Author: Wang, Jia-Bo ; Li, Lin ; Luo, Guangbin ; Yi, Wei-Wei ; Gao, Dan ; Zeng, Li ; Yang, Cui-Cui ; Zhang, Cong-En ; Liu, Bo ; Ju, Zhen-Yu ; Zhang, Lan

INTRODUCTIONAging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now.OBJECTIVESWe aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms.METHODSWe screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging.RESULTSTSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay.CONCLUSIONTSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

01 Jan 2025·Advanced Science

Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair

Article

Author: Mu, Chunlan ; Wu, Ji ; Tian, Geng G. ; Bai, Hepeng ; Lin, Wenhui ; Yang, Jiamei ; Wang, Linhui ; Li, Xiaoyong

AbstractOvarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant‐derived compounds are screened for in vitro activity upon ovarian organoids derived from feeder‐free female germline stem cells. Tetrahydroxy stilbene glucoside (TSG) is found to promote the development of ovarian organoids. Single nucleus transcriptome sequencing and spatial transcriptome sequencing are used to establish a comprehensive spatiotemporal map to elucidate the role of TSG in ovarian organoid development, encompassing cell types and subtypes, transcription factors, pseudo‐time sequence, and cell communication dynamics. This analysis indicates that TSG promotes ovarian organoid development through the vascular endothelial growth factor A‐Eph receptor B2 ligand‐receptor pair between granulosa cells and oocytes. This study has enhanced the understanding of the mechanisms of ovarian organoid development, establishes a technical platform for screening compounds for treating infertility and related diseases, and lays a foundation for clinically applying plant‐derived compounds.

01 Dec 2024·Alzheimer's & Dementia

Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer’s disease via cGAS‐STING

Article

Author: Gao, Dan

AbstractBackgroundAlzheimer’s disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear.MethodAPP/PS1 AD mice were treated with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) at 40 mg/kg/day and 80 mg/kg/day respectively for 5 consecutive months, and then the Morris water maze test (MWM) and the novel object recognition test were performed to assess the effect of TSG on the cognitive and memory ability of AD mice. Moreover, central microglia activation, peripheral inflammation as well as the correlated cGAS‐STING signal pathway were analysed by Immunostaining and ELISA, which was further verified in BV2 cell experiments.ResultTreating with TSG, learning‐memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP‐AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN‐γ induced microglia activation showed that TSG reversed the polarization status of M1‐type microglia to restore the quiescence, and cGAS‐STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL‐1β, IL‐6, TNF‐ α, IFN‐ αand IFN‐β, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN‐γ‐stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS‐STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS‐STING inhibitors.ConclusionOur findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS‐STING signaling pathway in AD.

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Indication	Highest Phase	Country/Location	Organization	Date
Ischemic stroke	Preclinical	China	Anhui Normal University	14 Dec 2022

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