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Year 2025, Volume: 29 Issue: 5, 2017 - 2022, 01.09.2025
https://doi.org/10.12991/jrespharm.1765113

Abstract

References

  • [1] Ramos-Lima MJM, Brasileiro IC, Lima TL, Braga-Neto P. Quality of life after stroke: impact of clinical and sociodemographic factors. Clinics. 2018; 73: e418. https://doi.org/10.6061/clinics/2017/e418.
  • [2] Das UN. Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?. J Assoc Physicians India. 2005; 53: 623–627.
  • [3] Zhao L, Fang J, Zhou M, Zhou J, Yu L, Chen N, He L. Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population. BMC Neurol. 2019; 19 (1): 291. https://doi.org/10.1186/s12883-019-1505-1.
  • [4] Prakoso YA, Sigit M, Aliviameita A. Standardization of the simple methodology for experimentally induced ischemic stroke in rat models. World Vet J. 2023; 13 (4): 510-519. https://doi.org/10.54203/scil.2023.wvj54.
  • [5] Comin J and Kallmes D. Clopidogrel (plavix). AJNR Am J Neuroradiol. 2011; 32(11): 2002–2004. https://doi.org/10.3174/ajnr.A2913.
  • [6] Kuszynski DS and Lauver DA. Pleiotropic effects of clopidogrel. Purinergic Signal. 2022; 18(3): 253–265. https://doi.org/10.1007/s11302-022-09876-0.
  • [7] Yang Y, Huang Z, Zhang X. Efficacy and safety of clopidogrel and/or aspirin for ischemic stroke/transient ischemic attack: An overview of systematic reviews and meta-analysis. Medicine. 2021; 100 (50): e27804. https://doi.org/10.1097/MD.0000000000027804.
  • [8] Wilujeng S, Wirjaatmadja R, Prakoso YA. Effects of extraction, fermentation, and storage processes on the levels of choline derived from calabash fruit (Crescentia cujete L.). J Res Pharm. 2023; 27 (2): 620-626. https://doi.org/10.29228/jrp.344.
  • [9] Javaid S, Farooq T, Rehman Z, Afzal A, Ashraf W, Rasool MF, Alqahtani F, Alsanea S, Alasmari F, Alanazi MM, Alharbi M, Imran I. Dynamics of Choline-Containing Phospholipids in Traumatic Brain Injury and Associated Comorbidities. Int J Mol Sci. 2021;22(21):11313. https://doi.org/10.3390/ijms222111313.
  • [10] Hidayah JH, Prakoso YA, Widyarini S. Brain histopathological changes after treatment using calabash fruit (Crescentia cujete L.) in rat model with artificially induced ischemic stroke. Adv Anim Vet Sci. 2023; 11 (12): 2003- 2009. https://doi.org/10.17582/journal.aavs/2023/11.12.2003.2009.
  • [11] Xu Y, Liu Y, Li K, Yuan D, Yang S, Zhou L, Zhao Y, Miao S, Lv C, Zhao J. COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion. Mol Neurobiol. 2022;59(3):1619-1631. doi: 10.1007/s12035- 021-02706-1. Erratum in: Mol Neurobiol. 2022;59(12):7542-7543. https://doi.org/10.1007/s12035-021-02706-1.
  • [12] Oliveira-Filho J, Ornellas AC, Zhang CR, Oliveira LM, Araújo-Santos T, Borges VM, Ventura LM, Reis FJ, Aras R, Fernandes AM, Rosand J, Greenberg SM, Furie KL, Rost NS. COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease. J Stroke Cerebrovasc Dis. 2015;24(8):1817-1822. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.04.018.
  • [13] Merhi M, Demirdjian S, Hariri E, Sabbah N, Youhanna S, Ghassibe-Sabbagh M, Naoum J, Haber M, Othman R, Kibbani S, Chammas E, Kanbar R, Bayeh HE, Chami Y, Abchee A, Platt DE, Zalloua P, Khazen G. Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk. Inflamm Res. 2015;64(6):415- 422. https://doi.org/10.1007/s00011-015-0821-1.
  • [14] Kansakar U, Trimarco V, Mone P, Varzideh F, Lombardi A, Santulli G: Choline supplements: An update. Front Endocrinol. 2023; 14: 1148166. https://doi.org/10.3389/fendo.2023.1148166.
  • [15] Zhang N, Li Y, Feng Z. Inhibition effect of choline and parecoxib sodium on chronic constriction nerve injury- induced neuropathic pain in rats. BMC Anesthesiol. 2023;23(1):22. https://doi.org/10.1186/s12871-022-01913-0
  • [16] Tudor DV, Bâldea I, Lupu M, Kacso T, Kutasi E, Hopârtean A, Stretea R, Gabriela Filip A. COX-2 as a potential biomarker and therapeutic target in melanoma. Cancer Biol Med. 2020;17(1):20-31. https://doi.org/10.20892/j.issn.2095-3941.2019.0339.
  • [17] Paul M, Paul JW, Hinwood M, Hood RJ, Martin K, Abdolhoseini M, Johnson SJ, Pollack M, Nilsson M, Walker FR. Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice. Int J Mol Sci. 2023;24(14):11706. https://doi.org/10.3390/ijms241411706.
  • [18] Kral JB, Schrottmaier WC, Salzmann M, Assinger A. Platelet Interaction with Innate Immune Cells. Transfus Med Hemother. 2016;43(2):78-88. https://doi.org/10.1159/000444807.
  • [19] Kamarova M, Baig S, Patel H, Monks K, Wasay M, Ali A, Redgrave J, Majid A, Bell SM. Antiplatelet Use in Ischemic Stroke. Ann Pharmacother. 2022;56(10):1159-1173. https://doi.org/10.1177/10600280211073009.
  • [20] Xu LB, Yue JK, Korley F, Puccio AM, Yuh EL, Sun X, Rabinowitz M, Vassar MJ, Taylor SR, Winkler EA, Puffer RC, Deng H, McCrea M, Stein MB, Robertson CS, Levin HS, Dikmen S, Temkin NR, Giacino JT, Mukherjee P, Wang KKW, Okonkwo DO, Markowitz AJ, Jain S, Manley GT, Diaz-Arrastia R; TRACK-TBI Investigators. High- Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study. J Neurotrauma. 2021;38(7):918-927. https://doi.org/10.1089/neu.2020.7177.
  • [21] Finck T, Sperl P, Hernandez-Petzsche M, Boeckh-Behrens T, Maegerlein C, Wunderlich S, Zimmer C, Kirschke J, Berndt M. Inflammation in stroke: initial CRP levels can predict poor outcomes in endovascularly treated stroke patients. Front Neurol. 2023;14:1167549. https://doi.org/10.3389/fneur.2023.1167549.
  • [22] Sun Y, Venugopal J, Guo C, Fan Y, Li J, Gong Y, Chen YE, Zhang H, Eitzman DT. Clopidogrel Resistance in a Murine Model of Diet-Induced Obesity Is Mediated by the Interleukin-1 Receptor and Overcome With DT-678. Arterioscler Thromb Vasc Biol. 2020;40(6):1533-1542. https://doi.org/10.1161/atvbaha.120.314146.

