Journal of Functional Foods
·
2018
·
IF 3.47
Hong Ding,Xiaofei Li,Jian Li,Zhike Li,Yunhui Niu,Wanying Ren,Jianyang Tan,Shanye Yin
The present study examined the effects of procyanidin B2 (PB2) on L-NAME (nitric oxide synthase inhibitor)-induced hypertensive nephropathy. After 4 weeks of treatment with daily PB2 supplementation, lower blood pressure levels were observed in rats. The potential mechanisms were combined with amelioration of renal function impairment. The L-NAME–induced renal histological damage were reduced by PB2 treatment, which showed similar protective tendency in kidney injury molecule–1, nephrin, fibronectin and α–smooth muscle actin protein expression. This appears to be due to PB2 inducing a less pronounced generation of renal reactive oxygen species and inflammatory mediators than in the model group. Downregulation of Ang II type 1 receptor and NADPH oxidase subunit (NOX4, gp91phox and p47phox) played a critical role in the effect of PB2 reducing oxidative stress production. These activities could further support the use of PB2 commercially in food for the prevention of hypertension and its complications.
研究领域:
药理学
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肾病学
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高血压研究
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分子生物学
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产品关联
DOI
高影响因子
ULTRASONICS SONOCHEMISTRY
·
2018
·
IF 6.012
Zaizhi Liu,Lei Yang
An improved method of ultrasonic antisolvent precipitation was used to prepare micronized high polymeric procyanidins (HPC). Response surface methodology (Plackett–Burman and Box–Behnken design) was employed to predict the optimal preparation conditions and satisfactory mean particle size. Among seven parameters, three parameters (i.e., ultrasonic irradiation power, ultrasonic-stirring time, and stirring speed) were identified as the most significant variables using Plackett–Burman design; thus, these three parameters were further optimized using Box–Behnken design. The optimal preparation conditions for micronized HPC were obtained as follows: dropping speed of 4 mL/min, HPC solution concentration of 0.3 mg/mL, ratio of antisolvent and solvent of 5 mL/mL, precipitation temperature of 10 °C, ultrasonic-stirring time of 14 min, ultrasonic irradiation power of 620 W, and stirring speed of 760 r/min. A minimum mean particle size of 96 ± 2 nm was achieved under the aforementioned conditions. The obtained micronized HPC was analysed by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric and X-ray powder diffraction patterns. Micronized HPC enjoyed the higher quantity dissolved and exhibited stronger antioxidant activity in compared to the unprocessed HPC. These results demonstrated that the improved method has great potential for the production of micronized particles.
研究领域:
食品科学
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化学工程
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药理学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2019
·Vol. 63
·期 18
·1801255
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IF 4.653
Peng Cao,Yu Zhang,Zi Huang,Mitchell A. Sullivan,Zihao He,Jinglin Wang,Zehong Chen,Huiping Hu,Kaiping Wang
Scope Autophagy plays an important role in alleviating alcoholic liver disease (ALD). In this study, it is discovered that a dimer procyanidin (DPC) significantly prevented ALD by promoting hepatic autophagy. Methods and results Both cell and animal disease models stimulated by excessive ethanol are employed to evaluate the protective actions of DPC. Specifically, in vitro, DPC significantly decreased intracellular lipid deposition, diminished reactive oxygen species (ROS) formation, and elevated the level of mitochondrial membrane potential. These beneficial effects can be remarkably blocked by 3-methyladenine, a potent autophagy inhibitor, suggesting the autophagy-dependent protective role of DPC. In vivo, DPC pretreatment can also significantly reduce lipid accumulation, ROS overproduction, and elevated GSH content in the liver. Similarly, these protective effects of DPC can be partially reversed by chloroquine, a lysosomal inhibitor used to block the late-stage autophagy flux. Moreover, the determinations of LC3 and p62 protein expressions, autophagic flux assessments, and transmission electron microscopy observation further demonstrate the pro-autophagic effect of DPC. Conclusions DPC may activate hepatic autophagy to eliminate lipid droplets and damaged mitochondria, thereby reducing hepatic lipid disposition and ROS overproduction. This study demonstrates that DPC is a protective reagent on ALD, providing a novel strategy of fighting ALD.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
Brain Sciences
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2022
·Vol. 12
·期 5
·571
·
IF 3.333
Chao Song,Chao Gao,Zhenxin Wang
