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1.
BMC Neurol ; 24(1): 207, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886670

ABSTRACT

OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.


Subject(s)
Endovascular Procedures , Ischemic Stroke , Humans , Male , Female , Ischemic Stroke/surgery , Ischemic Stroke/therapy , Aged , Endovascular Procedures/methods , Middle Aged , Aged, 80 and over , Medical Futility , Thrombectomy/methods , Prospective Studies , Prognosis
2.
Clin Appl Thromb Hemost ; 30: 10760296231223192, 2024.
Article in English | MEDLINE | ID: mdl-38166411

ABSTRACT

To investigate the predictive role of the neutrophil-platelet ratio (NPR) before intravenous thrombolysis (IVT) on hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). AIS patients treated with IVT without endovascular therapy between June 2019 and February 2023 were included. Patients were divided into high NPR (>35) and low NPR (≤35) groups according to the optimal threshold NPR value for identifying high-risk patients before IVT. The baseline data and the incidence of HT and symptomatic intracranial hemorrhage (sICH) were compared between the two groups. The predictive role of the NPR and other related factors on HT after IVT was analyzed by multivariate logistic regression. A total of 247 patients were included, with an average age of 67.5 ± 12.4 years. Post-thrombolytic HT was observed in 18.6% of the patients, and post-thrombolytic sICH was observed in 1.2% of the patients. There were 69 patients in the high NPR group and 178 patients in the low NPR group. The incidence of HT in the high NPR group was significantly higher than that in the low NPR group (30.4% vs 16.3%, P < .05). The incidence of sICH was significantly higher in the high NPR group than in the low NPR group (14.5% vs 1.7%, P < .001). Multivariate logistic regression analysis showed that NPR > 35 was positively correlated with HT (odds ratio (OR) = 3.236, 95% confidence interval (CI): 1.481-7.068, P = .003) and sICH (OR = 13.644, 95% CI: 2.392-77.833, P = .003). A high NPR (>35) before IVT may be a predictor of HT in AIS patients. This finding may help clinicians make clinical decisions before IVT in AIS patients.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Middle Aged , Aged , Stroke/etiology , Tissue Plasminogen Activator/adverse effects , Ischemic Stroke/drug therapy , Ischemic Stroke/etiology , Neutrophils , Brain Ischemia/etiology , Thrombolytic Therapy/adverse effects , Fibrinolytic Agents/therapeutic use , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/drug therapy , Treatment Outcome
3.
J Clin Neurosci ; 117: 120-124, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37801876

ABSTRACT

Long-term prognosis and factors influencing endovascular therapy (EVT) remain unclear. This study aimed to investigate the association between computed tomography perfusion (CTP) parameters and long-term prognosis of patients with acute ischemic stroke (AIS) treated with EVT. Patients with AIS due to large vessel occlusion treated with EVT were prospectively included for a 1-year follow-up. All patients and their data were grouped based on the hypoperfusion intensity ratio (HIR, <0.3 vs. ≥ 0.3) and cerebral blood volume (CBV) index (>0.7 vs. ≤ 0.7). The primary outcome was favorable prognosis, defined as a modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression was used to analyze factors influencing long-term favorable prognosis. Of 69 patients included, 35 (50.7 %) achieved mRS 0-2 at one year. A favorable prognosis was observed predominantly in patients with higher CBV index (75.0 % vs. 34.1 %, p= 0.001) and lower HIR (72.0 % vs. 38.6 %, p=0.008). In the multivariate logistic regression, CBV index (odds ratio (OR) = 4.362; 95 % confidence interval (CI): 1.052, 18.082; p = 0.042), baseline National Institutes of Health Stroke Scale (NIHSS) score (OR = 0.913; 95 % CI: 0.836, 0.997; p = 0.044), and symptomatic intracranial hemorrhage (sICH) (OR = 0.089; 95 % CI: 0.009, 0.925; p = 0.043) were independently associated with a long-term favorable prognosis. The CBV index may serve as a predictor of the long-term prognosis of patients treated with EVT. The novel finding is that the baseline NIHSS score and sICH were associated with long-term prognosis.


Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Humans , Stroke/diagnostic imaging , Stroke/surgery , Stroke/etiology , Ischemic Stroke/etiology , Cerebral Blood Volume , Treatment Outcome , Endovascular Procedures/methods , Prognosis , Thrombectomy/methods , Intracranial Hemorrhages/etiology , Brain Ischemia/diagnostic imaging , Brain Ischemia/surgery , Brain Ischemia/etiology , Retrospective Studies
4.
J Vasc Interv Radiol ; 34(11): 1875-1881.e3, 2023 11.
Article in English | MEDLINE | ID: mdl-37460059

ABSTRACT

PURPOSE: To evaluate the physical and cognitive functions of patients with stroke who underwent either direct or bridging thrombectomy within 6 hours of stroke onset. MATERIALS AND METHODS: Patients with large vessel occlusion in anterior circulation treated with direct (direct group) or bridging thrombectomy (bridging group) were prospectively analyzed between June 2020 and February 2022. The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, the safety outcome was symptomatic intracranial hemorrhage (sICH), and cognitive function was assessed using the Clinical Dementia Rating (CDR) scale at 6 months after stroke. RESULTS: A total of 125 patients (direct group, n = 75; bridging group, n = 50) who had completed follow-up at 3 months by telephone call were included. No significant differences were observed between the direct and bridging groups in terms of an mRS score of 0-2 (25.3% vs 22.0%, respectively; P = .83), an mRS score of 0-3 (37.3% vs 44.0%, respectively; P = .58), sICH (17.3% vs 14.0%, respectively; P = .80), or 3-month all-cause mortality (36.3% vs 30.0%, respectively; P = .34). Sixty-nine patients (direct group, n = 38; bridging group, n = 31) completed the CDR assessment at 6 months after stroke. There was no significant difference in poststroke dementia, defined as a CDR score of ≥1 point between the direct group (42.1%) and bridging group (22.6%) (P = .12). Ordinal regression analyses showed that the CDR score at 6 months was not associated with treatment type (direct thrombectomy vs bridging thrombectomy). CONCLUSIONS: With regard to physical and cognitive functions at 3 and 6 months, direct thrombectomy was comparable with bridging thrombectomy in patients who were treated within 6 hours of stroke onset.


Subject(s)
Brain Ischemia , Stroke , Humans , Prospective Studies , Treatment Outcome , Thrombectomy/adverse effects , Intracranial Hemorrhages/etiology , Brain Ischemia/drug therapy , Fibrinolytic Agents/therapeutic use , Thrombolytic Therapy/adverse effects
5.
BMC Neurol ; 23(1): 244, 2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37353783

ABSTRACT

PURPOSE: To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response. RESULTS: A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266-0.927, P = 0.028). CONCLUSION: hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Aged , Humans , Middle Aged , Brain Ischemia/drug therapy , C-Reactive Protein , Fibrinolytic Agents/therapeutic use , Ischemic Stroke/diagnosis , Ischemic Stroke/drug therapy , Retrospective Studies , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Urokinase-Type Plasminogen Activator/therapeutic use
6.
Purinergic Signal ; 19(1): 173-183, 2023 03.
Article in English | MEDLINE | ID: mdl-36370253

ABSTRACT

Pathogenesis of ischemic stroke is mainly characterized by thrombosis and neuroinflammation. Purinergic signaling pathway constitutes adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO). ATP is hydrolyzed to ADP and then to AMP by extracellular nucleotidase CD39; AMP is subsequently converted to adenosine by CD73. All these nucleotides and nucleosides act on purinergic receptors protecting against thrombosis and inhibit inflammation. In addition, many physical methods have been found to play a neuroprotective role through purinergic signaling. This review mainly introduces the role and potential mechanism of purinergic signalings in the treatment of ischemic stroke, so as to provide reference for seeking new treatment methods for stroke.


