Abstract
This study identifies the anti-inflammatory, antioxidant, and immunomodulatory potential of a fatty acid methyl ester segregated from the brown algae Turbinaria ornata and identified by nuclear magnetic resonance and mass spectrometry as methyl 6,12-dimethyltridecanoate (ET). Antioxidant and anti-inflammatory effects of ET were studied on lipopolysaccharide (LPS)-induced inflammatory reaction in RAW 264.7 macrophages. Moreover, in silico docking studies of isolated ET with inflammatory markers TNFα, NFκB, and COX-2 showed potent binding scores suggesting anti-inflammatory potential. ET significantly reduced LPO and increased LPS-induced SOD, catalase, and GSH levels. Molecular docking results were further confirmed by checking mRNA levels of selected cytokines (IL6 and IL10), followed by protein expression of iNOS and NFκB in LPS-induced macrophages. ET significantly upregulated the expression of IL10 and downregulated the expression of IL6, iNOS, and NFκB, confirming the inhibition of LPS-induced inflammation via the iNOS/NFκB pathway.
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Data availability
The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
Abbreviations
- LD:
-
Low dose
- MD:
-
Mid dose
- HD:
-
High dose
- IL6:
-
Interleukin 6
- iNOS:
-
Inducible nitric oxide synthase
- NFκB:
-
Nuclear factor kappa B
- LPO:
-
Lipid peroxidation
- GSH:
-
Reduced glutathione
- SOD:
-
Superoxide dismutase
References
Bhardwaj M et al (2020) Neophytadiene from Turbinaria ornata suppresses LPS-induced inflammatory response in RAW 264.7 macrophages and sprague dawley rats. Inflammation 43(3):937–950. https://doi.org/10.1007/s10753-020-01179-z
Bhardwaj M, Padmavathy TK, Mani S, Malarvizhi R, Sali VK, Vasanthi HR (2021) Sulfated polysaccharide from Turbinaria ornata suppress lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages. Int J Biol Macromol 164:4299–4305
Bowler RP et al (2004) Extracellular superoxide dismutase attenuates lipopolysaccharide-induced neutrophilic inflammation. Am J Respir Cell Mol Biol 31(4):432–439. https://doi.org/10.1165/rcmb.2004-0057OC
Chatterjee S (2016) Chapter two—oxidative stress, inflammation, and disease. In: Dziubla T, Butterfield DA (eds). Academic Press, Amsterdam, pp 35–58. https://doi.org/10.1016/B978-0-12-803269-5.00002-4
El-Kenawi A, Ruffell B (2017) Inflammation, ROS, and mutagenesis. Cancer Cell 32(6):727–729. https://doi.org/10.1016/j.ccell.2017.11.015
Fiordelisi A et al (2019) NFkappaB is a key player in the crosstalk between inflammation and cardiovascular diseases. Int J Mol Sci. https://doi.org/10.3390/ijms20071599
Gokhale AS, Satyanarayanajois S (2014) Peptides and peptidomimetics as immunomodulators. Immunotherapy 6(6):755–774. https://doi.org/10.2217/imt.14.37
Han S et al (2017) Activation of macrophages by lipopolysaccharide for assessing the immunomodulatory property of biomaterials. Tissue Eng Part A 23(19–20):1100–1109. https://doi.org/10.1089/ten.tea.2016.0501
Heffernan N et al (2015) Profiling of the molecular weight and structural isomer abundance of macroalgae-derived phlorotannins. Mar Drugs 13(1):509–528. https://doi.org/10.3390/md13010509
Hussain T et al (2016) Oxidative stress and inflammation: what polyphenols can do for us?. In: Rupasinghe V (eds) Oxidative medicine and cellular longevity. Hindawi Publishing Corporation, London.: https://doi.org/10.1155/2016/7432797.
