Research Article
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Central possible antinociceptive mechanism of naringin

Year 2021, Volume: 51 Issue: 2, 204 - 211, 31.08.2021

Abstract

Background and Aims: The object of this study was the investigation of the central antinociceptive effects of naringin as well as the association of stimulation of opioidergic, serotonergic, adrenergic, and cholinergic (muscarinic and nicotinic) receptors to the central analgesia of mice due to naringin. Methods: Several intraperitoneal doses (20, 40, and 80 mg/kg) were injected into mice models and analyzed via hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) for the possible antinociceptive effects of naringin. Moreover, the involved action mechanism was investigated using 80 mg/kg naringin (i.p.) administered to the mice which were previously pre-treated with opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT2A/2C receptor antagonist ketanserin (1 mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) and muscarinic antagonist atropine (5 mg/kg, i.p.), as well as nicotinic antagonist mecamylamine (1 mg/kg, i.p.). Results: It can be claimed that a dose-dependant antinociceptive effect of naringin was noticed for 40 and 80 mg/kg doses in tail-immersion and hot-plate tests, respectively. Furthermore, the improvement of inactivity of naringin-induced response to thermal stimuli was counteracted by mecamylamine and naloxone when tested with the tail-immersion test, and hot-plate analyses. Conclusion: From the data, it was confirmed that naringin presents central antinociceptive effects which may be coordinated by supraspinal/spinal mediated opioidergic and nicotinic (cholinergic) inflection. Nevertheless, it is unclear how naringin organizes the interactions of the aforementioned modulatory systems. To conclude, naringin could be a possible candidate for pain relief management.

