2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) from Polygonum multiflorum Thunb.: A Systematic Review on Anti-Aging
Abstract
1. Introduction
2. Methods
2.1. Search Strategy
2.2. Eligibility and Study Selection
3. Results and Discussion
Effects | Aging Model (Inducer; Object) | TSG Treatment (Dose; Duration) | Chemical Purity | Potential Mechanisms | Author (Year) | References |
---|---|---|---|---|---|---|
Lifespan extension | H2O2; larval zebrafish | 25, 50, and 100 μg/mL; 24 h | >98% | Oxidative stress↓, inflammation↓ (SA-β-gal↓, ROS↓, SOD↑, catalase↑, il-1β↓, il-6↓, cxcl-c1c↓, il-8↓) | Xia et al. (2023) | [9] |
C. elegans | 100, 200, and 400 μM; until death | Unclear (standard) | Mean lifespan↑, mitochondrial function↑ (DAF-16/SKN-1/SIR-2.1 pathways; DAF-16↑, SKN-1↑, SIR-2.1↑, SIRT1↑, Aβ↓, Tau↓, ROS↓, MMP↑) | Sun et al. (2024) | [10] | |
Neuroprotection | Radiation; C57BL/6J mice, or Tet2−/− mice | 40, 80, and 120 mg/kg/d; 5 months | 98% | Inflammation↓, neurogenesis↑ (AMPK/Tet2 pathway; AMPK↑, Tet2↑, NLRP3↓) | Miao et al. (2022) | [11] |
LPS/ATP + Aβ; BV2, N2a, and SH-SY5Y cells, and primary microglia | 10, 100 nM, and 1, 10 μM; 24 h | >98% | Inflammation↓, mitophagy↑, mitosis↑ (AMPK/PINK1/Parkin pathway; AMPK↑, PINK1↑, Parkin↑, NLRP3↓, LC3-II/LC3-I↑, p62↓; iNOS↓, COX-2↓, Drp1↑, MIRO↓, Mfn2↑, MFF↓) | Gao et al. (2020) | [12] | |
Okadaic acid; SH⁃SY5Y cells | 100 μM; 24 h | Unclear (standard) | Apoptosis↓ (PI3K/AKT pathway; PI3K↑, AKT↑, Bcl⁃2↑, Bax↓) | Kang et al. (2024) | [13] | |
High-glucose; HT-22 cells | 200 µM; 48 h | Unclear (standard) | Apoptosis↓ (HAT↓, HDAC↑, Bcl-2↑, Bax↓, caspase-3↓) | Chen et al. (2022) | [14] | |
Alleviating AD | ① AD model: APP/PS1 double transgenic mice ② LPS/IFN-γ; BV2 cells | ① 40 and 80 mg/kg/d; 5 months ② 25, 50, and 100 μM; 20 h | Unclear (standard) | Inflammation↓ (cGAS-STING pathway; cGAS↓, STING↓, NF-κB↓, NLRP3↓; IL-1β↓, IL-6↓, TNF-α↓, IFN-α↓, IFN-β↓, IFIT1↓, IRF7↓) | Gao et al. (2023) | [15] |
AD model: APP/PS1/Tau triple transgenic mice | 0.033, 0.1, and 0.3 g/kg/d; 60 days | ≥70% | CDK5↓, MAPK1↓, PP1↑, Tau↓, p39↓ | Wu et al. (2022) | [16] | |
AD model: Aβ25–35; SD rats | 0.033, 0.1, and 0.3 g/kg; 4 or 8 weeks | 98% | Apoptosis↓, improving neuronal morphology (PI3K/AKT/GSK-3β pathway; MKK7/JNK pathway; PI3K↑, AKT↑, GSK-3β↓, Tau↓; MKK7↓, JNK↓) | Xia et al. (2023); Li, YB et al. (2023); Li, Y et al. (2023) | [17,18,19] | |
AD model: N2a/APP695swe cells | 100 μM; 48h | 98% | Apoptosis↓, improving mitochondrial function (MMP↑; PACS-2↓) | Wang et al. (2024) | [20] | |
AD model: APP/PS1 mouse | 120 mg/kg; 8 weeks | Unclear (standard) | MAPK pathway, chemokine pathway and autophagy—animal | Gao et al. (2024) | [21] | |
Ameliorating PD | ① PD model: MPTP; C57BL/6J mice ② MPP+; mesencephalic DA neurons or SH-SY5Y cells | ① 20 mg/kg; 7 days ② unclear | ≥98% | Apoptosis↓, neurotoxicity↓ (FGF2-Akt, BDNF-TrkB axis; FGF2↑, Akt↑, DA↑, TH↑, BDNF↑, TrkB↑, Bcl⁃2↑, caspase-3↓) | Yu et al. (2019) | [22] |