Effects of fermented calabash fruit (Crescentia cujete L.) on the Nissl’s Body, C-RP and COX-2 in rat models with artificial-induced ischemic stroke

Year 2025, Volume: 29 Issue: 5, 2017 - 2022, 01.09.2025
https://doi.org/10.12991/jrespharm.1765113

Abstract

Ischemic stroke is an essential disease in human life that causes disability and death. Ischemic stroke is commonly treated using clopidogrel, which potentially causes various side effects. Hence, alternative therapy against ischemic stroke must be elucidated, and this study used fermented calabash fruit (FC) due to its choline compound. This study aimed to analyse the effects of FC in rat models with artificial-induced ischemic stroke. This study conducted an experiment involving 40 male Sprague Dawley rats that were divided as follows: K1 (sham-operated) and K2-K4 (artificial-induced ischemic stroke groups). While, K2 (untreated); K3 (FC); and K4 (clopidogrel). The serum and brain were tested using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry against C-RP and COX-2, respectively. The data was then tabulated and analysed using SPSS. The results indicated that utilisation of FC improves the presentation of Nissl’s bodies, increases the brain immune expression of COX-2, and decreases the level of circulatory COX-2 and C-RP compared to the other treatments (P<0.05). Surprisingly, the utilization of clopidogrel in group K4 promotes the decrease of level and immune expression of COX-2 compared to group K3 (P>0.05), but lower than group K2 (P<0.05). This study proved that FC benefits the Nissl’s body presentation, increasing the brain’s COX-2 immune expression and decreasing circulatory levels of C-RP and COX-2. An advance study is needed to evaluate the potential for toxicity and side effects after acute, subchronic, and chronic utilization of FCC.

