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.

Moraea sisyrinchium inhibits proliferation, cell cycle, and migration of cancerous cells, and decreases angiogenesis in chick chorioallantoic membrane.

Objectives: Experimental studies reported that some plants in the genus of Moraea (Iridaceae family) show anticancer potential. This study aimed to evaluate the effects of Moraea sisyrinchium on U87 glioblastoma multiforme and HepG2 liver cancer cells. Materials and Methods: The cells were incubated for 24 hr with hydroalcoholic extract of the stem, flower, and bulb of M. sisyrinchium. Then, the cell proliferation (MTT) assay, cell cycle analysis (propidium iodide staining), cell migration test (scratch), Western blotting (Bax and Bcl-2 expression), and gelatin zymography (for matrix metalloproteinases, MMPs) were performed. Oxidative stress was evaluated by determining the levels of reactive oxygen species and lipid peroxidation. Angiogenesis was evaluated on chick embryo chorioallantoic membrane. Results: The extracts of the flower, stem, and bulb significantly decreased the proliferation of HepG2 and U87 cells. This effect was more for U87 than HepG2 and for the bulb and stem than the flower. In U87 cells, the bulb extract increased oxidative stress, cell cycle arrest, and the Bax/Bcl-2 ratio. Also, this extract suppressed the migration ability of HepG2 and U87 cells, which was associated with the inhibition of MMP2 activity. In addition, it significantly reduced the number and diameter of vessels in the chorioallantoic membrane. Liquid chromatography-mass spectrometry revealed the presence of xanthones (bellidifolin and mangiferin), flavonoids (quercetin and luteolin), isoflavones (iridin and tectorigenin), and phytosterols (e.g., stigmasterol) in the bulb. Conclusion: M. sisyrinchium bulb decreased the proliferation and survival of cancer cells by inducing oxidative stress. It also reduced the migration ability of the cells and inhibited angiogenesis.

Plant Gel-Mediated Synthesis of Gold-Coated Nanoceria Using Ferula gummosa: Characterization and Estimation of Its Cellular Toxicity toward Breast Cancer Cell Lines.

In this study, a novel method using Ferula gummosa gums as a capping agent was used to synthesize the nanoceria for the first time. The method was economical and performed at room temperature. Furthermore, it was coated with gold (Au/nanoceria) and fully characterized using X-ray powder diffraction (XRD), field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FESEM-EDX), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and zeta potential (ζ potential). The crystallite size obtained from the results was 28.09 nm for Au/nanoceria. The energy-dispersive X-ray spectroscopy (EDX) analysis of Au/nanoceria revealed the compositional constituents of the product, which display the purity of the Au/nanoceria. The cell toxicity properties of the non-doped and Au-coated nanoceria were identified by a MTT analysis on a breast cancer cell line (MCF7). Additionally, human foreskin fibroblast cells (HFF) were used as a normal cell line. The cytotoxicity results indicated that the toxicological effect of Au/nanoceria on cancer cells was significant while having little toxic effect on normal cells. The toxicity effect of nanoceria clearly shows the dependence on dose and time, so, with increasing the dose of Au/nanoceria, the death of cancer cells also increases.

Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering.

Among scaffolds used in tissue engineering, natural biomaterials such as plant-based materials show a crucial role in cellular function due to their biocompatibility and chemical indicators. Because of environmentally friendly behavior and safety, green methods are so important in designing scaffolds. A key bioactive flavonoid of the Epimedium plant, Icariin (ICRN), has a broad range of applications in improving scaffolds as a constant and non-immunogenic material, and in stimulating the cell growth, differentiation of chondrocytes as well as differentiation of embryonic stem cells towards cardiomyocytes. Moreover, fusion of ICRN into the hydrogel scaffolds or chemical crosslinking can enhance the secretion of the collagen matrix and proteoglycan in bone and cartilage tissue engineering. To scrutinize, in various types of cancer cells, ICRN plays a decisive role through increasing cytochrome c secretion, Bax/Bcl2 ratio, poly (ADP-ribose) polymerase as well as caspase stimulations. Surprisingly, ICRN can induce apoptosis, reduce viability and inhibit proliferation of cancer cells, and repress tumorigenesis as well as metastasis. Moreover, cancer cells no longer grow by halting the cell cycle at two checkpoints, G0/G1 and G2/M, through the inhibition of NF-κB by ICRN. Besides, improving nephrotoxicity occurring due to cisplatin and inhibiting multidrug resistance are the other applications of this biomaterial.

