Natural stilbenoid; anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic, anti-obesity

Pterostilbene exhibits inhibitory action on HeLa cell growth at concentrations of 0, 5, 25, 50, 100, 200, and 400 μM. At 24 and 48 hours, the IC50 values are 101.2 μM and 65.9 μM, respectively. HeLa cells can undergo apoptosis when exposed to ipterostilbene at concentrations of 0, 25, 100, and 200 μM [2]. High antioxidant activity against DPPH, ABTS, hydroxyl, superoxide, and hydrogen peroxide is exhibited by pterostilbene (0.05, 0.1, 0.15, and 0.2 mM) in a dose-dependent manner. When proteins are damaged by TBHP and As-Fe2+, pterostilbene can mitigate the effects by reducing lipid peroxides and hydroperoxides, as well as restoring protein sulfhydryl groups. Additionally, in pBR322, pterostilbene prevents single-strand breaks [4].

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In breast cancer cells (MDA-MB-231, MCF-7), Pterostilbene induced apoptosis in a concentration- and time-dependent manner via mitochondrial depolarization, increased superoxide anion (O₂⁻) production, and caspase-3/7 activation. It also increased O₂⁻ production, mitochondrial depolarization, and caspase release [1]. Pterostilbene induced apoptosis through caspase-3, Bax, and p53, increased GPx antioxidant activity and H₂O₂/singlet oxygen production; catalase treatment inhibited cell death, confirming H₂O₂ involvement [1]. Pterostilbene increased BAX, cytochrome C, Smac/Diablo, and MnSOD expression, inducing intrinsic mitochondrial apoptosis [1]. Pterostilbene showed additive inhibitory effect with tamoxifen [1].
In vascular smooth muscle cells (VSMCs), Pterostilbene reduced PDGF-induced proliferation and Akt, downregulated CDK-2, CDK-4, cyclin E, cyclin D1, Rb, and PCNA [1]. In vascular endothelial cells (VECs), Pterostilbene inhibited oxLDL-induced apoptosis and induced autophagy via AMPK, Ca²⁺, and mTOR signaling; it reduced oxLDL-induced oxidative stress, suppressed Bax and p53, inhibited NF-κB activation, and reduced MMP, caspase-3/9, and LOX-1 signaling [1].
In gastric adenocarcinoma cells, Pterostilbene inhibited cell proliferation in a dose-dependent manner and induced apoptosis by increasing cytochrome C, Bad, Bax, and caspases 1,2,3,8,9 [1].
In colon cancer cells, Pterostilbene downregulated iNOS and COX-2, decreased expression of aldose reductase, increased GR and HO-1 via Nrf2 upregulation, and increased catalase, GPx, GR, and TR-1 by less than 2-fold, with a 5.7-fold increase in SOD2 activity; it downregulated Bcl-2 [1].
In human erythrocytes, Pterostilbene inhibited AAPH-induced hemolysis and AAPH-induced GSH depletion, and inhibited H₂O₂-induced lipid peroxidation [1].
In rat liver cells (WB-F344), Pterostilbene (0.5, 1.0, 5.0 μM for 24 h) prevented H₂O₂-induced inhibition of gap junction intercellular communication (GJIC) through dephosphorylation of connexin 43 (Cx43) [1]. In HepG2 hepatoma and Chang liver cells, Pterostilbene (6.25-100 μM) increased endogenous antioxidant activity (higher in HepG2) and decreased cell viability of HepG2 cells [1].
In pancreatic cancer cells (MIA PaCa-2, PANC-1), Pterostilbene induced apoptosis via mitochondrial membrane depolarization, cytochrome C release, Smac/DIABLO, and caspase-3/7 activation; genomic analysis revealed downregulation of MnSOD, DDIT-3, GDF-15 (MIC-1) and upregulation of MnSOD enzymatic activity [1].
In 3T3-L1 preadipocytes, Pterostilbene decreased cell population growth, fat droplet formation, and triacylglycerol accumulation; it altered gene expression of PPAR-γ, C/EBP-α, resistin, and FAS [1].
In prostate cancer cells, Pterostilbene prevented cell cycle progression at G1 phase in p53 wild-type cells by inducing p53 and p21; in p53-negative PC3 cells it induced apoptosis; it modified Bcl-2, Bax, caspase-3, increased GPx, GR, GSH (1.4-1.6- and 2.1-fold), and increased ROS by 5-fold; it also induced G1/S arrest and upregulated CDKN1A and CDKN1B, and decreased PSA [1]. [1]

