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Article: Zhuang-Gu-Fang intervenes vasculogenic and osteogenic coupling in GK rats through Notch1/Noggin/VEGF pathway.

Jin, Xinyan / Sun, Yuyu / Bai, Rui / Shi, Jun / Zhai, Linna / Jiang, Yunxia / Jiang, Mengchun / He, Jiali / Li, Junyu / Wang, Ting / Li, Shuanglei / Chen, Wenhui

Heliyon

2024 Volume 10, Issue 6, Page(s) e28014

Abstract: Background: Zhuang-Gu-Fang (ZGF) has been proved to treat osteoporosis in ovariectomized rats ...

Abstract	Background: Zhuang-Gu-Fang (ZGF) has been proved to treat osteoporosis in ovariectomized rats by increasing osteogenic related factors Leptin, Ghrelin and Peptide YY(PYY). However, the mechanism of ZGF in the treatment of diabetic osteoporosis (DOP) remains unclear. The aim of this study was to explore the therapeutic effect of ZGF on DOP and its potential molecular mechanism. Methods: Using GK rats as models, the pharmacodynamic effects of ZGF on bone loss were evaluated by hematoxylin-eosin (H&E) staining and micro-computed.tomography (micro-CT). The expression levels of CD31 and endomucin (Emcn) were detected by immunofluorescence to assess the role of ZGF in angiogenic osteogenic coupling. Finally, real-time quantitative PCR (RT-PCR) and Western Blot (WB)were used to detect the expression levels of osteogenic and angiogenesis-related genes and proteins Notch1, Noggin and vascular endothelial growth factor (VEGF). Results: Administration of ZGF demonstrated a significant mitigation of bone loss attributable to elevated glucose levels. H&E staining and micro-CT showed that ZGF notably improved the integrity of the trabecular and cortical bone microarchitecture. Moreover, ZGF was found to augment the density of type H vessels within the bone tissue, alongside elevating the expression levels of Osterix, a transcription factor pivotal for bone formation. Furthermore, our findings suggest that ZGF facilitates the activation of the Notch1/Noggin/VEGF pathway, indicating a potential mechanism through which ZGF exerts its osteoprotective effects. Conclusion: Our results suggest that ZGF potentially facilitates the formation of type H vessels through the Notch1/Noggin/VEGF pathway. This action not only enhances angiogenic-osteogenic coupling but also contributes to the improvement of bone structure and density. Consequently, ZGF emerges as a promising therapeutic agent for the prevention and management of DOP, offering a novel approach by leveraging angiogenesis-dependent osteogenesis.
Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e28014
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Article ; Online: Mechanisms of Dangua Fang in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.

Xianpei, Heng / Zhita, Wang / Liang, L I / Liuqing, Yang / Suping, Huang / Lang, Jin / Weidong, H E

Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan

2024 Volume 44, Issue 2, Page(s) 334–344

Abstract: Objective: To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method ...

Abstract	Objective: To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics. Methods: Sprague-Dawley rats with normal glucose levels were randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose [PBG; using the oral glucose tolerance test (OGTT)], hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting. Results: DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies. Conclusion: DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.
MeSH term(s)	Rats ; Animals ; Rats, Sprague-Dawley ; Blood Glucose/metabolism ; Glycated Hemoglobin ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Liver ; Lipid Metabolism ; Glycolipids/metabolism ; Glycolipids/pharmacology ; Triglycerides/metabolism ; Peptides/metabolism ; Peptides/pharmacology ; Diet, High-Fat
Chemical Substances	Blood Glucose ; Glycated Hemoglobin ; Glycolipids ; Triglycerides ; Peptides
Language	English
Publishing date	2024-03-19
Publishing country	China
Document type	Journal Article
ZDB-ID	603186-9
ISSN	2589-451X ; 0254-6272 ; 0255-2922
ISSN (online)	2589-451X ; 0254-6272
ISSN	0255-2922
DOI	10.19852/j.cnki.jtcm.20230908.001
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Article ; Online: Chang-Kang-Fang alleviates diarrhea predominant irritable bowel syndrome (IBS-D) through inhibiting TLR4/NF-κB/NLRP3 pathway.

