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The utilization of genetically modified microbial cells for rosmarinic acid (RA) production is gaining increased attention as a cost-effective and sustainable approach. However, the substrate promiscuity of 4-coumarate: CoA ligase and RA synthase has been considered as a critical factor for low RA yields. In this study, we rationally engineered the substrate preference of 4-coumarate: CoA ligase (OPc4CL2) from Petroselinum crispum , resulting in a significant enhancement in RA production. Particularly, the introduction of the Y240C mutation led to a remarkable 176 % increase in RA yield. Subsequent enzymatic analysis of OPc4CL2 variants revealed diminished activity towards p -coumaric acid, resulting in insufficient time for the transformation of p -coumaric acid to 4-coumaroyl CoA to generate byproduct. Furthermore, to minimize the formation of undesired byproducts, the overexpression of 4-hydroxyphenylacetate 3-monooxygenase (OHpaB) and NADPH-flavin oxidoreductase (HpaC) was carried out to facilitate the conversion of p -coumaric acid to caffeic acid and 4-hydroxyphenyllactate to salvianic acid A, thus achieving a significant increase in RA yield of up to 329.9 mg/L (16.5 mg/g yield on glucose) in shake-flask cultivation. Finally, the engineered strain YRA113–24BHM achieved a notable RA production of 3.6 g/L (about 20.2 mg/g yield on glucose) by fed-batch fermentation. This study serves as a foundation for the sustainable biosynthesis of RA and other caffeic acid derivatives. • Structure-guided engineering of OPc4CL2 for the efficient production of Caffeic acid derivatives. • Mutant Y240C was obtained with 2.75-fold enhanced rosmarinic acid yield. • The enzymatic properties of OPc4CL2 and its mutants were investigated. • Combining protein engineering and expression regulation of rate-limiting enzymes. • Highest rosmarinic acid production ever reported in yeast (a 3.6 g/L titer and a 20.2 mg/g yield on glucose). [ABSTRACT FROM AUTHOR]

Objectives: To achieve a more beautiful and younger appearance, reducing wrinkles is a key concern. The process of wrinkle formation is complex and the development of truly effective cosmetic ingredients to reduce wrinkles remains a challenge. Recent studies have revealed a close relationship between wrinkles and skin thinning, suggesting that preventing skin thinning could also prevent wrinkle formation. In this study, we examined the role of extracellular adenosine triphosphate (eATP) in the progression of thinning, as eATP reportedly increases skin ageing factors, such as senescence‐associated secreted phenotype (SASP) factors in epidermal cells. We determined the effects of Mentha piperita leaf extract on suppressing eATP to reduce thinning and wrinkles. Methods: Adenosine triphosphate (ATP) levels were measured in normal human epidermal keratinocytes (NHEK) in the presence of M. piperita leaf extract. Dryness, high pH, and UVB radiation were used as extrinsic ageing factors. Intrinsic skin ageing was evaluated by comparing cells from adults (AD‐NHEK) and newborns (NB‐NHEK). A placebo‐controlled in vivo study was carried out with a formulation containing 1% M. piperita leaf extract. Results: The eATP levels were significantly higher in AD‐NHEK compared with that in NB‐NHEK cells. M. piperita leaf extract significantly decreased eATP levels in adult cells. Extrinsic ageing factors increased eATP levels in NHEK, whereas M. piperita leaf extract significantly suppressed eATP under all conditions. The active components of M. piperita leaf extract, luteolin glucuronide and rosmarinic acid, also decreased eATP. Moreover, compared with placebo lotion, M. piperita leaf extract‐formulated lotion markedly increased dermal thickness and reduced wrinkles associated with crow's feet and the neck area. Conclusion: We demonstrated for the first time that M. piperita leaf extract containing rosmarinic acid and luteolin‐7‐O‐glucuronide has the potential to reduce eATP release from epidermal keratinocytes. An increase in eATP was observed not only during inflammation but also during natural ageing. Furthermore, the in vivo experiment revealing that 1% M. piperita leaf extract‐containing lotion improved dermal thinning and wrinkles across multiple areas is attributed to the amelioration of dermal thinning. Thus, our data suggest the possibility of a novel cosmetic approach for reducing skin ageing by reducing eATP‐mediated dermal thinning. [ABSTRACT FROM AUTHOR]

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]

Numerous natural antioxidants have been developed into agents for neurodegenerative diseases (NDs) treatment. Rosmarinic acid (RA), an excellent antioxidant, exhibits neuroprotective activity, but its anti-NDs efficacy remains puzzling. Here, Caenorhabditis elegans models were employed to systematically reveal RA-mediated mechanisms in delaying NDs from diverse facets, including oxidative stress, the homeostasis of neural and protein, and mitochondrial disorders. Firstly, RA significantly inhibited reactive oxygen species accumulation, reduced peroxide malonaldehyde production, and strengthened the antioxidant defense system via increasing superoxide dismutase activity. Besides, RA reduced neuronal loss and ameliorated polyglutamine and ɑ-synuclein-mediated dyskinesia in NDs models. Further, in combination with the data and molecular docking results, RA may bind specifically to Huntington protein and ɑ-synuclein to prevent toxic protein aggregation and thus enhance proteostasis. Finally, RA ameliorated mitochondrial dysfunction including increasing adenosine triphosphate and mitochondrial membrane potential levels and rescuing mitochondrial membrane proteins' expressions and mitochondrial structural abnormalities via regulating mitochondrial dynamics genes and improving the mitochondrial kinetic homeostasis. Thus, this study systematically revealed the RA-mediated neuroprotective mechanism and promoted RA as a promising nutritional intervention strategy to prevent NDs. [ABSTRACT FROM AUTHOR]

Monarda fistulosa L. above-ground organs, collected at three phases of plant phenology, were investigated as potential raw materials for application in the food industry. They were evaluated regarding essential oil (EO) content, composition, and antimicrobial activity, as well as characteristics of phenolic fractions and antioxidant properties, which may determine health benefits and potential use in food preservation. The dominant constituent of leaf EO was carvacrol. In the inflorescence EO carvacrol content was especially high at the full flowering phase (45.12%), while during the fruit setting phase its content was lower than that of p-cymene (39.75%) and thymoquinone (25.04%). In the agar dilution test, leaf and inflorescence EOs inhibited the growth of the six tested microorganisms at the concentration range of 0.156–0.625 µL/mL. Leaves collected at the vegetative phase of plant growth were characterised by the highest content of rosmarinic acid and didymin. Inflorescences harvested during the flowering of plants were rich in linarin. Flavonoid content was highly correlated with antioxidant activity of extracts. Due to these properties, M. fistulosa extracts and essential oils could be used in the food industry as natural preservatives or antioxidants, thereby contributing to the development of safer and more sustainable food products. [ABSTRACT FROM AUTHOR]

