Current Pharmaceutical Design - Volume 26, Issue 1, 2020

Advances in various fields were discussed in the reviews and original research articles published in 2019 in Current Pharmaceutical Design. Here, I review some of the major highlights for selected areas. A better understanding of disease mechanisms was a prominent recurrent theme and new therapeutic targets based on those mechanisms are highlighted here. Inflammation and oxidative stress are major features of many diseases, therefore, interventions to address these processes are reviewed. Although repurposing of old drugs occurred in several fields, drug targeting and drug delivery, especially of nanoparticles, also continues to be a major area of interest.

In the present review, associations between traditional vascular risk factors (VRFs) and carotid intimamedial thickness progression (C-IMTp) as well as the effects of therapies for VRFs control on C-IMTp were appraised to infer causality between each VRF and C-IMTp. Cohort studies indicate that smoking, binge drinking, fatness, diabetes, hypertension and hypercholesterolemia are associated with accelerated C-IMTp. An exception is physical activity, with mixed data. Interventions for the control of obesity, diabetes, hypertension and hypercholesterolemia decelerate C-IMTp. Conversely, scarce information is available regarding the effect of smoking cessation, stop of excessive alcohol intake and management of the metabolic syndrome. Altogether, these data support a causative role of several traditional VRFs on C-IMTp. Shortcomings in study design and/or ultrasonographic protocols may account for most negative studies, which underlines the importance of careful consideration of methodological aspects in investigations using C-IMTp as the outcome.

Background: Radix Stephaniae Tetrandrine (RST), known as FangJi (Pinyin name) in Chinese, is the dried root of Stephania tetrandra S.Moore, and has been prescribed in combination with other herbs to treat cardiovascular diseases and breast cancer in traditional Chinese medicine (TCM) clinical trials. Objective: The aim of the review is to provide a comprehensive evaluation about the application of RST in breast cancer management in TCM clinical trials, its ingredients, and its action on preventing the development of breast cancer in vitro and in vivo studies. Methods: Literature sources used were Pubmed, CNKI.net, Cqvip.com, and the Web of Science. For the inquiry, keywords such as Fangji, breast cancer, clinical trials, Radix Stephaniae Tetrandrine, tetrandrine, and fangchinoline were used in various combinations. About 150 research papers and reviews were consulted. Results: In TCM, RST exhibited the anti-tumor ability through its action on the bladder and lungs through dispersing phlegm and blood stasis. 10 clinical trials were identified which used RST in combination with other herbs to treat breast cancer. On average, the trials were characterized by high efficacy (>85%) and low toxicity. However, most of the clinical trials are characterized as small patient samples, poor design, and different combinations of herbs in prescriptions. To date, more and more compounds have been isolated from this plant. RST exhibited anti-tumor activities by targeting reversing multidrug resistance, inhibiting cell proliferation, inducing apoptosis, preventing tumor angiogenesis, anti-oxidation, anti-inflammation, and enhancing the sensitization and attenuating the toxicity of radiotherapy. Conclusion: The successful applications of RST in TCM clinical trials and preclinical experiments to beating breast cancer will provide potent lead compounds in the identification of novel anti-cancer drugs, which further contributes to the scientific exploration of functions of RST in TCM.

C-reactive Protein (CRP) is an acute phase reactant, belonging to the pentraxin family of proteins. Its level rises up to 1000-fold in response to acute inflammation. High sensitivity CRP level is utilized as an independent biomarker of inflammation and cardiovascular disease. The accumulating data suggests that CRP has two distinct forms. It is predominantly produced in the liver in a native pentameric form (nCRP). At sites of local inflammation and tissue injury it may bind to phosphocholine-rich membranes of activated and apoptotic cells and their microparticles, undergoing irreversible dissociation to five monomeric subunits, termed monomeric CRP (mCRP). Through dissociation, CRP deposits into tissues and acquires distinct proinflammatory properties. It activates both classic and alternative complement pathways, binding complement component C1q and factor H. mCRP actively participates in the development of endothelial dysfunction. It activates leukocytes, inducing cytokine release and monocyte recruitment. It may also play a role in the polarization of monocytes and T cells into proinflammatory phenotypes. It may be involved in low-density lipoproteins (LDL) opsonization and uptake by macrophages. mCRP deposits were detected in samples of atherosclerotic lesions from human aorta, carotid, coronary and femoral arteries. mCRP may also induce platelet aggregation and thrombus formation, thus contributing in multiple ways in the development of atherosclerosis and atherothrombosis. In this mini-review, we will provide an insight into the process of conformational rearrangement of nCRP, leading to dissociation, and describe known effects of mCRP. We will provide a rationalization for mCRP involvement in the development of atherosclerosis and atherothrombosis.

