Natural Phytochemicals as SIRT Activators—Focus on Potential Biochemical Mechanisms

Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a part of crucial cellular pathways and are regulated by many factors, such as chemicals, environmental stress, and phytochemicals. Several in vitro and in vivo studies have presented their involvement in anti-inflammatory, antioxidant, and antiapoptotic processes. Recent findings imply that phytochemicals such as resveratrol, curcumin, quercetin, fisetin, berberine, and kaempferol may regulate the activity of sirtuins. Resveratrol mainly activates SIRT1 and indirectly activates AMPK. Curcumin influences mainly SIRT1 and SIRT3, but its activity is broad, and many pathways in different cells are affected. Quercetin mainly modulates SIRT1, which triggers antioxidant and antiapoptotic responses. Fisetin, through SIRT1 regulation, modifies lipid metabolism and anti-inflammatory processes. Berberine has a wide spectrum of effects and a significant impact on SIRT1 signaling pathways. Finally, kaempferol triggers anti-inflammatory and antioxidant effects through SIRT1 induction. This review aims to summarize recent findings on the properties of phytochemicals in the modulation of sirtuin activity, with a particular focus on biochemical aspects.

[1]  Minghui Cai,et al.  Resveratrol attenuates hydrogen peroxide-induced injury of rat ovarian granulosa-lutein cells by resisting oxidative stress via the SIRT1/Nrf2/ARE signaling pathway. , 2023, Current pharmaceutical design.

[2]  Yashu Liu,et al.  The sirtuin family in health and disease , 2022, Signal Transduction and Targeted Therapy.

[3]  J. DiNicolantonio,et al.  Nutraceutical activation of Sirt1: a review , 2022, Open Heart.

[4]  N. Soliman,et al.  Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation , 2022, Redox report : communications in free radical research.

[5]  Xiaoling Zhao,et al.  Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism , 2022, Frontiers in Immunology.

[6]  Xuemin Song,et al.  Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1/AMPK pathways. , 2022, Cellular signalling.

[7]  F. A. Lagunas-Rangel SIRT7 in the aging process , 2022, Cellular and Molecular Life Sciences.

[8]  N. Shrivastava,et al.  Kaempferol and Apigenin suppresses the stemness properties of TNBC cells by modulating Sirtuins , 2022, Molecular Diversity.

[9]  Xiaonan Li,et al.  Curcumin alleviates hepatic steatosis by improving mitochondrial function in postnatal overfed rats and fatty L02 cells through the SIRT3 pathway. , 2022, Food & function.

[10]  N. Tran,et al.  Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States , 2022, American journal of biomedical science & research.

[11]  Hui Huang,et al.  SIRT6 protects vascular smooth muscle cells from osteogenic transdifferentiation via Runx2 in chronic kidney disease , 2021, The Journal of clinical investigation.

[12]  A. Hayes,et al.  The modulation of SIRT1 and SIRT3 by natural compounds as a therapeutic target in doxorubicin‐induced cardiotoxicity: A review , 2021, Journal of biochemical and molecular toxicology.

[13]  M. Migaud,et al.  Temporal dynamics of base excision/single-strand break repair protein complex assembly/disassembly are modulated by the PARP/NAD+/SIRT6 axis , 2021, Cell reports.

[14]  J. Qu,et al.  Mitochondrial sirtuins, metabolism, and aging. , 2021, Journal of genetics and genomics = Yi chuan xue bao.

[15]  K. G. Akbulut,et al.  SIRT2 and FOXO3a expressions in the cerebral cortex and hippocampus of young and aged male rats: antioxidant and anti-apoptotic effects of melatonin , 2021, Biologia Futura.

[16]  A. Heshmati,et al.  Evaluation of Protective Effects of Curcumin and Nanocurcumin on Aluminium Phosphide‑Induced Subacute Lung Injury in Rats: Modulation of Oxidative Stress through SIRT1/FOXO3 Signalling Pathway , 2021, Drug Research.

[17]  Xianrong Lai,et al.  Pharmacokinetics and Pharmacological Activities of Berberine in Diabetes Mellitus Treatment , 2021, Evidence-based complementary and alternative medicine : eCAM.

