Preparation and Characterization of Nanostructured Lipid Carriers (NLCs) Containing Glycyrrhiza glabra Extract for the Treatment of Skin Hyperpigmentation.

PURPOSE: This study aimed to prepare, characterize, and in vitro and in vivo evaluate a novel nanostructured lipid carriers (NLCs) formulation containing two fractions of Glycyrrhiza glabra L. (licorice) extract for the treatment of hyperpigmentation. METHODS: Two fractions, one enriched with glabridin (FEG) and the other enriched with liquiritin (FEL), were obtained by partitioning the methanol (MeOH) extract of licorice roots with ethyl acetate (EtOAc) and partitioning the EtOAc fraction with butanol (n-BuOH) and water. The quantities of glabridin (Glab) and liquiritin (LQ) in the fractions were determined by high-performance liquid chromatography (HPLC). FEG and FEL were loaded in different NLC formulations, and surface characterization and long-term stability were studied using Dynamic Light Scattering (DLS). The best formulation was chosen for further surface characterization, including Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), and Fouriertransform infrared (FTIR) spectroscopy. Moreover, entrapment efficiency percentage (EE%), in vitro drug release, in vivo skin penetration, cytotoxicity on B16F10 melanoma cells, effect on melanin production, and anti- tyrosinase activity were tested for the selected formulation. RESULTS: Based on HPLC results, FEG contained 34.501 mg/g of Glab, and FEL contained 31.714 mg/g of LQ. Among 20 different formulations, NLC 20 (LG-NLCs) showed desirable DLS results with a Z-average size of 185.3±1.08 nm, polydispersity index (PDI) of 0.229±0.35, and zeta potential of -16.2±1.13 mV. It indicated good spherical shape, high EE% (79.01% for Glab and 69.27% for LQ), two-stage release pattern (an initial burst release followed by sustained release), efficient in vivo skin penetration, and strong anti-tyrosinase activity. LG-NLCs had acceptable physiochemical stability for up to 9 months and were non-cytotoxic. CONCLUSION: The LG-NLC formulation has revealed desirable surface characterization, good physiochemical stability, efficient drug release pattern and in vivo penetration, and high EE%. Therefore, it can be a suitable nanosystem for the delivery of licorice extract in the treatment of hyperpigmentation.

Cytotoxic and apoptotic effects of Ferula gummosa Boiss: extract on human breast adenocarcinoma cell line.

PURPOSE: Ferula gummosa Boiss. is a well-known and valuable medicinal plant in Iran. Research has shown that this plant has several pharmacological properties, including anti-bacterial, anti-cancer and etc. In the present study, we investigated the cytotoxic properties of F. gummosa Boiss. extract in MCF-7 breast adenocarcinoma cells. METHODS: The cytotoxicity and pro-apoptotic properties of the extract were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test and propidium iodide (PI) stained cells, respectively. Apoptosis and necrosis were evaluated by annexin V-PI staining. The levels of reactive oxygen species (ROS),malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) was determined to evaluate oxidative stress. The cell migration and the gene expression were assessed by scratch assay and quantitative real-time polymerase chain reaction (q-RT-PCR), respectively. RESULTS: The extract of F. gummosa decreased the viability and cell cycle progression of MCF-7 cells by inducing apoptosis and necrosis, increasing ROS and MDA levels, and decreasing GSH levels and SOD activity. It also lowered the cells' migration capability by enhancing p53 mRNA levels and reducing MMP-9 mRNA expression. CONCLUSION: F. gummosa exhibited pro-apoptotic, anti-proliferative, and anti-metastatic effects on MCF-7 cells. It is therefore recommended that detailed future research be done on different parts of the plant or its secondary metabolites to find anti-cancer lead compounds.

Ethnobotanical and phytochemical aspects of the edible herb Coriandrum sativum L.

Coriandrum sativum (coriander) is an edible herb in the family Apiaceae. The leaves, fruits, and stems of C. sativum have long been used as culinary spice due to their favorable odor. Traditional practitioners used this plant for treating different diseases like blepharitis, scabies, aphthous stomatitis, laryngitis, headache, and palpitation. In modern researches, coriander has demonstrated anxiolytic, anticonvulsant, antimigraine, neuroprotective, analgesic, diuretic, hypoglycemic, hypolipidemic, hypotensive, anticancer, and antioxidant activities. Coriander contains a wide range of bioactive phytochemicals among which phenylpropenes, terpenoids, isocoumarins, phytosterols, and fatty acids are the most important. This review provides information about the botanical and ethnobotanical aspects, chemical profile, therapeutic uses in Islamic traditional medicine (ITM), and recent pharmacological studies of coriander effects. The results have shown that coriander and its monoterpenoid compound, linalool, can be considered as potential drug candidates for treating metabolic syndrome and different inflammatory conditions especially neural and CNS diseases.

