RESUMEN
The present study evaluated three green extraction methods, accelerated solvent extraction (ASE), ultrasound-assisted extraction (UAE), and laser irradiation extraction (LE), for the polyphenolic compounds and vitamin C extraction of Cornus mas L. and Crataegus monogyna fruit extracts. The polyphenols and vitamin C of extracts were quantified using HPLC-DAD, and the total phenolic content, flavonoid content, antioxidant activity (DPPH and reducing power), and antidiabetic activity were also studied. The antidiabetic activity was examined by the inhibition of α-amylase and α-glucosidase, and in vitro on a beta TC cell line (ß-TC-6). The results showed significant differentiation in the extraction yield between the methods used, with the ASE and LE presenting the highest values. The C. mas fruit extract obtained by ASE exhibited the best antioxidant activity, reaching an IC50 value of 31.82 ± 0.10 µg/mL in the DPPH assay and 33.95 ± 0.20 µg/mL in the reducing power assay. The C. mas fruit extracts obtained by ASE and LE also have the highest inhibitory activity on enzymes associated with metabolic disorders: α-amylase (IC50 = 0.44 ± 0.02 µg/mL for the extract obtained by ASE, and 0.11 ± 0.01 µg/mL for the extract obtained by LE at combined wavelengths of 1270 + 1550 nm) and α-glucosidase (IC50 of 77.1 ± 3.1 µg/mL for the extract obtained by ASE, and 98.2 ± 4.7 µg/mL for the extract obtained by LE at combined wavelengths of 1270 + 1550 nm). The evaluation of in vitro antidiabetic activity demonstrated that the treatment with C. mas and C. monogyna fruit extracts obtained using ASE stimulated the insulin secretion of ß-TC-6 cells, both under normal conditions and hyperglycemic conditions, as well. All results suggest that C. mas and C. monogyna fruit extracts are good sources of bioactive molecules with antioxidant and antidiabetic activity.
Asunto(s)
Antioxidantes , Cornus , Crataegus , Frutas , Hipoglucemiantes , Extractos Vegetales , alfa-Amilasas , Crataegus/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antioxidantes/farmacología , Antioxidantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Cornus/química , Frutas/química , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Animales , alfa-Glucosidasas/metabolismo , Polifenoles/farmacología , Polifenoles/química , Línea Celular , Flavonoides/farmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Fenoles/farmacología , Fenoles/química , Cromatografía Líquida de Alta Presión , Ácido Ascórbico/farmacologíaRESUMEN
Based on the processing and compatibility, this study explored the effects of components in Corni Fructus(CF) and Astragali Radix(AR) on plasma metabolomics in diabetic nephropathy rats. SD rats were randomly divided into four groups and diabetic nephropathy rat model was induced by high-fat diet combined with 30 mg·kg~(-1) streptozotocin(STZ). Histopathological observations of kidney tissue sections of rats in each group were conducted using HE, PAS, and Masson staining. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) metabolomics method was employed to investigate the effects of CF before and after wine-processing combined with AR-related components on plasma metabolites in diabetic nephropathy rats. After drug treatment, kidney tissue damage and interstitial collagen fiber deposition area in diabetic nephropathy rats were improved to varying degrees(P<0.001). The detection results of plasma metabolomics showed that 71 biomarkers related to the pathogenesis of diabetic nephropathy were identified in diseased rats, mainly involving linoleic acid metabolism, caffeine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism, retinol metabolism, and ether lipid metabolism. After drug intervention, 26 of them were significantly downregulated, with better efficacy observed in precision processed herb-pair group(P-CG_5). This study elucidated from the perspective of plasma metabolomics that P-CG_5 could improve metabolic disorders in diabetic nephropathy through pathways such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and caffeine metabolism, providing theoretical support and experimental basis for the clinical application of CF and AR compatibility in traditional Chinese medicine.
