EBioMedicine
·
2018
·
IF 6.183
Aiyun Li,Qun Liu,Qiang Li,Baolin Liu,Yang Yang,Ning Zhang
Background Mitochondrial pyruvate import via mitochondrial pyruvate carrier (MPC) is a central step in hepatic gluconeogenesis. Berberine inhibits hepatic gluconeogenesis, but the mechanism is incompletely understood. This study aims to investigate whether berberine could reduce excessive hepatic glucose production (HGP) by limiting mitochondrial import of pyruvate through MPC1. Methods High-fat diet (HFD) feeding augmented HGP. The effects of berberine on hepatic fatty acid oxidation, sirtuin3 (SIRT3) induction and mitochondrial pyruvate carrier 1 (MPC1) function were examined. Findings HFD feeding increased hepatic acetyl coenzyme A (acetyl CoA) accumulation with impaired pyruvate dehydrogenase (PDH) activity and increased pyruvate carboxylase (PC) induction. Berberine reduced acetyl CoA accumulation by limiting fatty acid oxidation and prevented mitochondrial pyruvate shift from oxidation to gluconeogenesis through carboxylation. Upon pyruvate response, SIRT3 binded to MPC1 and stabilized MPC1 protein via deacetylation modification, facilitating mitochondrial import of pyruvate. Berberine preserved the acetylation of MPC1 by suppression of SIRT3 induction and impaired MPC1 protein stabilization via protein degradation, resultantly limiting mitochondrial pyruvate supply for gluconeogenesis. Interpretation Berberine reduced acetyl CoA contents by limiting fatty acid oxidation and increased MPC1 degradation via preserving acetylation, thereby restraining HGP by blocking mitochondrial import of pyruvate. These findings suggest that limitation of mitochondrial pyruvate import might be a therapeutic strategy to prevent excessive hepatic glucose production.
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Lu Li,Bo Lin,Yu Ting,Maohui Li,Jinjin Hu,Jingjing Song,Yingjuan Yan,Jiaxin Chen,Hong Xiao,Nengguo Tao
Citrus sour rot is a common postharvest citrus disease caused by Geotrichum citri-aurantiiti , which has led to enormous economic losses, particularly during rainy seasons. In this study, we aimed to clarify the impact of berberine hydrochloride (BH), the hydrochloride form of an isoquinoline alkaloid, on the control efficiency of citrus sour rot and its antifungal mode against G. citri-aurantii . Results demonstrated that BH markedly impede the propagation of G. citri-aurantii by delaying the spores development from dormant stage into swollen and germinating stages, with the MIC and MFC value of 0.08 and 0.16 g L −1 , respectively. When the artificially inoculated citrus fruit in control group were totally rotted, the disease incidence of BH-treated groups decreased by 35.00%–73.30%, which effectively delayed the disease progression and almost did not negatively affect fruit quality. SEM observation, CFW and PI staining images revealed that BH caused significant damage to both the cell membrane and cell wall of G. citri-aurantii spores, whereas only the cell membrane of the mycelium was affected. The impact of cell wall was related to the block of chitin and β-1,3-glucan synthesis. Transcriptome results and further verification proved that 0.5 × MIC BH treatment affected the glycolysis pathway and TCA cycle mainly by inhibiting the production of acetyl-CoA and pyruvate. Subsequently, the activities of key enzymes declined, resulting in a further decrease in ATP levels, ultimately inhibiting the germination of spores. In conlusion, BH delays citrus sour rot mainly by disrupting carbohydrate and energy metabolism of G. citri-aurantii spores.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Cunliang Guo,Lilong Du,Xiaoxun Du,Rui Gao,Xinyi Jiao,Zhenhua Li,Tongxing Zhang,Pingsheng Huang,Chuangnian Zhang,Zujian Feng,Weiwei Wang,Baoshan Xu
Intervertebral disc degeneration (IVDD) is closely associated with mitochondrial dysfunction caused by the excessive accumulation of reactive oxygen species (ROS). Current therapeutic strategies are limited in their ability to precisely intervene in mitochondrial dynamics imbalance. This study develops a ROS-responsive hydrogel crosslinked via dynamic borate ester bonds between boric acid-modified hyaluronic acid and polyvinyl alcohol (PVA), which was further loaded with berberine liposomes (HP-Lipo@BBR), aiming to scavenge excessive ROS, and restore mitochondrial function. The hydrogel exhibited excellent degradability, injectability, self-healing properties, antioxidative effects, and biocompatibility. It triggers intelligent drug release in the high-ROS microenvironment of degenerated discs. The liposomes efficiently encapsulate berberine, facilitating intracellular drug delivery via the endocytosis of nucleus pulposus cells. Mechanistically, berberine scavenges ROS, inhibits abnormal phosphorylation of dynamin-related protein 1 (p-Drp1), and reduces excessive mitochondrial fission, thereby blocking the caspase-3-mediated apoptosis pathway. In a rat disc puncture degeneration model, intradiscal injection of HP-Lipo@BBR effectively maintains intervertebral disc height and the hydration of nucleus pulposus tissue, inhibits mitochondrial fission-apoptosis axis, and improves the regeneration of extracellular matrix, with therapeutic effects significantly superior over free berberine or hydrogel. This study provides a new strategy for minimally invasive treatment of IVDD and other related degenerative diseases.