Obesity is associated with fatty liver disease. Available therapies show modest efficacy, and nutraceuticals with good effectiveness and safety are largely investigated. We focused on five natural compounds, three plant phenolic compounds (carvacrol, rosmarinic acid, silybin), and two thyroid hormones (T2: 3,5-diiodo-l-thyronine; T3: 3,5,3'-triiodo-L-thyronine) as comparison, to assess their beneficial effects on two cellular models of hepatosteatosis and adipogenesis. All compounds ameliorated the lipid accumulation and oxidative stress in both models, but with different potencies. The peroxisome proliferator-activated receptors (PPARs) are pivotal controllers of adipogenesis and lipid metabolism. For the main isoforms, PPARγ and PPARa, we assessed their possible binding to the compounds by molecular docking calculations, and their expression pattern by real-time PCR. All compounds bind both PPARs with different affinity, while not all compounds affect their expression. The results may clarify the distinctive molecular mechanisms underlying the action of the five compounds in the different cell models with possible applications to treat obesity. [ABSTRACT FROM AUTHOR]

Increasing research is being directed toward the production of value-added products using plant extracts that are super-fortified with antioxidants. In this study, the extraction parameters for bioactive compounds (such as polyphenols) from Nasturtium officinale leaves and their antioxidant properties were optimized using response surface methodology. The optimization procedure examined the effects of the extraction temperature, time, and solvent composition on conventional magnetic stirring (ST). In addition, the impacts of two green techniques—pulsed electric field (PEF) and ultrasound (US)—were evaluated individually and in combination to assess their potential to enhance the extraction of the compounds. According to our findings, under the proposed extraction conditions (a combination of PEF, US, and ST as a extraction technique, 50% ethanolic solvent, for 30 min at 80 °C). N. officinale leaf extract proved to be an excellent source of bioactive compounds, with extracts containing rosmarinic acid (3.42 mg/g dried weight (dw)), chlorogenic acid (3.13 mg/g dw), total polyphenol content (28.82 mg of gallic acid equivalents (GAE)/g dw), and strong antioxidant properties. The FRAP method measured 57.15 μmol ascorbic acid equivalents (AAE)/g dw, while the DPPH radical scavenging activity method measured 47.55 μmol AAE/g dw. This study was carried out to evaluate and improve the concentration of bioactive compounds in N. officinale leaf extract, resulting in a product with multiple applications across the food, cosmetic, and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Objective To screen quality markers of Prunellae Spica and develop a method for determining their content. Methods The total component analysis were conducted by using a UPLC Q Exactive Plus Orbitrap high resolution liquid mass spectrometer. The fingerprints of Prunellae Spica were produced using HPLC. Twenty batches of Prunellae Spica were subjected to chemometric analysis to determine their contents and screen quality marker. In addition, a thorough examination of data from the literature was done to study the content changes in rosmarinic acid of Prunellae Spica from various origins and to evaluate the quality of Prunellae Spica. Results A total of 72 compounds from Prunellae Spica were found, 36 of them were organic acids, accounting for 50% of the total compounds. Eight common peaks were observed by fingerprint analysis of 20 batches of Prunellae Spica. Four key constituents including caffeic acid, rutin, hyperoside, and rosmarinic acid were identified. The similarity between the batches was higher than 0.900. The results of chemometric analysis indicated that rosmarinic acid may be a potential quality marker of Prunellae Spica. Rosmarinic acid content in twenty batches of Prunellae Spica showed that five batches were unqualified. After comprehensive literature analysis on 158 batches of Prunellae Spica was conducted, it was found that the overall qualification rate of rosmarinic acid content was 59.77%. Conclusion Rosmarinic acid is identified as a potential quality marker for Prunellae Spica, and its content can be used to assess the quality of Prunellae Spica from various origins. [ABSTRACT FROM AUTHOR]

Candida species, opportunistic pathogens that cause various infections, pose a significant threat due to their ability to form biofilms that resist antifungal treatments and immune responses. The increasing resistance of Candida spp. and the limited availability of effective treatments have prompted the research of natural compounds as alternative therapies. This study assessed the antifungal properties of RA against Candida species, focusing on its impact on C. albicans biofilms and the underlying mechanisms. The antifungal efficacy of RA was evaluated using the CLSI M27-A3 microdilution method on both fluconazole-susceptible and -resistant strains. Biofilm formation by C. albicans was assessed through a crystal violet assay, while its antibiofilm activity was analyzed using an MTT assay and field emission scanning electron microscopy (FESEM). Gene expression related to biofilm formation was studied using quantitative real-time PCR (qRT-PCR), and statistical analysis was performed with an ANOVA. Among the 28 Candida strains tested, RA exhibited minimum inhibitory concentration (MIC) values ranging from 160 to 1280 μg/mL. At a 640 μg/mL concentration, it significantly reduced the expression of genes associated with adhesion (ALS3, HWP1, and ECE1), hyphal development (UME6 and HGC1), and hyphal cAMP-dependent protein kinase regulators (CYR1, RAS1, and EFG1) in RAS1-cAMP-EFG1 pathway (p < 0.05). FESEM analysis revealed a reduction in hyphal networks and disruptions on the cell surface. Our study is the first to demonstrate the effects of RA on C. albicans adhesion, hyphae development, and biofilm formation through gene expression analysis with findings supported by FESEM. This approach distinguishes our study from previous studies on the effect of RA on Candida. However, the high MIC values of RA limit its antifungal potential. Therefore, more extensive research using innovative methods is required to increase the antifungal effect of RA. [ABSTRACT FROM AUTHOR]

Doxorubicin (Dox), an effective anticancer agent, is known for its genotoxic effects on normal cells. Phenolic compounds, renowned for their antitumor, antioxidant, and antigenotoxic properties, have gained prominence in recent years. This study investigates the individual and combined protective effects of rosmarinic acid (RA) and epigallocatechin gallate (EGCG) against Dox-induced genotoxicity using various in vitro test systems. The synergistic/antagonistic interaction of these combinations on Dox's chemotherapeutic effect is explored in breast cancer cell lines. Both RA and EGCG significantly mitigate Dox-induced genotoxicity in comet, micronucleus, and Ames assays. While Dox exhibits higher selectivity against MCF-7 cells, EGCG and RA show greater selectivity against MDA-MB-231 cells. The coefficient of drug interaction reveals a synergistic effect when RA or EGCG is combined with Dox in breast cancer cells. In conclusion, both EGCG and RA effectively reduce Dox-induced genetic damage and enhance Dox's cell viability-reducing effect in breast cancer cells. HIGHLIGHTS: Rosmarinic acid (RA) showed protective effect against doxorubicin-induced genotoxicity. Epigallocatechin gallate (EGCG) demonstrated pro-oxidant properties at high concentrations. EGCG and RA selectively targeted MDA-MB-231 cells. Synergistic effect was observed when EGCG or RA was administered together with Dox on breast cancer cells. [ABSTRACT FROM AUTHOR]