Zhang, Sihao / Tian, Danmei / Xia, Zixuan / Yang, Fengge / Chen, Yanhui / Yao, Zhihong / He, Yi / Miao, Xinglong / Zhou, Guirong / Yao, Xinsheng / Tang, Jinshan

Journal of ethnopharmacology

2024 Volume 330, Page(s) 118236

Abstract: Ethnopharmacological relevance: Chang-Kang-Fang (CKF), originated ...

Abstract	Ethnopharmacological relevance: Chang-Kang-Fang (CKF), originated from traditional Chinese medicine (TCM) formulas, has been utilized to treat diarrhea predominant irritable bowel syndrome (IBS-D) based on clinical experience. However, the underlying mechanism of CKF for treating IBS-D remains unclear and need further clarification. Aim of the study: The objective of this present investigation was to validate the efficacy of CKF on IBS-D model rats and to uncover its potential mechanism for the treatment of IBS-D. Materials and methods: We first established the IBS-D rat model through neonatal maternal separation (NMS) in combination with restraint stress (RS) and the administration of senna decoction via gavage. To confirm the therapeutic effect of CKF on treating IBS-D, abdominal withdrawal reflex (AWR) scores, the quantity of fecal pellets, and the fecal water content (FWC) were measured to evaluate the influence of CKF on visceral hypersensitivity and the severity of diarrhea symptom after the intragastric administration of CKF for 14 days. Subsequently, enzyme linked immunosorbent assay (ELISA) was applied to assess the effect of CKF on neuropeptides substance P (SP) and 5-hydroxytryptamine (5-HT), as well as inflammatory cytokines in serum and in intestinal tissues. Further, colonic pathological changes, the amount of colonic mast cells, and the expression level of occludin in rat colon tissues, were investigated by hematoxylin-eosin (HE) staining, toluidine blue staining, and immunohistochemistry, respectively. To explore the underlying mechanisms, alterations in colonic RNA transcriptomics for the normal, model, and CKF treatment groups were assessed using RNA sequencing (RNA-Seq). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunofluorescence (IF) assays were applied to validate the effect of CKF on predicted pathways in vivo and in vitro. In addition, to elucidate the potential active compounds in CKF, 11 representative components found in CKF were selected, and their anti-inflammation potentials were evaluated using LPS-treated RAW264.7 cell models. Results: CKF treatment significantly reduced the number of fecal pellets, attenuated visceral hypersensitivity, and decreased 5-HT and SP concentrations in serum and colon tissues, along with a reduction in colonic mast cell counts, correlating with improved symptoms in IBS-D rats. Meanwhile, CKF treatment reduced the colonic inflammatory cell infiltration, lowered the levels of IL-6, TNF-α, and IL-1β in serum and colon tissues, and increased the occludin protein expression in colon tissues to improve inflammatory response and colonic barrier function. RNA-Seq, in conjugation with our previous network pharmacology analysis, indicated that CKF might mitigate the symptoms of IBS-D rats by inhibiting the Toll like receptor 4/Nuclear factor kappa-B/NLR family pyrin domain-containing protein 3 (TLR4/NF-κB/NLRP3) pathway, which was confirmed by WB, IF, and qRT-PCR experiments in vivo and in vitro. Furthermore, coptisine, berberine, hyperoside, epicatechin, and gallic acid present in CKF emerged as potential active components for treating IBS-D, as they demonstrated in vitro anti-inflammatory effects. Conclusion: Our findings demonstrate that CKF effectively improves the symptoms of IBS-D rats, potentially through the inhibition of the TLR4/NF-κB/NLRP3 pathway. Moreover, this study unveils the potential bioactive components in CKF that could be applied in the treatment of IBS-D.
Language	English
Publishing date	2024-04-24
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2024.118236
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Article: Possible mechanisms associated with immune escape and apoptosis on anti-hepatocellular carcinoma effect of Mu Ji Fang granules.

