Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model

By activating PPAR-γ, thiazolidinediones normalize glucose levels in animal models of type 2 diabetes and in patients with this pathology. The aim of the present study was to analyze 219 new derivatives in silico and select the best for synthesis, to be evaluated for acute oral toxicity in female rats and for control of diabetes-related parameters in a rat model of streptozotocin-induced diabetes. The best compound was chosen based on pharmacokinetic, pharmacodynamic, and toxicological parameters obtained in silico and binding orientation observed by docking simulations on PPAR-γ. Compound 1G was synthesized by a quick and easy Knoevenagel condensation. Acute oral toxicity was found at a dose greater than 2000 mg/Kg. Compound 1G apparently produces therapeutic effects similar to those of pioglitazone, decreasing glycaemia and triglyceride levels in diabetic animals, without liver damage. Moreover, it did not cause a significant weight gain and tended to reduce polydipsia and polyphagia, while diminishing systemic inflammation related to TNF-α and IL-6. It lowered the level of endogenous antioxidant molecules such as reduced glutathione and glutathione reductase. In conclusion, 1G may be a candidate for further testing as an euglycemic agent capable of preventing the complications of diabetes.

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Correction: In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model

Biomaterials Science ◽

10.1039/d0bm90110e ◽

2021 ◽

Author(s):

Xiuying Li ◽

Zhenhong Wei ◽

Binxi Li ◽

Jing Li ◽

Huiying Lv ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Rat Model ◽

Burn Injury ◽

Therapeutic Effects

Correction for ‘In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model’ by Xiuying Li et al., Biomater. Sci., 2019, 7, 2861–2872, DOI: 10.1039/C9BM00242A.

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Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells

Pharmaceutics ◽

10.3390/pharmaceutics13050647 ◽

2021 ◽

Vol 13 (5) ◽

pp. 647

Author(s):

Henry T. Hsueh ◽

Yoo-Chun Kim ◽

Ian Pitha ◽

Matthew D. Shin ◽

Cynthia A. Berlinicke ◽

...

Keyword(s):

Retinal Ganglion Cells ◽

Rat Model ◽

Kinase Inhibitor ◽

Ganglion Cells ◽

Corneal Neovascularization ◽

Therapeutic Effects ◽

Subconjunctival Injection ◽

Retinal Ganglion ◽

Drug Concentrations ◽

Complementary Strategy

Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.

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Modified Yukmijihwangtang Suppresses the Production of Proinflammatory Cytokines in the Intravesical Hydrochloric Acid-Induced Cystitis Rat Model via the NF-κB Pathway

The American Journal of Chinese Medicine ◽

10.1142/s0192415x12500255 ◽

2012 ◽

Vol 40 (02) ◽

pp. 321-334 ◽

Cited By ~ 9

Author(s):

Jeong-Won Lee ◽

Sok Cheon Pak ◽

Songhee Jeon ◽

Dong-Il Kim

Keyword(s):

Medicinal Plants ◽

Rat Model ◽

In Vitro Study ◽

Intravesical Instillation ◽

Bladder Function ◽

No Production ◽

Therapeutic Effects ◽

T24 Cells ◽

Injury Group

Yukmijihwangtang (YM), a boiled extract of medicinal plants, has been prescribed for patients with kidney dysfunction in Korea; however, the mechanism underlying its therapeutic effects has not been fully elucidated. This study was conducted to evaluate the beneficial effects on bladder function by using modified YM (M-YM), which included Ulmi radicis cortex in addition to the six traditional medicinal plants in YM. Bladder irritation of the rats was caused by intravesical instillation of HCl . The animals were divided into six groups: sham group, cystitis-injury group with no treatment, cystitis-injury group with prednisolone treatment (5 mg/kg), and cystitis-injury with M-YM treatment (100, 200 or 500 mg/kg groups). Whole bladders were collected at day eight after injury. Samples were analyzed by histological and immunological examinations. An in vitro study was performed to determine whether M-YM extracts inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production and I κ B phosphorylation in a human uroepithelial cell line of T24 cells. Administration of M-YM notably improved bladder histological changes, and suppressed IL-6/TNF α production and I κ B phosphorylation in a rat model of chronic cystitis. M-YM also inhibited LPS-induced NO production and I κ B phosphorylation in T24 cells. This study suggests that administration of M-YM might be an applicable therapeutic traditional medicine for the treatment of interstitial cystitis.

