Nutrients
·
2023
·Vol. 16
·期 1
·9
·
IF 5.9
Huijie Duan,Junya Hu,Yang Deng,Junqing Zou,Wangli Ding,Qiang Peng,Rui Duan,Jianguo Sun,Junrong Zhu
Ischemic stroke (IS) is a vascular disease group concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has been known to improve stroke, but its mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, the mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes in intestinal flora in model mice after BBR administration using 16SrRNA sequencing. Chromatography–mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes in the microglia and astroglia in the mice brains. Our findings suggest that berberine improves stroke outcomes by modulating the gut microbiota. Specifically, after MCAO/R mice were given berberine, the beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. The administration of butyric acid and an inhibitor of butyric acid synthesis, heptanoyl-CoA, showed that butyric acid improved the stroke outcomes in the model mice. In addition, butyric acid could inhibit the activation of the microglia and astrocytes in the brains of model mice, thereby inhibiting the generation of pro-inflammatory factors IL-6, IL-1β and TNF-α as well as improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment.Keywords:stroke;gut microbiota;butyric acid;microglia;astrocytes;NLRP3
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Xinyu Fan,Jiachen Shi,Ye Liu,Mengqiu Zhang,Min Lu,Ding Qu
Background Berberine (BR) shows promise as a candidate for treating irritable bowel syndrome with diarrhea (IBS-D). However, the undesired physicochemical properties and poor oral absorption limit its clinical translation. A ketogenic diet (KD) can induce intestinal overexpression of cannabidiol (CB) receptors, which may offer a potential target for IBS-D-specific delivery of BR.Methods The microemulsions loaded with BR and decorated with cannabidiol (CBD/BR-MEs) were developed through a one-step emulsion method. The pharmaceutical behaviors of the CBD/BR-MEs were measured using dynamic light scattering and high-performance liquid chromatography. The efficacy of the anti-IBS-D therapy was evaluated by assessing fecal water content, Bristol score, and AWR score. The intestinal permeability were assessed through immunofluorescent staining of CB1 and ZO-1, respectively. The signaling of CREB/BDNF/c-Fos was also studied along with immunofluorescent and immunohistochemical examination of brain sections.Results The CBD/BR-MEs, which had a particle size of approximately 30 nm and a surface density of 2% (wt%) CBD, achieved greater than 80% (wt%) encapsulation efficiency of BR. The pharmacokinetics performance of CBD/BR-MEs was significantly improved in the KD-fed IBS-D rats than the standard diet-fed ones, which is highly related to intestinal expression of CB1 receptors. The treatment with CBD/BR-MEs and KD exhibited evident comprehensive advantages over the other groups in terms of anti-IBS-D efficacy. CBD/BR-MEs and KD synergistically decreased intestinal permeability. Moreover, the treatment with CBD/BR-MEs and KD not only blocked the CREB/BDNF/c-Fos signaling in the brain but also decreased the levels of neurotrophic factors, neurotransmitters, and inflammatory cytokines in the serum of IBS-D model rats.Conclusion Such a design represents the first attempt at IBS-D-targeted drug delivery for improved oral absorption and efficacy through KD-induced target exposure, which holds promising potential for the treatment of IBS-D.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2023
·
IF 3.7
Yuehao Tan,Can Li,Jiali Zhou,Fengmei Deng,Yilun Liu
Berberine (BBR) is an effective drug against liver fibrosis (LF). Autophagy is involved in the pathogenesis of LF; however, the mechanism linking BBR to autophagy in LF remains unresolved. To explore the underlying mechanism, we assessed the effects of BBR on autophagy and apoptosis of activated hepatic stellate cells (HSCs) in vitro and in a murine model of fibrosis. The decreased expression of the autophagy activation marker ATG5 , autophagosome formation, and autophagy flux in the HSC model confirmed that BBR inhibited autophagy in activated HSCs and in mice with liver fibrosis. Moreover, ATG5 was necessary for inducing autophagy and HSC activation. BBR suppressed ATG5 expression by upregulating miR-30a-5p expression, which affected the stability of ATG5 mRNA by binding to its 3′-untranslated region, an effect that was attenuated by treatment with a miR-30a-5p inhibitor. BBR also markedly induced HSC apoptosis, as indicated by the upregulated expression of the pro-apoptosis markers p53, BAX, and cleaved PARP and the downregulated expression of the anti-apoptosis marker BCL-2, effects that were reversed by ATG5 overexpression. In vivo, BBR improved mouse LF by decreasing collagen deposition, inflammatory cell infiltration , and expression of fibrosis markers hydroxyproline, α-smooth muscle actin, and collagen type 1-A1 and the autophagy marker LC3. BBR had a protective effect on mouse fibrotic livers and reduced serum aspartate aminotransferase and alanine aminotransferase levels . Collectively, these results reveal a novel mechanism of BBR-induced autophagy inhibition triggering apoptosis in HSCs, providing a reliable experimental and theoretical basis for developing BBR-based candidate drugs for LF.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2018
