RESUMEN
Leonurus japonicus Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from L. japonicus on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from L. japonicus were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins 1 and 2 significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins 3-5 showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin 1) significantly increased the level of Ca2+ in uterine tissues by promoting extracellular Ca2+ influx and intracellular Ca2+ release, which were related to the activation of L-type Ca2+ channels and α-receptors. By contrast, osthole (coumarin 5), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca2+ in uterine tissues via inhibition of extracellular Ca2+ influx and intracellular Ca2+ release. This study demonstrates that the coumarins from L. japonicus are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of L. japonicus in the treatment of dysmenorrhea and postpartum hemorrhage.
Asunto(s)
Calcio , Cumarinas , Leonurus , Músculo Liso , Contracción Uterina , Útero , Animales , Femenino , Cumarinas/farmacología , Cumarinas/química , Leonurus/química , Ratas , Calcio/metabolismo , Contracción Uterina/efectos de los fármacos , Útero/efectos de los fármacos , Útero/metabolismo , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Contracción Muscular/efectos de los fármacos , Ratas Sprague-Dawley , Extractos Vegetales/farmacología , Extractos Vegetales/química , Canales de Calcio Tipo L/metabolismo , Oxitocina/farmacologíaRESUMEN
Synchronous fluorescence spectroscopy (SFS) technology exhibits significant advantages in identifying target fluorescence signals within complex mixtures of multiple fluorescent compounds, owing to their closely overlapping spectra. In this study, a SFS method is reported for the first time for the direct analysis of leonurine in drugs containing concurrent natural products. By setting the wavelength interval (Δλ) to 30 nm, the characteristic emission peak of leonurine is observed at 307 nm, which increases proportionally with the concentration of leonurine without spectral overlap from other fluorescent species. The limit of detection (LOD) is estimated to be about 0.22 µM, and a low linear range of 0 to 20 µM is obtained. The common cations, anions and concomitant compounds display no interference with the SFS signal of leonurine, supporting the practical application of this method. Thus, we successfully applied this SFS method to detect leonurine in several real samples (leonurus granules, capsules, ointment and pills), in which the good relative standard deviation (RSD) values (0.04-4.24%) and recoveries (95.63-113%) were obtained. As a result, this work provides an efficient and convenient method to identify the target active compound from natural products without complex pre-treatment to diminish the fluorescent chaos that might be serving a potential role in the study of traditional Chinese medicine.
Asunto(s)
Medicamentos Herbarios Chinos , Ácido Gálico , Espectrometría de Fluorescencia , Ácido Gálico/análogos & derivados , Ácido Gálico/análisis , Espectrometría de Fluorescencia/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Medicina Tradicional China , Límite de Detección , Leonurus/químicaRESUMEN
The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.
Asunto(s)
Leonurus , Extractos Vegetales , Probióticos , Humanos , Método Doble Ciego , Masculino , Femenino , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Persona de Mediana Edad , Leonurus/química , Probióticos/administración & dosificación , Lactobacillus plantarum , Anciano , Resultado del Tratamiento , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/microbiología , AdultoRESUMEN
Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dysfunction. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, thromboembolism, and kidney and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta blockers, calcium inhibitors, ACE inhibitors, and anti-platelet drugs remains a second-line treatment after dietary interventions and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be effective and free from side effects, either taken together with or before the standard pharmacological intervention. Such herbal-originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea-buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (motherwort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and potential therapeutic option in the management of cardiovascular disorders.
