Microbial Cell Factories
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2023
·Vol. 22
·期 1
·1-11
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IF 6.4
Lin Yu,Chen Wen-wen,Ding Bo,Guo Man,Liang Meng,Pang Hao,Wei Yu-tuo,Huang Ri-bo,Du Li-qin
Background Icaritin is an aglycone of flavonoid glycosides from Herba Epimedii. It has good performance in the treatment of hepatocellular carcinoma in clinical trials. However, the natural icaritin content of Herba Epimedii is very low. At present, the icaritin is mainly prepared from flavonoid glycosides by α-L-rhamnosidases and β-glucosidases in two-step catalysis process. However, one-pot icaritin production required reported enzymes to be immobilized or bifunctional enzymes to hydrolyze substrate with long reaction time, which caused complicated operations and high costs. To improve the production efficiency and reduce costs, we explored α-L-rhamnosidase SPRHA2 and β-glucosidase PBGL to directly hydrolyze icariin to icaritin in one-pot, and developed the whole-cell catalytic method for efficient icaritin production.Results The SPRHA2 and PBGL were expressed in Escherichia coli, respectively. One-pot production of icaritin was achieved by co-catalysis of SPRHA2 and PBGL. Moreover, whole-cell catalysis was developed for icariin hydrolysis. The mixture of SPRHA2 cells and PBGL cells transformed 200 g/L icariin into 103.69 g/L icaritin (yield 95.23%) in 4 h in whole-cell catalysis under the optimized reaction conditions. In order to further increase the production efficiency and simplify operations, we also constructed recombinant E. coli strains that co-expressed SPRHA2 and PBGL. Crude icariin extracts were also efficiently hydrolyzed by the whole-cell catalytic system.Conclusion sCompared to previous reports on icaritin production, in this study, whole-cell catalysis showed higher production efficiency of icaritin. This study provides promising approach for industrial production of icaritin in the future.
研究领域:
生物技术
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药学
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生物化学
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DOI
PubMed
高影响因子
Phytochemistry Letters
·
2023
·
IF 1.7
Yu-Chen Chen,Qiong Zheng,Hui Lu,Yi-Xin Zhuang,Ting-Ting Gong,Lie-Feng Ma,Zha-Jun Zhan
A new flavonoid glycoside bearing an unusual furan ring, epimedokoreanin F ( 1 ), was isolated from Epimedium brevicornu , along with 17 known flavonoids ( 2−18 ). The structures of these flavonoids were identified based on interpretation of spectroscopic data and comparison with literature data. Biologically, compounds 1−4 exhibited significant neuroprotective effects on the model of RSL3-induced ferroptosis in HT22 cells. Among them, compound 1 displayed the best activity with EC 50 values of 0.95 μ M, and can be used as lead compound for the development of neuroprotective agent to treat neurological diseases .
