The Effect Of Indigofera Tinctoria Extract On Cdk5 Expression And Signs Of Inflammation In A Chronic Pain Rat Model
DOI:
https://doi.org/10.29303/jku.v12i4.1010Keywords:
Indigofera tinctoria; Cdk5; analgesic, anti-inflammatoryAbstract
Chronic pain is a challenging case that requires efforts to find effective drugs with minimal side effects. In last decade, Cdk5 become a potential target of chronic pain traetment. Indigofera tinctoria is a plant that grows a lot in Indonesia and has been used for various purposes. This plant is proven to contain indirubin which was proven as a Cdk5 (Cycline dependent kinases 5) inhibitor. The Objective of this research is analyze the effect of Indigofera tinctoria in a chronic pain model. This research was involving 35 rats divided into 5 groups. CFA (Complete Freud’s Adjuvant) solution was injected into the right plantar area to make a chronic pain model. Indigofera tinctoria extract was given orally in 200 mg/KgBW (D1 group), 300 mg/KgBW (D2 group), and 400 mg/KgBW (D3 group). Treatment was given for 7 days after the sign of chronic inflammation were detected (28 days after CFA induction). The analgesic effect was determined by pain latency on the hotplate, the anti-inflammatory effect was evaluated by measuring the hind paw volume. The Cdk5 expression was detected at the dorsal root ganglia by immunohistochemistry method. Results: The mean pain latency value of the D2 and D3 groups was greater than that of the other groups. The inflammatory sign in the treatment group was smaller and significantly different than in the positive control group. Cdk5 expression is not statistically different, however, the treatment group showed a lower Cdk5 expression. Conclusions: Indigofera extract has potential analgesic, anti-inflammatory, and Cdk5 inhibitory effects.
References
Al- Rasyid, MYA ; Saade, A. T., & I. (2019). Effect of Indigofera Leaf Meal on the Carcass Quality of Broiler. Jurnal Agrisistem, 15(1), 29–34.
Blažević, T., Heiss, E. H., Atanasov, A. G., Breuss, J. M., Dirsch, V. M., & Uhrin, P. (2015). Indirubin and Indirubin Derivatives for Counteracting Proliferative Diseases. Evidence-Based Complementary and Alternative Medicine, 2015. https://doi.org/10.1155/2015/654098
Fang-Hu, Zhang, H. H., Yang, B. X., Huang, J. L., Shun, J. L., Kong, F. J., Peng-Xu, Chen, Z. G., & Lu, J. M. (2015). Cdk5 contributes to inflammation-induced thermal hyperalgesia mediated by the p38 MAPK pathway in microglia. Brain Research, 1619, 166–175. https://doi.org/10.1016/j.brainres.2015.01.056
Gobina, I., Villberg, J., Välimaa, R., Tynjälä, J., Whitehead, R., Cosma, A., Brooks, F., Cavallo, F., Ng, K., de Matos, M. G., & Villerusa, A. (2019). Prevalence of self-reported chronic pain among adolescents: Evidence from 42 countries and regions. European Journal of Pain (London, England), 23(2), 316–326. https://doi.org/10.1002/ejp.1306
Gomez, K., Vallecillo, T. G. M., Moutal, A., Perez-Miller, S., Delgado-Lezama, R., Felix, R., & Khanna, R. (2020). The role of cyclin-dependent kinase 5 in neuropathic pain. Pain, 161(12), 2674–2689. https://doi.org/10.1097/j.pain.0000000000002027
Keziah, J. E. J., Sharmila, S., & Rebecca, L. J. (2016). Effect of heavy metals and UV irradiation on the production of flavonoids in Indigofera tinctoria. International Journal of Pharmaceutical Sciences Review and Research, 39(2), 104–107.