Asunto(s)
Cornus , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Metabolómica , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Ratas , Masculino , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Cornus/química , Astragalus propinquus/química , Vino/análisis , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismoRESUMEN
This meta-analysis aimed to summarise clinical evidence regarding the effect of supplementation with cornelian cherry (Cornus mas L.) on different cardiometabolic outcomes. An extensive literature survey was carried out until 10 April 2024. A total of 415 participants from six eligible studies were included. The overall results from the random-effects model indicated that cornelian cherry supplementation significantly reduced body weight (standardised mean difference [SMD] = -0.27, confidence interval [CI]: -0.52, -0.02, p = 0.03), body mass index (SMD = -0.42, CI: -0.73, -0.12, p = 0.007), fasting blood glucose (SMD = -0.46, CI: -0.74, -0.18, p = 0.001), glycated haemoglobin (SMD = -0.70, CI: -1.19, -0.22, p = 0.005), and HOMA-IR (SMD = -0.89, CI: -1.62, -0.16, p = 0.02), while high-density lipoprotein cholesterol significantly increased (SMD = 0.38, CI: 0.10, 0.65, p = 0.007). A sensitivity analysis showed that cornelian cherry supplementation significantly reduced total plasma triglycerides, total cholesterol, low-density lipoprotein cholesterol, and insulin levels. Cornelian cherry supplementation did not significantly affect waist circumference and liver parameters among the participants. Considering these findings, this meta-analysis indicates that supplementation with cornelian cherry may impact diverse cardiometabolic risk factors among individuals considered to be at a high risk.
Asunto(s)
Glucemia , Factores de Riesgo Cardiometabólico , Cornus , Suplementos Dietéticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Cornus/química , Masculino , Índice de Masa Corporal , Femenino , Hemoglobina Glucada/metabolismo , Adulto , Persona de Mediana Edad , Peso Corporal , Enfermedades Cardiovasculares/prevención & control , HDL-Colesterol/sangreRESUMEN
Corni fructus (CF) is always subjected to wine processing before prescription in clinic, for an enhancing effect of nourishing liver and kidney. While, the underlying mechanism for this processing on CF remains obscure. In this study, a sensitive ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method combined multi-dimensional analyses was established to monitor chemical characterizations of raw and wine-processed CF (WCF) and hence reveal the effects and underlying mechanism of wine processing on CF. As indicated, a total of 216 compounds were tentatively identified, including 98 structurally complex and variable home/hetero-polymers, that were composed of iridoid glucosides, gallic acids, caffeic acid and/or 5-HMF. Interestingly, 53 of these compounds probably characterized potential novel, including 35 iridoid glucosides or their dimers, 9 iridoid glucoside-gallic acid dimers, 7 gallic acids derivatives and 2 gallic acid-caffeic acid dimers, which provides ideas for natural product researchers. Meanwhile, the multi-dimensional analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regression analysis were used to explore the differences between CF and WCF. The results showed that 23 compounds as chemical markers greatly contributing to the distinction were screened out, and 3 of which (7α/ß-O-ethyl-morroniside, gallic acid and 5-HMF) in WCF indicated an increasing trend in intensities in relative to those in CF. Additionally, linear regression analysis showed that in WCF 53 compounds exhibited an increasing in intensities, while 132 ones did a decreasing trend, compared with those in CF. As our investigation demonstrated, acetal reaction of morroniside, ester hydrolysis in different organic acid derivatives as well as glycoside bond cleavage during wine processing probably resulted in the distinctions. The findings of this study provide a further understanding of the effect and mechanism of wine processing on CF.
Asunto(s)
Cornus , Análisis de Componente Principal , Espectrometría de Masas en Tándem , Vino , Vino/análisis , Cromatografía Líquida de Alta Presión/métodos , Cornus/química , Espectrometría de Masas en Tándem/métodos , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Ácido Gálico/química , Ácido Gálico/análisis , Frutas/química , Análisis de los Mínimos CuadradosRESUMEN
Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin.
Asunto(s)
Acuaporina 4 , Edema Encefálico , Cornus , Glicósidos Iridoides , Iridoides , Simulación del Acoplamiento Molecular , Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Masculino , Ratas , Acuaporina 4/metabolismo , Encéfalo/efectos de los fármacos , Edema Encefálico/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Cornus/química , Glicósidos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Glicósidos Iridoides/farmacología , Glicósidos Iridoides/aislamiento & purificación , Iridoides/farmacología , Estructura Molecular , Fármacos Neuroprotectores/farmacología , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
Ultraviolet B (UVB) exposure can contribute to photoaging of skin. Cornus officinalis is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the Cornus officinalis extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of Cornus officinalis. The effect of COE on UVB damage was assessed using Caenorhabditis elegans. The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of C. elegans exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the skn-1 downstream gene and the extension of the lifespan in skn-1 mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in C. elegans via the SKN-1/Nrf2 pathway.