Supporting Institution

Health Sciences University Scientific Research Projects Coordination Unit

Project Number

2020/033

References

  • • Abubakar, A., Nazifi, A. B., Odoma, S., Shehu, S., & Danjuma, N. M. (2020). Antinociceptive activity of methanol extract of Chlorophytum alismifolium tubers in murine model of pain: Possible involvement of α2-adrenergic receptor and KATP channels. Journal of Traditional and Complementary Medicine, 10(1), 1–6.
  • • 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. Frontiers in Neurology, 8(69), 1–12.
  • • Alghamdi, S. (2020) Antinociceptive effect of the citrus flavonoid eriocitrin on postoperative pain conditions. Journal of Pain Research, 13, 805-815.
  • • AlSharari, S. D., Carroll, F. I., McIntosh, J. M., & Damaj, M. I. (2012). The antinociceptive effects of nicotinic partial agonists varenicline and sazetidine-A in murine acute and tonic pain models. Journal of Pharmacology and Experimental Therapeutics, 342(3), 742–749.
  • • Araújo, I. W. F., Chaves, H. V., Pachêco, J. M., Val, D. R., Vieira, L. V., Santos, R. … Benevides, N. M. B. (2017). Role of central opioid on the antinociceptive effect of sulfated polysaccharide from the red seaweed Solieria filiformis in induced temporomandibular joint pain. International Immunopharmacology, 44, 160–167.
  • • Arihan, O., Boz, M., Iskit, A. B., & Ilhan, M. (2009). Antinociceptive activity of coniine in mice. Journal of Ethnopharmacology, 125, 274–278.
  • • Arslan, R., Aydin, S., Samur, D. N., & Bektas, N. (2018). The possible mechanisms of protocatechuic acid-induced central analgesia. Saudi Pharmaceutical Journal, 26(4), 541–545.
  • • Bektaş, N., & Arslan, R. (2016). The centrally-mediated mechanisms of action of ferulic acid–induced antinociception. Marmara Pharmaceutical Journal, 20, 303–310.
  • • Ben-Azu, B., Nwoke, E. E., Umukoro, S., Aderibigbe, A. O., Ajayi, A. M., & Iwalewa, E. O. (2018). Evaluation of the neurobehavioral properties of naringin in swiss mice. Drug Research, 68(08), 465– 474.
  • • Bharti, S., Rani, N., Krishnamurthy, B., & Arya, D. S. (2014). Preclinical evidence for the pharmacological actions of naringin: A Review. Planta Medica, 80(06), 437–451.
  • • Chen, R., Qi, Q. L., Wang, M. T., & Li, Q. Y. (2016). Therapeutic potential of naringin: an overview. Pharmaceutical Biology, 54(12), 3203–3210.
  • • Chung, T. W., Li, S., Lin, C. C., & Tsai, S. W. (2019). Antinociceptive and anti-inflammatory effects of the citrus flavanone naringenin. Tzu-Chi Medical Journal, 31(2), 81–85.
  • • Dallazen, J. L., da Silva, C. F., Hamm, L., Córdova, M. M., Santos, A. R., Werner, M. F. P., & Baggio, C. H. (2017). Further antinociceptive properties of naringenin on acute and chronic pain in mice. Natural Product Communications, 12(9), 11443–1446.
  • • Dziechciaż, M., Balicka-Adamik, L., & Filip, R. (2013). The problem of pain in old age. Annals of Agricultural and Environmental Medicine, 20(1), 35–38.
  • • Hui, W., Xu, Y. S., Wang, M. L., Cheng, C., Bian, R., Yuan, H. … Zhou, H. (2017). Protective effect of naringin against the LPS-induced apoptosis of PC12 cells: implications for the treatment of neurodegenerative disorders. International Journal of Molecular Medicine, 39(4), 819–830.
  • • Jung, U. J., & Kim, S. R. (2014). Effects of naringin, A flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regeneration Research, 9(16), 1514–1517.
  • • Jung, U. J., Leem, E., & Kim, S. R. (2014). Naringin: a protector of the nigrostriatal dopaminergic projection. Experimental Neurobiology, 23(2), 124–129.
  • • Kola, P. K., Akula, A., NissankaraRao, L. S., & Danduga, R. (2017). Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection. Epilepsy & Behavior, 75, 114–126
  • • Leem, E., Nam, J. H., Jeon, M. T., Shin, W. H., Won, S. Y., Park, S. J. … Kim, S. R. (2014). Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of parkinson’s disease. Journal of Nutritional Biochemistry, 25(7), 801–806.
  • • Li, P., Wang, S., Guan, X., Liu, B., Wang, Y., Xu, K. … Zhang, K. (2013). Acute and 13 weeks subchronic toxicological evaluation of naringin in sprague-dawley rats. Food and Chemical Toxicology, 60, 1–9.
  • • Li, P., Wu, H., Wang, Y., Peng, W., & Su, W. (2020). Toxicological evaluation of naringin: acute, subchronic, and chronic toxicity in beagle dogs. Regulatory Toxicology and Pharmacology, 111, 104580.
  • • Mahmoudvand, H., Khaksarian, M., Ebrahimi, K., Shiravand, S., Jahanbakhsh, S., Niazi, M., & Nadri, S. (2020). Antinociceptive effects of green synthesized copper nanoparticles alone or in combination with morphine. Annals of Medicine and Surgery, 51, 31–36.
  • • Meshram, G. G., Kumar, A., Rizvi, W., Tripathi, C. D., & Khan, R. A. (2015). Central analgesic activity of the aqueous and ethanolic extracts of the leaves of albizia lebbeck: role of the GABAergic and serotonergic pathways. Zeitschrift für Naturforschung, 70(1-2), 25–30.
  • • Moniruzzaman, M., & Imam, M. Z. (2014). Evaluation of antinociceptive effect of methanolic extract of leaves of crataeva nurvala buch.-ham. BMC Complementary Medicine and Therapies, 14, 354.
  • • Nagi, K., Pineyro, G., Swayne, L. A., Tian, L., & Dascal, N. (2014). Kir3 channel signaling complexes: focus on opioid receptor signaling. Frontiers in Cellular Neuroscience, 8(186), 1–15.
  • • Naser, P. V., & Kuner, R. (2018). Molecular, cellular and circuit basis of cholinergic modulation of pain. Neuroscience, 387, 135–148.
  • • Nissen, N. I., Anderson, K. R., Wang, H., Lee, H. S., Garrison, C., Eichelberger, S. A. ... Miwa, J. M. (2018). Augmenting the antinociceptive effects of nicotinic acetylcholine receptor activity through lynx1 modulation, Plos One, 13(7), e0199643
  • • Okumura, T., Nozu, T., Kumei, S., Takakusaki, K., Miyagishi, S., & Ohhira, M. (2015). Involvement of the dopaminergic system in the central orexin-induced antinociceptive action against colonic distension in conscious rats. Neuroscience Letters, 605, 34–38.
  • • Oliveira, P. de A., de Almeida, T. B., de Oliveira, R. G., Gonçalves, G. M., de Oliveira, J. M., Alves dos Santos, B. B. … Marinho, B. G. (2018). Evaluation of the antinociceptive and anti-inflammatory activities of piperic acid: Involvement of the cholinergic and vanilloid systems. European Journal of Pharmacology, 834, 54–64.
  • • Shytle, R. D., Penny, E., Silver, A. A., Goldman, J., Sanberg, P. R., & Repair, B. (2002). Mecamylamine (Inversine): an old antihypertensive with new research directions. Journal of Human Hypertension, 16, 453–457.
  • • Sousa, F. S. S., Anversa, R. G., Birmann, P. T., de Souza, M. N., Balaguez, R., Alves, D. ... Savegnago, L. (2017). Contribution of dopaminergic and noradrenergic systems in the antinociceptive effect of α-(phenylalanyl) acetophenone. Pharmacological Reports, 69(5), 871–877.
  • • Tdulu, T. D., Kanui, T. I., Towett, P. K., Maloiy, G. M., & Abelson, K. S. (2014). The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber). In Vivo (Athens, Greece), 28(1), 39–48.
  • • Xue, N., Wu, X., Wu, L., Li, L., & Wang, F. (2019). Antinociceptive and anti-inflammatory effect of naringenin in different nociceptive and inflammatory mice models. Life Sciences, 217, 148–154.
  • • Yow, T. T., Pera, E., Absalom, N., Heblinski, M., Johnston, G. A., Hanrahan, J. R., & Chebib, M. (2011). Naringin directly activates inwardly rectifying potassium channels at an overlapping binding site to tertiapin-Q. British Journal of Pharmacology, 163(5), 1017–1033.
  • • Zeng, X., Su, W., Zheng, Y., He, Y., He, Y., Rao, H. ... Yao, H. (2019). Pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats. Frontiers in Pharmacology, 10, 34.
Year 2021, Volume: 51 Issue: 2, 204 - 211, 31.08.2021

