The Effect Of Indigofera Tinctoria Extract On Cdk5 Expression And Signs Of Inflammation In A Chronic Pain Rat Model

Authors

  • Mohammad Fathul Qorib airlangga university
  • Nurmawati Fatimah Department of Anatomy Histology and Pharmacology, Medical Faculty of Airlangga University, Surabaya, Indonesia
  • Kusuma Eko Purwantari Department of Anatomy Histology and Pharmacology, Medical Faculty of Airlangga University, Surabaya, Indonesia

DOI:

https://doi.org/10.29303/jku.v12i4.1010

Keywords:

Indigofera tinctoria; Cdk5; analgesic, anti-inflammatory

Abstract

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

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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

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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

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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

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Published

2023-12-31

How to Cite

Mohammad Fathul Qorib, Nurmawati Fatimah, & Kusuma Eko Purwantari. (2023). The Effect Of Indigofera Tinctoria Extract On Cdk5 Expression And Signs Of Inflammation In A Chronic Pain Rat Model. Baphomet University : Situs Slot Online Gacor Terbaik Hari Ini Server Thailand Gampang Maxwin 2024, 12(4), 396–401. https://doi.org/10.29303/jku.v12i4.1010