[18]  Xiaodan Zhang,et al.  Curcumin Alleviates Aβ42-Induced Neuronal Metabolic Dysfunction via the Thrb/SIRT3 Axis and Improves Cognition in APPTG Mice , 2021, Neurochemical Research.

[19]  E. Barreiro,et al.  Curcumin and Resveratrol Improve Muscle Function and Structure through Attenuation of Proteolytic Markers in Experimental Cancer-Induced Cachexia , 2021, Molecules.

[20]  Liu Cao,et al.  Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway , 2021, International journal of biological sciences.

[21]  G. Du,et al.  Quercetin attenuates ischemia reperfusion injury by protecting the blood-brain barrier through Sirt1 in MCAO rats , 2021, Journal of Asian natural products research.

[22]  L. Roshangar,et al.  Ameliorative effects of fisetin in letrozole-induced rat model of polycystic ovary syndrome , 2021, The Journal of Steroid Biochemistry and Molecular Biology.

[23]  Agnieszka Piwkowska,et al.  Involvement of nitric oxide synthase/nitric oxide pathway in the regulation of SIRT1-AMPK crosstalk in podocytes: Impact on glucose uptake. , 2021, Archives of biochemistry and biophysics.

[24]  Tingting Wang,et al.  The Protective Effect of Kaempferol Against Ischemia/Reperfusion Injury Through Activating SIRT3 to Inhibit Oxidative Stress , 2021, Brazilian journal of cardiovascular surgery.

[25]  Fatemeh Rezaei Kahmini,et al.  A comprehensive review of Sirtuins: With a major focus on redox homeostasis and metabolism. , 2021, Life sciences.

[26]  Hongqiao Zhang,et al.  Targeting oxidative stress in disease: promise and limitations of antioxidant therapy , 2021, Nature Reviews Drug Discovery.

[27]  Qingyang Wang,et al.  Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway , 2021, Renal failure.

[28]  X. Yao,et al.  Resveratrol-induced Sirt1 phosphorylation by LKB1 mediates mitochondrial metabolism , 2021, The Journal of biological chemistry.

[29]  M. Kabir,et al.  A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer’s Disease, Aging, Cancer, Inflammation, and Diabetes , 2021, International journal of molecular sciences.

[30]  Tianshu Xu,et al.  Anti-inflammatory effects of curcumin in acute lung injury: In vivo and in vitro experimental model studies. , 2021, International immunopharmacology.

[31]  Jie Cao,et al.  Quercetin induces pro‐apoptotic autophagy via SIRT1/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro , 2021, Thoracic cancer.

[32]  Wenkai Yang,et al.  Kaempferol Alleviates Oxidative Stress and Apoptosis Through Mitochondria-dependent Pathway During Lung Ischemia-Reperfusion Injury , 2021, Frontiers in Pharmacology.

[33]  Liming Yang,et al.  Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages , 2021, Aging.

[34]  U. Das “Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications , 2021, Biomolecules.

[35]  M. Fabbrini,et al.  Nutraceutical based SIRT3 activators as therapeutic targets in Alzheimer's disease , 2021, Neurochemistry International.

[36]  N. AlFaris,et al.  Kaempferol suppresses acetaminophen-induced liver damage by upregulation/activation of SIRT1 , 2021, Pharmaceutical biology.

[37]  Haiying Chen,et al.  Emerging roles of SIRT6 in human diseases and its modulators , 2020, Medicinal research reviews.

[38]  H. H. Park,et al.  Phytochemicals as Anti-Inflammatory Agents in Animal Models of Prevalent Inflammatory Diseases , 2020, Molecules.

[39]  S. Dobrowolski,et al.  Impaired mitochondrial medium-chain fatty acid oxidation drives periportal macrovesicular steatosis in sirtuin-5 knockout mice , 2020, Scientific Reports.

[40]  Jie Shen,et al.  Dietary Phytochemicals that Can Extend Longevity by Regulation of Metabolism , 2020, Plant Foods for Human Nutrition.

[41]  Xiaofeng Yu,et al.  Ginsenoside Rb2 alleviates myocardial ischemia/reperfusion injury in rats through SIRT1 activation. , 2020, Journal of food science.

