Malaysian brown macroalga Padina australis mitigates lipopolysaccharide-stimulated neuroinflammation in BV2 microglial cells

Document Type : Original Article

Authors

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

2 Sungai Buloh Training Institute of Ministry of Health Malaysia, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia

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

4 Department of Chemistry, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia

5 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

Objective(s): Neuroinflammation and microglial activation are pathological features in central nervous system disorders. Excess levels of reactive oxygen species (ROS) and pro-inflammatory cytokines have been implicated in exacerbation of neuronal damage during chronic activation of microglial cells. Padina australis, a brown macroalga, has been demonstrated to have various pharmacological properties such as anti-neuroinflammatory activity. However, the underlying mechanism mediating the anti-neuroinflammatory potential of P. australis remains poorly understood. We explored the use of Malaysian P. australis in attenuating lipopolysaccharide (LPS)-stimulated neuroinflammation in BV2 microglial cells. 
Materials and Methods: Fresh specimens of P. australis were freeze-dried and subjected to ethanol extraction. The ethanol extract (PAEE) was evaluated for its protective effects against 1 µg/ml LPS-stimulated neuroinflammation in BV2 microglial cells. 
Results: LPS reduced the viability of BV2 microglia cells and increased the levels of nitric oxide (NO), prostaglandin E2 (PGE2), intracellular reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). However, the neuroinflammatory response was reversed by 0.5–2.0 mg/ml PAEE in a dose-dependent manner. Analysis of liquid chromatography-mass spectrometry (LC-MS) of PAEE subfractions revealed five compounds; methyl α-eleostearate, ethyl α-eleostearate, niacinamide, stearamide, and linoleic acid. 
Conclusion: The protective effects of PAEE against LPS-stimulated neuroinflammation in BV2 microglial cells were found to be mediated by the suppression of excess levels of intracellular ROS and pro-inflammatory mediators and cytokines, denoting the protective role of P. australis in combating continuous neuroinflammation. Our findings support the use of P. australis as a possible therapeutic for neuroinflammatory and neurodegenerative diseases.