Subject(s)
Ischemic Stroke , Thrombosis , Humans , Antigens, CD/metabolism , Adenosine/metabolism , Adenosine Triphosphate/metabolism , Signal Transduction , Adenosine Diphosphate/metabolism , Adenosine Monophosphate/metabolism , 5'-Nucleotidase/metabolism , Apyrase/metabolism
7.
J Clin Neurosci ; 103: 188-192, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35917724

ABSTRACT

INTRODUCTION: To evaluate the predictors for efficacy and safety of patients with acute ischemic stroke (AIS) and Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) <6 undergoing endovascular therapy (EVT). METHODS: This study retrospectively analyzed consecutive patients presented between December 2020 and December 2021 with large vessel occlusions (LVO) within the anterior circulation and an ASPECTS <6, followed by EVT. The efficacy outcome was 90-day functional independence, defined as modified Rankin Scale (mRS) score 0-3. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Secondary safety outcomes included 90-day all-cause mortality and 24-hour any ICH. RESULTS: A total of 22 patients were included. The percentage of patients with mRS 0-3 at 90 days was 36.4% (8/22). The occurrence of sICH was 22.7% (5/22). The occurrence of any ICH was 45.5% (10/22). The 90-day all-cause mortality was 36.4% (8/22). Median (interquartile range, IQR) cerebral blood volume (CBV) index was 0.5 (0.4-0.7). CBV index in mRS 0-3 group (n = 8) was higher than mRS 4-5 group (n = 14) (P<0.05). There was no significant difference of age, gender, comorbidities, baseline National Institutes of Health Stroke Scale (NIHSS) score, mismatch ratio, CBV index, interval between stroke onset and re-perfusion, good re-perfusion rate between sICH group (n = 5) and non-sICH group (n = 17). CONCLUSIONS: AIS patients with low ASPECTS can still benefit from EVT and gain good functional outcome, especial those had higher CBV index on pre-EVT computed tomography perfusion (CTP). Further studies with larger sample size are needed to validate our findings.


Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Alberta , Cerebral Blood Volume , Humans , Intracranial Hemorrhages , Retrospective Studies , Thrombectomy , Treatment Outcome
8.
Int Immunopharmacol ; 84: 106470, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32304991

ABSTRACT

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, characterized by enhanced retinoic acid signals. Although up-regulated retinoic acid signal responds further to maintain HSC activation, the underlying molecular mechanisms are largely unknown. In this study, we sought to investigate the role of lncRNA-H19 in regulation of retinoic acid signals, and to further examine the underlying mechanism in this molecular context. We found that lncRNA-H19 upregulation could enhance retinoic acid signals to induce HSC activation, whereas lncRNA-H19 knockdown completely disturbed retinoic acid signals. Moreover, the activation of retinoic acid signals impaired the lncRNA-H19 knockdown mediated HSC inactivation. Interestingly, we also found that enhanced retinoic acid signals by lncRNA-H19 was associated with a coordinate increase in retinol metabolism during HSC activation. Increased retinol metabolism contributed to obvious lipid droplet consumption. Importantly, we identified that alcohol dehydrogenase III (ADH3) was essential for lncRNA-H19 to enhance retinoic acid signals. The inhibition of ADH3 completely abrogated the lncRNA-H19 mediated retinoic acid signals and HSC activation. Of note, we identified dihydroartemisinin (DHA) as a natural inhibitor for lncRNA-H19. Treatment with DHA significantly decreased the expression of lncRNA-H19, reduced the expression of ADH3, blocked retinoic acid signals, and in turn, inhibited HSC activation. Overall, these results provided novel implications to reveal the molecular mechanism of increased retinoic acid signals during HSC activation, and identify lncRNA-H19/ADH3 pathway as a potential target for the treatment of liver fibrosis.


