Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases
Abstract
:1. Introduction
2. Biosynthesis of the Phytosterols in Plants
3. Plant Sterols in the Brain
4. Neuroprotective Effects of the Selected Phytosterols
4.1. β-Sitosterol
4.2. Stigmasterol
4.3. Campesterol
4.4. Brassicasterol
4.5. Lanosterol
4.6. 24(S)-Saringosterol
4.7. 4,4-Dimethyl Phytosterols
4.8. Ergosterol
Phytosterol | Mode of Action | Study | References |
---|---|---|---|
β–Sitosterol | AChE and BChE inhibitory activity | in vivo (mice), in vitro, in silico | [45,46] |
Increased levels of antioxidant enzymes by activating estrogen receptor/PI3-kinase pathway | in vitro (RAW 264.7; HT22) | [47,48] | |
Anti-inflammatory | in vitro (BV12) | [59] | |
Increase mitochondrial potential | in vitro (HT22) | [58] | |
Stigmasterol | AChE inhibitory activity | in vitro | [60] |
Reduced the β-secretase activity. Reduced the expression of all γ-secretase components Reduced the cholesterol and presenilin distribution in lipid rafts implicated in amyloidogenic APP cleavage. Decreased the BACE1 internalization to endosomal compartments, involved in APP β-secretase cleavage | in vivo (mice), in vitro (HT22) | [31,55] | |
Decrease ROS | in vitro (SH-SY5Y) | [61,62] | |
Anti-inflammatory | in vitro (mouse chondrocytes and human osteoarthritis chondrocytes) | [66] | |
Brassicasterol | Marker in CSF of AD patients | cerebrospinal fluid (CSF) | [69] |
Minor or no effect on Aβ secretion | in vivo (mice) | [31] | |
Campesterol | Minor or no effect on Aβ secretion | in vivo (mice) | [31] |
Lanosterol | Reduced the accumulations and cytotoxicity of Aβ aggregation through induction of co-chaperone and by promoting autophagy | in silico, in vitro (HeLa, PC12, HEK-293A), in vivo (mice) | [71,72,73,74] |
24(S)-Saringosterol | Reduced the in vivo expressions of Iba1 | in vivo (mice) | [77] |
Dietary supplementation of S. fusiforme enriched in 24(S)-saringosterol | Reduced secretion of Aβ plaques. Improves memory in AD mice model | in vivo (mice), in vitro (N2a) | [78] |
α-Amyrin | Elevated levels of memory related proteins through the activation of ERKGSK-3β | in vivo (mice) | [79] |
β-Amyrin | Elevated levels of memory related proteins through the activation of ERKGSK-3β. AChE inhibitory activity | in vivo (mice) | [79,80] |
Taraxerol | AChE inhibitory activity | in vivo (mice) | [83] |
High affinity of taraxerol for fibrils and amyloid- β | in silico | [84] | |
Lupeol | BACE-I inhibitory activity | in vitro, in silico | [85,86] |
Ergosterol | Reduced the β- and γ-secretase activity | in vitro | [44] |
5. Physiological versus Pathological Features of Phytosterols
6. Safety Concerns for the Phytosterols
7. Future Perspectives and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sharma, N.; Tan, M.A.; An, S.S.A. Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases. Int. J. Mol. Sci. 2021, 22, 12255. https://doi.org/10.3390/ijms222212255
Sharma N, Tan MA, An SSA. Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases. International Journal of Molecular Sciences. 2021; 22(22):12255. https://doi.org/10.3390/ijms222212255
Chicago/Turabian StyleSharma, Niti, Mario A. Tan, and Seong Soo A. An. 2021. "Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases" International Journal of Molecular Sciences 22, no. 22: 12255. https://doi.org/10.3390/ijms222212255