References

  • [1] Ramos-Lima MJM, Brasileiro IC, Lima TL, Braga-Neto P. Quality of life after stroke: impact of clinical and sociodemographic factors. Clinics. 2018; 73: e418. https://doi.org/10.6061/clinics/2017/e418.
  • [2] Das UN. Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?. J Assoc Physicians India. 2005; 53: 623–627.
  • [3] Zhao L, Fang J, Zhou M, Zhou J, Yu L, Chen N, He L. Interaction between COX-1 and COX-2 increases susceptibility to ischemic stroke in a Chinese population. BMC Neurol. 2019; 19 (1): 291. https://doi.org/10.1186/s12883-019-1505-1.
  • [4] Prakoso YA, Sigit M, Aliviameita A. Standardization of the simple methodology for experimentally induced ischemic stroke in rat models. World Vet J. 2023; 13 (4): 510-519. https://doi.org/10.54203/scil.2023.wvj54.
  • [5] Comin J and Kallmes D. Clopidogrel (plavix). AJNR Am J Neuroradiol. 2011; 32(11): 2002–2004. https://doi.org/10.3174/ajnr.A2913.
  • [6] Kuszynski DS and Lauver DA. Pleiotropic effects of clopidogrel. Purinergic Signal. 2022; 18(3): 253–265. https://doi.org/10.1007/s11302-022-09876-0.
  • [7] Yang Y, Huang Z, Zhang X. Efficacy and safety of clopidogrel and/or aspirin for ischemic stroke/transient ischemic attack: An overview of systematic reviews and meta-analysis. Medicine. 2021; 100 (50): e27804. https://doi.org/10.1097/MD.0000000000027804.
  • [8] Wilujeng S, Wirjaatmadja R, Prakoso YA. Effects of extraction, fermentation, and storage processes on the levels of choline derived from calabash fruit (Crescentia cujete L.). J Res Pharm. 2023; 27 (2): 620-626. https://doi.org/10.29228/jrp.344.
  • [9] Javaid S, Farooq T, Rehman Z, Afzal A, Ashraf W, Rasool MF, Alqahtani F, Alsanea S, Alasmari F, Alanazi MM, Alharbi M, Imran I. Dynamics of Choline-Containing Phospholipids in Traumatic Brain Injury and Associated Comorbidities. Int J Mol Sci. 2021;22(21):11313. https://doi.org/10.3390/ijms222111313.
  • [10] Hidayah JH, Prakoso YA, Widyarini S. Brain histopathological changes after treatment using calabash fruit (Crescentia cujete L.) in rat model with artificially induced ischemic stroke. Adv Anim Vet Sci. 2023; 11 (12): 2003- 2009. https://doi.org/10.17582/journal.aavs/2023/11.12.2003.2009.
  • [11] Xu Y, Liu Y, Li K, Yuan D, Yang S, Zhou L, Zhao Y, Miao S, Lv C, Zhao J. COX-2/PGE2 Pathway Inhibits the Ferroptosis Induced by Cerebral Ischemia Reperfusion. Mol Neurobiol. 2022;59(3):1619-1631. doi: 10.1007/s12035- 021-02706-1. Erratum in: Mol Neurobiol. 2022;59(12):7542-7543. https://doi.org/10.1007/s12035-021-02706-1.
  • [12] Oliveira-Filho J, Ornellas AC, Zhang CR, Oliveira LM, Araújo-Santos T, Borges VM, Ventura LM, Reis FJ, Aras R, Fernandes AM, Rosand J, Greenberg SM, Furie KL, Rost NS. COX-2 rs20417 Polymorphism Is Associated with Stroke and White Matter Disease. J Stroke Cerebrovasc Dis. 2015;24(8):1817-1822. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.04.018.
