Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases

doi:10.1007/s13659-024-00451-1

Natural Products and Bioprospecting ›› 2024, Vol. 14 ›› Issue (4): 27-27.DOI: 10.1007/s13659-024-00451-1

Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases

Nasreddine El Omari¹, Saad Bakrim², Asaad Khalid^3,4, Ashraf N. Abdalla⁵, Mohamed A. M. Iesa¹¹, Kawtar El Kadri⁶, Siah Ying Tang⁷, Bey Hing Goh^8,9,10, Abdelhakim Bouyahya⁶

1. High Institute of Nursing Professions and Health Techniques of Tetouan, Tetouan, Morocco;
2. Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, 80000 Agadir, Morocco;
3. Substance Abuse and Toxicology Research Center, Jazan University, P. O. Box:114, 45142 Jazan, Saudi Arabia;
4. Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, P. O. Box 2404, Khartoum, Sudan;
5. Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, 21955 Makkah, Saudi Arabia;
6. Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, 10106 Rabat, Morocco;
7. Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia;
8. Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Malaysia;
9. Sunway Biofunctional Molecules Discovery Centre (SBMDC), School of Medical and Life Sciences, Sunway University, 47500 Sunway City, Malaysia;
10. Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia;
11. Department of Physiology, Al Qunfudah Medical College, Umm Al Qura University, Mecca, Saudi Arabia

Received:2024-03-19 Online:2024-08-01
Contact: Asaad Khalid,E-mail:akahmed@jazanu.edu.sa;Bey Hing Goh,E-mail:goh.bey.hing@monash.edu;Abdelhakim Bouyahya,E-mail:a.bouyahya@um5r.ac.ma
Supported by:
This study was funded by the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia (Project number ISP23-81) & Sunway University Research Accelerator Grant Scheme (GRTIN-RAG-SBMDC-10-2024).

Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases

Nasreddine El Omari¹, Saad Bakrim², Asaad Khalid^3,4, Ashraf N. Abdalla⁵, Mohamed A. M. Iesa¹¹, Kawtar El Kadri⁶, Siah Ying Tang⁷, Bey Hing Goh^8,9,10, Abdelhakim Bouyahya⁶

1. High Institute of Nursing Professions and Health Techniques of Tetouan, Tetouan, Morocco;
2. Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, 80000 Agadir, Morocco;
3. Substance Abuse and Toxicology Research Center, Jazan University, P. O. Box:114, 45142 Jazan, Saudi Arabia;
4. Medicinal and Aromatic Plants and Traditional Medicine Research Institute, National Center for Research, P. O. Box 2404, Khartoum, Sudan;
5. Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, 21955 Makkah, Saudi Arabia;
6. Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, 10106 Rabat, Morocco;
7. Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia;
8. Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Malaysia;
9. Sunway Biofunctional Molecules Discovery Centre (SBMDC), School of Medical and Life Sciences, Sunway University, 47500 Sunway City, Malaysia;
10. Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia;
11. Department of Physiology, Al Qunfudah Medical College, Umm Al Qura University, Mecca, Saudi Arabia

通讯作者: Asaad Khalid,E-mail:akahmed@jazanu.edu.sa;Bey Hing Goh,E-mail:goh.bey.hing@monash.edu;Abdelhakim Bouyahya,E-mail:a.bouyahya@um5r.ac.ma
基金资助:
This study was funded by the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia (Project number ISP23-81) & Sunway University Research Accelerator Grant Scheme (GRTIN-RAG-SBMDC-10-2024).

Abstract

Abstract: Until recently, the main pharmaceuticals used to control cholesterol and prevent cardiovascular disease (CVD) were statin-related drugs, known for their historical side effects. Therefore, there is growing interest in exploring alternatives, such as nutritional and dietary components, that could play a central role in CVD prevention. This review aims to provide a comprehensive understanding of how natural phytosterols found in various diets combat CVDs. We begin with a description of the overall approach, then we explore in detail the different direct and indirect mechanisms that contribute to reducing cardiovascular incidents. Phytosterols, including stigmasterol, β-sitosterol, ergosterol, and fucosterol, emerge as promising molecules within nutritional systems for protection against CVDs due to their beneficial effects at different levels through direct or indirect cellular, subcellular, and molecular mechanisms. Specifically, the mentioned phytosterols exhibit the ability to diminish the generation of various radicals, including hydroperoxides and hydrogen peroxide. They also promote the activation of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, while inhibiting lipid peroxidation through the activation of Nrf2 and Nrf2/heme oxygenase-1 (HO-1) signaling pathways. Additionally, they demonstrate a significant inhibitory capacity in the generation of pro-inflammatory cytokines, thus playing a crucial role in regulating the inflammatory/immune response by inhibiting the expression of proteins involved in cellular signaling pathways such as JAK3/STAT3 and NF-κB. Moreover, phytosterols play a key role in reducing cholesterol absorption and improving the lipid profile. These compounds can be used as dietary supplements or included in specific diets to aid control cholesterol levels, particularly in individuals suffering from hypercholesterolemia.

Key words: Phytosterols, β-sitosterol, Stigmasterol, Cardiovascular disease, Nutritional protection

摘要： Until recently, the main pharmaceuticals used to control cholesterol and prevent cardiovascular disease (CVD) were statin-related drugs, known for their historical side effects. Therefore, there is growing interest in exploring alternatives, such as nutritional and dietary components, that could play a central role in CVD prevention. This review aims to provide a comprehensive understanding of how natural phytosterols found in various diets combat CVDs. We begin with a description of the overall approach, then we explore in detail the different direct and indirect mechanisms that contribute to reducing cardiovascular incidents. Phytosterols, including stigmasterol, β-sitosterol, ergosterol, and fucosterol, emerge as promising molecules within nutritional systems for protection against CVDs due to their beneficial effects at different levels through direct or indirect cellular, subcellular, and molecular mechanisms. Specifically, the mentioned phytosterols exhibit the ability to diminish the generation of various radicals, including hydroperoxides and hydrogen peroxide. They also promote the activation of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione, while inhibiting lipid peroxidation through the activation of Nrf2 and Nrf2/heme oxygenase-1 (HO-1) signaling pathways. Additionally, they demonstrate a significant inhibitory capacity in the generation of pro-inflammatory cytokines, thus playing a crucial role in regulating the inflammatory/immune response by inhibiting the expression of proteins involved in cellular signaling pathways such as JAK3/STAT3 and NF-κB. Moreover, phytosterols play a key role in reducing cholesterol absorption and improving the lipid profile. These compounds can be used as dietary supplements or included in specific diets to aid control cholesterol levels, particularly in individuals suffering from hypercholesterolemia.

