Current Medicinal Chemistry - Volume 28, Issue 23, 2021

Type 2 diabetes mellitus is a complicated metabolic disorder characterized by hyperglycemia and glucose intolerance. It is considered a new pandemic and its control involves numerous challenges. Although many of the measures are based on improving life habits, diet is also of vital importance due to bioactive compounds present in food. In this regard, several raw materials have been investigated whose bioactivities seem to slow the progression of this disease. Within these matrices, there are algae of importance, such as brown algae, showing to have beneficial effects on glycemic control. These pieces of evidence are increasing every day due to the development of cell or animal models, which lead to the conclusion that bioactive compounds may have direct effects on decreasing hyperglycemia, enhancing insulin secretion and preventing the formation of amyloid plaques.

Diabetes mellitus is one of the fastest-growing non-communicable diseases. Diabetes mellitus is caused due by the destruction of pancreatic β-cell or due to insulin resistance and characterized by hyperglycemia. Diabetes imposes a very serious economic crisis as the diabetic drug market is growing very rapidly. Even after very path-breaking scientific discoveries, the availability of better healthcare infrastructure, and a rise in literacy rates, the diabetes burden is continuously spreading in various sections all over the world but more especially in low- and middle-income countries. The recent developments in scientific discoveries have given several new generations of antidiabetic medicines such as sulphonylurea, biguanides, thiazolidinedione, α-glucosidase inhibitors. All these drugs have proved a significant reduction in blood glucose level. There are some new classes of hypoglycaemic drugs that have also been developed and reported, such as GLP-1 analogous, DPP-IV inhibitors, amylin inhibitors, and peroxisome proliferator- activated receptors. There are some active molecules and bioactive substances that have been purified from herbs and plants, which add value to the war against diabetes. These phytoconstituents have overturned drug development and lead identification for drugs against diabetes. The review also focuses on some critical areas of diabetes with more focus on statin-based diabetes management approach and stem cell therapy based next generation antidiabetic therapy.

Background: Diabetes Mellitus (DM) is a severe endocrine metabolic disease coupled with various long-term complications. A plethora of targets have been identified, however, with possible adverse effects. Therefore, researchers are in the perpetual quest for safe and more effective therapeutics. Natural products, particularly derived from plants, have proven to exert anti-diabetic effects via diverse mechanisms. Methods: An overview of DM pathogenesis and its associated micro- and macro-vascular complications is presented. Possible underlying mechanisms of herbal remedies in DM management are provided, highlighting some key therapeutic targets. The review also appraises the recent progress of herbal products in treating DM through regulating inflammation and gut microbiota. Finally, currently available pharmacological treatments are discussed. Results: The results show that numerous plants have proven to be promising sources of insulin secreting agents, α-glucosidase and α-amylase inhibitors. Among the non- conventional targets, inhibition of key enzymes such as lipase, cholinesterases and angiotensin converting enzyme has been directly and/or indirectly linked to DM and DM complications. For instance, hypericin, pseudohypericin and I3,II8-biapigenin isolated from Hypericum perforatum L., and palmatine and columbamine isolated from Dichocarpum auriculatum (Franch.) W. T. Wang & P. K have been found to be powerful lipase and cholinesterase inhibitors, respectively. Moreover, a number of plant-derived compounds such as feruloylated oligosaccharides from maize bran, baicalein and berberine are reported to mediate anti-diabetic property via modulation of gut microbiota. Conclusion: The information amassed in this review is anticipated to provide useful scientific baseline information to support advanced research in natural antidiabetic drug development.

Background: The increasing incidence of diabetes worldwide has urged researchers to explore novel antidiabetic agents from natural products. Ethnomedicinal field studies on diabetes have expanded across the globe, documenting large numbers of folk medicinal plants against diabetes. Nonetheless, a systematic review of these surveys has not been conducted so far. This study documents the medicinal plants traditionally used globally for managing diabetes. Methods: Key databases including Sciencedirect, Medline/PubMed, and Google Scholar were scrutinized. The Plant List and The International Plant Names Index (IPNI) were used to validate the scientific plant names. Results: 2004 traditionally used plants belonging to 1112 genera and 197 families were reported across 92 countries for the management of diabetes. Leguminosae (105 genera and 193 species), Compositae (97 genera and 188 species), and Lamiaceae (47 genera and 121 species) were the main plant families reported. Momordica charantia L., Syzygium cumini (L.) Skeels, Allium sativum L., Azadirachta indica A.Juss., Catharanthus roseus (L.) G.Don, Olea europaea L., Trigonella foenum-graecum L., Gymnema sylvestre (Retz.) R.Br. ex Sm., Aloe vera (L.) Burm.f., and Allium cepa L were the species mostly reported. Indeed, the antidiabetic properties of these main species have been evidenced by experimental studies. Several antidiabetic compounds acting via different mechanisms have been identified, including momordicoside, karaviloside, cucurbitacin, charantin, and charantoside from M. charantia, cuminoside from S. cumini, S-allyl cysteine sulfoxide from A. sativum, limonoids from A. indica, alkaloids including vindoline, vindolidine, vindolicine and vindolinine from C. roseus, oleuropein and oleanolic acid from O. europaea, flavone C-glycosides such as vicenin-1, isoschaftoside, and schaftoside from T. foenum-graecum seeds, gymnemosides, gymnemagenin, and pregnane glycosides from G. sylvestre, chysalodin from A. vera, and quercetin from A. cepa. Conclusion: This review is the first to provide a compiled list of traditional medicinal plants used worldwide against diabetes.

