The biological activities and molecular effects of pterostilbene.

Modes/treatments Model used Mechanism References
Inflammation
pterostilbene (1–10μM) 3T3-L1 & RAW 264.7 coculture ↓IL-6 & TNF-α secretion
↓COX-2, ↓iNOS, ↓IL-6, ↓TNF-α, ↓PAI-1, ↓CRP, ↓MCP-1, ↓resistin, ↓leptin,
↓Migration of macrophages toward adipocytes		 Hsu et al, 2013 [1]
Pterostilbene (0.1–1μM) HUVECs ↓Monocyte binding, ↓sICAM1, ↓IL-8, ↓MCP-1, ↓sE-selectin, ↓p-eIF2α, ↓ICAM1, ↓MMP9, ↓CRP78 Liu et al, 2016 [2]
Breast cancer
Pterostilbene (40–80μM) MCF-7 ↓Cell viability, ↑Apoptosis, ↑Caspase-3, ↑Bax, ↓Bcl-2, ↑ROS generation, ↓MMP, ↑AMACR Chakraborty et al, 2010 [3]
Pterostilbene (50–100μM) MCF-7 & Bcap-37 ↓Cell viability, ↑Apoptosis, ↑PARP, ↑G1 phase arrest, ↓cyclin D1, ↓β-catenin, ↑autophagy, ↑LC3 II Wang et al, 2012 [4]
Pterostilbene (15–50μM) MCF-7 ↑Autophagy, ↑Beclin 1, ↑LC3 II, ↑ROS generation Chakraborty et al, 2012 [5]
Prostate cancer
Pterostilbene (1–25μM) LNCaP ↓Cell viability, ↑G1 phase arrest, ↑CDNK1A, ↑CDNK1B, ↓prostate-specific antigen Wang et al, 2010 [6]
Pterostilbene (40–80μM) PC-3 ↑Apoptosis, ↑caspase-3, ↑Bax, ↓Bcl-2, ↑ROS generation, ↓MMP, ↑AMACR Chakraborty et al, 2010 [7]
Pterostilbene (40–100μM) LNCaP ↓Cell viability, ↑G1 phase arrest, ↑p53, ↑p21, ↑p-AMPK, ↓fatty acid synthase, ↓acetyl CoA carboxylase Lin et al, 2012 [8]
Pterostilbene (40–100μM) PC-3 ↓Cell viability, ↑apoptosis, ↑caspase-3, ↑Caspase-9, ↑p-AMPK, ↓fatty acid synthase, ↓acetyl CoA carboxylase Lin et al, 2012 [8]
Colon cancer
Pterostilbene (1–30μM) HT-29 ↓Cell viability, ↓cyclin D1, ↓c-Myc, ↑PARP, ↓TNF -α, ↓IL-1β, ↓IFN-γ, ↓iNOS, ↓COX-2 Paul et al, 2009 [9]
Pterostilbene (0.004%) AOM-induced colonic carcinogenesis rat ↓Tumor multiplicity, ↓PCNA, ↓TNF-α, ↓IL-1β, ↓IL-4 Paul et al, 2010 [10]
Pterostilbene (50μM) HT-29 ↓β-catenin, ↓cyclin D1, ↓c-Myc, ↓IκBα,↓phosphorylation of p65 Paul et al, 2010 [10]
Pterostilbene (5–100μM) HCT-116, HT-29, & Caco-2 ↓Cell viability, ↓colony formation capacity, ↑apoptosis, ↑caspase-3, ↑PARP Nutakul et al, 2011 [11]
Pterostilbene (50 ppm & 250 ppm) AOM-induced colonic carcinogenesis mice ↓Aberrant crypt foci, lymphoid nodules & tumors, ↓NF-κB, ↓iNOS,↓COX-2, ↑heme oxygenase-1, ↑Glutathione reductase, ↑Nrf2 Chiou et al, 2011 [12]
Pterostilbene (5–50μM) COLO 205, HCT-116 & HT-29 ↑Apoptosis, ↑caspase-3, -8, -9, ↓mTOR/p70S6K, ↓PI3K/Akt, ↓MAPKs, ↓p-ERK1/2, ↓p-JNK1/2, ↑autophagy, ↑LC3 II Cheng et al, 2014 [13]
Pterostilbene (10 mg/kg BW) COLO 205 xenograft nude mice ↓Tumor volume, ↓tumor weight, ↓COX-2, ↓MMP-9, ↓VEGF, ↓cyclin D1, ↑caspase-3 Cheng et al, 2014 [13]
Diabetes
Pterostilbene (40 mg/kg BW) Diabetic rats ↓Blood glucose, ↓Glycosylated hemoglobin, ↑Hexokinase, ↓Glucose-6-phosphatase, ↓Fructose-1,6-bisphosphatase Pari et al, 2006 [14]
Pterostilbene (4μM & 8μM) INS-1E (insulin-secreting rat insulinoma) β-cell line ↑Nuclear Nrf2, ↑HO-1, ↑CAT, ↑SOD, ↑GPx, ↑Bcl-2, ↓Bax, ↓caspase-3 Bhakkiyalakshmi et al, 2014 [15]
Pterostilbene (15 mg/kg & 50 mg/kg BW) Wistar rats fed an obesogenic diet ↓HOMA-IR, ↑GLUT4, ↑p-Akt/total Akt ratio, ↑cardiotrophin-1, ↑glucokinase Gómez-Zorita et al, 2015 [16]
