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The extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum mixture ameliorates diabetes-associated cognitive dysfunction

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Abstract

Diabetes-associated cognitive dysfunction is linked to chronic hyperglycemia, oxidative stress, inflammation, cholinergic dysfunction, and neuronal degeneration. We investigated the antidiabetic and neuroprotective activity of a mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) in type 2 diabetic (T2D) rat model-induced memory impairment. Fructose (10%) and streptozotocin (35 mg/kg) were used to induce T2D in male Wistar rats. Diabetic animals received distilled water, metformin (200 mg/kg), or SNP mixture (75, 150, or 300 mg/kg). HPLC–MS profiling of the mixture was performed. Behavioral testing was conducted using the Y-maze, NORT, and Morris water mazes to assess learning and memory. Biochemical markers were evaluated, including carbohydrate metabolism, oxidative/nitrative stress, pro-inflammatory markers, and acetylcholinesterase activity. Histopathological examination of the pancreas and hippocampus was also performed. Fructose/STZ administration resulted in T2D, impaired short- and long-term memory, significantly increased oxidative/nitrative stress, pro-inflammatory cytokine levels, acetylcholinesterase activity (AChE), hippocampal neuronal loss and degeneration in CA1 and CA3 subfields, and neuronal vacuolation in DG. SNP mixture at 150 and 300 mg/kg significantly improved blood glucose and memory function in diabetic rats. The mixture reduced oxidative/nitrative stress and increased endogenous antioxidant levels. It also reduced serum IL-1β, INF-γ and TNF-α levels and ameliorated AChE activity. Histologically, SNP protected hippocampus neurons against T2D-induced neuronal necrosis and degeneration. We conclude that the aqueous extract of SNP mixture has antidiabetic and neuroprotective activities thanks to active metabolites identified in the plant mixture, which consequently normalized blood glucose, protected hippocampus neurons, and improved memory function in diabetic rats.

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Data availability

The figures and tables supporting the results of this study are included in the article and the original datasets are available from the first author or corresponding author upon request.

Code availability

Not applicable.

Abbreviations

SNP:

Sclerocarya birrea-Nauclea latifolia-Piper longum

CNS:

Central nervous system

T2D:

Type 2 diabetes

STZ:

Streptozotocin

BGL:

Blood glucose level

MWM:

Morris water maze

NORT:

Novel object recognition test

AChE:

Acetylcholinesterase

ROS:

Reactive oxygen species

MDA:

Malondialdehyde

GSH:

Reduced glutathione

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor-α

INF-γ:

Interferon-γ

HPLC-MS:

High performance liquid chromatography-mass spectrometry

ELISA:

Enzyme-linked immunosorbent assay

i.v.:

Intravenously

p.o. :

Per os

HOMA:

Homeostasis model assessment

CV:

Cresyl violet

H-E:

Hematoxylin-eosin

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Acknowledgements

The authors would like to acknowledge “Pathologie Cytologie Développement” for providing histological reagents. The authors are very thankful to the University of Yaoundé 1 (Cameroon) for their support in providing apparatus for behavioral testing.

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Authors and Affiliations

  1. Laboratory of Animal Physiology, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

    Jean Philippe Djientcheu Tientcheu, Florence Tsofack Ngueguim, Racéline Kamkumo Gounoue, Rodrigue Ngapout, Antoine Kavaye Kandeda & Théophile Dimo

  2. Department of Biochemistry, Laboratory of Biochemistry, Faculty of Science, University of Douala, PO Box 24 157, Douala, Cameroon

    Michel Arnaud Mbock

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  1. Jean Philippe Djientcheu Tientcheu
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Contributions

Conceptualization: Théophile Dimo, Florence Ngueguim Tsofack; Methodology: Jean Philippe Djientcheu Tientcheu, Florence Ngueguim Tsofack, Kandeda kavaye Antoine; Formal analysis and investigation: Jean Philippe Djientcheu Tientcheu, Rodrigue Fifen, Michel Arnaud Mbock; Writing – original draft preparation: Jean Philippe Djientcheu Tientcheu, Florence Ngueguim Tsofack; Writing – review and editing: Racelyne Kamkumo Gounoue, Théophile Dimo; Supervision: Théophile Dimo. All authors read and approved its final version.

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Correspondence to Florence Tsofack Ngueguim.

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All the experiments were conducted in accordance with the approval of the Cameroon National Ethical Committee (Ref No. FwIRb00001954, 04/09/2006), which adopted the guidelines of the National Research Council's Guide for the Care and Use of Laboratory Animals. All animal experiments also comply with the ARRIVE guidelines 2.0.

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Highlights

• The aqueous extract of the mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) demonstrated neuroprotective and memory-strengthening properties by protecting hippocampus neurons in diabetic rats.

• Antidiabetic properties of the SNP mixture were exhibited via normalization of blood glucose levels and pancreas protection.

• SNP activity was due to the main naturally-occurring substances identified.

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Tientcheu, J.P.D., Ngueguim, F.T., Gounoue, R.K. et al. The extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum mixture ameliorates diabetes-associated cognitive dysfunction. Metab Brain Dis 38, 2773–2796 (2023). https://doi.org/10.1007/s11011-023-01291-7

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  • DOI: https://doi.org/10.1007/s11011-023-01291-7

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