关键词: Phytosterols, β-sitosterol, Stigmasterol, Cardiovascular disease, Nutritional protection

Nasreddine El Omari, Saad Bakrim, Asaad Khalid, Ashraf N. Abdalla, Mohamed A. M. Iesa, Kawtar El Kadri, Siah Ying Tang, Bey Hing Goh, Abdelhakim Bouyahya. Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases[J]. Natural Products and Bioprospecting, 2024, 14(4): 27-27.

References

[1] Tehrani-Banihashemi A, Moradi-Lakeh M, El Bcheraoui C, Charara R, Khalil I, Afshin A, Collison M, Daoud F, Krohn KJ, Chew A, Cornaby L, Foreman KJ, Frostad J, Kassebaum NJ, Kemmer L, Kutz M, Liu P, Mirarefin M, Nguyen G, Wang H, Zipkin B, Abajobir AA, Abouzeid M, Abu-Rmeileh NME, Ahmad Kiadaliri A, Ahmed MB, Aksut B, Alam K, Alasfoor D, Ali R, Alizadeh-Navaei R, Al-Raddadi R, Alsharif U, Altirkawi KA, Alvis-Guzman N, Anber N, Anwari P, Ärnlöv J, Asgedom SW, Atey TM, Awasthi A, Bärnighausen T, Bacha U, Barac A, Barker-Collo SL, Bedi N, Bennett DA, Berhe DF, Biadgilign S, Butt ZA, Carapetis JR, Castro RE, Chitheer AA, Davletov K, Dharmaratne SD, Djalalinia S, Do HP, Dubey M, Ebrahimi H, Eshrati B, Esteghamati A, Farvid MS, Fereshtehnejad S-M, Fischer F, Gebrehiwot SW, Gebrehiwot TT, Gillum RF, Gona PN, Gupta R, Hafezi-Nejad N, Hamadeh RR, Hamidi S, Hsairi M, Jee SH, Jonas JB, Karimkhani C, Kasaeian A, Khader YS, Khan EA, Kim D, Lal DK, Larson HJ, Latif AA, Linn S, Lotufo PA, Lunevicius R, Abd El Razek HM, Majeed A, Malekzadeh R, Malta DC, Meier T, Memiah P, Memish ZA, Mendoza W, Mensah GA, Meretoja A, Miller TR, Mirrakhimov EM, Mohammed S, Nguyen QL, Nong VM, Pearson-Stuttard J, Pishgar F, Pourmalek F, Qorbani M, Radfar A, Rafay A, Rahimi-Movaghar V, Rai RK, Rana SM, Rawaf DL, Rawaf S, Renzaho AMN, Rezaei S, Roba KT, Roshandel G, Safdarian M, Safi S, Safiri S, Sahraian MA, Salamati P, Samy AM, Milicevic MMS, Sartorius B, Sepanlou SG, Shaikh MA, Silva DAS, Singh JA, Sobaih BHA, Stroumpoulis K, Abdulkader RS, Szoeke CEI, Temsah M-H, Tran BX, Ukwaja KN, Uthman OA, Vasankari T, Vlassov VV, Vollset SE, Wakayo T, Weintraub RG, Wessly PR, Wijeratne T, Wolfe CDA, Workicho A, Yaghoubi M, Yano Y, Yaseri M, Yonemoto N, Younis MZ, Yu C, Zaki MES, Jumaan AO, Vos T, Roth GA, Hay SI, Naghavi M, Murray CJL, Mokdad AH, GBD 2015 Eastern Mediterranean Region Cardiovascular Disease Collaborators. Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990-2015: findings from the Global Burden of Disease 2015 study. Int J Public Health. 2018;63(2018):137-49. https://doi.org/10.1007/s00038-017-1012-3. [2] Ahmed SA, Hasan MdN, Altass HM, Bera A, Alsantali RI, Pan N, Alzahrani AYA, Bagchi D, Al-Fahemi JH, Khder AS, Pal SK. Tetracycline encapsulated in Au nanoparticle-decorated ZnO nanohybrids for enhanced antibacterial activity. ACS Appl Nano Mater. 2022;5:4484-92. https://doi.org/10.1021/acsanm.2c00655. [3] Khushhal A, Alsubaiei M. Barriers to establishing outpatient cardiac rehabilitation in the Western Region of Saudi Arabia: a cross-sectional study. J Multidiscip Healthc. 2023;16:653-61. https://doi.org/10.2147/JMDH.S398687. [4] Makhmudova U, Schulze PC, Lütjohann D, Weingärtner O. Phytosterols and cardiovascular disease. Curr Atheroscler Rep. 2021;23:68. [5] Alshaikh MK, Filippidis FT, Baldove JP, Majeed A, Rawaf S. Women in Saudi Arabia and the prevalence of cardiovascular risk factors: a systematic review. J Environ Public Health. 2016;2016: e7479357. https://doi.org/10.1155/2016/7479357. [6] Adam T, Sharif AIA, Alamri TSM, Al-Nashri RAO, Alluwimi AIM, Samkri AY, Alharthi MA, Moafa AY, Alsaadi NA, Alraimi AMS, Alquzi RHM, Rasheid TM, Sharif AIA, Alamri TSM, Al-Nashri RAO, Alluwimi AI, Samkri AY, Alharthi MA, Moafa AY, Alsaadi N, Alraimi AM, Alquzi RH. The State of cardiac rehabilitation in saudi arabia: barriers, facilitators, and policy implications. Cureus. 2023. https://doi.org/10.7759/cureus.48279. [7] Wang L, Lei J, Wang R, Li K. Non-traditional risk factors as contributors to cardiovascular disease. Rev Cardiovasc Med. 2023;24:134. [8] Lara-Guzmán OJ, Gil-Izquierdo Á, Medina S, Osorio E, Álvarez-Quintero R, Zuluaga N, Oger C, Galano J-M, Durand T, Muñoz-Durango K. Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. Redox Biol. 2018;15:1-11. [9] Strobel NA, Fassett RG, Marsh SA, Coombes JS. Oxidative stress biomarkers as predictors of cardiovascular disease. Int J Cardiol. 2011;147:191-201. [10] Abdul-Rahman T, Bukhari SMA, Herrera EC, Awuah WA, Lawrence J, de Andrade H, Patel N, Shah R, Shaikh R, Capriles CAA. Lipid lowering therapy: an era beyond statins. Curr Probl Cardiol. 2022;47:101342. [11] Horodinschi R-N, Stanescu AMA, Bratu OG, Pantea Stoian A, Radavoi DG, Diaconu CC. Treatment with statins in elderly patients. Medicina. 2019;55:721. [12] Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, Fiol M, Gómez-Gracia E, López-Sabater MC, Vinyoles E. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006;145:1-11. [13] Shen J, Wilmot KA, Ghasemzadeh N, Molloy DL, Burkman G, Mekonnen G, Gongora MC, Quyyumi AA, Sperling LS. Mediterranean dietary patterns and cardiovascular health. Annu Rev Nutr. 2015;35:425-49. https://doi.org/10.1146/annurev-nutr-011215-025104. [14] Feng S, Dai Z, Liu AB, Huang J, Narsipur N, Guo G, Kong B, Reuhl K, Lu W, Luo Z, Yang CS. Intake of stigol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet. Biochim Biophys Acta BBA Mol Cell Biol Lipids. 