Kolaviron protects rats from cognitive decline induced by Lipopolysaccharide in Wistar rat
Click to view file (PDF)

How to Cite

Onasanwo , S. A., Adebimpe-John , O. E., Olopade, F. E., & Olajide, O. O. . (2021). Kolaviron protects rats from cognitive decline induced by Lipopolysaccharide in Wistar rat: The memory-enhancing activity of kolaviron in Wistar rat. Nigerian Journal of Physiological Sciences, 36(1), 67–76. Retrieved from http://ojshostng.com/index.php/njphysiologicalsciences/article/view/1358



Kolaviron is a mixture of bi-flavonoids from seed Garcinia kola seed, and has been previously shown to exhibit Nrf2 antioxidant-mediated inhibition of neuroinflammation in LPS-activated BV2 microglia. In this study, we investigated neuroprotective effects of kolaviron in LPS-induced memory impairment in rats. Wistar rats (225–250) g was used for this study. Memory impairment was induced with the systematic administration of 250 µg/mg lipopolysaccharide (LPS). The effect of kolaviron on the cognition and learning processes were assessed using the behavioral responses in the Morris water maze model. Effects of LPS injections on the physiological activities were assessed by biochemical assays before and after treatment. Peripheral administration of LPS showed reduction in the cognitive and locomotor process. It also led to reductions in the core body temperature, superoxide dismutase (SOD), and catalase levels, with an increase in Membrane lipid-peroxidation (MDA), intracellular glutathione (GSH) and nitric oxide (NO2). These pro-inflammatory mediators produced in response to LPS are hypothesized to affect cognition, and kolaviron was able to ameliorate the effect by significantly improving the cognitive and learning processes, revealed in the reduction of escape latency and path-length during the probe trial and increase in time spent within the quadrant during retrieval using Morris water maze. Similarly, LPS at 250 µg/kg induced a hypothermic effect in the treated animals. Kolaviron significantly was able to ameliorate the level of SOD and CAT by causing a significant increase while it caused a significant reduction in the level of NO2, GSH, and MDA. Kolaviron has considerable anti-inflammatory potentials, reducing lipopolysaccharide activation of macrophages. The memory-enhancing activity of kolaviron was comparable to Sulindac sulfide (a non-steroidal anti-inflammatory drug).

Click to view file (PDF)



Abarikwu, S.O. (2014). Kolaviron, a natural flavonoid from the seeds of Garcinia kola, reduces LPS-induced inflammation in macrophages by combined inhibition of IL-6 secretion, and inflammatory transcription factors, ERK1/2, NF-κB, p38, Akt, p-c-JUN and JNK. Biochem Biophys. Acta. 1840: 2373-2381.

Abarikwu, S. O., Farombi, E. O. and Pant, A. B. (2011). Biflavanone-kolaviron protects human dopaminergic SH-SY5Y cells against atrazine induced toxic insult. Toxicol. In Vitro. 25: 848-858.

Arai, K., Matsuki, N., Ikegaya, Y. and Nishiyama, N. (2001). Deterioration of spatial learning performances in lipopolysaccharide treated mice. Jpn J Pharmacol. 87: 195-201.

Aubert, A. and Dantzer, R. (2005). The taste of sickness: lipopolysaccharide-induced finickiness in rats. Physiol Behav. 84: 437–444.

Bluthe, R. M., Castanon, N., Pousset, F., R. M., Bristow, A., Ball, C., Lestage, J., Michaud, B., Kelley, K. W. and Dantzer, R. (1999): Central injection of IL-10 antagonizes the behavioral effects of lipopolysaccharide in rats. Psychoneuroendocrinology 24(3): 301–311.

Chance, B., Grenstein, D. S. and Roughton, R. J. W. (1952). The mechanism of catalase action 1- steady state analysis. Arch Biochem Biophy. 37(2): 301-321.

Chelikani, P., Fita, I. and Loewen, P. (2004). "Diversity of structures and properties among catalases". Cell Mol Life Sci. 61 (2): 192–208

Christen, Y. (2000). Oxidative stress and Alzheimer disease, Am J Clin Nutr. 71(2): 621S–629S.

Cookson, M. and Shaw P. (1999). Oxidative stress and motor neuron disease. Rain Pathol. 9 (1): 165–186.

Das, S., Vasisht, S., Snehlata, R., Das, N. and Srivastava, L. M. (2000). Correlation between total antioxidant status and lipid peroxidation in hypercholesterolemia. Curr. Sci. 78: 486-487.

