pinosylvin and 3-3--4-5--tetrahydroxystilbene

Stilbenes are small molecular weight (approximately 200-300 g/mol), naturally occurring compounds and are found in a wide range of plant sources, aromatherapy products, and dietary supplements. These molecules are synthesized via the phenylpropanoid pathway and share some structural similarities to estrogen. Upon environmental threat, the plant host activates the phenylpropanoid pathway and stilbene structures are produced and subsequently secreted. Stilbenes act as natural protective agents to defend the plant against viral and microbial attack, excessive ultraviolet exposure, and disease. One stilbene, resveratrol, has been extensively studied and has been shown to possess potent anti-cancer, antiinflammatory and anti-oxidant activities. Found primarily in the skins of grapes, resveratrol is synthesized by Vitis vinifera grapevines in response to fungal infection or other environmental stressors. Considerable research showing resveratrol to be an attractive candidate in combating a wide variety of cancers and diseases has fueled interest in determining the disease-fighting capabilities of other structurally similar stilbene compounds. The purpose of this review is to describe four such structurally similar stilbene compounds, piceatannol, pinosylvin, rhapontigenin, and pterostilbene and detail some current pharmaceutical research and highlight their potential clinical applications.

Topics: Humans; Resveratrol; Stilbenes

Topics: Australia; Cyperaceae; Neoprene; Quinone Reductases; Resveratrol; Stilbenes

Prenylated stilbenoids synthesized in some legumes exhibit plant pathogen defense properties and pharmacological activities with potential benefits to human health. Despite their importance, the biosynthetic pathways of these compounds remain to be elucidated. Peanut (Arachis hypogaea) hairy root cultures produce a diverse array of prenylated stilbenoids upon treatment with elicitors. Using metabolic inhibitors of the plastidic and cytosolic isoprenoid biosynthetic pathways, we demonstrated that the prenyl moiety on the prenylated stilbenoids derives from a plastidic pathway. We further characterized, to our knowledge for the first time, a membrane-bound stilbenoid-specific prenyltransferase activity from the microsomal fraction of peanut hairy roots. This microsomal fraction-derived resveratrol 4-dimethylallyl transferase utilizes 3,3-dimethylallyl pyrophosphate as a prenyl donor and prenylates resveratrol to form arachidin-2. It also prenylates pinosylvin to chiricanine A and piceatannol to arachidin-5, a prenylated stilbenoid identified, to our knowledge, for the first time in this study. This prenyltransferase exhibits strict substrate specificity for stilbenoids and does not prenylate flavanone, flavone, or isoflavone backbones, even though it shares several common features with flavonoid-specific prenyltransferases.

Topics: Arachis; Dimethylallyltranstransferase; Hemiterpenes; Organophosphorus Compounds; Plant Proteins; Plant Roots; Plastids; Prenylation; Resveratrol; Seeds; Stilbenes; Substrate Specificity; Terpenes

Stilbenes are valuable phenolic compounds that are synthesized in plants via the phenylpropanoid pathway where stilbene synthase (STS) directly catalyzes resveratrol or pinosylvin formation. Currently, there is a lack of information about the stilbene biosynthetic pathway in spruce (Picea). Resveratrol and piceatannol derivatives have been detected in the spruce bark, needles, and roots. We analyzed seasonal variation in stilbene spectrum and content in the needles of different ages of one tree of spruce Picea jezoensis. HPLC analysis revealed the presence of nine stilbenes: t- and cis-astringin, t- and cis-piceid, t- and cis-isorhapontin, and t-piceatannol were present in amounts of 0.01-6.07 mg/g of dry weight (DW), while t-isorhapontigenin and t-resveratrol were present in traces (0.001-0.312 μg/g DW). T-astringin prevailed over other stilbenoid compounds (66-86% of all stilbenes). The highest total stilbene content was detected in one-year-old needles collected in the autumn and spring (5.4-7.77 mg/g DW). We previously cloned and sequenced full-length cDNAs of the four STS transcripts (PjSTS1a, PjSTS1b, PjSTS2, and PjSTS3) of P. jezoensis. This study presents a detailed analysis of seasonal variations in PjSTS1a, 1b, 2, and 3 transcript levels in the needles of P. jezoensis of different ages using qRT-PCR. PjSTS1a and PjSTS1b transcription was higher in the needles collected in the autumn, spring, or summer than in the winter. PjSTS2 was actively transcribed in the needles of all ages collected in the winter, spring, and summer. PjSTS3 expression did not significantly change during the year and did not depend on the age of the needles. Therefore, the data show that high levels of the stilbene glucosides and PjSTS expression are present in the needles of P. jezoensis.

Topics: Acyltransferases; Glucosides; Phenols; Picea; Plant Bark; Plant Roots; Resveratrol; Stilbenes

The pharmacokinetics of piceatannol, pinosylvin and rhapontigenin were characterized in male Sprague-Dawley rats after single intravenous doses of 10 mg kg(-1) of each stilbene. Serial blood samples were collected via a catheter inserted into the right jugular vein and plasma samples were analysed for the selected stilbenes concentrations using reverse phase HPLC methods. After an acute intravenous dose of piceatannol, plasma AUC, urine t(1/2), CL and V(d) were 8.48+/-2.48 micro g h mL(-1), 19.88+/-5.66 h, 2.13+/-0.92 Lh(-1) kg(-1) and 10.76+/-2.88 L kg(-1)(mean+/-s.e.m.), respectively. The acute intravenous dose of pinosylvin yielded the plasma AUC, urine t(1/2), CL and V(d) values of 5.23+/-1.20 micro g h mL(-1), 13.13+/-2.05 h, 1.84+/-0.44 Lh(-1) kg(-1) and 2.29+/-0.56 L kg(-1)(mean+/-s.e.m.), respectively. Rhapontigenin intravenous dosing yielded the plasma AUC, urine t(1/2), CL and V(d) values of 8.39+/-0.10 micro g h mL(-1), 25.31+/-1.46 h, 1.18+/-0.035 Lh(-1) kg(-1) and 11.05+/-0.17 L kg(-1)(mean+/-s.e.m.), respectively. Each stilbene was extensively glucuronidated. These stilbenes were predominantly eliminated via non-urinary routes. All three stilbenes were highly distributed into tissues and were highly extracted by the liver. The detectable plasma half-lives of these xenobiotics appear to be relatively short. However, utilizing urinary concentration-time data, much longer elimination half-lives were evident. The estimates of oral bioavailability characterize these stilbenes as poorly bioavailable compounds.

Topics: Animals; Area Under Curve; Biological Availability; Chromatography, High Pressure Liquid; Half-Life; Injections, Intravenous; Male; Mass Spectrometry; Rats; Rats, Sprague-Dawley; Stilbenes; Tissue Distribution

A series of hydroxylated trans-stilbenes related to the antileukemic natural product trans-3,3',4,5'-tetrahydroxystilbene (piceatannol) (1) has been prepared and tested for inhibition of the lymphoid cell lineage-specific protein-tyrosine kinase p56lck, which plays an important role in lymphocyte proliferation and immune function. A number of the analogues displayed enhanced enzyme inhibitory activity relative to the natural product. Reduction of the double bond bridging the two aromatic rings and benzylation of the phenolic hydroxyl groups was found to decrease activity significantly. The most potent compounds in the series proved to be trans-3,3',5,5'-tetrahydroxystilbene, trans-3,3',5-trihydroxystilbene, and trans-3,4,4'-trihydroxystilbene.

Topics: Hydroxylation; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Lymphocytes; Molecular Structure; Phenols; Protein-Tyrosine Kinases; Stilbenes; Structure-Activity Relationship