1863;2018:1274-84. https://doi.org/10.1016/j.bbalip.2018.08.004. [15] Morales D, Tejedor-Calvo E, Jurado-Chivato N, Polo G, Tabernero M, Ruiz-Rodríguez A, Largo C, Soler-Rivas C. In vitro and in vivo testing of the hypocholesterolemic activity of ergosterol- and β-glucan-enriched extracts obtained from shiitake mushrooms (Lentinula edodes). Food Funct. 2019;10:7325-32. https://doi.org/10.1039/C9FO01744E. [16] Moselhy SS, Kamal I, Kumosani TA, Huwait E. Possible inhibition of hydroxy methyl glutaryl CoA reductase activity by nicotinic acid and ergosterol: as targeting for hypocholesterolemic action. Afr H Sci. 2016;16:319. https://doi.org/10.4314/ahs.v16i1.42. [17] Soleimanian Y, Goli SAH, Varshosaz J, Di Cesare Mannelli L, Ghelardini C, Cirri M, Maestrelli F. β-sitosterol loaded nanostructured lipid carrier: physical and oxidative stability, in vitro simulated digestion and hypocholesterolemic activity. Pharmaceutics. 2020;12:386. https://doi.org/10.3390/pharmaceutics12040386. [18] Cheng Y, Chen Y, Li J, Qu H, Zhao Y, Wen C, Zhou Y. Dietary β-sitosterol regulates serum lipid level and improves immune function, antioxidant status, and intestinal morphology in broilers. Poult Sci. 2020;99:1400-8. https://doi.org/10.1016/j.psj.2019.10.025. [19] Cheng Y, Chen Y, Li J, Qu H, Zhao Y, Wen C, Zhou Y. Dietary β-sitosterol improves growth performance, meat quality, antioxidant status, and mitochondrial biogenesis of breast muscle in broilers. Animals. 2019;9:71. https://doi.org/10.3390/ani9030071. [20] Elkeilsh A, Awad YM, Soliman MH, Abu-Elsaoud A, Abdelhamid MT, El-Metwally IM. Exogenous application of β-sitosterol mediated growth and yield improvement in water-stressed wheat (Triticum aestivum) involves up-regulated antioxidant system. J Plant Res. 2019;132:881-901. https://doi.org/10.1007/s10265-019-01143-5. [21] Sun X, Feng X, Zheng D, Li A, Li C, Li S, Zhao Z. Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo. Clin Sci. 2019;133:1523-36. https://doi.org/10.1042/CS20190331. [22] Khan MA, Sarwar AHMG, Rahat R, Ahmed RS, Umar S. Stigol protects rats from collagen induced arthritis by inhibiting proinflammatory cytokines. Int Immunopharmacol. 2020;85:106642. [23] Sampath SJP, Rath SN, Kotikalapudi N, Venkatesan V. Beneficial effects of secretome derived from mesenchymal stem cells with stigol to negate IL-1β-induced inflammation in-vitro using rat chondrocytes—OA management. Inflammopharmacology. 2021;29:1701-17. [24] Jie F, Yang X, Yang B, Liu Y, Wu L, Lu B. Stigol attenuates inflammatory response of microglia via NF-κB and NLRP3 signaling by AMPK activation. Biomed Pharmacother. 2022;153:113317. [25] Kirindage KGIS, Jayasinghe AMK, Han E-J, Jee Y, Kim H-J, Do SG, Fernando IPS, Ahn G. Fucosterol isolated from dietary brown alga Sargassum horneri protects TNF-α/IFN-γ-stimulated human dermal fibroblasts via regulating Nrf2/HO-1 and NF-κB/MAPK pathways. Antioxidants. 2022;11:1429. https://doi.org/10.3390/antiox11081429. [26] Sun P, Li W, Guo J, Peng Q, Ye X, Hu S, Liu Y, Liu W, Chen H, Qiao J, Sun B. Ergosterol isolated from Antrodia camphorata suppresses LPS-induced neuroinflammatory responses in microglia cells and ICR mice. Molecules. 2023;28:2406. https://doi.org/10.3390/molecules28052406. [27] Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411-5. [28] Adebiyi OE, Olopade JO, Olayemi FO. Sodium metavanadate induced cognitive decline, behavioral impairments, oxidative stress and down regulation of myelin basic protein in mice hippocampus: ameliorative roles of β-spinasterol, and stigol. Brain Behavior. 2018;8: e01014. https://doi.org/10.1002/brb3.1014. [29] Chen H, Tang X, Liu T, Jing L, Wu J. Zingiberene inhibits in vitro and in vivo human colon cancer cell growth via autophagy induction, suppression of PI3K/AKT/mTOR pathway and caspase 2 deactivation. J BUON. 2019;24:1470-5. [30] Chen S, Wang R, Cheng M, Wei G, Du Y, Fan Y, Li J, Li H, Deng Z. Serum cholesterol-lowering activity of β-sitosterol laurate is attributed to the reduction of both cholesterol absorption and bile acids reabsorption in hamsters. J Agric Food Chem. 2020;68:10003-14. https://doi.org/10.1021/acs.jafc.0c04386. [31] Devaraj E, Roy A, Royapuram Veeraragavan G, Magesh A, Varikalam Sleeba A, Arivarasu L, Marimuthu Parasuraman B. β-Sitosterol attenuates carbon tetrachloride-induced oxidative stress and chronic liver injury in rats. Naunyn-Schmiedeberg’s Arch Pharmacol. 2020;393:1067-75. https://doi.org/10.1007/s00210-020-01810-8. [32] Dong H, Wang X, Huang J, Xing J. Effects of post-harvest stigol treatment on quality-related parameters and antioxidant enzymes of green asparagus (Asparagus officinalis L.). Food Addit Contam Part A. 2016;33:1785-92. [33] Gupta R, Sharma AK, Dobhal MP, Sharma MC, Gupta RS. Antidiabetic and antioxidant potential of β-sitosterol in streptozotocin-induced experimental hyperglycemia: antidiabetic activity of β-sitosterol. J Diabetes. 2011;3:29-37. https://doi.org/10.1111/j.1753-0407.2010.00107.x. [34] Han N-R, Kim K-C, Kim J-S, Park H-J, Ko S-G, Moon P-D. SBT (Composed of Panax ginseng and Aconitum carmichaeli) and stigol enhances nitric oxide production and exerts curative properties as a potential anti-oxidant and immunity-enhancing agent. Antioxidants. 