Asunto(s)
Enfermedades Cardiovasculares , Crataegus , Ajo , Hippophae , Morus , Extractos Vegetales , Crataegus/química , Morus/química , Animales , Hippophae/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Leonurus/química , Elaeagnaceae/química , Humanos , FitoterapiaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt (L. japonicus, Chinese motherwort), known as Yi Mu Cao which means "good for women", has long been widely used in China and other Asian countries to alleviate gynecological disorders, often characterized by estrogen dysregulation. It has been used for the treatment of polycystic ovary syndrome (PCOS), a common endocrine disorder in women but the underlying mechanism remains unknown. AIM OF THE STUDY: The present study was designed to investigate the effect and mechanism of flavonoid luteolin and its analog luteolin-7-methylether contained in L. japonicus on aromatase, a rate-limiting enzyme that catalyzes the conversion of androgens to estrogens and a drug target to induce ovulation in PCOS patients. MATERIALS AND METHODS: Estrogen biosynthesis in human ovarian granulosa cells was examined using ELISA. Western blots were used to explore the signaling pathways in the regulation of aromatase expression. Transcriptomic analysis was conducted to elucidate the potential mechanisms of action of compounds. Finally, animal models were used to assess the therapeutic potential of these compounds in PCOS. RESULTS: Luteolin potently inhibited estrogen biosynthesis in human ovarian granulosa cells stimulated by follicle-stimulating hormone. This effect was achieved by decreasing cAMP response element-binding protein (CREB)-mediated expression of aromatase. Mechanistically, luteolin and luteolin-7-methylether targeted tumor progression locus 2 (TPL2) to suppress mitogen-activated protein kinase 3/6 (MKK3/6)-p38 MAPK-CREB pathway signaling. Transcriptional analysis showed that these compounds regulated the expression of different genes, with the MAPK signaling pathway being the most significantly affected. Furthermore, luteolin and luteolin-7-methylether effectively alleviated the symptoms of PCOS in mice. CONCLUSIONS: This study demonstrates a previously unrecognized role of TPL2 in estrogen biosynthesis and suggests that luteolin and luteolin-7-methylether have potential as novel therapeutic agents for the treatment of PCOS. The results provide a foundation for further development of these compounds as effective and safe therapies for women with PCOS.
Asunto(s)
Aromatasa , Estrógenos , Células de la Granulosa , Leonurus , Luteolina , Síndrome del Ovario Poliquístico , Femenino , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Luteolina/farmacología , Luteolina/aislamiento & purificación , Animales , Humanos , Aromatasa/metabolismo , Aromatasa/genética , Leonurus/química , Estrógenos/farmacología , Estrógenos/biosíntesis , Ratones , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/aislamiento & purificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.
Asunto(s)
Apoptosis , Hemorragia Cerebral , Leonurus , Simulación del Acoplamiento Molecular , Farmacología en Red , Neuronas , Animales , Apoptosis/efectos de los fármacos , Leonurus/química , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratones , Masculino , Hemorragia Cerebral/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Janus Quinasa 1/metabolismo , Factor de Transcripción STAT1/metabolismo , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: This study aimed to investigate the curative effect of motherwort combined with ethinylestradiol-cyproterone acetate (EE/CPA) on dysfunctional uterine bleeding (DUB). METHODS: Atotal of 68 patients with DUB were divided into a single medication group (treated with EE/CPA) and a combination medication group(treated with motherwort and EE/CPA). The clinical efficacy, uterine hemodynamic parameters, sex hormone levels, coagulation index levels, blood routine test levels, and adverse reactions of patients were evaluated. RESULTS: After three months of treatment, total treatment response rate of the combination medication group was significantly higher than that of the single medication group. Decreased uterine volume, endometrial thickness and resistance index (RI), increased pulsatility index(PI), average flow rate, and uterine artery blood flow, as well asreduced follicle-stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (P), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB), thrombin time(TT), platelet count (PLT), red blood cell (RBC), and hemoglobin (Hb)levels were witnessed in patients of the two groups. In thecombination medication group, there exhibited reduced uterine volume, endometrial thickness and RI, elevated PI, average flow rate, and uterine artery blood flow, reduced P, E2, FSH, LH, aPTT, PT, FIB, TT,PLT, RBC, and Hb levels in comparison to the single medication group. CONCLUSION: The combination of motherwort and EE/CPA is clinically effective in the treatment of DUB.
