical Properties, Source and Targets, Antioxidant Consumption and Health. Oxygen, 2(2): 48-78. https://doi.org/10.3390/oxygen2020006
79. 79. Martínez-Cámara, S., Ibañez, A., Rubio, S., Barreiro, C. & Barredo, J.-L. 2021. Main Carotenoids Produced by Microorganisms. Encyclopedia, 1(4): 1223-1245. https://doi.org/10.3390/encyclopedia1040093
80. 80. Mashhadi, N.S., Zakerkish, M., Mohammadiasl, J., Zarei, M., Mohammadshahi, M. & Haghighizadeh, M.H. 2018. Astaxanthin improves glucose metabolism and reduces blood pressure in patients with type 2 diabetes mellitus. Asia Pacific Journal of Clinical Nutrition, 27(2): 341-346. https://doi.org/10.6133/apjcn.052017.11
81. 81. Masoudi, A., Jorjani, M., Alizadeh, M., Mirzamohammadi, S. & Mohammadi, M. 2021. Anti-inflammatory and antioxidant effects of astaxanthin following spinal cord injury in a rat animal model. Brain Research Bulletin, 177: 324-331. https://doi.org/10.1016/j.brainresbull.2021.10.014
82. 82. Mussagy, C.U., Pereira, J.F.B., Dufossé, L., Raghavan, V., Santos-Ebinuma, V.C. & Pessoa, A. 2023. Advances and trends in biotechnological production of natural astaxanthin by Phaffia rhodozyma yeast. Critical Reviews in Food Science and Nutrition, 63(13): 1862-1876. https://doi.org/10.1080/10408398.2021.1968788
83. 83. Naito, Y., Uchiyama, K., Aoi, W., Hasegawa, G., Nakamura, N., Yoshida, N., Maoka, T., Takahashi, J. & Yoshikawa, T. 2004. Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. BioFactors, 20(1): 49-59. https://doi.org/10.1002/biof.5520200105
84. 84. Odeberg, J.M., Lignell, Å., Pettersson, A. & Höglund, P. 2003. Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations. European Journal of Pharmaceutical Sciences, 19(4): 299-304. https://doi.org/10.1016/S0928-0987(03)00135-0
85. 85. Ohgami, K., Shiratori, K., Kotake, S., Nishida, T., Mizuki, N., Yazawa, K. & Ohno, S. 2003. Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Investigative Ophthalmology and Visual Science, 44(6): 2694-2701. https://doi.org/10.1167/iovs.02-0822
86. 86. Park, J.S., Chyun, J.H., Kim, Y.K., Line, L.L. & Chew, B.P. 2010. Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutrition & Metabolism (Lond), 7: 18. https://doi.org/10.1186/1743-7075-7-18
87. 87. Park, S.Y., Binkley, R.M., Kim, W.J., Lee, M.H. & Lee, S.Y. 2018. Metabolic engineering of Escherichia coli for high-level astaxanthin production with high productivity. Metabolic Engineering, 49: 105-115. https://doi.org/10.1016/j.ymben.2018.08.002
88. 88. Pereira, C.P.M., Souza, A.C.R., Vasconcelos, A.R., Prado, P.S. & Name, J.J. 2021. Antioxidant and anti‑inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review). International Journal of Molecular Medicine, 47(1): 37-48. https://doi.org/10.3892/ijmm.2020.4783
89. 89. Pérez-Rodríguez, L., Jesús, M.-P. & Mougeot, F. 2020. Carotenoid-Based Ornaments as Signals of Health Status in Birds: Evidences from Two Galliform Species, The Red-legged Partridge (Alectoris rufa) and the Red Grouse (Lagopus lagopus scoticus). pp. 227-251. In: Lawton, J.A. & John, W.V. (eds). Encyclopedia of Avian Science, Volume 1-4, 1568 pp.
