Drug Design Development and Therapy
·
2025
·
IF 5.1
Yudong Su,Jinman Shui,Danshi Qi,Jie Bai,Xiaoxia Xu,Yongchun Huang,Ruilian Li,Qiong Wu,Haiyan Wang,Chengzhu Cao,Zhanhai Su,Shoude Zhang
Purpose Erectile dysfunction (ED), a prevalent form of male sexual dysfunction, is predominantly treated with Phosphodiesterase type 5 inhibitors (PDE5Is). Our previous research highlighted procyanidin, a natural compound, as a notably effective PDE5I. In the current study, we intend to further validate the inhibitory activity of procyanidin on PDE5A through in vitro and in vivo assessments. This study aims to validate the efficacy of procyanidin as a treatment for ED.Methods The binding affinity of procyanidin for PDE5A was assessed by molecular docking, molecular dynamics (MD) simulations, and microscale thermophoresis (MST) assay. The toxicity of procyanidin on penile corpus cavernosum smooth muscle (CCSM) cells (n=5) was evaluated. Additionally, its effects on intracellular cyclic guanosine monophosphate (cGMP) levels in CCSM cells (n=5) were evaluated. The absorption of procyanidin was evaluated by measuring plasma levels at various times after oral gavage to Sprague-Dawley (SD) rats (n=6). Subsequently, the effects of procyanidin on intracavernous pressure (ICP) and cGMP levels in penile cavernous tissue were evaluated in SD rats (n=6).Results Procyanidin forms three hydrogen bonds with PDE5A and stabilizes the complex structure, exhibiting equilibrium dissociation constants (KD) value of 7.77 ± 2.39 µmol/L. Additionally, procyanidin exhibits minimal cytotoxicity toward CCSM cells and significantly elevates intracellular cGMP levels compared to the control group. In vivo studies demonstrate that procyanidin is rapidly absorbed, achieving peak blood concentrations within one hour. Simultaneously, procyanidin significantly increases ICP and cGMP levels in rats compared to the control group.Conclusion These findings indicate that procyanidin sustains elevated cGMP levels within cells by targeting PDE5A, thereby exhibiting therapeutic efficacy in improving ICP. Procyanidin emerges as a promising PDE5I for treating ED and potentially other related conditions.
研究领域:
药理学
·
泌尿学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Jun-Han Wang,Min Li,Peng-Fei Xie,Jia-Yao Si,Zhen-Jie Feng,Chuan-Feng Tang,Jian-Mei Li
Background Aging-related skin fibrosis (SF) is a complex condition with limited treatment options. Procyanidin C1 (PCC1), a natural polyphenolic compound with demonstrated senolytic activity, has emerged as a potential therapeutic agent for fibrotic disorders through its selective elimination of senescent cells. However, its therapeutic efficacy and mechanisms in aging-related SF remain unclear. Purpose This study aimed to investigate the mechanisms of PCC1 in aging-related SF. Results In D-galactose-induced L929 cells, PCC1 treatment significantly attenuated the expression of both senescence-associated markers (IL-1β, P16, P21 and LMNB1) and fibrosis-related markers (α-SMA, LOXL2 and COL1). Network pharmacology and experimental validation (molecular docking, DARTS, CETSA, MST) identified EGFR as a primary target, with PCC1 directly binding to and inhibiting EGFR phosphorylation. Furthermore, PCC1 treatment effectively down-regulated TGFβ1 expression and suppressed SMAD2/3 phosphorylation in D-galactose-induced L929 cells. Notably, PCC1 blocked NSC228155-induced EGFR phosphorylation and inhibited ERK/MAPK, AKT/mTOR and TGFβ/SMAD pathway activation. In bleomycin-induced SF mice, PCC1 significantly attenuated epidermal hyperplasia, improved collagen structure, restored the collagen I/III ratio, and reduced EGFR phosphorylation along with TGFβ1 expression and SMAD2/3 phosphorylation. Conclusion This study elucidates that PCC1 exerts its anti-fibrotic effects through dual mechanisms: resistance to cellular senescence and modulation of fibroblast heterogeneity. By directly binding to EGFR and inhibiting its phosphorylation, PCC1 subsequently suppresses multiple downstream signaling cascades, ultimately ameliorating TGFβ/SMAD-mediated SF. These findings establish PCC1 as a promising therapeutic candidate for aging-related skin fibrosis, offering a novel approach through targeted EGFR inhibition and comprehensive pathway modulation .