[42]  Yuanyuan Tie,et al.  Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1‐Foxo1 and PI3K‐Akt signalling pathways , 2020, Journal of cellular and molecular medicine.

[43]  Shixian Li,et al.  Curcumin improves necrotising microscopic colitis and cell pyroptosis by activating SIRT1/NRF2 and inhibiting the TLR4 signalling pathway in newborn rats , 2020, Innate immunity.

[44]  L. Altucci,et al.  SIRT1 Activation by Natural Phytochemicals: An Overview , 2020, Frontiers in Pharmacology.

[45]  Yan Li,et al.  Hypoxic preconditioning combined with curcumin promotes cell survival and mitochondrial quality of bone marrow mesenchymal stem cells, and accelerates cutaneous wound healing via PGC-1α/SIRT3/ HIF-1α signaling. , 2020, Free radical biology & medicine.

[46]  Baohua Liu,et al.  SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice , 2020, The EMBO journal.

[47]  B. Pourheydar,et al.  Cyclosporine a induces testicular injury via mitochondrial apoptotic pathway by regulation of mir-34a and sirt-1 in male rats: The rescue effect of curcumin. , 2020, Chemico-biological interactions.

[48]  S. Zhang,et al.  Iron overload adversely effects bone marrow haematogenesis via SIRT-SOD2-mROS in a process ameliorated by curcumin , 2020, Cellular & molecular biology letters.

[49]  E. Barreiro,et al.  Satellite Cells and Markers of Muscle Regeneration during Unloading and Reloading: Effects of Treatment with Resveratrol and Curcumin , 2020, Nutrients.

[50]  V. Singh,et al.  Role of Silent Information Regulator 1 (SIRT1) in Regulating Oxidative Stress and Inflammation , 2020, Inflammation.

[51]  Jiun-Jr Wang,et al.  Curcumin Attenuates Hemorrhagic Shock and Blood Replenish Resuscitation-induced Impairment of Pulmonary Barrier Function by Increasing SIRT1 and Reducing Malondialdehyde and TNF-α Contents and Neutrophil Infiltration in Lung in a Dose-Dependent Fashion. , 2020, Transplantation proceedings.

[52]  D. Fan,et al.  Biological properties and clinical applications of berberine , 2020, Frontiers of Medicine.

[53]  Jiansong Fang,et al.  Quercetin ameliorates diabetic encephalopathy through SIRT1/ER stress pathway in db/db mice , 2020, Aging.

[54]  A. Mai,et al.  Sirt4: A Multifaceted Enzyme at the Crossroads of Mitochondrial Metabolism and Cancer , 2020, Frontiers in Oncology.

[55]  Y. Li,et al.  The Effects and Mechanism of Quercetin Dietary Supplementation in Streptozotocin-Induced Hyperglycemic Arbor Acre Broilers , 2020, Oxidative medicine and cellular longevity.

[56]  M. Abdollahifar,et al.  The antioxidant curcumin postpones ovarian aging in young and middle-aged mice. , 2020, Reproduction, fertility, and development.

[57]  R. Hu,et al.  Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up‐regulating SIRT1 , 2020, Brain and behavior.

[58]  M. Rosini,et al.  Modulation of Keap1/Nrf2/ARE Signaling Pathway by Curcuma- and Garlic-Derived Hybrids , 2020, Frontiers in Pharmacology.

[59]  Wenkai Yang,et al.  Kaempferol Improves Lung Ischemia-Reperfusion Injury via Antiinflammation and Antioxidative Stress Regulated by SIRT1/HMGB1/NF-κB Axis , 2020, Frontiers in Pharmacology.

[60]  W. Sippl,et al.  Natural Products as Modulators of Sirtuins , 2020, Molecules.

[61]  F. Shidfar,et al.  The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor γ coactivator 1α gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial. , 2020, Diabetes & metabolic syndrome.

[62]  S. Hodge,et al.  Lymphocyte senescence in COPD is associated with decreased sirtuin 1 expression in steroid resistant pro-inflammatory lymphocytes , 2020, Therapeutic advances in respiratory disease.

