Anthraquinones from Rhamnus alaternus L.: A Phytocosmetic Ingredient with Photoprotective and Antimelanogenesis Properties.

The purpose of the present work was to develop a phytocosmetic sunscreen emulsion with antioxidant activity and an anti-melanogenic effect, containing an anthraquinone-enriched extract of Rhamnus alaternus (A.E.). Our findings demonstrated that A.E. decreased the levels of reactive oxygen species, DNA damage, and malondialdehyde induced by UVA in human keratinocytes and melanocytes. Furthermore, the calculated SPF value in vitro of the cream containing A.E. was 14.26±0.152. Later, it was shown that A.E. extract had an inhibitory effect on the amount of melanin. This extract could also reduce B16F10 intracellular tyrosinase activity. Besides, docking studies were carried out to provide a logical justification for the anti-tyrosinase potential. The findings showed that, A.E. may provide protection against UVA-induced oxidative stress and could be thought of as a viable treatment for hyperpigmentation disorders.

Thymoquinone-loaded lipid nanocapsules with promising anticancer activity for colorectal cancer.

Colorectal cancer (CRC) is the third most common worldwide. Depending on its stage, chemotherapy is usually given after surgery when CRC has already metastasized to other organs like the liver or lungs. Unfortunately, the current antineoplastics used for CRC therapies involve toxicity and side effects due to their lack of site-specificity. To overcome the drawbacks of heavy chemotherapy, this study proposes to assess the efficacy of thymoquinone (TQ), a bioactive constituent of black seeds (Nigella sativa), as an antiproliferative and pro-apoptotic agent on an experimental CRC model in mice. TQ was encapsulated in lipid nanocapsules (LNCs), used as nanocarriers, in order to increase its specificity and cell absorption. TQ-loaded LNCs (TQ-LNCs) have a diameter of 58.3 ± 3.7 nm and 87.7 ± 4.5% TQ encapsulation efficiency. In turn, in vivo studies showed that the intratumoral administration of TQ-LNCs decreased the tumor size in colorectal cancer bearing mice compared to the control group. TQ-LNCs were more effective than free TQ for inducing tumor cell death. These results highlight the potential of TQ entrapped in LNCs as an anticancer agent for CRC treatment.

Two calix[4]pyrroles as potential therapeutics for castration-resistant prostate cancer.

Macrocyclic compounds meso-(p-acetamidophenyl)-calix[4]pyrrole and meso-(m-acetamidophenyl)-calix[4]pyrrole have previously been reported to exhibit cytotoxic properties towards lung cancer cells. Here, we report pre-clinical in vitro and in vivo studies showing that these calixpyrrole derivatives can inhibit cell growth in both PC3 and DU145 prostatic cancer cell lines. We explored the impact of these compounds on programmed cell death, as well as their ability to inhibit cellular invasion. In this study we have demonstrated the safety of these macrocyclic compounds by cytotoxicity tests on ex-vivo human peripheral blood mononuclear cells (PBMCs), and by in vivo subcutaneous administration. Preliminary in vivo tests demonstrated no hepato-, no nephro- and no genotoxicity in Balb/c mice compared to controls treated with cisplatin. These findings suggest these calixpyrroles might be novel therapeutic tools for the treatment of prostate cancer and of particular interest for the treatment of androgen-independent castration-resistant prostate cancer.

Pituranthos chloranthus Oil as an Antioxidant-Based Adjuvant Therapy against Cisplatin-Induced Nephrotoxicity.

The therapeutic outcome of cisplatin is limited due to its adverse side effects in normal tissues. Despite its potent antineoplastic effect, cisplatin is known by a relevant collateral action, for instance, acute renal failure. The aim of this study was to assess the effectiveness of Pituranthos chloranthus (PC) essential oil for contracting cisplatin-induced toxicity, in Balb/c mice. The standard mouse model of cisplatin-induced acute kidney injury (AKI), consisting of one intraperitoneal injection of cisplatin (20 mg/kg), was adopted. Mice were pretreated by intraperitoneal administration of PC (5 and 10 mg/Kg b.w) for one week. Cisplatin induced alteration in renal and liver functions, evidenced by increased serum biomarkers levels (creatinine, ALT, and AST). Significant mitigation of cisplatin-induced toxicity was confirmed by lowered levels of serum biomarkers and reduced DNA damage in liver and kidney. PC also restored the alterations in oxidative stress markers and proinflammatory cytokine IFN-γ level. Overall, this study provides, for the first time, that PC can be applied as an antioxidant-adjuvant treatment to mitigate cisplatin-induced renal failure.