研究领域:
药理学
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神经科学
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生物化学
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植物化学
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产品关联
DOI
高影响因子
Metabolites
·
2023
·Vol. 13
·期 2
·294
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IF 4.1
Linlin Yang,Fei Zhang,Yueci Yan,Xupeng Gu,Shengwei Zhou,Xiuhong Su,Baoyu Ji,Hua Zhong,Chengming Dong
The harvesting period is a critical period for the accumulation of flavonoids in the leaves of the important medicinal plantEpimedium sagittatum. In this study, we conducted an experiment onE. sagittatumleaves sprayed with mineral elements with the aim of improving the quality of the herbal leafage during the harvesting period. We elucidated the changes in flavonoids (icariin, epimedin A, epimedin B, and epimedin C) inE. sagittatumleaves. The sum of main flavonoids content reached a maximum (11.74%) at 20 days after the high-concentration Fe2+(2500 mg·L−1) treatment. We analyzed the FT-IR spectra characteristics ofE. sagittatumleaf samples using the FT-IR technique, and constructed an OPLS-DA model and identified characteristic peaks to achieve differentiated identification ofE. sagittatum. Further, widely untargeted metabolomic analysis identified different classes of metabolites. As the most important characteristic flavonoids, the relative contents of icariin, icaritin, icariside I, and icariside II were found to be up-regulated by high-Fe2+treatment. Our experimental results demonstrate that high-concentration Fe2+treatment is an effective measure to increase the flavonoids content inE. sagittatumleaves during the harvesting period, which can provide a scientific basis for the improvement ofE. sagittatumleaf cultivation agronomic measures.Keywords:Epimedium sagittatum;flavonoids;icariin;FT-IR;metabolomic
研究领域:
生药学
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植物生理学
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分析化学
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代谢组学
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DOI
PubMed
高影响因子
Chemistry Africa-A Journal of the Tunisian Chemical Society
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2025
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IF 2.2
Chen Wang,Zhang Fen,Xu Jianghe,Lai Feifan
Purpose To immobilize snailase on SBA-15 to enhance the efficient conversion of Epimedium wushanense extracts for the preparation of rhamnosyl icariside II. Methods The snailase was covalently coupled to amino and aldehyde modified SBA-15, and the immobilization conditions were optimized. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), N 2 adsorption-desorption analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the physicochemical properties of immobilized snailase. The optimal enzymatic hydrolysis conditions, enzymatic kinetic parameters, storage stability and reusability of the immobilized snailase were investigated. Results The optimal immobilization conditions were pH 5.0, temperature 30℃, immobilization time 3 h and snailase concentration 10 mg⋅mL − 1 . The immobilized snailase showed a retained activity of 235.8 µmol⋅(h⋅g) −1 and a high enzyme loading capacity of 249.6 mg⋅g − 1 support. The optimum hydrolysis conditions for immobilized snailase were pH 5.5, temperature 50℃, substrate concentration 3.0 mg⋅mL − 1 , and reaction time 6 h. The V max and K m of the immobilized snailase were 3.92 µg⋅min − 1 and 1.18 mmol⋅L − 1 , respectively. Conclusion The immobilized snailase has a high enzyme loading capacity, strong conversion capability, better storage stability and good reusability, making it suitable for the efficient conversion of Epimedium wushanense extracts to produce rhamnosyl icariside II.
研究领域:
酶学
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生物催化
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植物化学
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纳米技术
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生物技术
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2020
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IF 3.263
Yanzheng Xie,Lei Xie,Ailan Chen,Shengnan Wu,Yuxiao Mo,Xiaoqiang Guo,Changchun Zeng,Xinan Huang,Jinyang He
AIDS , a serious fatal disease caused by the human immunodeficiency virus (HIV), is an epidemic disease for which no effective vaccine has been established. The current therapeutic interventions for AIDS have limited efficacy because they are unable to clear HIV infections and the continuous occurrence of resistant HIV strains. Therefore, the exploitation of new drugs to prevent the spread of AIDS remains a high priority. In this study, the effects of icariin and its metabolite anhydroicaritin on SIV/HIV replication were investigated. In CEM × 174 cells and PBMC cells, both icariin and anhydroicaritin can significantly inhibit HIV-1 or SIVmac251 replication. Furthermore, molecular docking studies revealed that icariin and anhydroicaritin can act on both HIV reverse transcriptase and protease but could not bind to integrase . Reverse transcriptase and protease inhibition biological assays showed that both icariin and anhydroicaritin could significantly inhibit only HIV reverse transcriptase. In summary, the two compounds can significantly inhibit HIV/SIV in vitro and their targets may be mainly involved with HIV reverse transcriptase.