Asunto(s)
Antioxidantes , Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Cornus , Estrés Oxidativo , Extractos Vegetales , Triterpenos , Rayos Ultravioleta , Ácido Ursólico , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/metabolismo , Triterpenos/farmacología , Triterpenos/química , Rayos Ultravioleta/efectos adversos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Estrés Oxidativo/efectos de los fármacos , Cornus/química , Antioxidantes/farmacología , Antioxidantes/química , Especies Reactivas de Oxígeno/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Longevidad/efectos de los fármacos , Longevidad/efectos de la radiación , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genéticaRESUMEN
Cornus mas L. is a rich source of vitamin C and polyphenols. Due to their health-benefit properties, C. mas L. extracts have been used in, e.g., dermatology and cosmetology, and as a food supplement. Peroxisome proliferator-activated receptor gamma (PPARγ) and its co-activator (PGC-1α) are now suspected to be the main target of active substances from C. mass extracts, especially polyphenols. Moreover, the PPARγ pathway is involved in the development of different diseases, such as type 2 diabetes mellitus (DM2), cancers, skin irritation, and inflammation. Therefore, the aim of the present study was to evaluate the PPARγ pathway activation by the most popular water and ethanol extracts from specific C. mas L. cultivars in an in vitro model of the human normal fibroblast (BJ) cell line. We analyzed the content of biologically active compounds in the extracts using the UPLC-DAD-MS technique and revealed the presence of many polyphenols, including gallic, quinic, protocatechuic, chlorogenic, and ellagic acids as well as iridoids, with loganic acid being the predominant component. In addition, the extracts contained cyanidin 3-O-galactoside, pelargonidin 3-O-glucoside, and quercetin 3-glucuronide. The water-ethanol dark red extract (DRE) showed the strongest antioxidant activity. Cytotoxicity was assessed in a normal skin cell line, and positive effects of all the extracts with concentrations ranging from 10 to 1000 µg/mL on the cells were shown. Our data show that the studied extracts activate the PPARγ/PGC-1α molecular pathway in BJ cells and, through this mechanism, initiate antioxidant response. Moreover, the activation of this molecular pathway may increase insulin sensitivity in DM2 and reduce skin irritation.
Asunto(s)
Antioxidantes , Cornus , Extractos Vegetales , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Humanos , Cornus/química , Polifenoles/farmacología , Polifenoles/química , PPAR gamma/metabolismo , Línea Celular , Citoprotección/efectos de los fármacosRESUMEN
Plant extracts can be a valuable source of biologically active compounds in many cosmetic preparations. Their effect depends on the phytochemicals they contain and their ability to penetrate the skin. Therefore, in this study, the possibility of skin penetration by phenolic acids contained in dogwood extracts of different fruit colors (yellow, red, and dark ruby red) prepared using different extractants was investigated. These analyses were performed using a Franz chamber and HPLC-UV chromatography. Moreover, the antioxidant properties of the tested extracts were compared and their impact on the intracellular level of free radicals in skin cells was assessed. The cytotoxicity of these extracts towards keratinocytes and fibroblasts was also analyzed and their anti-inflammatory properties were assessed using the enzyme-linked immunosorbent assay (ELISA). The analyses showed differences in the penetration of individual phenolic acids into the skin and different biological activities of the tested extracts. None of the extracts had cytotoxic effects on skin cells in vitro, and the strongest antioxidant and anti-inflammatory properties were found in dogwood extracts with dark ruby red fruits.
