RESUMEN
Garciyunnanol A (1), an unprecedented 1,2-seco-bicyclic polyprenylated acylphloroglucinol (BPAP) possessing a unique 6/6/6 tricyclic core, was characterized from Garcinia yunnanensis together with 16 BPAPs, including eight new compounds (garciyunnanols B-I, 2-9). Biogenetically, the bicyclo[3.3.1]nonane-2,4,9-trione moiety of 12 reconstructed the bicyclic δ-lactone core of 2 through Norrish type â cleavage and cyclization, followed by a cyclization of two side chains to form an intriguing 6/6/6 tricyclic core of 1. Their structures were elucidated through analysis of spectroscopic data, calculation and comparison of ECD spectra. Bioactivity evaluation manifested that compounds 1, 2, 5, 6 and 14 demonstrated superior inhibition of NO production compared to the positive control dexamethasone. Notably, compound 5 exhibited a dose-dependent inhibitory effect on NO production, with an IC50 value of 0.25 ± 0.87 µM. Furthermore, experiments involving ELISA, Western blotting, and immunofluorescence staining revealed that 5 effectively reduced the secretion of interleukin-1ß in LPS plus nigericin-stimulated THP-1 macrophages by inhibiting the activation of the NLRP3 inflammasome.
RESUMEN
Interleukin (IL)-1ß is a culprit of adipose tissue inflammation, which in turn causes systematic inflammation and insulin resistance in obese individuals. IL-1ß is mainly produced in monocytes and macrophages and marginally in adipocytes, through cleavage of the inactive pro-IL-1ß precursor by caspase-1, which is activated via the NLRP3 inflammasome complex. The nuclear factor-κB (NF-κB) transcription factor is the master regulator of inflammatory responses. Brindle berry (Garcinia cambogia) has been widely used as health products for treating obesity and related metabolic disorders, but its active principles remain unclear. We previously found a series of polyisoprenylated benzophenones from brindle berry with anti-inflammatory activities. In this study we investigated whether 14-deoxygarcinol (DOG), a major polyisoprenylated benzophenone from brindle berry, alleviated adipose tissue inflammation and insulin sensitivity in high-fat diet fed mice. The mice were administered DOG (2.5, 5 mg · kg-1 · d-1, i.p.) for 4 weeks. We showed that DOG injection dose-dependently improved insulin resistance and hyperlipidemia, but not adiposity in high-fat diet-fed mice. We found that DOG injection significantly alleviated adipose tissue inflammation via preventing macrophage infiltration and pro-inflammatory polarization of macrophages, and adipose tissue fibrosis via reducing the abnormal deposition of extracellular matrix. In LPS plus nigericin-stimulated THP-1 macrophages, DOG (1.25, 2.5, 5 µM) dose-dependently suppressed the activation of NLRP3 inflammasome and NF-κB signaling pathway. We demonstrated that DOG bound to and activated the deacetylase Sirtuin 2, which in turn deacetylated and inactivated NLRP3 inflammasome to reduce IL-1ß secretion. Moreover, DOG (1.25, 2.5, 5 µM) dose-dependently mitigated inflammatory responses in macrophage conditioned media-treated adipocytes and suppressed macrophage migration toward adipocytes. Taken together, DOG might be a drug candidate to treat metabolic disorders through modulation of adipose tissue remodeling.
Asunto(s)
Resistencia a la Insulina , FN-kappa B , Animales , Ratones , Tejido Adiposo/metabolismo , Dieta Alta en Grasa/efectos adversos , Inflamasomas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Ratones Obesos , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Sirtuina 2/metabolismoRESUMEN
The tuberous root of Ophiopogon japonicus (Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the geographic origins. Meanwhile, the root of Liriope spicata (Thunb.) Lour. var. prolifera Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.
