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Carbon nanotubes as novel plant elicitors are intensively studied in biotechnology due to their concentration-dependent effects on plant health. This emphasizes the importance of studying nanomaterials in the field of plant nanotoxicology and enables a better understanding of their advantages and disadvantages for plant health. Researchers examined how various concentrations of multi-walled carbon nanotubes (MWCNTs) affect growth and polyphenolic accumulation in the medicinal herb, Melissa officinalis. Two-month-old plant shoots were sprayed with various concentrations (0–250 mg L−1) of COOH- functionalized MWCNTs and harvested two and three weeks after elicitation. TEM images confirmed MWCNTs uptake into the mesophyll and the vessels of leaves. Low to moderate MWCNT concentrations (50–100 mg L−1) boosted growth indices and increased total amount of phenols, flavonoids, and phenolic acids, peaking three weeks after treatment with 100 mg L−1 MWCNTs, without destroying the cells and subcellular organelles. HPLC analysis showed this treatment yielded the highest content of rosmarinic acid, salvianolic acid B, apigenin, and kaempferol. However, 250 mg L−1 MWCNTs damaged cells without boosting metabolite production. We suggest that elicitation with low to moderate MWCNT concentrations can be a useful tool for laboratory-scale production of phenolic metabolites in M. officinalis. [ABSTRACT FROM AUTHOR]

This study primarily aims to evaluate the phenolic content and biological activity of Salvia macrochlamys both in vitro and in silico. The antioxidant activities of Salvia macrochlamys were assessed using various methods. Additionally, cytotoxic effects and the α-amylase, α-glucosidase, and acetylcholinesterase (AChE) enzyme inhibitory abilities of ethanolic extract of the aerial parts of Salvia macrochlamys (EESM) were evaluated. Then, the molecular docking interactions and molecular dynamic calculations of EESM against α-amylase, α-glycosidase, and AChE enzymes were carried out. High antioxidant activity was determined in both ethanol and water extracts. The IC50 values of EESM against AChE (EC 3.1.1.7), α-glycosidase (E.C.3.2.1.20), and α-amylase (E.C.3.2.1.1) were determined as 1.622 μg/mL, 0.530 μg/mL, and 1.320 μg/mL, respectively. High enzyme-inhibiting properties of EESM were determined in also in silico. Rosmarinic acid was identified as one of the most abundant phenolic compounds in both EESM and water extract of the aerial parts of Salvia macrochlamys (WESM) (3919.65 mg/kg and 10520.77 mg/kg, respectively). Their high level of flavonoids and phenolics, as well as the potent antioxidant and enzyme-inhibitory properties displayed by extracts, may contribute to broadening the use of Salvia macrochlamys in both traditional and modern therapeutic applications. [ABSTRACT FROM AUTHOR]

Glycogen synthase kinase-3 (GSK-3) plays important roles in the pathogenesis of cardiovascular, metabolic, neurological disorders and cancer. Isoform-specific loss of either GSK-3α or GSK-3β often provides cytoprotective effects under such clinical conditions. However, available synthetic small molecule inhibitors are relatively non-specific, and their chronic use may lead to adverse effects. Therefore, screening for natural compound inhibitors to identify the isoform-specific inhibitors may provide improved clinical utility. Here, we screened 70 natural compounds to identify novel natural GSK-3 inhibitors employing comprehensive in silico and biochemical approaches. Molecular docking and pharmacokinetics analysis identified two natural compounds Psoralidin and Rosmarinic acid as potential GSK-3 inhibitors. Specifically, Psoralidin and Rosmarinic acid exhibited the highest binding affinities for GSK-3α and GSK-3β, respectively. Consistent with in silico findings, the kinase assay-driven IC50 revealed superior inhibitory effects of Psoralidin against GSK-3α (IC50 = 2.26 μM) vs. GSK-3β (IC50 = 4.23 μM) while Rosmarinic acid was found to be more potent against GSK-3β (IC50 = 2.24 μM) than GSK-3α (IC50 = 5.14 μM). Taken together, these studies show that the identified natural compounds may serve as GSK-3 inhibitors with Psoralidin serving as a better inhibitor for GSK-3α and Rosmarinic for GSK-3β isoform, respectively. Further characterization employing in vitro and preclinical models will be required to test the utility of these compounds as GSK-3 inhibitors for cardiometabolic and neurological disorders and cancers. Schematic diagram shows the molecular docking to simulate how natural compounds might bind to the crystal structure of GSK-3 enzymes. This was followed by additional in silico analyses, including assessments of druglikeness, potential toxicity, bioactivity scores, and pharmacokinetic properties. Through this multi-step screening process, Psoralidin and Rosmarinic acid emerged as potential inhibitors of GSK-3α and GSK-3β isoforms, respectively. Finally, based on their predicted high binding energy with both GSK-3α and GSK-3β, Psoralidin and Rosmarinic acid were selected for further testing using a kinase assay. This assay confirmed their inhibitory potential, demonstrating higher potency against GSK-3α and GSK-3β, respectively. [Display omitted] • Current GSK-3 inhibitors lack specificity and cause side effects. • This study identifies potential GSK-3 isoform-specific natural compounds. • Psoralidin is likely a better inhibitor for GSK-3α while Rosmarinic for GSK-3β. • These natural compounds may be promising future treatments. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Inhibition of methyl-coenzyme M reductase can suppress the activity of ruminal methanogens, thereby reducing enteric methane emissions of ruminants. However, developing specific and environmentally friendly inhibitors is a challenging endeavor. To identify a natural and effective methane inhibitor that specifically targets methyl-coenzyme M reductase, molecular docking technology was employed to screen a library of phytogenic compounds. A total of 52 candidate compounds were obtained through molecular docking technique. Rosmarinic acid (RA) was one of the compounds that could traverse a narrow channel and bind to the active sites of methyl-coenzyme M reductase, with a calculated binding free energy of −9.355 kcal/mol. Furthermore, the effects of RA supplementation on methane production, rumen fermentation, and the microorganism community in dairy cows were investigated through in vitro rumen fermentation simulations according to a random design. Supplementation of RA resulted in a 15% decrease in methane production compared with the control. In addition, RA increased the molar proportion of acetate and propionate, whereas the sum of acetate and butyrate divided by propionate was decreased. At the bacterial level, the relative abundance of Rikenellaceae RC9 gut group, Christensenellaceae R7 group, Candidatus Saccharimonas , Desulfovibrio , and Lachnospiraceae FE2018 group decreased with RA supplementation. Conversely, the addition of RA significantly increased the relative abundance of DNF00809 (a genus from Eggerthellaceae), Denitrobacterium , an unclassified genus from Eggerthellaceae , an unclassified genus from Bacteroidales , and an unclassified genus from Atopobiaceae. At the archaeal level, the relative abundance of Methanobrevibacter decreased, whereas that of Methanosphaera increased with RA supplementation. These findings suggested that RA has the potential to be used as a novel natural additive for inhibiting ruminal methane production. [ABSTRACT FROM AUTHOR]

• Salvia multicaulis (wild) × Salvia officinalis (cultivated) produced F1 hybrid. • F1 hybrid has the highest content of rosmarinic acid and quercetin. • PAL and CYP expressions strongly correlate with rosmarinic acid content. • Cineole contents negatively correlate with the expression of the CS gene. • Salvia has antioxidant, anticancer, anti-inflammatory, antibacterial effects. The Salvia genus, particularly the wild genotypes, received significant attention due to its antibacterial, antioxidant, antiviral, and anticancer properties. Crossbreeding wild and cultivated plants can conserve the genetic resources of wild plants and develop new hybrids with high yields and high resistance to climatic changes. In this study, Salvia multicaulis (P1, wild) and Salvia officinalis (P2, cultivated) have been crossed to produce a novel hybrid (F1 hybrid) in the Saint Catherin protectorate - Egypt. In P1, P2, and F1 hybrid, heterosis, phytochemical composition, gene expression of PAL (Phenylalanine ammonia-lyase), RAS1 (Rosmarinic acid synthase I), CYP (Cytochrome P450), and CS (1,8-Cineole synthase), besides antioxidant, anticancer, anti-inflammatory, and antibacterial effects were assessed. The F1 hybrid recorded the highest means of plant height in the two seasons. Heterosis over the mid-parents was positively associated with various traits, including stem thickness, number of branches, fresh yield, and percentage of oil in both seasons. Total phenolic and flavonoid content were found in the following order: P2 > P1 > F1. DPPH antioxidant effect was found in the following order: P2 > F1 > P1. The F1 hybrid had the highest content of rosmarinic acid (12.379 mg/g), quercetin (0.595 mg/g), and naringenin (0.152 mg/g), followed by P1 and P2. The 1,8-cineol and α-pinene were the main compounds in the essential oils of P1, P2, and F1. The 1,8-cineol was found in the following order: P2 > F1 > P1, while α-pinene was found in the following order: P1 > F1 > P2. The RAS1 expression showed a weak correlation with the concentration of rosmarinic acid, while the expressions of PAL and CYP were strongly correlated with the concentrations of main phenolics, including rosmarinic acid, quercetin, and naringenin. The 1,8-cineol content was negatively correlated with the expression of the CS gene. The P2 extract and the F1 hybrid essential oil showed potent anticancer, anti-inflammatory, and antibacterial properties. Crossbreeding S. multicaulis (P1, wild) and S. officinalis (P2, cultivated) in this study developed a new hybrid (F1) with good growth characteristics, high essential oil yields, high levels of bioactives, and good bioactivity. This makes it suitable for large-scale production for use in food and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Unhealthy lifestyles, such as chronic consumption of a Western Diet (WD), have been associated with increased systemic inflammation and oxidative stress (OS), a condition that may favour cognitive dysfunctions during aging. Polyphenols, such as rosmarinic acid (RA) may buffer low-grade inflammation and OS, characterizing the aging brain that is sustained by WD, promoting healthspan. The aim of this study was to evaluate the ability of RA to prevent cognitive decline in a mouse model of WD-driven unhealthy aging and to gain knowledge on the specific molecular pathways modulated within the brain. Aged male and female C57Bl/6N mice were supplemented either with RA or vehicle for 6 weeks. Following 2 weeks on RA they started being administered either with WD or control diet (CD). Successively all mice were tested for cognitive abilities in the Morris water maze (MWM) and emotionality in the elevated plus maze (EPM). Glucose and lipid homeostasis were assessed in trunk blood while the hippocampus was dissected out for RNAseq transcriptomic analysis. RA prevented insulin resistance in males while protecting both males and females from WD-dependent memory impairment. In the hippocampus, RA modulated OS pathways in males and immune- and sex hormones-related signalling cascades (Lhb and Lhcgr genes) in females. Moreover, RA overall resulted in an upregulation of Glp1r, recently identified as a promising target to prevent metabolic derangements. In addition, we also found an RA-dependent enrichment in nuclear transcription factors, such as NF-κB, GR and STAT3, that have been recently suggested to promote healthspan and longevity by modulating inflammatory and cell survival pathways. Oral RA supplementation may promote brain and metabolic plasticity during aging through antioxidant and immune-modulating properties possibly affecting the post-reproductive hormonal milieu in a sex-dependent fashion. Thus, its supplementation should be considered in the context of precision medicine as a possible strategy to preserve cognitive functions and to counteract metabolic derangements. [Display omitted] • Western diet (WD) precipitates aging in mice in a sex-dependent manner. • Rosmarinic acid (RA) prevents WD-mediated metabolic derangements in males. • RA decreases anxiety and enhances cognition in both sexes. • RA modulates oxidative stress, immune- and sex hormones-related pathways in the hippocampus. • RA supplementation could be a feasible strategy to promote healthspan. [ABSTRACT FROM AUTHOR]