90. 90. Perozeni, F., Cazzaniga, S., Baier, T., Zanoni, F., Zoccatelli, G., Lauersen, K.J., Wobbe, L. & Ballottari, M. 2020. Turning a green alga red: engineering astaxanthin biosynthesis by intragenic pseudogene revival in Chlamydomonas reinhardtii. Plant Biotechnology Journal, 18(10): 2053-2067. https://doi.org/10.1111/pbi.13364
91. 91. Polotow, T.G., Vardaris, C.V., Mihaliuc, A.R., Goncalves, M.S., Pereira, B., Ganini, D. & Barros, M.P. 2014. Astaxanthin supplementation delays physical exhaustion and prevents redox imbalances in plasma and soleus muscles of Wistar rats. Nutrients, 6(12): 5819-5838. https://doi.org/10.3390/nu6125819
92. 92. Pulcini, D., Capoccioni, F., Franceschini, S., Martinoli, M., Faccenda, F., Secci, G., Perugini, A., Tibaldi, E. & Parisi, G. 2021. Muscle pigmentation in rainbow trout (Oncorhynchus mykiss) fed diets rich in natural carotenoids from microalgae and crustaceans. Aquaculture, 543: 736989-736989. https://doi.org/10.1016/j.aquaculture.2021.736989
93. 93. Radice, R.P., Limongi, A.R., Viviano, E., Padula, M.C., Martelli, G. & Bermano, G. 2021. Effects of astaxanthin in animal models of obesity-associated diseases: A systematic review and meta-analysis. Free Radical Biology and Medicine, 171: 156-168. https://doi.org/10.1016/j.freeradbiomed.2021.05.008
94. 94. Ramamoorthy, K. 2020. Anticancer effects and lysosomal acidification in A549 cells by astaxanthin from Haematococcus lacustris. Bioinformation, 16(11): 965-973. https://doi.org/10.6026/97320630016965
95. 95. Rao, A.R., Sarada, R., Shylaja, M.D. & Ravishankar, G.A. 2015. Evaluation of hepatoprotective and antioxidant activity of astaxanthin and astaxanthin esters from microalga-Haematococcus pluvialis. Journal of Food Science and Technology, 52(10): 6703-6710. https://doi.org/10.1007/s13197-015-1775-6
96. 96. Res, P.T., Cermak, N.M., Stinkens, R., Tollakson, T.J., Haenen, G.R., Bast, A. & Van Loon, L.J.C. 2013. Astaxanthin supplementation does not augment fat use or improve endurance performance. Medicine and Science in Sports and Exercise, 45(6): 1158-1165. https://doi.org/10.1249/MSS.0b013e31827fddc4
97. 97. Ribeiro, E.A., Genofre, G.C. & McNamara, J.C. 2001. Identification and quantification of carotenoid pigments during the embryonic development of the freshwater shrimp Macrobrachium olfersii (crustacea, decapoda). Marine and Freshwater Behaviour and Physiology, 34(2): 105-116. https://doi.org/10.1080/10236240109379063
98. 98. Rivera-Madrid, R., Carballo-Uicab, V.M., Cárdenas-Conejo, Y., Aguilar-Espinosa, M. & Siva, R. 2019. Overview of carotenoids and beneficial effects on human health. pp 1-40. In. Galanakis G.M. (ed.). Carotenoids: Properties, Processing and Applications. Academic Press, 385pp. https://doi.org/10.1016/B978-0-12-817067-0.00001-4
99. 99. Rodriguez-Ruiz, V., Salatti-Dorado, J.Á., Barzegari, A., Nicolas-Boluda, A., Houaoui, A., Caballo, C., Caballero-Casero, N., Sicilia, D., Venegas, J.B., Pauthe, E., Omidi, Y., Letourneur, D., Rubio, S., Gueguen, V. & Pavon-Djavid, G. 2018. Astaxanthin-loaded nanostructured lipid carriers for preservation of antioxidant activity. Molecules, 23(10): 2601. https://doi.org/10.3390/molecules23102601
100. 100. Rodríguez-Sáiz, M., De La Fuente, J.L. & Barredo, J.L. 2010. Xanthophyllomyces dendrorhous for the industrial production of astaxanthin. Applied Microbiology and Biotechnology, 88(3): 645-658. https://doi.org/10.1007/s00253-010-2814-x
101. 101. Roy, V.C., Getachew, A.T., Cho, Y.J., Park, J.S. & Chun, B.S. 2020. Recovery and bio-potentialities of astaxanthin-rich oil from shrimp (Peneanus monodon) waste and mackerel (Scomberomous niphonius) skin using concurrent supercritical CO2 extraction. Journal of Supercritical Fluids, 159: 104773-104773. https://doi.org/10.1016/j.supflu.2020.104773
102. 102. Rüfer, C.E., Moeseneder, J., Briviba, K., Rechkemmer, G. & Bub, A. 2008. Bioavailability of astaxanthin stereoisomers from wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon in healthy men: a randomised, double-blind study. British Journal of Nutrition, 99(5): 1048-1054. https://doi.org/10.1017/s0007114507845521
103. 103. Saeidi, A., Nouri-Habashi, A., Razi, O., Ataeinosrat, A., Rahmani, H., Mollabashi, S.S., Bagherzadeh-Rahmani, B., Aghdam, S.M., Khalajzadeh, L. & Al Kiyumi, M.H. 2023. Astaxanthin supplemented with high-intensity functional training decreases adipokines levels and Cardiovascular Risk factors in men with obesity. Nutrients, 15(2): 286.