Asunto(s)
Acetato de Ciproterona , Etinilestradiol , Humanos , Femenino , Acetato de Ciproterona/uso terapéutico , Etinilestradiol/uso terapéutico , Adulto , Resultado del Tratamiento , Metrorragia/tratamiento farmacológico , Metrorragia/etiología , Combinación de Medicamentos , Persona de Mediana Edad , Quimioterapia Combinada , Leonurus/químicaRESUMEN
Chinese motherwort (Leonurus japonicus), a member of Lamiaceae family, is a commonly used medicinal herb for treating obstetrical and gynecological diseases, producing over 280 officinal natural products. Due to limited genomic resources, little progress has been made in deciphering the biosynthetic pathway of valuable natural products in L. japonicus. Here, we de novo assembled the L. japonicus genome using high-coverage ONT long reads and Hi-C reads. The chromosome-level genome assembly contained ten chromosomes representing 99.29% of 489.34 Mb genomic sequence with a contig and scaffold N50 of 7.27 Mb and 50.86 Mb, respectively. Genome validations revealed BUSCO and LAI score of 99.2% and 21.99, respectively, suggesting high quality of genome assembly. Using transcriptomic data from various tissues, 22,531 protein-coding genes were annotated. Phylogenomic analysis of 13 angiosperm plants suggested L. japonicus had 58 expanded gene families functionally enriched in specialized metabolism such as diterpenoid biosynthesis. The genome assembly, annotation, and sequencing data provide resources for the elucidation of biosynthetic pathways behind natural products of pharmaceutical applications in L. japonicus.
Asunto(s)
Genoma de Planta , Leonurus , Productos Biológicos , China , Perfilación de la Expresión Génica , Genómica , Leonurus/genéticaRESUMEN
Little or no information is available concerning online high-performance liquid chromatography (HPLC) antioxidants and the antibiofilm effect of Leonurus cardiaca. Five distinct extractions of methanolic, ethyl acetate, dichloromethane, hexane, and water were obtained from L. cardiaca. In the online-HPLC-antioxidant analysis of all examined samples, rosmarinic acid emerged as the primary antioxidant, registering concentrations ranging from 6 to 15 ppm at wavelengths of 517 and 734 nm. Notably, the water extract exhibited robust antioxidant activity In vitro. Regarding acetylcholinesterase and butrylcholinesterase inhibition, the n-hexane extract exhibited superior inhibition with values of 3.08 and 5.83 galanthamine equivalent, respectively. Except for the water extract, all tested extracts (at a concentration of 20 µg/mL) exhibited substantial inhibitory activity against biofilm formation, in many cases superior to 80%, and reached even 94.52% against Escherichia coli. Although less vigorous, the extracts also acted against the mature biofilm (inhibition up 76.50% against Staphylococcus aureus). They could work against the metabolism inside an immature and mature biofilm, with inhibition percentages up to 93.18% (vs. Pseudomonas aeruginosa) and 76.50% (vs. Acinetobacter baumannii), respectively. Considering its significant antioxidants, enzyme inhibition, and antimicrobial activity, L. cardiaca emerges as a promising candidate for therapeutic potential.
Asunto(s)
Leonurus , Leonurus/química , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión , Acetilcolinesterasa , Agua , Extractos Vegetales/química , Antibacterianos/análisisRESUMEN
The Lamiaceae family is renowned for its terpenoid-based medicinal components, but Leonurus, which has traditional medicinal uses, stands out for its alkaloid-rich composition. Leonurine, the principal active compound found in Leonurus, has demonstrated promising effects in reducing blood lipids and treating strokes. However, the biosynthetic pathway of leonurine remains largely unexplored. Here, we present the chromosome-level genome sequence assemblies of Leonurus japonicus, known for its high leonurine production, and Leonurus sibiricus, characterized by very limited leonurine production. By integrating genomics, RNA sequencing, metabolomics, and enzyme activity assay data, we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase (ADC), uridine diphosphate glucosyltransferase (UGT), and serine carboxypeptidase-like (SCPL) acyltransferase enzymes that catalyze key reactions in this pathway. Further analyses revealed that the UGT-SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in L. japonicus, which contributed to the accumulation of leonurine specifically in L. japonicus. Collectively, our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.
Asunto(s)
Lamiaceae , Leonurus , Leonurus/genética , Multiómica , Extractos VegetalesRESUMEN
Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.