Antimicrobial potential of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima L. fruits and leaves extracts CMF, CML, LAF and LAL, respectively were evaluated. Gas chromatography–mass spectrometry (GC-MS) analysis for lipoidal matters revealed a high percentage of non-oxygenated compounds. Phytol was the major in LAL. Palmitic and linoleic acid were the major in CML and LAL, respectively. Rutin and P-hydroxy benzoic acid were the main compounds identified by High-performance liquid chromatography (HPLC) analysis. The antibacterial and antifungal activities of the plants extract were determined by the well diffusion method. Antimicrobial investigation for different successive fractions of active methanol extracts of CML, LAL, LAF and CMF showed the highest activity (CML), whereas the petroleum ether (CML PE) and MeOH (CML) fractions exhibit a significant antifungal activity against Candida albicans minimum inhibitory concentration (MIC) 12 and 15 µg/mL, respectively. The antifungal activity prevailed by C. medica leaves may be attributed to its polyphenolics (rutin, chlorogenic and rosmarinic acid) in addition to phenylated hydrocarbon. [ABSTRACT FROM AUTHOR]

Ephedra alata Decne is a medicinal plant widely used in traditional medicine for the management of bronchial asthma and cancer. Phytochemical analysis and biological activities, including antioxidant and anticancer effects, were investigated in the current work as new findings for the plant E. alata, a species growing wildly in the marsh and saline environments of the central area of Saudi Arabia. The Ultra Pressure Liquid Chromatography coupled with Electron spray ionization-Quadropole-Time of flight (UPLC-ESI-Q-TOF) system was used for the phytochemical analysis of the plant constituents. In addition, Polyphenolic profiling including the total phenolic (TPC) and flavonoid (TFC) contents of the plant extracts were measured. Phenolic acids were found at the highest relative percentages among all the identified compounds and were measured at 66.07 mg GAE (Gallic acid equivalent). The UPLC analysis of the E. alata extract indicated the presence of chlorogenic acid, syringic acid, caffeic acid, vanillic acid, rosmarinic acid, umbelliferone, isorhoifolin, and apigenin at the highest relative percentages. Mineral analysis indicated that the microelement content of E. alata was relatively low, except for magnesium (Mg). In vitro antioxidant assays revealed the ability of the plant to scavenge DPPH free radicals, reduced molybdenum ions, and ferrous at levels of 14.63, 19.97, and 27.78 mg Trolox equivalents, respectively. The extract induced transition metal chelation at 31.36 mg EDTA equivalents. The extract induced cytotoxic effects against MDA-231 and A549 cell lines at IC50 levels of 25.31 and 39.81 µg/mL, respectively. The plant extract inhibited the colonization and migration of cancer cells as part of its potential anticancer effects. In addition, major E. alata constituents like isorhoifolin, chlorogenic acid, apigenin, and rosmarinic acid exhibited the lowest binding energy to the CAIX enzyme at − 8.41, − 6.64, − 6.32, and − 6.26 kcal/mol, respectively, compared to the binding energy (− 7.72 kcal/mol) of the co-crystallized ligand (Y0R). The docking results further supported the selection of the CAIX enzyme as a standard predictive therapeutic target, since it exhibited significant binding interactions with the major constituents of the plant. [ABSTRACT FROM AUTHOR]

AbstractRosmarinic acid (RosA), a hydrophilic phenolic compound found in various plants, has several biological effects such as anti-inflammatory and anti-apoptosis activities. However, its potential impact on chronic obstructive pulmonary disease (COPD) and its underlying mechanism has not been investigated. In this study, we explored the potential therapeutic effects and mechanism of RosA on COPD airway inflammation and alveolar epithelial apoptosis in vivo and in vitro. Our data suggested that RosA may be a therapeutic candidate for COPD with low toxicity. The corresponding mechanism lies in its anti-inflammatory effect on macrophage and bronchial epithelial cells, as well as protective effect on lung epithelial apoptosis via the jointly cross-target spleen tyrosine kinase (Syk). [ABSTRACT FROM AUTHOR]

In this study, the fatty acid content, phenolic compounds, and antimicrobial activity of seed oils from Ege Özbaş (EO), Sarıbağlar 407 (S407) and Akhisar 98 (A98) tobacco plants grown in the Aegean region were investigated. The ozonation process altered fatty acid and phenolic compound compositions and affected antimicrobial activities against Gram-positive and Gram-negative bacteria in the oils. Tobacco seed oils (TSOs) were extracted via cold pressing (CP) and Soxhlet extraction (SE). Fatty acids and phenolic compounds were analyzed using GC-FID and LC-MS/MS, respectively. Non-ozonated oils averaged 73% linoleic acid, 13% oleic acid, 9% palmitic acid, and 3% stearic acid, while ozonated oils contained 41% linoleic acid, 18% oleic acid, 22% palmitic acid, and 11% stearic acid. The presence of 33 phenolic compounds was investigated and 22 common phenolic compounds were detected in both ozonated and non-ozonated TSOs, including gallic acid, protocatechuic acid, chlorogenic acid, 3-hydroxybenzoic acid, (-)-epicatechin, 2,5-dihydroxybenzoic acid, caffeic acid, verbascoside, luteolin-7-glucoside, hesperidin, and rosmarinic acid. The increased antimicrobial activity of fatty acids and phenolic compounds following ozonation suggests the potential for developing creams to treat skin diseases and wounds caused by antibiotic-resistant pathogens, and to reduce the effects of aging skin wrinkles. [ABSTRACT FROM AUTHOR]

The infusions prepared from some Quercus L. species are used in folk medicine for medicinal purposes and consumed as tea. Quercus pontica K. Koch was selected in this study, for which no phytochemical isolation studies have been performed so far. Quercetin 3-O- β-D-glucopyranoside, kaempferol 3-O-(6”“-O-galloyl)-β-D-glucopyranoside, kaempferol 3-O-β-D-glucopyranoside, kaempferol 3-O-(6”’-coumaroyl-β-D-glucopyranoside, phlorizin, rosmarinic acid, and catechin were isolated from the titled plant for the first time. Some polyphenolic compounds have been shown to inhibit histone deacetylase (HDAC) enzymes. However, there is no study on the any activities of Quercus species in the literature. In this study, we demonstrated that the extract has in vitro pan-HDAC inhibition activity. Through a virtual screening study, the compounds were found to inhibit HDAC7 more strongly than the other HDAC isoforms; therefore, the HDAC7 inhibition activities were studied in vitro. Kaempferol 3-O-β-D-glucopyranoside and kaempferol 3-O-(6’”-coumaroyl-β-D-glucopyranoside) showed the best anti-HDAC7 activity with 37% and 41% inhibition at 500 μM. [ABSTRACT FROM AUTHOR]

Digitalis purpurea L. is one of the important plant species of Nilgiris, Kashmir and Darjeeling regions of India, belonging to the family Plantaginaceae, with well-known pharmacological applications. In the present investigation, an in vitro culture technique of indirect shoot organogenesis of D. purpurea is being explored; the biochemical attributes, the antioxidant activities and the metabolomic analyses were made by utilizing untargeted Gas Chromatography-Mass Spectrometry (GC-MS) and Ultra Performance Liquid Chromatography coupled with electronspray ionization/quadrupole-time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) approaches. Initially, the leaf explants were used for callus induction and proliferation and maximum callusing frequency (94.44%) and fresh biomass (4.9 g) were obtained on MS, fortified with 8.8 µM BAP (6-benzyl amino purine) + 0.9 µM 2,4-D (2,4-dichlorophenoxyacetic acid), subsequently shoot formation (indirect organogenesis) was noted on the same MS medium with a shoot induction frequency of 83.33%. Later on, the biochemical and antioxidant potential of in vivo-, in vitro grown leaf and leaf derived callus were assessed. Significantly higher total phenol, flavonoid, DPPH (2,2-diphenyl-1-picrylhydrazyl), POD (peroxidase) and SOD (superoxide dismutase) activities were noticed in in vitro grown callus and leaf tissues compared with field grown leaf. The GC-MS analysis of each methanolic extract (in vivo-, in vitro derived leaf and leaf derived callus) displayed the presence of more than 75 bioactive compounds viz loliolide, stigmasterin, alpha-tocopherol, squalene, palmitic acid, linoleic acid, beta-amyrin, campesterol etc. possessing immense therapeutic importance. The UPLC-MS based metabolite fingerprinting of each methanolic extracts were conducted in both positive and negative ionization mode. The obtained results revealed variation in phytochemical composition in field - and laboratory grown tissues, indicating the impact of in vitro culture conditions on plant tissues. The detected phytocompounds belongs to various classes such as flavonoids, steroids, terpenoids, carbohydrates, tannins, lignans etc. The medicinally important metabolites identified were 20, 22-dihydrodigoxigenin, digoxigenin monodigitoxoside, apigenin, luteolin, kaempferide, rosmarinic acid, nepitrin and others. The results of the present study suggest that in vitro culture of D. purpurea could successfully be utilized for the novel drug discovery by producing such important phytocompounds of commercial interest in shorter duration without harming the plants' natural population. [ABSTRACT FROM AUTHOR]

