Search Results (49)

Background: Tendinopathy remains a prevalent musculoskeletal disorder with limited disease-modifying pharmacotherapy. This study aimed to identify a reparative agent from the traditional medicinal herb Eucommiae Cortex and elucidate its mechanism of action. Methods: A bioactive fraction was first identified through a bioactivity-guided strategy using tenocyte cytoprotection and migration assays, then characterized by UHPLC-HRMS/MS. Its major constituent, aucubin (AU), which mirrors the fraction’s key pharmacological activities, was evaluated both in vitro and in vivo. In H₂O₂-injured tenocytes, AU’s effects on viability, apoptosis, oxidative stress (ROS, MDA, SOD) and inflammation (IL-1β, TNF-α) were assessed, with specific focus on estrogen receptor (ER) pathway involvement using pharmacological tools (17β-estradiol and (R, R)-THC). In a collagenase-induced Achilles tendinopathy model using male SD rats, AU’s therapeutic efficacy was evaluated via multimodal assessment: ultrasonography, histopathology (H&E, Masson’s trichrome, Sirius red), TEM, immunohistochemistry, and biochemical analysis of tissue markers. Results: AU effectively attenuated H₂O₂-induced tenocyte injury by enhancing viability, reducing apoptosis, and mitigating oxidative/inflammatory stress. These effects were mimicked by 17β-estradiol and reversed by the selective ERβ antagonist (R, R)-THC, indicating ERβ dependence. In vivo, AU treatment promoted structural and functional recovery, improved collagen maturity (increased Col I/Col III ratio and fibril diameter), suppressed matrix degradation (MMP-3, MMP-13) and apoptosis, and reduced oxidative stress and inflammation in tendon tissue. Conclusions: This study identifies aucubin as a novel phytoestrogenic compound from Eucommiae Cortex that promotes tendon repair through an ERβ-mediated mechanism. These findings position ERβ activation as a promising therapeutic strategy for tendinopathy and highlight AU as a promising lead compound for further development. Full article

This study investigates the antioxidant properties of aucubin (AU), an iridoid compound, focusing on its ability to scavenge hydroxyl radicals (^•OH) through its hydroxyl functional groups. Gaussian software was employed to model and validate the underlying antioxidant reaction mechanisms. Three primary pathways were examined: hydrogen atom transfer (HAT), sequential electron transfer-proton transfer (SET-PT), and sequential proton loss–electron transfer (SPLET). All calculations were performed using the M06-2X functional within density functional theory (DFT) at the def2-TZVP level, incorporating Grimme’s D3 dispersion correction and the implicit solvation model based on solute electron density (SMD) for water. Various thermodynamic parameters were determined to analyze and compare the antioxidant reactions, including the O-H bond dissociation energy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), electron transfer enthalpy (ETE), and proton affinity (PA) of the hydroxy groups. The results indicated that the HAT mechanism is the dominant pathway in the scavenging of ^•OH radicals by AU. The key active sites were identified as the 6-OH group in the aglycone structure and the 6′-OH group in the sugar moiety. Moreover, the polar aqueous environment promoted O-H bond homolysis to enhance the antioxidant activity. Full article

Scrophularia aestivalis Griseb. is a Balkan endemic species whose phytochemical composition and medicinal properties have not been previously investigated. The therapeutic potential of Scrophularia species has attracted considerable attention, resulting in extensive studies on their chemical and pharmacological properties, with over 200 secondary metabolites identified to date. The present study aimed to explore the phytochemical composition of Bulgarian-origin S. aestivalis, including isolation and characterization of individual secondary metabolites. From methanol extract of the plant’s aerial parts, aucubin, harpagide, 8-O-acetylharpagide, cis- and trans-harpagoside, 6-O-methyl catalpol, acylated derivatives of catalpol, and linarin were isolated and identified. The anti-obesity activity of the extract and primary fractions was evaluated in a Caenorhabditis elegans model of obesity. Significant lipid-reducing activity was demonstrated in four fractions, indicating promising anti-obesogenic properties. Following chemical profiling and quantitative analysis, the main components of the most active fractions were identified, namely the cis- and trans-harpagoside isomers. Subsequent experiments demonstrated that treatment with harpagoside reduced lipid accumulation and improved mitochondrial function in glucose-supplemented worms, with the data suggesting potential involvement of the SKN-1 signaling pathway. Full article