Asunto(s)
Medicamentos Herbarios Chinos , Ophiopogon , Neoplasias Ováricas , Saponinas , Compuestos de Espiro , Humanos , Femenino , Ophiopogon/química , Línea Celular Tumoral , Saponinas/farmacología , Saponinas/química , Medicamentos Herbarios Chinos/químicaRESUMEN
Interleukin-1ß (IL-1ß), a key pro-inflammatory cytokine, is majorly produced by macrophages through NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, which has been identified as the culprit to deteriorate the inflammatory crosstalk between macrophages and adipocytes. Ainsliadimer C (AC) is a disesquiterpenoid isolated from Ainsliaea macrocephala. In the current study, we investigated the effects of AC on adipose tissue inflammation in co-culture of macrophages and adipocytes in vitro as well as in LPS-treated mice in vivo. We showed that AC (20-80 µM) dose-dependently inhibited the secretion of IL-1ß from LPS plus ATP-stimulated THP-1 macrophages by inhibiting the activation of NLRP3 inflammasome. Furthermore, we found that AC treatment activated NAD+-dependent deacetylase Sirtuin 1 (SIRT1), resulting in reduced acetylation level of NLRP3. Molecular modeling analysis revealed that binding of AC to sirtuin-activating compound-binding domain increased the affinity of the substrate to the catalytic domain of SIRT1. Moreover, AC (80 µM) significantly attenuated macrophage-conditioned medium-induced inflammatory responses in 3T3-L1 adipocytes. In LPS-induced acute inflammatory mice, administration of AC (20, 60 mg·kg-1·d-1, ip) for 5 days significantly suppressed the pro-inflammatory cytokine levels in serum and epididymal white adipose tissue (eWAT), attenuated macrophage infiltration into eWAT, and mitigated adipose tissue inflammation. The beneficial effects of AC were blocked by co-administration of a selective SIRT1 inhibitor EX-527 (10 mg·kg-1·d-1). Taken together, AC suppresses NLRP3-mediated IL-1ß secretion through activating SIRT1, leading to attenuated inflammation in macrophages and adipose tissue, which might be a candidate to treat obesity-associated metabolic diseases.
Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Tejido Adiposo/metabolismo , Animales , Citocinas/metabolismo , Inflamasomas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos NOD , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sirtuina 1/metabolismoRESUMEN
Adipose tissue remodelling is considered a critical pathophysiological hallmark of obesity and related metabolic diseases. Berberine (BBR), a natural isoquinoline alkaloid, has potent anti-hyperlipidaemic and anti-hyperglycaemic effects. This study aimed to explore the role of BBR in modulating adipose tissue remodelling and the underlying mechanisms. BBR protected high fat diet (HFD)-fed mice against adiposity, insulin resistance and hyperlipidemia. BBR alleviated adipose tissue inflammation and fibrosis by inhibiting macrophage infiltration, pro-inflammatory macrophage polarization and the abnormal deposition of extracellular matrix, and the effect was mediated by BBR directly binding and activating the deacetylase Sirtuin 3 (SIRT3) and suppressing the activation of the mitogen-activated protein kinases and nuclear factor-κB signalling pathways. Furthermore, BBR decreased microRNA-155-5p secretion by macrophages, which in turn ameliorated liver injury. Moreover, BBR mitigated inflammatory responses in both LPS-stimulated macrophages and TNF-α-treated adipocytes and suppressed macrophage migration towards adipocytes by activating SIRT3. Collectively, this study revealed that BBR improved adipose tissue remodelling, and subsequently inhibited the secretion of microRNA-155-5p by macrophages, which alleviated adiposity, insulin resistance and liver injury in obese mice. The modulation of adipose tissue remodelling by activating SIRT3 could contribute to the anti-hyperlipidemic and anti-hyperglycemic effects of BBR.
Asunto(s)
Berberina , Resistencia a la Insulina , MicroARNs , Sirtuina 3 , Tejido Adiposo , Animales , Berberina/farmacología , Berberina/uso terapéutico , Dieta Alta en Grasa , Inflamación , Ratones , MicroARNs/farmacología , Obesidad/tratamiento farmacológico , Obesidad/metabolismoRESUMEN
Pulmonary fibrosis is a prototypic chronic progressive lung disease with high morbidity and mortality worldwide. Novel effective therapeutic agents are urgently needed owing to the limited treatment options in clinic. Herein, nagilactone D (NLD), a natural dinorditerpenoid obtained from Podocarpus nagi, was found to suppress transforming growth factor-ß1 (TGF-ß1)-mediated fibrotic process in vitro and bleomycin (BLM)-induced pulmonary fibrosis in vivo. NLD attenuated TGF-ß1-induced expression of fibrotic markers including type I and III collagen, fibronectin, α-SMA, and CTGF in human pulmonary fibroblasts (WI-38 VA-13 and HLF-1 cells). Mechanism study indicated that NLD suppressed TGF-ß1-induced up-regulation of TßR I, and Smad2 phosphorylation, nuclear translocation, and transcriptional activation. Moreover, NLD ameliorated BLM-induced histopathological abnormalities in the lungs of experimental fibrotic mice, suppressed synthesis of relative fibrotic markers and fibroblast-to-myofibroblast transition, as well as BLM-induced up-regulation of TßR I expression and Smad signaling in mouse lungs. These data collectively support NLD to be a potential therapeutic agent for pulmonary fibrosis.
