Identification of Metabolite Compounds from A Ethanol Extract of Caulerpa racemosa using LC-MS/MS with Inhibitory Activity of Interleukin-1β and Expression Inhibitory Nitric Oxide Synthase Enzyme; In Silico Virtual Screening
DOI:
https://doi.org/10.48048/tis.2024.8026Keywords:
Caulerpa racemosa, Inhibitor interleukin-1β, Inhibitory Nitric Oxide Synthase Enzyme, LC-MS/MS, Molecular docking, OsteoarthritisAbstract
Osteoarthritis (OA) is the prevailing kind of arthritis, impacting a substantial number of individuals globally. The incidence of OA is on the rise and is projected to further increase due to the aging population and escalating rates of obesity. This study aims to evaluate the anti-OA potential of Caulerpa racemosa. The Caulerpa racemosa 96 % ethanol extract of the plant was analysed using LC-MS/MS. The metabolite compositions were identified as polyunsaturated fatty acids, terpenes, bisindole alkaloids and diterpenoids. The 18 compounds analysed by LC-MS/MS, and the binding affinity of the compounds to the target proteins Interleukin-1 (PDB ID: 1ITB) was assessed by molecular docking fucosterol (∆G = –8.29 kcal/mol), variolin A (∆G = –8.02 kcal/mol), and clionasterol (∆G = –7.50 kcal/mol) and Nitric Oxide Synthase Inducible (3E7G) was assessed by molecular docking. Brassicasterol (∆G = –9.25 kcal/mol), fucosterol (∆G = –9.20 kcal/mol) and 24-methylenecholesterol (∆G = –9.04 kcal/mol) exhibited the highest docking scores, indicating their strong potential as inhibitors of IL1β and nitric oxide (NO). This knowledge is valuable for the future bioassay investigations about the possible applicability of these medicines as innovative solutions for OA.
HIGHLIGHTS
- The ethanol extract of Caulerpa racemosa, with a concentration of 96 %, comprises polyunsaturated fatty acids, terpenes, bisindole alkaloids and diterpenoids.
- Analysis utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified a total of 18 chemicals.
- The efficiency of 5 phytoconstituents (fucosterol, variolin A, clionasterol, brassicasterol and 24-methylenecholesterol) in silico antiosteoarthritis was evaluated. Fucosterol exhibited the highest negative average value of energy affinity, indicating stronger binding affinities for inhibiting IL-1β and the Inhibitory Nitric Oxide Synthase Enzyme compared to the other components studied.
GRAPHICAL ABSTRACT
Downloads
References
VB Kraus, FJ Blanco, M Englund, MA Karsdal and LS Lohmander. Stratification for clinical trials and clinical use. Osteoarthritis Cartilage 2016; 23, 1233-41.
R Sen and JA Hurley. Osteoarthritis. StatPearls, Treasure Island, Florida, 2023.
JD Steinmetz. Global, regional, and national burden of osteoarthritis and projections to 2050: A systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023; 5, e508-e522.
A Cui, H Li, D Wang, J Zhong, Y Chen and H Lu. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine 2020; 29-30, 100587.
TL Vincent. IL-1 in osteoarthritis: Time for a critical review of the literature. F1000Research 2019; 8, F1000.
A Tonutti. The role of WNT and IL-1 signaling in osteoarthritis: Therapeutic implications for platelet-rich plasma therapy. Front. Aging 2023; 4, 1201019.
Z Tong, X Yang and J Li. Research progress on the mechanism of interleukin-1β on epiphyseal plate chondrocytes. Eur. J. Med. Res. 2022; 27, 313.
A Eitner, S Müller, C König, A Wilharm, R Raab, GO Hofmann, T Kamradt and HG Schaible. Inhibition of inducible nitric oxide synthase prevents IL-1β induced mitochondrial dysfunction in human chondrocytes. Int. J. Mol. Sci. 2021; 22, 2477.
