Neurodegenerative disorders have recently emerged as one of the most difficult worldwide health challenges. Neuronal cell injury is a major factor in neurodegenerative diseases. There seems to be rising interest in developing effective neuroprotective drugs from natural sources. Nutraceuticals, or compounds produced from natural sources have shown neuroprotective effects in both in vitro and in vivo models of neuronal cell death and neurodegeneration. Carnosic acid (CA), a natural compound majorly obtained from rosemary and other herbs, has emerged as a promising neuroprotective agent in neurodegenerative diseases, particularly Alzheimer's and Parkinson's. This review covers the latest findings on the methods by which carnosic acid mitigates key pathological features such as oxidative stress, neuroinflammation, apoptosis, and protein aggregation as well as other pathways related to Parkinson's and Alzheimer's disease induction. Furthermore, we describe preclinical and clinical research that demonstrates the ability of carnosic acid to improve cognitive function and motor performance. This study will give a detailed overview of carnosic acid as a possible therapeutic agent, opening the path for future research into viable therapies for Alzheimer's and Parkinson's disorders.

SummaryThe prevention and treatment of neurodegenerative diseases are a critical global public health concern. The search for novel therapeutic strategies, including the development of new, innovative, effective, and safe medicinal products, as well as the elucidation of their mechanisms of action, represents a rapidly expanding area of scientific research. A promising medicinal plant that has generated renewed therapeutic interest in recent years is rosemary (Rosmarinus officinalis L.), which exhibits a wide spectrum of pharmacological activities. This review provides a concise summary of the current state of knowledge regarding the neuroprotective potential of rosemary and its bioactive constituents, which include rosmarinic acid, carnosic acid, ursolic acid, carnosol, as well as essential oil fractions and aqueous–ethanolic and ethanolic extracts. These effects are mediated through multiple mechanisms at the molecular, biochemical, and cellular levels, including inhibition of cholinesterases, modulation of the dopaminergic system, and regulation of oxidative stress and inflammatory mediators. Furthermore, rosemary has been shown to counteract the deleterious effects of β-amyloid, attenuate scopolamine-induced amnesic effects, and exert cytoprotective activity against numerous neurotoxic compounds of endogenous or environmental origin (xenobiotics), such as aluminium chloride, bisphenol, lipopolysaccharides (LPS; e.g. from Escherichia coli and Salmonella spp.), ibotenic acid (from Amanita muscaria), chlorpyrifos (an organophosphate pesticide), 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenylpyridinium (MPP⁺), paraquat (1,1′-dimethyl-4,4′-bipyridinium dichloride), and acrylamide (ACR). Available clinical studies have also been analysed, indicating improvements in various types of memory following rosemary administration. The current state of knowledge was analysed using a selective review of the literature from PubMed, SCOPUS, and ScienceDirect (Elsevier), selecting relevant keywords and restricting the scope to the past ten years.

This study investigates the use of RADA16 hydrogels for delivering carnosic acid (CA) in glaucoma treatment. Rheological tests at 0.5% (w/v), 1% (w/v), and 2% (w/v) concentrations showed significant elasticity, with Young's moduli of 30.18Pa, 16.22Pa, and 26.66Pa, respectively. The 1% (w/v) concentration had the lowest stiffness, ideal for intravitreal injection. SEM revealed the hydrogel's porous microstructure. The RADA16-CA system provided sustained CA release over 72h, peaking at 6h. In vitro, high CA concentrations (≥ 256μg/mL) were cytotoxic, but RADA16 and RADA16-CA enhanced cell proliferation. RADA16-CA demonstrated superior efficacy and biocompatibility. In an acute ocular hypertension model, RADA16-CA improved retinal health in rats by reducing retinal nerve fiber layer thickness, ROS-positive cells, and pro-inflammatory cytokines, while boosting cell survival and antioxidant activity.These findings highlight the potential of the RADA16-CA sustained-release system as an optimized approach for glaucoma treatment.

