RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra rhizome has a long history been used for clinical purposes in traditional Chinese medicinal for treating various inflammatory conditions. Engeletin1 (ENG) is one of the most abundant bioactive compounds found in Smilax glabra rhizome, with anti-inflammatory, antioxidant, and ulcer-preventing activities. AIM OF THE STUDY: The purpose of this study was to investigate the ability of ENG to alleviate inflammatory symptoms and improve epithelial barrier integrity utilize a 2,4,6-trinitrobenzene sulfonic acid2 (TNBS)-induced murine model in Crohn's disease3 (CD)-like colitis, and to characterize the underlying anti-inflammatory mechanisms of action. MATERIALS AND METHODS: A colitis model was established in BALB/c mice and treated with ENG for 7 days. RAW264.7 macrophages were pre-treated with ENG and lipopolysaccharide4 (LPS) stimulation. The mice's weight and colon length were assessed. qPCR and Western blotting were used to analyze gene expression and TLR4-NFκB pathway. Flow cytometry was used to analyze the polarization states of the macrophages. RESULTS: Treatment with ENG was sufficient to significantly alleviate symptoms of inflammation and colonic epithelial barrier integrity in treated mice. Significant inhibition of TNF-α, IL-1ß, and IL-6 expression was observed following ENG treatment in vivo and in vitro. ENG was also determined to be capable of inhibiting the expression of iNOS and CD86, inhibited M1 macrophage polarization in vitro, as well as the TLR4-NFκB signaling pathway. Molecular docking showed a highly stable binding between ENG and TLR4. CONCLUSION: ENG has been proven to alleviate inflammation and ameliorate the damage of epithelial barrier in CD-like colitis. ENG also suppressed the M1 macrophages polarization and the inhibited inflammatory cytokines. TLR4-NFκB signaling pathway, especially TLR4, may be the target of ENG. These data offer a new insight into the therapeutic mechanisms of ENG.
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Antiinflamatorios , Colitis , Enfermedad de Crohn , FN-kappa B , Transducción de Señal , Receptor Toll-Like 4 , Ácido Trinitrobencenosulfónico , Animales , Masculino , Ratones , Antiinflamatorios/farmacología , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/metabolismo , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Enfermedad de Crohn/tratamiento farmacológico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Flavonoles , Glicósidos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Smilax/química , Receptor Toll-Like 4/metabolismoRESUMEN
Recently, the intestinal lymphatic transport based on Peyer's patches (PPs) is emerging as a promising absorption pathway for natural polysaccharides. Herein, the aim of this study is to investigate the PP-based oral absorption of a pectic polysaccharide from Smilax china L. (SCLP), as well as its uptake and transport mechanisms in related immune cells. Taking advantages of the traceability of fluorescently labeled SCLP, we confirmed that SCLP could be absorbed into PPs and captured by their mononuclear phagocytes (dendritic cells and macrophages) following oral administration. Subsequently, the systematic in vitro study suggested that the endocytic mechanisms of SCLP by model mononuclear phagocytes (BMDCs and RAW264.7 cells) mainly involved caveolae-mediated endocytosis, macropinocytosis and phagocytosis. More importantly, SCLP directly binds and interacts with toll-like receptor 2 (TLR2) and galectin 3 (Gal-3) receptor, and was taken up by mononuclear phagocytes in receptor-mediated manner. After internalization, SCLP was intracellularly transported primarily through endolysosomal pathway and ultimately localized in lysosomes. In summary, this work reveals novel information and perspectives about the in vivo fate of SCLP, which will contribute to further research and utilization of SCLP and other pectic polysaccharides.
