Anti-Methanogenic Traits of Safflower Oil Compounds Against Methyl-Coenzyme M Reductase Receptor in Equines: An In Silico Docking Analysis.

Greenhouse gases emission from livestock is the major concern for the ecosystem. Despite the lower contribution of non-ruminants towards greenhouse gas emission as compared to the ruminants, the emission of methane (CH4) gas from equines is expected to be increased in future due to its increasing population. Thus, it is essential to find or screen potential anti-methanogenic agent in a cost-effective and quicker manner. Considering this, the present investigation was aimed to analyze anti-methanogenic characteristic of bioactive compounds of safflower oil by targeting methanogenesis catalyzing enzyme (Methyl-coenzyme M reductase; MCR) via in silico tool. Initially, a total of 25 compounds associated with safflower oil were selected and their drug-likeness traits were predicted through Lipinski's rule of 5. Of 25 compounds, 9 compounds passed all the parameters of Lipinski's rule of five. These 9 ligands were further submitted for ADME traits analysis using Swiss ADME tool. Results revealed the absence of Lipinski's violation and approval of drug-likeness attributes of methyl tetradecanoate, 3-isopropyl-6-methylenecyclohex-1-ene, trans-2,4-decadienal, cis-6-nonenal, limonene, syringic acids, matairesinol, acacetin, and 2,5-octanedione. Molecular docking analysis was performed for analyzing the affinity between the selected 9 ligands and MCR receptor using FRED v3.2.0 from OpenEye Scientific Software and Discovery Studio client v16.1.0. Results showed maximum binding interaction of acacetin with MCR with the chemguass4 score of -13.35. Other ligands showed comparatively lower binding affinity in the order of matairesinol (-12.43) > methyl tetradecanoate (-9.25) > cis-6-nonenal (-7.88) > syringic acids (-7.73) > limonene (-7.18) > trans-2,4-decadienal (-7.07) > 3-isopropyl-6-methylenecyclohex-1-ene (-7.01) > 2,5-octanedione (-7.0.). In a nutshell, these identified compounds were observed as potential agents to reduce CH4 production from equines by targeting MCR. This in silico study emphasized the role of safflower-associated compounds in developing anti-methanogenic drug for equines in future.

Counteracting the Ramifications of UVB Irradiation and Photoaging with Swietenia macrophylla King Seed.

In this day and age, the expectation of cosmetic products to effectively slow down skin photoaging is constantly increasing. However, the detrimental effects of UVB on the skin are not easy to tackle as UVB dysregulates a wide range of molecular changes on the cellular level. In our research, irradiated keratinocyte cells not only experienced a compromise in their redox system, but processes from RNA translation to protein synthesis and folding were also affected. Aside from this, proteins involved in various other processes like DNA repair and maintenance, glycolysis, cell growth, proliferation, and migration were affected while the cells approached imminent cell death. Additionally, the collagen degradation pathway was also activated by UVB irradiation through the upregulation of inflammatory and collagen degrading markers. Nevertheless, with the treatment of Swietenia macrophylla (S. macrophylla) seed extract and fractions, the dysregulation of many genes and proteins by UVB was reversed. The reversal effects were particularly promising with the S. macrophylla hexane fraction (SMHF) and S. macrophylla ethyl acetate fraction (SMEAF). SMHF was able to oppose the detrimental effects of UVB in several different processes such as the redox system, DNA repair and maintenance, RNA transcription to translation, protein maintenance and synthesis, cell growth, migration and proliferation, and cell glycolysis, while SMEAF successfully suppressed markers related to skin inflammation, collagen degradation, and cell apoptosis. Thus, in summary, our research not only provided a deeper insight into the molecular changes within irradiated keratinocytes, but also serves as a model platform for future cosmetic research to build upon. Subsequently, both SMHF and SMEAF also displayed potential photoprotective properties that warrant further fractionation and in vivo clinical trials to investigate and obtain potential novel bioactive compounds against photoaging.

Isolation, Structure Elucidation and In Silico Prediction of Potential Drug-Like Flavonoids from Onosma chitralicum Targeted towards Functionally Important Proteins of Drug-Resistant Bad Bugs.

