PHYTOMEDICINE
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2022
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IF 6.656
Qingqiu Chen,Guang Xin,Shiyi Li,Yuman Dong,Xiuxian Yu,Chengyu Wan,Zeliang Wei,Yuda Zhu,Kun Zhang,Yilan Wang,Fan Li,Cuicui Zhang,E Wen,Yulong Li,Hai Niu,Wen Huang
Background Accumulation of age-associated senescent cells accompanied with increased reactive oxygen species (ROS) and inflammatory factors contributes to the progression of age-related macular degeneration (AMD), the main cause of blindness in the elderly. Berberine (BBR) has shown efficacy in the treatment of age-related diseases including diabetes and obesity by decreasing ROS. However, the pharmacological effect of BBR on alleviating retinal aging remains largely unknown. Purpose Our study aimed to investigate the pharmacological effect of BBR as an anti-aging agent in retinal aging and its further molecular mechanisms. Methods D-galactose (DG)-induced ARPE-19 cell senescence and retinal aging were employed to evaluate the anti-aging effect of BBR in vivo and in vitro . The siRNA transfection, Western-Blot analyses, SA-β-Gal assay and immunofluorescence were performed to investigate the potential mechanisms of BBR on anti-aging of RPE . Results In RPE-choroid of both natural aged and DG-induced accelerated aged mice, oxidative stress was increased along with the up-regulation of p21 expression, which was ameliorated by BBR treatment. BBR down-regulated the expression of REDD1 to decrease intracellular ROS content, attenuating DG-induced senescence in vitro and in vivo . Furthermore, p53 instead of HIF-1α was identified as the transcriptional regulator of REDD1 in DG-induced premature senescence. Importantly, NAC and BBR reversed the expression of p53 and the content of 8-OHdG, indicating that the positive feedback loop of ROS-DNA damage response (DDR) was formed, and BBR interrupted this feedback loop to alleviate DG-induced premature senescence by reducing REDD1 expression. In addition, BBR restored DG-damaged autophagy flux by up-regulating TFEB-mediated lysosomal biosynthesis by inhibiting REDD1 expression, thereby attenuating cellular senescence . Conclusion BBR down-regulates REDD1 expression to interrupt the ROS-DDR positive feedback loop and restore autophagic flux, thereby reducing premature senescence of RPE. Our findings elucidate the promising effects of REDD1 on cellular senescence and the great potential of BBR as a therapeutic approach.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Zhaoxia Tang,Jiali Luo,Yahya Faqir,Yu Zhang,Wenqian Xue,Hongmei Zhao,Ali Murad Jakhar,Chengjia Tan,Jiahua Ma
Berberine hydrochloride (BH) has long been known for its therapeutic efficacy. In the present study, we aimed to treat mice with colitis using dung beetle chitosan (DCS) -transported BH. To achieve this, BH-loaded DCS/sodium alginate microspheres (SA-DCS-BH) were prepared. The SA-DCS-BH was characterized using SEM, DLS , FT-IR, and XRD, then was used for administration and anti-inflammatory examination in mice. SEM and DLS confirmed the surface morphology of the microspheres, and the particle size was relatively uniform. FT-IR and XRD results confirmed that BH was successfully loaded. In vitro and in vivo studies showed that SA-DCS-BH had slow-release ability. After treatment with SA-DCS-BH, DAI was significantly reduced, colon weight and length increased, spleen length and weight reduced, concentrations of pro-inflammatory cytokines in colonic tissues were reduced, and gut microbiota species abundance was modulated. In addition, this study found a correlation between specific microbes and colitis indicators, Muribaculaceae showed sequential growth after receiving BH, SA-CS-BH, and SA-DCS-BH treatments, respectively. It was concluded that SA-DCS-BH effectively delivered the BH to the intestine with slow-release ability and exhibited anti-inflammatory effects by immune response. Compared to commercial chitosan, DCS has potential for modulating intestinal microorganisms and more suitable carrier for intestinal drug delivery systems.