Kumar Pareek, T. (2012). Cdk5: An Emerging Kinase in Pain Signaling. Brain Disorders & Therapy, 01(s1). https://doi.org/10.4172/2168-975x.s1-003
Laitonjam, W. S., & Wangkheirakpam, S. D. (2011). Comparative study of the major components of the indigo dye obtained from Strobilanthes flaccidifolius Nees. and Indigofera tinctoria Linn. International Journal of Plant Physiology and Biochemistry, 3(7), 108–116. http://www.academicjournals.org/ijppb
Leclerc, S., Garnier, M., Hoessel, R., Marko, D., Bibb, J. A., Snyder, G. L., Greengard, P., Biernat, J., Wu, Y. Z., Mandelkow, E. M., Eisenbrand, G., & Meijer, L. (2001). Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease. A property common to most cyclin-dependent kinase inhibitors? The Journal of Biological Chemistry, 276(1), 251—260. https://doi.org/10.1074/jbc.m002466200
Liu, J., Yang, J., Xu, Y., Guo, G., Cai, L., Wu, H., Zhao, Y., & Zhang, X. (2017). Roscovitine, a CDK5 Inhibitor, Alleviates Sevoflurane-Induced Cognitive Dysfunction via Regulation Tau/GSK3β and ERK/PPARγ/CREB Signaling. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 44(2), 423–435. https://doi.org/10.1159/000485008
Lynch, M. E. (2016). Cannabinoids in the management of chronic pain: A front line clinical perspective. Journal of Basic and Clinical Physiology and Pharmacology, 27(3), 189–191. https://doi.org/10.1515/jbcpp-2015-0059
Mills, S. E. E., Nicolson, K. P., & Smith, B. H. (2019). Chronic pain: a review of its epidemiology and associated factors in population-based studies. British Journal of Anaesthesia, 123(2), e273–e283. https://doi.org/10.1016/j.bja.2019.03.023
Muzayyinah. (2014). Indigofera: “Kini dan Nanti.” Bioedukasi: Jurnal Pendidikan Biologi, 7(2), 23. https://doi.org/10.20961/bioedukasi-uns.v7i2.2932
Pfänder, P., Fidan, M., Burret, U., Lipinski, L., & Vettorazzi, S. (2019). Cdk5 Deletion Enhances the Anti-inflammatory Potential of GC-Mediated GR Activation During Inflammation. 10(July), 1–13. https://doi.org/10.3389/fimmu.2019.01554
Qorib, M. F., Reny, I., Sudjarwo, S. A., & Basori, A. (2021). The Role of Cdk5 and TRPV1 in Meloxicam Resistance Signal Transduction in Rat Experiencing Chronic Pain. Indian Journal of Forensic Medicine & Toxicology, 15(3), 3775–3784. https://doi.org/10.37506/ijfmt.v15i3.15884
Schultz, M. J., & Licciardone, J. C. (2022). The effect of long-term opioid use on back-speci fi c disability and health-related quality of life in patients with chronic low back pain. 122(9), 469–479.
Schwan, J., Sclafani, J., & Tawfik, V. L. (2019). Chronic Pain Management in the Elderly. Anesthesiology Clinics, 37(3), 547–560. https://doi.org/10.1016/j.anclin.2019.04.012
Tan, V. B. C., Lim, K., Tay, T. E., & Zhuang, S. (2007). Study of the inhibition of cyclin-dependent kinases with roscovitine and indirubin-3 ’-oxime from molecular dynamics simulations. Journal of Molecular Modeling, 13, 79–89. https://doi.org/10.1007/s00894-006-0127-x
Utreras, E., Terse, A., Keller, J., Iadarola, M. J., & Kulkarni, A. B. (2011). Resveratrol inhibits Cdk5 activity through regulation of p35 expression. Molecular Pain, 7. https://doi.org/10.1186/1744-8069-7-49
Wahyuningsih, S., Ramelan, A. H., Wardani, D. K., Aini, F. N., Sari, P. L., Tamtama, B. P. N., & Kristiawan, Y. R. (2017). Indigo Dye Derived from Indigofera Tinctoria as Natural Food Colorant. IOP Conference Series: Materials Science and Engineering, 193(1). https://doi.org/10.1088/1757-899X/193/1/012048
Wilkaniec, A., Gąssowska-Dobrowolska, M., Strawski, M., Adamczyk, A., & Czapski, G. A. (2018). Inhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity. Journal of Neuroinflammation, 15(1), 1. https://doi.org/10.1186/s12974-017-1027-y
Wu, J., Zhao, Z., Zhu, X., Renn, C. L., Dorsey, S. G., & Faden, A. I. (2016). Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury. Pain, 157(2), 488–503. https://doi.org/10.1097/j.pain.0000000000000393
Xing, B. M., Yang, Y. R., Du, J. X., Chen, H. J., Qi, C., Huang, Z. H., Zhang, Y., & Wang, Y. (2012). Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B. Journal of Neuroscience, 32(42), 14709–14721. https://doi.org/10.1523/JNEUROSCI.1634-12.2012
Al- Rasyid, MYA ; Saade, A. T., & I. (2019). Effect of Indigofera Leaf Meal on the Carcass Quality of Broiler. Jurnal Agrisistem, 15(1), 29–34.