Asunto(s)
Antiinflamatorios , Antioxidantes , Cornus , Extractos Vegetales , Piel , Extractos Vegetales/farmacología , Extractos Vegetales/química , Cornus/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antioxidantes/farmacología , Antioxidantes/química , Piel/metabolismo , Piel/efectos de los fármacos , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Hidroxibenzoatos/farmacología , Hidroxibenzoatos/química , Frutas/química , Animales , Cromatografía Líquida de Alta PresiónRESUMEN
BACKGROUND: Cornus officinalis Sieb. Et Zucc. has the efficacy of tonifying the marrow and filling up the essence, breaking up the accumulation and opening up the orifices. Our research team found that CoS extracts were protective against Aß25-35-induced memory impairment in mice. However, the pharmacodynamic components and mechanisms by which CoS improves AD have yet to be thoroughly explored and investigated. PURPOSE: This study focused on exploring the bioactive components and pharmacodynamic mechanisms of CoS aqueous extract underlying mitochondrial damage and neuroinflammation to improve Aß25-35-induced AD. METHODS: AD mouse models were generated using Aß25-35 brain injections. Different doses of CoS aqueous extract were orally administered to mice for 28 days. The cognitive function, neuronal and synaptic damage, mitochondrial damage (mitochondrial length, mitochondrial fusion fission-related protein expression), neuroglial activation, and immune inflammatory factor and ERK pathway-related protein levels of mice were assessed. The CoS aqueous extracts components were identified using UPLC-TQ/MS and screened for cellular activity. Midivi-1 (Drp1 inhibitor) or PD98059 (ERK inhibitor) was added to Aß25-35-exposed PC12 cells to assess whether CoS and its active compounds mMorB and CorE regulate mitochondrial fission through ERK/Drp1. PC12-N9 cells were cocultured to investigate whether mMorB and CorE could regulate mitochondrial division through the ERK pathway to modulate neuroinflammation. RESULTS: CoS improved exploration and memory in AD mice, reduced synaptic and mitochondrial damage in their hippocampus, and modulated disturbed mitochondrial dynamics. Moreover, CoS inhibited ERK pathway signaling and attenuated abnormal activation of glial cells and secondary immune inflammatory responses. Additionally, in vitro experiments revealed that CoS and its compounds 7ß-O-methylmorroniside (mMorB) and Cornusdiridoid E (CorE) ameliorated mitochondrial injury caused by Aß25-35 in PC12 cells through inhibition of the ERK/Drp1 pathway. Meanwhile, mMorB and CorE ameliorated cellular inflammation by inhibiting the Ras/ERK/CREB signaling pathway. CONCLUSION: CoS aqueous extract ameliorates behavioral deficits and brain damage in Aß25-35-induced AD mice by modulating the ERK pathway to attenuate mitochondrial damage and neuroinflammation, and the compounds mMorB and CorE are the therapeutically active ingredients.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Cornus , Modelos Animales de Enfermedad , Fragmentos de Péptidos , Extractos Vegetales , Animales , Péptidos beta-Amiloides/metabolismo , Ratones , Cornus/química , Enfermedad de Alzheimer/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Masculino , Ratas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Células PC12 , Hipocampo/efectos de los fármacos , Ratones Endogámicos C57BL , Sistema de Señalización de MAP Quinasas/efectos de los fármacosRESUMEN
BACKGROUND: Acute liver injury (ALI) often precipitates severe liver function impairment and is associated with high mortality rates. Traditional Chinese Medicine (TCM) has demonstrated efficacy in mitigating hepatic damage by exhibiting anti-inflammatory effects, enhancing antioxidant activity, and modulating gut microbiota (GM). Numerous studies have identified similar or identical bioactive compounds within the Cornus Officinalis Fruit Coreon(COFO) and its flesh. Notably, Cornus Officinalis has been shown to possess potent hepatoprotective properties. However, studies on the pharmacological effects and mechanism of action of COFO for hepatoprotection have received little attention. PURPOSE: To elucidate the mechanisms underlying the COFO effect in ALI by integrating GM gene sequencing, quantifying Short-Chain Fatty Acids (SCFAs), and examining relevant signaling pathways. MATERIALS AND METHODS: A rat model for carbon tetrachloride (CCl4)-induced ALI was established, and the best liver protective components of COFO were selected by pathological observation and biochemical determination. The therapeutic efficacy of COFO in mitigating liver injury was elucidated through an integrated approach that included network pharmacology, biochemical indexes, 16S rDNA sequencing analyses, short-chain fatty acids, Western blotting analysis of protein levels, and immunohistochemical evaluations. RESULTS: Pharmacological evaluation established that the n-butanol fraction (CNBP) provided optimal hepatoprotective effects. Firstly, the chemical constituents of CNBP were characterized, and its principal anti-ALI targets, such as ALI, AKT1, TNF, and IL-6, were identified through network pharmacology analysis. Secondly, experimental validation revealed that CNBP may enhance the genetic diversity of the GM, augmenting the diversity of the microbial community, increasing the levels of three SCFAs, and activating key proteins in the AKT/Nrf2 signaling pathway (AKT1, TNF-α, IL-6, NF-κB p65, Nrf2, and HO-1). Consequently, CNBP exhibited hepatoprotective effects, with antioxidative and anti-inflammatory properties. CONCLUSION: CNBP may mitigate GM-induced disturbances, augment the levels of three SCFAs, activate the AKT/Nrf2 signaling pathway, and exhibit antioxidant and anti-inflammatory effects, thereby conferring hepatoprotective benefits.