The Citrus species from family Rutaceae has worldwide applications such as cardiovascular and gastrointestinal problems. Phytochemical investigations have shown that these plants have constituents including flavonoids, limonoids and carotenoids. There are many reports on a wide range of activities such as antiinflammatory, anti-oxidant, immunomodulatory, metabolic, cardiovascular and neuroprotective effects. In the current review, we discuss information regarding botany, phytochemistry, ethnobotany uses, traditional knowledge and pharmacological aspects of the Citrus species.

Regular physical activity significantly affects lipid status. In this literature review, the specific features of athletes blood lipid profiles were analysed. Professional athletes blood lipid status was found considerably preferable compared to sex- and age-matched sedentary population. Regardless of endurance or power type of sports activities, athletes perform lower levels of TC, LDL-C and TG and comparable or higher blood levels of HDL-C. The differences in blood lipids levels and sports disciplines were introduced. Although there are much more factors as diet, place of origin, training regime, and even genetic predisposition that should be taken into consideration for future research.

Mitochondrial dysfunction underlies several human chronic pathologies, including cardiovascular disorders, cancers and neurodegenerative diseases. Impaired mitochondrial function associated with oxidative stress can be a result of both nuclear and mitochondrial DNA (mtDNA) mutations. Neurological disorders associated with mtDNA mutations include mitochondrial encephalomyopathy, chronic progressive external ophthalmoplegia, neurogenic weakness, and Leigh syndrome. Moreover, mtDNA mutations were shown to play a role in the development of Parkinson and Alzheimer’s diseases. In this review, current knowledge on the distribution and possible roles of mtDNA mutations in the onset and development of various neurodegenerative diseases, with special focus on Parkinson’s and Alzheimer’s diseases has been discussed.

Ethnopharmacological relevance: Borago L., (family Boraginaceae) is a small genus of annual or perennial herbs with branched flowers, which is commonly found in the Mediterranean region. Some species known as Gavzabân in Asian and some African countries are traditionally used instead of Borago. Aims of the review: The purpose of this study was to provide comprehensive scientific information on phytochemistry, traditional uses and pharmacological activities of Borago species to provide an insight into further research on the therapeutic potential of these plants. In many studies, it has been shown that different parts of Borago species, including leaves, flowers, seeds, roots and aerial parts possess numerous ethnobotanical values. Materials and methods: All ethnobotanical, phytochemical, pharmacological, and clinical data were collected from online journals, magazines and books (all of which were published in English, Arabic, and Persian) from 1968 to 2018. Electronic databases such as Google, Google Scholar, PubMed, Science Direct, Researchgate, and other online collections were used. Results: The phytochemical studies on five species showed a wide range of phytochemicals belonging to different classes of secondary metabolites. From a pharmacological point of view, different extracts and fractions, essential oils, and pure compounds isolated from various Borago species have shown diverse activities in in vitro, in vivo, and clinical studies confirming various traditional uses of Borago genus. Conclusion: Considering the reported activities of the Borago genus both in traditional and modern medicine, further studies on biological aspects and identification of the mechanism of action for drug discovery are highly required.