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Ganglios Linfáticos Agregados , Smilax , Animales , Ratones , Células RAW 264.7 , Ganglios Linfáticos Agregados/metabolismo , Smilax/química , Endocitosis , Pectinas/química , Pectinas/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Fagocitos/metabolismo , Fagocitos/efectos de los fármacos , Receptor Toll-Like 2/metabolismo , Ratones Endogámicos BALB C , Masculino , Células Dendríticas/metabolismo , Células Dendríticas/efectos de los fármacos , Administración OralRESUMEN
Hyperuricemia (HUA) is a metabolic disorder caused by excessive production of uric acid (UA) or impaired uric acid metabolism. Smilax China L. has a wide range of pharmacological activities such as immunomodulatory, anti-inflammatory, and antioxidant. Its roots and rhizomes have been widely used for the treatment of HUA. However, its mechanisms for treating HUA and reducing renal impairment have not been fully elucidated. In the present study, we evaluated the effect of Smilax China L. extract (SC) on UA metabolism and further explored its mechanism of action by feeding a high-calcium and high-protein diet to chickens to induce a model of HUA in chickens. SC significantly reduced serum UA levels and improved renal function in hyperuricemic chickens. Meanwhile, SC was able to inhibit the activity of xanthine oxidase (XOD) in vivo and in vitro, reducing the production of uric acid. In addition, SC was able to increase the expression of Breast Cancer Resistance Protein (BCRP) in the kidney and ileum and increase uric acid excretion. Therefore, our results suggest that SC may be a candidate for anti-hyperuricemia.
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Pollos , Hiperuricemia , Extractos Vegetales , Smilax , Ácido Úrico , Xantina Oxidasa , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/veterinaria , Smilax/química , Xantina Oxidasa/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Enfermedades de las Aves de Corral/tratamiento farmacológico , Dieta/veterinaria , Masculino , Alimentación Animal/análisis , Distribución AleatoriaRESUMEN
Smilax glabra Roxb. (SGR) is known for its high nutritional and therapeutic value. However, the frequent appearance of counterfeit products causes confusion and inconsistent quality among SGR varieties. Herein, this study collected the proportion of SGR adulteration and used high-performance liquid chromatography (HPLC) to measure the astilbin content of SGR. Then Fourier-transform near-infrared (FT-NIR) technology, combined with multivariate intelligent algorithms, was used to establish partial least squares regression quantitative models for detecting SGR adulteration and measuring astilbin content, respectively. The method conducted a quantitative analysis of dual indicators through single-spectrum data acquisition (QADS) to comprehensively evaluate the authenticity and superiority of SGR. The coefficients of determination (R2) for both the calibration and prediction sets exceeded 0.96, which successfully leverages FT-NIR combined with multivariate intelligent algorithms to considerably enhance the accuracy and reliability of quantitative models. Overall, this research holds substantial value in the comprehensive quality evaluation in functional health foods.
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Algoritmos , Smilax , Espectroscopía Infrarroja Corta , Smilax/química , Espectroscopía Infrarroja Corta/métodos , Cromatografía Líquida de Alta Presión , Control de Calidad , Espectroscopía Infrarroja por Transformada de Fourier , Extractos Vegetales/química , Extractos Vegetales/análisis , Análisis de los Mínimos CuadradosRESUMEN
This study was to investigate the effects of Smilax China L. saponins (SCS) on non-alcoholic fatty liver disease (NAFLD). Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, followed by SCS treatment for 8 weeks. The effect of SCS on liver injury was observed by H&E staining and the regulative mechanism of SCS on lipid formation was exposed by detecting Oil red O, insulin resistance (IR), and fatty acids synthesis (FAS). Furthermore, transcriptomics and metabolomics were performed to analyze the potential targets. The experimental results indicated that SCS exerted a positive curative effect in alleviating HFD-induced overweight, hepatic injury, steatosis, and lipid formation and accumulation in rats, and the preliminary mechanism studies showed that SCS could alleviate IR, inhibit FAS expression, and reduce Acetyl-CoA levels. Besides, the integrative analysis of transcriptomics and metabolomics exposed the targets of SCS to regulate lipid production likely being the sphingolipid metabolism and glycerophospholipid metabolism pathways. This study demonstrates that SCS significantly ameliorates lipid metabolic disturbance in rats with NAFLD by relieving insulin resistance, inhibiting the FAS enzymes, and regulating the sphingolipid and glycerophospholipid metabolism pathways.
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Dieta Alta en Grasa , Resistencia a la Insulina , Metabolismo de los Lípidos , Metabolómica , Enfermedad del Hígado Graso no Alcohólico , Saponinas , Smilax , Transcriptoma , Animales , Smilax/química , Saponinas/farmacología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/genética , Masculino , Metabolómica/métodos , Dieta Alta en Grasa/efectos adversos , Transcriptoma/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Esfingolípidos/metabolismo , Glicerofosfolípidos/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.
