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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Arabian Journal of Chemistry
·
2024
·
IF 5.3
Yi Chen,Shasha Song,Yongfang Wang,Xiaoli Zhang,Jiafen Zhang,Lili Wu,Jianbing Wu,Xinyu Li
Psoriasis is a common chronic inflammatory skin disease, which has seriously affected human health. Berberine is a plant alkaloid with significant anti-inflammatory effect. In this study, we aimed to determine whether topical application of berberine could ameliorate skin inflammation in psoriasis and explore the potential molecular mechanism. Imiquimod (IMQ)-induced psoriasis-like dermatitis in mice was firstly used to reveal the potential pathogenic mechanism. The transcriptome analysis showed that Janus kinase (JAK)-Signal transducer and activator of transcription (STAT) signaling pathway was significantly enriched in IMQ-induced dermatitis, which included the key genes such as Janus kinase 1 (JAK1), Interleukin-2 (IL2), Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) and Signal transducer and activator of transcription 1 (STAT1). Network pharmacology and molecular docking then predicted that topical berberine may treat psoriasis by JAK-STAT signaling pathway, especially act on JAK1, IL2, PIK3CA and PIK3CB. Experimental studies in vivo further demonstrated that topical application of berberine could ameliorate IMQ-induced psoriasis-like skin inflammation by suppressing JAK-STAT signaling pathway. In addition, experimental studies in vitro showed that berberine could directly act on and enter into human immortalized keratinocytes (HaCaT cells). Meanwhile, berberine may inhibit the hyperproliferation and proinflammatory functions of HaCaT cells induced by Interferon-gamma (IFN-γ) via suppressing JAK1/STAT1 signaling pathway. In conclusion, this study suggested that berberine may be a promising topical agent to ameliorate skin inflammation in psoriasis.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiaoqi Wang,Jue Hu,Chunjing Chen,Jun Lu,Chang Liu,Yi Ning,Fangguo Lu
Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial strain resistant to multiple antibiotics frequently encountered in clinical settings. Excessive antibiotic use has increased bacterial resistance, leaving a lack of effective treatments for MRSA infections. MRSA often colonizes the surface of skin wounds, resulting in chronic inflammation and protracted wound healing. The biofilm formation hinders the complete eradication of the bacteria, exacerbating the local inflammatory response and impeding wound healing. This study presents an innovative methodology for managing MRSA-infected skin wounds. The novel immunomodulatory hydrogel composed of Berberine, silver nanoparticles (AgNPs), and carboxylated chitosan (designated as Ber@AgNPs@CHI hydrogel) demonstrates enhanced therapeutic efficacy in a murine model of MRSA skin infection. This hydrogel is effective in eradicating MRSA and preventing biofilm formation. Furthermore, it modulates the local immune microenvironment by facilitating the transition of macrophages from the M1 to M2 phenotype and increasing the production of vascular endothelial growth factor (VEGF). These actions collectively facilitate the progression of the wound from the inflammatory to the proliferative phase, enhancing the early stages of wound healing. Hence, this safe and effective hydrogel mediates wound healing from multiple perspectives and targets, providing a new potential avenue for treating persistent infected wounds caused by clinical MRSA.
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JOURNAL OF SEPARATION SCIENCE
·
2017
·Vol. 40
·期 14
·2933-2940
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IF 2.557
Ling-Feng Jiang,Bo-Cheng Chen,Ben Chen,Xue-Jian Li,Hai-Lin Liao,Wen-Yan Zhang,Lin Wu
The extraction adsorbent was fabricated by immobilizing the highly specific recognition and binding of aptamer onto the surface of Fe 3 O 4 magnetic nanoparticles, which not only acted as recognition elements to recognize and capture the target molecule berberine from the extract of Cortex phellodendri , but also could favor the rapid separation and purification of the bound berberine by using an external magnet. The developed solid-phase extraction method in this work was useful for the selective extraction and determination of berberine in Cortex phellodendri extracts. Various conditions such as the amount of aptamer-functionalized Fe 3 O 4 magnetic nanoparticles, extraction time, temperature, pH value, Mg 2+ concentration, elution time and solvent were optimized for the solid-phase extraction of berberine. Under optimal conditions, the purity of berberine extracted from Cortex phellodendri was as high as 98.7% compared with that of 4.85% in the extract, indicating that aptamer-functionalized Fe 3 O 4 magnetic nanoparticles-based solid-phase extraction method was very effective for berberine enrichment and separation from a complex herb extract. The applicability and reliability of the developed solid-phase extraction method were demonstrated by separating berberine from nine different concentrations of one Cortex phellodendri extract. The relative recoveries of the spiked solutions of all the samples were between 95.4 and 111.3%, with relative standard deviations ranging between 0.57 and 1.85%.
