Drug Design Development and Therapy
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2022
·
IF 4.319
Yu Li,Ximei Wang
Purpose High glucose environment in diabetes mellitus induces the dysfunction of bone marrow-derived mesenchymal stromal cells (BMSCs) and impairs bone regeneration. Chrysin is a natural polyphenol with outstanding anti-inflammation and anti-oxidation ability. However, whether and how chrysin affects BMSCs in high glucose conditions remain poorly understood. The present study aimed to explore the effects and underlying mechanisms of chrysin on the BMSCs exposed to high glucose environment.Materials and Methods Cell viability was detected by cell counting kit 8 assay and 5-ethynyl-2’-deoxyuridine staining, while cell apoptosis was determined through flow cytometry using Annexin V-FITC/PI kit. The oxidative stress in BMSCs was evaluated by detecting the reactive oxygen species production, malondialdehyde content, and superoxide dismutase activity. Alkaline phosphatase staining, Alizarin Red staining, and quantitative real-time PCR were performed to determine the osteogenic differentiation. Western blot was used to examine the expression of the PI3K/ATK/Nrf2 signaling pathway. Furthermore, chrysin was injected into calvarial defects of type 1 diabetic SD rats to assess its in vivo bone formation capability.Results Chrysin reduced oxidative stress, increased cell viability, and promoted osteogenic differentiation in BMSCs exposed to high glucose. Blocking PI3K/ATK/Nrf2 signaling pathway weakened the beneficial effects of chrysin, indicating that chrysin at least partly worked through the PI3K/ATK/Nrf2 pathway.Conclusion Chrysin can protect BMSCs from high glucose-induced oxidative stress via the activation of the PI3K/AKT/Nrf2 pathway, and promote bone regeneration in type 1 diabetic rats.
研究领域:
细胞生物学
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分子生物学
·
糖尿病研究
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DOI
PubMed
高影响因子
Food and Bioprocess Technology
·
2024
·
IF 5.3
Fu Jin-Xian,Jiao Jiao,Gai Qing-Yan,He Xiao-Jia,Fu Yu-Jie,Feng Xue,Gao Jie
Baicalein and wogonin, two health-promoting flavonoid aglycones in Scutellaria baicalensis Georgi roots, have better bioactivity and bioavailability than their glycoside precursors (baicalin and wogonoside). The search for novel microorganisms for the fermentation of S. baicalensis roots to improve the yields of baicalein and wogonin is of great interest in the food and nutraceutical industries. In this study, a novel endophytic fungus ( Penicillium rubens ) capable of producing cellulase (0.82 ± 0.12 U/mL) and β-glucosidase (4.55 ± 0.97 U/mL) was used to ferment S. baicalensis roots to obtain high yields of baicalein and wogonin. Semi-solid-state fermentation with homogeneous fungal cultures was found to be the appropriate strategy. Under the optimal fermentation parameters (temperature 30 °C, inoculation dose of fungal cultures 4 mL/g, and time 60 h), the yields of baicalein and wogonin (46.95 ± 4.98 mg/g DW and 31.41 ± 9.36 mg/g DW) from S. baicalensis roots were tremendously increased by 16.13-fold and 15.47-fold over control, respectively. Results of industrial enzyme bioprocessing and scanning electron microscope indicated that the remarkable increase in aglycone product yields could be due to the synergistic effects of cellulase and β-glucosidase produced by P. rubens on cell wall hydrolysis and glycoside deglycosylation. In addition, extracts of S. baicalensis roots fermented by P. rubens showed a significant increase in antioxidant and antimicrobial activities. Overall, the semi-solid-state fermentation of S. baicalensis roots using the novel P. rubens was an effective strategy that could yield high quantities of baicalein and wogonin, which had promising potential in the food and nutraceutical industries. Graphical Abstract
研究领域:
药用植物学
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微生物学
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食品科学
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天然产物化学
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产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Xiao Tang,Kun Wang,Zihan Liu,Xu Luo,Ming Wu,Hui Ding,Gang Liu,Qian Du