研究领域:
病毒学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
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2019
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IF 4.462
Yongqiang Zheng,Lingli Lu,Zhengli Yan,Sufang Jiang,Shanyi Yang,Yingzi Zhang,Kangwei Xu,Chunlian He,Xiaojun Tao,Qiufang Zhang
Icariin (ICA), a major active ingredient from Chinese medicine, has unique pharmacological effects on ischaemic heart disease. However, its hydrophobic property limits its administration and leads to poor efficacy. This work aimed to change its hydrophobic property and improve the treatment efficacy. We designed a new nano-drug to increase the ICA delivery. ICA was modified with hydrophilic polyethylene glycol monomethyl ether (mPEG) by a succinic anhydride linker to form a polyethylene glycol-icariin (mPEG-ICA) polymer. The structure of this polymer was identified by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The content of ICA in the polymer was 32% as detected by ultraviolet spectrophotometry. mPEG-ICA nanoparticles, of 143.3 nm, were prepared by the dialysis method, and zeta potential was 0.439 mV by dynamic light scattering. The nanoparticles had a spherical shape on transmission electron microscopy. In media with pH 7.4 and 6.8, ICA release from mPEG-ICA nanoparticles after 72 h was about 0.78% and 64.05%, respectively, so the ICA release depended on the release media pH. On MTT and lactate dehydrogenase activity assay, mPEG-ICA nanoparticles could reduce cell damage induced by oxgen-glucose deprivation. Hoechst 33258 staining and TUNEL and AnnexinV-FITC/PI double staining showed that ICA nanoparticles could increase the activity of H9c2 cardiomyocytes under oxgen-glucose deprivation conditions by decreasing apoptosis. ICA modified by hydrophilic mPEG could improve its efficacy.
研究领域:
药理学
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纳米医学
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心脏病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Jingjing Zhang,Jing Huang,Yufan Yang,Daxin Zhao,Cong Wang,Peng Zhong,Jianhua Jia,Weifan Dang,Qiwei Lu,Chengyu Zhang,Xiaohui Yan
Icaritin (ICT), a compound with diverse biological activities derived from Epimedium folium, is typically present in low concentrations in EFs. However, the abundant glycosyl-modified ICT compounds facilitate its transformation into ICT. Current biocatalytic production faces challenges, including low conversion rates and limited enzyme activity. This study developed a one-pot enzymatic cascade strategy for directly biotransform crude extracts of Epimedium folium (EEF) to produce ICT. The feasibility of catalyzing different ICT-related compounds in EEF was validated through molecular docking and substrate reactions. The selected glycosidase exhibited simultaneous activities as a glucosidase, xylosidase, and α-1,6-rhamnosidase, with the rhamnosidase showing outer-rhamnosidic activity and weak glucosidase activity. By using EFs as the substrate and employing whole-cells ( Escherichia coli ) containing LacS and BtRha proteins for synergistic catalysis, icariin can be efficiently synthesized within 6 h, achieving a conversion rate of 100 %. The enzymatic cascade for ICT production from crude extracts was elucidated by analyzing catalytic intermediates via HPLC. Compared to strategies using single or traditional multi-enzyme applications, this method shows advantages of ease to operation, high efficiency, and large production yield performance. This method has the potential to become an eco-friendly catalytic strategy for the large-scale production of icaritin.
