Oleanolic acid enhances neural stem cell migration, proliferation, and differentiation in vitro by inhibiting GSK3β activity

Zhang, Shi Qing; Lin, Kaili; Law, Cheuk Yu; Liu, Bin; Fu, Xiu‐Qiong; Tse, Wing Sze; Wong, Samantha Sze Man; Sze, Stephen Cho Wing; Yung, Kin Lam

doi:10.1038/s41420-018-0111-0

Cited by 16 publications

(12 citation statements)

References 26 publications

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“…CCK-8 assay 30 was performed to detect RLE’s effects on the proliferation of RA-FLS, L929 cells and MIHA cells. 100 ng/mL each of IL-6/sIL-6R (PeproTech, NY, USA) was used to stimulate cells in this study.…”

Section: Ihc Stainingmentioning

confidence: 99%

“…After a 12-h incubation, transduced RA-FLS were used for cell viability assays. RA-FLS Empty vector and RA-FLS STAT3C seeded in 96-well plates (5,000 cells/well) were separately pre-treated with RLE (0, 150, 300 μg/mL) for 1 h and then treated with IL-6/sIL-6R for 48 h. Cell viability was assessed using CCK-8 assays 30 . Viability of RLE-untreated RA-FLS Empty vector or RLE-untreated RA-FLS STAT3C was regarded as 100%.…”

Section: Ihc Stainingmentioning

confidence: 99%

“…IHC staining results were quantified by counting the DAPI and cleaved caspase- Cell Counting Kit-8 (CCK-8) and crystal violet staining assays. CCK-8 assay 30 was performed to detect RLE's effects on the proliferation of RA-FLS, L929 cells and MIHA cells. 100 ng/mL each of IL-6/sIL-6R (PeproTech, NY, USA) was used to stimulate cells in this study.…”

Section: Ihc Stainingmentioning

confidence: 99%

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A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes

Chen

Liu

et al. 2021

Sci Rep

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Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.

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Section: Ihc Stainingmentioning

confidence: 99%

Section: Ihc Stainingmentioning

confidence: 99%

Section: Ihc Stainingmentioning

confidence: 99%

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A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes

Chen

Liu

et al. 2021

Sci Rep

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“…In another study, migration, proliferation, and differentiation of neural stem cells (NSCs) were elevated by OA. The mechanism of action was determined as suppressing glycogen synthase kinase 3β (GSK3β) activity, which has a role in peripheral and CNS inflammation in various neurological disorders [111].…”

Section: Oleanolic Acidmentioning

confidence: 99%

Pistacia Genus as a Potential Source of Neuroprotective Natural Products

et al. 2019

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Neuroprotective agents are able to defend the central nervous system against acute or chronic neuronal injuries. Even with the progress made over the last decades, most of the medications prescribed for the management of neurodegenerative diseases can only reduce their symptoms and slow down their progression. Based on natural product research, there are potential effective medicinal plants and phytochemicals for modulating neuronal functions and protecting against neurodegeneration. Plants in the genus Pistacia are also among valuable natural resources for neuroprotection research based on experiences in traditional medicine. Studies have supported the value of bioactive compounds of the genus Pistacia for central nervous system disorders such as Alzheimerʼs, Parkinsonʼs, multiple sclerosis, cerebral ischemia, depression, and anxiety. Related literature has also revealed that most of the evidence on neuroprotection in the genus Pistacia is in the form of preliminary studies, mainly including models of behavior, motor function, and memory impairments in animals, neural toxicity, cerebral ischemia and seizure models, evaluation of their effects on antioxidant and inflammatory biomarkers, amyloid β aggregation, and acetylcholinesterase as well as investigations into some cellular pathways. Along with the phytonutrients in kernels such as pistachios, various phytochemicals, mostly terpenes, and phenolic compounds have also been identified in different plant parts, in particular their oleoresins, of species in the genus Pistacia. In this review, the pharmacology of neurological effects and related molecular mechanisms of the plants belonging to the genus Pistacia and its active constituents, as well as pharmacokinetics aspects, are discussed.

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“…20( S )-protopanaxadiol (PPD) and oleanolic acid (OA) are two of the active compounds found in ginseng, which has been extensively used to treat AD in Asia. Previous work conducted in our lab found that both PPD and OA can enhance NSC proliferation and neural differentiation in vitro by targeting GSK-3β in the Wnt/GSK-3β/β-catenin signaling pathway [ 9 , 10 ]. These findings indicate that PPD and OA have the potential to promote neurogenesis in vivo .…”

Section: Introductionmentioning

confidence: 99%

20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis

Lin

Sze

Liu

et al. 2021

Journal of Ginseng Research

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Background Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20( S )-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro . However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.

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Oleanolic acid enhances neural stem cell migration, proliferation, and differentiation in vitro by inhibiting GSK3β activity

Cited by 16 publications

References 26 publications

A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes

A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes

Pistacia Genus as a Potential Source of Neuroprotective Natural Products

20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis

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