[63]  Su Jin Lee,et al.  Curcumin Ameliorates Nonalcoholic Fatty Liver Disease through Inhibition of O-GlcNAcylation , 2019, Nutrients.

[64]  Liu Pengcheng,et al.  Quercetin attenuates oxidative stress‐induced apoptosis via SIRT1/AMPK‐mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model , 2019, Journal of cellular physiology.

[65]  Chunhua Ling,et al.  Curcumin ameliorates chronic obstructive pulmonary disease by modulating autophagy and endoplasmic reticulum stress through regulation of SIRT1 in a rat model , 2019, The Journal of international medical research.

[66]  S. Rizvi,et al.  Fisetin, a potential caloric restriction mimetic, modulates ionic homeostasis in senescence induced and naturally aged rats , 2019, Archives of physiology and biochemistry.

[67]  Chang-Shun Liu,et al.  Nanoemulsion improves hypoglycemic efficacy of berberine by overcoming its gastrointestinal challenge. , 2019, Colloids and surfaces. B, Biointerfaces.

[68]  E. Sikora,et al.  Curcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence , 2019, Biogerontology.

[69]  M. Pallàs,et al.  Role of Resveratrol and Selenium on Oxidative Stress and Expression of Antioxidant and Anti-Aging Genes in Immortalized Lymphocytes from Alzheimer’s Disease Patients , 2019, Nutrients.

[70]  Kai Le,et al.  SIRT1-regulated HMGB1 release is partially involved in TLR4 signal transduction: A possible anti-neuroinflammatory mechanism of resveratrol in neonatal hypoxic-ischemic brain injury. , 2019, International immunopharmacology.

[71]  Catalina Carrasco-Pozo,et al.  The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism , 2019, International journal of molecular sciences.

[72]  Shiqiang Yu,et al.  Quercetin improve ischemia/reperfusion‐induced cardiomyocyte apoptosis in vitro and in vivo study via SIRT1/PGC‐1α signaling , 2019, Journal of cellular biochemistry.

[73]  B. Salehi,et al.  Kaempferol: A Key Emphasis to Its Anticancer Potential , 2019, Molecules.

[74]  Z. Zuo,et al.  The role of different SIRT1-mediated signaling pathways in toxic injury , 2019, Cellular & Molecular Biology Letters.

[75]  K. Feng,et al.  Curcumin Inhibits the PERK-eIF2α-CHOP Pathway through Promoting SIRT1 Expression in Oxidative Stress-induced Rat Chondrocytes and Ameliorates Osteoarthritis Progression in a Rat Model , 2019, Oxidative medicine and cellular longevity.

[76]  Yu Cao,et al.  Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway , 2019, Oxidative medicine and cellular longevity.

[77]  I. Cristea,et al.  Mitochondrial Function, Metabolic Regulation, and Human Disease Viewed through the Prism of Sirtuin 4 (SIRT4) Functions. , 2019, Journal of proteome research.

[78]  H. Zeng,et al.  Emerging role of SIRT3 in endothelial metabolism, angiogenesis, and cardiovascular disease , 2018, Journal of cellular physiology.

[79]  H. Hosseinzadeh,et al.  Berberine and barberry (Berberis vulgaris): A clinical review , 2019, Phytotherapy research : PTR.

[80]  Hui Xue,et al.  Curcumin and resveratrol suppress dextran sulfate sodium-induced colitis in mice , 2019, Molecular medicine reports.

[81]  Yang Yu,et al.  The Roles of Mitochondrial SIRT4 in Cellular Metabolism , 2019, Front. Endocrinol..

[82]  Kyung‐Jin Min,et al.  Sirtuin signaling in cellular senescence and aging , 2019, BMB reports.

[83]  K. Jang,et al.  SIRT6 Is Involved in the Progression of Ovarian Carcinomas via β-Catenin-Mediated Epithelial to Mesenchymal Transition , 2018, Front. Oncol..

[84]  Agnieszka Piwkowska,et al.  The TRPC6-AMPK Pathway is Involved in Insulin-Dependent Cytoskeleton Reorganization and Glucose Uptake in Cultured Rat Podocytes , 2018, Cellular Physiology and Biochemistry.

