BRITISH POULTRY SCIENCE
·
2025
·
IF 1.7
Y. S. Miao,Q. X. Han,K. X. Wang,X. D. Fan,Z. Zhang,L. Chen,D. Z. Zheng,S. Yue,L. Lei,L. Y. Liu,J. C. Li,G. J. Liu
1. This study evaluated the mechanism of action of indirubin in alleviating the structural damage induced by Mycoplasma gallisepticum (MG) in the lungs and trachea.2. A total of 250 one-day-old white leghorn chickens, specific-pathogen-free were divided into six treatment groups, including (A) indirubin high concentration treatment group (50 mg/kg; IHC); (B) indirubin medium concentration treatment group (25 mg/kg; IMC); (C) indirubin low concentration treatment group (12.5 mg/kg; ILC); (D) tylosin control group (0.5 g/l); (E) control group (CON) and (F) challenge model group (MG).3. Results from antioxidant activity analysis demonstrated that indirubin treatment significantly decreased the amount of MG-mediated oxidative stress in the lungs of chickens. Histopathological examination revealed abnormal morphological signs and cell damage in MG birds. This included lung lymphocytic infiltration, overlapping nuclear debris and inflammatory cell infiltration. In addition, ultrastructural examination revealed signs of apoptosis in the lungs. However, indirubin treatment partially relieved these abnormal morphological changes.4. The TUNEL analysis showed extensive apoptosis in the lungs of the model group compared to the control and positive drug control group. Apoptosis-related protein expression levels were significantly upregulated in the model group, which confirmed the phenomena of apoptosis induced by MG. The indirubin treatment significantly reduced apoptosis in the lungs and trachea compared to the model group. Meanwhile, the effect of MG challenge was reduced in the lungs by indirubin in a dose-dependent manner.5. These results showed that the inhibition of oxidative stress and apoptosis by indirubin contributed to its therapeutic effects against MG infection.
研究领域:
兽医学
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药理学
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微生物学
·
病理学
·
生物化学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Donghan Bai,Zihao Zhang,Jingyue Gao,Qiaochu Wang,Remy Macdonald,Ziwen Xu,Shumin Chen,Nanxi Huang,Lu Luo
Background: Leukemia is a malignant hematologic disease that poses a serious threat to human health. Realgar-Indigo Naturalis formula (RIF), a traditional Chinese medicine formula, have demonstrated anti-tumor activity, but its mechanisms of action remain unclear.Objective: This study aimed to establish a zebrafish HL-60 tumor transplantation model to investigate the anti-leukemic effects of RIF and explore its underlying mechanisms.Methods: The zebrafish HL-60 tumor transplantation model was established, with RIF as the intervention drug and all-trans retinoic acid (ATRA) as the control. Anti-tumor efficacy was assessed via pharmacodynamic analysis. Transcriptomic analysis further elucidated gene expression profiles, differentially expressed genes, and relevant biological pathways.Results: RIF significantly reduced tumor cell fluorescence intensity, demonstrating anti-tumor efficacy. Additionally, it improved HL-60-induced liver damage in zebrafish, as evidenced by a reduction in fatty vacuolar degeneration in liver tissue. Transcriptomic analysis revealed that ATRA mainly affected the FoxO signaling pathway, PI3K-Akt signaling pathway, apoptosis, and complement and coagulation cascades in leukemia treatment. RIF primarily influenced the ubiquitin-proteasome system, ferroptosis, and glutathione metabolism. The combination of ATRA and RIF also affected autophagosome and lysosome pathways, in addition to the aforementioned pathways.Conclusion: RIF exhibit significant anti-tumor effects through modulation of multiple pathways. This study provides a theoretical foundation for the potential clinical application of RIF in leukemia treatment.