104. 104. Sajilata, M.G. & Singhal, R.S. 2008. Isolation and stabilisation of natural pigments for food applications. Stewart Postharvest Review, 2(5): 1-29. https://doi.org/10.2212/spr.2006.5.11
105. 105. Sanz, A.B., Santamaría, B., Ruiz-Ortega, M., Egido, J. & Ortiz, A. 2008. Mechanisms of renal apoptosis in health and disease. Journal of the American Society of Nephrology, 19(9): 1634-1642. https://doi.org/10.1681/ASN.2007121336
106. 106. Seabra, L.M.A.J. & Pedrosa, L.F.C. 2010. Astaxantina: Aspectos estruturais e funcionais. Revista de Nutricao, 23(6): 1041-1050. https://doi.org/10.1590/S1415-52732010000600010
107. 107. Sedmak, J.J., Weerasinghe, D.K. & Jolly, S.O. 1990. Extraction and quantitation of astaxanthin from Phaffia rhodozyma. Biotechnology Techniques, 4(2): 107-112. https://doi.org/10.1007/BF00163282
108. 108. Sekikawa, T., Kizawa, Y., Li, Y. & Miura, N. 2023. Effects of diet containing astaxanthin on visual function in healthy individuals: a randomized, double-blind, placebo-controlled, parallel study. Journal of Clinical Biochemistry and Nutrition, 72(1): 74-81. https://doi.org/10.3164/jcbn.22-65
109. 109. Shah, M.D., Ransangan, J. & Venmathi Maran, B.A. 2023. Marine Biotechnology: Applications in Food, Drugs and Energy, Springer, 367 pp.
110. 110. Shah, M.M.R., Liang, Y., Cheng, J.J. & Daroch, M. 2016. Astaxanthin-producing green microalga Haematococcus pluvialis: from single cell to high value commercial products. Frontiers in Plant Science, 7: 531.
111. 111. Si, P. & Zhu, C. 2022. Biological and neurological activities of astaxanthin (Review). Molecular Medicine Report, 26(4): 300. https://doi.org/10.3892/mmr.2022.12816
112. 112. Song, G., Zhao, Y., Lu, J., Liu, Z., Quan, J. & Zhu, L. 2024. Effects of Astaxanthin on Growth Performance, Gut Structure, and Intestinal Microorganisms of Penaeus vannamei under Microcystin-LR Stress. Animals, 14(1): 58-58. https://doi.org/10.3390/ani14010058
113. 113. Spiller, G.A. & Dewell, A. 2003. Safety of an astaxanthin-rich Haematococcus pluvialis algal extract: A randomized clinical trial. Journal of Medicinal Food, 6(1): 51-56. https://doi.org/10.1089/109662003765184741
114. 114. Storebakken, T., Foss, P., Schiedt, K., Austreng, E., Liaaen-Jensen, S. & Manz, U. 1987. Carotenoids in diets for salmonids. IV. Pigmentation of Atlantic salmon with astaxanthin, astaxanthin dipalmitate and canthaxanthin. Aquaculture, 65(3-4): 279-292. https://doi.org/10.1016/0044-8486(87)90241-9
115. 115. Suescun, J., Chandra, S. & Schiess, M.C. 2019. The Role of Neuroinflammation in Neurodegenerative Disorders. Translational Inflammation, 241-267. https://doi.org/10.1016/B978-0-12-813832-8.00013-3
116. 116. Suhel Alam, M.A. 2024. Complications of cardiovascular disease: the impact of diabetes, dyslipidemia, and metabolic disorders. World Journal of Pharmaceutical Reserch, 13(21): 321-356. https://doi.org/10.20959/WJPR202421-34375
117. 117. Sun, J., Yan, J., Dong, H., Gao, K., Yu, K., He, C. & Mao, X. 2023. Astaxanthin with different configurations: sources, activity, post modification, and application in foods. Current Opinion in Food Science, 49: 100955-100955. https://doi.org/10.1016/j.cofs.2022.100955
118. 118. Sun, S.Q., Zhao, Y.X., Li, S.Y., Qiang, J.W. & Ji, Y.Z. 2020. Anti-tumor effects of astaxanthin by inhibition of the expression of STAT3 in prostate cancer. Marine Drugs, 18(8): 415. https://doi.org/10.3390/MD18080415
119. 119. Supamattaya, K., Kiriratnikom, S., Boonyaratpalin, M. & Borowitzka, L. 2005. Effect of a Dunaliella extract on growth performance, health condition, immune response and disease resistance in black tiger shrimp (Penaeus monodon). Aquaculture, 248(1-4): 207-216. https://doi.org/10.1016/j.aquaculture.2005.04.014