[85]  N. Elguindy,et al.  Berberine chloride ameliorated PI3K/Akt-p/SIRT-1/PTEN signaling pathway in insulin resistance syndrome-induced rats , 2018, bioRxiv.

[86]  J. Tatebe,et al.  Curcumin Inhibits Age-Related Vascular Changes in Aged Mice Fed a High-Fat Diet , 2018, Nutrients.

[87]  Junjian Zhang,et al.  Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro , 2018, Behavioural Brain Research.

[88]  Do-Hee Kim,et al.  Curcumin suppresses oncogenicity of human colon cancer cells by covalently modifying the cysteine 67 residue of SIRT1. , 2018, Cancer letters.

[89]  S. Atkin,et al.  Impact of curcumin on sirtuins: A review , 2018, Journal of cellular biochemistry.

[90]  Li-Ping Liu,et al.  DPP‐4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high‐glucose conditions, potentially through the SIRT1/HIF‐1/VEGF pathway , 2018, CNS neuroscience & therapeutics.

[91]  F. Wang,et al.  SIRT4 is the last puzzle of mitochondrial sirtuins. , 2018, Bioorganic & medicinal chemistry.

[92]  Shihab U. Sobuz,et al.  SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix , 2018, Nature Communications.

[93]  Guoyu Huang,et al.  Sirtuin-4 (SIRT4), a therapeutic target with oncogenic and tumor-suppressive activity in cancer , 2018, OncoTargets and therapy.

[94]  J. Ko,et al.  Kaempferol protects against propacetamol-induced acute liver injury through CYP2E1 inactivation, UGT1A1 activation, and attenuation of oxidative stress, inflammation and apoptosis in mice. , 2018, Toxicology letters.

[95]  M. Yousefi,et al.  Nanocurcumin is a potential novel therapy for multiple sclerosis by influencing inflammatory mediators , 2018, Pharmacological reports : PR.

[96]  Lina Ma,et al.  Resveratrol prevents high-calorie diet-induced learning and memory dysfunction in juvenile C57BL/6J mice , 2018, Neurological research.

[97]  C. Martini,et al.  An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[98]  Chunhong Ma,et al.  Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome , 2018, The Journal of Immunology.

[99]  D. Sinclair,et al.  Sirtuin activators and inhibitors: Promises, achievements, and challenges. , 2018, Pharmacology & therapeutics.

[100]  K. G. Akbulut,et al.  The effects of melatonin and curcumin on the expression of SIRT2, Bcl-2 and Bax in the hippocampus of adult rats , 2018, Brain Research Bulletin.

[101]  T. Tsuda Curcumin as a functional food-derived factor: degradation products, metabolites, bioactivity, and future perspectives. , 2018, Food & function.

[102]  Caixia Liu,et al.  SIRT3: A New Regulator of Cardiovascular Diseases , 2018, Oxidative medicine and cellular longevity.

[103]  Meili Zhai,et al.  Curcumin attenuates IR-induced myocardial injury by activating SIRT3. , 2018, European review for medical and pharmacological sciences.

[104]  S. Rizvi,et al.  Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration , 2018, Life sciences.

[105]  H. Yoon,et al.  Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury , 2018, Aging.

[106]  Yangang Wang,et al.  Resveratrol pretreatment attenuates traumatic brain injury in rats by suppressing NLRP3 inflammasome activation via SIRT1. , 2017, Molecular medicine reports.

[107]  You Zhou,et al.  Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB pathway in vivo and in vitro , 2017, Redox biology.

[108]  Jingjing Tang,et al.  Curcumin attenuates skeletal muscle mitochondrial impairment in COPD rats: PGC-1α/SIRT3 pathway involved. , 2017, Chemico-biological interactions.

[109]  N. Ahmad,et al.  The Role of Sirtuins in Antioxidant and Redox Signaling. , 2017, Antioxidants & redox signaling.

[110]  Xueqian Wang,et al.  SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress , 2017, Cell Death and Differentiation.