研究领域:
肿瘤学
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药理学
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中医学
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发育生物学
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毒理学
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基因组学
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DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2023
·
IF 3.1
Hui Huang,Yabin Dai,Yuefen Zhang,Yongning Li,Huazhen Ye,Dan Guo,Qiaomei Lu,Xiaohua Cai
Analytical screening and validation systems based on a combination of cell membrane chromatography and two-dimensional chromatography-tandem mass spectrometry are incapable of providing prepared samples containing the active ingredients found in traditional Chinese medicine; therefore, these samples cannot be directly used in subsequent studies. In this study, a semi-preparative cell membrane chromatography column was developed using a hydrogel-modified carrier and human umbilical vein endothelial cells to optimize prepared conditions, such as hydrogel polymerization, cell fragmentation, and cell membrane volume. This increased the binding ratio of membrane protein and carrier to 15.79 mg/g. The column was systematically evaluated using multitarget tyrosine kinase inhibitors that displayed good specificity and reproducibility. Subsequently, using the column coupled with a semi-preparative high-performance liquid chromatography-offline-high-performance liquid chromatography-mass spectrometry system, 15 active ingredients were screened and purified from Indigo naturalis , and five main components were identified: l -lysine, oxyresveratrol, tryptanthrin, isorhamnetin, and indirubin. Furthermore, the pharmacological effects of the ingredients were confirmed using cell proliferation and apoptosis assays. Results revealed potent proliferation-inhibiting and apoptosis-promoting abilities on human chronic myelogenous leukemic cells and human promyelocytic leukemic cells ( p < 0.001). Overall, the system presented screening and purification functions that could be used to prepare I. naturalis samples acting on the epidermal growth factor receptor and vascular endothelial cell growth factor.
研究领域:
药理学
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分析化学
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中医药
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2024
·
IF 5.3
Changwei Zhang,Hua Yuan,Hong Shen,Chuan Li,Jianzhong Ye,Huaxing Zhang,Chengzhang Wang
The effect of acidolysis time, hydrochloric acid concentration, ozonization time and pH on the yield of indigo were investigated by single factor experiment using dried leaves of Baphicacanthus cusia (Nees) Bremek (DLB) as raw material. On this basis, the technological condition for preparing new indigo extract (NIE) by directional chemical conversion method was optimized by orthogonal experiment. Then, the physiochemical properties of NIE were analyzed by combustion assay, nitric acid assay, thin layer chromatography identification assay, moisture detection and water-soluble pigment observation assay. Moreover, UPLC-Q-TOF-MS/MS technology was utilized to compare chemical composition difference between the NIE and traditional indigo naturalis (TIN). Finally, NIE emulsion was prepared by ultrasound assisted high pressure homogenization method and its stability, antibacterial activity as well as antibacterial mechanism were evaluated. The experimental results showed that optimum process for preparing NIE were hydrochloric acid concentration of 2 %, ozonization time of 3 min, pH of 7 and acidolysis time of 1 h; Under this condition, the content and yield of indigo in the NIE were significantly improved, which could reach up to 42.6 ± 0.28 % and 2.26 ± 0.04 %, separately. NIE possessed similar physiochemical properties with TIN described in Chinese pharmacopoeia 2020, and had more diverse active ingredients than TIN. The prepared NIE emulsion demonstrated excellent stability, whether at dark or bright place, and no matter at low temperature (4 ℃) or room temperature (25 ℃), the particle size, PDI, pH and indigo content of which displayed little variation. In addition, the NIE emulsion owned good inhibitory activity against S. aureus , and its MIC and MBC values were 40 and 80 μg/mL, respectively. Moreover, NIE emulsion exhibited antibacterial effect by influencing cell membrane integrity, Ca 2+ -Mg 2+ -ATPase activity on the cell membrane and intracellular Ca 2+ levels of S. aureus. All of above results will lay the foundation for the green and sustainable utilization of Baphicacanthus cusia (Nees) Bremek.
