PHYTOMEDICINE
·
2025
·
IF 8.3
Xiaoyu Tao,Yifei Gao,Zhengsen Jin,Shan Lu,Zhiqi Li,Siyu Guo,Qiqi Fan,Jiaqi Li,Chuanqi Qiao,Huiling Lei,Zhiqiang Zhang,Chongjun Zhao,Jiarui Wu
Background The combined therapeutic mechanisms of evodiamine (EVO) and berberine (BBR), which are the primary bioactive components contributing to the pharmacological effects of Euodiae Fructus and Rhizoma Coptidis , a classic herb pair used for colitis, have not yet been fully elucidated Purpose This study aimed to investigate the critical mechanisms by which co-administration EVO and BBR mitigated EVO-induced hepatotoxicity while exerting therapeutic effects against colitis. Methods Safety and therapeutic outcomes of EVO alone and combined BBR were validated in normal and colitis models. RNA-seq sequencing was performed on liver and colon tissues from different groups, while metagenomic sequencing was utilized to analysis fecal samples. An integrated bioinformatics analysis of transcriptomic and metagenomic data was conducted to reveal the mechanisms underlying EVO-induced hepatotoxicity and the protective and synergistic effects of BBR against colitis. Molecular biology experiments were employed to validate the regulatory mechanism, with a particular emphasis on the interactions within the gut- liver axis, including those related to lipid metabolism and inflammatory pathways. Results BBR attenuated EVO-induced hepatotoxicity in C57 mice by ameliorating pathological injuries and hepatic steatosis as well as inhibiting abnormal AST/ALT elevation, thereby revealing its hepatoprotective effects. In colitis mice, the combination therapy exhibited enhanced efficacy in reducing mucosal damage, restoring goblet cells populations, and suppressing pro-inflammatory cytokines production compared to monotherapy. Integrated analysis of RNA-seq combined with experimental validation revealed that EVO-induced hepatotoxicity was associated with the disrupted fatty acid β-oxidation and cholesterol synthesis homeostasis. Notably, co-administration of BBR effectively rescued metabolic disturbance through modulating core regulatory targets such as ACSL1, CPT1B, SQLE, DHCR7. Additionally, the combination treatment synergistically inhibited IL-17/NF-κB signaling, upregulated tight junction proteins, and rectified gut microbiota dysbiosis, thereby alleviating intestinal injury in colitis mice. Furthermore, ACSL3, a central regulator of fatty acid β-oxidation, was identified as a pivotal target through which the combination of EVO combined BBR suppressed lipid peroxidation-mediated activation of IL-17/NF-κB, leading to alleviate inflammation in LPS-induced NCM460 cell. Conclusion ACSL3 was identified as the critical therapeutic target through underlying the amelioration of fatty acid metabolism-mediated inflammatory injury in colitis by the combined administration of EVO and BBR, thereby offering a scientific foundation for precise and safe clinical drug administration.
研究领域:
药理学
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毒理学
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胃肠病学
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系统生物学
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生物信息学
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分子生物学
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民族药理学
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代谢
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2024
·Vol. 416
·期 29
·6869-6877
·
IF 3.8
Cui Xiaoqing,Geng Haoyuan,Guo Huanying,Wang Lei,Zhu Zihan,Zhang Yaqi,Chen Panpan,Wang Xiao,Sun Chenglong
Berberine (BR), an alkaloid isolated from the Chinese traditional medicine Coptidis rhizoma, exhibits therapeutic effects on several diseases including bacterial infections, diabetes, and hyperlipidemia, but the oral availability is poor. In this work, we prepared the chitosan microneedle array–loaded BR (BR-CS MNAs) to transdermally deliver BR, and the spatial distribution of BR in heterogeneous skin tissues was analyzed and imaged by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Some endogenous phospholipids with specific spatial distribution were used to differentiate the epidermis and dermis regions of the skin. The results showed that BR was effectively delivered and could permeate to both epidermis and dermis regions of the skin. This demonstrated the feasibility of MALDI-MSI to evaluate the transdermal delivery efficiency of microneedle arrays and suggested BR could be transdermally delivered by CS MNAs. Graphical Abstract The chitosan microneedle array–loaded BR (BR-CS MNAs) was prepared and used to transdermal deliver BR. The spatial distribution of BR during the transdermal deliver process was analyzed and imaged by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Some endogenous phospholipids with specific spatial distribution were used to help differentiate the epidermis and dermis regions of skin
研究领域:
药学
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生物医学工程
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2016
·
IF 2.687
Wenchao Wang,Qin Shen,Hui Liang,Changlong Hua,Yuhui Liu,Fengzhi Li,Qingyong Li
An ultra-performance liquid chromatography with tandem mass spectrometric detection method was developed for the detection of berberine and its derivatives (A4, B4) in rat plasma and other organs. This validated method was successfully applied to our pharmacokinetic study of BBR derivatives in rats. At the same dose of administration, the C max of B4 was about eight times higher than BBR, and its half-life was approximately two times longer than BBR, according to the bigger areas under plasma concentration curves. Inversely, the pharmacokinetic parameter levels of A4 were all inferior to BBR, suggesting a tight structure-activity relationship of these compounds. Small dose of parenteral administration was used for the study of absolute oral bioavailability of A4, B4, and BBR, and the results calculated were 0.12%, 3.4% and 0.7%, respectively. The accumulations of B4 among all organs were intestine > liver > heart > kidney > lung > spleen > plasma, proving a deeply targeting property of B4, which met our experimental assumption. Together, the experimental results proved that compared with BBR and A4, the derivative B4 had higher absolute oral bioavailability and the ability of deeply targeting so that can be likely used in some organ-targeted diseases.