Mouse neural stem cells | 10 μM; 2 weeks | ≥98% | DA neuron differentiation (Wnt/β-catenin pathway; Wnt1↑, Wnt3a↑, Wnt5a↑, β-catenin↑, Nurr1↑) | Zhang et al. (2021) | [23] | |
Inhibiting AS | High-fat diet; ApoE-deficient (ApoE−/−) mice | 0.035 and 0.07 mg/g/d; 8 weeks | ≥98% | Inflammation↓, lipid accumulation↓, AS plaque↓, and regulating intestinal microbiota (TG↓, ox-LDL↓, IL- 6↓, TNF-α↓, VCAM-1↓, MCP-1↓) | Li et al. (2020) | [24] |
① ox-LDL; BMDCs ② ApoE−/− mice | ① 40 and 80 µM, 2 h ② 40 mg/kg/d, 5 weeks | ≥98% | Autophagy↓, DCs maturation↓, Treg differentiation↑, inflammation↓, lipid accumulation↓, (PI3K/AKT/mTOR pathway; PI3K↓, AKT↓, mTOR↓, P62↓; TC↓, TG↓, LDL-C↓; IL-6↓, IL-17A↓, IL-10↑) | Yang et al. (2024) | [25] | |
① ApoE−/− mice ② Macrophages in the aorta cells of mice (in ①) | 100 mg/kg/d, 8 weeks | 99% | Atherosclerotic lesions↓, dyslipidemia symptoms↓, and regulating lipid metabolism (Srepb-1c↓, Fasn↓, Scd1↓, Gpat1↓, Dgat1↓, Pparα↑ and Cpt1α↑; Srebp2↓, Hmgcr↓, Ldlr↑, Acat1↓, Acat2↓, and Cyp7a1↑) | Li et al. (2024) | [26] | |
① High-fat diet; LDLr−/− mice ② ox-LDL; HAECs | ① 50 and 100 mg/kg/d; 12 weeks ② 1, 10, and 100 μM; 24 h | >98% | Oxidative stress↓, endothelial senescence↓, telomerase activity↑, mitochondrial damage↓, and improving lipid profiles (PGC-1α pathway; PGC-1α↑, TC↓, TG↓, LDL-c↓, ox-LDL↓; γ-H2AX↓, p53↓, p21↓, p16↓; TERT↑; mitoROS↓, NRF1↑, TFAM↑; ROS↓, MDA↓; β-gal↓, MMP↑, mtDNA↓, SOD↑, CAT↑) | Wang et al. (2022) | [27] | |
Cardiovascular protection | ① Natural aging C57BL/6J mice, Tet2 Mut mice ② IMR-90 fibroblasts | ① 120 mg/kg/d; 60 days ② 10 and 100 μM; 48 h | Unclear (standard) | HSC aging↓, repopulation potential↑, epigenetic reprograming↑, stemness↑ (AMPK-Tet2 axis; CLPs↑, B lymphocytes↑) | Gao et al. (2024) | [28] |
Ang Ⅱ; HUVECs | 50 and 100 μM; 24 h | Unclear (standard) | Endothelial senescence↓ (SA-β-gal↓, p53↓, PAI-1↓, SIRT1↑) | Fan et al. (2021) | [29] | |
Anti-hypertension | U46619; superior mesenteric artery of SD rats | Concentration accumulation: 10−5 ∼10−2 M; | ≥98% | Vasodilation (SIRT1/TP pathway; SIRT1↑, TP↓) | Chen et al. (2022) | [30] |
HHcy; C57BL/6 mice | 40, 80, and 160 mg/kg; 4 weeks | 98% | Inhibiting vasoconstriction (ERK1/2/NF-κB pathway; p-ERK1/2↓, p-p65↓, endothelin-1↓; BP↓, Hcy↓) | Jia et al. (2022) | [31] | |
① ZDF rats, OMT−/− mice ② HUVEC and mature adipocyte co-culture | ① 50, 100, and 200 mg/kg/d; 2 weeks ② 100 μM; 24 h | ≥98% | Oxidative/nitrative stress↓, improving endothelial function (Akt/eNOS/NO pathway; SBP↓, omentin-1↑, Akt↓, eNOS↓, NO↓; NOX2↓, p22phox↓, SOD↓, peroxynitrite anion↓, PPAR-γ↑, Itln-1↑) | Dong et al. (2021) | [32] | |
Reproductive protection | H2O2 + FeSO4; rat testicular Leydig cells | 150 μM; 48 h | Unclear (standard) | Oxidative stress↓, cell senescence↓ (Insulin/IGF-1pathway; SA-β-gal↓, IRS1↑, IGF-1↑, IRS2↑, INSR↑, IGFBP3↓) | Li et al. (2021) | [33] |
