Discovery of a Secalonic Acid Derivative from Aspergillus aculeatus, an Endophyte of Rosa damascena Mill., Triggers Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cells.
ABSTRACT: A new secalonic acid derivative, F-7 (1), was isolated from the endophytic Aspergillus aculeatus MBT 102, associated with Rosa damascena. The planar structure of 1 was established on the basis of 1D and 2D NMR and ESI-TOF-MS spectra. The relative configuration of 1 was determined applying a combined quantum mechanical/NMR approach and, afterward, the comparison of calculated and experimental electronic circular dichroism spectra determined the assignment of its absolute configuration. The compound possesses strong cytotoxic activity against triple negative breast cancer (TNBC) cells. It was found to induce apoptosis, as evidenced by scanning electron microscopy and phase contrast microscopy. Furthermore, flow cytometry analyses demonstrated that 1 induced mitochondrial damage and reactive oxygen species mediated apoptosis, arresting the G1 phase of the cells in a dose-dependent manner. Also, the compound causes significant microtubule disruption in TNBC cells. Subsequently, 1 restricted the cell migration leading to the concomitant increase in expression of cleaved caspase and PARP.
Project description:Insulin resistance is a condition in which insulin signaling and action are impaired in insulin sensitive tissues and result in hyperglycemia, hyperlipidemia, and type 2 diabetes mellitus. Our previous studies have shown that Rosa damascena has antihyperglycemic effects on diabetic and normal rats. Therefore, we conducted a study to evaluate the effect of this medicinal plant on insulin sensitivity in rats. This study was performed on high fructose diet insulin resistant rats and pioglitazone, an insulin sensitizing drug, was used as a positive control. Insulin resistance was developed in animals by high fructose diet within six weeks. Then, Rosa damascena extract and pioglitazone were administered by gavage for two weeks and results were compared with two control groups. After treatment period, serum glucose, insulin, adiponectin, triglyceride, and cholesterol were assayed in fasting state. Plasma free fatty acid profile was analyzed by GC. Liver PPAR.? and muscle GLUT.4 gene expressions were assessed by real time PCR and western blotting. Animals were treated with rosa damascena extract showed levels of insulin (42 ± 2.7 pmol/L). adiponectin (5.6±0.17 ?g/mL). glucose (129±4.7 mg/dL). and triglyceride (75 ± 9 mg/dl) which were significantly improved as compared with control group insulin (137 ± 34 pmol/L), adiponectin (3.9±0.15 ?g/mL). glucose (187±15 mg/dL). and triglycerides (217±18 mg/dL). PPAR? protein level was also significantly increased in Rosa damascene treated group. Our results demonstrated that rosa damascena extract has useful effects on insulin resistant animals and by increasing insulin sensitivity can be considered as a potential agent in control of diabetes.
Project description:Six sesquiterpenoids 1-6, including two new ones, an ent-daucane-type sesquiterpenoid, asperaculane A (1), and a nordaucane one, asperaculane B (2), and four known nordaucane derivatives, aculenes A-D 3-6, together with the known secalonic acid D (7), were isolated from a fermentation culture of the fungus Aspergillus aculeatus. Their structures and absolute configurations were established by analyses of their spectroscopic data, including 1D and 2D-NMR spectra, HR-ESIMS, electronic circular dichroism (ECD) data, and quantum chemical calculations. These metabolites were evaluated for in vitro cytotoxic activity against two cell lines, human cancer cell lines (HeLa) and one normal hamster cell line (CHO).
Project description:Diabetes mellitus is a multisystemic metabolic disorder that may affect the eyes, kidneys, vessels, and heart. Chronic hyperglycemia causes non-enzymatic glycation of proteins and elevation of the polyol pathway resulting in oxidative stress that damages organs. The current study aimed to investigate the dose-dependent effects of orally consumed Rosa damascena Mill. hydrosol on hematology, clinical biochemistry, lens enzymatic activity, and lens pathology in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male Sprague-Dawley rats by intraperitoneal administration of STZ (40 mg/kg body weight). Rose hydrosols containing 1515 mg/L and 500 mg/L total volatiles (expressed as citronellol) were introduced to rats orally for 45 days. Consumption of 1515 mg/L volatile containing rose hydrosol successfully ameliorated hematologic, hepatic, and renal functions. Hydrosols also attenuated hyperglycemia and decreased the advanced glycation end-product formation in a dose-dependent manner. Rose hydrosol components significantly increased the lens enzymatic activities of glutathione peroxidase and decreased the activity of aldose reductase to prevent cataractogenesis. Histopathological examinations of rat lenses also indicated that increasing the dose of rose hydrosol had a protective effect on lenses in diabetic conditions. Additionally, in silico modeling of aldose reductase inhibition with rose hydrosol volatiles was carried out for extrapolating the current study to humans. The present results suggest that rose hydrosol exerts significant protective properties in diabetes mellitus and has no toxic effect on all studied systems in healthy test groups.