·Vol. 40
·期 1
·133-142
·
IF 3.562
Zhang Yi-ting,Yu Yu-qi,Yan Xiao-xia,Wang Wen-jie,Tian Xiao-ting,Wang Le,Zhu Wei-liang,Gong Li-kun,Pan Guo-yu
Berberine, berberrubine, thalifendine, demethyleneberberine, jatrorrhizine, and columbamine are six natural protoberberine alkaloid (PA) compounds that display extensive pharmacological properties and share the same protoberberine molecular skeleton with only slight substitution differences. The oral delivery of most PAs is hindered by their poor bioavailability, which is largely caused by P-glycoprotein (P-gp)-mediated drug efflux. Meanwhile, P-gp undergoes large-scale conformational changes (from an inward-facing to an outward-facing state) when transporting substrates, and these changes might strongly affect the P-gp-binding specificity. To confirm whether these six compounds are substrates of P-gp, to investigate the differences in efflux capacity caused by their trivial structural differences and to reveal the key to increasing their binding affinity to P-gp, we conducted a series of in vivo, in vitro, and in silico assays. Here, we first confirmed that all six compounds were substrates of P-gp by comparing the drug concentrations in wild-type and P-gp-knockout mice in vivo. The efflux capacity (net efflux) ranked as berberrubine > berberine > columbamine ~ jatrorrhizine > thalifendine > demethyleneberberine based on in vitro transport studies in Caco-2 monolayers. Using molecular dynamics simulation and molecular docking techniques, we determined the transport pathways of the six compounds and their binding affinities to P-gp. The results suggested that at the early binding stage, different hydrophobic and electrostatic interactions collectively differentiate the binding affinities of the compounds to P-gp, whereas electrostatic interactions are the main determinant at the late release stage. In addition to hydrophobic interactions, hydrogen bonds play an important role in discriminating the binding affinities.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2018
·Vol. 94
·期 4
·650-658
·
IF 2.214
Rong Liu,Yonggang Zhang
Photoelectrocatalytic (PEC) system greatly improves the migration of photoexcited charges, retards the fast recombination of electron-hole and increases the lifetime of photogenerated holes. In this article, we constructed a novel PEC system to degrade berberine chloride form (BCF). XRD patterns indicated aging time was an important condition for the crystal type of TiO 2, and the best proportion of anatase/rutile was 80/20. The band gap energy of the TiO 2 was 3.01 eV. We demonstrated that a synergistic effect existed between photocatalysis (PC) and electrocatalysis (EC). Besides, we discussed the influence of pH, current density, the amount of catalyst and initial BCF concentration on the degradation of BCF. Electron spin resonance (ESR) through spin trap 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) and the scavenging experiments suggested that the reactive oxygen species (ROS) were superoxide radicals ( ), hydroxyl radicals (·OH) and sulfate radical ( ) in PEC system. Furthermore, we compared the two pathway of formation DMPO-SO 4 adducts and found that was the most major oxidized species in degrading BCF. We proposed a plausible reaction mechanism. Intriguingly, even under lower current and weaker light conditions, the PEC process maintained its effectiveness, demonstrating the feasibility of the PEC approach.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Qian Ding,Jinlu Shang,Liuxuan Yang,Li Deng,Siqiong Wu,Jing Chen,Jing Yang,Ke Wang,Chunhong Li,Junyan Chen,Meiling Zhou