This is the first study to report on high performance thin layer chromatography (HPTLC) generated spectrophotometric data to systematically capture flavonoid compounds using optimized derivatization with either AlCl3 or NaNO2-AlCl3-NaOH as visualisation reagents. While the traditional AlCl3 colorimetric method using UV–Vis analysis provides valuable insights into the presence of flavonoids and allows derivation of the total flavonoid content (TFC) of a sample, HPTLC fingerprints obtained after spraying with AlCl3 or NaNO2-AlCl3-NaOH enable the visualization of the various flavonoids present in a sample based on their respective absorption shifts, thus complementing the traditional TFC assay. In this study, 40 different flavonoids representing different classes (flavonols, flavanolols, flavan-3-ol, flavones, flavanones, and isoflavonoids) were analysed. Upon derivatization with AlCl3 most of the investigated flavonoids recorded bathochromic shifts, yielding characteristic λmax values between 370 and 420 nm, while spraying with NaNO2-AlCl3-NaOH triggered hyperchromic shifts, and thus an increase in absorbance intensity in flavonoids with particular substitution patterns. A few non-flavonoid components with structural similarities to flavonoids (e.g., rosmarinic acid, gallic acid, aspirin, salicylic acid) served as the negative control in this study to determine whether the derivatization reagents allowed exclusive detection of flavonoids. The method was then applied to the analysis of flavonoid containing supplements as well as red clover honey to demonstrate the method's application in the analysis of natural products. [ABSTRACT FROM AUTHOR]

One of the challenges of the pharmaceutical and cosmetic industries is to deliver biochemical compounds that can be advantageous for the skin. Research on Boraginaceae taxa has confirmed their use in traditional medicine and proved the potential biological importance of various molecules in cosmetology. The main classes of valuable compounds associated with Boraginaceae taxa are fatty acids, including γ-linolenic acid, essential oils, phenolic acids (e.g., rosmarinic acid), flavonoids, anthocyanins, tannins, and saponins. Highly specific are naphthoquinone pigments (including shikonin) and allantoin. Another distinguishing feature is the accumulation of silica (silicon dioxide) in trichomes. Some taxa produce mucilages. However, pyrrolizidine alkaloids (PAs) with toxic properties are also found (mainly in Symphytum spp.); therefore, their applications should be avoided. Extracts or individual compounds of Boraginaceae plants are characterized by antioxidant, anti-inflammatory, antiseptic, anti-irritant, antiaging, and photoprotective activities. Boraginaceae products are widespread in the cosmetic industry as ingredients of creams, balms, lotions, gels, shampoos, lipsticks, perfumes, and deodorants. The most valuable for the cosmetic industry are raw materials obtained from the genera Alcanna Anchusa, Arnebia, Borago, Buglossoides, Cerinthe, Cordia, Echium, Ehretia, Eriodictyon, Glendora, Lappula, Lithospermum, Lycopsis, Macrotomia, Maharanga, Mertensia, Messerschmidia, Myosotis, Omphalodes, Onosma, Pulmonaria, Rindera, Symphytum, Trachystemon, and Trigonotis. Further research should focus on the search for active substances in other plants of the family. [ABSTRACT FROM AUTHOR]

Ocimum basilicum is a valuable plant widely consumed worldwide and considered a rich source of polyphenols. This study examined the impact of the polyphenolic fraction isolated from basil (ObF) on human normal colon epithelial cells and human colorectal adenocarcinoma cells, evaluating its anti-inflammatory and protective activity against oxidative stress. The phytochemical characterization of the fraction was performed using ultra-performance liquid chromatography (UPLC) with a photodiode detector (DAD) and mass spectrometry (MS). UPLC-DAD-MS revealed that ObF predominantly contains caffeic acid derivatives, with rosmarinic acid and chicoric acid being the most abundant. The fraction demonstrated high antioxidant potential, as shown by DPPH assays, along with significant reducing power (FRAP). Furthermore, it prevented the depletion of antioxidant enzymes, including superoxide dismutase and catalase, and decreased malonylodialdehyde (MDA) in induced oxidative stress condition. Additionally, it exhibited a significant protective effect against H2O2-induced cytotoxicity in human normal colon epithelial cells. Although it had no impact on the viability of adenocarcinoma cells, it significantly reduced IL-1β levels in the neoplastic microenvironment. Our study demonstrated that basil polyphenols provide significant health benefits due to their antioxidant and protective activities. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancers are still the leading cause of death worldwide. This is related, among other things, to the non-specific symptoms, especially in the initial stages, and also to the limited possibilities for treatment. Therefore, research is still being conducted to improve the detection of this type of cancer and increase the effectiveness of therapy. The potential application of natural compounds in cancer management deserves special attention. In the group of such products, there are polyphenolic compounds that reveal, e.g., anti-oxidative, anti-carcinogenic, anti-inflammatory, anti-diabetic, and neuroprotective properties. One of these polyphenols is rosmarinic acid, commonly found in plants such as the Boraginaceae and Nepetoideae subfamilies of the Lamiaceae (mint) family. A number of studies have considered the positive effects of rosmarinic acid in the treatment of many cancers, including gastrointestinal ones such as oral, stomach, pancreas, colon, and liver cancers. The main aim of this paper was to summarize the mechanisms of action of rosmarinic acid in gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Gastric and duodenal ulcers are increasingly becoming global health burdens. The side effects of conventional treatments such as non-steroid anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), antibiotics, and cytoprotective agents have necessitated the search for new medications. Plants are a rich source of active metabolites and herbal medicines have been used in the treatment of ulcers and cancers. In this study, we used in silico methods like molecular docking and MM-GBSA calculations to evaluate the effects of some anti-ulcer and anti-inflammatory phytochemicals on some key enzymes, cyclooxygenase (COX), and lipoxygenase (LOX), which are implicated in the protection and destruction of the gastric mucosa. The phytochemicals were retrieved from the literature and docked toward the binding sites of the three enzymes (COX-1, COX-2, and 5-LOX). Five compounds, rhamnetin, kaempferol, rutin, rosmarinic acid, and chlorogenic acid were observed to putatively bind to cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) but not to cyclooxygenase 1 (COX-1). The interaction mechanisms between these phytochemicals and the target proteins are discussed. The compounds' drug metabolism, pharmacokinetics, and toxicity have been evaluated to assess their suitability as potential next-generation anti-ulcer and anti-inflammatory drugs. [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]