[111]  J. Pedraza-Chaverri,et al.  Curcumin prevents cisplatin-induced renal alterations in mitochondrial bioenergetics and dynamic. , 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[112]  Jianxin Chen,et al.  FOXO Transcriptional Factors and Long-Term Living , 2017, Oxidative medicine and cellular longevity.

[113]  W. Xiao,et al.  One-Pot Synthesis of Hyperoside by a Three-Enzyme Cascade Using a UDP-Galactose Regeneration System. , 2017, Journal of agricultural and food chemistry.

[114]  Y. Kanbay,et al.  The effect of hesperidin and quercetin on oxidative stress, NF-κB and SIRT1 levels in a STZ-induced experimental diabetes model. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[115]  Shijie Cao,et al.  The metabolism of berberine and its contribution to the pharmacological effects , 2017, Drug metabolism reviews.

[116]  Wenhao Zheng,et al.  Fisetin inhibits IL‐1&bgr;‐induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice , 2017, International immunopharmacology.

[117]  M. J. Ornstrup,et al.  Comprehensive Metabolomic Analysis in Blood, Urine, Fat, and Muscle in Men with Metabolic Syndrome: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Resveratrol after Four Months’ Treatment , 2017, International journal of molecular sciences.

[118]  Xianggui Chen,et al.  Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors , 2017, Science China Life Sciences.

[119]  K. Park,et al.  Polydatin improves the developmental competence of bovine embryos in vitro via induction of sirtuin 1 (Sirt1). , 2017, Reproduction, fertility, and development.

[120]  Stephen L. Abrams,et al.  Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs , 2017, Aging.

[121]  Akiyuki Taruno,et al.  Actions of Quercetin, a Polyphenol, on Blood Pressure , 2017, Molecules.

[122]  Agnieszka Piwkowska,et al.  SIRT1-AMPK crosstalk is involved in high glucose-dependent impairment of insulin responsiveness in primary rat podocytes. , 2016, Experimental cell research.

[123]  A. Sirotkin The Role and Application of Sirtuins and mTOR Signaling in the Control of Ovarian Functions , 2016, Cells.

[124]  N. Turner,et al.  The role of mitochondrial sirtuins in health and disease. , 2016, Free radical biology & medicine.

[125]  N. Jia,et al.  SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons. , 2016, Biochemical and biophysical research communications.

[126]  Xiaodong Xie,et al.  Protective effect of curcumin on TNBS-induced intestinal inflammation is mediated through the JAK/STAT pathway , 2016, BMC Complementary and Alternative Medicine.

[127]  M. Lahtela-Kakkonen,et al.  Sirtuin functions and modulation: from chemistry to the clinic , 2016, Clinical Epigenetics.

[128]  E. Niewiadomska,et al.  The role of sirtuins in cellular homeostasis , 2016, Journal of Physiology and Biochemistry.

[129]  Mengqi Guo,et al.  Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro , 2016, Drug design, development and therapy.

[130]  E. Sikora,et al.  Curcumin elevates sirtuin level but does not postpone in vitro senescence of human cells building the vasculature , 2016, Oncotarget.

[131]  Yulong Yin,et al.  Quercetin, Inflammation and Immunity , 2016, Nutrients.

[132]  T. Luo,et al.  Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling , 2016, Brain Research Bulletin.

[133]  R. Seong,et al.  SIRT4 regulates cancer cell survival and growth after stress. , 2016, Biochemical and biophysical research communications.

[134]  Shiqiang Yu,et al.  Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1 , 2015, Oxidative medicine and cellular longevity.

[135]  S. Nabavi,et al.  Curcumin: a natural product for diabetes and its complications. , 2015, Current topics in medicinal chemistry.

[136]  S. Pyo,et al.  Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells. , 2015, Biochemical and biophysical research communications.

[137]  C. Cavadas,et al.  Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism. , 2015, Trends in pharmacological sciences.

[138]  E. Fisher,et al.  SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology , 2015, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[139]  M. He,et al.  Kaempferol protects cardiomyocytes against anoxia/reoxygenation injury via mitochondrial pathway mediated by SIRT1. , 2015, European journal of pharmacology.