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Gota , Hiperuricemia , Hiperuricemia/tratamiento farmacológico , Gota/tratamiento farmacológico , Humanos , Animales , Fitoterapia , Smilax/química , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Ácido Úrico/sangre , Extractos Vegetales/uso terapéutico , Extractos Vegetales/farmacología , Plantas Medicinales/químicaRESUMEN
INTRODUCTION: Smilacis Glabrae Rhizoma (SGR) is rich in chemical constituents with a variety of pharmacological activities. However, in-depth research has yet to be conducted on the chemical and pharmacodynamic constituents of SGR. MATERIALS AND METHODS: In this study, the chemical constituents of SGR were analyzed using liquid chromatography-mass spectrometry, and the pharmacodynamic compounds responsible for the medicinal effects of SGR were elucidated through a literature review. RESULTS: In total, 20 potentially new compounds, including 16 flavonoids (C19, C20, and C27-C40) and four phenylpropanoids (C107, C112, C113, and C118), together with 161 known ones were identified in the ethanol extract of SGR using liquid chromatography-mass spectrometry, and 25 of them were unequivocally identified by comparison with reference compounds. Moreover, 17 known constituents of them were identified in the plants of genus Smilax for the first time, and 16 were identified in the plant Smilax glabra Roxb. for the first time. Of 161 known compounds, 84 constituents (including isomers) have been reported to have 17 types of pharmacological activities, covering all known pharmacological activities of SGR; among these 84 bioactive constituents, six were found in the plants of genus Smilax for the first time and five were found in S. glabra for the first time, which are new bioactive constituents found in the plants of genus Smilax and the plant S. glabra, respectively. CONCLUSION: The results provide further information on the chemical composition of SGR, laying the foundation for the elucidation of the pharmacodynamic substances of SGR.
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Rizoma , Smilax , Espectrometría de Masa por Ionización de Electrospray , Cromatografía Líquida de Alta Presión/métodos , Rizoma/química , Smilax/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Flavonoides/análisis , Flavonoides/química , Flavonoides/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estructura MolecularRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is an autoimmune disease characterized by dysfunctional T cells and dysregulated immune responses. Smilax glabra Roxb. (SGR) is a formulation used in Traditional Chinese Medicine for the treatment of inflammatory skin disorders, including psoriasis. This study explores the scientific basis for its use by examining the effects of SGR on T cell differentiation and insulin receptor signaling, relevant pathways implicated in the pathophysiology of psoriasis. AIM OF THE STUDY: This study investigates the therapeutic potential of SGR (a Chinese medicine) in psoriasis and its impact on T cell differentiation. MATERIALS AND METHODS: An integrated network pharmacology and bioinformatics approach was employed to elucidate the mechanisms of SGR in regulating T cell differentiation. A psoriasis mouse model was utilized to evaluate the effects of SGR on T cell subsets. Immunohistochemistry and gene expression analyses were conducted to investigate the modulation of insulin receptor signaling pathways by SGR. RESULTS: SGR treatment effectively reset the expression of various T cell subsets in the psoriasis mouse model, suggesting its ability to regulate T cell differentiation and immune function. Furthermore, SGR treatment inhibited insulin receptor signaling and downstream pathways, including PI3K/AKT and ERK, in psoriatic skin lesions. This indicates that SGR may exert its therapeutic effects through modulation of the insulin receptor signaling pathway. CONCLUSIONS: This study provides novel insights into the therapeutic potential of SGR in psoriasis. By modulating T cell differentiation and targeting the insulin receptor signaling pathway, SGR holds promise as a potential treatment option for psoriasis.
