Current Pharmaceutical Design - Volume 27, Issue 6, 2021

According to the global statistics, the incidence of metabolic syndrome (MetS), which is a multifactorial disease with multiple risk factors, has reached nearly one-quarter of the population, and poses a serious threat to public health. MetS is a cluster of conditions characterized by insulin resistance, hypertension, obesity, and cardiovascular-related risk factors. Various aspects, such as modern lifestyle (diet, sedentary behavior), aging and genes attribute to increasing the morbidity of MetS. While external interventions, prescribed drugs and natural materials play an indispensable role in the management of MetS. Intake of plant-based bioactive compounds and peptide-based drug delivery systems emerge as safe and effective pharmacological approaches to treat MetS complications. Natural biomaterials are able to decrease the adverse effects of drugs and enhance treatment efficiency. In this thematic issue, we explored the beneficial effects of various phytochemicals, marine drugs and cellpenetrating peptides (CPPs)-mediated drug delivery system in the management of MetS and associated disorders. The usage of CPPs in combination with other therapeutic agents like nanoparticles and peptides is a novel and efficient approach to conquer the components in MetS.

Background: Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress is made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds was collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries, herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, gymnea, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possess anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in the prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.

Background: Diabetes is a chronic disease affecting a large population worldwide and stands as one of the major global health challenges to be tackled. According to World Health Organization, about 400 million are having diabetes worldwide and it is the seventh leading cause of deaths in 2016. Plant-based natural products have been in use from ancient times as ethnomedicine for the treatment of several diseases, including diabetes. As a result of that, there are several reports on plant-based natural products displaying antidiabetic activity. In the current review, such antidiabetic potential compounds reported from all plant sources along with their chemical structures are collected, presented and discussed. These kinds of reports are essential to pool the available information to one source, followed by statistical analysis and screening to check the efficacy of all known compounds in a comparative sense. This kind of analysis can give rise to a few potential compounds from hundreds, which can further be screened through in vitro and in vivo studies, and human trails leading to the drug development. Methods: Phytochemicals, along with their potential antidiabetic property, were classified according to their basic chemical skeleton. The chemical structures of all the compounds with antidiabetic activities were elucidated in the present review. In addition to this, the distribution and their other remarkable pharmacological activities of each species are also included. Results: The scrutiny of literature led to the identification of 44 plants with antidiabetic compounds (70) and other pharmacological activities. For the sake of information, the distribution of each species in the world is given. Many plant derivatives may exert anti-diabetic properties by improving or mimicking insulin production or action. Different classes of compounds including sulfur compounds (1-4), alkaloids (5-11), phenolic compounds (12-17), tannins (18-23), phenylpropanoids (24-27), xanthanoids (28-31), amino acid (32), stilbenoid (33), benzofuran (34), coumarin (35), flavonoids (36-49) and terpenoids (50-70) were found to be potential active compounds for antidiabetic activity. Of the 70 listed compounds, majorly 17 compounds are obtained from triterpenoids, 13 from flavonoids and 7 from alkaloids. Among all the 44 plant species, the maximum number (7) of compounds were isolated from Lagerstroemia speciosa followed by Momordica charantia (6) and S. oblonga with 5 compounds. Conclusion: This is the first paper to summarize the established chemical structures of phytochemicals that have been successfully screened for antidiabetic potential and their mechanisms of inhibition. The reported compounds could be considered as potential lead molecules for the treatment of type-2 diabetes. Further, molecular and clinical trials are required to select and establish therapeutic drug candidates.

Background: Diabetes Mellitus (DM) is a major chronic metabolic disorder characterized by hyperglycemia that leads to several complications such as retinopathy, atherosclerosis, nephropathy, etc. In 2019, it was estimated that about 463 million people had diabetes, and it may increase up to 700 million in 2045. Marine macroalgae are the rich source of bioactive compounds for the treatment of diabetes mellitus. Objective: This review summarizes the recent epidemiology and possible use of marine macroalgae-derived bioactive compounds for the protection against chronic metabolic disease, diabetes mellitus and marine macroalgae as a nutraceutical supplement. Conclusion: The present therapies available for diabetes treatment are oral medicines and insulin injections. But continuous use of synthetic medicines provides low therapeutic with many side effects. In continuing search of anti-diabetic drugs, marine macroalgae remain as a promising source with potent bioactivity. Among existing marine algae, red and brown algae are reported to show anti-diabetic activity. Hence, the present review focuses on the epidemiology, diabetes biomarkers and different secondary bioactive compounds present in marine macroalgae to treat diabetes mellitus.