Zhang, Yi-Bing / Bao, Yong-Rui / Wang, Shuai / Li, Tian-Jiao / Tai, He / Leng, Jia-Peng / Yang, Xin-Xin / Wang, Bo-Cai / Meng, Xian-Sheng

World journal of gastrointestinal oncology

2023 Volume 15, Issue 3, Page(s) 504–522

Abstract: ... with high mortality rates worldwide. The main ingredients in Mu Ji Fang Granules (MJF) are alkaloids ...

Abstract	Background: Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers with high mortality rates worldwide. The main ingredients in Mu Ji Fang Granules (MJF) are alkaloids, flavonoids, and polysaccharides. MJF has been used in the clinical treatment of hepatitis, cirrhosis and HCC for more than 30 years. Few previous studies have focused on the mechanism of MJF on tumor immu-nology in the treatment of HCC. Aim: To explore the mechanism of action of MJF on tumor immunology in the treatment of HCC. Methods: The absorbable ingredients of MJF were identified using Molecule Network related to High Performance Liquid Chromatography-Electron Spray Ionization-Time of Flight- Mass Spectrometry, and hub potential anti-HCC targets were screened using network pharmacology and pathway enrichment analysis. Forty male mice were randomly divided into the Blank, Model, and MJF groups (1.8, 5.4, and 10.8 g/kg/d) following 7 d of oral administration. Average body weight gain, spleen and thymus indices were calculated, tumor tissues were stained with hematoxylin and eosin, and Interferon gamma (IFN-γ), Tumor necrosis factor α (TNF-α), Interleukin-2, aspartate aminotransferase, alanine aminotransferase, alpha-fetoprotein (AFP), Fas, and FasL were measured by Enzyme-linked Immunosorbent Assay. Relevant mRNA expression of Results: It was shown that MJF improved body weight gain and tumor inhibition rate in H22 tumor-bearing mice, protected immune organs and liver function, reduced the HCC indicator AFP, affected immunity and apoptosis, and up-regulated the TGF-β1/SMAD signaling pathway, by increasing the relative expression of TGF-β1, SMAD2, p-SMAD2 and SMAD4 and decreasing SMAD7, reducing immune factors TNF-α and IFN-γ, decreasing apoptosis cytokines Fas, FasL and Conclusion: MJF inhibits HCC by activating the TGF-β1/SMAD signaling pathway, and affecting immune and apoptotic cytokines, which may be due to MJF adjusting immune escape and apoptosis.
Language	English
Publishing date	2023-03-29
Publishing country	China
Document type	Journal Article
ZDB-ID	2573696-6
ISSN	1948-5204
ISSN	1948-5204
DOI	10.4251/wjgo.v15.i3.504
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Article ; Online: Tong-Xie-Yao-Fang strengthens intestinal feedback control of bile acid synthesis to ameliorate irritable bowel syndrome by enhancing bile salt hydrolase-expressing microbiota.

Jia, Fengjing / Du, Liqing / He, Jinchao / Zhang, Zhaozhou / Hou, Xinxin / Dong, Qinjun / Bian, Zhaoxiang / Zhao, Ling

Journal of ethnopharmacology

2024 , Page(s) 118256

Abstract: Ethnopharmacological relevance: A herbal formula Tong-Xie-Yao-Fang (TXYF) is traditionally used ...

