Search

To establish a structure–activity relationship for procyanidins, we verified the cyto‐protective effect of 13 grape seed procyanidins, ranging from monomers to trimers against H2O2‐induced oxidative stress in PC‐12 neuroblastoma cells. Our study demonstrated some procyanidins were able to significantly protect PC‐12 cells from the H2O2‐induced cytotoxicity suggesting they possess neuroprotective effects against oxidative stress. Procyanidins' protective effects against oxidative stress mainly depended on their polymerization degree in addition to their structural features. A positive correlation was found between procyanidins' polymerization degree and the protective effect against oxidative stress in PC‐12 cells. The presence of 3‐ or 3'‐galloylated groups in the C‐ring of procyanidin molecules significantly increased their protective activity as well. These results demonstrated that galloylated high‐molecular‐mass procyanidins would be of more interesting as promising antioxidant natural compounds. This work for the first time demonstrated the structure–activity relationships of 13 procyanidins' antioxidative stress activity, which could have a significant impact on future development of procyanidins for healthy food products or drugs to treat disease such as neurodegenerative disorders. Practical Application: This work evaluated the protective effect of procyanidins against oxidative stress in PC‐12 neuroblastoma cells and established their activity–structure relationships, which provides useful cellular evidence for the further investigating the structure‐optimizing and function‐exploiting of procyanidins. [ABSTRACT FROM AUTHOR]

Red wine is one of the most popular beverages worldwide. The benefit of moderate consumption of red wine on human health has been taken great interest recent years. In this present article, the anti-diabetic properties of red wine from Portugal were studied in vitro. The four fractions from solid phase extraction with reversed-phase material C18 were subjected to the anti-diabetic activity assay in vitro. Our findings show that dealcoholised red wine and the four fractions exhibited strong inhibitory activities both on α-glucosidase, which catalyses the cleavage of glucose from disaccharide and α-amylase, which breaks down long-chain carbohydrates, respectively. The results indicated that the main components responsible for such activities were found to be the monomeric and oligomeric flavan-3-ol compounds. Our data might provide further evidence that the prevention of hyperglycemia may be another beneficial effect of moderate consumption of red wine. Practical Applications The health benefits of moderate consumption of red wine have been well documented, and several techniques are used to investigate the potential activities of red wine polyphenols. However, there are few dates on the potential anti-diabetic activity of red wine from solid phase extraction (SPE) fractions. In this article, SPE technique was used to evaluate the activity of red wine polyphenols against diabetes, and our data indicate that another beneficial effect of consuming moderate amounts of red wine may be the prevention and treatment of diabetes. [ABSTRACT FROM AUTHOR]

The present study characterized in vitro metabolites of 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol (20(R)-25-OCH3-PPD) in mouse, rat, dog, monkey and human liver microsomes. 20(R)-25-OCH3-PPD was incubated with liver microsomes in the presence of NADPH. The reaction mixtures and the metabolites were identified on the basis of their mass profiles using LC-Q/TOF and were quantified using triple quadrupole instrument by multiple reaction monitoring. A total of 7 metabolites (M1–M7) of the phase I metabolites were detected in all species. 25(R)-OCH3-PPD was metabolized by hydroxylation, dehydrogenation, and O-demethylation. Enzyme kinetic of 20(R)-25-OCH3-PPD metabolism was evaluated in rat and human hepatic microsomes. Incubations studies with selective chemical inhibitors demonstrated that the metabolism of 20(R)-25-OCH3-PPD was primarily mediated by CYP3A4. We conclude that 20(R)-25-OCH3-PPD was metabolized extensively in mammalian species of mouse, rat, dog, monkey, and human. CYP3A4-catalyzed oxygenation metabolism played an important role in the disposition of 25(R)-OCH3-PPD, especially at the C-20 hydroxyl group. [ABSTRACT FROM AUTHOR]