In animal models of inflammation, pterostilbene (30 mg/kg per day, orally for 21 days) can inhibit the production of reactive oxygen species [3].
In breast cancer xenograft models, blueberry extract (not pure Pterostilbene) reduced tumor size and Ki-67, increased caspase-3; however, Pterostilbene alone inhibited pancreatic cancer in vivo (xenograft) reducing tumor volume and increasing apoptosis gene expression [1]. In streptozotocin-induced diabetic rats, oral Pterostilbene at 20 mg/kg significantly decreased plasma glucose by 42% and body weight by 20%; at 40 mg/kg for 6 weeks, it decreased plasma glucose by 56.54%, increased plasma insulin, reduced glycosylated hemoglobin (HbA1c), decreased gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6-biphosphatase), increased hexokinase, and reduced oxidative stress markers (TBARS, HP) in liver and kidney while increasing GSH, GST, SOD, GPx, catalase; histopathology showed reduced portal triad inflammation and renal damage, comparable to metformin 500 mg/kg [1]. In hypercholesterolemic hamsters, oral Pterostilbene at 20 ppm decreased plasma LDL by 29%, increased HDL by 7%, and decreased plasma glucose by 14%; it also increased PPAR-γ activation in rat liver cells [1]. In aged rats, dietary Pterostilbene at low (0.004%) and high (0.016%) doses improved cognitive and motor tasks in a dose-dependent manner (Morris water maze performance), with detectable hippocampal levels in high-dose animals; serum levels were 3.951±0.439 ng/mL (low) and 25.576±5.411 ng/mL (high) [1]. In SAMP8 aged mice, Pterostilbene at 120 mg/kg for 8 weeks improved radial arm water maze performance, increased MnSOD and PPAR-α, decreased phosphorylated JNK and tau [1]. In adjuvant arthritis rats, Pterostilbene (30 mg/kg daily p.o.) significantly lowered the number of neutrophils in blood on days 14 and 21 (p<0.05 and p<0.01) compared to arthritic controls; it did not significantly reduce spontaneous or PMA-stimulated ROS production; it nonsignificantly increased total peroxyl radical trapping capacity (TRAP) in plasma from 94 to 120 μmol/L (arthritic control 94, treated 120, healthy 267) [3]. [1][3]

Enzyme Assay: Pulse radiolysis was performed using a linear accelerator (LINAC) electron pulse radiolysis system. ABTS⁺ radicals were generated by reacting radiolytically produced azide radicals with ABTS. CO₃⁻ radicals were generated in a reaction mixture containing NaHCO3 and Na₂CO₃ saturated with N₂O. The decay of ABTS⁺ and CO₃⁻ radicals was monitored in the presence of different concentrations of Pterostilbene (0.05–0.20 mM) and correlated with ascorbic acid equivalents. For hydroxyl radical scavenging, competition kinetic methods were used: water was irradiated with 7 MeV electron pulses (50 ns pulse width, 17 Gy/pulse dose rate) to generate.OH, e-aq3 and H+; solutions were pre‑saturated with N₂O to convert e⁻ₐq and H• to •OH. •OH was made to react with KSCN in the absence or presence of Pterostilbene, and the decrease in (SCN)-formation (absorbance at 480 nm) was measured. The rate constant for •OH scavenging was calculated from the slope of the plot of the difference versus Pterostilbene concentration [4].
Xanthine/xanthine oxidase assay for superoxide radical scavenging: The reduction of nitroblue tetrazolium (NBT) by superoxide radicals generated from xanthine/xanthine oxidase was monitored spectrophotometrically at 560 nm. The percent inhibition of NBT reduction by Pterostilbene was calculated [4].
Hydroxyl radical scavenging by deoxyribose degradation method: •OH radicals generated by Fenton reaction degrade deoxyribose to malondialdehyde, which reacts with thiobarbituric acid to form a chromophore measured at 532 nm. The inhibition of this degradation by Pterostilbene was measured [4].
H₂O₂ scavenging assay: Decrease in H₂O₂ concentration in the presence of Pterostilbene was measured at 240 nm [4].
DPPH radical scavenging assay: DPPH (stable free radical) reduction was measured at 515 nm [4].
FRAP assay: Ferric to ferrous ion reduction at low pH leads to formation of ferrous‑tripyridyltriazine complex measured at 593 nm [4].
Ferrylmyoglobin/ABTS assay (total antioxidant capacity): Ability to scavenge ABTS radical cation was measured [4].

For the in vivo adjuvant arthritis model: Male Lewis rats were injected with a single intradermal injection of heat-killed Mycobacterium butyricum in Freund's adjuvant to induce arthritis. Pterostilbene (trans-pterostilbene, (E)-4'-hydroxy-3,5-dimethoxystilbene, synthesized and characterized by TLC, RP-HPLC, and ¹H NMR) was administered daily by oral gavage at a dose of 30 mg/kg body weight for 21 days. Blood was collected weekly (days 0, 7, 14, 21) to measure neutrophil numbers using a hemocytometer and to determine ROS production via chemiluminescence. At the end of the experiment (day 21), plasma was collected for the total peroxyl radical trapping capacity (TRAP) assay. Animals were kept in an air-conditioned room with 12h light/dark cycle and water ad libitum. The study was approved by the institutional Ethics Committee and State Veterinary and Food Administration [3].

