Antioxidant and anti hyperalgesia activity of ethanol extract and fraction from red ginger (Zingiber officinale var. Rubrum) in early painful diabetic neuropathy mice
DOI:
https://doi.org/10.46542/pe.2024.249.4957Keywords:
Hyperalgesia, Hyperglycemia, Oxidative stress, Shogaol, Spinal cordAbstract
Background: Gingerol and shogaol are two major bio-components of Zingiber officinale var. Rubrum (red ginger) has been widely reported as an antioxidant crucial in painful diabetic neuropathy (PDN).
Objective: Determines the activity of the ethanolic extract of red ginger rhizome and its fraction by in vitro antioxidant and the in vivo study in PDN mice.
Method: Red ginger was extracted using ethanol and fractionated with n-hexane, chloroform, ethyl acetate, and n-butanol. The antioxidant was tested using DPPH and CUPRAC. Diabetes was induced using alloxan 225 mg/kg BW ip in male BALB/c mice. After 14 days, mice were randomly divided into normal, diabetic, ethanol extract, chloroform fraction, ethyl acetate fraction on the same dose of 400 mg/kg BW, metformin (200 mg/kg BW), and gabapentin (100 mg/kg BW). Treatments were given orally, once daily, for 21 days. Latency time and blood glucose levels were measured every week. Histology of the spinal cord was analysed using Hematoxylin-eosin staining.
Result: The ethyl acetate fraction had the best antioxidant activity using DPPH (IC50 13.93 ± 0.06) and CUPRAC (IC50 4.07 ± 0.06). This fraction showed the most potent ability to decrease BGL (69.78 ± 18.36%), same as metformin, and hyperalgesia (59.34 ± 7.90%) better than gabapentin. This treatment repaired the spinal cord by reducing the number of inflammatory cells and neuron degeneration in PDN mice.
Conclusion: The EERG of 400 mg/kg BW significantly affects arthritis-induced hyperalgesia.
References
Apak, R., Guclu, K., Demirata, B., Ozyurek, M., Celik, S. E., & Bektasoglu, B. (2007). Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules, 160, 1496‒1547.
Aslam, A., Singh, J., & Rajbhandari, S. (2014). Pathogenesis of painful diabetic neuropathy. Pain Research and Treatment, 412041.
Azizah, N., Purnamaningsih, S. L., & Fajriani, S. (2019). Land characteristics impact productivity and quality of ginger (Zingiber officinale Rosc) in Java, Indonesia. AGRIVITA Journal of Agricultural Science, 41(3), 439‒49.
Bai, H-P., Liu, P., Wu, Y-M., Guo, W-Y., Guo, X-Y., & Wang, X-L. (2014). Activation of spinal GABAB receptors normalizes N-methyl-ᴅ-aspartate receptor in diabetic neuropathy. Journal of Neurological Sciences, 341(1-2), 68‒72.
Fajrin, F. A., Nurrochmad, A., Nugroho, A. E., & Susilowati, R. (2019). The improvement of pain behavior and sciatic nerves morphology in mice model of painful diabetic neuropathy upon administration of ginger (Zingiber officinale Roscoe.) extract and its pungent compound, 6-shogaol. J Nat Sc Biol Med, 10, 149-156.
Fajrin, F. A., Nurrochmad, A., Nugroho, A. E., & Susilowati, R. (2020). Ginger extract and its compound, 6-shogaol, attenuates painful diabetic neuropathy in mice via reducing TRPV1 and NMDAR2B expressions in the spinal cord. Journal of Ethnopharmacology, 249(2020), 112396.
Feldman, E. L., Callaghan, B. C., Pop-Busui, R., Zochodne, D. W., Wright, D. E., Bennett, D. L., Bril, V., Russell, J. W, & Viswanathan, V. (2019). Diabetic neuropathy. Nature Reviews: Disease Primer, 5, 41.
