Marine algae as emerging therapeutic alternatives for depression: A review

Document Type : Review Article

Authors

1 Department of Anatomy, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

2 Training Management Division, Ministry of Health Malaysia, 62675 Putrajaya, Malaysia

3 Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia

4 Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia

5 School of Biosciences, Faculty of Health & Medical Sciences, Taylor’s University Lakeside Campus, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia

6 Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong Special Administrative Region, China

Abstract

Depression is a complex heterogeneous brain disorder characterized by a range of symptoms, resulting in psychomotor and cognitive disabilities and suicidal thoughts. Its prevalence has reached an alarming level affecting millions of people globally. Despite advances in current pharmacological treatments, the heterogenicity of clinical response and incidences of adverse effects have shifted research focus to identification of new natural substances with minimal or no adverse effects as therapeutic alternatives. Marine algae-derived extracts and their constituents are considered potential sources of secondary metabolites with diverse beneficial effects. Marine algae with enormous health benefits are emerging as a natural source for discovering new alternative antidepressants. Its medicinal properties exhibited shielding efficacy against neuroinflammation, oxidative stress, and mitochondrial dysfunction, which are indicated to underlie the pathogenesis of many neurological disorders. Marine algae have been found to ameliorate depressive-like symptoms and behaviors in preclinical and clinical studies by restoring monoaminergic neurotransmission, hypothalamic-pituitary-adrenal axis function, neuroplasticity, and continuous neurogenesis in the dentate gyrus of the hippocampus via modulating brain-derived neurotrophic factors and antineuroinflammatory activity. Although antidepressant effects of marine algae have not been validated in comparison with currently available synthetic antidepressants, they have been reported to have effects on the pathophysiology of depression, thus suggesting their potential as novel antidepressants. In this review, we analyzed the currently available research on the potential benefits of marine algae on depression, including their effects on the pathophysiology of depression, potential clinical relevance of their antidepressant effects in preclinical and clinical studies, and the underlying mechanisms of these effects.