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BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2025
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IF 2.7
Ru Cheng,Aoqi Song,Jingjing Jiang,Xijier Qiaolongbatu,Zhenghua Wu,Feng Qian,Shuyu Shen,Liwen Zhang,Zhiyu Wang,Wenjuan Zhao,Yuefen Lou
The exact mechanism by which berberine alleviates depression remains unclear. In this study, we explored the relationship between the antidepressant effect of berberine and the microbiota–brain–gut axis. The levels of IL-1β, TNF-α, IL-6, corticosterone, serotonin, and brain-derived neurotrophic factor (BDNF) were quantified using enzyme-linked immunosorbent assays (ELISA) and Western blotting. Variations in the composition of the gut microbiota were examined using 16S rRNA gene sequencing. Berberine significantly mitigated depressive behaviors in mice with CRS, as manifested by increased total distance traveled and central zone duration in the open-field examination, increased time and number of entries into the outstretched arms during the elevated and maze tests, and an increase in the exercise time during the tail suspension and forced swimming tests. Histopathological analysis indicated that berberine ameliorated CRS-induced hippocampal and colonic damage in mice. Additionally, berberine substantially restrained the generation of proinflammatory cytokines and corticosterone in mice with CRS, while increasing the levels of BDNF and serotonin. Importantly, berberine significantly ameliorated CRS-induced depression-like behaviors ( p < 0.01) and restored gut microbial diversity and short-chain fatty acid (SCFA) levels (fold-change: acetate 1.8-fold, butyrate 2.2-fold; p < 0.05). Furthermore, berberine restored the CRS-induced alterations in SCFA production. Our results indicate that berberine may exert antidepressant effects via a pleiotropic mechanism that modulates the microbiome–brain–gut axis.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Yu Cheng,Zhenning Yan,Liuyang Hu
The interactions of three berberine mid-chain fatty acid salts ([BBR][C n ], n = 6, 7, 8) with lysozyme (Lyz) are investigated in detail using multi-spectroscopic and molecular docking techniques. Steady-state fluorescence and UV–visible absorption experiments suggest that the binding mechanism of [BBR][C n ] on Lyz is a static quenching with a binding ratio of 1:1. The compound [BBR][C n ] exhibits a moderate binding affinity toward Lyz. The findings from UV–vis, synchronous fluorescence, three-dimensional fluorescence and FT-IR spectral measurements manifested the alternation in the secondary structure, microenvironment and conformation of Lyz by the binding of [BBR][C n ]. The α-helix content of Lyz declines, while the β-sheet content increases. The theory of Förster resonance energy transfer (FRET) was employed to measure the molecular distance between Lyz and [BBR][C n ]. Thermodynamic parameters and molecular docking results indicate that hydrophobic interaction, van der Waals force, and hydrogen bond are the primary driving forces during the binding process. The binding event enhances the esterase-like activity of Lyz. Furthermore, the binding affinity is influenced by environmental factors such as pH and temperature, as well as the anionic alkyl chain length of [BBR][C n ].
