Asiaticoside Attenuates Cell Growth Inhibition and Apoptosis Induced by Aβ1-42 via Inhibiting the TLR4/NF-κB Signaling Pathway in Human Brain Microvascular Endothelial Cells
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Alzheimer`s disease (AD) is a very common progressive neurodegenerative disorder with the highest incidence in the world. Dysfunction of the blood brain barrier (BBB) may be responsible for the pathogenesis and pathology of AD for abnormally transporting amyloid-β (Aβ, the main component of the senile plaques) from the sera into the central nervous system. Aβ peptides induce apoptosis in human brain microvascular endothelial cells (hBMECs), the main component of BBB. Apoptosis in neuronal cells plays a critical role in the pathogenesis of AD. Asiaticoside, a natural glycoside extracted from Centella asiatica (L.) Urban, has an anti-apoptotic effect on hBMECs but the molecule mechanism remains unclear. Therefore, we investigate the protective effect of asiaticoside on Aβ1-42-induced cytotoxicity and apoptosis as well as associated mechanism in hBMECs with commonly used in vitro methods for clinical development of asiaticoside as a novel anti-AD agent. In the present study, we investigated the effects of asiaticoside on cytotoxicity by Cell Counting Kit-8 assay, mitochondrial membrane potential by JC-1 fluorescence analysis, anti-apoptosis by Hoechst 33258 staining and Annexin V-FITC (fluorescein isothiocyanate) and propidium iodide (PI) analyses, the expressions of TNF-α and IL-6 by enzyme-linked immunosorbent assay (ELISA) and TLR4, MyD88, TRAF6, p-NF-κB p65, and total NF-κB p65 by Western blotting, and nuclear translocation of NF-κB p65 by immunofluorescence analysis in hBMECs. The results showed that pretreatment of asiaticoside (25, 50, and 100 μM) for 12 h significantly attenuated cell growth inhibition and apoptosis, and restored declined mitochondrial membrane potential induced by Aβ1-42 (50 μM) in hBMECs. Asiaticoside also significantly down-regulated the elevated expressions of TNF-α, IL-6, TLR4, MyD88, TRAF6, and p-NF-κB p65, as well as inhibited NF-κB p65 translocation from cytoplasm to nucleus induced by Aβ1-42 in hBMECs in a concentration-dependent manner. The possible underlying molecular mechanism of asiaticoside may be through inhibiting the TLR4/NF-KB signaling pathway. Therefore, asiaticoside may be developed as a novel agent for the prevention and/or treatment of AD clinically.
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Pre-treatment with asiaticoside (25, 50, 100 μM) for 12 h reduces inhibition of cell growth and apoptosis and restores decreased mitochondrial membrane potential produced by Aβ1-42 (50 μM) in human brain microvascular endothelial cells.
“The findings demonstrated that pre-treatment with asiaticoside (25, 50, and 100 M) for 12 h dramatically reduced the inhibition of cell growth and apoptosis and restored the decreased mitochondrial membrane potential produced by Aβ 1-42 (50µM) in hBMECs.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [111]
Asiaticoside reduces raised expressions of TNF-, IL-6, TLR4, MyD88, TRAF6, and p-NF-κB p65 in human brain microvascular endothelial cells.
“Additionally, in hBMECs, asiaticoside dramatically reduced the raised expressions of TNF-, IL-6, TLR4, MyD88, TRAF6, and p-NF-κB p65.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [111]
Asiaticoside prevents concentration-dependent translocation of NF-κB p65 from cytoplasm to nucleus induced by Aβ.
“It also prevented the concentration-dependent translocation of NF-κB p65 from the cytoplasm to the nucleus that was brought about by Aβ .”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [111]
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- Authors
- Song, D., Jiang, X., Liu, Y., Sun, Y., Cao, S., & Zhang, Z.
- Affiliations
- Southwest Medical University (CN)
- Corresponding author
- Cao, Shousong
- Zhang, Zhuo
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2018-01-30
- Volume
- 9
- Pages
- 28-28
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC5797575
- OpenAlex
- W2793176866
- Cited by
- 72
- References
- 60
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 11 · 2021: 10 · 2020: 14 · 2019: 8 · 2018: 1
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Education Department of Sichuan Province (13ZB0267)
- Southwest Medical University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- asiaticoside, Centella asiatica, amyloid-beta 42, Alzheimer's disease, human brain microvascular endothelial cells, blood-brain barrier, apoptosis, TLR4/NF-κB signaling, MyD88, TRAF6, p65 nuclear translocation, mitochondrial membrane potential, TNF-α, interleukin-6
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