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Cornus , Frutas , Microbioma Gastrointestinal , Factor 2 Relacionado con NF-E2 , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Masculino , Ratas , Antioxidantes/farmacología , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cornus/química , Modelos Animales de Enfermedad , Ácidos Grasos Volátiles/metabolismo , Frutas/química , Microbioma Gastrointestinal/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Psoriasis is a chronic inflammatory skin disease substantially affecting the quality of life, with no complete cure owing to its complex pathogenesis. Cornuside, a major bioactive compound present in Cornus officinalis Sieb. et Zucc., which is a well-known traditional Chinese medicine with a variety of biological and pharmacological activities, such as anti-apoptotic, antioxidant, and anti-inflammatory properties. However, its effects on psoriasis remain unclear. Our preliminary analysis of network pharmacology showed that cornuside may be involved in psoriasis by regulating the inflammatory response and IL-17 signaling pathway. Thus, we investigated the protective role and mechanism of cornuside in the pathogenesis of psoriasis in an imiquimod (IMQ)-induced psoriasis mouse model. In-vivo experiments demonstrated that cornuside-treated mice had reduced skin erythema, scales, thickness, and inflammatory infiltration. The Psoriasis Area Severity Index score was significantly lower than that of the IMQ group. Flow cytometry analysis indicated that cornuside effectively inhibited Th1- and Th17-cell infiltration and promoted aggregation of Th2 cells in skin tissues. Cornuside also inhibited the infiltration of macrophages to the skin. Furthermore, in-vitro experiments indicated that cornuside also decreased the polarization of M1 macrophages and reduced the levels of associated cytokines. Western blotting demonstrated that cornuside suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular receptor kinase (ERK) in bone marrow-derived macrophages. Our findings indicate that cornuside has a protective effect against IMQ-induced psoriasis by inhibiting M1 macrophage polarization through the ERK and JNK signaling pathways and modulating the infiltration of immune cells as well as the expression of inflammatory factors.
Asunto(s)
Antiinflamatorios , Imiquimod , Ratones Endogámicos BALB C , Psoriasis , Piel , Células Th17 , Animales , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Psoriasis/inmunología , Piel/efectos de los fármacos , Piel/patología , Piel/inmunología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Ratones , Células Th17/inmunología , Células Th17/efectos de los fármacos , Modelos Animales de Enfermedad , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Cornus/química , Humanos , Interleucina-17/metabolismo , Citocinas/metabolismo , Femenino , Transducción de Señal/efectos de los fármacos , Células TH1/inmunología , Células TH1/efectos de los fármacos , MasculinoRESUMEN
BACKGROUND: Non-alcoholic steatohepatitis (NASH), the inflammatory subtype in the progression of non-alcoholic fatty liver disease, is becoming a serious burden threatening human health, but no approved medication is available to date. Mononoside is a natural active substance derived from Cornus officinalis and has been confirmed to have great potential in regulating lipid metabolism in our previous studies. However, its effect and mechanism to inhibit the progression of NASH remains unclear. PURPOSE: Our work aimed to explore the action of mononoside in delaying the progression of NASH and its regulatory mechanisms from the perspective of regulating lipophagy. METHODS AND RESULTS: Male C57BL/6 mice were fed with a high-fat and high-fructose diet for 16 weeks to establish a NASH mouse model. After 8 weeks of high-fat and high-fructose feeding, these mice were administrated with different doses of morroniside. H&E staining, ORO staining, Masson staining, RNA-seq, immunoblotting, and immunofluorescence were performed to determine the effects and molecular mechanisms of morroniside in delaying the progression of NASH. In this study, we found that morroniside is effective in attenuating hepatic lipid metabolism disorders and inflammatory response activation, thereby limiting the progression from simple fatty liver to NASH in high-fat and high-fructose diet-fed mice. Mechanistically, we identified AMPK signaling as the key molecular pathway for the positive efficacy of morroniside by transcriptome sequencing. Our results revealed that morroniside maintained hepatic lipid metabolism homeostasis and inhibited NLRP3 inflammasome activation by promoting AMPKα phosphorylation-mediated lipophagy and fatty acid oxidation. Consistent results were observed in palmitic acid-treated cell models. Of particular note, silencing AMPKα both in vivo and in vitro reversed morroniside-induced lipophagy flux enhancement and NLRP3 inflammasome inhibition, emphasizing the critical role of AMPKα activation in the effect of morroniside in inhibiting NASH progression. CONCLUSION: In summary, the present study provides strong evidence for the first time that morroniside inhibits NASH progression by promoting AMPK-dependent lipophagy and inhibiting NLRP3 inflammasome activation, suggesting that morroniside is expected to be a potential molecular entity for the development of therapeutic drugs for NASH.