Abstract

Project Number

2020/033

References

  • • Abubakar, A., Nazifi, A. B., Odoma, S., Shehu, S., & Danjuma, N. M. (2020). Antinociceptive activity of methanol extract of Chlorophytum alismifolium tubers in murine model of pain: Possible involvement of α2-adrenergic receptor and KATP channels. Journal of Traditional and Complementary Medicine, 10(1), 1–6.
  • • 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. Frontiers in Neurology, 8(69), 1–12.
  • • Alghamdi, S. (2020) Antinociceptive effect of the citrus flavonoid eriocitrin on postoperative pain conditions. Journal of Pain Research, 13, 805-815.
  • • AlSharari, S. D., Carroll, F. I., McIntosh, J. M., & Damaj, M. I. (2012). The antinociceptive effects of nicotinic partial agonists varenicline and sazetidine-A in murine acute and tonic pain models. Journal of Pharmacology and Experimental Therapeutics, 342(3), 742–749.
  • • Araújo, I. W. F., Chaves, H. V., Pachêco, J. M., Val, D. R., Vieira, L. V., Santos, R. … Benevides, N. M. B. (2017). Role of central opioid on the antinociceptive effect of sulfated polysaccharide from the red seaweed Solieria filiformis in induced temporomandibular joint pain. International Immunopharmacology, 44, 160–167.
  • • Arihan, O., Boz, M., Iskit, A. B., & Ilhan, M. (2009). Antinociceptive activity of coniine in mice. Journal of Ethnopharmacology, 125, 274–278.
  • • Arslan, R., Aydin, S., Samur, D. N., & Bektas, N. (2018). The possible mechanisms of protocatechuic acid-induced central analgesia. Saudi Pharmaceutical Journal, 26(4), 541–545.
  • • Bektaş, N., & Arslan, R. (2016). The centrally-mediated mechanisms of action of ferulic acid–induced antinociception. Marmara Pharmaceutical Journal, 20, 303–310.
  • • Ben-Azu, B., Nwoke, E. E., Umukoro, S., Aderibigbe, A. O., Ajayi, A. M., & Iwalewa, E. O. (2018). Evaluation of the neurobehavioral properties of naringin in swiss mice. Drug Research, 68(08), 465– 474.
  • • Bharti, S., Rani, N., Krishnamurthy, B., & Arya, D. S. (2014). Preclinical evidence for the pharmacological actions of naringin: A Review. Planta Medica, 80(06), 437–451.
  • • Chen, R., Qi, Q. L., Wang, M. T., & Li, Q. Y. (2016). Therapeutic potential of naringin: an overview. Pharmaceutical Biology, 54(12), 3203–3210.
  • • Chung, T. W., Li, S., Lin, C. C., & Tsai, S. W. (2019). Antinociceptive and anti-inflammatory effects of the citrus flavanone naringenin. Tzu-Chi Medical Journal, 31(2), 81–85.
  • • Dallazen, J. L., da Silva, C. F., Hamm, L., Córdova, M. M., Santos, A. R., Werner, M. F. P., & Baggio, C. H. (2017). Further antinociceptive properties of naringenin on acute and chronic pain in mice. Natural Product Communications, 12(9), 11443–1446.
  • • Dziechciaż, M., Balicka-Adamik, L., & Filip, R. (2013). The problem of pain in old age. Annals of Agricultural and Environmental Medicine, 20(1), 35–38.
  • • Hui, W., Xu, Y. S., Wang, M. L., Cheng, C., Bian, R., Yuan, H. … Zhou, H. (2017). Protective effect of naringin against the LPS-induced apoptosis of PC12 cells: implications for the treatment of neurodegenerative disorders. International Journal of Molecular Medicine, 39(4), 819–830.
  • • Jung, U. J., & Kim, S. R. (2014). Effects of naringin, A flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regeneration Research, 9(16), 1514–1517.
  • • Jung, U. J., Leem, E., & Kim, S. R. (2014). Naringin: a protector of the nigrostriatal dopaminergic projection. Experimental Neurobiology, 23(2), 124–129.
  • • Kola, P. K., Akula, A., NissankaraRao, L. S., & Danduga, R. (2017). Protective effect of naringin on pentylenetetrazole (PTZ)-induced kindling; possible mechanisms of antikindling, memory improvement, and neuroprotection. Epilepsy & Behavior, 75, 114–126
  • • Leem, E., Nam, J. H., Jeon, M. T., Shin, W. H., Won, S. Y., Park, S. J. … Kim, S. R. (2014). Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of parkinson’s disease. Journal of Nutritional Biochemistry, 25(7), 801–806.
