Current Pharmaceutical Design - Volume 26, Issue 39, 2020

Metabolic syndrome (MetS) which is caused by poor dietary habits and sedentary behavior is a serious global health problem. MetS is a cluster of risk factors, represented by central obesity, hyperglycemia, dyslipidemia, and hypertension. In the 21st century, MetS and associated comorbidities, including obesity, diabetes and cardiovascular diseases, are the major threats to human health. Practical dietary strategies, nutritional bioactive compounds and a healthy lifestyle are claimed to be efficient in the management of one or more components of MetS. Nevertheless successful management of MetS and commodities is still a major concern. Since hyperglycemia, inflammation and redox imbalance are intrinsically involved in the progression of MetS comorbidities, finding effective strategies that precisely target these systems is highly warranted. In this scenario, pharmacological and non-pharmacological approaches with or without dietary patterns, phytochemicals or exercise interventions are the practical strategies to combat MetS and associated diseases. However, designing and prescribing of optimal nutritional patterns and exercise regimens remains a big challenge to achieve the maximum beneficial effects. This thematic issue addressed the concerns and provided practical strategies to overcome the malady of MetS in the modern world.

Background: The prevalence of diabetes in the world population hás reached 8.8 % and is expected to rise to 10.4% by 2040. Hence, there is an urgent need for the discovery of drugs against therapeutic targets to sojourn its prevalence. Previous studies proved that NF-ΚB serves as a central agent in the development of diabetic complications. Objectives: This review intended to list the natural plant compounds that would act as inhibitors of NF-ΚB signalling in different organs under the diabetic condition with their possible mechanism of action. Methods: Information on NF-ΚB, diabetes, natural products, and relation in between them, was gathered from scientific literature databases such as Pubmed, Medline, Google scholar, Science Direct, Springer, Wiley online library. Results and Conclusion: NF-ΚB plays a crucial role in the development of diabetic complications because of its link in the expression of genes that are responsible for organs damage such as kidney, brain, eye, liver, heart, muscle, endothelium, adipose tissue and pancreas by inflammation, apoptosis and oxidative stress. Activation of PPAR-α, SIRT3/1, and FXR through many cascades by plant compounds such as terpenoids, iridoids, flavonoids, alkaloids, phenols, tannins, carbohydrates, and phytocannabinoids recovers diabetic complications. These compounds also exhibit the prevention of NF-ΚB translocation into the nucleus by inhibiting NF-ΚB activators, such as VEGFR, RAGE and TLR4 receptors, which in turn, prevent the activation of many genes involved in tissue damage. Current knowledge on the treatment of diabetes by targeting NF-ΚB is limited, so future studies would enlighten accordingly.

Metabolic syndrome is an aggregation of conditions and associated with an increased risk of developing diabetes, obesity and cardiovascular diseases (CVD). Edible mushrooms are widely consumed in many countries and are valuable components of the diet because of their attractive taste, aroma, and nutritional value. Medicinal mushrooms are higher fungi with additional nutraceutical attributes having low-fat content and a transisomer of unsaturated fatty acids along with high fiber content, biologically active compounds such as polysaccharides or polysaccharide β-glucans, alkaloids, steroids, polyphenols and terpenoids. In vitro experiments, animal models, and even human studies have demonstrated not only fresh edible mushroom but also mushroom extract that has great therapeutic applications in human health as they possess many properties such as antiobesity, cardioprotective and anti-diabetic effect. They are considered as the unmatched source of healthy foods and drugs. The focus of this report was to provide a concise and complete review of the novel medicinal properties of fresh or dry mushroom and extracts, fruiting body or mycelium and its extracts, fiber, polysaccharides, beta-glucan, triterpenes, fucoidan, ergothioneine from edible mushrooms that may help to prevent or treat metabolic syndrome and associated diseases.