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Dermatitis , Psoriasis , Smilax , Ratones , Animales , Smilax/química , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor de Insulina , Linfocitos T/metabolismo , Piel , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Inflamación/patología , Inmunidad , Modelos Animales de Enfermedad , Ratones Endogámicos BALB CRESUMEN
Smilax brasiliensis Sprengel is a monocotyledon of the Smilacaceae family, native to the Brazilian Cerrado, popularly known as "salsaparrilha" or "japecanga". In this study, the ethanol extract (EE) and the hexane (HEXF), dichloromethane (DCMF), ethyl acetate (ACF), and hydroethanol (HEF) fractions of the stems were obtained. The chemical composition was determined, the contents of phenolic compounds and flavonoids were quantified, and the antioxidant potential and the cytotoxic effect on Artemia salina were evaluated. Fatty acid esters, hydrocarbons, and phytosterols were identified in the HEXF analyzed by gas chromatography - mass spectrometry (GC-MS). The EE and DCMF, ACF, and HEF were analyzed by liquid chromatography coupled to a diode array detector and mass spectrometer (LC-DAD-MS), and the identified constituents included glycosylated (rutin, 3-O-ß-galactopyranosyl quercetin, 3-O-ß-glucopyranosyl quercetin, O-deoxyhexosyl-hexosyl quercetin, O-deoxyhexosyl-hexosyl kaempferol, O-deoxyhexosyl-hexosyl O-methyl quercetin, and others), and non-glycosylated (quercetin) flavonoids, phenylpropanoids (3-O-E-caffeoyl quinic acid, 5-O-E-caffeoyl quinic acid, O-caffeoyl shikimic acid, and others), neolignan, steroidal saponin (dioscin), and N-feruloyltyramine. The EE, DCMF, and ACF showed high total contents of phenolic compounds (112.99, 175.71, and 524.02 µg of GAE/mg, respectively), and in the ACF and DCMF a great content of flavonoids was also quantified (50.08 and 31.49 µg of QE/mg, respectively). The EE, DCMF, ACF, and HEF exhibited great antioxidant potential by DPPH (IC50 1.71 - 32.83 µg/mL) and FRAP (IC50 0.63 - 6,71 µg/mL) assays. A maximum cytotoxic activity on A. salina of 60% was observed for the DCMF (LC50 = 856.17 µg/mL). This study contributes to the phytochemical study of S. brasiliensis since these compounds were identified for the first time in the stems of this species. The S. brasiliensis stems demonstrated to be a rich source of polyphenols compounds and exhibited high antioxidant potential without toxicity. Thus, extract and fractions obtained from the S. brasiliensis stems can be used in food supplements or as natural antioxidants in the food industry.
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Smilacaceae , Smilax , Antioxidantes/análisis , Quercetina , Smilax/química , Ácido Quínico , Extractos Vegetales/química , Flavonoides/química , Fenoles/toxicidad , Fenoles/química , EtanolRESUMEN
Crude polysaccharides isolated from Smilax glabra were screened for anti-inflammatory activity using mice ear swelling animal experiments, during which the neutral polysaccharide S1 was identified. The structural characteristics and anti-inflammatory effects of the anti-inflammatory S1 polysaccharide were then investigated. The results showed that S1 was mainly composed of rhamnose, arabinose, galactose, glucose, xylose, and mannose. The structure of the main chain consisted of â6)-α-Galp-(1 â 6)-ß-Galp-(1 â 4)-α-Xylp-(1 â 6)-ß-Galp-(1â, with branched chains comprising α-Araf-(1 â 4)-α â Manp-(1 â and ß-Rhap-(1 â 4)-α-Glcp-(1 â units. Furthermore, S1 did not have a triple helix conformation. S1 could inhibit NO secretion, reduce the levels of pro-inflammatory factors (IL-6 and TNF-α), and significantly reduce LPS-stimulated inflammatory damage in RAW 264.7 cells by inhibiting activation of the NF-κB (p65) pathway. These results shed light on the possibility of S1 to be developed as a novel anti-inflammatory drug for therapeutic purposes.
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Smilax , Animales , Ratones , Smilax/química , Polisacáridos/química , Antiinflamatorios/farmacología , Células RAW 264.7 , GlucosaRESUMEN
An effective, sensitive, and rapid method was developed for the quality control evaluation of the standard decoction of Smilax glabra Roxb (SGR). SGR is a primary ingredient of the traditional functional foods of turtle jelly and SGR tea. Chemometrics, Network Pharmacology, and molecular docking were used to screen for six quality markers. Multiple extraction parameters were optimized. HPLC-UV/CAD-QAMS was used to rapidly quantify the six quality markers (neoastilbin, astilbin, neoisoastilbin, isoastilbin, quercitrin, and isoengeletin) in 10 batches of the standard decoction of SGR samples. The relative correction factor (RCF) values of the five compounds were close to 1, demonstrating that the charged aerosol detection (CAD) showed a consistent response to compounds with similar parent nucleus structures. This method can serve as a guide for rapid quantitative analysis of the multi-components of the SGR standard decoction and all the traditional functional foods of turtle jelly with the homology of medicine.
