VASCULAR PHARMACOLOGY
·
2020
·
IF 4.152
Mingguo Xu,Qi Qi,Lina Men,Shushui Wang,Meng Li,Min Xiao,Xiaozhou Chen,Sheng Wang,Guobing Wang,Hongling Jia,Cong Liu
Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis especially in coronary arteries. Berberine (BBR) shows several beneficial effects on cardiovascular system. The present study is to investigate whether BBR exerts protective effect against KD-induced damage of human coronary artery endothelial cell (HCAECs) and the underlying mechanisms. HCAECs exposed to medium with 15% serum from KD patients or healthy volunteers for 24 h. Stimulated HCAECs were treated with vehicle (without BBR) and BBR (20 μM) for 24 h, the cell apoptosis, cell cycle, induction of intracellular reactive oxygen species (ROS) and protein expression were examined by flow cytometry and western blot. The KD-induced differentially expressed proteins in HCAECs were determined by quantitative proteomics. BBR inhibited HCAECs from apoptosis and arrested cell cycle at G0/G1 stage. BBR protected HCAECs from injury by inhibiting expression of THBD, vWF and EDN1. Bioinformatics analysis suggested that the oxidative and ER stress were involved in KD-induced damage in HCAECs. ROS production and the protein expression of ATF4, p-EIF2α, p-PERK, XBP1, p-IRE1, HSP90B1, HSPG2, DNAJC3, P4HB and VCP were increased by serum from KD patients and decreased by BBR treatment. BBR exerts its protective effects on KD-induced damage of HCAECs through its inhibitory effects on oxidative and ER stress indicating BBR as a therapeutic candidate for KD.
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高影响因子
JACS Au
·
2026
·
IF 8.5
Yu Qin,Huiling Liu,Yan Zhang,Fei Li,Zhiwei Deng,Zhengshan Luo,Yuhao Zhuang,Kai Fu,Zhenbo Yuan,Yijian Rao
Sustainable and scalable production of plant natural products remains a major challenge at the interface of synthetic biology, metabolic engineering, and drug discovery, often constrained by plant-membrane-bound cytochrome P450s. To overcome the bottleneck in P450-catalyzed methylenedioxy-bridge (MDB) formation, we designed a concise, modular Escherichia coli pathway to the alkaloid berberine that bypasses multiple native steps and enables high-level accumulation of the P450-dependent intermediate. We then implemented integrated engineering of CjCYP719A1, including expression optimization, structure-guided design, consensus mutagenesis, and machine learning, to obtain a variant with 8.9-fold higher activity and improved thermostability. This enabled a berberine titer of 353 mg/L in scaled-up preparations, the highest reported to date, demonstrating industrial potential. Furthermore, mechanistic studies reveal their improved catalytic activity and thermostability. Together, this work provides a practical framework for functional expression and systematic optimization of plant-derived P450s to enable efficient production of plant natural products in E. coli.
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2025
·
IF 3.6
Xiaxuan Zhang,Jian-song Zhou,Hong-Jun Wu,Yang Guo
Alzheimer’s disease (AD) is a progressive neurological disorder and the predominant form of dementia among the elderly. Berberine (BBR) is an approved drug for Alzheimer’s disease (AD) that has demonstrated a substantial improvement in cognitive function, proficient management of neurobehavioral symptoms, and enhancement of performance in vital everyday activities. Nonetheless, the adverse effects of the drug encompass vomiting and nausea, considerable variations in blood concentrations, and inadequate patient adherence. Consequently, the primary objectives are to optimize the administration method and enhance therapeutic efficiency. Hence, we suggest utilizing a hierarchical hydrogel (HGL)-incorporated mesoporous silica nanocarrier (MSN) to incorporate BBR, aiming to reduce adverse effects in the stomach. These hydrogels facilitate the gradual release of drugs at a rate of 62% over a prolonged duration, aiming to decrease dose frequency, optimize the efficacy of drug administrations, and improve patient adherence. Due to these characteristics, drug-encapsulating MSN-BBR hydrogels can facilitate optimal drug administration and have developed into superior options for Alzheimer’s disease therapy, with innovation promising effective treatment.