Background & Aims: Nowadays, the world is facing a common problem that the population aging process is accelerating. How to delay metabolic disorders in middle-aged and elderly people, has become a hot scientific and social issue worthy of attention. The liver plays an important role in lipid metabolism, and abnormal lipid metabolism may lead to liver diseases. Exercise is an easily controlled and implemented intervention, which has attracted extensive attention in improving the health of liver lipid metabolism in the elderly. This article reviewed the body aging process, changes of lipid metabolism in the aging liver, and the mechanism and effects of different interventions on lipid metabolism in the aging liver, especially focusing on exercise intervention. Methods: A literature search was performed using PubMed-NCBI, EBSCO Host and Web of Science, and also a report from WHO. In total, 143 studies were included from 1986 to 15 February 2020. Conclusion: Nutritional and pharmacological interventions can improve liver disorders, and nutritional interventions are less risky relatively. Exercise intervention can prevent and improve age-related liver disease, especially the best high-intensity interval training intensity and duration is expected to be one of the research directions in the future.

Background: The increasing worldwide prevalence of diabetes mellitus confers heavy public health issues and points to a large medical need for effective and novel anti-diabetic approaches with negligible adverse effects. Developing effective and novel anti-diabetic approaches to curb diabetes is one of the most foremost scientific challenges. Objectives: This article aims to provide an overview of current pharmacological and non-pharmacological approaches available for the management of diabetes mellitus. Methods: Research articles that focused on pharmacological and non-pharmacological interventions for diabetes were collected from various search engines such as Science Direct and Scopus, using keywords like diabetes, glucagon-like peptide-1, glucose homeostasis, etc. Results: We review in detail several key pathways and pharmacological targets (e.g., the G protein-coupled receptors- cyclic adenosine monophosphate, 5′-adenosine monophosphate-activated protein kinase, sodium-glucose cotransporters 2, and peroxisome proliferator activated-receptor gamma signaling pathways) that are vital in the regulation of glucose homeostasis. The currently approved diabetes medications, the pharmacological potentials of naturally occurring compounds as promising interventions for diabetes, and the non-pharmacological methods designed to mitigate diabetes are summarized and discussed. Conclusion: Pharmacological-based approaches such as insulin, metformin, sodium-glucose cotransporters 2 inhibitor, sulfonylureas, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase IV inhibitors represent the most important strategies in diabetes management. These approved diabetes medications work via targeting the central signaling pathways related to the etiology of diabetes. Non-pharmacological approaches, including dietary modification, increased physical activity, and microbiota-based therapy are the other cornerstones for diabetes treatment. Pharmacological-based approaches may be incorporated when lifestyle modification alone is insufficient to achieve positive outcomes.

Background and Objective: The benefits of physical activity (PA) for children and adolescents with disabilities are well documented, and children and adolescents with visual impairments (VI) engage in less PA than their sighted peers. Two reviews have summarized studies on PA of children and adolescents with VI, but no systematic review with semi-quantitative assessment has been conducted to specifically identify the correlates of their PA. This review aims to systematically summarize the existing literature, which investigated the correlates of PA of children and adolescents with VI until 2019 and identify variables that contribute to their PA participation. Methods: A systematic search using Academic Search Premier (ASP), Education Resources Information Center (ERIC), Education Source (ES), PsycINFO, Psychology and Behavioral Sciences Collection (PBSC), MEDLINE, Scopus, and Web of Science (WOS) was conducted in September 2019 to identify studies examining the correlates of PA in children and adolescents with VI aged 5 to 17 years. Two researchers independently screened studies, assessed their methodological quality and extracted relevant data. The correlates of PA among children and adolescents with VI were synthesized and further assessed semi-quantitatively. Results: A total of 17 articles identified correlates of PA in children and adolescents with VI. Out of 21 variables identified from the reviewed studies, 3 were consistently associated with PA of children and adolescents with VI. Body mass index (BMI)/obesity, percent of body fat, and visual impairment level were consistently and negatively associated with PA of children and adolescents with VI. Gender and age were identified as having inconsistent relationships with PA in children and adolescents with VI. The level of parental education was identified to have “no association” with children and adolescents with VI. Conclusion: This review can aid in developing effective interventions to improve the PA of children and adolescents with VI and propose directions for future research.

