In Silico Screening and Molecular Dynamics Simulation of Potential Anti-Malarial Agents from Zingiberaceae as Potential Plasmodium falciparum Lactate Dehydrogenase (PfLDH) Enzyme Inhibitors.

Malaria continues to be a major public health issue in a number of countries, particularly in tropical regions-the emergence of drug-resistant Plasmodium falciparum encourages new drug discovery research. The key to Plasmodium falciparum survival is energy production up to 100 times greater than other parasites, primarily via the PfLDH. This study targets PfLDH with natural bioactive compounds from the Zingiberaceae family through molecular docking and molecular dynamic studies. Sulcanal, quercetin, shogosulfonic acid C, galanal A and naringenin are the Top 5 compounds with a lower binding energy value than chloroquine, which was used as a control in this study. By binding to NADH and substrate binding site residues, the majority of them are expected to inhibit pyruvate conversion to lactate and NAD+ regeneration. When compared to sulcanal and control drugs, the molecular dynamics (MD) simulation study indicated that quercetin may be the most stable molecule when interacting with PfLDH.

Assessing the Immunomodulatory Activity of Ethanol Extract of Sambucus javanica Berries and Leaves in Chloramphenicol-Induced Aplastic Anemia Mouse Model.

Aplastic anemia, life-threatened disease, is a hematologic disorder characterised by bone marrow hypoplasia. Multiple modalities such as bone marrow transplantation and immunosuppression treatment have been proposed to ameliorate this entity, however it remains ineffective. Sambucus, a group of herb plants, possesses a broad spectrum of medicinal properties such as antioxidant, insulin-like activity, anticancer and antiviral. However, the study about its activity toward aplastic anemia incidence is based on limited data. Thus, the research aim of this study was to evaluate the immunomodulatory activities of Sambucus javanica in chloramphenicol-induced anemia aplastic mouse model. In this present study, BALB/c mice were administrated with chloramphenicol (CMP) to induce aplastic anemia then followed by S. javanica extracts treatment. Additionally, cellular and molecular aspects were evaluated by flow cytometry and Hematoxylin-Eosin staining. Further analysis showed that S. javanica extracts could promote the population number of regulatory T-cells and naive cytotoxic T-cells. Moreover, those extract also reduced the inflammation and necrotic incidence in CMP-induced mouse aplastic anemia model. Together, these results suggest that S. javanica has therapeutically effect to aplastic anemia by altering the immune system as an immunomodulatory agent.

Immunomodulatory Activities of Sambucus javanica Extracts in DMBA-Exposed BALB/c Mouse.

Purpose: Accumulating evidence shows the genus of Sambucus exerts a broad spectrum of medicinal potencies such as anticancer, antiviral, antibacterial, and antidiabetes. Based on the previous studies, we hypothesized that bioactive compounds of Sambucus might alter several biological systems, including the immune system. Therefore, this study extensively aimed to evaluate the immunomodulatory activities of Sambucus javanica extracts in 7,12-dimethylbenz[a] anthracene (DMBA)-treated BALB/c mouse. Methods: The experimental mice were orally administrated with 2.8 mg.kg-1 BW of DMBA for ten times within a month. After that, the mice were treated by S. javanica berries and leaves extracts for 2 weeks. Subsequently, the inflammation rate was evaluated by using flow cytometry analysis, whereas the necrosis incidences were observed by hematoxylin & eosin staining. Results: Based on the results, we found the expression of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-É£) were increased however after treated by S. javanica berries and leaves extracts were significantly decreased. In the same way, necrosis incidence was increased in the DMBA-treated group however it was diminished with S. javanica extracts treatment. Conclusion: Together, these results suggested that S. javanica extracts have immunomodulatory activities to suppress inflammation and reduce necrosis incidence in experimental mice.

Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells.

The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. ©2016 AACR.