Facile green synthesis of Ag-doped ZnO/CaO nanocomposites with Caccinia macranthera seed extract and assessment of their cytotoxicity, antibacterial, and photocatalytic activity.

The current paper exhibited a green method for the manufacture of Ag-doped ZnO/CaO nanocomposites (NCPs) by the usage of Caccinia macranthera seed extract, zinc, calcium, and silver salts solution, for the first time. The chemical structure of NCPs was studied by the FT-IR technique. The XRD pattern shows a crystallite structure with an Fm3m group space and particle size of about 23 nm. The FESEM/PSA images displayed that NCPs have uniform distribution with spherical morphology. Also, the cytotoxicity of synthesized NCPs was examined on Huh-7 cells by MTT test and the IC50 value was 250 ppm. Additionally, the photocatalytic activity of NCPs was investigated to the methylene blue MB dye degradation, which resulted in a removal of about 90% after 100 min. According to the results of the broth microdilution process, which was done to evaluate the antibacterial activity of NCPs towards gram-positive and gram-negative bacteria, the MIC values were in the range of 0.97-125 ppm.

Resveratrol-Mediated Gold-Nanoceria Synthesis as Green Nanomedicine for Phytotherapy of Hepatocellular Carcinoma.

BACKGROUND: In the present study, resveratrol was used to prepare complexes of cerium and nanoceria, also coated with gold (CeO2@Au core-shells) to improve the surface interactions in physiological conditions. METHODS: The CeO2@Au core-shells were characterized using powder X-ray diffraction (PXRD), Fourier transforms infrared spectroscopy (FTIR), transmission electron microscope (TEM) analysis, dynamic light scattering (DLS) and ζ potential. RESULTS: The experiment was led to the successful synthesis of nanosized CeO2@Au core-shells, although agglomeration of particles caused the distribution of the larger particles. The TEM analysis demonstrated the particles sizes ranged from 20 nm to 170 nm. Moreover, the PXRD analysis showed that both nanoceria and gold with the same crystal systems and space groups. To investigate the anticancer activity of the CeO2@Au core-shells, the cytotoxicity of the nanoparticles was investigated against liver cancerous cell lines (HepG2). CONCLUSIONS: The results indicated biosynthesized NCs have significant cellular toxicity properties against HepG2 and could be utilized in hepatocarcinoma therapy. Further in vivo investigations is proposed to be designed to assess anti-cancer and safety effects of fabricated nanocomposites.

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.

Green synthesis of nickel oxide nanoparticles using Salvia hispanica L. (chia) seeds extract and studies of their photocatalytic activity and cytotoxicity effects.

The physical and chemical properties of Nickel oxide nanoparticles (NiO-NPs) have attracted the attention of many and in this regard, this study was performed to produce NiO-NPs by the means of Salvia hispanica L. (chia) seeds extract as the capping agent. Physical and morphological features of the obtained NiO-NPs were examined through the application of TGA, FTIR, UV-Vis, XRD, FESEM/EDAX/PSA, and VSM procedures. According to the FESEM/PSA images, the biosynthesized NiO-NPs contained a spherical shape and a size of about 30 nm, while the results of the EDAX study approved the existence of oxygen and nickel elements in the structure of this product. Furthermore, certain corresponding peaks to the crystal structure of NiO-NPs were observed throughout the XRD pattern. Next to the superparamagnetic behavior that was detected in the results of VSM analysis, the cytotoxicity effect of NiO-NPs was not reported to be dependent on concentration. Considering the high photocatalytic capacity along with the low cytotoxic effects of NiO-NPs, we can suggest the applicability of this product for various applications such as disease control and removal of residual toxins.