[Display omitted] • Phenolic compound of Diospyros kaki L. cv. Mopan. extracts were identified and quantified. • Diospyros kaki L. cv. Mopan. extracts were rich in phenolic compounds, mainly flavonols. • The orders of content of phenolic composition: leaf > calyx > fruit extract. • Diospyros kaki L. cv. Mopan. extracts exhibited strong neuroprotective activity. • Persimmon fruit extract has more potential as a neuroprotective agent. Persimmon (Diospyros kaki L. cv. Mopan.), an important commercial crop belonging to the genus of Diospyros in the Ebenaceae family, is rich in bioactive phenolic compounds. In this study, the phenolic compounds from fruits, leaves, and calyces of persimmon were qualitatively and quantitatively determined by UPLC-Q-Exactive-Orbitrap/MS and UPLC-QqQ-MS/MS, respectively. Furthermore, the role of phenolic extract from different parts of persimmon on neuroprotective activity in vitro , through against oxidative stress and anti-neuroinflammation effect was firstly evaluated. The results showed that 75 phenolic compounds, and 3 other kinds of compounds were identified, among which 44 of phenolic compounds were quantified from different parts of persimmon. It is the first time that epicatechin-epigallocatechin, catechin-epigallocatechin, catechin-epigallocatechin (A-type), and glycoside derivatives of laricitrin were identified in persimmon extract. The dominated phenolic compounds in three parts of persimmon were significantly different. All phenolic extracts from each part of persimmon showed strong neuroprotective activities against H 2 O 2 -induced oxidative stress in PC-12 cells and LPS-induced BV2 cells. The fruit extract presented the strongest activity, followed by calyx and leaf extract. The systematic knowledge on the phytochemical composition along with activity evaluation of different parts of persimmon could contribute to their targeted selection and development. [ABSTRACT FROM AUTHOR]

A series of thiol-nucleophiles, captopril, l-cysteine, and tiopronin, were introduced to the degradation reaction of grape seed extracts and the eight new bioactive flavan-3-ol derivatives were observed. Then, these derivatives were successfully separated and prepared in large quantity by high-speed counter-current chromatography (HSCCC) and semi-preparative HPLC under the optimized separation conditions. The appropriate two solvent systems consisted of n-hexane–ethyl acetate–methanol–water (0.05:1.5:0.5:1.2, v/v/v/v) and n-hexane–ethyl acetate–water (1:10:10, v/v/v) with head–tail mode were used for HSCCC two-step separation of captopril degradation products. N-butanol–ethyl acetate–methanol–water (2:4:0.5:6, v/v/v/v) with a combination of tail–head and head–tail elution modes in HSCCC run of l-cysteine degradation products, and n-hexane–ethyl acetate–methanol–water (0.15:1.6:0.4:1, v/v/v/v) was applied with head–tail and tail–head elution modes in HSCCC separation of tiopronin degradation products. The structures of these derivatives were confirmed by MS and 1H NMR analysis. Moreover, a systematic comparison of antioxidant activity of all the eleven degradation products was first implemented and found that most of the derivatives had stronger antioxidant activity than free catechins. [ABSTRACT FROM AUTHOR]

Eight-year-old Syrah red wines were produced using various winemaking technologies. The structural composition of purified polymeric polyphenols (PP pure) from traditional fermentation (W ctrl), prolonged maceration with skins (W skin), and prolonged maceration with stems (W stem) was comprehensively analyzed using various depolymerization methods, followed by HPLC-FT-ICR-MS and HPLC/UPLC-QqQ/MS analysis. The results revealed that PP pure consisted of proanthocyanidins, anthocyanins, amino acids, and phenolic acids. Proanthocyanidins were present as both extension and terminal units, with the former being predominant. Amino acids, phenolic acids, and anthocyanins, on the other hand, were exclusively present as terminal units. The proportions of these constituent units in PP pure varied significantly depending on winemaking technologies. When comparing W skin and W stem with W ctrl , it was observed that W skin and W stem had lower anthocyanins and higher phenolic acids. Furthermore, W stem exhibited the highest amino acids. Moreover, the mean degree of polymerization (MDP) of the PP pure was influenced by the different fermentation technologies, with MDP values of 25.25, 13.14, and 15.84 for W ctrl , W skin , and W stem , respectively. These results indicated that different winemaking technologies significantly affect the structural features of polymeric polyphenols. These findings are crucial in providing practical applications for winemakers to control the polymeric polyphenol composition of wines. [Display omitted] • Structural constituents of polymeric polyphenols were obtained. • Inclusion of skins or stems led to lower anthocyanins and higher phenolic acids. • Inclusion of stems exhibited the highest amino acids. • Normal fermentations had the highest mean degree of polymerization. [ABSTRACT FROM AUTHOR]