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PubMed
高影响因子
Animals
·
2026
·Vol. 16
·期 9
·1310
·
IF 3.2
Binwen Zhang,Zheng Wei,Mei Yang,Xin Wang,Qiang Shan,Zheng Cao
Simple SummaryMastitis is a common disease in dairy cows, with major pathogens includingStaphylococcus aureusandEscherichia coli. Although berberine has antibacterial and anti-inflammatory properties, it is poorly absorbed after oral administration. We developed a novel berberine-loaded hydrogel that can be applied to the udder, delivering the drug directly to the mammary tissue. Experimental results showed that this hydrogel is stable, safe, and capable of sustained drug release. Tests in a mouse model demonstrated that it effectively reduces bacteria-induced inflammation, protects the mammary barrier, and minimizes cell damage. Its mechanism of action is related to the regulation of intracellular NF-κB and PI3K/Akt signaling pathways. This study suggests that the hydrogel offers a new topical strategy for treating mastitis, solving the problem of poor oral absorption through local application. It holds promise for providing dairy cows with a more convenient and effective treatment option in the future.Mastitis is a common disease in dairy cows, mainly caused by Staphylococcus aureus and Escherichia coli. Berberine (BBR) has antibacterial and anti-inflammatory potential, but its application is limited due to poor oral absorption and difficulty in reaching mammary tissue. To address this, this study developed a BBR-loaded composite ethosome hydrogel (BBR-CEH) to achieve targeted mammary delivery through local transdermal administration. The experimental results showed that BBR-CEH has good chemical stability and biosafety. Subsequently, a mouse mastitis model was established by intraductal injection of 50 µL of bacterial mixture (E. coli:S. aureus= 1:1, each at 1 × 107CFU/mL). The results showed that after BBR-CEH treatment, the mRNA expression ofTNF-α(tumor necrosis factor-alpha),IL-6(interleukin-6), andIL-1β(interleukin-1 beta) was significantly decreased, the mRNA expression ofZO-1(zonula occludens-1),Occludin, andClaudin-4was significantly increased, andBax/Bcl-2(Bcl-2-associated X protein/B-cell lymphoma 2) was significantly reduced (p< 0.01), indicating alleviation of mastitis by reducing inflammation, improving tight junctions, and inhibiting apoptosis. Finally, network pharmacology and in vivo experiments confirmed that its mechanism involves the NF-κB (nuclear factor kappa-B) and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways. Thus, topical BBR-CEH may represent a promising new strategy for mastitis treatment.
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高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2026
·
IF 3.1
Jiaqi Dou,Yigong Zhang,Hai Wang,Zexu Ma,Pengli Jin,Guangda Li,Bianyun Cai
To address the limitations of traditional konjac glucomannan (KGM) crosslinking strategies relying on strong alkaline and oxidation conditions, as well as the growing challenge of antibiotic resistance in acne therapy, we designed a novel antibiotic-free berberine hydrochloride (BBR)-loaded KGM hydrogel via a one-pot method. Biocompatible borosilicate bioglass was used as a mild crosslinker to fabricate the hydrogel through bioglass-mediated chemical and physical interactions, with BBR synchronously encapsulated during the one-pot process. Three hydrogel formulations with gradient BBR loadings (1, 2, and 5 wt%) were prepared. All hydrogels exhibited porous structures, favorable swelling capacity, excellent self-healing, and injectable properties. In vitro transdermal tests demonstrated sustained and stable drug release. The BBR-loaded hydrogels showed comedolytic ability close to that of salicylic acid, strong antibacterial activity against Cutibacterium acnes and Staphylococcus aureus , favorable hemocompatibility, no cytotoxicity to L929 cells, and promoted cell proliferation and migration. Among them, the 2 wt% BBR-loaded hydrogel showed the optimal wound-healing effect and favorable anti-inflammatory efficacy. These findings suggest that the novel hydrogel containing 2 wt% BBR has potential for application in treating acne vulgaris.