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References

1.    Yamanaka G, Suzuki, S., Morishita, N., Takeshita, M., Kanou, K., Takamatsu, T, et al. Role of neuroinflammation and blood-brain barrier permutability on migraine. Int J Mol Sci 2021; 22: 8929. 
2.    Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010; 330: 841-845. 
3.    Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, et al. Synaptic pruning by microglia is necessary for normal brain development. Science 2011; 333: 1456-1458. 
4.    Simpson D, Oliver PL. ROS generation in microglia: Understanding oxidative stress and inflammation in neurodegenerative disease. Anti-oxidants (Basel) 2020; 9: 743.
5.    Zhang P, Yang M, Chen C, Liu L, Wei X, Zeng S. Toll-like receptor 4 (TLR4)/opioid receptor pathway crosstalk and impact on opioid analgesia, immune function, and gastrointestinal motility. Front Immunol 2020; 11: 1455. 
6.    Seow SL, Naidu M, Sabaratnam V, Vidyadaran S, Wong KH. Tiger’s Milk medicinal mushroom, Lignosus rhinocerotis (Agaricomycetes) sclerotium inhibits nitric oxide production in LPS-stimulated BV2 microglia. Int J Med Mushrooms 2017; 19: 405-418. 
7.    Pang JR, Goh VMJ, Tan CY, Phang SM, Wong KH, Yow YY. Neuritogenic and in vitro anti-oxidant activities of Malaysian Gracilaria manilaensis Yamamoto & Trono. J Appl Phycol 2018; 30: 3253-3260. 
8.    Pang JR, How SW, Wong KH, Lim SH, Phang SM, Yow YY. Cholinesterase inhibitory activities of neuroprotective fraction derived from red alga Gracilaria manilaensis. Fish Aquatic Sci 2022; 25: 49-63. 
9.    Ngu EL, Ko CL, Tan CY, Wong KH, Phang SM, Yow YY. Phytochemical profiling and in vitro screening for neuritogenic and anti-oxidant activities of Spirulina platensis. Indian J Pharm Educ Res 2021; 55: 812-822. 
10.    Subermaniam K, Teoh SL, Yow YY, Tang YQ, Lim LW, Wong KH. Marine algae as emerging therapeutic alternatives for depression: A review. Iran J Basic Med Sci 2021; 24: 997. 
11.    Yow YY, Goh TK, Nyiew KY, Lim LW, Phang SM, Lim SH, et al. Therapeutic potential of complementary and alternative medicines in peripheral nerve regeneration: A systematic review. Cells 2021; 10: 2194. 
12.    Bruno JF, Bertness MD. Habitat modification and facilitation in benthic marine communities. In: Bertness MD, Gaines SD, Hay ME, editors. Marine Community Ecology. Sinauer Associates; 2001.p. 201-218.
13.    Schiel DR, Foster MS. The population biology of large brown seaweeds: Ecological consequences of multiphase life histories in dynamic coastal environments. Annu Rev Ecol Evol Syst 2006; 37: 343-372.
14.    Mineur F, Arenas F, Assis J, Davies AJ, Engelen AH, Fernandes F, et al. European seaweeds under pressure: Consequences for communities and ecosystem functioning. J Sea Res 2015; 98: 91-108. 
15.    Teagle H, Hawkins SJ, Moore PJ, Smale DA. The role of kelp species as biogenic habitat formers in coastal marine ecosystems. J Exp Mar Biol Ecol 2017; 492: 81-98. 
16.    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. 
17.    Gany SA, Tan SC, Gan SY. Anti-oxidative, anticholinesterase and anti-neuroinflammatory properties of Malaysian brown and green seaweeds. Int J Ind Syst Eng 2014; 8: 1269-1275. 
18.    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 australis. J Chem Pharm Res 2015; 7: 355-362.
19.    Akbary P, Aminikhoei Z, Hobbi M, Samadi Kuchaksaraei B, Rezaei Tavabe K. Anti-oxidant properties and total phenolic contents of extracts from three macroalgae collected from Chabahar coasts. Proc Natl Acad Sci U S A 2021; 91: 327-334. 
20.    Chong C-W, Hii S-L, Wong C-L. Antibacterial activity of Sargassum polycystum C. Agardh and Padina australis Hauck (phaeophyceae). Afr J Biotechnol 2011; 10: 14125-14131. 
21.    Zailanie K. Study of Padina australis using UV-VIS, HPLC and antibacterial. J Life Sci Biomed 2016; 6: 01-05.
22.    Jaswir I, Noviendri D, Salleh HM, Taher M, Miyashita K. Isolation of fucoxanthin and fatty acids analysis of Padina australis and cytotoxic effect of fucoxanthin on human lung cancer (H1299) cell lines. Afr J Biotechnol 2011; 10: 18855-18862. 