Blažević, T., Heiss, E. H., Atanasov, A. G., Breuss, J. M., Dirsch, V. M., & Uhrin, P. (2015). Indirubin and Indirubin Derivatives for Counteracting Proliferative Diseases. Evidence-Based Complementary and Alternative Medicine, 2015. https://doi.org/10.1155/2015/654098
Fang-Hu, Zhang, H. H., Yang, B. X., Huang, J. L., Shun, J. L., Kong, F. J., Peng-Xu, Chen, Z. G., & Lu, J. M. (2015). Cdk5 contributes to inflammation-induced thermal hyperalgesia mediated by the p38 MAPK pathway in microglia. Brain Research, 1619, 166–175. https://doi.org/10.1016/j.brainres.2015.01.056
Gobina, I., Villberg, J., Välimaa, R., Tynjälä, J., Whitehead, R., Cosma, A., Brooks, F., Cavallo, F., Ng, K., de Matos, M. G., & Villerusa, A. (2019). Prevalence of self-reported chronic pain among adolescents: Evidence from 42 countries and regions. European Journal of Pain (London, England), 23(2), 316–326. https://doi.org/10.1002/ejp.1306
Gomez, K., Vallecillo, T. G. M., Moutal, A., Perez-Miller, S., Delgado-Lezama, R., Felix, R., & Khanna, R. (2020). The role of cyclin-dependent kinase 5 in neuropathic pain. Pain, 161(12), 2674–2689. https://doi.org/10.1097/j.pain.0000000000002027
Keziah, J. E. J., Sharmila, S., & Rebecca, L. J. (2016). Effect of heavy metals and UV irradiation on the production of flavonoids in Indigofera tinctoria. International Journal of Pharmaceutical Sciences Review and Research, 39(2), 104–107.
Kumar Pareek, T. (2012). Cdk5: An Emerging Kinase in Pain Signaling. Brain Disorders & Therapy, 01(s1). https://doi.org/10.4172/2168-975x.s1-003
Laitonjam, W. S., & Wangkheirakpam, S. D. (2011). Comparative study of the major components of the indigo dye obtained from Strobilanthes flaccidifolius Nees. and Indigofera tinctoria Linn. International Journal of Plant Physiology and Biochemistry, 3(7), 108–116. http://www.academicjournals.org/ijppb
Leclerc, S., Garnier, M., Hoessel, R., Marko, D., Bibb, J. A., Snyder, G. L., Greengard, P., Biernat, J., Wu, Y. Z., Mandelkow, E. M., Eisenbrand, G., & Meijer, L. (2001). Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease. A property common to most cyclin-dependent kinase inhibitors? The Journal of Biological Chemistry, 276(1), 251—260. https://doi.org/10.1074/jbc.m002466200
Liu, J., Yang, J., Xu, Y., Guo, G., Cai, L., Wu, H., Zhao, Y., & Zhang, X. (2017). Roscovitine, a CDK5 Inhibitor, Alleviates Sevoflurane-Induced Cognitive Dysfunction via Regulation Tau/GSK3β and ERK/PPARγ/CREB Signaling. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 44(2), 423–435. https://doi.org/10.1159/000485008
Lynch, M. E. (2016). Cannabinoids in the management of chronic pain: A front line clinical perspective. Journal of Basic and Clinical Physiology and Pharmacology, 27(3), 189–191. https://doi.org/10.1515/jbcpp-2015-0059
Mills, S. E. E., Nicolson, K. P., & Smith, B. H. (2019). Chronic pain: a review of its epidemiology and associated factors in population-based studies. British Journal of Anaesthesia, 123(2), e273–e283. https://doi.org/10.1016/j.bja.2019.03.023
