NanoStilbene

a nanoparticle formulation of pterostilbene

NanoStilbene PK Study

NanoStilbene Administration Results in Superior Pharmacokinetic Profi­le Compared to Pterostilbene Administration

NanoStilbene Clinical Trial in Cancer

These results suggest that NanoStilbene may be a useful adjuvant to immunotherapy of cancer rescuing T cell and NK cell activities.

Pterostilbene Literature Review

Cancer and Pterostilbene Comprehensive Literature Review

What is NanoStilbene?

NanoStilbene™, and now NanoStilbene PKE, is prepared by low-energy emulsification which allows for better solubility, stability, and the release performance of pterostilbene nanoparticles. The pterostilbene placed in a nanoemulsion droplet is free from air, light, and hard environment; therefore, as a delivery system, nanoemulsion can not only improve the bioavailability of pterostilbene but also protect it from oxidation and hydrolysis, while it possesses an ability of sustained release at the same time.

µmol pterostilbene calculation

1 mole of pterostilbene = 256 g

1 mmol pterostilbene = 256 mg

1 µmol pterostilbene = 256 µg = 0.256 mg

10 µmol pterostilbene = 2560 µg = 2.56 mg

100 µmol pterostilbene = 25,600 µg = 25.6 mg

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.

Frequently Asked Questions

Learn More About It!

What is Pterostilbene?

Pterostilbene is a natural dietary compound found in blueberries. We use the syntheic version due to limited amounts occuring naturally in the berries.

how much nanostilbene should i take daily?

We recommend up to 300mg daily which is approx 1.5 milliliters. However many find that 200mg daily is also suffice, therefore a range of 200-300mg daily is recommended.

can it be applied topically?

Yes small amounts may be applied locally but remember at 200mg per ml it is highly concentrated with a single drop containing 10mg.

What is nanostilbene?

NanoStilbene  is an easily absorbed nanoemulsion of nanoparticle pterostilbene in the range of 75-100nm at a concentration of 200 milligrams per milliliter

what is the concentration of nanostilbene?

NanoStilbene contains 200mg per ml or approximately 10mg per drop.

where can i obtain nanostilbene?

NanoStilbene can be obtained at our e-commerce site.