Asunto(s)
Leonurus , Enfermedades Respiratorias , Ratones , Animales , Leonurus/metabolismo , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Emisiones de Vehículos , Material Particulado , InflamaciónRESUMEN
Eleven undescribed labdane diterpenoids, sibiricusins K-U, and seven known analogues were obtained from the MeOH extract of the aerial parts of Leonurus sibiricus. The structures of the compounds were established by detailed spectroscopic data analysis, single-crystal X-ray diffraction analysis and ECD calculations. Among them, sibiricusins L-N featured a rare α, ß-unsaturated-γ-lactam moiety. Fourteen of the isolates were evaluated for their anti-inflammatory effect on the production of NO in LPS-induced RAW264.7 cells through Griess assay. Sibiricusin O displayed the strongest activity with an IC50 value of 9.0 ± 1.7 µM.
Asunto(s)
Diterpenos , Leonurus , Leonurus/química , Estructura Molecular , Antiinflamatorios/farmacología , Diterpenos/química , Componentes Aéreos de las Plantas/químicaRESUMEN
Leonurus japonicus Houtt (LJH) is a bulk medicinal material commonly used in clinical practice, but its complex constituents have not been completely understood, posing challenges to pharmacology, pharmacokinetic research, and scientific and rational drug use. As a result, it is critical to develop an efficient and accurate method for classifying and identifying the chemical composition of LJH. In this study, ultra-performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry (UPLC-Q-Orbitrap-MS) was successfully established, along with two data post-processing techniques, characteristic fragmentations (CFs) and neutral losses (NLs), to quickly classify and identify the chemical constituents in LJH. As a result, 44 constituents of LJH were identified, including four alkaloids, 20 flavonoids, two phenylpropanoids, 17 organic acids, and one amino acid. The method in this paper enables classification and identification of chemical compositions rapidly, providing a scientific foundation for further research on the effective and toxic substances of LJH.
Asunto(s)
Medicamentos Herbarios Chinos , Leonurus , Medicamentos Herbarios Chinos/química , Leonurus/química , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Extractos Vegetales/químicaRESUMEN
Leonurus japonicus Houtt. is a medicinal plant popular in Brazil as "rubim", used in local folk medicine for several applications as an anti-inflammatory, antioxidant, analgesic, and antimicrobial phytomedicine. The traditional use for wound healing is related; however, few studies have evaluated the wound healing activity. Thus, this study aimed to analyse the popular indication of the hydroalcoholic and aqueous extracts of L. japonicus aerial parts in a rat wound healing model. The initial chemical characterization was performed using flavonoid quantification and complemented with mass spectroscopy/chemometrics analysis. The wound's lesion contraction and tissue regeneration (histological study stained with hematoxylin-eosin and picrosirius) were determined. Hydroalcoholic and aqueous extracts presented high flavonoid content, and mass spectrometry analysis of the extracts demonstrated the presence of compounds with a mass between 100-650, reinforcing the presence of polyphenolic constituents. The extracts of L. japonicus improve various wound healing phases, like inflammatory modulation, wound contraction, and collagen synthesis, resulting in faster healing in rats. These effects could be related to the extracts' polyphenolic compounds.