Dermoprotective Effects of Saffron: A Mini Review.

Crocus sativus L. (Iridaceae), known as saffron, is widely used as a coloring agent, food additive, and medicinal spice. Saffron can be beneficial for treating convulsions, tumors, oxidative-related diseases, inflammation, memory impairments, and depression. These effects are due to its chemical components like anthocyanins, flavonoids and terpenoids. Saffron has been shown to be of benefit for treating skin diseases as a result of its anti-oxidant, anti-microbial, depigmenting, and repairing activities. Therefore, it is used for formulating various lotions, creams, and cosmetics emulsions, namely sunscreens, moisturizers, and anti-spot and anti-aging products. In this review, we have presented various skin protective effects of saffron and its components.

Ethnobotanical Uses, Phytochemistry and Pharmacology of Different Rheum Species (Polygonaceae): A Review.

Today, there is an increased tendency to use herbal remedies. Rhubarb refers to several species of the genus Rheum L. in the Polygonaceae family. This species-rich genus is mainly distributed in Asian countries. Several medicinal effects have been attributed to the Rheum spp. in the traditional and modern medicine such as healing lungs, liver, kidney, womb and bladder diseases, cancer, diabetes, insect bites, relapsing fevers, diarrhea and constipation. Various in vitro, in vivo and clinical studies have investigated the therapeutic effect of extracts, fractions and pure compounds isolated from different species of this genus. Considering the positive findings, several pharmaceutical formulations containing rhubarb extract like capsules, drops, mouthwashes and different topical formulations are now present in the market. However, there are other traditional therapeutic effects of rhubarb that have not been studied yet and it is of great importance to perform confirmatory experiments or clinical investigations. The current review summarizes general information regarding botany, phytochemistry, ethnobotany and pharmacological aspects of Rheum spp. It is hoped that the present review could motivate subsequent research on the other medicinal properties of these plants that have been neglected until today.

Protective effects of Lavandula stoechas L. methanol extract against 6-OHDA-induced apoptosis in PC12 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder associated with oxidative stress-induced neuronal damage and death. In European and Persian Traditional Medicine, aerial parts (leaves, stems, and flowers) of Lavandula stoechas L. have been widely used for treating neurodegenerative disorders including PD. AIM OF THE STUDY: Herein, the protective effects of L. stoechas methanol extract were investigated on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity and oxidative damage in PC12 cells. MATERIALS AND METHODS: The cells were pretreated with a standardized L. stoechas methanol extract (2.5-20 µg/mL) for 24 h and exposed to 6-OHDA (200 µM) thereafter. The cell viability percentage was determined by AlamarBlue test. Intracellular reactive oxygen species (ROS) production was determined by a fluorimetric method using 2',7'-dichlorodihydrofluorescein diacetate and cellular apoptosis was assessed by the fluorescent probe propidium iodide test. Finally, the expression of proteins involved in apoptosis pathway (Phospho SAPK/JNK, SAPK/JNK, p44/42 MAPK (ERK1/2) and Poly ADP ribose polymerase (PARP)) was measured via Western blot analysis. RESULTS: Treatment of PC12 cells with 6-OHDA could significantly increase cytotoxicity, ROS level, and cell apoptosis. Pretreatment of PC12 cells with the extract could significantly decrease 6-OHDA cytotoxicity, ROS production, (2.5 and 5 µg/mL) and cell apoptosis (5 µg/mL). Western blot analysis showed that 6-OHDA exposure could increase the expression of proteins involved in apoptosis signaling, while pretreatment with L. stoechas (5 µg/mL) reduced apoptotic proteins. CONCLUSIONS: The present study demonstrated that L. stoechas, which has been traditionally used in Persian Medicine for treating CNS diseases, is a valuable source of active compounds with neuroprotective, anti-oxidant, and anti-apoptotic activity.

Metabolic differences of two Ferula species as potential sources of galbanum: An NMR-based metabolomics study.

