Product name: Piceatannol
Synonym name:
Catalogue No.: BP1525
Cas No.: 10083-24-6
Formula: C₁₄H₁₂O₄
Mol Weight: 244.246
Botanical Source: Found in Norway spruce, Vouacapoua macropetala, Pericopsis angolensis and other spp. Constit. of peanuts, Vaccinium sp. berries and grapes
Physical Description: Powder
Type of Compound: Stibene glucosides

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams, up to kilograms
Inquire for bulk scale.

Descriptions:
Piceatannol , a resveratrol analogue, is a polyphenol present in the skins of grapes and in wine and other foods, it inhibits proliferation and migration of VSMC treated with TNF-α, therefore, piceatannol may be an effective therapeutic approach to treat atherosclerosis.[1]
Piceatannol inhibits the antigen-stimulated tyrosine phosphorylation of Syk and inhibit mast cell Fc epsilon R1-mediated signaling and effector function.[2]
Piceatannol is a closely related stilbene that has antileukaemic and anti-cancer activity, it is converted from resveratrol by the cytochrome P450 enzyme CYP1B1;resveratrol, as well as the hydroxylated analog piceatannol, are potent inducers of apoptotic cell death in BJAB Burkitt-like lymphoma cells with an ED50 concentration of 25 microM; piceatannol is a very efficient inducer of apoptosis in this ex vivo assay with leukemic lymphoblasts of 21 patients suffering from childhood lymphoblastic leukemia.[3,4]
Piceatannol sensitizes TRAIL-induced-apoptosis via Sp1- and ERK-dependent DR5 up-regulation. [5]
Piceatannol is an anti-inflammatory, immunomodulatory, and anti-proliferative stilbene that has been shown to interfere withthe cytokine signaling pathway; piceatannol inhibits TNF-induced NF-κB activation and NF-κB-mediated gene expression through suppression of IκBα kinase and p65 phosphorylation.[6]
Piceatannol inhibits phorbol ester-induced NF-κB activation and cyclooxygenase-2 expression in human breast epithelial cells, the cysteine 179 of IKKβ as a potential target.[7]
Piceatannol, resveratrol and 3,3',4,4',5,5'-hexahydroxy-trans-stilbene manifest potent antioxidant effects on three leukemic cell lines and the presence of ortho-dihydroxy structures enhanced the protective effect against DNA damage caused by .OH radicals.[8]
Piceatannol exerts much stronger protective effects on PC12 cells from oxidative stress than did resveratrol, piceatannol treatment attenuates the intracellular accumulation of ROS induced by treatment of PC12 cells with Beta-amyloid, inhibits Beta-amyloid-induced apoptotic features including internucleosomal DNA fragmentation, nucleus condensation, cleavage of poly(ADP-ribose) polymerase (PARP), and activation of caspase-3. [9]

References:
[1] Lee B, Lee E J, Kim D I, et al. Toxicol in Vitro, 2009, 23(7):1284-91.
[2] Oliver J M, Burg D L, Wilson B S, et al. J Biol Chem, 1994, 269(47):29697-703.
[3] Potter G A, Patterson L H, Wanogho E, et al. Brit J Cancer, 2002, 86(5):774-8.
[4] Wieder T, Prokop A, Bagci B, et al. Leukemia, 2001, 15(11):1735-42.
[5] Kang C H, Moon D O, Choi Y H, et al. Toxicol in Vitro, 2011, 25(3):605-12.
[6] Ashikawa K, Majumdar S, Banerjee S, et al. J Immunol, 2002, 169(11):6490-7.
[7] Pilsoon S, Sinaye P, Na H K, et al. Carcinogenesis, 2010, 31(8):1442-9.
[8] Ovesná Z, Kozics K, Bader Y, et al. Oncol Rep, 2006, 16(3):617-24.
[9] Jin K H, Won L K, Joo L H. Ann NY Acad Sci, 2007, 1095(1):473-82.
[10] Liu B, Xie Y Q. China Medical Herald, 2009, 6(4):40-1.

