Food Funct. 2020 Feb 18. doi: 10.1039/c9fo02611h. [Epub ahead of print]

The effects of caloric restriction and its mimetics in Alzheimer's disease through autophagy pathways.

Yang Y1, Zhang L1.

Author information


Alzheimer's disease (AD) is a neurodegenerative disorder that commonly occurs among older individuals. Increasing evidence suggests that a low-caloric diet might be a promising adjuvant therapeutic strategy for slowing or preventing the pathogenesis and progression of AD through the induction of autophagy. Several intracellular pathways have been implicated in caloric restriction (CR)-induced autophagy. In this review, we summarized the efficacy of CR as well as its mimetics (resveratrol, spermidine, aspirin, rapamycin, metformin, and curcumin) in improving cognitive function of rodent models of AD. On the basis of recent in vitro and animal studies, the beneficial effects of CR- or caloric restriction mimetics-induced autophagy in alleviating amyloid burden and tau pathology of AD were also discussed.

Food Funct. 2020 Feb 18. doi: 10.1039/c9fo02287b. [Epub ahead of print]

Ameliorative effects of resveratrol against cadmium-induced nephrotoxicity via modulating nuclear xenobiotic receptor response and PINK1/Parkin-mediated Mitophagy.

Zhang Q1, Zhang C1, Ge J1, Lv MW1, Talukder M2, Guo K1, Li YH1, Li JL3.

Author information


Cadmium (Cd) is a toxic pollutant with high nephrotoxicity in the agricultural environment. Resveratrol has been found to have a renoprotective effect but the underlying mechanisms of this have not yet been fully elucidated. The aim of this study is to illustrate the antagonism of resveratrol against Cd-induced nephrotoxicity. A total of 80 birds were divided randomly into 4 groups and treated via diet for 90 days as follows: control group (Con); 400 mg kg-1 resveratrol group (Resv); 140 mg kg-1 Cd group (Cd 140); and 140 mg kg-1 Cd + 400 mg kg-1 resveratrol group (Cd + Resv). It was observed that resveratrol treatment dramatically alleviated Cd-induced histopathological lesions of the kidney. Simultaneously, resveratrol mitigated Cd-induced oxidative stress by reducing MDA and H2O2 production, alleviating GSH depletion and restoring the activity of antioxidant enzymes (T-SOD, Cu-Zn SOD, CAT, GST and GSH-Px). Resveratrol activated NXRs (CAR/PXR/AHR/Nrf2) signaling pathways and exerted antidotal roles by enhancing the phase I and II detoxification systems to relieve oxidative damage. Moreover, resveratrol ameliorated Cd-induced ultrastructural abnormality and mitochondria dysfunction by recovering mitochondrial function-related factors VDAC1, Cyt C and Sirt3 upregulation and Sirt1, PGC-1α, Nrf1 and TFAM transcription restrictions. Resveratrol attenuated Cd-induced excessive mitochondrial fission and promoted mitochondrial fusion, which reversed PINK1/Parkin-mediated mitophagy initiation. Collectively, our findings explicate the potential protection against Cd-induced nephrotoxicity and mitochondria damage.

Lipids Health Dis. 2020 Feb 17;19(1):25. doi: 10.1186/s12944-020-1198-x.

The effects of resveratrol on lipid profiles and liver enzymes in patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials.

Akbari M1, Tamtaji OR2, Lankarani KB3, Tabrizi R1, Dadgostar E4, Haghighat N5, Kolahdooz F6, Ghaderi A7,8, Mansournia MA9, Asemi Z10.

Author information



There are current trials investigating the effect of resveratrol supplementation on lipid profiles and liver enzymes among patients with metabolic syndrome (MetS) and related disorders; however, their findings are controversial. This systematic review and meta-analysis were aimed to determine the effects of resveratrol supplementation on lipid profiles and liver enzymes among patients with MetS and related disorders.


We performed a comprehensive search of the following online databases up to November 2018: Cochrane Library, PubMed, Embase, and Web of Science. The relevant articles were assessed for quality of studies using the Cochrane risk of bias tool.


Out of 2459 citations, 31 articles were appropriate for including to the current meta-analysis. The pooled results indicated that resveratrol use significantly decreased total cholesterol [weighted mean difference (WMD) = - 7.65 mg/dL; 95% CI, - 12.93, - 2.37; P < 0.01; I2: 83.4%] and increased gamma-glutamyl transferase (GGT) concentrations (WMD = 1.76 U/l; 95% CI, 0.58, 2.94; P < 0.01; I2: 20.1%). We found no significant effect of resveratrol supplementation on triglycerides (WMD = - 5.84 mg/dL; 95% CI, - 12.68, 1.00; P = 0.09; I2: 66.8%), LDL- (WMD = -2.90 mg/dL; 95% CI, - 10.88, 5.09; P = 0.47; I2: 96.0%), HDL-cholesterol (WMD = 0.49 mg/dL; 95% CI, - 0.80, 1.78; P = 0.45; I2: 74.0%), alanine aminotransferase (ALT) (WMD = -0.14 U/l; 95% CI, - 3.69, 3.41; P = 0.93; I2: 79.6%), and aspartate aminotransferase (AST) (WMD = -0.34 U/l; 95% CI, - 2.94, 2.27; P = 0.80; I2: 88.0%) concentrations.


This meta-analysis demonstrated that resveratrol supplementation among patients with MetS and related disorders significantly reduced total cholesterol and increased GGT concentrations, but did not affect triglycerides, LDL-, HDL-cholesterol, ALT, and AST concentrations.

 * This data suggests that resveratrol may have a potential cardio-protective effect in patients with MetS and related disorders.

J Agric Food Chem. 2020 Feb 15. doi: 10.1021/acs.jafc.9b07860. [Epub ahead of print]

Occurrence, bioavailability, anti-inflammatory and anti-cancer effects of pterostilbene.

Ho CTLin WSLeland JVPan MH.


Supplementation with natural compounds found in fruits and vegetables has long been associated with a reduced risk of several types of cancer. Pterostilbene is a natural stilbenoid and a di-methylated analog of resveratrol which is found primarily in blueberries.

Pterostilbene exhibits a range of pharmacological properties, particularly anti-inflammatory and anti-cancer effects. Due to two methoxy groups in its skeleton, pterostilbene is more lipophilic than resveratrol and thus possesses higher intestinal permeability and cellular uptake, and enhanced stability. Moreover, pterostilbene exhibits less toxicity and fewer adverse effects, providing it with superior potential in cancer chemoprevention and chemotherapy applications. Numerous research studies have demonstrated that pterostilbene possesses detoxification activities, mediating the anti-inflammation response, regulating the cell cycle, augmenting apoptosis, enhancing autophagy, and inhibiting tumor angiogenesis, invasion, and metastasis by modulating signal transduction pathways which block multiple stages of carcinogenesis. In this review, we illustrate that pterostilbene is a natural compound having bioavailability. The extensive metabolism of pterostilbene will be discussed. We also summarize recent research on pterostilbene's anti-inflammatory and anti-cancer properties in the multi-stage carcinogenesis process and related molecular mechanism and conclude that it should contribute to improved cancer management.

Neurobiol Dis. 2018 Jun;114:164-173. doi: 10.1016/j.nbd.2018.03.006. Epub 2018 Mar 10.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection.


Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively.

Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity.

Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.