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2025
·Vol. 29
·期 15
·e70744
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IF 4.2
Xuan Li,Shiyu Meng,Jiayi Liu,Meixian Sun,Mao Zhou,Fengtao Ji,Yu Hong
In this study, we investigated the therapeutic potential of Berberine (BBR), an anti‐inflammatory agent capable of penetrating the blood–brain barrier, for mitigating postoperative cognitive dysfunction (POCD) in aged mice. BBR was administered at a dose of 10 mg/kg daily for 2 weeks and significantly improved cognitive impairments induced by surgical and anaesthesia‐related factors. Specifically, BBR markedly suppressed glial cell activation and reduced levels of pro‐inflammatory cytokines such as tumour necrosis factor alpha (TNF‐α) and interleukin‐1 beta (IL‐1β). Additionally, it alleviated oxidative stress markers and lipid accumulation. Using network pharmacology analysis, we demonstrated that BBR modulates neuroinflammation, oxidative processes and lipid metabolism by inhibiting the phosphorylation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) pathway. Furthermore, extended research revealed that BBR upregulated the expression of PPAR‐ γ mRNA, suggesting a neuroprotective mechanism via regulation of the PI3K‐Akt pathway. These findings support the potential application of BBR as a therapeutic agent for managing POCD in elderly populations.
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mSphere
·
2024
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IF 3.7
Xiao-die Cui,Xiao-kang Liu,Xiao-yuan Ma,Shuai-hua Li,Jun-kai Zhang,Rong-jia Han,Kai-fang Yi,Jian-hua Liu,Yu-shan Pan,Dan-dan He,Gong-zheng Hu,Ya-jun Zhai
The appearance and prevalence of multidrug-resistance (MDR) Gram-negative bacteria (GNB) have limited our antibiotic capacity to control bacterial infections. The clinical efficacy of colistin (COL), considered as the “last resort” for treating GNB infections, has been severely hindered by its increased use as well as the emergence and prevalence of mobile colistin resistance (MCR)-mediated acquired drug resistance. Identifying promising compounds to restore antibiotic activity is becoming an effective strategy to alleviate the crisis of increasing MDR. We first demonstrated that the combination of berberine (BBR) and EDTA substantially restored COL sensitivity against COL-resistant Salmonella and Escherichia coli. Molecular docking indicated that BBR can interact with MCR-1 and the efflux pump system AcrAB-TolC, and BBR combined with EDTA downregulated the expression level of mcr-1 and tolC. Mechanically, BBR combined with EDTA could increase bacterial membrane damage, inhibit the function of multidrug efflux pump, and promote oxidative damage, thereby boosting the action of COL. In addition, transcriptome analysis found that the combination of BBR and EDTA can accelerate the tricarboxylic acid cycle, inhibit cationic antimicrobial peptide (CAMP) resistance, and attenuate Salmonella virulence. Notably, the combination of BBR and EDTA with COL significantly reduced the bacterial load in the liver and spleen of a mice model infected with Salmonella. Our findings revealed that BBR and EDTA can be used as adjuvants collectively with COL to synergistically reverse the COL resistance of bacteria.
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ACS Infectious Diseases
·
2025
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IF 3.8
Hengxiu Wang,Hongchen Wang,Yue Yang,Tianming Wang,Changzhong Wang,Daqiang Wu,Caixia Zheng,Wenfan Wei
Berberine (BER), a natural isoquinoline alkaloid, exhibits broad-spectrum antifungal activity, yet its mechanism against Aspergillus fumigatus─a leading cause of invasive fungal infections─remains poorly understood. Here, we aim to unveil the mechanism of BER against the pathogenicity of A. fumigatus through mitochondrial dynamics and related pathways. In vitro assays revealed that berberine treatment triggered mitochondrial fragmentation, resulting in reactive oxygen species (ROS) overaccumulation. Subsequent proteomic analyses identified Hog1-MAPK as the central signaling hub activated by ROS stress. Upon activation, Hog1 localizes to the nucleus. ROS scavenging (N-acetylcysteine (NAC) treatment) abolished BER’s antifungal effects, confirming the ROS-Hog1-cell cycle axis. Crucially, in a murine invasive aspergillosis model, BER reduced the fungal burden in lungs and improved survival rates. Thus, we demonstrate that berberine suppresses A. fumigatus growth by disrupting mitochondrial dynamics, elevating reactive ROS, and activating the Hog1-MAPK signaling cascade, ultimately inducing cell cycle arrest. Our findings unveil a previously unrecognized mechanism linking mitochondrial morphology dysregulation to cell cycle control in fungi and establish BER as a promising therapeutic agent targeting mitochondrial-ROS-Hog1 signaling in A. fumigatus infections.