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Yue Bei,Gao Ruiyang,Lv Cheng,Yu Zhilun,Wang Hao,Geng Xiaolong,Wang Zhengtao,Dou Wei
Irinotecan (CPT11), a broad-spectrum cytotoxic anticancer agent, induces a series of toxic side-effects. The most conspicuous side-effect is gastrointestinal mucositis, including nausea, vomiting, and diarrhea. A growing body of evidence indicates that bacteria β-glucuronidase (GUS), an enzyme expressed by intestinal microbiota, converts the inactive CPT11 metabolite SN38G to the active metabolite SN38 to ultimately induce intestinal mucositis. We sought to explore the potential efficacy and underlying mechanisms of berberine on CPT11-induced mucositis. Our study showed that berberine (50 mg/kg; i. g.) mitigated the CPT11-induced loss of mucosal architecture, ulceration, and neutrophil infiltration. Meanwhile, berberine improved mucosal barrier function by increasing the number of globlet cells, protecting trans-endothelial electrical resistance (TEER), reducing permeability and increasing tight junction proteins expression. LC-MS analysis showed that berberine decreased the content of SN38 in feces, which correlated with decreases in both GUS activity and GUS-producing bacteria. Further molecular docking and Lineweaver-Burk plots analyses suggested that berberine functions as a potential non-competitive inhibitor against GUS enzyme. Of note, berberine maintained the anti-tumor efficacy of CPT11 in a tumor xenograft model while abrogating the intestinal toxicity of CPT11. Overall, we identified for the first time the remission effects of berberine on intestinal mucositis induced by CPT11 without impairing the anti-colorectal cancer efficacy of CPT11 partially via inhibiting bacterial GUS enzyme.
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高影响因子
POLYMER ENGINEERING AND SCIENCE
·
2023
·Vol. 63
·期 8
·2596-2612
·
IF 3.2
Chengde Liu,Wanting Du,Luyao Jiang,Yizheng Li,Cheng Liu,Xigao Jian
Medical devices and human implant materials carry a risk of bacterial infection. Biocompatible and adhesive antibacterial materials that prevent biofilm formation are commonly used to reduce the risk. Herein, a crosslinked chitosan/gelatin (CG) hybrid hydrogel with antibacterial and adhesive properties was developed by introducing berberine hydrochloride (BBR) and adhesive prepolymerized gallic acid (PGA) to the hydrogel. BBR self-assembles into nanoparticles and imparts AIE function to hydrogels by intermolecular electrostatic interactions and π–π stacking. The hydrogel was used as a stable carrier for BBR. The antibiofilm performance against Escherichia coli and Staphylococcus aureus after light exposure increased from 20% and 30% (CG hydrogel) to 74% and 85% (CGBBRPGA hydrogel), respectively. When used as a photodynamic agent, the hybrid hydrogel exhibited enhanced antibacterial and antibiofilm capabilities against both Gram-negative ( E. coli ) and Gram-positive ( S. aureus ) bacteria. The CGBBRPGA hydrogel showed strong adhesion to the surfaces of pig skin (9.2 kPa), glass (7.6 kPa), steel sheet (5.8 kPa), and PEEK sheet (5.5 kPa). Furthermore, it exhibits cell adhesion and shows negligible cytotoxicity, which indicates its cytocompatibility. Consequently, the fabricated hybrid hydrogel offers potential applications in biomedicine, particularly in wound dressing and surface modification of medical implants.
