Mechanism of antinociceptive activity of the methanol leaf extract of Senna italica (Mill) in murine model of pain

محورهای موضوعی : مجله گیاهان دارویی

Amina Busola Olorukooba ¹ (Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State-Nigeria;)
Asmau Nasir Hamza ² (Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Kaduna State-Nigeria;)
Aisha Oiza Musa ³ (Department of Botany, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State-Nigeria;)

تاریخ دریافت : 1401/10/08 تاریخ پذیرش : 1402/02/05 تاریخ انتشار : 1402/03/01

کلید واژه: Senna italica, Antinociception, Pain mechanism, Adrenergic, Opoidergic,

چکیده مقاله :

Background & Aim: Senna italica leaf (SIL) is extensively used in traditional medicine for the management of various types of pain including stomach cramps, back ache, joint pains, headache, and migraine. The current study was designed to scientifically investigate the purported uses of the leaves as an analgesic agent and to elucidate its possible mechanism of antinociceptive action.Experimental: Phytochemical screening and oral acute toxicity studies were conducted using standard protocols. Antinociceptive potentials were evaluated using acetic acid-induced writhing and hot plate tests in mice. The possible pharmacological mechanism(s) involved in the anti-nociceptive activity were investigated by pretreating mice with Naloxone (2 mg/kg), L-arginine (50 mg/kg), Propranolol (20 mg/kg), Glibenclamide (10 mg/kg), and Prazosin (1 mg/kg)15 min prior to SIL (1000 mg/kg) administration, then assessed using acetic acid-induced writhing 1 h later. Data was analyzed using One-way Anova followed by Bonferroni post hoc test.Results: Phytochemical screening revealed the presence of alkaloids, flavonoids, saponins, steroids and triterpenes. Oral median lethal dose of SIL was found to be greater than 5000 mg/kg. SIL at the doses of 250, 500 and 1000 mg/kg demonstrated significant (P<0.05) dose-dependent protection against acetic acid-induced writhes in mice. The extract at the highest dose (1000 mg/kg) also significantly (P<0.05) increased the reaction time of mice to thermal stimulus in the hot plate test. Pretreatment with naloxone, prazosin, L-arginine, and propranolol significantly (P<0.05) reduced the antinociceptive activity of the extract. However, pretreatment with glibenclamide showed no effect on its antinociceptive activity.Recommended applications/industries: The findings of this research has validated the traditional use of the plant in the management of pain through possible involvement of opioidergic, α-adrenergic, β-adrenergic systems including the L-arginine/nitric oxide pathway.

چکیده انگلیسی:

Background & Aim: Senna italica leaf (SIL) is extensively used in traditional medicine for the management of various types of pain including stomach cramps, back ache, joint pains, headache, and migraine. The current study was designed to scientifically investigate the purported uses of the leaves as an analgesic agent and to elucidate its possible mechanism of antinociceptive action.Experimental: Phytochemical screening and oral acute toxicity studies were conducted using standard protocols. Antinociceptive potentials were evaluated using acetic acid-induced writhing and hot plate tests in mice. The possible pharmacological mechanism(s) involved in the anti-nociceptive activity were investigated by pretreating mice with Naloxone (2 mg/kg), L-arginine (50 mg/kg), Propranolol (20 mg/kg), Glibenclamide (10 mg/kg), and Prazosin (1 mg/kg)15 min prior to SIL (1000 mg/kg) administration, then assessed using acetic acid-induced writhing 1 h later. Data was analyzed using One-way Anova followed by Bonferroni post hoc test.Results: Phytochemical screening revealed the presence of alkaloids, flavonoids, saponins, steroids and triterpenes. Oral median lethal dose of SIL was found to be greater than 5000 mg/kg. SIL at the doses of 250, 500 and 1000 mg/kg demonstrated significant (P<0.05) dose-dependent protection against acetic acid-induced writhes in mice. The extract at the highest dose (1000 mg/kg) also significantly (P<0.05) increased the reaction time of mice to thermal stimulus in the hot plate test. Pretreatment with naloxone, prazosin, L-arginine, and propranolol significantly (P<0.05) reduced the antinociceptive activity of the extract. However, pretreatment with glibenclamide showed no effect on its antinociceptive activity.Recommended applications/industries: The findings of this research has validated the traditional use of the plant in the management of pain through possible involvement of opioidergic, α-adrenergic, β-adrenergic systems including the L-arginine/nitric oxide pathway.

