Current Pharmaceutical Design - Volume 26, Issue 22, 2020

Inflammation is a pathogenic response to multiple factors, that causes over-activation of different molecules and pro-inflammatory cellular lines. Different behavioral factors and risk factors might enhance the inflammatory stress, and this might cause cardiovascular disease (CVD). CVD is the world’s leading cause of morbidity and mortality, and it is represented by hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, heart failure, rheumatic heart disease, congenital heart disease and cardiomyopathies. In this context, inflammation is both a cause and an aggravating factor in CVD, as well as a mediator of its worst prognostic. The mechanisms that link inflammation to CVD are multiple, complex and multi-factorial. To date, the role of inflammation in the genesis and progression of CVD has been extensively analyzed in recent studies. However, in the last decades, new biomarkers are joining the already known inflammatory biomarkers, such as Creactive protein, interleukins, tumor necrosis factor alpha and nitrotyrosine. Among these new biomarkers, we have to report sirtuins, microRNAs, ST2 protein, apolipoprotein E protein, adiponectin, and others. These biomarkers are preferentially expressed locally in the target tissue of inflammation, but also released in peripheral blood and then used as diagnostic and prognostic biomarkers. Indeed, these biomarkers might also predict future adverse cardiovascular events and worse prognosis in patients with CVD. Furthermore, these new inflammatory biomarkers can also be analyzed to evaluate therapeutic efficacy in patients with CVD. Furthermore, this might open up new fields and interesting research concerning the link between inflammation and CVD.

Atherosclerosis is a cardiovascular disease that involves vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis by affecting various factors that are involved in the disease. The present review discusses our current knowledge of the major cellular and molecular mechanisms of phytotherapeutics for the treatment of atherosclerosis. Numerous studies have evaluated the antiatherosclerotic activity of phytoconstituents to provide preliminary evidence of efficacy, but only a few studies have delineated the underlying molecular mechanisms. Plant-derived phytotherapeutics primarily targets abnormal levels of lipoproteins, endothelial dysfunction, smooth muscle cell migration, foam cell development, and atheromatous plaque formation. Nonetheless, the principal mechanisms that are responsible for their therapeutic actions remain unclear. Further pharmacological studies are needed to elucidate the underlying molecular mechanisms of the antiatherosclerotic response to these phytoconstituents.

Chronic inflammation plays an extensive role in the onset and progression of metabolic disorders such as atherosclerosis, type 2 diabetes, gout and obesity. Atherosclerosis accounts for up to 70% mortality in patients with type 2 diabetes and is also a chronic condition that causes atrial stenosis due to a lipometabolism imbalance. The purpose of this article is to consider the inflammatory factors implicated in atherosclerosis and their role in the development and progression of this vascular disease. The inflammasome signaling pathway is an important inflammatory mechanism involved in the development of atherosclerosis. The most important inflammasome pathway in this respect is the NLRP3 inflammasome (Nucleotide-binding oligomerization domain (NOD)-like receptor with a pyrin domain 3), whose activation leads to the generation of important inflammatory cytokines including interleukins 1β and 18 (IL-1β and 18). The activities of these mature cytokines and inflammatory factors produced by other inflammatory pathways lead to arterial inflammation and eventually arterial occlusion, which can result in life-threatening complications such as myocardial infarction and stroke. Therefore, it is essential to seek out more precise mechanisms for the activation of inflammasomes and other inflammatory pathways for the development of therapeutic strategies of atherosclerosis.

