The solar ultraviolet (UV) radiation is a predominant risk factor for skin diseases [1]. Despite accounting for <5% of total sunlight reaching the earth's surface, ultraviolet-B (UV-B) exposure is highly damaging to the skin because of its high energy and bio-molecule absorption. Although the amount of UV-B exposure is limited, it is more detrimental than UV-A. The UV-B photons are around 1000 times more harmful than UV-A [2]. Skin serves as the initial line of defense in the human body, functioning as a shield against environmental stresses [3].

Skin acts like an immunological organ and maintains homeostasis for its proper functioning. Nevertheless, overactive immune responses can result in chronic skin inflammation, culminating in inflammatory skin illnesses. UV-B causes acute inflammatory issues in the skin, including erythema and cell death. UV-B-induced inflammatory response activation and subsequent activation of a related signalling pathway would then drive the synthesis of specific inflammatory mediators such as different cytokines and prostaglandins (PGs). COX-2 cascades mediate the inflammatory process, producing pain, edema, and cellular proliferation and may lead to tumour initiation and progression [4,5]. Inflammation is a fundamental biological reaction to external toxic stimulants, which aids in the repairment of damage and the prevention of additional tissue or cell injury [6]. When the inflammatory response is not adequately suppressed, it leads to chronic inflammation or multi-organ failure [6]. It has been proven that inflammation is critical in the etiology and pathogenesis of skin disorders caused by UV-B exposure [7]. Furthermore, the inflammatory process mediates the aging process through alterations in redox balance and oxidative stress-mediated inflammatory responses [8], known as inflamm-aging [9].

UVB causes epidermal changes and skin damage by generating reactive oxygen species (ROS), which has been shown to cause mitochondrial aberrations in UV-B-irradiated skin [10]. In the physiology of mammals, mitochondria are small organelles within cells, essential for cellular metabolism [11]. The characteristics governing the mitochondrion's shape, size and location inside the cell are known as mitochondrial dynamics. Mitochondrial dynamics implies alterations in mitochondrial morphology and mobility, which allow cells to adapt to external stimuli. Concerning the size and shape, “Fusion” and “Fission” mechanisms are two critical drivers of mitochondrial fate. The journey of mitochondria from fusion to fission and vice versa is mediated by GTPases, illustrating the basic machinery of mitochondrial dynamics. Mitochondrial fusion is regulated by several essential proteins, including mitofusin 1 (MFN1) and mitofusin 2 (MFN2), whereas mitochondrial fission is primarily governed by dynamin-related protein 1 (DRP1) and mitochondrial fission 1 (FIS1). The precise expression and activity of these proteins are required to maintain a proper equilibrium between mitochondrial fusion and fission, ensuring mitochondrial and cellular homeostasis [12].

Several disorders have been linked to changes in the fission/fusion balance (mainly a shift towards fission) [13,14]. A recent study reported the involvement of mitochondrial fragmentation in triggering inflammation in myoblasts [15]. A 2020 study demonstrated the role of mitochondrial fission in inflammation in primary rat aortic endothelial cells [16]. These findings highlight the pathological significance of mitochondrial dynamics in inflammation. However, the exact molecular role of altered mitochondrial dynamics in UV-B-induced inflammation is yet to be adequately studied. So, we attempted to investigate the potential mechanism linking UV-B-induced impaired mitochondrial dynamics and inflammatory response in primary human dermal fibroblasts and Balb/c mice.

A new wave of recent interest in finding therapeutically competent natural compounds that can target mitochondrial function and modulate mitochondrial dynamics has emerged [17] [18]. Natural products act as potential drug candidates for mitochondrial dysfunction through various mechanisms, including regulating mitochondrial morphology. Quercetin has been reported to prevent the alleviation of hypobaric hypoxia-induced memory impairment in rats via inhibition of Drp1 [18]. Curcumin, a bioactive ingredient derived from the rhizome of Curcuma longa L. (Zingiberaceae), has been demonstrated to increase FIS1 and decrease OPA1 to prevent cisplatin-induced renal alterations [19]. Based on the above research findings, we intended to investigate the mito-protective potential of Naringenin, a naturally occurring flavonoid molecule found in Sea buckthorn berries, against UV-B-induced inflammation.

Naringenin is a flavonoid, usually found in citrus fruits that has been reported to protect from multiple diseases due to its anti-oxidant and anti-inflammatory properties [20] [21]. These properties strongly suggested the potential protective role of Naringenin in UV-B induced photodamage. In the current study, the therapeutic effects of Naringenin in UV-B induced photodamage particularly impaired mitochondrial dynamics and inflammation were evaluated using primary human dermal fibroblasts and Balb/c mice model.