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•Ten DES (neat and hydrated) were used for antioxidants extraction from rosemary leaves.•COSMO-RS was applied to estimate the solubility of rosemary biomolecules.•Choline chloride: ...1,2-propanediol led to promising results.•The optimal extract suppressed Salmonella strain with 64% of the antibiotic power.
Deep eutectic solvents (DES) have been explored as an alternative to hazardous solvents to extract natural bioactive compounds. In this work, choline chloride-based DES (neat and hydrated) were assessed in the extraction of phenolics from rosemary leaves. The DES studied on an initial screening showed a total phenolic content (TPC) up to 220% higher than the control. The solubilities of the main rosemary biocompounds, estimated by COSMO-RS, showed a positive correlation to TPC. Choline chloride:1,2-propanediol (CPH) was selected for further optimization. At the optimal conditions (65 °C, liquid: solid ratio of 40:1 and 50 %wt of water), the antioxidant activity and TPC were 80 mg of Trolox equivalent/g and 78 mg of gallic acid equivalent/g, respectively. The antimicrobial activity of the optimized extract revealed inhibition of 39–51% to all bacteria tested. In summary, an extract with good antioxidant and antimicrobial activities was obtained from rosemary leaves using CPH as solvent.
Salvia rosmarinus Spenn. is an aromatic/pharmaceutical plant belonging to the Lamiaceae family and is well-known for its pharmacological, culinary, and cosmetic properties, which seem to be ...associated with carnosic acid (CA)/carnosol (CO), content. Due to the high demand for S. rosmarinus genotypes rich in CA/CO, a multidisciplinary approach consisting of genetic, chemical and transcriptomic methodologies was utilized to evaluate 57 S. rosmarinus genotypes for high CA/CO content. These genotypes were analyzed for CA/CO contents, antioxidant activity, and genetic diversity from which 61% was detected within populations rather than among populations (39%). Transcriptomic analysis of two genotypes, G1 and A7 poor and rich in CA content, respectively, revealed a significant differential expression of genes involved in the CA biosynthetic pathway that was further confirmed by qRT-PCR, suggesting that ferruginol synthase (FS1) and carnosic acid synthase (CAS) can serve as potential molecular markers for high CA content in S. rosmarinus future breeding. The functional analysis of single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) within the coding regions of these genotypes revealed significant variants with high and moderate impact, potentially contributing to the increased CA accumulation in the A7 genotype.
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•Genetic analysis disclosed intrapopulation variance and moderate population structure.•Screening rosemary germplasm revealed genotypes with high and low CA accumulation.•Higher CA accumulation is due to the upregulation of CPS2, FS1, CAS genes.•InDels and SNPs with high and moderate impact, contribute to the increased CA accumulation.•CPS2, FS1 expression may be affected by the expression of C2H2, AP2/ERF, WD40.
Cancer is a serious global public health issue, and a great deal of research has been made to treat cancer. Of these, discovery of promising compounds that effectively fight cancer always has been ...the main point of interest in pharmaceutical research. Carnosic acid (CA) is a phenolic diterpenoid compound widely present in Lamiaceae plants such as Rosemary (Rosmarinus officinalis L.). In recent years, there has been increasing evidence that CA has significant anti-cancer activity, such as leukaemia, colorectal cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, stomach cancer, lymphoma, prostate cancer, oral cancer, etc. The potential mechanisms involved by CA, including inhibiting cell proliferation, inhibiting metastasis, inducing cell apoptosis, stimulating autophagy, regulating the immune system, reducing inflammation, regulating the gut microbiota, and enhancing the effects of other anti-cancer drugs. This article reviews the biosynthesis, pharmacokinetics and metabolism, safety and toxicity, as well as the molecular mechanisms and signaling pathways of the anticancer activity of CA. This will contribute to the development of CA or CA-containing functional foods for the prevention and treatment of cancer, providing important advances in the advancement of cancer treatment strategies.
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•Cancer is a huge global health burden. The challenges and serious side effects of developing drug resistance remain in cancer treatment. CA is a well-known natural compound that can prevent and treat various cancers.•The pharmacokinetics and metabolism, safety and toxicity, biosynthesis, as well as the molecular mechanisms and signaling pathways of the anticancer activity of CA are highlighted.•The potential of CA as a drug candidate was highlighted, providing a theoretical basis for the development of CA as an effective anti-cancer drug. In addition, CA exhibit broad application prospects in pharmaceuticals and functional foods.•Summarized the current research bottlenecks and possible solutions for developing the health value of CA.
