A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration

Chirlene Pinheiro Nascimento; Luan Oliveira Ferreira; Alex Luiz Menezes da Silva; Ana Beatriz Nardelli da Silva; Joao Cleiton Martins Rodrigues; Leonan Lima Teixeira; Julianne Elba Cunha Azevedo; Daniella Bastos de Araujo; Akira Otake Hamoy; Beatriz Holanda Gonçalves; Brenda Hosana De Oliveira Coelho; Dielly Catrina Favacho Lopes; Moisés Hamoy

doi:10.3389/fncel.2022.884813

A Combination of Curcuma longa and Diazepam Attenuates Seizures and Subsequent Hippocampal Neurodegeneration

Front Cell Neurosci. 2022 Jun 14:16:884813. doi: 10.3389/fncel.2022.884813. eCollection 2022.

Authors

Affiliations

¹ Laboratory of Pharmacology and Toxicology of Natural Products, Institute Biological Science, Federal University of Pará, Belém, Brazil.
² Laboratory of Experimental Neuropathology, João de Barros Barreto University Hospital, Federal University of Pará, Belém, Brazil.

Abstract

Epilepsy is one of the most common neurological disorders, which occurs due to the instability in the inhibitory and excitatory synaptic transmissions in the brain. However, many patients develop resistance to the available drugs, which results in cell degeneration caused due to inadequate control of the seizures. Curcumin, Curcuma longa, is known to be effective for the treatment of organic disorders and may prevent seizures, reduce oxidative stress, and decrease brain damage. Given this, the present study evaluated the antiepileptic effects of C. longa in comparison with both the diazepam and the combined application of these two substances, in terms of their effects on the brain activity and the potential histopathological changes in the hippocampus. This study used male Wistar rats (age: 10-12 weeks; weight: 260 ± 20 g), which were pretreated for 4 days with either saline, C. longa, diazepam, or C. longa + diazepam; and on the fifth day, pentylenetetrazol (PTZ) was administered to induce the seizure. In the C. longa group, a significant increase was observed in the latency of the onset of seizure-related behavior. Surprisingly, however, the combined treatment resulted in the best control of the seizure-related behavior, with the greatest latency of the onset of spasms and isolated clonic seizures. This group also obtained the best results in the electroencephalographic trace and seizure control, with a reduction in the frequency and amplitude of the spike-waves. In the saline group, PTZ significantly reduced the number of cells present in the CA1 and CA3 regions of the hippocampus, while the combined treatment obtained the best results in terms of the preservation of the neuron-like cells. These findings indicate that C. longa may contribute to the control of both seizures and the cell damage induced by PTZ, and that its association with diazepam may be a potentially effective option for the treatment of epilepsy in the future.

Keywords: Curcuma longa; diazepam; hippocampus; neurodegenaration; seizure.