Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation.

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

Evaluation of the anticancer activity of Origanum Marjoram as a safe natural drink for daily use.

BACKGROUND: Chemotherapeutic agents have numerous side effects. There is a major interest in using natural and safe plants as food or drink to prevent from cancer. Origanum marjoram (OMAE) is a medicinal plant that can be used as a tea, food, and additive in traditional medicine. OBJECTIVE: This study aimed to evaluate the potential anticancer effects of OMAE as a soft drink for daily use against a model cancer, prevention and treatment. METHOD: MCF-7 cells were chosen as model cancer cells. The MTT assay was used to assess the in vitro inhibitory effects of OMAE on cell growth. Moreover, quantitative real-time PCR (qRT-PCR) was used to detect specific genes associated with cancer, such as ESR1, Bax, Bcl-2, and p53. Furthermore, the DNA damage was evaluated using the comet assay. RESULTS: OMAE has IC50 of 53.1 and IC90 of 97.5 µg/ml dependent inhibition of cell proliferation after 48 h of treatment toward MCF-7. Also, a significant decrease in the expression level of the ESR1 gene in the MCF-7 cell line. Furthermore, there was a significant increase in the comet length and comet-positive cells after treatment with OMAE (88.7%) compared with those in the untreated control cells (9.5%), suggesting a high induction of DNA damage by OMAE. Also, OMAE showed a modification in bcl-2, tumor suppressor gene (p53), and Bax levels and influenced the BAX/BCL-2 ratio via releasing the cytochrome C. CONCLUSION: The results of the study were promising, suggesting that the reduced apoptotic rate of MCF-7 breast cancer cells in this work was correlated to the potential anticancer effect of OMAE which would be a suitable preventable drink against cancer. However, further studies are needed to fully understand the potential of OMAE as a cancer treatment.

Ginkgo biloba leaves extract's cosmeceutical evaluation: a preliminary assessments on human volunteers towards achieving improved skin condition and rejuvenation.

BACKGROUND: Ginkgo biloba (GB) leaves extract is known to possess potent antioxidants and other bioactivities such as improved skin conditions and rejuvenation. OBJECTIVE: This study aimed to develop a cosmeceutical preparation to utilize the strong antioxidant potential of GB leaves as part of the skincare formulation. METHODS: Cream incorporated GB (GBC) was prepared by mixing the obtained extract with stearic acid-sodium hydroxide components in an emulsion format. The obtained GBC was characterized for GB contents, uniformity, pH, compatibility, stability, and skin's human application. RESULTS: A homogeneous, physically, and chemically stable, with pH near the skin pH and shiny cream, was obtained. The prepared cream was easy to rub and pearly in appearance. It was effective and safe during the two-week trial conducted on human volunteers according to clinical trial registry protocols. The cream scavenged free radicals in DPPH assay tests. The cream incorporated GB made the skin more spirited and tauter. Furthermore, the wrinkles were reduced and the skin was renewed vigor. CONCLUSION: The GBC worked at the topical level and provided benefits when applied daily for the trial duration. The formulation also provided visually observable anti-wrinkle effects on the skin, with visible improvements in the skin's shape and texture. The prepared cream can be used to rejuvenate the skin.

Elucidating the promising role of traditional Chinese medicine in neuroprotection against oxidative stress encompassing Alzheimer's disease.

Medicinal plants are being used from time immemorial for their therapeutic benefits and have immense value in the therapy of neurodegenerative disorders. One of the most important neurological disorders is Alzheimer's disease (AD) which is a major contributor to dementia and is accompanied by abundant oxidative stress in the brain tissue. A critical pathway to target the increased oxidative stress is to administer agents with antioxidant potential. Despite currently available clinical treatments to treat AD such as cholinesterase inhibitors or NMDA antagonists which address only the symptoms and cannot hamper disease progression, no efficient available clinical treatment can break the vicious cycle of oxidative stress and neurodegeneration till date. The main objective of presenting this review is that traditional Chinese medicine (TCM) acts as a promising candidate in breaking this vicious cycle and improves the quality of life of the debilitating patients. The active constituents of various herbs in TCM including Angelica sinensis, Radix polygalae, Polygala tenuifolia, and members of the Lamiaceae family have acquired experience of managing oxidative stress as indicated in the review for more than a thousand years now, and the preclinical and clinical evidence of their therapeutic potential has been highlighted in the review. Most importantly, Chinese herbs provide a multiple-target approach rather than a single-target approach and thus can target multiple pathways involved in AD at once. The Chinese herbs can definitely untangle the issues in the current therapy regimen of AD.

