Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer’s disease

ABSTRACT

Background

Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties.

Objective

This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients.

Methods

This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester.

Results

The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalase_{before silymarin}= 9.29 ± 7.02 vs Catalase_{after silymarin}= 5.32 ± 2.97, p = 0.007 and MDA_{before silymarin}= 4.29 ± 1.90 vs MDA_{after silymarin}= 1.66 ± 0.84, p < 0.001) while MMSE increased notably (MMSE_{before silymarin}= 10.39 ± 6.42 vs MMSE_{after silymarin}= 13.37 ± 6.81, p < 0.001).

Conclusion

Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD.

KEYWORDS:

• Alzheimer's disease
• silymarin
• milk thistle
• neopterin
• catalase
• paraoxonase-1
• Malondialdehyde
• MMSE

Acknowledgements

This work was performed in partial fulfillment of the requirements for the Pharm.D thesis of Seyed Mohammad Navabi, in the School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. The authors gratefully acknowledge the Research Council of Kermanshah University of Medical Sciences (Grant Number: 97436) for financial support.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, and lab works were performed by Seyed Mohammad Navabi, Daniel Elieh-Ali-Komi, Daryoush Afshari, Farjam Goudarzi, Ehsan Mohammadi-Noori, and Kiana Heydari. Data analysis was performed by Fatemeh Heydarpour and Amir Kiani. The first draft of the manuscript was written by Daniel Elieh-Ali-Komi and Amir Kiani. Daniel Elieh-Ali-Komi generated figures and graphs.

Ethics approval statement

The study was done according to the ethical committee of Kermanshah University of Medical Sciences (IR.KUMS.REC.1397.350).

Consent to participate

Informed consent to participate in the study was obtained from participants.

Consent for publication

Informed consent to publishing the results was obtained from participants.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Research Council of Kermanshah University of Medical Sciences [grant number 97436].

Notes on contributors

Seyed Mohammad Navabi

Seyed Mohammad Navabi As a member of the Students Research Committee at Kermanshah University of Medical Sciences, Seyed Mohammad does research on drug toxicity and oxidative stress.

Daniel Elieh-Ali-Komi

Daniel Elieh-Ali-Komi (Ph.D. candidate), is a researcher in the field of allergy and immunology at Charite Medical University, Berlin. He is the sole writer of the book “Evolutionary History of Immunology”. He has authored over 55 publications on mast cell biology. His background is immunology but has years of experience in Electronics and Egyptology.

Daryoush Afshari

Daryoush Afshari (MD), Neurologist, at the Neurology Department of Kermanshah University of Medical Science with more than 30 years of research in neurological disorders.

Farjam Goudarzi

Farjam Goudarzi serves as an assistant professor of clinical biochemistry at Kermanshah University of Medical Sciences. He does research mostly on regenerative medicine with a focus on wound healing, wound dressing, and adhesive hydrogels.

Ehsan Mohammadi-Noori

Ehsan Mohammadi-Noori is a member of the Students Research Committee at Kermanshah University of Medical Sciences and his fields of interest are molecular genetics and Oxidative stress.

Kiana Heydari

Kiana Heydari (Pharm. D), serves as a medical advisor and patient support consultant in public health and neurological diseases with medicoMarketing project management in pharma.

Fatemeh Heydarpour

Fatemeh Heydarpour (Ph.D. in epidemiology), serves as the assistant professor at the Department of Epidemiology Faculty of Public Health (Kermanshah University of Medical Sciences). She is interested in performing research on the effectiveness of herbal drugs in the treatment of cancer.

Amir Kiani

Amir Kiani Serving as a Professor of toxicology, Amir's fields of interest include but are surely not limited to oxidative stress, neurobiology, herbal medicine, and enzymology. He has a piling up number of registered patents mostly on translational medicine and is an Iranian well-known Innovative researcher.