Anti-inflammatory effect and antihepatoma mechanism of carrimycin

BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin(CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.AIM To obtain a deeper understanding of CAM, its distribution, metabolism and antiinflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.METHODS In this paper, the content of isovaleryl spiramycin Ⅲ was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.RESULTS The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4(IL-4) levels in the lung and kidney and especially the liver and spleen;moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets,such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.CONCLUSION We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.

Metal-organic framework IRMOFs coated with a temperaturesensitive gel delivering norcantharidin to treat liver cancer

BACKGROUND Norcantharidin(NCTD)is suitable for the treatment of primary liver cancer,especially early and middle primary liver cancer.This compound can reduce tumors and improve immune function.However,the side effects of NCTD have limited its application.There is a marked need to reduce the side effects and increase the efficacy of NCTD.AIM To develop a nanomaterial carrier,NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel(NCTD-IRMOF-3-Gel),aiming to improve the anticancer activity of NCTD and reduce the drug dose.METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction.The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated.Cell cytotoxicity assays,flow cytometry,and apoptosis experiments in mouse hepatoma(Hepa1-6)cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm,and the particle size distribution was uniform.The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect.The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation,and the inhibition rate increased with increasing drug concentration.By flow cytometry,NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases,and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest.Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells.CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

A guinea pig model of Ciwujia Injection-induced anaphylaxis for allergic substance screening

Objective: Though especially efficient for cardiovascular and cerebrovascular diseases treatment, many serious anaphylactic diseases could be induced by Ciwujia Injection(CWJI). However, study of the mechanism and detection of allergies have been investigated by the unknown sources of allergenic substances.In this study, a guinea pig model which could mimic the symptoms of anaphylactic reactions induced by Ciwujia Injection(CWJI) was modeled and used to screen the allergenic substance of CWJI.Methods: Guinea pigs were sensitized three times every other day with CWJI and excitated 14 d after the last sensitization administration. Then, the histamine, trypsin, IL-4 and IFN-γ levels, and the Annexin V positive rate of peritoneal mast cells(PMC) were detected, the numbers of B lymphocyte and the pathological changes were also analyzed to verify the guinea pig allergy model, PCA test and Ig E antibody levels were determined to study the mechanism.Results: The levels of total IgE, histamine, and trypsin were significantly increased after CWJI sensitization, IL-4 level was elevated, Annexin V positive of PMC cell rate, local skin reactions, and declined IFN-γwere observed after excitation. Histological examination showed that mild pathological changes in lungs were found.Conclusion: This guinea pig model may provide a powerful tool to study the mechanism in CWJI induced anaphylaxis and screen the allergic source of CWJI.