Novel Stilbene Glycosides from Polygonum multiflorum

Two new stilbene glycosides (1 and 2), together with nine known compounds (3-11), were isolated from the water extract of Polygonum multiflorum Thunb. The structures of the new compounds were elucidated by their chemical properties and spectroscopic analyses, including extensive 2D NMR experiments. Compound 2 showed strong DNA cleavage activity, and compounds 1, 2 and 10 (2, 3, 4′, 5_tetrahydroxy_ trans _stilbene_2_O_β_ D _glucopyranoside) exhibited significant inhibition of lipid peroxidation.

Research on Correlation between Synthesis of Stilbenes and Aflatoxin Accumulation Caused by Aspergillus flavus in Peanut Seeds

In peanuts, a mechanism of resistance to fungal infection is reported on the synthesis of stilbene phytoalexins, which are antibiotic, low molecular weight metabolites. The phytoalexin-associated response of different peanut varieties to the inoculation with A. flavus has not been investigated and might be useful for breed- ing resistant peanut cultivars. In this study, peanut varieties resistant or susceptible to aflatoxin accumulation caused by A. flavus were selected to compare the synthe- sis differences of the four main stilbenes （resveratrol, ε-viniferin, 6-viniferin and pterostilbene） and the activities of their resistant enzymes （PAL, POD, PPO）, and explore the relationship between stilbene synthesis and resistance to aflatoxin accu- mulation. The results indicated that the synthesis speed of stilbenes was related to the resistance to aflatoxin accumulation in peanuts seeds. The total content of the four stilbenes reached the highest value of 47.37 μg/g in the resistant cultivars （Qian huasheng 3） after inoculation by A. flavus （54 times of the control） on the 3nd day, while the total content of stilbenes in susceptible cultivars （Huayu 22） was 5.5 μg/g. The content of stilbenes and the activities of their resistant enzymes from the resistant cultivars were both higher than from the susceptible one. The four peanut varieties with relative higher stilbene contents and lower disease index and aflatoxin content were selected by using the stilbene content. Very significant negative corre- lation, with correlation coefficients （r） of -0.789, -0.851 and -0.850, was observed between the stilbene content with disease index, the content of aflatoxin B1 and the total content of aflatoxins, respectively. Therefore, the study suggested that the total content of stilbene compounds might serve as an important chemical index in peanut seeds after inoculation with A. flavus on the 3nd day, during screening and breeding of peanut varieties resistant to aflatoxin accumulation.

Stilbene 420激光染料的光谱特性分析

配制了Stilbene 420染料溶液。测量了其吸收光谱。以调Q倍频Nd∶YAG激光为抽运源,实现了对Stilbene 420染料的激光光谱和荧光光谱的分析。激光光谱在425nm处获得最强峰值,半峰高宽(FWHM)为1nm,光谱范围为420～440nm。荧光光谱峰值在428.5nm,与激光最强峰值相差3.5nm。最高染料转换效率为9.26%。

VqMAPKKK38 is essential for stilbene accumulation in grapevine

Vitis species,including grapevine,produce a class of secondary metabolites called stilbenes that are important for plant disease resistance and can have positive effects on human health.Mitogen-activated protein kinase(MAPK)signaling cascades not only play key roles in plant defense responses but also contribute to stilbene biosynthesis in grapevine.MAPKKKs function at the upper level of the MAPK network and initiate signaling through this pathway.In this study,a Raf-like MAPKKK gene,VqMAPKKK38,was identified and functionally characterized from the Chinese wild grapevine V.quinquangularis accession‘Danfeng-2’.We observed that VqMAPKKK38 transcript levels were elevated by powdery mildew infection,high salinity conditions and chilling stresses,as well as in response to treatments by the hormones salicylic acid(SA),methyl jasmonate(MeJA),ethylene(Eth)and abscisic acid(ABA).In addition,based on both transient overexpression and gene suppression of VqMAPKKK38 in grapevine leaves,we found that VqMAPKKK38 positively regulates stilbene synthase transcription and stilbene accumulation probably by mediating the activation of the transcription factor MYB14.In addition,both hydrogen peroxide(H2O2)and calcium influx activated VqMAPKKK38 expression and stilbene biosynthesis,which suggests that VqMAPKKK38 may be involved in the calcium signaling and ROS signaling pathways.

Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice

Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.

Natural stilbenes effects in animal models of Alzheimer’s disease

Alzheimer’s disease is one of the most frequent neurodegenerative diseases.This pathology is characterized by protein aggregates,mainly constituted by amyloid peptide and tau,leading to neuronal death and cognitive impairments.Drugs currently proposed to treat this pathology do not prevent neurodegenerative processes and are mainly symptomatic therapies.However,stilbenes presenting multiple pharmacological effects could be good potential therapeutic candidates.The aim of this review is to gather the more significant papers among the broad literature on this topic,concerning the beneficial effects of stilbenes (resveratrol derivatives) in animal models of Alzheimer’s disease.Indeed,numerous studies focus on cellular models,but an in vivo approach remains of primary importance since in animals (mice or rats,generally),bioavailability and metabolism are taken into account,which is not the case in in vitro studies.Furthermore,examination of memory ability is feasible in animal models,which strengthens the relevance of a compound with a view to future therapy in humans.This paper is addressed to any researcher who needs to study untested natural stilbenes or who wants to experiment the most effective natural stilbenes in largest animals or in humans.This review shows that resveratrol,the reference polyphenol,is largely studied and seems to have interesting properties on amyloid plaques,and cognitive impairment.However,some resveratrol derivatives such as gnetin C,trans-piceid,or astringin have never been tested on animals.Furthermore,pterostilbene is of particular interest,by its improvement of cognitive disorders and its neuroprotective role.It could be relevant to evaluate this molecule in clinical trials.

Protective effect of tetrahydroxy stilbene glucoside on learning and memory by regulating synaptic plasticity

Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer＇s disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B （NR2B） expression. An APP695V7171 transgenic mouse model of Alzheimer＇s disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas- trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer＇s disease.

A New Stilbene Tetramer from Caragana rosea

Cararosinol A, a new stilbene tetramer, was isolated from Caragana rosea. Its structure has been established on the basis of spectroscopic evidence.

Prediction of the ^(13)C NMR Chemical Shifts of Stilbene Analogues by GIAO Method

After the geometry optimization at B3LYP/6-31＋G（d,p） level,the calculations of the NMR chemical shifts of a series of stilbene analogues were carried out by means of Gauge Including Atomic Orbitals（GIAO） method at HF/6-31＋G（d） level and B3LYP/6-311G＋（2d,p） level,respectively.The 13C NMR chemical shifts calculated at both HF/6-31＋G（d） and B3LYP/6-31＋G（d,p） levels are in agreement with the observed values.By virtue of a series of linear correction equations（δpred.=a＋bδcalcd.） of the 13C chemical shifts,accurate prediction of 13C chemical shifts was achieved for the new stilbene compounds.For the 13C NMR chemical shifts calculated at HF/6-31＋G（d） level,the linear correlation of δpred.with δexptl.is excellent,and the square of correlation coefficient,r2,is 0.9985.The maximum absolute difference between δpred.and δexptl.,Δδ,is 2.3,and the root-mean-square error between δpred.and δexptl.is 0.98.In the meantime,for those obtained at B3LYP/6-31＋G（d,p） level,the linear correlation of δpred.with δexptl.is also excellent,and the square of correlation coefficient,r2,is up to 0.9987.The maximum absolute difference between δpred.and δexptl.,Δδ,is 2.2,and the root-mean-square error between δpred.and δexptl.is only 0.88.