منابع و مأخذ:

Adjou, E.S., Koudoro, A.Y., Nonviho, G., Ahoussi, E.D. and Sohounhloue, D.C.K. 2021. Phytochemical profile and potential pharmacological properties of leaves extract of Senna italica Mill. American Journal of Pharmacology, 9: 36-39.
Al-Tahan, F.J., Al-Bayati, M.A. and Askar, S.J. 2011. The analgesic effects of L-arginine and its antagonist L-NAME in mice. Iraqi Journal of Veterinary Medicine, 36: 22–31.
Arena, A.C., Leite Kassuya, C.A., Konkiewitz, E.C. and Ziff, E.B. 2022. Natural products as sources of new analgesic drugs. Evidence-Based Complementary and Alternative Medicine, doi: 10.1155/2022/9767292.
Ashagrie, G., Abebe, A., and Umer, S. 2023. Analgesic and anti-Inflammatory activities of 80% methanol extract and solvent fractions of Ehretiacymosa Thonn (Boraginaceae) leaves in rodents. Journal of Experimental Pharmacology, 15: 63–79.
Azwanida, N.N. 2015. A review on the extraction methods used in medicinal plants, principle, strength, and limitation. Medicinal and Aromatic Plants, 4: 3-23.
Bentley, G.A., Newton, S.H. and Starr, J. 1983. Studies on the antinociceptive action of α‐agonist drugs and their interactions with opioid mechanisms. British Journal of Pharmacology, 79: 125-134.
Bittar, M., de Souza, M.M., Yunes, R.A., Lento, R., Delle Monache, F. and Cechinel Filho, V. 2000. Antinociceptive activity of I3, II8-binaringenin, a biflavonoid present in plants of the guttiferae. Planta Medica, 66: 84–86.
Calixto, J.B., Beirith, A., Ferreira, J., Santos, A.R., Filho, V.C. and Yunes, R.A. 2000. Naturally occurring antinociceptive substances from plants. Phytotherapy Research, 14: 401-18.
Chapman, C.R., Casey, K.L., Dubner, R., Foley, K.M., Gracely, R.H. and Reading, A.E., 1985. Pain measurement: an overview. Pain, 22: 1-31.
Chen, J., Wang, X., Qu, Y.G., Chen, Z.P., Cai, H., Liu, X., Xu, F., Lu, T.L. and Cai, B.C. 2012. Analgesic and anti-inflammatory activity and pharmacokinetics of alkaloids from seeds of Strychnosnux-vomica after transdermal administration: effect of changes in alkaloid composition. Journal of Ethnopharmacology, 139: 181-8.
Chen, J.S., Kandle, P.F., Murray, I., Patricia, F., Fitzgerald, L.A. and Sehdev, J.S. 2021. Physiology, Pain. [Updated 2021 Jul 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Dabai, Y.U., Kawo, A.H. and Aliyu, R.M. 2012. Phytochemical screening and antibacterial activity of the leaf and root extracts of Senna italica. African Journal of Pharmacy and Pharmacology, 6: 914-918.
Dragos, D., Gilca, M., Gaman, L., Vlad, A., Iosif, L., Stoian, I. and Lupescu, O. 2017. Phytomedicine in joint disorders. Nutrients, 9: 70- 79.
Drummond, E.S., Maker, G., Birklein, F., Finch, P.M. and Drummond, P.D. 2016. Topical prazosin attenuates sensitivity to tactile stimuli in patients with complex regional pain syndrome. European Journal of Pain, 20: 926-35.
El-Sayed, N.H., Dooh, A.A., El-Khrisy, S.A.M. and Mabry, T.J. 1992. Flavonoids of Cassia italica. Phytochemistry, 31: 2187-9.
Erhirhie, E.O., Ihekwereme, C.P. and Ilodigwe, E.E. 2018. Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance. Interdisciplinary Toxicology, 11: 5-12.
Evans, W.C., Evans, D., Trease, G.E., 2009. Trease and Evans pharmacognosy (16th ed.). Edinburgh; New York: Saunders/Elsevier.