Abstract	Ethnopharmacological relevance: A herbal formula Tong-Xie-Yao-Fang (TXYF) is traditionally used to treat irritable bowel syndrome (IBS), modern pharmacological evidence supports that the formula efficacy is associated with altered gut microbiota. Yet, the mechanistic role of gut microbiota in the therapy of TXYF remains unclear. We previously clarified that gut microbiota-dysregulated bile acid (BA) metabolism contribute to the pathogenesis of IBS, deriving a hypothesis that microbiota-BA metabolic axis might be a potential target of TXYF. Aim of the study: We aim to investigate a new gut microbiota-mediated mechanism underlying anti-IBS efficacy of TXYF. Materials and methods: We established an IBS rat model with a combination of stressors, compared the herbal efficacy in models undergone gut bacterial manipulations, also examined BA metabolism-related microbiota, metabolites, genes and proteins by 16S rRNA gene sequencing, targeted metabolomics, qPCR and multiplex immunofluorescence staining. Results: We observed that TXYF attenuated visceral hyperalgesia and diarrhea in IBS rats but not in those underwent gut bacteria depletion. Transferring gut microbiota from TXYF-treated donors also decreased visceral sensitivity and slightly relief diarrhea-like behaviors in IBS recipient rats. Fecal 16S rRNA gene sequencing revealed that TXYF modulated microbial β-diversity and taxonomic structure of IBS rats, with a significant increase in relative abundance of bile salt hydrolase (BSH)-expressing Bacteroidaceae. qPCR and culturing data validated that TXYF had a promotive effect on the growth and BSH activity of Bacteroides species. TXYF-reshaped microbiota upregulated the expression of intestinal Fgf15, a feedback signal to control BA synthesis in the liver. As a result, the BA synthetic and excretory levels in IBS rats were decreased by TXYF, so as that colonic BA membrane receptor Tgr5 sensing and its mediated Calcitonin gene-related peptide (Cgrp)-positive neuronal response were attenuated. Conclusion: This study poses a new microbiota-driven therapeutic action for TXYF, highlighting the potential of developing new anti-IBS strategies from the herbal formula targeting BSH-expressing gut bacteria.
Language	English
Publishing date	2024-04-25
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2024.118256
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Article ; Online: Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active components identification.

Yang, Fengge / Zhang, Sihao / Tian, Danmei / Zhou, Guirong / Tang, Xiyang / Miao, Xinglong / He, Yi / Yao, Xinsheng / Tang, Jinshan

Chinese journal of natural medicines

2023 Volume 21, Issue 6, Page(s) 459–480

Abstract: Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely ...

Abstract	Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.
MeSH term(s)	Humans ; Tandem Mass Spectrometry/methods ; Irritable Bowel Syndrome/drug therapy ; Molecular Docking Simulation ; Drugs, Chinese Herbal/chemistry ; Glycosides ; Chromatography, High Pressure Liquid/methods
Chemical Substances	chang-kang-fang ; N-acetyldopamine (2494-12-4) ; Drugs, Chinese Herbal ; Glycosides
Language	English
Publishing date	2023-06-12
Publishing country	China
Document type	Journal Article
ZDB-ID	2192577-X
ISSN	1875-5364 ; 2095-6975 ; 1672-3651
ISSN (online)	1875-5364
ISSN	2095-6975 ; 1672-3651
DOI	10.1016/S1875-5364(23)60474-1
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Article ; Online: Exploring the regulatory mechanism of Nao Tai Fang on vascular Dementia's biological network based on cheminformatics and transcriptomics strategy.

Zhao, Da / Yi, Yaqiao / He, Qi / Wang, Shanshan / Yang, Kailin / Ge, Jinwen

Journal of ethnopharmacology

2021 Volume 274, Page(s) 114065

Abstract: Ethnopharmacological relevance: Nao Tai Fang (NTF) is modified from Buyang Huanwu Decoction ...