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ChemMedChem
·
2013
·Vol. 9
·期 1
·207-216
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IF 2.835
Hong Liu,Liang Wang,Yan Li,Jiang Liu,Maomao An,Shaolong Zhu,Yongbing Cao,Zhihui Jiang,Mingzhu Zhao,Zhan Cai,Li Dai,Tingjunhong Ni,Wei Liu,Simin Chen,Changqing Wei,Chengxu Zang,Shujuan Tian,Jingyu Yang,Chunfu Wu,Dazhi Zhang,Hua Liu,Yuanying Jiang
Graphical Build it better: Structural optimization of berberine led to the identification of the novel scaffold of N -(2-(benzo[ d ][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acetamides 7 a – l , which exhibited remarkable in vitro synergistic antifungal activity against fluconazole-resistant Candida albicans in combination with fluconazole. Compound 7 d exhibited much lower cytotoxicity than berberine toward human umbilical vein endothelial cells. We have conducted systematic structural modification, deconstruction, and reconstruction of the berberine core with the aim of lowering its cytotoxicity, investigating its pharmacophore, and ultimately, seeking novel synergistic agents to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. A structure–activity relationship study of 95 analogues led us to identify the novel scaffold of N -(2-(benzo[ d ][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acetamides 7 a – l , which exhibited remarkable levels of in vitro synergistic antifungal activity. Compound 7 d ( N -(2-(benzo[ d ][1,3]dioxol-5-yl)ethyl)-2-(2-fluorophenyl)acetamide) significantly decreased the MIC 80 values of fluconazole from 128.0 μg mL −1 to 0.5 μg mL −1 against fluconazole-resistant C. albicans and exhibited much lower levels of cytotoxicity than berberine toward human umbilical vein endothelial cells.
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LUMINESCENCE
·
2020
·Vol. 36
·期 3
·668-673
·
IF 1.855
Xiao Gao,Mingwei Guo,Ming Liu,Li Zhang,Zhiyi Yao
In this report, we develop a dual-output sensor with fluorometric and colorimetric responses, for the rapid and simple detection of berberine hydrochloride (BRH) in 100% aqueous solution based on an anionic polythiophene derivative, poly(2-(2-(4-methylthiophen-3-yloxy)-ethyl) malonic acid) (PTMA). The sensing performance and mechanism were carefully examined by absorption and emission spectra. It can be applied to quantitatively detect BRH in aqueous solution with a detection limit 0.27 μM. The appealing performance of the sensor was demonstrated to originate from the electrostatic and π–π interactions between PTMA and BRH, which promoted the conformational change and aggregation of the PTMA backbone. Moreover, this method allowed rapid detection of BRH in urine samples and BRH tablets with high accuracy.
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-15
·
IF 3.9
Li Jiameng,Liu Xiaodan,Sun Chaofan,Wang Mingyang,Zhang Qianqian,Wang Hongyu,Ji Xu,Jin Erhui,Zhang Feng
Enterotoxigenic Escherichia coli (ETEC) causes diarrhea and triggers intestinal inflammation posing a significant threat to children which is a global health concern. Berberine (BBR) has diverse pharmacological properties can alleviate diarrhea and intestinal damage. This metabolomics study analyzed the effects of berberine on the hepatic function, lipid metabolism, and inflammatory responses in weaned piglet model infected with ETEC. A total of 18 piglets were randomly divided into three groups: basal diet (BD) + Saline, BD + ETEC, and BBR + ETEC. Compared with the BD + Saline group, ETEC infection significantly increased the contents of aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT), total protein, globulin, triglycerides, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, IL-8, IL-12, interferon γ (IFN-γ), IL-4, IL-10, and transforming growth factor β (TGF-β) and significantly decreased the contents of total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in the serum of weaned piglets. There were 14 metabolites upregulated and 21 metabolites downregulated after ETEC infection, and total cholesterol, LDL, IL-1β, IL-8, and TGF-β were correlated with fructose and mannose metabolism. Compared with the BD + ETEC group, dietary berberine significantly increased the contents of total cholesterol, LDL, and HDL and significantly decreased the contents of AST, AST/ALT, total protein, globulin, triglycerides, TNF-α, IL-1β, IL-6, IL-8, IL-12, IFN-γ, and IL-4 in the serum of weaned piglets. There were 111 metabolites upregulated and 48 metabolites downregulated after berberine addition, and total protein, IL-1β, IL-6, IL-8, and IL-12 were correlated with cholinergic synapse. Both ETEC infection and berberine addition can induce changes in taste transduction and affect the physiological functions of weaned piglets through metabolic pathways.
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PHYTOMEDICINE
·
2022
·
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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