  • • Li, P., Wang, S., Guan, X., Liu, B., Wang, Y., Xu, K. … Zhang, K. (2013). Acute and 13 weeks subchronic toxicological evaluation of naringin in sprague-dawley rats. Food and Chemical Toxicology, 60, 1–9.
  • • Li, P., Wu, H., Wang, Y., Peng, W., & Su, W. (2020). Toxicological evaluation of naringin: acute, subchronic, and chronic toxicity in beagle dogs. Regulatory Toxicology and Pharmacology, 111, 104580.
  • • Mahmoudvand, H., Khaksarian, M., Ebrahimi, K., Shiravand, S., Jahanbakhsh, S., Niazi, M., & Nadri, S. (2020). Antinociceptive effects of green synthesized copper nanoparticles alone or in combination with morphine. Annals of Medicine and Surgery, 51, 31–36.
  • • Meshram, G. G., Kumar, A., Rizvi, W., Tripathi, C. D., & Khan, R. A. (2015). Central analgesic activity of the aqueous and ethanolic extracts of the leaves of albizia lebbeck: role of the GABAergic and serotonergic pathways. Zeitschrift für Naturforschung, 70(1-2), 25–30.
  • • Moniruzzaman, M., & Imam, M. Z. (2014). Evaluation of antinociceptive effect of methanolic extract of leaves of crataeva nurvala buch.-ham. BMC Complementary Medicine and Therapies, 14, 354.
  • • Nagi, K., Pineyro, G., Swayne, L. A., Tian, L., & Dascal, N. (2014). Kir3 channel signaling complexes: focus on opioid receptor signaling. Frontiers in Cellular Neuroscience, 8(186), 1–15.
  • • Naser, P. V., & Kuner, R. (2018). Molecular, cellular and circuit basis of cholinergic modulation of pain. Neuroscience, 387, 135–148.
  • • Nissen, N. I., Anderson, K. R., Wang, H., Lee, H. S., Garrison, C., Eichelberger, S. A. ... Miwa, J. M. (2018). Augmenting the antinociceptive effects of nicotinic acetylcholine receptor activity through lynx1 modulation, Plos One, 13(7), e0199643
  • • Okumura, T., Nozu, T., Kumei, S., Takakusaki, K., Miyagishi, S., & Ohhira, M. (2015). Involvement of the dopaminergic system in the central orexin-induced antinociceptive action against colonic distension in conscious rats. Neuroscience Letters, 605, 34–38.
  • • Oliveira, P. de A., de Almeida, T. B., de Oliveira, R. G., Gonçalves, G. M., de Oliveira, J. M., Alves dos Santos, B. B. … Marinho, B. G. (2018). Evaluation of the antinociceptive and anti-inflammatory activities of piperic acid: Involvement of the cholinergic and vanilloid systems. European Journal of Pharmacology, 834, 54–64.
  • • Shytle, R. D., Penny, E., Silver, A. A., Goldman, J., Sanberg, P. R., & Repair, B. (2002). Mecamylamine (Inversine): an old antihypertensive with new research directions. Journal of Human Hypertension, 16, 453–457.
  • • Sousa, F. S. S., Anversa, R. G., Birmann, P. T., de Souza, M. N., Balaguez, R., Alves, D. ... Savegnago, L. (2017). Contribution of dopaminergic and noradrenergic systems in the antinociceptive effect of α-(phenylalanyl) acetophenone. Pharmacological Reports, 69(5), 871–877.
  • • Tdulu, T. D., Kanui, T. I., Towett, P. K., Maloiy, G. M., & Abelson, K. S. (2014). The effects of oxotremorine, epibatidine, atropine, mecamylamine and naloxone in the tail-flick, hot-plate, and formalin tests in the naked mole-rat (Heterocephalus glaber). In Vivo (Athens, Greece), 28(1), 39–48.
  • • Xue, N., Wu, X., Wu, L., Li, L., & Wang, F. (2019). Antinociceptive and anti-inflammatory effect of naringenin in different nociceptive and inflammatory mice models. Life Sciences, 217, 148–154.
  • • Yow, T. T., Pera, E., Absalom, N., Heblinski, M., Johnston, G. A., Hanrahan, J. R., & Chebib, M. (2011). Naringin directly activates inwardly rectifying potassium channels at an overlapping binding site to tertiapin-Q. British Journal of Pharmacology, 163(5), 1017–1033.
  • • Zeng, X., Su, W., Zheng, Y., He, Y., He, Y., Rao, H. ... Yao, H. (2019). Pharmacokinetics, tissue distribution, metabolism, and excretion of naringin in aged rats. Frontiers in Pharmacology, 10, 34.
There are 35 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Original Article
Authors