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Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2022
·Vol. 32
·期 5
·812-818
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IF 2.464
Zhou Meichen,Yin Shining,Yu Mingming,Wu Aiying,Wang Cong,Lu Jingguang
“Fufang huangliansu” prescription, as a Chinese patent herbal medicine, is widely applied in clinical practice, and its main physiologically active components are berberine hydrochloride and total glucosides of paeony. In this study, a rapid, simple, and accurate quantitative 1 H NMR method was developed and validated to determine the two main components of “fufang huangliansu” prescription, berberine hydrochloride and total glucosides of paeony. Dimethyl terephthalate was selected as an internal standard, and the signals for berberine hydrochloride at δ 8.94 ppm (H-13) and total glucosides of paeony at δ 7.55 ppm (H-3″, 5″) were selected for the construction of calibration curves. Method validation was performed in terms of specificity, precision, accuracy, repeatability, stability, and linearity. The results indicated that the assay was precise and in line with the China Food and Drug Administration guidance. The assay has been successfully applied to determine the content of berberine hydrochloride and total glucosides of paeony in “fufang huangliansu” obtained from two pharmaceutical companies. This finding indicates that this 1 H NMR method has the potential as a reliable method for quality control of Chinese patent medicines containing berberine. Graphical abstract
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POLYMER INTERNATIONAL
·
2014
·Vol. 63
·期 9
·1699-1706
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IF 2.247
Pengfei Li,Ting Wang,Fuhou Lei,Pingping Tang,Xuecai Tan,Zuguang Liu,Liqun Shen
A novel method for the separation of berberine hydrochloride has been developed. Berberine hydrochloride molecularly imprinted polymers were prepared by suspension polymerization in the aqueous phase using berberine hydrochloride as the template, methyl acrylic acid as a functional monomer, and ethylene glycol maleic rosinate acrylate (which contains a phenanthrene ring skeleton) and ethylene glycol dimethacrylate as combinatorial crosslinkers. The imprinted polymers were successfully used as a selective stationary phase in high-performance liquid chromatography. Separation performance of the chromatographic column was determined from the selectivity (evaluated by separation factor) and sorption selectivity (evaluated by imprinting factor) of the molecularly imprinted and non-imprinted polymers towards the template. The optimum conditions to maximize separation and imprinting factors were investigated. Acetic acid–methanol solution (0.05% v/v) was selected as the optimum mobile phase, while 0.2 mL min −1 was chosen as the optimized flow rate for selective separation of berberine hydrochloride. The highest imprinting and separation factors obtained were 1.924 and 18.52, respectively. Simultaneously, the chromatographic column backpressure was stable and showed good permeability. The chromatographic column was used to separate effectively template molecules from coptis root extract and other analogues. Such chromatographic columns with high selectivity can be used to selectively separate berberine hydrochloride from other compounds. © 2014 Society of Chemical Industry
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RSC Advances
·
2017
·Vol. 7
·期 55
·34746-34754
·
IF 3.108
Ziwei Hu,Mingshan Xie,Danting Yang,Dong Chen,Jingyi Jian,Haibin Li,Kaisong Yuan,Zhengjin Jiang,Haibo Zhou
Berberine is an important anti-inflammatory drug widely used for the treatment of heart and intestinal disorders. The quantification of berberine is usually required in clinic medical assays. Herein, we report simple, fast and sensitive colorimetric visualization of berberine in human plasma using citrate-stabilized gold nanoparticles (AuNPs). Upon exposure to μg mL−1 levels of berberine, the AuNP solution exhibits a highly sensitive color change from red to blue and rapid aggregation kinetics within the initial 10 min, which can be directly seen with the naked eye and monitored by UV-vis absorbance spectroscopy. As confirmed by comparison with potential coexisting foreign substances, the presence of positively charged berberine induces the aggregation of the AuNPs owing to the electrostatic attraction and coordination interactions between the ring nitrogen atoms of berberine and the AuNPs, causing a color change of the AuNP suspension. Further evidence is that the sensitivity is significantly improved when NaHSO4 is added to promote the ligand exchange between citrate and berberine at the surface of the AuNPs. The NaHSO4-optimized AuNP system provides a simple colorimetric assay for the rapid detection of berberine in human plasma. The limit of detection (LOD) is 0.24 μg mL−1 by the naked eye and 0.06 μg mL−1 by UV-vis spectroscopy.