N Ahmad, MY Ansari and TM Haqqi. Role of iNOS in osteoarthritis: Pathological and therapeutic aspects. J. Cell. Physiol. 2020; 235, 6366-76.
SB Abramson. Osteoarthritis and nitric oxide. Osteoarthritis Cartilage 2008; 16, S15-S20.
H Jiang, P Ji, X Shang and Y Zhou. Connection between osteoarthritis and nitric oxide: From pathophysiology to therapeutic target. Molecules 2023; 28, 1683.
SB Abramson. Nitric oxide in inflammation and pain associated with osteoarthritis. Arthritis Res. Ther. 2008; 10, S2.
M Daheshia and JQ Yao. The interleukin 1β pathway in the pathogenesis of osteoarthritis. J. Rheumatol. 2008; 35, 2306-12.
L Zhong, S Schivo, X Huang, J Leijten, M Karperien and JN Post. Nitric oxide mediates crosstalk between interleukin 1β and WNT signaling in primary human chondrocytes by reducing DKK1 and FRZB expression. Int. J. Mol. Sci. 2017; 18, 2491.
R Kurniawan, F Nurkolis, NA Taslim, D Subali, R Surya, WB Gunawan, D Alisaputra, N Mayulu, N Salihendo and B Kim. Carotenoids composition of green algae Caulerpa racemosa and their antidiabetic, anti-obesity, antioxidant, and anti-inflammatory properties. Molecules 2023; 28, 3267.
AQB Aroyehun, SA Razak, K Palaiveloo, T Nagappan, NSN Rahmah, GW Jin, DK Chellappan, J Chellian and AP Kunnath. Bioprospecting cultivated tropical green algae, Caulerpa racemosa (Frosskal) J. Agardh: A perspective on nutritional properties, antioxidative capacity and anti-diabetic potential. Foods 2020; 9, 1313.
AGO Kase, H Calumpong and A Rupidara. Secondary metabolites of some varieties of Caulerpa species. IOP Conf. Ser. Mater. Sci. Eng. 2020; 823, 12041.
SAA Shah, SSU Hassan, S Bungau, Y Si, H Xu, MH Rahman, T Behl, D Gitea, FM Pavel, RAC Aron, B Pasca and S Nemeth. Chemically diverse and biologically active secondary metabolites from marine Phylum chlorophyta. Mar. Drugs 2020; 18, 493.
NM Ozupek, GC Kocal, N Olgun, Y Basbinar, L Cavas and H Ellidokuz. In-silico molecular interactions among the secondary metabolites of Caulerpa spp. and colorectal cancer targets. Front. Chem. 2022; 10, 1046313.
G Sanger, D Wonggo, N Taher, V Dotulong, AA Setiawan, HK Permatasari, S Maulana, F Nurkolis, A Tsopmo and B Kim. Green seaweed Caulerpa racemosa - Chemical constituents, cytotoxicity in breast cancer cells and molecular docking simulation. J. Agr. Food Res. 2023; 12, 100621.
MI Rushdi, IAM Abdel-Rahman, EZ Attia, WM Abdelraheem, H Saber, HA Madkour, E Amin, HM Hassan and UR Abdelmohsen. A review on the diversity, chemical and pharmacological potential of the green algae genus Caulerpa. S. Afr. J. Bot. 2020; 132, 226-41.
HK Permatasari, ENB Ulfa, VPA Daud, HW Sulistomo and F Nurkolis. Caulerpa racemosa extract inhibits HeLa cancer cells migration by altering expression of epithelial-mesenchymal transition proteins. Front. Chem. 2022; 10, 1052238.
F Nurkolis, NA Taslim, D Subali, R Kurniawan, H Hardinsyah, WB Gunawan, RJ Kusuma, VM Yusuf, A Pramono, S Kang, N Mayulu, AY Syauki, TE Tallei, A Tsopmo and B Kim. Dietary supplementation of Caulerpa racemosa ameliorates cardiometabolic syndrome via regulation of PRMT-1/DDAH/ADMA pathway and gut microbiome in mice. Nutrients 2023; 15, 909.