Background: Diabetes mellitus (DM) represents a global health problem characterized by hyperglycemia due to insufficient insulin secretion or failure of insulin activity. There is an imperative need for the discovery of alternative therapeutic agents that overcome the drawbacks of the current synthetic antidiabetic drugs. Objectives: This review critically summarizes the reports on the known and novel natural compounds, including alkaloids, flavonoids, and saponins with a potent antidiabetic activity that were recently published from 2014 to 2019. We discussed the underlying mechanisms of action that put these compounds in the category of effective antidiabetic candidates. Methods: Information was obtained from Google Scholar, Scirus, PubMed, and Science Direct. Discussion and Conclusion: The reported natural compounds showed promising antidiabetic activity through different mechanisms such as the inhibition of α-amylase, α-glucosidase, insulin-sensitizing effect, direct action on protein tyrosine phosphatase 1B (PTP1B), peroxisome proliferator-activated receptors (PPARs), GLUT4 expression, insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) as well as dipeptidyl peptidase-4 (DPP-4) enzyme. Some compounds inhibited the formation of advanced glycation end products (AGEs). Other compounds prevented the risk of diabetic complications such as cardiovascular diseases, retinopathy, and nephropathy. This review provides a critical overview of the most recent discoveries of antidiabetic agents from natural sources. This overview could help researchers to focus on the most prominent candidates aiming to develop new drug leads.

Background: Pulmonary arterial hypertension is one of the chronic diseases that affect human health. Microvesicles participate in the communication between cells by fusing with the recipient cells to transfer the bioactive molecules, such as lipids, proteins, RNA, etc., to the target cells. Microvesicles are involved in various biological processes and have the functions of regulating immunity, promoting angiogenesis, and so on. Microvesicles derived from various cells may become the diagnostic biomarkers or therapeutic targets for the diseases. Therefore, exploring the role of microvesicles-mediated cell communication has become a potential therapeutic target for pulmonary arterial hypertension. Objective: It is to clarify the classification, features, and mechanism of microvesicles in cell communication and to discuss the potentially important roles of microvesicles-mediated cell communication in pulmonary arterial hypertension. Results: Inflammation is an important pathogenesis of pulmonary arterial hypertension. Many studies have shown that microvesicles from different cells can participate in the pathological process of pulmonary arterial hypertension by transferring the inflammatory factors contained in them. Conclusion: Microvesicles-mediated cell communication may become the therapeutic target for pulmonary arterial hypertension.

Background: Gold-based complexes represent a new class of potential metallodrugs. Although their action mechanism is not entirely understood, it was shown that gold complexes inhibit some enzymes’ activities. Among them, Na,K-ATPase is emerging as an essential target for various anticancer drugs. The functionalization of nanoparticles by gold(III) complexes could facilitate their delivery into the cells and enable the following of their distribution in the target tissues. Objective: The paper presents an overview of Na,K-ATPase interaction with representative and structurally related cytotoxic gold(III) complexes. The results obtained by the employment of theoretical methods (DFT and docking studies) combined with the experimental approach involving a variety of nanotechnology-base techniques (UV/Vis, Raman and fluorescence spectroscopy, CD, AFM, DLS) are discussed. Detailed information was obtained on the enzyme’s conformational and structural changes upon binding the gold(III) complexes. The experimentally determined reaction parameters (constants of dissociation and the reaction stoichiometry) were predicted theoretically. Conclusion: The presented results offer further support to the view that Na,K-ATPase may be a relevant biomolecular target for cytotoxic gold(III) compounds of medicinal interest.

Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, and oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. Therefore, to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals, including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol, were reported molecules for the treatment of AD. Several alkaloids, such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine and anatabine, have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.