Jiao P et al (2018) Small molecules as PD-1/PD-L1 pathway modulators for cancer immunotherapy. Curr Pharm Des 24(41):4911–4920. https://doi.org/10.2174/1381612824666181112114958
Kang CH et al (2011) Inhibition of lipopolysaccharide-induced iNOS, COX-2, and TNF-α expression by aqueous extract of orixa japonica in RAW 264.7 cells via suppression of NF-κB activity. Trop J Pharm Res 10(2):161–168. https://doi.org/10.4314/tjpr.v10i2.66558
Kang HK et al (2019) Antimicrobial and immunomodulatory properties and applications of marine-derived proteins and peptides. Mar Drugs. https://doi.org/10.3390/md17060350
Keeler DM, Grandal MK, McCall JR (2019) Brevenal, a marine natural product, is anti-inflammatory and an immunomodulator of macrophage and lung epithelial cells. Mar Drugs. https://doi.org/10.3390/md17030184
Kim ID, Ha BJ (2010) The effects of paeoniflorin on LPS-induced liver inflammatory reactions. Arch Pharmacal Res 33(6):959–966. https://doi.org/10.1007/s12272-010-0620-8
Kolac UK et al (2017) The anti-inflammatory and antioxidant effects of salvia officinalis on lipopolysaccharide-induced inflammation in rats. J Med Food 20(12):1193–1200. https://doi.org/10.1089/jmf.2017.0035
Kolar MJ et al (2019) Linoleic acid esters of hydroxy linoleic acids are anti-inflammatory lipids found in plants and mammals. J Biol Chem 294(27):10698–10707. https://doi.org/10.1074/jbc.RA118.006956
Lee HY et al (2002) Inducible nitric oxide synthase (iNOS) expression is increased in lipopolysaccharide (LPS)-stimulated diabetic rat glomeruli: Effect of ACE inhibitor and angiotensin II receptor blocker. Yonsei Med J. https://doi.org/10.3349/ymj.2002.43.2.183
Liu Q et al (2017) In vitro and in vivo immunomodulatory activity of sulfated polysaccharide from Porphyra haitanensis. Carbohyd Polym 165:189–196. https://doi.org/10.1016/j.carbpol.2017.02.032
Mukherjee PK et al (2014) Immunomodulatory leads from medicinal plants. Indian J Tradit Knowl 13(2):235–256
Nedeva C, Menassa J, Puthalakath H (2019) Sepsis: inflammation is a necessary evil. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2019.00108
Ortuño-Sahagún D et al (2017) Natural immunomodulators. J Immunol Res Hindawi 2017:7529408. https://doi.org/10.1155/2017/7529408
Pramitha VS, Kumari NS (2016) Anti-inflammatory, anti-oxidant, phytochemical and GC-MS analysis of marine brown macroalga, sargassum wighti. Ijpcbs 6(1):7–15
Recio MC, Andujar I, Rios JL (2012) Anti-inflammatory agents from plants: progress and potential. Curr Med Chem 19(14):2088–2103. https://doi.org/10.2174/092986712800229069
Rezayian M, Niknam V, Ebrahimzadeh H (2019) Oxidative damage and antioxidative system in algae. Toxicol Rep 6:1309–1313. https://doi.org/10.1016/j.toxrep.2019.10.001
Riyadi PH et al (2020) Tilapia viscera hydrolysate extract alleviates oxidative stress and renal damage in deoxycorticosterone acetate-salt-induced hypertension rats. Veterinary World 13(11):2477–2483. https://doi.org/10.14202/VETWORLD.2020.2477-2483
Sali VK, Malarvizhi R, Manikandamathavan VM, Vasanthi HR (2018) Isolation and evaluation of phytoconstituents from red alga Acanthophora spicifera as potential apoptotic agents towards A549 and HeLa cancer cells lines. Algal Res 32:172–181
Sohilait MR, Pranowo HD, Haryadi W (2017) Open access molecular docking analysis of curcumin analogues with COX-2. Bioinformation 13(11):11–14
Utami W et al (2020) ‘In silico anti-inflammatory activity evaluation of some bioactive compound from ficus religiosa through molecular docking approach. J Phys Confer Ser IOP Publ 1563(1):12024. https://doi.org/10.1088/1742-6596/1563/1/012024
Venkatalakshmi P, Vadivel V, Brindha P (2016) Role of phytochemicals as immunomodulatory agents: a review. Int J Green Pharm 10(1):1–18
Vijayabaskar P, Shiyamala V (2012) Antioxidant properties of seaweed polyphenol from Turbinaria ornata (Turner) J. Agardh, 1848. Asian Pac J Trop Biomed 2(1, Supplement):S90–S98. https://doi.org/10.1016/S2221-1691(12)60136-1
Yang J-T et al (2017) Propyl gallate exerts an antimigration effect on temozolomide-treated malignant glioma cells through inhibition of ROS and the NF-κB pathway. J Immunol Res Edit d. Ortuño-Sahagún Hindawi 2017:9489383. https://doi.org/10.1155/2017/9489383
Yates CR, Bruno EJ, Yates MED (2022) Tinospora cordifolia: a review of its immunomodulatory properties. J Dietary Suppl Taylor & Francis 19(2):271–285. https://doi.org/10.1080/19390211.2021.1873214
Yu T, Lao X, Zheng H (2016) Influencing COX-2 activity by COX related pathways in inflammation and cancer. Mini-Rev Med Chem. https://doi.org/10.2174/1389557516666160505115743
Acknowledgements
The authors wish to thank DST-FIST and UGC-SAP grants to the Department of Biotechnology, Pondicherry University for infrastructure facilities, and the UGC fellowship to the first author for executing the present study. The authors would like to thank Dr. Manikandamathavan, CSIR-RA for helping with the characterization in the present work.
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The study was designed by HV, SM, and MB. MB, VKS, PTK performed the isolation and characterization, SM, MR, and MB performed the experiments. PTK and MR performed the statistical analysis. MB wrote the manuscript and was edited by HRV.
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Bhardwaj, M., Sali, V.K., Malarvizhi, R. et al. Methyldecanoate isolated from marine algae Turbinaria ornata enhances immunomodulation in LPS-induced inflammatory reactions in RAW 264.7 macrophages via iNOS/NFκB pathway. Inflammopharmacol 31, 439–449 (2023). https://doi.org/10.1007/s10787-022-01116-6
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DOI: https://doi.org/10.1007/s10787-022-01116-6