Background: Rosmarinic acid (RA), a natural phenolic acid, exhibits promising anti-cancer properties. The abnormal expression of microRNA (miRNA) regulates the gene expression and plays a role as an oncogenic or tumor suppressor in TNBC. However, the biological role of RA in miR-30a-5p on BCL2L11 during MDA-MB-231 induced breast cancer stem-like cells (BCSCs) progression and its regulatory mechanism have not been elucidated. Objective: To investigate whether RA inhibited the silencing effect of miR-30a- 5p on the BCL2L11 gene and promoted apoptosis in BCSCs. Materials and Methods: We assessed the migration, colony formation, proliferation, cell cycle, and apoptosis of BCSCs after RA treatment using the wound-healing assay, colony formation assay, CCK-8 assay, and flowcytometry, respectively. The expression of mRNA and protein levels of BCL-2, Bax, BCL2L11, and P53 genes in BCSCs after RA treatment was obtained by real-time polymerase chain reaction and Western blot. DifferentialmiRNA expression in BCSCswas analyzed by high-throughput sequencing. Targetscan was utilized to predict the targets of miR-30a-5p. The dual luciferase reporter system was used for validation of the miR-30a-5p target. Results:Wound-healing assay, colony formation assay,CCK-8 assay, and cell cycle assay results showed that RA inhibited migration, colony formation and viability of BCSCs, and cell cycle arrest in the G0-G1 phase. At the highest dose of RA, we noticed cell atrophy, while the arrest rate at 100 μg/mL RA surpassed that at 200 μg/mL RA. Apoptotic cells appeared early (Membrane Associated Protein V FITC+, PI-) or late (Membrane Associated Protein V FITC+, PI+) upon administration of 200 µg/mL RA, Using high-throughput sequencing to compare the differences in miRNA expression, we detected downregulation ofmiR-30a-5p expression, and the results of dual luciferase reporter gene analysis indicated that BCL2L11 was a direct target of miR-30a-5p. Conclusion: RA inhibited the silencing effect of miR-30a-5p on the BCL2L11 gene and enhanced apoptosis in BCSCs. [ABSTRACT FROM AUTHOR]

Clerodendranthus spicatus (Thunb.) (Kidney tea) is a very distinctive ethnic herbal medicine in China. Its leaves are widely used as a healthy tea. Many previous studies have demonstrated its various longevity-promoting effects; however, the safety and specific health-promoting effects of Clerodendranthus spicatus (C. spicatus) as a dietary supplement remain unclear. In order to understand the effect of C. spicatus on the longevity of Caenorhabditis elegans (C. elegans), we evaluated its role in C. elegans; C. spicatus water extracts (CSw) were analyzed for the major components and the effects on C. elegans were investigated from physiological and biochemical to molecular levels; CSw contain significant phenolic components (primarily rosmarinic acid and eugenolinic acid) and flavonoids (primarily quercetin and isorhamnetin) and can increase the lifespan of C. elegans. Further investigations showed that CSw modulate stress resistance and lipid metabolism through influencing DAF-16/FoxO (DAF-16), Heat shock factor 1 (HSF-1), and Nuclear Hormone Receptor-49 (NHR-49) signalling pathways; CSw can improve the antioxidant and hypolipidemic activity of C. elegans and prolong the lifespan of C. elegans (with the best effect at low concentrations). Therefore, the recommended daily use of C. spicatus should be considered when consuming it as a healthy tea on a daily basis. [ABSTRACT FROM AUTHOR]

This research studied the phenolic content compared with the antioxidant properties of various O. vulgare (Lamiaceae) cultivars grown in Poland. The research results in this paper indicate that the dominant ingredient in all oregano cultivars was rosmarinic acid, known for its strong antioxidant properties. The highest amounts of rosmarinic acid (87.16 ± 4.03 mg/g dm) were identified in the O. vulgare spp. hirtum (Link) Ietsw. Other metabolites identified in the studied extracts include luteolin O-di-glucuronide-O-di-pentoside (30.79 ± 0.38 mg/g dm in the 'Aureum' cultivar), 4′-O-glucopyranosyl-3′, 4′-dihydroxy benzyl-protocatechuate (19.84 ± 0.60 mg/g dm in the 'Margerita' cultivar), and p-coumaroyl-triacetyl-hexoside (25.44 ± 0.18 mg/g dm in the 'Margerita' cultivar). 'Hot & spicy' and 'Margerita' cultivars were characterized by the highest activity in eliminating OH• and O2•− radicals. Extracts from Greek oregano had the highest ability to scavenge DPPH radicals and chelate iron ions. This research has also provided new evidence that oregano has anti-migratory, cytotoxic properties and influences the viability of gastric cancer cells (the highest cytotoxicity was attributed to the 'Hot & spicy' cultivar, which performed the worst in antioxidant properties tests). Extracts from the tested cultivars at a concentration of 0.625% effectively inhibited the growth of S. aureus and P. aeruginosa bacteria. It seems that the oregano grown in Poland is of good quality and can be successfully grown on a large scale if the appropriate use is found. [ABSTRACT FROM AUTHOR]

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography–mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC50 values ranging from 15.8 to 40.0 μg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph–mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties. [ABSTRACT FROM AUTHOR]

Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1β, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the ROS production, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions. [Display omitted] • The DRGNG nanogel could suppress reactive oxygen species, reduce inflammatory factors, and promote mucin secretion. • The DRGNG nanogel could prolong the ocular retention time and ensure extended intimate contact with the ocular surface. • Efficient alleviation of dry eye disease symptoms was verified in both evaporative and aqueous deficient dry eye disease animal models. [ABSTRACT FROM AUTHOR]

• Lemon balm postdistillation waste extracts are abundant source of rosmarinic acid. • Antioxidant, antibacterial and anticholinesterase effects are pronounced. • Deodorized lemon balm leaves extracts possess the hepatoprotective effect. • Herbal-drug interaction with midazolam was recorded in rotarod performace test. • Lemon balm leaves extract reduce the levels of anxiety in experimental animals. Melissa officinalis L., Lamiaceae (lemon balm) leaves, essential oil and extracts have a long tradition of use. This aromatic plant is cultivated worldwide and there is a growing demand for its mass production. The aim of this study was to chemically characterize lemon balm postdistillation waste such are deodorized leaves, decoction remaining after the hydrodistillation of essential oil and stems and to determine whether waste extracts possess pharmacological activities comparable to standard lemon balm extract. The potential usage of postdistillation waste would be important for both ecological and economic reasons. Prepared waste extracts were chemically characterized regarding total phenolics and flavonoids and using high performance liquid chromatography for quantification of specific phenolic compounds. Antioxidant effect was examined ex vivo on liver homogenate of experimental animals. Pharmacodynamic studies included rotarod performance, tail suspension, elevated plus maze and novel object recognition tests and potential interactions between examined lemon balm extracts and midazolam, fluoxetine and diazepam. Rosmarinic acid was determined as a dominant compound in all investigated extracts ranging from 15.82 to 42.98 mg/g of dried extracts. Ex vivo , hepatoprotective effect of deodorized leaves extract was confirmed. Examined lemon balm extracts influenced the metabolism of midazolam without interacting with fluoxetine or diazepam, nor expressing the antidepressant effect or influencing the memory of treated animals. However, anxiolytic effect of lemon balm extracts was recorded. Postdistillation waste of lemon balm could be used as a potential source for pharmaceutical industry for the isolation of pharmacologically active compounds and production of herbal medicinal products. [ABSTRACT FROM AUTHOR]

A central feature of a variety of related neurological disorders, including amyotrophic lateral sclerosis (ALS), is the deposition of misfolded protein aggregates in key regions of the human brain. Hence, targeting aggregation-prone SOD1 with small molecules can be used to design strategies to inhibit its aggregation. Based on molecular docking and molecular dynamics (MD) simulation, this study suggested that plant flavonoids can act as a potent anti-amyloidogenic polyphenol against SOD1 aggregation. Initial screening of flavonoids against protein aggregates identified Rosmarinic acid and Salvianolic acid A as promising drug leads that can effectively inhibit pathogenic behaviour. Our results showed that Salvianolic acid A reduces the β-sheet content and increases the structural stability, hydrophobicity, flexibility, and significantly the lost hydrogen bonds of the mutant compared to other compounds. Besides, we revealed changes in the free energy landscape (FEL) of WT-SOD1 and mutant states (unbound/bound) to differentiate aggregation. We deduced that the above-mentioned flavonoids can deviation the pathogenic behaviour of the D124 V mutant. Among them, Salvianolic acid A showed the greatest therapeutic potential against the D124 V mutant. Hence, Salvianolic acid A could serve as a drug candidate for the design of highly efficient inhibitors in reducing fatal and irreversible ALS. [ABSTRACT FROM AUTHOR]

