Cur(Que)min: A neuroactive permutation of Curcumin and Quercetin for treating spinal cord injury

Abstract

Among Spinal Cord Injury (SCI) intervention the administration of high-dose high-potency steroidal drugs such as methylprednisolone or dexamethasone is used to reduce the inflammation associated with primary injury and prevention of the subsequent secondary injury. The administration of steroids has several side-effects that jeopardize their use and therefore safer chemical neuro-entities are required. Natural compounds such as curcumin (anti-oxidant) and quercetin (anti-inflammatory) have been investigated as alternative neuroactive, but are not as potent as the steroids. Hence, they are required in very high doses which may lead to significant toxicity causing an increase in cellular levels of reactive oxygen species, active iron chelation, inhibiting the activity of the cytochrome P450 enzymes such as glutathione-S-transferase and UDP-glucuronosyltransferase. A reduction in the dose of these neuroactives is possible with the administration of a ‘chemically-variant’ permutation with additive or synergistic therapeutic benefits. Therefore, we hypothesize that curcumin and quercetin, both natural polyphenolic flavonoids, can “additively and synergistically” improve the physiological outcome after traumatic SCI when used in combination and termed ‘Cur(Que)min’ – thereby decreasing the dose levels and hence reducing the inherent high dose-cytotoxicity of the individual neuroactives. This hypothesis provides the first-account of a curcumin–quercetin combination for SCI intervention theorizing the possible biomolecular-mechanism that may provide the scientific community with a novel neuroprotective and neurotherapeutic treatment option for SCI.