brucine and Disease-Models--Animal

Myocardial infarction (MI) is the most extensive manifestations of cardiovascular disease (CVD), associated with prolonged supply and demand blood oxygen imbalance to the heart muscle. The treatment of MI includes several conventional medicines which are beta-blockers and calcium antagonists. Though, these were reported to be either not efficient or associated with life threatening adverse effects. Brucine, the main alkaloid bioactive compound from Strychnos nux-vomica seeds, offers unique compatibility advantages in inflammatory diseases associated clinical practices. Thus, the present investigation was projected to explore the activity of brucine towards MI provoked by isoprenaline hydrochloride (ISO) in rats. The cardioprotective properties of brucine were evaluated via detecting the infarct size, serum cardiac marker enzymes (CK, CK-MB, cTnT, and cTnI), endogenous antioxidants (CAT, SOD, GPx), and lipid peroxidation (TBARS and LOOH), inflammatory mediators (NF-κB, TNF-α and IL-6) and histopathological analysis. The results demonstrated, brucine effectively restored the infarct size by increasing the endogenous antioxidants and decreasing the status of TBARS and LOOH, marker enzymes and ameliorated the histopathological injuries. Brucine's cardioprotective effect might be associated with TNF-α, IL-6 signaling molecules activation, revealing its pharmacological actions.

Topics: Animals; Disease Models, Animal; Isoproterenol; Myocardium; Rats; Strychnine

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Licorice, one of the most widely used medicinal herbs in East Asia, has effects such as anti-inflammation, antioxidant, and detoxifying. This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity. Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice. The content of blood urea nitrogen and creatinine in serum, the activities of superoxide dismutase and content of glutathione, malonaldehyde in kidney tissue were detected. Hematoxylin-eosin staining was employed to observe the histopathological changes of kidney. The expression and phosphorylation levels of protein were evaluated by Western blotting and immunohistochemical analysis. The results illustrated that treatment with licorice extracts (LE) significantly protected against the brucine-induced nephrotoxicity by reducing the content of blood urea nitrogen and serum creatinine, attenuating pathologic damage. The unbalance of oxidative stress was repaired by LE via increasing the level of glutathione, promoting the activities of superoxide dismutase and decreasing the content of malonaldehyde. In addition, LE overturned the influence of brucine on apoptosis-related protein and signal transducer and activator of transcription-3 (STAT3) activation. Taken together, these data demonstrate that licorice may attenuate brucine-induced nephrotoxicity via inactivation of oxidative stress and mitochondrial-mediated apoptosis pathway. More importantly, the renoprotective effects may be mediated, at least partly, by preventing the activation of STAT3 protein.

Topics: Acute Kidney Injury; Animals; Apoptosis; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Gene Expression Regulation; Glutathione; Glycyrrhiza; Injections, Intraperitoneal; Male; Malondialdehyde; Mitochondria; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley; STAT3 Transcription Factor; Strychnine; Superoxide Dismutase

The seeds of

Topics: Administration, Cutaneous; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Cell Line; Cell Proliferation; Cell Survival; Cells, Cultured; Dinoprostone; Disease Models, Animal; Drug Delivery Systems; Edema; Formaldehyde; Gels; Humans; Macrophages; Male; Mice; Pain; Phytotherapy; Rats, Wistar; Strychnine; Strychnos nux-vomica; Synoviocytes

To study the effects of brucine on vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in a nude mouse model of bone metastasis due to breast cancer, and to assess the possible antitumor mechanism of brucine.. A syringe needle was used to directly inject 0.2 mL monoplast suspension (with 2×10(5) human breast cancer cells contained) into the bony femoral cortex of the right hind leg for modeling. Twenty-five nude mice were randomized into five groups and administered with an intraperitoneal injection of saline or drug for 8 consecutive days: model group (0.2 mL normal saline), low-dose brucine group (1.73 mg·kg(-1)), medium-dose brucine group (3.45 mg·kg(-1)), high-dose brucine group (6.90 mg·kg(-1)), and thalidomide group (200 mg·kg(-1)). Diet and activity were recorded, and the tumors were harvested 5 weeks later. The percentage of VEGF-positive cells was determined with hematoxylin and eosin staining and immunohistochemical staining, and MVD expression was determined by optical microscopy.. The VEGF expressions in brucine- or thalidomide-treated mice were significantly reduced as compared with mice in the model group (P <0.01). There were no significant difference between the high-dose brucine group and the thalidomide group (P >0.05). Significant difference was between the high- and low-dose brucine group P<0.05). Further, VEGF expression was significantly increased in the low- and medium-dose brucine groups compared with the thalidomide group (P <0.05). The MVD values in the three brucine and thalidomide groups were significantly lower than that in the model group (P <0.01). The MVD values in the medium- and high-dose brucine groups were not significantly different from those in the thalidomide group (P >0.05), while the MVD value showed a significant increase in the low-dose group compared with the thalidomide group (P <0.05).. Brucine could inhibit the growth of breast cancer to bone metastases, possibly by inhibiting tumor angiogenesis.

Topics: Animals; Bone Neoplasms; Breast Neoplasms; Cell Line, Tumor; Disease Models, Animal; Female; Humans; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Microvessels; Strychnine; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

To further understand the purpose of the traditional processing method of the seeds of Strychnos nux-vomica L. (Loganiaceae) as well as analgesic and anti-inflammatory activities of brucine and brucine N-oxide extracted from this medicinal plant, various pain and inflammatory models were employed in the present study to investigate their pharmacological profiles. Both brucine and brucine N-oxide revealed significant protective effects against thermic and chemical stimuli in hot-plate test and writhing test. However, on different phases they exerted analgesic activities in formalin test. Brucine N-oxide showed stronger inhibitory effect than brucine in carrageenan-induced rat paw edema, both of them significantly inhibited the release of prostaglandin E2 in inflammatory tissue, reduced acetic acid-induced vascular permeability and the content of 6-keto-PGF1a in Freund's complete adjuvant (FCA) induced arthritis rat's blood plasma. In addition, brucine and brucine N-oxide were shown to reduce the content of 5-hydroxytryptamine (5-HT) in FCA-induced arthritis rat's blood plasma, while increase the content of 5-hydroxytryindole-3-acetic acid (5-HIAA) accordingly. These results suggest that central and peripheral mechanism are involved in the pain modulation and anti-inflammation effects of brucine and brucine N-oxide, biochemical mechanisms of brucine and brucine N-oxide are different even though they are similar in chemical structure.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Capillary Permeability; Cyclic N-Oxides; Disease Models, Animal; Edema; Female; Male; Mice; Mice, Inbred ICR; Pain; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Serotonin; Strychnine; Strychnos nux-vomica