Emergence of nutriments as a nascent complementary therapy against antimicrobial resistance.

With these growing and evolving years, antimicrobial resistance has become a great subject of interest. The idea of using natural productive ways can be an effective measure against antimicrobial resistance. The growing prevalence of antimicrobial resistance indicates that advanced natural approaches are a topic of concern for fighting the resistance. Many natural products including essential oils, flavonoids, alkaloids and botanicals have been demonstrated as effective bactericidal agents. In this review, we will discuss in detail about the relevance of such natural products to tackle the problem of antimicrobial resistance, antibiotic adjuvants that aim towards non-essential bacterial targets to reduce the prevalence of resistant bacterial infections, latest bioinformatics approach towards antibacterial drug discovery along with an understanding of biogenic nanoparticles in antimicrobial activity.

Green Synthesis of Silver Nanoparticles Incorporated Aromatherapies Utilized for Their Antioxidant and Antimicrobial Activities against Some Clinical Bacterial Isolates.

There is a need to synthesize eco-friendly nanoparticles with more effective and potent antibacterial activities. A green and cost-effective method for the synthesis of silver nanoparticles (AgNPs) using Thymus vulgaris, Mentha piperita, and Zingiber officinale extracts was developed. The analytical instrumentation, namely, UV/Vis, absorption spectroscopy, FTIR, and scanning electron microscopy (SEM), was used to determine the developed AgNPs, confirming the functional groups involved in their reduction. Acidic molybdate, DPPH, and FRAP regents were reacted with AgNPs extract to evaluate their antioxidant, scavenging, and oxidative activities. The agar well diffusion method was used to determine the antibacterial potential of AgNPs extracts using clinical isolates. The developed AgNPs showed peaks at 25 cum\Diff, 50 cum\Diff, and 75 cum\Diff, respectively, of 16.59 ± 0.78, 45.94 ± 1.07, and 81.04 ± 0.98 nm, for Thymus vulgaris, Mentha piperita, and Zingiber officinale. SEM revealed uniform prepared and encapsulated AgNPs by plant extracts matrix. The FTIR shows the involvement of amide (-CO-NH2), carbonyl (-CO), and hydroxyl (-OH), which resulted in the reduction of AgNPs. The AgNPs extract showed significantly higher TAA, DPPH, and FRAP values than free AgNPs and plant extract (p < 0.05). Antibacterial of AgNPs extracts revealed various degrees of inhibition zones against Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus. The developed AgNPs extract showed acceptable antioxidant activities and noticeable antibacterial potential. The prepared green synthesized AgNPs showed a promising antibacterial activity against four multidrug-resistant clinical isolates, Escherichia coli, Acinetobacter baumannii, and Staphylococcus aureus. Further, fractionated extracts other than crude extracts will be utilized in the preparation of AgNPs to get more efficient antibacterial activities for future work.

Sage, Salvia officinalis L., Constituents, Hepatoprotective Activity, and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis.

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils' yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, ß-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs' essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema.

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

Thyme oil alleviates Ova-induced bronchial asthma through modulating Th2 cytokines, IgE, TSLP and ROS.

Bronchial asthma (BA) is a heterogeneous allergic respiratory disease with diverse inflammatory symptoms, pathology, and responses to treatment. Thyme is a natural product which is consisted of multiple phenolic compounds of therapeutic significance for treatment of cough and bronchitis. This study evaluated the efficacy of thyme oil against ovalbumin (OVA)-induced BA in an experimental rabbit model. Forty male rabbits were divided into four equal groups [control group (G1), OVA (G2), thyme oil (G3), and OVA plus thyme oil (G4)]. Animals were treated for 30 days, and clinical, histopathological (HP), histochemical (HC), immunohistochemical (IHC), morphometric, biochemical and flow cytometry methods were performed, followed by statistical analysis. All used methods revealed normal structure of the lung tissues in rabbits of G1 and G3. In contrast, the clinical examination of G2 rabbits revealed an obvious increase in the respiratory rate, sneezing and wheezing, whereas the HP, HC and IHC techniques exhibited substantial inflammatory changes in the peribronchio-vascular lung tissues with thinning, degeneration, apoptosis (using the TUNEL assay), necrosis, and shedding of the airway epithelium. Furthermore, the morphometric results confirmed significant increases in the numbers of inflammatory cells, goblet cells, eosinophils and apoptotic cells from (12, 0, 2, 2 cells) to (34,10, 16, 18 cells) respectively, as well as the area percentage of collagen fiber deposition and immunoexpression of eotaxin-1/10 high power fields. Additionally, the biochemical results revealed significant increases in the serum levels of TSLP, IL-4, IL-5, IL-9, IL-13, IgE and eotaxin-1 cytokines from (140, 40, 15, 38, 120, 100, 48) pg./ml to (360, 270, 130, 85, 365, 398, 110) pg./ml respectively, while analysis of ROS by flow cytometry revealed remarkable oxidative stress effects in G2 rabbits. On the other hand, treatment of rabbits with thyme oil in G4 substantially alleviated all OVA-induced alterations. Overall, our findings indicate for the first time that thyme oil can ameliorate OVA-induced BA via its immunomodulatory, anti-inflammatory, antiapoptotic, and antioxidant effects on the lung tissues of rabbits.

