Design of 3D Hybrid Plant Extract/Marine and Bovine Collagen Matrixes as Potential Dermal Scaffolds for Skin Wound Healing.

Tissue engineering involves the use of smart biomimetic hybrid matrices to reinforce the cellular interaction with the matrix and restore native properties after regeneration. In this study, we highlight the potential of 3D collagen sponges soaked with bioactive extract, to enhance the wound healing process in vivo. Acid-soluble collagen from two sources, marine and bovine, were extracted and characterized physiochemically using Fourier transform infrared spectroscopy (FTIR) and SDS-PAGE. Our results confirmed that the extracted collagens were mainly composed of collagen type I with slight molecular structure differences. Both collagens present two different α chains (α1 and α2) and one ß chain. Highly interconnected 3D scaffolds from collagen from the skin are designed and added by the widely known healing plants Pistacia lentiscus and Calendula officinalis. The resulting 3D collagen matrices possess fine biocompatibility with skin cells, Hacat (keratinocytes), and 3T3-L1 (fibroblasts) cells. To evaluate the potential wound healing effect, a collagen sponge soaked with the bioactive extract was tested on BALB/c mice. Our findings confirmed that sponges significantly improve animal re-epithelialization by increasing wound closure. Consequently, spongy collagen scaffolds loaded with Pistacia lentiscus and Calendula officinalis could be used as potential wound dressing material.

A Novel Anticancer Effect of Ephedra alata Decne in Breast Cancer Cells.

Cancer is a class of diseases characterized by uncontrolled cell growth. One of the main aims of developing new therapies is to use natural resources to induce apoptosis. LC-ms/ms analysis of a methanolic extract of Ephedra alata (E.A.) allowed the identification of 20 secondary metabolites, including flavonoids, phenolic acids, and proanthocyanidins. Antiproliferative effect was assessed by crystal violet assay. Antimigration effect was tested by wound healing assay and apoptosis induction was determined by annexin binding assays, Hoechst staining, ROS production, and activation of apoptotic proteins. The results indicated that exposure of breast cancer cells to E.A. extract significantly reduced cell viability in a dose and time-dependent manner and inhibited the migration of 4T1 cells at a low dose. Moreover, treatment of cells with E.A. extract induced apoptosis, as it was detected by Annexin V/7 AAD, Hoechst staining, ROS production, and the activation of caspases.Abbreviation:BSAbovine serum albuminDMSOdimethyl sulfoxideEDTAethylenediaminetetraacetic acidLC-ms/msliquid chromatography-mass spectrometryNACN-acetyl-l-cysteinePARPpoly(ADP-ribose) polymerasePMSFphenylmethylsulfonyl fluorideRIPAradioimmunoprecipitation assay bufferROSreactive oxygen speciesRPMIRoswell park memorial instituteSDS-PAGEsodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein.

The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combination of doxorubicin with PC or TR induced a synergism to increase cell death in resistant MES-SA/Dx5 cells and, subsequently, had the benefit of decreasing the resistance index to doxorubicin. These synergistic effects were reinforced by a decrease in P-gp expression and its P-gp adenosine triphosphatase (ATPase) activity, which subsequently led to intracellular doxorubicin accumulation in resistant sarcoma cells.

Erica multiflora extract rich in quercetin-3-O-glucoside and kaempferol-3-O-glucoside alleviates high fat and fructose diet-induced fatty liver disease by modulating metabolic and inflammatory pathways in Wistar rats.