The rationale for this research is the investigation of the potential health benefits as well as the antibacterial and antifungal properties of selected aromatic plants from the Lamiaceae family, which may lead to the development of improved functional foods. The present study investigated the effects of incorporating dried aromatic plants Thymus vulgaris, Thymus serpyllum, Thymus × citriodorus, Origanum vulgare and Rosmarinus officinalis at a concentration of 1% in refined wheat flour and wholemeal flour on the production of functional tortillas. Sensory analysis was employed to identify the optimal 1% addition, with the objective of achieving a favorable flavor and aroma profile. It was hypothesized that this addition would affect water activity, moisture, texture, color, antioxidant content and phenolic content, thereby enhancing the tortillas as a source of bioactive compounds. The results indicated that the type of flour used had a significant impact on the water activity of the tortillas, with wholemeal flour resulting in higher water activity than refined flour. The water activity ranged between 0.735 and 0.821, while the water content remained relatively stable. The water activity in whole-grain tortillas was significantly higher than that of refined flour tortillas, with a value exceeding 0.8, which makes them susceptible to mold growth and the production of mycotoxins. The sensory evaluations indicated that the enriched refined flour tortillas with common thyme (Thymus vulgaris), lemon thyme (Thymus × citriodorus) and rosemary (Rosmarinus officinalis) were rated highly; a similar result was observed for the whole-grain tortillas enriched with wild thyme (Thymus serpyllum) and lemon thyme. The whole-grain tortillas with rosemary were rated the highest of all the tortillas. The addition of aromatic plants increased the phenolic content and the antioxidant potential, depending on the flour type and the plant used. The addition of wild thyme and rosemary resulted in a significant increase in the phenolic content of wheat tortillas, while all enriched whole-grain tortillas exhibited a higher phenolic content than the control samples. The highest phenolic content in whole-grain tortillas was found in those fortified with rosemary, oregano and wild thyme. The highest antioxidant content was recorded in tortillas prepared with rosemary, irrespective of whether the flour used was refined or wholemeal. Fourteen phenolic compounds were tentatively identified in aromatic plants tested. The main phenolic compounds in Origanum vulgare were flavonoids. Rosmarinic acid was the dominant phenolic compound in rosemary and all thyme species, reaching the highest level in rosemary. Such high levels of rosmarinic acid may be responsible for the high antioxidant and total phenolic contents observed in rosemary extracts and also in tortillas when this plant is included in the recipe. The results of this study indicate that selected aromatic plants, particularly rosemary, have the potential to be utilized as functional ingredients in bakery products. By incorporating dried aromatic plants from the Lamiaceae family into wheat flour tortillas, food manufacturers can create products that not only taste better but also provide added health benefits. The use of selected herbs can improve the nutritional profile of tortillas by increasing antioxidant properties and, due to the properties of herbs, extend the shelf life of the product. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ischemia/reperfusion injury is one of the most challenging postoperative situations in vascular surgery, both in elective procedures with prolonged clamping time and in delayed emergency cases with vascular occlusion. The inflammatory response that develops during ischemia and the oxygen-free radicals that proliferate during reperfusion have detrimental effects on the brain, heart, and kidneys. In this study, we aimed to compare the effects of vanillic and rosmarinic acid in preventing ischemia/reperfusion injury in a lower limb ischemia-reperfusion model in rats. METHODS: Thirty-two female Sprague-Dawley rats weighing 185-240 g were randomly divided into four groups of eight animals each. Group 1 was designated as the control, Group 2 as ischemia/reperfusion (I/R), Group 3 as ischemia/reperfusion + vanillic acid (I/R + VA), and Group 4 as ischemia/reperfusion + rosmarinic acid (I/R + RA). In all groups except the control, the infrarenal abdominal aorta was clamped, and 60 minutes of ischemia followed by 120 minutes of reperfusion was performed. Vanillic acid was administered intra-abdominally 15 minutes before the start of reperfusion in Group 3, and rosmarinic acid in Group 4. At the end of the reperfusion phase, blood samples and hearts were collected, and the rats were euthanized. Histopathologically, myofibrillar edema, myocytolysis, focal hemorrhages, and infiltration of polymorphonuclear leukocytes (PMNL) in cardiac tissue were examined. Total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), 8-OH-deoxyguanosine, lactonase, and arylesterase activity were measured in blood samples. RESULTS: Myofibrillar edema was most pronounced in the I/R group and less pronounced in the I/R + VA and I/R + RA groups (p=0.005 and p=0.066, respectively). There was no difference between the ischemia/reperfusion groups regarding myocytolysis, focal hemorrhage, and PMNL infiltration (p>0.99). Among all groups, TOS and OSI were lowest in the control group, while TAC was highest. TAC was similar in the I/R + VA and I/R + RA groups but was significantly higher in these two groups than in the I/R group. The lactonase activity in the I/R + VA group was similar to that in the control group but was significantly higher compared to the I/R and I/R + RA groups. CONCLUSION: Our study shows that vanillic and rosmarinic acids reduce myofibrillar edema in the heart after lower limb ischemia and increase TAC. However, vanillic acid increases the activity of lactonase, an enzyme known for its antioxidant effect, more than rosmarinic acid. [ABSTRACT FROM AUTHOR]

Background: In the past two decades, the impacts of Helium-Neon (He–Ne) laser on stress resistance and secondary metabolism in plants have been studied, but the signaling pathway which by laser regulates this process remains unclear. Therefore, the current study sought to explore the role of RBOH-dependent signaling in He–Ne laser-induced salt tolerance and elicitation of secondary metabolism in Salvia officinalis. Seeds were primed with He–Ne laser (6 J cm− 2) and peroxide hydrogen (H2O2, 5 mM) and 15-old-day plants were exposed to two salinity levels (0, 75 mM NaCl). Results: Salt stress reduced growth parameters, chlorophyll content and relative water content (RWC) and increased malodialdehyde (MDA) and H2O2 contents in leaves of 45-old-day plants. After 48 h of salt exposure, higher transcription levels of RBOH (encoding NADPH oxidase), PAL (phenylalanine ammonia-lyase), and RAS (rosmarinic acid synthase) were recorded in leaves of plants grown from seeds primed with He–Ne laser and/or H2O2. Despite laser up-regulated RBOH gene in the early hours of exposing to salinity, H2O2 and MDA contents were lower in leaves of these plants after 30 days. Seed pretreatment with He–Ne laser and/or H2O2 augmented the accumulation of anthocyanins, total phenol, carnasol, and rosmarinic acid and increased total antioxidant capacity under non-saline and more extensively at saline conditions. Indeed, these treatments improved RWC, and K+/Na+ ratio, enhanced the activities of superoxide dismutase and ascorbate peroxidase and proline accumulation, and significantly decreased membrane injury and H2O2 content in leaves of 45-old-day plants under salt stress. However, applying diphenylene iodonium (DPI as an inhibitor of NADPH oxidase) and N, N-dimethyl thiourea (DMTU as a H2O2 scavenger) after laser priming reversed the aforementioned effects which in turn resulted in the loss of laser-induced salt tolerance and secondary metabolism. Conclusions: These findings for the first time deciphered that laser can induce a transient RBOH-dependent H2O2 burst, which might act as a downstream signal to promote secondary metabolism and salt stress alleviation in S. officinalis plants. [ABSTRACT FROM AUTHOR]

Background: Nowadays Alzheimer's disease and its treatment methods are global concerns. Patients with this disease have poor prognosis and need supportive treatment. The antioxidant activity, anti-acetylcholinesterase (anti-AChE), anti-butyryl cholinesterase (anti-BChE) and Aβ-amyloid-42 inhibition activities of the ethanolic extracts of both leaves and flowers (LEE and FEE) of Markhamia lutea were assessed. The antioxidant activity of LEE and FEE was evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate, oxygen radical absorbance capacity and ferrozine iron metal chelation assays. Additionally, their total flavonoids and total phenolics were determined. The phytochemicals of LEE were analysed using LC–MS/Q-TOF in both positive and negative modes. Also, molecular docking was done for phytochemicals identified in LEE. Result: LEE exhibited higher antioxidant and anti-Alzheimer activities in all techniques due to its high flavonoids content. LEE showed better activity than donepezil in case of anti-butyryl cholinesterase than both donepezil and rivastigmine in case of Aβ-amyloid-42 inhibition. A total of 62 compounds were tentatively identified using Ultra-performance Liquid Chromatography-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC–ESI–TOF–MS), viz. 35 flavonoids, 11 phenolic acids, 2 terpenoids, 2 phenylpropanoids derivatives, 7 polyphenols, 3 coumarins and 2 organic acids. The molecular docking of some constituents showed that isorhamnetin-O-rutinoside, sissotrin, 3,5,7-trihydroxy-4'-methoxyflavone (diosmetin), rosmarinic acid, kaempferol hexoside, kampferol-7-neohesperoside, acacetin, taxifolin and apigenin-O-hexoside exert a promising activity as anti-Alzheimer drugs. Conclusion: The LEE of Markhamia lutea contains secondary metabolites that is promising to act as natural antioxidants, acetylcholinesterase, butyryl cholinesterase and Aβ-amyloid-42 inhibition inhibitors, which can aid in the treatment of Alzheimer's. [ABSTRACT FROM AUTHOR]

Summary Kombucha has gained global attention for its beneficial bioactive compounds. This study aimed to evaluate Thunbergia laurifolia tea as a potential substrate for Kombucha production due to its rich polyphenol content and biological properties, including antioxidant and anticancer properties, through monoculture and simultaneous mixed coculture fermentation. The pH and brix of the teas decreased significantly during fermentation, indicating sugar hydrolysis and organic acid synthesis by fermenting microbes. The alcohol content was higher in yeast monocultures (45.80 ± 0.00¬50.23 ± 0.08 g L−1) compared to mixed coculture fermented (CBY) tea (20.16 ± 0.00 g L−1). Total phenolic and flavonoid contents and antioxidant activity increased significantly in CBY tea compared to non‐fermented and monoculture teas. CBY also exhibited the highest cumulative phenolic compound content, including rosmarinic acid, caffeic acid, gallic acid, rutin, catechin, and quercetin, compared to monoculture teas. Overall, Thunbergia laurifolia tea shows promise as a substrate for kombucha production, with improved bioactive constituents and antioxidant activity. [ABSTRACT FROM AUTHOR]