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Functional Recovery after Scutellarin Treatment in Transient Cerebral Ischemic Rats: A Pilot Study with18F-Fluorodeoxyglucose MicroPET

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/507091 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Jin-hui Li ◽

Jing Lu ◽

Hong Zhang

Keyword(s):

Cerebral Ischemia ◽

Rat Model ◽

Neurological Deficit ◽

Neuronal Maturation ◽

Vascular Density ◽

Sham Operation ◽

Therapeutic Effects ◽

Neuroprotective Effects ◽

Neuronal Marker ◽

Cerebral Ischemic

Objective. To investigate neuroprotective effects of scutellarin (Scu) in a rat model of cerebral ischemia with use of18F-fluorodeoxyglucose (18F-FDG) micro positron emission tomography (microPET).Method. Middle cerebral artery occlusion was used to establish cerebral ischemia. Rats were divided into 5 groups: sham operation, cerebral ischemia-reperfusion untreated (CIRU) group, Scu-25 group (Scu 25 mg/kg/d), Scu-50 group (Scu 50 mg/kg/d), and nimodipine (10 mg/Kg/d). The treatment groups were given for 2 weeks. The therapeutic effects in terms of cerebral infarct volume, neurological deficit scores, and cerebral glucose metabolism were evaluated. Levels of vascular density factor (vWF), glial marker (GFAP), and mature neuronal marker (NeuN) were assessed by immunohistochemistry.Results. The neurological deficit scores were significantly decreased in the Scu-50 group compared to the CIRU group (P<0.001).18F-FDG accumulation in the ipsilateral cerebral infarction increased steadily over time in Scu-50 group compared with CIRU group (P<0.01) and Scu-25 group (P<0.01). Immunohistochemical analysis demonstrated Scu-50 enhanced neuronal maturation.Conclusion.18F-FDG microPET imaging demonstrated metabolic recovery after Scu-50 treatment in the rat model of cerebral ischemia. The neuroprotective effects of Scu on cerebral ischemic injury might be associated with increased regional glucose activity and neuronal maturation.

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Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model

Chinese Medicine ◽

10.1186/s13020-021-00446-x ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Jiye Chen ◽

Yongjian Zhang ◽

Yongcheng Wang ◽

Ping Jiang ◽

Guofeng Zhou ◽

...

Keyword(s):

Signaling Pathway ◽

Rat Model ◽

Experimental Studies ◽

Matrix Metalloproteinase 2 ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Therapeutic Effects ◽

Active Ingredients ◽

Active Compounds ◽

Guizhi Decoction

Abstract Background Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. Methods The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. Results A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C–C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats. Conclusion The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis.

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Abstract 13810: TT-00920, a Clinical Stage Novel Phosphodiesterase 9 Inhibitor, Protects Against Heart Failure in a Rat Model of Myocardial Infarction

Circulation ◽

10.1161/circ.142.suppl_3.13810 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Zejuan Sheng ◽

Xiaoyan Qiang ◽

Guoyu Li ◽

Huimin Wang ◽

Wenxin Dong ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Cardiac Function ◽

Rat Model ◽

Cardiac Fibrosis ◽

Clinical Stage ◽

Left Ventricular ◽

Guanosine Monophosphate ◽

Therapeutic Effects ◽

Dependent Manner

Introduction: Phosphodiesterase 9 (PDE9) controls natriuretic-peptide-stimulated cyclic guanosine monophosphate in cardiac myocytes and is stongly upregulated in human heart failure, suggesting its potential as a promising therapeutic target in heart failure. Here we investigated the potential effects of TT-00920, a clinical stage novel and highly selective PDE9 inhibitor, on heart failure in a rat model of myocardial infarction. Methods: Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation in male Sprague Dawley rats. After 4-week treatment of vehicle, LCZ696, TT-00920, or TT-00920/Valsartan by oral gavage, efficacy was assessed by echocardiography and cardiac histopathology. Results: TT-00920 had remarkably improved cardiac function, protected against cardiac remodeling and fibrosis in a dose-dependent manner. TT-00920/Valsartan combination showed superior beneficial efficacy when compared to TT-00920 or LCZ696 single agent.Figure 1. TT-00920 improved cardiac function and ventricular remodeling.Figure 2. TT-00920 attenuated cardiac fibrosis in peri-infarct zone. Conclusions: TT-00920 reversed LAD-induced left ventricular dysfunction and remodeling, supporting its potential as a novel therapeutic agent for heart failure. The superior efficacy of TT-00920/Valsartan combination suggests that TT-00920 and renin-angiotensin-aldosterone system inhibitors may have additive therapeutic effects in heart failure.TT-00920 is currently being evaluated in Phase 1 clinical study for safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers (NCT04364789).

