Chemical properties of thymoquinone, a monoterpene isolated from the seeds of Nigella sativa Linn.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Thymoquinone is the main ingredient of the essential oil extracted from the seeds of Nigella sativa L. (Ranunculaceae). The monoterpene is considered to be the active pharmaceutical ingredient in the seeds, which have traditionally been highly prized for their medicinal properties. The compound has been the focus of a considerable number of pharmacological investigations and has been reviewed regularly for its action against a variety of inflammatory diseases, its effect on metabolic syndrome, and its potential anticancer properties. While discussing the chemical and pharmacological properties of thymoquinone, recent reviews have reflected on the keto-enol tautomerism of thymoquinone. Specifically, thymoquinone is described as a tautomeric compound, where the keto-form is said to be the major configuration that is responsible for its pharmacological properties [1, 2]. In both reviews, reference is made to a 2005 review by Salem [3]. The latter review discusses a range of activities of thymoquinone, mainly on cell signalling and antioxidant (scavenging) molecular mediators involved in the process of inflammation. However, no mention is made in this review of keto- or enol forms of thymoquinone. Moreover, the chemical structure of thymoquinone does not allow keto-enol tautomerism

Role of Naturally Occurring Anti-Inflammatory Steroid Analogues in the Prevention of Neurodegeneration

In collaboration with Hacettepe University, Faculty of Pharmacy, Department of Pharmacognosy, Sıhhiye, 06100, Ankara, TurkeyThe immune response contributes to human homeostasis by preparing the body to fight off infections and help the healing process in case harm has occurred. Inflammation is an important part of the immune response and is a tightly regulated process. Glucocorticoids are a key part of the feedback mechanism in the immune system, and tune immune activity (inflammation) down. Failing of this feedback mechanism results in chronic inflammation, which is at the basis of a variety of degenerative diseases. A wide range of natural products that have anti-inflammatory properties has been identified. These compounds are thought to contribute to the prevention of neurodegenerative diseases through alleviation of chronic inflammation. The natural products may act as analogues of the steroid hormones that normally regulate the human immune response. The compounds under consideration are triterpenes, phytosterols, and phytoestrogens - notably flavones and isoflavones - which are known to interact with sterol receptors in the human body, and are likely to directly interfere with the cell signalling pathways that lie at the base of the inflammation process

The protective effects of flavonoids and carotenoids against diabetic complications—A review of in vivo evidence

open access articleDiabetes mellitus is a chronic metabolic disorder caused either by inadequate insulin secretion, impaired insulin function, or both. Uncontrolled diabetes is characterized by hyperglycemia which over time leads to fatal damage to both macro-and microvascular systems, causing complications such as cardiovascular diseases, retinopathy and nephropathy. Diabetes management is conventionally delivered through modifications of diet and lifestyle and pharmacological treatment, using antidiabetic drugs, and ultimately insulin injections. However, the side effects and financial cost of medications often reduce patient compliance to treatment, negatively affecting their health outcomes. Natural phytochemicals from edible plants such as fruits and vegetables (F&V) and medicinal herbs have drawn a growing interest as potential therapeutic agents for treating diabetes and preventing the onset and progression of diabetic complications. Flavonoids, the most abundant polyphenols in the human diet, have shown antidiabetic effects in numerous in vitro and preclinical studies. The underlying mechanisms have been linked to their antioxidant, anti-inflammatory and immunomodulatory activities. Carotenoids, another major group of dietary phytochemicals, have also shown antidiabetic potential in recent in vitro and in vivo experimental models, possibly through a mechanism of action similar to that of flavonoids. However, scientific evidence on the efficacy of these phytochemicals in treating diabetes or preventing the onset and progression of its complications in clinical settings is scarce, which delays the translation of animal study evidence to human applications and also limits the knowledge on their modes of actions in diabetes management. This review is aimed to highlight the potential roles of flavonoids and carotenoids in preventing or ameliorating diabetes-related complications based on in vivo study evidence, i.e., an array of preclinical animal studies and human intervention trials. The current general consensus of the underlying mechanisms of action exerted by both groups of phytochemicals is that their anti-inflammatory action is key. However, other potential mechanisms of action are considered. In total, 50 in vivo studies were selected for a review after a comprehensive database search via PubMed and ScienceDirect from January 2002 to August 2022. The key words used for analysis are type-2 diabetes (T2DM), diabetic complications, flavonoids, carotenoids, antioxidant, anti-inflammatory, mechanisms of prevention and amelioration, animal studies and human interventions