Natural products in drug discovery are in high demand. Thus, researchers are driven to investigate existing and new technologies for effective separation and fractionation of bioactive compounds for ...industrial applications. Rosmarinus officinalis L. is a medicinal and aromatic herb whose compounds hold global interest for their diverse ethno-pharmacological properties in the medicinal field. This study includes the brief history, chemical composition and an extensive in-depth analysis of R. officinalis L. into various extraction technologies (traditional, current and those with promising future prospects). According to the reviewed studies, carnosic acid, carnosol and rosmarinic acid are the most investigated compounds because they are the primary contributors of the bioassays with the highest potential in natural drugs. For the production of fractions enriched with these compounds, pressurized liquid and supercritical (SC) fluid extraction followed by SC antisolvent fractionation are amongst the most extensively investigated technologies. Moreover, this study highlights the exploitation of deep eutectic solvent-based aqueous two-phase system for the production of enriched fraction from R. officinalis L.
•Traditional and advanced extraction technologies for rosemary are critically reviewed.•The advantages, limitations and main findings are highlighted.•Fractionation technologies for main constituents are discussed.•Future prospective technologies are proposed on the basis of the findings.
•The highest occupied molecular orbital (HOMO) was found to have an energy value of −5.788 eV and was majorly concentrated on the C4, C6 and C8 of the benzene ring of carnosic acid.•Carnosic acid was ...observed to have an αTotal, Δα and βTotal values that are 7.149, 7.121 and 3.901 times greater than the reference molecule indicating greater NLO properties.•Carsonic acid has better interaction with the nicotinic acetylcholine receptor when compared to diazepam and toleterodine.•Carsonic acid is a novel antispasmodic agent and represent a class of smooth muscle relaxant drug.
This research work focuses on the isolation, spectroscopic characterization (FT-IR, UV–vis, and NMR), density functional theory (DFT) studies, and the potential application of carnosic acid as an antispasmodic agent drug evaluated by molecular docking with various spasmolytic receptors proteins and the results compared with diazepam (DZP) and toleterodine (TTD) as standard drugs. All computational calculations of the isolated and spectroscopic determined structure was performed at the B3LYP/6–311++G(d,p) theoretical method within the framework of DFT approach. The theoretical vibrational assignments of the various functional groups along with the potential energy distributions (PEDs) were performed using the vibrational energy distribution analysis (VEDA) program and carefully compared with the experimental data. The natural bond orbital (NBO), nonlinear optics (NLO), and frontier molecular orbital (FMO) molecular electronic properties were also investigated and reported. While the binding affinity showed that carnosic acid has better interaction with the nicotinic acetylcholine receptor when compared to DZP and TTD, however, it is not a GABAa receptor agonist but a much better nicotinic acetylcholine receptor agent when juxtaposed with a similar agent like DZP and TTT as an antispasmodic agent as a smooth muscle relaxant.
Salvia officinalis has been used as a traditional remedy against diabetes in many countries and its glucose-lowering effects have been demonstrated in animal studies. The active compounds and their ...possible mode of action are still unknown although it has been suggested that diterpenes may be responsible for the anti-diabetic effect of
Salvia officinalis.
To investigate whether the reported anti-diabetic effects of
Salvia officinalis are related to activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ and to identify the bioactive constituents.
From a dichloromethane extract of
Salvia officinalis able to activate PPARγ several major metabolites were isolated by chromatographic techniques. To assess bioactivity of the isolated metabolites a PPARγ transactivation assay was used.
Eight diterpenes were isolated and identified including a new abietane diterpene being the epirosmanol ester of 12-
O-methyl carnosic acid and 20-hydroxyferruginol, which was isolated from
Salvia officinalis for the first time, as well as viridiflorol, oleanolic acid, and α-linolenic acid. 12-
O-methyl carnosic acid and α-linolenic acid were able to significantly activate PPARγ whereas the remaining metabolites were either unable to activate PPARγ or yielded insignificant activation.
Selected metabolites from
Salvia officinalis were able to activate PPARγ and hence, the anti-diabetic activity of this plant could in part be mediated through this nuclear receptor.
The mostly native species from Argentina are used in traditional medicine generally for the treatment of pain and inflammation, respiratory, gastro-intestinal and urinary disorders and as ...antiseptics.
Since these ailments may be associated with bacterial infections and that it is necessary to discover alternative compounds with antibacterial activity, 69 extracts from these plants were screened for their activity against pathogenic bacteria. The most effective extract was then submitted to bioguided isolation to obtain the compounds responsible for this activity.
Extracts and fractions were screened using agar dilution, and compounds using microbroth dilution methods. A large panel of pathogenic bacteria was used, especially methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Bioguided fractionation was performed using successive chromatographic techniques, while the chemical structures of the isolated compounds were determined by nuclear magnetic resonance (NMR). Additionally, a series of derivatives of the most active compound were prepared in order to study the chemical features required for achieving the antibacterial effect.