HPLC of Piceatannol

HNMR of Piceatannol

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Polyphenolic compounds are highly regarded in the treasure trove of natural products due to their extensive biological activity and potential health benefits. Piceatannol (CAS number: 10083-24-6), as a naturally occurring stilbene polyphenol, is a hydroxylated analogue of resveratrol. Since its discovery, research has revealed its unique biological activity spectrum beyond its "star precursor" resveratrol. Bai Pi Shan Chun was initially recognized for its properties as a spleen tyrosine kinase (Syk) inhibitor, which can inhibit the expression of inducible nitric oxide synthase (iNOS) induced by tumor necrosis factor (TNF), demonstrating significant anti-inflammatory potential. Subsequent studies have continuously expanded its pharmacological boundaries, confirming its clear activities in anti-cancer, inducing cell apoptosis and autophagy, and protecting against acute lung injury (ALI). In recent years, with the deepening of research on aging biology, the role of resveratrol in regulating aging related signaling pathways (such as AMPK, SIRT1, NRF2, etc.) has become increasingly prominent, making it a rising star in the field of anti-aging research. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of resveratrol, in order to provide comprehensive academic references for the in-depth development and transformation research of this natural product.

Chemical structure and physicochemical properties

The chemical name of white bark cedar alcohol is 3,5,3 ', 4' - tetrahydroxystilbene, with a molecular formula of C ₁₄ H ₁₂ O ₄ and a molecular weight of 244.2460. Its structural core consists of two benzene rings connected by an vinyl group, belonging to the class of stilbene compounds. Compared with resveratrol (3,5,4 '- trihydroxystilbene), resveratrol has an additional hydroxyl group at the 3' position of the benzene ring, forming a hydroxyl substitution pattern of 3,5,3 ', 4'. This structural difference significantly affects its physicochemical properties and biological activity.

In terms of physical and chemical properties, the lipid water partition coefficient (LogP) of resveratrol is 2.5595, indicating that it has a certain degree of lipophilicity, but not highly hydrophobic. Its topological polar surface area (TPSA) is 80.9200 Å ², reflecting the polarity brought by multiple hydroxyl groups in the molecule. The water solubility data is 0.2697 mg/mL, which belongs to the category of slightly soluble to poorly soluble, posing a challenge for its formulation development. Preliminary evaluation of its pharmacological properties shows that its ability to penetrate the blood-brain barrier is relatively low, suggesting that its direct effects on central nervous system diseases may be limited. In terms of safety warning indicators, the hERG channel inhibition test result was negative, reducing its potential risk of inducing QT interval prolongation in the heart; The Ames test value is 1.2, indicating that there is no significant mutagenicity, but further in vitro and in vivo experiments are needed to confirm.

Plant sources and extraction methods

Bai Pi Shan Chun is widely distributed in nature, but its content is usually low. Its main plant sources include:
1. Grape family plants It is one of the most famous sources of resveratrol, especially in grape skins, grape seeds, and red wine. It is a metabolite formed by the hydroxylation of resveratrol catalyzed by cytochrome P450 enzyme CYP1B1 in grapes under stress or UV irradiation.
2. passion fruit The skin and seeds of passion fruit contain high concentrations of resveratrol, which is an important dietary source for it.
3. Other fruits and vegetables Blueberries, kiwis, sweet potatoes, and the roots of Japanese knotweed also contain a certain amount of resveratrol.
4. Wood It has also been found in the heartwood of some spruce plants.

The method for extracting resveratrol needs to be optimized based on the characteristics of the raw materials, and commonly used techniques include:
- Organic solvent extraction method The most commonly used method is to use methanol, ethanol, acetone, or their aqueous solutions for leaching or reflux extraction. Ethanol is often preferred due to its safety and environmental friendliness.
- Ultrasound assisted extraction/Microwave assisted extraction Using physical field effects to destroy plant cell walls significantly improves extraction efficiency and shortens extraction time.
- Supercritical fluid extraction Mainly using supercritical CO ₂, this method has mild conditions, no solvent residue, and good selectivity, but the equipment cost is high, making it suitable for the preparation of high value-added products.
- Separation and purification The crude extract is usually refined through liquid-liquid distribution, column chromatography (such as silica gel column, macroporous adsorption resin column, polyamide column), and high performance liquid chromatography (HPLC) or preparative thin layer chromatography (PTLC) to obtain high-purity resveratrol.

Pharmacological activity research

Numerous in vitro and in vivo studies have confirmed that resveratrol has diverse pharmacological activities.