Normal C57BL/6J mice | 10 mg/kg/d; 32, or 16 weeks | 95% | Oocyte quantity and quality↑, mitochondrial biogenesis↑, steroidogenesis ↑ (AMH↑, PR-B↑, atp6↑, pgc1α↑, cyp11a↑, cyp19↑, er-β↑) | Lin et al. (2022) | [34] | |
Estrogenic activity | ER (+) MCF-7 cells | 100 nM; 24 h | Unclear (standard) | Cell proliferation↑, acting as phytoestrogen (ERα↑, ERβ↑, pS2↑) | Akter et al. (2023) | [35] |
Reducing OP | ① OP model: OVX; SD rats ② H2O2; MC3T3-E1 cells | ① 80 mg/kg/d; 3 months ② 10 μM; 24 h | ≥98% | Oxidative stress↑, apoptosis↓, bone resorption↓ (miR-34a↑, SIRT1↓; Conn.D↑, Tb.N↑, BMD↑, MDA↓, GSH-Px↑; ALP↑, OPN↑, COL-1↑, OCN↑) | Wang et al. (2022) | [36] |
Diabetic OP model: Streptozotocin; C57BL/6J mice | 10 and 40 mg/kg; 8 weeks | Unclear (standard) | Regulating osteogenesis and osteoclast genesis (Ca↑, RUNX-2↑, COL-I↑, OCN↑, β-catenin↑, RAS↓, OPG↑, RANKL↓, sclerostin↓) | Zhang et al. (2019) | [37] | |
Bone protection | BMSCs | 10−6, 10−5, and 10−4 M; 3 or 7 days | Unclear (standard) | Cell proliferation↑, osteogenic differentiation↑ (ALP↑, OCN↑, Col1a1↑, Runx2↑, β-catenin↑) | Liang et al. (2022) | [38] |
3.1. Lifespan-Extending Effects of TSG
3.2. Neuroprotective Effects of TSG
3.2.1. Attenuation of Alzheimer’s Disease (AD)
3.2.2. Amelioration of Parkinson’s Disease (PD)
3.3. Cardiovascular Protective Effects of TSG
3.3.1. Inhibition of Vascular Senescence and Atherosclerosis (AS)
3.3.2. Anti-Hypertensive Effects
3.4. Reproductive Protective Effects of TSG
3.5. Bone Protective Effects of TSG
3.6. Other Protective Effects of TSG
3.7. Effects of Other P. multiflorum Extracts Against Aging and Age-Related Diseases
3.7.1. Identified Compounds
3.7.2. Ethanol Extract
3.7.3. Aqueous Extract
4. Conclusions and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
Aβ | β-Amyloid |
AD | Alzheimer’s disease |
AKT | Protein kinase B |
Ang II | Angiotensin II |
APP | Amyloid precursor protein |
AS | Atherosclerosis |
BALP | Bone alkaline phosphatase |
Bcl-2 | B-cell lymphoma-2 |
Bax | Bcl-2-associated X protein |
BDNF | Brain-derived neurotrophic factor |
BMD | Bone mineral density |
BMSCs | Bone mesenchymal stem cells |
BP | Blood pressure |
CDKN1A | Cyclin-dependent kinase inhibitor 1A |
C. elegans | Caenorhabditis elegans |
cGAS | Cyclic GMP-AMP synthase |
CLPs | Common lymphoid progenitors |
Conn.D | Connectivity density |
DA | Dopaminergic |
DAF-16 | Abnormal dauer formation-16 |
DCs | Dendritic cells |
DE | Diabetic encephalopathy |
D-gal | D-galactose |
DOR | Diminished ovarian reserve |
ERK | Extracellular signal-regulated kinase |
ET-1 | Endothelin-1 |
FGF2 | Fibroblast growth factor 2 |
FOXO | Forkhead box O |
GSH-Px | Glutathione peroxidase |
GSK-3β | Glycogen synthase kinase-3β |
HAECs | Human aortic endothelial cells |
HDAC | Histone deacetylase |
HHcy | Hyperhomocysteinemia |
HSCs | Hematopoietic stem cells |
HUVECs | Human umbilical vein endothelial cells |
IGF | Insulin-like growth factor |