Del Río, L., Sandalio, L., Palma, J., Bueno, P. and Corpas, F. (1992). "Metabolism of oxygen radicals in peroxisomes and cellular implications". Free Radic. Biol. Med. 13 (5): 557-80.

Di Matteo, V. and Esposito, E. (2003). Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Curr. Drug Targets - CNS Neurol. Disord. 2(2): 95–107.

Farokhnia, M., Shafiee Sabet, M., Iranpour, N., Gougol, A., Yekehtaz, H., Alimardani, R., Farsad, F., Kamalipour, M. and Akhondzadeh, S. (2014). Comparing the efficacy and safety of Crocus sativus L. with memantine in patients with moderate to severe Alzheimer's disease: a double-blind randomized clinical trial. Hum Psychopharmacol. 29: 351-359.

Farombi, E. O., Shrotriya, S. and Surh, Y. J. (2009). Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-kappaB and AP-1. Life Sci. 84: 149-155.

Garthwaite, J. (2008). Concepts of neural nitric oxide-mediated transmission. Eur J Neurosci. 27: 2783-2802.

Hiner, A., Raven, E., Thorneley, R., García-Cánovas, F. and Rodríguez-López, J. (2002). "Mechanisms of compound I formation in heme peroxidases". J. Inorg. Biochem. 91 (1): 27–34.

Hrupka, B. J. and Langhans, W. (2001). A role for serotonin in lipopolysaccharide-induced anorexia in rats. Pharmacol Biochem Behav. 68: 355–362.

Igado, O. O., Olopade, J. O., Adesida, A., Aina, O. O. and Farombi, E. O. (2012). Morphological and biochemical investigation into the possible neuroprotective effects of kolaviron (Garcinia kola bioflavonoid) on the brains of rats exposed to vanadium. Drug Chem Toxicol. 35: 371-380.

Iwu, M. M. (1985). Antihepatoxic constituents of Garcinia kola seeds. Experientia. 41: 699-700.

Jacoby, S., Sims, R. E. and Hartell, N. A. (2001). Nitric oxide is required for the induction and heterosynaptic spread of long-term potentiation in rat cerebellar slices. J Physiol.; 535 825-839.

Khan, M. A., Tania, M., Zhang, D. and Chen, H. (2010). Antioxidant enzymes and cancer, Chin J Cancer Res. 22(2): 87–92.

Lattal, K. M., Mullen, M. T. and Abel, T. (2003). Extinction, renewal, and spontaneous recovery of a spatial preference in the water maze. Behav Neurosci. 117 (5): 1017-1028.

Lee, Y., Kim, M. S. and Lee, J. (2017). Neuroprotective strategies to prevent and treat Parkinson's disease based on its pathophysiological mechanism. Arch Pharm Res. 40(10): 1117-1128.

Lee, J., Torosyan, N. and Silverman, D. H. (2017)., Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: a double-blinded placebo-controlled pilot study. Exp. Gerontol. 87: 121-128.

Lugarini, F., Hrupka, B. J., Schwartz, G. J., Plata-Salaman C. R. and Langhans W. (2002) A role for cyclooxygenase 2 in lipopolysaccharide-induced anorexia in rats. Am J Physiol Regul Integr Comp Physiol. 283: R862–R868.

Mao, X. Y., Jin, M. Z., Chen, J. F., Zhou, H. H. and Jin, W. L. (2018). Live or let die: Neuropro

Minett, T., Classey, J., Matthews, F. E., Fahrenhold, M., Taga, M., Brayne, C., Ince, P. G., Nicoll, J. A. and Boche, D. (2016). Microglial immunophenotype in dementia with Alzheimer's pathology. J Neuroinflammation. 13 (1): 135.

Morn, M. S., Defierre, J. W. and Mannervik, B., (1979). Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochem. Biophys. Acta. 582: 67–68.

Morris, R. (1984) Developments of a water-maze procedure for studying spatial learning in the rat. Journal of Neuroscience Methods, 11: 47-60.

Nunomura, A., Castellan, R., Zhu., X., Moreira P., Perry G., Smith M. (2006). Involvement of oxidative stress in Alzheimer disease, J Neuro-pathol Exp Neurol. 65(7): 631–641.

Olajide, O. J., Enaibe, B. U., Bankole, O. O., Akinola, O. B., Laoye, B. J. and Ogundele, O. M. (2015) Kolaviron was protective against sodium azide (NaN3) induced oxidative stress in the prefrontal cortex. Metab Brain Dis. 31(1): 25-35.

Olaleye, S. B., Onasanwo, S. A., Ige, A. O., Wu, K. and Cho, C. (2010). Anti-inflammatory activities of a Kolaviron inhibition of nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha production in activated macrophage-like cell line. Afr J Med Med Sci. 39: 41-46.