Estrogenic Effect of Salvia officinalis Extract on Reproductive Function of Female Mice and Identification of Its Phenolic Content.

BACKGROUND: Natural Phytoestrogens present in plants are effective hormonal replacement therapy. They are converted to estrogenic substances in the gastrointestinal tract, which is considered as the natural alternative to estrogen substitute treatment for postmenopausal women. AIMS AND OBJECTIVE: Salvia officinalis, a herb traditionally used to ameliorate postmenopausal complications, can provide a safe alternative to synthetic pharmaceuticals for the treatment of menopause. Therefore, it is conceivable to detect the possible estrogenic effect of Salvia Officinalis extract as an estrogen replacement therapy in female mice. METHODS: Phytochemical, pharmacological, and immune histopathological techniques are adopted in this study. HPLC is used for the identification of extracted constituents of sage herb. The uterotrophic activity of the extract was determined in immature female mice. Moreover, the mean thickness and luminal epithelium and the photomicrographs of the luminal epithelium of the uterus were also studied. RESULTS: HPLC revealed that quercetin is the major extracted constituent (28.6%) of the total components. Saliva officinalis extract produced a significant increase in the uterine dry weight of equal potency to estrogen. The uterus exhibited a significant increase in luminal epithelial cell height (43.3 ± 6.1µm and 36.5 ± 2.5µm) for estradiol and sage extract, respectively, compared with the control group (18.2 ± 3.5µm). Furthermore, the endometrium showed the lining epithelium formed of a single layer of columnar epithelium. The stroma seemed more voluminous with dilated vasculature. Conversely, the myometrium within the uterus was not affected in any of the experimental groups. CONCLUSION: The sage herbs induced proliferative changes in the uteri of treated mice, which suggest possible estrogenic properties. Saliva officinalis extract can be used as a hormonal replacement for women during menopause and could be further explored for contraceptive use.

Development and evaluation of fluorescent gold nanoparticles.

OBJECTIVE: It is difficult to identify the gold nanoparticles (AuNPs) intracellularly due to their non-fluorescent nature. Although gold can quench the fluorescence of any fluorophore, hence it is also difficult to combine gold with a fluorophore such as a semiconductor quantum dots (QDs). The aim of this study was to prepare a single fluorescent stable AuNPs combined with QDs (QDs-Au-NPs) which can be easily detected intracellularly. METHODS: QDs-Au-NPs were prepared via a simple one-step process through controlling the spacing between them using polyethylene glycol (PEG) as space linker in the form of PEGylated QDs. Furthermore, the applicability of this system was evaluated after coating the particles with somatostatin citrate, SST, to active target somatostatin receptors (SSTRs), and identification of the internalized particles via confocal laser scanning spectroscopy. RESULTS: The results showed that the produced Au shell has a thickness of 2.0 ± 0.2 nm and QDs-Au-NPs showed the same fluorescence intensity compared to the unmodified QDs. Additionally, a stable monodisperse QDs-Au-NPs coated with SST were prepared after coating with 11-Mercaptoundecanoic acid. Moreover, cellular uptake study in Human Caucasian breast adenocarcinoma cell lines showed that QDs-Au-SST-NPs could be detected easily using the confocal microscope. In addition, they showed a significant (p ≤ .05) internalization per cell compared to untreated QDs-Au-NPs as detected by flow cytometry. CONCLUSION: It could be concluded that the produced QDs-Au-NPs has a strong fluorescence property like QDs which enable them to be easily detected after cells internalization.