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JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Jia Song,Chuchu Lin,Xuan Yang,Yanqi Xie,Ping Hu,Huatian Li,Wenbo Zhu,Haiyan Hu
Mitochondria are ideal anti-tumor target due to mitochondria's central regulation role in cell apoptosis and tumor resistance to apoptosis. There are several challenges for mitochondrial targeting drug delivery, including complex multistep preparations, low drug- loading and systemic toxicity from the carriers. To address these issues, we firstly constructed mitochondria-targeting nanodrugs self-assembled from 9-O-octadecyl substituted berberine derivative (BD) using simple nano-precipitation approach. BD-based nanodrugs were modified by DSPE-PEG2000 (distearylphosphatidylethanolamine- methoxypolyethylene glycol 2000) to increase stability. Negatively charged hyaluronic acid (HA) was further coated to conceal positive charges and achieve tumor targeting. PEG and HA dually modified BD NDs (HA/PEG/BD NDs) were prepared with surface charge of −25.8 mV and high drug loading >70%. The degradation of HA by hyaluronidase (HAase) at tumor tissue allowed the exposure of the positively charged PEG/BD NDs to the cells, which is beneficial for cell uptake and further lysosome escape and mitochondrial targeting. Then, HA/PEG/BD NDs were investigated to induce apoptosis through dissipating mitochondria membrane potential, releasing cytochrome C , increasing the activities of caspase 9/3, activating the pro-apoptotic Bax, suppressing the anti-apoptotic Bcl-2 and upregulating ROS levels. In the A549 xenografted tumor model, HA/PEG/BD NDs exhibited obvious tumor cell mitochondrial targeting and significant anti-tumor efficacy. Overall, comparing to conventional nanoparticles , mitochondrial targeting HA/PEG/BD NDs provide a new strategy for cancer treatment with enhanced drug-loading, relatively simplified preparation processes and reduced carrier toxicities.
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高影响因子
RSC Advances
·
2018
·Vol. 8
·期 44
·25201-25209
·
IF 2.936
Li-rong Nie,Hang Song,Alula Yohannes,Siwei Liang,Shun Yao
A magnetic ionic liquids (MILs)-based aqueous two-phase system (MIL-ATPs) obtained by mixing with a series of inorganic salts, which involves five cholinium MILs with the piperidinyloxy radical anion is reported for the first time. Phase diagrams for the new ATPs were experimentally determined at different temperatures (298.15–318.15 K) and the liquid–liquid equilibrium data for two-phase systems were correlated according to the empirical nonlinear expression. The effects of the types of MILs, temperature and inorganic salts on the binodal curve are discussed in detail. The MIL-ATPs coupled with HPLC-UV analysis was developed in the quantitation of berberine hydrochloride in Rhizoma coptidis. Under optimal conditions, the partition coefficient of berberine hydrochloride was 127.68 with the precision values (RSD%) of 1.40% and 2.83% for intra-day (n = 6) and inter-day (n = 3), respectively. The limit of detection (LOD) and limit of quantification (LOQ) for berberine hydrochloride were 0.023 mg L−1 and 0.077 mg L−1, respectively. The recoveries were obtained in the acceptable range of 97.4–101.2%. Moreover, the content of berberine hydrochloride in the raw material of Rhizoma coptidis was measured as 123.95 mg g−1 with this method. Finally, 99.8% MIL was recovered for cycle application after the removal of berberine hydrochloride by using D101 resin. This study provides a meaningful reference for the application of MIL-ATPs with great prospects.
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高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Wang Yue,Zhang Ziting,Du Min,Ji Xu,Liu Xiaodan,Zhao Chunfang,Pang Xunsheng,Jin Erhui,Wen Aiyou,Li Shenghe,Zhang Feng
Introduction: Enterotoxigenic Escherichia coli (ETEC) is the main diarrhea-causing pathogen in children and young animals and has become a global health concern. Berberine is a type of “medicine and food homology” and has a long history of use in China, particularly in treating gastrointestinal disorders and bacterial diarrhea.Methods: In this study, we explored the effects of berberine on growth performance, intestinal inflammation, oxidative damage, and intestinal microbiota in a weaned piglet model of ETEC infection. Twenty-four piglets were randomly divided into four groups—a control group (fed a basal diet [BD] and infused with saline), a BD+ETEC group (fed a basal diet and infused with ETEC), a LB+ETEC group (fed a basal diet with 0.05% berberine and infused with ETEC infection), and a HB+ETEC group (fed a basal diet with 0.1% berberine and infused with ETEC).Results: Berberine significantly improved the final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) (P<0.05) of piglets, and effectively decreased the incidence of diarrhea among the animals (P<0.05). Additionally, berberine significantly downregulated the expression levels of the genes encoding TNF-α, IL-1β, IL-6, IL-8, TLR4, MyD88, NF-κB, IKKα, and IKKβ in the small intestine of piglets (P<0.05). ETEC infection significantly upregulated the expression of genes coding for Nrf2, CAT, SOD1, GPX1, GST, NQO1, HO-1, GCLC, and GCLM in the small intestine of the animals (P<0.05). Berberine significantly upregulated 12 functional COG categories and 7 KEGG signaling pathways. A correlation analysis showed that berberine significantly increased the relative abundance of beneficial bacteria (Gemmiger, Pediococcus, Levilactobacillus, Clostridium, Lactiplantibacillus, Weissella, Enterococcus, Blautia, and Butyricicoccus) and decreased that of pathogenic bacteria (Prevotella, Streptococcus, Parabacteroides, Flavonifractor, Alloprevotella) known to be closely related to intestinal inflammation and oxidative stress in piglets. In conclusion, ETEC infection disrupted the intestinal microbiota in weaned piglets, upregulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, and consequently leading to intestinal inflammation and oxidative stress-induced damage.Discussion: Our data indicated that berberine can optimize intestinal microbiota balance and modulate the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, thus helping to alleviate intestinal inflammation and oxidative damage caused by ETEC infection in weaned piglets.