As an active ingredient in Eucommia leaf, aucubin (AU) is natural and safe, and studies have shown that aucubin (AU) demonstrates great potential in its anti-inflammatory, antioxidant, neuroprotective, and anti-osteoporotic properties. However, AU has been less studied in colitis. In this experiment, we used DSS-induced mice to establish a colitis model to investigate the ability of AU to alleviate colitis. The results show that, in animal experiments, AU increased body weight, reduced disease activity index (DAI) scores and organ indices, restored colon morphology, and increased superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT) levels in mouse serum and colon. It also reduced malondialdehyde (MDA) levels, decreased the relative mRNA expression levels of inflammatory factors IL-1β, TNF-α, IL-18, MyD88, and NF-κB, and increased the relative mRNA expression levels of intestinal barrier-related genes OCLN, CLDN1, CLDN2, ZO-2, and MUC1. AU also upregulated the abundance of bacterial groups such as Bacteroidota, Firmicutes, and Verrucomicrobiota, and downregulated the abundance of bacterial groups such as Proteobacteria and Deferribacterota, thereby regulating the intestinal microbiota. In cell experiments, AU increased the relative mRNA expression levels of intestinal barrier-related genes MUC2, ZO-1, OCLN, and CLDN1, reduced the relative expression levels of inflammatory factors IL-1β and TNF-α, and increased the relative expression level of the anti-inflammatory factor IL-10. Additionally, AU significantly reduced the relative expression levels of IL-1β, IL-1R, MyD88, TAK1, IKKα, and RelA. This study provides a theoretical and technical basis for the large-scale preparation of aucubin and the alleviation of inflammatory bowel disease. Full article

To investigate how sweating–drying processing affects the components, antioxidant activity, and hepatoprotective mechanisms of Eucommia ulmoides (EUB) against acute liver injury (ALI), this study constructed a “processing–active components–ALI targets” network. Eight processed EUB samples were analyzed using HPLC fingerprinting, multi-assay antioxidant tests (DPPH/ABTS·+/pyrogallol), network pharmacology, and molecular docking. Sweating–drying significantly altered EUB’s chemical profile, with HPLC fingerprint similarities ranging from 0.715 to 1.000, the lowest being for FG4 (40 °C dried after sweating) and FD (freeze-dried after sweating). Key components (chlorogenic acid (CA), pinoresinol diglucoside (PDG), aucubin (AU), geniposidic acid (GPA)) varied: XS (sun-dried) had the highest CA/PDG, while FG4 showed increased AU/GPA. FY (shade-dried after sweating) exhibited the strongest free radical scavenging (DPPH/ABTS·+/pyrogallol IC₅₀ = 0.828, 0.134, 14.200 mg/mL), which correlated with CA/PDG/liriodendrin (PD) synergy. Network pharmacology identified 205 EUB-ALI intersection targets (core: TNF, PTGS2, GAPDH) and the AGE-RAGE pathway; molecular docking confirmed strong CA/PDG binding to GAPDH/PTGS2. This study clarifies how processing regulates EUB’s components and their links to antioxidant and hepatoprotective effects, providing scientific support for EUB’s clinical application against ALI. Full article