120. 120. Taghiyar, S., Aarabi, M.H., Pourrajab, F., Rad, N.R. & Sharifi-Rigi, A. 2023. Supplement astaxanthin affects PPAR-γ/miR-27a axis and metabolic profile. Gene Reports, 33: 101838-101838. https://doi.org/10.1016/j.genrep.2023.101838
121. 121. Torrissen, O.J., Christiansen, R., StruksnÆS, G. & Estermann, R. 1995. Astaxanthin deposition in the flesh of Atlantic Salmon, Salmo salar L., in relation to dietary astaxanthin concentration and feeding period. Aquaculture Nutrition, 1(2): 77-84. https://doi.org/10.1111/j.1365-2095.1995.tb00022.x
122. 122. Ukibe, K., Hashida, K., Yoshida, N. & Takagi, H. 2009. Metabolic engineering of Saccharomyces cerevisiae for astaxanthin production and oxidative stress tolerance. Applied and Environmental Microbiology, 75(22): 7205-7211. https://doi.org/10.1128/AEM.01249-09
123. 123. Urakaze, M., Kobashi, C., Satou, Y., Shigeta, K., Toshima, M., Takagi, M., Takahashi, J. & Nishida, H. 2021. The beneficial effects of astaxanthin on glucose metabolism and modified low-density lipoprotein in healthy volunteers and subjects with prediabetes. Nutrients, 13(12): 4381.
124. 124. Visioli, F. & Artaria, C. 2017. Astaxanthin in cardiovascular health and disease: Mechanisms of action, therapeutic merits, and knowledge gaps. Food and Function, 8(1): 39-63. https://doi.org/10.1039/c6fo01721e
125. 125. Wade, N., Goulter, K.C., Wilson, K.J., Hall, M.R. & Degnan, B.M. 2005. Esterified astaxanthin levels in lobster epithelia correlate with shell colour intensity: Potential role in crustacean shell colour formation. Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology, 141(3): 307-313. https://doi.org/10.1016/j.cbpc.2005.04.004
126. 126. Wang, X., Willen, R. & Wadstrom, T. 2000. Astaxanthin-rich algal meal and vitamin C inhibit Helicobacter pylori infection in BALB/cA mice. Antimicrobial Agents and Chemotherapy, 44(9): 2452-2457. https://doi.org/10.1128/AAC.44.9.2452-2457.2000
127. 127. Wei, Q. & Guo, J.S. 2022. Developing natural marine products for treating liver diseases. World Journal of Clinical Cases, 10(8): 2369-2381. https://doi.org/10.12998/wjcc.v10.i8.2369
128. 128. White, E.S. & Mantovani, A.R. 2013. Inflammation, wound repair, and fibrosis: Reassessing the spectrum of tissue injury and resolution. Journal of Pathology, 229(2): 141-144. https://doi.org/10.1002/path.4126
129. 129. Winiarska-Mieczan, A., Kwiecień, M., Jachimowicz-Rogowska, K., Donaldson, J., Tomaszewska, E. & Baranowska-Wójcik, E. 2023. Anti-Inflammatory, Antioxidant, and Neuroprotective Effects of Polyphenols—Polyphenols as an Element of Diet Therapy in Depressive Disorders. International Journal of Molecular Sciences, 24(3): 2258-2258. https://doi.org/10.3390/ijms24032258
130. 130. Xia, W., Tang, N., Kord-Varkaneh, H., Low, T.Y., Tan, S.C., Wu, X. & Zhu, Y. 2020. The effects of astaxanthin supplementation on obesity, blood pressure, CRP, glycemic biomarkers, and lipid profile: A meta-analysis of randomized controlled trials. Pharmacological Research, 161: 105113-105113. https://doi.org/10.1016/j.phrs.2020.105113
131. 131. Xiang, M., Lu, Y., Xin, L., Gao, J., Shang, C., Jiang, Z., Lin, H., Fang, X., Qu, Y., Wang, Y., Shen, Z., Zhao, M. & Cui, X. 2021. Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments. Oxidatie Medecine Cellular Longevity, 2021: 6614009. https://doi.org/10.1155/2021/6614009