Keywords

References

1. World Health Organization. Depression and other common mental disorders: global health estimates. Geneva, Switzerland: World Health Organization, 2017.
2.  Wong SK, Chin KY, Ima-Nirwana S. Vitamin D and depression: the evidence from an indirect clue to treatment strategy. Curr Drug Targets 2018; 19:888-897.
3. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392:1789-1858.
4.  Institute for Public Health. National Health and Morbidity Survey (NHMS) 2019: non-communicable diseases, healthcare demand and health literacy-key findings (pp 21-22). Selangor, Malaysia: National Institutes of Health (NIH), Ministry of Health Malaysia, 2020.
5. Indu PS, Anilkumar TV, Pisharody R, Russell PSS, Raju D, Sarma PS, et al. Prevalence of depression and past suicide attempt in primary care. Asian J Psychiatr 2017; 27:48-52.
6.  Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of depression in the community from 30 countries between 1994 and 2014. Sci Rep 2018; 8:2861-2870.
7. Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, et al. Canadian network for mood and anxiety treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 3. Pharmacological Treatments. Can J Psychiatry 2016; 61:540-560.
8. Wang SM, Han C, Bahk WM, Lee SJ, Patkar AA, Masand PS, et al. Addressing the side effects of contemporary antidepressant drugs: A comprehensive review. Chonnam Med J 2018; 54:101-112.
9. Chong PS, Fung ML, Wong KH, Lim LW. Therapeutic potential of Hericium erinaceus for depressive disorder. Int J Mol Sci 2020; 21:163-180.
10. Lew SY, Lim SH, Lim LW, Wong KH. Neuroprotective effects of Hericium erinaceus (Bull.: Fr.) Pers. against high-dose corticosterone-induced oxidative stress in PC-12 cells. BMC Complement Med Ther 2020; 20:340-355.
11.  Lew SY, Teoh SL, Lim SH, Lim LW, Wong KH. Discovering the potentials of medicinal mushrooms in combating depression-A review. Mini Rev in Med Chem 2020; 20:1518-1531.
12. Subermaniam K, Yow YY, Lim SH, Koh OH, Wong KH. Malaysian macroalga Padina australis Hauck attenuates high dose corticosterone-mediated oxidative damage in PC12 cells mimicking the effects of depression. Saudi J Biol Sci 2020; 27:1435-1445.
13. Chong CW, Hii SL, Wong CL. Antibacterial activity of Sargassum polycystum C. Agardh and Padina australis Hauck (Phaeophyceae). Afr J Biotechnol 2011; 10:14125-14131.
14.  Murugan AC, Vallal D, Karim MR, Govidan N, Yusoff MBM, Rahman MM. In vitro antiradical and neuroprotective activity of polyphenolic extract from marine algae Padina autralis. J Chem Pharm Res 2015; 7:355-362.
15.  Gany SA, Tan SC, Gan SY. Antioxidative, anticholinesterase and anti-neuroinflammatory properties of Malaysian brown and green seaweeds. Int J Biol Biomol Agric Food Biotechnol Eng 2014; 8:1269-1275.
16. Hannan MA, Dash R, Haque MN, Mohibbullah M, Sohag AAM, Rahman MA, et al. Neuroprotective potentials of marine algae and their bioactive metabolites: pharmacological insights and therapeutic advances. Mar Drugs 2020; 18:347.
17. Jiang X, Chen L, Shen L, Chen Z, Xu L, Zhang J, et al. Trans-astaxanthin attenuates lipopolysaccharide-induced neuroinflammation and depressive-like behavior in mice. Brain Res 2016; 1649(Part A):30-37.
18. Jiang X, Zhu K, Xu Q, Wang G, Zhang J, Cao R, et al. The antidepressant-like effect of trans-astaxanthin involves the serotonergic system. Oncotarget 2017;8:25552-25563.
19. Sasaki K, Othman MB, Demura M, Watanabe M, Isoda H. Modulation of neurogenesis through the promotion of energy production activity is behind the antidepressant-like effect of colonial green alga, Botryococcus braunii. Front Physiol 2017; 8:900-908.
20. Violle N, Rozan P, Demais H, Collen PN, Bisson JF. Evaluation of the antidepressant- and anxiolytic-like effects of a hydrophilic extract from the green seaweed Ulva sp. in rats. Nutr Neurosci 2018; 21:248-256.
21. Moradi-Kor N, Ghanbari A, Rashidipour H, Bandegi AR, Yousefi B, Barati M., et al. Therapeutic effects of Spirulina platensis against adolescent stress-induced oxidative stress, brain-derived neurotrophic factor alterations and morphological remodeling in the amygdala of adult female rats. J Exp Pharmacol 2020; 2:75-85.
22. Matraszek-Gawron R, Chwil M, Terlecka P, Skoczylas MM. Recent studies on anti-depressant bioactive substances in selected species from the genera Hemerocallis and Gladiolus: a systematic review. Pharmaceuticals 2019; 12:172-203.