Chronic, low-grade inflammation is a key contributor to the development of numerous non-communicable diseases (NCDs), including cardiovascular, metabolic, and neurodegenerative disorders. Conventional anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, often present safety concerns with prolonged use, highlighting the need for safer, multi-targeted therapeutic options. Iridoids, a class of monoterpenoid compounds abundant in several medicinal plants, have emerged as promising bioactive agents with diverse pharmacological properties. They exert anti-inflammatory and metabolic regulatory effects by modulating key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor (PPAR) pathways. This review provides a comprehensive summary of the major iridoid metabolites derived from ten Bulgarian medicinal plant species, along with mechanistic insights from in vitro and in vivo studies. Documented biological activities include anti-inflammatory, antioxidant, immunomodulatory, antifibrotic, organoprotective, antibacterial, antiviral, analgesic, and metabolic effects. By exploring their phytochemical profiles and pharmacodynamics, we underscore the therapeutic potential of iridoid-rich Bulgarian flora in managing inflammation-related and metabolic diseases. These findings support the relevance of iridoids as complementary or alternative agents to conventional therapies and highlight the need for further translational and clinical research. Full article

For plant-derived raw materials, there are very few studies regarding the effect of intraocular administration on intraocular pressure (IOP) and associated blood flow. Traditional folk medicine uses many natural resources for eye disorders. However, in the main, these exhibit an anti-inflammatory and moisturizing effect. The intraocular pressure reduction and neuroprotective effects are known, but only for orally administered products. In the work presented here, the effect of eight natural iridoids in concentrations of 0.1 and 0.5% in saline on IOP and blood flow in iris vessels was studied in white New Zealand rabbits. No ocular adverse effects were observed during the whole experiment. We demonstrated, for the first time, significant reductions in IOP for five of the eight iridoids tested at a concentration of 0.5%. These were verbenalin, aucubin, oleuropein, gentiopicroside, and secologanin. The highest effect of IOP lowering, a nearly 1.5 mmHg difference from baseline, was observed for verbenalin 2 h after administration. An increase in vascular inflow was observed only with the administration of aucubin, catalpol, and gentiopicroside at 2 and 3 h after administration of the 0.5% solution. This effect was contrary to the result for the reference—timolol—which significantly reduced flow by more than 100 flux during the first hours of the experiment. In summary, selected iridoids could be considered, after further investigation, as natural components for ophthalmic formulation in the prevention of eye diseases. Full article

Aucubin (AU) is one of the main components of the traditional Chinese medicine Eucommia ulmoides Oliv (EU). This study investigated the effects of AU on aging-related skeletal muscle atrophy in vitro and in vivo. The results of network pharmacology revealed the potential therapeutic effects of AU on muscle atrophy. In vitro, AU effectively attenuated D-gal-induced cellular damage, reduced the number of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, down-regulated the expression levels of muscle atrophy-related proteins Atrogin-1 and MuRF1, and improved myotube differentiation, thereby mitigating myotube atrophy. Notably, AU was found to attenuate oxidative stress and apoptosis in skeletal muscle cells by reducing ROS production, regulating Cleaved caspase3 and BAX/Bcl-2 expression in apoptotic pathways, and enhancing Sirt1 and PGC-1α signaling pathways. In vivo studies demonstrated that AU treatment extended the average lifespan of Caenorhabditis elegans (C. elegans), increased locomotor activity, improved body wall muscle mitochondrial content, and alleviated oxidative damage in C. elegans. These findings suggested that AU can ameliorate aging-related muscle atrophy and show significant potential in preventing and treating muscle atrophy. Full article

Morinda citrifolia L. (M. citrifolia), commonly referred to as noni, a Polynesian medicinal plant with over 2000 years of traditional use, has garnered global interest for its rich repertoire of antioxidant phytochemicals, including flavonoids (kaempferol, rutin), iridoids (aucubin, asperulosidic acid, deacetylasperulosidic acid, asperuloside), polysaccharides (nonioside A), and coumarins (scopoletin). This comprehensive review synthesizes recent advances (2018–2023) on noni’s bioactive constituents, pharmacological properties, and molecular mechanisms, with a focus on its antioxidant potential. Systematic analyses reveal that noni-derived compounds exhibit potent free radical scavenging capacity (e.g., 2,2-Diphenyl-1-picrylhydrazyl/2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonicacid) (DPPH/ABTS) inhibition), upregulate endogenous antioxidant enzymes (Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx)), and modulate key pathways such as Nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) and Nuclear Factor kappa-B (NF-κB). Notably, polysaccharides and iridoids demonstrate dual antioxidant and anti-inflammatory effects via gut microbiota regulation. This highlights the plant’s potential for innovation in the medical and pharmaceutical fields. However, it is also recognized that further research is needed to clarify its mechanisms of action and ensure its safety for widespread application. We emphasize the need for mechanistic studies to bridge traditional knowledge with modern applications, particularly in developing antioxidant-rich nutraceuticals and sustainable livestock feed additives. This review underscores noni’s role as a multi-target antioxidant agent and provides a roadmap for future research to optimize its health benefits. Full article

