Phototoxic Effects Research Articles

On the photobehaviour of curcumin in biocompatible hosts: The role of H-abstraction in the photodegradation and photosensitization.

Curcumin (CUR) is a naturally occurring pigment extensively studied due to its therapeutic activity and delivered by suitable nanocarriers to overcome poor solubility in aqueous media. The significant absorption of CUR in the visible blue region has prompted its use as a potential phototherapeutic agent in treating infectious and cancer diseases, although the mechanism underlying the phototoxic effects is still not fully understood. This contribution investigates the photobehaviour of CUR within polymeric micelles, microemulsions, and zein nanoparticles, chosen as biocompatible nanocarriers, and human serum albumin as a representative biomolecule. Spectroscopic studies indicate that in all host systems, the enolic tautomeric form of CUR is converted in a significant amount of the diketo form because of the perturbation of the intramolecular hydrogen bond. This leads to intermolecular H-abstraction from the host components by the lowest excited triplet state of CUR with the formation of the corresponding ketyl radical, detected by nanosecond laser flash photolysis. This radical is oxidized by molecular oxygen, likely generating peroxyl and hydroperoxyl radical species, unless in Zein, reasonably due to the poor availability of oxygen in the closely packed structure of this nanocarrier. In contrast, no detectable formation of singlet oxygen was revealed in all the systems. Overall these results highlight the key role of the H-abstraction process over singlet oxygen sensitization as a primary photochemical pathway strictly dictated by the specific features of the microenvironment, providing new insights into the photoreactivity of CUR in biocompatible hosts that can also be useful for a better understanding of its phototoxicity mechanism.

Obtaining emulsions of furanocoumarins from Sosnowsky’s hogweed and <i>in vitro</i> assessment of their phototoxic effect

Background. Furanocoumarin-based drugs are used for photochemotherapy of various diseases. Sosnovsky’s hogweed can be an available source of furanocoumarins for the development of drugs.The aim of the study. To obtain stable emulsions containing furanocoumarins from Sosnowski’s hogweed and to evaluate their photocytotoxicity.Materials and methods. To obtain the emulsions, furanocoumarins were extracted with chloroform from the sap of the aerial part of the Sosnowski’s hogweed. The chloroform extract was clarified by silica gel gradient column chromatography. The extractive fraction containing furanocoumarins was analyzed by high performance liquid chromatography with ultraviolet (UV) detection. An extract with a high content of 8-methoxypsoralen was used to prepare two types of emulsions. The extract was dissolved in peach oil and emulsified in water with tween-80 (emulsion No. 1) and in an aqueous glycerin solution with lecithin (emulsion No. 2).The emulsions were tested for dark and photo-induced toxicity for human lung fibroblasts. The dose of UV radiation for the photoactivation of furanocoumarins was 9 J/cm2. A solution of chlorine e6 was used as a comparison photosensitizer.Results. The obtained emulsions contained 1 mg/ml 8-methoxypsoralen. Both emulsions were homogeneous at macro- and microscopic visualization, remained stable when stored under various temperature conditions for 14 days. Emulsion No. 2 did not show dark toxicity and caused a statistically significant inhibition of cell viability under UV irradiation at a concentration of 12.5–31.3 µg/mL. Emulsion No. 1 had a toxic effect on cells regardless of UV irradiation due to the content of tween-80. According to fluorescent microscopy, the phototoxic effect of emulsion No. 2 was manifested mainly due to apoptosis, in contrast to the effect of chlorine e6, in which there were more pronounced signs of cell necrosis.Conclusion. The developed experimental emulsions of furanocoumarins from Sosnovski’s hogweed are an example of promising medicinal photosensitizers of plant origin for phototherapy of various dermatological and oncological diseases.