研究领域:
药理学
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分析化学
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药物代谢
✓ 已验证
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2020
·
IF 4.545
Aiting Wang,Wei Yang,Xinyu Yang,Xuan Mei,Tingting Hu,Ruizheng Liang,Dali Meng,Dan Yan
Berberine (BBR) is a potential novel agent to treat diabetes, but its oral bioavailability is restricted by the poor solubility, which greatly limits its clinical application. Here, a new drug delivery system of BBR-MgAl monolayer hydrotalcite (BBR/MLDH) was prepared to increase the solubility and bioavailability of BBR. The results showed that BBR/MLDH presented as a uniform hexagonal plate-like particle with a loading capacity of 28.61 %, a diameter of ∼70 nm and a thickness of ∼1.5 nm. The solubility and dissolution of BBR increased when loading onto MLDH. Compared with BBR, pharmacokinetics of BBR/MLDH in rats showed significant enhancement ( P < 0.01) in area under the curve (AUC) and the peak plasma concentration ( C max ), suggesting the bioavailability of BBR was improved. Furthermore, BBR/MLDH showed more potent effects in reducing fasting blood glucose, ameliorating glucose tolerance and insulin resistance comparing to the equivalent dose of BBR. In a word, the solubility, oral bioavailability and hypoglycemic effect of BBR could be improved by loading onto MLDH.
研究领域:
药剂学
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糖尿病研究
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药物递送系统
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药理学
✓ 已验证
DOI
高影响因子
Journal of Natural Medicines
·
2017
·Vol. 72
·期 2
·390-398
·
IF 1.982
Lu Jianrao,Yi Yang,Pan Ronghua,Zhang Chuanfu,Han Haiyan,Chen Jie,Liu Wenrui
Renal ischemia reperfusion injury (RIRI) refers to the irreversible damage for renal function when blood perfusion is recovered after ischemia for an extended period, which is common in clinical surgeries and has been regarded as a major risk for acute renal failures (ARF) that is accompanied with unimaginably high morbidity and mortality. Hypoxia during ischemia followed by reoxygenation via reperfusion serves as a major event contributing to cell apoptosis, which has been widely accepted as the vital pathogenesis in RIRI. Preventing apoptosis in renal tubular epithelial cell has been considered as effective method for blocking RIRI. In this paper, we established a hypoxia/reoxygenation (H/R) injury model in human proximal tubular epithelial HK-2 cells. Here, we found increased SPHK1 levels in H/R injured HK-2 cells, which could be significantly down regulated after berberine treatment. Berberine has been reported to exert a protective effect on H/R-induced apoptosis of HK-2 cells. So, in our present study, we planned to investigate whether SPHK1 participated in the anti-apoptosis process of berberine in H/R injured HK-2 cells. Our study confirmed the protective effect of berberine against H/R-induced apoptosis in HK-2 cells through promoting cells viability, inhibiting cells apoptosis, and down-regulating p-P38, caspase-3, caspase-9 as well as SPHK1, while up regulating the ratio of Bcl-2/Bax. However, SPHK1 overexpression in HK-2 cells induced severe apoptosis, which can be significantly ameliorated with additional berberine treatment. We concluded that berberine could remarkably prevent H/R-induced apoptosis in HK-2 cells through down-regulating SPHK1 expression levels, and the mechanisms included the suppression of p38 MAPK activation and mitochondrial stress pathways.