Asunto(s)
Diterpenos/farmacología , Fibroblastos/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Proteína Smad2/metabolismo , Terpenos/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Biomarcadores/metabolismo , Bleomicina/farmacología , Células Cultivadas , Femenino , Fibroblastos/metabolismo , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones , Ratones Endogámicos C57BL , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Fibrosis Pulmonar/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Norditerpenoids and dinorditerpenoids represent diterpenoids widely distributed in the genus Podocarpus with notable chemical structures and biological activities. We previously reported that nagilactone E (NLE), a dinorditerpenoid isolated from Podocarpus nagi, possessed anticancer effects against lung cancer cells in vitro. In this study we investigated the in vivo effect of NLE against lung cancer as well as the underlying mechanisms. We administered NLE (10 mg·kg-1·d-1, ip) to CB-17/SCID mice bearing human lung cancer cell line A549 xenograft for 3 weeks. We found that NLE administration significantly suppressed the tumor growth without obvious adverse effects. Thereafter, RNA sequencing (RNA-seq) analysis was performed to study the mechanisms of NLE. The effects of NLE on A549 cells have been illustrated by GO and pathway enrichment analyses. CMap dataset analysis supported NLE to be a potential protein synthesis inhibitor. The inhibitory effect of NLE on synthesis of total de novo protein was confirmed in Click-iT assay. Using the pcDNA3-RLUC-POLIRES-FLUC luciferase assay we further demonstrated that NLE inhibited both cap-dependent and cap-independent translation. Finally, molecular docking revealed the low-energy binding conformations of NLE and its potential target RIOK2. In conclusion, NLE is a protein synthesis inhibitor with anticancer activity.
Asunto(s)
Factor de Transcripción Activador 4/antagonistas & inhibidores , Antineoplásicos/farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/antagonistas & inhibidores , Diterpenos/farmacología , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Inhibidores de la Síntesis de la Proteína/farmacología , Factor de Transcripción STAT3/antagonistas & inhibidores , Células A549 , Factor de Transcripción Activador 4/biosíntesis , Factor de Transcripción Activador 4/genética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Biología Computacional , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Diterpenos/administración & dosificación , Diterpenos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones SCID , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2/biosíntesis , Factor 2 Relacionado con NF-E2/genética , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Inhibidores de la Síntesis de la Proteína/administración & dosificación , Inhibidores de la Síntesis de la Proteína/aislamiento & purificación , Factor de Transcripción STAT3/biosíntesis , Factor de Transcripción STAT3/genética , Células Tumorales CultivadasRESUMEN
Psidium guajava, a popular food and medicine dual purposes plant cultivated in tropical and subtropical regions, has been widely used as food crop and folk medicine, such as anti-diabetes agent, around the world. Triterpenoids have been considered as the major active ingredients of P. guajava. In the present study, a high-performance liquid chromatography coupled with diode array and evaporative light scattering detectors (HPLC-DAD-ELSD) method was developed for simultaneous determination of nine triterpenoids in P. guajava. Pressurized liquid extraction (PLE) was performed for sample preparation, and the analysis was achieved on a Cosmosil 5C18-MS-II (Nacalai Tesque, Kyoto, Japan) column eluted with gradient 0.1% aqueous formic acid-methanol system. The drift tube temperature of ELSD was set at 40 °C, and nitrogen flow-rate was at 1.6 L/min. All calibration curves for the analytes showed good linear regression (R2 > 0.9992) within test ranges. The established method was validated for intra-day and inter-day precisions (RSDs < 5%) and accuracy (recovery 94.23-106.87%). The validated method was successfully applied to determinate nine triterpenoids in 15 samples from the leave or fruit of P. guajava. In addition, the α-glucosidase inhibition assay showed good α-glucosidase inhibition activity in almost all the determined triterpenoids. The present study suggested that triterpenoids should be the quality control markers for P. guajava and HPLC-DAD-ELSD was an effective tool for the quality control of P. guajava.
