Current medicinal chemistry
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Among 484 Hypericum L. (Guttiferae/Hypericaceae) species, widespread in warm temperate areas throughout the world, only H. perforatum is widely used in official medicine. Hypericum perforatum has been reported as an antidepressant, antiviral, antimicrobial, anti-inflammatory, and a healing agent. The main constituents of the Hypericum species are naphthodianthrones, primarily represented by hypericin and pseudohypericin, phloroglucinol derivatives, especially hyperforin, and flavonoids, such as quercetin, quercitrin, hyperoside and rutin. ⋯ However, only a few studies concerning the activity of extracts and isolated compounds were done in vivo. Also, data on the safe usage of Hypericum constituents as phytotherapeutics are scarce. Since some of Hypericum species are scarcely distributed or endemic as well as some of the secondary metabolites are presented in very small amounts, bio-production, especially endophytes, could represent an abundant and reliable source of pharmacologically active metabolites of Hypericum species for exploitation in pharmaceutical industry.
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The progression and exacerbations of chronic obstructive pulmonary disease (COPD) are intimately associated with tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress. Alterations in redox signaling proinflammatory kinases and transcription factors, steroid resistance, unfolded protein response, mucus hypersecretion, extracellular matrix remodeling, autophagy/apoptosis, epigenetic changes, cellular senescence/aging, endothelial dysfunction, autoimmunity, and skeletal muscle dysfunction are some of the pathological hallmarks of COPD. In light of the above it would be prudent to target systemic and local oxidative stress with agents that can modulate the antioxidants/ redox system or by boosting the endogenous levels of antioxidants for the treatment and management of COPD. ⋯ This includes specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, lipid peroxidation and protein carbonylation blockers/inhibitors, such as edaravone and lazaroids/tirilazad, myeloperoxidase inhibitors, as well as specialized pro-resolving mediators/inflammatory resolving lipid mediators, omega-3 fatty acids, vitamin D, and hydrogen sulfide. According to various studies it appears that the administration of multiple antioxidants could be a more effective mode used in the treatment of COPD. In this review, various pharmacological and dietary approaches to enhance lung antioxidant levels and beneficial effects of antioxidant therapeutics in treating or intervening the progression of COPD have been discussed.
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Bronchodilators, generally administered via metered dose or dry powder inhalers, are the mainstays of pharmacological treatment of stable COPD. Inhaled long-acting beta-agonists (LABA) and anticholinergics are the bronchodilators primarily used in the chronic treatment of COPD. Anticholinergics act as muscarinic acetylcholine receptor antagonists and are frequently preferred over beta-agonists for their minimal cardiac stimulatory effects and greater efficacy in most studies. ⋯ Some new LAMAs, including glycocpyrrolate, are suitable for once daily administration and, unlike tiotropium, have a rapid onset of action. New LAMAs and their combination with ultra-LABA and, possibly, inhaled corticosteroids, seem to open new perspectives in the management of COPD. Dual-pharmacology muscarinic antagonist-beta2 agonist (MABA) molecules present a novel approach to the treatment of COPD by combining muscarinic antagonism and beta2 agonism in a single molecule.
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Oxygen (O(2)) is a vital element. Shortage of O(2) results in deranged metabolism and important changes in vascular tone with opposite effects on the systemic and pulmonary circulation. During hypoxemia, oxidative stress exposes the organism to a sort of accelerated senescence as well as to several acute untoward effects. ⋯ Consistent with this aim also is a careful scrutiny of instruments and procedures for monitoring the individual response to O(2) over time. Thus, at variance from classical pharmacological therapy, performing O(2) therapy requires a vast array of clinical and technical competences. The optimal integration of these competences is needed to optimize O(2) therapy on individual bases.
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RNA interference (RNAi) is an efficient process of posttranscriptional gene silencing. In recent years it has been developed into a new technology in biopharmaceutical fields of science. RNAi products include short interference RNA (siRNA) but also short hairpin RNA (shRNA), bifunctional short hairpin RNA (bi-shRNA) and microRNA (miRNA). ⋯ Among over 20 therapeutics that reached clinical trials, only few are still investigated. Another few are clinical candidates. The review focuses on RNAi products under clinical evaluation and their most promising new applications.