Background: Asthma is a heterogeneous, inflammatory disease with several phenotypes and endotypes. Severe asthmatics often exhibit mixed granulocytosis with reduced corticosteroid sensitivity. Bronchom is a newly developed Ayurvedic prescription medicine, indicated for the treatment of obstructive airway disorders. The purpose of the present study was to evaluate the in-vivo efficacy of Bronchom in mouse model of mixed granulocytic asthma with steroidal recalcitrance. Methods: High-performance thin layer chromatography (HPTLC) and Ultra-high performance liquid chromatography (UHPLC) were employed to identify and quantitate the phytometabolites present in Bronchom. The preclinical effectiveness of Bronchom was assessed in house dust mite (HDM) and Complete Freund's adjuvant (CFA)-induced mixed granulocytic asthma model in mice. High dose of dexamethasone was tested parallelly. Specific-pathogen-free C57BL/6 mice were immunized with HDM and CFA and nineteen days later, they were intranasally challenged with HDM for four consecutive days. Then the mice were challenged with nebulized methacholine to evaluate airway hyperresponsiveness (AHR). Inflammatory cell influx was enumerated in the bronchoalveolar lavage fluid (BALF) followed by lung histology. Additionally, the concentrations of Th2 and pro-inflammatory cytokines was assessed in the BALF by multiplexed immune assay. The mRNA expression of pro-inflammatory cytokines and Mucin 5AC (MUC5AC) was also evaluated in the lung. Results: HPTLC fingerprinting and UHPLC quantification of Bronchom revealed the presence of bioactive phytometabolites, namely, rosmarinic acid, gallic acid, methyl gallate, piperine, eugenol and glycyrrhizin. Bronchom effectively reduced AHR driven by HDM-CFA and the influx of total leukocytes, eosinophils and neutrophils in the BALF. In addition, Bronchom inhibited the infiltration of inflammatory cells in the lung as well as goblet cell metaplasia. Further, it also suppressed the elevated levels of Th2 cytokines and pro-inflammatory cytokines in the BALF. Similarly, Bronchom also regulated the mRNA expression of pro-inflammatory cytokines as well as MUC5AC in mice lungs. Reduced effectiveness of a high dose of the steroid, dexamethasone was observed in the model. Conclusions: We have demonstrated for the first time the robust pharmacological effects of an herbo-mineral medicine in an animal model of mixed granulocytic asthma induced by HDM and CFA. The outcomes suggest the potential utility of Bronchom in severe asthmatics with a mixed granulocytic phenotype. [ABSTRACT FROM AUTHOR]

To investigate the mechanism of rosmarinic acid in alleviating food allergy, an integrated approach, involving network pharmacology, molecular docking and lipid-omics were employed to investigate the potential mechanism of rosmarinic acid (RA) in alleviating food allergy. To obtain potential therapeutic targets for RA, database analysis platform such as database and analysis platform (TCMSP), Swiss Target Prediction, Pharm Mapper, Super Pred and Gene Cards were employed. The ''active ingredient-target'' protein-protein (PPI) network was constructed using Cytoscape software and the String database. The validation of molecular docking was performed using AutoDockTools software. Furthermore, a food allergy mouse model using ovalbumin (OVA) and lipid metabolism studies on mouse serum based on high-resolution mass spectrometry were applied to investigate the antiallergic effect of RA and the underling mechanism. Results showed that, through the network pharmacology analysis, a total of 46 associated target proteins were identified. The geno ontology (GO) enrichment analysis of the target proteins indicated that RA primarily exerted its effects through modulation of protein phosphorylation and the binding between glycosphingolipids, phospholipids and steroids. The kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that the associated targets were mainly enriched in the Th1/Th2 cell differentiation pathways, lipid metabolism and inflammatory bowel disease pathways. The results indicated that RA intervention could significantly suppress the elevation of allergic mediators in the serum of mice sensitizes with OVA. In addition, the RA intervention group showed a decrease in the levels of total cholesterol and triglycerides in the mouse serum. In lipidomics analysis, 25 and 36 differentially expressed lipid metabolites were screened in positive and negative ion modes, respectively. Enrichment analysis of the differentially expressed lipid metabolites indicated that the serum lipid metabolism in mice affected glycerophospholipid metabolism and sphingolipid metabolic pathways. Therefore, this study demonstrated that RA primarily exerted its alleviating effect on food allergies by regulating lipid metabolism and the body's inflammatory response. [ABSTRACT FROM AUTHOR]

Satureja rechingeri Jamzad (known as "Jatra" in Persian), which belongs to the Lamiaceae family, is a rich source of essential oil particularly carvacrol, and rosmarinic acid. Drought stress has a detrimental impact on the physiological and biochemical parameters of plants, leading to a decline in plant productivity. Melatonin (MT), a new plant growth regulator found abundantly in plants, has been found to enhance the plant's internal resistance to various environmental stresses. The present study aimed to examine the impact of exogenously applied MT on the agro-morphological, physio-biochemical, and phytochemical traits of S. rechingeri plants cultivated under different levels of drought stress. The results indicated that plants treated with 200 µM MT obtained the highest plant height, length and width of leaf, fresh, dry and drug weight under different drought stress levels. The highest values of relative water content (RWC) (93.5%) and chlorophyll content (15.4 mg/g FW) were recorded by MT 200 µM and 100 µM, respectively, in 100% FC. Drought stress treatments (40, 60, and 80% FC) without foliar spray of MT significantly enhanced the H2O2 content, electrolyte leakage, and malondialdehyde content in leaves, whereas MT treatment under drought stress significantly decreased the above parameters. The lowest H2O2 content (11.5 nmol/g), electrolyte leakage (3.08%), and malondialdehyde content (0.78 µM/g) were obtained by 200 µM MT at 100% FC. In contrast, drought stress treatment increased the total phenol content (TPC), rosmarinic acid (RA), essential oils (EOs) content and yield, and carvacrol. The maximum values of TPC (28.1 mg GAE/g DW), EOs content (3.63%) and yield (0.96%), and carvacrol (95.66%) were achieved by 200 µM MT at 40% FC. The highest RA content (7.43 mg GAE/g DW) was recorded in 100 µM MT at 40% FC. Thus, foliar spray MT has the potential to enhance plant growth through the mitigation of reactive oxygen species (ROS)-induced oxidative harm, as well as the augmentation of photosynthesis pigments, secondary metabolites such as phenolics, EOs levels, overall antioxidant scavenging capacity, and the preservation of RWC during periods of drought stress. [ABSTRACT FROM AUTHOR]

Magnetic drug delivery systems using nanoparticles present a promising opportunity for clinical treatment. This study explored the potential anti-inflammatory properties of RosA- CrFe2O4 nanoparticles. These nanoparticles were developed through rosmarinic acid (RosA) co-precipitation via a photo-mediated extraction technique. XRD, FTIR, and TEM techniques were employed to characterize the nanoparticles, and the results indicated that they had a cubic spinel ferrite (FCC) structure with an average particle size of 25nm. The anti-inflammatory and antioxidant properties of RosA- CrFe2O4 nanoparticles were evaluated by using LPS-induced raw 264.7 macrophages and a hydrogen peroxide scavenging assay, respectively. The results showed that RosA- CrFe2O4 nanoparticles had moderate DPPH scavenging effects with an IC50 value of 59.61±4.52μg/ml. Notably, these nanoparticles effectively suppressed the expression of pro-inflammatory genes (IL-1β, TNF-α, IL-6, and iNOS) in LPS-stimulated cells. Additionally, the anti-inflammatory activity of RosA- CrFe2O4 nanoparticles was confirmed by reducing the release of secretory pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-stimulated macrophages. This investigation highlights the promising potential of Phyto-mediated CrFe2O4-RosA as an anti-inflammatory and antioxidant agent in biomedical applications. [ABSTRACT FROM AUTHOR]

A number of dengue viruses can seriously impact public health, and their spread has long been a concern. The development and administration of antiviral drugs have played a crucial role in combating viral infections in recent years. These drugs have shown that they can effectively inhibit viral replication and alleviate associated viral complications. The aim of this article is to provide an overview of current evidence on the effectiveness of administered antiviral drugs in controlling viral replication and treating viral problems. In the present study, the PyRx tool was used to docked proteins and ligands. In summary, the present study shows that rosmarinic acid has remarkable docking values against various dengue viral targets. Specifically, it shows a docking value of -8.0 for DENV1-E111, -8.1 for the RNA-dependent RNA polymerase (NS5), -8.2 for the non-structural A chain protein 1 (NS1), and -8.6 for the RNA helicase. These results suggest that rosmarinic acid may have an antiviral effect against the virus's target proteins. Further research is needed to investigate the therapeutic effects of rosmarinic acid in fighting viral infections. In addition, many enzymatic activities of rosmarinic acid have been reported by the PASS (Prediction of Activity Spectra for Substances) tool. The present investigation led to the definitive conclusion that rosmarinic acid possesses remarkable antiviral properties. The present study is promising for future applications, particularly in the search for a drug molecule that can effectively combat a variety of viral infections. [ABSTRACT FROM AUTHOR]

