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Lasia spinosa (L.) Thwaites is a medicinal plant of enormous traditional use with insufficient scientific evidence. This research screened the antioxidative effect of L. spinosa extracts by measuring the total phenolic content, total flavonoid content, DPPH free radical scavenging activity, ABTS scavenging activity, Iron-chelating activity, and Ferric reducing power followed by an evaluation of in vivo cardioprotective effect in doxorubicin-induced Wistar Albino rats. Phytochemical characterization was made by Gas Chromatography–Mass Spectroscopic analysis. L. spinosa showed an excellent antioxidative effect while methanol leaf extract (LSM) was found to be more potent than ethyl acetate leaf extract (LSE) in scavenging the free radicals. Intraperitoneal injection of doxorubicin caused a significant (P < 0.001) increase in lactate dehydrogenase (LDH), creatine kinase (CK-MB), C-reactive protein (CRP), and Cardiac troponin I. Pretreatment with orally administrated (LSM100 and LSM200 mg/kg b.w.) daily for 10 days showed a decrease in the cardiac markers, lipid profiles, especially triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and an increase of high-density lipoprotein (HDL) compared to the disease control group. LSM200 was found to significantly (P < 0.05) decrease the levels of CK-MB and LDH. It also restored TC, TG, and LDL levels compared to the doxorubicin-induced cardiac control group. The protective role of LSM was further confirmed by histopathological examination. This study thus demonstrates that L. spinosa methanol extract could be approached as an alternative supplement for cardiotoxicity, especially in the chemical-induced toxicity of cardiac tissues. [ABSTRACT FROM AUTHOR]

Proline specific serine protease enzyme, dipeptidyl peptidase IV (DPP-4) has become a promising target for diabetes, as it stops glucagon-like peptide 1 (GLP-1) from becoming inactive, resulting in higher levels of active GLP-1. This lowers glucose levels by increasing insulin secretion and decreasing glucagon secretion. DPP-4 is also linked to a higher BMI and a 0.7 to 1% reduction in HbA1c. Currently available DPP-4 inhibitor drugs showed less promising anti-diabetic activity as this class associated with many side effects due to non-selectivity and therefore searching on more potent DPP-4 inhibitors are still ongoing. In our present study, we investigate the inhibition of DPP-4 through a series of antibiotic compounds which were previously reported to be used in diabetic foot infections and compared with existing DPP-4 inhibitors. To obtain this objective, three-dimensional crystal structure of DPP-4 was retrieved from the protein data bank (PDB id: 1 × 70). A systematic computational method combining molecular docking, MM-GBSA binding energy calculation, MD simulations, MM-PBSA binding free energy calculations and ADME were used to find best DPP-4 inhibitor. Molecular docking results revealed that clindamycin has a higher affinity towards the catalytic sides of DPP-4 and built solid hydrophobic and polar interactions with the amino acids involved in the binding region of DPP-4, such as S1 subsite, S2 subsite and S2 extensive subsite. MD simulations results showed clindamycin as potent virtual hit and suggested that it binds with DPP-4 in competitive manner, which virtually indicate that besides antibiotic activity clindamycin has anti-diabetic activity. [ABSTRACT FROM AUTHOR]