miRNAs as Regulators of Antidiabetic Effects of Fucoidans

open access articleDiabetes mellitus is a metabolic disease with a high mortality rate worldwide. MicroRNAs (miRNAs), and other small noncoding RNAs, serve as endogenous gene regulators through binding to specific sequences in RNA and modifying gene expression toward up- or down-regulation. miRNAs have become compelling therapeutic targets and play crucial roles in regulating the process of insulin resistance. Fucoidan has shown potential function as an a-amylase inhibitor, which may be beneficial in the management of type 2 diabetes mellitus. In recent years, many studies on fucoidan focused on the decrease in blood glucose levels caused by ingesting low-glucose food or glucose-lowering components. However, the importance of miRNAs as regulators of antidiabetic effects was rarely recognized. Hence, this review emphasizes the antidiabetic mechanisms of fucoidan through regulation of miRNAs. Fucoidan exerts a vital antidiabetic effect by regulation of miRNA expression and thus provides a novel biological target for future research

Leveraging New Plans in AgentSpeak(PL)

Many papers have been written on the anticancer properties of dietary flavonoids, and a range of potential mechanisms of action of flavonoids. However, most dietary flavonoids - notably polyphenolic flavonoids—have very poor ADME properties, and the levels necessary to stop growth of tumour cells cannot be sustained in a human body trough dietary intake alone. At present no flavonoid based drugs are clinically used in cancer therapy. Thus, whereas epidemiological and pre-clinical data seem to indicate a high potential for flavonoids, from the point of view of the pharmaceutical industry and drug developers, they are considered poor candidates. The flavones—which constitute a subgroup of the flavonoids—show some structural analogy with oestrogen and are known to interact with human oestrogen receptors, either as agonist or as antagonist. They are classed as phytoestrogens, and may play a role in cancer prevention through a mechanism of action possibly similar to that of the clinically used medication tamoxifen. Flavones are abundantly present in common fruits and vegetables, many of which have been associated with cancer prevention. Their phytoestrogen activity makes that they can assert their biological action at concentrations that are realistically achievable in the human systemic circulation

Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol.

Collaboration between Leicester School of Pharmacy - De Montfort Universit, Department of Life, Health and Environmental Sciences - University of L'Aquila, and Department of Biochemistry and Biotechnology - University of Thessaly The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Saffron fromthe province of L'Aquila, in the Abruzzo region of Italy, is highly prized and has been awarded a formal recognition by the European Union with EU Protected Designation of Origin (PDO) status. Despite this, the saffron regions are abandoned by the younger generations because the traditional cultivation of saffron (Crocus sativus L.) is labour intensive and yields only one crop of valuable saffron stamens per year. Petals of the saffron Crocus have had additional uses in traditional medicine and may add value to the crops for local farmers. This is especially important because the plant only flowers between October andNovember, and farmers will need to make the best use of the flowers harvested in this period. Recently, the petals of C. sativus L., which are considered a wastematerial in the production of saffron spice,were identified as a potential source of natural antioxidants. The antioxidants crocin and kaempferol were purified by flash column chromatography, and identified by thin layer chromatography (TLC), HPLC–DAD, infrared (IR), and nuclear magnetic resonance (1H & 13C NMR) spectroscopy. The antioxidant activity was determined with the ABTS and DPPH tests. The antioxidant activities are mainly attributed to carotenoid and flavonoid compounds, notably glycosides of crocin and kaempferol. We found in dried petals 0.6% (w/w) and 12.6 (w/w) of crocin and kaempferol, respectively. Petals of C. sativus L. have commercial potential as a source for kaempferol and crocetin glycosides, natural compounds with antioxidant activity that are considered to be the active ingredients in saffron-based herbal medicine

Flavonols with a catechol or pyrogallol substitution pattern on ring B readily form stable dimers in phosphate buffered saline at four degrees Celsius.

Collaboration between: College of Food Science, Fujian Agriculture and Forestry University, Fuzhou China; Institut für Pharmazie und Lebensmittelchemie, Universität Würzburg, Würzburg, Germany; De Montfort University – Leicester School of Pharmacy, Leicester, UK; Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Phosphate buffered saline (PBS) is a buffer commonly used in biological research. The stability of a series of flavonoids, i.e. myricetin, kaempferol, baicalein, luteolin and quercetin in PBS was assessed. Apigenin proved very stable when incubated with PBS and was used as a control. Kaempferol and baicalein were less stable, and small amounts of oxidized and hydroxylated products could be detected. Flavonols with catechol or pyrogallol structure in ring B are unstable in PBS (pH=7.4) at 4 ºC and were converted into their stable dimers and oxidized products within 5 seconds. The chosen experimental conditions improved the stability of dimers and allowed their detection