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Proteínas Quinasas Activadas por AMP , Dieta Alta en Grasa , Metabolismo de los Lípidos , Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Masculino , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Cornus/química , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Fructosa , Glicósidos/farmacología , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológicoRESUMEN
The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compoundsâ 1-â7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12â cells. Compoundsâ 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12â cells. The underlying mechanism study suggested that compoundsâ 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12â cells.
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Apoptosis , Cornus , Frutas , Fármacos Neuroprotectores , Cornus/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Animales , Frutas/química , Ratas , Células PC12 , Apoptosis/efectos de los fármacos , Corticosterona/farmacología , Supervivencia Celular/efectos de los fármacos , Estructura Molecular , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/química , Relación Estructura-Actividad , Calcio/metabolismoRESUMEN
Morroniside (MOR) is an iridoid glycoside and the main active principle of the medicinal plant, Cornus officinalis Sieb. This phytochemical is associated with numerous health benefits due to its antioxidant properties. The primary objective of the present study was to assess the pharmacological effects and underlying mechanisms of MOR, utilizing published data obtained from literature databases. Data collection involved accessing various sources, including PubMed/Medline, Scopus, Science Direct, Google Scholar, Web of Science, and SpringerLink. Our findings demonstrate that MOR can be utilized for the treatment of several diseases and disorders, as numerous studies have revealed its significant therapeutic activities. These activities encompass anti-inflammatory, antidiabetic, lipid-lowering capability, anticancer, trichogenic, hepatoprotective, gastroprotective, osteoprotective, renoprotective, and cardioprotective effects. MOR has also shown promising benefits against various neurological ailments, including Alzheimer's disease, Parkinson's disease, spinal cord injury, cerebral ischemia, and neuropathic pain. Considering these therapeutic features, MOR holds promise as a lead compound for the treatment of various ailments and disorders. However, further comprehensive preclinical and clinical trials are required to establish MOR as an effective and reliable therapeutic agent.
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Cornus , Glicósidos , Fitoquímicos , Animales , Humanos , Antioxidantes/farmacología , Cornus/química , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Estructura Molecular , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificaciónRESUMEN
Cornus iridoid glycosides (CIGs), including loganin and morroniside, are the main active components of Cornus officinalis. As one of the key enzymes in the biosynthesis of CIGs, geranyl pyrophosphate synthase (GPPS) catalyzes the formation of geranyl pyrophosphate, which is the direct precursor of CIGs. In this study, the C. officinalis geranyl pyrophosphate synthase (CoGPPS) sequence was cloned from C. officinalis and analyzed. The cDNA sequence of the CoGPPS gene was 915 bp (GenBank No. OR725699). Phylogenetic analysis showed that CoGPPS was closely related to the GPPS sequence of Actinidia chinensis and Camellia sinensis, but relatively distantly related to Paeonia lactiflora and Tripterygium wilfordii. Results from the quantitative real-time PCR showed the spatiotemporal expression pattern of CoGPPS; that is, CoGPPS was specifically expressed in the fruits. Subcellular localization assay proved that CoGPPS was specifically found in chloroplasts. Loganin and morroniside contents in the tissues were detected by high-performance liquid chromatography, and both compounds were found to be at higher levels in the fruits than in leaves. Thus, this study laid the foundation for further studies on the synthetic pathway of CIGs.