Subject(s)
Aldehyde Oxidoreductases/metabolism , Hepatic Stellate Cells/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Tretinoin/metabolism , Animals , Artemisinins/pharmacology , Carbon Tetrachloride/adverse effects , Cell Line , Gene Knockdown Techniques , Lipid Metabolism , Liver/pathology , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Male , Mice , Mice, Inbred ICR , RNA, Long Noncoding/antagonists & inhibitors , Receptors, Retinoic Acid/drug effects , Receptors, Retinoic Acid/genetics , Receptors, Retinoic Acid/metabolism , Signal Transduction , Vitamin A/metabolism
9.
BMC Complement Altern Med ; 18(1): 205, 2018 Jul 04.
Article in English | MEDLINE | ID: mdl-29973206

ABSTRACT

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) plays an important role in the progression of renal interstitial fibrosis, which finally leads to renal failure. Oleanolic acid (OA), an activator of NF-E2-related factor 2 (Nrf2), is reported to attenuate renal fibrosis in mice with unilateral ureteral obstruction. However, the role of OA in the regulation of EMT and the underlying mechanisms remain to be investigated. This study aimed to evaluate the effects of OA on EMT of renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-ß1, and to elucidate its underlying mechanism. METHODS: Cells were incubated with TGF-ß1 in the presence or absence of OA. The epithelial marker E-cadherin, the mesenchymal markers, α-smooth muscle actin (α-SMA), fibronectin, Nrf2, klotho, the signal transducer (p-Smad2/3), EMT initiator (Snail), and ILK were assayed by western blotting. RESULTS: Our results showed that the NRK-52E cells incubated with TGF-ß1 induced EMT with transition to the spindle-like morphology, down-regulated the expression of E-cadherin but up-regulated the expression of α-SMA and fibronectin. However, the treatment with OA reversed all EMT markers in a dose-dependent manner. OA also restored the expression of Nrf2 and klotho, decreased the phosphorylation of Smad2/3, ILK, and Snail in cells which was initiated by TGF-ß1. CONCLUSION: OA can attenuate TGF-ß1 mediate EMT in renal tubular epithelial cells and may be a promising therapeutic agent in the treatment of renal fibrosis.


Subject(s)
Epithelial-Mesenchymal Transition/drug effects , Oleanolic Acid/pharmacology , Transforming Growth Factor beta1/metabolism , Animals , Cell Line , Rats , Signal Transduction/drug effects
10.
Mol Med Rep ; 13(4): 3709-10, 2016 04.
Article in English | MEDLINE | ID: mdl-26956998

ABSTRACT

Mol Med Rep 12:[Related article:] 7992­8002, 2015; DOI: 10.3892/mmr.2015.4449 Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Fig. 2; essentially, an image had been inadvertently selected from the same original photomicrograph to represent Fig. 2D, the centre panel [+80 nM phorbol-12-myristate-13-acetate (TPA), + 20 µM calycosin (Cal)] and Fig. 2F, the second panel from the right (+ 80 nM TPA, + 30 µM Cal). After having re-examined our original data, the panel originally featured in Fig. 2F was identified as having been selected incorrectly for the Figure. A corrected version of Fig. 2 is presented on next page, which features the proper data for Fig. 2F. Fig. 2D and F showed the effect of different concentrations of Cal on the migration and invasive ability of the TPA-treated A549 cells, respectively; Cal was demonstrated to inhibit the migration, and to suppress the invasive ability, of the A549 cells induced by TPA. Therefore, this error did not affect the overall conclusions reported in the present study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused.

