Diversity and homeostasis of gut bacterial composition is highly associated with the pathogenesis of insulin dysfunction and type 1 diabetes melittus (T1D), hence emerged in parallel with the activation of autoimmunity. We aimed to study the bioactive potential of essential oil from Zanthoxylum myriacanthum var. pubescens Huang (Maqian) through computational approaches. Twelve chemical constituents derived from Maqian essential oil were docked with selected proteins (i.e., 3pig, 1kho, 7dmq, 4m4d, 2z65, 4glp, and 3fxi) in which are involved in gut microbiota modulation in T1D. Subsequently, the prediction of bioavailability properties of the small molecules were evaluated. Among all chemical constituents, the post-docking interaction analysis demonstrated that α-phellandrene exhibits the strongest binding affinity and induces gut microbiota modulation with β-fructofuranosidase from Bifidobacterium longum. The current result revealed the potential of 3-Carene and α-Pinene in inducing specific changes in gut microbiota downregulating Clostridium perfringens and quenching Leptotrichia shahii respectively. β-Pinene possess exceptionally strong binding affinity that effectively disrupt the interaction between lipopolysaccharide and its cognate receptors, while α-Phellandrene was exhibited the uppermost binding affinity with TLR4/MD2 and could likely target TLR4 stimulating lipopolysaccharide. Our results are the first to report on the gut microbiota modulation effects of α-Phellandrene and β-Phellandrene via actions on LPS binding to CD14 and the TLR4 co-receptor signaling. In conclusion, our findings based on computational approaches, small molecules from Maqian present as promising agents which could regulate inflammatory response and modulate gut microbiota in type 1 diabetes mellitus.
Memory loss is becoming an increasingly significant health problem, largely due to Alzheimer's disease (AD), which disrupts the brain in several ways, including causing inflammation and weakening the body's defenses. This study explores the potential of medicinal plants as a source of novel therapeutic agents for AD. First, we tested various plant extracts against acetylcholinesterase (AChE) in vitro, following molecular docking simulations with key AD-related protein targets such as MAO-B, P-gp, GSK-3β, and CD14. Rosemary extract was found to be the most inhibitory towards AChE. The compounds found in rosemary (oleanolic acid), sage (pinocembrin), and cinnamon (italicene) showed promise in potentially binding to MAO-B. These chemicals may interact with a key protein in the brain and alter the production and removal of amyloid-β. Luteolin (from rosemary), myricetin (from sage), chamigrene, and italicene (from cinnamon) exhibited potential for inhibiting tau aggregation. Additionally, ursolic acid found in rosemary, sage, and chamigrene from cinnamon could modulate CD14 activity. For the first time, our findings shed light on the intricate interplay between neuroinflammation, neuroprotective mechanisms, and the immune system's role in AD. Further research is needed to validate the in vivo efficacy and safety of these plant-derived compounds, as well as their interactions with key protein targets, which could lead to the development of novel AD therapeutics.
The arid mountainous region of Hail in Saudi Arabia has a variety of desert vegetation, some of which are conventionally used in Bedouin traditional medicine. These plants need scientific examination. This research seeks to examine Blepharis ciliaris using a thorough multi-analytical methodology that includes antibacterial and antioxidant assessments as well as computational modeling. GC-MS analysis of the methanolic extract revealed 17 organic compounds, including pentadecanoic acid, ethyl methyl ester (2.63%); hexadecanoic acid, methyl ester (1.00%); 9,12-octadecadienoic acid (Z,Z)-, methyl ester (2.74%); 9-octadecenoic acid, methyl ester (E) (2.78%); octadecanoic acid (5.88%); 9-tetradecenoic acid (Z) (3.22%); and undec-10-enoic acid, undec-2-n-1-yl ester (5.67%). The DPPH test evaluated antioxidant activity, revealing a notable increase with higher concentrations of the methanolic extract, achieving maximum inhibition of 81.54% at 1000 µg/mL. The methanolic extract exhibited moderate antibacterial activity, with average inhibition zones of 10.33 ± 1.53 mm, 13.33 ± 1.53 mm, 10.67 ± 1.53 mm, and 10.00 ± 2.00 mm against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Serratia marcescens, respectively, as determined by the disk diffusion method. The minimum inhibitory concentration (MIC) values were 500 µg/mL for S. aureus and B. subtilis, whereas E. coli and S. marcescens showed susceptibility at 1000 µg/mL. Computational simulations were employed to assess the toxicity, drug-likeness, and ADMET profiles of compounds derived from Blepharis ciliaris. Thirteen bioactive compounds were assessed in silico against Staphylococcus aureus sortase A (PDB: 1T2O), Bacillus subtilis BsFabHb (PDB: 8VDB), Escherichia coli LPS assembly protein (LptD) (PDB: 4RHB), and a modeled Serratia marcescens outer-membrane protein TolC, focusing on cell wall and membrane structures. Compound 3, (+)-Ascorbic acid 2,6-dihexadecanoate, shown significant binding affinities to B. subtilis BsFabHb, E. coli LPS assembly protein, and S. marcescens TolC.