Ulcerative colitis (UC) remains a major challenge in clinical treatment due to its multivariate pathology. Developing an oral formulation that encapsulates and delivers multiple active ingredients to target colon tissues by suppressing intestinal inflammation and restoring the intestinal barrier is crucial for effectively treating UC. Here, we developed rhubarb-derived nanovesicles (RNs) and a supramolecular hydrogel platform formed by furfural-functionalized chitosan-mannose polymer and synthesized 3-maleimide HP-β-CD, with kaempferol (Kae) integrated into the hydrophobic cavity. The hydrogel's cross-linking network effectively encapsulates RNs, forming the Kae/CMCHD@RNs system. Rheology, SEM, TGA, degradation behavior, in vitro drug release, and a macrophage-targeted permeability test were performed. The results indicate that the hydrogel utilizes pH/enzyme sensitivity to ensure sustained release in the colon, while also facilitating targeted delivery to macrophages. In vivo imaging further reveals a prolonged local drug retention time in the colon. Moreover, both in vitro and in vivo studies demonstrate RNs and Kae exhibit synergistic therapeutic effects for UC, including inflammation reduction, oxidative stress alleviation, M1-to-M2 macrophage repolarization, and restoration of the intestinal barrier. Consequently, this study underscores the potential of Kae/CMCHD@RNs as a promising therapeutic approach for managing UC.
研究领域:
药剂学
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炎症性肠病研究
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生物材料科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Shen Yunfu,Guo Kaiqiang,Ma Aijun,Huang Zhe,Du Jingjing,Chen Junhe,Lin Qianyu,Wei Chengming,Wang Zi,Zhang Fuming,Zhang Juan,Lin Wanjun,Feng Na,Ma Wenzhe
There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.
研究领域:
药理学
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毒理学
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中药
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Sa Yang,Shijie Cao,Congyu Li,Jichao Zhang,Chang Liu,Feng Qiu,Ning Kang
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia , while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides , and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum . Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.
研究领域:
药理学
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代谢学
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胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2024
·
IF 4.3
Xingzhu Tang,Lingling Wang,Yajie Zhang,Chaofan Sun
Antioxidant activity, as a topic of current interest, is discussed together with the excited state intramolecular proton transfer (ESIPT) process for three flavonoid derivatives, based on density functional theory (DFT)and time-dependent DFT (TD-DFT) methods, as well as DPPH free radical scavenging assay. The potential energy curves and transition states demonstrate that the three molecules can undergo only single proton transfer in the excited state, and all of them are ultrafast ESIPT processes. The absorption spectra of all the molecules show effective protection against UV radiation with low fluorescence intensity, especially Baicalein (Bai), which demonstrates their great potential for sunscreen applications. The density of states, HOMO energy values, global and local indices reveal that the antioxidant activity of the molecules after ESIPT process is enhanced, with Bai having the highest antioxidant activity, which is significantly attributed to the number and position of phenolic hydroxyl groups. Moreover, by comparing the DPPH free radical scavenging activity under the dark and UV radiation conditions, the radical scavenging activity (RSA) value in the UV radiation is remarkably higher than that in the dark condition, in which Bai achieves RSA value of 93.4%. Overall, the antioxidant activity of all three ESIPT-based flavonoid derivatives, especially Bai, is significantly elevated in the keto* form, which reinforces the significant relationship between antioxidant activity and ESIPT process, and provides new application prospects for molecules with ESIPT properties.