Helicobacter pylori (H. pylori) is a significant global human pathogen intricately linked to gastritis, peptic ulcers, and gastric cancer. The escalating challenge of antimicrobial resistance and the adverse effects of conventional antibiotics on the gut microbiome necessitate the development of novel, targeted therapeutics. In this study, we demonstrate that carnosic acid (CA), a natural compound derived from traditional Chinese medicine, exhibits potent and specific anti-H. pylori activity in vitro, with no detectable resistance observed after prolonged serial passaging. CA also displayed enhanced antibacterial efficacy under physiologically relevant acidic conditions, correlating with its strong inhibition of urease, a key colonization factor for H. pylori. Beyond urease suppression, CA acted through multiple mechanisms, including inhibiting biofilm formation and disrupting mature biofilms, impairing bacterial motility, and compromising cell membrane integrity. In vivo, the combination of CA and omeprazole achieved superior eradication in a mouse model of multidrug-resistant H. pylori infection compared to standard triple therapy. Furthermore, CA treatment showed negligible toxicity to host tissues and minimal disruption to the diversity and composition of the gut microbiota. These findings position CA as a promising lead compound against drug-resistant H. pylori, offering a multi-targeting and microbiota-friendly strategy to combat this pathogen.

Multivariate analysis and ADME profiling of Rosmarinus officinalis L. leaf vs. stem extracts: Extraction method-driven bioactivity and pharmacokinetic implications.

Carnosic acid ameliorates methotrexate-induced male infertility: targeting testicular redox imbalance and nitric oxide/CGMP signaling.

Drug-loaded nanomicelles with ROS-responsive controlled release of carnosic acid for the treatment of ulcerative colitis

Depression is one of the most common mental disorders, and more than half of individuals with depression have reduced or discontinued antidepressant use due to side effects. Medicinal plants are safer, cheaper, and more readily available than synthetic medications. This study will employ bioinformatics to assess the impact of compounds discovered in plants used in traditional Persian medicine (TPM) on key proteins involved in depressive pathways. Compounds derived from plants used in TPM for the treatment of depression were identified and subsequently evaluated for ADME properties and toxicity. The potential target genes of these compounds, along with genes associated with depression, were identified, and the intersecting genes were selected to construct a protein-protein interaction (PPI) network. Molecular docking analysis of the plant compounds and their key target proteins was conducted, followed by the selection of the most effective compound based on molecular dynamics (MD) simulation. In this study, 23 genes were identified as target genes of the plant compounds, and 582 genes associated with depression were identified, nine of which were shared, including ABCB1, AKT1, CAT, CDH1, CYP2B6, ESR1, ESR2, PPARG, and TRPV1. The PPI network identified ABCB1, AKT1, CDH1, ESR1, and PPARG as key proteins. Among them, ABCB1 and AKT1 exhibited favorable docking energies with carnosic acid. MD simulations further revealed the stability of the ABCB1-carnosic acid and AKT1-carnosic acid complexes. Our findings indicate that carnosic acid may represent a potential therapeutic option for the treatment of depression. However, further in vivo and clinical trials are required to validate these findings.

Plants have evolved sophisticated innate immune systems to combat pathogens, starting with pattern recognition receptors that detect microbial signals to trigger PAMP-triggered immunity (PTI), countered by pathogen effectors that lead to effector-triggered immunity (ETI) via resistance proteins. Systemic defenses like salicylic acid-driven systemic acquired resistance (SAR) and jasmonic acid/ethylene-dependent induced systemic resistance (ISR) amplify protection. Specialized metabolites, such as carnosic acid, selectively activate JA/ET pathways against necrotrophs, such as Botrytis cinerea, in Arabidopsis thaliana, as shown by phenotypic and gene expression analyses (e.g., PDF1.2 upregulation). Bioinformatics tools advance this field by enabling transcriptome profiling, R-gene identification via databases such as PRGdb, and the prediction of stress-responsive pathways, offering future insights for crop improvement and chemical defense studies.

Poly(2-oxazoline) (POx) amphiphilic block copolymers are highly effective carriers for poorly water-soluble small molecules, yet the structural features governing drug incorporation remain incompletely understood. Motivated by the unusually high loading of diterpene taxanes in POx micelles, we systematically examined whether shared terpene motifs support micellization with POx using natural compounds with established safety profiles. Representative mono-, di-, and triterpenes-α-pinene, carnosic acid (CA), carnosol (CARN), squalene, lupeol, betulin, and ursolic acid-were evaluated with a well-defined POx triblock copolymer. Only the diterpenes CA and CARN showed efficient solubilization, forming small, stable, and uniform micelles, whereas α-pinene produced polydisperse assemblies and all triterpenes were insoluble. CA exhibited the best performance, forming reproducible 22-29nm micelles at a 2/10 (w/w) CA/polymer feed ratio with ~ 17% loading capacity and quantitative efficiency; higher feed ratios generated large, polydisperse aggregates by DLS and TEM. CA-loaded micelles were colloidally stable for at least 48h at room temperature, although CA chemical stability varied across batches. Lyophilization markedly improved stability, enabling 67-89% recovery upon reconstitution. Experimental solubilization data were further used to benchmark existing computer-aided prediction models, which failed to capture the behavior of several terpene classes, underscoring the need to expand their chemical space and incorporate environmental effects. Overall, a rigid diterpene scaffold combined with ortho-hydroxyl functionality emerges as a key determinant of POx incorporation, identifying CA as a robust and reproducible formulation candidate for further POx-based delivery and pharmaceutical development.

