Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Body Weight ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Toxic Effect ◽  
Treatment Period ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
The Body ◽  
Therapeutic Effects ◽  
Toxicology Study

Abstract Background : Angong Niuhuang Pill (ANP) is one of the most famous drugs to treat stroke in China, but there is no definite treatment period in drug instruction. In this study, we used middle cerebral artery occlusion (MCAO) model to evaluate its therapeutic effects of different treatment periods and studied its toxic effect in rats. Methods : Protective effect of ANP was observed in the cerebral ischemia-reperfusion model in rats; ANP (270 mg/kg) three different treatment period included 1 day, 4 days and 7 days. The observation period was 30 days. Therapeutic effect was evaluated by detecting neurological function, cerebral infraction volume, brain histology and cytokines. Three dose including 550, 1640, 4910 mg/kg were studied in toxicology study. The administration period was 30 days. Toxic effect was evaluated by detecting appearance, behavior, excrement character, food-intake, body weight, hematological parameters and biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP. Results : Seven days treatment period of ANP had better effect than 1 day and 4 days treatment periods in rat MCAO model from neurological function scores, the volume of cerebral infarction, brain histology and the serum content of IL-1β, TNF-α and NO; the brain content of IL-1β and NO. The results of 30 days multiple dose toxicology study showed no animal death in all groups; in ANP 4910 mg/kg group, the kidney and liver coefficient increased about 10%, the body weight grew more slowly, the TBA increased slightly. There was no abnormal change in histology. These all recovered after drug withdraw for 8 weeks. Conclusion: Seven days treatment period of ANP had more protective effect than 1 day and 4 days treatment periods in ischemic stroke rat. No observed adverse effect level (NOAEL) of ANP was 1640 mg/kg; the safety margin of ANP was 270-1640 mg/kg. These data provided reference to modify drug instruction.

Preclinical toxicology studies with Y15, a novel focal adhesion kinase (FAK) inhibitor.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13561-e13561
Author(s):  
William G. Cance ◽  
Leslie Curtin ◽  
Sandra Buitrago ◽  
Vita Golubovskaya
Keyword(s):  
Body Weight ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Oral Delivery ◽  
Clinical Chemistry ◽  
Small Animal ◽  
The Body ◽  
Large Animal ◽  
Toxicology Study ◽  
High Doses

e13561 Background: Focal Adhesion Kinase (FAK) is overexpressed in many types of tumors and plays a major role in survival signaling. Recently, we developed a FAK scaffolding inhibitor, Y15 that targeted the main FAK autophosphorylation site (Y397) and had high efficacy in blocking tumor growth in many xenograft mice models. We performed a small animal toxicology study of Y15 and detected the maximal tolerated dose of this drug in mice. Methods: The toxicology study was performed in CD-1 albino [Hsd:ICR(CD-1)] mice with Y15 inhibitor delivered either by intraperitoneal injection (IP) or by oral delivery. Clinical chemistry data were collected by Hemagen Analyst II automatic Chemistry analyzer. In addition, hematology, body weight, mortality, and histopathology on different organs were analyzed in all mice. Results: We delivered Y15 by IP injection at 15 (low), 30 (medium) and 45 mg/kg (high) doses daily for 5 days/week during a 28 day study, or orally by gavage at 100 and 200 mg/kg daily during a 7 day study. The maximal tolerated dose by IP during 28 day study was 30 mg/kg. The maximal tolerated dose during single oral dose administration was 200 mg/kg and 100 mg/kg during 7 day study. Y15 did not cause any mortality or statistically significant differences in the body weight at 30mg/kg IP delivery during a 28-day study and at 100 mg/kg by oral delivery during a 7 day study. There were no significant clinical chemistry changes in alkaline phosphatase, gamma glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, amylase, blood urea nitrogen, glucose, phosphorus, calcium, albumin, cholesterol, creatine kinase, total bilirubin, total protein and globulin. Finally, no significant histopathological changes were observed by necropsy in different organs at 30 mg/kg by IP and at 100 mg/kg dose by oral delivery. Conclusions: The Y15 FAK autophosphorylation inhibitor is well tolerated in mice and caused no significant toxicity by IP and oral delivery, suggesting it is a promising candidate for further large animal toxicology study prior to human trials.

