Current Pharmaceutical Design - Volume 27, Issue 38, 2021

One of the major health concerns in the world is the global increase in intractable bacterial infectious diseases due to the emergence of multi- and extensively drug-resistant bacterial pathogens as well as increase in compromised hosts around the world. Particularly, in the case of mycobacteriosis, the high incidence of tuberculosis in developing countries, resurgence of tuberculosis in industrialized countries, and increase in the prevalence of Mycobacterium avium complex infections are important worldwide health concerns. However, the development of novel antimycobacterial drugs is currently making slow progress. Therefore, it is considered that devising improved administration protocols for clinical treatment against refractory mycobacteriosis using existing chemotherapeutics is more practical than awaiting the development of new antimycobacterial drugs. The regulation of host immune responses using immunoadjunctive agents may increase the efficacy of antimicrobial treatment against mycobacteriosis. The same situations also exist in cases of intractable infectious diseases due to common bacteria other than mycobacteria. The mild and long-term up-regulation of host immune reactions in hosts with intractable chronic bacterial infections, using herbal medicines and medicinal plants, may be beneficial for such immunoadjunctive therapy. This review describes the current status regarding basic and clinical studies on therapeutic regimens using herbal medicines, useful for the clinical treatment of patients with intractable bacterial infections. In particular, we focus on immunoadjunctive effects of herbal medicines on the establishment and manifestation of host antibacterial immunity related to the immunological roles of Th17 cell lineages.

Chagas disease is a Neglected Tropical Disease (NTD), and although it is endemic in Latin America, it affects around 6-7 million people worldwide. The treatment of Chagas disease is based on benznidazole and nifurtimox, which are the only available drugs. However, they are not effective during the chronic phase and cause several side effects. Furthermore, BZ promotes cure in 80% of the patients in the acute phase, but the cure rate drops to 20% in adults in the chronic phase of the disease. In this review, we present several studies published in the last six years, which describe the antiparasitic potential of distinct drugs, from the synthesis of new compounds, aiming to target the parasite, as well as the repositioning and the combination of drugs. We highlight several compounds that have shown equivalency or superiority to BZ, which means that they should be further studied, either in vitro or in vivo. Furthermore, we highlight the differences in the effects of BZ on the same strain of T. cruzi, which might be related to methodological differences, such as parasite and cell ratios, host cell type, and the time of adding the drug. In addition, we discussed the wide variety of strains and also the cell types used as host cells, making it difficult to compare the trypanocidal effect of the compounds.

Background and Objective: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly pathogenic virus, is responsible for a respiratory disease termed coronavirus disease 2019 (COVID-19). SARS-CoV-2 genome encodes various structural and non-structural proteins, which are necessary for viral entry and replication. Among these proteins, papain-like protease (PLpro), 3C-like protease (3CLpro), RNAdependent RNA polymerase (RdRp), helicase, serine protease, and spike protein are potential targets of herbal remedies and phytocompounds for inhibition of viral infection and replication. There is, at present, no confirmed cure for the COVID-19. Various plants and their components have been introduced against SARS-CoV-2. A number of review articles have also been published on them. This article is focused on the mechanistic aspects of these plants and their derivatives on SARS-CoV-2. Methods: The material in this review article was prepared from significant scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. Results: Different medicinal plants and their phytocompounds interact with important structural and nonstructural of SARS-CoV-2 proteins. Natural compounds form strong bonds with the active site of SARS-CoV-2 protease and make large conformational changes. These phytochemicals are potential inhibitors of structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro. Some important anti- SARS-CoV-2 actions of medicinal plants and their metabolites are: inhibition of the virus replication or entry, blocking the angiotensin-converting enzyme 2 (ACE-2) receptor and “Transmembrane protease, serine 2 (TMPRSS2), regulation of inflammatory mediators, inhibition of endothelial activation, toll-like receptors (TLRs) and activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2). Some of these important natural immune boosters that are helpful for the prevention and cure of various symptoms related to COVID-19 include Allium sativum, Nigella sativa, Glycyrrhiza glabra Zingiber officinalis, Ocimum sanctum, Withania somnifera, Tinospora cordifolia, and Scutellaria baicalensis. Also, Kaempferol, Quercetin, Baicalin, Scutellarin, Glycyrrhizin, Curcumin, Apigenin, Ursolic acid, and Chloroquine are the best candidates for treating the symptoms associated with SARS-CoV-2 infection. Conclusion: Medicinal plants and/or their bioactive compounds with inhibitory effects against SARS-CoV-2 support the human immune system and help in fighting against COVID-19 and rejuvenating the immune system.

Polypharmacy is an important aspect of medication management and particularly affects elderly and chronically ill people. Patients with dementia, Parkinson’s disease (PD), or multiple sclerosis (MS) are at high risk of multi medication due to their complex symptomatology. Our aim was to provide an overview of different definitions of polypharmacy and to present the current state of research on polypharmacy in patients with dementia, PD, or MS. The most common definition of polypharmacy in the literature is the concomitant use of ≥5 medications (quantitative definition approach). Polypharmacy rates of up to >50% have been reported for patients with dementia, PD, or MS, although MS patients are on average significantly younger than those with dementia or PD. The main predictor of polypharmacy is the complex symptom profile of these neurological disorders. Potentially inappropriate medication (PIM), drug-drug interactions, poor treatment adherence, severe disease course, cognitive impairment, hospitalisation, poor quality of life, frailty, and mortality have been associated with polypharmacy in patients with dementia, PD, or MS. For patients with polypharmacy, either the avoidance of PIM (selective deprescribing) or the substitution of PIM with more suitable drugs (appropriate polypharmacy) is recommended to achieve a more effective therapeutic management.

Monoamine oxidases (MAOs) are a family of flavin adenine dinucleotide-dependent enzymes that have a crucial role in the metabolism of neurotransmitters of the central nervous system. Impaired function of MAOs is associated with copious brain diseases. The alteration of monoamine metabolism is a characteristics feature of aging. MAO plays a crucial role in the pathogenesis of Alzheimer’s disease (AD), a progressive neurodegenerative disorder associated with an excessive accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles (NFTs). Activated MAO plays a critical role in the development of amyloid plaques from Aβ as well as the formation of the NFTs. In the brain, MAO mediated metabolism of monoamines is the foremost source of reactive oxygen species formation. The elevated level of MAO-B expression in astroglia has been reported in the AD brains adjacent to amyloid plaques. Increased MAO-B activity in the cortical and hippocampal regions is associated with AD. This review describes the pathogenic mechanism of MAOs in aging as well as the development and propagation of Alzheimer’s pathology.