132. 132. Yang, H., Jin, X., Lam, C.W.K. & Yan, S.K. 2011. Oxidative stress and diabetes mellitus. Clinical Chemistry and Laboratory Medicine, 49(11): 1773-1782. https://doi.org/10.1515/CCLM.2011.250
133. 133. Yang, J., Yin, H.S., Cao, Y.J., Jiang, Z.A., Li, Y.J., Song, M.C., Wang, Y.F., Wang, Z.H., Yang, R., Jiang, Y.F., Sun, J.P., Liu, B.Y. & Wang, C. 2018. Arctigenin Attenuates Ischemia/Reperfusion Induced Ventricular Arrhythmias by Decreasing Oxidative Stress in Rats. Cellular Physiology and Biochemistry, 49(2): 728-742. https://doi.org/10.1159/000493038
134. 134. Yaqoob, Z., Arshad, M.S., Imran, M., Munir, H., Qaisrani, T.B., Khalid, W., Asghar, Z. & Suleria, H.A.R. 2022. Mechanistic role of astaxanthin derived from shrimp against certain metabolic disorders. Food Science and Nutrition, 10(1): 12-20. https://doi.org/10.1002/fsn3.2623
135. 135. Yasui, Y., Hosokawa, M., Mikami, N., Miyashita, K. & Tanaka, T. 2011. Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chemico-Biological Interactions, 193(1): 79-87. https://doi.org/10.1016/j.cbi.2011.05.006
136. 136. Yeh, P.T., Huang, H.W., Yang, C.M., Yang, W.S. & Yang, C.H. 2016. Astaxanthin Inhibits Expression of Retinal Oxidative Stress and Inflammatory Mediators in Streptozotocin-Induced Diabetic Rats. PLoS One, 11(1): e0146438. https://doi.org/10.1371/journal.pone.0146438
137. 137. Yokoyama, A. & Miki, W. 1995. Composition and presumed biosynthetic pathway of carotenoids in the astaxanthin-producing bacterium Agrobacterium aurantiacum. FEMS Microbiology Letters, 128(2): 139-144. https://doi.org/10.1111/j.1574-6968.1995.tb07513.x
138. 138. Yook, J.S., Okamoto, M., Rakwal, R., Shibato, J., Lee, M.C., Matsui, T., Chang, H., Cho, J.Y. & Soya, H. 2016. Astaxanthin supplementation enhances adult hippocampal neurogenesis and spatial memory in mice. Molecular Nutrition and Food Research, 60(3): 589-599. https://doi.org/10.1002/mnfr.201500634
139. 139. Ytrestøyl, T. & Bjerkeng, B. 2007. Dose response in uptake and deposition of intraperitoneally administered astaxanthin in Atlantic salmon (Salmo salar L.) and Atlantic cod (Gadus morhua L.). Aquaculture, 263(1-4): 179-191. https://doi.org/10.1016/j.aquaculture.2006.10.021
140. 140. Zaafan, M.A. & Abdelhamid, A.M. 2021. The cardioprotective effect of astaxanthin against isoprenaline-induced myocardial injury in rats: Involvement of TLR4/NF-κB signaling pathway. European Review for Medical and Pharmacological Sciences, 25(11): 4099-4105. https://doi.org/10.26355/eurrev_202106_26052
141. 141. Zhang, C., Jin, Y., Yu, Y., Xiang, J. & Li, F. 2021. Effects of natural astaxanthin from microalgae and chemically synthetic astaxanthin supplementation on two different varieties of the ridgetail white prawn (Exopalaemon carinicauda). Algal Research, 57: 102347-102347. https://doi.org/10.1016/j.algal.2021.102347
142. 142. Zhang, X., Hou, Y., Li, J. & Wang, J. 2021. The role of astaxanthin on chronic diseases. Crystals, 11(5): 505. https://doi.org/10.3390/cryst11050505
143. 143. Zheng, Y., Xie, L., Yang, D., Luo, K. & Li, X. 2023. Small-molecule natural plants for reversing liver fibrosis based on modulation of hepatic stellate cells activation: An update. Phytomedicine, 113: 154721-154721. https://doi.org/10.1016/j.phymed.2023.154721
144. 144. Zhuang, P., Greenberg, Z. & He, M. 2021. Biologically Enhanced Starch Bio-Ink for Promoting 3D Cell Growth. Advanced Materials Technologies, 6(12): 2100551. https://doi.org/10.1002/admt.202100551
145. 145. Zhuge, F., Ni, Y., Wan, C., Liu, F. & Fu, Z. 2021. Anti-diabetic effects of astaxanthin on an stz-induced diabetic model in rats. Endocrine Journal, 68(4): 451-459. https://doi.org/10.1507/endocrj.EJ20-0699