11.
Mol Med Rep ; 12(6): 7992-8002, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26498639

ABSTRACT

The migration and invasion of lung cancer cells into the extracellular matrix contributes to the high mortality rates of lung cancer. The protein kinase C (PKC) and downstream signaling pathways are important in the invasion and migration of lung cancer cells. Calycosin (Cal), an effector chemical from Astragalus has been reported to affect the recurrence and metastasis of cancer cells via the regulation of the protein expression of matrix metalloproteinases (MMPs). The inhibition of Cal on the migration and invasion of A549 cells was investigated in the present study. Cell viability and apoptosis assays were performed using MTT and flow cytometric analyses. A wound healing assay and Transwell invasion assay were performed to evaluate the effect of Cal on A549 cell migration and invasion. Invasion­associated proteins, including MMP­2, MMP­9, E­cadherin (E­cad), integrin ß1, PKC­α and extracellular signal­regulated kinase 1/2 (ERK1/2) were detected using western blotting. In addition, PKC­α inhibitor, AEB071, and ERK1/2 inhibitor, PD98059, were used to determine the association between the suppression of PKC­α /ERK1/2 and invasion, MMP­2, MMP­9, E­cad and integrin ß1. Cal was observed to suppress cell proliferation and induce apoptosis. There were significant differences between the phorbol­12­myristate­13­acetate (TPA)­induced A549 cells treated with Cal and the untreated cells in the rates of migration and invasion. The levels of MMP­2, MMP­9, E­cad and integrin ß1 in the TPA­induced A549 cells changed markedly, compared with the untreated cells. In addition, the suppression of Cal was affected by the PKC inhibitor, AEB071, an ERK1/2 inhibitor, PD98059. The results of the present study indicated that Cal inhibited the proliferation, adhesion, migration and invasion of the TPA­induced A549 cells. The Cal­induced repression of PKC­α/ERK1/2, increased the expression of E­Cad and inhibited the expression levels of MMP­2, MMP­9 and integrin ß1, which possibly demonstrates the mechanism underlying the biological anticancer effects of Cal.


Subject(s)
Cell Proliferation/drug effects , Isoflavones/pharmacology , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Protein Kinase C-alpha/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cadherins/metabolism , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Flavonoids/pharmacology , Humans , Integrin beta1/metabolism , Isoflavones/chemistry , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Phorbol Esters/pharmacology , Protein Kinase C-alpha/antagonists & inhibitors , Pyrroles/pharmacology , Quinazolines/pharmacology , Signal Transduction/drug effects
12.
Zhongguo Zhong Yao Za Zhi ; 40(4): 758-64, 2015 Feb.
Article in Chinese | MEDLINE | ID: mdl-26137704

ABSTRACT

Development of the disease is the result of several factors involved in biological network changes. The nature of drug intervention is to regulate these pathological changes to the normal range. Advantages of traditional Chinese medicine (TCM) are to integrally and systematically regulate this biological networks and systematic pathology through multi-targets, multi-levels, multi-channels. Structural components TCM provides the controlled and precise basis "substance" for this regulation and also to clarify the "truth" of the nature of the regulation by the network pharmacology. Network pharmacology provides new strategy for the research on mechanism of structural components TCM. This study not only reflects the overall characteristics of the development of the disease, but also fully embodies the essence of TCM for preventing and treating diseases through changing traditional model on "one drug, one gene, one disease". This paper explores systematically the integration essence, features and research strategies of structural components TCM and the network pharmacology, understand the interaction of structural components TCM and body from the perspective of the overall concept of improving or restoring the balance of.biological networks. It is effective measure to reveal the structure of a multi-component for regulating biological networks mechanisms, and also provide new ideas and methods for further scientific research and innovation of structural component TCM.


Subject(s)
Drug Therapy , Drugs, Chinese Herbal/pharmacology , Drug Interactions , Drugs, Chinese Herbal/chemistry , Gene Regulatory Networks/drug effects , Humans , Medicine, Chinese Traditional
13.
Zhongguo Zhong Yao Za Zhi ; 40(5): 840-6, 2015 Mar.
Article in Chinese | MEDLINE | ID: mdl-26087543

ABSTRACT

Alisma orientalis is a traditional herb medicine commonly used in clinical. With the increasing report of its toxicity in clinical, the renal toxicity of Alisma orientalis has got gradually attention. This paper systematically reviews the research on the chemical material basis of Alisma orientalis including its chemical composition and toxicity of ingredients; and also declares its toxic ingredients and targets according to Network toxicology. Based on the controversy on renal toxicity of Alisma orientalis, we analyzed the possible reasons that may be associated with renal toxicity. It might be associated with the differences of the material basis composition and regulatory toxicology network, differences in employed processing technology, the metabolic function leading to accumulation of compounds, dosage and duration of the experiment and compatibility. The review provides possible reference and ideas for the quality control and rational use of Alisma orientalis.


