BETA-SITOSTEROL AND ITS ANTINOCICEPTIVE MECHANISM ACTION

Year 2021, , 238 - 252, 31.05.2021

Ayşe Arzu Şakul , Mehmet Evren Okur

https://doi.org/10.33483/jfpau.882831

Cited By: 2

Abstract

Objective: In this study, the possible central antinociceptive activity of beta-sitosterol is investigated along with its association of stimulation of opioidergic, serotonergic, adrenergic, and cholinergic receptors to mice central analgesia because of the beta-sitosterol administration.

Material and Method: The beta-sitosterol was administrated to mice in various doses, such as 5, 10 and 20 mg/kg. Then, the mice analyzed via hot-plate and tail-flick assay to investigate the possible antinociceptive effects of beta-sitosterol. Additionally, in order to associate the mechanism of action mechanism, 20 mg/kg of beta-sitosterol was intraperitoneally administered to the animal which were previously pre-treated with opioid antagonist naloxone (5 mg/kg), serotonin 5-HT2A/2C receptor antagonist ketanserin (1 mg/kg), serotonin 5-HT3 receptor antagonist – ondansetron (1 mg/kg), α2-adrenoceptor antagonist yohimbine (1 mg/kg) and muscarinic antagonist atropine (5 mg/kg), as well as nicotinic antagonist mecamylamine (1 mg/kg).

Result and Discussion: The antinociceptive effect of beta-sitosterol was confirmed as dose-dependent for 5, 10, and 20 mg/kg doses in tail-flick and hot-plate tests. It can be concluded that beta-sitosterol promotes central antinociception effects associated with the spinal and supraspinal mediated cholinergic and opioidergic modulation.

Keywords

Antinociception, beta-sitosterol, cholinergic receptors, opioidergic receptors

Supporting Institution

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Project Number

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Thanks

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BETA-SİTOSTEROL VE ANTİNOSİSEPTİF ETKİ MEKANİZMASI

Abstract

Amaç: Bu çalışmada, farelerde beta-sitosterol uygulamasına bağlı santral analjezide opioiderjik, serotonerjik, adrenerjik ve kolinerjik reseptörleri ile ilişkili olası antinosiseptif aktivitesi araştırılmıştır.

Gereç ve Yöntem: Beta-sitosterol, farelere 5, 10 ve 20 mg/kg dozlarında uygulandı. Daha sonra, fareler beta-sitosterolün olası antinosiseptif etkilerini araştırmak için tail-flick ve hot-plate testleri ile analiz edildi. Ek olarak, etki mekanizmasını değerlendirmek için, farelere, beta-sitosterol (20 mg/kg, intraperitonel) uygulamasından önce opioid antagonisti nalokson (5 mg/kg), serotonin 5-HT3 reseptör antagonisti ondansetron (1 mg/kg), serotonin 5-HT2A/2C reseptör antagonisti ketanserin (1 mg/kg), α2-adrenoseptör antagonisti yohimbin (1 mg/kg) ve muskarinik antagonist atropin (5 mg/kg) ve ayrıca nikotinik antagonisti mekamilamin (1 mg/kg) uygulandı.

Sonuç ve Tartışma: Beta-sitosterolün doza-bağlı antinosiseptif etkisi, tail-flick ve hot-plate testlerinde 5, 10 ve 20 mg/kg dozlarında tespit edilmiştir. Beta-sitosterolün, spinal ve supraspinal aracılı kolinerjik ve opioiderjik modülasyon ile ilişkili merkezi antinosisepsiyon etkilerini teşvik ettiği sonucuna varılabilir.

Keywords

Antinosisepsiyon, beta-sitosterol, kolinerjik reseptörler, opioiderjik reseptörler