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MOLECULAR PHARMACEUTICS
·
2026
·
IF 4.5
Wanyu Jin,Shujun Xu,Hongyan Zhang,Yujie Li,Mengna Shi,Ninghui Ma,Xin Zhang,Lujia Zhu,Yang Xiong
The limited efficacy of programmed death-ligand-1 (PD-L1) monoclonal antibodies (aPD-L1) in triple-negative breast cancer (TNBC) is largely attributable to the immunosuppressive tumor microenvironment (TME). Notably, the abundance of cancer-associated adipocytes (CAAs) constitutes a distinctive feature of the TNBC microenvironment, contributing significantly to its immunosuppressive nature. CAAs upregulate cluster of differentiation 36 (CD36), a fatty acid translocase on tumor cells, thereby promoting excessive fatty acids (FAs) uptake and lipid droplet (LD) accumulation, which starve immune cells and reinforce immunosuppression through this metabolic adaptation. Berberine (BBR), a bioactive alkaloid derived from Rhizoma coptidis, has previously been shown to ameliorate lipid metabolism disorders through downregulation of CD36 in metabolic diseases such as hepatic steatosis. We therefore hypothesize that BBR inhibits CD36-mediated FAs uptake and reduces LD accumulation in tumor cells, representing a novel mechanism that remains unexplored in the context of TNBC. In this study, we demonstrated that BBR counteracts the tumor-promoting effects of CAAs in 4T1 cells by inhibiting CD36 upregulation and its mediated FAs uptake, thereby reducing CAA-induced LD accumulation and ultimately suppressing tumor cell proliferation. Furthermore, BBR remodeled the TME by enhancing CD8+ T cell recruitment and activity, while reducing immunosuppressive factors. In order to improve the sustained release of BBR at the tumor site and overcome its poor aqueous solubility, we created a thermosensitive hydrogel-based nanoparticle system (BBR-NPs-GEL). This injectable hydrogel demonstrated favorable thermosensitive gelation and shear-thinning behavior, making it suitable for localized administration. It exhibited a gelation temperature of 35.3 ± 0.2 °C and a sustained release profile with 52% of BBR released within 48 h. In 4T1Fluc tumor-bearing mice, BBR-NPs-GEL significantly suppressed tumor growth and remodeled the TME, as evidenced by increased infiltration of CD8+ T cells (+8.49%), activation of dendritic cells (+8.39%), and a shift toward M1-macrophages (+39.9%), accompanied by a reduction in M2-macrophages (−19.13%). Importantly, when combined with aPD-L1 therapy, the treatment elicited synergistic antitumor effects, resulting in enhanced tumor regression. This combination strategy effectively overcame metabolic immunosuppression and reversed immune resistance in TNBC.
