Natural autophagy activators: A promising strategy for combating photoaging.

BACKGROUND: Photodamage to the skin stands out as one of the most widespread epidermal challenges globally. Prolonged exposure to sunlight containing ultraviolet radiation (UVR) instigates stress, thereby compromising the skin's functionality and culminating in photoaging. Recent investigations have shed light on the importance of autophagy in shielding the skin from photodamage. Despite the acknowledgment of numerous phytochemicals possessing photoprotective attributes, their potential to induce autophagy remains relatively unexplored. PURPOSE: Diminished autophagy activity in photoaged skin underscores the potential benefits of restoring autophagy through natural compounds to enhance photoprotection. Consequently, this study aims to highlight the role of natural compounds in safeguarding against photodamage and to assess their potential to induce autophagy via an in-silico approach. METHODS: A thorough search of the literature was done using several databases, including PUBMED, Science Direct, and Google Scholar, to gather relevant studies. Several keywords such as Phytochemical, Photoprotection, mTOR, Ultraviolet Radiation, Reactive oxygen species, Photoaging, and Autophagy were utilized to ensure thorough exploration. To assess the autophagy potential of phytochemicals through virtual screening, computational methodologies such as molecular docking were employed, utilizing tools like AutoDock Vina. Receptor preparation for docking was facilitated using MGLTools. RESULTS: The initiation of structural and functional deterioration in the skin due to ultraviolet radiation (UVR) or sunlight-induced reactive oxygen species/reactive nitrogen species (ROS/RNS) involves the modulation of various pathways. Natural compounds like phenolics, flavonoids, flavones, and anthocyanins, among others, possess chromophores capable of absorbing light, thereby offering photoprotection by modulating these pathways. In our molecular docking study, these phytochemicals have shown binding affinity with mTOR, a negative regulator of autophagy, indicating their potential as autophagy modulators. CONCLUSION: This integrated review underscores the photoprotective characteristics of natural compounds, while the in-silico analysis reveals their potential to modulate autophagy, which could significantly contribute to their anti-photoaging properties. The findings of this study hold promise for the advancement of cosmeceuticals and therapeutics containing natural compounds aimed at addressing photoaging and various skin-related diseases. By leveraging their dual benefits of photoprotection and autophagy modulation, these natural compounds offer a multifaceted approach to combatting skin aging and related conditions.

Smart Nanofibrous Hydrogel Wound Dressings for Dynamic Infection Diagnosis and Control: Soft but Functionally Rigid.

Chronic wounds, such as burns and diabetic foot ulcers, pose significant challenges to global healthcare systems due to prolonged hospitalization and increased costs attributed to susceptibility to bacterial infections. The conventional use of antibiotic-loaded and metal-impregnated dressings exacerbates concerns related to multidrug resistance and skin argyrosis. In response to these challenges, our research introduces a unique approach utilizing antibiotic-free smart hydrogel wound dressings with integrated infection eradication and diagnostic capabilities. Electrospinning stands out as a method capable of producing hydrogel nanofibrous materials possessing favorable characteristics for treating wounds and detecting infections under conditions utilizing sustainable materials. In this study, innovative dressings are fabricated through electrospinning polycaprolactone (PCL)/gelatin (GEL) hybrid hydrogel nanofibers, incorporating pDA as a cross-linker, εPL as a broad-spectrum antimicrobial agent, and anthocyanin as a pH-responsive probe. The developed dressings demonstrate exceptional antioxidant (>90% radical scavenging) and antimicrobial properties (95-100% killing). The inclusion of polyphenols/flavonoids and εPL leads to absolute bacterial eradication, and in vitro assessments using HaCaT cells indicate increased cell proliferation, decreased reactive oxygen species (ROS) production, and enhanced cell viability (100% Cell viability). The dressings display notable alterations in color that correspond to different wound conditions. Specifically, they exhibit a red/violet hue under healthy wound conditions (pH 4-6.5) and a green/blue color under unhealthy wound conditions (pH > 6.5). These distinctive color changes provide valuable insights into the versatile applications of the dressings in the care and management of wounds. Our findings suggest that these antibiotic-free smart hydrogel wound dressings hold promise as an effective and sustainable solution for chronic wounds, providing simultaneous infection control and diagnostic monitoring. This research contributes to advancing the field of wound care, offering a potential paradigm shift in the development of next-generation wound dressings.

Toxic potential assessment of hair dye developer 2,4,5,6-tetraaminopyrimidine sulfate exposed under ambient UVB radiation.