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Cornus , Iridoides , Fosfatos de Poliisoprenilo , Cornus/genética , Cornus/química , Filogenia , Glicósidos Iridoides , Clonación MolecularRESUMEN
Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impacts on the functions of the cardiovascular system and the liver. This study aims to assess and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of sterol regulatory element-binding protein 1c (SREBP-1c) and CCAAT/enhancer binding protein α (C/EBPα), and various liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor-α (PPAR-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) target genes. Moreover, the aim is to evaluate the resistive index (RI) of common carotid arteries (CCAs) and aortas, and histopathological changes in CCAs. For this purpose, the levels of SREBP-1c, C/EBPα, ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), fatty acid synthase (FAS), endothelial lipase (LIPG), carnitine palmitoyltransferase 1A (CPT1A), and adiponectin receptor 2 (AdipoR2) in liver tissue were measured. Also, the levels of lipoprotein lipase (LPL), visceral adipose tissue-derived serine protease inhibitor (Vaspin), and retinol-binding protein 4 (RBP4) in visceral adipose tissue were measured. The RI of CCAs and aortas, and histopathological changes in CCAs, were indicated. The oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and decreased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigations in atheromatous changes in rabbits' CCAs were also observed. The obtained outcomes were compared to the results of our previous works. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.
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Cornus , Lagomorpha , Extractos Vegetales , Animales , Conejos , Antocianinas , Transportadoras de Casetes de Unión a ATP , Proteína alfa Potenciadora de Unión a CCAAT/genética , Cornus/química , Dieta , Frutas/química , Hígado , Receptores X del Hígado/genética , Extractos Vegetales/farmacología , PPAR alfa/genética , PPAR gamma/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis var. koreana Kitam (Cornus officinalis) is a commonly used Chinese herbal medicine and has a good clinical efficacy in kidney and liver diseases. Recent years, a number of studies reported the significant effects of Cornus officinalis on renal fibrosis. However, it is still unclear about the underlying specific mechanism, the bioactive ingredients, and the target gene regulatory network. AIM OF THE STUDY: We investigated the impact of Cornus officinalis extract on cadmium-induced renal fibrosis, screened the bioactive ingredients of Cornus officinalis using a pharmacological sub-network analysis, and explored the regulatory effects of Cornus officinalis extracts on target gene matrix metallopeptidase 9 (MMP9). METHODS: Male C57BL/6N mice were treated with single or combinatorial agents such as saline, cadmium chloride, Cornus officinalis, Isoginkgetin and FSL-1. Isoginkgetin is a compound with anti-MMP9 activity. FSL-1 can induce MMP9 expression. Masson staining and Western blot and immunohistochemistry analyses were used for assessing renal fibrosis. In addition, wound healing model was established using BUMPT (Boston university mouse proximal tubular) cells to investigate how Cornus officinalis affected cadmium-induced cell migration. The main Cornus officinalis bioactive compounds were identified by UHPLC-MS (Ultra-high-performance liquid chromatography - mass spectrometry). The MMP9 target for Cornus officinalis active ingredients were confirmed through a pharmacological sub-network analysis. RESULTS: Aqueous extracts of Cornus officinalis protected from renal dysfunction and kidney fibrosis induced by cadmium chloride in mice. In vitro experiments validated that Cornus officinalis extracts inhibited cell migration ability especially in cadmium chloride condition. The sub-network analysis and chemical components profiling technique revealed the active compounds of Cornus officinalis. Cellular thermal shift assay verified the binding abilities of three active components Daidzein, N-Acetyl-L-tyrosine or Swertisin with matrix metalloproteinase-9. Gelatin zymography assay revealed that the activity of MMP9 was inhibited by the three active components. We further confirmed that MMP9 was involved in the process of Cornus officinalis extracts reducing renal fibrosis. Cornus officinalis attenuated the cadmium-induced renal fibrosis was correlated with decreased expression of MMP9, collagen I, α-SMA (alpha-smooth muscle actin) and vimentin. CONCLUSIONS: This study demonstrated that Cornus officinalis extracts could alleviate the cadmium chloride-induced renal fibrosis by targeting MMP9, and might provide new insights into the mechanism of treating renal fibrosis by Cornus officinalis.