2022;11:199. https://doi.org/10.3390/antiox11020199. [35] Hanafy RS, Sadak MS. Foliar spray of stigol regulates physiological processes and antioxidant mechanisms to improve yield and quality of sunflower under drought stress. J Soil Sci Plant Nutr. 2023. https://doi.org/10.1007/s42729-023-01197-4. [36] Hassanein RA, Hashem HA, Khalil RR. Stigol treatment increases salt stress tolerance of faba bean plants by enhancing antioxidant systems. Plant Omics. 2012;5:476-85. https://doi.org/10.3316/informit.777282637775162. [37] Lee S, Lee YS, Jung SH, Kang SS, Shin KH. Anti-oxidant activities of fucosterol from the marine algae Pelvetia siliquosa. Arch Pharm Res. 2003;26:719-22. https://doi.org/10.1007/BF02976680. [38] Liang Q, Yang J, He J, Chen X, Zhang H, Jia M, Liu K, Jia C, Pan Y, Wei J. Stigol alleviates cerebral ischemia/reperfusion injury by attenuating inflammation and improving antioxidant defenses in rats. Biosci Rep. 2020;40: BSR20192133. https://doi.org/10.1042/BSR20192133. [39] Mekki BB, Da Silva JA, Orabi SA. Yield, fatty acids and antioxidant enzymes of two canola (Brassica napus L.) cultivars in response to stigol. Afr J Plant Sci Biotechnol. 2010;4:28-35. [40] Panda S, Jafri M, Kar A, Meheta BK. Thyroid inhibitory, antiperoxidative and hypoglycemic effects of stigol isolated from Butea monosperma. Fitoterapia. 2009;80:123-6. https://doi.org/10.1016/j.fitote.2008.12.002. [41] Vivancos M, Moreno JJ. β-Sitosterol modulates antioxidant enzyme response in RAW 264.7 macrophages. Free Radic Biol Med. 2005;39:91-7. https://doi.org/10.1016/j.freeradbiomed.2005.02.025. [42] Xu J, Lin C, Wang T, Zhang P, Liu Z, Lu C. Ergosterol attenuates LPS-induced myocardial injury by modulating oxidative stress and apoptosis in rats. Cell Physiol Biochem. 2018;48:583-92. https://doi.org/10.1159/000491887. [43] Yongxia Z, Jian X, Suyuan H, Aixin N, Lihong Z. Isolation and characterization of ergosterol from Monascus anka for anti-lipid peroxidation properties. J Mycol Méd. 2020;30:101038. https://doi.org/10.1016/j.mycmed.2020.101038. [44] Wong HS, Chen N, Leong PK, Ko KM. β-sitosterol enhances cellular glutathione redox cycling by reactive oxygen species generated from mitochondrial respiration: protection against oxidant injury in H9c2 cells and rat hearts. Phytother Res. 2014;28:999-1006. [45] Ganapathy P, Rajadurai M, Ashokumar N. Cardioprotective effect of β-sitosterol on lipid peroxides and antioxidant in isoproterenol-induced myocardial infarction in rats: a histopathological study. Int J Curr Res. 2014;6:7260-6. [46] Nemat Alla MM, Hassan NM, Budran IG, El-Bastawisy ZM, El-Harary EH. Stigol alleviates the impacts of drought in flax and improves oil yield via modulating efficient antioxidant and ROS homeostasis. Iran J Plant Physiol. 2022;12:3973-84. https://doi.org/10.30495/ijpp.2022.689073. [47] Sujila SMR, Rajadurai M, Shairibha SMR. Hepatoprotective effect of β-sitosterol on lipid peroxidation and antioxidant status in ethanol-induced hepatotoxic rats. 2014. [48] Shi C, Wu F, Zhu X, Xu J. Incorporation of β-sitosterol into the membrane increases resistance to oxidative stress and lipid peroxidation via estrogen receptor-mediated PI3K/GSK3β signaling. Biochim Biophys Acta BBA Gener Subj. 1830;2013:2538-44. https://doi.org/10.1016/j.bbagen.2012.12.012. [49] Dupont S, Fleurat-Lessard P, Cruz RG, Lafarge C, Grangeteau C, Yahou F, Gerbeau-Pissot P, Abrahão Júnior O, Gervais P, Simon-Plas F, Cayot P, Beney L. Antioxidant properties of ergosterol and its role in yeast resistance to oxidation. Antioxidants. 2021;10:1024. https://doi.org/10.3390/antiox10071024. [50] Medina ME, Galano A, Trigos Á. Scavenging ability of homogentisic acid and ergosterol toward free radicals derived from ethanol consumption. J Phys Chem B. 2018;122:7514-21. https://doi.org/10.1021/acs.jpcb.8b04619. [51] Jaiswal AK. Nrf2 signaling in coordinated activation of antioxidant gene . Free Radical Biol Med. 2004;36:1199-207. [52] Jayawardena TU, Sanjeewa KKA, Lee H-G, Nagahawatta DP, Yang H-W, Kang M-C, Jeon Y-J. Particulate matter-induced inflammation/oxidative stress in macrophages: fucosterol from Padina boryana as a potent protector, activated via NF-κB/MAPK pathways and Nrf2/HO-1 involvement. Mar Drugs. 2020;18:628. https://doi.org/10.3390/md18120628. [53] Liao H, Zhu D, Bai M, Chen H, Yan S, Yu J, Zhu H, Zheng W, Fan G. Stigol sensitizes endometrial cancer cells to chemotherapy by repressing Nrf2 signal pathway. Cancer Cell Int. 2020;20:480. https://doi.org/10.1186/s12935-020-01470-x. [54] Xie Q, Li S, Gao Y, Jin L, Dai C, Song J. Ergosterol attenuates isoproterenol-induced myocardial cardiotoxicity. Cardiovasc Toxicol. 2020;20:500-6. https://doi.org/10.1007/s12012-020-09574-6. [55] Karolkiewicz J, Michalak E, Pospieszna B, Deskur-Śmielecka E, Nowak A, Pilaczyńska-Szcześniak L. Response of oxidative stress markers and antioxidant parameters to an 8-week aerobic physical activity program in healthy, postmenopausal women. Arch Gerontol Geriatr. 2009;49:e67-71. [56] Taravati A, Tohidi F. Comprehensive analysis of oxidative stress markers and antioxidants status in preeclampsia. Taiwan J Obstet Gynecol. 2018;57:779-90. [57] Krishnan M, Babu S, Rajagopal P, Nazar SP, Chinnaiyan M, Jayaraman S. Effect of β-sitosterol on insulin receptor, glucose transporter 4 protein and glucose oxidation in the gastrocnemius muscle of high fat diet induced type-2 diabetic experimental rats. IJPER. 