Oxidative cross-linking of biocompatible chitosan injectable hydrogel by perylene-dopamine to boost phototoxicity of perylene on in vitro melanoma and breast cancer therapy

This research focused on improving the photodynamic properties of perylene through a hydrogel formulation in which PBI-DOPA cross-links chitosan chains. Photosensitive CS/PBI-DOPA hydrogel was synthesized through an oxidative cross-linking method and exhibited a biocompatible microporous structure capable of shear thinning behavior and outstanding singlet oxygen quantum efficiency. An in vitro comparative study on the phototoxic and anticancer effects of perylene tetracarboxylic dihydride (PTCDA), free PBI-DOPA and its CS/PBI-DOPA hydrogel formulation on skin cancer (A375), breast cancer (MDA- MB-231) and normal fibroblast cells were performed. The hydrogel formula showed its superiority in reducing the survival of cancer cells while minimizing toxicity in normal cells, compared to both free perylene compounds. Therefore, CS/PBI-DOPA hydrogel could be introduced as a promising biocompatible carrier system with significant efficiency for perylene delivery.

Novel anthraquinone photosensitizers: Synthesis, photoactivity, and 3D-QSAR studies

In this study, three-dimensional quantitative conformational relationship (3D-QSAR) analysis was conducted on 38 known anthraquinone derivatives. Additionally, five pH-responsive anthraquinone photosensitizers (A1 to A5) were designed and synthesized through addition, elimination, and substitution mechanisms using the anthraquinone derivative chrysophanol as the raw material. The structures of the products were characterized using 1HNMR, 13CNMR , LCMS, and the UV–Vis absorption spectra and fluorescent spectra at different pH values were obtained. To investigate the photodynamic antibacterial activity of the compounds, their inhibitory activities against Pseudomonas aeruginosa and Staphylococcus aureus were tested in vitro under different light and pH conditions. The results showed that the compounds exhibited good photodynamic antibacterial activity and selectivity in light and weak acid environments. MTT experiments were conducted to evaluate the cytotoxicity of the compounds on the human cancer cell line HeLa. It was found that the phototoxicity and dark toxicity effects of compound A3 at concentrations of 0.625 μM and lower were similar to those of the reference photosensitizer Chlorin e6 (Ce6). However, the amount of singlet oxygen produced by A3 was approximately 7.6 times that produced by Ce6, indicating its potential for application in the photodynamic therapy of tumours and providing a reference for research on anthraquinone photosensitizers.

New Insights into the Phototoxicity of Anthracene-Based Chromophores: The Chloride Salt Effect†.

Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature. Toward this end, we have studied the DNA interactions and photochemistry of N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride in the presence and absence of NaF, KF, NaCl, KCl, NaBr, KBr, NaI, and KI (350 nm hν, pH 7.0). Exposing pUC19 plasmid to UV light in solutions containing 400 mM KCl formed significantly more direct strand breaks in DNA compared to no-salt control reactions. In contrast, NaCl increased DNA damage moderately, while the sodium(I) and potassium(I) fluoride, bromide, and iodide salts generally inhibited cleavage (I- > Br- > F-). A halide anion-induced heavy-atom effect was indicated by monitoring anthracene photodegradation and by employing the hydroxyl radical (•OH) probe hydroxyphenyl fluorescein (HPF). These studies revealed that among no-salt controls and the eight halide salts, only NaCl and KCl enabled the anthracene to photosensitize the production of high levels of DNA-damaging reactive oxygen species (ROS). Pre-irradiation of N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride at 350 nm increased the amounts of chloride salt-induced •OH detected by HPF in subsequent anthracene photoactivation experiments. Taking into consideration that •OH and other highly reactive ROS are extremely short-lived, this result suggests that the pre-irradiation step might lead to the formation of oxidized anthracene photoproducts that are exceedingly redox-active. The fluorometric probes HPF and Singlet Oxygen Sensor Green revealed that KCl concentrations ranging from 150 to 400 mM and from 100 to 400 mM, respectively, enhanced N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride photosensitized •OH and singlet oxygen (1O2) production over no-salt controls. Considering the relatively high levels of Na+, K+, and Cl- ions that exist in the environment and in living organisms, our findings may be relevant to the phototoxic effects exhibited by anthracenes and other polycyclic hydrocarbons in vivo.

Ultraviolet light affects the color vocabulary: evidence from 834 languages.

