cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.15170538
title: Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in <i>db/db</i> mice

description: Faecal microbiota transplantation (FMT) from Kazak individuals with normal glucose tolerance (KNGT) significantly reduces plasma glycolipid levels in type 2 diabetes mellitus <i>db/db</i> mice. However, the mechanism behind this effect has not been reported. To study the mechanism of improved glycolipid disorders in <i>db/db</i> mice by FMT from a KNGT donor. The normal diet group consisted of <i>db/m</i> mice orally administered 0.2 mL phosphate buffer saline (PBS) (<i>db/m + PBS</i>). For the <i>db/db + PBS</i> (Vehicle) and <i>db/db + KNGT</i> (FMT intervention group) groups, <i>db/db</i> mice received oral 0.2 mL PBS or faecal microorganisms from a KNGT donor, respectively. All mice were treated daily for 0, 6 or 10 weeks. Faecal DNA samples were sequenced and quantified using 16S rRNA gene sequencing and RT-qPCR, respectively. Short-chain fatty acid (SCFA) levels in the mouse faeces were determined by gas chromatography. G protein-coupled receptor 43 (GPR43) and glucagon-like peptide-1 (GLP-1) expression levels were determined. FMT intervention significantly increased the relative abundance of <i>Bacteroides uniformis</i> (0.038%, <i>p</i> &lt; 0.05). <i>Clostridium</i> levels (LogSQ) were increased (<i>p</i> &lt; 0.01), while <i>Mucispirillum schaedleri</i> levels (LogSQ) were decreased (<i>p</i> &lt; 0.01). Acetate and butyrate levels in the faeces were significantly increased (acetate; butyrate: 22.68 ± 1.82 mmol/L; 4.13 ± 1.09 mmol/L, <i>p</i> &lt; 0.05). GPR43 mRNA expression and GLP-1 protein expression increased in colon tissue (<i>p</i> &lt; 0.05). Mechanistically, FMT-KNGT could improve glycolipid disorders by changing the bacterial composition responsible for producing SCFAs and activating the GPR43/GLP-1 pathway.
DOI: 10.6084/m9.figshare.14182662
title: Naoxintong accelerates diabetic wound healing by attenuating inflammatory response

description: Naoxintong (NXT), a prescribed traditional Chinese medicine, widely used in cerebrovascular and cardiovascular diseases, could be effective in diabetic wounds. This study evaluates the wound healing activity of NXT by employing an excisional wound splinting model. NXT was dissolved in saline and given daily by gavage. Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with saline or 700 mg/kg/d NXT for 16 days. Wound closure was measured every four days. Extracellular matrix (ECM) remodelling, collagen deposition, leukocyte infiltration and expression of Col-3, CK14, CXCL1, CXCL2, MPO, Ly6G, CD68, CCR7, CD206, p-JAK1, p-STAT3 and p-STAT6 was analysed. NXT significantly accelerated rate of wound closure increased from 70% to 84%, accompanied by up-regulation of collagen deposition and ECM at days 16 post-injury. Moreover, NXT alleviated neutrophil infiltration, accompanied by down-regulation of CXCL1 and CXCL2 mRNA expression. In addition, NXT markedly augmented neutrophil efferocytosis. In diabetic wounds, the levels of M1 marker gene (CCR7) increased, while M2 marker gene (CD206) decreased, demonstrating a pro-inflammatory shift. Application of NXT increased M2 macrophage phenotype in db/db mice. Mechanistically, NXT treatment increased expression level of p-STAT3 and p-STAT6 at days 3 post-injury, indicating NXT mediated macrophages towards M2 phenotype and alleviated inflammation in diabetic wounds by activation of STAT3 and STAT6. Our study provides evidence that NXT accelerates diabetic wound healing by attenuating inflammatory response, which provides an important basis for use of NXT in the treatment of chronic diabetic wound healing.
DOI: 10.6084/m9.figshare.14182662.v1
title: Naoxintong accelerates diabetic wound healing by attenuating inflammatory response

