JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2021
·
IF 3.981
Hongji Liu,Hongqing Lin,Zhengzheng Zhou,Liang Li
Bergenin ( BER ) is a bioactive compound used for the treatment of chronic bronchitis in China. However, its low solubility and permeation limits its oral bioavailability. In this study, a new BER : isonicotinamide ( ISN ) cocrystal (1: 1, molar ratio) was reported for the first time. BER-ISN shows better solubility and intrinsic dissolution rates (IDRs) in aqueous medias such as water, buffer solutions with pH = 1.2, 4.5, and 6.8 in comparison to BER monohydrate. For instance, the solubilities of BER-ISN and BER monohydrate in water were 3.72 ± 0.22 and 1.42 ± 0.006 mg/mL, respectively, showing 2.62 times improvement. IDRs of BER-ISN and BER monohydrate were 29.90 ± 0.04 and 18.64 ± 0.27 mg/min/cm 2 , respectively, which was consistent with the solubility results. To explain the solubility behavior, phase solubility diagrams of BER monohydrate, ISN and BER-ISN in three pure organic solvents (ethanol, isopropanol and ethyl acetate) were performed according to the solubility product ( K sp ) and complexes formation ( K 11 ) theory. The predicted solubilities are consistent with experimental solubilities considering complexation effects. The Hildebrand solubility parameter (HSP) calculations support the results. Thus, BER-ISN cocrystal (1: 1) with improved solubility is a good candidate for further formulation development.
研究领域:
药学
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生物化学
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DOI
高影响因子
LUMINESCENCE
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2015
·Vol. 30
·期 8
·1269-1273
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IF 1.518
Yinggui Zhu,Lili Zou,Qin Dong,Derong Jiang
Quenching effects of bergenin, based on the electrochemiluminescence (ECL) of the tris(2,2′-bipyridyl)-ruthenium(II) (Ru(bpy) 3 2+ )/tri-n-propylamine (TPrA) system in aqueous solution, is been described. The quenching behavior can be observed with a 100-fold excess of bergenin over Ru(bpy) 3 2+ . In the presence of 0.1 m TPrA, the Stern–Volmer constant ( K SV ) of the ECL quenching is as high as 1.16 × 10 4 M −1 for bergenin. The logarithmic plot of the inhibited ECL versus logarithmic plot of the concentration of bergenin was linear over the range 3.0 × 10 −6 –1.0 × 10 −4 mol/L. The corresponding limit of detection was 6.0 × 10 −7 mol/L for bergenin (S/N = 3). In the mechanism of quenching it is believed that the competition of the active free radicals between Ru(bpy) 3 2+ /TPrA and bergenin was the key factor for the ECL inhibition of the system. Photoluminescence, cyclic voltammetry, coupled with bulk electrolysis, supports the supposition mechanism of the Ru(bpy) 3 2+ /TPrA–bergenin system. Copyright © 2015 John Wiley & Sons, Ltd.
研究领域:
分析化学
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药学
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PubMed
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Chinese Journal of Natural Medicines
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2014
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IF 0
De-Biao YAN,Dong-Ping ZHANG,Ming LI,Wen-Yuan LIU,Feng FENG,Bin DI,Qing-Long GUO,Ning XIE
To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro . The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH 2 Cl 2 , followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1 H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro . Several triply-substituted ( 3a, 4a, 5a, 6a, 7a ) and doubly-substituted ( 8b, 9b ) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.