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Medicamentos Herbarios Chinos , Smilax , Smilax/química , Cromatografía Líquida de Alta Presión , Farmacología en Red , Quimiometría , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/químicaRESUMEN
Nine compounds were isolated and elucidated from this species, among which, two new compounds (1, 2) and seven known compounds (3-9). Their structures were determined by means of extensively spectroscopic analysis including HR-ESI-MS, 1H NMR, 13C NMR, HSQC and HMBC. The bioactivities evaluation was referred to the cytotoxic assay on four human tumor cell lines of the ethanol extract, different fractions and 6 compounds. The results demonstrated that the dichloromethane fraction showed the strongest cytotoxicity, followed by the ethyl acetate fraction. Compounds 4 and 6 had significant effects on SMMC-7721 and Hela cells.
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Antineoplásicos , Smilax , Humanos , Células HeLa , Smilax/química , Línea Celular Tumoral , Antineoplásicos/farmacología , Fitoquímicos/farmacología , Fitoquímicos/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
Four new furostanol saponins (1: â-â4: ) and a new pregane-type saponin (5: ) along with six known steroidal saponins (6: â-â11: ) were isolated from the rhizomes of Smilax china. The structures of 1: â-â5: were elucidated by extensive analysis of NMR and HR-ESI-MS data in addition to enzymatic hydrolysis and other chemical methods. Compounds 1, 4: , and 11: showed inhibitory activity against the expression of proinflammatory mediators, inducible nitric oxide synthase, interleukin-1ß, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-induced RAW264.7 cells. Compound 1: , at a concentration of 20 µM, decreased the production of inducible nitric oxide synthase, interleukin-1ß, interleukin-6, and tumor necrosis factor-α by 36, 62, 72, and 67%, respectively, which is comparable to that of the positive control dexamethasone.
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Citocinas , Saponinas , Smilax , China , Citocinas/metabolismo , Interleucina-1beta , Interleucina-6 , Lipopolisacáridos , Óxido Nítrico Sintasa de Tipo II , Rizoma/química , Saponinas/química , Smilax/química , Factor de Necrosis Tumoral alfa , Animales , Ratones , Células RAW 264.7RESUMEN
The root of Smilax china L. is used in traditional Korean medicine. We found that the Smilax china L. root extract has strong antimicrobial activity against two Cutibacterium acnes strains (KCTC 3314 and KCTC 3320). The aim of this study was to identify the beneficial properties of Smilax china L. extracts for their potential use as active ingredients in cosmetics for the treatment of human skin acne. The high-performance liquid chromatography (HPLC) and liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC/QTOF/MS) methods were used to obtain the profile of secondary metabolites from the ethyl acetate-soluble fraction of the crude extract. Agar diffusion and resazurin-based broth microdilution assays were used to evaluate antimicrobial activity and minimum inhibitory concentrations (MIC), respectively. Among the 24 metabolites, quercetin, resveratrol, and oxyresveratrol were the most potent compounds against Cutibacterium acnes. Minimum inhibitory concentrations of quercetin, resveratrol, and oxyresveratrol were 31.25, 125, and 250 µg/mL, respectively.
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Acné Vulgar , Antiinfecciosos , Smilax , Humanos , Smilax/química , Quercetina , Propionibacterium acnes/metabolismo , Extractos Vegetales/química , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Pruebas de Sensibilidad Microbiana , Resveratrol , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
Smilax glabra Roxb. (SGB) is a medicinal plant widely distributed in 17 countries worldwide. It is the primary raw material of the world-famous and best-selling functional food and beneficial tea. SGB was first recorded in Ben Cao Jing Ji Zhu of the Southern and Northern Dynasties (420-589 AD) and was reported for nutritional and medicinal properties for thousands of years. This review searched PubMed, Web of Science, and other databases for relevant literature on SGB species until April 2022. It aims to provide more integrated thinking, detailed awareness, and better knowledge of SGB. More than 200 chemical components have been discovered, including flavonoids, phenolic, phenolic acids, stilbenes, organic acids, phenylpropanoids, and others. Previous studies have demonstrated that SGB and its active ingredients show a wide range of pharmacological effects, including anti-infective, anti-cancer, anti-inflammatory, antioxidant, cardiovascular protection, etc. However, many studies on the biological activity of this plant were mainly based on crude extracts and active ingredients, and there is a lack of clinical studies and toxicity studies to support the development of drug design, development, and therapy. In summary, this review will provide specific and valuable suggestions and guidelines for further research and application of this plant in the medicinal field.