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Cornus , Enfermedades Renales , Humanos , Masculino , Ratones , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Cornus/química , Cadmio/toxicidad , Metaloproteinasa 9 de la Matriz , Cloruro de Cadmio , Ratones Endogámicos C57BL , Enfermedades Renales/inducido químicamente , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/prevención & control , FibrosisRESUMEN
Due to the growing popularity of herbal extract-loaded hydrogels, this study assessed the biological activity of extracts and hydrogels containing three types (water (WE), water-ethanol (EE) and water-glycerin (GE)) of Cornus mas L. (dogwood) extracts. The content of biologically active compounds in the extracts was assessed using the UPLC-DAD-MS technique. Antioxidant properties were assessed by using DPPH and ABTS radicals and measuring the intracellular level of reactive oxygen species. Alamar Blue and Neutral Red tests were used to measure the cytotoxicity of the tested samples on skin cells-fibroblasts and keratinocytes. Cell migration and the anti-aging activity of the tested extracts and hydrogels were assessed. Transepidermal water loss and skin hydration after applying the hydrogels to the skin were also determined. A chromatographic analysis revealed that the extracts contained polyphenols, including gallic, caftaric, protocatechuic, chlorogenic, ellagic and p-coumaroylquinic acids, as well as iridoids, with loganic acid as the predominant component. Additionally, they contained cyanidin 3-O-galactoside, pelargonidin 3-O-glucoside and quinic acid. The obtained results show that the tested extracts and hydrogels had strong antioxidant properties and had a positive effect on the viability of skin cells in vitro. Additionally, it was shown that they stimulated the migration of these cells and had the ability to inhibit the activity of collagenase and elastase. Moreover, the tested hydrogels increased skin hydration and prevented transepidermal water loss. The obtained results indicate that the developed hydrogels may be effective delivery systems for phytochemicals contained in dogwood extracts.
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Cornus , Dermatología , Antioxidantes/química , Cornus/química , Hidrogeles , Agua , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce the renal oxidative stress induced by gentamicin. Therefore, the main objective of this research was to investigate the nephroprotective properties of Cornus mas and Sorbus aucuparia fruits in an experimental model of nephrotoxicity. The 3-week study was performed on male Wistar rats, which were randomly divided into six experimental groups, being subcutaneously treated with 50 mg/kg gentamicin and orally given Cornus mas and Sorbus aucuparia extracts, in doses of 40 mg/kg and 10 mg/kg, respectively. Antioxidant therapy significantly improved the nitro-oxidative stress parameters as well as the specific renal biomarkers KIM-1 and iNAG, demonstrating a considerable renal tubular protective impact. These outcomes were reinforced by biochemical and histopathological enhancements. Nevertheless, neither of the tested extracts succeeded in substantially diminishing BUN levels. Additionally, CysC did not significantly decline following extracts treatment, suggesting that the remedies did not effectively protect renal glomeruli against gentamicin stress. Future studies are required in order to determine the underlying mechanisms of these berries.
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Cornus , Insuficiencia Renal , Sorbus , Ratas , Humanos , Animales , Antioxidantes/farmacología , Antioxidantes/química , Ratas Wistar , Cornus/química , Gentamicinas/toxicidad , Sorbus/química , Estrés Oxidativo , Extractos Vegetales/farmacología , Extractos Vegetales/química , BiomarcadoresRESUMEN
Background: Berry fruits are recognized as a "superfood" due to their high content of bioactive compounds and health benefits. Scope and approach: Herein, extracts of Cornus sanguinea and Cornus mas fresh and dried fruits obtained by different extraction procedures (ethanolic and hydroalcoholic maceration, ultrasound-assisted extraction, and Soxhlet apparatus) were analysed using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) and compared to identify the main healthy compounds and their impact on the inhibition of key enzymes (pancreatic lipase, α-glucosidase, and α-amylase) associated with metabolic disorders. The antioxidant activity and inhibition of nitric oxide (NO) and NF-κB pathway were also investigated. Key findings and conclusions: Flavonoids, iridoids, and phenolic acids were the main classes of identified compounds. Herein, kaempferol 3-O-galactoside, kaempferol 3-O-glucoside, quercetin, quercetin 3-O-xyloside, and myricetin 3-O-galactoside were detected for the first time in C. sanguinea. Remarkable antioxidant effects and promising α-glucosidase and lipase inhibitory activity were observed with extracts obtained by hydroalcoholic maceration of both Cornus dried fruits. Consequently, these extracts were subjected to fractionation using Amberlite XAD-16 resin. The most promising biological activities, which are attributed to the presence of some flavonoids and iridoids, were detected with the C. sanguinea fractions, in particular SD2(II). The results of this study offer new insights into the potential development of functional foods, nutraceuticals, and food supplements using the Cornus species.