研究领域:
药物化学
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肿瘤学
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PubMed
MOLECULES
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2023
·Vol. 28
·期 14
·5496
·
IF 4.6
Ting Li,Chaoyue Yang,Houkang Cao,Siyi Mo,Bo Li,Zhipeng Huang,Ruobing Zhang,Jianzhao Wu,Kefeng Zhang,Ya Gao
Bergenin (BER), a natural component of polyphenols, has a variety of pharmacological activities, especially in improving drug metabolism, reducing cholestasis, anti-oxidative stress and inhibiting inflammatory responses. The aim of this study was to investigate the effects of BER on liver injury induced by isonicotinic acid hydrazide (INH) and rifampicin (RIF) in mice. The mice model of liver injury was established with INH (100 mg/kg)+RIF (100 mg/kg), and then different doses of BER were used to intervene. The pathological morphology and biochemical indicators of mice were detected. Meanwhile, RNA sequencing was performed to screen the differentially expressed genes and signaling pathways. Finally, critical differentially expressed genes were verified by qRT-PCR and Western blot. RNA sequencing results showed that 707 genes were significantly changed in the INH+RIF group compared with the Control group, and 496 genes were significantly changed after the BER intervention. These differentially expressed genes were mainly enriched in the drug metabolism, bile acid metabolism, Nrf2 pathway and TLR4 pathway. The validation results of qRT-PCR and Western blot were consistent with the RNA sequencing. Therefore, BER alleviated INH+RIF-induced liver injury in mice. The mechanism of BER improving INH+RIF-induced liver injury was related to regulating drug metabolism enzymes, bile acid metabolism, Nrf2 pathway and TLR4 pathway.Keywords:bergenin;isonicotinic acid hydrazide;rifampicin;liver injury;RNA sequencing
研究领域:
药理学
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分子生物学
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毒理学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Yao Sun,Shihao Cai,Hongting Liu,Conglu Zhao,Xiang Xu,Xiaoting Wang,Jia Zhang,Chaoyue Zheng,Keran Li,Shouchun Peng,Honggang Zhou,Aiguo Xu,Xiaoting Gu,Xiaoyu Ai,Cheng Yang
Idiopathic pulmonary fibrosis (IPF) is characterized by symptoms such as shortness of breath, persistent dry cough, and hypoxemia. The disease can progress rapidly, often leading to respiratory failure. Given its complex and multifactorial nature, pulmonary fibrosis involves multiple pathological progress, such as inflammation, oxidative stress, and fibroblast activation. A single drug cannot effectively address pulmonary fibrosis through multiple mechanisms, but combining drugs maybe create a synergistic effect, target different aspects of the pathological process and improve treatment efficacy. In our previous study, bergenin can improve pulmonary fibrosis. Vitexin is reported to have anti-inflammatory, antioxidant, and anticancer properties, which maybe influence pathways associated with pulmonary fibrosis. Therefore, bergenin and vitexin were chosen for the combined treatment of pulmonary fibrosis. To improve the targeting ability and the affinity of lung fibroblasts, mouse lung fibroblasts-derived exosomes are used as the carriers for drugs. In this study, exosomes loaded with bergenin and vitexin (Exo-Ber + Vit) were successfully prepared using ultracentrifugation and ultrasonication, with an average particle size of approximately 180 nm. Wound-healing assay showed that Exo-Ber + Vit significantly inhibited the excessive proliferation of TGF-β1 induced Mlg and NIH-3 T3 cells compared with bergenin and vitexin alone. Cell uptake experiments showed that exosomes enhanced the uptake of coumarin 6 in Mlg and 3 T3 cells. In vivo studies, compared to bergenin-loaded exosomes, vitexin-loaded exosomes, and the combination of bergenin and vitexin, Exo-Ber + Vit demonstrated superior effects in reducing pulmonary fibrosis area, collagen deposition, and improving lung function. In conclusion, the co-delivery strategy of bergenin and vitexin via Mlg-derived exosomes offers a promising new approach to the treatment of IPF.
研究领域:
药理学
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呼吸病学
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PULMONARY PHARMACOLOGY & THERAPEUTICS
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2020
·
IF 2.681
Min Chen,Cuifen Chen,Yun Gao,Dongming Li,Dan Huang,Ziyu Chen,Xuanna Zhao,Qiu Huang,Dong Wu,Tianwen Lai,Guomei Su,Bin Wu,Beixian Zhou
Background Bergenin , a type of polyphenol compound, exhibits antiulcerogenic, anti-inflammatory, antitussive , and burn wound-healing properties. However, its therapeutic effect on tumor necrosis factor α (TNF-α)-induced proinflammatory responses in the airway and potential mechanisms of actions are still unclear. This study aimed to investigate the anti-inflammatory effects and mechanism of bergenin in TNF-α-stimulated human bronchial epithelial (16-HBE) cells. Methods Cell Counting Kit-8 was used to evaluate cytotoxicity. Cytokine expression was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay. Immunofluorescence, western blot , and sirtuin-1 (SIRT1) activity assays were employed to investigate potential molecular mechanisms. Results Bergenin obviously decreased both mRNA and protein expression levels of interleukins 6 and 8 (IL-6 and IL-8) in TNF-α-stimulated 16-HBE cells. Bergenin blocked TNF-α-mediated activation of nuclear factor κB (NF-κB) signaling and NF-κB nuclear translocation. Interestingly, RT-qPCR and western blotting results revealed that bergenin did not affect SIRT1 expression, but significantly increased its activity. Bergenin-mediated SIRT1 activation was further confirmed by results indicating decreased acetylation levels of NF-κB-p65 and p53. Moreover, the inhibitory effects of bergenin on mRNA and protein expression levels of IL-6 and IL-8 were reversed by a SIRT1 inhibitor. In addition, combining bergenin and dexamethasone (DEX) yielded additive effects on the reduction of IL-6 and IL-8 expression. Conclusions These findings demonstrate that bergenin could suppress TNF-α-induced proinflammatory responses by augmenting SIRT1 activity to block the NF-κB signaling pathway , which may provide beneficial effects for the treatment of airway inflammation associated with asthma.