Asunto(s)
Medicamentos Herbarios Chinos/química , Inhibidores de Glicósido Hidrolasas/química , Hipoglucemiantes/química , Psidium/química , Triterpenos/química , alfa-Glucosidasas/química , Calibración , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Formiatos/química , Frutas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Hipoglucemiantes/aislamiento & purificación , Extracción Líquido-Líquido/métodos , Metanol/química , Variaciones Dependientes del Observador , Hojas de la Planta/química , Control de Calidad , Solventes/química , Triterpenos/aislamiento & purificaciónRESUMEN
A pair of new glycosidic epimers, cablinosides A (1a) and B (1b) were isolated from the leaves of Pogostemon cablin. The structures with absolute configurations of 1a and 1b were elucidated by extensive NMR investigation, and quantum chemical CD calculations. The epimer mixture 1 showed moderate α-glucosidase inhibitory activity and no significant cytotoxic activity against HepG2 cells.
Asunto(s)
Glicósidos/química , Fenilacetatos/química , Pogostemon/química , Supervivencia Celular/efectos de los fármacos , Dicroismo Circular , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Conformación Molecular , Fenilacetatos/aislamiento & purificación , Fenilacetatos/farmacología , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Pogostemon/metabolismo , Estereoisomerismo , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismoRESUMEN
Four previously undescribed compounds, including three rarely occurring seco-dammarane triterpenoid glycosides and a pentacyclic triterpenic acid, were isolated from a 70% ethanol extract of the leaves of Cyclocarya paliurus (Juglandaceae), along with eleven known triterpenoids. Their structures were determined by spectroscopic techniques, including 2D NMR and HRESIMS, as well as chemical methods. Among them, several triterpenoids enhanced insulin stimulated glucose uptake in both 3T3-L1 adipocytes and C2C12 myotubes. Furthermore, compound 1 dose-dependently increased glucose uptake through activating AMP-activated protein kinase (AMPK)-p38 pathway. Collectively, triterpenoids from C. paliurus could be developed as insulin sensitizers, which might have therapeutic potential for insulin resistance and hyperglycemia.
Asunto(s)
Adipocitos/efectos de los fármacos , Glucosa/metabolismo , Juglandaceae/química , Terpenos/farmacología , Células 3T3-L1 , Quinasas de la Proteína-Quinasa Activada por el AMP , Adipocitos/citología , Animales , Transporte Biológico , Supervivencia Celular/efectos de los fármacos , Descubrimiento de Drogas , Glicósidos/química , Insulina , Ratones , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Proteínas Quinasas/metabolismo , Transducción de Señal , Relación Estructura-Actividad , Terpenos/aislamiento & purificaciónRESUMEN
Ganoderma resinaceum has been used as an ethnomedicine for lowering blood sugar. To clarify the bioactive chemical constituents contributing to lower blood sugar, chemical investigation on the fruiting bodies of Ganoderma resinaceum was conducted by chromatographic techniques, and led to the isolation of 14 compounds. Their structures were elucidated as triterpenoid lactones (1â»4 and 8) and ganoderma acids (5â»7 and 9â»14) based on the analysis of extensive spectroscopy (mass spectrometry (MS), nuclear magnetic resonance (NMR), infrared (IR), and ultraviolet (UV)) and comparison with literature data. Compounds 3, 5, 6, and 9â»14 were evaluated for α-glucosidase inhibitory activity. Compounds 1â»7 are new compounds. Compounds 1â»4 and 8 were characteristic of an oxaspirolactone moiety, consisting of a five-membered ether ring, a five-membered lactone ring, and a characteristic C-23 spiro carbon. It is rare for natural products that such an oxaspirolactone moiety occurred in the lanostane-type triterpenoids. Compounds 5â»7 and 9â»14 may be important intermediates of the biosynthetic pathways of 1â»4 and 8. Compounds 1 and 2 showed more potent inhibitory activity against α-glucosidase compared with the positive control drug acarbose with IC50 value of 0.75 ± 0.018 mM and 1.64 ± 0.022 mM, respectively.