研究领域:
化学
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生物学
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DOI
PubMed
高影响因子
MACROMOLECULES
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2025
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IF 5.2
Rui Yang,Kan Zhang
Designing smart chemical structures and gaining insight into the structure–property relationship can effectively guide the development of advanced green thermosetting resins. Herein, four flavonoid-based biophenols were used as sustainable raw materials for achieving novel mono-, bis-, and trifunctional benzoxazine monomers (HYD-a, CHR-a, API-a, and LUT-a). These monomers were developed to discover the roles of the oxazine ring number and hydrogen bonding on their polymerization mechanisms and thermal properties. Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance, and high-resolution mass spectrometry were employed to confirm the successful synthesis of benzoxazine monomers. Polymerization behavior of each benzoxazine was investigated using differential scanning calorimetry, thermogravimetric analysis (TGA), and in situ FT-IR. The thermal properties of the resulting thermosets were evaluated by TGA and microscale combustion calorimetry. With the designed varieties of flavonoid-based benzoxazine structures, it has been found that the intramolecular hydrogen bonding can act as a latent curing agent for reducing the curing temperature while maintaining excellent shelf life. In addition, the onset curing temperature decreases progressively with increasing the number of oxazine rings in the benzoxazine monomer. Interestingly, the polybenzoxazine derived from bis-benzoxazine (API-a) rather than trifunctional monomer shows the best thermal stability (Td10: 438 °C, Yc: 62%) and flame retardancy (HRC: 11.4 J g–1 K–1, THR: 2.22 kJ g–1), indicating the advantage of designing high-performance thermosets based on flavonoid-based bis-benzoxazines.
研究领域:
材料科学
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有机化学
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产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 8
·e5931
·
IF 1.8
Xu Ji,Liangxi Li,Kaiyue Zhang,Xinyi Yuan,Qian Li,Ge Bai
As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT 1 R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT 1 R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT 1 R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT 1 R. The association constants were (2.40 ± 0.02) × 10 4 M −1 for naringenin (5.22 ± 0.26) × 10 4 M −1 for pinocembrin, and (4.27 ± 0.14) × 10 4 M −1 for chrysin, respectively. These compounds can bind with AT 1 R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT 1 R column for screening and analyzing bioactive compounds in Tibetan medicines.
研究领域:
药理学
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中药学
·
分析化学
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DOI
PubMed
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Detao Li,Zichen Ning,Zhuoshan Gong,Limin Zhou,Li Xu,Feiqiang He,Hamza Shehzad,Heng Jerry,Shichao Du,Jinbo Ouyang
According to in-depth research on cocrystals of polyhydroxylated natural products, we previously summarized the substitution model to elucidate the formation mechanism of cocrystals. However, when refers to salt formation of natural products, the substitution model reveals numerous deficiencies. To compensate for the shortcomings of substitution model in predicting salt formation, this study conducts a comprehensive exploration of natural product salts. By supplementing the energy difference rule to the substitution model, it endows the modified model with broader applicability. Simultaneously, the transfer of protons within salts structures is verified by this modified model. Furthermore, we apply competitive cocrystallization technique to separate flavonoid natural products (quercetin, hesperetin, and naringenin). In view of the characteristics of various natural products as well as their cocrystals/salts, numerous separation processes are developed, and the separation effects of these processes are analyzed in detail. The purity of the products obtained from separation process all reaches above 70%, strongly demonstrating the feasibility of using cocrystallization for the binary separation of flavonoids. This work not only refines the substitution model for predicting cocrystals/salts formation of natural products but also indicates the promising application prospects of cocrystallization in industrial separation of natural products.