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BIOMEDICINE & PHARMACOTHERAPY
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2021
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IF 6.53
Yaoxing Dou,Ronglei Huang,Qiaoping Li,Yuhong Liu,Yucui Li,Hanbin Chen,Gaoxiang Ai,Jianhui Xie,Huifang Zeng,Jiannan Chen,Chaodan Luo,Ziren Su
Berberine (BBR) is a promising anti-diabetic isoquinoline alkaloid from Rhizoma coptidis, while its bioavailability was extremely low. Here, the existing form and pharmacokinetics of BBR were comparatively characterized in conventional and antibiotic-induced pseudo germ-free (PGF) rats. Furthermore, we comparatively investigated the antidiabetic effect and potential mechanism of BBR and its intestinal oxidative metabolite oxyberberine (OBB) in STZ-induced diabetic rats. Results showed that BBR and OBB existed mainly as protein-bound form in blood, while protein-bound OBB was significantly depleted in PGF rats. Treatment with OBB and BBR effectively decreased clinical symptoms of diabetic rats, reduced blood glucose level, ameliorated the pancreatic damage, and mitigated oxidative stress and inflammatory markers. However, the anti-diabetes effect of BBR was obviously compromised by antibiotics. In addition, OBB exerted superior anti-diabetes effect to BBR of the same dose, significantly up-regulated the mRNA expression of Nrf2 signaling pathway and substantially promoted the pancreatic levels of PI3K/Akt signaling pathway. In conclusion, BBR and its absorbed oxidative metabolite OBB were mainly presented and transported in the protein-bound form in vivo . The gut microbiota may play an important role in the anti-diabetes effect of BBR through transforming itself into the superior hypoglycemic metabolite OBB. OBB possessed favorable hypoglycemic and pancreatic β-cells protective effects, which may stand a huge potential to be further developed into a promising anti-diabetes candidate.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2020
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IF 5.162
Lin Xiao,Abishek Jung Poudel,Lixia Huang,Yang Wang,Ahmed M.E. Abdalla,Guang Yang
Berberine hydrochloride (BBH) has been used to treat diarrhea and other gastrointestinal diseases, however its therapeutic efficacy is compromised because of poor aqueous solubility and dissolution. In this work, BBH was solubilized with β-cyclodextrin (β-CD) in aqueous solution through formation of the BBH/β-CD inclusion complex (IC), which was confirmed by the combination of different techniques including FT-IR, XRD , DSC , 1 H NMR and 1 H NOESY. The aqueous solubility of BBH at 25 °C was increased by ca. 102% in the presence of 16 mM β-CD. BBH/β-CD IC-loaded bacterial cellulose (BC) hydrogels (denoted as BC/IC) were prepared by physical absorption method, resulting in higher drug loading capacity (DLC) than BC/BBH hydrogels. In vitro drug release showed that sustained drug release was achieved at different pH conditions simulating the gastrointestinal fluids by BC/IC hydrogels due to the hyperfine network of BC matrix. Furthermore, in vitro anti-bacterial test demonstrated the BC/IC hydrogels induced effective bacterial inhibition. Together with the good biocompatibility and edibility of the BC matrix, these BC/IC hydrogels appear to be promising candidates of oral administration medicine against gastrointestinal infections.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Shijiao Fan,Zechuan Lu,Zhenning Yan,Liuyang Hu
In this paper, the interaction of three berberine mid-chain fatty acid salts ([BBR][FAs]), viz. berberine caproate ([BBR][CAP]), berberine heptylate ([BBR][HEP]) and berberine octoate ([BBR][OCT]), with bovine serum albumin (BSA) was studied by means of UV–visible absorption spectroscopy , fluorescence spectroscopy, fourier transform infrared spectroscopy (FT-IR) and molecular docking techniques. Fluorescence experiments revealed that three berberine salts quench the fluorescence of BSA by static quenching mechanism resulted from a stable [BBR][FAs]-BSA complex formation. The stoichiometric numbers of [BBR][FAs]-BSA complexes were found to be 1:1. Synchronous and three-dimensional fluorescence spectra as well as FT-IR demonstrated that the binding of [BBR][FAs] altered the microenvironment and conformation of BSA. The binding average distance from [BBR][FAs] to BSA (3.2–3.5 nm) was determined according to Förster energy transfer theory. Site probe investigation showed that [BBR][FAs] bound to BSA active site I (sub-domain IIA). The binding promotes the esterase-like activity of BSA. The molecular docking results confirmed the fluorescence competition findings and provided the type of binding forces. Furthermore, the relationship between the anionic chain length of [BBR][FAs] and the interaction was explored, and the positive correlation was found.