Bio-indicators in cadmium toxicity: Role of HSP27 and HSP70.

Heat shock proteins (HSPs) are a family of proteins that are expressed by cells in reply to stressors. The changes in concentration of HSPs could be utilized as a bio-indicator of oxidative stress caused by heavy metal. Exposure to the different heavy metals may induce or reduce the expression of different HSPs. The exposure to cadmium ion (Cd2+) could increase HSP70 and HSP27 over 2- to 10-fold or even more. The in vitro and in vivo models indicate that the HSP70 family is more sensitive to Cd intoxication than other HSPs. The analyses of other HSPs along with HSP70, especially HSP27, could also be useful to obtain more accurate results. In this regard, this review focuses on examining the literature to bold the futuristic uses of HSPs as bio-indicators in the initial assessment of Cd exposure risks in defined environments.

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.

Genus Rosas : A Review of Ethnobotany, Phytochemistry and Traditional Aspects According to Islamic Traditional Medicine (ITM).

Rosa spp. is an important genus in the Rosaceae family which is a source of medicinal natural products, particularly polyphenolic and terpenoid compounds and is used in several traditional medicines such as Islamic Traditional Medicine (ITM) to cure various diseases. Plants in this genus are known to possess anti-inflammatory, antidiabetic, anti-constipation, cardioprotective and neuroprotective activities. Furthermore, phytochemical investigations have reported Rosa species to contain a wide range of chemical compounds including quercetin, kaempferol, catechin, citronellol, limonene, lycopene, carvacrol, thymol, ascorbic acid (vitamin C), rosmarinic acid, etc. The current review is an attempt to cover the available findings on the ethnobotany and photochemistry of this genus as well as its medicinal aspects in ITM.

Ethnobotany, Phytochemistry and Pharmacological Features of Centella asiatica: A Comprehensive Review.

Centella asiatica (CA) or Gotu cola is an herbal plant from the Apiaceae family with a long history of usage in different traditional medicines. It has long been used for the treatment of various ailments such as central nervous system (CNS), skin and gastrointestinal disorders especially in the Southeast Asia. This chapter focused on the phytochemical constituent and pharmacological activities of CA based on preclinical and clinical studies. Additionally, botanical description and distribution, traditional uses, interactions, and safety issues are reviewed. Electronic databases of Google Scholar, Scopus, PubMed, and Web of Science were searched to obtain relevant studies on the pharmacological activities of CA. Approximately, 124 chemical compounds including triterpenoids, polyphenolic compounds, and essential oils have been isolated and identified from CA. Ethnomedicinal applications of CA mostly include treatment of gastrointestinal diseases, wounds, nervous system disorders, circulatory diseases, skin problems, respiratory ailments, diabetes and sleep disorders in various ethnobotanical practices. Pharmacological studies revealed a wide range of beneficial effects of CA on CNS, cardiovascular, lung, liver, kidney, gastrointestinal, skin, and endocrine system. Among them, neuroprotective activity, wound healing and treatment of venous insufficiency, as well as antidiabetic activity seem to be more frequently reported. At the moment, considering various health benefits of CA, it is marketed as an oral supplement as well as a topical ingredient in some cosmetic products. Additional preclinical studies and particularly randomized controlled trials are needed to clarify the therapeutic roles of CA.

Stem cell therapy in the heart: Biomaterials as a key route.