Lepechinia meyenii (Walp.) Epling (Lamiaceae) extract showed itself the most effective, with minimum inhibitory concentration (MIC) against Gram positive and negative bacteria ranging from 62.5 to 500 μg/mL, and showing better activity on MRSA than on MSSA. Activity-guided fractionation yielded the abietanes carnosol (1), rosmanol (2) and carnosic acid (3) as active principles, with MICs ranging from 15.6-31.2, 15.6–62.5 and 7.8–15.6 μg/mL, respectively against 15 MRSA strains, and 15.6–31.2, 31.2–62.5 and 7.8–15.6 μg/mL, respectively against 11 MSSA strains, maintaining higher activity against the resistant bacteria, as does the extract. In addition, Enterococcus faecalis was sensitive to 1–3 with MICs of 15.6–62.5 μg/mL. The structure activity analysis showed that 12-OH is necessary for remarkable activity, but methylation in C-20 significantly increased this, as observed with 20-methyl carnosate (5) displaying the greatest effect, even more so than 3, with MICs of 3.9 μg/mL against all the tested MRSA and 3.9–7.8 μg/mL against the MSSA.
The results of this study contribute to validate the traditional antibacterial use of species native to Argentina, particularly of L. meyenii. The chemical structures of the compounds obtained may aid the design of antibacterial agents, especially those effective against MRSA.
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PB125® is a phytochemical composition providing potent Nrf2 activation as well as a number of direct actions that do not involve Nrf2. Nrf2 is a transcription actor that helps maintain metabolic ...balance by providing redox-sensitive expression of numerous genes controlling normal day-to-day metabolic pathways. When ordinary metabolism is upset by extraordinary events such as injury, pathogenic infection, air or water pollution, ingestion of toxins, or simply by the slow but incessant changes brought about by aging and genetic variations, Nrf2 may also be called into action by the redox changes resulting from these events, whether acute or chronic. A complicating factor in all of this is that Nrf2 levels decline with aging, leaving the elderly less able to maintain proper redox balance. The dysregulated gene expression that results can cause or exacerbate a wide variety of pathological conditions, including susceptibility to viral infections. This review examines the characteristics desirable in Nrf2 activators that have therapeutic potential, as well as some of the patterns of dysregulated gene expression commonly observed during pulmonary infections and the normalizing effects possible by judicious use of phytochemicals to increase the activation level of available Nrf2.
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•Carnosic acid activates Nrf2 with minimal electrophilic toxicity to the cell.•Luteolin and withaferin A enhance Nrf2 activity and duration in the nucleus.•Nrf2 activation downregulates ACE2 and TMPRSS2, points-of-entry for SARS-Cov-2.•Nrf2 activation quells the hyperinflammatory “cytokine storm” caused by Covid-19.
The worldwide interest in the use of medicinal plants has been growing, and its beneficial effects being rediscovered for the development of new drugs. Based on their vast ethnopharmacological ...applications, which inspired current research in drug discovery, natural products can provide new and important leads against various pharmacological targets. This work pioneers an extensive and an updated literature review on the current state of research on
L., elucidating which compounds and biological activities are the most relevant. Therefore, a search was made in the databases PubMed, ScienceDirect and Web of Science with the terms 'rosemary', '
', 'rosmarinic acid' 'carnosol' and 'carnosic acid', which included 286 articles published since 1990 about rosemary's pharmacological activities and their isolated compounds. According to these references, there has been an increasing interest in the therapeutic properties of this plant, regarding carnosic acid, carnosol, rosmarinic acid and the essential oil. The present manuscript provides an updated review upon the most reported activities on
and its active constituents.
This work aimed to reveal the protective mechanism of CA against Dox (doxorubicin)-induced cardiotoxicity. In isolated murine cardiomyocytes, CA showed a concentration-dependent cytoprotective effect ...against Dox. Dox treatment significantly (p < 0.01) increased the formation of reactive oxygen species (ROS), increased NO levels, activated NADPH oxidase, and inactivated the cellular redox defense mechanism in cardiac cells, resulting in augmented oxidative stress in cardiomyocytes and rat hearts. Dox-induced oxidative stress significantly (p < 0.01) upregulated several pathogenic signal transductions, which induced apoptosis, inflammation, and fibrosis in cardiomyocytes and murine hearts. In contrast, CA significantly (p < 0.05–0.01) reciprocated Dox-induced cardiac apoptosis, inflammation, and fibrosis by suppressing oxidative stress and interfering with pathological signaling events in both isolated murine cardiomyocytes and rat hearts. CA treatment significantly (p < 0.05–0.01) countered Dox-mediated pathological changes in blood parameters in rats. Histological examinations backed up the pharmacological findings. In silico chemometric investigations predicted potential interactions between CA and studied signal proteins, as well as the drug-like features of CA. Thus, it would be concluded that CA has the potential to be regarded as an effective agent to alleviate Dox-mediated cardiotoxicity in the future.
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