It has been suggested that people living in regions with a high incidence of ultraviolet light, particularly in the B band (UV-B), suffer a phototoxic effect during their lifetime. This effect, known as lens brunescence, negatively impacts the perception of visible light in the "blue" part of the spectrum, which, in turn, reduces the probability that the lexicon of languages spoken in such regions contains a word specifically denoting "blue." This hypothesis has been recently tested using a database of 142 unique populations/languages using advanced statistical methods, finding strong support. Here, this database is extended to 834 unique populations/languages in many more language families (155 vs. 32) and with a much better geographical spread, ensuring a much better representativity of the present-day linguistic diversity. Applying similar statistical methods, supplemented with novel piecewise and latent variable Structural Equation Models and phylogenetic methods made possible by the much denser sampling of large language families, found strong support for the original hypothesis, namely that there is a negative linear effect of UV-B incidence on the probability that a language has a specific word for "blue." Such extensions are essential steps in the scientific process and, in this particular case, help increase our confidence in the proposal that the environment (here, UV-B incidence) affects language (here, the color lexicon) through its individual-level physiological effects (lifetime exposure and lens brunescence) amplified by the repeated use and transmission of language across generations.

A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression.

Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.

UVA/UVB Irradiation Exerts a Distinct Phototoxic Effect on Human Keratinocytes Compared to Human Malignant Melanoma Cells.

Solar ultraviolet radiation (UVR) is responsible for the development of many skin diseases, including malignant melanoma (MM). This study assessed the phototoxic effects of UVA, and UVB radiations on healthy and pathologic skin cells by evaluating the behavior of human keratinocytes (HaCaT) and MM cells (A375) at 24 h post-irradiation. The main results showed that UVA 10 J/cm2 exerted no cytotoxicity on HaCaT and A375 cells, while UVB 0.5 J/cm2 significantly reduced cell viability and confluence, induced cell shrinkage and rounding, generated nuclear and F-actin condensation, and induced apoptosis by modulating the expressions of Bax and Bcl-2. The association of UVA 10 J/cm2 with UVB 0.5 J/cm2 (UVA/UVB) induced the highest cytotoxicity in both cell lines (viability < 40%). However, the morphological changes were different-HaCaT cells showed signs of necrosis, while in A375 nuclear polarization and expulsion from the cells were observed, features that indicate enucleation. By unraveling the impact of different UVR treatments on the behavior of normal and cancer skin cells and describing enucleation as a novel process involved in the cytotoxicity of UVA/UVB irradiation, these findings bridge the gap between the current and the future status of research in the field.

Effect of Hypericin-Mediated Photodynamic Therapy on the Secretion of Soluble TNF Receptors by Oral Cancer Cells.

Squamous cell carcinoma is the most common cancer of the head and neck region. In addition to the classic surgical treatment method, alternative therapy methods are sought. One such method is photodynamic therapy (PDT). In addition to the direct cytotoxic effect, it is essential to determine the effect of PDT on persistent tumor cells. The study used the SCC-25 oral squamous cell carcinoma (OSCC) cell line and the HGF-1 healthy gingival fibroblast line. A compound of natural origin-hypericin (HY)-was used as a photosensitizer (PS) at concentrations of 0-1 µM. After two hours of incubation with the PS, the cells were irradiated with light doses of 0-20 J/cm2. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test was used to determine sublethal doses of PDT. Cell supernatants subjected to sublethal PDT were assessed for soluble tumor necrosis alpha receptors (sTNF-R1, sTNF-R2). The phototoxic effect was observed starting with a light dose of 5 J/cm2 and amplified with the increase in HY concentration and light dose. A statistically significant increase in sTNF-R1 secretion by SCC-25 cells was demonstrated after the PDT with 0.5 µM HY and irradiation with 2 J/cm2 (sTNF-R1 concentration = 189.19 pg/mL ± 2.60) compared to the control without HY and irradiated with the same dose of light (sTNF-R1 concentration = 108.94 pg/mL ± 0.99). The baseline production of sTNF-R1 was lower for HGF-1 than for SCC-25, and secretion was not affected by the PDT. The PDT had no effect on the sTNF-R2 production in the SCC-25 or HGF-1 lines.

