Jojoba ( Simmondsia chinensis L.) wax was previously reported to increase cutaneous wound healing, ameliorate acne and psoriasis manifestations, and reduce oxidative stress and inflammation. However, its potential cosmetic properties have not been fully investigated. Thus, the current study aimed to evaluate the anti-inflammatory activities of jojoba wax and its impact on the synthesis of extracellular components following topical application. The fatty acid and fatty alcohol profiles of two industrial and two lab-scale cold-press jojoba waxes were analyzed along with total tocopherol and phytosterol content. The dermo-cosmetic effect of all jojoba wax preparations was evaluated ex-vivo , using the human skin organ culture model, which emulates key features of intact tissue. The ability of jojoba wax to reduce secreted levels of key pro-inflammatory cytokines and the safety of the applications in the ex-vivo model were evaluated. In addition, the impact on the synthesis of pro-collagen and hyaluronic acid levels upon treatment was investigated. The results demonstrate that topically applied jojoba wax can reduce LPS-induced secretion of IL-6, IL-8, and TNFα by approx. 30% compared to untreated skin. This effect was enhanced when treatment was combined with low non-toxic levels of Triton X-100, and its efficacy was similar to the anti-inflammatory activity of dexamethasone used as a positive control. In addition, mRNA and protein levels of collagen III and synthesis of hyaluronic acid were markedly increased upon topical application of jojoba. Moreover, the enhanced content of extracellular matrix (ECM) components correlated with the enhanced expression of TGFβ1. Collectively, our results further demonstrate that jojoba can reduce local skin inflammation, and this effect may be increased by emulsifier which increases its bioavailability. In addition, the finding that topical application of jojoba wax enhances the synthesis of pro-collagen and hyaluronic acid and may be beneficial in the treatment of age-related manifestations.

Background

Skin aging manifestation, such as coarse wrinkles, loss of elasticity, pigmentation, and rough-textured appearance, is a multifactorial process that can be exacerbated by air pollution, smoking, poor nutrition, and sun exposure. Exposure to UV radiation is considered the primary cause of extrinsic skin aging and accounts for about 80% of facial aging. Extrinsic skin aging signs can be reduced with demo-cosmetic formulations. Both cannabidiol (CBD) and eicosapentaenoic acid (EPA) have been previously suggested as potent active dermatological ingredients.

Aims

The objective of the current research was to evaluate the compatibility of both agents in the prevention and treatment of skin aging. First, the impact of both agents was assessed using standard photoaging models of UV-induced damage, both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Then, a clinical validation study (n = 33) was performed using an optimized topical cream formulation tested at different time points (up to Day 56).

Results

EPA was found to potentiate the protective effects of CBD by reducing the secretion of prostaglandin E2 (PGE₂) and interleukin-8 (IL-8), two primary inflammatory agents associated with photoaging. In addition, a qualitative histological examination signaled that applying the cream may result in an increase in extracellular matrix (ECM) remodeling following UV radiation. This was also evidenced clinically by a reduction of crow's feet wrinkle area and volume, as well as a reduction of fine line wrinkle volume as measured by the AEVA system. The well-established age-dependent subepidermal low-echogenic band (SLEB) was also reduced by 8.8%. Additional clinical results showed significantly reduced red spots area and count, and an increase in skin hydration and elasticity by 31.2% and 25.6% following 56 days of cream application, respectively. These impressive clinical results correlated with high satisfaction ratings by the study participants.

Discussion and Conclusions

Collectively, the results show a profound anti-aging impact of the developed formulation and strengthen the beneficial derm-cosmetic properties of CBD-based products.

Herein, we report biocompatible hydrogel for wound healing that was prepared using nature-sourced building blocks. For the first time, OCS was employed as a building macromolecule to form bulk hydrogels along with the nature-sourced nucleoside derivative (inosine dialdehyde, IdA) as the cross-linker. A strong correlation was obtained between the mechanical properties and stability of the prepared hydrogels with a cross-linker concentration. The Cryo-SEM images of IdA/OCS hydrogels showed an interconnected spongy-like porous structure. Alexa 555 labeled bovine serum albumin was incorporated into the hydrogels matrix. The release kinetics studies under physiological conditions indicated that cross-linker concentration could also control the release rate. The potential of hydrogels in wound healing applications was tested in vitro and ex vivo on human skin. Topical application of the hydrogel was excellently tolerated by the skin with no impairment of epidermal viability or irritation, determined by MTT and IL-1α assays, respectively. The hydrogels were used to load and deliver epidermal growth factor (EGF), showing an increase in its ameliorating action, effectively enhancing wound closure inflicted by punch biopsy. Furthermore, BrdU incorporation assay performed in both fibroblast and keratinocyte cells revealed an increased proliferation in hydrogel-treated cells and an enhancement of EGF impact in keratinocytes.

Acne vulgaris, the most common form of acne, is characterized by a mixed eruption of inflammatory and noninflammatory skin lesions primarily affecting the face, upper arms, and trunk. The pathogenesis of acne is multifactorial and includes abnormal keratinization and plugging of the hair follicles, increased sebum production, proliferation and activation of Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes, P. acnes), and finally inflammation. Recent studies have found that cannabidiol (CBD) may be beneficial in the treatment of acne. The aim of this study was to explore natural plant extracts that, when combined with CBD, act synergistically to treat acne by targeting different pathogenic factors while minimizing side effects. The first stage of the study investigated the capacity of different plant extracts and plant extract combinations to reduce C. acnes growth and decrease IL-1β and TNFα secretion from U937 cells. The results found that Centella asiatica triterpene (CAT) extract as well as silymarin (from Silybum marianum fruit extract) had significantly superior anti-inflammatory activity when combined with CBD compared to either ingredient alone. In addition, the CAT extract helped potentiate CBD-induced C. acnes growth inhibition. The three ingredients were integrated into a topical formulation and evaluated in ex vivo human skin organ cultures. The formulation was found to be safe and effective, reducing both IL-6 and IL-8 hypersecretion without hampering epidermal viability. Finally, a preliminary clinical study of this formulation conducted on 30 human subjects showed a statistically significant reduction in acne lesions (mainly inflammatory lesions) and porphyrin levels, thereby establishing a tight correlation between in vitro, ex vivo, and clinical results. Further studies must be conducted to verify the results, including placebo-controlled clinical assessment, to exclude any action of the formulation itself.