Heat treatment and protective potentials of luteolin-7-O-glucoside against cisplatin genotoxic and cytotoxic effects.

Cisplatin is an effective chemotherapeutic agent that has pronounced adverse effects. Using flavonoids is currently eliciting considerable interest. During extraction and conditioning, they usually undergo several physical treatments such as heat treatment, although it is not known whether thermal treatment might influence the pharmacological effects of flavonoids such as luteolin-7-O-glucoside (L7G). This study was undertaken to explore the protective role of native and heated L7G against DNA damage and oxidative stress induced by cisplatin. Balb/c mice were administered L7G before a single intraperitoneal injection of cisplatin (10 mg/kg). Animals were sacrificed 24 h after treatment with drugs. The geno-protective role of native and heated L7G was evaluated by comet assay. In addition to monitoring the activities of antioxidant enzymes, levels of malondialdehyde and reduced glutathione were assessed in the liver, kidney, brain, and spleen tissues. The results of the present study demonstrate that both heated and native L7G, at a dose of 40 mg/kg b.w, were able to reduce the genotoxicity of cisplatin. They attenuate the oxidative stress (malondialdehyde, catalase, GPx, SOD, and GSH) and tissue damage (creatinine, IFNγ). Heat treatment did not alter the antigenotoxic effect observed for native L7G and showed similar effects to those of native L7G for all of the evaluated parameters. Our study reveals that L7G attenuates the side effects of anticancer drug and heat treatment did not alter his antigenotoxic and antioxidant the potential.

Heat processing effect of luteolin on anti-metastasis activity of human glioblastoma cells U87.

Among the flavonoïds, luteolin is a flavone that has been identified in many plants. It is known for its apoptotic potential with damage to DNA and cell cycle blockage. Many studies have shown that luteolin has anti-oxidant, anti-inflammatory, and anti-cancer activities. However, it is known that heat treatment (boiling, cooking, and treating with microwaves …) can influence the structure of flavonoïds, which often leads to changes in their activities. The present study was conducted to study the effect of heated luteolin on anti-tumor activity of glioblastoma cells U87. Glioblastoma cell viability was evaluated by MTT assay. Adhesion assay was performed on different protein matrices (collagen type 1, vitronectin, fibronectin, and poly-L-lysine); migration assay was determined by modified Boyden chambers and videomicroscopy, and finally, angiogenesis was tested in vitro by capillary network formation on Matrigel™. The results obtained show that the thermal treatment significantly reduces its cytotoxic activity and ability to inhibit cell adhesion to different protein matrices. It was also found that the heat processed significantly reduced the ability of luteolin to inhibit cell migration, cell invasion, and endothelial cell angiogenesis (HMEC-1). This suggests that heat treated luteolin has a lower anti-tumor potential than native luteolin. Graphical abstract ᅟ.

Thermal treatment of luteolin-7-O-ß-glucoside improves its immunomodulatory and antioxidant potencies.

Phytochemicals extracted from flowers, roots and bark, leaves, and other plant sources have been used extensively throughout human history with varying levels of efficacy in prevention and treatment of disease. Recently, advanced methods for characterization and clinical use of these materials have allowed modern understanding of their properties to be used as immunomodulatory agents that act by enhancement of endogenous cytoprotective mechanisms, avoiding interference with normal physiologic signaling and highly effective medical treatment with minimal adverse side effects. Simple methods have been identified for improving their biological effects, such as thermal conditioning by heating or freezing-prominent example being heat treatment of lycopene and tetrahydrocannabinol. The present investigation shows improvement of the ability of heat to augment splenocyte proliferation, natural killer (NK) cell activities, and antioxidant capacity of the flavonoid luteolin-7-O-ß-glucoside (L7G) in comparison with the native (non heat-treated) molecule, while further demonstrating that both the native and the heat-treated variants exhibit comparable antioxidant properties, as evidenced by their effects in macrophages by inhibition of nitric oxide production and lysosomal enzyme activity in experiments that strengthen lysosomal membrane integrity. Outcomes of these studies suggest that heat-treated L7G shows promise for use in immunotherapy, including anti-cancer regimens, as shown by its improvement of NK cell cytotoxicity.