Injectable hydrogels (IHs) have demonstrated huge potential in promoting repair of infected bone defects (IBDs), but how to endow them with desired anti-bacterial, immunoregulatory, and osteo-inductive properties as well as avoid mechanical failure during their manipulation are challenging. In this regard, we developed a multifunctional AOHA-RA/Lap nanocomposite IH for IBDs repair, which was constructed mainly through two kinds of reversible cross-links: (i) the laponite (Lap) crystals mediated electrostatic interactions; (ii) the phenylboronic acid easter bonds between the 4-aminobenzeneboronic acid grafted oxidized hyaluronic acid (AOHA) and rosmarinic acid (RA). Due to the specific structural composition, the AOHA-RA/Lap IH demonstrated superior injectability, self-recoverability, spatial adaptation, and self-reinforced mechanical properties after being injected to the bone defect site. In addition, the RA molecules could be locally released from the hydrogel following a Weibull model for over 10 days. Systematic in vitro/vivo assays proved the strong anti-bacterial activity of the hydrogel against Staphylococcus aureus (S. aureu s) and Escherichia coli (E. coli). Moreover, its capability of inducing M 2 polarization of macrophages (M φ) and osteogenic differentiation of bone marrow stromal cells (BMSCs) was verified either, and the mechanism of the former was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways and that of the latter was identified to be related to the calcium signaling pathway, extracellular matrix (ECM) receptor interaction and TGF-β signaling pathway. After being implanted to a S. aureus infected rat skull defect model, the AOHA-RA/Lap IH significantly accelerated repair of IBDs without causing significant systemic toxicity. Rosmarinic acid and laponite were utilized to develop an injectable hydrogel, promising for accelerating repair of infected bone defects in clinic. The gelation of the hydrogel was completely driven by two kinds of reversible cross-links, which endow the hydrogel superior spatial adaption, self-recoverability, and structural stability. The as-prepared hydrogel demonstrated superior anti-bacterial/anti-biofilm activity and could induce M 2 polarization of macrophages and osteogenic differentiation of BMSCs. The mechanism behind macrophages polarization was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways. The mechanism behind osteogenic differentiation of BMSCs was identified to be related to the ECM receptor interaction and calcium signaling/TGF-β signaling pathways. [Display omitted] [ABSTRACT FROM AUTHOR]

Rosemary extract (Rosmarinus officinalis) is a natural source of bioactive compounds with significant antioxidant properties. Among these, rosmarinic acid is celebrated for its potent antioxidant, anti-inflammatory, antimicrobial, and neuroprotective properties, making it a valuable component in both traditional medicine and modern therapeutic research. Neurodegenerative diseases like Alzheimer's and Parkinson's are closely linked to oxidative damage, and research indicates that rosmarinic acid may help protect neurons by mitigating this harmful process. Rosmarinic acid is able to bind cupric ions (Cu2+) and interfere with the production of reactive oxygen species (ROS) produced by copper through Fenton-like reactions. This study aims to further evaluate the contribution of rosmarinic acid within rosemary extract by comparing its activity to that of isolated rosmarinic acid. By using a detailed approach that includes chemical characterization, antioxidant capacity assessment, and neuroprotective activity testing, we have determined whether the combined components in rosemary extract enhance or differ from the effects of rosmarinic acid alone. This comparison is crucial for understanding whether the full extract offers added benefits beyond those of isolated rosmarinic acid in combating oxidative stress and Aβ-induced toxicity. [ABSTRACT FROM AUTHOR]

Rosmarinic acid (RA), a polyphenolic compound found in herbs, such as rosemary, basil, and mint, has garnered significant attention due to its potent antioxidant and anticancer properties. This review examined the molecular mechanisms underlying these properties and their potential application in cancer prevention and therapy. It focuses specifically on RA's role in modulating cancer-related pathways and presents a detailed analysis of recent advancements in this area. A systematic review of PubMed, Scopus, and Web of Science databases was conducted in accordance with PRISMA (Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, focusing on studies published between 2019 and 2024. A total of 25 articles providing evidence from in vitro, in vivo, and in silico studies were selected. These findings elucidate the role of RA in inhibiting tumor cell proliferation, inducing apoptosis, and preventing metastasis in various types of cancer through diverse mechanisms, including its antioxidant properties. Despite these promising results, RA's bioavailability challenges limit its therapeutic efficacy, underscoring the necessity for improved delivery methods. This review concludes that RA exhibits significant potential as a natural agent for cancer prevention and treatment, although further clinical trials are warranted. [ABSTRACT FROM AUTHOR]

A new triterpene saponin, 2, 3, 21, 23-tetrahydroxyolean-12-en-28-oic-acid-28-O-β-D- glucosyl-(2"→1')-β-D-glucoside (1), was isolated from the n-butanol extract of dried aerial parts of Salvia argentea L. (Lamiaceae) in addition to two known flavonoids, apigenin 7-O-β-D-glucoside (2), threo-guaiacylglycerol 3-O-[6-O-p-hydroxybenzoyl]-β-D-glucoside (3), luteolin 7-O-β-D-glucoside (4), verbascoside (5) and rosmarinic acid (6). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D-, 2D-NMR and HR-ESI-MS techniques and by comparing their NMR data with those reported in the literature. Compound 6 exhibited the highest antioxidant activity in DPPH assay (IC50<3.00 µg/mL) which was better than the standards BHA, BHT, Trolox and ascorbic acid. [ABSTRACT FROM AUTHOR]

Transformed roots of Salvia austriaca were cultivated for 45 days in various systems, including Erlenmeyer flasks, a temporary immersion system (TIS) bioreactor, and a mist-trickling bioreactor, under controlled light conditions. The mist-trickling bioreactor yielded the highest biomass, with fresh and dry weights of 155.4 g/L and 10.2 g/L, respectively. Quantitative UHPLC analysis of hydromethanolic extracts revealed the biosynthesis of significant phenolic acids: caffeic acid, rosmarinic acid, and salvianolic acid A. Among these, rosmarinic acid was the most abundant, with its concentration varying based on the cultivation system. The highest total phenolic acid content, 165 mg/L, was obtained in the mist-trickling bioreactor, demonstrating its superiority in both biomass production and phenolic acid biosynthesis. This study highlights the potential of mist-trickling bioreactors for optimizing growth and metabolite production in S. austriaca transformed root cultures. [ABSTRACT FROM AUTHOR]