Synthesis, Structure of a Symmetrically Substituted Stilbene with Strong Two-photon Absorption and Up-converted Blue Fluorescence

Efficient Ti-catalyzed reductive coupling methodology was first employed to synthesize the symmetrical bis-donor stilbene, trans-4, 4'-bis[diphenyl amino] stilbene (BDPAS). X-ray diffraction analyses reveal that this new crystal belongs to the triclinic crystal system of centro-symmetric P-1 space group. The DBPAS solution, with the linear transmission at wavelength of greater than or equal to 450 nm, possesses large two-photon absorption cross section as high as 39.4x10(-48) cm(4).s/photon resulting in strong two-photon induced blue fluorescence of 460 nm, pumped by 740 nm laser irradiation.

A Pair of Dimeric Stilbene Epimers from Gnetum Montanum

A pair of dimeric stilbenes, gnetifolin M and gnetifolin N were isolated from the lianas of Gnetum montanum. All attempts to separate them by HPLC were unsuccessful. Their str-uctures were elucidated by the spectroscopic analysis including 2D-NMR studies on the peracetate.

Gnetifolin L and O, Two Dimeric Stilbenes from Gnetum Montanum

Two new dimeric stilbenes, named gnetifolin L and gnetifolin O, were isolated from the alcoholic extract of lianas of Gnetum montanum. Their structures were elucidated mainly on the basis of spectroscopic data including 2D-NMR studies on peracetate derivatives.

In situ absorption and metabolism of stilbene glycoside in rat

Stilbene glycoside(TSG)has been shown to have many beneficial properties.It is therefore essential to understand the absorption and metabolism of TSG in detail.We determined the recovery of TSG and its metabolites(TSG sulfate/glucuronides)in rat gastric contents,gastric mucosa,portal vein plasma,celiac arterial plasma,bile,and urine after administration of 15 mg of TSG in 0.5 mL physiological saline or incubation for 20 min in situ in the stomach of rats.Within 20 min,(64.0±9.8)% of the administered TSG disappeared from the stomach;later,TSG was recovered in both free and conjugated forms in plasma and bile,but not in urine.On the other hand,only free TSG was detected in the gastric contents and mucosa;it was also detected in the portal vein plasma as(48.1±3.5)% of the total TSG(all forms of TSG).However,the proportion of free TSG in the celiac arterial plasma and bile decreased to 4%-10%.In addition,the proportion of free TSG to total TSG in the liver microsome incubation mixture after TSG was incubated in liver microsome at 37 ℃ for 30 min was very low [(10.6 ± 2.6)%].These results indicate that TSG could be quickly absorbed from the rat stomach,conjugated in liver and excreted in bile.Such novel information would be helpful for the use of TSG as a beneficial natural product which may improve its proposed efficacy in preventing chronic diseases.

The first chromosome-level Fallopia multiflora genome assembly provides insights into stilbene biosynthesis

Fallopia multiflora(Thunb.)Harald,a vine belonging to the Polygonaceae family,is used in traditional medicine.The stilbenes contained in it have significant pharmacological activities in anti-oxidation and anti-aging.This study describes the assembly of the F.multiflora genome and presents its chromosome-level genome sequence containing 1.46 gigabases of data(with a contig N50 of 1.97 megabases),1.44 gigabases of which was assigned to 11 pseudochromosomes.Comparative genomics confirmed that F.multiflora shared a whole-genome duplication event with Tartary buckwheat and then underwent different transposon evolution after separation.Combining genomics,transcriptomics,and metabolomics data to map a network of associated genes and metabolites,we identified two FmRS genes responsible for the catalysis of one molecule of p-coumaroyl-CoA and three molecules of malonyl-CoA to resveratrol in F.multiflora.These findings not only serve as the basis for revealing the stilbene biosynthetic pathway but will also contribute to the development of tools for increasing the production of bioactive stilbenes through molecular breeding in plants or metabolic engineering in microbes.Moreover,the reference genome of F.multiflora is a useful addition to the genomes of the Polygonaceae family.

