Skin Aging, Cellular Senescence and Natural Polyphenols

The skin, being the barrier organ of the body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found to accumulate with age and may contribute to age-related skin changes and pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on skin aging. By affecting molecular pathways of senescence, polyphenols are able to prevent or delay the senescence formation and, consequently, avoid or ameliorate aging and age-associated pathologies of the skin. This review aims to provide an overview of the current state of knowledge in skin aging and cellular senescence, and to summarize the recent in vitro studies related to the anti-senescent mechanisms of natural polyphenols carried out on keratinocytes, melanocytes and fibroblasts. Aged skin in the context of the COVID-19 pandemic will be also discussed.

PARP-1-Associated Pathological Processes: Inhibition by Natural Polyphenols

Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in processes of cell cycle regulation, DNA repair, transcription, and replication. Hyperactivity of PARP-1 induced by changes in cell homeostasis promotes development of chronic pathological processes leading to cell death during various metabolic disorders, cardiovascular and neurodegenerative diseases. In contrast, tumor growth is accompanied by a moderate activation of PARP-1 that supports survival of tumor cells due to enhancement of DNA lesion repair and resistance to therapy by DNA damaging agents. That is why PARP inhibitors (PARPi) are promising agents for the therapy of tumor and metabolic diseases. A PARPi family is rapidly growing partly due to natural polyphenols discovered among plant secondary metabolites. This review describes mechanisms of PARP-1 participation in the development of various pathologies, analyzes multiple PARP-dependent pathways of cell degeneration and death, and discusses representative plant polyphenols, which can inhibit PARP-1 directly or suppress unwanted PARP-dependent cellular processes.

The Role of Polyphenols in the Treatment of Alzheimer's Disease: Narrative Review

Many epidemiological studies have suggested that consuming a diet rich in polyphenols can help prevent Alzheimer's disease (AD). Based on well-known in vitro and in vivo models of cerebral Aβ amyloidosis, we examined the data on the effects of various natural polyphenols on the aggregation of amyloid-protein (Aβ). These polyphenols effectively prevent oligomerization and fibril formation of Aβ through differential binding patterns, lowering Aβ oligomer-induced synaptic and neuronal toxicity, according to in vitro investigations. Furthermore, in a transgenic mouse model fed orally with such polyphenolic compounds, soluble Aβ oligomers as well as insoluble Aβ deposits in the brain were significantly reduced. Natural polyphenols exhibit anti-amyloidogenic effects on Aβ, in addition to well-known anti-oxidative and anti-inflammatory activities, according to an updated assessment of the literature, implying their potential as therapeutic and/or preventive agents for AD treatment. To prove polyphenols' efficacy as disease-modifying agents, well-designed clinical trials or preventive treatments using various polyphenols are required.

Natural Polyphenols Inhibit the Dimerization of the SARS-CoV-2 Main Protease: The Case of Fortunellin and Its Structural Analogs

3CL-Pro is the SARS-CoV-2 main protease (MPro). It acts as a homodimer to cleave the large polyprotein 1ab transcript into proteins that are necessary for viral growth and replication. 3CL-Pro has been one of the most studied SARS-CoV-2 proteins and a main target of therapeutics. A number of drug candidates have been reported, including natural products. Here, we employ elaborate computational methods to explore the dimerization of the 3CL-Pro protein, and we formulate a computational context to identify potential inhibitors of this process. We report that fortunellin (acacetin 7-O-neohesperidoside), a natural flavonoid O-glycoside, and its structural analogs are potent inhibitors of 3CL-Pro dimerization, inhibiting viral plaque formation in vitro. We thus propose a novel basis for the search of pharmaceuticals as well as dietary supplements in the fight against SARS-CoV-2 and COVID-19.

Polyphenols as Therapeutic Approach to High Altitude Mediated Skeletal Muscle Impairments

Skeletal muscle impairments at high altitudes resulted into various consequences in un-acclimatised individuals thus hampering their physical activities by imposing severe oxidative stress, skeletal muscle atrophy, mitochondrial dysfunction/autophagy, and regeneration disability. Researchers have described many natural and synthetic supplements to alleviate oxidative stress-induced muscle impairments. In this review article we are focusing on the skeletal muscle impairments and their alleviation by using natural polyphenols. Polyphenols are plant-based compounds showing anti-oxidative and anti-inflammatory properties like Curcumin, Catechins, Resveratrol, Quercetin and Salidrosides appear to mainly act by reversing oxidative stress and mitochondrial dysfunction eventually ameliorate skeletal muscle impairments under various imposed pathological conditions. This review also drew attention on the molecular targets of polyphenols and their possible therapeutic effects in preventing HA induced muscle impairments. Unavailability of suitable intervention, there is a need to find a probable solution having highly protective anti-atrophic, anti-oxidative, anti-inflammatory properties with the tint of performance enhancer.

Nanoencapsulation of Polyphenols as Drugs and Supplements for Enhancing Therapeutic Profile - A Review

: Polyphenolic phytoconstituents have been widely in use worldwide since ages and are categorised as secondary metabolites of plants. The application of polyphenols such as quercetin, resveratrol. curcumin as nutritional supplement has been researched widely. The use of polyphenols, and specifically quercetin for improving the memory and mental endurance have shown significant effects among rats. Even though similar results has not been resonated among human but encouraging preclinical results have encouraged researchers to explore other polyphenols to study the effects as supplements among athletes. The phytopharmacological research has elucidated the use of natural polyphenols to prevent and treat various physiological and metabolic disorders owing to its free radical scavenging properties, anti-inflammatory, anti-cancer and immunomodulatory effects. In spite of the tremendous pharmacological profile, one of the most dominant problem regarding the use of polyphenolic compounds is their low bioavailability. Nanonization is considered as one of the most prominent approaches among many. This article aims to review and discuss the molecular mechanisms of recently developed nanocarrier-based drug delivery systems for polyphenols and its application as drugs and supplements. Nanoformulations of natural polyphenols are bioactive agents, such as quercetin, kaempferol, fisetin, rutin, hesperetin, and naringenin epigalloccatechin-3-gallate, genistein, ellagic acid, gallic acid, chlorogenic acid, ferulic acid, curcuminoids and stilbenes is expected to have better efficacy. These delivery systems are expected to provide higher penetrability of polyphenols at cellular levels and exhibit a controlled release of the drugs. It is widely accepted that natural polyphenols do demonstrate significant therapeutic effect. However, the hindrances in their absorption, specificity and bioavailability can be overcome using nanotechnology.