Discussion on rationality of administration of Angong Niuhuang Pills from pharmacological and toxicological perspectives

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Normal Control ◽  
Ischemia Reperfusion ◽  
Hematological Parameters ◽  
Scientific Basis ◽  
Neurological Function ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
Toxicology Study ◽  
Body Weights

Abstract Background: Investigate the different treatment course of ANP from pharmacology and toxicology to provide scientific basis for clinic use. Method: In pharmacology study, cerebral ischemia-reperfusion model was made; rats were divided into six groups, Sham, model, aspirin 25 mg/kg, ANP 270 mg/kg (1 day, 4 days and 7 days) groups. Rats were fed for 30 days. Neurological function, cerebral infraction volume, brain histopathology, cytokines were detected; in toxicology study, rats were divided into four groups, normal control, ANP (550, 1640, 4910 mg/kg) group. ANP was daily administered by gavage for 30 days. Detection indicators included appearance, behavior, excrement character, food-intake, body weight, hematological parameters, etc. In addition, biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP were also detected. Result: In pharmacology study, compared with model group, the neurological function scores of ANP 270mg/kg (1 day, 4 days and 7 days) were decreased (P<0.11 or P<0.05); the volume of ANP 270mg/kg (1 day and 7 days) were decreased (P<0.05); the R value of ANP 270mg/kg (1 day, 4 days and 7 days) groups were decreased (P<0.11 or P<0.05); the serum content of IL-1β, TNFα and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P< 0.05); the brain content of IL-1β and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P<0.05). In toxicology study, no mortality, ophthalmic abnormalities were identified. Compared with normal control group, body weights were significantly lower in ANP 4910 mg/kg group; TBA was significantly increased in ANP 4910mg/kg group; liver organ coefficient of female rats of ANP 4910 mg/kg group was increased (P < 0.05); kidney organ coefficient of male rats of ANP 1640mg/kg, 4910 mg/kg groups were increased (P < 0.05), these all recovered after drug withdraw for 8 weeks. Conclusion: The effect of ANP 270 mg/kg (7 days) was much better than ANP (1 day and 4 days). ANP 550mg/kg is non toxicity dose. So, ANP is taken one pill peer day for 7 days is safety and effective, it can be used as the scientific basis for clinic use.

scholarly journals Oxymatrine Improves the Integrity of the Blood-Brain Barrier after Cerebral Ischemia-Reperfusion Injury through the Caveolin-1/MMP-9 Signaling Pathway

2020 ◽  
Author(s):  
Jiaoyan Yu ◽  
Qingqing Liu ◽  
Xi Li ◽  
Mei Zhao ◽  
Ting Sun ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Brain Barrier ◽  
High Morbidity ◽  
Cerebral Ischemia Reperfusion ◽  
Blood Brain

Abstract BackgroundIschemic stroke (IS) is a major neurological disease worldwide and is associated with extremely high morbidity and mortality. Oxymatrine (OMT) has neuroprotective properties and protects against IS. However, whether its protective effect involves the blood-brain barrier (BBB) integrity is unknown.MethodsHere, we used in vivo and in vitro models of IS to evaluate the protective effect of OMT and its mechanism with regard to the BBB. We assayed the role of OMT using neurological function scores and triphenyltetrazolium chloride, Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining.ResultsOMT significantly improved the neurological function and brain state and reduced BBB permeability in a mouse model of cerebral ischemia-reperfusion. Additionally, OMT improved the tight junction of bEend.3 cells under oxygen-glucose deprivation. Moreover, intracranial lentivirus injection-induced Cav-1 knockdown reduced the neuroprotective effects of OMT.ConclusionsOMT could improve I/R injury-induced damage to the BBB, and its effects may be related to the regulation of the Cav-1/MMP-9 signaling pathway. This suggests that OMT may offer effective protection against BBB injury after I/R.

scholarly journals The Caprine Casein-Alpha-S2 Protein Modulates the Molecular Mechanism 2 of Insulin Signal Transduction in Type2 Diabetes Rat

2020 ◽  
Author(s):  
Fatchiyah Fatchiyah ◽  
Rista Nikmatu Rohmah ◽  
Lidwina Faraline Triprisila ◽  
Takeshi Ohta ◽  
Hazna Noor Meidinna
Keyword(s):  
Body Weight ◽  
Diabetes Management ◽  
Diabetic Rats ◽  
The Body ◽  
Therapeutic Effects ◽  
Mrna Levels ◽  
Caprine Milk ◽  
Type2 Diabetes ◽  
Tnf Α ◽  
Protein Treatment

