It has been thought that caloric restriction favors longevity and healthy aging where autophagy plays a vital role. However, autophagy decreases during aging and that can lead to the development of aging-associated diseases such as cancer, diabetes, neurodegeneration, etc. It was shown that autophagy can be induced by mechanical or chemical stress. In this regard, various pharmacological compounds were proposed, including natural polyphenols. Apart from the ability to induce autophagy, polyphenols, such as resveratrol, are capable of modulating the expression of pro- and anti-apoptotic factors, neutralizing free radical species, affecting mitochondrial functions, chelating redox-active transition metal ions, and preventing protein aggregation. Moreover, polyphenols have advantages compared to chemical inducers of autophagy due to their intrinsic natural bio-compatibility and safety. In this context, polyphenols can be considered as a potential therapeutic tool for healthy aging either as a part of a diet or as separate compounds (supplements). This review discusses the epigenetic aspect and the underlying molecular mechanism of polyphenols as an anti-aging remedy. In addition, the recent advances of studies on NAD-dependent deacetylase sirtuin-1 (SIRT1) regulation of autophagy, the role of senescence-associated secretory phenotype (SASP) in cells senescence and their regulation by polyphenols have been highlighted as well. Apart from that, the review also revised the latest information on how polyphenols can help to improve mitochondrial function and modulate apoptosis (programmed cell death).

Autologous red blood cell ghosts (RBC ghosts) can carry cytokines to the sites of inflammation. The targeting moiety of the RBC ghosts is associated with the nature of purulent inflammation, where the erythrocytes are phagocyted and encapsulated drugs are released. In the present study we have investigated the healing potential of RBC ghosts loaded with cytokine IL-1β and antibiotic. Additionally, the pharmacokinetic properties of RBC ghosts loaded with IL-1β were studied. 35 Male Wistar rats (250-300g) were used in the pharmacokinetic study and in a wound infection model where a suspension of Staphylococcus aureus was placed into a surgical cut of the skin and subcutaneous tissue in the femoral region. In order to monitor progression of the wound repair processes, wound swabs or aspiration biopsies were taken for analyses on the 1st-6th days. Wound repair dynamics assessment was based on suppression of S. aureus growth, signs of pain, time of disappearance of pus and infiltration around the wound. Visual observations, as well as microbiological and cytological analysis of wound exudates demonstrated a significant acceleration of healing processes in a group of animals treated with a local injection of IL-1β and ceftriaxone encapsulated into RBC ghosts when compared to the animals treated either with a local or IM injection of free drugs. For the pharmacokinetic study, single IV injections of either free or encapsulated IL-1β were made and the concentration of IL-1β in serum samples and tissue homogenates were determined. Encapsulation in RBC ghosts improved pharmacokinetic profiles of IL-1β by increasing the half-life, reducing its clearance, and increasing the deposition of the drug in the liver, spleen and lungs. These data suggest that RBC ghosts are effective drug carriers for targeted delivery of cytokines to the sites of inflammation, and have a potential for improving the treatment outcomes of purulent diseases.

Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare’s milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare’s milk-derived exosomes as potential therapeutic carriers. Three extraction methods—immunoprecipitation, size exclusion chromatography, and total exosome isolation—were compared in terms of exosome characteristics, purity, and content. The isolated exosomes were then loaded with quercetin, and their ability to increase its bioavailability was tested in vitro and in vivo. Total exosome isolation was identified as the most efficient method for producing high-quality exosomes. These exosomes were loaded with quercetin and compared to free quercetin and exosomes alone. Exosomes loaded with 80 µM quercetin significantly restored β-galactosidase activity and cellular viability in doxorubicin-treated cells, exhibiting similar potency to 160 µM free quercetin. In aged model animals, treatment with quercetin-loaded exosomes resulted in significantly less acute and subacute damage to the myocardium, kidneys, and liver compared to untreated control animals. This study provides a proof-of-concept that mare’s milk-derived exosomes can be effectively absorbed by cells and animal tissues, supporting their potential use as drug carriers.

Впервые проведено исследование химического состава полифенольных соединений плодов клюквы (Vaccinium oxycoccus L.), черники (Vaccinium myrtillus L.) и брусники (Vaccinium vitis-idaea L.), произрастающих на территории Сургутского района Ханты-Мансийского автономного округа – Югры. Свежие ягоды пятикратно экстрагировали 80%-ной водно-спиртовой смесью при комнатной температуре. Полученные экстракты объединяли, фильтровали, растворитель из фильтрата отгоняли под вакуумом на ротационном испарителе. В составе полученных экстрактов методом ВЭЖХ идентифицировано 15 гликозидов антоцианидинов, а также 30 фенольных соединений, относящихся к гидроксибензойным и гидроксикоричным кислотам, флавонолам, катехинам и процианидинам. Идентификация фенольных соединений проводилась в соответствии с временами удерживания и спектрами поглощения соответствующих аналитических стандартов. Основным фенольным соединением экстракта ягод клюквы является хлорогеновая кислота. Установлен рост содержания полифенолов в ряду: клюква–брусника–черника. Полученные данные в целом по содержанию полифенолов сопоставимы с результатами исследования клюквы и черники из региона Аляски, несущественно отличаясь по содержанию антоцианов и отдельных флавонов. Значительные отличия по фенольным компонентам выявляются при сравнении наших данных с литературными данными по бруснике и клюкве из районов севера и востока Европы (Польша, Белоруссия, Норвегия). Обнаруженные количественные различия по отдельным полифенолам, вероятно, связаны с географическими и местными природными условиями. Высокое содержание полифенолов в изученных нами ягодах позволяет предполагать возможность использования их в качестве фармацевтического сырья.

Several studies reveal that the phenolic compounds present in the wine and their concentrations determine physiological activities of the red wine. In this study, the main polyphenol components, including hydroxycinnamic acids, flavones, flavan-3-ols and stilbenoids, were investigated via HLPC-UV in the “Cabernet Sauvignon” and “Saperavi” wines selected from different regions and different years. In assistance of a meta-analysis, we found that there are no fundamental differences in phenolic compounds between the wines Cabernet Sauvignon and Saperavi. However, the amounts of several important phenolic materials such as catechin, caffeic acid, p-coumaric acid, chlorogenic acid and myricetin significantly higher in Saperavi wine as compared to Cabernet Sauvignon. Moreover, on the basis of the correlation analysis, we assume that flavones synthesis and regulation of stilbenoids coordinated to a greater extent in “Saperavi” than in “Cabernet Sauvignon”.

Kozhakhmetov S, Babenko D, Nurgaziyev M, Tuyakova A, Nurgozhina A, Muhanbetganov N, Chulenbayeva L, Sergazy S, Gulyayev A, Saliev T, Kushugulova A. 2020. The combination of mare's milk and grape polyphenol extract for treatment of dysbiosis induced by dextran sulfate sodium. Biodiversitas 21: 2275-2280. This study showed the potential of a biological product based on mare's milk and a complex of grape polyphenols to modulate intestinal microflora after dextran sulfate sodium (DSS)-induced dysbiosis. Rat ulcerative colitis has been developed using intra-gastric administration of 10% DSS solution. To track changes in the structure of the microbiome at all stages of the study, the next-generation sequencing of the 16S rRNA gene section and LotuS conveyor were used. The results of sequencing demonstrated a decrease in biological diversity of microbiota after the induction of colitis, and recovery after 7 days of use of the (MMGPE). The product induced the structural changes of the microbiome damaged by DSS. Representatives of SCFA producing bacteria increased concentrations of Prevotella, Alloprevotella, Lactobacillus, Ruminococcaceae, and Blautia.