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1.
J Neurotrauma ; 38(6): 734-745, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33121345

RESUMEN

Spinal cord injury (SCI) invariably results in neuronal death and failure of axonal regeneration. This is attributed mainly to the hostile microenvironment and the poor intrinsic regrowth capacity of the injured spinal neurons. We have reported previously that electro-acupuncture on Governor Vessel acupoints (GV-EA) can promote neuronal survival and axonal regeneration of injured spinal cord. However, the underlying mechanism for this has remained uncertain. The present study aimed to explore the neural afferent pathway of GV-EA stimulation and the possible mechanism by which GV-EA can activate the intrinsic growth ability of injured spinal neurons. By cholera toxin B (CTB) retrograde labeling, immunostaining, and enzyme-linked immunosorbent assay (ELISA), we showed here that GV-EA could stimulate the spinal nerve branches of the dorsal root ganglion cells. This would then increase the release of calcitonin gene-related peptide (CGRP) from the afferent terminals in the spinal cord. It is of note that the effect was abrogated after dorsal rhizotomy. Additionally, both in vivo and in vitro results showed that CGRP would act on the post-synaptic spinal cord neurons and triggered the synthesis and secretion of neurotrophin-3 (NT-3) by activating the calcitonin gene-related peptide (CGRP)/ receptor activity-modifying protein (RAMP)1/calcium/calmodulin-dependent protein kinase (αCaMKII) pathway. Remarkably, the observed effect was prevented by the dorsal rhizotomy and the blockers of the CGRP/RAMP1/αCaMKII pathway. More importantly, increase in NT-3 promoted the survival, axonal regrowth, and synaptic maintenance of spinal cord neurons in the injured spinal cord. Therefore, it is concluded that increase in NT-3 production is one of the mechanisms by which GV-EA can activate the intrinsic growth ability of spinal neurons after SCI. The experimental results have reinforced the theoretical basis of GV-EA for its clinical efficacy in patients with SCI.


Asunto(s)
Péptido Relacionado con Gen de Calcitonina/metabolismo , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Electroacupuntura/métodos , Neurotrofina 3/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Nervios Espinales/metabolismo , Animales , Femenino , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiología , Traumatismos de la Médula Espinal/terapia
2.
Org Biomol Chem ; 18(6): 1135-1139, 2020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-31967630

RESUMEN

Biomimetic total syntheses of baefrutones A-D (1-4), baeckenon B (5), and frutescones A, D-F (6-9), isolated from the leaves of Baeckea frutescens, were achieved in 9, 8, and 5 steps, respectively, in moderate to good yields (72-83%). The synthetic routes feature the Michael addition, oxidative [4 + 2] cycloaddition, and water-promoted Diels-Alder click reactions as the key steps. This study helped gain thorough mechanistic insights into the biosynthetic origins and provided a facile approach for the construction of a library of natural tasmanone-based meroterpenoid analogues. Moreover, compounds 1-9 show potent inhibitory effects against S. paratyphi and/or C. albicans with MIC values of 3.125-25 µg mL-1, and they could be promising lead molecules for the design of new antibiotic agents.


Asunto(s)
Materiales Biomiméticos/farmacología , Monoterpenos/farmacología , Terpenos/farmacología , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/química , Candida albicans/efectos de los fármacos , Reacción de Cicloadición , Teoría Funcional de la Densidad , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Monoterpenos/síntesis química , Monoterpenos/química , Oxidación-Reducción , Pseudomonas aeruginosa/efectos de los fármacos , Salmonella/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Estereoisomerismo , Relación Estructura-Actividad , Terpenos/síntesis química , Terpenos/química
4.
Planta Med ; 85(9-10): 692-700, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30791058