2021;55:s479-91. https://doi.org/10.5530/ijper.55.2s.119. [58] Manisha P, Chandrashekhar P, Raghunath M. Phytochemical investigation and validation of antioxidant potential of β-sitosterol from tubers of Eulophia herbacea and Eulophia ochreata. Int J Pharmacogn Phytochem Res. 2018;10:309-16. [59] AL-Rawi A, Hassan FM, Alwash BMJ. In vitro stiumlation of ergosterol from coelastrella terrestris by using squalene and studying antioxidant effect. Syst Rev Pharm. 2020;11:1795-803. [60] Abdollahnezhad H, Bahadori MB, Pourjafar H, Movahhedin N. Purification, characterization, and antioxidant activity of daucosterol and stigol from Prangos ferulacea. Lett Appl NanoBioSci. 2021;10:2174-80. https://doi.org/10.33263/LIANBS102.21742180. [61] Dighe SB, Kuchekar BS, Wankhede SB. Analgesic and anti-inflammatory activity of β-sitosterol isolated from leaves of Oxalis corniculata. Int J Pharmacol Res. 2016;6:109-13. [62] Phatangare ND, Deshmukh KK, Murade VD, Naikwadi PH, Hase DP, Chavhan MJ, Velis HE. Isolation and characterization of β-sitosterol from Justicia gendarussa burm. F.—an anti-inflammatory compound. Phyto. 2017. https://doi.org/10.25258/phyto.v9i09.10317. [63] Prieto JM, Recio MC, Giner RM. Anti-inflammatory activity of β-sitosterol in a model of oxazolone- induced contact-delayed-type hypersensitivity. 2006. [64] Zhang F, Liu Z, He X, Li Z, Shi B, Cai F. β-Sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund’s adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway. Drug Deliv. 2020;27:1329-41. https://doi.org/10.1080/10717544.2020.1818883. [65] Antwi AO, Obiri DD, Osafo N, Essel LB, Forkuo AD, Atobiga C. Stigol alleviates cutaneous allergic responses in rodents. BioMed Res Int. 2018. https://doi.org/10.1155/2018/3984068. [66] Kariuki DK, Kanui TI, Mbugua PM, Githinji CG. Analgesic and anti-inflammatory activities of 9-hexacosene and stigol isolated from Mondia whytei. 2012. http://erepository.uonbi.ac.ke/handle/11295/28485. Accessed 15 May 2023. [67] Morgan LV, Petry F, Scatolin M, de Oliveira PV, Alves BO, Zilli GAL, Volfe CRB, Oltramari AR, de Oliveira D, Scapinello J, Müller LG. Investigation of the anti-inflammatory effects of stigol in mice: insight into its mechanism of action. Behav Pharmacol. 2021;32:640-51. https://doi.org/10.1097/FBP.0000000000000658. [68] Santos ES, de Sousa Machado ST, Rodrigues FB, da Silva YA, Matias LCX, Lopes MJP, Gomes ADS, Ribeiro TF, de Oliveira Garcia FA, Coutinho HDM. Potential anti-inflammatory, hypoglycemic, and hypolipidemic activities of alpha-pinene in diabetic rats. Process Biochem. 2023;126:80-6. [69] Feng S, Dai Z, Liu A, Wang H, Chen J, Luo Z, Yang CS. β-Sitosterol and stigol ameliorate dextran sulfate sodium-induced colitis in mice fed a high fat Western-style diet. Food Funct. 2017;8:4179-86. https://doi.org/10.1039/C7FO00375G. [70] Hoang M-H, Jia Y, Jun H, Lee JH, Lee BY, Lee S-J. Fucosterol is a selective liver X receptor modulator that regulates the of Key genes in cholesterol homeostasis in macrophages, hepatocytes, and intestinal cells. J Agric Food Chem. 2012;60:11567-75. https://doi.org/10.1021/jf3019084. [71] Kim K-A, Lee I-A, Gu W, Hyam SR, Kim D-H. β-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-κB pathway. Mol Nutr Food Res. 2014;58:963-72. https://doi.org/10.1002/mnfr.201300433. [72] Lee I-A, Kim E-J, Kim D-H. Inhibitory effect of β-sitosterol on TNBS-induced colitis in mice. Planta Med. 2012;78:896-8. https://doi.org/10.1055/s-0031-1298486. [73] Liz R, Zanatta L, dos Reis GO, Horst H, Pizzolatti MG, Silva FRMB, Fröde TS. Acute effect of β-sitosterol on calcium uptake mediates anti-inflammatory effect in murine activated neutrophils. J Pharm Pharmacol. 2012;65:115-22. https://doi.org/10.1111/j.2042-7158.2012.01568.x. [74] Bell D, Jackson M, Nicoll JJ, Millar A, Dawes J, Muir AL. Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment. Heart. 1990;63:82-7. [75] Mottola C, Romeo D. Calcium movement and membrane potential changes in the early phase of neutrophil activation by phorbol myristate acetate: a study with ion-selective electrodes. J Cell Biol. 1982;93:129-34. [76] Moreau R. The pathogenesis of ACLF: the inflammatory response and immune function. Semin Liver Dis. 2016;36:133-40. [77] Santos MF, Moreira MA, Maiolini T, Dias DF, Chagas-Paula DA, Azevedo L, Soares MG. In vivo anti-inflammatory activity of the crude extract, fractions, and ergosterol peroxide from Sclerotinia sclerotiorum. Nat Prod J. 2022;12:73-6. [78] Zhang P, Liu N, Xue M, Zhang M, Liu W, Xu C, Fan Y, Meng Y, Zhang Q, Zhou Y. Anti-inflammatory and antioxidant properties of β-sitosterol in copper sulfate-induced inflammation in zebrafish (Danio rerio). Antioxidants. 2023;12:391. [79] Jung HA, Jin SE, Ahn BR, Lee CM, Choi JS. Anti-inflammatory activity of edible brown alga Eisenia bicyclis and its constituents fucosterol and phlorotannins in LPS-stimulated RAW264.7 macrophages. Food Chem Toxicol. 2013;59:199-206. https://doi.org/10.1016/j.fct.2013.05.061. [80] Sun Y, Gao L, Hou W, Wu J. β-sitosterol alleviates inflammatory response via inhibiting the activation of ERK/p38 and NF-κB pathways in LPS-exposed BV2 cells. Biomed Res Int. 2020;2020:1-10. https://doi.org/10.1155/2020/7532306. [81] Yoo M-S, Shin J-S, Choi H-E, Cho Y-W, Bang M-H, Baek N-I, Lee K-T. Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines via the inactivation of nuclear factor-κB and p38 mitogen-activated protein kinase in RAW264.7 macrophages. Food Chem. 2012;135:967-75. https://doi.org/10.1016/j.foodchem.2012.05.039. [82] Zhang L, Wu J, Ling MT, Zhao L, Zhao K-N. The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses. Mol Cancer. 2015;14:1-13. [83] Coleman JW. Nitric oxide in immunity and inflammation. Int Immunopharmacol. 2001;1:1397-406. [84] Csont T, Viappiani S, Sawicka J, Slee S, Altarejos JY, Batinić-Haberle I, Schulz R. The involvement of superoxide and iNOS-derived NO in cardiac dysfunction induced by pro-inflammatory cytokines. J Mol Cell Cardiol. 2005;39:833-40. [85] Koc K, Geyikoglu F, Cakmak O, Koca A, Kutlu Z, Aysin F, Yilmaz A, Aşkın H. The targets of β-sitosterol as a novel therapeutic against cardio-renal complications in acute renal ischemia/reperfusion damage. Naunyn-Schmiedeberg’s Arch Pharmacol. 2021;394:469-79. https://doi.org/10.1007/s00210-020-01984-1. [86] Mei J, Ma X, Xie J. Review on natural preservatives for extending fish shelf life. Foods. 2019;8:490. [87] Nallathamby N, Guan-Serm L, Vidyadaran S, Malek SNA, Raman J, Sabaratnam V. Ergosterol of Cordyceps militaris attenuates LPS induced inflammation in BV2 microglia cells. Nat Prod Commun. 2015;10:1934578X1501000. https://doi.org/10.1177/1934578X1501000623. [88] Hwang E, Park S-Y, Shin H-S, Lee D-G, Yi TH. Effect of oral administration of fucosterol from Hizikia fusiformis on DNCB-induced atopic dermatitis in NC/Nga mice. Food Sci Biotechnol. 2014;23:593-9. https://doi.org/10.1007/s10068-014-0081-9. [89] Wong CH, Gan SY, Tan SC, Gany SA, Ying T, Gray AI, Igoli J, Chan EWL, Phang SM. Fucosterol inhibits the cholinesterase activities and reduces the release of pro-inflammatory mediators in lipopolysaccharide and amyloid-induced microglial cells. J Appl Phycol. 2018;30:3261-70. https://doi.org/10.1007/s10811-018-1495-1. [90] Loizou S, Lekakis I, Chrousos GP, Moutsatsou P. β-Sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol Nutr Food Res. 2010;54:551-8. https://doi.org/10.1002/mnfr.200900012. [91] Choi H, Mevers E, Byrum T, Valeriote FA, Gerwick WH. Lyngbyabellins K-N from two palmyra atoll collections of the marine cyanobacterium Moorea bouillonii. Eur J Org Chem. 2012;2012:5141-50. [92] Duan C, Ge X, Wang J, Wei Z, Feng W, Wang J. Ergosterol peroxide exhibits antiviral and immunomodulatory abilities against porcine deltacoronavirus (PDCoV) via suppression of NF-κB and p38/MAPK signaling pathways in vitro. Int Immunopharmacol. 2021;93:107317. https://doi.org/10.1016/j.intimp.2020.107317. [93] Fernando IPS, Jayawardena TU, Kim H-S, Lee WW, Vaas APJP, De Silva HIC, Abayaweera GS, Nanayakkara CM, Abeytunga DTU, Lee D-S, Jeon Y-J. Beijing urban particulate matter-induced injury and inflammation in human lung epithelial cells and the protective effects of fucosterol from Sargassum binderi (Sonder ex J. Agardh). Environ Res. 2019;172:150-8. https://doi.org/10.1016/j.envres.2019.02.016. [94] He W-S, Cui D, Li L, Tong L-T, Rui J, Li H, Zhang H, Liu X. Cholesterol-reducing effect of ergosterol is modulated via inhibition of cholesterol absorption and promotion of cholesterol excretion. J Funct Foods. 2019;57:488-96. https://doi.org/10.1016/j.jff.2019.04.042. [95] Huan W, Tianzhu Z, Yu L, Shumin W. Effects of Ergosterol on COPD in Mice via JAK3/STAT3/NF-κB Pathway. Inflammation. 2017;40:884-93. https://doi.org/10.1007/s10753-017-0533-5. [96] Kangsamaksin T, Chaithongyot S, Wootthichairangsan C, Hanchaina R, Tangshewinsirikul C, Svasti J. Lupeol and stigol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α. PLoS ONE. 2017;12: e0189628. https://doi.org/10.1371/journal.pone.0189628. [97] Kasirzadeh S, Ghahremani MH, Setayesh N, Jeivad F, Shadboorestan A, Taheri A, Beh-Pajooh A, Azadkhah Shalmani A, Ebadollahi-Natanzi A, Khan A, Sabzevari S, Sabzevari O. β-sitosterol alters the inflammatory response in CLP rat model of sepsis by modulation of NFκB signaling. BioMed Res Int. 2021;2021:1-11. https://doi.org/10.1155/2021/5535562. [98] Kobori M, Yoshida M, Ohnishi-Kameyama M, Shinmoto H. Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells: antitumour, anti-inflammation of ergosterol peroxide. British J Pharmacol. 2007;150:209-19. https://doi.org/10.1038/sj.bjp.0706972. [99] Kuo C-F, Hsieh C-H, Lin W-Y. Proteomic response of LAP-activated RAW 264.7 macrophages to the anti-inflammatory property of fungal ergosterol. Food Chem. 2011;126:207-12. https://doi.org/10.1016/j.foodchem.2010.10.101. [100] Li Y, Li X, Liu G, Sun R, Wang L, Wang J, Wang H. Fucosterol attenuates lipopolysaccharide-induced acute lung injury in mice. J Surg Res. 2015;195:515-21. https://doi.org/10.1016/j.jss.2014.12.054. [101] Liao P-C, Lai M-H, Hsu K-P, Kuo Y-H, Chen J, Tsai M-C, Li C-X, Yin X-J, Jeyashoke N, Chao LK-P. Identification of β-sitosterol as in vitro anti-inflammatory constituent in Moringa oleifera. J Agric Food Chem. 2018;66:10748-59. https://doi.org/10.1021/acs.jafc.8b04555. [102] Liu C, Zhao S, Zhu C, Gao Q, Bai J, Si J, Chen Y. Ergosterol ameliorates renal inflammatory responses in mice model of diabetic nephropathy. Biomed Pharmacother. 