One pot synthesis of bis-silicon-bridged stilbene derivatives

Bis-silicon-bridged stilbene derivatives were synthesized in a modified procedure that combined the preparation of bis[2- （silyl）phenyl]acetylene and its intramolecular reductive cyclization in one pot. The results indicated that the one pot approach produced target products in a comparable yield to that of the two-step method reported previously.

The effect and mechanism of stilbene glycosides on improving neuronal injury in Alzheimer's disease rats by regulating ASK/MKK7/JNK pathway

Objective:To investigate the mechanism of action of tetrahydroxy stilbene glycosides(TSG)in ameliorating neuronal damage in Alzheimer's disease rats by regulating MKK7 and JNK kinases.Methods:A total of 24-month-old 42 SD rats were randomly selected for the experiment in 7 groups:normal group,sham-operated group,model group,positive drug group,low,medium and high dose TSG group at 0.033 g/kg,0.1 g/kg,0.3 g/kg.The Model Group and the TSG groups were established by stereotaxic Aβ25-35 solution.After 28 days,the model rats were selected by passive avoidance test.After screening,each dosage group of TSG and positive drug group was given intragastrically according to the corresponding dosage,and the experiment was carried out after 28 days.The pathological changes of hippocampal CA1 region were observed by tissue staining,and the amount of MKK7 and JNK proteins and the expression content of MKK7 and JNK mRNA by histochemical method of protein,and qRTPCR assay.Results:(1)He staining observation:Compared with the normal group and the sham-operated group,the number of nerve cells in the model group decreased and arranged irregularly,the cell membrane shrank,and the nucleus deformed and dissolved.The number of neurons in the positive drug group and TSG Group also increased significantly,the order is also relatively well.(2)From the results of the Tunel staining experiments:the positive apoptotic cells in the model group were higher than control group and sham-operated group,positive drug group and TSG drugs group was significantly smaller than that in the model group(P<0.05).(3)Compared with the control group and the Virtual Operation Group,the MKK7 and JNK protein concentrations in the brain of the model group were increased(P<0.05)by data analysis of immunohistochemistry:Compared with the model group,the protein expression of positive drug and TSG each dose group were reduced(P<0.05).(4)The results of QRTPCR data showed that the levels of MKK7 and JNK mRNA in the brain tissue of the model group were increased compared with the normal group and sham-operated groups(P<0.05).Conclusion:Stilbene glycoside has a certain effect on neuronal injury and repair which may be related to the changes of mRNA transcription and protein expression of MKK7 and JNK kinases.

Discovery of New Stilbene Antioxidants of the Bio-Elicited Peanut Sprout Powder (BPSP) and Longevity Extension of Mice Fed with BPSP-Supplemented Diets

Biosynthesis of peanut stilbenes, including resveratrol as the secondary metabolites, could be enhanced by subjecting the kernels to germination and wound-stress. Investigations of the bio-elicited peanut sprout powder (BPSP) addressed on characterization of the comprising stilbenes and effectiveness in longevity extension deserves intensive research. In this study, peanut kernels were subjected to germination and wound-stress in preparation of BPSP. The methanol extracts of BPSP were medium pressure liquid chromatographic (MPLC) fractionated and semi-preparative HPLC recovered and followed by instrumental identification and biological activity determinations of the isolated stilbenes. In longevity experiments, 16 female 11-mon-old BALB/c mice and both genders of 12-mon-old ICR mice were daily fed with BPSP supplemented diets at doses of 0, 0.1 and 0.5 g BPSP/kg bw for 750 and 762 days, respectively. Based on chemical characterization, enriched quantity of stilbenes in the BPSP up to ca. 1% (w/w) was detected. Two new stilbene compounds, namely, 4, 5’-dihydroxy-6’’-hydroxymethyl, 6’’-methylpyrano [2’’, 3’’: 3’, 4’] stilbene and 3, 4, 5’-trihydroxy-6’’, 6’’-dimethylpyrano [2’’, 3’’: 3’, 4’]stilbene along with 5 known stilbenes were isolated. The 7 stilbenes exhibited potent antioxidative and antiglycative activities and varied with structure-activity nature. Based on the resultant survival curves and average lifespans of both mouse models, basal diets supplemented with BPSP are effective to extend mouse longevity by a dose dependent manner. It is of merit to demonstrate that peanut kernels as a potent producer could be bio-elicited to biosynthesize a broad spectrum of bioactive stilbenes to prepare BPSP which is effective to extend mouse longevity as science-evidenced by the two long-term animal experiments.