Background: Guidelines have previously suggested that atrial fibrillation (AF) is associated with an increased risk of arrhythmic death in Brugada syndrome (BrS) patients. However, only two articles consisting of 17 AF patients with BrS supported these views. The risk stratification of BrS patients with AF remains controversial. Thus, a meta-analysis is used to estimate the risk stratification of BrS patients with AF. Methods: We searched for relevant studies published from 2000 to December 30, 2018. A total of 1712 patients with BrS from five studies were included: 200 patients (12%) were reported with AF, among whom 37 patients (19%) had arrhythmic events. Results: BrS patients with AF in all studies (OR 1.92, 95% CI:0.91to 4.04, P =0.09; Heterogeneity: P = 0.03, I2=61%) and some European studies (OR 1.12, 95% CI: 0.18 to 6.94, P=0.91; Heterogeneity: P = 0.006, I2=80%) did not display a higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japanese studies (OR 2.32, 95% CI: 1.37 to 3.93, P=0.002; Heterogeneity: P = 0.40, I2=0%) had a higher risk of arrhythmic events than those without AF. The proportion of BrS patients with AF was greater in Japanese studies than in some European studies (16% vs. 9%, P<0.001). Conclusion: On the whole, BrS patients with AF showed no higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japan had a higher risk of arrhythmic events than those without AF.

Plants of the genus Vitex (Verbenaceae) are mainly distributed throughout tropical and temperate regions, and many Vitex plants have been traditionally used in folk medicine. Plants of this genus are a rich source of diterpenoids, which not only displayed versatile structural diversity with potential chemotaxonomical significance but also exhibited a wide range of biological activities, mainly including in vitro cytotoxic, antiinflammatory, antimicrobial, hormone level-regulating and antiangiogenic activities. Recently, a series of bioactive diterpenoids, with interesting carbon skeletons, have been reported and gathered considerable interest. This article systematically reviewed diterpenoids isolated from the genus Vitex that appeared in the literature up to December 2018, critically highlighting their structural diversity and pharmacological activities. Up to now, a total of 154 diterpenoids with diverse structures have been isolated and identified from Vitex plants. The authors also summarized the reported structure-activity relationships of those well explored Vitex diterpenoids. Finally, the authors discussed the challenges and potential applications of these diterpenoids in the future.

Scutellaria barbata has a long history of medical use in Traditional Chinese Medicine for removing heat and toxic material, promoting blood circulation and removing blood stasis, and inducing diuresis to reduce edema. Recent pharmacology investigations have provided evidence for its anti-cancer, bacteriostasis, anti-virus, anti-inflammation, anti-oxidation and immunity enhancement properties. The efficacy of activating blood circulation and removing blood stasis has unique advantages in the treatment of cardiovascular and cerebrovascular diseases. A total of 84 compounds have been isolated from S. barbata and are characterized mainly as flavonoids, diterpenoids, followed by polysaccharide, volatile oil and steroids. Peer-reviewed articles published over the last few years were gathered by consulting the databases PubMed, Elsevier, Springer, and Chinese Herbal Classics. This review mainly focuses on the pharmacologically active constituents isolated from S. barbata#140;which have been subjected to in vitro and/or in vivo studies. Although, the chemical components, pharmacological activities, toxicology, clinical applications and mechanisms of action of S. barbata have been investigated, many constituents remain unknown. Further investigations are required to investigate the medicinal properties of S. barbata.

Heart attack, stroke, and deep vein thrombosis are among the conditions that alter blood coagulation and are modulated by antithrombogenic drugs. Natural products are an important source of antithrombogenic agents and have been considered remarkable alternatives with greater efficacy and usually with fewer side effects. However, the efficacy and toxicity of many of these plants that are used in traditional medicine must be scientifically tested. Despite a large number of published articles that report that plants or plant-derived components may act as antithrombogenic agents, few studies have investigated the mechanism of action of medicinal plants. This review presents the current knowledge about the major cellular and molecular mechanisms of antithrombogenic plants and their main components. Many well-established mechanisms (e.g., platelet aggregation, coagulation factors, and thrombolysis) are related to the antithrombogenic activity of many natural products. However, the central pathways that are responsible for their activity remain unclear. Further studies are needed to clarify the central role of each of these pathways in the pleiotropic response to these agents.