Breaking a Dogma: High-Throughput Live-Cell Imaging in Real-Time with Hoechst 33342.

Automated high-throughput live cell imaging (LCI) enables investigation of substance effects on cells in vitro. Usually, cell number is analyzed by phase-contrast imaging, which is reliable only for a few cell types. Therefore, an accurate cell counting method, such as staining the nuclei with Hoechst 33342 before LCI, will be desirable. However, since the mid-1980s, the dogma exists that Hoechst can only be used for endpoint analyses because of its cytotoxic properties and the potentially phototoxic effects of the excitation light. Since microscopic camera sensitivity has significantly improved, this study investigates whether this dogma is still justified. Therefore, exposure parameters are optimized using a 4× objective, and the minimum required Hoechst concentration is evaluated, allowing LCI at 30-min intervals over 5days. Remarkably, a Hoechst concentration of only 57× 10-9 m significantly inhibits proliferation and thus impairs cell viability. However, Hoechst concentrations between 7 × 10-9 and 28× 10-9 m can be determined, which are neither cytotoxic nor impacting cell viability, proliferation, or signaling pathways. The method can be adapted to regular inverted fluorescence microscopes and allows, for example, to determine the cytotoxicity of a substance or the transduction efficiency, with the advantage that the analysis can be repeated at any desired time point.

Titanium Dioxide Nanoparticles in sunscreens and skin photo-damage. Development, synthesis and characterization of a novel biocompatible alternative based on their in vitro and in vivo study

Titanium dioxide nanoparticles are widely used in cosmetics, especially in sunscreens due to their capacity to absorb UV harmful wavelengths. However, their biocompatibility remains controversial. In this work, the effect of titanium dioxide nanoparticles, particularly Degussa P25 (P25TiO2NPs) under solar-simulated radiation was studied in vitro and in vivo. Cell viability and tissue integrity were affected after exposure to P25TiO2NPs and light for 6 h, showing signs of significant oxidative stress markers and reduced tissue integrity observed by TEM. In order to avoid these undesired effects, a novel biocompatible alternative was presented based on titanium dioxide nanoparticle functionalization with vitamin B2 through a rapid sol-gel method. None of the phototoxicity effects were observed with these functionalized nanoparticles.

Metal-Induced Energy Transfer (MIET) for Live-Cell Imaging with Fluorescent Proteins

Metal-induced energy transfer (MIET) imaging is an easy-to-implement super-resolution modality that achieves nanometer resolution along the optical axis of a microscope. Although its capability in numerous biological and biophysical studies has been demonstrated, its implementation for live-cell imaging with fluorescent proteins is still lacking. Here, we present its applicability and capabilities for live-cell imaging with fluorescent proteins in diverse cell types (adult human stem cells, human osteo-sarcoma cells, and Dictyostelium discoideum cells), and with various fluorescent proteins (GFP, mScarlet, RFP, YPet). We show that MIET imaging achieves nanometer axial mapping of living cellular and subcellular components across multiple time scales, from a few milliseconds to hours, with negligible phototoxic effects.

Drug Delivery Strategies for Avobenzone: A Case Study of Photostabilization.

Several developments and research methods are ongoing in drug technology and chemistry research to elicit effectiveness regarding the therapeutic activity of drugs along with photoprotection for their molecular integrity. The detrimental effect of UV light induces damaged cells and DNA, which leads to skin cancer and other phototoxic effects. The application of sunscreen shields to the skin is important, along with recommended UV filters. Avobenzone is widely used as a UVA filter for skin photoprotection in sunscreen formulations. However, keto-enol tautomerism propagates photodegradation into it, which further channelizes the phototoxic and photoirradiation effects, further limiting its use. Several approaches have been used to counter these issues, including encapsulation, antioxidants, photostabilizers, and quenchers. To seek the gold standard approach for photoprotection in photosensitive drugs, combinations of strategies have been implemented to identify effective and safe sunscreen agents. The stringent regulatory guidelines for sunscreen formulations, along with the availability of limited FDA-approved UV filters, have led many researchers to develop perfect photostabilization strategies for available photostable UV filters, such as avobenzone. From this perspective, the objective of the current review is to summarize the recent literature on drug delivery strategies implemented for the photostabilization of avobenzone that could be useful to frame industrially oriented potential strategies on a large scale to circumvent all possible photounstable issues of avobenzone.