(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been investigated. (2) Method: Adult male mice received 2.3 mg/kg cisplatin or saline injections for three cycles consisting of five daily injections followed by 5 days of rest. Procyanidin or saline was administered 1 h prior to cisplatin treatment. Cognitive testing, gelatin zymography, and blood–brain-barrier (BBB) penetration tests were performed after treatment cessation. RAW264.7 cells were treated by stimulated supernatant of SHSY5Y cells. In addition, high-mobility group protein B1 (HMGB1) expression and MMP-9 activity were tested. (3) Results: Repeated cisplatin treatment increased BBB penetration, MMP-9 activity, impaired performance in contextual fear conditioning, and novel object recognition tasks. The knockout of MMP-9 rescues cognitive impairment and cisplatin-induced upregulation of HMGB1 in SHSY5Y cells. HMGB1/TLR4/IP3K/AKT signaling contributes to the increased MMP-9 activity in RAW264.7 cells. Procyanidin treatment attenuates MMP-9 activity, BBB damage, and CICI. (4) Conclusions: The results indicated that MMP-9 activation and BBB disruption is involved in CICI. Procyanidin may effectively alleviate the harmful effects of cisplatin.Keywords:cisplatin;chemotherapy;MMP-9;RAW264.7 cells;procyanidin;blood–brain barrier (BBB);chemotherapy-induced cognitive impairment (CICI)
研究领域:
肿瘤学
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神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Binhong Hu,Songqing Liu,Yuanyue Luo,Jingyu Pu,Xin Deng,Wenjing Zhou,Yuqing Dong,Yichuan Ma,Gang Wang,Fan Yang,Tianhui Zhu,Jiasui Zhan
Environmental exposure to hazardous materials causes enormous socioeconomic problems due to its deleterious impacts on human beings, agriculture and animal husbandry. As an important hazardous material, cadmium can promote uterine oxidative stress and inflammation, leading to reproductive toxicity. Antioxidants have been reported to attenuate the reproductive toxicity associated with cadmium exposure. In this study, we investigated the potential protective effect of procyanidin oligosaccharide B2 (PC-B2) and gut microbiota on uterine toxicity induced by cadmium exposure in rats. The results showed that the expression levels of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were reduced in utero. Proinflammatory cytokines (including tumor necrosis factor-α, interleukin-1β and interleukin-6), the NLRP3 inflammasome, Caspase-1 and pro-IL-1β were all involved in inflammatory-mediated uterine injury. PC-B2 prevented CdCl 2 -induced oxidative stress and inflammation in uterine tissue by increasing antioxidant enzymes and reducing proinflammatory cytokines. Additionally, PC-B2 significantly reduced cadmium deposition in the uterus, possibly through its significant increase in MT1, MT2, and MT3 mRNA expression. Interestingly, PC-B2 protected the uterus from CdCl 2 damage by increasing the abundance of intestinal microbiota, promoting beneficial microbiota, and inhibiting harmful microbiota. This study provides novel mechanistic insights into the toxicity of environmental cadmium exposure and indicates that PC-B2 could be used in the prevention of cadmium exposure-induced uterine toxicity.
研究领域:
毒理学
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生殖健康
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环境科学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Gen Li,Chunxiu Cai,Ning Zhang,Zijia Wang,Mingzhe Zhang,Quan Liu,Siyu Chen,Yanfei Shang,Chengqing Zhao,Shenzhen Ren,Hailong An
The calcium-activated chloride channel TMEM16A is frequently overexpressed in breast cancer, establishing a reciprocal activation loop with EGFR signaling pathways that play a crucial role in the proliferation of breast cancer. Consequently, the simultaneous targeting of TMEM16A and EGFR may be a promising, yet underexplored, therapeutic strategy for breast cancer. Herein, we developed a carrier-free polyphenol nanonetwork (PFGH) using procyanidin (PC), a natural polyphenolic TMEM16A inhibitor, via coordination with Fe 3+ , for co-delivering PC and gefitinib (Gef), an EGFR inhibitor. The resulting nanosystem, eliminating the requirement for additional nanocarriers, exhibited remarkable photothermal properties, pH-responsive drug release, and CD44-mediated tumor targeting. Functional assays confirmed that PFGH, under NIR irradiation, potently inhibited TMEM16A channel currents and exhibited superior antiproliferative effects compared to free PC, Gef, or their combination. RNA sequencing analysis confirmed the transcriptomic alterations in apoptosis, cell proliferation, and cancer-related pathways induced by the PFGH. In vivo studies further demonstrated that PFGH augments tumor-targeted combinatorial therapy, leveraging its photothermal properties, targeted co-delivery, and loop-suppressing activity. For the first time, our work presents a carrier-free polyphenol nanonetwork specifically engineered to co-target the TMEM16A-EGFR mutual activation loop, offering a novel, synergistic therapeutic approach for breast cancer.