Ischemic stroke ranks as the second leading cause of global mortality. The limited time for effective thrombolytic treatment has prompted the exploration of alternative prevention approaches. Eucommia ulmoides (E. ulmoides) Oliv. bark has shown multiple pharmacological effects, including neuroprotection, anti-inflammation and autophagy modulation. This study aims to elucidate the neuroprotective effects of water extract of E. ulmoides (WEU) supplementation in a middle cerebral artery occlusion (MCAO) mouse model and to further explore the underlying molecular mechanisms. Seven bioactive compounds in WEU—aucubin, chlorogenic acid, geniposidic acid, quercetin, protocatechuic acid, betulin and pinoresinol diglucoside—were identified using HPLC-MS. Our results showed that WEU supplementation significantly decreased infarct volume and ameliorated neurological dysfunction in mice following MCAO/reperfusion (MCAO/R) injury. Furthermore, the administration of WEU significantly attenuated microglia activation induced by cortical ischemia in mice and inhibited the production of pro-inflammatory mediators, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Importantly, in contrast with the vehicle group, the protein expression levels of Toll-like receptor 4 (TLR4), phospho-p38 (p-p38) and nuclear factor kappa B (NF-κB) were reduced in the WEU group. Therefore, this present study provides evidence that E. ulmoides improves neurological behaviors by suppressing neuroinflammation and inhibiting the activation of the TLR4/ p38 MAPK and NF-κB pathways in mice after ischemia, which indicates that E.ulmoides is a promising candidate for alleviating gray matter ischemic change. Full article

This study aimed to scientifically validate the traditional use of Garrya laurifolia (Gl) leaves as an antidiabetic agent attributed to a community in Mexico. The descriptive ethnobotanical study was conducted in San Miguel Tecpan, a municipality of Jilotzingo, State of Mexico, Mexico, where a structured questionnaire was applied to 44 inhabitants. In vivo studies evaluated the acute oral toxicity of Gl leaves in murine and the effects of a leaf infusion on glycemia in normoglycemic and diabetic rats; in addition, the interaction between Gl and metformin (Met) was also evaluated. The in vitro antioxidant activity of Gl was determined. The phytochemical screening and quantification of phenolic and flavonoid content of Gl leaves were performed. Gl had a high relative frequency of citation (0.68) among respondents. Gl had a low acute toxicity risk with LD₅₀ > 5000 mg/kg. The extract had no hypoglycemic effect in normoglycemic rats, but it did have hypoglycemic and antihyperglycemic effects (250 and 500 mg/kg) in diabetic rats. The interaction between Gl (500 mg/kg) + Met (300 mg/kg) resulted in antidiabetic synergism. Gl showed strong antioxidant activity (93.1 ± 0.4%). Phytochemical screening revealed the presence of alkaloids, flavonoids, and some other phenolic compounds. The total phenol content was 77.9 ± 0.6 mg EQ/g and 87.7 ± 0.7 mg EAG/g, and the flavonoids content was 5.32 ± 0.2 mg EQ/g. UHPLC-MS/MS analysis identified chlorogenic acid, rutin, aucubin, luteolin 7-O-neohesperoside, and myricitrin. The findings support the potential use of Gl as a safe and effective antidiabetic agent. Full article

