Sesamum indicum diet prevents hyperlipidemia in experimental rats.

Cardiovascular diseases and metabolic complications caused by hyperlipidemia are the leading cause of death globally. In this study, the hypolipidemic potency of Sesamum indicum (SI) seeds was investigated. Of the thirty-five (35) male rats used in the study, five (5) were randomly selected for baseline measurements and thirty (30) were fed high fat diet (HFD) for four (4) weeks before random assignment into three (3) groups. The experimental group was treated with 50% SI seed, the positive control group was given a hypolipidemic drug, atorvastatin (5 mg/kg/day) while the untreated group served as the negative control. With SI administration, the dyslipidemia induced by the HFD consumption in the plasma and the investigated body organs was reversed to a comparable degree with that of atorvastatin treatment. Taken together, this study demonstrates the hypolipidemic potency of SI in ameliorating hyperlipidemia and its associated complications, facilitated by the inhibition of HMG-CoA reductase activity.

Molecular Dynamics Simulations of a Cytochrome P450 from Tepidiphilus thermophilus (P450-TT) Reveal How Its Substrate-Binding Channel Opens.

Cytochrome P450s (P450) are important enzymes in biology with useful biochemical reactions in, for instance, drug and xenobiotics metabolisms, biotechnology, and health. Recently, the crystal structure of a new member of the CYP116B family has been resolved. This enzyme is a cytochrome P450 (CYP116B46) from Tepidiphilus thermophilus (P450-TT) and has potential for the oxy-functionalization of organic molecules such as fatty acids, terpenes, steroids, and statins. However, it was thought that the opening to its hitherto identified substrate channel was too small to allow organic molecules to enter. To investigate this, we performed molecular dynamics simulations on the enzyme. The results suggest that the crystal structure is not relaxed, possibly due to crystal packing effects, and that its tunnel structure is constrained. In addition, the simulations revealed two key amino acid residues at the mouth of the channel; a glutamyl and an arginyl. The glutamyl's side chain tightens and relaxes the opening to the channel in conjunction with the arginyl's, though the latter's side chain is less dramatically changed after the initial relaxation of its conformations. Additionally, it was observed that the effect of increased temperature did not considerably affect the dynamics of the enzyme fold, including the relative solvent accessibility of the amino acid residues that make up the substrate channel wall even as compared to the changes that occurred at room temperature. Interestingly, the substrate channel became distinguishable as a prominent tunnel that is likely to accommodate small- to medium-sized organic molecules for bioconversions. That is, P450-TT has the ability to pass appropriate organic substrates to its active site through its elaborate substrate channel, and notably, is able to control or gate any molecules at the opening to this channel.