Current Enzyme Inhibition - Volume 17, Issue 2, 2021

Background: Obesity is a worldwide lifestyle disorder and its incidence is growing at an alarming rate. Pancreatic lipase (PL) plays a key role in lipid metabolism and hence is a potential target for obesity treatment. There have been reports that many bioactive compounds from natural sources constitute a vast pool of PL inhibitors. Objective: In search of natural pancreatic lipase inhibitors, the review summarizes the potential of natural products for their pancreatic lipase inhibitory activity. Methods: In this review, the data obtained from literature search of various electronic databases and journal article publications have been reviewed. Results: The pancreatic lipase inhibitory activities of 61 biological sources reviewed in this paper are backed by preclinical experimental evidence, either in vivo or in vitro. Conclusion: This article can be used as a ready-to-use reference for therapeutic lead molecules from plants, marine and insect-derived natural products with PL inhibitory activity. The research is more focused on the discovery of more ingenious pancreatic lipase inhibitors with lesser consequences.

Background: COVID-19 has spread rapidly in many countries of the world and poses a serious threat to global public health, yet no specific drug has been identified or currently available for its treatment. Since it may take years to design a drug for its treatment, the shortest and most effective way now is to screen the available drugs or active substances by molecular docking methods. Objective: The aim of this study is to investigate the potential for use in COVID-19 treatment by investigating the inhibitory effects of Glycyrrhiza glabra, main active ingredients on COVID-19, main protease (SARS-CoV-2,), SARS-CoV-2 - ACE2 Complex and ACE-2 by molecular docking method, which are known to have antiviral effects on SARS-CoV. Material and Methods: Molecular docking was performed by using Autodock 4.2 to analyse the probability of docking. Several compounds extracted from the root of the licorice plant (glycyrrhizic acid, glabridin, 6-azauridine, pyrazofurin and mycophenolic acid) were docked to inhibit COVID-19 M^pro and docking results were analysed by Autodock 4.2 and Biovia Discovery Studio Visualizer 2020. The evaluation was based on the docking score (binding energies) calculated by Autodock 4.2. Nelfinavir was used as standards for comparison. Results: As a result of the study, the compounds of Glabridin in COVID-19 main protease (6LU7), ACE-2 (1R4L) and SARS-CoV-2, - ACE2 Complex (6LZG) have very low binding energy (-8.75 to - 7.64) and low potential to inhibition constant has been found. Conclusion: These results suggest that Glabridin appeared to have the best potential to act as a COVID-19 M^pro inhibitor. However, further research is necessary to investigate their potential medicinal use.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Maternal consumption of alcohol is known to produce deleterious effects in the progeny, generating ADHD-related phenotypes. Phosphodiesterase-3 (PDE3) has been shown to provide benefits in various brain conditions. Objective: To investigate the role of a selective PDE3 inhibitor, effects of cilostazol administration on core phenotypes of Prenatal Alcohol Exposure (PAE) model of ADHD were assessed. Methods: PAE was established by exposing animals to 6/4 g.kg^-1 (weekdays/weekends) ethyl alcohol from gestational days 8-20 and cilostazol (30/60 mg.kg^-1 p.o.) was administered to the offspring (PND21- 48) of females exposed to ethyl alcohol. To identify probable mechanisms involved, the effects on protein markers of neuronal function such as, neuronal survival-BDNF, neuronal transcription factor-pCREB, brain inflammation (IL-6, IL-10 and TNF-α) and brain oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum, and striatum. Also, effects on behaviour such as hyperactivity, inattention and anxiety were assessed. Results: PAE induced hyper-locomotion, inattention, and anxiety in tested animals. Administration of cilostazol to PAE group of animals resulted in amelioration of behavioural deficits. Also, cilostazol resulted in a significant increase in the levels of BDNF, pCREB, IL-10 and GSH along with a significant decrease in TNF-α, IL-6 and TBARS in different brain areas of PAE group. Conclusion: Cilostazol, a selective PDE3 inhibitor rectified behavioural phenotypes associated with ADHD, possibly by altering protein markers associated with neuronal survival, neuronal transcription factor, brain inflammation, and brain oxidative stress.