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Heliyon
·
2024
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IF 3.4
Changhong Wu,Jie Yang,Chenxiao Ye,Hui Wu,Wenxi Shu,Rongrong Li,Sihan Wang,Yi Lu,Haitao Chen,Zewei Zhang,Qinghua Yao
Background 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1β), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.
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高影响因子
MOLECULAR BIOLOGY REPORTS
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2024
·Vol. 52
·期 1
·1-13
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IF 2.6
Ming Huiyun,Lu Tingting,Zhou Han,Song Wencheng,Dai Haiming
Background Non-small cell lung cancer (NSCLC) is a type of lung cancer, the incidence and mortality rate have been high, and the use of monotherapy is easy to make patients develop tolerance. Atmospheric pressure plasma (APP) is an emerging technology for killing cancer cells in recent years, and combination of berberine (BBR) mechanism has not been fully elucidated for NSCLC. The article’s primary goal is to investigate the effect of combination on NSCLC and its associated characterization. Methods and results Antiproliferative effects were detected by cell viability assay and colony formation, and flow cytometry analysis of apoptosis and cycling showed that the combination synergistically induced apoptosis. Then, extracellular reactive oxygen species (ROS)levels and DCFH-DA-based kits examined intracellular ROS levels, and their effects on mitochondrial membrane potential were measured. Study reveals that co-induced apoptosis is associated with ROS accumulation. Subsequently, Western blotting (WB) detected the expression of epidermal growth factor receptor (EGFR), and the important signaling pathway proteins Ras/ERK and AKT/mTOR. Results showed that it could downregulation of EGFR protein expression and inhibit of activation of ERK/AKT signaling pathways. Simultaneous wound healing assay and epithelial-to-mesenchymal transition (EMT) marker detection were performed for the assessment of migration and EMT ability of NSCLC cells. Combination therapy inhibited migration and EMT of NSCLC cells. Conclusion The results of this study show that the combination can synergistically induce apoptosis of NSCLC by regulating ROS production. EGFR downregulation and AKT/ERK signaling pathway inhibition are linked to the synergistic effect.
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JOURNAL OF INORGANIC BIOCHEMISTRY
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2025
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IF 3.2
Meixuan Zhang,Qin Zhang,Xuemin Mu,Xiaolin Wang,Shuhui Zhang,Wenyi Zhao,Xiaoming Song,Lulu Pan,Yanyan Li
The escalating threat of bacterial infections underscores the pressing need for innovative antibacterial solutions. In this study, BA-BBR@MPN nanoparticles (BA-BBR@MPN NPs) were synthesized through the self-assembly of berberine (BBR) and baicalin (BA), followed by modification with a metal-phenolic network (MPN) derived from caffeic acid and Fe 3+ . In the slightly acidic environment of the infected site, the MPN decomposes to release iron ions, BBR, and BA. The iron ions catalyze the generation of hydroxyl radicals (·OH) from hydrogen peroxide (H 2 O 2 ), enabling chemodynamic therapy (CDT) while simultaneously depleting glutathione levels. When combined with 808 nm laser-induced photothermal therapy (PTT), the system demonstrates synergistic antibacterial effects. Both in vitro and in vivo studies confirmed the platform's broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria, along with excellent biocompatibility and significant wound-healing promotion. This multifunctional nanoplatform represents a promising strategy for combating bacterial infections while simultaneously promoting tissue repair.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Yueting Lv,Sajid Asghar,Panting Ye,Haijuan Dong,Rongfeng Hu,Chengjun Yuan,Yan Zheng,Zhipeng Chen,Yanyu Xiao