Abstract	Ethnopharmacological relevance: Nao Tai Fang (NTF) is modified from Buyang Huanwu Decoction. Modern pharmacological research showed that NTF has a good anti-cerebral ischemic effect and can improve the learning and memory ability of cerebrovascular disease. Aim: The purpose of this study is to explore the regulation mechanism of NTF on the regulation mechanism of vascular dementia (VD)'s biological network based on chemoinformatics and transcriptomics strategies. Method: First, the bilateral common carotid artery ligation method was used to create a rat VD model. After NTF intervention for 30 days, the treatment effect was evaluated by HE staining and water maze experiment. Then, the Agilent mRNA expression profiling chip was used to obtain mRNA expression data of hippocampal tissues of VD model rats before and after NTF intervention, and microarray analysis was used to screen for genes with significant differential expression. The BATMAN database was utilized to obtain the potential targets of NTF and the Genecards and OMIM were utilized to collect the VD potential genes. The cytoscape was utilized to construct and analyze the networks. Result: The animal experiments showed that NTF can improve VD. A total of 180 up-regulated proteins and 289 down-regulated proteins were identified. The top 20 up- and down-regulated differentially expressed genes were utilized to construct differentially expressed gene's protein-protein interaction (PPI) network. A total of 677 NTF potential targets and 550 VD genes were obtained and were utilized to construct NTF-VD PPI network. The cheminformatics analysis showed that NTF can regulate a lot of biological processes and signaling pathways (such as inflammation modules, vasodilation and contraction modules, hypoxia modules, angiogenesis, coagulation, neurovascular unit modules, Neuroactive ligand-receptor interaction, Calcium signaling pathway, Serotonergic synapse). Conclusion: NTF may play a role in the treatment of VD through the targets, signaling pathways and biological processes discovered in this study.
MeSH term(s)	Animals ; Biomarkers ; Cheminformatics ; Dementia, Vascular/drug therapy ; Dementia, Vascular/genetics ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Gene Expression Profiling ; Hippocampus/drug effects ; Hippocampus/metabolism ; Male ; Maze Learning/drug effects ; Protein Interaction Maps ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Transcriptome/drug effects ; Rats
Chemical Substances	Biomarkers ; Drugs, Chinese Herbal ; naotaifang
Language	English
Publishing date	2021-03-23
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2021.114065
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Article ; Online: Co-existing polysaccharides affect the systemic exposure of major bioactive ingredients in Chang-Kang-Fang, a multi-herb prescription for treatment of irritable bowel syndrome.

Zhong, Ping / Zhou, Jing / Fan, Yan-Ting / Guo, Meng-Fei / Zhu, He / Zhou, Shan-Shan / Zhu, Jin-Hao / Zhang, Huan-Huan / Zhou, Gui-Rong / Miao, Xing-Long / Li, Song-Lin / Mao, Qian

Journal of ethnopharmacology

2022 Volume 298, Page(s) 115601

Abstract: Ethnopharmacological relevance: Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used ...