The development of innovative therapeutic strategies that combine multiple treatment modalities is essential for effective cancer therapy. In this study, we engineered berberine (BER)-loaded mesoporous polydopamine (MPDA) nanoparticles (BER-MPDA) to enhance anti-tumor efficacy through synergistic chemotherapy and photothermal therapy (PTT). The mesoporous structure of MPDA allowed for a high loading capacity of BER, a natural isoquinoline alkaloid with known anticancer properties. Upon near-infrared laser irradiation, BER-MPDA exhibited marked photothermal conversion efficiency, leading to effective tumor cell ablation. Both in vitro and in vivo experiments indicated that the combined treatment of BER-MPDA with near-infrared laser irradiation resulted in superior tumor inhibition compared to monotherapy. The synergistic effect was attributed to the enhanced cellular uptake and the simultaneous induction of chemo- and photothermal cytotoxicity. Our findings suggest that BER-MPDA represents a promising platform for multimodal cancer therapy, offering a potent approach to overcoming the limitations of conventional chemotherapy and PTT.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 12
·e18407
·
IF 4.3
Zijun Zhou,Qiusheng Zhao,Yuting Huang,Shan Meng,Xin Chen,Guoxin Zhang,Yanbang Chi,Dengyue Xu,Zongtao Yin,Hui Jiang,Liming Yu,Huishan Wang
Chronic intermittent hypoxia (CIH) is associated with an increased risk of cardiovascular diseases. Previously, we have shown that berberine (BBR) is a potential cardioprotective agent. However, its effect and mechanism on CIH-induced cardiomyopathy remain uncovered. This study was designed to determine the effects of BBR against CIH-induced cardiac damage and to explore the molecular mechanisms. Mice were exposed to 5 weeks of CIH with or without the treatment of BBR and adeno-associated virus 9 (AAV9) carrying SIRT6 or SIRT6-specific short hairpin RNA. The effect of BBR was evaluated by echocardiography, histological analysis and western blot analysis. CIH caused the inactivation of myocardial SIRT6 and AMPK-FOXO3a signalling. BBR dose-dependently ameliorated cardiac injury in CIH-induced mice, as evidenced by increased cardiac function and decreased fibrosis. Notably, SIRT6 overexpression mimicked these beneficial effects, whereas infection with recombinant AAV9 carrying SIRT6-specific short hairpin RNA abrogated them. Mechanistically, BBR reduced oxidative stress damage and preserved mitochondrial function via activating SIRT6-AMPK-FOXO3a signalling, enhancing mitochondrial biogenesis as well as PINK1-Parkin-mediated mitophagy. Taken together, these data demonstrate that SIRT6 activation protects against the pathogenesis of CIH-induced cardiac dysfunction. BBR attenuates CIH-induced myocardial injury by improving mitochondrial biogenesis and PINK1-Parkin-dependent mitophagy via the SIRT6-AMPK-FOXO3a signalling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-16
·
IF 15.7
Bian Xufei,Guo Qian,Yau Lee-Fong,Yang Ling,Wang Xiaoyou,Zhao Shikang,Wu Shiqiong,Qin Xurong,Jiang Zhi-Hong,Li Chong
Lipid nanoparticles have shown success in targeting major organs such as the liver, spleen, and lungs, but crossing the blood-brain barrier (BBB) remains a major challenge. Effective brain-targeted delivery systems are essential for advancing gene therapy for neurological diseases but remain limited by low transport efficiency and poor nucleic acid stability. Here, we report a library of ionizable lipids based on the tetrahydroisoquinoline structure of protoberberine alkaloids, designed to improve BBB penetration via dopamine D3 receptor-mediated endocytosis. These nanoparticles offer three key advantages: enhanced brain uptake, improved nucleic acid stability through poly(A) self-assembly, and minimal immunogenicity with inherent neuroprotective properties. In murine models, they demonstrate therapeutic potential in Alzheimer’s disease, glioma, and cryptococcal meningitis. This berberine-inspired delivery system integrates precise receptor targeting with nucleic acid stabilization, offering a promising platform for brain-targeted therapeutics.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Yi Tan,Huan Sun,Yuanchen Lan,Haider Mohammed Khan,Hui Zhang,Linli Zhang,Fengying Zhang,Yujia Cui,Lan Zhang,Dingming Huang,Xinmei Chen,Changchun Zhou,Jianxun Sun,Xue-Dong Zhou
The repair of mandibular defects remained a challenging problem in the clinic, and the associated infection often hinders the treatment, leading to failure in bone regeneration. Herein, a multifunctional platform is designed against the shortages of existing therapies for infected bone deficiency. 2D Ti3C2 MXene and berberine (BBR) are effectively loaded into 3D printing biphasic calcium phosphate (BCP) scaffolds. The composite scaffolds take the feature of the excellent photothermal capacity of Ti3C2 for antibacterial and mediating the NIR-responsive BBR release under laser stimuli. Meanwhile, the sustained release of BBR enhances the antibacterial effect and further accelerates the bone healing process. Importantly, the integration of Ti3C2 improves the mechanical properties of 3D scaffolds, beneficial for new bone formation. The remarkable biomedical performances in vitro and in vivo present the outstanding antibacterial and osteogenic properties of Ti3C2-BBR functionalized BCP scaffolds, which the synergetic therapy makes it highly promising for repairing infected bone defects, as well as provides insight into the broader applications of 2D nanosheets in biomedicine.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2018
