Bioactive terpenoids from Euonymus verrucosus var. pauciflorus showing NO inhibitory activities

In our continuous search for new nitric oxide (NO) inhibitory compounds as potential anti-inflammatory agents or lead compounds for inflammatory diseases, the chemical constituents of Euonymus verrucosus var. pauciflorus were investigated, leading to the isolation of eleven terpenoids including six new diterpenoids, designated as euonymupenes A–F. The structures were elucidated on the basis of NMR and ECD data analysis. Euonymupenes A, C, and F feature rare labdane-type norditerpenoid skeletons. The NO inhibitory effects were evaluated and all of the isolates were found to inhibit lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. Western blotting analysis indicated that the most active compound (5) can regulate iNOS (inducible nitric oxide synthase) expression. The further molecular docking studies exhibited the affinities of bioactive compounds with iNOS.     

Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis,structure-activity relationship and molecular docking studies

To explore new scaffolds for the treat of Alzheimer’s disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, ¹H-, ¹³C NMR) and mass spectrometry (EI-MS). All the derivatives (1–24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC₅₀ values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC₅₀ values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes.     

Contribution of Lithologic and Anthropogenic Factors to Surface Soil Heavy Metals in Western Iran Using Multivariate Geostatistical Analyses

Heavy metals’ origin, accumulation, and distribution in soil have been the focus of much attention by many researchers. The objective of this study was to recognize the sources of heavy metals in surface soils in Hamadan Province in western Iran using multivariate geostatistical techniques. A total of 263 surface (0–10 cm) soil samples and 18 rock samples from major parent materials were collected. Cobalt (Co), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), and zinc (Zn) contents of the samples were determined. Selected soil physical and chemical characteristics were also measured. A multivariate geostatistical analysis was performed to identify the common source of heavy metals. The quantities of Co, Cr, and Ni were found to be associated with parent rocks, corresponding to the first factor termed the “lithologic component.” The second factor was mainly attributed to Cu, which also comprised the first and third factors, indicating a mixed source both from lithologic and anthropogenic inputs. Zn and Pb contents were related to the anthropogenic activities and comprised the third factor. A significant correlation was found between metals from the lithogenic sources and selected soil properties such as soil organic matter, clay, CEC, and carbonate, indicating an interaction among them. Generally, Zn and Pb showed a less significant correlation with soil properties.     

Properties of ACE inhibitory peptide prepared from protein in green tea residue and evaluation of its anti-hypertensive activity

Green tea contains active ingredients which are beneficial for health. While numerous studies have been conducted on the components extracted from green tea, few studies have investigated the active ingredients in tea residue. In this study, proteins were extracted from green tea residue via an optimised alkaline extraction combined with enzymatic hydrolysis, of which, an acidic protease was selected to prepare an enzymatic hydrolysate because of its high angiotensin converting enzyme (ACE) inhibitory activity. The composition characteristics of extracted green tea proteolysis products were elucidated, including amino acid composition, molecular weight distribution and possible amino acid sequences. In addition, the protein hydrolysate had anti-digestive properties, maintained its activity of inhibiting ACE enzyme at different temperatures, pH and metal ions, and exhibited antihypertensive activity in animals. In conclusion, the optimised alkaline extraction and enzymatic hydrolysis conditions of a ACE inhibitory peptide from green tea residue is an optimal extraction method to maintain its antihypertensive activity, providing the basis for the clinical application of green tea for blood pressure reduction.     

Identification of a potent Angiotensin-I converting enzyme inhibitory peptide from Black cumin seed hydrolysate using orthogonal bioassay-guided fractionations coupled with in silico screening

Black cumin (Nigella sativa) seed protein (BCSP) was individually hydrolyzed with pepsin, trypsin, and α-chymotrypsin. After ultrafiltration, the α-chymotrypsin hydrolysate (< 3 kDa) exhibited the highest ACE inhibitory (ACEI) activity with an IC₅₀ value of 34.4 ± 1.5 μg/mL. This hydrolysate was orthogonally fractionalized using reversed-phase high-performance liquid chromatography (RP-HPLC) and strong cation exchange (SCX) chromatography, and the most active RP-HPLC and SCX fractions (F7 and H4, respectively) were individually screened out by ACEI assay. These two fractions were analyzed with liquid chromatography-tandem mass spectrometry (LC–MS/MS) followed by automated de novo peptide sequencing, and totally 43 ACEI candidate peptides were identified. Three overlapping peptides (VTPVGVPKW, VVTPVGVPKW, and LVLTL) were simultaneously contained in both fractions, and VTPVGVPKW (VW-9) was speculated as to the most potent ACEI peptide based on the in silico analysis. Synthetic VW-9 was used to confirm the identity, and a remarkable IC₅₀ value of VW-9 (1.8 ± 0.09 μM) was determined. Preincubation and inhibition mechanism studies indicated that VW-9 was a true inhibitor as well as a non-competitive inhibitor on ACE, which was further illustrated with the molecular docking simulation. Our study revealed that the application of VW-9 to antihypertensive products is promising.     