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MATERIALS & DESIGN
·
2025
·
IF 7.9
Hongyu Lv,Siyuan Wang,Mou He,Xue Zhu,Peng He,Ruochen Sun,Zitong Jia,Ziming Wang,Wenwen Zhao,Zhangfeng Zhong,Yantao Han
The development of innovative wound dressings that can accelerate diabetic wound healing and alleviate hypertrophic scar has aroused intensive attraction in the clinics. In this study, the nanofibrous wound dressings constructed with a blend of silk fibroin (SF) and poly-3-hydroxybutyric acid-co-3-hydroxyvaleric acid (PHBV) were designed and fabricated. Meanwhile, berberine (BBR) were loaded in the SF/PHBV nanofibers to enhance the pharmacological effects. Firstly, material characterisation and biological characteristics of SF/PHBV-BBR dressings were investigated. The addition of BBR didn’t change the mechanical properties and biocompatibility of SF/PHBV nanofiber dressings. Then in vitro experiment proved that SF/PHBV-BBR nanofiber dressings obviously decreased the releases of inflammatory factors TNF-ɑ and IL-6, inhibited inflammatory proteins COX-2 and iNOS expression, and also suppressed oxidative stress responses of activated macrophages. Subsequently, in vivo study showed that SF/PHBV-BBR nanofiber dressings with high dose of BBR significantly promoted the healing of diabetic wounds in mice by significantly enhancing wound closure rates, accelerating angiogenesis, and improving collagen matrix deposition. Additionally, SF/PHBV-BBR obviously alleviated scar hyperplasia in rabbit by inhibiting fibroblast activation mediated by transforming growth factor-β1 (TGF-β1)/Smad3 pathway. Our study offered a promising alternative dressing materials for the treatment of hard-to-heal diabetic wounds and hypertrophic scars.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Zan Yang,Zheng Wang,Pan Liu,Wenya Liu,Yingran Xu,Yibin Zhou,Zhenyu Yu,Mingming Zheng,Yaqing Xiao,Yingnan Liu
In this study, the β-cyclodextrin encapsulated betanin (BET@β-CD) with improved thermal stability and retention as well as the berberine (BBR) with aggregate induced luminescence effect were incorporated into corn amylose (CA) biomatrix to develop colorimetric/fluorescent dual-channel smart film. Results shown that the added functional components were uniformly distributed in the film matrix. The high tensile strength (78.87%), low water solubility (31.15%) and water vapor permeability (1.24 × 10 −10 g Pa −1 s −1 m −1 ) of the film predicted its acceptable stability. It was worth mentioning that the film displayed excellent responsiveness to volatile ammonia (0.025–25 mg/mL) with at least 4 times recyclability. Application experiment demonstrated that the film can achieve macroscopic dynamic monitoring of the freshness of shrimps stored at 25 °C, 4 °C, −20 °C under daylight (red to yellow) and UV light (yellow-green to blue-green). Thus, the study suggests an attractive and effective strategy for constructing dual-mode smart packaging materials for food freshness detection.
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