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BioNanoScience
·
2026
·Vol. 16
·期 9
·592
·
IF 4
Yan Qi,Wang Shiyu,Gao Qian,Wang Jian,Xiong Ni,Zhu Yue,Chen Tianyu,Cheng Yuhang,Li Jiafen,Cao Jie,Ying Xue,Ming Xin,Wu Min
Systemic chemotherapy remains the most frequent treatment for triple-negative breast cancer (TNBC) because the tumors do not express any of the three surface receptors targeted by selected treatments. A more selective alternative may be delivering drugs such as the well established anti-tumor drug as well as mitochondrial toxin doxorubicin to mitochondria in tumor cells by carriers containing TNBC surface proteins and delocalized lipophilic cations such as berberine derivatives that can target TNBC tumors and mitochondria, respectively. Once they enter tumor cells, the drug-loaded carriers will target to the mitochondria and inactivate them in the presence of cations. Here we synthesized amphiphilic 9- O -cetyl-berberine, which retained the anti-tumor activity of berberine, through a method involving microwave irradiation, then allowed the molecules to co-assemble spontaneously with doxorubicin into micelles. The micelles were coated with membranes derived from erythrocytes and the TNBC cell line MDA-MB-231 to shield their cytotoxic and hemolytic positive charge. The resulting nanovesicles showed good stability in the short term and good safety, and synergistically inhibited proliferation and migration of TNBC cells by reducing mitochondrial membrane potential and promoting the generation of reactive oxygen species and activating apoptotic signaling. These results establish the potential of this system to co-deliver doxorubicin and delocalized lipophilic cations to treat TNBC.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2022
·Vol. 75
·期 1
·129-138
·
IF 4.81
Li Shi-ying,Shi Chuan-jian,Fu Wei-ming,Zhang Jin-fang
BackgroundBerberine, a non-prescription medicine clinically applied for diarrhoea and gastroenteritis. Recent studies have demonstrated that it possesses anti-tumour properties in colorectal cancer, but the exact molecular mechanism remains obscure.ObjectivesTo elucidate the underly molecular mechanisms of berberine in colorectal cancer from a perspective of epigenetics, and tried to explore the role of lincROR-Wnt/β-catenin molecular axis in the berberine induced the anti-tumour activity in colorectal cancer.MethodsThe effects of berberine on cell growth, cell cycle and apoptosis were examined in CRC cells. The in vivo effect of berberine on tumour growth was investigated using a xenograft mice model. Moreover, lincROR and Wnt/β-catenin signalling were detected by luciferase activity, qRT-PCR and western blotting assays.Key findingsBerberine suppressed cell growth in vitro via inducing cell cycle arrest and apoptosis in CRC cell, and inhibited tumourigenesis in vivo. LincROR was significantly down-regulated by berberine, inducing the inactivation of the canonical Wnt/β-catenin signalling, meanwhile, the overexpression of lincROR partially reversed the suppressive effects on tumour growth and Wnt/β-catenin signalling induced by berberine.ConclusionsBerberine inhibits tumour growth partially via regulating the lincROR-Wnt/β-catenin regulatory axis, which provides a strategy for the design of anti-tumour drugs for CRC patients after our advanced validation.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-18
·
IF 10.435
Chen Yi,Jiang Zhaohui,Xu Jinzhuan,Zhang Jiyuan,Sun Runbin,Zhou Jia,Lu Yuan,Gong Zipeng,Huang Jing,Shen Xiangchun,Du Qianming,Peng Jianqing
Background The combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated (DEAE-DEX@LSDBC) for the treatment of NAFLD.Results DEAE-DEX@LSDBC with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that DEAE-DEX@LSDBC profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by DEAE-DEX@LSDBC, which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathwaysConclusion DEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.Graphic abstract
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Guanghui Xu,Huiqi Wan,Litao Yi,Wei Chen,Youhua Luo,Yiqi Huang,Xiaojuan Liu
Accumulating evidence showed that berberine possessed the anti-inflammatory action in various diseases caused by inflammation. However, it was still unclear whether both inhalation and injection with berberine produced pulmonary protective role in acute respiratory distress syndrome (ARDS). This study was aimed to evaluate the effects of both administration routes including inhalation and injection with berberine in ARDS induced by lipopolysaccharide (LPS) inhalation. Histopathological examination and weight of lung were evaluated. Phosphorylation of NF-κB, JAK2 and STAT3 were measured to assess the activity of inflammation related signaling pathways. Proinflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the bronchoalveolar lavage fluid (BALF) and serum were also detected. The results showed that LPS caused the lung injury, while both administration routes with berberine attenuated the injury and improved the pulmonary morphology. In addition, the primary TLR4/NF-κB and secondary JAK2/STAT3 signaling pathways which were activated by LPS in lung were totally inhibited by berberine administration. Moreover, proinflammatory cytokines in both BALF and serum were decreased by berberine. Considering that molecular docking simulation indicated that berberine could bind with TLR4, the present suggested that the inhibition of the inflammation related TLR4/NF-κB and JAK2/STAT3 signaling pathways might be involved in the pulmonary protective effect of berberine in LPS-induced ARDS.
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