Abstract	Ethnopharmacological relevance: Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used for treatment of irritable bowel syndrome (IBS) in China. Decoction is the administration form of CKF in clinical practice. Previously, CKF has been confirmed with activities of releasing pain and reversing disorders of intestinal propulsion. And alkaloids, monoglycosides, chromones were found as the main bioactive components potentially contributing to the efficacy of CKF. Polysaccharide was also a major constituent in CKF. But if and how polysaccharides influence the systemic exposure of bioactive components in CKF is unknown. Aim of the study: In this study, we aimed to demonstrate the contribution of the co-existed polysaccharides on the systemic exposure of the major bioactive components from CKF in normal and IBS model rats. Materials and methods: An UPLC-TQ-MS with multiple reaction monitoring (MRM) scan method was developed and validated for quantifying six major small molecular bioactive ingredients of CKF in the plasma samples, including magnoflorine (MAG), berberine (BBR), albiflorin (ALB), paeoniflorin (PAE), 5-O-methylvisamminol (5-OM) and prim-O-glucosylcimifugin (POG). The rats received CKF decoction (CKF) and CKF small molecule portion (knockout of polysaccharides, CKFSM), respectively. IBS model rats were induced by daily bondage and gavage of Sennae Folium decoction (derived from the leaf of Cassia angustifolia Vahl). The effects of the co-existing polysaccharides on the pharmacokinetic parameters of six small molecular bioactive components in normal and IBS model rats were systematically evaluated. The potential gut microbiota involved mechanisms of the effects was validated by broad-spectrum antibiotic (ABX) treatment. Results: The selectivity, precision, accuracy, recovery and matrix effect of the established quantification method were all within acceptable limits of biological sample. In normal rats, the co-existing polysaccharides significantly reduced the AUC Conclusions: A reliable and sensitive UPLC-TQ-MS method was successfully developed and validated for evaluating influence of co-existing polysaccharides on pharmacokinetic behavior of six major small molecules components in CKF. The co-existing polysaccharides enhanced the systemic exposure of six bioactive small molecules in CKF under IBS pathological state potentially via gut microbiota involvement.
MeSH term(s)	Animals ; Chromatography, High Pressure Liquid/methods ; Drugs, Chinese Herbal/pharmacokinetics ; Drugs, Chinese Herbal/therapeutic use ; Irritable Bowel Syndrome/drug therapy ; Irritable Bowel Syndrome/pathology ; Polysaccharides/pharmacology ; Polysaccharides/therapeutic use ; Prescriptions ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Drugs, Chinese Herbal ; Polysaccharides ; chang-kang-fang
Language	English
Publishing date	2022-08-10
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2022.115601
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Article ; Online: Snake fang-inspired stamping patch for transdermal delivery of liquid formulations.

Bae, Won-Gyu / Ko, Hangil / So, Jin-Young / Yi, Hoon / Lee, Chan-Ho / Lee, Dong-Hun / Ahn, Yujin / Lee, Sang-Hyeon / Lee, Kyunghun / Jun, Joonha / Kim, Hyoung-Ho / Jeon, Noo Li / Jung, Woonggyu / Song, Chang-Seon / Kim, Taesung / Kim, Yeu-Chun / Jeong, Hoon Eui

Science translational medicine

2019 Volume 11, Issue 503

Abstract: ... because of technical limitations. Here, we present a snake fang-inspired microneedle patch that can administer existing ... that the snake fang-inspired open groove architectures enable rapid capillary force-driven delivery ... influenza virus with the snake fang-inspired microneedle patch induces robust antibody production and protective ...

Abstract	A flexible microneedle patch that can transdermally deliver liquid-phase therapeutics would enable direct use of existing, approved drugs and vaccines, which are mostly in liquid form, without the need for additional drug solidification, efficacy verification, and subsequent approval. Specialized dissolving or coated microneedle patches that deliver reformulated, solidified therapeutics have made considerable advances; however, microneedles that can deliver liquid drugs and vaccines still remain elusive because of technical limitations. Here, we present a snake fang-inspired microneedle patch that can administer existing liquid formulations to patients in an ultrafast manner (<15 s). Rear-fanged snakes have an intriguing molar with a groove on the surface, which enables rapid and efficient infusion of venom or saliva into prey. Liquid delivery is based on surface tension and capillary action. The microneedle patch uses multiple open groove architectures that emulate the grooved fangs of rear-fanged snakes: Similar to snake fangs, the microneedles can rapidly and efficiently deliver diverse liquid-phase drugs and vaccines in seconds under capillary action with only gentle thumb pressure, without requiring a complex pumping system. Hydrodynamic simulations show that the snake fang-inspired open groove architectures enable rapid capillary force-driven delivery of liquid formulations with varied surface tensions and viscosities. We demonstrate that administration of ovalbumin and influenza virus with the snake fang-inspired microneedle patch induces robust antibody production and protective immune response in guinea pigs and mice.
MeSH term(s)	Administration, Cutaneous ; Adult ; Animals ; Drug Delivery Systems/methods ; Female ; Guinea Pigs ; Hemagglutination ; Humans ; Hydrodynamics ; Male ; Mice ; Mice, Inbred BALB C ; Microinjections ; Microscopy, Electron, Scanning ; Needles ; Skin/metabolism ; Snakes ; Surface Tension ; Tooth
Language	English
Publishing date	2019-07-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.aaw3329
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: [Linggui Fang protects the reproductive system of asthenospermia rats: An experimental study based on the L-carnitine pathway].

