Nitrous oxide emission in altered nitrogen cycle and implications for climate change.

Natural processes and human activities play a crucial role in changing the nitrogen cycle and increasing nitrous oxide (N2O) emissions, which are accelerating at an unprecedented rate. N2O has serious global warming potential (GWP), about 310 times higher than that of carbon dioxide. The food production, transportation, and energy required to sustain a world population of seven billion have required dramatic increases in the consumption of synthetic nitrogen (N) fertilizers and fossil fuels, leading to increased N2O in air and water. These changes have radically disturbed the nitrogen cycle and reactive nitrogen species, such as nitrous oxide (N2O), and have impacted the climatic system. Yet, systematic and comprehensive studies on various underlying processes and parameters in the altered nitrogen cycle, and their implications for the climatic system are still lacking. This paper reviews how the nitrogen cycle has been disturbed and altered by anthropogenic activities, with a central focus on potential pathways of N2O generation. The authors also estimate the N2O-N emission mainly due to anthropogenic activities will be around 8.316 Tg N2O-N yr-1 in 2050. In order to minimize and tackle the N2O emissions and its consequences on the global ecosystem and climate change, holistic mitigation strategies and diverse adaptations, policy reforms, and public awareness are suggested as vital considerations. This study concludes that rapidly increasing anthropogenic perturbations, the identification of new microbial communities, and their role in mediating biogeochemical processes now shape the modern nitrogen cycle.

Potential Therapeutic Applications of Plant-Derived Alkaloids against Inflammatory and Neurodegenerative Diseases.

Alkaloids are a type of natural compound possessing different pharmacological activities. Natural products, including alkaloids, which originate from plants, have emerged as potential protective agents against neurodegenerative disorders (NDDs) and chronic inflammations. A wide array of prescription drugs are used against these conditions, however, not free of limitations of potency, side effects, and intolerability. In the context of personalized medicine, further research on alkaloids to unravel novel therapeutic approaches in reducing complications is critical. In this review, a systematic survey was executed to collect the literature on alkaloids and their health complications, from which we found that majority of alkaloids exhibit anti-inflammatory action via nuclear factor-κB and cyclooxygenase-2 (COX-2), and neuroprotective interaction through acetylcholinesterase (AChE), COX, and ß-site amyloid precursor protein activity. In silico ADMET and ProTox-II-related descriptors were calculated to predict the pharmacological properties of 280 alkaloids isolated from traditional medicinal plants towards drug development. Out of which, eight alkaloids such as tetrahydropalmatine, berberine, tetrandrine, aloperine, sinomenine, oxymatrine, harmine, and galantamine are found to be optimal within the categorical range when compared to nicotine. These alkaloids could be exploited as starting materials for novel drug synthesis or, to a lesser extent, manage inflammation and neurodegenerative-related complications.

LC-HRMS Profiling and Antidiabetic, Antioxidant, and Antibacterial Activities of Acacia catechu (L.f.) Willd.

Acacia catechu (L.f.) Willd is a profoundly used traditional medicinal plant in Asia. Previous studies conducted in this plant are more confined to extract level. Even though bioassay-based studies indicated the true therapeutic potential of this plant, compound annotation was not performed extensively. This research is aimed at assessing the bioactivity of different solvent extracts of the plant followed by annotation of its phytoconstituents. Liquid chromatography equipped with high resolution mass spectrometry (LC-HRMS) is deployed for the identification of secondary metabolites in various crude extracts. On activity level, its ethanolic extract showed the highest inhibition towards α-amylase and α-glucosidase with an IC50 of 67.8 ± 1 µg/mL and 10.3 ± 0.1 µg/mL respectively, inspected through the substrate-based method. On the other hand, the plant extract showed an antioxidant activity of 23.76 ± 1.57 µg/mL, measured through radical scavenging activity. Similarly, ethyl acetate and aqueous extracts of A. catechu showed significant inhibition against Staphylococcus aureus with a zone of inhibition (ZoI) of 13 and 14 mm, respectively. With the LC-HRMS-based dereplication strategy, we have identified 28 secondary metabolites belonging to flavonoid and phenolic categories. Identification of these metabolites from A. catechu and its biological implication also support the community-based usage of this plant and its medicinal value.

Antidiabetic, Antimicrobial, and Molecular Profiling of Selected Medicinal Plants.

Natural products have been the center of attraction ever since they were discovered. Among them, plant-based natural products were popular as analgesics, anti-inflammatory, antidiabetic, and cosmetics and possess widespread biotechnological applications. The use of plant products as cosmetics and therapeutics is deep-rooted in Nepalese society. Although there are few ethnobotanical studies conducted, extensive research of these valuable medicinal plants has not been a priority due to the limitation of technology and infrastructure. Here, we selected 4 traditionally used medicinal plants to examine their bioactive properties and their enzyme inhibition potential. α-Glucosidase and α-amylase inhibitory activities were investigated using an in vitro model followed up by antioxidant and antimicrobial activities. The present study shows that ethyl acetate fraction of Melastoma melabathrium (IC50 9.1 ± 0.3 µg/mL) and water fraction Acacia catechu (IC50 9.0 ± 0.6 µg/mL) exhibit strong α-glucosidase inhibition. Likewise, the highest α-amylase inhibition was shown by crude extracts of Ficus religiosa (IC50 29.2 ± 1.2 µg/mL) and ethyl acetate fractions of Shorea robusta (IC50 69.3 ± 1.1 µg/mL), and the highest radical scavenging activity was shown by F. religiosa with an IC50 67.4 ± 0.6 µg/mL. Furthermore, to identify the metabolites within the fractions, we employed high-resolution mass spectrometry (LC-HRMS) and annotated 17 known metabolites which justify our assumption on activity. Of 4 medicinal plants examined, ethyl acetate fraction of S. robusta, ethyl acetate fraction of M. melabathrium, and water or ethyl acetate fraction of A. catechu extracts illustrated the best activities. With our study, we set up a foundation that provides authentic evidence to the community for use of these traditional plants. The annotated metabolites in this study support earlier experimental evidence towards the inhibition of enzymes. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of diabetes and pathogens.

Potential natural inhibitors of xanthine oxidase and HMG-CoA reductase in cholesterol regulation: in silico analysis.

BACKGROUND: Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generate atherosclerosis and cholesterol crystals. ß-Hydroxy ß-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced cholesterol levels, most of them have failed to meet potential drug candidates' requirements. Here, we have carried out an in-silico analysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR in a wet lab setup. METHODS: Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were selected based on the IC50 values reported in in vitro assays. Further, receptor-based virtual screening was carried out against secondary metabolites using GOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-silico ADMET analysis was carried out to explore their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. RESULTS: The molecular docking of amentoflavone (GOLD score 70.54, ∆G calc. = - 10.4 Kcal/mol) and ganomycin I (GOLD score 59.61, ∆G calc. = - 6.8 Kcal/mol) displayed that the drug has effectively bound at the competitive site of XO and HMGR, respectively. Besides, 6-paradol and selgin could be potential drug candidates inhibiting XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl (6' → 1″)-O-α-D-glucopyranoside could be potential drug candidates to maintain serum cholesterol. In-silico ADMET analysis has shown that these sixteen metabolites were optimal within the categorical range compared to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through ProTox-II revealed that 6-gingerol, ganoleucoin K, and ganoleucoin Z are toxic for human use. CONCLUSION: This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.