Dyslipidemia
Pterostilbene (40 mg/kg BW) Streptozotocin-nicotinamide induced type II diabetes rats ↓VLDL-C, ↓LDL-C, ↑HDL-C, ↓triglycerides, ↓free fatty acids, ↓phospholipids Satheesh & Pari, 2008 [17]
Pterostilbene (15 mg/kg & 30 mg/kg BW) Wistar rats fed an obesogenic diet ↓ Adipose tissue weight, ↓ ME, ↓FAS, ↓G6PDH, ↓CPT-1a, ↓ACO Gómez-Zorita et al, 2014 [18]
Pterostilbene (10–50μM) H4IIEC3 cells PPARα ligand, ↑PPARα gene expression Rimando et al, 2015 [19]
Aging
Pterostilbene (0.004% or 0.016%) Aged male Fischer rats (19-mo-old) ↓Cognitive behavioral deficits, ↓dopamine release, ↑pterostilbene levels in hippocampus, ↑working memory Joseph et al, 2008 [20]
Pterostilbene (120 mg/kg diet) SAMP8 mice ↓The number of errors over 2-day radial arm water maze test, ↑MnSOD, ↑PPAR-α, ↓phosphorylated JNK, ↓PHF Chang et al, 2012 [21]

ACO=acetyl-coA carboxylase; AMACR=a-methylacyl-CoA recemase; Bcl-2=B-cell leukemia/lymphoma 2; CAT=catalase; CDNK1A=cyclin-dependent kinase inhibitor 1A; CDNK1B=cyclin-dependent kinase inhibitor 1B; COX-2=cyclooxygenase-2; CPT-1a=carnitine palmitoyl-transferase 1a; CRP=C-reactive protein; FAS=fatty acid synthase; G6PDH=glucose-6-phosphate dehydrogenase; GLUT4=glucose transporter4; GPx=glutathione peroxidase; HDL-C=high density lipoprotein cholesterol; HO-1=heme oxygenase-1; HOMA-IR=homeostatic modelassessment-insulin resistance; IFN-g=interferon gamma; IkBa=inhibitor of kappa B; IL-1b=interleukin 1 beta; IL-4=interleukin 4; IL-6=interleukin 6; IL-8=interleukin 8; iNOS=inducible nitric oxide synthase; LC3 II=autophagy-related protein light chain 3 II; LDL-C=low densitylipoprotein cholesterol; MAPKs=mitogen-activated protein kinases; MCP-1=monocyte chemoattractant protein-1; ME=malic enzyme; MMP=matrix metallopeptidase; mTOR=mammalian target of rapamycin; Nrf2=NF-E2-related factor 2; p70S6K=70 kDa ribosomal protein S6kinase; PAI-1=plasminogen activator inhibitor-1; p-AMPK=phosphorylated adenosine monophosphate activated protein kinase; PARP=polyADP-ribose polymerase; PCNA=proliferating cell nuclear antigen; p-eIF2a=phospho-eIF2a; p-ERK1/2=phosphorylated-extracellular signal-regulated kinase 1/2; PHF=paired helical filaments; PI3K=phosphatidylinositol 3-kinase; p-JNK1/2=phospho-JNK1/2; sICAM1=solubleintercellular adhesion molecule-1; PPARa=peroxisome proliferator activated receptor alpha; ROS=reactive oxygen species; SOD=superoxidedismutase; TNF-a=tumor necrosis factor-a; VEGF=vascular endothelial growth factor; VLDL-C=very low density lipoprotein cholesterol.

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References
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[1] Hsu CL, Lin YJ, Ho CT, Yen GC. The inhibitory effect of pterostilbene on inflammatory responses during the interaction of 3T3-L1 adipocytes and RAW 264.7macrophages. J Agric Food Chem 2013;61:602e10.
[2] Liu J, Fan C, Yu L, Yang Y, Jiang S, Ma Z, Hu W, Li T, Yang Z, Tian T. Pterostilbene exerts an anti-inflammatory effect viaregulating endoplasmic reticulum stress in endothelial cells. Cytokine 2016;77:88e97.
