Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K/AKT/mTOR and AMPK/SIRT1/FOXO3 pathways

Zhang, Chao; Li, Chuwen; Chen, Shenghui; Li, Zhiping; Ma, Lijuan; Jia, Xuejing; Wang, Kai; Bao, Jiaolin; Liang, Yeer; Chen, Meiwan; Peng, Li; Su, Huanxing; Lee, Simon Ming‐Yuen; Liu, Kechun; He, Chengwei

doi:10.1038/srep41082

Cited by 68 publications

(49 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Selected enzymes' activity in Spodoptera litura larvae [80] and mutagenic activity tested by Salmonella typhimurium assay were modulated in a biphasic manner [35,36]. In transgenic mouse models [20,88] as well as in the zebrafish larvae model [71,88] solely the effects of low doses of compounds tested were demonstrated to be consistent with in vitro findings, however, no opposite effects of high doses were recorded. We found only two experiments on rodents in which regular biphasic dose-response was shown.…”

Section: Commentssupporting

confidence: 58%

“…Concentrations 0.01-0.1 mg/mL reversed the dopamine neuron loss induced by 6-OHDA. The higher concentration of PTS (10 mg/mL) neither exerted protection against neuron loss nor caused the opposite effect [88].…”

Section: Other Phytochemicalsmentioning

confidence: 94%

“…The authors postulated that PTS exerted neuroprotection against 6-OHDA-induced cell damage in PC-12 cells through activating the PI3K/AKT/mTOR cell proliferation pathway and AMPK/SIRT1/FOXO3 cell survival pathway. They also pointed out the potential application of PTS for the prevention and treatment of neurodegenerative diseases [88]. The biphasic effect of PTS was not confirmed in the zebrafish larvae model.…”

Section: Other Phytochemicalsmentioning

confidence: 98%

“…The current review supports the opinion of many authors that the stimulatory effects of low doses/concentrations are not always beneficial [8,95] as evidenced by the increased proliferation of tumor cells exposed to phytochemicals. On the other hand, the enhanced proliferation of neuron-like PC-12 cells induced by some phytochemicals accounts for their neuroprotective action [71,88]. Moreover, the interpretation of the impact of a stimulatory effect depends on the context of a potentially therapeutic application.…”

Section: Commentsmentioning

confidence: 99%

See 3 more Smart Citations

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Jodynis‐Liebert

Kujawska

2020

JCM

View full text Add to dashboard Cite

Many phytochemicals demonstrate nonmonotonic dose/concentration-response termed biphasic dose-response and are considered to be hormetic compounds, i.e., they induce biologically opposite effects at different doses. In numerous articles the hormetic nature of phytochemicals is declared, however, no experimental evidence is provided. Our aim was to present the overview of the reports in which phytochemical-induced biphasic dose-response is experimentally proven. Hence, we included in the current review only articles in which the reversal of response between low and high doses/concentrations of phytochemicals for a single endpoint was documented. The majority of data on biphasic dose-response have been found for phytoestrogens; other reports described these types of effects for resveratrol, sulforaphane, and natural compounds from various chemical classes such as isoquinoline alkaloid berberine, polyacetylenes falcarinol and falcarindiol, prenylated pterocarpan glyceollin1, naphthoquinones plumbagin and naphazarin, and panaxatriol saponins. The prevailing part of the studies presented in the current review was performed on cell cultures. The most common endpoint tested was a proliferation of tumor and non-cancerous cells. Very few experiments demonstrating biphasic dose-response induced by phytochemicals were carried out on animal models. Data on the biphasic dose-response of various endpoints to phytochemicals may have a potential therapeutic or preventive implication.

show abstract

Section: Commentssupporting

confidence: 58%

Section: Other Phytochemicalsmentioning

confidence: 94%

Section: Other Phytochemicalsmentioning

confidence: 98%

Section: Commentsmentioning

confidence: 99%

See 2 more Smart Citations

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Jodynis‐Liebert

Kujawska

2020

JCM

View full text Add to dashboard Cite

show abstract

“…Important in the signaling cascade of mTOR is AMP activated protein kinase (AMPK). AMPK can prevent mTORC1 activity through the activation of the hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) (TSC1/TSC2) complex and can lead to the induction of autophagy (46, 58, 93-95). …”

Section: Circadian Rhythm Mtor and Sirt1mentioning

confidence: 99%

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

Maiese¹

2017

CNR

View full text Add to dashboard Cite

Background The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. Methods In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis. Results In experimental models, lifespan is significantly reduced with the introduction of arrhythmic mutants and leads to an increase in oxidative stress exposure. Interestingly, patients with Alzheimer's disease and Parkinson's disease may suffer disease onset or progression as a result of alterations in the DNA methylation of clock genes as well as prolonged pharmacological treatment for these disorders that may lead to impairment of circadian rhythm function. Tumorigenesis also can occur with the loss of a maintained circadian rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast cancer, and metastatic colorectal cancer. Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/β-catenin pathway to foster cell survival during injury and block tumor cell growth. Conclusions Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging- related disorders, neurodegenerative disease, and tumorigenesis.

show abstract

Synergistically Detachable Microneedle Dressing for Programmed Treatment of Chronic Wounds

Ning

Yang

Chen

et al. 2022

Adv Healthcare Materials

View full text Add to dashboard Cite

Chronic wounds such as diabetic feet undergo a lifetime risk of developing into incurable ulcers. Current treatments for chronic wounds remain unsatisfactory due to the lack of ideal wound dressings that integrate facile dressing change, long‐acting treatment, and high therapeutic efficacy into one system. Herein, a synergistically detachable microneedle (MN) dressing with a dual‐layer structure is presented to enable programmed treatment via one‐time dressing application. Such a dual‐layer dressing MN system (DDMNS) is composed of chitosan (CS) hydrogel dressing (CSHD) on top of a detachable MN patch with a CS tip and a polyvinyl pyrrolidone (PVP) backing substrate incorporated with magnesium (Mg). The synergistic detachment is achieved with the backing Mg/PVP substrate dissolving within minutes due to the local moist environment of the CSHD enhancing the reaction between Mg and inflammation microenvironment. The combined treatment of Mg and panax notoginseng saponins (PNS) loaded in DDMNS achieves antibacterial, neovascularization, and activating a benign immune response so that the three overlapping periods of the inflammation, tissue proliferation, and tissue remodeling of wound healing reach a dynamic balance. This advanced DDMNS provides a facile approach for the programmed treatment of chronic wound management indicating potential value in wound healing and other related biomedical fields.

show abstract

Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K/AKT/mTOR and AMPK/SIRT1/FOXO3 pathways

Cited by 68 publications

References 61 publications

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

Synergistically Detachable Microneedle Dressing for Programmed Treatment of Chronic Wounds

Contact Info

Product

Resources

About