Asunto(s)
Ganoderma/química , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Lactonas/farmacología , Triterpenos/farmacología , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Lactonas/química , Lactonas/aislamiento & purificación , Estructura Molecular , Análisis Espectral/métodos , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
A high-performance liquid chromatography (HPLC) method was investigated for the simultaneous quantification of two chemical types of bioactive compounds in the rhizome of Curcuma longa Linn. (turmeric), including three curcuminoids: Curcumin, bisdemethoxycurcumin, and demethoxycurcumin; and three volatile components: ar-turmerone, ß-turmerone, and α-turmerone. In the present study, the sample extraction system was optimized by a pressurized liquid extraction (PLE) process for further HPLC analysis. The established HPLC analysis conditions were achieved using a Zorbax SB-C18 column (250 mm × 4.6 mm i.d., 5 µm) and a gradient mobile phase comprised of acetonitrile and 0.4% (v/v) aqueous acetic acid with an eluting rate of 1.0 mL/min. The curcuminoids and volatile components were detected at 430 nm and 240 nm, respectively. Moreover, the method was validated in terms of linearity, sensitivity, precision, stability and accuracy. The validated method was successfully applied to evaluate the quality of twelve commercial turmeric samples.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Curcuma/química , Extractos Vegetales/química , Curcumina/análogos & derivados , Curcumina/química , Diarilheptanoides , Cetonas/química , Reproducibilidad de los Resultados , Rizoma/química , Sesquiterpenos/químicaRESUMEN
Nine new norditerpenoids and dinorditerpenoids, 2-oxonagilactone A (1), 7ß-hydroxynagilactone D (2), nagilactones K and L (3 and 4), 3ß-hydroxynagilactone L (5), 2ß-hydroxynagilactone L (6), 3-epi-15-hydroxynagilactone D (7), 1α-chloro-2ß,3ß,15-trihydroxynagilactone L (8), and 15-hydroxynagilactone L (9), were isolated from the seeds of Podocarpus nagi, along with eight known analogues. The structures of the new compounds were established based on detailed NMR and HRESIMS analysis, as well as from their ECD spectra. The absolute configuration of the known compound 1-deoxy-2α-hydroxynagilactone A (16) was confirmed by single-crystal X-ray diffraction. All of the isolates were tested for their cytotoxic activities against cancer cells. The results indicated that compounds 4 and 6, as well as several known compounds, displayed cytotoxicity against A2780 and HEY cancer cells. Among the new compounds, 2ß-hydroxynagilactone L (6) showed IC50 values of less than 2.5 µM against the two cell lines used. Furthermore, compound 6 induced autophagic flux in A2780 cells, as evidenced by an enhanced expression level of the autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and increased mRFP-GFP-LC3 puncta. Also, compound 6 activated the c-Jun N-terminal kinase (JNK) pathway, while pretreatment with the JNK inhibitor SP600125 decreased compound 6-induced autophagy.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Semillas/química , Antracenos/química , Antineoplásicos Fitogénicos/química , Autofagia/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citotoxinas , Diterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Seven new cucurbitane glucosides, 11-oxomogrosides III E and IV (1 and 2), 11-oxoisomogroside V (3), 7-oxomogrosides III E and IV (4 and 5), and mogrosides VI A and VI B (6 and 7), were separated from the crude extract of Siraitia grosvenorii. The new structures were defined by analysis of their 1H and 13C NMR, 2D NMR, and HRESIMS data. Especially, the band-selective constant time HSQC and band-selective constant time HMBC techniques were recuited to elucidate the structures of the complex glucoside moieties. Using the PGC-1α promoter driven luciferase reporter assay, the isolated compounds were examined for PGC-1α promoter activity.