This study purpose was to investigate the association of casein-alpha-S2 protein of Caprine milk and molecular mechanismofinsulin signaltransduction in type2 diabetes mellitus (T2DM). The Caprine milk CSN1S2 protein treatment of 0, 375, 750, and 1500mg/kg BW were conducted to the control and T2DM rats. We observed several physiological parameters of all rats. The levels of insulin and TNF-α in the plasma were measured using ELISA.The expressions of proteins and mRNA levels of diabetes-related genes in the pancreas tissues were analyzed using Western Blotting and Real-Time PCR, respectively. Our study found that diabetic rats had lower body weight, food intake, and fecal weight compared with control rats. The Caprine milk CSN1S2 protein consumption affected the body weight of diabetic rats to increase, especially at the dose of 750mg/kg BW.Interestingly, the genes associated with insulin signaling were improved by the CSN1S2 protein treatment in diabetic rats, although their blood glucose and cholesterol level were not affected. The diabetic rats showed an elevated insulin level and GLUT4 protein expression after treatment. We also reported that the CSN1S2-treated diabetic rats had a gradually reduced expression of TNF-α and VCAM-1 in dose-dependent. Moreover, the 750mg/kg BW of CSN1S2 treatment enhanced the mRNA expressions of INS-receptor, GLUT4, IGF-1, CAMKK, and CAMKIV in diabetic rats. The ability of Caprine milk CSN1S2 protein to regulate the molecular mechanisms in the diabetes-signaling pathway indicated its potential therapeutic effects on diabetes management.

scholarly journals Ekstrak Propolis Memperbaiki Profil Berat Badan Tikus Model Kanker Payudara yang Diinduksi dengan 7,12-dymethyilbenz(a) antracene (DMBA)

2019 ◽  
Vol 29 (2) ◽  
pp. 135-142
Author(s):  
Zauhani Kusnul ◽  
Suryono Suryono ◽  
Anas Tamsuri
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Corn Oil ◽  
Histopathological Examination ◽  
The Body ◽  
Therapeutic Effects ◽  
Female Rat ◽  
Sprague Dawley ◽  
Propolis Extract ◽  
Sprague Dawley Rats

Abstract Body weight is a general indicator for assessing health status. Various diseases cause drastic weight loss, including cancer. Propolis is a bee product that has various therapeutic effects such as; anti-bacterial, antitumor, antioxidant and immunomodulatory. Propolis is also reported to be able to reduce digestive organ disorders, increase appetite and improve metabolic processes. Chemicals such as 7.12-dymethyilbenz (a) antracene (DMBA) are widely reported to have strong carcinogenic effects, especially in Sprague–Dawley rat. This study aims to assess the effect of propolis extract on the weight of Sprague–Dawley female rat induced with DMBA (7,12-dymethylbenz (a) antracene). Twenty-four female Sprague–Dawley rats 45-50 days old were induced by DMBA with a combination of injection and oral methods, as negative controls 6 Sprague–Dawley rats without DMBA induction. At the 11th week randomized negative control rats and DMBA treated rats were taken for histopathological examination of breast tissue. After it was found that rat with DMBA treatment were positive for breast cancer, in the 12th week the rat that had received DMBA treatment were divided into 4 groups, 3 groups received oral propolis extract through a gastric sonde with doses 50, 100 and 200 mg in 1 ml of corn oil, 1 group as a positive control did not get the treatment of propolis extract. Body weight is weighed before starting treatment and monitored every two weeks to 15 weeks. The results of weighing showed that the group of rat that received DMBA increased their body weight lower than the group without DMBA, and then the treatment group of propolis extract increased their body weight higher than the group without the treatment of propolis extract. The results showed that the treatment of propolis extract had a potency to improve the body weight profile of rat breast cancer model induced by DMBA. Abstrak Berat badan merupakan indikator umum untuk menilai status kesehatan. Berbagai penyakit menyebabkan penurunan berat badan yang drastis, diantaranya adalah kanker. Propolis merupakan produk lebah yang memiliki berbagai efek terapi seperti; anti bakteri, anti tumor, antioksidan dan imunomodulator. Propolis juga dilaporkan mampu menurunkan gangguan organ pencernaan, peningkatan nafsu makan, dan perbaikan proses metabolisme. Bahan kimia seperti 7,12-dymethyilbenz(a)antracene (DMBA) banyak dilaporkan memiliki efek karsinogenik yang kuat khususnya terhadap tikus Sprague–Dawley. Penelitian ini bertujuan untuk menilai pengaruh pemberian ekstrak propolis terhadap berat badan tikus Sprague–Dawley betina yang diinduksi untuk mengalami kanker payudara dengan DMBA. Sebanyak 24 ekor tikus Sprague– Dawley betina berumur 45-50 hari diinduksi dengan DMBA dengan kombinasi metode injeksi dan oral, sebagai kontrol negatif 6 ekor tikus Sprague–Dawley tanpa induksi DMBA. Pada minggu ke-11 diambil secara acak tikus kontrol negatif dan tikus perlakuan DMBA untuk dilakukan pemeriksaan histolopatogi jaringan payudara. Setelah didapatkan bahwa tikus dengan perlakuan DMBA positif mengalami kanker payudara, pada minggu ke-12 tikus yang telah mendapat perlakuan DMBA dibagi menjadi 4 kelompok, 3 kelompok mendapat ekstrak propolis oral melalui sonde dengan dosis masing-masing 50, 100, dan 200 mg dalam 1 ml minyak jagung, 1 kelompok sebagai kontrol positif tidak mendapat perlakuan ekstrak propolis. Berat badan ditimbang sebelum mulai perlakuan dan dipantau tiap dua minggu sampai 15 minggu. Hasil penimbangan berat badan menunjukkan bahwa kelompok tikus yang mendapat DMBA peningkatan berat badannya lebih rendah dibanding kelompok tanpa DMBA, dan selanjutnya kelompok perlakuan ekstrak propolis kenaikan berat badannya lebih tinggi dibanding kelompok tanpa perlakuan ekstrak propolis. Hasil penelitian menunjukkan bahwa perlakuan ekstrak propolis memiliki potensi memperbaiki profil berat badan tikus model kanker payudara yang diinduksi dengan DMBA.