description: Naoxintong (NXT), a prescribed traditional Chinese medicine, widely used in cerebrovascular and cardiovascular diseases, could be effective in diabetic wounds. This study evaluates the wound healing activity of NXT by employing an excisional wound splinting model. NXT was dissolved in saline and given daily by gavage. Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with saline or 700 mg/kg/d NXT for 16 days. Wound closure was measured every four days. Extracellular matrix (ECM) remodelling, collagen deposition, leukocyte infiltration and expression of Col-3, CK14, CXCL1, CXCL2, MPO, Ly6G, CD68, CCR7, CD206, p-JAK1, p-STAT3 and p-STAT6 was analysed. NXT significantly accelerated rate of wound closure increased from 70% to 84%, accompanied by up-regulation of collagen deposition and ECM at days 16 post-injury. Moreover, NXT alleviated neutrophil infiltration, accompanied by down-regulation of CXCL1 and CXCL2 mRNA expression. In addition, NXT markedly augmented neutrophil efferocytosis. In diabetic wounds, the levels of M1 marker gene (CCR7) increased, while M2 marker gene (CD206) decreased, demonstrating a pro-inflammatory shift. Application of NXT increased M2 macrophage phenotype in db/db mice. Mechanistically, NXT treatment increased expression level of p-STAT3 and p-STAT6 at days 3 post-injury, indicating NXT mediated macrophages towards M2 phenotype and alleviated inflammation in diabetic wounds by activation of STAT3 and STAT6. Our study provides evidence that NXT accelerates diabetic wound healing by attenuating inflammatory response, which provides an important basis for use of NXT in the treatment of chronic diabetic wound healing.
DOI: 10.6084/m9.figshare.14854335
title: Therapeutic effects of Sheng Xue Fang in a cyclophosphamide-induced anaemia mouse model

description: Sheng Xue Fang (SXF) has been used to treat anaemia for decades with good efficacy. To study the effect and possible mechanism of SXF to restore haematopoietic function. Balb/c mice (10 per/group, half male, half female) were treated with SXF (three dose groups, 8.5, 17, and 22.1 g/kg) by gavage for 14 days, and cyclophosphamide (80 mg/kg) was injected on days 10–12. Only injection of cyclophosphamide (negative control) or physiological saline (blank control) were included as controls. The spleen and femur were processed for histopathology. Active components and the target of SXF were screened. The target was used for gene enrichment and protein-protein interaction (PPI) analysis. Red blood cell relative changes in the SXF group (low: −5.50 ± 1.58%; medium: −11.11 ± 4.15%; high: −8.81 ± 2.67%) and relative negative control (26.21 ± 2.51%) significantly increased (all <i>p</i> &lt; 0.01) in female mice. Haemoglobin and red blood cell-specific volume showed the same trend. However, SXF did not have significant effects on male mice. Splenic index in the medium group (4.44 ± 0.46%) relative negative control (3.38 ± 0.10%) significantly improved (<i>p</i> &lt; 0.01) in female mice. Using network pharmacology, 77 active components and 337 targets were screened from SXF. These targets are closely related to the mitogen-activated protein kinase pathway. SXF has good clinical application potential. However, the mechanism requires in-depth research. Our findings are of great significance in anaemia treatment and provide a new perspective for Chinese medicine research.
DOI: 10.6084/m9.figshare.14854335.v1
title: Therapeutic effects of Sheng Xue Fang in a cyclophosphamide-induced anaemia mouse model

