Design, synthesis and biological evaluation of new H2S-releasing rivastigmine derivatives as neuroprotective molecules.

Alzheimer's disease (AD) represents one of the main challenges for the 21st century medical research as no disease-modifying agent has been successfully progressed to the market, while the number of people affected by AD is estimated to grow exponentially over the next years. The complex network of triggering factors involved in the insurgence and progression of AD can be rightly addressed as one of the main reasons behind the difficulty in identifying new pharmacological approaches. For this reason, the discovery and development of drugs endowed with pleiotropic activity remain the most valuable, but at the same time challenging, approaches to tackle down AD.

Models of Diabetes: Focus on Diabetic Retinopathy.

Diabetic retinopathy is a major eye complication in patients with diabetes mellitus, and it is the leading cause of blindness and visual impairment in the world. Chronic hyperglycemia induces endothelial damage with consequent vascular lesions, resulting in global vasculitis, which affects the small vessels of the retina. These vascular lesions cause ischemic conditions in certain areas of the retina, with a consequent increase in the release of pro-angiogenic mediators.

Recent Advancements in Production and Extraction Methods of Phycobiliprotein C-phycocyanin by Arthrospira (Spirulina) platensis: A Mini Review.

Arthrospira platensis has been utilized as a food source since ancient times due to its rich nutrient profile. In recent years, its popularity as a dietary supplement has soared, especially due to the presence of a water-soluble phycobiliprotein, C-phycocyanin C (C-PC), which is abundant and notable for its fluorescent properties. C-PC contains the chromophore phycocyanobilin B (PCB-B), a tetrapyrrole molecule, that is why it plays a dual role as a food colorant and as nutraceutical.

Isothiocyanate-Corticosteroid Conjugates against asthma: Unity makes strength.

Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need for chronic pharmacological treatments. The standard gold therapy of inflammation in asthmatic patients involves the use of glucocorticoids even if their chronic use is often related to serious adverse effects. Growing evidence suggests the biological relevance of hydrogen sulfide (HS) in the pathogenesis of airway diseases.

Nutraceutical Features of the Phycobiliprotein C-Phycocyanin: Evidence from ().

, commonly known as , is a photosynthetic filamentous cyanobacterium (blue-green microalga) that has been utilized as a food source since ancient times. More recently, it has gained significant popularity as a dietary supplement due to its rich content of micro- and macro-nutrients. Of particular interest is a water soluble phycobiliprotein derived from known as phycocyanin C (C-PC), which stands out as the most abundant protein in this cyanobacterium.

Sirtuin 1-activating derivatives belonging to the anilinopyridine class displaying cardioprotective activities.

Sirtuin 1 (SIRT1) is an enzyme that relies on NAD cofactor and functions as a deacetylase. It has been associated with various biological and pathological processes, including cancer, diabetes, and cardiovascular diseases. Recent studies have shown that compounds that activate SIRT1 exhibit protective effects on the heart.

Anti-Proliferative Properties of the Novel Hybrid Drug Met-ITC, Composed of the Native Drug Metformin with the Addition of an Isothiocyanate HS Donor Moiety, in Different Cancer Cell Lines.

Metformin (Met) is the first-line therapy in type 2 diabetes mellitus but, in last few years, it has also been evaluated as anti-cancer agent. Several pathways, such as AMPK or PI3K/Akt/mTOR, are likely to be involved in the anti-cancer Met activity. In addition, hydrogen sulfide (HS) and HS donors have been described as anti-cancer agents affecting cell-cycle and inducing apoptosis.

Plants and Mushrooms as Possible New Sources of HS Releasing Sulfur Compounds.

Hydrogen sulfide (HS), known for many decades exclusively for its toxicity and the smell of rotten eggs, has been re-discovered for its pleiotropic effects at the cardiovascular and non-cardiovascular level. Therefore, great attention is being paid to the discovery of molecules able to release HS in a smart manner, i.e.