23.    Wang H, Ooi EV, Ang PO Jr. Antiviral activities of extracts from Hong Kong seaweeds. J Zhejiang Univ Sci B 2008; 9: 969-976. 
24.    Canoy JL, Bitacura JG. Cytotoxicity and antiangiogenic activity of Turbinaria ornata Agardh and Padina australis Hauck ethanolic extracts. Anal Cell Pathol (Amst) 2018; 2018: 3709491. 
25.    Tirtawijaya G, Mohibbullah M, Meinita MDN, Moon IS, Hong YK. The ethanol extract of the rhodophyte Kappaphycus alvarezii promotes neurite outgrowth in hippocampal neurons. J Appl Phycol 2016; 28: 2515-2522. 
26.    Trono GC Jr. Field Guide and Atlas of the Seaweed Resources of the Philippines. Bookmark Inc.; 1997. 
27.    Harun A, Vidyadaran S, Lim SM, Cole AL, Ramasamy K. Malaysian endophytic fungal extracts-induced anti-inflammation in lipopolysaccharide-activated BV-2 microglia is associated with attenuation of NO production and, IL-6 and TNF-α expression. BMC Complement Altern Med 2015; 15: 166. 
28.    Oh S-J, Joung E-J, Kwon M-S, Lee B, Utsuki T, Oh C-W, et al. Anti-inflammatory effect of ethanol extract of Sargassum serratifolium in lipopolysaccharide-stimulate BV2 microglia. J Med Food 2016; 19: 1023-1031. 
29.    Kim N, Yoo H-S, Ju Y-J, Oh MS, Lee K-T, Inn K-S, et al. Synthetic 3’,4’-dihydroxyflavone exerts anti-neuroinflammatory effects in BV2 microglia and a mouse model. Biomol Ther (Seoul) 2018; 26: 210-217. 
30.    Yap WF, Tay V, Tan SH, Yow YY, Chew J. Decoding anti-oxidant and antibacterial potentials of Malaysian green seaweeds: Caulerpa racemosa and Caulerpa lentillifera. Antibiotics (Basel) 2019; 8: 152. 
31.    Bertin MJ, Zimba PV, Beauchesne KR, Huncik KM, Moeller PDR. Identification of toxic fatty acid amides isolated from the harmful alga Prymnesium parvum Carter. Harmful Algae 2012; 20: 111-116. 
32.    Song SB, Park JS, Chung GJ, Lee IH, Hwang ES. Diverse therapeutic efficacies and more diverse mechanisms of nicotinamide. Metabolomics 2019; 15: 137. 
33.    Cai Y, Liu J, Wang B, Sun M, Yang H. Microglia in the neuroinflammatory pathogenesis of Alzheimer’s disease and related therapeutic targets. Front Immunol 2022; 13: 856376. 
34.    Bachiller S, Jiménez-Ferrer I, Paulus A, Yang Y, Swanberg M, Deierborg T, et al. Microglia in neurological diseases: A road map to brain-disease dependent-inflammatory response. Front Cell Neurosci 2018; 12: 488. 
35.    Jayasooriya R, Moon D, Choi YH, Yoon CH, Kim GY. Methanol extract of Hydroclathrus clathratus inhibits production of nitric oxide, prostaglandin E2 and tumor necrosis factor-α in lipopolysaccharide-stimulated BV2 microglial cells via inhibition of NF-κB activity. Trop J Pharm Res 2011; 10: 723-730. 
36.    Jayasooriya RGPT, Lee K-T, Choi YH, Moon S-K, Kim W-J, Kim G-Y. Antagonistic effects of acetylshikonin on LPS-induced NO and PGE2 production in BV2 microglial cells via inhibition of ROS/PI3K/Akt-mediated NF-κB signaling and activation of Nrf2-dependent HO-1. In Vitro Cell Dev Biol Anim 2015; 51: 975-986. 
37.    Chan C-K, Tan LT-H, Andy SN, Kamarudin MNA, Goh B-H, Abdul Kadir H. Anti-neuroinflammatory activity of Elephantopus scaber L. via activation of Nrf2/HO-1 signaling and inhibition of p38 MAPK pathway in LPS-induced microglia BV-2 cells. Front Pharmacol 2017; 8: 397. 
38.    Zang C, Yang H, Wang L, Wang Y, Bao X, Wang X, et al. A novel synthetic derivative of phloroglucinol inhibits neuroinflammatory responses through attenuating kalirin signaling pathway in murine BV2 microglial cells. Mol Neurobiol 2019; 56: 2870-288. 
39.    Fischer R, Maier O. Interrelation of oxidative stress and inflammation in neurodegenerative disease: Role of TNF. Oxid Med Cell Longev 2015; 2015: 610813. 
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.    Velagapudi R, El-Bakoush A, Lepiarz I, Ogunrinade F, Olajide OA. AMPK and SIRT1 activation contribute to inhibition of neuroinflammation by thymoquinone in BV2 microglia. Mol Cell Biochem 2017; 435: 149-162. 