研究领域:
有机化学
·
药学
·
分离工程
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产品关联
DOI
高影响因子
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
·
2024
·
IF 2.7
Yuqing Zhang,Yaping Li,Yuhan Zhai,Xing Zhao,Mingxing Lv,Shaoxuan Yu,Haifang Xiao,Yuanda Song
Inhibition of α-glucosidase activity is a promising method to prevent postprandial hyperglycemia. The inhibitory effect and interaction of chrysin and diosmetin on α-glucosidase were studied in this study. The results of inhibition kinetics showed that chrysin and diosmetin reversibly inhibited α-glucosidase activity with IC50 value of 26.445 ± 1.406 μmol L−1 and 18.380 ± 1.264 μmol L−1, respectively. Further research revealed that chrysin exhibited a mixed-type inhibitory pattern against α-glucosidase, while diosmetin was noncompetitive inhibitory with Ki value of (2.6 ± 0.04) ×10−4 mol L−1. Fluorescence spectroscopy showed that both chrysin and diosmetin could quench the intrinsic fluorescence of α-glucosidase, the maximum emission wavelength of tyrosine (Tyr) and tryptophan (Trp) were not moved by chrysin, but red shifted by diosmetin. UV-Vis, fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) measurements showed that the secondary structure and microenvironment of α-glucosidase were changed by chrysin and diosmetin. Further analysis of molecular docking showed that chrysin and diosmetin could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The results of molecular dynamics (MD) simulation showed that the stability of chrysin (or diosmetin)-α-glucosidase complex system was changed during binding process. In conclusion, chrysin and diosmetin are good α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma
研究领域:
生物化学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Li-Feng Li,Meng-Di Wang,Chen-Yang Zhang,Meng-Yao Jin,Hua-Lei Chen,Huan Luo,Tian-Yu Hou,Zhi-Jun Zhang,He Li
Advanced glycation end products (AGEs) generated from the Maillard reaction (MR) during food processing in the human physiological environment, have been proven to be significantly associated with various chronic metabolic diseases. In this study, 18 flavonoids were investigated to study their effects on AGEs formation during MR within a glucose-lysine-arginine model system. Five AGEs— N ε -carboxymethyl-lysine (CML), N ε -carboxyethyl-lysine (CEL), pyrraline, pentosidine, and argpyrimidine—were determined by high-performance liquid chromatography-mass spectrometry, with inhibitory rates ranging between 0 % and 71.35 %. Isorhamnetin and naringenin exhibited the strongest inhibitory effect on the formation of CML and CEL, respectively, whereas myricetin exhibited the strongest inhibitory effect on pyrraline, pentosidine, and argpyrimidine formation. In addition, each flavonoid was reacted with glyoxal (GO) and methylglyoxal (MGO) to investigate their trapping activities and adducts. The results showed that the 18 flavonoids could effectively clear GO and MGO, with clearance rates of 1.03 %–71.42 % and 0.93 %–69.37 % for GO and MGO, respectively. Six flavonoids—chrysin, naringenin, apigenin, luteolin, diosmetin, and kaempferol—could form adduct products with mono-/di-MGO, with flavonoid to mono-/di-MGO adduct ratios of approximately 6:1, 2:1, 8:1, 23:1, 10:1, and 3:1, respectively. The number and site of phenolic hydroxyl groups, as well as methoxy substitution on the B-ring in flavonoids, had little effect, but phenolic hydroxyl groups at the C-3 position in the C-ring impeded adduct formation. The flavonoids lowered the degradation of glucose itself, and decreased ammonia-induced degradation and Amadori rearrangement product oxidation due to their antioxidant activities, and they trapped the reactive 1,2-di‑carbonyl species via nucleophilic addition reaction to form AGEs.
研究领域:
食品科学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Small Methods
·
2024
·
IF 10.7
Yijia Kang,Zhilan Qian,Haishuang Yu,Jian Lu,Qing Zhao,Xue Qiao,Min Ye,Xiangshan Zhou,Menghao Cai
Previous data established 4′-deoxyflavone glycosides (4′-DFGs) as important pharmaceutical components in the roots of rare medical plants like Scutellaria baicalensis Georgi. Extracting these compounds from plants involves land occupation and is environmentally unfriendly. Therefore, a modular (“plug-and-play”) yeast-consortium platform is developed to synthesize diverse 4′-DFGs de novo. By codon-optimizing glycosyltransferase genes from different organisms for Pichia pastoris , six site-specific glycosylation chassis are generated to be capable of biosynthesizing 18 different 4′-DFGs. Cellular factories showed increased 4′-DFG production (up to 18.6-fold) due to strengthened synthesis of UDP-sugar precursors and blocked hydrolysis of endogenous glycosides. Co-culturing upstream flavone-synthesis-module cells with downstream glycoside-transformation-module cells alleviated the toxicity of 4′-deoxyflavones and enabled high-level de novo synthesis of 4′-DFGs. Baicalin is produced at the highest level (1290.0 mg L −1 ) in a bioreactor by controlling the consortium through carbon-source shifting. These results provide a valuable reference for biosynthesizing plant-derived 4′-DFGs and other glycosides with potential therapeutic applications.
研究领域:
生物技术
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药学
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合成生物学
·
植物代谢
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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）