Olaleye, S. B., Onasanwo, S. A., Ige, A. O., Wu, K. K. and Cho. C. H. (2010). Anti-inflammatory activities of a kolaviron-inhibition of nitric oxide, prostaglandin E2 and tumor necrosis factor-alpha production in activated macrophage-like cell line. Afr J Med Med Sci. 39 Suppl 41-46.

Onasanwo, S. A., Velagapudi, R., El-Bakoush, A., Olajide, O. A. (2016). Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism. Mol Cell Biochem. 414 (1-2): 23-36.

Plata-Salaman, C. R. and Borkoski. J. P. (1993). Centrally administered bacterial lipopolysaccharide depresses feeding in rats. Pharmacol Biochem Behav. 46: 787–791.

Rao, A., Balachandran, B. (2002). Role of oxidative stress and antioxidants in neurodegenerative diseases, Nutr Neurosci 5 (5) 291–309.

Rosi, S., Vazdarjanova, A., Ramirez-Amaya, V., Workey, P. F., Barnes, C. A. and Wenk G. L. (2006). Memantine protects against LPS-induced neuroinflammation, restores behaviorally induced gene expression and spatial learning in the rat. Neurosci. 142: 1303-1315.

Rotruck, J. T., Pope A. L., Ganther, H. L. and Swanson A. B. (1984). Selenium: Biochemical roles as a component of glutathione peroxidase. Science. 179: 588.

Shibanuma, M., Kuroki, T. and Nose, K. (1988). Induction of DNA replication and expression of proto oncogenes c-myc and c-fos in quiescent Balb/3T3 cells by xanthine/xanthine oxidase. Oncogene 3 17–21.

Sita, G., Hrelia, P., Tarozzi, A. and Morroni, F. (2016). Isothiocyanates are promising compounds against oxidative stress, neuroinflammation and cell death that may benefit neurodegeneration in Parkinson's disease. Int J Mol Sci. 17 (9): 1454. https://doi.org/10.3390/ijms17091454

Smid, S. D., Maag, J, L., Musgrave, I. F. (2012). Dietary polyphenol-derived protection against neurotoxic β-amyloid protein: from molecular to clinical. Food Funct. 3 (12): 1242-1250.

Solanki, I., Parihar, P., Mansuri, M. L. and Parihar, M. S. (2015). Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr. 6 (1): 64-72.

Sorce, S., Stocker, R., Seredenina, T., Holmdahl, R., Aguzzi, A., Chio, A., Depaulis, A., Heitz, F., Olofsson, P., Olsson, T., Duveau, V., Sanoudou, D., Skosgater, S., Vlahou, A., Wasquel, D., Krause, K. H. and Jaquet, V. (2017). NADPH oxidases as drug targets and biomarkers in neurodegenerative diseases: What is the evidence? Free Radic Biol Med. 112: 387-396.

Takeda, K. and Akira, S. (2004). TLR signaling pathways. Seminars in Immun. 16: 3-9.

Ullah, F., Liang, A., Rangel, A., Gyengesi, E., Niedermayer, G. and Münch, G. (2017). High bioavailability curcumin: an anti-inflammatory and neurosupportive bioactive nutrient for neurodegenerative diseases characterized by chronic neuroinflammation. Arch Toxicol. 91: 1623-1634.

Valko, M., Leibfritz, D., Moncol, J., Cronin, M., Mazur, M. and Telser J. (2007). Free radicals and antioxidants in normal physiological functions and human disease, The International Journal of Biochemistry & Cell Biology. 39 (1): 44-84.

Van Eldik, L. J., Carrillo, M. C., Cole, P. E., Feuerbach, D., Greenberg, B. D., Hendrix, J. A., Kennedy, M., Kozauer, N., Margolin, R.A.; Molinuevo, J.L., et al (2016). The roles of inflammation and immune mechanisms in Alzheimer’s disease. Alzheimer’s Dement. Transl. Res. Clin. Interv. 2: 99–109.

Yirmiya, R., Pollak, Y., Barak, O., Avitsur, R., Ovadia, H., Bette, M., Weihe, E. and Weidenfeld, J. (2001). Effects of antidepressant drugs on the behavioral and physiological responses to Lipopolysaccharide (LPS) in rodents. Neuro-psychopharmacology. 24: 531–544.

Zámocký, M. and Kollerv, F. (1999). "Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis". Prog Biophys Mol Biol. 72 (1): 19–66.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2021 Nigerian Journal of Physiological Sciences