研究领域:
生物技术
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生物化学
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生药学
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酶学
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DOI
PubMed
高影响因子
MOLECULES
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2024
·Vol. 29
·期 22
·5280
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IF 4.2
Xiaoling Zhang,Yitong Wang,Tiantian Zhang,Ziqiao Yuan,Yongjun Wei
Epimedium Folium(EF) is a traditional Chinese herbal medicine, and its primary bioactive ingredients, such as icariin, are flavonoid glycosides. A rare EF flavonoid, baohuoside I, exhibits superior bioactivities and enhanced bioavailability compared to its metabolic precursor icariin. The biotransformation of icariin to baohuoside I can be effectively and specifically achieved by β-glucosidases. In this study, 33 candidate full-length β-glucosidase genes were screened from a previously built carbohydrate active enzyme (CAZyme) gene dataset derived from cow fecal microbiota. Thirteen of them exhibited β-glucosidase activity, with DCF-bgl-26 and DCF-bgl-27 showing relatively high expression levels and β-glucosidase activity. The maximum β-glucosidase activity of DCF-bgl-26 and DCF-bgl-27 was achieved at 45 °C and pH 6.0, with DCF-bgl-26 demonstrating better thermostability and pH tolerance compared to DCF-bgl-27. The activities of DCF-bgl-26 and DCF-bgl-27 were 123.2 U/mg protein and 157.9 U/mg protein, respectively, both of which are higher than those of many bacterial β-glucosidases. Structure analysis suggested that both β-glucosidases possess canonical (β/α)8-TIM barrel fold structure of GH1 family β-glucosidases. Thin-layer chromatography results showed that both enzymes could efficiently convert icariin to baohuoside I in 30 min, indicating they have potential application in the production of high value rare baohuoside I.
研究领域:
生物化学
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生物技术
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药理学
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微生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Hong Chen,Yang Lili,Zhang Yifan,Li Yiming,Wu Huali
Epimedium brevicornum Maxim. (Epimedii Folium) is a traditional medicine widely utilized in China for sexual dysfunction and osteoporosis treatment. Recently, studies have reported that Epimedium flavonoid icariin displayed hair growth and melanogenic ability by targeting tyrosinase activity. Nevertheless, icariin hydrolysate icariside II and icaritin cause depigmentation due to their tyrosinase inhibition. These pigment functional discrepancies from Epimedium constituents arouse our great interest. Then, this study focused on the pigmentation effects of Epimedii Folium extract (EFE) on melanin synthesis and melanosome biogenesis/transfer, and further identified the bioactive constituents. First, in in vitro systemic studies, we discovered that the potent melanogenic and repigmented effects of EFE were dependent on concentration and amount of time in multi-melanocytes, normal human skin tissue, and vitiligo perilesional areas. In vivo, EFE exhibited repigmented effect on two kinds of depigmented models of N-phenylthiourea-induced zebrafish and hydroquinone-induced mice. Mechanistically, EFE strongly promoted tyrosinase activity and upregulated the protein expression of tyrosinase families which finally contribute to melanin biosynthesis by activating the MAPK/ERK1/2 signal pathway. In addition, EFE effectively increased melanosome number, accelerated melanosome maturity and cytoplasmic transport through the growth/extension of melanocyte dendrites, and induced melanosome transfer from melanocyte to keratinocyte for pigmentation. The six main flavonoid ingredients were identified among EFE. Compared to others, epimedin B (EB) was confirmed as a high-content, low-toxicity, and effective melanogenic compound in EFE. Taking all these together, this study systematically demonstrates the potential pigmentation effect of Epimedium brevicornum Maxim., and clarifies its related molecular mechanisms and melanogenesis basis. These results give additional insight into Epimedium herb pharmacology and may provide a novel therapy basis for hypopigmentation disorders.