To explore the neuroprotective mechanisms of terpenoids, including their modulation of inflammation, mitigation of oxidative stress, regulation of apoptotic pathways, and promotion of neurogenesis, a wide variety of naturally occurring chemicals, known as terpenoids, have shown promise as neuroprotective agents for the treatment of Parkinson's disease (PD). In this paper, we summarize known methods, which include reducing oxidative stress, enhancing neurogenesis and neurotrophic factors, and modulating apoptotic signaling. In preclinical models of Parkinson's disease, compounds such as triptolide, andrographolide, carnosic acid, betulinic acid, and asiatic acid have demonstrated significant efficacy by modulating critical pathways, including the Nrf2/ARE, PI3K/Akt, and NF-κB pathways. In addition, terpenoids show potential as a treatment for PDrelated symptoms, such as impaired mitochondrial activity, protein misfolding, and blood-brain barrier breakdown. Although terpenoids have demonstrated some research potential, their limited target selectivity, poor solubility, and low bioavailability still hinder their clinical application. The primary objectives of future research should be to enhance formulations, explore methods for incorporating terpenoids into conventional pharmacotherapies, and investigate innovative drug delivery systems. Individualized PD therapy may be transformed by terpenoid-based personalized medicine techniques, in addition to genetics and high-throughput screening. Terpenoids should only be considered as a possible treatment option for PD after rigorous clinical trials that clarify pharmacokinetics and safety characteristics.

This study developed a green extraction paradigm for rosemary absolute oil (RAO) as a sustainable natural antioxidant to inhibit lipid oxidation in frying oils. RAO was prepared via three methods: heat reflux extraction (HRE) with n-hexane, solvent-free oil extraction (OE) using refined soybean oil, and ultrasound-assisted solvent-free oil extraction (UOE). Under optimized UOE conditions (solid-to-liquid ratio 1:10, 400W, 25°C, 13min), RAO yield reached 19.09%, with total phenolic content (TPC) of 347.16±2.81 mg GAE/g, significantly exceeding values from HRE and OE. UOE-RAO contained elevated concentrations of bioactive compounds: carnosic acid (CA, 89.45±1.89mg/g), ursolic acid (UA, 7.43±0.02mg/g), and carnosol (16.81mg/g), accompanied by a pronounced CA-to-carnosol conversion. In vitro antioxidant assays (DPPH) demonstrated UOE-RAO's potent radical scavenging activity (IC50: 71.26±0.81 μg/mL), on par with synthetic butylated hydroxytoluene (BHT). When fortifying soybean oil with 0.1% UOE-RAO, oxidative stability during 180°C frying was markedly enhanced: total polar materials (TPM) accumulation was retarded, extending oil usability from 31h (control) to 63h, while acid value (AV) remained consistently lower throughout frying. Differential scanning calorimetry (DSC) further validated improved oxidative resistance, with induction times for primary (12.75±3.51→14.14±0.20min) and secondary oxidation (40.47±6.02→61.41±3.10min) significantly prolonged. Collectively, these findings highlight that UOE enables the production of RAO with superior antioxidant efficacy, positioning it as a green, high-performance alternative to synthetic antioxidants for lipid-rich food processing, particularly high-temperature frying applications.