Nowadays, eco-friendly extraction techniques are often used to develop natural plant extracts for commercial use. In the current investigation, Greek oregano (Origanum vulgare) phenolic extracts from different cultivated accessions were recovered employing ultrasonic-assisted extraction (UAE), microwave-assisted extraction (MAE), and accelerated solvent extraction (ASE). The phytochemical profile of the oregano extracts, as determined by spectrophotometric and chromatographic techniques, as well as antioxidant activity (ABTS, DPPH, and FRAP assays), was used to compare the three extraction approaches. The results showed that oregano phenolic extracts obtained by MAE held the highest total phenolic content, total flavonoid content, and also a higher content of the main phenolic compounds identified, rosmarinic acid, salvianolic acid B and carvacrol, as determined by LC-MS analysis, followed by those extracted by UAE and ASE. All of the tested extracts exhibited relatively high antioxidant activities, especially the MAE extracts. Oregano extracts produced by various extraction techniques were subjected to a multivariate data analysis to highlight differences in phytochemical profiles, and their correlation to antioxidant activity. According to our findings, it was evident that MAE offers more efficient and effective extraction of bioactive compounds in terms of obtaining phytochemical-rich oregano extracts, with applications in the food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Historically, botanical preparations have been used to improve human health. Their active ingredients are influenced by multiple factors such as intraspecies variations, environmental conditions, collection time and methods, and the part of the plant used. To ensure the efficiency and safety of these herbal drugs, qualitative and quantitative analyses are required. A Tessaria absinthioides decoction (DETa) was reported as having hypocholesterolemic, anti-inflammatory, cytotoxic, antitumor, and antioxidative properties. This work aimed to analyze DETa by correlating its chemical composition with cytotoxic and antioxidative properties, with the aim of promoting research on it as an anticancer agent. DETa collections (2017, 2018, 2019, and 2022) were analyzed by UHPLC-DAD, UHPLC-DAD-FLD, and UPLC-MS/MS; cytotoxicity was assessed on the MCF-7 breast cancer cell line; antioxidative capacity was evaluated by the DPPH and FRAP methods; and correlation analysis was used to determine biological and chemical markers. The results provide evidence that biological activities were consistent across the collections. Among the quantified compounds, apigenin, naringin, gallocatechin gallate, ginnalin A, myricetin, epicatechin, OH-tyrosol, quercetin, and chlorogenic, tessaric, p-coumaric, vanillic, caffeic, caftaric, ellagic, and rosmarinic acids correlated as bioactive and chemical markers. Moreover, tessaric acid could be established as a species marker. Altogether, these findings add relevant information to DETa properties, encouraging further exploration of its potential application as an anticancer botanical. [ABSTRACT FROM AUTHOR]

ABSTRACT Nanoparticles (NPs) are well‐known biostimulants in plant biotechnology, utilised to enhance the physical properties of plants and exhibit positive effects on them. The important key role is the most suitable type, effective dose and size of NP to be used in plant tissue culture systems. In this study, various concentrations of silver nanoparticles (AgNPs; 0, 25, 50, 75 and 100 μg L−1) were tested as elicitors in callus culture with the aim of enhancing secondary metabolite production in lemon balm (Melissa officinalis L.). According to the results obtained, callus formation rates have shown an increase in all applications compared to the control group. The highest callus formation, weight and diameter were observed in 50 μg L−1 application. In this application, the callus structure was compact and its colour was green. However, the aromatic compounds, neral and geranial increased significantly in 25 μg L−1 application. The maximum increase in phenolic compounds such as caffeic acid, chlorogenic acid, proto‐catechic acid, hesperidin and p‐coumaric acid was observed in the 75 μg L−1 AgNP and the highest increase in rosmarinic acid compound was determined in the 50 μg L−1 application. The study found that AgNP applications are an effective method for increasing the production of secondary metabolites in medicinal and aromatic plants, such as lemon balm, in vitro. [ABSTRACT FROM AUTHOR]

Ocimum tenuiflorum, commonly known as Tulsi, is revered in Ayurveda for its extensive medicinal properties. However, there is a need to consolidate current knowledge on its phytochemical constituents and their pharmacological activities to identify potential areas for further research and drug development. This review aims to bridge this gap by providing a comprehensive analysis of the bioactive secondary metabolites found in O. tenuiflorum, such as rosmarinic acid, oleanolic acid, luteolin, ursolic acid, and limonene, and their associated therapeutic effects. The review will highlight the pharmacological importance of these metabolites, which exhibit antioxidant, neuroprotective, anticancer, and anti‐inflammatory properties. Additionally, this study will explore the plant's wide range of beneficial qualities, including anti‐inflammatory, antioxidant, anticholinergic, pain‐relieving, antimicrobial, stress‐reducing, antidiabetic, anticancer, liver‐protective, ulcer‐inhibiting, antifungal, and wound‐healing attributes. Furthermore, this review focuses on the plant's potential in treating conditions such as asthma, persistent fever, tuberculosis, malaria, skin discoloration, itching, digestive issues, hemorrhoids, bone fractures, gout, urinary tract infection, and diabetes. By reviewing the current literature, the aim is to identify the gaps in the existing research and propose directions for future studies. This comprehensive review will serve as a valuable resource for researchers in the development and investigation of novel drugs derived from O. tenuiflorum. [ABSTRACT FROM AUTHOR]

This research presents an effective method for synthesizing new derivatives of bis(indole)methane using rosmarinic acid supported magnetic nanoparticles (nano‐Fe3O4@RA) as a catalyst. The reaction offers numerous advantages, such as high yield, catalyst reusability, short reaction time, product purification without column chromatography, and a simple procedure. These factors make it an attractive and efficient option in the field of bis(indole)methane construction. [ABSTRACT FROM AUTHOR]

Protein aggregation is associated with various diseases caused by protein misfolding. Among them, amylin deposition is a prominent feature of type 2 diabetes. At present, the mechanism of amylin aggregation remains unclear, and this has hindered the treatment of type 2 diabetes. In this study, we analyzed the aggregation process of amylin using the quantum dot (QD) imaging method. QD fluorescence imaging revealed that in the presence of 100 μM amylin, aggregates appeared after 12 h of incubation, while a large number of aggregates formed after 24 h of incubation, with a standard deviation (SD) value of 5.435. In contrast, 50 μM amylin did not induce the formation of aggregates after 12 h of incubation, although a large number of aggregates were observed after 24 h of incubation, with an SD value of 2.883. Confocal laser microscopy observations revealed that these aggregates were deposited in three dimensions. Transmission electron microscopy revealed that amylin existed as misfolded fibrils in vitro and that QDs were uniformly bound to the amylin fibrils. In addition, using a microliter-scale high-throughput screening (MSHTS) system, we found that rosmarinic acid, a polyphenol, inhibited amylin aggregation at a half-maximal effective concentration of 852.8 μM. These results demonstrate that the MSHTS system is a powerful tool for evaluating the inhibitory activity of amylin aggregation. Our findings will contribute to the understanding of the pathogenesis of amylin-related diseases and the discovery of compounds that may be useful in the treatment and prevention of these diseases. [ABSTRACT FROM AUTHOR]