Highlights • Grape seed PPCs were converted into OPCs by simultaneous reaction with C and EC. • The semisynthetic method was efficient and simple to gain dimers and trimers. • 13 individual procyanidins were obtained by one-step HSCCC and prep-HPLC. • The method could be applied to grape pomace and other procyanidin-rich plants. Abstract Polymeric procyanidins (PPCs) were the major constituents of procyanidins, while they have poor bioactivity. To better utilize PPCs, a semisynthetic approach for converting PPCs to oligomeric procyanidins (OPCs) was proposed. Grape seed PPCs were simultaneously reacted with catechin (C) and epicatechin (EC) under acid condition. Combining response surface methodology (RSM) and single-factor experiments, an optimized semisynthetic condition was confirmed with the ratio of PPCs with C and EC of 1:1:1, temperature of 40 °C, reaction time of 20 min and 0.1 M methanolic HCl. High-speed counter-current chromatography (HSCCC) was adopted to obtain three fractions from semisynthetic products and preparative-HPLC was used to isolate individual procyanidins. Thirteen B-type procyanidins including monomers, dimers and trimers were got with high yield of 0.8–17.8 mg from 200 mg semisynthetic products and high purity over 91%. The developed semisynthesis combined with separation method was efficient to obtain individual OPCs in preparative scale. [ABSTRACT FROM AUTHOR]

Plucking position and harvest time influence the metabolites of vine tea which are closely related to the taste quality and antioxidant activity. In this study, 75 vine tea samples produced by three plucking positions and harvested in five months were analyzed by untargeted metabolomics, and in vitro and in vivo antioxidant activities of different vine teas were evaluated. 37 compounds were tentatively identified through various methods. Compared with the high-concentration results, VIP scores of the major components in the low-concentration model were much higher and were filtered as characteristic markers. Chemometrics analysis showed that plucking position had a stronger influence on vine tea quality than harvest time. 16 identified metabolites, including flavonoids, organic acids and catechins, were found to be responsible for the recognition of the plucking position. Vine tea infusion made of young green leaves exhibited higher scavenge radical activity in vitro , and tender tip leaves exhibited higher antioxidant activities in vivo zebrafish, which may be due to the presence of a higher concentration of flavonoids in their phytochemical profile. This research is anticipated to provide useful enlightenment for the effective utilization of vine tea resources. • Influence of plucking position and harvest season on vine tea quality was evaluated. • Diverse characteristic markers were obtained with different concentrations. • Plucking position led to distinctive metabolite profiling signatures. • Vine tea made of young green leaves has the strongest antioxidant power in vitro. • Vine tea made of tender tip leaves has the highest antioxidant activity in vivo. [ABSTRACT FROM AUTHOR]

Synthesis of N-acyl AASs process. [Display omitted] • The paper summarized the classification, synthetic methods, physicochemical properties and applications of amino acid surfactants (AASs) with the latest research and application literature. • Various synthetic methods so far and their advantages and disadvantages were reviewed. • The paper can also provide the key directions on the research and development and application of AASs in related fields. Surfactants are widely used in washing, cosmetics, food, medicine, energy, construction, and other industrial fields. Biomass based surfactants have attracted attention because of their renewability and excellent performance. The number of related research and applications is increasing due to the varieties and excellent properties of amino acid surfactants (AASs). Based on the latest research and application literature, the paper summarized the classification; synthetic methods; and physicochemical properties of AASs, including surface activity, aggregate, gel, biodegradation, and safety and its applications in daily chemical, biological medicine, food, agriculture, and industry. The key research directions and good application prospects of AASs were summarized and prospected to provide reference for research and application in related fields. [ABSTRACT FROM AUTHOR]

[Display omitted] • HSCCC is an effective separation method with its special liquid–liquid mechanism. • The application of HSCCC in the separation of different polyphenols is reviewed. • HSCCC deserves to be promoted as a mainstream technology in separation of polyphenol. Polyphenols, which are commonly found in fruits, vegetables, cereals, and legumes, are the most abundant dietary antioxidants. To date, numerous studies have demonstrated the ability of polyphenols to prevent the development of several diseases and established the corresponding structure–activity relationships. However, polyphenol standards are either not commercially available or very expensive, mainly because the structural complexity and diversity of polyphenols complicate their fractionation and isolation from plant extracts by conventional separation techniques. High-speed countercurrent chromatography (HSCCC) is based on continuous liquid–liquid partitioning, which enables one to eliminate irreversible adsorption on solid supports. This technique has been extensively used for natural product isolation and is well suited to the effective large-scale separation of polyphenols and their derivatives, achieving high purities and yields of up to several hundred milligrams per run within several hours. The present review briefly introduces briefly HSCCC technology and summarizes its applications in the separation and purification of plant polyphenols, including the recent achievements in the large-scale preparation of proanthocyanidins and anthocyanins by our laboratory. [ABSTRACT FROM AUTHOR]