研究领域:
医学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2018
·
IF 3.977
Ying Xiao,Jialin Dong,Zhiting Yin,Qiguo Wu,Yiming Zhou,Xiaoli Zhou
To elucidate the possible mechanisms for the preventive effect of procyanidin B2 on aging, a combined analysis of metabolic profile and gut microbiome was carried out in the present study. The mimetic aged mice induced by d -galactose injection (500 mg/kg, sc daily), and the preventive group was fed with the diet plus 0.2% procyanidin B2. After 7 weeks of treatment, the spatial memory was assayed using the Morris water maze test. Procyanidin B2 significantly ameliorated the impaired memory and antioxidant abilities induced by d -galactose. Furthermore, metabolomics analysis of plasma based on LC/Q-TOF-MS demonstrated that phosphatidyl cholines , oleic acid , linoleic acid , carnitine , pantothenic acid , and taurocholic acid were significantly increased in the mice treated with procyanidin B2, and pyruvic acid , hydroxybutyric acid , hippuric acid , and cholic acid were decreased significantly. Together, gut microbiome analysis using Illumina sequencing showed that there were significant differences in the Firmicutes / Bacteroidetes ratio and abundance of Roseburia , Lachnospiraceae , and Bifidobacterium between the aging and supplemental procyanidin B2 groups. In summary, procyanidin B2 possessed potential prevention of the cognitive and oxidative impairment via the metabolic pathway regulation related to citrate cycle, fatty acid, and bile acid in the aged mice, accompanied by remodeling the gut flora.
研究领域:
生物化学
·
分子生物学
·
老年医学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2022
·
IF 4.225
Shen Duan,Xin-Yao Wang,Xu Feng,Yue Ma,Zhong Zheng,Chao-Mei Ma
ABSTRACT Cynomorium songaricum is a traditional medicine and also a food material that is eaten raw or processed as tea or beverages. As a featured plant in semi-desert grasslands, C. songaricum is also eaten by the cattle and sheep in the area. This research study fed dairy sheep C. songaricum to determine the flavan-3-ols in sheep milk. Catechin (Cat), epicatechin (Epi), procyanidin A1 (A1), procyanidin A2 (A2), and procyanidin B1 (B1) were detected in sheep milk with the concentration being Epi > A2 > Cat > B1 > A1 at 24 h after the administration of C. songaricum . Neither A1 nor A2 were detected in the methanol extract of C. songaricum . Cysteine degradation of the plant revealed that in addition to Epi, A2 was the extending unit of the polymeric flavan-3-ols in C. songaricum , indicating that A2 is released digestively from the polymers and enters the milk. Procyanidin B-1 was converted to A1 on incubation in raw but not heated milk, indicating that the A1 in milk is the enzymatically transformed product of B1. Accelerated oxidation showed that the flavan-3-ols, B1, Cat, and Epi significantly protects the unsaturated triacyglycerols in the milk from oxidation. The flavan-3-ol could slow down the oxidation of glutathione and the latter may play an important role in preventing the milk triglycerides from oxidation. Flavan-3-ols are polyphenols with many health benefits. The present research revealed the antioxidant activities of flavan-3-ols that could be absorbed to sheep milk, adding new evidences for the values of these flavan-3-ols and for the milk.