description: Sheng Xue Fang (SXF) has been used to treat anaemia for decades with good efficacy. To study the effect and possible mechanism of SXF to restore haematopoietic function. Balb/c mice (10 per/group, half male, half female) were treated with SXF (three dose groups, 8.5, 17, and 22.1 g/kg) by gavage for 14 days, and cyclophosphamide (80 mg/kg) was injected on days 10–12. Only injection of cyclophosphamide (negative control) or physiological saline (blank control) were included as controls. The spleen and femur were processed for histopathology. Active components and the target of SXF were screened. The target was used for gene enrichment and protein-protein interaction (PPI) analysis. Red blood cell relative changes in the SXF group (low: −5.50 ± 1.58%; medium: −11.11 ± 4.15%; high: −8.81 ± 2.67%) and relative negative control (26.21 ± 2.51%) significantly increased (all <i>p</i> &lt; 0.01) in female mice. Haemoglobin and red blood cell-specific volume showed the same trend. However, SXF did not have significant effects on male mice. Splenic index in the medium group (4.44 ± 0.46%) relative negative control (3.38 ± 0.10%) significantly improved (<i>p</i> &lt; 0.01) in female mice. Using network pharmacology, 77 active components and 337 targets were screened from SXF. These targets are closely related to the mitogen-activated protein kinase pathway. SXF has good clinical application potential. However, the mechanism requires in-depth research. Our findings are of great significance in anaemia treatment and provide a new perspective for Chinese medicine research.
DOI: 10.6084/m9.figshare.17076480
title: Protective effect of Qingre Huoxue decoction against myocardial infarction via PI3K/Akt autophagy pathway based on UPLC-MS, network pharmacology, and <i>in vivo</i> evidence

description: Qingre Huoxue (QRHX) decoction, a traditional Chinese medicine, has been widely used to prevent and treat myocardial infarction (MI). This study elucidates the possible mechanisms of QRHX in preventing or treating MI in a rat model. The chemical constituents of QRHX were identified by UPLC-MS. Sprague-Dawley rats were randomly divided into the Sham (normal saline), Model (normal saline), QRHX-L, QRHX-M and QRHX-H group (<i>n</i> = 10 per group). QRHX decoction was administered by gavage to the rats for 14 days (5, 10 and 20 g/kg/day). The left anterior descending ligation method was performed to develop MI in Model and QRHX groups, and the same surgical procedures excluding ligation sutures were performed for the sham group. Finally, we evaluated cardiac function, myocardial fibrosis degree, serum inflammatory factors, autophagy levels and verified the signalling pathways <i>in vivo</i>. A total of 68 active components of QRHX corresponding to 223 active targets were obtained and 2558 MI-related disease targets were collected. After integration, 123 QRHX anti-MI targets were obtained, and 70 signalling pathways, such as PI3K/Akt, were identified by enrichment analysis. <i>In vivo</i> experiments suggest that QRHX could reduce the degree of myocardial fibrosis, downregulate serum inflammatory factors, and promote autophagy in MI rats. QRHX plays a protective role in the myocardium by mediating PI3K/Akt signalling pathway to activate autophagy and inhibiting inflammatory factor expression. These findings provide a scientific basis for further research and validation of QRHX as a potential therapeutic for MI.
DOI: 10.6084/m9.figshare.17076480.v1
title: Protective effect of Qingre Huoxue decoction against myocardial infarction via PI3K/Akt autophagy pathway based on UPLC-MS, network pharmacology, and <i>in vivo</i> evidence

description: Qingre Huoxue (QRHX) decoction, a traditional Chinese medicine, has been widely used to prevent and treat myocardial infarction (MI). This study elucidates the possible mechanisms of QRHX in preventing or treating MI in a rat model. The chemical constituents of QRHX were identified by UPLC-MS. Sprague-Dawley rats were randomly divided into the Sham (normal saline), Model (normal saline), QRHX-L, QRHX-M and QRHX-H group (<i>n</i> = 10 per group). QRHX decoction was administered by gavage to the rats for 14 days (5, 10 and 20 g/kg/day). The left anterior descending ligation method was performed to develop MI in Model and QRHX groups, and the same surgical procedures excluding ligation sutures were performed for the sham group. Finally, we evaluated cardiac function, myocardial fibrosis degree, serum inflammatory factors, autophagy levels and verified the signalling pathways <i>in vivo</i>. A total of 68 active components of QRHX corresponding to 223 active targets were obtained and 2558 MI-related disease targets were collected. After integration, 123 QRHX anti-MI targets were obtained, and 70 signalling pathways, such as PI3K/Akt, were identified by enrichment analysis. <i>In vivo</i> experiments suggest that QRHX could reduce the degree of myocardial fibrosis, downregulate serum inflammatory factors, and promote autophagy in MI rats. QRHX plays a protective role in the myocardium by mediating PI3K/Akt signalling pathway to activate autophagy and inhibiting inflammatory factor expression. These findings provide a scientific basis for further research and validation of QRHX as a potential therapeutic for MI.
DOI: 10.6084/m9.figshare.14515427
title: Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model

