European journal of pharmacology
-
SARS-CoV-2, a newly emerged pathogen in December 2019, marked as one of the highly pathogenic Coronavirus, and altogether this is the third coronavirus attack that crossed the species barrier. As of 1st July 2020, it is spreading around 216 countries, areas or territories, and a total of 10,185,374 and 503,862 confirmed cases and death reports, respectively. The SARS-CoV-2 virus entered into the target cells by binding with the hACE2 receptors. ⋯ Vaccine development from various pharmaceutical companies and research institutes is under progress, and more than ten vaccine candidates are in the various phases of clinical trials. This review work highlighted the origin, emergence, structural features, pathogenesis, and clinical features of COVID-19. We have also discussed the in-line treatment strategies, preventive measures, and vaccines to combat the emergence of COVID-19.
-
The first cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or COVID-19) infections were recorded in China in November 2019. Since its appearance in China at the end of last year, the virus has spread to all continents causing a "global pandemic". To date, some aspects remain to be investigate about the pathophysiology of this viral infection. ⋯ RAS is a physiological system playing a key role in different human body functions regulation. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE-2), a component of RAS, as a potential factor of cell penetration and infectivity; in addition, in the different infection stages, a functional variation of the RAS has been noted. In this article, we discuss the correlation between the role of RAS and system-modifying agents, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and direct renin inhibitors (DRIs), with SARS-CoV-2 infection.
-
The calcineurin (CaN)/nuclear factor of activated T-cell (NFAT) signalling pathway plays an important role in pathological cardiac hypertrophy. Here, we investigated the potential effects of stachydrine hydrochloride, a bioactive constituent extracted from the Chinese herb Leonurus japonicus Houtt. (Yimucao), on pathological cardiac hypertrophy during chronic α1-adrenergic receptor (α1-AR) activation and the underlying mechanisms. First, by transcriptome analysis, we determined that pathological hypertrophy models could be prepared after phenylephrine stimulation. ⋯ Interestingly, stachydrine hydrochloride inhibited CaN activation and reduced NFATc3 nuclear translocation in phenylephrine-stimulated neonatal rat ventricular myocytes. In mice treated with phenylephrine, stachydrine hydrochloride treatment decreased cardiac hypertrophy and regulated heart function. Collectively, our data show that stachydrine hydrochloride decreases cardiac hypertrophy in phenylephrine-stimulated hearts by inhibiting the CaN/NFAT pathway, which might contribute to alleviation of pathological cardiac hypertrophy and cardiac dysfunction by stachydrine hydrochloride after phenylephrine stimulation This also indicated that governing of CaN/NFAT pathway might serve as a preventive or therapeutic strategy for pathological cardiac hypertrophy.
-
As a primary tool in first-line treatment of severe extremity hemorrhage, tourniquet and subsequent reperfusion also induce ischemia-reperfusion (IR) injuries including severe dysfunction of the neuromuscular junction (NMJ). Here, we observed the effect of dexamethasone (Dex) on NMJs suffering from IR-cause damage in mouse hindlimb. Unilateral hindlimb of mice was subjected to 3 h of tourniquet application by placing a rubber band, and then releasing the rubber band for reperfusion during different periods of time (1, 2, 4, and 6 weeks). ⋯ IL-1β and TNFα were over-produced in gastrocnemius muscles at 1 week, gradually decreased to the sham level at 4 weeks, and returned back to a high level at 6 weeks of tourniquet-induced IR. Treatment with Dex mitigated fragmentation of nAChR clusters, increased the amplitude of EPPs, and decreased levels of TNFα and IL-1β during the first two weeks of tourniquet-induced IR. The present study suggests that anti-inflammation is a potentially important strategy for promoting the morphological and functional recovery processes of NMJs after tourniquet-induced IR injuries.
-
The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. ⋯ However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.