Mehmet Evren Okur 0000-0001-7706-6452

Çinel Köksal Karayıldırım This is me 0000-0002-8431-1230

Project Number 2020/033
Publication Date August 31, 2021
Submission Date January 23, 2021
Published in Issue Year 2021 Volume: 51 Issue: 2

Cite

APA Okur, M. E., & Köksal Karayıldırım, Ç. (2021). Central possible antinociceptive mechanism of naringin. İstanbul Journal of Pharmacy, 51(2), 204-211.
AMA Okur ME, Köksal Karayıldırım Ç. Central possible antinociceptive mechanism of naringin. iujp. August 2021;51(2):204-211.
Chicago Okur, Mehmet Evren, and Çinel Köksal Karayıldırım. “Central Possible Antinociceptive Mechanism of Naringin”. İstanbul Journal of Pharmacy 51, no. 2 (August 2021): 204-11.
EndNote Okur ME, Köksal Karayıldırım Ç (August 1, 2021) Central possible antinociceptive mechanism of naringin. İstanbul Journal of Pharmacy 51 2 204–211.
IEEE M. E. Okur and Ç. Köksal Karayıldırım, “Central possible antinociceptive mechanism of naringin”, iujp, vol. 51, no. 2, pp. 204–211, 2021.
ISNAD Okur, Mehmet Evren - Köksal Karayıldırım, Çinel. “Central Possible Antinociceptive Mechanism of Naringin”. İstanbul Journal of Pharmacy 51/2 (August 2021), 204-211.
JAMA Okur ME, Köksal Karayıldırım Ç. Central possible antinociceptive mechanism of naringin. iujp. 2021;51:204–211.
MLA Okur, Mehmet Evren and Çinel Köksal Karayıldırım. “Central Possible Antinociceptive Mechanism of Naringin”. İstanbul Journal of Pharmacy, vol. 51, no. 2, 2021, pp. 204-11.
Vancouver Okur ME, Köksal Karayıldırım Ç. Central possible antinociceptive mechanism of naringin. iujp. 2021;51(2):204-11.