description: Cryptotanshinone (CT), a lipophilic compound extracted from roots of <i>Salvia miltiorrhiza</i> Bunge (Lamiaceae) (Danshen), has multiple properties in diseases, such as pulmonary fibrosis, lung cancer, and osteoarthritis. Our previous findings suggest that CT plays a protective role in cerebral stroke. However, the molecular mechanisms underlying CT protection in ischaemic stroke remain unclear. This study examines the effect of CT on ischaemic stroke. We used the middle cerebral artery occlusion (MCAO) rat (Sprague-Dawley rats, 200 ± 20 g, <i>n</i> = 5) model with a sham operation group was treated as negative control. MCAO rats were treated with 15 mg/kg CT using intragastric administration. Moreover, TGF-β (5 ng/mL) was used to treat MCAO rats as a positive control group. The 50% inhibitory concentration (IC<sub>50</sub>) of CT on CD4<sup>+</sup> cell damage was 485.1 μg/mL, and median effective concentration (EC<sub>50</sub>) was 485.1 μg/mL. CT attenuates the infarct region in the MCAO model. The percentage of CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> Treg cells in the peripheral blood of the MCAO group was increased with CT treatment. The protein level of FOXP3 and the phosphorylation of STAT5 were recovered in the CD4<sup>+</sup>CD25<sup>+</sup> Treg cells of model group after treated with CT. Importantly, the effects of CT treatment were blocked by treatment with the inhibitor STAT5-IN-1 in CD4<sup>+</sup> T cells of the MCAO model. Our findings not only enhance the understanding of the mechanisms underlying CT treatment, but also indicate its potential value as a promising agent in the treatment of ischaemic stroke. Further study will be valuable to examine the effects of CT on patients with ischaemic stroke.
DOI: 10.6084/m9.figshare.14515427.v1
title: Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model

description: Cryptotanshinone (CT), a lipophilic compound extracted from roots of <i>Salvia miltiorrhiza</i> Bunge (Lamiaceae) (Danshen), has multiple properties in diseases, such as pulmonary fibrosis, lung cancer, and osteoarthritis. Our previous findings suggest that CT plays a protective role in cerebral stroke. However, the molecular mechanisms underlying CT protection in ischaemic stroke remain unclear. This study examines the effect of CT on ischaemic stroke. We used the middle cerebral artery occlusion (MCAO) rat (Sprague-Dawley rats, 200 ± 20 g, <i>n</i> = 5) model with a sham operation group was treated as negative control. MCAO rats were treated with 15 mg/kg CT using intragastric administration. Moreover, TGF-β (5 ng/mL) was used to treat MCAO rats as a positive control group. The 50% inhibitory concentration (IC<sub>50</sub>) of CT on CD4<sup>+</sup> cell damage was 485.1 μg/mL, and median effective concentration (EC<sub>50</sub>) was 485.1 μg/mL. CT attenuates the infarct region in the MCAO model. The percentage of CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> Treg cells in the peripheral blood of the MCAO group was increased with CT treatment. The protein level of FOXP3 and the phosphorylation of STAT5 were recovered in the CD4<sup>+</sup>CD25<sup>+</sup> Treg cells of model group after treated with CT. Importantly, the effects of CT treatment were blocked by treatment with the inhibitor STAT5-IN-1 in CD4<sup>+</sup> T cells of the MCAO model. Our findings not only enhance the understanding of the mechanisms underlying CT treatment, but also indicate its potential value as a promising agent in the treatment of ischaemic stroke. Further study will be valuable to examine the effects of CT on patients with ischaemic stroke.
DOI: 10.6084/m9.figshare.14946066
title: <i>In vitro</i> study on the effect of peucedanol on the activity of cytochrome P450 enzymes