Asunto(s)
Mezclas Complejas/aislamiento & purificación , Mezclas Complejas/farmacología , Cucurbitaceae/química , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Mezclas Complejas/química , Cristalografía por Rayos X , Glucósidos/química , Glicósidos/química , Proteínas de Choque Térmico , Estructura Molecular , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Triterpenos/químicaRESUMEN
Panacis Japonici Rhizoma (Zhu-Jie-Shen in Chinese), the root of P. japonicus C.A. Mey., is commonly used in traditional Chinese Medicine. Saponins are the major bioactive compounds in this herb. The similarity of polarity and structure of the natural products in herb caused the difficulty of purification and resulted in the shortage and high cost of the reference compounds, which has greatly hindered efforts toward quantification in quality control. A novel strategy using a standardized reference fraction for qualification of the major saponins in Panacis Japonici Rhizoma was proposed to easily and effectively control the quality of PJR. The strategy is feasible and reliable, and the methodology of the developed approach is also validated. The standardized reference fraction was used for quantification, which might solve the shortage of the pure reference compounds in the quality control of herbal medicines.
Asunto(s)
Ginsenósidos/química , Extractos Vegetales/química , Raíces de Plantas/química , Rizoma/química , Saponinas/química , Cromatografía Líquida de Alta Presión/métodos , Ginsenósidos/aislamiento & purificación , Límite de Detección , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/normas , Plantas Medicinales/química , Control de Calidad , Estándares de Referencia , Reproducibilidad de los Resultados , Saponinas/aislamiento & purificaciónRESUMEN
Diterpenoid dimers are rare in nature and mainly found in higher plants including the families Acanthaceae, Annonaceae, Asteraceae, Calceolariaceae, Chrysobalanaceae, Cupressaceae, Euphorbiaceae, Fabaceae, Lamiaceae, Liliaceae, Meliaceae, Rhizophoraceae, Taxaceae, Velloziaceae, and Zingiberaceae. In addition, a few diterpenoid dimers have been also reported from fungi (Psathyrellaceae), liverworts (Scapaniaceae), and a gorgonian (Gorgoniidae). They feature a wide variety of structures due to different core skeletons, linkage patterns, substituents, and configurations. Accordingly, diterpenoid dimers exhibit a broad range of bioactivities, including cytotoxic, anti-inflammatory, antimicrobial, antimalarial, and antifouling properties, which have attracted more and more research interests in the past decades. This review with 176 metabolites from 109 references provides a comprehensive and up-to-date overview of the source, biosynthesis, structure, synthesis, and bioactivities of diterpenoid dimers.
Asunto(s)
Diterpenos/química , Diterpenos/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antimaláricos/química , Antimaláricos/farmacología , Diterpenos/síntesis química , Diterpenos/metabolismo , Fabaceae/química , Hongos , Liliaceae/química , Meliaceae/química , Estructura Molecular , Rhizophoraceae/químicaRESUMEN
Hepatitis C virus (HCV) infects 200 million people worldwide, and 75% of HCV cases progress into chronic infections, which consequently cause cirrhosis and hepatocellular carcinoma. HCV infection is treated with currently considered standard drugs, including direct anti-viral agents (DAAs), alone or in combination with peginterferon-α plus ribavirin. However, sustained viral responses vary in different cohorts, and high costs limit the broad use of DAAs. In this study, the ethanol and water extracts of 12 herbs from Lingnan in China were examined in terms of their inhibitory effect on HCV replication. Among the examined extracts, Spatholobus suberectus ethanol extracts suppressed HCV replication. By comparison, Extracts from Fructus lycii, Radix astragali (root), Rubus chingii Hu (fruit), Flos chrysanthemi Indici (flower), Cassia obtusifolia (seed), Lonicera japonica Thunb (flower), Forsythia suspense Thunb (fruit), Poria cocos (sclerotia), Carthamus tinctorius L. (flower), Crataegus pinnatifida Bge. (fruit), and Leonurus japonicas Houtt. (leaf) extracts failed to show a similar activity. Active S. suberectus fractions containing tannins as the major component also inhibited the in vitro translation of HCV RNA. The combination treatments of single compounds, such as epigallocatechin gallate and epicatechin gallate, were not as potent as crude S. suberectus fractions; therefore, crude S. suberectus extract may be a potential alternative treatment against HCV either alone or in combination with other agents.