Serum amyloid A (SAA) is one of the most important precursor amyloid proteins discovered during the study of amyloidosis, but its underlying aggregation mechanism has not yet been well elucidated. Since SAA aggregation is a key step in the pathogenesis of AA amyloidosis, amyloid inhibitors can be used as a tool to study its pathogenesis. Previously, we reported a novel microliter-scale high-throughput screening (MSHTS) system for screening amyloid β (Aβ) aggregation inhibitors based on quantum dot (QD) fluorescence imaging technology. In this study, we report the aggregation of human SAA (hSAA) in phosphate-buffered saline, in which we successfully visualized hSAA aggregation by QD using fluorescence microscopy and confocal microscopy. Two-dimensional and three-dimensional image analyses showed that most aggregations were observed at 40 μM hSAA, which was the optimal aggregation concentration in vitro. The accuracy of this finding was verified by a Thioflavin T assay. The transmission electron microscopy results showed that QD uniformly bound to hSAA aggregation. hSAA aggregation inhibitory activity was also evaluated by rosmarinic acid (RA). The results showed that RA, which is a compound with high inhibitory activity against Aβ aggregation, also exhibited high inhibitory activity against 40 μM hSAA. These results indicate that the MSHTS system is an effective tool for visualizing hSAA aggregation and for screening highly active inhibitors. [ABSTRACT FROM AUTHOR]

A combination of network pharmacology, molecular docking and ADME/drug-likeness predictions was employed to explore the potential of Salvia officinalis compounds to interact with key targets involved in the pathogenesis of T2DM. These were predicted using the SwissTargetPrediction, Similarity Ensemble Approach and BindingDB databases. Networks were constructed using the STRING online tool and Cytoscape (v.3.9.1) software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis and molecular docking were performed using DAVID, SHINEGO 0.77 and MOE suite, respectively. ADME/drug-likeness parameters were computed using SwissADME and Molsoft L.L.C. The top-ranking targets were CTNNB1, JUN, ESR1, RELA, NR3C1, CREB1, PPARG, PTGS2, CYP3A4, MMP9, UGT2B7, CYP2C19, SLCO1B1, AR, CYP19A1, PARP1, CYP1A2, CYP1B1, HSD17B1, and GSK3B. Apigenin, caffeic acid, oleanolic acid, rosmarinic acid, hispidulin, and salvianolic acid B showed the highest degree of connections in the compound-target network. Gene enrichment analysis identified pathways involved in insulin resistance, adherens junctions, metabolic processes, IL-17, TNF-α, cAMP, relaxin, and AGE-RAGE in diabetic complications. Rosmarinic acid, caffeic acid, and salvianolic acid B showed the most promising interactions with PTGS2, DPP4, AMY1A, PTB1B, PPARG, GSK3B and RELA. Overall, this study enhances understanding of the antidiabetic activity of S. officinalis and provides further insights for future drug discovery purposes. [ABSTRACT FROM AUTHOR]

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Dermal damage is inducible by several factors including UV exposure, oxidative stress and inflammation exacerbating skin senescence and degradation of the skin elastic fibers accumulated in ageing accordingly. Which, phenolics of food hydroxycinnamates with a myriad of health benefits are potentially applicable for ageing treatment. Particularly those of food hydroxycinnamic acids, i.e., caffeic, sinapic and rosmarinic acids, that would be efficient against skin ageing. Effectiveness of caffeic, sinapic and rosmarinic acids alleviating ageing was indicated in human dermal fibroblasts (HDF) and co-culture of human keratinocytes (HaCaT) and HDF. Caffeic acid was exhibited as the strongest (p < 0.01) anti-senescent phenolic examined. The studied food hydroxycinnamic acids were shown to induce collagen synthesis in aged HDF with the noted activities inhibiting MMP-1 and IL-6. Their photoaging protections were proved in the co-culture model with significant (p < 0.001) inhibitions against IL-6, IL-8, MMP-1 and MMP-9 (collagen and elastin degrading enzymes). Which, caffeic acid was demonstrated as the most potent photoaging agent among its counterparts. Caffeic, sinapic and rosmarinic acids were proved to be the efficient nutrients for ageing treatment. These functional food hydroxycinnamates are proven on their anti-senescent and photoprotection activities, and capable to maintain homeostasis of dermal cells. Food-derived hydroxycinnamic acids are therefore recommended for innovative product alleviates skin ageing. [ABSTRACT FROM AUTHOR]

This study reports the development of an effective high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of two analogs of rosmarinic acid (RA) in rat plasma, namely methyl (E)-2-(3-(3,4-difluorophenyl)acrylamido)-3-(3,4-dihydroxyphenyl)propanoate (A11) and methyl (E)-3-(3,4-dihydroxyphenyl)-2-(3-(3,4-dihydroxyphenyl)acrylamido)propanoate (A2). These analogs, featuring N atoms instead of O atoms, exhibit enhanced bioavailability and distinct pharmacological activities compared with RA. The HPLC separation was carried out on a C18 column (1.9 μm, 2.1 mm × 100 mm) coupled with a security guard C18 column (5 μm, 2.1 mm × 10 mm). A triple-quadrupole mass spectrometer equipped with an electrospray ionization ion source was utilized for ion generation. Pseudoephedrine hydrochloride was utilized as a standard, and a single-step protein precipitation method using isopropanol:ethyl acetate (v/v, 20:80) was employed for sample pretreatment. The developed method demonstrated excellent linearity over the concentration range of 5–750 ng/ml for both A11 and A2, with relative standard deviations of <15% and relative errors within 15% during daily course analysis. The method allowed for the unambiguous quantification and identification of A11 and A2 in vivo. The results of this study provide a meaningful foundation for evaluating the clinical applications of these analogs. [ABSTRACT FROM AUTHOR]

The plants Bauhinia rufescens, Ocimum basilicum and Salvadora persica are well known in traditional African medicine, and particularly in traditional Chadian medicine. They are commonly used to treat infectious diseases, inflammatory diseases, fevers, gastroenteritis and other medical conditions. The aim of this study was to perform a phytochemical screening to determine the antioxidant properties of different extracts and fractions from the three plants. Ethanolic extracts and solvent fractions were prepared and analyzed for total phenolic content (TPC), total flavonoid content (TFC) and total tannin content (TTC). LC-MS and an online screening HPLC-ABTS system identified phytochemicals with antioxidant activities. DPPH and ABTS reduction methods were used to test the extracts and fractions for their antioxidant potential. The results showed that the TPC of O. basilicum was higher than that of B. rufescens, ranging from 64.70 ± 5.2 to 411.16 ± 8.11 mgGAE/g DW. B. rufescens extracts and fractions, on the other hand, showed higher TFC, ranging from 69.5 ± 5.3 to 408.26 ± 8.42 mgQE/g DW, and higher TTC, ranging from 4.57 ± 2.45 to 62.19 ± 4.7 mgTAE/g DW. The maximum TPC, TFC and TTC in both plants were recorded in the ethyl acetate fractions. S. persica extracts and fractions showed a very low quantity of TPC, TFC and TTC. Based on LC-MS and HPLC-ABTS analysis, rosmarinic acid was identified as the major component in the extracts and all fractions of O. basilicum, and epicatechin, procyanidin B and quercetin were found in B. rufescens. S. persica did not exhibit specific substances with antioxidant activity and was therefore not considered for further assays. DPPH and ABTS results showed that ethyl acetate fractions of B. rufescens and O. basilicum have the strongest antioxidant activities. This study indicates that B. rufescens and O. basilicum are good sources of phytochemicals with antioxidant properties, suitable for medicinal use in Chadian communities. Additionally, the antioxidant-rich extracts from these plants hold significant potential for cosmetic development, enhancing skin health and protecting against oxidative-stress-induced damage. [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]