1. Anti inflammatory and immune regulatory activity Baipi Shanchun is a classic Syk kinase inhibitor that inhibits the activity of Syk, thereby blocking the activation of downstream signaling pathways such as NF - κ B, effectively reducing the expression of iNOS, COX-2 induced by pro-inflammatory factors such as TNF - α, and the production of inflammatory mediators such as NO and PGE ₂. In animal models of acute lung injury (ALI), resveratrol can alleviate pulmonary inflammatory cell infiltration, reduce pulmonary edema and oxidative stress, exhibiting protective effects.
2. anticancer activity Bai Pi Shan Chun has growth inhibitory and pro apoptotic effects on various cancer cell lines. For example, in diffuse large B-cell lymphoma (DLBCL) cells, it can induce caspase dependent apoptosis. In MOLT-4 leukemia cells, it induces both autophagy and apoptosis, and autophagy may play a pro apoptotic role in this context. Its anti-cancer mechanism involves multiple stages such as cell cycle arrest, induction of apoptosis, and inhibition of invasion and metastasis.
3. Anti aging and cell protective activity This is a field that has attracted much attention in recent years for Baipi Shanchun. It can activate AMPK and deacetylase SIRT1, two core proteins that regulate energy metabolism and aging. By activating these pathways, resveratrol can enhance cells' resistance to oxidative stress, promote mitochondrial function, and may affect telomerase activity. Potential for neuroprotection and cardiovascular protection has been demonstrated in aging related disease models.
4. Antioxidant and Nrf2 activation White spruce alcohol itself has the ability to scavenge free radicals, and more importantly, it can activate the nuclear factor E2 related factor 2 (NRF2) signaling pathway, promote the expression of downstream antioxidant enzymes such as heme oxygenase-1 (HMOX1), superoxide dismutase (SOD1), catalase (CAT), etc., thereby enhancing the overall antioxidant defense system of cells.

Mechanism of action and molecular targets

The pleiotropic pharmacological effects of resveratrol stem from its regulation of multiple key molecular targets and signaling pathways.

1. Direct target and kinase inhibition：Syk kinase It is one of its clear direct targets of action. By binding to the kinase domain of Syk, its phosphorylation and downstream signaling are inhibited, which is the core mechanism of its anti-inflammatory effect. In addition, it may also affect other kinases, but with relatively low specificity.

2. Aging and stress regulation network：

   • AMPK/SIRT1 axis Baipi Shanchun is an effective activator of AMPK, which may be achieved by affecting the cellular AMP/ATP ratio or through direct action. Activated AMPK can phosphorylate and activate SIRT1. SIRT1 regulates through deacetylation, including TP53、FOXO1、NF-κB Numerous transcription factors within it affect cell apoptosis, stress resistance, metabolism, and inflammation. For example, the deacetylation of TP53 by SIRT1 can weaken its pro apoptotic function; Deacetylation of FOXO1 enhances its transcriptional activity and promotes CDKN1A (p21) Waiting for the expression of cell cycle inhibitors and antioxidant genes.
   • NRF2/KEAP1 pathway White bark cedar alcohol can dissociate and translocate NRF2 to the nucleus by modifying the cysteine residue of KEAP1, and bind to antioxidant response elements (ARE) to drive HMOX1、NQO1、CAT、SOD1 By transcribing genes, the antioxidant capacity of cells is systematically enhanced.
   • Telomeres and TERT Preliminary studies suggest that resveratrol may affect Telomerase reverse transcriptase (TERT) Its activity or expression indirectly affects telomere maintenance, but its specific mechanism still needs further exploration.

3. Cell fate regulation：

   • Apoptosis induction Inducing cancer cell apoptosis through upregulation of pro apoptotic proteins (such as Bax), downregulation of anti apoptotic proteins (such as Bcl-2), activation of caspase cascade reaction, and regulation of TP53 via AMPK/SIRT1 axis.
   • Autophagy regulation In cells such as MOLT-4, resveratrol can induce autophagic flow, and its mechanism may be related to AMPK activation (inhibition of mTORC1) or endoplasmic reticulum stress. Autophagy may synergize with apoptosis in this context, promoting cell death.

Evaluation of drug properties and pharmacokinetics

Despite its broad pharmacological activity, the development of medicinal properties of resveratrol still faces challenges.