Admittedly, the disastrous emergence of drug resistance in prokaryotic and eukaryotic human pathogens has created an urgent need to develop novel chemotherapeutic agents. Onosma chitralicum is a source of traditional medicine with cooling, laxative, and anthelmintic effects. The objective of the current research was to analyze the biological potential of Onosma chitralicum, and to isolate and characterize the chemical constituents of the plant. The crude extracts of the plant prepared with different solvents, such as aqueous, hexane, chloroform, ethyl acetate, and butanol, were subjected to antimicrobial activities. Results corroborate that crude (methanol), EtoAc, and n-C6H14 fractions were more active against bacterial strains. Among these fractions, the EtoAc fraction was found more potent. The EtoAc fraction was the most active against the selected microbes, which was subjected to successive column chromatography, and the resultant compounds 1 to 7 were isolated. Different techniques, such as UV, IR, and NMR, were used to characterize the structures of the isolated compounds 1-7. All the isolated pure compounds (1-7) were tested for their antimicrobial potential. Compounds 1 (4',8-dimethoxy-7-hydroxyisoflavone), 6 (5,3',3-trihydroxy-7,4'-dimethoxyflavanone), and 7 (5',7,8-trihydroxy-6,3',4'-trimethoxyflavanone) were found to be more active against Staphylococcus aureus and Salmonella Typhi. Compound 1 inhibited S. typhi and S. aureus to 10 ± 0.21 mm and 10 ± 0.45 mm, whereas compound 6 showed inhibition to 10 ± 0.77 mm and 9 ± 0.20 mm, respectively. Compound 7 inhibited S. aureus to 6 ± 0.36 mm. Compounds 6 and 7 showed significant antibacterial potential, and the structure-activity relationship also justifies their binding to the bacterial enzymes, i.e., beta-hydroxyacyl dehydratase (HadAB complex) and tyrosyl-tRNA synthetase. Both bacterial enzymes are potential drug targets. Further, the isolated compounds were found to be active against the tested fungal strains. Whereas docking identified compound 7, the best binder to the lanosterol 14α-demethylase (an essential fungal cell membrane synthesizing enzyme), reported as an antifungal fluconazole binding enzyme. Based on our isolation-linked preliminary structure-activity relationship (SAR) data, we conclude that O. chitralicum can be a good source of natural compounds for drug development against some potential enzyme targets.

UHPLC-MS phytochemical profiling, biological propensities and in-silico studies of Alhagi maurorum roots: a medicinal herb with multifunctional properties.

The biological, chemical, and in silico properties of methanol and dichloromethane (DCM) extracts of Alhagi maurorum roots with respect to the antioxidant, enzyme inhibition, and phytochemical composition were evaluated. Total bioactive contents were determined spectrophotometrically, and the individual secondary metabolites composition was assessed via ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) analysis. Antioxidant capacities were evaluated using a panoply of assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging, ferric reducing antioxidant power (FRAP), cupric reducing antioxidant power (CUPRAC), phosphomolybdenum total antioxidant capacity (TAC), and metal chelating activity (MCA)). The enzyme inhibition potential was studied against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, α-glucosidase, tyrosinase, urease and lipoxygenase (LOX) enzymes. The methanol extract was found to contain higher total phenolic (105.91 mg GAE/g extract) and flavonoid (2.27 mg RE/g extract) contents which can be correlated to its more substantial antioxidant potential as well as AChE, BChE, tyrosinase and α-glucosidase inhibition. However, the DCM extract was the most effective against α-amylase (1.86 mmol ACAE/g extract) enzyme inhibition. The UHPLC-MS analysis of methanol extract identified the tentative presence of a total of 18 secondary metabolites, including flavonoids, saponins, phenolic and terpenoid derivatives. Three compounds named emmotin A, luteolin 5,3'-dimethyl ether, and preferrugone were further investigated for their in silico molecular docking studies against the tested enzymes. The selected compounds were found to have higher binding interaction with AChE followed by BChE, α-glucosidase, α-amylase, and tyrosinase. The results of the present study have demonstrated A. mauroram to be considered as a lead source of natural antioxidant and enzyme inhibitor compounds.

Polyphenolic profiling of Ipomoea carnea Jacq. by HPLC-DAD and its implications in oxidative stress and cancer.

Ipomoea carnea Jacq. is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 µg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 µg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 µg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 µg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC50 of 61.22 µg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC50 = 8 ± 0.05 µg/mL) and protein kinases (31 mm phenotype bald zone).