Background and Objective: China has experienced a rapid increase in the number of obese and overweight children, and sedentary behavior has been recognized as an important factor. The purpose of this review is to summarize studies on the relationship between sedentary behavior and obesity in school-age children in China. Methods: A systematic search was conducted to identify studies that investigate the relationship between sedentary behavior and obesity in children between the ages of 6 and 18 years in China. Two researchers independently screened studies, assessed their methodological quality, and extracted relevant data. Findings on the relationship between sedentary behavior and obesity in children were synthesized and analyzed. Results: A total of 17 studies were included in the review. Fifteen out of 17 studies indicated that spending too much time engaged in sedentary behavior, especially screen-based sedentary behavior, was associated with obesity in children and adolescents in China. Possible reasons for this association are less energy expenditure, increased energy intake, and insufficient sleep owing to overtime sedentary behavior. Moreover, seven, six, and three studies justified children’s physical activity, dietary intake, or sleep, and most of the studies (five, three, and two) indicated that association between sedentary behavior and obesity is independent of these justified variables. Although differences in gender and area of residence in the association between sedentary behavior and obesity were examined in five studies, definite conclusions could not be drawn because of inconsistent findings or limited research. Conclusion: Future research is necessary to enhance understanding of demographic differences in the association between sedentary behavior and obesity in children as well as on the contributions of different types of sedentary behavior to child obesity in China.

Background: Recent studies have focused on the nanoformulations of curcumin to enhance its solubility and bioavailability. The medicinal properties of curcumin-C3 complex, which is a combination of three curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) is less explored. Objective: The aim of this study was to prepare curcumin-C3 encapsulated in chitosan nanoparticles, characterize and evaluate their antioxidant and antibacterial potential. Methods: Ionic gelation method was used to prepare curcumin-C3 nanoparticles and was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy and nanoparticle tracking analysis. In vitro assays were performed to assess drug release, antioxidant and antibacterial activities. Results: Curcumin-C3-chitosan nanoparticle showed an increased entrapment efficiency of >90%, drug release and improved antioxidant potential. Moreover, curcumin-C3-chitosan nanoparticle showed stronger inhibition of Escherichia coli and Staphylococcus aureus. Conclusion: Chitosan is a suitable carrier for curcumin-C3 nanoparticle and can be used as a drug delivery system in the treatment of inflammatory and bacterial diseases.

Background: Buccal delivery is an alluring course of organization for fundamental medication conveyance and it leads direct access to the systemic flow through the interior jugular vein sidesteps drugs from the hepatic first-pass digestion gives high bioavailability. Objective: This article aims at buccal medication conveyance by discussing the structure and condition of the oral mucosa and the novel strategies utilized in evaluating buccal medication ingestion. Methods: This review highlights the various pharmaceutical approaches for buccal delivery such as buccal tablets, buccal lozenges, buccal micro/nanoparticle, wafer and semisolid dosage forms like chewing gums, buccal patch, buccal gel or ointment and some buccal liquid dosage forms like buccal solutions and buccal sprays and recent patents filed or granted for these approaches. Results: Recently, some patents are also reported where a combination of various approaches is being employed to achieve very effective mucosal delivery. The various patent search sites were used to collect and analyze the information on buccal drug delivery systems. Conclusion: The present study provides valuable information, advantages, limitations and future outlook of various buccal drug delivery systems.

Background: Toll like receptors (TLRs) are a group of transmembrane receptors belonging to the broad class pattern recognition receptors (PRR), involved in recognition of Pathogen Associated Molecular Patterns (PAMPs) thereby inducing an immune response. Apart from these exogenous PAMPs, numerous endogenous PAMPs are also ligands for various TLRs thereby activating the TLR dependent immune response, subsequently leading to the onset of an inflammatory response. Prolonged activation of TLR by these endogenous PAMPs leads to chronic inflammatory insults to the body and which in turn alters the proliferative patterns of the cells, which ultimately leads to the development of cancer. Objectives: The present review aims to provide a detailed outline of the differential roles of various TLRs in cancer and the possible use of them as a therapeutic target. Methods: Data were collected from PubMed/Sciencedirect/Web of Science database and sorted; the latest literature on TLRs was incorporated in the review. Results: Among the different TLRs, few are reported to be anti-neoplastic, which controls the cell growth and multiplication in response to the endogenous signals. On the contrary, numerous studies have reported the procarcinogenic potentials of TLRs. Hence, TLRs have emerged as a potential target for the prevention and treatment of various types of cancers. Several molecules, such as monoclonal antibodies, small molecule inhibitors and natural products have shown promising anticancer potential by effectively modulating the TLR signalling. Conclusion: Toll-like receptors play vital roles in the process of carcinogenesis, hence TLR targeting is a promising approach for cancer prevention.