Eze, E.F., Uzor, P.F., Obi, B.C. and Osadebe, P.O. 2019. Nigerian medicinal plants with analgesic and anti-inflammatory potentials. African Journal of Pharmaceutical Research and Development, 11: 165-188.
Fitzcharles, M.A., Cohen, S.P., Clauw, D.J., Littlejohn, G., Usui, C., and Häuser, W. 2021. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet, 397: 2098-2110.
Fürst, S. 1999. Transmitters involved in antinociception in the spinal cord. Brain Research Bulletin, 48: 129-141.
Gololo, S.S., Mapfumari, N.S., Sethoga, L.S., Olivier, M.T., Shai, L.J. and Mogale, M.A. 2016. Identification of phytochemical constituents within the n-hexane leaf extract of Senna italica (mill) using gas chromatography-mass spectrometry (GC-MS) analysis. Journal of Pharmaceutical Sciences and Research, 8: 1141–1143.
Han, B.F., Zhang, C., Qi. J.S. and Qiao, J.T. 2002. ATP-sensitive potassium channels and endogenous adenosine are involved in spinal antinociception produced by locus coeruleus stimulation. Sheng Li Xue Bao, 54: 139-44.
Hassan-Abdallah, A., Merito, A., Hassan, S., Aboubaker, D., Djama, M., Asfaw, Z. and Kelbessa, E. 2013. Medicinal plants and their uses by the people in the Region of Randa, Djibouti. Journal of Ethnopharmacology, 148: 701-13.
Hughes, J. 1975. Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Research, 88: 295-308.
Hutton, D., Mustafa, A., Patil, S., Rathod, S., Shrikhande, G., Advincula, A., Drummond, J., Gregersen, P., Hall, J., Metz, C., Milspaw, A., Orbuch, I.K., Stahl, P., Stein, A. and Shrikhande, A.S. 2023. The burden of chronic pelvic pain (CPP): Costs and quality of life of women and men with CPP treated in outpatient referral centers. PLoS ONE, 18(2): e0269828.
International Association for the Study of Pain (IASP, 2020). IASP announces revised definition of pain [Internet]. Washington: IASP; 2020 [cited 2020 August 26]. Available from: www.iasp-pain.org/PublicationsNews/NewsDetail.aspx?ItemNumber=10475.
Jothi, R.S., Bharathy, V. and Uthayakumari, F.U. 2015. Antioxidant potential of aerial part of Senna italica sub species micrantha Mill. Journal of Pharmaceutical Sciences and Research, 7: 621-625.
Khalaf, O.M., Ghareeb, M.A., Sa’ad, A. M., Madkour, H.M. F., El-zaity, A. K., and Abdul-Aziz, M. S. 2019. Phenolic constituent, antimicrobial and anticancer activity of ethyl acetate and butanol extract of Senna italica. Acta chromatograhica, 31: 138-145.
Kim, S.J. and Seo, J.T. 2020. Selection of analgesics for the management of acute and postoperative dental pain: a mini-review. Journal of Periodontal & Implant Science, 50: 68-73.
Koster, R., Anderson, M. and De Beer, E.J. 1959. Acetic acid for analgesic screening. Federal Proceedings, 18: 412-417.
Kuete, V., Wiench, B., Alsaid, M.S., Alyahya, M.A., Fankam, A.G., Shahat, A.A., Efferth, T. 2013. Cytotoxicity, mode of action and antibacterial activities of selected Saudi Arabian medicinal plants. BMC Complementary Medicine and Therapies, 13: 354.
Lee, H.S., Lee, I.H., Kang, K., Park, S.I., Kwon, T.W. and Lee, D.Y. 2020. An investigation of the molecular mechanisms underlying the analgesic effect of jakyak-gamcho decoction: A network pharmacology study. Evidence Based Complementary Alternative Medicine, 1: 2020.
Lorke, D. 1983. A new approach to practical acute toxicity testing. Archives of Toxicology, 54: 275-287.