Haroen, U., Syafwan, S., Kurniawan, K., & Budiansyah, A. (2024). Determination of total phenolics, flavonoids, and testing of antioxidant and antibacterial activities of red ginger (Zingiber officinale var. Rubrum). J Adv Vet Anim Res, 11(1), 114‒124.
Ighodaro, O. M., Adeosun, A. M., & Akinloye, O. A. (2017). Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in experimental studies. Medicina, 53(2017), 365‒374.
International Diabetes Federation. (2019). IDF Diabetes Atlas 9th edition. International Diabetes Federation, Brussels, Belgium.
Kaur, S., Pandhi, P., & Dutta, P. (2011). Painful diabetic neuropathy: An update. Annals of Neurosciences, 18(4), 168‒175.
Kedare, S. B., & Singh, R. P. (2011). Genesis and development of DPPH method of antioxidant assay. J Food Sci Technol, 48(4), 412–422.
Kizhakkayil, J., & Sasikumar, B. (2011). Diversity, characterization, and utilization of ginger: A review. Plant Genetic Resources: Characterization and Utilization, 9(3), 464–77.
Luongo, L., Costa, B., D'Agostino, B., Guida, F., Comelli, F., Gatta, L., Matteis, M., Sullo, N., De Petrocellis, L., de Novelis, V., & Maione, S. (2012). Palvanil, a non-pungent capsaicin analogue, inhibits inflammatory and neuropathic pain with little effects on bronchopulmonary function and body temperature. Pharmacol. Res, 66, 243‒250.
Mao, Q-Q., Xu, X-Y., Cao, S-Y., Gan, R-Y., Corke, H., Beta, T., & Li, H-B. (2019). Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods, 8, 185.
Oboh, G., Ademiluyi, A. O., & Akinyemi, A. J. (2012a). Inhibition of acetylcholinesterase activities and some pro-oxidant induced lipid peroxidation in rat brain by two varieties of ginger (Zingiber officinale). Experimental and Toxicologic Pathology, 64(2012), 315‒319.
Oboh, G., Akinyemi, A. J., & Ademiluyi, A. O. (2012b). Antioxidant and inhibitory effect of red ginger (Zingiber officinale var. Rubra) and white ginger (Zingiber officinale Roscoe) on Fe2+ induced lipid peroxidation in rat brain in vitro. Experimental and Toxicologic Pathology, 64(2012), 31‒36.
Pabbidi, R. M., Yu, S-Q., Peng, S., Khardori, R., Pauza, M. E., & Premkumar, L. S. (2008). Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity. Mol. Pain, 4, 9.
Pang, L., Lian, X., Liu, H., Zhang, Y., Li, Q., Cai, Y., Ma, H., & Yu, X. (2020). Understanding diabetic neuropathy: focus on oxidative stress. Oxidative Medicine and Cellular Longevity, 9524635.
Rackova, L., Cupakova, M., Tazky, A., Micova, J., Kolek, E., & Kostalova, D. (2013). Redox properties of ginger extracts: Perspectives of use of Zingiber officinale Rosc. as antidiabetic agent. Interdiscip Toxicol, 6(1), 26–33.
Sampath, C., Rashid, M. R., Sang, S., & Ahmedna, M. (2017). Specific bioactive compounds in ginger and apple alleviate hyperglycemia in mice with high fat diet-induced obesity via Nrf2 mediated pathway. Food Chem, 226, 79–88.
Singh, R., Kishore, L., & Kaur, N. (2014). Diabetic peripheral neuropathy: Current perspective and future directions. Pharmacol. Res, 80, 21–35.
Zangiabadi, N., Mohtashami, H., Shabani, M., & Jafari, M. (2014). Neuroprotective effect of cerebrolysin on diabetic neuropathy: a study on male rats. J. Diabetes Metab, 05, 355.
Zhuo, M. (2013). Long-term potentiation in the anterior cingulate cortex and chronic pain. Philos. Trans. R. Soc. B, 369, 20130146.
