JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2012
·
IF 2.905
Xiaohua Zhu,Qifang Jiao,Chuyi Zhang,Xiaoxi Zuo,Xin Xiao,Yong Liang,Junmin Nan
The graphene and 5-[ o -(4-Bromine amyloxy) phenyl]-10,15,20-triphenylporphrin ( o -BrPETPP) composite (GR- o -BrPETPP) film is prepared on the glassy carbon electrode (GCE) with graphene oxide (GO) modifier through a consecutive cyclic voltammetry process, and then its electrocatalytic oxidation to indirubin is investigated. The as-prepared GR- o -BrPETPP film exhibits wrinkling paper-like structure and lower electron transfer resistance. In comparison with the o -BrPETPP/GCE and GCE, the GR- o -BrPETPP film electrode prepared for five cycles indicates an excellent electrocatalytic oxidation activity toward indirubin with about 2.2 and 13.3 times higher current response, respectively. In addition, in the 0.1 mol L −1 acetate buffer solution (pH = 4.6), the film electrode displays a linear relationship between the oxidation current and the indirubin concentration in the range from 5.0 × 10 −7 mol L −1 to 2.4 × 10 −5 mol L −1 , and presents a detection limit of 1.0 × 10 −7 mol L −1 ( S / N = 3) by differential pulse voltammetry (DPV) with 220 s accumulation. Especially, this film electrode also shows a comparative sensitivity with high-performance liquid chromatography (HPLC) for the determination of the indirubin extractive of herbal medicines, showing its practical prospect in the electrochemical determination of indirubin.
研究领域:
分析化学
·
电化学
✓ 已验证
产品关联
DOI
高影响因子
ACS Omega
·
2021
·
IF 3.512
Huifang Yin,Hongping Chen,Meng Yan,Zhikun Li,Rongdi Yang,Yanjiao Li,Yanfang Wang,Jianyi Guan,Huili Mao,Yan Wang,Yuyang Zhang
Blue indigo dye, an important natural colorant, is used for textiles and food additives worldwide, while another red isomer, indirubin, is the major active ingredient of a traditional Chinese medicine named “Danggui Longhui Wan” for treating various diseases including granulocytic leukemia, cancer, and Alzheimer’s disease. In this work, we constructed a new and highly efficient indigoid production system by optimizing a novel terpenoid cyclase, XiaI, from the xiamycin biosynthetic pathway. Through introducing the flavin-reducing enzyme Fre, tryptophan-lysing and -importing enzymes TnaA and TnaB, and H2O2-degrading enzyme KatE and optimizing the fermentation parameters including temperature, the concentration of isopropyl-β-d-thiogalactopyranoside, and feeding of the l-tryptophan precursor, the final maximum productivity of indigoids by the recombinant strain Escherichia coli BL21(DE3) (XiaI-Fre-TnaAB-KatE) was apparently improved to 101.9 mg/L, an approximately 60-fold improvement to that of the starting strain E. coli BL21(DE3) (XiaI) (1.7 mg/L). In addition, when the fermentation system was enlarged to 1 L in the flask (feeding with 5 mM tryptophan and 10 mM 2-hydroxyindole), the indigoid productivity further increased to 276.7 mg/L at 48 h, including an indigo productivity of 26.0 mg/L and an indirubin productivity of 250.7 mg/L, which has been the highest productivity of indirubin so far. This work provided a basis for the commercial production of bio-indigo and the clinical drug indirubin in the future.