Eelgrass, Zostera marina L., is vital to marine ecosystems, providing habitat, filtering pollutants, improving water quality, and serving as a source of bioactive compounds for pharmaceuticals. This study aimed to isolate and identify phenolic compounds from Z. marina, biotransform the main metabolite, rosmarinic acid (RA), and evaluate the anti-tyrosinase activity of these compounds. Various chromatographic techniques were employed to isolate compounds from Z. marina (1-4). Compound 1, exhibiting broad pharmaceutical activity, was biotransformed by Deinococcus geothermalis amylosucrase (DgAS) into two new glycosylated products (5-6). The isolated and biotransformed compounds were tested for anti-tyrosinase activity using a mushroom tyrosinase assay. Molecular docking and quantum chemical calculations were conducted to clarify the binding mode and reactivity of the compounds. The isolated compounds were identified via NMR and HR-MS as rosmarinic acid (RA) 1, methyl rosmarinate 2, methyl isorinate 3, and pinoresinol 4′-O-β-D-glucopyranoside 4. This is the first report of isolating and identifying compounds (2-4) from the Zosteraceae family. The glycosylated compounds were identified as rosmarinic acid 4-O-α-D-glucopyranoside 5 and rosmarinic acid 3′-O-α-D-glucopyranoside 6. Among all compounds, (4-6) showed significant tyrosinase inhibition, with rates of 55.5%, 22.3%, and 30.8%, respectively, compared to arbutin. The two glycosylated products exhibited better anti-tyrosinase activity than 1. In silico results aligned with in vitro findings. This study highlights Z. marina's potential as a source of polyphenolic compounds with significant anti-aging activity, emphasizing the discovery of new anti-aging ingredients to enhance quality of life. [ABSTRACT FROM AUTHOR]

Melissa officinalis (MO) is a valuable medicinal herb from the Lamiaceae family, MO extracts possess different beneficial effects, including anti-inflammatory, antioxidant, memory enhancer, anxiolytic, and anti-depression. It seems that phytochemicals found in MO including flavonols (luteolin and apigenin) and polyphenols (rosmarinic acid and caffeic acid) are responsible for the beneficial effects of MO. The present study aimed to assess the role of opioid receptors in the effect of MO in anxiety and obsessive-compulsive disorder (OCD) in stressed rats. Male hooded rats received oral administration of MO (50, 100 and 200 mg/kg), with or without intraperitoneal injection of naloxone (1 mg/kg), and were exposed to 30 min stress, then anxiety-like and OCD-like behaviors were evaluated using light/dark box and marble burying test. Our results showed that oral administration of MO has anxiolytic effects and a reduction in OCD-like behavior in stressed rats that could be inhibited by injection of naloxone. On the other hand, in silico study showed that phytochemicals found in MO have a possible affinity for opioid receptors. Taken together, these data revealed that the opioid receptors may be involved in the anxiolytic effect of MO in stressed rats. [ABSTRACT FROM AUTHOR]

Rosmarinic acid (RA) has demonstrated anticancer effects on several types of malignancies. However, whether RA promotes the anticancer effect of cisplatin on colorectal cancer cells remains sketchy. This study aimed to explore whether RA potentiates the cytotoxicity of cisplatin against colon cancer cells and the underlying mechanism. Cell viability, cell cycle progression, and apoptosis was evaluated using sulforhodamine B (SRB) assay, flow cytometric analysis, and propidium iodide/Annexin V staining, respectively. Western blotting was utilized to analyze signaling pathways. Our findings showed that RA significantly enhanced the inhibitory effect on cell viability and the induction of apoptosis on the colon cancer cell lines DLD-1 and LoVo. Signaling cascade analysis revealed that the combination of RA and cisplatin jointly induced Bax and caspase activation while downregulating Bcl-2, glutathione peroxidase 4 (GPX4), and SLC7A11 in DLD-1 cells. Moreover, caspase inhibitor and ferroptosis inhibitor significantly reversed the inhibition of cell viability in response to RA combined with cisplatin. Collectively, these findings demonstrate that RA enhances the cytotoxicity of cisplatin against colon cancer cells, attributing to the promotion of apoptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

Natural compounds have been used since the earliest civilizations and remain, to this day, a safer alternative for treating various dental problems. These present antimicrobial, anti-inflammatory, antioxidant, analgesic, and antimutagenic effects, making them useful in the prophylactic and curative treatment of various oral diseases such as infections, gingivitis, periodontitis, and even cancer. Due to the high incidence of unpleasant adverse reactions to synthetic compounds, natural products tend to gradually replace conventional treatment, as they can be just as potent and cause fewer, milder adverse effects. Researchers use several methods to measure the effectiveness and safety profile of these compounds, and employing standard techniques also contributes to progress across all medical disciplines. [ABSTRACT FROM AUTHOR]

Objectives: The aim is to discover α-glucosidase/acetylcholinesterase inhibitors as lead compounds from a traditional herbal prescription of Qi-Li-Qiang-Xin capsule (QLQX). Methods: A novel strategy combining time-based fractionation, LC-QTOF-MS, enzymatic activity assay, molecular docking and component-target association analysis was performed to discover α-glucosidase/acetylcholinesterase inhibitors from QLQX. Time-based fractionation combined with enzymatic activity assay was used to find the distribution period of active compounds in the herbal prescription. LC-QTOF-MS was used to analyze the structure of active compounds. Molecular docking was applied to explore the interaction between active compounds and targets. Results: According to time-based fractionation, the active components of QLQX for acetylcholinesterase were primarily concentrated in the highly polar region, whereas the active components for α-glucosidase were predominantly found in the moderately polar area. A total of 33 compounds were identified by comparing with chemical reference substances. Dihydrotanshinone Ⅰ (16.98 µM), hydroxysafflor yellow A (84.57 µM), salvianolic acid A (76.62 µM) and cryptotanshinone (112.68 µM) were identified as acetylcholinesterase inhibitors from QLQX. Similarly, rosmarinic acid (62.29 µM), isochlorogenic acid A (17.95 µM), 4,5-dicaffeoylquinic acid (117.93 µM), danshensu (207.88 µM), salvianolic acid A (1.31 µM), 3,4-dicaffeoylquinic acid (91.71 µM), formononetin (67.26 µM), ginsenoside Rd (3.43 µM), ginsenoside Rb1 (26.37 µM) and ginsenoside F1 (18.79 µM) were discovered as α-glucosidase inhibitors. Notably, salvianolic acid A inhibited both acetylcholinesterase and α-glucosidase. The results of molecular docking indicated that hydrogen bonds, hydrophobic interactions and Pi-Pi T-shaped interactions were crucial for inhibiting acetylcholinesterase. Meanwhile, hydrogen bonds, hydrophobic interactions and Pi-Pi stacked interactions were significant in suppressing α-glucosidase. Conclusion: QLQX contains numerous acetylcholinesterase and α-glucosidase inhibitors, demonstrating its potential therapeutic benefits for Alzheimer's disease and diabetes. [ABSTRACT FROM AUTHOR]

The metabolic syndrome and its associated co-morbidities have been recognized as predisposing risk factors for the development of metabolic-associated fatty liver disease (MAFLD). The present study reports on the beneficial effect of the Tanacetum balsamita methanol-aqueous extract (ETB) at 150 and 300 mg/kg bw on biochemical parameters related to oxidative stress, metabolic syndrome, and liver function in rat animal models with induced MAFLD. ETB was found to be non-toxic with LD50 > 3000 mg/kg and did not affect cell viability of hepatic HEP-G2 cells in a concentration up to 800 μg/mL. The pathology was established by a high-calorie diet and streptozotocin. Acarbose and atorvastatin were used as positive controls. At the higher dose, ETB reduced significantly (p < 0.05) the blood glucose levels by about 20%, decreased lipase activity by 52%, total cholesterol and triglycerides by 50% and 57%, respectively, and restored the amylase activity and leukocytes compared to the MAFLD group. ETB ameliorated oxidative stress biomarkers reduced glutathione and malondialdehyde in a dose-dependent manner. At 300 mg/kg, the beneficial effect of the extract on antioxidant enzymes was evidenced by the elevated catalase, glutathione peroxidase, and superoxide dismutase activity by 70%, 29%, and 44%, accordingly, compared to the MAFLD rats. ETB prevents the histopathological changes related to MAFLD. ETB, rich in 3,5-dicafeoylquinic, chlorogenic, and rosmarinic acids together with the isorhamnetin- and luteolin-glucoside provides a prominent amelioration of MAFLD. [ABSTRACT FROM AUTHOR]

Introduction: Thunbergia laurifolia is used in traditional Thai medicine to reduce fever and treat mouth ulcers. However, the quantitative analysis of chemical markers has not yet been officially defined. Objective: The objective of this study is to develop a high‐performance liquid chromatography (HPLC) method using a design of experiment (DoE) for the quantitative analysis of multicomponents by single marker (QAMS) and fingerprinting of the T. laurifolia aqueous extract. Materials and Methods: Critical variables were screened using a two‐level fractional factorial design, followed by the optimization of the selected variables using a central composite design. The validated method was applied for quality assessment based on QAMS and fingerprinting of the extract. Results: Optimum conditions of DoE for the analysis of caffeic acid, vicenin‐2, and rosmarinic acid were determined. The relative correction factors for caffeic acid and vicenin‐2 were calculated using rosmarinic acid as an internal reference standard, and their contents in 30 samples were determined. The differences between the external standard method (ESM) and QAMS were compared. No significant difference was observed in the quantitative determination, proving the consistency QAMS and ESM. HPLC fingerprints of T. laurifolia were established with 8 of 12 characteristic peaks that were structurally characterized using HPLC‐diode array detection‐electrospray ionization/tandem mass spectrometry. The similarity of the fingerprints in all samples was ≥0.74, and the pattern recognition of the characteristic peaks was satisfied. Conclusion: The proposed method efficiently detected multiple components of the T. laurifolia extract. Thus, the method is beneficial in providing references for enhancing the quality control of other herbal medicines. The DoE approach was applied to develop an HPLC method for analyzing multicomponents by a single marker as well as fingerprinting the T. laurifolia aqueous extract. There was no significant difference between QAMS and ESM. HPLC fingerprints in all samples were found to be comparable, with 12 characteristic peaks. The proposed method was successful in determining various components of the T. laurifolia aqueous extract. As a result, the approach has the potential to improve quality control for other herbal medicines. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is an environmental toxicant which cause adverse health effects including male infertility and DNA damage in the germ line via altered oxidative stress activity. Rosmarinic acid (RA), one of the most important polyphenols, is a natural dietary nutraceutical with antioxidant property on adverse effects of toxicants. This study seeks to assess the restorative effect of RA on PFOA-induced toxicity in male Wistar rats. Twenty adult male rats (150-250g) were categorized into four groups (n =5). Animals in group 1 (control) took distilled water. Animals in categories 2 - 4 which were induced toxicity by PFOA (20 mg/kg body weight) were treated with distilled water, RA (40 mg/kg body weight) and Vitamin E (180 mg/kg body weight) respectively. Treatment was for 14 days. The epididymis was used for sperm analysis while blood sample was used for hormonal marker assay. Induction of PFOA substantively (p<0.05) lowered body weight, testes weight, sperm count, sperm motility, sperm morphology, testosterone, LH and FSH when compared with the distilled treated water treated control animals. Treatment of PFOA-induced toxic rats with RA significantly (p<0.05) restored epididymal sperm count, motility and morphology as well as body and testicular weight and those of serum hormone biomarkers in relation to Vitamin E. Results indicated that rosmarinic acid restored epididymal, testicular and hormonal PFOA-induced toxicity. This suggests that RA could be a potential therapeutic agent against PFOA-induced testicular damage. [ABSTRACT FROM AUTHOR]

