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The stimulator of interferon genes (STING) signaling pathway is crucial for the pathogenesis of autoimmune and inflammatory disorders, including acute lung injury (ALI). Apigenin (4 ′ ,5,7-trihydroxyflavone) is a natural flavonoid widely found in fruits, vegetables, and Chinese medicinal herbs that exhibits a range of pharmacological effects, such as antibacterial and anti-inflammatory activities. However, the efficacy of apigenin in STING pathway-mediated diseases remains unclear. Accordingly, this study screened Chinese medicines to identify potent agents that reduced the synthesis of type I interferons (IFNs). The results revealed apigenin as a potent compound with low cytotoxicity that markedly reduced the synthesis of type I IFNs in response to STING pathway agonists. Besides, apigenin markedly suppressed innate immune responses triggered by the STING agonist SR-717. Mechanistically, apigenin downregulated IFN beta 1 (IFNB1) expression mediated by the STING pathway via dose-dependent inhibition of STING expression, reduction of dimerization, nuclear translocation of phosphorylated IRF3, and disruption of the association between STING and IRF3. Moreover, apigenin effectively mitigated pathological pulmonary inflammation and lung edema in lipopolysaccharide (LPS)-induced ALI in mice. Apigenin further strongly attenuated the hallmarks of immoderate inflammation (interleukin (IL)-6, IL-1 β , and tumor necrosis factor α) and innate immune responses (IFNB1, C-X-C motif chemokine ligand 10, and IFN-stimulated gene 15) by preventing the activation of the STING/IRF3 pathway both in vitro and in vivo. Importantly, SR-717 significantly reversed the inhibitory effects of apigenin in LPS-induced THP1-BlueTM ISG macrophages. Collectively, apigenin effectively alleviated innate immune responses and mitigated inflammation in LPS-induced ALI via inhibition of the STING/IRF3 pathway. These findings suggest the potential of apigenin as a prophylactic and therapeutic candidate for managing STING-mediated diseases. [ABSTRACT FROM AUTHOR]

Apigenin (4,'5,7-trihydroxyflavone) is one of the most studied flavonoids with low toxicity and abundantly present phenolic compound in the plant kingdom. The main sources of apigenin are fruits, vegetables, nuts, herbs, honey, and plant-based drinks like tea. Numerous plants produce apigenin as a secondary metabolite and its intake is strongly related to its anti-inflammatory propensities. The purpose of present review was to wade through the literature on the anti-inflammatory mechanisms of this metabolite in various diseases and summarize the key objectives as they appear. Existing literature reported that apigenin is a promising candidate in managing a panoply of inflammatory-related diseases including cancer, diabetes, obesity, depression, insomnia, infection, and respiratory, cardiovascular, hepatoprotective, neurodegenerative, and skin diseases. Studies showed that apigenin significantly decreases the secretion of various proinflammatory cytokines specifically tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-10. Moreover, apigenin effectively blocks the nitric oxide-mediated cyclooxygenase-2 expression and monocyte attachment and Prostaglandin by lowering iNOS and COX-2 in both microglial and macrophage mouse cells. Apigenin can slow the course of nonalcoholic fatty liver disease (NAFLD) in vivo by reducing high fat diet (HFD)-induced deposition of lipids and oxidative stress. It also controlled redox imbalances, suppress neuronal death and showed memory enhancement/learning skills and a reduction of fibrillar amyloid deposits with lowered insoluble Aβ concentrations in vivo. Taken together, it can be argued that apigenin can wane inflammation and thus offers a promising future in slowing down the development of chronic diseases and associated complications. [ABSTRACT FROM AUTHOR]

Apigenin is one of the abundant flavonoids in fruits and vegetables of human diet with several demonstrated health benefits. The aim of the present study is to provide an overview of the current evidence regarding the effect of apigenin on different dermatological complications. Electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve all papers assessing the dermatological effects of apigenin. Preclinical studies support beneficial effects of apigenin on UV-induced skin damage, vitiligo, dermatitis, wounds, skin aging, and some types of skin cancer. The compound mostly acts via inhibition of inflammation through suppression of pro-inflammatory cytokines and intracellular inflammatory mediators, as well as antioxidant properties such as improvement of endogenous antioxidant defense mechanisms. There are also some studies for the design and development of novel drug delivery systems for apigenin to improve its oral and topical bioavailability. Nevertheless, no clinical study has evaluated apigenin as a natural supplement for skin conditions. Considering the benefits of apigenin in preclinical models of dermatological disorders, as well as the acceptable safety of this compound, apigenin may be a future candidate to be used in dermatological disorders. Future clinical studies are needed to further confirm the safety and efficacy of apigenin in skin care products. [Display omitted] • Apigenin is an abundant flavonoid in human diet. • Preclinical studies show the benefits of apigenin in dermatological disorders. • Dermatological benefits of apigenin appear in both oral and topical administration. • Apigenin can be considered as a future cosmeceutical in skin care products. • Dietary apigenin-rich products can also be used to have a healthy skin. [ABSTRACT FROM AUTHOR]