description: Peucedanol is a major extract of <i>Peucedanum japonicum</i> Thunb. (Apiaceae) roots, which is a commonly used herb in paediatrics. Its interaction with cytochrome P450 enzymes (CYP450s) would lead to adverse effects or even failure of therapy. The interaction between peucedanol and CYP450s was investigated. Peucedanol (0, 2.5, 5, 10, 25, 50, and 100 μM) was incubated with eight human liver CYP isoforms (CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1), in pooled human liver microsomes (HLMs) for 30 min with specific inhibitors as positive controls and untreated HLMs as negative controls. The enzyme kinetics and time-dependent study (0, 5, 10, 15, and 30 min) were performed to obtain corresponding parameters <i>in vitro</i>. Peucedanol significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC<sub>50</sub> values of 6.03, 13.57, and 7.58 μM, respectively. Peucedanol served as a non-competitive inhibitor of CYP3A4 with a <i>K<sub>i</sub></i> value of 4.07 μM and a competitive inhibitor of CYP1A2 and 2D6 with a <i>K<sub>i</sub></i> values of 3.39 and 6.77 μM, respectively. Moreover, the inhibition of CYP3A4 was time-dependent with the <i>K<sub>i</sub></i>/<i>K<sub>inact</sub></i> value of 5.44/0.046 min/μM. <i>In vitro</i> inhibitory effect of peucedanol on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. As these CYPs are involved in the metabolism of various drugs, these results implied potential drug-drug interactions between peucedanol and drugs metabolized by CYP1A2, 2D6, and 3A4, which needs further <i>in vivo</i> validation.
DOI: 10.6084/m9.figshare.14946066.v1
title: <i>In vitro</i> study on the effect of peucedanol on the activity of cytochrome P450 enzymes

description: Peucedanol is a major extract of <i>Peucedanum japonicum</i> Thunb. (Apiaceae) roots, which is a commonly used herb in paediatrics. Its interaction with cytochrome P450 enzymes (CYP450s) would lead to adverse effects or even failure of therapy. The interaction between peucedanol and CYP450s was investigated. Peucedanol (0, 2.5, 5, 10, 25, 50, and 100 μM) was incubated with eight human liver CYP isoforms (CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1), in pooled human liver microsomes (HLMs) for 30 min with specific inhibitors as positive controls and untreated HLMs as negative controls. The enzyme kinetics and time-dependent study (0, 5, 10, 15, and 30 min) were performed to obtain corresponding parameters <i>in vitro</i>. Peucedanol significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC<sub>50</sub> values of 6.03, 13.57, and 7.58 μM, respectively. Peucedanol served as a non-competitive inhibitor of CYP3A4 with a <i>K<sub>i</sub></i> value of 4.07 μM and a competitive inhibitor of CYP1A2 and 2D6 with a <i>K<sub>i</sub></i> values of 3.39 and 6.77 μM, respectively. Moreover, the inhibition of CYP3A4 was time-dependent with the <i>K<sub>i</sub></i>/<i>K<sub>inact</sub></i> value of 5.44/0.046 min/μM. <i>In vitro</i> inhibitory effect of peucedanol on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. As these CYPs are involved in the metabolism of various drugs, these results implied potential drug-drug interactions between peucedanol and drugs metabolized by CYP1A2, 2D6, and 3A4, which needs further <i>in vivo</i> validation.
DOI: 10.6084/m9.figshare.15128021
title: Anti-depressant effects of ethanol extract from <i>Cannabis sativa</i> (hemp) seed in chlorpromazine-induced <i>Drosophila melanogaster</i> depression model