  • [13] Merhi M, Demirdjian S, Hariri E, Sabbah N, Youhanna S, Ghassibe-Sabbagh M, Naoum J, Haber M, Othman R, Kibbani S, Chammas E, Kanbar R, Bayeh HE, Chami Y, Abchee A, Platt DE, Zalloua P, Khazen G. Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk. Inflamm Res. 2015;64(6):415- 422. https://doi.org/10.1007/s00011-015-0821-1.
  • [14] Kansakar U, Trimarco V, Mone P, Varzideh F, Lombardi A, Santulli G: Choline supplements: An update. Front Endocrinol. 2023; 14: 1148166. https://doi.org/10.3389/fendo.2023.1148166.
  • [15] Zhang N, Li Y, Feng Z. Inhibition effect of choline and parecoxib sodium on chronic constriction nerve injury- induced neuropathic pain in rats. BMC Anesthesiol. 2023;23(1):22. https://doi.org/10.1186/s12871-022-01913-0
  • [16] Tudor DV, Bâldea I, Lupu M, Kacso T, Kutasi E, Hopârtean A, Stretea R, Gabriela Filip A. COX-2 as a potential biomarker and therapeutic target in melanoma. Cancer Biol Med. 2020;17(1):20-31. https://doi.org/10.20892/j.issn.2095-3941.2019.0339.
  • [17] Paul M, Paul JW, Hinwood M, Hood RJ, Martin K, Abdolhoseini M, Johnson SJ, Pollack M, Nilsson M, Walker FR. Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice. Int J Mol Sci. 2023;24(14):11706. https://doi.org/10.3390/ijms241411706.
  • [18] Kral JB, Schrottmaier WC, Salzmann M, Assinger A. Platelet Interaction with Innate Immune Cells. Transfus Med Hemother. 2016;43(2):78-88. https://doi.org/10.1159/000444807.
  • [19] Kamarova M, Baig S, Patel H, Monks K, Wasay M, Ali A, Redgrave J, Majid A, Bell SM. Antiplatelet Use in Ischemic Stroke. Ann Pharmacother. 2022;56(10):1159-1173. https://doi.org/10.1177/10600280211073009.
  • [20] Xu LB, Yue JK, Korley F, Puccio AM, Yuh EL, Sun X, Rabinowitz M, Vassar MJ, Taylor SR, Winkler EA, Puffer RC, Deng H, McCrea M, Stein MB, Robertson CS, Levin HS, Dikmen S, Temkin NR, Giacino JT, Mukherjee P, Wang KKW, Okonkwo DO, Markowitz AJ, Jain S, Manley GT, Diaz-Arrastia R; TRACK-TBI Investigators. High- Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study. J Neurotrauma. 2021;38(7):918-927. https://doi.org/10.1089/neu.2020.7177.
  • [21] Finck T, Sperl P, Hernandez-Petzsche M, Boeckh-Behrens T, Maegerlein C, Wunderlich S, Zimmer C, Kirschke J, Berndt M. Inflammation in stroke: initial CRP levels can predict poor outcomes in endovascularly treated stroke patients. Front Neurol. 2023;14:1167549. https://doi.org/10.3389/fneur.2023.1167549.
  • [22] Sun Y, Venugopal J, Guo C, Fan Y, Li J, Gong Y, Chen YE, Zhang H, Eitzman DT. Clopidogrel Resistance in a Murine Model of Diet-Induced Obesity Is Mediated by the Interleukin-1 Receptor and Overcome With DT-678. Arterioscler Thromb Vasc Biol. 2020;40(6):1533-1542. https://doi.org/10.1161/atvbaha.120.314146.
There are 22 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Yos Adı Prakoso 0000-0003-4908-6661