Background: The rising incidence of diabetic complications necessitate the continuous search for safer, cheaper, and effective pharmacological agents. The polyol pathway is an underlying process implicated in the pathogenesis of diabetic complications. Inhibition of enzymes in the polyol pathway is a veritable means of ameliorating diabetic complications. Objective: This study evaluated the inhibitory potential of some spicy plants on the activities of polyol pathway enzymes (aldose reductase and sorbitol dehydrogenase). Methods: Aqueous extracts of Laurus nobilis (bay), Cinnamomum zeylanicum (cinnamon), Murraya koenigii (curry), Thymus vulgaris (thyme), and Curcuma longa (turmeric) were incubated with appropriate enzymes and substrates, and inhibition percentages were determined. Results: The results showed that bay extract had effective IC50 for the inhibition of both aldose reductase (174.87 μg/mL) and sorbitol dehydrogenase (37.08 μg/mL). It also revealed that bay extract inhibited aldose reductase and sorbitol dehydrogenase in a non-competitive and competitive manner, respectively. Conclusion: It is, therefore, concluded that bay extract effectively inhibited activities of polyol pathway enzymes and might contribute to the amelioration of diabetic complications.

Background: The bis(indolyl)methanes (BIMs) scaffold is reported for wide varieties of pharmacological profiles, including antibacterial, anti-proliferative, anticancer, cytotoxic, insecticidal, analgesic, antioxidant, and anti-inflammatory agents. Materials and Methods: A series of bis(indolyl)methanes have been synthesized by a greener and newer approach using the reaction of different substituted aldehydes and indole in the presence of an easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with ultraviolet–visible spectrophotometry (UV–Vis or UV/Vis), Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), etc. The antibacterial and antifungal activities were also carried out against Staphylococcus aureus (RCMB 000106) and Bacillis subtilis (RCMB 000107), as two Gram-positive bacterial strains, and Salmonella typhi and Escherichia coli (RCMB 000103), as two Gram-negative bacterial strains. Fungal species such as Candida Albicans, Penicillium chrysogenum, Aspergillus niger were also used for in vitro antifungal evaluation. All our newly synthesized 14 compounds (4a-4n) were subjected for anti-inflammatory activity in vitro and compared with the known standard drug aceclofenac. Results: Our newly synthesized compounds showed good to moderate antibacterial agents, in silico ADMET, and anti-inflammatory profiles. Conclusion: We hope that our current study would aid future developments of bis(indolyl)methanes as antibacterial and anti-inflammatory agents.

Background: Research on medicinal plant antioxidants has emerged as a potential therapeutic to prevent free radical generated damage in the human body. Hammada elegans Botsch (popularly known as “Ajram”) is a xerophytic plant widely found in Laghouat region, but there are only a few reports about the biological or chemical properties of these species. Hence, the aim of this study is to investigate the antioxidant and the antihemolytic activities of hexanic, acetonic, methanolic and aqueous extracts of aerial parts of Algerian Hammada elegans Botsch by employing different in vitro assay systems. Methods: The total phenolic content, the flavonoid content and the condensed tannin amount were analyzed using Folin-Ciocalteu, aluminum chloride and vanillin assays, respectively. The in vitro antioxidant capacity of extracts was assessed by CUPRAC, iron chelating, ABTS•+ and antihemolytic assays, and was expressed as EC50 values. Results: Among the analyzed extracts, the aqueous extract had the highest phenolic, flavonoid and tannin contents. Also, this extract displayed the highest antioxidant capacities compared to the other extracts and standards. Its EC50 value for ABTS radical-scavenging activity was 0.265 ± 0.003 mg/L. Moreover, this extract showed high iron (II) chelating ability (EC50 = 0.958 ± 0.001 mg/L), and good antioxidant activity in the cupric ion reducing activity (CUPRAC) in a concentration dependent manner (EC50 were 0.709 ± 0.002 mg/L). Additionally, this extract had the best antihemolytic activity against AAPH-induced hemolysis (EC50=0.090 ± 0.004 mg/L). Conclusion: Our study revealed that the aqueous extract of Hammada elegans Botsch, is a potential source of antioxidants which possess a high protective effect of membrane against free radical.