RESUMEN

Dammarane-type saponins, the main active ingredients of Panax notoginseng, have substantial neuroprotective effects in different animal models of neurodegenerative diseases. However, because these compounds have different structures, the level of protection provided by individual compounds varies, and highly active compounds can be selected based on structure-activity relationships. Glutamate is a major excitatory neurotransmitter that plays an important role in synaptic response development. However, excessive extracellular glutamate levels lead to neuronal dysfunctions in the central nervous system. Herein, we investigated the neuroprotective effects of nine saponins (compounds 1:  - 9: ) on glutamate-treated PC12 cells in the concentration range of 0.1 - 10 µM. The MTT assay revealed that these compounds increased cell viability to 65.6, 69.8, 76.9, 91.7, 74.4, 63.3, 59.9, 64.7, and 59.9%, respectively, compared with the glutamate-treated cells (44.6%). Protopanaxatriol (compound 4: ) was the most neuroprotective compound, and subsequent experiments revealed that pretreatment with compound 4: significantly reverses mitochondrial membrane potential collapse, increases superoxide dismutase activity, and decreases lactate dehydrogenase leakage, malondiadehyde levels, reactive oxygen species generation, and cell apoptosis. Compound 4: also decreased the Bax/Bcl-2 ratio, cleaved caspase-3, N-methyl-D-aspartic receptor 1, and Ca2+-/calmodulin-dependent protein kinase II expression, and inhibited glutamate-induced cytochrome C release and phosphorylation of apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38. Overall, the results indicate that protopanaxatriol has significant neuroprotective effects, and might be a promising neuroprotective agent for preventing and treating neurodegenerative diseases.


Asunto(s)
Ácido Glutámico/efectos adversos , Fármacos Neuroprotectores/farmacología , Panax notoginseng/química , Saponinas/química , Saponinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Malondialdehído/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/química , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Fosforilación/efectos de los fármacos , Proteínas/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Saponinas/administración & dosificación , Triterpenos/química , Damaranos
5.
Molecules ; 23(12)2018 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-30572638

RESUMEN

Ethyl rosmarinate (RAE) is one of the active constituents from Clinopodium chinense (Benth.) O. Kuntze, which is used for diabetic treatment in Chinese folk medicine. In this study, we investigated the protective effect of RAE on high glucose-induced injury in endothelial cells and explored its underlying mechanisms. Our results showed that both RAE and rosmarinic acid (RA) increased cell viability, decreased the production of reactive oxygen species (ROS), and attenuated high glucose-induced endothelial cells apoptosis in a dose-dependent manner, as evidenced by Hochest staining, Annexin V⁻FITC/PI double staining, and caspase-3 activity. RAE and RA both elevated Bcl-2 expression and reduced Bax expression, according to Western blot. We also found that LY294002 (phosphatidylinositol 3-kinase, or PI3K inhibitor) weakened the protective effect of RAE. In addition, PDTC (nuclear factor-κB, or NF-κB inhibitor) and SP600125 (c-Jun N-terminal kinase, or JNK inhibitor) could inhibit the apoptosis in endothelial cells caused by high glucose. Further, we demonstrated that RAE activated Akt, and the molecular docking analysis predicted that RAE showed more affinity with Akt than RA. Moreover, we found that RAE inhibited the activation of NF-κB and JNK. These results suggested that RAE protected endothelial cells from high glucose-induced apoptosis by alleviating reactive oxygen species (ROS) generation, and regulating the PI3K/Akt/Bcl-2 pathway, the NF-κB pathway, and the JNK pathway. In general, RAE showed greater potency than RA equivalent.


Asunto(s)
Cinamatos/farmacología , Depsidos/farmacología , Células Endoteliales/citología , Glucosa/efectos adversos , Antracenos/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromonas/farmacología , Humanos , Simulación del Acoplamiento Molecular , Morfolinas/farmacología , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Ácido Rosmarínico
6.
Huan Jing Ke Xue ; 39(10): 4817-4824, 2018 Oct 08.
Artículo en Chino | MEDLINE | ID: mdl-30229632

RESUMEN

Aerobic composting experiments were conducted using lincomycin mycelia wastes (dreg) and manure (T), using sewage sludge with manure as a control (CK). High performance liquid phase methods and high throughput sequencing were used to determine the concentration of lincomycin residue and to characterize the microbial community. The results showed that lincomycin was reduced significantly, with the concentration decreasing from 1800 mg·kg-1 to 483 mg·kg-1, accounting for 73% degradation. In addition, the bacterial community abundance and diversity indices were all lower than that of sludge-manure at the mesophilic and thermophilic phases, because of the high concentration of lincomycin residue in lincomycin mycelia dreg. By contrast, the fungal community abundance and diversity indices showed the reverse, due to the high content of organic matter and nitrogen in lincomycin mycelia dreg. Therefore, the microbial communities were greatly different between T and CK treatment with the domain genera of Paucisalibacillus, Cerasibacillus, Bacillus, Virgibacillus, Ureibacillus, Paenibacillus, and Sinibacillus in T compost and Truepera, Actinomadura, Pseudosphingobacterium, Pseudomonas, Luteimonas and Ureibacillus in CK compost. However, as the composting continued to a mature phase, most of the lincomycin was reduced, and the differences between the two microbial communities gradually decreased. This showed that composting could make lincomycin mycelia dreg harmless and could be used to turn it into a resource.