Synthetic cosmetics, particularly hair dyes, are becoming increasingly popular among people of all ages and genders. 2,4,5,6-tetraaminopyrimidine sulfate (TAPS) is a key component of oxidative hair dyes and is used as a developer in several hair dyes. TAPS has previously been shown to absorb UVB strongly and degrade in a time-dependent manner, causing phototoxicity in human skin cells. However, the toxic effects of UVB-degraded TAPS are not explored in comparison to parent TAPS. Therefore, this research work aims to assess the toxicity of UVB-degraded TAPS than TAPS on two different test systems, that is, HaCaT (mammalian cell) and Staphylococcus aureus (a bacterial cell). Our result on HaCaT has illustrated that UVB-degraded TAPS is less toxic than parent TAPS. Additionally, UVB-exposed TAPS and parent TAPS were given to S. aureus, and the bacterial growth and their metabolic activity were assessed via CFU and phenotype microarray. The findings demonstrated that parent TAPS reduced bacterial growth via decreased metabolic activity; however, bacteria easily utilized the degraded TAPS. Thus, this study suggests that the products generated after UVB irradiation of TAPS is considered to be safer than their parent TAPS.

Benzo(ghi)perylene (BgP) a black tattoo ingredient induced skin toxicity via direct and indirect mode of DNA damage under UVA irradiation.

Tattooing is a very common fashion trend across all the ages and gender of the society worldwide. Although skin inflammatory diseases are very frequent among tattoo users because of the active chemical ingredients used in tattoo ink, yet no ingredient-specific toxicity study has been performed. Benzo(ghi)perylene (BgP) is one of the PAHs and an important ingredient of black tattoo ink that shows strong absorption in UVA and UVB radiation of sunlight. Therefore, understanding the hazardous potential of BgP especially under UVA exposure is important for the safety of skin of tattoo users by considering the fact that penetration of UVA is in the dermis region where tattoo ingredients reside. To evaluate the hazardous potential of BgP on human skin under UVA exposure, different experimental tools i.e., in-chemico, in-silico and in-vitro were utilized. Our results illustrated that BgP photosensitized under UVA (1.5 mW/cm2) irradiation shows a degradation pattern till 4 h exposure. Photosensitized BgP reduced significant cell viability (%) at 1 µg/ml concentration. However, the pretreatment of singlet and hydroxyl radical quenchers, restoration of cell viability observed, confirmed the role of type-I and type-II photodynamic reactions in phototoxicity of BgP. Further, intracellular uptake of BgP in HaCaT cells was estimated and confirmed by UHPLC analysis. Molecular docking of BgP with DNA and formation of γ-H2AX foci demonstrated the DNA intercalation and double-stranded DNA damaging potential of BgP. Furthermore, acridine orange and ethidium bromide (AO/EB) dual staining showed apoptotic cell death via photosensitized BgP under UVA irradiation. The above findings suggest that BgP reached the human skin cell and induced dermal toxicity via direct and indirect mode of DNA damage under UVA exposure finally promoting the skin cell death. Thus, BgP-containing tattoo ink may be hazardous and may induce skin damage and diseases, especially in presence of UVA radiation of sunlight. To minimize the risk of skin diseases from synthetic ingredients in tattoo ink, the study highlights the importance of developing eco-friendly and skin-friendly tattoo ingredients by companies.

Involvement of type-1 pathway in phototoxicity of benzo[ghi]perylenean ingredient of tattoo ink at ambient exposure of UVR and sunlight.

Tattooing on different parts of the body is a very common fashion trend in all sections of society globally. Skin allergies and other related skin diseases are very common among tattoo users. Benzo[ghi]perylene (BP) is a PAH and an important component of tattoo ink that showed prominent absorption under ultraviolet radiation (UVR) region. Therefore, to provide safety to the skin, a thorough safety study of BP exposed under UVR and Sunlight is very essential to understand their hazardous impact on the skin. BP showed a strong absorption of UVA and UVB radiation of sunlight. It is photolabile and degraded under UVA, UVB, and Sunlight in progressing order of time (1-4 h) without generating any novel photoproducts. Further, BP showed a specific generation of O2.- and OH radicals via activation of type I photodynamic reaction under exposure to UVA, UVB and Sunlight. Photocytotoxicity results illustrated concentration-dependent cell viability reduction in all exposure conditions of UVA, UVB, and Sunlight, respectively. Fluorescent probes (2',7'-dichlorofluorescein diacetate and dihydroethidium) for intracellular reactive oxygen species (ROS) generation supported the involvement of ROS in the phototoxicity of BP in the HaCaT cell line. Hoechst staining showed significant genomic insult induced by BP under UVA and UVB. Photoexcited BP promoted cell cycle arrest in the G1 phase and induced apoptosis confirmed via acridine orange/ethidium bromide staining. The findings of gene expression also supported apoptotic cell death in photoexcited BP via an increase in the level of pro-apoptotic gene (Bax) and a decrease in the level of anti-apoptotic gene (Bcl-2). The aforementioned finding indicates that tattoo users should avoid using BP since it can cause skin damage/diseases if they are exposed to UVR or Sunlight while tattooing on the body.