Subject(s)
Alisma/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/toxicity , Alisma/toxicity , Animals , Humans , Molecular Structure
14.
Molecules ; 19(11): 18881-96, 2014 Nov 17.
Article in English | MEDLINE | ID: mdl-25407723

ABSTRACT

Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological actions and pharmacology. In the present study, an ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)-based approach was developed to profile the metabolites of astragaloside IV in rat plasma, bile, urine and feces samples. Twenty-two major metabolites were detected. The major components found in plasma, bile, urine and feces included the parent chemical and phases I and II metabolites. The major metabolic reactions of astragaloside IV were hydrolysis, glucuronidation, sulfation and dehydrogenation. These results will help to improve understanding the metabolism and reveal the biotransformation profiling of astragaloside IV in vivo. The metabolic information obtained from our study will guide studies into the pharmacological activity and clinical safety of astragaloside IV.


Subject(s)
Drugs, Chinese Herbal/chemistry , Saponins/metabolism , Triterpenes/metabolism , Animals , Astragalus propinquus/chemistry , Bile/chemistry , Bile/metabolism , Chromatography, High Pressure Liquid , Feces/chemistry , Male , Medicine, Chinese Traditional , Rats , Rats, Sprague-Dawley , Saponins/blood , Saponins/urine , Tandem Mass Spectrometry/methods , Triterpenes/blood , Triterpenes/urine
15.
Zhongguo Zhong Yao Za Zhi ; 39(5): 941-5, 2014 Mar.
Article in Chinese | MEDLINE | ID: mdl-25204195

ABSTRACT

Most Chinese medicine has good clinical efficacy and application. However, the material basis is vague for the lack of basic research, the value of Chinese medicine is hard to reflect for the low technology level and product quality is difficult to maintain for the quality control indicator selection is incorrect. Chinese medicine Jinfukang oral liquid is a typical product of Chinese medicines. Jinfukang oral liquid was selected as a model drug in this article. Based on the overall concept and systems theory of traditional Chinese medicine, the research idea and technology system for modern Chinese medicine secondary exploitation was formed. The system includes three parts, for the first, basic research to make clear the components structure and their action mechanism, for the second, technology upgraded to optimize process and improve the product quality, for the last, exploring the associated industry to form the industrial chain. The research ideas and technology system based on the material basis research and development of modern Chinese medicine, guided with component structure in Chinese medicine and aimed clinical needs. This research ideas and technology system provides strategies and methods for the development of modern Chinese medicine secondary exploitation.


Subject(s)
Chemistry, Pharmaceutical , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/standards , Administration, Oral , Chemistry, Pharmaceutical/standards , Drug Therapy/standards , Humans , Quality Control
16.
Zhongguo Zhong Yao Za Zhi ; 39(3): 370-7, 2014 Feb.
Article in Chinese | MEDLINE | ID: mdl-24946533

ABSTRACT

Based on practice of Epimedium processing mechanism for many years and integrated multidisciplinary theory and technology, this paper initially constructs the research system for processing mechanism of traditional Chinese medicine based on chemical composition transformation combined with intestinal absorption barrier, which to form an innovative research mode of the " chemical composition changes-biological transformation-metabolism in vitro and in vivo-intestinal absorption-pharmacokinetic combined pharmacodynamic-pharmacodynamic mechanism". Combined with specific examples of Epimedium and other Chinese herbal medicine processing mechanism, this paper also discusses the academic thoughts, research methods and key technologies of this research system, which will be conducive to systematically reveal the modem scientific connotation of traditional Chinese medicine processing, and enrich the theory of Chinese herbal medicine processing.