42.    Kim S, Lee M-S, Lee B, Gwon W-G, Joung E-J, Yoon N-Y, et al. Anti-inflammatory effects of sargachromenol-rich ethanol extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells. BMC Complement Altern Med 2014; 14: 231. 
43.    Park C, Cha HJ, Hong SH, Kim S, Kim HS, Choi YH. Carpomitra costata extract alleviates lipopolysaccharide-induced neuroinflammatory responses in BV2 microglia through the inactivation of NF-κB associated with the blockade of the TLR4 pathway and ROS generation. Hanguk Haeyang Paio Hakhoe 2020; 12: 29-39. 
44.    Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2: 17023. 
45.    Wang H, Vidyadaran S, Mohd Moklas MA, Baharuldin MTH. Inhibitory activity of Ficus deltoidea var. trengganuensis aqueous extract on lipopolysaccharide-induced TNF-α production from microglia. Evid Based Complement Alternat Med 2017; 2017: 2623163. 
46.    Wong CH, Gan SY, Tan SC, Gany SA, Ying T, Gray AI, et al. Fucosterol inhibits the cholinesterase activities and reduces the release of pro-inflammatory mediators in lipopolysaccharide and amyloid-induced microglial cells. J Appl Phycol 2018; 30: 3261-3270. 
47.    Mekinić IG, Skroza D, Šimat V, Hamed I, Čagalj M, Popović Perković Z. Phenolic content of brown algae (Pheophyceae) species: Extraction, identification, and quantification. Biomolecules 2019; 9: 244. 
48.    Yasui Y, Hosokawa M, Sahara T, Suzuki R, Ohgiya S, Kohno H, et al. Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPARgamma in human colon cancer Caco-2 cells. Prostaglandins Leukot Essent Fatty Acids 2005; 73: 113-119. 
49.    Riyadi PH. The effectivity of Kerandang fish (Channa pleurophthalma Blkr) fin waste as an anti-skin allergies agent. Syst Rev Pharm 2020; 11: 26-31. 
50.    Reid T, Kashangura C, Chidewe C, Benhura MA, Stray-Pedersen B, Mduluza T. Characterization of anti-Salmonella typhi compounds from medicinal mushroom extracts from Zimbabwe. Int J Med Mushrooms 2019; 21: 713-724. 
51.    Ramsden CE, Ringel A, Feldstein AE, Taha AY, Maclntosh BA, Hibbeln JR, et al. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids 2012; 87: 135-141. 
52.    Pradhan B, Nayak R, Patra S, Jit BP, Ragusa A, Jena M. Bioactive metabolites from marine algae as potent pharmacophores against oxidative stress-associated diseases: A comprehensive review. Molecules 2021; 26: 37. 
53.    Taha AY. Linoleic acid-good or bad for the brain? NPJ Sci Food 2020; 4: 1. 
54.    Navarro-Xavier RA, de Barros KV, de Andrade IS, Palomino Z, Casarini DE, Flor Silveira VL. Protective effect of soybean oil- or fish oil-rich diets on allergic airway inflammation. J Inflamm Res 2016; 9: 79-89. 
55.    Lowry JR, Marshall N, Wenzel TJ, Murray TE, Klegeris A. The dietary fatty acids α-linolenic acid (ALA) and linoleic acid (LA) selectively inhibit microglial nitric oxide production. Mol Cell Neurosci 2020; 109: 103569. 
56.    Nallathamby N, Serm LG, Raman J, Malek S, Vidyadaran S, Naidu M, et al. Identification and in vitro evaluation of lipids from sclerotia of Lignosus rhinocerotis for anti-oxidant and anti-neuroinflammatory activities. Nat Prod Commun 2016; 11: 1485-1490.
57.    Ma QL, Zhu C, Morselli M, Su T, Pelligrini M, Lu Z, et al. The novel omega-6 fatty acid docosapentaenoic acid positively modulates brain innate immune response for resolving neuroinflammation at early and late stages of humanized APOE-based Alzheimer’s disease models. Front Immunol 2020; 11: 558036. 
58.    Salech F, Ponce DP, Paula-Lima AC, SanMartin CD, Behrens MI. Nicotinamide, a poly [ADP-ribose] polymerase 1 (PARP-1) inhibitor, as an adjunctive therapy for the treatment of Alzheimer’s disease. Front Aging Neurosci 2020; 12: 255. 
59.    Spector R. Niacinamide transport through the blood-brain barrier. Neurochem Res 1987; 12: 27-31. 
60.    Giri B, Belanger K, Seamon M, Bradley E, Purohit S, Chong R, et al. Niacin ameliorates neuro-inflammation in Parkinson’s disease via GPR109A. Int J Mol Sci 2019; 20: 4559. 
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 6
June 2023
Pages 669-679

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