மருத்துவ வேதியியல்

The CASSCF geometry optimization of the adenosylcobalamin cofactor dependent processes common models with 12 orbitals and 12 electrons in the active space has been performed. The MCSCF geometry optimization shows a strong HOMO-LUMO coupling during the CASSCF orbitals mixing process. The HOMO-LUMO coupling causes an electronic density transfer from the HOMO, which at the beginning of the optimization process is constituted from the substrate atoms orbitals, to the LUMO, which is constituted from the adenosylco(III)balamin structure atomic orbitals. The Co-C bond cleavage reaction is starting from the beginning of the geometry optimization process due to the intermolecular transferred electronic density from the substrates to the adenosylco(III)balamin cofactor compound. Then, the HOMO and LUMO of the calculated models are converting into a bonding and an antibonding pair of orbitals with a central atom plus σ-axial ligands orbitals contribution and with a corrin ring plus axial ligands orbitals contribution, respectively. The HOMO-LUMO mixing process in the CASSCF procedure causes the intermolecular charge transfer process that converts into intramolecular charge transfer process, which is increasing up to about 1e- at the Co-C bond cleavage distance. The substrates of the adenosylcobalamin cofactor dependent bio-processes from one side and the 5'- deoxy-5’-adenosyl radical from another side are permanently growing their direct interactions along with the Co-C bond rupture process up to a strong direct interaction at the Co-C bond cleavage distance. Evidently, this is allowing for a hydrogen atom transfer between them. Altogether, the total energy barrier of the hydrogen transfer reaction from the substrate to the 5'- deoxy-5’-adenosyl radical reaction, the CASSCF HOMO and LUMO surface orbitals of the substrate and 5'-adenosyl radical interaction common model before and after the hydrogen transfer and a strong Pseudo-Jahn-Teller effect for only direct reaction demonstrate that the hydrogen transfer is an irreversible tunneling process, which certainly leads to the final products. All these results are pointing out to the Co-C bond cleavage and hydrogen transfer from substrate to 5'- deoxy-5’-adenosyl ligand concerted reactions in full agreement with the experimental data.

Excessive consumption of foods high in calories, lack of exercise and oxidative stress play crucial roles in diabetic physiopathology, and if not diagnosed and treated early, damages to kidney, eyes, heart and nerves are inevitable. Medicinal plants have long been utilized in traditional medicine for the treatment of diseases. In this study, qualitative and quantitative phytochemicals analyses of ethanolic extract of Physalis angulata were carried out using standard biochemical methods. In addition, evaluation of the antioxidant activity and inhibitory potential of the plant extract against key enzymes associated with hyperglycemia-a symptom that characterizes diabetes were done. Antioxidant activities were determined using DPPH (2, 2-diphenyl-1-picryl-hydrazyl-hydrate), FRAP (Ferric Reducing Antioxidant Power), ABTS (2, 2l-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid), lipid peroxidation assays while the alpha–glucosidase and α-amylase inhibitory activities were also evaluated. The ethanolic extract of Physalis angulata exhibited significant strong scavenging activity on DPPH, lipid peroxidation, reducing power, ABTS activity as compared with the standard drug Ascorbic Acid against the diabetic group (p<0.05). Furthermore, the ethanolic extract did exhibit significant α-amylase and α–glucosidase activities with IC₅₀ (23.88, 15.10), when compared with standard drug acarbose with IC₅₀ (24.75, 41.74). The findings of this study indicate that the ethanolic extract of Physalis angulata leaves possess anti hyperglycemic properties; and thus provide pharmacological benefits to the ethnomedical use of this plant in the treatment, management and control of type 2 diabetes mellitus.

Procarbazine (Pcb) is a component of a chemotherapeutic cocktail in the treatment of melanoma. Unfortunately, Pcb brings about very common adverse effects. In this study, we tried to improve the therapeutically efficacy of Pcb by combination of N-acetyl-L-tyrosine (NAT). We investigated the effect of Pcb/NAT and its underlying mechanism in melanoma via MTT assay, cell cycle assay, ΔΨ_m assay, Western blotting and in vivo animal model. It was found that combination of Pcb with NAT in 1:1 mole ratio (Pcb/NAT) enhanced the inhibition sensitivity against murine melanoma cells B16/F10 with IC50 value changed from 31.9 ± 1.1 to 14.2 ± 1.1 μM. Similar result was found in K1735 cell line. Compared to Pcb solely, the inhibitory rate of Pcb/NAT against B16/F10-bearing tumor in C57BL/6 mice was 89.4% by 5.8% increase; whilst the volume inhibition rate was 95.6% by 10.1% increase. Pcb/NAT was confirmed with more significant effects on cell differentiation, apoptosis, cycle and mitochondrial membrane potential in B16/F10 cells than Pcb solely. It was found that the present of NAT increased the transformation of Pcb. Involvement of NAT intensified the upregulation of tyrosinase activity/protein level, and the expression of GADPH in vitro and in vivo. Pcb/NAT also enhanced the activation of p53 leading to a more decrease of Bcl-2/Bax ratio than Pcb solely. It was found that sensitivity increase of Pcb/NAT against melanoma brings no increase in toxicity. All the data support that Pcb/NAT is a promising anti-melanoma agent to replace Pcb.