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.
The physicochemical and biological properties of the blended fibroin/aloe gel film as a wound dressing were investigated to support the wound healing efficacy of the film described in our previous study. In the current study, protein content, molecular weight pattern, and chemical characteristics of the silk fibroin and the aloe gel extracts were analyzed. The two extracts were then dissolved in lactic acid solution and casted to obtain the blended fibroin/aloe gel film. We found that gamma irradiation did not affect any physicochemical properties of the film, i.e., the irradiated and the non-sterilized films had similar physical appearance, surface morphology, mechanical properties, and chemical characteristics. On normal human fibroblast cultures, the film induced non-cytotoxicity and stimulated the expression of vascular epidermal growth factor. The film-treated cells were shown to proliferate by shifting from G 0 /G 1 phase (76.26 ± 0.72%) to S phase (7.19 ± 0.23%) and G 2 /M phase (16.09 ± 0.58%) which are higher than the untreated cells. The film-treated cells provided a completely healed scratch at 36 h after scratch creation, while the created scratch of the untreated cells was not healed, indicating that the biological activity of the film enhanced the proliferation and the migration of fibroblast cells. We speculated that the prepared film might be able to use as wound dressing for the diabetic foot ulcer.
Natural substances have gained considerable attention for skin protection against UV light reactions. Artocarpus altilis plant’s heartwood extract is comprised of artocarpin as a major substance, already known for its interesting biological attributes as an antimicrobial, an anti-inflammatory, an antioxidant, and a melanogenesis inhibitor. The present work clarified the mechanism of natural artocarpin (NAR) with a purity of approximately 99% against the effects of UVB-induced HaCaT keratinocyte apoptosis. The indicated results showed that NAR suppresses free radical production (ROS and nitrite) and apoptosis-related molecule activation (caspase-3, p-p53, p-p38, and NF-κB p65) and secretion (TNF-α). Additionally, NAR prevented structural damages (nuclei condensation and fragmentation, apoptotic body formation, impaired cell adherence and round cell shape, disruption of F-actin filament, and clustering of cell death receptor CD95/Fas) and biophysical changes (plasma membrane rigidification). Thus, NAR acts directly from scavenging free radicals generated by UV and indirectly by suppressing morphological and biochemical UV-induced cell damages. Its biological effects are mainly attributed to antioxidant and antiapoptotic properties. Taken together, NAR could be considered as an effective natural product for photoprotective formulations.
Skin fungal infection is still a serious public health problem due to the high number of cases. Even though medicines are available for this disease, drug resistance among patients has increased. Moreover, access to medicine is restricted in some areas. One of the therapeutic options is herbal medicine. This study aims to develop an ethosome formulation loaded with Zingiber zerumbet (L.) Smith. rhizome extract for enhanced antifungal activity in deep layer skin, which is difficult to cure. Ethosomes were successfully prepared by the cold method, and the optimized formulation was composed of 1% (w/v) phosphatidylcholine and 40% (v/v) ethanol. Transmission electron microscope (TEM) images revealed that the ethosomes had a vesicle shape with a diameter of 205.6–368.5 nm. The entrapment of ethosomes was 31.58% and could inhibit the growth of Candida albicans at a concentration of 312.5 μg/mL. Finally, the ethosome system significantly enhanced the skin penetration and retention of the active compound (zerumbone) compared with the liquid extract. This study showed that Z. zerumbet (L.) rhizome extract could be loaded into ethosomes. The findings could be carried over to the next step for clinical application by conducting further in vivo penetration and permeation tests.
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