研究领域:
食品科学
·
动物营养学
·
植物化学
✓ 已验证
DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2023
·
IF 4.2
Jiawen Fu,Chenxi Dong,Miaoli Hao,Xinping He,Dongyun Wu,Chunhai Yi,Suitao Qi
In this study, a highly hydrophilic membrane was developed by an interfacial reaction using two aqueous monomers for pervaporation (PV) desalination. Two water-soluble monomers, procyanidin (PC) and vinyl alcohol-vinylamine copolymer (VA-co-VAm), were applied to prepare membranes on hydrophobic polyvinylidene difluoride (PVDF) membranes through interfacial reactions. Catechol groups of PC were oxidized to quinone groups under weakly alkaline conditions, which could react with amino groups of VA-co-VAm to form a cross-linked network. The PVDF membrane was first dipped into a PC aqueous solution to form a thin PC liquid layer on the surface. Accompanied by the PC liquid layer, the PVDF membrane was then dipped into the VA-co-VAm solution to induce the interfacial reaction. The composition and structure of membranes were observed, and the effects of different factors on the desalination performance were investigated. By applying two aqueous monomers in the interfacial reaction process, the obtained thin membrane showed good hydrophilicity with a water contact angle of less than 42°. A water flux of 42.16 kg/(m2·h) at 60 °C was obtained by treating a feed solution (3.5 wt % NaCl). At all testing procedures, the salt rejection remained higher than 99.99%. Besides, the membrane displayed superior stability over 48 h of testing. According to the above results, the prepared membranes showed great potential in the process of PV desalination. This work provides a new approach for highly permeable PV membrane preparation through an interfacial reaction using two water-soluble materials.
研究领域:
材料科学
·
环境工程
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2025
·
IF 5.4
Qi-Yuan Feng,Jiang-Tao Zhong,Hai-Ming Sun,Zheng Luo,Yu-Chen Jiang,Jian Song
Procyanidin B1 (PB1) is a natural polyphenol abundant in whole-grain highland barley as well as in many fruits, vegetables, and medicinal plants. The current study investigated the hepatoprotective effect and potential mechanism of PB1 against hepatic fibrosis. C57BL/6 mice with hepatic fibrosis were induced with thioacetamide (TAA), followed by the administration of PB1 or a positive control, silymarin, or followed by gene silencing of the thyroid hormone-responsive protein (THRSP). Hepatic stellate cells (HSCs) were stimulated with transforming growth factor β (TGF-β) or an isolated mouse peritoneal macrophage (MPM)-primed conditioned medium and cultured with PB1, silymarin or the THRSP agonist. MPMs were cultured in the presence of LPS/ATP and/or PB1. It was found that PB1 decreased the release of inflammatory factors, such as caspase-1 and IL-1β. Moreover, PB1 could activate THRSP and decrease P2X7r-modulated NLRP3 inflammasome activation in the TAA-induced mice. Additionally, PB1 inhibited the expressions of α-SMA, collagen I, the TIMP-1/MMP13 ratio, inflammatory factors, P2X7r, and NLRP3 and increased THRSP expression in activated HSCs and macrophages. THRSP deficiency attenuated the regulatory effect of PB1 on the reverse inflammation of activated HSCs, promoting hepatic fibrosis in vivo and in vitro. PB1 reversed the activation of HSCs by increasing the THRSP-mediated P2X7r/NLRP3 axis, similar in function to THRSP overexpression. PB1 could reverse the activation of HSCs and mitigate hepatic inflammation and fibrogenesis in TAA-induced hepatic fibrosis. Targeting THRSP-mediated P2X7r/NLRP3 is crucial for PB1's action against hepatic fibrosis, underscoring a promising approach and the utility of PB1 for the treatment of hepatic fibrosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Yao Shi,Haojie Zhang,Shuang Li,Danqing Xin,Shiyang Li,Bing Yan,Shuanglian Wang,Chuanyong Liu
Background Inflammatory bowel disease (IBD) is a chronic disease with an unclear pathogenesis for which successful treatments are still lacking. It has been reported that procyanidin, a natural antioxidant, relieves colitis, but the specific mechanism is elusive. Purpose Our present study was designed to investigate the effects of procyanidin on colitis and the regulation of the M1 macrophage phenotype and related signaling pathways. Methods In vivo, we used two classic colitis models to observe the effect of procyanidin on macrophage polarization. In vitro, we further validated the therapeutic effect of procyanidin in the RAW264.7 cell line and peritoneal macrophages. Results The current findings provide new evidence that procyanidin ameliorated dextran sulfate sodium (DSS)-induced colitis by preventing the polarization of macrophages to the M1 type and downregulating the levels of proinflammatory factors in cells. We also showed that procyanidin prevented lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines and the activation of proinflammatory macrophages, which was achieved by activating the STAT3 and NF-κB pathways. Conclusions This is the first study to demonstrate that procyanidin alleviates experimental colitis by inhibiting the polarization of proinflammatory macrophages. These data reveal new ideas for the pathogenesis and treatment of inflammatory diseases.