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PubMed
高影响因子
International Journal of Biological Sciences
·
2026
·Vol. 22
·期 1
·161-177
·
IF 10
Huo Ran,Gu Chen-Zheng,Liu Yang,Wei Zi-Xian,Liu Te,Zhu Jie,Ding Lin,Liu Yu,Wang Chu-Yu,Li Yi-Ni,He Xin-Yi,Yang Wen-Jing,Wang Bei-Li,Wei Yun-Wei,Guo Wei
The mortality of hepatocellular carcinoma (HCC) is high. Plant-derived bioactive compounds have emerged as potential therapies for HCC. Procyanidin (PAC) has been shown to possess immune-modulating and anti-tumor properties. However, the role and mechanism of total PAC in treating HCC remain unclear. We established subcutaneous and orthotopic HCC mouse models to assess the effect of PAC on tumor growth. Multi-omics analyses and in vitro experiments were conducted to investigate the changes in the gut microbiota, related-metabolites, and the tumor microenvironment (TME). 16S rDNA sequencing revealed that PAC could reshape the gut microbiota, notably increasing Lactobacillus murinus abundance. Furthermore, transplantation of Lactobacillus murinus reduced tumor volumes in mice. Single-cell RNA sequencing showed upregulation of the MAPK pathway in B cells within the TME. Metabolomic analysis suggests that 5-Hydroxytryptophan (5-HTP) derived from Lactobacillus murinus was significantly increased in B cells from mesenteric lymph nodes (MLNs) in the PAC-treated group. In vitro experiments revealed that 5-HTP could significantly upregulate the MAPK pathway in B cells. Additionally, 5-HTP-educated B cells could activate IFN-γ+CD8+T cells through B cell-T cell interactions, indicating that 5-HTP is a key metabolite in the therapeutic effect of PAC. Finally, feeding 5-HTP to HCC mice reduced tumor volume, upregulated the MAPK pathway in B cells from MLNs, and activated IFN-γ+CD8+T cells in the TME. PAC reshapes the gut microbiota and metabolites, upregulates the MAPK pathway in B cells from MLNs, and activates CD8+T cells in the TME through the gut-liver axis, thereby inhibiting HCC progression.
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2023
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IF 8.1
Ling Liu,Qi Dong,Youmeng Kong,Yiru Kong,Ziyin Yu,Bin Li,Haixia Yan,Xu Chen,Yixiao Shen
Procyanidin is a group of dietary flavonoids abundant in berry fruits. In this study, the effects and underlying mechanisms of B type procyanidin (PC) on free radical and metal ion (H 2 O 2 , AAPH and Fe 3+ ) induced milk protein β-lactoglobulin (BLG) glyco-oxidation were investigated. The results indicated that PC protected BLG structure changes from cross-link and aggregation induced by free radicals and metal ion. Additionally, it effectively inhibited BLG oxidation by reducing approximately 21%-30% carbonyls and 15%-61% schiff base crosslink formation. Also, PC suppressed BLG glycation by inhibiting 48–70% advanced glycation end-products (AGEs) and reduced the accumulation of intermediate product methylglyoxal (MGO). The corresponding mechanisms were elucidated that PC exhibited great free radical scavenging and metal chelating properties; PC had non-covalent bind with the amino acid residues (preferably lysine and arginine) of BLG and blocked them from glycation; PC interrupted BLG glycation by forming procyanidin-MGO conjugates. Therefore, B type procyanidin was an effective glyco-oxidation inhibitor in milk products.
研究领域:
食品科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
PLoS One
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2013
·Vol. 8
·期 8
·e71071
·
IF 3.73
Bo-xin Zhao,Ya-bin Sun,Sheng-qi Wang,Lian Duan,Qi-lu Huo,Fei Ren,Guo-feng Li
The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Yanxia Yu,Chunying Zuo,Mingrui Li,Yuanyuan Tang,Lingxi Li,Fang Wang,Shuting Zhang,Baoshan Sun
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.
研究领域:
药理学
·
生物化学
·
分子生物学
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药学
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神经科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）