Relevant Enzymes, Genes and Regulation Mechanisms in Biosynthesis Pathway of Stilbenes

Stilbenes are natural phenolic compounds which function as antimicrobial phytoalexins in plants and affect human health as cardioprotective, antibaceteria, antioxidative and antineoplastic agents. In this review, the progresses of study on relevant enzymes, genes, and regulation mechanism in biosynthesis pathway of stilbenes are described. Here we introduce a holistic and systematic method of researching relevant enzymes, genes and other regulatory factors in biosynthesis pathway of stilbenes—Systems biology. The application of knowledge of relative enzymes, genes and regulation mechanisms in stilbenes biosynthesis in metabolic engineering which is used as a tool of improving the disease resistance of plants and health caring quality of crops is also discussed.

Tetrahydroxy stilbene glucoside reduces the cognitive impairment and overexpression of amyloid precursor protein induced by aluminum exposure

Objective Excessive aluminum （Al） exposure impairs neurocognitive function in humans and animals. Epidemiologic studies have shown a potential linkage between chronic Al exposure and Alzheimer’s disease. The present study aims to evaluate the effects of tetrahydroxy stilbene glucoside （TSG）, the extract from herbal medicine Polygoni Multiflori, on cognitive impairment and the over-expression of hippocampal amyloid precursor protein （APP） induced by chronic exposure to Al in rats. Methods Rats were treated with 0.3% aluminum chloride （AlCl3） prepared in the drinking water for 90 d. AlCl3-treated animals were then randomly assigned to receive vehicle, TSG （4 g/kg）, or Vitamin E （VE; 40 mg/kg） treatment for 5 months. VE served as a positive control. The effect of TSG was evaluated by passive avoidance task, and APP expression was evaluated by Western blotting. Results Following exposure to AlCl3 for 90 d, animals displayed a striking decrease （〉80%） in step-through latency in the passive avoidance task and a significant increase in the expression of APP in the hippocampus. Both TSG and VE significantly ameliorated the performance impairment in the passive avoidance task, and suppressed the over-expression of APP. Moreover, the effects of TSG, but not of VE, were in a time-dependent manner. Conclusion TSG may possess therapeutic effects against Alzheimer’s disease.

Two New Isoprenylated Stilbenes from Artocarpus chama

Two new stllbenes with two Isoprenoid groups, namely artostllbenes A （compound 1） and B （compound 2）, were Isolated from the stems of Arfocarpus chama Buch.-Ham. by repeated column chromatography. The＆ structures were elucldated as （E）-4-[2-（7-meth-xy-2-2-d-methy-6-（3-methy-but-2-eny-）-2H-1-benz-pyran-5-y-）v-ny-]benzene-1- 2-dlol （compound 1） and （Z）-4-[2-（7-meth-xy-2-2-dimethy--6-（3-methy-but-2-eny-）-2H-1-benz-pyran-5-y-）v-ny-]ben- zene-l,2-dlol （compound 2） by spectroscopic methods, mainly by 1D-, 2D-NMR and MS spectra. Compounds 1 and 2 are two cls- and trans-lsomers and compound 2 is the flrst cis-stllbene isolated from Moraceous plants.