[140]  Hong Jiang,et al.  Curcumin Attenuates Hydrogen Peroxide-Induced Premature Senescence via the Activation of SIRT1 in Human Umbilical Vein Endothelial Cells. , 2015, Biological & pharmaceutical bulletin.

[141]  Matthew J. Rardin,et al.  SIRT5 Regulates both Cytosolic and Mitochondrial Protein Malonylation with Glycolysis as a Major Target. , 2015, Molecular cell.

[142]  M. Concha,et al.  Nutraceutical activators of AMPK/Sirt1 axis inhibit viral production and protect neurons from neurodegenerative events triggered during HSV-1 infection. , 2015, Virus research.

[143]  K. Kaarniranta,et al.  Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases , 2015, Oxidative medicine and cellular longevity.

[144]  F. Amicarelli,et al.  Sirtuin Functions in Female Fertility: Possible Role in Oxidative Stress and Aging , 2015, Oxidative medicine and cellular longevity.

[145]  E. Sikora,et al.  Curcumin induces oxidation-dependent cell cycle arrest mediated by SIRT7 inhibition of rDNA transcription in human aortic smooth muscle cells. , 2015, Toxicology letters.

[146]  M. Yun,et al.  Synergic chemoprevention with dietary carbohydrate restriction and supplementation of AMPK-activating phytochemicals: the role of SIRT1 , 2015, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[147]  I. Yigit,et al.  The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity , 2015, Renal failure.

[148]  M. Russo,et al.  SIRT5 regulation of ammonia-induced autophagy and mitophagy , 2015, Autophagy.

[149]  E. Sikora,et al.  Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner , 2015, AGE.

[150]  Youming Peng,et al.  Protective effects of curcumin on acute gentamicin-induced nephrotoxicity in rats. , 2015, Canadian journal of physiology and pharmacology.

[151]  Xuemin Wang,et al.  Roles of SIRT1 in granulosa cell apoptosis during the process of follicular atresia in porcine ovary. , 2014, Animal reproduction science.

[152]  L. Altucci,et al.  Natural compounds in epigenetics: a current view. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[153]  M. Oshimura,et al.  Deacetylation of the mitotic checkpoint protein BubR1 at lysine 250 by SIRT2 and subsequent effects on BubR1 degradation during the prometaphase/anaphase transition. , 2014, Biochemical and biophysical research communications.

[154]  F. Cecconi,et al.  Oxidative stress and autophagy: the clash between damage and metabolic needs , 2014, Cell Death and Differentiation.

[155]  Robert W Sobol,et al.  ARTD1/PARP1 negatively regulates glycolysis by inhibiting hexokinase 1 independent of NAD+ depletion. , 2014, Cell reports.

[156]  Z. Ying,et al.  Curcumin attenuates D-galactosamine/lipopolysaccharide-induced liver injury and mitochondrial dysfunction in mice. , 2014, The Journal of nutrition.

[157]  D. Sinclair,et al.  SIRT2 induces the checkpoint kinase BubR1 to increase lifespan , 2014, The EMBO journal.

[158]  C. Dalmaz,et al.  Resveratrol treatment has neuroprotective effects and prevents cognitive impairment after chronic cerebral hypoperfusion , 2014, Neurological research.

[159]  S. López-Briones,et al.  A PPARγ, NF-κB and AMPK-Dependent Mechanism May Be Involved in the Beneficial Effects of Curcumin in the Diabetic db/db Mice Liver , 2014, Molecules.

[160]  N. Jia,et al.  Activation of SIRT1 by curcumin blocks the neurotoxicity of amyloid-β25-35 in rat cortical neurons. , 2014, Biochemical and biophysical research communications.

[161]  Yingming Zhao,et al.  Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. , 2014, Cell metabolism.

[162]  M. Garg,et al.  Dietary resveratrol supplementation normalizes gene expression in the hippocampus of streptozotocin-induced diabetic C57Bl/6 mice. , 2014, The Journal of nutritional biochemistry.

[163]  Jeffrey S. Smith,et al.  Yeast sirtuins and the regulation of aging. , 2014, FEMS yeast research.

[164]  D. Tan,et al.  Beneficial effect of resveratrol on bovine oocyte maturation and subsequent embryonic development after in vitro fertilization. , 2014, Fertility and sterility.