Recent advances in chemistry, therapeutic properties and sources of polydatin

Joint review by Hacettepe University, Faculty of Pharmacy, Department of Pharmacognosy and De Montfort University, Leicester School of Pharmacy.Polydatin (PLD), the 3-O-β-glucopyranoside of the well-known stilbenoid compound resveratrol, is a major compound of Fallopia japonica (Houtt.) R. Decr. (Japanese knotweed), which is widely used in traditional Chinese medicine to treat infection, inflammatory diseases and circulatory problems. It has shown a wide range of biological activities including anti-inflammatory, anti-oxidant, anti-cancer, neuroprotective, hepatoprotective, nephroprotective and immunostimulatory effects. Although resveratrol has similar beneficial effects, its low bioavailability has remained a problem. Glycosylation increases solubility of resveratrol in an aqueous environment, thus improving its bioavailability. This has led to a growing interest in PLD. Promising results obtained from bioactivity studies have boosted an intense research on this compound. The aim of this review is to give a comprehensive overview of the botanical sources, pharmacology, biosynthesis, biotechnological production, and bioactivities of PLD, and to discuss clinical studies on this compound

Polymer-drug nanoconjugate – an innovative nanomedicine: challenges and recent advancements in rational formulation design for effective delivery of poorly soluble drugs.

The published manuscript is available at EurekaSelect via - See more at: http://dx.doi.org/10.2174/2211738504666160213001714Abstract Background: Over the last four decades, the use of water soluble polymers in rational formulation design has rapidly evolved into valuable drug delivery strategies to enhance the safety and therapeutic effectiveness of poorly soluble drugs, particularly anticancer drugs. Novel advances in polymer chemistry have provided new generations of well defined polymeric architectures for specific applications in polymer-drug conjugate design. However, total control of crucial parameters such as particle size, molecular weight distribution, polydispersity, localization of charges, hydrophilic-lipophilic balance and non site-specific coupling reactions during conjugation has been a serious challenge. Objective: This review briefly describes the current advances in polymer-drug nanoconjugate design and various challenges hindering their transformation into clinically useful medicines. Method: Existing literature was reviewed. Results: This review provides insights into the significant impact of covalent and non-covalent interactions between drug and polymer on drug loading [or conjugation] efficiency, conjugate stability, mechanism of drug release from the conjugate and biopharmaceutical properties of poorly soluble drugs. The utility values and application of Quality by Design principles in rational design, optimization and control of the Critical Quality Attributes [CQA] and Critical Process Parameters [CPP] that underpin the safety, quality and efficacy of the nanoconjugates are also presented. Conclusion: It was apparent that better understanding of the physicochemical properties of the nanoconjugates as well as the drug-polymer interaction during conjugation process is essential to be able to control the biodistribution, pharmacokinetics, therapeutic activity and toxicity of the nanoconjugates which will in turn enhance the prospect of successful transformation of these promising nanoconjugates into clinically useful nanomedicines

Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4′ hydroxy tangeretin

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Tangeretin is a polymethoxylated flavone with multifaceted anticancer activity. In the present study, the metabolism and further antiproliferative activity of tangeretin was evaluated in the CYP1 expressing human breast cancer cell lines MCF7 and MDA–MB–468 and the normal breast cell line MCF10A. Tangeretin was converted to 4ʹ OH tangeretin by recombinant CYP1 enzymes and in MCF7 and MDA–MB–468 cells. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Tangeretin exhibited submicromolar IC50 (0.25±0.15 μM) in MDA–MB–468 cells, whereas it was less active in MCF7 cells (13.5±0.8 μM) and completely inactive in MCF10A cells (>100 μM). In MDA–MB–468 cells that were coincubated with the CYP1 inhibitor acacetin, an approximately 70–fold increase was noted in the IC50 (18±1.6 μM) of tangeretin. In the presence of the CYP1 inhibitor acacetin, the conversion of tangeretin to 4ʹ OH tangeretin was significantly reduced in MDA–MB–468 cells (2.55±0.19 μM vs. 6.33±0.12 μM). The mechanism of antiproliferative action involved cell cycle arrest at the G1 phase for MCF7 and MDA–MB–468 cells, whereas the cell cycle of MCF10A cells was unaffected by 10 μM of tangeretin treatment for 24 and/or 48 h. Tangeretin was further shown to induce CYP1 enzyme activity and CYP1A1/CYP1B1 protein expression in MCF7 and MDA–MB–468 cells. Taken collectively, the results suggest that tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4ʹ hydroxy tangeretin