Field bio-efficacy, phytotoxicity of different insecticides against invasive leafminer, Liriomyza huidobrensis in potato and its safety to natural enemies

In order to assess the efficiency of different pesticides, their phytotoxicity, and the safety of natural enemies in potato fields of the Nilgiris district against the recently existing invasive pest, Liriomyza huidobrensis, two field experiments were conducted at two different locations, namely Kukkal in Kotagiri and Kappachi in Ooty, both located in the district Nilgiris, Tamil Nadu. The outcomes showed that cyantraniliprole 10.26 OD @ 75 g a.i. /ha and chlorantraniliprole 18.5 S @ 30 g a.i. /ha were helpful for managing L. huidobrensis. Following spraying, coccinellid and spider populations first declined, but gradually rose. Following it, Profenofos 50 EC @ 500 g a.i. /ha was also demonstrated to yield favourable results, but it was rejected because it significantly reduced the population of natural enemies. Additionally, it was discovered that none of the pesticides had any phototoxic effects on potato during the trial. In light of the fact that profenofos 50 EC has a similar impact on the natural enemy population as cyantraniliprole 10.26 OD and chlorantraniliprole 18.5 S @ 30 g a.i. ha-1, they can be used successfully as a management strategy for potato leaf miner.

Light-Induced Clusterization of Gold Nanoparticles: A New Photo-Triggered Antibacterial against E. coli Proliferation

Metallic nanoparticles show plasmon resonance phenomena when irradiated with electromagnetic radiation of a suitable wavelength, whose value depends on their composition, size, and shape. The damping of the surface electron oscillation causes a release of heat, which causes a large increase in local temperature. Furthermore, this increase is enhanced when nanoparticle aggregation phenomena occur. Local temperature increase is extensively exploited in photothermal therapy, where light is used to induce cellular damage. To activate the plasmon in the visible range, we synthesized 50 nm diameter spherical gold nanoparticles (AuNP) coated with polyethylene glycol and administered them to an E. coli culture. The experiments were carried out, at different gold nanoparticle concentrations, in the dark and under irradiation. In both cases, the nanoparticles penetrated the bacterial wall, but a different toxic effect was observed; while in the dark we observed an inhibition of bacterial growth of 46%, at the same concentration, under irradiation, we observed a bactericidal effect (99% growth inhibition). Photothermal measurements and SEM observations allowed us to conclude that the extraordinary effect is due to the formation, at low concentrations, of a light-induced cluster of gold nanoparticles, which does not form in the absence of bacteria, leading us to the conclusion that the bacterium wall catalyzes the formation of these clusters which are ultimately responsible for the significant increase in the measured temperature and cause of the bactericidal effect. This photothermal effect is achieved by low-power irradiation and only in the presence of the pathogen: in its absence, the lack of gold nanoparticles clustering does not lead to any phototoxic effect. Therefore, it may represent a proof of concept of an innovative nanoscale pathogen responsive system against bacterial infections.

Efficient Synthesis of Chlorin e6 and Its Potential Photodynamic Immunotherapy in Mouse Melanoma by the Abscopal Effect.

Photodynamic therapy (PDT) can eradicate not only cancer cells but also stimulate an antitumor immune response. Herein, we describe two efficient synthetic methodologies for the preparation of Chlorin e6 (Ce6) from Spirulina platensis and address the phototoxic effect of Ce6 in vitro along with antitumor activity in vivo. Melanoma B16F10 cells were seeded and phototoxicity was monitored by the MTT assay. The C57BL/6 mice were subcutaneously inoculated on the left and right flank with B16F10 cells. The mice were intravenously injected with Ce6 of 2.5 mg/kg and then exposed to red light (660 nm) on the left flank tumors 3 h after the injection. The immune response was studied by analyzing Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and Interleukin-2 (IL-2) of the right flank tumors through qPCR. Our results revealed that the tumor was suppressed not only in the left flank but also in the right flank, where no PDT was given. The upregulated gene and protein expression of IFN-γ, TNF-α, and IL-2 revealed antitumor immunity due to Ce6-PDT. The findings of this study suggest an efficient methodology of Ce6 preparation and the efficacy of Ce6-PDT as a promising antitumor immune response.