23. Perez-Caballero L, Torres-Sanchez S, Romero-López-Alberca C, González-Saiz F, Mico JA, Berrocoso E. Monoaminergic system and depression. Cell Tissue Res 2019; 377:107-113.
24.  Lemieux G, Davignon A, Genest J. Depressive states during Rauwolfia therapy for arterial hypertension; a report of 30 cases. Can Med Assoc J 1956; 74:522-526.
25. Loomer HP, Saunders JC, Kline NS. A clinical and pharmacodynamic evaluation of iproniazid as a psychic energizer. Psychiatr Res Rep Am Psychiatr Assoc 1957; 8:129-141.
26. Stahl SM. Selecting an antidepressant by using mechanism of action to enhance efficacy and avoid side effects. J Clin Psychiatry 1998; 59(Suppl 18):23-29.
27.  Watkins M. Antianxiety Pharmacology. Encyclopedia of the Neurological Sciences 2014; 1:204-206.
28. Siddiqui PJA, Khan A, Uddin N, Khaliq S, Rasheed M, Nawaz S, et al. Antidepressant-like deliverables from the sea: evidence on the efficacy of three different brown seaweeds via involvement of monoaminergic system. Biosci Biotechnol Biochem 2017; 81:1369-1378.
29. Herman JP, McKlveen JM, Ghosal S, Kopp B, Wulsin A, Makinson R, et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response. Compr Physiol 2016; 6:603-621.
30.  Chen J, Evans AN, Liu Y, Honda M, Saavedra JM, Aguilera G. Maternal deprivation in rats is associated with corticotrophin releasing hormone (CRH) promoter hypomethylation and enhances CRH transcriptional responses to stress in adulthood. J Neuroendocrinol 2012; 24:1055-1064.
31.  Juruena MF, Cleare AJ, Bauer M, Pariante CM. Molecular mechanisms of glucocorticoid receptor sensitivity and relevance to affective disorders. Acta Neuropsychiatr 2003; 15: 354-367.
32. Wardle RA, Poo MM. Brain-derived neurotrophic factor modulation of GABAergic synapses by postsynaptic regulation of chloride transport. J Neurosci 2003; 23:8722-8732.
33. Sirianni RW, Olausson P, Chiu AS, Taylor JR, Saltzman WM. The behavioral and biochemical effects of BDNF containing polymers implanted in the hippocampus of rats. Brain Res 2010; 1321:40-50.    
34. Kim NH, Jeong HJ, Lee JY, Go H, Ko SG, Hong SH, et al. The effect of hydrolyzed Spirulina by malted barley on forced swimming test in ICR mice. Int J Neurosci 2008; 118:1523-1533.
35. Martinowich K, Manji H, Lu B. New insights into BDNF function in depression and anxiety. Nat Neurosci 2007; 10:1089-1093.
36. Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997; 54:597-606.
37.  Friedman WJ. Proneurotrophins, seizures, and neuronal apoptosis. Neuroscientist 2010; 16: 244-252.
38. Volosin M, Song W, Almeida RD, Kaplan DR, Hempstead BL, Friedman WJ. Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J. Neurosci 2006; 26:7756-7766.
39. Bakunina N, Pariante CM, Zunszain PA. Immune mechanisms linked to depression via oxidative stress and neuroprogression. Immunology 2015; 144:365-373.
40. Troubat R, Barone P, Leman S, Desmidt T, Cressant A, Atanasova B, et al. Neuroinflammation and depression: a review. Eur J Neurosci 2021; 53:151-171
41.  Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment-resistant depression. Cytokine 1997; 9(11):853-858.
42.  Verduijn J, Milaneschi Y, Schoevers RA, van Hemert AM, Beekman ATF, Penninx BWJH. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression. Transl Psychiatry 2015; 5:1-9.
43. Suzuki E, Yagi G, Nakaki T, Kanba S, Asai M. Elevated plasma nitrate levels in depressive states. J Affect Disord 2001; 63:221–224.
44. Dhir A, Kulkarni S. Involvement of nitric oxide (NO) signaling pathway in the antidepressant action of bupropion, a dopamine reuptake inhibitor. Eur J Pharmacol. 2007; 568:177-185.
45. Brites D, Fernandes A. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation. Front Cell Neurosci 2015; 9:1-20.
46.  Peirce J, Alviña K. The role of inflammation and the gut microbiome in depression and anxiety. J Neurosci Res 2019; 97:1223-1241.
47. Müller N. Immunological aspects of the treatment of depression and schizophrenia. Dialogues Clin Neurosci 2017; 19:55-63.
48. Yoon RSY, Ravindran N, Ravindran A. Complementary and alternative therapies for treatment-resistant depression: a clinical perspective. In: Shivakumar K, Amanullah S (eds). Complex clinical conundrums in psychiatry. Cham, Switzerland: Springer; 2018.p. 123-142.