研究领域:
肾病学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 11
·6075-6082
·
IF 2.936
Qing Liu,Zhihai Xie,Tao Liu,Jin Fan
The interaction of silica nanoparticles (SiO2NPs) with berberine hydrochloride (BRH) was studied in aqueous solution at pH 9.0 and room temperature by using fluorophotometry. Based on a significant enhancement of the fluorescence intensity of the SiO2NPs–BRH aggregates, a spectrofluorimetric method which was simple, sensitive and green was developed for the determination of BRH in aqueous solution. The linear range of the method was from 2.0–50.0 μg L−1 with a detection limit of 0.73 μg L−1. There was no interference from the compounds normally used to formulate pharmaceutical tablets. The proposed method was applied to the determination of BRH in tablets with satisfactory results and good consistency with the results obtained by standard methods.
研究领域:
分析化学
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药学
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 30
·4972-4984
·
IF 4.776
Shiwei Wang,Yi Hou,Shurong Zhang,Jing Li,Qian Chen,Mingan Yu,Wei Li
The environmental risk from antibiotics is an issue of increasing concern. So, carboxymethyl β-cyclodextrin-functionalized montmorillonite nanosheets were for the first time successfully synthesized through a cheap, environmentally friendly and scalable approach and confirmed by FTIR, XRD and TGA. FE-SEM investigation showed that the resulting functional material could be further self-assembled into dense supramolecular organoclay networks (D-networks). The antibacterial properties of the D-networks loaded with natural berberine hydrochloride (BBH) were investigated toward E. coli and S. aureus by using colony growth on agar plates, bacterial growth curves based on optical densities, and confocal and fluorescence microscopy. Our studies demonstrated that the BBH loaded D-network antibacterial activity was concentration dependent and significantly exceeded that of free BBH. FE-SEM observation confirmed that E. coli and S. aureus can directly contact the D-networks and confocal and fluorescence microscopy showed that free BBH was only very poorly internalized, while the BBH released from the BBH-loaded D-network could be internalized efficiently into bacterial cells, resulting in an increment of the intracellular BBH level compared with the free BBH group. Time-dependent antibacterial activity was observed and it was found that the BBH-loaded D-network dispersion at the BBH dosage of 600 μg mL−1 almost completely suppressed the growth of E. coli, leading to a viability loss of up to 98.45 ± 1.22%, while the BBH-loaded D-network dispersion at the BBH concentration of 250 μg mL−1 exhibited a growth inhibition of 97.81 ± 0.83% toward S. aureus over three days. Our results suggest that supramolecular organoclay networks, in the future, may function as promising antibacterial drug carrier systems to promote BBH delivery in E. coli and S. aureus, which can reduce the environmental risk of antibiotics.
研究领域:
材料科学
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微生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2021
·
IF 4.598
Jia Zeng,Mukaram Mamitimin,Ya Song,Weibin Sun,Zhenghong Wu,Xiaole Qi
Bone substitutes and biological materials are commonly employed in alveolar ridge preservation after tooth extraction. Here, we established a novel chairside administrated antibacterial hydrogel system as dental temporary stopping, based on chitosan (CS) crosslinked by dialdehyde-functionalized polyethylene glycol (DF-PEG) and β -glycerophosphate disodium salt hydrate ( β -GP). In addition, free berberine (BBR) and BBR microspheres are embedded into the gel for osteogenic differentiation and bacterial inhibition. We demonstrated that those gels could exhibit satisfied thermosensitive, shapeable and self-healing properties in vitro and in vivo . Besides, the long-acting sustained releasing for 20 days and antibacterial behaviors for 14 days of BBR was demonstrated. The osteogenic differentiation ability of BBR/MS-CGD gels for 21 days was found to increase 3.63 times higher than that of saline treated group, evaluated by alizarin red staining experiment. Overall, those gels offered an easily operated, chairside administrated, and personally tailored dental temporary stopping, achieving potential bacteriostatic and mineralization-promoting effect.
研究领域:
牙科材料
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生物材料
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药学
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组织工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Meng Wang,Jinglan Zhang,Huayan Zhao,Dingming Wan,Zhongxing Jiang
Graft-versus-host disease (GVHD) causes significant mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Berberine (BBR) is primarily used to alleviate inflammation caused by autoimmune disorders. Herein the effect of BBR and cyclosporine A (CsA) on GVHD prevention in murine models is explored. Acute GVHD was induced by total body irradiation and tail vein injection with the mixture of bone marrow cells and spleen lymphocytes. Then models were treated with BBR (10 mg/kg), CsA (5 mg/kg) or the combination of BBR and CsA (10 mg/kg and 5 mg/kg) once a day for 10 days. The survival rate, weight loss and GVHD index were monitored. Then the histological changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, apoptosis and the levels of inflammatory cytokines, oxidative stress and nuclear factor-κB (NF-κB) signaling in liver and intestine were analyzed. Moreover, the levels of inflammatory cytokines and oxidative stress, and the count of T helper 1 (Th1) cells and Th17 cells in peripheral blood were determined. The results showed that BBR reduced GVHD-induced weight loss and GVHD index scores, attenuated liver and intestinal injury, and inhibited ALT and AST activities, inflammation, oxidative stress and NF-κB activation in liver and intestine. Additionally, BBR inhibited inflammation and reduced Th1 cell counts but had no effect on Th17 cell counts. Interestingly, the concomitant therapy of BBR and CsA was more potent than either BBR or CsA and effectively elevated the survival rate of GVHD models. This present study provides a new therapeutic strategy for alleviation of acute GVHD.