Background: Phytoestrogens are non-endocrine, non-steroidal secondary derivatives of plants and consumed through a plant-based diet also named as “dietary estrogens”. The major sources of phytoestrogens are soy and soy-based foods, flaxseed, chickpeas, green beans, dairy products, etc. The dietary inclusion of phytoestrogen based foods plays a crucial role in the maintenance of metabolic syndrome cluster, including obesity, diabetes, blood pressure, cancer, inflammation, cardiovascular diseases, postmenopausal ailments and their complications. In recent days, phytoestrogens are the preferred molecules for hormone replacement therapy. On the other hand, they act as endocrine disruptors via estrogen receptor-mediated pathways. These effects are not restricted to adult males or females and identified even in development. Objective: Since phytoestrogenic occurrence is high at daily meals for most people worldwide, they focused to study for its beneficiary effects towards developing pharmaceutical drugs for treating various metabolic disorders by observing endocrine disruption. Conclusion: The present review emphasizes the pros and cons of phytoestrogens on human health, which may help to direct the pharmaceutical industry to produce various phytoestrongen based drugs against various metabolic disorders.

Background/Purpose: Type 2 diabetes (T2D) is characterized by hyperglycemia resulting from the body’s inability to produce and/or use insulin. Patients with T2D often have hyperinsulinemia, dyslipidemia, inflammation, and oxidative stress, which then lead to hypertension, chronic kidney disease, cardiovascular disease, and increased risk of morbidity and mortality (9^th leading cause globally). Insulin and related pharmacological therapies are widely used to manage T2D, despite their limitations. Efficient drug delivery systems (DDS) that control drug kinetics may decrease side effects, allow for efficient targeting, and increase the bioavailability of drugs to achieve maximum therapeutic benefits. Thus, the development of effective DDS is crucial to beat diabetes. Methods: Here, we introduced a highly bioavailable vector, cell-penetrating peptides (CPPs), as a powerful DDS to overcome limitations of free drug administration. Results: CPPs are short peptides that serve as a potent tool for delivering therapeutic agents across cell membranes. Various cargoes, including proteins, DNA, RNA, liposomes, therapeutic molecules, and nanomaterials, generally retain their bioactivity upon entering cells. The mechanisms of CPPs/cargoes intracellular entry are classified into two parts: endocytic pathways and direct membrane translocation. In this article, we focus on the applications of CPPs/therapeutic agents in the treatment of diabetes. Hypoglycemic drugs with CPPs intervention can enhance therapeutic effectiveness, and CPP-mediated drug delivery can facilitate the actions of insulin. Numerous studies indicate that CPPs can effectively deliver insulin, produce synergistic effects with immunosuppressants for successful pancreatic islet xenotransplantation, prolong pharmacokinetics, and retard diabetic nephropathy. Conclusion: We suggest that CPPs can be a new generation of drug delivery systems for effective treatment and management of diabetes and diabetes-associated complications.

Background: MiRNAs are a class of small non-coding RNAs that are involved in the post-transcriptional regulation of gene expression. MiRNAs are considered a class of epigenetic biomarkers. These biomarkers can investigate disease at different stages: diagnosis, therapy or clinical follow-up. Objective: The aim of this paper is to highlight the innovative use of miRNAs in several childhood diseases. Methods: We conducted a literature review to search the usage of miRNAs in pediatric clinical routine or experimental trials. Results: We found a possible key role of miRNAs in different pediatric illnesses (metabolic alterations, coagulation defects, cancer). Conclusion: The modest literature production denotes that further investigation is needed to assess and validate the promising role of miRNAs as non-invasive biomarkers in pediatric disorders.

Edema is a gradual accumulation of fluid in the interstitial tissues or luminal cavities, which is regulated by ion transport pathways and reflects dysfunction of fluid and salt homeostasis. Increasing evidence suggests that some herbal monomers significantly reduce organ/tissue edema. In this review, we briefly summarized the electrolyte permeability involved in pathomechanisms of organ edema, and the benefits of herbal monomers on ionic transport machinery, including Na⁺-K⁺-ATPase, Na⁺ and Cl^- channels, Na⁺-K⁺-2Cl^- co-transporter, etc. Pharmaceutical relevance is implicated in developing advanced strategies to mitigate edematous disorders. In conclusion, the natural herbal monomers regulate electrolyte permeability in many edematous disorders, and further basic and clinical studies are needed.