INTRODUCTION: Ferula gummosa Boiss. and Ferula galbaniflua Boiss. & Buhse (Apiaceae) are two important Iranian plants that are considered as potential sources of galbanum (barijeh). Galbanum is traditionally used for treating different diseases including flatulence and memory impairment. OBJECTIVE: According to a phylogenetic analysis of the nrDNA ITS sequence and the Flora Iranica, F. gummosa has been considered as a synonym of F. galbaniflua. However, F. galbaniflua and F. gummosa grow in two different geographical locations and have different metabolic patterns. Some researchers believe that F. gummosa and F. galbaniflua are two distinct species. To discriminate these species, we compared metabolic profiles of F. gummosa and F. galbaniflua samples. METHODS: 1 H-NMR-based metabolomics analysis was used for classification of F. gummosa and F. galbaniflua samples collected from northeast Iran. The acquired data were analyzed using hierarchical cluster analysis (HCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA). RESULTS: The result showed a clear separation between the two species that may be related to the quantity and diversity of their metabolites. Ferula gummosa had higher mogoltacin levels, while F. galbaniflua had higher feselol levels. Ligupersin A and conferdione were significantly detected in F. gummosa, whereas sterol compounds were significantly detected in F. galbaniflua. CONCLUSION: Our findings indicate that clear metabolomics discrimination of F. gummosa and F. galbaniflua makes their chemotaxonomic classification possible.

Protective effects of Cinnamomum verum, Cinnamomum cassia and cinnamaldehyde against 6-OHDA-induced apoptosis in PC12 cells.

Cinnamon (Cinnamomum verum and C. cassia) is a medicinal plant, widely-used as a culinary spice. It possesses various therapeutic effects and can slow down the progression of neurological disorders impressively. In this article, the effects of hydro-alcohol extract and essential oil of C. verum and C. cassia and its main bioactive component cinnamaldehyde, has been examined on 6-OHDA-exposed PC12 cells as an in vitro model of Parkinson's disease. The cytotoxicity and cell apoptosis has been induced by 6-OHDA in PC12 cells. The protective effect was determined by measuring cell viability, the amount of reactive oxygen species (ROS), and apoptosis. Cell viability and apoptosis were assessed using resazurin assay, flow cytometry of propidium iodide (PI) stained cells, and western blot analysis. 6-OHDA resulted in the death and apoptosis of cells while, pretreatment with the extract and essential oil of C. verum and C. cassia at 20 µg/ml and cinnamaldehyde at 5 and 10 µM for 24 h could significantly increase the viability (p < 0.001), and decrease ROS content (p < 0.05). Pretreatment with the extracts increased survivin and decreased cyt-c whereas, pretreatment with the essential oil decreased cyt-c, increased survivin, and reduced P-p44/42/p44/42 levels to a level near that of the related control. The extract and essential oil of C. verum and C. cassia can be effective against 6-OHDA cytotoxicity. It is suggested that, the synergistic effects of cinnamaldehyde and other components of extract and essential oil promote cinnamon's medicinal properties.

Galbanic Acid-Coated Fe3O4 Magnetic Nanoparticles with Enhanced Cytotoxicity to Prostate Cancer Cells.

Galbanic acid is a natural sesquiterpene coumarin compound with different biological activities, particularly cytotoxicity against LNCaP (an androgen-dependent prostate cancer cell line). Galbanic acid induces apoptosis in LNCaP via down-regulation of androgen receptor. However, the poor water-solubility of galbanic acid limits further in vitro and in vivo studies. In this study we present the synthesis of galbanic acid-coated Fe3O4 magnetic nanoparticles and their cytotoxicity evaluation on three prostate cancer cell lines, including PC3 (an androgen-independent cell line), LNCaP, and DU145 (an androgen-independent cell line). The synthesized nanoparticles were characterized by X-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, scattering electron microscopy, energy-dispersive X-ray spectroscopy, dynamic light scattering, and vibrating sample magnetometry. Our cytotoxicity evaluation demonstrated that galbanic acid was cytotoxic only against LNCaP cells, while the galbanic acid-coated Fe3O4 nanoparticles showed cytotoxicity on all tested cells, including androgen-dependent and -independent cell lines. This indicates that other mechanisms are involved in the cytotoxicity of galbanic acid in addition to androgen receptor down-regulation. In conclusion, the loading of galbanic acid on the surface of Fe3O4 magnetic nanoparticles turned out to be a successful approach to enhance the solubility and cytotoxicity of this compound.