Due to the existence of the blood–brain barrier (BBB) and the complicated pathological mechanisms of Alzheimer’s disease (AD), current therapeutic approaches for AD show limited efficacy. To overcome these challenges, a multi-strategy drug delivery system (SA-BP-MB/BBR NPs) was developed: photothermal conversion polydopamine nanoparticles (PDA NPs) were decorated with sialic acid-modified bovine serum albumin (SA-BSA) to prepare SA-modified and BSA-stabilized PDA NPs (SA-BP NPs) for targeting the BBB and co-loaded with photosensitizer methylene blue (MB) and berberine (BBR) to target multiple neuropathological factors, including Aβ aggregation and tau hyperphosphorylation. The prepared SA-BP-MB/BBR NPs had spherical morphology with a uniform particle size of 143.43 nm and PDI of 0.095. Drug loading capacities were 6.98 % for MB and 3.50 % for BBR. Our investigations demonstrated that the cellular uptake efficiency of biocompatible SA-BP-MB/BBR NPs increased by 1.74 times when combined with photothermal and photodynamic therapy, which effectively inhibited Aβ aggregation, Aβ fibril depolymerization, and tau hyperphosphorylation. Pharmacokinetics and in vivo biodistribution studies revealed a higher area under the curve (AUC 0-t ) of SA-BP-MB/BBR NPs (9.75 and 7.52 times higher) than free MB and BBR, and SA modification promoted brain accumulation. Overall, SA-BP-MB/BBR NPs have the potential to be an effective treatment for AD.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Shiwen Gong,Wentao Ma,Die Hu,Haixing Xu,Binbin Li,Xinyu Wang
Inflammatory bowel disease ( IBD) is an idiopathic, lifelong, and devastating chronic inflammatory disease of the gastrointestinal tract. Berberine, an alkaloid extracted from the Chinese herb Huanglian, is a pharmaceutical ingredient with antibacterial, anti-inflammatory, and antiviral pharmacological effects in Chinese medicine. However, direct administration of berberine requires high doses due to its low bioavailability and high waste in the stomach. In this study, we prepared berberine-loaded pH-responsive Eudragit® FS 30D-attapulgite (FS-ATT) microspheres for the targeted treatment of colitis. The microspheres had pH-responsive release behavior, with minimal berberine release (about 5.97%) in simulated gastric fluid and high berberine release in simulated colonic fluid (about 69.27%). In addition, it was revealed by in vivo biological evaluations that, compared with drugs in an equivalent solution form taken orally, a significant improvement in IBD symptoms was observed after oral administration of drug-loaded FS-ATT microspheres, leading to an increase in the diversity of intestinal microbiota, inhibition of inflammatory cytokines, and enhanced therapeutic effects of berberine. The pH-responsive FS-ATT microspheres could offer a promising drug delivery platform for managing and treating many gastrointestinal diseases.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Peiyuan Li,Huan Liao,Yingbin Lv,Siyan Liang,Jingwen Zhong,Wei Su
Wound infections are a primary cause of delayed wound healing, and film dressings have garnered significant attention in wound management. However, the development of biologically sourced and green-synthesized film dressings with rapid antimicrobial functionality remains an urgent technological breakthrough. In this study, we successfully developed gelatin sodium alginate/sea sheath molecularly modified berberine hydrochloride film (GS/CB). The incorporation of sea sheath powder significantly enhances the mechanical properties of the gelatin‑sodium alginate film.The calcium ions (Ca 2+ ) provided by the sea sheath create a cross-linking effect within the sodium alginate-gelatin network, resulting in tensile properties of the GS/CB films that are 2.6 times greater than those of the control films. This enhancement allows the films to meet the requirements for wound applications. In in vitro antimicrobial experiments, the films incorporated with sodium oleate-modified berberine hydrochloride showed good antimicrobial effects, with an inhibition rate of 97.79 % against Staphylococcus aureus ( S. aureus ) and 98.57 % against methicillin-resistant Staphylococcus aureus ( MRSA ). In in vivo wound healing experiments, the film effectively eliminated MRSA from the wound, achieving a bacterial clearance rate of 98.5 %. Compared to transparent film dressings, the GS/CB film demonstrated superior wound care efficacy and significantly accelerated wound healing. Furthermore, both in vivo and in vitro tests indicated that the film possesses excellent biocompatibility. Therefore, the GS/CB film holds great potential and application value as a new wound dressing for the treatment of infectious wounds.
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VASCULAR PHARMACOLOGY
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2020
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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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