Evaluation of photodynamic therapy effects of novel zinc (II) phthalocyanine through a possible interaction with toll‐like receptor signaling pathway

In this work, 3‐({6‐[3‐(dimethylamino)phenoxy]hexyl}oxy)phthalonitrile (2) and the target zinc (II) phthalocyanine (3) and its ammonium derivative (3a) are synthesized, and the phototoxic effects of 3a were examined using different methods on A549 lung cancer cells. Then, the toll‐like receptor (TLR) signaling pathway was examined to determine the cell death mechanism in the A549 cancer cells. The results showed that 3a did not have noticeable cytotoxic actions on A549 cells at used concentrations. However, the compound markedly reduced the cell viability when irradiated by the red light for 5 and 15 min (LumaCare/LC‐122A/LC2020‐09‐784, Prob: LUM L [700 nm CL] [15 mW cm−2]). Additionally, Annexin V/PI staining suggested that the cells were induced apoptosis in the presence of 3a (1 μM) when irradiated with red light for 15 min. Furthermore, the expression of TLR2, TLR4, and caspase‐3 significantly increased and phospho‐nuclear factor kappa B/total nuclear factor kappa B decreased compared with that of control group (p &lt; 0.05). These results provide strong evidence that 3a is able to induce A549 cell death in a dose and a red‐light irradiation time‐dependent manner via apoptosis. Therefore, 3a might be an effective photodynamic therapy candidate for lung cancer treatment.

Long-term effects of combined brilliant blue G and xenon light induced retinal toxicity following macular hole repair surgery

BackgroundThe purpose of this study was to look at the long-term effects of retinal phototoxicity after macular hole repair surgery using xenon endolight illumination and Brilliant blue G (BBG) dye.Case presentationAn elderly man in his late seventies underwent para plana vitrectomy with BBG dye to repair an idiopathic full-thickness macular hole (MH) in his right eye. Prior to macular hole surgery, his visual acuity in the right eye was 6/60, N24 at the time of presentation. The MH closed with type 1 closure immediately after surgery, but there was extensive damage to the outer retinal layers and retinal pigment epithelium (RPE) at the macula, resulting in a reduction in visual acuity to 2/60. We presumed that the combination of BBG and xenon light, is the probable reason of retinotoxicity in the current patient. There was a progressive increase in the area of retinal and RPE layer damage and choroidal thinning over a 4-year period.ConclusionDue to combined BBG-induced dye and endoilluminator toxicity, a rare case of continuously progressing RPE layer damage with choroidal thinning over a long follow-up interval was described. Such long-term effects of BBG and endolight induced retinotoxicity have not been reported in the literature, to the best of our knowledge.

Finding the right Bakuchiol: Choose wisely.