Asunto(s)
Leonurus , Plantas Medicinales , Ratas , Animales , Leonurus/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Plantas Medicinales/química , Cicatrización de Heridas , Flavonoides/farmacologíaRESUMEN
Leonurus sibiricus L. has great ethnobotanical and ethnomedicinal significance. This study aimed to assess the antioxidant and anti-inflammatory properties of Leonurus sibiricus L. transgenic roots extracts transformed by Rhizobium rhizogenes, with and without the AtPAP1 transcriptional factor. The study determined the total phenolic and flavonoid contents, as well as in vitro antioxidant assays, including hydrogen peroxide and nitric oxide scavenging activity. In addition, in silico computational studies and molecular docking were conducted to evaluate the antioxidant and anti-inflammatory potential of the identified compounds. The ligands were docked to NADPH oxidase, cyclooxygenase 2,5-lipoxygenase, inducible nitric synthase and xanthine oxidase: enzymes involved in the inflammatory process. The total phenolic and flavonoid contents ranged from 85.3 ± 0.35 to 57.4 ± 0.15 mg/g GAE/g and 25.6 ± 0.42 to 18.2 ± 0.44 mg/g QUE/g in hairy root extracts with and without AtPAP1, respectively. H2O2 scavenging activity (IC50) was found to be 29.3 µg/mL (with AtPAP1) and 37.5 µg/mL (without AtPAP1 transcriptional factor), and NO scavenging activity (IC50) was 48.0 µg/mL (with AtPAP1) and 68.8 µg/mL (without AtPAP1 transcriptional factor). Leonurus sibiricus L. transformed root extracts, both with and without AtPAP1, are a source of phytochemicals belonging to different classes of molecules, such as flavonoids (catechin and rutin), phenolic compounds (caffeic acid, coumaric acid, chlorogenic acid, ferulic acid) and phenylpropanoid (verbascoside). Among the radicals formed after H removal from the different -OH positions, the lowest bond dissociation enthalpy was observed for rutin (4'-OH). Rutin was found to bind with cyclooxygenase 2, inducible nitric synthases and xanthine oxidase, whereas chlorogenic acid demonstrated optimal binding with 5-lipoxygenase. Therefore, it appears that the Leonurus sibiricus L. transformed root extract, both with and without the AtPAP1 transcriptional factor, may serve as a potential source of active components with antioxidant and anti-inflammatory potential; however, the extract containing AtPAP1 demonstrates superior activities. These properties could be beneficial for human health.
Asunto(s)
Antioxidantes , Leonurus , Humanos , Antioxidantes/farmacología , Araquidonato 5-Lipooxigenasa , Ciclooxigenasa 2 , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , Xantina Oxidasa , Flavonoides/farmacología , Rutina , Antiinflamatorios/farmacología , Ácido Clorogénico , Extractos Vegetales/farmacologíaRESUMEN
Nine undescribed labdane diterpenoids (1-9) and one undescribed ent-halimane diterpenoid (10) were isolated from the aerial parts of Leonurus sibiricus, together with four known analogues (11-14) during our searching for naturally occurring antitumor agents. Their structures were established by detailed spectroscopic analyses and electronic circular dichroism analysis. Compound 4 possessed a rare 10-epi labdane scaffold. All compounds except 5 were evaluated for their inhibitory activities against interleukin (IL)-6-stimulated signal transducer and activator of transcription (STAT3) expression using a luciferase reporter assay. Compound 1 showed the most inhibitory effect with the IC50 value 20.31 µM. Compound 1 inhibited the activation of JAK2/STAT3 signal pathway through binding to Gln326 of STAT3 in CNE cells. The antiproliferative evaluation of compound 1 against CNE, CAL-27, A549 and PANC-1 cells demonstrated that CNE cells were the most sensitive to 1. Furthermore, compound 1 showed moderate efficacy in inhibiting cell migration, invasion, and epithelial-mesenchymal transition in CNE cells. In addition, compound 1 also promoted ferroptosis in CNE cells in a dose-dependent manner. These results suggest that compound 1 might be a potential candidate lead for treating nasopharyngeal carcinoma.
Asunto(s)
Diterpenos , Leonurus , Dicroismo Circular , Diterpenos/farmacología , Diterpenos/química , Leonurus/química , Estructura Molecular , Factor de Transcripción STAT3/antagonistas & inhibidoresRESUMEN
Phytochemical investigation on the ethanol extract of a well-known medicinal herb Leonurus japonicus, led to the separation of 18 labdane type diterpenoids (1-18). Through comprehensive spectroscopic analyses and quantum chemical calculations, these compounds were structurally characterized as six new interesting 5,5,5-di-spirocyclic ones (1-6), two new (7 and 8) and six known (13-18) interesting 6,5,5-di-spirocyclic ones, a new rare 14,15-dinor derivative (9), and three new ones incorporating a γ-lactone unit (10-12). An in vitro neuroprotective assay in RSC96 cells revealed that compounds 7 and 12 exhibited neuroprotective activity in a concentration-dependent way, comparable to the reference drug N-acetylcysteine.
