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Biochemical profiling of berberine-enriched extract in aluminum chloride induced oxidative damage and neuroinflammation

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Abstract

Despite the numerous treatment strategies used for Alzheimer’s disease (AD), only a few cholinesterase inhibitor drugs, such as memantine, are effective in symptomatically relieving the hallmarks of AD, providing momentary recovery of memory and cognitive decline. These available drugs do not treat the underlying causes of AD, and their chronic use is associated with serious adverse effects and disease progression. Berberine is an isoquinoline alkaloid that has been reported to possess therapeutic potential against AD. Therefore, its activity was evaluated against an aluminum chloride (AlCl3)-induced AD rat model, and a berberine-enriched extract (BEE) was used to determine if its activity is equivalent to pure berberine (PB). The rats were administered 300 mg/kg of oral AlCl3 to induce AD and were then treated with oral PB at a dosage of 50 mg/kg, BEE at a dosage of 50 mg/kg, and rivastigmine at a dosage of 1 mg/kg as a standard drug for 21 days. In this study, various parameters were assessed to evaluate cognitive functions, such as behavioral analysis, antioxidant enzyme levels, acetylcholinesterase (AChE) activity, proinflammatory cytokine levels, real-time polymerase chain reaction (RT-PCR) analysis of different biomarkers (AChE, IL-1α, IL-1β, BACE-1, TNF-α) linked to AD, and histopathological changes in the rats’ brains. After 21 days, the disease control group showed a significant decline in cognitive function, decreased levels of antioxidant enzymes, upregulated activity of the AChE enzyme, increased levels of proinflammatory cytokines, and marked elevation in mRNA expression of AD-associated biomarkers. On the other hand, the treatment groups showed significant improvements in memory deficits, elevated levels of antioxidant enzymes, reduced levels of proinflammatory cytokines, decreased AChE activity, and significant downregulation of the expression of predefined biomarkers. Histological examination of the treatment groups showed less neuroinflammation and fewer amyloid plaques compared to the disease control group. In conclusion, both PB and BEE have comparable neuroprotective potential to mitigate the pathological hallmarks of AD. However, controlled clinical trials are needed to assess their efficacy and safety.

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Data availability

All data generated and/or analyzed during this study are included in this published article.

Abbreviations

AD:

Alzheimer’s disease

AChE:

Acetylcholinesterase

Amyloid plaques:

Aβ plaques

AlCl3:

Aluminum chloride (disease control group)

BEE:

Berberine-enriched extract

BACE-1:

Beta-site amyloid precursor protein cleaving enzyme

CNT:

Control group

IL-1α:

Interleukin-1 alpha

IL-1β:

Interleukin-1 beta

NFTs:

Neurofibrillary tangles

PB:

Pure berberine

Riva:

Rivastigmine

TNF-α:

Tumor necrosis factor alpha

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Acknowledgements

The authors would like to express their appreciation to the Deanship of Scientific Research at King Khalid University, Saudi Arabia, for providing funding for this research through the research group program under grant number RGP-2/370/44.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan

    Muhammad Sajid Hamid Akash

  2. Department of Pharmacy, The University of Faisalabad, Faisalabad, Pakistan

    Moazzama Akbar

  3. Department of Pharmacy, The Women University, Multan, Pakistan

    Kanwal Rehman

  4. Department of Pharmacy, Hazara University, Mansehra, Pakistan

    Muhammad Ajmal Shah

  5. Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Thailand

    Pharkphoom Panichayupakaranant

  6. Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha, 62413, Saudi Arabia

    Muhammad Imran & Mohammed A. Assiri

  7. Department of Chemistry, Faculty of Science, King Khalid University, Abha, 62413, Saudi Arabia

    Muhammad Imran & Mohammed A. Assiri

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  1. Muhammad Sajid Hamid Akash
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Contributions

MSHA, MAS, PP, and KR designed the research. MA and MSHA performed the experiment. KR, MI, MAS, and MAA analyzed the findings and prepared manuscript. All the authors read the final draft approved for publication.

Corresponding author

Correspondence to Kanwal Rehman.

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This study was ethically approved by the Institutional Review Board (GCUF/ERC/2192) of Government College University Faisalabad (GCUF).

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Akash, M.S.H., Akbar, M., Rehman, K. et al. Biochemical profiling of berberine-enriched extract in aluminum chloride induced oxidative damage and neuroinflammation. Environ Sci Pollut Res 30, 85263–85275 (2023). https://doi.org/10.1007/s11356-023-28392-1

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