49.   Pereira L. Therapeutic and nutritional uses of algae. Boca Raton, Florida: CRC Press; 2018.
50. Pandey A. Microalgae biomass production for CO2 mitigation and biodiesel production. J Microbiol Exp 2017; 4:00117.
51. Pangestuti R, Kim SK. Neuroprotective effects of marine algae. Mar Drugs 2011; 9:803-818.
52.  Suresh D, Madhu M, Saritha C, Raj Kumar V, Shankaraiah P. Antidepressant activity of Spirulina platensis in experimentally induced depressed mice. Int J Pharm Arch 2014; 3(2):317-326.
53. Soetantyo GI, Sarto M. The antidepressant effect of Chlorella vulgaris on female Wistar rats (Rattus norvegicus Berkenhout, 1769) with chronic unpredictable mild stress treatment. J Trop Biodivers Biotechnol 2019; 4:72-81.
54. Qiao J, Rong L, Wang Z, Zhang M. Involvement of Akt/GSK3b/CREB signaling pathway on chronic omethoate induced depressive-like behavior and improvement effects of combined lithium chloride and astaxanthin treatment. Neurosci Lett 2017; 649:55-61.
55. Abreu TM, Monteiro VS, Martins ABS, Teles FB, da Conceicao Rivanor RL, Mota EF, et al. Involvement of the dopaminergic system in the antidepressant-like effect of the lectin isolated from the red marine alga Solieria filiformis in mice. Int J Biol Macromol 2018; 111:534-541.
56. Panahi Y, Badeli R, Karami GR, Badeli Z, Sahebkar A. A randomized controlled trial of 6-week Chlorella vulgaris supplementation in patients with major depressive disorder. Complement Ther Med 2015; 23:598-602.
57.  Talbott S, Hantla D, Capelli B, Ding L, Li Y, Artaria C. Astaxanthin supplementation reduces depression and fatigue in healthy subjects. EC Nutrition 2019; 14:239-246.
58. Miyake, Y, Tanaka K, Okubo H, Sasaki S, Arakawa M. Seaweed consumption and prevalence of depressive symptoms during pregnancy in Japan: baseline data from the Kyushu Okinawa maternal and child health study. BMC Pregnancy Childbirth 2014; 14:301-307.
59.  Allaert FA, Demais H, Collen PN. A randomized controlled double-blind clinical trial comparing versus placebo the effect of an edible algal extract (Ulva lactuca) on the component of depression in healthy volunteers with anhedonia. BMC Psychiatry 2018; 18:215-224.
60.  Guo F, Huang C, Cui Y, Momma H, Niu K, Nagatomi R. Dietary seaweed intake and depressive symptoms in Japanese adults: a prospective cohort study. Nutr J 2019; 18:1-8.
61.  Xu T, Qin S, Hu Y, Song Z, Ying J, Li P, et al. Whole genomic DNA sequencing and comparative genomic analysis of Arthrospira platensis: high genome plasticity and genetic diversity. DNA Res 2016; 23:325-338.
62. Okechukwu PN, Ekeuku SO, Sharma M, Chong PN, Chan HK, Mohamed N, et al. In vivo and in vitro antidiabetic and anti-oxidant activity of Spirulina. Pharmacogn Mag 2019; 15:17-29.
63.  Zajecka JM, Albano D. SNRIs in the management of acute major depressive disorder. J Clin Psychiatry 2004; 65(Suppl 17):11-18.
64.  Brydges NM, Jin R, Seckl J, Holmes MC, Drake AJ, Hall J. Juvenile stress enhances anxiety and alters corticosteroid receptor expression in adulthood. Brain and Behav 2014; 4:4-13.
65. Kanwal JS, Jung Y, Zhang M. Brain plasticity during adolescence: effects of stress, sleep, sex and sounds on decision making. Anat Physiol 2016; 6:e135.
66. Cheng P, Okada S, Zhou C, Chen P, Huo S, Li K, et al. High-value chemicals from Botryococcus braunii and their current applications - A review. Bioresour Technol 2019; 291:121911.
67.  Jaafar F, Durani LW, Makpol S. Chorella vulgaris modulates the expression of senescence-associated genes in replicative senescence of human diploid fibroblasts. Mol Biol Rep 2020; 47:369-379.
68. Safi C, Zebib B, Merah O, Pontalier P, Vaca-Garcia C. Morphology, composition, production, processing and applications of Chlorella vulgaris: a review. Renew Sust Energ Rev 2014; 35:265-278.
69. Lorenz RT, Cysewski GR. Commercial potential for Haematococcus microalgae as a natural source of astaxanthin. Trends Biotechnol 2000; 18:160-167.
70. Allewaert CC, Vanormelingen P, Proschold T, Gomez PI, Gonzalez MA, Bilcke G, et al. Species diversity in European Haematococcus pluvialis (Chlorophyceae, Volvocales). Phycologia 2019; 54:583-598.
71. Maeng SH, Hong H. Inflammation as the potential basis in depression. Int Neurol J 2019; 23(Suppl 2):S63-71.
72. Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, et al. Astaxanthin as a potential neuroprotective agent for neurological diseases. Mar Drugs 2015; 13:5750-5766.