研究领域:
药用植物学
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天然产物化学
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微生物学
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Yancen Li,Chengyu Wan,Fan Li,Guang Xin,Tao Wang,Qilong Zhou,Tingyu Wen,Shiyi Li,Xiaoting Chen,Wen Huang
Background: Isatidis Folium, a botanical drug widely used in traditional medicine, is known for its anti-inflammatory properties, including heat-clearing, detoxifying, and blood-cooling effects. Although its potential in sepsis treatment has been suggested, the bioactive metabolites and underlying mechanisms remain poorly understood.Methods: Network pharmacology and molecular docking were employed to identify the therapeutic effects and mechanisms of Indirubin, the major bioactive metabolite of Isatidis Folium, in sepsis treatment. In vivo, a cecal ligation and puncture (CLP)-induced mouse sepsis model was used to evaluate the protective effects of Indirubin through histopathological analysis, ELISA, and biochemical assays. In vitro, RAW264.7 cells were stimulated with LPS and treated with varying concentrations of Indirubin. The anti-inflammatory effects of Indirubin were assessed using ELISA, apoptosis assays, and Western blotting.Results: Network pharmacology analysis identified Indirubin as the major bioactive metabolite of Isatidis Folium and EGFR and SRC as its key molecular targets. Experimental validation demonstrated that Indirubin significantly improved survival rates, alleviated tissue injury, and suppressed inflammatory responses in sepsis models. Mechanistically, Indirubin inhibited LPS-induced activation of the EGFR/SRC/PI3K and NF-κB/MAPK pathways in macrophages, significantly reducing cell death and inflammation in RAW264.7 cells.Conclusion: Indirubin, the primary bioactive metabolite of Isatidis Folium, exerts protective effects against sepsis by targeting the EGFR/SRC/PI3K and NF-κB/MAPK signaling pathways in macrophages. These findings provide a mechanistic basis for the development of Indirubin as a multi-target therapeutic agent for sepsis treatment.
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2026
·
IF 3.9
Ma Ke-Yu,Hou Bao-Long,Fan An-Qi,Huang An-Li,Li Bo-Rui,Liang Yan-Ni,Wang Zheng
Indigo Naturalis (IN), utilized for thousands of years in China, is known for its effects in clearing heat, removing toxins, and alleviating diarrhea. Studies indicate that IN possesses anti-ulcerative colitis (UC) effects. However, the molecular processes that explain its therapeutic outcomes are still not fully understood. This study was to clarify the mechanism of IN against UC using both in vitro and vivo research methods. RAW264.7 cells were activated by lipopolysaccharide (LPS) (1 µg/mL) to found an inflammatory model; MTT and NO test was conducted to examine the influence of IN, indigo, indirubin, isatin, and MIX (indigo, indirubin, and isatin) on cell viability and anti-inflammatory activity. Inflammatory cytokines expression was evaluated with ELISA. Western Blotting was employed to analyze the MAPK, STAT3, and NF-κB pathways. UC model was generated by 2.5% DSS in C57BL/6 mice. Disease activity index (DAI) scoring , myeloperoxidase (MPO), and H&E staining are all for mice status. We demonstrated that IN, indirubin, and isatin can all regulate the expression of inflammatory cytokines. NF-κB, STAT3, and MAPK pathways was closely associated with IN, whereas indirubin acted to block the activation of both the NF-κB and STAT3 pathways. Contrastingly, the isatin mechanism of action was tightly connected with the regulation of the NF-κB and MAPK pathways. Additionally, MIX inhibited the activation of STAT3 pathway while suppressing the level of p-P38 expression in the MAPK pathway. MIX can enhance multiple indicators and conditions in UC mice. The active ingredients in IN (indigo, indirubin, and isatin, MIX) can significantly improve the condition of UC mice. MIX exerts anti-inflammatory effects by inhibiting the activation of the STAT3 pathway and expression of p-P38 in the MAPK pathway.
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产品关联
DOI
PubMed
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
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生物工程
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微生物学
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制药
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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
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肿瘤学
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中医
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色谱学
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生物信息学
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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
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药理学
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细胞生物学
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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
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生物技术
·
酶工程
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代谢途径优化
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2023
·
IF 4.8
Mingyi Yao,Jian Liu,Narengaowa,Yonggu Li,Feng Zhao
Accurate detection of natural dyes in archaeological textiles is challenging due to limited sample availability. In situ detection of fibers by surface-enhanced Raman scattering (SERS) can overcome this challenge. In this study, we present two methods for the preparation of SERS substrates based on the laser photoreduction reaction and the galvanic displacement reaction, respectively. Our results show that the substrates prepared by these methods, including 450 nm-AgNPs, Cu-based Ag, and Zn-based Ag, offer several advantages such as rapid preparation, easy handling, low cost, high sensitivity and excellent reproducibility. Using these substrates, we successfully detected anthraquinones (alizarin, purpurin), indigoids (indigotin, indirubin), and protoberberine-type dyes in archaeological textiles from the Wei and Jin Dynasties. Notably, we were able to detect both indigo and protoberberine-type dyes in one archaeological fiber. The minimally invasive, in situ analytical approach developed provides a valuable tool for analytical applications where sampling is limited to microscopic amounts.
研究领域:
考古学
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分析化学
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材料科学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）