Photoprotective Potential of the Natural Artocarpin against In Vitro UVB-Induced Apoptosis

Abstract

Apoptosis, a well-known pattern of programmed cell death, occurs in multicellular organisms not only for controlling tissue homeostasis but also for getting rid of severely damaged cells in order to protect the redundant growth of abnormal cells undergoing cancerous cells. The epidermis of the human skin, composed largely of keratinocytes (KCs), is renewed continuously. Therefore, KCs apoptosis plays a critical role in the maintenance of epidermis structure and function. However, regulated cell death can be disturbed by environmental factors especially ultraviolet radiation (UV) B, leading to the formation of sunburn cells (KCs undergoing UVB-induced apoptosis) and impairing the skin integrity. In the present study, we firstly reported the potential of the natural artocarpin (NAR) to regulate UVB-induced human KCs apoptosis. The NAR showed antilipid peroxidation with an IC50 value of 18.2±1.6 μg/mL, according to TBARS assay while the IC50 value of trolox, a well-known antioxidant, was 7.3±0.8 μg/mL. For cell-based studies, KCs were pretreated with 3.1 μg/mL of the NAR for 24 hr and then exposed to UVB at 55 mJ/cm2. Our data indicated that the NAR pretreatment reduces UVB-induced oxidative stress by scavenging free radicals and nitric oxide and therefore prevents reactive oxygen species (ROS) and reactive nitrogen species- (RNS-) mediated apoptosis. The NAR pretreatment has been shown also to reduce the UVB-induced cyclobutane pyrimidine dimer (CPD) lesions by absorbing UVB radiation and regulating the cell cycle phase. Additionally, the NAR pretreatment was found to modulate the expression of cleaved caspases-3 and 8 that trigger different signalling cascades leading to apoptosis. Thus, these results provide a basis for the investigation of the photoprotective effect of the NAR isolated from A. altilis heartwood and suggest that it can be potentially used as an agent against UVB-induced skin damages.

Prevention by the Natural Artocarpin of Morphological and Biochemical Alterations on UVB‐Induced HaCaT Cells

“…We reported that the NAR pretreatment prevents membrane rigidification induced by ROS and nitrite. Our previous data supported that NAR reduces lipid peroxidation products (LPOs) in vitro [33]. In addition, it has been shown that a topical treatment with artocarpin on hairless mice before UVB exposure decreases LPOs [30].…”

“…Sorting from low, moderate, and high amounts of UVB, the diverse features of cell death can be induced by running from apoptosis without inflammation, to apoptosis with a proinflammatory cytokine, and eventually up to necrosis with inflammation [35]. Our previous data showed that apoptosis 9 Oxidative Medicine and Cellular Longevity induced with a physiological dose of 55 mJ/cm 2 UVB was initiated by CPD lesions in DNA as well as ROS production, and mediated by caspase-3 and 8 activation [33]. In this work, we investigated other relevant markers of apoptosis to analyze the complete UVB response.…”

“…Purification of Natural Artocarpin. Natural artocarpin was purified from the heartwood of the A. altilis plant according to the method described in previously published papers [32,33]. Briefly, the heartwood was chipped into small pieces and dried at 45°C until dryness.…”

“…UVB Exposure. Cells were exposed to UVB irradiation with an intensity of 55 mJ/cm 2 , as previously described [33]. The UV source was provided by UVB tubes (8 W, F8T5, Sankyo Denki, Japan) which radiate UV rays during 280-360 nm (peak wavelength from 305 to 315 nm).…”

“…Several reports have shown interest in flavonoids in the prevention of diseases due to their pharmacological actions, mainly their antioxidant and chelating properties [ 26 ]. Notably, it has been shown that the Artocarpus altilis plant possesses biological efficacy, and in vitro as well as in vivo research is focused on antioxidation [ 27 – 33 ], antilipid peroxidation [ 30 , 33 ], anti-inflammation [ 30 , 32 ], antityrosinase activity [ 27 – 29 ], and antiapoptotic [ 33 ] activity. Our previous data have demonstrated the photoprotection activities of the natural artocarpin (NAR) isolated from Artocarpus altilis 's heartwood extract in UVB-induced keratinocyte apoptosis [ 33 ].…”