研究领域:
免疫学
·
药理学
·
血液学
·
移植学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2021
·
IF 5.293
Li Xiaobo,Song Yanqing,Wang Lina,Kang Guangbo,Wang Ping,Yin Huabing,Huang He
Multidrug-resistant (MDR) Acinetobacter baumannii strains can cause severe infections in intensive care units, and are rapidly developing resistance to the last-resort of existing antibiotics, posing a major global threat to health care system. Berberine hydrochloride (BBH), a kind of isoquinoline alkaloids extracted from Berberis and other plants, has been widely used as an antibacterial medicine for its reliable therapeutic efficiency. The in vitro synergistic effects of BBH with antibiotics against MDR A. baumannii were determined. BBH alone had weak antimicrobial activity (e.g., MIC≥256 mg/L) against MDR A. baumannii. However, it dramatically increased the susceptibility of MDR strains against antibiotics with FICI values <0.5, even reversed their resistance to antibiotics (e.g., tigecycline, sulbactam, meropenem and ciprofloxacin). In vivo study has suggested BBH with sulbactam had stronger antimicrobial efficiency than monotherapy in a neutropenic murine thigh infection model. The antibiotic-sensitizing mechanism of action of BBH was evaluated as well. BBH boosted adeB gene expression and bound to the AdeB transporter protein, resulting in low uptake of BBH, which may contribute to less extrusion of antibiotics by the AdeABC pump. Knockout of the adeB gene increased uptake of BBH and diminished the antibiotic sensitization and synergistic effects between antibiotics and BBH in MDR strains. Together, BBH effectively re-sensitizes this MDR pathogen to a range of antibiotics that have become barely effective due to antibiotic resistance, which indicates BBH may be a promising therapeutic adjuvant candidate to combat MDR A. baumannii.
研究领域:
微生物学
·
药理学
·
传染病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 2
·1087-1098
·
IF 6.1
Chengzhu Song,Dongning Li,Jie Zhang,Xiaoyan Zhao
Imatinib mesylate (IMA) belonging to the selective tyrosine kinase inhibitor family has been proven to induce cardiotoxic effects along with therapeutic strategies. Nrf2-dependent ferroptosis has been implicated in the cardiotoxicity induced by IMA. The present study was designed to investigate the protective effects of berberine hydrochloride (Ber) on cardiac injuries induced by IMA and to explore its potential mechanisms. In H9c2 cells, cell viability, the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and labile iron pool (LIP) levels were measured. In a mouse model of IMA-induced cardiomyopathy, serum biomarkers and cardiac tissues were examined. A western blot assay was performed to evaluate the expression of ferroptosis-related proteins in vitro and in vivo. Our results indicated that Ber increased cell viability and MMP and decreased cellular ROS and iron levels in comparison to the IMA group of H9c2 cells. In mice, Ber significantly improved cardiac status and attenuated the level of ferroptosis biomarkers including malonaldehyde (MDA) and iron content. Additionally, Ber downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partly via inhibiting Nrf2-dependent ferroptosis.
研究领域:
药理学
·
心脏病学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Chunxia Tan,Zizhen Huang
Four organic-polyoxometalate hybrids were fabricated by the polyoxoanions and berberine cations from active ingredients of traditional Chinese medicine. Four hybrids were constructed with different topological kernels and number of cations on the surface. The structures of hybrids were characterized and confirmed by elemental analysis, thermogravimetric (TG) analysis, infrared spectra and 1 HNMR. The TG results indicate that hybrids have higher thermal stability than BR. The sites of interaction between BR caitons and POMs based on electrostatic attraction were near the nitrogen atom of isoquinoline skeleton. Self-assembly behaviors and aggregates morphology of four hybrids were obtained by fluorescence microscope, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Hybrids dispersed in methanol show multilayered vesicle structure. Especially, the two hybrids containing Eu show fluorescence property. Relatively, XRD results imply that BR-SiW appears as specially ordered layered structure with cubic symmetry in solid state resulting from aggregates accumulation.
研究领域:
材料科学
·
化学
·
药学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）