研究领域:
免疫学
·
药理学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Shanshan Tie,Wentao Su,Yannan Chen,Shida Wu,Hao Wu,Yukun Song,Siyuan Fei,Mingqian Tan
The purpose of this study is to design a cell membrane and mitochondrial targeting nanoparticle with glutathione stimulus response to deliver procyanidin for effective treatment of inflammatory bowel disease (IBD). The dual targeting procyanidin nanoparticles were prepared with amphiphilic stearic acid modified hyaluronic acid using cystamine dihydrochloride as a linker for encapsulation of (5-carboxypentyl) (triphenyl) phosphonium bromide conjugated procyanidins. As expected, the procyanidin nanoparticles showed good mitochondrial targeting ability, with a Pearson’s correlation coefficient of 0.91 at 4 h. In vivo imaging of IBD mice model demonstrated a remarkable colon accumulation of the targeting procyanidin nanoparticles. Significant glutathione stimulus release of procyanidin was found in the presence of 10 mM of glutathione at pH 7.4. In vivo experiments showed that the colon length of targeting procyanidin nanoparticle-treated IBD mice increased by 20.84% compared with the IBD mice. The weight loss, disease activity index score, oxidative stress level and the release of proinflammatory cytokines were significantly ameliorated. The composition and relative abundance of gut microbiota, and the number of short chain fatty acids were improved upon the uptake of targeting procyanidin nanoparticles. This study provided a dual targeting and glutathione response strategy to improve the bioavailability of procyanidin in IBD treatment.
研究领域:
纳米技术
·
药学
·
炎症
·
胃肠病学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF FOOD AND DRUG ANALYSIS
·
2022
·
IF 6.157
Shuai Quan,Kaixiang Ji,Fangshuo Liu,Tesfaye Hailemariam Barkae,Mohamed Ibrahim Halawa,Saima Hanif,Baohua Lou,Jianping Li,Guobao Xu
Tetracycline was reported to trigger intense lucigenin chemiluminescence (CL). Based on its significant quenching to lucigenin-tetracycline CL, procyanidin was detected. The mechanism of the lucigenin-tetracycline CL and its quenching by procyanidin were proposed. Under the optimum conditions, the calibration curve is linear in the range of 10–1000 nM for procyanidin with a detection limit of 4.4 nM. The RSD for nine replicate determinations of procyanidin was less than 1.7%. Moreover, this method was satisfactorily applied to the determination of procyanidin in human urine samples and health food capsule of grape seed.