Ribwort plantain (Plantago lanceolata L.) is expected to open up new crop cultivation perspectives in arable farming in order to significantly reduce nitrogen losses through leaching, N₂O emissions and to increase resilience under drought conditions. Therefore, this study investigated the properties of the roots as an alternative to grasses for forage production under drought conditions. Ten genotypes of ribwort plantain were compared under field conditions in northern Switzerland, focusing on the characteristics of the root system and the aucubin content in the leaves and roots. Aucubin, known for inhibiting the nitrification process in the soil, varied according to genotype and season. All tested genotypes showed higher aucubin content in leaves than in roots, which may indicate the greater importance of leaves in reducing soil nitrification. Dry matter yield and for the first time root characteristics, such as root length density (RLD) and specific root length (SRL), were evaluated at two different soil depths, and at different distances from the plants. The results showed that ribwort is well adapted to acquire water and nutrients in terms of rooting in topsoil. In addition, a second field experiment conducted in eastern Germany (Saxony) confirmed the plant’s ability to root deeply after one year of cultivation, reaching depths of up to even 1.88 m. The obtained results indicate the high capacity of ribwort plantain to take up water and nutrients also from deeper soil layers. To reduce N₂O emissions through the cultivation of ribwort plantain, the choice of genotype seems to be of great importance due to varying aucubin contents. Full article

About one-third of the global food supply is wasted. Brewers’ spent grain (BSG), being produced in enormous amounts by the brewery industry, possesses an eminence nutritional profile, yet its recycling is often neglected for multiple reasons. We employed integrated metagenomics and metabolomics techniques to assess the effects of enzyme treatments and Lactobacillus fermentation on the antioxidant capacity of BSG. The biotreated BSG revealed improved antioxidant capability, as evidenced by significantly increased (p < 0.05) radical scavenging activity and flavonoid and polyphenol content. Untargeted metabolomics revealed that Lactobacillus fermentation led to the prominent synthesis (p < 0.05) of 15 novel antioxidant peptides, as well as significantly higher (p < 0.05) enrichment of isoflavonoid and phenylpropanoid biosynthesis pathways. The correlation analysis demonstrated that Lactiplantibacillus plantarum exhibited strong correlation (p < 0.05) with aucubin and carbohydrate-active enzymes, namely, glycoside hydrolases 25, glycosyl transferases 5, and carbohydrate esterases 9. The fermented BSG has potential applications in the food industry as a culture medium, a functional food component for human consumption, and a bioactive feed ingredient for animals. Full article

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system’s effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw^® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity. Full article

Iridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid components (catalpol (CAT), genipin (GE), geniposide (GEN), geniposidic acid (GPA), aucubin (AU), ajugol (AJU), rehmannioside C (RC), and rehmannioside D (RD)) based on corticosterone (CORT)-induced injury in PC12 cells. PC12 cells were randomly divided into a normal control group (NC), model group (M), positive drug group (FLX), and eight iridoid administration groups. Firstly, PC12 cells were induced with CORT to simulate neuronal injury. Then, the MTT method and flow cytometry were applied to evaluate the protective effects of eight iridoid components on PC12 cell damage. Thirdly, a cell metabolomics study based on ultra-performance liquid chromatography–quadrupole–time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was performed to explore changes in relevant biomarkers and metabolic pathways following the intervention of administration. The MTT assay and flow cytometry analysis showed that the eight iridoid components can improve cell viability, inhibit cell apoptosis, reduce intracellular ROS levels, and elevate MMP levels. In the PCA score plots, the sample points of the treatment groups showed a trend towards approaching the NC group. Among them, AU, AJU, and RC had a weaker effect. There were 38 metabolites (19 metabolites each in positive and negative ion modes, respectively) identified as potential biomarkers during the experiment, among which 23 metabolites were common biomarkers of the eight iridoid groups. Pathway enrichment analysis revealed that the eight iridoid components regulated the metabolism mainly in relation to D-glutamine and D-glutamate metabolism, arginine biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism. In conclusion, the eight iridoid components could reverse an imbalanced metabolic state by regulating amino acid neurotransmitters, interfering with amino acid metabolism and energy metabolism, and harmonizing the level of oxidized substances to exhibit neuroprotective effects. Full article