In this study, the antioxidant capacity, the effect on anti-acetylcholinesterase and anti-urease enzyme inhibition, and kidney stone-reducing effects of different extracts from M.myrtifolia. In addition, the phytochemical content of the bioactive methanol extract was analyzed by HPLC-DAD. The methanol extract showed strong DPPH (IC50:0.036 mg/mL) radical scavenging, Cu (II) ion (6.535 mmTroloxE) and Fe3+ (6.476 FeSO4) ion reducing antioxidant activity compared to other extracts. The methanol extract contained the highest amount of phenolic (400 mgGAE) and flavonoid (2.519 QuE) compounds. Moreover, the methanol extract had significant anticholinesterase (78.935%), anti-urease (71.014%) and calcium oxalate anti-crystallization (18.22%, 37.427%) activities. The findings show that all extracts exhibited varying amounts of antibacterial activity against Staphylococcus aureus. The bioactive methanol extract contained rosmarinic acid (31.35 µg), quercetin (12.99 µg) and chlorogenic acid (3.55 µg). The analyzed compounds are thought to contribute significantly to the pharmacological effect of the methanol extract. [ABSTRACT FROM AUTHOR]

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]

Featured Application: This research underscores the potential of Portuguese oregano and thyme accessions as rich sources of diverse phenolic compounds, particularly flavonoids and phenolic acids, which have been less studied compared to the dominant monoterpenes thymol and carvacrol. These compounds contribute significantly to the antioxidant properties of the plants, offering potential applications in the food industry. By incorporating these unique phenolic profiles into food formulations or active packaging, the antioxidant benefits can enhance the food shelf life, improve the nutritional value, and support health and well-being. This makes these accessions valuable for developing innovative, healthier food products. Oregano (Origanum vulgare L.) and thyme (Thymus mastichina L.) are popular aromatic plants used in the culinary sphere and are known for their antioxidant capacity. This study investigates the variability in the antioxidant capacity and phenolic profiles, focusing on flavonoids and phenolic acids, of oregano and thyme accessions from the Portuguese Bank of Plant Germplasm. The antioxidant capacity was assessed by measurements using the ferric-ion-reducing antioxidant power and DPPH radical scavenging activity assays, Total Phenolic Content, and individual phenolic compounds. Oregano extracts presented the highest total phenolic content (~2152 mg GAE/g DW), while thyme extracts showed the highest ferric-reducing antioxidant powers. However, both aromatic plants (~0.58 mmol TE/g DW) presented similar DPPH radical scavenging capacities. Rosmarinic acid was the major phenolic compound in methanolic extracts from oregano and thyme, but higher amounts were found in thyme (23.11 to 40.45 mg/g DW). The accessions of oregano and thyme showed statistical differences in the phenolic content and antioxidant capacity. This study provides valuable insights into the phenolic profile of Portuguese oregano and thyme, which could constitute potential sources of natural antioxidants and bioactive compounds, to be used by the food industry as natural food additives. [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]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with worldwide increasing incidence. Maternal separation (MS) stress at the beginning of life with its own neuroendocrine changes can provide the basis for development of ASD. Rosmarinic acid (RA) is a phenolic compound with a protective effect in neurodegenerative diseases. The aim of this study was to determine the effect of RA on autistic-like behaviors in maternally separated mice focusing on its possible effects on neuroimmune response and nitrite levels in the hippocampus. In this study, 40 mice were randomly divided into five groups of control (received normal saline (1 ml/kg)) and MS that were treated with normal saline (1 ml/kg) or doses of 1, 2, and 4 mg/kg RA, respectively, for 14 days. Three-chamber sociability, shuttle box, and marble burying tests were used to investigate autistic-like behaviors. Nitrite level and gene expression of inflammatory cytokines including TNF-α, IL-1β, TLR4, and iNOS were assessed in the hippocampus. The results showed that RA significantly increased the social preference and social novelty indexes, as well as attenuated impaired passive avoidance memory and the occurrence of repetitive and obsessive behaviors in the MS mice. RA reduced the nitrite level and gene expression of inflammatory cytokines in the hippocampus. RA, probably via attenuation of the nitrite level as well as of the neuroimmune response in the hippocampus, mitigated autistic-like behaviors in maternally separated mice. [ABSTRACT FROM AUTHOR]

This study determined the effects of cooking Taşköprü garlic, which is grown with a geographical indication in Turkiye, in three cooking materials (unbleached parchment paper (UP), bleached parchment paper (BP), and oven bag (OB)) and four vegetable oils (sunflower oil (SO), hazelnut oil (HO), corn oil (CO), and olive oil (OO)) on total phenolic content, antioxidant activity, phenolic compound profile, and chemical compound profile. The effects of cooking material (CM) and oil type (OT) on garlic samples' TPC were found to be insignificant (p > 0.05). However, cooking material (CM) and oil type (OT) impacted antioxidant activity. According to cooking material, statistically, the highest antioxidant activity with the DPPH method was identified in garlic cooked using UP and BP, while the highest antioxidant activity with the ABTS method was found in garlic cooked with BP and OB. The garlic samples roasted with the mentioned oils and cooking materials were analyzed by LC-MS/MS in terms of thirty-five phenolic compounds. However, only five of these compounds (quinic acid, fumaric acid, hesperidin, ferulic acid, and rosmarinic acid) were detected in the samples. The chemical components of the cooked garlic samples primarily consist of terpenoids (β–sitosterol and squalene). The use of cooking material affected the amount of squalene compound in all garlic samples cooked with olive oil. Among these samples, the lowest squalene rate (52.11%) was found in only roasted garlic. In addition, according to GC-MS results, we can say that the use of hazelnut oil and unbleached parchment paper in the roasting process has a protective effect on the cis-vaccenic acid compound, which is known to show anticancer properties. [ABSTRACT FROM AUTHOR]