研究领域:
药理学
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免疫学
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细胞生物学
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呼吸医学
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2023
·
IF 3.8
Yiheng Quan,Pengchao Su,Chenhong Shangguan,Hao Hao,Lijuan Yue,Chen Chen
Bergenin (BG) is a polyphenolic substance which has therapeutic potential in the treatment of diabetic nephropathy (DN), a common complication of type II diabetes. However, the mechanisms underlying these effects remain unclear. We studied the protective effects and mechanisms of BG in DN mice, focusing on the TLR4/MyD88/NF-κB signalling pathway. C57BL/6J mice were used as experiments (n=60), and 10 animals were randomly selected as normal control. The DN model was developed by administering an intraperitoneal injection of streptozotocin (40 mg/kg BW for three days) and a high-fat diet (n=50). BG (20, 40, and 80 mg/kg BW, once a day) was administered orally for four weeks. After BG treatment, the food and water intake of DN mice decreased, blood glucose levels decreased, and insulin resistance reduced. As a result, serum LDL-C, TC, and TG levels decreased; HDL-C levels increased; SOD, CAT, and GSH-Px levels decreased; and MDA levels increased. BG administration reduced AST, ALT, BUN, and CRE levels and inflammatory factors (including TNF-α, MCP-1, IL-1β, and IL-6). Histopathology revealed a significant improvement in pathological damage to the liver, kidney, and spleen of mice treated with BG, and TLR4, MyD88, and NF-κB p65 were down-regulated at both mRNA and protein levels in the BG-treated group. Based on these results, BG therapeutic type II DN by hypoglycaemia, improving liver and kidney function, and anti-oxidative stress; reducing inflammation; and inhibiting the TLR4/MyD88/NF-κB signalling pathway. The results of this study suggest that BG can be used as an effective treatment for type II DN.
研究领域:
药理学
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内分泌学
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分子生物学
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病理学
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PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Huang Dan,Sun Chaoqun,Chen Min,Bai Shuyou,Zhao Xuanna,Wang Weiming,Geng Kang,Huang Wenbo,Zhao Tingting,Wu Bin,Zhang Guilin,Wu Dong,Xu Youhua
Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1fl/fl-LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1fl/fl-LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1β, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1fl/fl-LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor κB and hinders its nuclear translocation, thereby affecting IL-1β, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.
研究领域:
免疫学
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药理学
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呼吸医学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Yu Wenjing,Luo Rongsiqing,He Chunxiang,Li Ze,Yang Miao,Zhou Jinyong,He Jiawei,Chen Qi,Song Zhenyan,Cheng Shaowu
Background: The escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models.Methods: The experimental subjects included zebrafish larvae (CZ98:Tg (mpeg1:EGFP)ihb20Tg/+), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 μm Aβ1-42), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin’s effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin’s regulation of PPAR/NF-κB pathway in these three models.Results: 1) In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased ins expression and increased expression of irs1, irs2a, and irs2b, suggesting a reduction in insulin resistance. It also altered the expression of pparg and rela. 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.Conclusion: Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.
研究领域:
药理学
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神经科学
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糖尿病
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炎症
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代谢
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行为科学
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2022
·
IF 5.304
Lu Wang,Lan Zhang,Baoxian Ye
Herein, an efficient method for in-situ assembly of silver (Ag) nanoparticles on glycine functionalized graphene (Gly-Gr) has been proposed, which only requires a simple one-step hydrothermal reaction. The microstructure of the material (Ag-Gly-Gr) was characterized by a series of methods, such as FT-IR, XRD, and TEM. For comparison, glycine functionalized graphene (Gly-Gr) was prepared by the same way without adding silver nitrate. The electrochemical sensor (Ag-Gly-Gr/GCE or Gly-Gr/GCE) was prepared by coating the glassy carbon electrode (GCE) surface with dispersive droplets of the related material. The outcomes of the electrochemical impedance test showed that the charge transfer resistance of Ag-Gly-Gr/GCE was less than that of Gly-Gr/GCE and GCE. Compared with the other two sensors, Ag-Gly-Gr/GCE showed a more sensitive response for bergenin. By studying the influence of the pH and sweep rate on the peak potential, the dynamics parameters were discussed to understand the electrochemical reaction mechanism of bergenin. The strategy for quantitative analysis of bergenin was further established at the working potential of 0.8 V (vs SCE). The peak current of bergenin displayed a linear dependence for concentration in 0.01–1 μM with a detection limit of 3.0 nM. Additionally, the analytical availability of Ag-Gly-Gr/GCE was demonstrated by determining bergenin in real-life samples.