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Moxibustion Alleviates Injury in a Rat Focal Segmental Glomerulosclerosis Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/7169547 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yi Li ◽

Yuxia Sun ◽

Chunling Zhang ◽

Ke Wang ◽

Peicheng Shen ◽

...

Keyword(s):

Focal Segmental Glomerulosclerosis ◽

Rat Model ◽

Interstitial Fibrosis ◽

Similar Efficacy ◽

Glomerular Sclerosis ◽

Control Group ◽

Therapeutic Effects ◽

Repeated Injection ◽

Moxibustion Group ◽

Segmental Glomerulosclerosis

Objectives. To evaluate the therapeutic effects of moxibustion at Shenshu (BL-23) and Geshu (BL-17) acupoints in a focal segmental glomerulosclerosis (FSGS) model in rats. Methods. A FSGS rat model was established by single nephrectomy and repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, losartan (positive control) group, Shenshu moxibustion group, and Geshu moxibustion group. Molecular indicators of kidney function and renal pathological changes were monitored. Results. Urinary protein, serum creatinine, urea nitrogen, and serum uric acid were significantly reduced after 12-week intervention with losartan, Shenshu, or Geshu moxibustion. Renal α-SMA, FN, and TGF-β were also decreased, while podocin and nephrin protein and mRNA were increased. The pathological damage in renal tissue was obviously alleviated by all three treatments, which suggests that moxibustion may have similar efficacy to losartan in the treatment of FSGS. Conclusion. Moxibustion alleviates podocyte injury and inhibits renal interstitial fibrosis in the FSGS rat model, thereby minimizing the progression of glomerular sclerosis and improving renal function.

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Therapeutic effects of Cyathula officinalis Kuan and its active fraction on acute blood stasis rat model and identification constituents by HPLC-QTOF/MS/MS

Pharmacognosy Magazine ◽

10.4103/pm.pm_560_16 ◽

2017 ◽

Vol 13 (52) ◽

pp. 693 ◽

Cited By ~ 5

Author(s):

Lian Yin ◽

Yanmei Cao ◽

Cuicui Gu ◽

Fangli Zhao ◽

Yuanlin Tang ◽

...

Keyword(s):

Rat Model ◽

Blood Stasis ◽

Therapeutic Effects ◽

Active Fraction

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Effects of Haima Duobian Pill in a Rat Model of Kidney Yang Deficiency Syndrome

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6696234 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yijia Zeng ◽

Tingna Li ◽

Xiaorui Zhang ◽

Yuanyuan Ren ◽

Qinwan Huang ◽

...

Keyword(s):

Rat Model ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Cyclic Guanosine Monophosphate ◽

Deficiency Syndrome ◽

Guanosine Monophosphate ◽

Network Pharmacology ◽

Enzyme Linked Immunosorbent Assay ◽

Therapeutic Effects ◽

Kidney Yang Deficiency

Objective. Modern research shows that Haima Duobian pill (HDP) can relieve the kidney yang deficiency syndrome (KYDS), but the mechanism is still unclear. The aim of this work was to study the effects of HDP in a rat model of KYDS. Materials and Methods. The network pharmacology methods were used to predict the therapeutic effects of Haima Duobian pill. Adenine was used to establish the rat model of kidney yang deficiency syndrome. The general physical signs of rats were observed after different doses of Haima Duobian pill (HDP) were given. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), and gonadotropin-releasing hormone (GnRH) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Then, the histopathologic changes and sperm activity were detected. Results. HDP could improve the general signs of kidney yang deficiency syndrome rats. After the rats were treated with HDP, the expression of cGMP and E2 was significantly inhibited and the expression of cAMP and T was significantly increased. The pathological damage of testis, epididymis, and seminal vesicle was alleviated, and the sperm activity was improved. Conclusion. For adenine-induced kidney yang deficiency syndrome in rats, HDP had a significant therapeutic effect.

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