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Smilax , Estilbenos , Smilax/química , Antioxidantes/farmacología , Flavonoides/farmacología , Fitoquímicos/farmacología , Extractos Vegetales/química , Antiinflamatorios , TéRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Smilax china L. is a well-known traditional medicinal plant. In China, it is a common anti-cancer drug that has been inherited for thousands of years. Some in vitro and in vivo studies have confirmed its potential lipid-lowering, anti-inflammatory and anti-ovarian cancer effects. However, there is no research on the material basis and mechanism of the rhizome of Smilax china L. against hepatocellular carcinoma. AIM OF THE STUDY: To explore the material basis and mechanism of scopolin from Smilax china L. against hepatocellular carcinoma. METHODS: The potential targets and active components of Smilax china L. against hepatocellular carcinoma were screened by transcriptomics, network pharmacology and molecular docking. Microscale Thermophoresis (MST) detection was used to verify the affinity of small molecule compounds with potential proteins and protein-protein interaction. The Extract from HepG2 cells was used to measure the expression of glycolysis-related proteins, glucose consumption and lactate production. The expression of apoptosis-related factors and glycolysis-related proteins in vivo was detected by immunohistochemistry. RESULTS: The glycolysis-related proteins glucose-6-phosphate isomerase (GPI), glycerol-3-phosphate dehydrogenase, mitochondrial (GPD2) and phosphoglycerate kinase 2 (PGK2) screened by transcriptomics, network pharmacology showed strongly binding with scopolin by molecular docking. MST detection has also verified the affinity of scopolin with GPI and GPD2. It was the first time found that Heat shock protein HSP 90-alpha (Hsp90α) bound strongly to GPI and GPD2 in the worldwide, while scopolin was able to affect the interaction between Hsp90α and GPD2. In vitro and in vivo experiments further demonstrated that scopolin may play an anti-cancer role by affecting the stability of tumor-associated proteins. The results showed that scopolin obtained from Smilax china L. could regulate the expression of GPI, GPD2 and PGK2 and inhibit the interaction of protein-protein, reduce the energy metabolism of tumor tissue, thereby inhibit tumor growth. CONCLUSION: Scopolin obtained from Smilax china L. plays the role of anti-hepatocellular carcinoma by regulating the expression of glycolysis proteins GPI, GPD2 and PGK2. Scopolin could affect the interaction between Hsp90α and GPD2 may provide a novel potential treatment direction for hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Smilax , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Cumarinas , Glucósidos , Glucólisis , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Simulación del Acoplamiento Molecular , Farmacología en Red , Extractos Vegetales/farmacología , Smilax/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra Roxb., the dry rhizome of Sarsaparilla, which is also known as Tu fuling (TFL) in China, is a well-known traditional CHINESE medicine that is widely used for detoxication, relieving dampness and as a diuretic. We have previously shown that the extracted TFL flavonoids (designated TFLF) possess anti-cardiac hypertrophy effects in vitro. However, the anti-cardiac hypertrophy effects of TFLF in vivo and the underlying mechanisms remain to be elucidated. AIM OF THE STUDY: To reveal the underlying therapeutic mechanism of TFLF on cardiac hypertrophy by using transverse aortic constriction (TAC) model and cellular assays in vitro. MATERIAL & METHODS: Cardiac hypertrophy was replicated by TAC surgery in rats or by isoprenaline treatment of rat H9C2 myocardial cells in vitro. Cardiac structure and function were evaluated by echocardiographic and hemodynamic examinations in vivo and histological analysis of tissues ex vivo. Biochemical kits and quantitative PCR were used to analyze markers of cardiac hypertrophy. Expression and phosphorylation of key proteins in the Raf/MEK/ERK pathway were quantified by Western blotting. We further confirmed our findings in H9C2 rat cardiomyocytes treated with isoprenaline and the ERK inhibitor in vitro. RESULTS: TFLF attenuated cardiac hypertrophy and fibrosis and improved cardiac dysfunction in TAC rats. TFLF treatment induced a strong reduction in serum NT-proBNP levels. Cardiac hypertrophy marker gene (ANP, BNP and ß-MHC) expression and the phosphorylation levels of c-Raf and ERK1/2 were decreased by TFLF treatment. TFLF also protected H9C2 cells from isoprenaline-induced hypertrophy in vitro via a similar molecular mechanism as that observed in the rat heart. Moreover, pretreatment with TRLF and the ERK inhibitor further inhibited the mRNA overexpression of hypertrophic genes in vitro. CONCLUSIONS: TFLFs may protect against pathological cardiac hypertrophy via negative regulation of the Raf/MEK/ERK pathway. Thus, TFLFs are implicated as a potential pharmacological agent for treating cardiac hypertrophy in clinical practice.