Subject(s)
Drug Compounding/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Epimedium/chemistry , Intestinal Absorption , Medicine, Chinese Traditional/methods , Animals , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/pharmacology
17.
Int J Nanomedicine ; 9: 2327-33, 2014.
Article in English | MEDLINE | ID: mdl-24872695

ABSTRACT

In this study, a novel carbon nanopowder (CNP) drug carrier was developed to improve the oral bioavailability of apigenin (AP). Solid dispersions (SDs) of AP with CNP were prepared, and their in vitro drug release and in vivo performance were evaluated. The physicochemical properties of the formulations were examined by differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. Drug release profiles showed that AP dissolution from the CNP-AP system (weight ratio, 6:1) after 60 minutes improved by 275% compared with that of pure AP. Moreover, the pharmacokinetic analysis of SD formulations in rats showed that the AP area under the curve0-t value was 1.83 times higher for the CNP-AP system than for pure AP, indicating that its bioavailability was significantly improved. In addition, compared with pure AP, SDs had a significantly higher peak and shorter time to peak. Preliminary intestinal toxicity tests indicated that there was no significant difference in the tissues of the rats treated with the CNP-AP system, rats treated with the CNP alone, and controls. In conclusion, CNP-based SDs could be used for enhancing the bioavailability of poorly water-soluble drugs while also improving drug safety.


Subject(s)
Apigenin/administration & dosage , Apigenin/pharmacokinetics , Emulsions/chemical synthesis , Nanocapsules/chemistry , Nanotubes, Carbon/chemistry , Oral Mucosal Absorption/physiology , Administration, Oral , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Apigenin/chemistry , Biological Availability , Diffusion , Drug Synergism , Male , Metabolic Clearance Rate , Nanocapsules/toxicity , Nanocapsules/ultrastructure , Nanotubes, Carbon/toxicity , Nanotubes, Carbon/ultrastructure , Particle Size , Powders , Rats , Rats, Sprague-Dawley , Solubility
18.
Article in English | MEDLINE | ID: mdl-24631806

ABSTRACT

In our research, ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS) was established for analyzing the metabolite profiles of Danshensu (DSS) in rat feces, bile, urine, plasma and the possible metabolic pathways were subsequently proposed after the oral dose of 80mg/kg; rat biological samples were collected and pretreated by protein precipitation. Then, the samples were injected into an Acquity ultraperformance liquid chromatography BEHC column with mobile phase consisted of acetonitrile (solvent A)-0.1% formic acid-water (solvent B) with a linear gradient elution program. Totally, 17 metabolites of DSS were identified, including 4, 5, 4 and 4 metabolites in the feces, urine, blood, and bile samples respectively. Most of them were to our knowledge reported for the first time. The results indicated that DSS was metabolized via dehydrogenation, deoxygenation, methylation, glucuronidation, and sulfation pathways in vivo. Among these, methylation was considered as the main physiologic processes of it. This study revealed that U-HPLC/Q-TOF-MS was more accurate and sensitive to detect and identify the possible metabolites and to better understand the metabolism of DSS in vivo.


Subject(s)
Chromatography, High Pressure Liquid/methods , Lactates/analysis , Lactates/metabolism , Animals , Bile/chemistry , Feces/chemistry , Lactates/chemistry , Male , Mass Spectrometry/methods , Metabolic Networks and Pathways , Rats , Rats, Sprague-Dawley
19.
Zhongguo Zhong Yao Za Zhi ; 39(21): 4272-6, 2014 Nov.
Article in Chinese | MEDLINE | ID: mdl-25775807