WF Yap, V Tay, SH Tan, YY Yow and J Chew. Decoding antioxidant and antibacterial potentials of Malaysian green seaweeds: Caulerpa racemosa and Caulerpa lentillifera. Antibiotics 2019; 8, 152.
NW Muyumba, SC Mutombo, H Sheridan, A Nachtergael and P Duez. Quality control of herbal drugs and preparations: The methods of analysis, their relevance and applications. Talanta Open 2021; 4, 100070.
E Tejera, Y Pérez-Castillo, G Toscano, AL Noboa, V Ochoa-Herrera, F Giampieri and JM Álvarez-Suarez. Computational modeling predicts potential effects of the herbal infusion “horchata” against COVID-19. Food Chem. 2022; 366, 130589.
B Zhong, NA Robinson, RD Warner, CJ Barrow, FR Dunshea and HAR Suleria. LC-ESI-QTOF-MS/MS characterization of seaweed phenolics and their antioxidant potential. Mar. Drugs 2020; 18, 331.
ASR Anjaneyulu, CVS Prakash and UV Mallavadhani. Two caulerpin analogues and a sesquiterpene from Caulerpa racemosa. Phytochemistry 1991; 30, 3041-2.
ÉTD Souza, DPD lira, ACD Queroz, DJCD Silva, ABD Aquino, EAC Mella, VP Lorenzo, GECD Miranda, JXD Araújo-Júnior, MCDO Chaves, JM Barbosa-Filho, PFD Athayde-Filho, BVDO Santos and MS Alexandre-Moreira. The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa. Mar. Drugs 2009; 7, 689-704.
NRPV Macedo, MS Ribeiro, RC Villaca, W Ferreira, AM Pinto, VL Teixeira, C Cirne-Santos, ICNP Paixão and V Giongo. Caulerpin as a potential antiviral drug against herpes simplex virus type 1. Revista Brasileira De Farmacognosia 2012; 22, 861-7.
MDN Meinita, D Harwanto, G Tirtawijaya, BFSP Negara, JH Sohn, JS Kim and JS Choi. Fucosterol of marine macroalgae: Bioactivity, safety and toxicity on organism. Mar. Drugs 2021; 19, 545.
HK Permatasari, SB Bdira, M Moon, N Amalia, HW Sulistomo, W Riawan, J Choi, S Chung, MN Park, BK Seo, F Nurkolis and B Kim. A randomized in vitro investigation on the modulation of the TGF-β signaling pathway and induction of apoptosis in colorectal cancer cells by green seaweed Caulerpa racemosa. J. Agr. Food Res. 2023; 14, 100796.
DH Utomo, N Widodo and M Rifa’i. Identifications small molecules inhibitor of p53-mortalin complex for cancer drug using virtual screening. Bioinformation 2012; 8, 426-9.
X Du, Y Li, YL Xia, SM Ai, J Liang, P Sang, XL Ji and SQ Liu. Insights into protein-ligand interactions: Mechanisms, models, and methods. Int. J. Mol. Sci. 2016; 17, 144.
Z Sun, MAA Mohamed, SY Park and TH Yi. Fucosterol protects cobalt chloride induced inflammation by the inhibition of hypoxia-inducible factor through PI3K/Akt pathway. Int. Immunopharm. 2015; 29, 642-7.
STS Hassan. Brassicasterol with dual anti-infective properties against HSV-1 and Mycobacterium tuberculosis, and cardiovascular protective effect: Nonclinical in vitro and in silico assessments. Biomedicines 2020; 8, 132.
KW Samarakoon, AI Kuruppu, JY Ko, JH Lee and YJ Jeon. Structural characterization and anti-inflammatory effects of 24-methylcholesta-5(6), 22-diene-3β-ol from the cultured marine diatom Phaeodactylum tricornutum; Attenuate inflammatory signaling pathways. Mar. Drugs 2023; 21, 231.