Muzayyinah. (2014). Indigofera: “Kini dan Nanti.” Bioedukasi: Jurnal Pendidikan Biologi, 7(2), 23. https://doi.org/10.20961/bioedukasi-uns.v7i2.2932
Pfänder, P., Fidan, M., Burret, U., Lipinski, L., & Vettorazzi, S. (2019). Cdk5 Deletion Enhances the Anti-inflammatory Potential of GC-Mediated GR Activation During Inflammation. 10(July), 1–13. https://doi.org/10.3389/fimmu.2019.01554
Qorib, M. F., Reny, I., Sudjarwo, S. A., & Basori, A. (2021). The Role of Cdk5 and TRPV1 in Meloxicam Resistance Signal Transduction in Rat Experiencing Chronic Pain. Indian Journal of Forensic Medicine & Toxicology, 15(3), 3775–3784. https://doi.org/10.37506/ijfmt.v15i3.15884
Schultz, M. J., & Licciardone, J. C. (2022). The effect of long-term opioid use on back-speci fi c disability and health-related quality of life in patients with chronic low back pain. 122(9), 469–479.
Schwan, J., Sclafani, J., & Tawfik, V. L. (2019). Chronic Pain Management in the Elderly. Anesthesiology Clinics, 37(3), 547–560. https://doi.org/10.1016/j.anclin.2019.04.012
Tan, V. B. C., Lim, K., Tay, T. E., & Zhuang, S. (2007). Study of the inhibition of cyclin-dependent kinases with roscovitine and indirubin-3 ’-oxime from molecular dynamics simulations. Journal of Molecular Modeling, 13, 79–89. https://doi.org/10.1007/s00894-006-0127-x
Utreras, E., Terse, A., Keller, J., Iadarola, M. J., & Kulkarni, A. B. (2011). Resveratrol inhibits Cdk5 activity through regulation of p35 expression. Molecular Pain, 7. https://doi.org/10.1186/1744-8069-7-49
Wahyuningsih, S., Ramelan, A. H., Wardani, D. K., Aini, F. N., Sari, P. L., Tamtama, B. P. N., & Kristiawan, Y. R. (2017). Indigo Dye Derived from Indigofera Tinctoria as Natural Food Colorant. IOP Conference Series: Materials Science and Engineering, 193(1). https://doi.org/10.1088/1757-899X/193/1/012048
Wilkaniec, A., Gąssowska-Dobrowolska, M., Strawski, M., Adamczyk, A., & Czapski, G. A. (2018). Inhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity. Journal of Neuroinflammation, 15(1), 1. https://doi.org/10.1186/s12974-017-1027-y
Wu, J., Zhao, Z., Zhu, X., Renn, C. L., Dorsey, S. G., & Faden, A. I. (2016). Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury. Pain, 157(2), 488–503. https://doi.org/10.1097/j.pain.0000000000000393
Xing, B. M., Yang, Y. R., Du, J. X., Chen, H. J., Qi, C., Huang, Z. H., Zhang, Y., & Wang, Y. (2012). Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B. Journal of Neuroscience, 32(42), 14709–14721. https://doi.org/10.1523/JNEUROSCI.1634-12.2012
Yang, Y.-R., He, Y., Zhang, Y., Li, Y., Li, Y., Han, Y., Zhu, H., & Wang, Y. (2007). Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia. Pain, 127(1), 109–120. https://doi.org/https://doi.org/10.1016/j.pain.2006.08.008
Zhu, X., Yue, L., Fan, C., Liu, Y., Wang, Y., & Zhao, H. (2021). Mechanism of Cdk5-synaptophysin-SNARE pathway in acute and chronic inflammatory pain. American Journal of Translational Research, 13(3), 1075–1084.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Jurnal Kedokteran
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