Copper is known for its strong biocidal and anti-inflammatory properties, and as an accelerator of angiogenesis, cell proliferation and secretion of Extra Cellular Matrix (ECM) proteins. It is therefore an excellent candidate in the treatment of wounds. The role of few factors which presumably mediate copper’s ability to promote wound healing processes is already established. However, the molecular mechanism by which copper facilitates healthy wound healing in a way that can explain the connection between the early events in the wound microenvironment with later healing processes such as tissue formation and remodeling is not entirely clear.

Several chemophysical methods that facilitates the transport of bioactive macromolecules, including insulin, across the skin barrier have been reported. These methods include the use of transdermal photopolymerization and skin electroporation, microneedles and ultrasound-mediated penetration. Delivery methods enabling the transport of insulin without the auxiliary physical penetration for passive transdermal delivery have also attracted a great deal of attention. We have recently designed and synthesized novel biocompatible nanocarriers based on modified polysaccharides.

Background: The Dead Sea basin is the lowest terrestrial site on the globe and is internationally recognized as a photoclimatotherapy center. Since the last century, questions were raised regarding a possible presence of unique incident ultraviolet irradiation, allowing the successful treatment of psoriasis, atopic dermatitis and other dermatological diseases. Aim: This research study aims to determine the characteristics of solar ultraviolet irradiation and to understand the mechanism of action of photoclimatotherapy while applying results to clinical protocols of treatments. Methods: A meteorological station was established at the Dead Sea basin to continuously measure global, UVB and UVA irradiation. The same irradiation parameters are also monitored continuously by a set of identical ultraviolet irradiation instruments installed on the campus of the Ben-Gurion University of the Negev in Beer Sheva. Results: This study details the results of these long-term measurements, as well as their correlation with the success obtained by clinicians treating psoriasis patients. Conclusions: A database of more than 25 years has enabled medical staff to establish tailor-made protocols for sun-exposure time intervals as a function of particular month and hour of day. The availability of such information significantly improved the results of photoclimatotherapy for psoriasis and simultaneously increased the safety of sun exposure at the Dead Sea.

IFN-β is a cytokine that plays a significant role in the immune system. Inhibition of IFN-β might be used as a therapeutic approach to treat septic shock. A peptidomimetic previously developed by our research team, 1-benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one (LT87), was used as an cardioprotective agent in a myocardial ischemia (MI) mouse model. We have developed new LT87 derivatives by synthetizing its dimers in an attempt to extend its structural variety and enhance its biological activity. A dimeric derivative, LT127, exhibited a dose-dependent inhibition of LPS-mediated IFN-β and subsequent CXCL10 mRNA transcription. The effect was selective and transduced through TLR4- and TRAM/TRIF-mediated signaling, with no significant effect on MyD88-dependent signaling. However, this effect was not specific to TLR4, since a similar effect was observed both on TLR8- and MDA5/RIG-I-stimulated IFN-β expression. Nevertheless, LT127 might serve as a drug candidate, specifically as an inhibitor for IFN-β production in order to develop a novel therapeutic approach to prevent septic shock.

The skin barrier and its endogenous protective mechanisms cope daily with exogenous stressors, of which ultraviolet radiation (UVR) poses an imminent danger. Although the skin is able to reduce the potential damage, there is a need for comprehensive strategies for protection. This is particularly important when developing pharmacological approaches to protect against photocarcinogenesis. Activation of NRF2 has the potential to provide comprehensive and long-lasting protection due to the upregulation of numerous cytoprotective downstream effector proteins that can counteract the damaging effects of UVR. This is also applicable to photodermatosis conditions that exacerbate the damage caused by UVR. This review describes the alterations caused by UVR in normal skin and photosensitive disorders, and provides evidence to support the development of NRF2 activators as pharmacological treatments. Key natural and synthetic activators with photoprotective properties are summarized. Lastly, the gap in knowledge in research associated with photodermatosis conditions is highlighted.

Environmental risk factors, including noise, air pollution, chemical agents, ultraviolet radiation (UVR) and mental stress have a considerable impact on human health. Oxidative stress and inflammation are key players in molecular pathomechanisms of environmental pollution and risk factors. In this review, we delineate the impact of environmental risk factors and the protective actions of the nuclear factor erythroid 2-related factor 2 (NRF2) in connection to oxidative stress and inflammation. We focus on well-established studies that demonstrate the protective actions of NRF2 and its downstream pathways against different environmental stressors. State-of-the-art mechanistic considerations on NRF2 signaling are discussed in detail, e.g. classical concepts like KEAP1 oxidation/electrophilic modification, NRF2 ubiquitination and degradation. Specific focus is also laid on NRF2-dependent heme oxygenase-1 induction with detailed presentation of the protective down-stream pathways of heme oxygenase-1, including interaction with BACH1 system. The significant impact of all environmental stressors on the circadian rhythm and the interactions of NRF2 with the circadian clock will also be considered here. A broad range of NRF2 activators is discussed in relation to environmental stressor-induced health side effects, thereby suggesting promising new mitigation strategies (e.g. by nutraceuticals) to fight the negative effects of the environment on our health.