N Sharma, MA Tan and SSA An. Phytosterols: Potential metabolic modulators in neurodegenerative diseases. Int. J. Mol. Sci. 2021; 22, 12255.
M Martini, I Altomonte, I Sodi, Y Vasylieva and F Salari. Sterols, tocopherols, and bioactive fatty acids differences between conventional, high quality, and organic cow milk. J. Dairy Sci. 2023; 106, 8239-48.
CRM Souza, WP Bezerra and JT Souto. Marine alkaloids with anti-inflammatory activity: Current knowledge and future perspectives. Mar. Drugs 2020; 18, 147.
H Fikrika, L Ambarsari and T Sumaryada. Molecular docking studies of catechin and its derivatives as anti-bacterial inhibitor for glucosamine-6-phosphate synthase. IOP Conf. Ser. Earth Environ. Sci. 2016; 31, 12009.
BW Matthews. Hydrophobic interactions in proteins. Encyclopedia Life Sci. 2001, https://doi.org/10.1038/npg.els.0002975
F Nurkolis, Hardiyansyah, VM Yusuf, M Yusuf, RJ Kusuma, WB Gunawan, IW Hendra, S Radu, NA Taslim, N Mayulu, N Sabrina, A Tsopmo, R Kurniawan, CF Theodorea, E Idrus and TE Tallei. Metabolomic proling, in vitro antioxidant and cytotoxicity properties of Caulerpa racemosa: Functional food of the future from algae. Res. Square 2022, https://doi.org/10.21203/rs.3.rs-2158307/v1.
A Aboulkas, H Hammani, ME Achaby, E Bilal, A Barakat and KE harfi. Valorization of algal waste via pyrolysis in a fixed-bed reactor: Production and characterization of bio-oil and bio-char. Bioresource Tech. 2017; 243, 400-8.
IGP Wirawan, NKES Dewi, MMV Sasadara, IGNA Sunyamurthi, IM Jawi, IN Wijaya, IAP Darmawati, IK Suada and AAK Krisnandika. Phytochemical analysis and molecular identification of green macroalgae Caulerpa spp. from Bali, Indonesia. Molecules 2022; 27, 4879.
KX Yu, CL Wong, R Ahmad and I Jantan. Mosquitocidal and oviposition repellent activities of the extracts of seaweed Bryopsis pennata on Aedes aegypti and Aedes albopictus. Molecules 2015; 20, 14082-102.
G Trimurtulu, DJ Faulkner, NB Perry, L Ettouati, M Litaudon, JW Blunt, MHG Munro and GB Jameson. Alkaloids from the antarctic sponge Kirkpatrickia varialosa. Part 2: Variolin A and N(3’)-methyl tetrahydrovariolin B. Tetrahedron 1994; 50, 3993-4000.
M Aknin, R Moellet-Nzaou, JM Kornprobst, EM Gaydou, A Samb and J Miralles. Sterol composition of twelve chlorophyceae from the senegalese coast and their chemotaxonomic significance. Phytochemistry 1992; 31, 4167-9.
Y Zou, Y Li, MM Kim, SH Lee and SK Kim. Ishigoside, a new glyceroglycolipid isolated from the brown alga Ishige okamurae. Biotechnol. Bioproc. Eng. 2009; 14, 20-6.
JC Ng, L Qi and MR Moore. HPLC measurement of harderoporphyrin in the harderian glands of rodents as a biomarker for sub-lethal or chronic arsenic exposure. Toxicol. Lett. 2002; 133, 93-101.
SDA Aziz, NF Jafarah and ZNB Yusof. Phytol-containing seaweed extracts as control for ganoderma boninense. J. Oil Palm Res. 2019; 31, 238-47.
V Smyrniotopoulos, D Abatis, LA Tziveleka, C Tsitsimpikou, V Roussis, A Loukis and C Vagias. Acetylene sesquiterpenoid esters from the green alga Caulerpa prolifera. J. Nat. Prod. 2003; 66, 21-4.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Walailak University
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