Yan, Bin / Wang, Fu / Gao, Qing-He / Zhang, Ji-Wei / Zhang, Xiu-Ju / Yu, Guo-Jin / Qiu, Jun-Feng / Liu, Yu / Liu, Sheng-Jing / Guo, Jun

Zhonghua nan ke xue = National journal of andrology

2020 Volume 25, Issue 12, Page(s) 1113–1117

Abstract: Objective: To explore the protective effect of the Chinese medicinal prescription Linggui Fang ...

Abstract	Objective: To explore the protective effect of the Chinese medicinal prescription Linggui Fang (LGF) on the reproductive system of the ornidazole-induced asthenospermia (AS) rat and its possible action mechanisms. Methods: Forty male SD rats weighing 200－230 g were equally randomized into four groups, blank control, AS model control, LGF treatment and L-carnitine (LC) intervention. The AS models were made in the latter three groups by intragastrical administration of ornidazole at 400 mg/kg. Meanwhile, the rats in the LGF group were treated intragastrically with LGF at 17.5 g/kg, those in the LC group with LC at 100 mg/kg, and the control animals with 0.5% sodium carboxymethylcellulose (CMC-Na), all once a day for 4 successive weeks. Then, all the rats were sacrificed for examination of the semen parameters, determination of the LC content and OCTN2 mRNA expression in the epididymis and observation of the histopathological changes in the testis. Results: Compared with the AS model controls, the rats in the other groups showed significantly higher percentages of progressively motile sperm and total motile sperm (P < 0.01) as well as a higher LC content in the epididymis (P < 0.01), but no statistically significant difference in sperm concentration (P > 0.05). The expression of OCTN2 mRNA was remarkably upregulated in the LGF and LC groups in comparison with that in the AS model control (P < 0.05). Compared with the rats in the blank control group, the AS model controls exhibited markedly increased morphologically abnormal seminiferous tubules, irregularly arranged, with narrowed lumens and reduced numbers of sperm and sperm cells, as well as significantly increased hollow seminiferous tubules with deficient and disorderly arranged spermatogenic cells and partial epithelial degeneration and vacuolization. Those in the LGF and LC groups, however, manifested almost normal testicular histomorphology, with basically regular arrangement of different layers of seminiferous tubules. Conclusions: ①Ornidazole induces AS in rats by reducing the LC content in the epididymis, while LGF can improve the sperm motility and testicular morphology of the rats and upregulate the expression of OCTN2 mRNA in the epididymis by increasing the LC concentration.
MeSH term(s)	Animals ; Asthenozoospermia/chemically induced ; Asthenozoospermia/drug therapy ; Carnitine/analysis ; Drugs, Chinese Herbal/therapeutic use ; Epididymis/chemistry ; Epididymis/drug effects ; Humans ; Male ; Ornidazole ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Solute Carrier Family 22 Member 5/metabolism ; Sperm Count ; Sperm Motility ; Spermatozoa ; Testis/drug effects ; Testis/pathology
Chemical Substances	Drugs, Chinese Herbal ; Slc22a5 protein, rat ; Solute Carrier Family 22 Member 5 ; Ornidazole (62XCK0G93T) ; Carnitine (S7UI8SM58A)
Language	Chinese
Publishing date	2020-04-05
Publishing country	China
Document type	Journal Article
ZDB-ID	2267480-9
ISSN	1009-3591
ISSN	1009-3591
Database	MEDical Literature Analysis and Retrieval System OnLINE

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