Project Number

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References

• Abdolrazaghnejad, A., Banaie, M., Tavakoli, N., Safdari, M., Rajabpour-Sanati, A. (2018). Pain management in the emergency department: a review article on options and methods. Adv J Emerg Med., 2(4), e45.
• Nicholson, B. (2006). Differential diagnosis: nociceptive and neuropathic pain. Am J Manag Care, 12(9), 256-262.
• Mitsi, V., Zachariou, V. (2016). Modulation of pain, nociception, and analgesia by the brain reward center. Neuroscience, 338, 81–92.
• Falk, S., Dickenson, A.H. (2014). Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol, 32(16), 1647–1654.
• Armstrong, S., Herr, M. (2020). Physiology, Nociception. In: StatPearls. Treasure Island (FL): StatPearls.
• Prieto Rodríguez, J.A., Patiño Ladino, O.J., Lesmes, L., Lozano, J.M., Cuca Suárez, L.E. (2011). Phytochemical study of uncaria guianensis leaves and antibacterial activity evaluation. Acta Amazonica, 41(2), 303–310.
• Yepes-Pérez, A.F., Herrera-Calderon, O., Sánchez-Aparicio, J.-E., Tiessler-Sala, L., Maréchal, J.-D., Cardona-G, W. (2020). Investigating potential inhibitory effect of uncaria tomentosa (cat’s claw) against the main protease 3CLpro of SARS-CoV-2 by molecular modeling. Evid Based Complement Alternat Med., 2020, 4932572.
• Vissers, M.N., Zock, P.L., Meijer, G.W., Katan, M.B. (2000). Effect of plant sterols from rice bran oil and triterpene alcohols from sheanut oil on serum lipoprotein concentrations in humans. Am J Clin Nutr., 72(6), 1510–1515.
• Elkeilsh, A., Awad, Y.M., Soliman, M.H., Abu-Elsaoud, A., Abdelhamid, M.T., El-Metwally, I.M. (2019). Exogenous application of β-sitosterol mediated growth and yield improvement in water-stressed wheat (Triticum aestivum) involves up-regulated antioxidant system. J Plant Res., 132(6), 881–901.
• Delgado-Zammarreno, M.M., Bustamante-Rangel, M., Martinez-Pelarda, D., Carabias-Martinez, R. (2009). Analysis of beta-sitosterol in seeds and nuts using pressurized liquid extraction and liquid chromatography. Anal Sci, 25(6), 765–768.
• Kim, S.-J. (2017). The ameliorative effect of β-sitosterol on DNCB-induced atopic dermatitis in mice. Biomed Sci Letters, 23(4), 303–309.
• Saeidnia, S., Manayi, A., Gohari, A.R., Abdollahi, M. (2014). The story of beta-sitosterol- a review. EJMP, 4(5), 590–609.
• Heitzman, M., Neto, C.C., Winiarz, E., Vaisberg, A.J., Hammond, G.B. (2005). Ethnobotany, phytochemistry and pharmacology of (Rubiaceae). Phytochemistry, 66(1), 5–29.
• Tapiero, H., Townsend, D.M., Tew, K.D. (2003). Phytosterols in the prevention of human pathologies. Biomed Pharmacother., 57(8), 321–325.
• Ododo, M.M., Choudhury, M.K., Dekebo, A.H. (2016). Structure elucidation of β-sitosterol with antibacterial activity from the root bark of Malva parviflora. Springerplus, 5(1), 1210.
• Feng, S., Dai, Z., Liu, A.B., Huang, J., Narsipur, N., Guo, G., Guo, G., Kong, B., Reuhl, K., Lu, W., Luo, Z., Yang, C.S. (2018). Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet. Biochim Biophys Acta Mol Cell Biol Lipids, 1863(10), 1274–1284.
• Liu, R., Hao, D., Xu, W., Li, J., Li, X., Shen, D., Sheng, K., Zhao, L., Xu, W., Gao, Z., Zhao, X., Liu, Q., Zhang, Y. (2019). β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice. Pharm Biol., 57(1), 161–168.
• Paniagua-Pérez, R., Flores-Mondragón, G., Reyes-Legorreta, C., Herrera-López, B., Cervantes-Hernández, I., Madrigal-Santillán, O., Morales-González, J.A.,Álvarez-González, I., Madrigal-Bujaidar, E. (2016). Evaluation of the anti-inflammatory capacity of beta-sitosterol in rodent assay. Afr J Tradit Complement Altern Med., 14(1), 123–130.
• Dighe, S. B., Kuchekar, B. S., Wankhede, S. B. (2019). Analgesic and anti-inflammatory activity of β-sitosterol isolated from leaves of Oxalis corniculata. International Journal of Pharmacological Research, 09(05), 109–113.
• Arslan, R., Bektas, N. (2015). Evaluation of the centrally-acting mechanisms of some non- steroidal anti-inflammatory drugs. American Journal of Pharmacy & Health Research, 3(6), 191–202.
• Arslan, R., Aydin, S., Nemutlu Samur, D., Bektas, N. (2018). The possible mechanisms of protocatechuic acid-induced central analgesia. Saudi Pharm J., 26(4), 541–545.
• Majumder, R., Adhikari, L., Dhara, M., Sahu, J. (2020). Evaluation of anti-inflammatory, analgesic and TNF-α inhibition (upon RAW 264.7 cell line) followed by the selection of extract (leaf and stem) with respect to potency to introduce anti-oral-ulcer model obtained from Olax psittacorum (Lam.) Vahl in addition to GC-MS illustration. J Ethnopharmacol., 263, 113146.