Digallic acid from Pistascia lentiscus fruits induces apoptosis and enhances antioxidant activities.

The antioxidant and apoptotic activities of digallic acid, isolated from the fruits of Pistascia lentiscus, were investigated. The study demonstrated that digallic acid possessed pro-apoptotic effects, as shown by provoking DNA fragmentation of K562 cells. It also revealed a significant antioxidant potential and effective scavenging activity against 2,2-diphenyl-1-picrylhdrazyl (DPPH·) and O2·â» radicals, and reduced cupric ions. We conclude that this integrated approach to apoptotic and antioxidant assessment may be useful to maximize the beneficial effects associated with using P. lentiscus derivatives as medicinal and dietary compounds.

Degradation and detoxification of acid orange 52 by Pseudomonas putida mt-2: a laboratory study.

INTRODUCTION: Acid orange 52 (AO52), extensively used in textile industries, was decolorized by Pseudomonas putida mt-2. AO52 azoreduction products such as N,N'-dimethyl-p-phenylenediamine (DMPD) and 4-aminobenzenesulfonic acid (4-ABS), were identified in the static degradation mixture. These amines were identified only in media of static incubation, which is consistent with their biotransformation under shaken incubation (aerobic conditions). MATERIALS AND METHODS: Tests with azo products were carried out, and whole cells were found able to easily degrade DMPD contrary to 4-ABS. However, this last could be attacked by cell extract, and an oxygen uptake was observed during the reaction. RESULTS: Degradation of DMPD by entire cells led to the formation of catechol. These results show that P. putida was able to decolorize AO52 and metabolize its derivative amines. In addition, the ability of tested compounds was evaluated in vitro to reduce human plasma butyrylcholinesterase (BuChE) activity. CONCLUSION: Azoreduction products seem to be responsible for BuChE inhibition activity observed in static biodegradation extract. However, toxicity of AO52 completely disappears after shaken incubation with P. putida, suggesting that bacterium has a catabolism which enables it to completely degrade AO52 and especially, to detoxify the dye mixture.

Evaluation of antioxidant and antigenotoxic activity of two flavonoids from Rhamnus alaternus L. (Rhamnaceae): kaempferol 3-O-ß-isorhamninoside and rhamnocitrin 3-O-ß-isorhamninoside.

The antioxidant activity of kaempferol 3-O-ß-isorhamninoside (K3O-ir) and rhamnocitrin 3-O-ß-isorhamninoside (R3O-ir), isolated from the leaves of Rhamnus alaternus L., was determined by the ability of each compound to inhibit NBT photoreduction and to scavenge the free radical ABTS(+)(.). Genotoxic and antigenotoxic activities were assessed using the SOS chromotest. At a concentration of 150 µg/assay the two compounds showed the most potent inhibitory activity against superoxide anion by respectively 80.4% and 85.6%. K3O-ir was a very potent radical scavenger with an IC(50) value of 18.75 µg/ml. Moreover, these two compounds exhibit an inhibitory activity against genotoxicity induced by nitrofurantoine and aflatoxine B1 using the SOS chromotest bacterial assay system in the presence of Escherichia coli PQ37 strain. In this study, we have also evaluated correlation between antigenotoxic and antioxidant effects of K3O-ir and R3O-ir. The highest correlation was showed with R3O-ir (r=0.999).

A comparative evaluation of mutagenic, antimutagenic, radical scavenging and antibacterial activities of essential oils of Pituranthos chloranthus (Coss. et Dur.).

The Salmonella typhimurium/microsome assay is a widely used bacterial genotoxicity assay to test potential carcinogens. The aim of this work was to evaluate the mutagenic and antimutagenic activities with and without the addition of an extrinsic metabolic activation system of essential oils obtained from an aerial part of Pituranthos chloranthus harvested from different stations in Tunisia. The oils showed no mutagenicity when tested with S. typhimurium strains TA98, TA100, and TA1535. On the other hand, we showed that these essential oils reduced significantly Benzo [a] pyrene (B[a] P) and sodium-azide-induced mutagenicity. The scavenging capacity of these essential oils was also estimated by evaluating the inhibition of DPPH radical. Essential oils harvested at Medenine and Gabes in November were more effective in scavenging activity. The essential oils were tested for their antimicrobial properties against five different bacteria, and were found to be weakly active, with MIC and MBC values in the range 0.6-4 and 2.2-5 mg/mL, respectively.