Asunto(s)
Diterpenos , Leonurus , Plantas Medicinales , Espectroscopía de Resonancia Magnética , Leonurus/química , Diterpenos/farmacología , Diterpenos/química , Componentes Aéreos de las Plantas , Estructura MolecularRESUMEN
BACKGROUND: Leonurus japonicus, a significant medicinal plant known for its therapeutic effects on gynecological and cardiovascular diseases, has genetic diversity that forms the basis for germplasm preservation and utilization in medicine. Despite its economic value, limited research has focused on its genetic diversity and divergence. RESULTS: The avg. nucleotide diversity of 59 accessions from China were 0.00029 and hotspot regions in petN-psbM and rpl32-trnL(UAG) spacers, which can be used for genotype discrimination. These accessions divided into four clades with significant divergence. The four subclades, which split at approximately 7.36 Ma, were likely influenced by the Hengduan Mountains uplift and global temperature drop. The initial divergence gave rise to Clade D, with a crown age estimated at 4.27 Ma, followed by Clade C, with a crown age estimated at 3.39 Ma. The four clades were not showed a clear spatial distribution. Suitable climatic conditions for the species were identified, including warmest quarter precipitation 433.20 mm ~ 1,524.07 mm, driest month precipitation > 12.06 mm, and coldest month min temp > -4.34 °C. The high suitability distribution showed contraction in LIG to LGM, followed by expansion from LGM to present. The Hengduan Mountains acted as a glacial refuge for the species during climate changes. CONCLUSIONS: Our findings reflected a clear phylogenetic relationships and divergence within species L. japonicus and the identified hotspot regions could facilitate the genotype discrimination. The divergence time estimation and suitable area simulation revealed evolution dynamics of this species and may propose conservation suggestions and exploitation approaches in the future.
Asunto(s)
Leonurus , Biodiversidad , Filogenia , Temperatura , China , Variación GenéticaRESUMEN
Twenty-two labdane-type diterpenoids, including ten pairs of 15-epimers and a pair of 13,15-epimers, were obtained from the aerial parts of a well-known medicinal plant Leonurus japonicus Houtt. While these epimers were separated by chiral HPLC, their structures were established mainly via spectroscopic methods especially NMR, X-ray crystallography and ECD techniques. Among them, seventeen compounds, encompassing three pairs of solvolysis artefacts likely due to the use of ethanol as extracting solvent, were reported for the first time in the current work. Our preliminary anti-inflammatory screening demonstrated that seven diterpenoids displayed noteworthy inhibitory effect on the NO production in LPS-induced RAW264.7 cells. In addition, the release of pro-inflammatory factors TNF-α, IL-1ß and IL-6, as well as the expression of iNOS and COX-2 proteins, was also suppressed by the unreported 15,16-epoxy-6ß-hydroxy-15α-methoxy-7,16-dioxolabd-8,13-diene. Further investigation into the preliminary anti-inflammatory mechanism of this compound indicated that it could block the activation of NF-κB signaling pathway.
Asunto(s)
Diterpenos , Leonurus , Leonurus/química , Antiinflamatorios/farmacología , Espectroscopía de Resonancia Magnética , Diterpenos/química , Componentes Aéreos de las Plantas/química , Lipopolisacáridos/farmacologíaRESUMEN
Cardiovascular disease (CVD) is the leading cause of death globally and poses at significant challenge in terms of effective medical treatment. Leonurus japonicus Houtt, a traditional Chinese herb, is widely used in China for the treatment of obstetrical and gynecological disorders, including menstrual disorders, dysmenorrhea, amenorrhea, blood stasis, postpartum bleeding, and blood-related diseases such as CVD. Stachydrine, the main alkaloid component of Leonurus, has been shown to exhibit a wide range of biological activities including anti-inflammatory, antioxidant, anti-coagulant, anti-apoptotic, vasodilator, angiogenic promoter. Additionally, it has been demonstrated to have unique advantages in the prevention and treatment of CVD through regulation of various disease-related signaling pathways and molecular targets. In this comprehensive review, we examine the latest pharmacological effects and molecular mechanisms of Stachydrine in treating cardiovascular and cerebrovascular diseases. Our aim is to solid scientific basis for the development of new CVD drug formulations.