Salmonella enteritidis (SE) infection disrupts the homeostasis of the intestinal microbiota, causing an intestinal inflammatory response and posing a great threat to human and animal health. The unreasonable use of antibiotics has led to an increase in the prevalence of drug-resistant SE, increasing the difficulty of controlling SE. Therefore, new drug strategies and research are urgently needed to control SE. Rosmarinic acid (RA) is a natural phenolic acid with various pharmacological activities, including antioxidant, anti-inflammatory and antibacterial properties. However, the protective effects and mechanism of RA on intestinal inflammation and the gut microbial disorders caused by SE have not been fully elucidated. In this study, RAW264.7 cells, MCECs and BALB/c mice were challenged with SE to assess the protective effects and mechanisms of RA. The results showed that RA enhanced the phagocytic ability of RAW264.7 cells, reduced the invasion and adhesion ability of SE in MCECs, and inhibited SE-induced inflammation in cells. Moreover, RA inhibited the activation of the NF-κB signaling pathway by upregulating TLR9 expression. Importantly, we found that RA provided protection against SE and increased the diversity and abundance of the intestinal microbiota in mice. Compared with infection control, RA significantly increased the abundance of Firmicutes and Acidibacteria and decreased the abundance of Proteobacteria, Epsilonbacteraeota and Bacteroidota. However, RA failed to alleviate SE-induced inflammation and lost its regulatory effects on the TLR9/NF-κB signaling pathway after destroying the gut microbiota with broad-spectrum antibiotics. These results indicated that RA attenuated SE-induced inflammation by regulating the TLR9/NF-κB signaling pathway and maintaining the homeostasis of the gut microbiota. Our study provides a new strategy for preventing SE-induced intestinal inflammation. [ABSTRACT FROM AUTHOR]

Herbal teas are used in South Africa as digestives to lower glycaemia and for other indications. However, the chemical composition of the infusions and their effect on enzymes related to metabolic syndrome is poorly known. The composition of infusions and methanol extracts of B. saligna (Scrophulariaceae), Lippia javanica, L. scaberrima, and Phyla dulcis (Verbenaceae) was assessed and the effect of the infusions and extract was determined towards α-glucosidase, α-amylase, and pancreatic lipase. The commercial herbal products were extracted separately with MeOH or hot water to obtain the extract/infusion for comparative studies. Total phenolic, total flavonoid and antioxidant capacity were assessed. The fingerprints of the MeOH extracts and infusions were compared by HPLD-DAD. The extract constituents were tentatively identified by HPLC-MS/MS and NMR analyses. From the extracts/infusions, 57 compounds were identified, including iridoids, phenylpropanoid glycosides, flavonoids, and caffeic acid derivatives, among others. The MeOH extracts and infusions showed strong inhibition towards α-glucosidase with IC50 in the range of 0.13–0.84 µg/mL for the phenolic-enriched infusion extract (PEI) and 0.47–0.50 µg/mL for the MeOH extracts, respectively. The P. dulcis PEI showed higher inhibition towards α-glucosidase, and the MeOH extract of L. scaberrima was better than the PEI. At 100 µg/mL, the PEI from the four herbal teas reduces the activity of α-amylase by 23.03–28.61%, with L. javanica as the most active tea. Three of the species are high in phenylpropanoid glycosides, while P. dulcis contains rosmarinic acid. Some 26 compounds were identified in the infusion from B. saligna, 28 from L. scaberrima, and 21 from P. dulcis. Four of them are common in all the teas, namely decaffeoylverbascoside, verbascoside, isoverbascoside, and tuberonic acid hexoside. Ten compounds occur in two of the teas and seventeen, fifteen, and eleven compounds were detected only in B. saligna, L. scaberrima, and P. dulcis, respectively. Most of the compounds are reported for the first time from the crude drug infusions. The results give some support for the traditional use of herbal teas as digestives and/or indications for diabetes. The chemical fingerprints set the basis for quality control of the crude drugs, based on the main constituents and differential compounds occurring in the samples. [ABSTRACT FROM AUTHOR]

Nowadays, interest in natural antioxidants (especially phenolics) for the prevention of oxidative stress-related diseases is increasing due to their fewer side effects and more potent activity than some of their synthetic analogues. New chemical and pharmacological studies of well-known herbal substances are among the current trends in medicinal plant research. Meadowsweet (Filipendula ulmaria) is a popular herb used in traditional medicine to treat various diseases (including rheumatic-, inflammatory- and tumor-related disease, etc.). The dry tincture of Filipendulae ulmariae herba, collected from the Bulgarian flora, was analyzed using the HPLC method and bioassayed for antioxidant, antiproliferative and DNA-protective activities against oxidative damage. The HPLC phenolic profile showed 12 phenolics, of which salicylic acid (18.84 mg/g dry extract), rutin (9.97 mg/g de), p-coumaric acid (6.80 mg/g de), quercetin (4.47 mg/g de), rosmarinic acid (4.01 mg/g de) and vanillic acid (3.82 mg/g de) were the major components. The high antioxidant potential of the species was confirmed by using four methods, best expressed by the results of the CUPRAC assay (10,605.91 μM TE/g de). The present study reports for the first time the highly protective activities of meadowsweet dry tincture against oxidative DNA damage and its antiproliferative effect against hepatocellular carcinoma (HepG2 cell line). Meadowsweet dry tincture possesses great potential to prevent diseases caused by oxidative stress. [ABSTRACT FROM AUTHOR]

Background and purpose: Renal injury is a serious disorder that can be caused by some diseases or agents. Rosmarinic acid (RA) is a natural and safe compound with powerful antioxidant and anti-inflammatory properties. In this study, the ameliorative effects of RA were assayed in folic acid (FA)-induced renal injury by involving the SIRT1/NOX1 pathway. Experimental approach: Thirty-six male C57/BL6 mice were divided into 6 groups (n = 6) including control, vehicle, FA, RA, FA + RA 50, and FA + RA 100. After 10 days, blood urea nitrogen (BUN), creatinine, and oxidative stress were measured. The expression of SIRT1 and NOX1 proteins was evaluated by western blot. Also, histopathological alterations were assayed by H&E and PAS staining methods. Findings/Results: BUN and creatinine were significantly higher in the FA group compared to the control group; however, their levels decreased after RA treatment in both doses. A significant decrease was observed in swelling, necrosis, and desquamation of tubular epithelial cells in the FA + RA 50 and FA + RA 100 groups compared to the FA group. RA in the animals receiving FA increased SIRT1 expression and the levels of GSH and SOD compared to the FA group. RA in the animals receiving FA showed a significant decrease in NOX1 expression and MDA level compared to the FA group. Conclusion and implications: The findings declared that the administration of RA has positive effects against renal damage induced by FA. The effect might result from involvement in the SIRT1/NOX1 pathway and thereby attenuation of oxidative stress.

ABSTRACT: 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.