Background and objective: Atherosclerosis is one of the leading causes of human morbidity globally and reduced bioavailability of vascular nitric oxide (NO) has a critical role in the progression and development of the atherosclerotic disease. Loss of NO bioavailability, for example via a deficiency of the substrate (L-arginine) or cofactors for endothelial nitric oxide synthase (eNOS), invariably leads to detrimental vascular effects such as impaired endothelial function and increased smooth muscle cell proliferation, deficiency of the substrate (Larginine) or cofactors for eNOS. Various medicinal plants and their bioactive compounds or secondary metabolites with fewer side effects are potentially implicated in preventing cardiovascular disease by increasing NO bioavailability, thereby ameliorating endothelial dysfunction. In this review, we describe the most notable medicinal plants and their bioactive compounds that may be appropriate for enhancing NO bioavailability, and treatment of atherosclerosis. Methods: The material in this article was obtained from noteworthy scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. Results: Medicinal plants and their bioactive compounds influence NO production through diverse mechanisms including the activation of the nuclear factor kappa B (NF-ΚB) signaling pathway, activating protein kinase C (PKC)-α, stimulating protein tyrosine kinase (PTK), reducing the conversion of nitrite to NO via nitrate-nitrite reduction pathways, induction of eNOS, activating the phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase B (AKT) (PI3K/AKT/eNOS/NO) pathway and decreasing oxidative stress. Conclusion: Medicinal plants and/or their constituent bioactive compounds may be considered as safe therapeutic options for enhancing NO bioavailability and prospective preventative therapy for atherosclerosis.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease in mankind. SLE's downregulation of T and B lymphocytes could cause the development of autoantibodies, which in turn attack cell surface, nuclear, and cytoplasmic molecules, creating immune complexes that harm tissues. Objective: The objective of the present review is to evaluate SLE's present therapeutic policies and raise consciousness about the disease. Methods: New therapies are rare for SLE. This is due to the complexity of the disease and its various manifestations. Three techniques are used to develop biological treatments for the illness: B-cell modulation, T-cell regulation and cytokine inhibition. This paper reviews the present trends in SLE therapy. Results: Each arm of the immune system is a prospective therapeutic development target for this disease; it involves B-cells, T-cells, interferon (IFN) and cytokines. To date, only one of these agents is been approved for use against lupus, belimumab which comes under B-cell therapy. Both the innate and the adaptive immune systems are the objectives. Currently, although there is no full SLE remedy, drug therapy can minimize organ injury and control active disease, which relies on immunosuppressants and glucocorticoids. Conclusion: It is possible to access SLE treatment in the form of T-cell, B-cell and anticytokine therapies. In these therapies, antibodies and antigens interactions play a major part. Another medication for treating SLE is the non-steroidal anti-inflammatory drug such as hydroxychloroquine. Glucocorticoids (GCs) are another antiinflammatory treatment that suppresses the growth of cytokines related to inflammation and prevents the recruitment of leukocyte by reducing endothelial cell permeability.

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-ΚB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

Systemic inflammation is a common denominator to a variety of cardiovascular (CV) and non-CV diseases and relative risk factors, including hypertension and its control, metabolic diseases, rheumatic disorders, and those affecting the gastrointestinal tract. Besides medications, a non-pharmacological approach encompassing lifestyle changes and other complementary measures is mentioned in several updated guidelines on the management of these conditions. We performed an updated narrative review on the mechanisms behind the systemic impact of inflammation and the role of non-pharmacological, complementary measures centered on lowering systemic phlogosis for preserving or restoring a good global health. The central role of genetics in shaping the immune response is discussed in conjunction with that of the microbiome, highlighting the interdependence and mutual influences between the human genome and microbial integrity, diversity, and functions. Several plausible strategies to modulate inflammation and restore balanced crosstalk between the human genome and the microbiome are then recapitulated, including dietary measures, active lifestyle, and other potential approaches to manipulate the resident microbial community. To date, evidence from high-quality human studies is sparse to allow the unconditioned inclusion of understudied, though plausible solutions against inflammation into public health strategies for global wellness. This gap claims further focused, well-designed research targeted at unravelling the mechanisms behind future personalized medicine.

In animals, the gastrointestinal microbiota are reported to play a major role in digestion, nutrient absorption and the release of energy through metabolism of food. Therefore, microbiota may be a factor for association between diet and enteric diseases and oxidative stress. The gut microbial composition and concentration are affected by diet throughout the life of an animal, and respond rapidly and efficiently to dietary alterations, in particular to the use of prebiotics. Prebiotics, which play an important role in mammalian nutrition, are defined as dietary ingredients that lead to specific changes in both the composition and activity of the gastrointestinal microbiota through suppressing the proliferation of pathogens and by modifying the growth of beneficial microorganisms in the host intestine. A review of the evidence suggests possible beneficial effects of prebiotics on host intestinal health, including immune stimulation, gut barrier enhancement and the alteration of the gastrointestinal microbiota, and these effects appear to be dependent on alteration of the bacterial composition and short-chain fatty acid (SCFA) production. The production of SCFAs depends on the microbes available in the gut and the type of prebiotics available. The SCFAs most abundantly generated by gastrointestinal microbiota are acetate, butyrate and propionate, which are reported to have physiological effects on the health of the host. Nowadays, prebiotics are widely used in a range of food products to improve the intestinal microbiome and stimulate significant changes to the immune system. Thus, a diet with prebiotic supplements may help prevent enteric disease and oxidative stress by promoting a microbiome associated with better growth performance. This paper provides an overview of the hypothesis that a combination of ingestible prebiotics, chitosan, fructooligosaccharides and inulin will help relieve the dysbiosis of the gut and the oxidative stress of the host.

