Low and high doses of oral maslinic acid protect against Parkinson’s disease via distinct gut microbiota-related mechanisms
Open accessAbstract
The use of oral agents that can modify the gut microbiota (GM) could be a novel preventative or therapeutic option for Parkinson's disease (PD). Maslinic acid (MA), a pentacyclic triterpene acid with GM-dependent biological activities when it is taken orally, has not yet been reported to be effective against PD. The present study found both low and high dose MA treatment significantly prevented dopaminergic neuronal loss in a classical chronic PD mouse model by ameliorating motor functions and improving tyrosine hydroxylase expressions in the substantia nigra pars compacta (SNpc) and increasing dopamine and its metabolite homovanillic acid levels in the striatum. However, the effects of MA in PD mice were not dose-responsive, since similar beneficial effects for low and high doses of MA were observed. Further mechanism studies indicated that low dose MA administration favored probiotic bacterial growth in PD mice, which helped to increase striatal serotonin, 5-hydroxyindole acetic acid, and γ-aminobutyric acid levels. High dose MA treatment did not influence GM composition in PD mice but significantly inhibited neuroinflammation as indicated by reduced levels of tumor necrosis factor alpha and interleukin 1β in the SNpc; moreover, these effects were mainly mediated by microbially-derived acetic acid in the colon. In conclusion, oral MA at different doses protected against PD via distinct mechanisms related to GM. Nevertheless, our study lacked in-depth investigations of the underlying mechanisms involved; future studies will be designed to further delineate the signaling pathways involved in the interactive actions between different doses of MA and GM.
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High-dose maslinic acid treatment increases fecal acetic acid and demonstrates neuroprotective effects against PD pathologies in MPTP-treated mice.
“This is further complicated by a recent study which reported that both reduced fecal propionic acid and butyric acid following low-dose maslinic acid treatment, as well as increased fecal acetic acid following high-dose maslinic acid treatment, demonstrated neuroprotective effects against PD pathologies in MPTP-treated mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [335]
Only high-dose maslinic acid treatment reduces microglial activation and neuroinflammation in MPTP-treated mice.
“However, only high-dose maslinic acid treatment reduced microglial activation and neuroinflammation, and the effects are speculated to be mediated by acetic acid.335”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [335]
Low-dose maslinic acid treatment reduces fecal propionic acid and butyric acid and demonstrates neuroprotective effects against PD pathologies in MPTP-treated mice.
“This is further complicated by a recent study which reported that both reduced fecal propionic acid and butyric acid following low-dose maslinic acid treatment, as well as increased fecal acetic acid following high-dose maslinic acid treatment, demonstrated neuroprotective effects against PD pathologies in MPTP-treated mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [335]
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- Authors
- Cao, X., Du, Z.-R., Liu, X., Wang, X., Li, C., Zhou, S.-N., Liu, J.-R., Xu, P.-Y., Ye, J.-L., Zhao, Q., Zhao, F., Wong, K.-H., & Dong, X.-L.
- Affiliations
- Shenzhen University (CN)
- Hong Kong Polytechnic University (HK)
- BGI Group (China) (CN)
- Corresponding author
- Wong, Ka-Hing
- Dong, Xiao-Li
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2023-09
- Volume
- 165
- Pages
- 115100
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4383336544
- Cited by
- 15
- References
- 43
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PolyU Institutional Research Archive (Hong Kong Polytechnic University) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Health and Medical Research Fund (06173176)
- Shenzhen Fundamental Research and Discipline Layout Project (JCYJ20200109142019319)
- Shenzhen Fundamental Research Program
- Basic and Applied Basic Research Foundation of Guangdong Province (2022B1515230004)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- maslinic acid, Parkinson's disease, gut microbiota, dose-dependent effects, dopaminergic neuron loss, substantia nigra pars compacta, tyrosine hydroxylase, dopamine, homovanillic acid, serotonin, neuroinflammation, TNF-α, IL-1β, probiotic bacteria, neuroprotection
- MeSH terms
- Gastrointestinal Microbiome, Animals, Disease Models, Animal, Dopamine, Mice, Inbred C57BL, Oleanolic Acid, Parkinson Disease, Substantia Nigra, Mice, Dopaminergic Neurons
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