Madkour, H.M.F., Ghareeb, M.A., Abdel-Aziz, M.S., Khalaf, O.M., Saad, A.M., El-Ziaty, A.K. and Abdel-Mogib, M. 2017. Gas chromatography-mass spectrometry analysis, antimicrobial, anticancer and antioxidant activities of n-hexane and methylene chloride extracts of Senna italica. Journal of Applied Pharmaceutical Science, 7: 023-032.
Magano, S.R., Thembo, K.M., Ndlovu, S.M. and Makhubela, N.F.H. 2008. The anti-tick properties of the root extracts of Senna italica subsp. arachoides. African Journal of Biotechnology, 7: 476-481.
Mahmoud, T. and Gairola, S. 2013. Traditional knowledge and use of medicinal plants in the Eastern Desert of Egypt: a case study from Wadi El-Gemal National Park. Journal of Medicinal Plants, 1: 10-17.
Mahmuda, A., Sani, M., Adamu, T., Sanda, A. and Gobir, L.G. 2020. In vivo anthelminthic activity of ethanolic leaf extract of Senna italica on rats with Hymenolepisdiminuta infection. Advances in Research, 21: 18-27.
Malematja, R.O., Bagla, V.P., Njanje, I., Mbazima, V., Poopedi, K.W., Mampuru, L. and Mokgotho, M.P. 2018. Potential hypoglycaemic and antiobesity effects of Senna italica leaf acetone extract. Evidence-Based Complementary and Alternative Medicine,19: 2018:5101656.
Masoko, P., Gololo, S.S., Mokgotho, M.P., Eloff, J.N., Howard, R.I. and Mampuru, L.J. 2010. Evaluation of the antioxidant, antibacterial, and antiproliferative activities of the acetone extract of the roots of Senna italica (Fabaceae). African Journal of Traditional, Complementary and Alternative Medicines, 7: 138-48.
Millan, M.J. 2002. Descending control of pain. Progress in Neurobiology, 6: 355–474
Mishra, S.B., Mukerjee, A. and Vijayakumar, M. 2010. Pharmacognostical and phytochemical evaluation of leaves extract of Jatropha curcas Linn. Pharmacognosy Journal, 2: 9–14.
Mokgotho, M.P., Gololo, S.S., Masoko, P., Mdee, L.K., Mbazima, V., Shai, L.J., Bagla, V.P., Eloff, J.N. and Mampuru, L. 2013. Isolation and chemical structural characterisation of a compound with antioxidant activity from the roots of Senna italica. Evidence-Based Complementary and Alternative Medicine, 2013: 519174.
Mondal, H., Saha, S., Awang, K., Hossain, H., Ablat, A., Islam, M. K., Ismet Ara Jahan, Sadhu, S.K., Hossain, M.G., Shilpi, J.A., Uddin, S.J., 2014. Central-stimulating and analgesic activity of the ethanolic extract of Alternanthera sessilis in mice. BMC Complementary Medicine and Therapies, 14: 398.
Nunez-Guillen, M.E., da Silva Emim, J.A., Souccar, C. and Lapa, A.J. 1997. Analgesic and anti-inflammatory activities of the aqueous extract of Plantago major L. International Journal of Pharmacognosy, 35: 99–104.
Ocana M., Cendan C.M., Cobos E.J., Entrena J.M. and Baeyens J.M. 2004. Potassium channels and pain: present realities and future opportunities. European Journal of Pharmacology, 500: 203–219.
OECD 425 Guideline for the Testing of Chemicals. 2008. Acute oral toxicity: Up and down procedure. pp. 1-2.
Osikowicz, M., Mika, J. and Przewlocka, B. 2013. The glutamatergic system as a target for neuropathic pain relief. Experimental Physiology, 98: 372-84.
Ozdoğan, U.K., Lähdesmäki, J. and Scheinin, M. 2003. Influence of prazosin and clonidine on morphine analgesia, tolerance and withdrawal in mice. European Journal of Pharmacology, 460: 127-134.