Influence of Polyphenols on Adipose Tissue: Sirtuins as Pivotal Players in the Browning Process.

Adipose tissue (AT) can be classified into two different types: (i) white adipose tissue (WAT), which represents the largest amount of total AT, and has the main function of storing fatty acids for energy needs and (ii) brown adipose tissue (BAT), rich in mitochondria and specialized in thermogenesis. Many exogenous stimuli, e.g.

Anti-Inflammatory and Vasorelaxant Effects Induced by an Aqueous Aged Black Garlic Extract Supplemented with Vitamins D, C, and B12 on Cardiovascular System.

Multiple studies demonstrated biological activities of aged black garlic, including anti-inflammatory, antioxidant, and cardioprotective effects. We aimed to investigate the protective effects of an aged black garlic water extract (ABGE) alone or in association with multivitamins consisting of combined Vitamins D, C, and B12, on mouse heart specimens exposed to E. coli lipopolysaccharide (LPS).

Anti-Inflammatory Effect of the Natural HS-Donor Erucin in Vascular Endothelium.

Vascular inflammation (VI) represents a pathological condition that progressively affects the integrity and functionality of the vascular wall, thus leading to endothelial dysfunction and the onset of several cardiovascular diseases. Therefore, the research of novel compounds able to prevent VI represents a compelling need. In this study, we tested erucin, the natural isothiocyanate HS-donor derived from Mill.

New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways.

Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells.

Design, Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and HS Donors.

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (HS) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease.

Regulation of blood pressure by natural sulfur compounds: Focus on their mechanisms of action.

Natural sulfur compounds are emerging as therapeutic options for the management of hypertension and prehypertension. They are mainly represented by polysulfides from Alliaceae (i.e.

Sirtuin 1-Activating Compounds: Discovery of a Class of Thiazole-Based Derivatives.

Sirtuin 1 (SIRT1) is a NAD-dependent deacetylase implicated in various biological and pathological processes, including cancer, diabetes, and cardiovascular diseases. In recent years, SIRT1-activating compounds have been demonstrated to exert cardioprotective effects. Therefore, this enzyme has become a feasible target to treat cardiovascular diseases, and many SIRT1 activators, of a natural or synthetic origin, have been identified.

Cardiovascular benefits of Eruca sativa mill. Defatted seed meal extract: Potential role of hydrogen sulfide.

Eruca sativa Mill. is an edible plant belonging to the Brassicaceae botanical family with a long story as a medicinal material, mainly linked to the presence of glucoerucin. One of the main products of this glucosinolate is erucin, a biologicallly active isothiocyanate recently recognized as a hydrogen sulfide (H S) donor.

Potential Effects of Natural HS-Donors in Hypertension Management.

After the discovery of hydrogen sulfide (HS) in the central nervous system by Abe and Kimura in 1996, the physiopathological role of HS has been widely investigated in several systems such as the cardiovascular. In particular, HS plays a pivotal role in the control of vascular tone, exhibiting mechanisms of action able to induce vasodilation: for instance, activation of potassium channels (KATP and Kv7) and inhibition of 5-phosphodiesterase (5-PDE). These findings paved the way for the research of natural and synthetic exogenous HS-donors (i.

New Synthetic Analogues of Natural Polyphenols as Sirtuin 1-Activating Compounds.

NAD-dependent deacetylase SIRT1 regulates many different biological processes, thus being involved in pathogenic conditions such as metabolic diseases, neurogenerative disorders and cancer. Notably, experimental evidence underlined that the activation of SIRT1 had promising cardioprotective effects. Consequently, many efforts have been so far devoted to finding new SIRT1 activators, both derived from natural sources or prepared by synthetic procedures.

Glucoraphanin Increases Intracellular Hydrogen Sulfide (HS) Levels and Stimulates Osteogenic Differentiation in Human Mesenchymal Stromal Cell.