Ultrasound-assisted liquid-state fermentation of soybean meal with Bacillus subtilis: Effects on peptides content,ACE inhibitory activity and biomass

This work studied the effects of ultrasound-assisted liquid-state fermentation on the content of peptides and bioactivity of fermented soybean meal (FSBM) with Bacillus subtilis. Based on the optimization of basic ultrasonic parameters, effects of the main parameters including power density, incubation temperature and ultrasonic time on in vitro ACE inhibitory activity, peptides content and biomass of B. subtilis were investigated via Box-Behnken experimental design. Three mathematical models were determined to show the effects of each variable and their combinatorial interactions on dependent variables. A set of preferred condition was determined to be at power density of 0.08 W/mL for 1 h with an initial incubation temperature of 36.7 °C, according to the desirability function analyses. Under these conditions, the experimental values of in vitro ACE inhibitory activity, peptides content and biomass increased by 26.4%, 36.2% and 55.0% compared to those of the control, respectively, accompanied by the improvement of the peptides yield, purity and conversion rate in varying degrees. Additionally, FSBM resulted in a significant decrease of systolic blood pressure by 20.7 ± 1.8 mmHg in spontaneously hypertensive rats at 3 h. These results suggest that ultrasonication is an efficient solution for enhancing fermentation to produce bioactive components from agroindustrial by-products.     

Comparative toxicity,growth inhibitory and biochemical effects of terpenes and phenylpropenes on Spodoptera littoralis (Boisd.)

Eleven monoterpenes, phenylpropenes and sesquiterpenes were evaluated for their insecticidal and growth inhibitory activities against the second and fourth larval instars of Spodoptera littoralis. Among the tested compounds, 1,8-cineole revealed the highest fumigant toxicity against the 2nd and 4th larval instars with LC₅₀ values of 2.32 and 3.13 mg/L air, respectively. The monoterpenes, p-cymene, α-terpinene, (−)α-pinene and (−)-carvone were highly toxic to both larval stages as their LC₅₀ values ranged between 7.35 and 13.79 mg/L air against 2nd larval instar and between 14.66 and 32.02 mg/L air against 4th larval instar. In topical application assay against the 4th larval instar, (−)-carvone (LD₅₀ = 0.15 mg/larva) and cuminaldehyde (LD₅₀ = 0.27 mg/larva) were the most potent contact toxicants. In residual film assay, trans-cinnamaldehyde, (−)-citronellal and p-cymene showed the highest insecticidal activity against the 2nd larval instar, while α-terpinene and (−)-carvone were most effective compounds against the 4th larval instar. Moreover, the tested compounds caused strong growth reduction of both larval stages with growth inhibition higher than 80% in the 2nd larval instar and higher than 70% in the 4th larval instar. On the other hand, (−)-carvone, cuminaldehyde and (Z,E)-nerolidol showed pronounced inhibitory effects on acetylcholinesterase (AChE) and adenosine triphosphatases (ATPases) activity of S. littoralis larvae. Cuminaldehyde (IC₅₀ = 1.04 mM) and (Z,E)-nerolidol (IC₅₀ = 0.02 mM) caused the highest inhibition of AChE and ATPases, respectively. Taken together, the results indicate that monoterpenes, phenylpropenes and phenylpropenes could be used to develop new botanical insecticides for S. littoralis management.     

Effects of flavonoids on tongue squamous cell carcinoma

Squamous cell carcinoma (SCC) of the tongue is associated with tobacco use, alcohol abuse, and human papillomavirus (HPV) infections. While clinical outcomes have recently improved for HPV‐positive patients in general, 50% of patients suffering from tongue cancer die within 5 years of being diagnosed. Flavonoids are secondary plant metabolites with a wide range of biological activities including antioxidant, anti‐inflammatory, and anticancer activities. Flavonoids have generated high interest as therapeutic agents owing to their low toxicity and their effects on a large variety of cancer cell types. In this literature review, we evaluate the actions of flavonoids on SCC of the tongue demonstrated in both in vivo and in vitro models.