Resveratrol (Res), as a naturally occurring polyphenol mainly found in grapes and red wine, gives neuroprotection in a variety of experimental models for neurodegenerative diseases in vitro and in vivo ¹⁾.

Resveratrol, has shown promising effects in inhibiting proliferation and cancer progression in several tumor models. However, its molecular mechanisms and applications in chemotherapy and radiotherapy have yet to be fully determined. In a concise review, Jiang et al. highlight the role and related molecular mechanisms of resveratrol in cancer treatment. In particular, they focus on the role of resveratrol in the tumor microenvironment and the sensitization of cancer cells for chemotherapy and radiotherapy. Resveratrol shows promising efficacies in cancer treatment and may be applied in clinical therapy, but it requires further clinical study ²⁾.

Yang et al. from the School of Basic Medicine, Department of Neurosurgery, Department of Gastroenterology, Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), Zhengzhou, China, carried out the study with the aim to shed light on the sensitization of resveratrol to temozolomide (TMZ) against glioma through the Wnt signaling pathway. Initially, glioma cell lines with strong resistance to TMZ were selected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then, the glioma cells were subjected to resveratrol, TMZ, Wnt signaling pathway inhibitors, and activators. Cell survival rate and inhibitory concentration at half maximum value were detected by MTT, apoptosis by flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, in vitro proliferation by hanging drop method and β-catenin translocation into nuclei by TOP/FOP-FLASH assay. The expressions of the Wnt signaling pathway-related and apoptosis-related factors were determined by western blot analysis. Nude mice with glioma xenograft were established to detect tumorigenic ability. Glioma cell lines T98G and U138 which were highly resistant to TMZ were selected for subsequent experiments. Resveratrol increased the efficacy of TMZ by restraining cell proliferation, tumor growth, and promoting cell apoptosis in glioma cells. Resveratrol inhibited Wnt2 and β-catenin expressions yet elevated GSK-3β expression. Moreover, the Wnt signaling pathway participates in the sensitivity enhancing of resveratrol to TMZ via regulating O 6 -methylguanine-DNA methyltransferase (MGMT) expression. Resveratrol sensitized TMZ-induced glioma cell apoptosis by repressing the activation of the Wnt signaling pathway and downregulating MGMT expression, which may confer new thoughts to the chemotherapy of glioma ³⁾.

The aim of a study was to investigate the neuroprotective effect of resveratrol and elucidate the underlying mechanisms of resveratrol associated regulation of the NLRP3 inflammasome in TBI. The results demonstrated that the activation of NLRP3, caspase‑1 and sirtuin 1 (SIRT1), enhanced the production of inflammatory cytokines and reactive oxygen species (ROS) following TBI. Administration of resveratrol alleviated the degree of TBI, as evidenced by the reduced neuron‑specific enolase (NSE) and brain water content (WBC). Resveratrol pretreatment also inhibited the activation of NLRP3 and caspase‑1, and reduced the production of inflammatory cytokines and ROS. In addition, resveratrol further promoted SIRT1 activation. Furthermore, the suppressing effect of resveratrol on the NLRP3 inflammasome and ROS was blocked by the SIRT1 inhibitor, sirtinol. The results revealed that the activation of the NLRP3 inflammasome and the subsequent inflammatory responses in the cerebral cortex were involved in the process of TBI. Resveratrol may attenuate the inflammatory response and relieve TBI by reducing ROS production and inhibiting NLRP3 activation. The effect of resveratrol on NLRP3 inflammasome and ROS may also be SIRT1 dependent ⁴⁾.

Resveratrol inhibits microglial over-activation and alleviates neuronal injuries induced by microglial activation ⁵⁾.

Resveratrol suppresses vascular endothelial growth factor secretion via inhibition of CXC-chemokine receptor 4 expression in ARPE-19 cells ⁶⁾.

Resveratrol pretreatment protects against Ethanol (EtOH) -induced defects in neurogenesis in postnatal mice and may thus play a critical role in preventing EtOH-mediated toxicity in the developing hippocampus ⁷⁾.