1. Pharmacokinetic characteristics After oral administration, resveratrol is rapidly absorbed, but its bioavailability is generally low (much lower than resveratrol). This is mainly attributed to:

   • First pass metabolic effect In the intestine and liver, resveratrol undergoes extensive II binding metabolism, mainly through glucuronidation and sulfation, forming corresponding complexes.
   • Physical and chemical property limitations Moderate LogP and low water solubility affect its dissolution and transmembrane absorption.
   • Low blood-brain barrier permeability The large size and strong polarity of TPSA restrict its entry into the central nervous system.
     It has a wide distribution in the body, but is eliminated quickly and has a short half-life.

2. Formulation strategy To improve its bioavailability and efficacy, researchers have developed various delivery systems:

   • nano-formulation Including liposomes, nanoparticles, nanoemulsions, solid lipid nanoparticles, etc., they can improve solubility, protect against rapid metabolism, and achieve targeted delivery.
   • Prodrug modification By chemically modifying hydroxyl groups, lipophilic or targeted prodrugs are prepared, which are hydrolyzed in vivo to release the original drug.
   • Phospholipid complex/cyclodextrin inclusion complex Improve its solubility and membrane permeability.

3. safety Existing in vitro and partial animal experiments have shown that resveratrol has low toxicity. HERG inhibition negativity is an important cardiovascular safety advantage. The preliminary results of Ames test are optimistic, but comprehensive genetic toxicity, subchronic and chronic toxicity studies still need to be improved.

Clinical application prospects and prospects

The clinical application development of Bai Pi Shan Chun is advancing in the following directions:

1. Disease Prevention and Health Products As a natural ingredient found in various fruits, resveratrol has inherent advantages in the development of functional foods, dietary supplements, and cosmetics. Its anti-inflammatory, antioxidant, and potential anti-aging properties make it promising in preventing diseases related to oxidative stress and chronic inflammation, such as metabolic syndrome, early intervention in neurodegenerative diseases, and skin photoaging.

2. As a development of therapeutic drugs：

   • Anti inflammatory and immune related diseases Targeting its clear Syk inhibitory activity, it can be explored for the treatment of autoimmune or inflammatory diseases such as rheumatoid arthritis, asthma, and allergic dermatitis.
   • neoadjuvant therapy Given its multi-target anti-cancer properties and relatively low toxicity to normal cells, it can be considered as a sensitizer for chemotherapy or radiotherapy, or for chemoprevention of cancer.
   • Acute lung injury/acute respiratory distress syndrome (ALI/ARDS)Preclinical studies have demonstrated efficacy and are a promising direction for transformation.
   • Anti aging related diseases: It has shown potential in disease models closely related to aging, such as diabetes, cardiovascular disease, Alzheimer's disease, and so on, and is a hot spot for future research.

3. Challenges and Future Directions：

   • Improved bioavailability This is the biggest obstacle to its clinical application, and it is necessary to continue optimizing the new drug delivery system.
   • Deep exploration of mechanisms Especially its interaction between various targets (such as TERT) in the anti-aging network, as well as tissue-specific effects.
   • Preclinical and clinical research At present, the vast majority of research is still at the cellular and animal level, and there is an urgent need to design well-designed preclinical pharmacodynamics, pharmacokinetics, and safety evaluations, and ultimately advance them to human clinical trials to verify their effectiveness and safety.
   • Structural optimization and development of analogues Structural modification based on the parent nucleus of resveratrol is aimed at obtaining derivatives with stronger activity, more stable metabolism, and higher targeting.

Conclusion

As a natural derived stilbene polyphenol, Bai Pi Shan Chun has shown remarkable pharmacological potential in anti-inflammatory, anticancer, and especially in regulating aging core signaling pathways due to its unique chemical structure and multi-target properties. From being recognized as a Syk inhibitor to playing a key regulatory role in aging regulatory networks such as AMPK/SIRT1/NRF2, its research value is constantly being redefined. Despite significant challenges in drug formulation, particularly in terms of oral bioavailability, modern pharmaceutical and medicinal chemistry strategies provide feasible solutions for this. In the future, through interdisciplinary collaboration, the complex network of its functions will be thoroughly elucidated, delivery bottlenecks will be overcome, and systematic clinical translational research will be promoted. Baipi Shanchun is expected to develop from a promising natural active molecule into a drug or functional factor with practical application value in disease prevention, health maintenance, and even specific disease treatment, contributing its unique strength to the human health cause.