[Display omitted] • M2 (PD) is the main metabolite of dammarane ginsenoside AD-1 in vivo. • Compound M3 was isolated from metabolites in vivo for the first time. • PD could significantly inhibit the proliferation and migration of MDA-MB-231 cells and induce G1-phase arrest. • PD could significantly inhibit the proliferation and migration of breast cancer in nude mice. • PD inhibited proliferation and metastasis of breast cancer cells by inducing the p38 MAPK/MMP9 pathway. Previous studies have shown that 20 (R)-25-methoxyl-dammarane-3 β , 12 β , 20 triol (AD-1) can inhibit various cancer cell lines. This study aimed to explore the effect and mechanism of AD-1 metabolite M2 (Panaxadiol; PD) on breast cancer cells of nude mice. Five AD-1 metabolites were isolated and identified using various chromatographic techniques. PD was the main component. In vitro results showed that PD could inhibit the proliferation and migration of MDA-MB-231 cells by inducing G1-phase arrest. In addition, PD down-regulated the expression of Cyclin D1, cdk2, cdk4, cdk6, P-p38, and MMP9, and up-regulated p21 and p27. In vivo results showed that PD could effectively reduce the volume, weight, and migration of breast cancer Transcriptomics analyzed 491 differentially expressed genes by GO and KEGG enrichment. RT-PCR verification confirmed that the significant down-regulation of MMP9 was consistent with transcriptomics results. In further research showed that PD regulated the protein expression of P-p38 and MMP9 in MAPK pathway. In summary, in vivo and in vitro studies showed that PD significantly inhibit the occurrence and development of breast cancer, possibly through the MAPK pathway. [ABSTRACT FROM AUTHOR]

• Endogenous E and NE enantiomers were quantified in rat plasma with a new LC–MS/MS method. • The LLOQ for both E enantiomers was 1.0 ng/mL and for both NE enantiomers was 1.5 ng/mL. • First report of d- and l-E enantiomer differences in pharmacokinetics. • There was no evidence of in vivo inversion of d-enantiomer or l-enantiomer to its antipode. Epinephrine and norepinephrine are a class of chiral endogenous catecholamines, which are known as major neurotransmitters. This work described a new LC–MS/MS method coupled with pre-column derivatization, enabling the simultaneous enantiomeric separation of epinephrine and norepinephrine in rat plasma. After protein precipitation procedure, the samples were derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, [(S)-NIFE]. The derivatives resolved with good baseline separation on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with mobile phase composed of methanol with 0.2% formic acid in water at a flow rate of 0.2 mL/min. Analysis was performed by multiple reaction monitoring in positive ionization mode. The linear ranges were 1.0–500 ng/mL for epinephrine enantiomers and 1.5–750 ng/mL for norepinephrine enantiomers. The lower limits of quantification for epinephrine and norepinephrine enantiomers were 1.0 and 1.5 ng/mL, respectively. The intra-day and inter-day precision were all less than 10.7% and accuracy ranged from 96.0 to 101.5%. Recoveries for all the analytes were more than 80.3%. The proposed method was successfully applied to simultaneously determine endogenous epinephrine and norepinephrine enantiomers in rat plasma. l -epinephrine and l -norepinephrine were sensitively and accurately quantified while both the d -enantiomers were not detected. Additionally, epinephrine enantiomers were analyzed for stereoselective pharmacokinetics in rats after intravenous administration of racemic epinephrine for the first time. The pharmacokinetic results indicated that the disposition of epinephrine enantiomers was stereoselective and chiral inversion did not occur in rats. [ABSTRACT FROM AUTHOR]

An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'- O -gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis. Furthermore, the protective effect of B2-3'-G against alcohol-induced liver injury (ALI) was investigated. Compared with the parent compounds, B2-3'-G exhibited a stronger capacity for inhibiting ALI, attributed to its polymerization degree and galloyl group. Subsequent experiments revealed that the pretreatment of BRL-3A cells with B2-3'-G prior to ethanol improved ALI through activation of the Nrf2-HO-1/NQO1 pathway and initiation of enzymatic antioxidant systems. These findings suggest that GPC B2-3'-G is a potential hepatoprotective agent, which provides a new perspective for functional development of GPCs.