研究领域:
分析化学
·
药物分析
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2026
·
IF 5.2
Cheng Wang,Shaoyin Wei,Qingtian Tang,Kaixian Deng,Hongjun Jin,Huali Weng,Xingjie Zan,Qiangqiang Li
Hypertriglyceridemic acute pancreatitis (HAP) is characterized by mitochondrial oxidative phosphorylation (OXPHOS) impairment and excessive reactive oxygen species (ROS), leading to severe inflammation and organ damage. Existing therapies often lack targeted antioxidant efficacy and long-term stability. In this study, we innovatively designed and synthesized procyanidin capsules using a one-step calcium carbonate template method, which enables sustained release of procyanidin for over one month and exhibits exceptional scavenging capacity for both ROS and RNS. The capsules demonstrated high biocompatibility in macrophage and dendritic cell lines and significantly reduced inflammatory cytokines and pancreatic damage in a HAP mouse model. Proteomic analysis revealed that the therapeutic effect is mediated through the restoration of the aqueous OXPHOS function. This work provides a novel, biocompatible, and potent antioxidant strategy for the targeted treatment of HAP.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2021
·Vol. 37
·期 2
·201-211
·
IF 4.119
Rong Li,Hongsong Li,Qian Zhang
Purpose The damage of hyperglycemia to the retinal pigment epithelial (RPE) cells is a critical event in diabetic retinopathy (DR). Procyanidin (PC), a kind of polyphenol compounds, has shown to be effective in preventing and treating diabetes as well as its complications, in which autophagy disorder is involved in the pathological mechanism. However, it remains unclear whether PC can play a protective role in DR by regulating the autophagy of RPE. Here, the effect of PC on RPE under high glucose conditions and the role of autophagy were investigated. Materials and Methods The cell viability of ARPE-19, a human RPE cell line, was detected by cell counting kit-8 (CCK-8) and the apoptosis rate was measured by flow cytometry. The protein expressions of apoptosis markers, including Bax, Bcl-2, and Caspase-3, as well as autophagy markers including LC3, p62, p53, and mTOR were detected by Western blotting. Autophagic flux in ARPE-19 cells was detected by transfection with Ad-mCherry-GFP-LC3B. Results Under high glucose conditions, the viability of ARPE-19 was decreased and the apoptosis rate increased, the protein expressions of Bax, Caspase-3, LC3-II/LC3-I, and p-p53 were all increased and the expressions of Bcl-2, p62, and p-mTOR decreased, and autophagic flux was increased compared with that of the controls. Treatment with PC weakened all these changes caused by high glucose. When rapamycin (RPM), an autophagy agonist was added, the cell viability of ARPE-19 by PC treatment was decreased while the apoptosis was increased. Conclusions Our findings indicate that through the p53/mTOR autophagy pathway, PC may protect RPE cells from high glucose-induced injury.
研究领域:
眼科学
·
药理学
·
细胞生物学
·
糖尿病
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2019
·
IF 3.372
Mingyue Liu,Renliang Huang,Chuanxi Li,Mingda Che,Rongxin Su,Shuzhou Li,Jing Yu,Wei Qi,Zhimin He
Nanoscale zero-valent iron has been widely applied in environmental remediation and toxic waste treatment, especially for the degradation of persistent organic pollutants (POPs). However, the dechlorination activity of Fe nanoparticles (Fe NPs) can be suppressed by the precipitation of iron oxides generated from the corrosion of Fe-Pd NPs under alkaline conditions, leading to a decreased dechlorination efficiency. Faced with this challenge, we report a highly effective dechlorination system that functions over a broad pH range and especially well under alkaline conditions in this work. Procyanidin (PROC), a natural polyphenol, was utilized as a stabilizer to manipulate the size distribution of Fe-Pd NPs and, more importantly, as a scavenger of Fe ions to prevent iron oxide precipitation. Experiments and theoretical calculations reveal that the generated Fe ions was mainly present in the form of bis- and tris-PROC-Fe complexes in the reaction solution. Compared with pristine Fe-Pd NPs, the PROC-modified Fe-Pd NPs had a dechlorination efficiency that was increased 20-fold (pH 9.0). Notably, a normalized rate constant was enhanced by more than 2 orders of magnitude compared to the previously reported dechlorination systems. The PROC-modified Fe-Pd NPs showed excellent dechlorination efficiency over a wide pH range (2.3–13.0).
研究领域:
环境科学
·
纳米技术
·
化学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）