研究领域:
生物技术
·
生物工程
·
微生物学
·
制药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioresources and Bioprocessing
·
2022
·Vol. 9
·期 1
·1-16
·
IF 4.983
Sun Bing-Yao,Sui Hua-Lu,Liu Zi-Wei,Tao Xin-Yi,Gao Bei,Zhao Ming,Ma Yu-Shu,Zhao Jian,Liu Min,Wang Feng-Qing,Wei Dong-Zhi
Indirubin is a bisindole compound for the treatment of chronic myelocytic leukemia. Here, we presented a structure-guided method to improve the activity of a flavin-containing monooxygenase (bFMO) for the efficient production of indirubin in Escherichia coli. A flexible loop interlocked with the active pocket through a helix and the substrate tunnel rather than the active pocket in bFMO were identified to be two reconfigurable structures to improve its activity, resulting in K223R and N291T mutants with enhanced catalytic activity by 2.5- and 2.0-fold, respectively. A combined modification at the two regions (K223R/D317S) achieved a 6.6-fold improvement in catalytic efficiency (kcat/Km) due to enhancing π–π stacking interactions stabilization. Finally, an engineered E. coli strain was constructed by metabolic engineering, which could produce 860.7 mg/L (18 mg/L/h) indirubin, the highest yield ever reported. This work provides new insight into the redesign of FMOs to boost their activities and an efficient approach to produce indirubin.
研究领域:
生物化学
·
生物技术
·
酶工程
·
代谢途径优化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Ruodan Xu,Pengyu Wang,Can Cao,Mengru Cai,Xuyao Dai,Yilin Peng,Yaqi Yue,Yu Sun,Hongjie Gao,Ping Song,Ning Li
Local side effects, such as skin dryness and irritation, present significant challenges for topical therapies for psoriasis. There is an urgent need for innovative and safer topical treatments, especially for individuals with mild to moderate psoriasis. In this study, we developed a double-sided Janus-structured nanofibrous patch characterized by asymmetric wettability, with the inner hydrophilic layer topped with a hydrophobic outer polycaprolactone (PCL) layer. The hydrophobic PCL layer functions to facilitate directional hydration through controlled water transport, while the hydrophilic inner layer containing two anti-psoriatic compounds, indirubin and tryptanthrin, ensures optimal anti-psoriasis efficacy. By coaxial electrospinning, the core of the hydrophilic layer contains hyaluronic acid (HA), polyethylene oxide (PEO) and indirubin, while the shell is composed of PCL, PEO, and tryptanthrin. Investigations into the release of anti-psoriatic compounds indicated that both indirubin and tryptanthrin were liberated in bursts. In vitro assessments using psoriatic skin from mice demonstrated notable skin retention and permeation of both compounds within the first 30 min following topical application. Further biological analyses confirmed favorable in vitro biocompatibility, supporting the anticipated therapeutic outcomes, as assessed by severity index scoring and pathological evaluations in vivo . Additionally, an initial human test demonstrated that the efficacy of the double-sided Janus-structured patch was comparable to that of the first-line drug Calcipotriol Ointment during a 4-week topical treatment, with no adverse effects like erythema or pruritus. The unique Janus-structured design effectively combines asymmetric wettability with potent anti-psoriatic ingredients, offering a novel and comprehensive approach to topical therapies for psoriasis.
