The effect of membrane composition on the interaction between human CYP51 and its flavonoid inhibitor - luteolin 7,3'-disulfate.

Cytochromes P450 (CYP) are a family of membrane proteins involved in the production of endogenous molecules and the metabolism of xenobiotics. It is well-known that the composition of the membrane can influence the activity and orientation of CYP proteins. However, little is known about how membrane composition affects the ligand binding properties of CYP. In this study, we utilized surface plasmon resonance and fluorescence lifetime analysis to examine the impact of membrane micro-environment composition on the interaction between human microsomal CYP51 (CYP51A1) and its inhibitor, luteolin 7,3'-disulphate (LDS). We observed that membranes containing cholesterol or sphingomyelin exhibited the lowest apparent equilibrium dissociation constant for the CYP51A1-LDS complex. Additionally, the tendency for relation between kinetic parameters of the CYP51A1-LDS complex and membrane viscosity and overall charge was observed. These findings suggest that the specific composition of the membrane, particularly the presence of cholesterol and sphingomyelin, plays a vital role in regulating the interaction between CYP enzymes and their ligands.

Carotenoids from Starfish Patiria pectinifera: Therapeutic Activity in Models of Inflammatory Diseases.

The carotenoids mixture (MC) isolated from the starfish Patiria. pectinifera contains more than 50% astaxanthin, 4-6% each zeaxanthine and lutein, and less pharmacologically active components such as free fatty acids and their glycerides. Astaxanthin, the major component of MC, belongs to the xanthophyll class of carotenoids, and is well known for its antioxidant properties. In this work, in vitro and in vivo studies on the biological activity of MC were carried out. The complex was shown to exhibit anti-inflammatory, anti-allergic and cancer-preventive activity, without any toxicity at a dose of 500 mg/kg. MC effectively improves the clinical picture of the disease progressing, as well as normalizing the cytokine profile and the antioxidant defense system in the in vivo animal models of inflammatory diseases, namely: skin carcinogenesis, allergic contact dermatitis (ACD) and systemic inflammation (SI). In the skin carcinogenesis induced by 7,12-dimethylbenzanthracene, the incidence of papillomas was decreased 1.5 times; 1% MC ointment form in allergic contact dermatitis showed an 80% reduced severity of pathomorphological skin manifestations. Obtained results show that MC from starfish P. pectinifera is an effective remedy for the treatment and prevention of inflammatory processes.

Antitumor Properties of Matrikines of Different Origins: Prospects and Problems of Their Application.

Matrikines (MKs) can be a rich source of functional nutrition components and additional therapy, thereby contributing to human health care and reducing the risk of developing serious diseases, including cancer. Currently, functionally active MKs as products of enzymatic transformation by matrix metalloproteinases (MMPs) are used for various biomedical purposes. Due to the absence of toxic side effects, low species specificity, relatively small size, and presence of various targets at the cell membranes, MKs often exhibit antitumor properties and, therefore, are promising agents for antitumor combination therapy. This review summarizes and analyzes the current data on the antitumor activity of MKs of different origins, discusses the problems and prospects for their therapeutic use, and evaluates the experimental results of studying the antitumor properties of MKs from different echinoderm species generated with the help of a complex of proteolytic enzymes from red king crab Paralithodes camtschatica. Special attention is paid to the analysis of possible mechanisms of the antitumor action of various functionally active MKs, products of the enzymatic activity of various MMPs, and the existing problems for their use in antitumor therapy.

Comparative Study of the Pharmacological Properties of Luteolin and Its 7,3'-Disulfate.

The global spread of the metabolic syndrome, oncological and viral diseases forces researchers to pay increased attention to the secondary metabolites of marine hydrobionts, which often have a high therapeutic potential in the treatment of these pathologies and are effective components of functional food. The flavone luteolin (LT), as one of the most widely distributed and studied plant metabolites, is distinguished by a diverse spectrum of biological activity and a pleiotropic nature of the mechanism of action at the molecular, cellular and organismal levels. However, there is still practically no information on the spectrum of biological activity of its sulfated derivatives, which are widely represented in seagrasses of the genus Zostera. In the present work, a comparative study of the pharmacological properties of LT and its 7,3'-disulfate was carried out with a brief analysis of the special role of sulfation in the pharmacological activity of flavonoids.

Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets.

The effect of low doses of echinochrome A (EchA), a natural polyhydroxy-1,4-naphthoquinone pigment from the sea urchin Scaphechinus mirabilis, has been studied in clinical trials, when it was used as an active substance of the drug Histochrome® and biologically active supplement Thymarin. Several parameters of lipid metabolism, antioxidant status, and the state of the immune system were analyzed in patients with cardiovascular diseases (CVD), including contaminating atherosclerosis. It has been shown that EchA effectively normalizes lipid metabolism, recovers antioxidant status and reduces atherosclerotic inflammation, regardless of the method of these preparations' administrations. Treatment of EchA has led to the stabilization of patients, improved function of the intracellular matrix and decreased epithelial dysfunction. The increased expression of surface human leukocyte antigen DR isotype (HLA-DR) receptors reflects the intensification of intercellular cooperation of immune cells, as well as an increase in the efficiency of processing and presentation of antigens, while the regulation of CD95 + expression levels suggests the stimulation of cell renewal processes. The immune system goes to a different level of functioning. Computer simulations suggest that EchA, with its aromatic structure of the naphthoquinone nucleus, may be a suitable ligand of the cytosolic aryl cell receptor, which affects the response of the immune system and causes the rapid expression of detoxification enzymes such as CYP and DT diaphorase, which play a protective role with CVD. Therefore, EchA possesses not only an antiradical effect and antioxidant activity, but is also a SOD3 mimetic, producing hydrogen peroxide and controlling the expression of cell enzymes through hypoxia-inducible factors (HIF), peroxisome proliferator-activated receptors (PPARs) and aryl hydrocarbon receptor (AhR).