Project description:Parkinson disease (PD) is a multifactorial disease that takes a leading place among contemporary frequent diseases of the central nervous system (CNS) with not well-established mechanism. One of the most popular and effective therapy for patients with PD is Levodopa (L-dopa), but clinical effect of the drug diminished by motor complications resulting from prolonged treatment. Due to the L-dopa neurotoxic effect in the disease treatment, the L-dopa administration is delayed as long as possible in order to avoid side effects. In addition, combining L-dopa therapy with antioxidants, may decrease side-effects and provide symptomatic relief. The aim of the current research was to explore the possibility to reduce the oxidative stress (OS) induced by the L-dopa after its combining with two different antioxidants an essential oil isolated from Rosa damascena Mill., and vitamin C through experimental model of healthy mice. For this purpose, some oxidative stress indicators were evaluated - the lipid and protein oxidation end products - such as lipid peroxidation products measured as malondialdehyde (MDA) levels, protein carbonyl content (PCC), and advanced glycation end products (AGEs) in blood plasma of the experimental mice. For this purpose, was studied blood isolated from healthy mice after i.p. treatment with L-dopa (100?mg/kg). The groups with combining therapy were pre-treated first with Ascorbic acid (400?mg/kg), Rose oil (400?mg/kg). Statistically significant increased MDA levels, PCC and AGEs were found in the blood L-dopa treated mice compared to the controls, while the same parameters were significantly decreased in group pre-treated with antioxidants compared to the same controls. As a conclusion, the studied antioxidants can protect organisms from induced L-dopa oxidative toxicity and may play a key role in end products protection.
Project description:The most commonly used plant source of ?-elemene is <i>Curcuma wenyujin</i> Y. H. Chen & C. Ling (syn. of <i>Curcuma aromatic</i> Salisb.) with its content in supercritical CO? extract up to 27.83%. However, the other rich source of this compound is <i>Nigella damascena</i> L. essential oil, in which ?-elemene accounts for 47%. In this work, the effective protocol for preparative isolation of ?-elemene from a new source-<i>N. damascena</i> essential oil-using high performance counter-current chromatography HPCCC was elaborated. Furthermore, since sesquiterpens are known as potent antimicrobials, the need for finding new agents designed to combat multi-drug resistant strains was addressed and the purified target compound and the essential oil were tested for its activity against a panel of Gram-positive and Gram-negative bacteria, fungi, and mycobacterial strains. The application of the mixture of petroleum ether, acetonitrile, and acetone in the ratio 2:1.5:0.5 (<i>v/v</i>) in the reversed phase mode yielded ?-elemene with high purity in 70 min. The results obtained for antimicrobial assay clearly indicated that <i>N. damascena</i> essential oil and isolated ?-elemene exert action against <i>Mycobacterium tuberculosis</i> strain H37Ra.
Project description:Investigation of the chemical profile of the industrially important black filamentous fungus Aspergillus aculeatus by UHPLC-DAD-HRMS and subsequent dereplication has led to the discovery of several novel compounds. Isolation and extensive 1D and 2D NMR spectroscopic analyses allowed for structural elucidation of a dioxomorpholine, a unique okaramine, an aflavinine and three novel structures of mixed biosynthetic origin, which we have named aculenes A-C. Moreover, known analogues of calbistrins, okaramines and secalonic acids were detected. All novel compounds were tested for antifungal activity against Candida albicans, however all showed only weak or no activity. Aspergillus aculeatus IBT 21030 was additionally shown to be capable of producing sclerotia. Examination of the sclerotia revealed a highly regulated production of metabolites in these morphological structures.
Project description:Pseudonectaries, or false nectaries, the glistening structures that resemble nectaries or nectar droplets but do not secrete nectar, show considerable diversity and play important roles in plant-animal interactions. The morphological nature, optical features, molecular underpinnings and ecological functions of pseudonectaries, however, remain largely unclear. Here, we show that pseudonectaries of Nigella damascena (Ranunculaceae) are tiny, regional protrusions covered by tightly arranged, non-secretory polygonal epidermal cells with flat, smooth and reflective surface, and are clearly visible even under ultraviolet light and bee vision. We also show that genes associated with cell division, chloroplast development and wax formation are preferably expressed in pseudonectaries. Specifically, NidaYABB5, an abaxial gene with ectopic expression in pseudonectaries, is indispensable for pseudonectary development: knockdown of it led to complete losses of pseudonectaries. Notably, when flowers without pseudonectaries were arrayed beside those with pseudonectaries, clear differences were observed in the visiting frequency, probing time and visiting behavior of pollinators (i.e., honey bees), suggesting that pseudonectaries serve as both visual attractants and nectar guides.