IRS1 | Insulin receptor substrate 1 |
JNK | Jun N-terminal kinase |
LPS | Lipopolysaccharide |
MAPK | Mitogen-activated protein kinase |
MCP-1 | Monocyte chemotactic protein-1 |
MMP | Mitochondrial membrane potential |
MPTP | 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine |
MPP+ | 1-Methyl-4-phenylpyridinium |
mTOR | Mechanistic target of rapamycin |
NLRP3 | Nod-like receptor protein 3 |
Nrf2 | Nuclear factor erythroid 2-related factor 2 |
NSCs | Neural stem cells |
OCN | Osteocalcin |
OPG | Osteoprotegerin |
OPN | Osteopontin |
OVX | Ovariectomized |
PACS-2 | Phosphofurin acidic cluster sorting protein-2 |
PAI-1 | Plasminogen activator inhibitor-1 |
PD | Parkinson’s disease |
PGC-1α | Proliferator-activated receptor γ coactivator 1α |
PI3K | Phosphatidylinositol-3-kinase |
PMOP | Postmenopausal osteoporosis |
POF | Premature ovarian failure |
POI | Premature ovarian insufficiency |
P.multiflorum | Polygonum multiflorum Thunb. |
PPAR-γ | Peroxisome proliferator-activated receptor-γ |
RANKL | Receptor activator for nuclear factor kappa B ligand |
ROS | Reactive oxygen species |
RUNX-2 | Runt-related transcription factor 2 |
SA-β-gal | Senescence-associated β-galactosidase |
SIRT1 | Silent information regulator 1 |
SKN-1 | Skinhead-1 |
SOD | Superoxide dismutase |
STING | Stimulator of interferon genes |
Tb.N | Trabecular number |
TC | Total cholesterol |
TG | Triglyceride |
TNF-α | Tumor necrosis factor-α |
TRAP | Tartrate-resistant acid phosphatase |
TrkB | Tropomyosin receptor kinase-B |
TSG | 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside |
VaD | Vascular dementia |
VCAM-1 | Vascular cell adhesion molecule-1 |
ZDF | Zucker diabetic fatty |
6-OHDA | 6-Hydroxydopamine |
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Zhu, C.; Li, J.; Tang, W.; Li, Y.; Lin, C.; Peng, D.; Yang, C. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) from Polygonum multiflorum Thunb.: A Systematic Review on Anti-Aging. Int. J. Mol. Sci. 2025, 26, 3381. https://doi.org/10.3390/ijms26073381
Zhu C, Li J, Tang W, Li Y, Lin C, Peng D, Yang C. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) from Polygonum multiflorum Thunb.: A Systematic Review on Anti-Aging. International Journal of Molecular Sciences. 2025; 26(7):3381. https://doi.org/10.3390/ijms26073381
Chicago/Turabian StyleZhu, Can, Jinhong Li, Wenchao Tang, Yaofeng Li, Chang Lin, Danhong Peng, and Changfu Yang. 2025. "2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) from Polygonum multiflorum Thunb.: A Systematic Review on Anti-Aging" International Journal of Molecular Sciences 26, no. 7: 3381. https://doi.org/10.3390/ijms26073381
APA StyleZhu, C., Li, J., Tang, W., Li, Y., Lin, C., Peng, D., & Yang, C. (2025). 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) from Polygonum multiflorum Thunb.: A Systematic Review on Anti-Aging. International Journal of Molecular Sciences, 26(7), 3381. https://doi.org/10.3390/ijms26073381