Depression is a widespread and persistent psychiatric disease. Due to various side effects and no curative treatments of conventional antidepressant drugs, botanical medicines have attracted considerable attention as a complementary and alternative approach. The pathogenesis of depression is quite complicated and unclear. Metabolomics is a promising new technique for the discovery of novel biomarkers for exploring the potential mechanisms of diverse diseases and assessing the therapeutic effects of drugs. In this article, we systematically reviewed the study of botanical medicine for the treatment of depression using metabolomics over a period from 2010 to 2019. Additionally, we summarized the potential biomarkers and metabolic pathways associated with herbal medicine treatment for depression. Through a comprehensive evaluation of herbal medicine as novel antidepressants and understanding of their pharmacomechanisms, a new perspective on expanding the application of botanical medicines for the treatment of depression is provided.

Being the second most frequent cancer, breast cancer is emerging worldwide with an alarming rate, specifically in post-menopausal women. Targeted drug delivery has been in the focus for the successful treatment of breast cancer by enhancing the drug delivery efficiency and reducing the systemic toxicity of drugs. Also, it eliminates the drawbacks associated with conventional chemotherapy, including neuropathy, memory loss, cardiotoxicity and low RBCs count. This review elaborates the polymeric nanoparticles based formulation approaches for selective and sustained delivery for effective cure of breast cancer. However, breast cancer, a life-threatening disease, is mostly caused because of estrogen, thus aromatase inhibitors and estrogen synthesis inhibitors could prevent chances of breast cancer. The disease is associated with drug resistance and some side effects, which could be easily eliminated by using novel therapeutic approaches. Aromatase inhibitors, when entrapped in nanoparticles, have shown sustained drug release, advocating themselves to be beneficial for the treatment of breast cancer.

Background: COVID-19 pandemic is caused by coronavirus also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The viral infection continues to impact the globe with no vaccine to prevent the infection or highly effective therapeutics to treat the millions of infected people around the world. The disease starts as a respiratory infection, yet it may also be associated with a hypercoagulable state, severe inflammation owing to excessive cytokines production, and a potentially significant oxidative stress. The disease may progress to multiorgan failure and eventually death. Objective: In this article, we summarize the potential of dipyridamole as an adjunct therapy for COVID-19. Methods: We reviewed the literature describing the biological activities of dipyridamole in various settings of testing. Data were retrieved from PubMed, SciFinder-CAS, and Web of Science. The review concisely covered relevant studies starting from 1977. Results: Dipyridamole is an approved antiplatelet drug, that has been used to prevent stroke, among other indications. Besides its antithrombotic activity, the literature indicates that dipyridamole also promotes a host of other biological activities including antiviral, anti-inflammatory, and antioxidant ones. Conclusion: Dipyridamole may substantially help improve the clinical outcomes of COVID-19 treatment. The pharmacokinetics profile of the drug is well established which makes it easier to design an appropriate therapeutic course. The drug is also generally safe, affordable, and available worldwide. Initial clinical trials have shown a substantial promise for dipyridamole in treating critically ill COVID-19 patients, yet larger randomized and controlled trials are needed to confirm this promise.

Medication and patient adherence are the two main aspects of any successful treatment of chronic disease. Even though diseases and its treatment existed for several hundred years, the treatment optimization for a given patient is still a researcher question for scientists. There are differences in treatment duration, prognostic signs and symptoms between patient to patient. Hence, designing ideal formulation to suit individual patient is a challenging task. The conventional formulations like oral solids and liquids gives a partial or incomplete treatment because the patient needs to follow the daily pills for a longer time. In such cases, the long-acting formulations will have better patient compliances as drug will be released for a longer duration. Many such approaches are under the clinical investigation. The favorable pharmacokinetic and pharmacodynamic relationships, will be promising option for the treatment of chronic diseases. In this review, we have highlighted the importance of long-acting formulations in the treatment of chronic diseases and the advent of newer formulation technologies.