Nonenzymatic glycation of dairy products induced by α-dicarbonyl compounds (α-DCs) occurs during thermal processing, leading to the formation of advanced glycation end products (AGEs) that pose potential health risks to human health. Rosemary extract (RE) is a common food antioxidant additive. In this study, RE was employed to counteract two representative α-DCs, that is, methylglyoxal (MGO, 1mM) and glyoxal (GO, 1mM), during simulated thermal processing (75°C for 2h) of whey protein isolate (WPI, 7mg/mL). Results showed that RE (0.1, 1, and 2mg/mL) significantly suppressed MGO/GO-induced formation of fluorescent AGEs and concomitant glycoxidation products in a dose-dependent way. Western blotting analyses confirmed that RE interrupted the binding of MGO/GO to WPI, as evidenced by the reduced immunoreactivity of modified proteins. HPLC analysis revealed near‑complete elimination of MGO and GO at 2mg/mL RE. Molecular docking simulations further demonstrated that the representative compounds (rosmarinic acid and carnosic acid) exhibited strong binding affinities to the protein and effectively shielded potential glycation sites from MGO/GO. However, phenol-protein interactions may compromise the structural properties of WPI proteins at high RE concentrations, which was manifested by the reductions in surface hydrophobicity and intrinsic fluorescence. Collectively, RE was validated as an effective anti-glycation agent to alleviate α-DC-mediated damage in dairy proteins in this study, which might extend its role from a conventional food antioxidant to a potent glycation inhibitor.

Integrated genetic and -omics analyses revealed Salvia officinalis genotypes high in carnosic acid content linked to distinct genetic backgrounds

Background: Colorectal cancer is the third most frequent cancer globally. Incidence rises with age and has been highest in developed countries, but it is rapidly increasing in many less developed countries and among younger generations in both developed and developing nations. MMP-7 is a key enzyme in the progression of colon cancer, making it a potential therapeutic target.Methods: This study used a computational screening method to determine the efficacy of natural terpenoids as MMP-7 inhibitors. The MMP-7 inhibitor TQI was used as a positive control. A total of 355 natural terpenoid compounds were gathered from literature and public databases. Each compound was obtained in SDF format, converted into 3D structures for molecular docking analyses. PyRx (0.8 version), utilizing the AutoDock Vina docking engine was employed for virtual screening through molecular docking.Results: Three potential candidates, retinol (vitamin A), carnosic acid, and gibberellic acid, were identified as showing strong binding affinities toward MMP-7 compared with the co-crystallized inhibitor TQI. ADMET analysis indicated compound-specific pharmacokinetic and safety profiles: retinol exhibited high predicted oral bioavailability but lower solubility, whereas carnosic acid and gibberellic acid showed more favorable non-toxicity and hERG safety percentiles.Conclusion: These findings highlight the promise of natural terpenoids as novel MMP-7 inhibitors in colon cancer treatment, necessitating further validation and experimental research to determine their efficacy and therapeutic potential.Keywords:Colon cancer, Natural compounds, Terpenoids, Computational analysis

Spectroscopic analysis reveals an opposite pattern between carnosic and rosmarinic acid concentrations in rosemary (Salvia rosmarinus).

The presented review article provides a systematic analysis of the current state and prospects for applying supercritical CO2 extraction technology to obtain extracts from spices raw materials for use in the food industry. The relevance of the study is driven by the rapid growth in consumer demand for food products with a natural composition ("clean label"), which requires manufacturers to completely abandon traditional oleoresins obtained using synthetic organic solvents. The paper considers in detail the physicochemical principles of fluid extraction with carbon dioxide, which combines high selectivity, energy efficiency, and the ability to preserve thermolabile biologically active compounds in their native state.A critical comparative analysis of the three main types of extracts-oleoresins, essential oils, and supercritical CO2 extracts-was conducted. The authors highlight the key advantages of CO2 technology, including the absence of oxidative processes, the microbiological purity of the final product and the meal, and the possibility of flexible regulation of extractant prop-erties by changing pressure and temperature parameters. The analysis established that most existing scientific works focus on maximizing the total extract yield, while the issue of pur-poseful production of products with a specified ratio of volatile (flavour) and non-volatile (taste) fractions remains insufficiently studied.The review details the specifics of supercritical processing of common spices such as coriander, black pepper, nutmeg, and rosemary. In particular, it substantiates the need to con-trol the content of linalool in coriander, piperine in black pepper, macelignan in nutmeg, and phenolic diterpenes (carnosic acid and carnosol) in rosemary. Special attention is paid to the problem of the lack of uniform industry standards for the quantitative determination of essen-tial oils within CO2 extracts, which complicates their standardization during the development of formulations for complex flavor and aroma mixtures in the meat and confectionery indus-tries.The scientific novelty of the work is supported by references to the results of the au-thors' own experimental studies, which demonstrated the possibility of obtaining coriander extract with a yield of 9.0 % and an essential oil content of 28 %. This extract is identical to oleoresin in terms of physicоchemical characteristics but exceeds it in purity and safety. The concept of two-stage selective extraction is proposed, which allows for the separate recovery of flavoring fractions and natural antioxidants from a single raw material load. The practical significance of the review lies in forming a scientific basis for replacing synthetic additives with natural analogs, which will increase the competitiveness of domestic food products in the international market.