[3] Chakraborty A, Gupta N, Ghosh K, Roy P. In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from Pterocarpus marsupium. Toxicol In Vitro 2010;24:1215e28.
[4] Wang Y, Ding L, Wang X, Zhang J, Han W, Feng L, Sun J, Jin H, Wang XJ. Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells. Am J Transl Res 2012;4:44e51
[5] Chakraborty A, Bodipati N, Demonacos MK, Peddinti R, Ghosh K, Roy P. Long term induction by pterostilbene results in autophagy and cellular differentiation in MCF-7 cells via ROS dependent pathway. Mol Cell Endocrinol 2012;355:25e40.
[6] Wang TT, Schoene NW, Kim YS, Mizuno CS, Rimando AM. Differential effects of resveratrol and its naturally occurring methyl ether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells. Mol Nutr Food Res2010;54:335e44.
[7] Chakraborty A, Gupta N, Ghosh K, Roy P. In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from Pterocarpus marsupium. Toxicol In Vitro 2010;24:1215e-28.
[8] Lin VC, Tsai YC, Lin JN, Fan LL, Pan MH, Ho CT, Wu JY, Way TD. Activation of AMPK by pterostilbene suppresses lipogenesis and cell-cycle progression in p53 positive and negative human prostate cancer cells. J Agric Food Chem2012;60:6399e407.
[9] Paul S, Rimando AM, Lee HJ, Ji Y, Reddy BS, Suh N. Anti-inflammatory action of pterostilbene is mediated through the p38 mitogen-activated protein kinase pathway in colon cancer cells. Cancer Prev Res 2009;2:650e7.
[10] Paul S, DeCastro AJ, Lee HJ, Smolarek AK, So JY, Simi B,Wang CX, Zhou R, Rimando AM, Suh N. Dietary intake of pterostilbene, a constituent of blueberries, inhibits theb-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats. Carcinog 2010;31:1272e-8.
[11] Nutakul W, Sobers HS, Qiu P, Dong P, Decker EA,McClements DJ, Xiao H. Inhibitory effects of resveratrol and pterostilbene on human colon cancer cells: a side-by-side comparison. J Agric Food Chem 2011;59:10964e70.
[12] Takemoto JK, Remsberg CM, Davies NM. Pharmacologica ctivities of 30-hydroxypterostilbene: cytotoxic, anti-Oxidant, anti-adipogenic, anti-inflammatory, histone deacetylase and sirtuin 1 inhibitory activity. J Pharm Pharm Sci2015;18:713e27.
[13] Cheng TC, Lai CS, Chung MC, Kalyanam N, Majeed M, Ho CT,Ho YS, Pan MH. Potent anti-cancer effect of 30-hydroxypterostilbene in human colon xenograft tumors. PLoS One 2014;9:e111814.
[14] Pari L, Satheesh MA. Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin and nicotinamide-induced diabetic rats. Life Sci 2006;79:641e-5.
[15] Bhakkiyalakshmi E, Shalini D, Sekar TV, Rajaguru P, Paulmurugan R, Ramkumar KM. Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through Nrf2. Br J Pharmacol 2014;171:1747e57.
[16] Gomez-Zorita S, Fernandez-Quintela A, Aguirre L, Macarulla M, Rimando A, Portillo M. Pterostilbene improves glycaemic control in rats fed an obesogenic diet: involvement of skeletal muscle and liver. Food Funct2015;6:1968e76.
[17] Satheesh MA, Pari L. Effect of pterostilbene on lipids and lipid profiles in streptozotocine nicotinamide induced type 2diabetes mellitus. J Appl Biomed 2008;6:31e7.
[18] Gomez-Zorita S, Fernandez-Quintela A, Lasa A, Aguirre L, Rimando AM, Portillo MP. Pterostilbene, a dimethyl ether derivative of resveratrol, reduces fat accumulation in rats fed an obesogenic diet. J Agric Food Chem 2014;62:8371e8.
[19] Rimando AM, Khan SI, Mizuno CS, Ren G, Mathews ST, Kim H, Yokoyama W. Evaluation of PPARa activation by known blueberry constituents. J Sci Food Agric2016;96:1666e71.
[20] Joseph JA, Fisher DR, Cheng V, Rimando AM, Shukitt-Hale B. Cellular and behavioral effects of stilbene resveratrol analogues: implications for reducing the deleterious effects of aging. J Agric Food Chem 2008;56:10544e51.journal of food and drug analysis 25 (2017) 134e147146
[21] Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt-Hale B, Smith MA, Joseph JA, Casadesus G. Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease. Neurobiol Aging 2012;33:2062e71.