73. Balietti M, Giannubilo SR, Giorgetti B, Solazzi M, Turi A, Casoli T, et al. The effect of astaxanthin on the aging rat brain: gender-related differences in modulating inflammation. J Sci Food Agric 2016; 96:615-618.
74. Shannon E, Abu-Ghannam N. Antibacterial derivatives of marine algae: an overview of pharmacological mechanisms and application. Mar Drugs 2016; 14:81.
75.  Phang SM, Yeong HY, Ganzon-Fortes ET, Lewmanomont K, Prathep A, Hau LN, et al. Marine algae of the South China Sea bordered by the Philiphines, Indonesia, Singapore, Malaysia, Thailand and Vietnam. Raffles Bull Zool 2016; Supplement 34:13-59.
76.  Guiry MD, Guiry GM. No Title [Internet] AlgaeBase. World-wide electronic publication, National University of Ireland, Galway (taxonomic information republished from Algae Base with permission of M.D. Guiry). Solieria filiformis (Kützing) Gabrielson 1985. 2020 [cited 2020 May 30]. Available from: http://www.algaebase.org/search/species/detail/?species_id=686.
77. Shimada S, Yokoyama N, Arai S, Hiraoka M. Phylogeography of the genus Ulva (Ulvophyceae, Chlorophyta), with special reference to the Japanese freshwater and brackish taxa. J Appl Phycol 2009; 20:529-539.
78. Pangestuti R, Kurnianto D. Green seaweeds-derived polysaccharides ulvan: Occurrence, medicinal value and potential applications. In: Venkatesan J, Anil S, Kim S, (eds.). Seaweed polysaccharides: Isolation, biological and biomedical applications. Amsterdam, Netherlands: Elsevier; 2017.p. 205-221.
79. Hughey JR, Maggs CA, Mineur F, Jarvis C, Miller KA, Shabaka SH, et al. Genetic analysis of the Linnaean Ulva lactuca (Ulvales, Chlorophyta) holotype and related type specimens reveals name misapplications, unexpected origins, and new synonymies. J Phycol 2019; 55:503-508.
80. Zou D, Ji Z, Chen W, Li G. High temperature stress might hamper the success of sexual reproduction in Hizikia fusiformis from Shantou, China: a photosynthetic perspective. Phycologia 2018; 57:394-400.
81. Watanabe Y, Yamada H, Mine T, Kawamura Y, Nishihara GN, Terada R. Photosynthetic responses of Pyropia yezoensis f. narawaensis (Bangiales, Rhodophyta) to a thermal and PAR gradient vary with the life-history stage. Phycologia 2016; 55:665-672.
82. Pal Singh H, Sharma S, Chauhan SB, Kaur I. Clinical trials of traditional herbal medicines in India: current status and challenges. Int J Pharmacogn 2014; 1:415-421.
83. Rasia-Filho AA, Fabian C, Rigoti KM, Achaval M. Influence of sex, estrous cycle and motherhood on dendritic spine density in the rat medial amygdala revealed by the Golgi method. Neuroscience 2004; 126:839-847.
84. Slattery DA, Cryan JF. Using the rat forced swim test to assess antidepressant-like activity of rodents. Nat Protoc 2012; 7:1009-1014.
85. Mao QQ, Huang Z, Ip SP, Xian YF, Che CT. Protective effects of piperine against corticosterone-induced neurotoxicity in PC12 cells. Cell Mol Neurobiol 2012; 32:531-537.
86.  Fillingim RB, Price DD. What is controlled for in placebo-controlled trials? Mayo Clin Proc 2005; 80:1119-1121.
87. Moka D, Dietlein M, Schicha H. Radioiodine therapy and thyrostatic drugs and iodine. Eur J Nucl Med Mol Imaging 2002; 29(Suppl 2):S486-491.
88.  Fleurence J, Morançais M, Dumay J, Decottignies P, Turpin V, Munier M, et al. What are the prospects for using seaweed in human nutrition and for marine animals raised through aquaculture? Trends Food Sci Technol 2012; 27:57-61.
89. Nabavi SM, Daglia M, Braidy N, Nabavi SF. Natural products, micronutrients, and nutraceuticals for the treatment of depression: a short review. Nutr Neurosci 2017; 20:180-194.
90.  Bocquier A, Cortaredona S, Verdoux H, Casanova L, Sciortino V, Nauleau S, et al. Social inequalities in early antidepressant discontinuation. Psychiatr Serv 2014; 65:618-625.
91.  Liu L, Liu C, Wang Y, Wang P, Li Y, Li B. Herbal medicine for anxiety, depression and insomnia. Curr Neuropharmacol 2015; 13:481-493.
92. Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immun 2016; 16:22-34.
93.  Lindqvist D, Dhabhar FS, James SJ, Hough CM, Jain FA, Bersani FS, et al. Oxidative stress, inflammation and treatment response in major depression. Psychoneuroendocrinology 2017; 76:197-205.
Iranian Journal of Basic Medical Sciences
Volume 24, Issue 8
August 2021
Pages 997-1013

Files

Share

How to cite

Statistics