Pterostilbene (PTE), a natural dimethylated analog of resveratrol from blueberries, is a strong natural antioxidant. PTE has been shown to be beneficial for some nervous system diseases and may regulate HO-1 signaling.

PTE treatment attenuates cerebral Ischemia reperfusion injury (IRI) by reducing IR-induced mitochondrial oxidative damage through the activation of HO-1 signaling ⁸⁾.

Resveratrol protects the brain against focal cerebral ischemia-induced injury, but most of all is its antidepressant-like effect on Post-stroke depression (PSD) , which might at least in part be mediated by regulation of hypothalamus-pituitary-adrenal axis function ⁹⁾.

Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. Jiao et al. aimed to evaluate whether RES can inhibit glioblastoma-initiating cells (GICs) invasion in vitro and in vivo.

GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo.

The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay. Western blotting analysis and immunofluorescence staining were used to determine the expression of signaling effectors in GICs. We demonstrated that RES suppressed the adhesion, invasion and migration of GICs in vitro and in vivo. Moreover, we proved that RES inhibited the invasion of GICs via the inhibition of PI3K/Akt/NF-κB signal transduction and the subsequent suppression of MMP-2 expression ¹⁰⁾.

In a preclinical in vivo experimental study using a murine model ¹¹⁾ Dang et al., from the Hamamatsu University School of Medicine, Hamamatsu, Japan, published in the Journal of Neuroscience Research whether dietary resveratrol reduces the formation and/or ruptured intracranial aneurysms in mice, and explored associated inflammatory pathways. While resveratrol did not significantly reduce the incidence of aneurysm formation, it significantly lowered aneurysmal rupture rates (from 88% to 40%). Mechanistically, this was associated with upregulation of Sirt1 and downregulation of pro-inflammatory markers Nfkb1 and Tnf.

The model used—combining elastase injection and DOCA-salt-induced hypertension—is well-established for mimicking aneurysm pathogenesis in rodents. The dietary intervention and timing are sound. However, the small sample sizes (not detailed in the abstract but implied by murine preclinical context) and absence of dose-response data or long-term outcomes weaken the generalizability. There is no discussion of potential toxicity or systemic effects of resveratrol, which undermines translational value.

Novelty:

The use of resveratrol in intracranial aneurysm models has limited precedent, and the study contributes new data suggesting that rupture risk, rather than aneurysm formation per se, may be the therapeutic target. Nonetheless, the reliance on transcriptional endpoints (mRNA levels) without protein confirmation (e.g., SIRT1 activity assays or histological inflammatory scoring) is a substantial limitation.

Methodological Robustness:

While the experimental induction method is adequate, the study lacks critical controls, such as resveratrol-treated animals without aneurysm induction to assess baseline inflammation modulation. Moreover, no functional or histopathological correlates of aneurysm rupture are provided, raising concerns over how “rupture” was defined or confirmed. Data on animal mortality, blood pressure effects, and systemic metabolic impacts are missing.

Clinical Relevance:

Given that resveratrol is a dietary compound with plausible safety, the translational intrigue is modestly justified. However, the clinical leap—from dietary polyphenols in rodents to rupture prevention in humans—is premature and speculative. The findings are, at best, hypothesis-generating and should not be overinterpreted.

Final Verdict

This is a modestly interesting preclinical paper that suggests resveratrol may affect aneurysm rupture risk, but not formation. The study is methodologically sound but scientifically underpowered and mechanistically superficial. Its translational relevance is thin without confirmatory studies or dose validation. Overall, this is a niche contribution with limited impact.

Takeaway Message

Resveratrol may modulate inflammation to reduce aneurysm rupture in mice, but without clearer mechanistic, dose-response, and histological data, these results remain preliminary and should not guide clinical practice.

Bottom Line

A cautiously intriguing animal study, weakened by a lack of mechanistic depth and absence of translational scaffolding. Suitable for generating hypotheses, not changing practice.

Rating: 4/10