2020;128:110252. https://doi.org/10.1016/j.biopha.2020.110252. [103] Sun Z, Mohamed MAA, Park SY, Yi TH. Fucosterol protects cobalt chloride induced inflammation by the inhibition of hypoxia-inducible factor through PI3K/Akt pathway. Int Immunopharmacol. 2015;29:642-7. https://doi.org/10.1016/j.intimp.2015.09.016. [104] Zhang S, Xu L, Li A, Wang S. Effects of ergosterol, isolated from Scleroderma polyrhizum Pers., on lipopolysaccharide-induced inflammatory responses in acute lung injury. Inflammation. 2015;38:1979-85. https://doi.org/10.1007/s10753-015-0178-1. [105] Gilbert NC, Gerstmeier J, Schexnaydre EE, Börner F, Garscha U, Neau DB, Werz O, Newcomer ME. Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products. Nat Chem Biol. 2020;16:783-90. [106] Rubbo H, Wood I. 5-LOX inhibition by natural products. Nat Chem Biol. 2020;16:714-5. [107] Al-Rabia MW, Mohamed GA, Ibrahim SRM, Asfour HZ. Anti-inflammatory ergosterol derivatives from the endophytic fungus Fusarium chlamydosporum. Nat Prod Res. 2021;35:5011-20. https://doi.org/10.1080/14786419.2020.1762185. [108] He D, Wang S, Fang G, Zhu Q, Wu J, Li J, Shi D, Lian X. LXRs/ABCA1 activation contribute to the anti-inflammatory role of phytosterols on LPS-induced acute lung injury. J Funct Foods. 2022;89:104966. https://doi.org/10.1016/j.jff.2022.104966. [109] Gabriely G, Wheeler MA, Takenaka MC, Quintana FJ. Role of AHR and HIF-1α in glioblastoma metabolism. Trends Endocrinol Metab. 2017;28:428-36. [110] Nirmal SA, Pal SC, Mandal SC, Patil AN. Analgesic and anti-inflammatory activity of β-sitosterol isolated from Nyctanthes arbortristis leaves. Inflammopharmacol. 2012;20:219-24. https://doi.org/10.1007/s10787-011-0110-8. [111] Choi JN, Choi Y-H, Lee J-M, Noh IC, Park JW, Choi WS, Choi JH. Anti-inflammatory effects of β-sitosterol-β-d-glucoside from Trachelospermum jasminoides (Apocynaceae) in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Nat Prod Res. 2012;26:2340-3. [112] Yang Q, Yu D, Zhang Y. β-sitosterol attenuates the intracranial aneurysm growth by suppressing TNF-α-mediated mechanism. Pharmacology. 2019;104:303-11. https://doi.org/10.1159/000502221. [113] Sillapachaiyaporn C, Mongkolpobsin K, Chuchawankul S, Tencomnao T, Baek SJ. Neuroprotective effects of ergosterol against TNF-α-induced HT-22 hippocampal cell injury. Biomed Pharmacother. 2022;154:113596. https://doi.org/10.1016/j.biopha.2022.113596. [114] Olajubutu OG, Ogunremi BI, Adewole AH, Awotuya OI, Fakola EG, Anyim G, Faloye KO. Topical anti-inflammatory activity of petiveria alliacea, chemical profiling and computational investigation of phytoconstituents identified from its active fraction. Chem Afr. 2022;5:557-65. https://doi.org/10.1007/s42250-022-00339-y. [115] Schoenheimer R. New contributions in sterol metabolism. Science. 1931;74:579-84. [116] Batta AK, Xu G, Honda A, Miyazaki T, Salen G. Stigol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat. Metabolism. 2006;55:292-9. https://doi.org/10.1016/j.metabol.2005.08.024. [117] Chandler RF, Hooper SN, Ismail HA. Antihypercholesterolemic studies with sterols: β-sitosterol and stigol. J Pharm Sci. 1979;68:245-7. https://doi.org/10.1002/jps.2600680235. [118] Chung D-W, Kim W-D, Noh SK, Dong M-S. Effects of hydrophilic and lipophilic β-sitosterol derivatives on cholesterol absorption and plasma cholesterol levels in rats. J Agric Food Chem. 2008;56:6665-70. https://doi.org/10.1021/jf8004405. [119] Gil-Ramírez A, Ruiz-Rodríguez A, Marín FR, Reglero G, Soler-Rivas C. Effect of ergosterol-enriched extracts obtained from Agaricus bisporus on cholesterol absorption using an in vitro digestion model. J Funct Foods. 2014;11:589-97. https://doi.org/10.1016/j.jff.2014.08.025. [120] Gil-Ramírez A, Caz V, Martin-Hernandez R, Marín FR, Largo C, Rodríguez-Casado A, Tabernero M, Ruiz-Rodríguez A, Reglero G, Soler-Rivas C. Modulation of cholesterol-related gene by ergosterol and ergosterol-enriched extracts obtained from Agaricus bisporus. Eur J Nutr. 2016;55:1041-57. https://doi.org/10.1007/s00394-015-0918-x. [121] Hwang S-L, Kim H-N, Jung H-H, Kim J-E, Choi D-K, Hur J-M, Lee J-Y, Song H, Song K-S, Huh T-L. Beneficial effects of β-sitosterol on glucose and lipid metabolism in L6 myotube cells are mediated by AMP-activated protein kinase. Biochem Biophys Res Commun. 2008;377:1253-8. https://doi.org/10.1016/j.bbrc.2008.10.136. [122] Ikeda I, Morioka H, Sugano M. The effect of dietary β-sitosterol and β-sitostanol on the metabolism of cholesterol in rats. Agric Biol Chem. 1979;43:1927-33. https://doi.org/10.1080/00021369.1979.10863733. [123] Ikeda I, Sugano M. Comparison of absorption and metabolism of β-sitosterol and β-sitostanol in rats. n.d. [124] Ikeda I, Sugano M. Comparison of absorption and metabolism of β-sitosterol and β-sitostanol in rats. Atherosclerosis. 1978;30:227-37. https://doi.org/10.1016/0021-9150(78)90049-7. [125] Olaiya CO, Omolekan TO, Esan AM, Adediran BJ. Renal, cardiac and osteo-protective effects of beta-sitosterol glycoside in hypertensive rats. Adv Life Sci Technol. 2015;39(1):13-8. [126] Shidoji Y, Watanabe M, Oku T, Muto Y, Hosoya N. Inhibition of β-sitosterol on intestinal cholesterol absorption in rat using in vivo dual isotope ratio method. J Nutr Sci Vitaminol. 