description: Depression is a severe mental illness caused by a deficiency of dopamine and serotonin. <i>Cannabis sativa</i> L. (Cannabaceae) has long been used to treat pain, nausea, and depression. This study investigates the anti-depressant effects of <i>C. sativa</i> (hemp) seed ethanol extract (HE) in chlorpromazine (CPZ)-induced <i>Drosophila melanogaster</i> depression model. The normal group was untreated, and the control group was treated with CPZ (0.1% of media) for 7 days. The experimental groups were treated with a single HE treatment (0.5, 1.0, and 1.5% of media) and a mixture of 0.1% CPZ and HE for 7 days. The locomotor activity, behavioural patterns, depression-related gene expression, and neurotransmitters level of flies were investigated. The behavioural patterns of individual flies were significantly reduced with 0.1% CPZ treatment. In contrast, combination treatment of 1.5% HE and 0.1% CPZ significantly increased subjective daytime activity (<i>p</i> &lt; 0.001) and behavioural factors (<i>p</i> &lt; 0.001). These results correlate with increased transcript levels of dopamine (<i>p</i> &lt; 0.001) and serotonin (<i>p</i> &lt; 0.05) receptors and concentration of dopamine (<i>p</i> &lt; 0.05), levodopa (<i>p</i> &lt; 0.001), 5-HTP (<i>p</i> &lt; 0.05), and serotonin (<i>p</i> &lt; 0.001) compared to those in the control group. Collectively, HE administration alleviates depression-like symptoms by modulating the circadian rhythm-related behaviours, transcript levels of neurotransmitter receptors, and neurotransmitter levels in the CPZ-induced <i>Drosophila</i> model. However, additional research is needed to investigate the role of HE administration in behavioural patterns, reduction of the neurotransmitter, and signalling pathways of depression in a vertebrate model system.
DOI: 10.6084/m9.figshare.15128021.v1
title: Anti-depressant effects of ethanol extract from <i>Cannabis sativa</i> (hemp) seed in chlorpromazine-induced <i>Drosophila melanogaster</i> depression model

description: Depression is a severe mental illness caused by a deficiency of dopamine and serotonin. <i>Cannabis sativa</i> L. (Cannabaceae) has long been used to treat pain, nausea, and depression. This study investigates the anti-depressant effects of <i>C. sativa</i> (hemp) seed ethanol extract (HE) in chlorpromazine (CPZ)-induced <i>Drosophila melanogaster</i> depression model. The normal group was untreated, and the control group was treated with CPZ (0.1% of media) for 7 days. The experimental groups were treated with a single HE treatment (0.5, 1.0, and 1.5% of media) and a mixture of 0.1% CPZ and HE for 7 days. The locomotor activity, behavioural patterns, depression-related gene expression, and neurotransmitters level of flies were investigated. The behavioural patterns of individual flies were significantly reduced with 0.1% CPZ treatment. In contrast, combination treatment of 1.5% HE and 0.1% CPZ significantly increased subjective daytime activity (<i>p</i> &lt; 0.001) and behavioural factors (<i>p</i> &lt; 0.001). These results correlate with increased transcript levels of dopamine (<i>p</i> &lt; 0.001) and serotonin (<i>p</i> &lt; 0.05) receptors and concentration of dopamine (<i>p</i> &lt; 0.05), levodopa (<i>p</i> &lt; 0.001), 5-HTP (<i>p</i> &lt; 0.05), and serotonin (<i>p</i> &lt; 0.001) compared to those in the control group. Collectively, HE administration alleviates depression-like symptoms by modulating the circadian rhythm-related behaviours, transcript levels of neurotransmitter receptors, and neurotransmitter levels in the CPZ-induced <i>Drosophila</i> model. However, additional research is needed to investigate the role of HE administration in behavioural patterns, reduction of the neurotransmitter, and signalling pathways of depression in a vertebrate model system.