Psoralea corylifolia also referred to as the Babchi or Bakuchi plant is a plant grown mostly in India and China that has been shown to have medicinal properties through their anti-oxidant activity.1 [Correction added on 9th March 2023, after first online publication: In the previous sentence "an endangered" was changed to "a."] The plant contains may chemically active compounds including flavonoids, coumarins (psoralidin, psoralen, isopsoralen and angelicin) and meroterpenes such as bakuchiol and 3-hydroxybakuchiol.2 Several parts of the plant can be used, either topically or internally, including the root, the stem, the leaves, and the seeds. The different variations include Babchi plant extract, whole Babchi plant, Bakuchi oil and the phytochemical bakuchiol, which is contained within the Babchi plant (Table 1). The topical seed oil has frequently been used in treatments for psoriasis and other conditions affecting the skin.1 Bakuchiol is a meroterpene phenol, which is sourced from the seeds of Psoralea corylifolia, that has anti-inflammatory, anti-microbial and anti-proliferative properties. It has recently gained increased popularity for use in anti-aging products amongst others, comparative to retinol3; however, bakuchiol is a natural alternative and lacks the photosensitive effects.4 Backuchiol must be properly isolated from the Babchi plant, which proposes a limitation due to differing levels of purity in the isolated component. The isolation is difficult because there are low concentrations in natural sources. The co-existence of phototoxic components in the Babchi plant increases the potential for ultraviolet radiation related effects when these constituents are not removed. For example, the presence of psoralens and isopsoralens will increase the photosensitivity when they are applied topically. While psoralens may be beneficial when used for conditions such as vitiligo or psoriasis when used in conjunction with phototherapy, when used for facial care, the presence of psoralens can have unintended effects by causing psoralen-based photosensitivity. For this reason, the use of an isolated and purified compound such as bakuchiol may eliminate this risk.5 Furthermore, the leaf, root, and stems of P. corylifolia contain furocoumarins.6 Skin photosensitivity is a well-known property of furocoumarins when exposed to sunlight demonstrates varied levels of erythema, pigmentation and damage to human skin after a latent period.7 Due to these phototoxic side effects, it is important to have purified isolates of bakuchiol rather than unpurified extractions of P. corylifolia when considering facial care. Overall, bakuchiol is a component extracted from the P. corylifolia plant and has been shown to have retinol-like properties. For this reason, many companies are using bakuchiol in their products. However, not all products may have the purified form of bakuchiol. The extraction process of bakuchiol from the Psoralea plant requires purification through liquid–liquid partitioning, and column chromatography followed by characterization of the isolated product via nucleic magnetic resonance (NMR) as well as gas chromatography and mass spectrometry (GCMS).8 Based on the complex isolation process, bakuchiol may be extracted in a less pure form such as the compound of bakuchiol as a racemic mixture, a whole plant P. corylifolia extract, or as bakuchi oil. Consumers may not be aware of these impurities which can increase exposure to phototoxic psoralens and furocoumarins. Therefore, consumers should choose wisely when considering bakuchiol containing products and look for purified bakuchiol sources in their facial care products. Study conception, literature search, manuscript draft, critical revisions: Najiba Afzal; critical revisions: Raja Sivamani. All authors reviewed and approved the final version of the manuscript. Najiba Azfal declares no conflicts of interest. Raja Siavmani serves as a scientific advisor for LearnHealth, Codex Labs Corp, and Arbonne and as a consultant to Burt’s Bees, Novozymes, Nutrafol, Incyte, Fotona, Biogena, Bristol Myer Squibb, Novartis, Element Apothec, Abbvie, Leo, UCB, Sun, Sanofi, Regeneron Pharmaceuticals. Authors declare human ethics approval was not needed for this study. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

The Assessment of the Phototoxic Action of Chlortetracycline and Doxycycline as a Potential Treatment of Melanotic Melanoma-Biochemical and Molecular Studies on COLO 829 and G-361 Cell Lines.

Melanoma is still one of the most dangerous cancers. New methods of treatment are sought due to its high aggressiveness and the relatively low effectiveness of therapies. Tetracyclines are drugs exhibiting anticancer activity. Previous studies have also shown their activity against melanoma cells. The possibility of tetracycline accumulation in pigmented tissues and the increase in their toxicity under the influence of UVA radiation creates the possibility of developing a new anti-melanoma therapy. This study aimed to analyze the phototoxic effect of doxycycline and chlortetracycline on melanotic melanoma cells COLO 829 and G-361. The results indicated that tetracycline-induced phototoxicity significantly decreased the number of live cells by cell cycle arrest as well as a decrease in cell viability. The simultaneous exposure of cells to drugs and UVA caused the depolarization of mitochondria as well as inducing oxidative stress and apoptosis. It was found that the combined treatment activated initiator and effector caspases, caused DNA fragmentation and elevated p53 level. Finally, it was concluded that doxycycline demonstrated a stronger cytotoxic and phototoxic effect. UVA irradiation of melanoma cells treated with doxycycline and chlortetracycline allows for the reduction of therapeutic drug concentrations and increases the effectiveness of tested tetracyclines.