ABSTRACT

Chinese medicine prescriptions are the wisdom outcomes of traditional Chinese medicine (TCM) clinical treatment determinations which based on differentiation of symptoms and signs. Chinese medicine prescriptions are also the basis of secondary exploitation of TCM. The study on prescription helps to understand the material basis of its efficacy, pharmacological mechanism, which is an important guarantee for the modernization of traditional Chinese medicine. Currently, there is not yet dissertation n the method and technology system of basic research on the prescription of Chinese medicine. This paper focuses on how to build an effective system of prescription research technology. Based on "component structure" theory, a technology system contained four-step method that "prescription analysis, the material basis screening, the material basis of analysis and optimization and verify" was proposed. The technology system analyzes the material basis of the three levels such as Chinese medicine pieces, constituents and the compounds which could respect the overall efficacy of Chinese medicine. Ideas of prescription optimization, remodeling are introduced into the system. The technology system is the combination of the existing research and associates with new techniques and methods, which used for explore the research thought suitable for material basis research and prescription remodeling. The system provides a reference for the secondary development of traditional Chinese medicine, and industrial upgrading.


Subject(s)
Drug Prescriptions , Medicine, Chinese Traditional
20.
J Ethnopharmacol ; 151(1): 591-600, 2014.
Article in English | MEDLINE | ID: mdl-24269777

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Moutan Cortex (MC, family: Paeonia suffruticosa Andr.) is a well-known traditional herbal medicine that has been shown to hold a protective effect on inflammation in several diseases. However, its anti-inflammatory activity on diabetic nephropathy (DN) has been less reported. The present study was conducted to evaluate the potential attenuation activities of MC on inflammation in AGEs-induced rat mesangial cells dysfunction and high-glucose-fat diet and streptozotocin (STZ)-induced DN rats and explore the possible mechanism underlying its DN effect. MATERIALS AND METHODS: The inflammation in mesangial cells (HBZY-1) was induced by 200 µg/ml advanced glycation end products (AGEs). DN rats model was established by an administration high-glucose-fat diet and an intraperitoneal injection of STZ (30 mg/kg). Interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) level in cell supernatant and rats serum were detected by appropriate kits. A co-culture system of mesangial cells and macrophages was performed to evaluate the migration of macrophages. Immunohistochemical assay was applied to examine transforming growth factor beta1 (TGF-ß1), IL-6, MCP-1 and intercellular adhesion molecule-1 (ICAM-1) expression in kidney tissues of rats. Furthermore, western blot analysis was carried out to examine TGF-ß1, IL-6, MCP-1, ICAM-1 and RAGE protein expressions in mesangial cells. RESULTS: Pretreatment with MC could significantly inhibit AGEs-induced migration of macrophages in the co-culture system of mesangial cell and macrophage. MC could decrease IL-6 and MCP-1 levels in serum of DN rats in a dose-dependent manner. Furthermore, MC also improved the blood glucose, serum creatinine and urine protein levels. Both immunocytochemistry analysis and western blot analysis showed that MC decreased significantly the over-expression of IL-6, MCP-1, TGF-ß1, ICAM-1 and RAGE in mesangial cells or kidney tissues. Additionally, the protein expression of proinflammatory cytokine could also be down-regulated by the pretreatment of RAGE-Ab (5 µg/ml). CONCLUSION: These findings indicated that the extract of MC had an amelioration activity on the inflammation in AGEs-induced mesangial cells dysfunction and high-glucose-fat diet and STZ-induced DN rats. The protective effect might be associated with the intervention of MC via target of RAGE. These findings suggested that MC might be a benefit agent for the prevention and treatment of DN.


Subject(s)
Diabetes Mellitus, Experimental/complications , Dietary Fats/adverse effects , Drugs, Chinese Herbal/pharmacology , Glucose/adverse effects , Glycation End Products, Advanced/toxicity , Mesangial Cells/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Line , Diabetic Nephropathies/drug therapy , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Gene Expression Regulation/drug effects , Glucose/administration & dosage , Mesangial Cells/metabolism , Paeonia/chemistry , Random Allocation , Rats
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