Cardiovascular diseases are one of the main concerns, nowadays causing a high rate of mortality in the world. The majority of conventional treatment protects the heart from failure progression. As a novel therapeutic way, Regenerative medicine in the heart includes cellular and noncellular approaches. Despite the irrefutable privileges of noncellular aspects such as administration of exosomes, utilizing of miRNAs, and growth factors, they cannot reverse necrotic or ischemic myocardium, hence recruiting of stem cells to help regenerative therapy in the heart seems indispensable. Stem cell lineages are varied and divided into two main groups namely pluripotent and adult stem cells. Not only has each of which own regenerative capacity, benefits, and drawbacks, but their turnover also close correlates with the target organ and/or tissue as well as the stage and level of failure. In addition to inefficient tissue integration due to the defects in delivering methods and poor retention of transplanted cells, the complexity of the heart and its movement also make more rigorous the repair process. Hence, utilizing biomaterials can make a key route to tackle such obstacles. In this review, we evaluate some natural products which can help stem cells in regenerative medicine of the cardiovascular system.

Pharmacological properties of Rheum turkestanicum Janisch.

Medicinal herbs have been increasingly used worldwide for diseases prevention and treatment. Rheum turkestanicum Janisch. is a perennial shrub of the Polygonaceae family. Genus Rheum includes more than 60 species growing around the world which are used in foods and traditional medicines. R. turkestanicum is believed to be able to improve different kinds of disorders including diabetes, hypertension, jaundice and cancer. In recent years, this medicinal plant has been a subject of many experimental studies to document its health-beneficial properties. These studies have revealed antidiabetic, anticancer, nephroprotective, cardioprotective, and hepatoprotective properties of R. turkestanicum. The presence of flavonoids (e.g. epicatechin and quercetin) and anthraquinones (e.g. chrysophanol, physcion, and emodin) in R. turkestanicum justifies its health-beneficial effects. Nevertheless, possible therapeutic applications and safety of this plant still need to be elucidated in further clinical studies.

Ethnobotany, Phytochemistry and Traditional Uses of Curcuma spp. and Pharmacological Profile of Two Important Species (C. longa and C. zedoaria): A Review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Curcuma, which is the most important source of curcumin, has been widely used in different traditional medicines. Various species of Curcuma have long been used for several purposes such as healing wounds, liver disorders, jaundice and also as a blood purifier. AIM OF THE STUDY: This review focused on the ethnopharmacological uses and phytochemical aspects of Curcuma. Additionally, in this study, the different properties of two species of Curcuma in Islamic Traditional Medicine (ITM), C. longa and C. zedoaria, as well as their pharmacological aspects in modern medicine are reviewed. MATERIALS AND METHODS: ITM literatures were searched to find Curcuma's applications. Also, electronic databases including PubMed and Scopus were searched to obtain studies giving any in vitro, in vivo or human evidence of the efficacy of C. longa and C. zedoaria in the treatment of different diseases. ChemOffice software was used to find chemical structures. RESULTS: The analysis showed that ethno-medical uses of Curcuma have been recorded for centuries. Approximately, 427 chemical compounds have been isolated and identified from Curcuma spp. This genus is rich in flavonoids, tannins, anthocyanin, phenolic compounds, oil, organic acids and inorganic compounds. Curcumin is one of the main active ingredients in Curcuma which has strong anti-inflammatory and antioxidant effects. Besides, pharmacological studies have indicated wide range of Curcuma's activities, such as hepato-protective, antifungal, antihypertensive and neuroprotective. CONCLUSIONS: In this study, we reviewed various studies conducted on ethno-medicinal, ITM properties and photochemistry of Curcuma spp. Also, pharmacological activities of two species, C. longa and C. zedoaria are summarized. Pre-clinical investigations have demonstrated some of the traditional aspects of Curcuma, such as wound healing, anti-arthritic, anti-tumor and liver protective activities. These could be related to antioxidant and anti-inflammatory properties of Curcuma which might be due to high amounts of phenolic compounds. Curcuma is mentioned to have neural tonic properties in ITM which have been confirmed by some animal studies. Considering various preclinical studies on C. longa and C. zedoaria and their active ingredient, curcumin, randomized controlled trials are warranted to confirm their promise as a clinically effective hepato and neuro-protective agents.

The Evaluation and Comparing of Cytotoxic Effects of Ferula gummosa Gum, Scutellaria lindbergii, Kelussia odoratissima and Artemisia kopetdaghensis Extracts on ACHN Cell Line.