研究领域:
材料科学
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分析化学
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纳米技术
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电化学
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高影响因子
REPRODUCTIVE TOXICOLOGY
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2024
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IF 3.3
Yanrong Zhu,Lichen Yao,Yilei Guo,Jing Zhang,Yufeng Xia,Zhifeng Wei,Yue Dai
Tripterygium wilfordii (TW) preparations have been utilized in China for treating rheumatoid arthritis and autoimmune diseases. However, their clinical use is limited due to reproductive toxicity, notably premature ovarian failure (POF). Our study aimed to investigate the effect and mechanism of bergenin in attenuating POF induced by triptolide in mice. POF was induced in female ICR mice via oral triptolide administration (50 μg/kg) for 60 days. Mice received bergenin (25, 50, 100 mg/kg, i.g.) or estradiol valerate (EV) (0.1 mg/kg, i.g.) daily, 1 h before triptolide treatment. In vitro , ovarian granulosa cells (OGCs) were exposed to triptolide (100 nM) and bergenin (1, 3, 10 μM). Antioxidant enzyme activity, protein expression, apoptosis rate, and reactive oxygen species (ROS) levels were assessed. The results showed that triptolide-treated mice exhibited evident atrophy, along with an increase in atretic follicles. Bergenin (50, 100 mg/kg) and EV (0.1 mg/kg), orally administered, exerted significant anti-POF effect. Bergenin and EV also decreased apoptosis in mouse ovaries. In vitro , bergenin (1, 3, 10 μM) attenuated triptolide-induced OGCs apoptosis by reducing levels of apoptosis-related proteins. Additionally, bergenin reduced oxidative stress through downregulation of antioxidant enzymes activity and overall ROS levels. Moreover, the combined use with Sh-Nrf2 resulted in a reduced protection of bergenin against triptolide-induced apoptosis of OGCs. Together, bergenin counteracts triptolide-caused POF in mice by inhibiting Nrf2-mediated oxidative stress and preventing OGC apoptosis. Combining bergenin with TW preparations may effectively reduce the risk of POF.
研究领域:
药理学
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生殖生物学
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肿瘤学
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毒理学
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PubMed
高影响因子
Lipids in Health and Disease
·
2023
·Vol. 22
·期 1
·1-16
·
IF 4.5
Zhang Li,Tong Yingying,Fang Yan,Pei Jinjin,Wang Qilan,Li Gang
Objective The goal of this study was to explore the hypolipidemic effects of bergenin extracted from Saxifraga melanocentra Franch ( S. melanocentra ), which is a frequently utilized Tibetan medicinal plant known for its diverse bioactivities. Establishing a quality control system for black stem saxifrage is crucial to ensure the rational utilization of its medicinal resources. Methods A one-step polyamide medium-pressure liquid chromatography technique was applied to isolate and prepare bergenin from a methanol extract of S. melanocentra . A zebrafish model of hyperlipidemia was used to investigate the potential hypolipidemic effects of bergenin. Results The results revealed that bergenin exhibited substantial hypo efficacy in vivo. Specifically, bergenin significantly reduced the levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-c) while simultaneously increasing high-density lipoprotein cholesterol (HDL-c) levels. At the molecular level, bergenin exerted its effects by inhibiting the expression of FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-1β, and TNF while promoting the expression of IL-4 at the transcriptional level. Molecular docking analysis further demonstrated the strong binding affinity of bergenin to proteins such as FASN, SREBF1, HMGCRα, RORα, LDLRα, IL-4, IL-1β, and TNF. Conclusions Findings indicate that bergenin modulates lipid metabolism by regulating lipid and cholesterol synthesis as well as inflammatory responses through signaling pathways associated with FASN, SREBF1, and RORα. These results position bergenin as a potential candidate for the treatment of hyperlipidemia.
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