• De Caro, C., Raucci, F., Saviano, A., Cristiano, C., Casillo, G. M., Di Lorenzo, R., Sacchi, A., Laneri, S., Dini, I., De Vita, S., Chini, M. G., Bifulco, G., Calignano, A., Maione, F., Mascolo, N. (2020). Pharmacological and molecular docking assessment of cryptotanshinone as natural-derived analgesic compound. Biomed Pharmacother., 126, 110042.
• Devaraj, E., Roy, A., Royapuram Veeraragavan, G., Magesh, A., Varikalam Sleeba, A., Arivarasu, L., Marimuthu Parasuraman, B. (2020). β-Sitosterol attenuates carbon tetrachloride–induced oxidative stress and chronic liver injury in rats. Naunyn Schmiedebergs Arch Pharmacol., 393(6), 1067–1075.
• Babu, S., Krishnan, M., Rajagopal, P., Periyasamy, V., Veeraraghavan, V., Govindan, R., Jayaraman, S. (2020). Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats. Eur J Pharmacol., 873, 173004.
• Afify, E. A., Alkreathy, H. M., Ali, A.S., Alfaifi, H.A., Khan, L.M. (2017). Characterization of the antinociceptive mechanisms of khat extract (Catha edulis) in mice. Front Neurol., 8, 69.
• Wang, Y., Su, D. M., Wang, R.H., Liu, Y., Wang, H. (2005). Antinociceptive effects of choline against acute and inflammatory pain. Neuroscience, 132(1), 49–56.
• Scapinello, J., Müller, L. G., Schindler, M., Anzollin, G. S., Siebel, A. M., Boligon, A. A., Niero, R., Saraiva, T., Maus, N. P., Betti, A. H., Oliveira, J. V., Magro, J. D., & de Oliveira, D. (2019). Antinociceptive and anti-inflammatory activities of Philodendron bipinnatifidum Schott ex Endl (Araceae). J Ethnopharmacol., 236, 21–30.
• Jang, Y., Kim, M., Hwang, S. W. (2020). Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception. J Neuroinflammation, 17(1), 30.
• Das, N., Bhattacharya, A., Kumar Mandal, S., Debnath, U., Dinda, B., Mandal, S. C., Kumar Sinhamahapatra, P., Kumar, A., Dutta Choudhury, M., Maiti, S., & Palit, P. (2018). Ichnocarpus frutescens (L.) R. Br. root derived phyto-steroids defends inflammation and algesia by pulling down the pro-inflammatory and nociceptive pain mediators: An in-vitro and in-vivo appraisal. Steroids, 139, 18–27.
• Nirmal, S. A., Pal, S. C., Mandal, S. C., Patil, A. N. (2012). Analgesic and anti-inflammatory activity of β-sitosterol isolated from Nyctanthes arbortristis leaves. Inflammopharmacology, 20(4), 219–224.
• Tamaddonfard, E., Erfanparast, A., Abbas Farshid, A., Delkhosh-Kasmaie, F. (2017). Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats. Eur J Pharmacol., 815, 399–404.
• Zhao, X., Ye, J., Sun, Q., Xiong, Y., Li, R., Jiang, Y. (2011). Antinociceptive effect of spirocyclopiperazinium salt compound LXM-15 via activating peripheral α7 nAChR and M4 mAChR in mice. Neuropharmacology, 60(2–3), 446–452.
• Pinheiro, M.M.G., Boylan, F., Fernandes, P.D. (2012). Antinociceptive effect of the Orbignya speciosa Mart. (Babassu) leaves: Evidence for the involvement of apigenin. Life Sci., 91(9–10), 293–300.
• Guginski, G., Luiz, A.P., Silva, M.D., Massaro, M., Martins, D.F., Chaves, J., Mattos, R.W., Silveira, D., Ferreira, V.M.M. Calixto, J. B., Santos, A.R. (2009). Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice. Pharmacol Biochem Behav., 93(1), 10–16.
• Li, W., Cai, J., Wang, B.H., Huang, L., Fan, J., Wang, Y. (2018). Antinociceptive effects of novel epibatidine analogs through activation of α4β2 nicotinic receptors. Sci China Life Sci., 61(6), 688–695.
• Atzori, M., Cuevas-Olguin, R., Esquivel-Rendon, E., Garcia-Oscos, F., Salgado-Delgado, R. C., Saderi, N., Miranda-Morales, M., Treviño, M., Pineda, J. C., Salgado, H. (2016). Locus ceruleus norepinephrine release: A central regulator of cns spatio-temporal activation? Front Synaptic Neurosci, 8, 25.
• Mwobobia, R.M., Kanui, T.I., Abelson, K.S.P. (2020). Investigation of noradrenergic receptor system in anti-nociception using formalin test in the naked mole rat (Heterocephalus glaber). Heliyon, 6(10), e05216.
• Cortes-Altamirano, J. L., Olmos-Hernandez, A., Jaime, H.B., Carrillo-Mora, P., Bandala, C., Reyes-Long, S., Alfaro-Rodríguez, A. (2018). Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 receptors and their role in the modulation of pain response in the central nervous system. Curr Neuropharmacol., 16(2), 210–221.
• Anversa, R.G., Sousa, F.S.S., Birmann, P.T., Lima, D.B., Lenardão, E.J., Bruning, C.A., Savegnago, L. (2018). Antinociceptive and anti-inflammatory effects of 1,2-bis-(4 methoxyphenylselanyl) styrene in mice: involvement of the serotonergic system. J Pharm Pharmacol., 70(7), 901–909.