This study explores the biological synthesis of silver nanoparticles (AgNPs) using elicitors (ML) from the beneficial bacterium Bacillus G36 and evaluates their potential to enhance bioactive compound production in postharvest rosemary (Salvia rosmarinus Spenn.). To determine optimal synthesis conditions, different ratios of ML to AgNO3 1mM were mixed, for 24 h, evaluating a range of temperatures (28–37) and pH (5, 7, 9), with and without rosemary extracts, which were characterized by TEM, FTIR, XRD and Zpotential. Two NP were selected based on size and organic crown for biological assay on rosemary. The best conditions were a 1:1 (vv) mixture of ML and silver nitrate, pH 9, 37 °C, producing nanoparticles with an average size of 7.5 nm (S3). These small AgNPs have shown great biological activity. In contrast, adding rosemary extract (RE) to nucleation media, in order to increase reductive media potential, yielded larger particles (≈ 63.9 nm) and reduced their effectiveness. Biological assays showed that S3 AgNPs significantly increased total phenol and flavonol contents in rosemary when applied in postharvest, while ML alone did not, highlighting the better effect of elicitors when formulated in NP. Remarkably, only S3 AgNPs enhanced rosmarinic acid levels by 50%. Both S3 AgNPs and live Bacillus G36 cells also boosted diterpene (carnosic acid equivalents) concentrations. Despite effects on bioactives, only S3 and ML treatments increased the total antioxidant capacity of the extracts. Overall, the study demonstrates that biosynthesized S3 AgNPs from Bacillus G36 metabolites offer a sustainable and efficient approach to producing small, bioactive nanoparticles capable of improving and maintaining valuable phytochemicals in rosemary postharvest.

Rosmarinic acid (RA) and Carnosic acid (CA) are key compounds in Salvia rosmarinus Spenn. In order to perform rapid detection of RA and CA, a method based on hyperspectral imaging technology (HSI) and machine learning was proposed. Preprocessing involved the denoising and smoothing via Savitzky-Golay (SG) smoothing, Multiplicative Scatter Correction (MSC) and Standard Normal Variate (SNV). Then by comparing the results of Continuous Projection Algorithm (SPA), Competitive Adaptive Reweighted Sampling (CARS) and Interval Random Frog Leap (IRF). 57 and 47 most suitable characteristic wavelengths for RA and CA were selected by CARS, respectively, further the interpretability of the characteristic wavelength to the RA and CA was investigated. Prediction models of RA and CA were constructed based on characteristic wavelength using Random Forest (RF), Back Propagation Neural Network (BPNN), Partial Least Squares Regression (PLSR) and Long Short-Term Memory Network (LSTM). For RA, the SNV-CARS-PLSR model performed the best, the model’s correlation coefficients were 0.97 (R²c) and 0.96 (R²p), the Root Mean Square Error (RMSE) were 0.09 and 0.10 for training set and testing set. For CA, the SNV-CARS-LSTM model performed the best, the model’s correlation coefficients were 0.96 (R²c) and 0.92 (R²p), the Root Mean Square Error (RMSE) were 0.02 and 0.02 for training set and testing set. The result proved that the proposed method can accurately detect the content of RA and CA in Salvia rosmarinus Spenn. The research provides valuable insights for the development of HSI applying in real-time and online quality detection of Salvia rosmarinus Spenn.

Osteosarcoma (OS) is a highly aggressive bone cancer with limited therapeutic options. Carnosic acid (CA), a phenolic diterpene with well-established antioxidant properties, has shown anticancer activity, yet its mechanisms in OS remain unclear. In this study, we found that CA suppressed proliferation and induced apoptosis in human osteosarcoma cells in a dose-dependent manner. Mechanistically, CA activated the STING/IRF3 signaling pathway and enhanced nitric oxide (NO) production, factors closely linked to redox modulation and mitochondrial apoptotic signaling. Pharmacological inhibition or siRNA-mediated knockdown of STING, as well as blockade of NO synthesis, significantly reduced CA-induced apoptosis in vitro. In a xenograft mouse model, CA treatment suppressed tumor growth, and this effect was partially reversed by STING inhibition. These findings suggest that CA exerts antitumor effects in OS through modulation of innate immune and redox-related signaling pathways, supporting its potential as a therapeutic compound that links antioxidant and immunomodulatory actions.