Osteopenia and osteoporosis are among the most prevalent consequences of ageing, urging the promotion of healthy nutritional habits as a tool in preventing bone fractures. Glucosinolates (GLSs) are organosulfur compounds considered relatively inert precursors of reactive derivatives isothiocyanates (ITCs). Recent evidence suggests that GLSs may exert biological properties based on their capacity to release hydrogen sulfide (HS).

HS donating corticosteroids: Design, synthesis and biological evaluation in a murine model of asthma.

Introduction: Hydrogen sulfide (HS) is a fundamental biological endogenous gas-mediator in the respiratory system. It regulates pivotal patho-physiological processes such as oxidative stress, pulmonary circulation, airway tone and inflammation.

Objectives: We herein describe the design and synthesis of molecular hybrids obtained by the condensation of several corticosteroids with different hydrogen sulfide releasing moieties.

The HS-Donor Erucin Exhibits Protective Effects against Vascular Inflammation in Human Endothelial and Smooth Muscle Cells.

Preservation of vascular wall integrity against degenerative processes associated with ageing, fat-rich diet and metabolic diseases is a timely therapeutical challenge. The loss of endothelial function and integrity leads to cardiovascular diseases and multiorgan inflammation. The protective effects of the HS-donor erucin, an isothiocyanate purified by Mill.

Pharmacological evaluation of innovative eye drop formulations containing TS-polysaccaride, hyaluronic acid and glycyrrhizin for irritative ocular diseases using in vitro reconstituted human corneal epithelium model.

In vitro reconstructed human corneal tissue models are closer to in vivo human corneal tissue in term of morphology, biochemical and physiological properties, and represent a valid alternative to animal use for evaluating the pharmacological effects ophthalmic topically applied medical devices. In this experimental work the in vitro reconstructed human corneal tissues have been used for assessing the potential beneficial effects of an innovative ophthalmic formulation containing hyaluronic acid, glycyrrhizin and TS-polysaccharide for the treatment of symptomatic states on the eye surface including dry eye, itching, foreign body sensation and redness due allergic reaction. Corneal tissues have been treated with benzalkonium chloride for 24 h to induce cell damage and then treated with the tested items for 16 h.

Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications.

, commonly known as krill, is a small marine crustacean from the Antarctic Ocean that plays an important role in the marine ecosystem, serving as feed for most fish. It is a known source of highly bioavailable omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid). In preclinical studies, krill oil showed metabolic, anti-inflammatory, neuroprotective and chemo preventive effects, while in clinical trials it showed significant metabolic, vascular and ergogenic actions.

Hybrids between HS-donors and betamethasone 17-valerate or triamcinolone acetonide inhibit mast cell degranulation and promote hyperpolarization of bronchial smooth muscle cells.

Glucocorticoids represent the standard gold treatment of inflammation in asthmatic patients. More recently, HS has been described to exert positive effect on this disease. Bearing in mind that an improved pharmacological activity and a reduced toxicity can be obtained through hybridization of different molecules, simultaneously modulating multiple targets, we designed and synthesized novel betamethasone 17-valerate and triamcinolone acetonide hybrids with well-known HS-donor moieties.

Role of hydrogen sulfide in endothelial dysfunction: Pathophysiology and therapeutic approaches.

Background: The vascular endothelium represents a fundamental mechanical and biological barrier for the maintenance of vascular homeostasis along the entire vascular tree. Changes in its integrity are associated to several cardiovascular diseases, including hypertension, atherosclerosis, hyperhomocysteinemia, diabetes, all linked to the peculiar condition named endothelial dysfunction, which is referred to the loss of endothelial physiological functions, comprehending the regulation of vascular relaxation and/or cell redox balance, the inhibition of leukocyte infiltration and the production of NO. Among the endothelium-released vasoactive factors, in the last years hydrogen sulfide has been viewed as one of the main characters involved in the regulation of endothelium functionality, and many studies demonstrated that H2S behaves as a vasoprotective gasotransmitter in those cardiovascular diseases where endothelial dysfunction seems to be the central issue.