Asunto(s)
Antivirales/farmacología , Medicamentos Herbarios Chinos/farmacología , Fabaceae/química , Hepacivirus/efectos de los fármacos , Antivirales/química , Mezclas Complejas/farmacología , Medicamentos Herbarios Chinos/química , Regulación Viral de la Expresión Génica/efectos de los fármacos , Hepacivirus/fisiología , Técnicas In Vitro , Taninos/farmacología , Proteínas Virales/metabolismo , Replicación Viral/efectos de los fármacosRESUMEN
The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins RâT (1-3) and caesalsappanins M and N (4 and 5), together with seven known compounds 6-12. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute configurations of compounds 1 and 4 were determined by the corresponding CD spectra. All the isolated compounds were tested for their cytotoxicity against ovarian cancer A2780 and HEY, gastric cancer AGS, and non-small cell lung cancer A549 cells. Compound 1 displayed significant toxicity against the four cell lines with the IC50 values of 9.9 ± 1.6 µM, 12.2 ± 6.5 µM, 5.3 ± 1.9 µM, and 12.3 ± 3.1 µM, respectively. Compound 1 induced G1 phase cell cycle arrest in A2780 cells. Furthermore, compound 1 dose-dependently induced A2780 cells apoptosis as evidenced by Hoechst 33342 staining, Annexin V positive cells, the up-regulated cleaved-PARP and the enhanced Bax/Bcl-2 ratio. What's more, compound 1 also promoted the expression of the tumor suppressor p53 protein. These findings indicate that cassane diterpenoids might have potential as anti-cancer agents, and further in vivo animal studies and structural modification investigation are needed.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Diterpenos/química , Neoplasias/tratamiento farmacológico , Antineoplásicos Fitogénicos/química , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Caesalpinia/química , Proliferación Celular/efectos de los fármacos , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Semillas/químicaRESUMEN
Phytochemical investigation of the twigs of Podocarpus nagi (Podocarpaceae) led to the isolation of two new abietane-type diterpenoids, named 1ß,16-dihydroxylambertic acid (1) and 3ß,16-dihydroxylambertic acid (2), along with two new ent-pimarane-type diterpenoids, named ent-2ß,15,16,18-tetrahydroxypimar-8(14)-ene (3) and ent-15-oxo-2ß,16,18-trihydroxypimar-8(14)-ene (4). Their respective structures were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, IR, CD, and HR-ESI-MS. This is the first time ent-pimarane-type diterpenoids from the genus Podocarpus has been reported. All four new compounds were tested for cytotoxic activity. The MTT assay results showed that compounds 3 and 4 significantly inhibited the proliferation of human cervical cancer Hela cells, human lung cancer A549 cells, and human breast cancer MCF-7 cells at a concentration of 10 µM. Furthermore, using the lipopolysaccharide (LPS)-stimulated RAW264.7 cells, compounds 2 and 4 were found to significantly inhibit nitrogen oxide (NO) production with IC50 values of 26.5 ± 6.1 and 17.1 ± 1.5 µM, respectively.
RESUMEN
Homoisoflavonoids, a special subclass of flavonoids, are rarely found in nature, mainly existing in Fabaceae and Asparagaceae families and being less common in Polygonaceae, Portulacaceae, Orchidaceae, and Gentianaceae families. Until now, approximately 240 natural occurring homoisoflavonoids have been identified from roots, barks, heartwood, bulbs, leaves, and seeds of the plants from the above mentioned families, which have often been used in traditional medicine. Homoisoflavonoids have been reported with a broad range of bioactivities, including anti-microbial, anti-mutagenic, anti-oxidant, immunomodulatory, anti-diabetic, cytotoxic, anti-angiogenic, vasorelaxant, and anti-inflammatory effects. To organize this review, the homoisoflavonoids were classified into five groups based on their structures: sappanin-type (I), scillascillin-type (II), brazilin-type (III), caesalpin-type (IV), and protosappanin-type (V). The structures of natural occurring homoisoflavonoids are described, and their proposed biosynthetic pathway and recent pharmacological studies are discussed. The main purpose of this review is to provide a comprehensive and up-to-date state of knowledge from phytochemical and pharmacological studies performed on homoisoflavonoids during the past decades. Homoisoflavonoids might have a large potential for further investigations of their bioactivities in order to identify important leads.