Background: Currently, daily consumption of green herb functional food or medicinal herbs has increased as adopted by many people worldwide as a way of life or even as an alternative to the use of synthetic medicines. Phytochemicals, which are a series of compounds of relatively complex structures and restricted distribution in plants, usually perform the defensive functions for plants against insects, bacteria, fungi or other pathogenic factors. A series of studies have found their effectiveness in the treatment or prevention of systemic diseases such as autoimmune diseases, cancer, neurodegenerative diseases, Crohn's disease and so on. Objective: This review systematizes the literature on the mechanisms of the phytochemicals that react against unique free radicals and prevent the oxidative stress and also summarizes their role in gut microbiota inhibiting bacterial translocation and damage to the intestinal barrier and improving the intestinal membrane condition. Conclusion: The gut microbiota modulation and antioxidant activities of the phytochemicals shall be emphasized on the research of the active principles of the phytochemicals.

In the era of precision medicine, establishing a patient-derived cell model is crucial, whether in vitro or in vivo. Compared to the traditional cell lines, patient-derived primary cells represent precise genetic features from specific patients, but poor proliferative activity of human primary cells restricts their popular application. Conditional reprogramming (CR) is a new cell culture technique to achieve rapid growth of patient-derived cells in vitro, making it possible to identify the individual difference and screen drugs sensitivity. In this review, we will summarize the application and limitation of CR in tumor and inflammatory-related diseases, indicating the prospect of this technique for preclinical research.

Aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia. Decreased numbers of hematopoietic stem cells and impaired bone marrow microenvironment caused by abnormal immune function describe the major pathogenesis of AA. Hematopoietic stem cell transplantation and immunesuppressive therapy are the first-line treatments for AA. Porcine anti-lymphocyte globulin (p-ALG) is a new product developed in China. Several studies have shown that p-ALG exhibited good therapeutic effects in AA.

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic relapsing conditions resulting from immune system activity in a genetically predisposed individual. IBD is based on progressive damage to the inflamed gut tissue. As its pathogenesis remains unknown, recent accumulating data have demonstrated that IBD is a complex and multi-factorial disorder correlated with host luminal factors, which lead to an imbalance between pro- and anti-inflammatory signaling. The growing understanding of the molecular mechanisms responsible for IBD has suggested a wide range of potential therapeutic targets to treat this condition. Some patients do not have a satisfactory response to current therapeutic medications such as antitumor necrosis factor (TNF) agents, or their response decreases over time. As a result, IBD therapeutics have been changed recently, with several new agents being evaluated. The identification of various inflammatory cascades has led to forming the idea to have novel medications developed. Medications targeting Janus kinases (JAK), leukocyte trafficking Interleukin (IL) 12/23, and Sphingosine 1 phosphate (S1P) are among these newly developed medications and highlight the role of microbial-host interaction in inflammation as a safe promising strategy. This systematic review aims to summarize different molecular targeting therapeutics, the most potent candidates for IBD treatment in recent studies.

Osteoarthritis (OA) is a leading cause of musculoskeletal disorders that mainly affects the elderly population. Some herbal medicines have the potential to alleviate the pain associated with OA and improve physical activity mostly through anti-inflammatory and anti-oxidative properties. The aim of this study was to investigate the effects of herbal medicines, especially topical types, on osteoarthritis. In this systematic review, the keywords “osteoarthritis”, “herbal compounds”, “herbal medicine”, “topical drug”, “hydrogels”, “cream” and “treatment” were used to search publications published from 2010 to 2019 and indexed in databases including PubMed, SCOPUS, Web of Science and Google Scholar. After screening of titles and abstracts and detection of duplicate publications, 38 eligible articles were included in the main review. We also included herbal formulations in vivo. Bioactive fractions of herbal medicines mostly worked on OA through suppression of interleukin-1β (IL-1β), inducing nuclear factor-ΚB (NF-ΚB) activation by inhibition of inhibitor of NF-ΚB (IΚBα) phosphorylation, IΚBα degradation, p65 phosphorylation, and p65 nuclear translocation, downregulation of NF-ΚB targets including COX-2 and MMPs, upregulation of collagen type II, cartilage-specific proteoglycans (CSPGs), β1-integrin, and expression of cartilage-specific transcription factor SOX-9 protein. Noticeably, herbal medicines do not produce desirable effects, thereby using their combinations with other therapeutic agents seem to exert substantial clinical outcomes. Herbal gels have demonstrated robustly significant healing effects on knee pain, stiffness and mobility. It is worth considering that because OA is a chronic disease, longer duration of the studies/trials would even lead to obtaining more reliable judgments regarding topical treatment tolerability, safety and efficacy and clarify local or systemic adverse effects. Stability and standardization of a defined amount or concentrations of herbal gels would give promising effects on OA treatment and pain relief.

Due to an overlook on the author's side, author’s affiliation in the article entitled as: “Treatment of Glucocorticoid-Induced Osteoporosis with Bisphosphonates Alone, Vitamin D Alone or a Combination Treatment in Eastern Asians: A Meta-Analysis” by Dr. Junjie Wang (Co-author) published in the journal “Current Pharmaceutical Design” Volume 25, No 14, Page no- 1653-1662 was incomplete.