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Smilax , Animales , Cardiomegalia/inducido químicamente , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/prevención & control , Flavonoides/farmacología , Flavonoides/uso terapéutico , Isoproterenol/farmacología , Sistema de Señalización de MAP Quinasas , Quinasas de Proteína Quinasa Activadas por Mitógenos , Miocitos Cardíacos , Ratas , Smilax/químicaRESUMEN
Herein, five new steroidal glycosides (Smilnipponicoside A-E) with five known congeners were isolated from the ethanol extracts of the rhizomes of Smilax nipponica Miq. Their structures were established by 2D NMR spectroscopic techniques (HMBC, HSQC, 1H,1H-COSY and NOESY), together with mass spectrometry, then comparison with the data in literature. The new compounds were subjected to evaluate anti-inflammatory in vitro. Compounds 1, 2 and 3 were found to have modest anti-inflammatory effects through suppression of TNF-α production in LPS-stimulated RAW 264.7 cells.
Asunto(s)
Smilax , Animales , Antiinflamatorios/farmacología , Glicósidos/química , Ratones , Estructura Molecular , Células RAW 264.7 , Rizoma/química , Smilax/químicaRESUMEN
Ulcerative colitis (UC) is an inflammatory bowel disease that affects the colon and rectum. Although galectin-3 (Gal-3) has been reported to play a proinflammatory role in UC, it is unknown whether pectic polysaccharide, a Gal-3 inhibitor in tumor metastasis, can alleviate UC by inhibiting Gal-3. The aim of this study was to investigate the anti-inflammatory effects and underlying mechanisms of SCLP, a pectic polysaccharide purified from Smilax china L. in our previous work, on dextran sulfate sodium-induced UC in BALB/c mice. The results showed that SCLP could significantly improve symptoms, alleviate histopathological damage and reduce the secretion of inflammatory mediators in mice with UC. Analysis of the anti-colitis mechanisms indicated that SCLP could inhibit the Gal-3/NLRP3 inflammasome/IL-1ß pathway by suppressing the expression of Gal-3 and the interaction of Gal-3 and NLRP3. Our results suggested that SCLP could be a promising candidate for prevention and treatment of UC.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Colitis Ulcerosa/tratamiento farmacológico , Inflamasomas/antagonistas & inhibidores , Pectinas/farmacología , Polisacáridos/farmacología , Smilax/química , Animales , Antiinflamatorios no Esteroideos/química , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Sulfato de Dextran , Galectina 3/antagonistas & inhibidores , Galectina 3/metabolismo , Inflamasomas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pectinas/química , Polisacáridos/químicaRESUMEN
The aim of the study was to investigate the in vitro and in vivo antitumor activity of leaves ethanol extract from Smilax fluminensis on murine melanoma. The extract was performed by ethylic alcohol and submitted to classical chemical analysis. Cytotoxicity test were performed on neoplastic cells, where antitumor activity was expressed in GI50 (concentration that inhibits 50% of cell growth) and the determination of selectivity index using a normal cell line. In addition, BALB/c mice models were used to evaluate the in vivo antitumor activity of extract in two different concentrations against B16-F10 melanoma cells. The tumor inhibition ratio was determined and the histopathological analyses of nodules and liver were compared. The chemical analysis indicated a major presence of phenolic compounds and flavonoids. Cytotoxicity test results that S. fluminensis extract was active in B16-F10 line (GI50: 4.37 µg/mL), being the extract considered a promising antineoplastic agent. In the experimental model, the inhibition percentage of tumoral growth was between 78.77 and 83.49%. Histopathology analysis of nodules showed necrotic cells reduction, adipocytes presence, melanin deposition, vascularization, and inflammatory process in a concentration-dependent manner. On the liver, the animals treated with the extract on both concentrations showed normal hepatic organization, normal hepatocytes, and absence of inflammatory focus. The results indicate that S. fluminensis extract demonstrated both in vitro and in vivo antitumor activity, reducing the tumoral growth in B16-F10 and could therefore be a promising antineoplastic agent.