[165]  X. Chen,et al.  SIRT5 desuccinylates and activates SOD1 to eliminate ROS. , 2013, Biochemical and biophysical research communications.

[166]  B. Neuschwander‐Tetri,et al.  Steatosis in the liver. , 2013, Comprehensive Physiology.

[167]  P. Sachdev,et al.  The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer's disease , 2013, Ageing Research Reviews.

[168]  Yanjie Jia,et al.  Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia , 2013, Neural regeneration research.

[169]  W. Abbas,et al.  Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1 , 2013, Clinical Epigenetics.

[170]  E. Richter,et al.  Exercise, GLUT4, and skeletal muscle glucose uptake. , 2013, Physiological reviews.

[171]  J. Denu,et al.  Sirtuin Catalysis and Regulation* , 2012, The Journal of Biological Chemistry.

[172]  Y. Taketani,et al.  Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary , 2012, Reproductive Biology and Endocrinology.

[173]  V. H. Liao,et al.  Curcumin-mediated lifespan extension in Caenorhabditis elegans , 2011, Mechanisms of Ageing and Development.

[174]  J. Pezzuto,et al.  What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol , 2011, PloS one.

[175]  M. López-Lázaro,et al.  A review on the dietary flavonoid kaempferol. , 2011, Mini reviews in medicinal chemistry.

[176]  Suresh I. S. Rattan,et al.  Curcumin induces stress response and hormetically modulates wound healing ability of human skin fibroblasts undergoing ageing in vitro , 2011, Biogerontology.

[177]  G. Kelly A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 2. , 2010, Alternative medicine review : a journal of clinical therapeutic.

[178]  Á. Tósaki,et al.  Resveratrol: a multifunctional cytoprotective molecule. , 2010, Current pharmaceutical biotechnology.

[179]  P. Davies,et al.  Therapeutic potential of resveratrol in Alzheimer's disease , 2008, BMC Neuroscience.

[180]  B. Aggarwal,et al.  Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane). , 2007, Free radical biology & medicine.

[181]  Joseph A. Baur,et al.  Therapeutic potential of resveratrol: the in vivo evidence , 2006, Nature Reviews Drug Discovery.

[182]  M. Neuhouser Review: Dietary Flavonoids and Cancer Risk: Evidence From Human Population Studies , 2004, Nutrition and cancer.

[183]  B. Joe,et al.  Biological Properties of Curcumin-Cellular and Molecular Mechanisms of Action , 2004, Critical reviews in food science and nutrition.

[184]  A. Melk Senescence of renal cells: molecular basis and clinical implications. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[185]  D. Drucker,et al.  Effects of Aging and a High Fat Diet on Body Weight and Glucose Tolerance in Glucagon-Like Peptide-1 Receptor-/- Mice. , 1998, Endocrinology.

[186]  Lan Zhou,et al.  Curcumin promotes cholesterol efflux by regulating ABCA1 expression through miR-125a-5p/SIRT6 axis in THP-1 macrophage to prevent atherosclerosis. , 2021, The Journal of toxicological sciences.

[187]  A. Chuturgoon,et al.  Curcumin Upregulates Antioxidant Defense, Lon Protease, and Heat-Shock Protein 70 Under Hyperglycemic Conditions in Human Hepatoma Cells. , 2017, Journal of medicinal food.

[188]  A. Cicero,et al.  Berberine and Its Role in Chronic Disease. , 2016, Advances in experimental medicine and biology.

[189]  Zuo Wang,et al.  Curcumin enhanced cholesterol efflux by upregulating ABCA1 expression through AMPK-SIRT1-LXRα signaling in THP-1 macrophage-derived foam cells. , 2015, DNA and cell biology.

[190]  A. Hevener,et al.  Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training. , 2013, Comprehensive Physiology.

[191]  E. Siemann,et al.  Concentration of the Phytoalexin Resveratrol in Wine , 1992, American Journal of Enology and Viticulture.

[192]  M. Takaoka Of the phenolic substrate of hellebore (Veratrum grandiflorum Loes. fil.) , 1940 .