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3'- O -gallate (B2-3'-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure-activity relationship of B2-3'-G was further evaluated in vitro through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. The results suggested that the better protective effects of B2-3'-G against inflammation were attributed to its polymerization degree and the introduction of the galloyl group, compared to its four corresponding structural units. In vivo experiments demonstrated that the B2-3'-G prototype was distributed in plasma, small intestine, liver, lung, and brain. Remarkably, B2-3'-G was able to penetrate the blood-brain barrier and appeared to play an important role in improving brain health. Furthermore, a total of 18 metabolites were identified in tissues. Potential metabolic pathways, including reduction, methylation, hydration, desaturation, glucuronide conjugation, and sulfation, were suggested.

Accurate segmentation of medical images is essential for clinical decision-making, and deep learning techniques have shown remarkable results in this area. However, existing segmentation models that combine transformer and convolutional neural networks often use skip connections in U-shaped networks, which may limit their ability to capture contextual information in medical images. To address this limitation, we propose a coordinated mobile and residual transformer UNet (MRC-TransUNet) that combines the strengths of transformer and UNet architectures. Our approach uses a lightweight MR-ViT to address the semantic gap and a reciprocal attention module to compensate for the potential loss of details. To better explore long-range contextual information, we use skip connections only in the first layer and add MR-ViT and RPA modules in the subsequent downsampling layers. In our study, we evaluated the effectiveness of our proposed method on three different medical image segmentation datasets, namely, breast, brain, and lung. Our proposed method outperformed state-of-the-art methods in terms of various evaluation metrics, including the Dice coefficient and Hausdorff distance. These results demonstrate that our proposed method can significantly improve the accuracy of medical image segmentation and has the potential for clinical applications. Illustration of the proposed MRC-TransUNet. For the input medical images, we first subject them to an intrinsic downsampling operation and then replace the original jump connection structure using MR-ViT. The output feature representations at different scales are fused by the RPA module. Finally, an upsampling operation is performed to fuse the features to restore them to the same resolution as the input image., (© 2023. International Association of Scientists in the Interdisciplinary Areas.)

Neuronal mitochondrial dysfunction caused by excessive reactive oxygen species (ROS) is an early event of sporadic Alzheimer's disease (AD), and considered to be a key pathologic factor in the progression of AD. The targeted delivery of the antioxidants to mitochondria of injured neurons in brain is a promising therapeutic strategy for AD. A safe and effective drug delivery system (DDS) which is able to cross the blood-brain barrier (BBB) and target neuronal mitochondria is necessary. Recently, bioactive materials-based DDS has been widely investigated for the treatment of AD. Herein, we developed macrophage (MA) membrane-coated solid lipid nanoparticles (SLNs) by attaching rabies virus glycoprotein (RVG29) and triphenylphosphine cation (TPP) molecules to the surface of MA membrane (RVG/TPP-MASLNs) for functional antioxidant delivery to neuronal mitochondria. According to the results, MA membranes camouflaged the SLNs from being eliminated by RES-rich organs by inheriting the immunological characteristics of macrophages. The unique properties of the DDS after decoration with RVG29 on the surface was demonstrated by the ability to cross the BBB and the selective targeting to neurons. After entering the neurons in CNS, TPP further lead the DDS to mitochondria driven by electric charge. The Genistein (GS)- encapsulated DDS (RVG/TPP-MASLNs-GS) exhibited the most favorable effects on reliveing AD symptoms in vitro and in vivo by the synergies gained from the combination of MA membranes, RVG29 and TPP. These results demonstrated a promising therapeutic candidate for delaying the progression of AD via neuronal mitochondria-targeted delivery by the designed biomimetic nanosystems., Competing Interests: The authors declare that they have no conflicts of interests., (© 2020 [The Author/The Authors].)