1980;26:183-8. [127] Smith D, Espino-Montoro A, Perez-Jimenez F, Pedro-Botet J, Pereperez JJ, Ordovas JM. Effect of a high saturated fat and cholesterol diet supplemented with squalene or β-sitosterol on lipoprotein profile in fib hamsters. Nutr Res. 2000;20:1309-18. [128] Sugano M, Morioka H, Ikeda I. A comparison of hypocholesterolemic activity of β-sitosterol and β-sitostanol in rats. J Nutr. 1977;107:2011-9. https://doi.org/10.1093/jn/107.11.2011. [129] Teshima S, Kanazawa A, Yoshioka M, Kitahara K. Hypocholesterolemic effect of 24-methylenecholesterol and 7-cholestenol in the rat. J Steroid Biochem. 1974;5:69-72. https://doi.org/10.1016/0022-4731(74)90030-2. [130] Vahouny GV, Connor WE, Subramaniam S, Lin DS, Gallo LL. Comparative lymphatic absorption of sitosterol, stigol, and fucosterol and differential inhibition of cholesterol absorption. Am J Clin Nutr. 1983;37:805-9. https://doi.org/10.1093/ajcn/37.5.805. [131] Ikeda I, Kawasaki A, Samezima K, Sugano M. Antihypercholesterolemic activity of β-sitostanol in rabbits. J Nutr Sci Vitaminol. 1981;27:243-51. [132] Jung HA, Jung HJ, Jeong HY, Kwon HJ, Kim M-S, Choi JS. Antiadipogenic activity of the edible brown alga Ecklonia stolonifera and its constituent fucosterol in 3T3-L1 adipocytes. Arch Pharm Res. 2014;37:713-20. https://doi.org/10.1007/s12272-013-0237-9. [133] Jeong D, Lee J, Jeong S-G, Hong YH, Yoo S, Han SY, Kim JH, Kim S, Kim JS, Chung YS. Artemisia asiatica ethanol extract exhibits anti-photoaging activity. J Ethnopharmacol. 2018;220:57-66. [134] Jeong Y-U, Park Y-J. Ergosterol peroxide from the medicinal mushroom ganoderma lucidum inhibits differentiation and lipid accumulation of 3T3-L1 adipocytes. IJMS. 2020;21:460. https://doi.org/10.3390/ijms2 1020460. [135] Song Y, Oh GH, Kim M-B, Hwang J-K. Fucosterol inhibits adipogenesis through the activation of AMPK and Wnt/β-catenin signaling pathways. Food Sci Biotechnol. 2017;26:489-94. https://doi.org/10.1007/ s10068-017-0067-5. [136] Ikeda I, Sugano M. Some aspects of mechanism of inhibition of cholesterol absorption by β-sitosterol. Biochim Biophys Acta (BBA)-Biomembr. 1983;732:651-8. [137] Desai AJ, Dong M, Miller LJ. Beneficial effects of β-sitosterol on type 1 cholecystokinin receptor dysfunction induced by elevated membrane cholesterol. Clin Nutr. 2016;35:1374-9. https://doi.org/10.1016/j.clnu. 2016.03.003. [138] Kim D-H, Jung SJ, Chung I-S, Lee Y-H, Kim D-K, Kim S-H, Kwon B-M, Jeong T-S, Park M-H, Seoung N-S, Baek N. Ergosterol peroxide from flowers of Erigeron annuus L. as an anti-atherosclerosis agent. Arch Pharm Res. 2005;28:541-5. https://doi.org/10.1007/BF02977755. [139] Leon C, Hill JS, Wasan KM. Potential role of acyl-coenzyme A: cholesterol transferase (ACAT) inhibitors as hypolipidemic and antiatherosclerosis drugs. Pharm Res. 2005;22:1578-88. [140] Tangedahl TN, Thistle JL, Hofmann AF, Matseshe JW. Effect of β-sitosterol alone or in combination with chenic acid on cholesterol saturation of bile and cholesterol absorption in gallstone patients. Gastroenterology. 1979;76:1341-6. https://doi.org/10.1016/0016-5085(79) 90398-6. [141] Cicero AFG, Fiorito A, Panourgia MP, Sangiorgi Z, Gaddi A. Effects of a new soy/beta-sitosterol supplement on plasma lipids in moderately hypercholesterolemic subjects. J Am Diet Assoc. 2002;102:1807-11. https://doi.org/10.1016/s0002-8223(02)90388-3. [142] Normén L, Dutta P, Lia Å, Andersson H. Soy sterol esters and β-sitostanol ester as inhibitors of cholesterol absorption in human small bowel. Am J Clin Nutr. 2000. https://doi.org/10.1093/ajcn/71.4.908. [143] Sugano M, Ikeda I, Imaizumi K, Watanabe M, Andoh M. Effects of β-sitosterol on the concentrations of serum and liver cholesterol and serum apolipoproteins in rats fed butter fat. J Nutr Sci Vitaminol. 1982;28:117-26. [144] Namama ST, Diary IT. Citrullus colocynthis as a bioavailable source of beta-sitosterol, anti hyperlipidic effect of oil in rabbits. Int J Med Arom Plants. 2012;2:536-9. [145] Alappat L, Valerio M, Awad AB. Effect of vitamin D and β-sitosterol on immune function of macrophages. Int Immunopharmacol. 2010;10:1390-6. https://doi.org/10.1016/j.intimp.2010.08.003. [146] 146. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 2010;10:482-96. [147] Lee JH, Parveen A, Do MH, Lim Y, Shim SH, Kim SY. Lespedeza cuneata protects the endothelial dysfunction via eNOS phosphorylation of PI3K/ Akt signaling pathway in HUVECs. Phytomedicine. 2018;48:1-9. https://doi.org/10.1016/j.phymed.2018.05.005. [148] Lin F, Xu L, Huang M, Deng B, Zhang W, Zeng Z, Yinzhi S. β-sitosterol protects against myocardial ischemia/reperfusion injury via targeting PPAR γ/NF-κB signalling. Evid-Based Complement Altern Med. 2020;2020:1-9. https://doi.org/10.1155/2020/2679409. [149] El-Shoura EAM, Salem M, Ahmed YH, Ahmed LK, Zaafar D. Combined β-sitosterol and trimetazidine mitigate potassium dichromate-induced cardiotoxicity in rats through the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways. Environ Sci Pollut Res. 2023. https://doi.org/10.21203/rs.3.rs-2524702/v1. [150] Hassan STS. 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. https://doi.org/10.3390/biomedicines8050132.

Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases

Unveiling the molecular mechanisms: dietary phytosterols as guardians against cardiovascular diseases

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 1

Recommended Articles

Metrics

Comments