研究领域:
皮肤病学
·
药剂学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2015
·Vol. 9
·期 4
·1940-1946
·
IF 1.554
Ling Wang,Xianglu Li,Xinyu Liu,Kang Lu,Na Chen,Peipei Li,Xiao Lv,Xin Wang
The aim of the present study was to investigate the indirubin‑enhanced effects of arsenic disulfide (As2S2) on the proliferation and apoptosis of diffuse large B‑cell lymphoma (DLBCL) cells in order to identify an optimum combination therapy. The human DLBCL cells, LY1 and LY8, were treated with different concentrations of indirubin for 24, 48 and 72 h. Next, the cells were treated with 10 µM As2S2 or a combination of 10 µM As2S2 and 20 µM indirubin for 48 h. Cell proliferation inhibition was detected using cell counting kit‑8 and cell apoptosis was determined using flow cytometry. The expression levels of Bcl‑2, Bcl‑2‑associated X protein (Bax) and caspase‑3 were analyzed by quantitative polymerase chain reaction (qPCR) and western blotting. The DLBCL cell viability exhibited no significant changes at 24, 48 or 72 h with increasing indirubin concentration. In addition, the apoptotic rates of the LY1 and LY8 cells demonstrated no noticeable effects at 48 h with increasing indirubin concentration. Following treatment with the combination of indirubin and As2S2, the inhibitory and apoptotic rates of the cells were notably increased compared with those of the As2S2‑treated group. The qPCR results revealed that indirubin alone had no enhancing effect upon the Bax/Bcl‑2 mRNA expression ratio and caspase-3 mRNA expression. Western blot analysis revealed that indirubin alone had an enhancing effect upon the Bax/Bcl‑2 protein ratio and procaspase‑3 protein expression. In addition, the results demonstrated that the 21‑KDa Bax protein was proteolytically cleaved into an 18‑KDa Bax in the DLBCL cells treated with the combination of indirubin and As2S2. Indirubin alone did not inhibit proliferation or induce the apoptosis of the LY1 and LY8 cells. However, the combination of indirubin and As2S2 yielded enhancing effects. Therefore, the results of the present study demonstrated that with regard to antitumor activities, As2S2 served as the principal drug, whereas indirubin served as the adjuvant drug. The enhancing effect was due, in part, to the induction of the mitochondrial apoptotic pathway, which involves the cleavage of Bax.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Junyu Wang,Chaojie Yang,Zhixin Liang,Junping Sun,Mingyue Zhang,Shaofu Qiu,Xinying Du,Xi He,Xiaoying Pang,Xidong Ma,Mei Xie,Xinjie Han,Ru Fan,Enlu Zhou,Hairong Yu,Danyang She,Hongbin Song,Jianxin Wang
Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3′-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.
研究领域:
病毒学
·
药理学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Pengyu Wang,Junwei Gao,Shijie Guo,Hongmei Liu,Can Cao,Shihao Hong,Yu Sun,Chen Wang,Wei Xiao,Ping Song,Ning Li,Ruodan Xu
Indigo naturalis (IN) has been extensively used as a topical treatment for psoriasis. However, clinical applications of IN in ointment were hampered by its limited transdermal efficiency and dark stains. To address the aforementioned issues, nanopatches carrying IN were fabricated using poly(ε-caprolactone, PCL)/poly(ethylene oxide, PEO) and topically applied to psoriasiform skin. The ideal ratio of 5% PCL/PEO was established to be 80:20 (w/w), and 15% IN as payload was confirmed. Investigations on the three principal active components of IN release indicated that indirubin and tryptanthrin were released in bursts, while indigo was released in a limited and controlled manner. Further biological analyses confirmed a favorable biocompatibility of amphiphilic IN-PCL/PEO, which coincided with the intended therapeutic outcomes as measured by severity index scoring and pathological evaluations in vivo . The advantages of IN as nanopatches over ointment could be due to improved transdermal distribution of indirubin and tryptanthrin, resulting in effective management of epidermal hyperplasia and blood vessel remodeling. Meanwhile, due to the lower preservation of epidermal indigo, IN-PCL/PEO nanopatches caused no skin coloration. Similarly, during a 4-week topical treatment of IN-PCL/PEO nanopatches, the safety and anti-psoriatic benefits were obtained in an initial human test. The conversion of IN from topical cream to electrospun nanofibers opens up new avenues for bench-to-bedside translation of this herbal therapy and provides mechanistic insight into IN's roles in the management of psoriasis.
研究领域:
药学
·
纳米技术
·
皮肤科
·
草药医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-13
·
IF 5.228
Wu Xunxun,Chen Xiaofei,Jia Dan,Cao Yan,Gao Shouhong,Guo Zhiying,Zerbe Philipp,Chai Yifeng,Diao Yong,Zhang Lei
Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis , a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines.
研究领域:
药理学
·
肿瘤学
·
中医
·
色谱学
·
生物信息学
✓ 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）