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are only a few effective therapies. Here, we summarized that the energy sensor adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK), and its agonist berberine can combat the common underlying pathological events of neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder, and disruption of neurovascular units. The abovementioned effects of berberine may primarily depend on activating AMPK and its downstream targets, such as the mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1), nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-ΚB (NF-ΚB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a strong basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.

Background and Aim: Depression is a mood disorder with high global prevalence. Depression is associated with a reduction in the hippocampal volume and change in its neurotransmitters function. Trigonelline is an alkaloid with neuroprotective activity. The aim of this study was to investigate the possible role of N-methyl-Daspartate (NMDA) receptor in the antidepressant-like effect of trigonelline, considering histopathological modifications of the hippocampus. Methods: 60 Naval Medical Research Institute (NMRI) male mice were divided into 6 groups including group 1 (normal saline), groups 2, 3 and 4 (trigonelline at doses of 10, 50 and 100 mg/kg), group 5 (effective dose of trigonelline plus NMDA agonist) and group 6 (sub-effective dose of trigonelline plus NMDA antagonist). Forced swimming test (FST) was used to assess depressive-like behavior. Hippocampi were separated under deep anesthesia and used for histopathological evaluation as well as NMDA receptor gene expression assessment. Results: Trigonelline at doses of 10, 50 and 100 significantly reduced the immobility time in the FST in comparison to the control group. The administration of the sub-effective dose of trigonelline plus ketamine (an NMDA receptor antagonist) potentiated the effect of the sub-effective dose of trigonelline. In addition, co-treatment of an effective dose of trigonelline with NMDA mitigated the antidepressant-like effect of trigonelline. Trigonelline at doses of 50 and 100 mg/kg significantly increased the diameter of the CA1 area of the hippocampus. Conclusion: Trigonelline showed an antidepressant-like effect in mice, probably via attenuation of NMDA receptor activity and an increase in the CA1 region of the hippocampus.

Background: The increased bone loss after spinal cord injury (SCI) is associated with an increase in the morbidity and mortality of fragility fractures, which can constitute a substantial cost to health care systems. Bisphosphonates (BPs) are now the principal class of medications used for osteoporosis. Objective: To demonstrate the effect of BPs on treating osteoporosis after SCI. Methods: A comprehensive search in PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for randomized controlled trials (RCTs), exploring the effect of BPs on osteoporosis after SCI. The primary outcome measures were the BMD of different locations, serum bone turnover marker levels, serum biochemistry marker levels and adverse effect (AE) risks. The final search was performed in September 2019. Reporting was carried out according to PRISMA Guidelines. Results: Six RCTs were included. A total of 147 patients met the inclusion criteria. BPs were found to statistically prevent bone loss in the total hip, femoral neck and trochanter at the 6- and 12-month follow-up points and to increase the BMD of the lumbar spine at the 12-month follow-up time point. BPs had no clear effect on serum PINP or serum calcium levels at the 12-month follow-up time point. Conclusion: BP therapy may prevent bone loss in the lumbar spine and hip when administered early after SCI and has relatively high safety.

Background: There are controversial results available about using angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the development of cancers or improvement of clinical outcomes. Studies reported that using ACEI/ARB may enhance the development of hepatocellular carcinoma (HCC) and clinical outcomes. Objective: This meta-analysis aimed to assess the relationship between ACEI/ARB therapy and the development of HCC. Methods: PubMed, EMBASE and the Cochrane library were reviewed to identify clinical studies investigating the association between ACEI/ARB therapy and the risk of HCC development. The pooled risk ratio (RR) with 95% confidence intervals collected for the association between using ACEIs/ARBs and HCC development. Results: Patients with HCC benefit from the treatment with both ACEIs and ARBs (RR 0.704, 95% CI 0.526- 0.944, p = 0.019). However, only using ARBs was related to HCC risk (0.545 95% CI 0.470-0.632, P<0.0001). Moreover, the study types were significantly related to the observed effects of using both ARBs and ACEIs. Only cohort studies were significantly related to achieving better results (RR=0.513, 95% CI= 0.442-0.597, P<0.0001). Conclusion: Despite the small number and heterogeneity of the studies evaluating the relationship between treatment with ARBs and ACEIs and the development of HCC, our meta-analysis demonstrates that they may reduce the risk of HCC.