研究领域:
药理学
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皮肤科
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中医药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2025
·Vol. 20
·期 1
·1-12
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IF 2.8
He Zhenhong,Zeng Shengqiang,Qin Bo,Liu Gang,Liu Huan,Bao Dingsu
ObjectiveTendon injury is a common and frequent disease in the field of sports medicine, and tendon repair after injury is a common clinical difficulty. Repair strategy based on tendon stem cells (TDSCs) therapy is considered a promising therapeutic option for the treatment of tendon injuries. Icariin (ICA) has been shown to be an effective herbal monomer for the treatment of tendon-bone healing and may be effective in the repair of tendon injuries.Methods In vitro, TDSCs isolated from C57 mice were treated with ICA (0.01–100 µM) to assess proliferation (CCK-8 assay) and tendonogenic differentiation (qRT-PCR). In vivo, 42 C57 mice with surgically induced patellar tendon defects were randomized into three groups (n = 14/group): (1) 20 mg/kg ICA, (2) 40 mg/kg ICA, and (3) control group (DMSO), administered intraperitoneally for 14 days. Half of each group (n = 7) underwent histopathological (hematoxylin-eosin staining, Masson staining) and molecular (qRT-PCR) analyses at 2 and 4 weeks post-surgery.Results In vitro, after 7 days of ICA intervention in TDSC, the expression of Mohawk (MKX), Scleraxis (SCX), fibromodulin (FMOD), and Tenomodulin (TNC) were higher in the ICA group than in the control group. In vivo, the expression of MKX, SCX, FMOD, and TNC was higher in the 20 mg/kg ICA group and 40 mg/kg ICA group than in the control group at 2 and 4 weeks after surgery. Histological evaluation revealed superior tendon repair in both ICA-treated groups compared to controls at both 2 and 4 weeks postoperative intervals. The 20 mg/kg ICA group demonstrated a significant enhancement in tissue continuity and collagen fiber organization, exhibiting greater defect filling, fewer interstitial gaps, and reduced vascular infiltration. In contrast, control specimens exhibited disorganized collagen architecture with prominent interstitial gaps. The 40 mg/kg ICA group showed intermediate repair outcomes between the 20 mg/kg ICA and control groups.Conclusion ICA can improve tendon injury repair by enhancing tendonogenic differentiation of TDSC.
研究领域:
运动医学
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
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IF 4.539
Lu Zhao,Jie Liu,Yunfeng Bai,Feng Feng,Xiaoming Yang
Herein, an innovative method to synthesize carbon dots (CDs) has been successfully established, and these CDs emitted the yellow fluorescence while epimedium served as the carbon source. To be specific, the CDs prepared here were equipped with the functional groups of -COOH, -NH 2 , -OH, C C and C O, providing the possibility of functioning as the fluorescent sensor . Importantly, introducing dopamine leaded to their fluorescence quenching of the as-prepared CDs, which was due to the electrostatic interaction between CDs and DA. Meanwhile, the proposed CDs achieved detecting DA with the linear range of 1.0 × 10 −7 to 1.0 × 10 −3 M at a detection limit of 8.7 × 10 −8 M. Moreover, the further addition of H 2 O 2 gradually resulted in the fluorescence recovering through destroying the electrostatic interaction as the concentration of H 2 O 2 varied from 10 −6 to 10 −2 M with the detection limit of 7.2 × 10 −7 M. Thereby, the CDs described here exhibited the potentiality of broadening the ways for assaying DA and H 2 O 2 .
研究领域:
材料科学
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生物化学
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分析化学
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产品关联
DOI
高影响因子
ULTRASONICS SONOCHEMISTRY
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2022
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IF 9.336
Jinping Wang,Hong Zhu,Yueming Jiang,Jianbo Xiao,Bao Yang,Lingrong Wen
Ultrasound is effective to fabricate nanocomplex. Soymilk is a natural nanocarrier with good compatibility. However, information about soymilk-nutraceuticals nanocomplex is limited. In this work, soymilk was used to encapsulate icariin, a well known nutraceutical with poor bioavailability. The effect of ultrasound on the quality of icariin-soymilk nanocomplexes (ISNCs) was investigated. Ultrasound could reduce the particle size, improve the surface hydrophobicity and change the microstructure of soymilk. With increasing ultrasound treatment time, an increased surface hydrophobicity was observed. The highest encapsulation efficiency (89.67 %) and loading capacity (28.92 µg/mg) were found for USI-20, whereas the smallest particle size (132.47 nm) was observed for USI-120. USI-60 showed the lowest ζ-potential (-31.33 mV) and the highest bioaccessibility (76.08 %). Ultrasound could enhance the storage stability of ISNCs. The data of NMR and fluorescence indicated that ISNCs were mainly stabilized by hydrophobic interaction.
研究领域:
食品科学
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药剂学
✓ 已验证
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）