Renal cell carcinoma (RCC) is one of most fatal cancers. In most patients it is resistant to chemotherapy. Ferula gummosa gum, Scutellaria lindbergii, Kelussia odoratissima, and Artemisia kopetdaghensis are herbs about which there are some cytotoxic activity reports. In this study, cytotoxic and apoptotic activity of these four extracts on RCC cell line (ACHN) were evaluated and compared (ACHN) cells were treated with different concentrations of herbal extracts (15-500 µg/mL). Cell proliferation was determined after 24, 48, and 72 h. by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry. Cell viability decreased with all herbal extracts in ACHN cells by 24, 48, and 72 h. as compared with control. Extracts induced a sub-G1 peak in flow cytometry histogram of treated cells indicating apoptotic cell death is involved in extracts induced-toxicity. Results imply that four herbal extracts inhibit the growth of ACHN cells as a concentration- and time-dependent manner. Also, results show that apoptosis is proposed as the possible mechanism of action. So, four herbal extracts could be considered as good anticancer agents in RCC after further studies.

Cytotoxic and apoptogenic effects of Bryonia aspera root extract against Hela and HN-5 cancer cell lines.

OBJECTIVE: Bryonia aspera (Stev. ex Ledeb) is a plant that grows in northeast of Iran. In the present study, cytotoxic and apoptogenic properties of B. aspera root extract was determined against HN-5(head and neck squamous cell carcinoma) and Hela (cervix adenocarcinoma) cell lines. MATERIALS AND METHODS: HN-5 and Hela cell lines were cultured in DMEM medium and incubated with different concentrations of B. aspera root extract. Cell viability was quantitated by MTT assay and the optical absorbance was measured at 570 nm (620 nm as the reference) by an ELISA reader, in each experiment. Apoptotic cells were assessed using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). The B. aspera inhibited 50% growth (IC50) of Hela and HN-5 cell lines at 100±28 µg/ml and 12.5±4 µg/ml, respectively after 48 hr of incubation. RESULTS: Cell viability assay showed that inhibitory effects of B. aspera were time and dose-dependent in both cell lines, which were consistent with morphological changes, observed under light microscope. Apoptosis was investigated by flow cytometry in which percentage of apoptotic cells increased in a dose and time-dependent manner. CONCLUSION: Based on our data, B. aspera has cytotoxic effects in which apoptosis played an important role. Further evaluations are needed to assess the possible anti-tumor properties of this plant.

Cytotoxic and Apoptotic Potential of Rheum turkestanicum Janisch Root Extract on Human Cancer and Normal Cells.

Rheum turkestanicum Janischew. (Polygonaceae) is a plant that grows in central Asia and in north-east of Iran. Traditionally, people use roots of R. turkestanicum as an anti-diabetic and anti-hypertensive as well as anticancer agent. In this study the cytotoxicity and apoptogenic properties of ethyl acetate (EtOAc), n-hexane and H2O extracts from Rheum turkestanicum Janischew. (Polygonaceae) root were determined against HeLa and MCF-7 cell lines and human blood lymphocytes. Malignant and non-malignant cells were cultured in RPMI 1640 medium and incubated with different concentrations of plant extracts. Cell viability was measured by MTS assay. Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). The degree of DNA fragmentation was analyzed using agarose gel electrophoresis based on the formation of inter-nucleosomal units. The expression of apoptosis-related protein Bax and PARP cleavage were detected by Western blotting. EtOAc and n-hexane extracts decreased cell viability in malignant but not in non-malignant cells, as a concentration and time dependent manner. EtOAc extract induced a sub-G1 peak in flow cytometry histogram of treated cells compared to the control. DNA fragmentation indicating apoptotic cell death was involved in R. turkestanicum induced toxicity and cleaved PARP fragment was also detected. In conclusion, this is the first report on the cytotoxic effects of R. turkestanicum in which apoptosis played an important role. However, further evaluations are needed to fully understand the possible anti-tumor properties.