Introduction: Na + -K + -2Cl - cotransporter isoform 1 (NKCC1) is important in regulating intracellular K + and Cl - homeostasis and cell volume. In this study, we investigated a role of NKCC1 in regulating glioma K + influx and proliferation in response to apoptosis inducing chemotherapeutic drug temozolomide (TMZ). The efficacy of a new bumetanide (BMT)-derivative NKCC1 inhibitor STS66 [3-(butylamino)-2-phenoxy-5-[(2, 2, 2-trifluoroethylamino) methyl] benzenesulfonamide] in blocking NKCC1 activity was compared with well-established NKCC1 inhibitor BMT. Methods: NKCC1 activity in cultured mouse GL26 and SB28-GFP glioma cells was measured by Rb + (K + ) influx. The WNK1-SPAK/OSR1-NKCC1 signaling and AKT/ERK-mTOR signaling protein expression and activation were assessed by immunoblotting. Cell growth was determined by bromodeoxyuridine (BrdU) incorporation assay, MTT proliferation assay, and cell cycle analysis. Impact of STS66 and BMT on cell Rb + influx and growth was measured in glioma cells treated with or without TMZ. Results: Rb + influx assay showed that 10 μM BMT markedly decreased the total Rb + influx and no additional inhibition detected at >10 μM BMT. In contrast, the maximum effects of STS66 on Rb + influx inhibition were at 40-60 μM. Both BMT and STS66 reduced TMZ-mediated NKCC1 activation and protein upregulation. Glioma cell growth can be reduced by STS66. The most robust inhibition of glioma growth, cell cycle, and AKT/ERK signaling was achieved by the TMZ + STS66 treatment. Conclusion: The new BMT-derivative NKCC1 inhibitor STS66 is more effective than BMT in reducing glioma cell growth in part by inhibiting NKCC1-mediated K + influx. TMZ + STS66 combination treatment reduces glioma cell growth via inhibiting cell cycle and AKT-ERK signaling., (Copyright © 2020 Luo, Wang, Ding, Hasan, Yang, Lin, Schreppel, Sun, Yin, Erker and Sun.)

Grape skin can be considered as an excellent and inexpensive source of polyphenol antioxidant compounds. A high-efficiency accelerated solvent extraction (ASE) method was developed for antioxidant polyphenols from grape skin. A three-factors three-level Box-Behnken design by response surface methodology was employed for optimization of extraction parameters in terms of total phenolic content, total anthocyanins content and antioxidant activity. The optimized condition was ethanol concentration of 48.80%, temperature of 50.79 °C and extraction time of 14.82 min. Under these conditions, the highest yields of polyphenol, the total phenolic content (15.24 mg GAE/g), total anthocyanins content (346.68 mg CGE/100 g) in grape skin, were obtained with significant antioxidant properties by DPPH, ABTS and FRAP assays. Moreover, the extracts from various grape skins by ASE, possessed ten main antioxidant polyphenols with the highest concentration of p-hydroxybenzoic acid and malvidin-3- O -glucoside. Compared with conventional solvent extraction, ASE extracted more amounts of polyphenols, exhibited more extraction level with shorter time and higher reproducibility., (© Association of Food Scientists & Technologists (India) 2019.)

To establish a structure-activity relationship for procyanidins, we verified the cyto-protective effect of 13 grape seed procyanidins, ranging from monomers to trimers against H 2 O 2 -induced oxidative stress in PC-12 neuroblastoma cells. Our study demonstrated some procyanidins were able to significantly protect PC-12 cells from the H 2 O 2 -induced cytotoxicity suggesting they possess neuroprotective effects against oxidative stress. Procyanidins' protective effects against oxidative stress mainly depended on their polymerization degree in addition to their structural features. A positive correlation was found between procyanidins' polymerization degree and the protective effect against oxidative stress in PC-12 cells. The presence of 3- or 3'-galloylated groups in the C-ring of procyanidin molecules significantly increased their protective activity as well. These results demonstrated that galloylated high-molecular-mass procyanidins would be of more interesting as promising antioxidant natural compounds. This work for the first time demonstrated the structure-activity relationships of 13 procyanidins' antioxidative stress activity, which could have a significant impact on future development of procyanidins for healthy food products or drugs to treat disease such as neurodegenerative disorders., Practical Application: This work evaluated the protective effect of procyanidins against oxidative stress in PC-12 neuroblastoma cells and established their activity-structure relationships, which provides useful cellular evidence for the further investigating the structure-optimizing and function-exploiting of procyanidins., (© 2018 Institute of Food Technologists®.)