Achmadi Susilo This is me 0000-0003-2504-2891

Sitarina Widyarini This is me 0000-0003-4461-8454

Puput Ade Wahyuningtyas This is me 0009-0002-5378-8551

Jasir Hakim Hidayah This is me 0000-0001-9457-5558

Publication Date September 1, 2025
Submission Date August 29, 2024
Acceptance Date October 4, 2024
Published in Issue Year 2025 Volume: 29 Issue: 5

Cite

APA Prakoso, Y. A., Susilo, A., Widyarini, S., … Wahyuningtyas, P. A. (2025). Effects of fermented calabash fruit (Crescentia cujete L.) on the Nissl’s Body, C-RP and COX-2 in rat models with artificial-induced ischemic stroke. Journal of Research in Pharmacy, 29(5), 2017-2022. https://doi.org/10.12991/jrespharm.1765113
AMA Prakoso YA, Susilo A, Widyarini S, Wahyuningtyas PA, Hidayah JH. Effects of fermented calabash fruit (Crescentia cujete L.) on the Nissl’s Body, C-RP and COX-2 in rat models with artificial-induced ischemic stroke. J. Res. Pharm. September 2025;29(5):2017-2022. doi:10.12991/jrespharm.1765113
Chicago Prakoso, Yos Adı, Achmadi Susilo, Sitarina Widyarini, Puput Ade Wahyuningtyas, and Jasir Hakim Hidayah. “Effects of Fermented Calabash Fruit (Crescentia Cujete L.) on the Nissl’s Body, C-RP and COX-2 in Rat Models With Artificial-Induced Ischemic Stroke”. Journal of Research in Pharmacy 29, no. 5 (September 2025): 2017-22. https://doi.org/10.12991/jrespharm.1765113.
EndNote Prakoso YA, Susilo A, Widyarini S, Wahyuningtyas PA, Hidayah JH (September 1, 2025) Effects of fermented calabash fruit (Crescentia cujete L.) on the Nissl’s Body, C-RP and COX-2 in rat models with artificial-induced ischemic stroke. Journal of Research in Pharmacy 29 5 2017–2022.
IEEE Y. A. Prakoso, A. Susilo, S. Widyarini, P. A. Wahyuningtyas, and J. H. Hidayah, “Effects of fermented calabash fruit (Crescentia cujete L.) on the Nissl’s Body, C-RP and COX-2 in rat models with artificial-induced ischemic stroke”, J. Res. Pharm., vol. 29, no. 5, pp. 2017–2022, 2025, doi: 10.12991/jrespharm.1765113.
ISNAD Prakoso, Yos Adı et al. “Effects of Fermented Calabash Fruit (Crescentia Cujete L.) on the Nissl’s Body, C-RP and COX-2 in Rat Models With Artificial-Induced Ischemic Stroke”. Journal of Research in Pharmacy 29/5 (September2025), 2017-2022. https://doi.org/10.12991/jrespharm.1765113.
JAMA Prakoso YA, Susilo A, Widyarini S, Wahyuningtyas PA, Hidayah JH. Effects of fermented calabash fruit (Crescentia cujete L.) on the Nissl’s Body, C-RP and COX-2 in rat models with artificial-induced ischemic stroke. J. Res. Pharm. 2025;29:2017–2022.
MLA Prakoso, Yos Adı et al. “Effects of Fermented Calabash Fruit (Crescentia Cujete L.) on the Nissl’s Body, C-RP and COX-2 in Rat Models With Artificial-Induced Ischemic Stroke”. Journal of Research in Pharmacy, vol. 29, no. 5, 2025, pp. 2017-22, doi:10.12991/jrespharm.1765113.
Vancouver Prakoso YA, Susilo A, Widyarini S, Wahyuningtyas PA, Hidayah JH. Effects of fermented calabash fruit (Crescentia cujete L.) on the Nissl’s Body, C-RP and COX-2 in rat models with artificial-induced ischemic stroke. J. Res. Pharm. 2025;29(5):2017-22.