Metabolism / Metabolites
Known human metabolites of pterostilbene include (2S,3S,4S,5R)-6-[4-[(E)-2-(3,5-dimethoxyphenyl)vinyl]phenoxy]-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid.

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Oral bioavailability in rats is approximately 80%, which is higher than that of resveratrol (20%) [1]. No other pharmacokinetic parameters (half-life, Cmax, AUC, etc.) are reported in the specified文献. [1]

In a randomized double-blind placebo-controlled trial in adults with hyperlipidemia, Pterostilbene at daily doses of 100 mg to 250 mg did not produce significant adverse drug events [1]. In healthy volunteers, treatment with 450 mg daily Pterocarpus marsupium extract (containing pterostilbene) did not produce signs of toxicity and resulted in detectable serum pterostilbene levels up to two weeks after administration [1]. No in vitro or in vivo toxicity data (e.g., LD50, organ toxicity) are reported in the specified文献. [1]

[1]. A review of pterostilbene antioxidant activity and disease modification. Oxid Med Cell Longev. 2013;2013:575482.

[2]. Pterostilbene (3',5'-dimethoxy-resveratrol) exerts potent antitumor effects in HeLa human cervical cancer cells via disruption of mitochondrial membrane potential, apoptosis induction and targeting m-TOR/PI3K/Akt signalling pathway. J BUON. 2018 Sep-Oct;23(5):1384-1389.

[3]. The effects of pterostilbene on neutrophil activity in experimental model of arthritis. Biomed Res Int. 2013;2013:106041.

[4]. Protective effect of Pterostilbene against free radical mediated oxidative damage. BMC Complement Altern Med. 2013 Sep 26;13:238.

Pterostilbene is a stilbene compound composed of a trans-stilbene molecule with a hydroxyl group at the 4-position and two methoxy substituents at the 3' and 5' positions, respectively. It possesses various activities, including antioxidant, antitumor, neurotransmitter, plant metabolite, apoptosis inducer, neuroprotective agent, anti-inflammatory agent, free radical scavenger, and hypoglycemic agent. Pterostilbene belongs to the stilbene alcohol, methoxybenzene, and diether class of compounds, derived from the hydride of trans-stilbene. It has been reported to exist in Vitis riparia, Vitis vulpina, and other organisms with relevant data. Pterostilbene is a naturally derived stilbene compound with a structure related to resveratrol, possessing potential antioxidant, anti-inflammatory, apoptosis-promoting, antitumor, and cytoprotective activities. After administration, pterostilbene exerts its antioxidant effect by scavenging reactive oxygen species (ROS), thereby preventing oxidative stress and ROS-induced cell damage. It may also activate the nuclear factor E2-related factor 2 (Nrf2)-mediated signaling pathway and increase the expression of various antioxidant enzymes, such as superoxide dismutase (SOD). Furthermore, pterocarpus marsupium can inhibit inflammation by reducing the expression of various inflammatory mediators, such as interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX), and nuclear factor κB (NF-κB). It can also inhibit or prevent the activation of many signaling pathways associated with carcinogenesis and increase the expression of various tumor suppressor genes while decreasing the expression of certain oncogenes. It can also directly induce tumor cell apoptosis.
See also: Pterocarpus marsupium wood (partial).

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Pterostilbene is structurally similar to resveratrol but has two methoxy groups, which increase its lipophilicity and oral absorption, resulting in 80% bioavailability in animal studies compared to 20% for resveratrol [1]. It is found naturally in blueberries (99-520 ng/gram) and Pterocarpus marsupium heartwood [1]. The compound exhibits both pro-oxidant effects in cancer cells (increasing ROS to induce apoptosis) and antioxidant effects in normal cells (scavenging ROS and upregulating antioxidant enzymes), depending on the cellular context [1]. In the adjuvant arthritis model, the decrease in neutrophil number by Pterostilbene may be due to interference with cytokine signaling rather than direct inhibition of oxidative burst, as its in vivo effects were less pronounced than in vitro [3]. [1][3]

C16H16O3

256.2964

256.109

537-42-8

5281727

White to off-white solid powder

1.2±0.1 g/cm3

420.5±35.0 °C at 760 mmHg

89-92ºC

208.1±25.9 °C

0.0±1.0 mmHg at 25°C

1.640

4.13

1

3

4

19

270

0

COC1=CC(=CC(=C1)/C=C/C2=CC=C(C=C2)O)OC

VLEUZFDZJKSGMX-ONEGZZNKSA-N

InChI=1S/C16H16O3/c1-18-15-9-13(10-16(11-15)19-2)4-3-12-5-7-14(17)8-6-12/h3-11,17H,1-2H3/b4-3+

4-[(E)-2-(3,5-Dimethoxyphenyl)ethenyl]phenol

Pterostilbene PS

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~110 mg/mL (~429.18 mM)

Solubility in Formulation 1: ≥ 3.93 mg/mL (15.33 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 39.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.75 mg/mL (10.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.75 mg/mL (10.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)