·Vol. 25
·期 10
·9873-9886
·
IF 2.8
Liu Rong,Zhang Yonggang
Fe 2 O 3 /graphite (Fe 2 O 3 /C) and nano-TiO 2 -coated glass bead were prepared by impregnation and sol–gel method respectively and employed as the catalyst of a novel three-dimensional electrode photoelectrocatalytic (3-D PEC) system. The photoexcited electrons can transfer from TiO 2 , Fe 2 O 3 to counter electrode. It improves the migration of photoexcited charges, retards the fast recombination of electron–hole, and increases the lifetime of photogenerated holes (h + ). In addition, the cycle reaction of Fe 3+ /Fe 2+ on Fe 2 O 3 /C surface enhanced the Fenton reaction which can produce more hydroxyl radicals (·OH) and promote the capacity of mineralization of the pollutants. This novel 3-D PEC system showed excellent performance for the degradation of berberine chloride form (BCF). At the pH value of 3, 93% BCF was removed within 60 min; besides, 98.64% COD removal rate, 78.96% mineralization, 21.47% mineralization current efficiency, and just 3.16 kW h g −1 TOC energy cost were obtained in 120 min. In this study, we proposed the 3-D PEC mechanism. Electron spin resonance (ESR) and scavenging experiments suggest that the major reactive oxygen species (ROS) are superoxide radicals (O 2 ·− ), ·OH, and h + , while the role of sulfate radical (SO 4 ·− ) is insignificant. This work provides a new dimension for the design of reactors for wastewater treatment and the construction of the 3-D PEC system can potentially be utilized in water purification.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmacology Research & Perspectives
·
2025
·Vol. 13
·期 3
·e70126
·
IF 2.3
Yuanxia Yang,Yue Zhang,Yingdong Qu,Liwan Cui
Sirolimus is a third-generation immunosuppressant with multiple efficacies, including antifungal, antitumor, and immunosuppressive properties. We conducted a pharmacokinetic study to determine the effect of berberine hydrochloride (BBR) on the pharmacokinetics of sirolimus in rats. Thirty-six rats were randomly divided into six groups, and blood samples were collected from the posterior orbital venous plexus at different time points after the last administration to determine the plasma concentration of sirolimus. Liquid chromatography tandem mass spectrometry (LC–MS/MS) was used for detection, and DAS 2.0 software was employed for pharmacokinetic analysis. A single administration of BBR significantly reduced the pharmacokinetic parameter AUC 0-12h of sirolimus. Repeated administration of BBR resulted in an upward trend in C max AUC 0-12h , AUC 0-∞ , and CLz all show an upward trend. This study indicates that BBR has a certain impact on the pharmacokinetics of sirolimus in rats. However, further validation of the role of gene polymorphism in pharmacokinetics and clinical efficacy is needed for further research in a wider population.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhiyue Feng,Shiqi Chen,Ke Han,Qiang Ma,Boyan Sun,Chujun Liu,Qiqi Wang,Hao Zhao,Zimo Liu,Junying He,Zhimeng Zhang,Haiyang Jiang
Infections caused by multidrug-resistant bacteria significantly hinder wound healing, highlighting the need for non-antibiotic alternatives. Here, we developed a multifunctional hydrogel platform, LAMC@PCN-224@BBR, by incorporating photodynamic PCN-224 and the natural product berberine (BBR) into lipoic acid-modified chitosan (LAMC). This design combines photo-crosslinking for enhanced tissue adhesion with photodynamic therapy (PDT) for antimicrobial activity. Upon light irradiation, the hydrogel generates reactive oxygen species (ROS), effectively eradicating methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli ( E. coli ) with an efficiency exceeding 99 %. Its excellent biocompatibility and adaptive adhesion allow conformal coverage of irregular wounds. In a full-thickness skin defect model, the hydrogel accelerated healing by suppressing inflammation, promoting collagen deposition, enhancing angiogenesis, and polarizing macrophages toward the pro-regenerative M2 phenotype. These findings demonstrate that the LAMC@PCN-224@BBR hydrogel is a promising clinical strategy for controlling resistant infections and promoting tissue regeneration.
✓ 已验证
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）