Featured Application: Utilization of Rosmarinus officinalis extracts and/or its bioactives as ingredients in functional products, foods, cosmetics, and pharmaceuticals, with anti-inflammatory health-promoting neuroprotective effects against inflammation-related neurodegenerative disorders, such as Alzheimer's and Parkinson's Diseases. Neurodegenerative disorders (NDs) are conditions marked by progressively escalating inflammation that leads to the degeneration of neuronal structure and function. There is an increasing interest in natural compounds, especially those from pharmaceutical plants, with neuroprotective properties as part of potential therapeutic interventions. Thus, the rich bioactive content of the perennial herb rosemary (Rosmarinus officinalis) is thoroughly reviewed in this article, with an emphasis on its pleiotropic pharmacological properties, including its antioxidant, anti-inflammatory, and neuroprotective health-promoting effects. In addition, a comprehensive analysis of the existing scientific literature on the potential use of rosemary and its bioactive constituents in treating neurodegenerative disorders was also conducted. Rosemary and its bioactives' chemical properties and neuroprotective mechanisms are discussed, focusing on their ability to mitigate oxidative stress, reduce inflammation, and modulate neurotransmitter activity. The role of rosemary in enhancing cognitive function, attenuating neuronal apoptosis, and promoting neurogenesis is outlined. Key bioactive components, such as rosmarinic acid and carnosic acid, are also highlighted for their neuroprotective act. The promising outcomes of the conducted pre-clinical studies or clinical trials confirm the efficacy of rosemary in preventing or alleviating Alzheimer's and Parkinson's diseases both in vitro (in cells) and in vivo (in animal models of NDs). From this perspective, the applications of rosemary's bio-functional compounds and extracts in the food, cosmetics, and pharmaceutical sectors are also presented; in the latter, we discuss their use against neurodegenerative disorders, either alone or as adjuvant therapies. This paper critically evaluates these studies' methodological approaches and outcomes, providing insights into the current state of the clinical research and identifying potential avenues for future investigation. All findings presented herein contribute to the growing body of literature and support the exploration of natural compounds as promising candidates for novel applications and neuroprotective interventions, paving the way for more applied scientific research. [ABSTRACT FROM AUTHOR]

Salvia miltiorrhiza is one of the famous traditional Chinese medicines for treating cardiovascular and cerebrovascular diseases. Tanshinone and phenolic acids are the main active compounds of Salvia miltiorrhiza, whereas the distribution patterns of the two kinds of components are still unclear among Salvia spp. In this work, high-performance liquid chromatography was applied to analyze the distribution patterns of major components in the roots and leaves of 58 Salvia spp. The results showed that the distribution patterns of tanshinone and phenolic acids in Salvia spp. varied significantly. Phenolic acid components such as rosmarinus acid, caffeic acid, and danshensu are widely distributed in the roots and leaves, and phenolic acids in the leaves of Salvia spp. are generally higher than that in roots. Tanshinones are mainly detected in the roots of Salvia przewalskii, Salvia trijuga, Salvia castanea, and Salvia yunnanensis. The content of major components of the different species varied significantly. The content of phenolic acids in most Salvia spp. generally followed the pattern of salvianolic acid B > rosmarinic acid > danshensu > caffeic acid both in the roots and leaves. Tanshinone IIA and cryptotanshinone were the main lipophilic components of Salvia spp. distributed in southwest China. A correlation between the distribution pattern of tanshinone and the genetic relationship of species was indicated in the work. This research systematically reveals the distribution patterns of tanshinone and phenolic acids in Salvia spp., providing a theoretical basis for the development and utilization of medicinal resources of Salvia. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) induces the production of reactive oxygen species, which may lead to cell injury and death. This study aimed to assess the effects of rosmarinic acid (RA) on testicular damage, oxidative stress, and apoptosis in streptozotocin (STZ)-induced diabetic albino mice. DM in four- to six-week-old BALB/c male albino mice was induced via 50 mg/kg STZ, IP for 5 days. Twelve mice were randomly assigned into each of following groups: a control group, a diabetic (DM) group, RA5 mg/kg and RA15 mg/kg groups, and DM + RA5 mg/kg and DM + RA15 mg/kg groups. RA doses were intraperitoneally injected six times a week for seven weeks. Diabetes increased blood sugar and HbA1c levels and decreased all assessed sperm parameters. Testicular tissues of the diabetic mice showed increased lipid peroxidation, decreased reduced glutathione levels and catalase and superoxide dismutase activities, and increased apoptosis associated with histological abnormalities. Both RA doses had no effects on final body weight, blood sugar, and HbA1c in the diabetic mice. It is concluded that the administration of the potent antioxidant RA to diabetic mice improved the redox status in testicular tissues, protected them from diabetes-induced oxidative damage, and improved the quality of spermatozoa, mostly in a dose-dependent manner, which suggests a potential application value of RA in treating DM-related testicular injury and perhaps other complications.

Tingting Zhang,1– 3,&ast; Jinglin Mi,1– 3,&ast; Xinling Qin,1– 3,&ast; Zhechen Ouyang,1– 3 Yiru Wang,1– 3 Zhixun Li,1– 3 Siyi He,1– 3 Kai Hu,1– 3 Rensheng Wang,1– 3 Weimei Huang1– 3 1Department of Radiation Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi, People’s Republic of China; 3Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumors (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimei Huang; Rensheng Wang, Department of Radiation Oncology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email huangweimei@gxmu.edu.cn; wangrensheng@gxmuhospital.cnBackground: Radiation-induced pulmonary fibrosis (RIPF) is a common complication after radiotherapy in thoracic cancer patients, and effective treatment methods are lacking. The purpose of this study was to investigate the protective effect of rosmarinic acid (RA) on RIPF in mice as well as the mechanism involved.Methods: m7G-tRNA-seq and tRNA-seq analyses were conducted to identify m7G-modified tRNAs. Western blotting, immunohistochemistry, northwestern blotting, northern blotting, immunofluorescence, wound-healing assays and EdU experiments were performed to explore the molecular mechanism by which RA regulates fibroblast-to-myofibroblast transformation (FMT) by affecting the exosomes of lung epithelial cells. Ribo-seq and mRNA-seq analyses were used to explore the underlying target mRNAs. Seahorse assays and immunoprecipitation were carried out to elucidate the effects of RA on glycolysis and FMT processes via the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) acetylation.Results: We found that RA had an antifibrotic effect on the lung tissues of RIPF model mice and inhibited the progression of FMT through exosomes derived from lung epithelial cells. Mechanistically, RA reduced the transcription and translation efficiency of sphingosine kinase 1 in lung fibroblasts by decreasing N7-methylguanosine modification of tRNA, downregulating the expression of tRNAs in irradiated lung epithelial cell-derived exosomes, and inhibiting the interaction between sphingosine kinase 1 and the N-acetyltransferase 10 protein in fibroblasts. Furthermore, the acetylation and cytoplasmic translocation of PFKFB3 were reduced by exosomes derived from irradiated lung epithelial cells, which following RA intervention. This suppression of the FMT process, which is triggered by glycolysis, and ultimately decelerating the progression of RIPF.Conclusion: These findings suggest that RA is a potential therapeutic agent for RIPF.Keywords: rosmarinic acid, exosomes, tRNA, N7-methylguanosine, radiation-induced pulmonary fibrosis

Abstract Satureja rechingeri Jamzad (known as “Jatra” in Persian), which belongs to the Lamiaceae family, is a rich source of essential oil particularly carvacrol, and rosmarinic acid. Drought stress has a detrimental impact on the physiological and biochemical parameters of plants, leading to a decline in plant productivity. Melatonin (MT), a new plant growth regulator found abundantly in plants, has been found to enhance the plant's internal resistance to various environmental stresses. The present study aimed to examine the impact of exogenously applied MT on the agro-morphological, physio-biochemical, and phytochemical traits of S. rechingeri plants cultivated under different levels of drought stress. The results indicated that plants treated with 200 µM MT obtained the highest plant height, length and width of leaf, fresh, dry and drug weight under different drought stress levels. The highest values of relative water content (RWC) (93.5%) and chlorophyll content (15.4 mg/g FW) were recorded by MT 200 µM and 100 µM, respectively, in 100% FC. Drought stress treatments (40, 60, and 80% FC) without foliar spray of MT significantly enhanced the H2O2 content, electrolyte leakage, and malondialdehyde content in leaves, whereas MT treatment under drought stress significantly decreased the above parameters. The lowest H2O2 content (11.5 nmol/g), electrolyte leakage (3.08%), and malondialdehyde content (0.78 µM/g) were obtained by 200 µM MT at 100% FC. In contrast, drought stress treatment increased the total phenol content (TPC), rosmarinic acid (RA), essential oils (EOs) content and yield, and carvacrol. The maximum values of TPC (28.1 mg GAE/g DW), EOs content (3.63%) and yield (0.96%), and carvacrol (95.66%) were achieved by 200 µM MT at 40% FC. The highest RA content (7.43 mg GAE/g DW) was recorded in 100 µM MT at 40% FC. Thus, foliar spray MT has the potential to enhance plant growth through the mitigation of reactive oxygen species (ROS)-induced oxidative harm, as well as the augmentation of photosynthesis pigments, secondary metabolites such as phenolics, EOs levels, overall antioxidant scavenging capacity, and the preservation of RWC during periods of drought stress. Graphical Abstract