scholarly journals Protective Effect of Naringenin on Cadmium-induced Toxicity in Rat Liver

2021 ◽  
Author(s):  
Ke Wang ◽  
Lulu Ding ◽  
Congying Kou ◽  
Ruxue Huang ◽  
Pengli Zhao ◽  
...  
Keyword(s):  
Body Weight ◽  
Protective Effect ◽  
Rat Liver ◽  
Cell Apoptosis ◽  
Structural Damage ◽  
Morphological Changes ◽  
The Body ◽  
Protective Effects ◽  
Toxic Heavy Metal ◽  
Malondialdehyde Content

Background: Cadmium (Cd) is a widespread environmental toxic heavy metal. Naringin (Nar) is reported to have a protective effect on Cd-induced liver injury. This study aimed to explore the hepatic injury induced by Cd and the protective effects of Nar on Cd-induced oxidative stress and apoptosis in rat liver. Methods: In accordance with groups, male SD rats were injected intraperitoneally with Cd and orally with Nar every day. The treatment period was 3 weeks. Body weight, the morphological changes in liver, the activity of antioxidant indices and expression of the apoptotic genes caspase-3 and -9 were assessed. Result: Results showed that the body weight of Cd-exposed rats decreased, the superoxide dismutase and catalase activities in liver decreased, the glutathione content decreased and the malondialdehyde content increased. Further, Cd-induced hepatic structural damage and cell apoptosis were observed. However, Nar could alleviate liver damage caused by Cd. Therefore, Cd caused oxidative damage and cell apoptosis in rat liver, while Nar had preventive and ameliorative effects on these injuries.

scholarly journals Anti-Platelet Aggregation of Panax Notoginseng Triol Saponins by Regulating GP1BA for Ischemic Stroke Therapy

2021 ◽  
Author(s):  
Zhiyi Xu ◽  
Yang Xu ◽  
Xiaofang Xie ◽  
Yin Tian ◽  
Junhui Sui ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Ischemia Reperfusion ◽  
Panax Notoginseng ◽  
Molecular Evidence ◽  
Therapeutic Effects ◽  
Stroke Therapy ◽  
Related Factors ◽  
Model Animal

Abstract Background: Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) in China for more than seventeen years due to its anti-platelet aggregation and neuro-protective effects, but its mechanism of action is not fully understand. In this study, anti-platelet aggregation-related protein analysis and computer simulations of drug-protein binding interactions were performed to explore the mechanism of the effects of PTS against ischemic stroke in an ischemia reperfusion model. Methods: Three oral doses of PTS were administered in a model of middle cerebral artery occlusion (MCAO) in rats. Panax notoginseng total saponins (PNS) and a combination of PTS and aspirin were chosen for comparison. To evaluate therapeutic effects and explore possible mechanisms of anti-platelet aggregation, we measured cerebral infarct size and water content in brain tissue, histomorphological changes, expression of related factors (such as arachidonic acid metabolites) and platelet receptors in serum, as well as the binding affinity of PTS for platelet adhesion receptors. Results: Compared with PNS, PTS showed a stronger and more potent anti-platelet aggregation effect in MCAO model rats. The combination of PTS and aspirin could reduce adverse gastrointestinal effects by regulating the TXA2/PGI2 ratio. We demonstrated for the first time that PTS was able to regulate Glycoprotein Ib-α (GP1BA) in a model animal. The binding of ginsenoside Rg1 and GP1BA could form a stable structure. Moreover, PTS could reduce von Willebrand factor (VWF)-mediated platelet adhesion to damaged vascular endothelium, and thus enhance the probability of anti-platelet aggregation and anti-thrombosis under pathological conditions.Conclusions: Our results showed that GP1BA was closely related to the anti-platelet aggregation action of PTS, which provided new scientific and molecular evidence for its clinical application.

Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases

2020 ◽  
Vol 26 ◽  
Author(s):  
Ikuroh Ohsawa
Keyword(s):  
Oxidative Stress ◽  
Hydroxyl Radical ◽  
Inflammatory Diseases ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Therapeutic Effects ◽  
Ophthalmic Surgery ◽  
Protective Function ◽  
Oxidation Of H2 ◽  
Anti Inflammatory

: Because multicellular organisms do not have hydrogenase, H2 has been considered to be biologically inactive in these species, and enterobacteria to be largely responsible for the oxidation of H2 taken into the body. However, we showed previously that inhalation of H2 markedly suppresses brain injury induced by focal ischemia–reperfusion by buffering oxidative stress. Although the reaction constant of H2 with hydroxyl radical in aqueous solution is two to three orders of magnitude lower than that of conventional antioxidants, we showed that hydroxyl radical generated by the Fenton reaction reacts with H2 at room temperature without a catalyst. Suppression of hydroxyl radical by H2 has been applied in ophthalmic surgery. However, many of the anti-inflammatory and other therapeutic effects of H2 cannot be completely explained by its ability to scavenge reactive oxygen species. H2 administration is protective in several disease models, and preculture in the presence of H2 suppresses oxidative stress-induced cell death. Specifically, H2 administration induces mitochondrial oxidative stress and activates Nrf2; this phenomenon, in which mild mitochondrial stress leaves the cell less susceptible to subsequent perturbations, is called mitohormesis. Based on these findings, we conclude that crosstalk between antioxidative stress pathways and the anti-inflammatory response is the most important molecular mechanism involved in the protective function of H2 , and that regulation of the immune system underlies H2 efficacy. For further medical applications of H2 , it will be necessary to identify the biomolecule on which H2 first acts.

scholarly journals Protective Effect of Polysaccharides fromInonotus obliquuson Streptozotocin-Induced Diabetic Symptoms and Their Potential Mechanisms in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Bao-zhong Diao ◽  
Wei-rong Jin ◽  
Xue-jing Yu
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Protective Effect ◽  
Proinflammatory Cytokines ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Inonotus Obliquus ◽  
Metabolizing Enzymes ◽  
Oxidative Stresses

The present study aimed to evaluate the therapeutic effects of polysaccharides fromInonotus obliquus(PIO) on streptozotocin- (STZ-) induced diabetic symptoms and their potential mechanisms. The effect of PIO on body weight, blood glucose, damaged pancreaticβ-cells, oxidative stresses, proinflammatory cytokines, and glucose metabolizing enzymes in liver was studied. The results show that administration of PIO can restore abnormal oxidative indices near normal levels. The STZ-damaged pancreaticβ-cells of the rats were partly recovered gradually after the mice were administered with PIO 6 weeks later. Therefore, we may assume that PIO is effective in the protection of STZ-induced diabetic rats and PIO may be of use as antihyperglycemic agent.

A Patient Compliance Comparative Study of Three Diuretics in the Treatment of Oedema

1980 ◽  
Vol 8 (5) ◽  
pp. 351-353 ◽  
Author(s):  
A G Wade
Keyword(s):  
Body Weight ◽  
Comparative Study ◽  
Treatment Period ◽  
Patient Compliance ◽  
Previous Treatment ◽  
The Body ◽  
Trial Period ◽  
Comparative Efficacy ◽  
Patient Acceptability ◽  
Amiloride Hydrochloride

Diurexan® (xipamide*) 40 mg daily was substituted for Navidrex-K® (cyclopenthiazide 0.25 mg plus potassium 600 mg) or Moduretic® (amiloride hydrochloride 5 mg plus hydrochlorthiazide 50 mg) in nineteen patients with oedema of cardiac origin. Comparative efficacy and patient acceptability were examined over a 4-week treatment period. In six patients their oedema was resolved and in a further seven their oedema was markedly reduced (six patients had no overt oedema pre-trial). The body-weight of nine patients decreased by an average of 1.4 kg whilst in seven patients it remained static and in three patients it increased by an average of 1.8 kg. Thirteen of the patients preferred Diurexan at the end of the 4-week trial period, four patients had no preference and two patients preferred their previous treatment.

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