The wide morbidity of obesity has heightened interest in providing natural and safe compounds to maintain optimal health. The present study was designed to determine the chemical constituents and the effects of methanol leaf extract from Erica multiflora (M-EML) on mitigating high-fat and high-fructose diet (HFFD)-induced metabolic syndrome (MS). LC-MS/MS characterization of M-EML allowed the identification of 14 secondary metabolites and showed that quercetin-3-O-glucoside and kaempferol-3-O-glucoside were the main compounds of our extract. In the in vivo study, the oral administration of M-EML (250 mg/kg) during the last 4 weeks of the experimentation alleviated HFFD-induced obesity, insulin resistance (IR) and cardiovascular diseases. Thus, M-EML treatment significantly normalized body and liver weight, allowed to a sharp decline in plasma levels of TC, TG and LDL-c by 32%, 35% and 66%, respectively. Moreover, hepatic enzymes, total and direct bilirubin, lipase and uric acid levels have been diminished in treated group. Histopathology of the liver confirmed the changes induced by HFFD and the hepatoprotective effect of M-EML. The supply of M-EML reduced NO production and cellular lysosomal enzyme activity by 44% and 60%, respectively compared to HFFD. Besides, M-EML showed decreased pro-inflammatory cytokines levels (259.5±47.35 pg/ml and 56.08±1.56 pg/ml) of TNF-α and IL-6, respectively. In addition, M-EML reduced liver malondialdehyde (MDA) content and enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. In contrast, these enzymatic activities have been disrupted in HFFD rats. Overall, M-EML prevented obesity through the modulation of metabolic syndrome, reducing inflammation and promoting antioxidant enzymes activities.

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.

A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo.

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.

Methanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity.

Cisplatin (CP) is a powerful anticancer agent used in the treatment of a diverse type of cancers. Oxidative stress is one of the most important side effects limiting the use of cisplatin. The protective effects of methanolic extract (ME) and ephedrine (EP), major compound, of Ephedra alata on CP-induced damages were here assessed. Treatment with CP-induced nephrotoxicity and hepatotoxicity characterized by biochemical alterations. In fact, using CP reduced significantly glutathione (GSH) levels, enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and increased malondialdehyde (MDA) content. Nonetheless, CP-treatment induced DNA damage at renal, hepatic, and blood cells and increased interferon gamma (IFNγ) level in serum. Co-treatments of mice with ME normalized relative kidney/body weight, restored biochemical and oxidative stress parameters, reduced DNA damage and IFNγ level. In conclusion, ME exhibited the best protective effect against CP damage compared with ephedrine. This is could be attributed to the presence of polysaccharides, organic acids, flavonoids, and tannins in addition to ephedrine alkaloids. These compounds were reported to play a major role in inhibiting and scavenging free radicals, providing an effective protection against CP- induced oxidative damage. Graphical abstract.

Antitumoral Potency by Immunomodulation of Chloroform Extract from Leaves of Nitraria retusa, Tunisian Medicinal Plant, via its Major Compounds ß-sitosterol and Palmitic Acid in BALB/c Mice Bearing Induced Tumor.

This study evaluated the antitumoral effect of Chloroform extract from Nitraria retusa leaves, via its major compounds ß-sitosterols and palmitic acid. BALB/c mice were subcutaneously inoculated with B16-F10 cells, then treated intra-peritoneally after 7 days with the chloroform extract for 21 days. They were then euthanized, and the tumors were weighed. Lung parenchyma was analyzed. Lymphocyte and macrophages proliferation, cytotoxic T lymphocyte (CTL) activities were evaluated using the MTT assay. Macrophage phagocytosis was evaluated by measuring the lysosomal activity and nitric oxide production. Antioxidant activity was studied by cellular antioxidant activity on macrophage and splenocytes and by lipid peroxidation inhibitory activity in liver cells, kidney, and serum. ß-sitosterols and palmitic acid, major compounds of chloroform extract, impeded remarkably the expansion of the transplantable tumor, protected the lung parenchyma, and increased splenocytes proliferation and both CTL activities in tumor-bearing mice. ß-sitosterols and palmitic acid were also seen to have enhanced lysosomal activity of host macrophages and antioxidant cellular activity. Also, they showed an inhibitory effect of lipid peroxidation. Our results suggest that antitumoral effect of ß-sitosterols and palmitic acid from chloroform extract is related with its immunomodulatory activity, and opens the way for a nutrition application and coprocessing phytotherapy against cancer.