Pavao-de-Souza, G.F., Zarpelon, A.C., Tedeschi, G.C., Mizokami, S.S., Sanson, J.S., Cunha, T.M., Ferreira, S.H., Cunha, F.Q., Caspgrande, R. and Verri, W.A. Jr. 2012. Acetic acid-and phenyl-p-benzoquinone-induced overt pain-like behavior depends on spinal activation of MAP kinases, PI(3)K and microglia in mice. Pharmacology Biochemistry and Behavior, 101: 320-8.
Pepe S., Brink O. W., Lakatta E. G. and Xiao R. P. 2004. Crosstalk of opioid peptide receptor and beta-adrenergic receptor signalling in the heart. Cardiovascular Research, 6: 3 414–422.
Pinardi, G., Sierralta, F. and Miranda, H.F. 2001. Interaction between the antinociceptive effect of ketoprofen and adrenergic modulatory systems. Journal of Inflammation, 25: 233-9.
Qureshi, R., Bhatti, G. R. and Memon, R. A. 2010). Ethnomedicinal uses of herbs from northern part of Nara desert, Pakistan. Pakistan Journal of Botany, 42: 839-851.
Randell, B.R. and Barlow, B.A., 1998. Senna. In: George AS (ex ed) Flora of Australia, vol 12. Australian Government Publishing Service, Canberra. pp 89–138.
Rangel, R.A., Marinho, B.G., Fernandes, P.D., de Moura, R.S. and Lessa, M.A. 2012. Pharmacological mechanisms involved in the antinociceptive effects of dexmedetomidine in mice. Fundamental & Clinical Pharmacology, 28: 104-13.
Roczniak, W., Wróbel, J., Dolczak, L. and Nowak, P. 2013. Influence of central noradrenergic system lesion on the serotoninergic 5-HT3 receptor mediated analgesia in rats. Advances in Clinical and Experimental Medicine, 22: 629-38.
Russo, M.M. and Sundaramurthi, T. 2019. An overview of cancer pain: epidemiology and pathophysiology. Seminars in Oncology Nursing, 35: 223-228.
Sabina, E.P., Chandel, S. and Rasool, M. 2009. Evaluation of analgesic, antipyretic and ulcerogenic effect of Withaferin A. International Journal of Integrative Biology, 6: 52–56.
Smith, T. J., and Hillner, B. E. 2019. The cost of pain. JAMA Network Open, 2(4): e191532.
Sofowora, A., 2008. Medicinal plant and traditional medicine in Africa. 3rd Edition, Spectrum Books Limited Ibadan, Nigeria.
Trescot, A.M., Datta, S., Lee, M. and Hansen, H. 2008. Opioid pharmacology. Pain Physician, 11: 133-53.
Turner, R.A. 1965: Analgesics. In: Turner RA, ed., Screening methods in Pharmacology. London: Academic Press. p. 100.
Verma, P.R., Joharapurkar, A.A., Chatpalliwar, V.A. and Asnani, A.J. 2005. Antinociceptive activity of alcoholic extract of Hemidesmus indicus R.Br. in mice. Journal of Ethnopharmacology, 102: 298-301.
Wang, J.L., Shen, X.L., Chen, Q.H., Qi, G., Wang, W. and Wang, F.P. 2009. Structure-analgesic activity relationship studies on the C(18)- and C(19)-diterpenoid alkaloids. Chemical and Pharmaceutical Bulletin, 57: 801-7.
Yagi, S.M., Tigani, S.E., Ali, M., Elkhidir, I.H. and Mohammed, A.M. 2013. Chemical constituents and insecticidal activity of Senna italica Mill. from the Sudan. Int Lett Chem Phys Astron. 9: 146-151.
Yasmen, N., Aziz, M.A., Tajmim, A., Akter, M.I., Hazra, A.K. and Rahman, S.M.M. 2018. Analgesic and anti-inflammatory activities of diethyl ether and n-Hexane extract of Polyalthia suberosa leaves. Evidence Based Complementary and Alternative Medicine, 23: 2018:5617234.
Yekkirala, A.S., Roberson, D.P., Bean, B.P. and Woolf, C.J. 2017. Breaking barriers to novel analgesic drug development. Nature Reviews Drug Discovery, 16: 545-564.
Zhang, X.C., Kainz, V., Burstein, R. and Levy, D. 2011. Tumor necrosis factor-α induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions. Pain, 152: 140-149.