To investigate the mechanism of rosmarinic acid in alleviating food allergy, an integrated approach, involving network pharmacology, molecular docking and lipid-omics were employed to investigate the potential mechanism of rosmarinic acid (RA) in alleviating food allergy. To obtain potential therapeutic targets for RA, database analysis platform such as database and analysis platform (TCMSP), Swiss Target Prediction, Pharm Mapper, Super Pred and Gene Cards were employed. The ''active ingredient-target'' protein-protein (PPI) network was constructed using Cytoscape software and the String database. The validation of molecular docking was performed using AutoDockTools software. Furthermore, a food allergy mouse model using ovalbumin (OVA) and lipid metabolism studies on mouse serum based on high-resolution mass spectrometry were applied to investigate the antiallergic effect of RA and the underling mechanism. Results showed that, through the network pharmacology analysis, a total of 46 associated target proteins were identified. The geno ontology (GO) enrichment analysis of the target proteins indicated that RA primarily exerted its effects through modulation of protein phosphorylation and the binding between glycosphingolipids, phospholipids and steroids. The kyoto encyclopedia of genes and genomes (KEGG) analysis indicated that the associated targets were mainly enriched in the Th1/Th2 cell differentiation pathways, lipid metabolism and inflammatory bowel disease pathways. The results indicated that RA intervention could significantly suppress the elevation of allergic mediators in the serum of mice sensitizes with OVA. In addition, the RA intervention group showed a decrease in the levels of total cholesterol and triglycerides in the mouse serum. In lipidomics analysis, 25 and 36 differentially expressed lipid metabolites were screened in positive and negative ion modes, respectively. Enrichment analysis of the differentially expressed lipid metabolites indicated that the serum lipid metabolism in mice affected glycerophospholipid metabolism and sphingolipid metabolic pathways. Therefore, this study demonstrated that RA primarily exerted its alleviating effect on food allergies by regulating lipid metabolism and the body's inflammatory response.

Endometritis is an inflammatory and histopathologic disease in uterine tissues that interferes with the proper decidualization and implantation of the embryo. In this study, rosmarinic acid (RA) is used as an anti-inflammatory agent that encapsulates in exosomes and is used to attenuate lipopolysaccharide (LPS)-induced endometritis and improve implantation. For this purpose, exosomes were loaded with RA and then administrated into the animal groups, including RA, exosome, RA plus exosome (RA + Exo), and RA-loaded exosomes (RALExo) groups. The concentrations of RA or exosomes used in this study were 10 mg/kg, and the compounds were injected into the uterine horn 24 h following the induction of endometritis. Upon the presence of inflammation detected by the histopathological method, the most proper groups were mated with male mice. The effect of the treatment group on the implantation rate, progesterone levels, and gene expressions were assessed by Chicago Blue staining, enzyme-linked immunosorbent assay (ELISA), and Quantitative PCR (qPCR), respectively. Results showed RALExo10 and RA10 + Exo10 groups improved pathological alterations, enhanced progesterone levels, increased implantation rate, as well as heightened expression levels of Leukemia inhibitory factor (LIF) and Mucin-16 (MUC-16) genes. Besides, the expression levels of inflammatory cytokines, including Transforming growth factor-β (TGF-β), Interlukine-10 (IL-10), Interlukine-15 (IL-15), and Interlukine-18 (IL-18), were regulated. Our findings indicated that the expression of LIF, Muc-16 genes as well as IL-18, were significantly correlated with serum progesterone concentrations and the implantation rate in the treatment groups. The RALExo10 and RA10 + Exo10 groups showed ameliorated implantation rates in experimental groups. [ABSTRACT FROM AUTHOR]

The significance of Thymus species in the scientific community is growing steadily due to their extensive utilization in traditional medicine, food industry, and pharmaceutical sector, owing to their abundance in essential oil and phytochemical content, rendering them commercially significant species. The current work focuses on conducting a comprehensive analysis of the ethanol extract and essential oil derived from the root and aerial portions of Thymus brachychilus Jalas, an endemic species that has not been previously investigated. Additionally, a novel GC-MS (gas chromatography–mass spectrometry) technique was developed to quantify the levels of triterpenoids, which are frequently found in many plants, particularly those belonging to the Lamiaceae family. The approach was then used to assess the triterpenoid content of the species. While the phenolic content of the species was determined by LC-MS/MS (liquid chromatography–tandem mass spectrometry), the chemical composition of triterpenoid, essential oil and flavor (aroma) of the plant was determined by GC-MS. Eucalyptol was the primary ingredient in both the essential oil and the flavor, accounting for 11.05% and 12.35%, respectively. In the DPPH and ABTS radical scavenging techniques, the root ethanol extract exhibited the greatest antioxidant activity with IC50 values of 26.70 ± 0.23 and 19.16 ± 0.11 µg/mL, respectively. There was a high level of urease (59.54 ± 1.67% at 100 µg/mL) inhibitory activity observed in the root ethanol extract in enzyme inhibition assays, as well as angiotensin (94.80 ± 0.56%), elastase (40.19 ± 0.39%), and collagenase (48.26 ± 0.12%) inhibition in the aerial ethanol extract. Moreover, the MCF-7 cell line for breast cancer had a strong cytotoxic impact when exposed to the essential oil of the species (vitality%: 1.45 ± 0.01 at 200 µg/mL. The LC-MS/MS and GC-MS studies revealed that the roots had a significant concentration of rosmarinic acid (15,801 µg analyte/g extract), but the aerial portions had a substantial quantity of ursolic acid (152,374 µg analyte/g extract). The plant exhibits potential in the food, cosmetic, and pharmaceutical sectors on account of its elevated levels of rosmarinic and ursolic acid, superior antioxidant capacity, and angiotensin and urease inhibitory effect. [ABSTRACT FROM AUTHOR]

Objective(s): Right ventricular hypertrophy (RVH) often results in failure of the right ventricle or even the left ventricle. Rosmarinic acid (RA), a natural polyphenol, is commonly found in Boraginaceae species and some species of ferns and hornworts. This study looked at how RA affects oxidative stress and left ventricular hemodynamic functions as well as RVH in monocrotaline (MCT) induced RVH model rats.Materials and Methods: To cause RVH, MCT (60 mg/kg) was intraperitoneally (IP) injected. Rats were given saline or RA (10, 15, and 30 mg/kg, gavage, over 21 days). In anesthetized rats, the lead II electrocardiogram was recorded. The hemodynamic functions of the isolated heart were measured using the Langendorff apparatus (at constant pressure). Investigations were made into the right ventricular hypertrophy index (RVHI), the activities of superoxide dismutase, catalase, glutathione, and Wnt and β-catenin gene expressions in the left ventricle. H&E staining was used.Results: A significant decline in electrocardiogram parameters and anti-oxidant enzyme activities, an increase in QTc (Q-T corrected) intervals, MDA (Malondialdehyde), RVHI, and Wnt/β-catenin gene expression, and also significant changes in the hemodynamic parameters were demonstrated in the MCT group. RA improved the above-mentioned factors.Conclusion: According to the findings, RA may act as a cardioprotective agent against cardiovascular complications brought on by RVH due to its capacity to boost the activity of cardiac anti-oxidant enzymes and decrease the expression of genes involved in vascular calcification.

ABSTRACT: Noncovalent interactions of 4 selected phenolic acids, including gallic acid (GA), caffeic acid (CA), chlorogenic acid (CGA), and rosmarinic acid (RA) with lactoferrin (LF) were investigated. Compound combined with LF in the binding constant of CA > GA > RA > CGA, driven by van der Waals and hydrogen bonding for GA, and hydrophobic forces for others. Conformation of LF was affected at secondary and ternary structure levels. Molecular docking indicated that GA and CA located in the same site near the iron of the C-lobe, whereas RA and CGA bound to the C2 and N-lobe, respectively. Significantly enhanced antioxidant activity of complexes was found compared with pure LF, as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(2-ethylbenzothiazoline-6-sulfonate) (ABTS), and ferric reducing antioxidant power (FRAP) models. Caffeic acid, CGA, and RA significantly decreased the emulsifying stability index and improved foam ability of LF, and the effect of CA and RA was the most remarkable, respectively.

The present study aimed to investigate the effect of covalent coupling with the dietary polyphenol rosmarinic acid (RA) on the structure and properties of β-lactoglobulin (β-LG). β-LG-RA complexes were prepared using the free radical and alkaline methods. The structural changes of β-LG after coupling with RA were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared (FTIR) spectroscopy, ultraviolet (UV) absorption spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy. The antioxidant activity of β-LG and its complexes with RA was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation scavenging methods. Furthermore, their binding capacity to serum-specific immunoglobulin G (IgG) were evaluated using enzyme-linked immunosorbent assay (ELISA). The results revealed that the secondary structure of β-LG transformed from α-helix to β-sheet and random coil after RA covalent conjugation. The protein underwent changes in its secondary and tertiary structures. Additionally, compared to β-LG, the β-LG-RA covalent conjugates showed significantly enhanced antioxidant activity and reduced binding ability with serum specific IgG. In conclusion, covalent coupling with RA led to a significant improvement in the antioxidant activity of β-LG and a significant decrease in its binding capacity to serum-specific IgG by introducing phenolic hydroxyl groups.