Asunto(s)
Bacterias/clasificación , Compostaje , Lincomicina/metabolismo , Estiércol/microbiología , Microbiología del Suelo , Aguas del Alcantarillado , Suelo
7.
J Nat Prod ; 80(8): 2204-2214, 2017 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-28753309

RESUMEN

Frutescones H-R (1-11), new sesqui- or monoterpene-based meroterpenoids, were isolated from the aerial parts of Baeckea frutescens. Their structures and absolute configurations were established by means of spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ECD), as well as single-crystal X-ray crystallography of 1, (-)-7, and 9. The anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages, and the structure-activity relationships of 1-11 are also discussed. Compound 8 exhibited anti-inflammatory activity with an IC50 value of 0.36 µM, which might be related to the regulation of the NF-κB signaling pathway via the suppression of p65 nuclear translocation and the consequent decrease of IL-6 and TNF-α.


Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Myrtaceae/química , FN-kappa B/antagonistas & inhibidores , Componentes Aéreos de las Plantas/química , Transducción de Señal/efectos de los fármacos , Terpenos/aislamiento & purificación , Terpenos/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Animales , Antiinflamatorios/química , Cristalografía por Rayos X , Interleucina-6/química , Lipopolisacáridos/química , Macrófagos/química , Estructura Molecular , FN-kappa B/química , Relación Estructura-Actividad , Terpenos/química , Factor de Necrosis Tumoral alfa/química
8.
J Org Chem ; 82(3): 1448-1457, 2017 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-28029250

RESUMEN

Frutescone A-G [(1-6), (+)-7, (-)-7], a new group of naturally occurring tasmanone-based meroterpenoids, were isolated from the aerial parts of Baeckea frutescens L. Compounds 1 and 4 featured a rare carbon skeleton with an unprecedented oxa-spiro[5.8] tetradecadiene ring system, existing as two favored equilibrating conformers in CDCl3 solution, identified by variable-temperature NMR. The regioselective syntheses of 4-7 were achieved in a concise manner by a biomimetically inspired key hetero-Diels-Alder reaction "on water". Compounds 1, 4, and 5 exhibited moderate cytotoxicities in vitro.


Asunto(s)
Myrtaceae/química , Componentes Aéreos de las Plantas/química , Terpenos/aislamiento & purificación , Estructura Molecular , Estereoisomerismo , Terpenos/química
9.
Nat Prod Res ; 30(9): 1001-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26511166

RESUMEN

A new triterpene saponin, 3ß,16ß,23α,28ß,30ß-pentahydroxyl-olean-11,13(18)-dien-3ß-yl-[ß-D-glucopyranosyl-(1→2)]-[ß-D-glucopyranosyl-(1→3)]-ß-D-fucopyranoside, was named Clinoposaponin D (1), together with six known triterpene saponins, buddlejasaponin IVb (2), buddlejasaponin IVa (3), buddlejasaponin IV (4), clinopodisides D (5), 11α,16ß,23,28-Tetrahydroxyolean-12-en-3ß-yl-[ß-D-glucopyranosyl-(1→2)]-[ß-D-glucopyranosyl-(1→3)]-ß-D-fucopyranoside (6) and prosaikogenin A (7), and two known triterpenes, saikogenin A (8) and saikogenin F (9) were isolated from Clinopodium chinense (Benth.) O. Kuntze. Their structures were elucidated on the basis of 1D, 2D NMR and MS analysis. Meanwhile, the effects of all compounds on rabbit platelet aggregation and thrombin time (TT) were investigated in vitro. Compounds 4 and 7 had significant promoting effects on platelet aggregation with EC50 value at 53.4 and 12.2 µM, respectively. In addition, the highest concentration (200 µM) of compounds 2 and 9 shortened TT by 20.6 and 25.1%, respectively.


Asunto(s)
Lamiaceae/química , Saponinas/análisis , Triterpenos/análisis , Animales , Coagulación Sanguínea/efectos de los fármacos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Medicina Tradicional China , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análisis , Agregación Plaquetaria/efectos de los fármacos , Conejos , Sapogeninas/análisis , Espectrometría de Masa por Ionización de Electrospray , Tiempo de Trombina
10.
Molecules ; 20(8): 14879-88, 2015 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-26287144

RESUMEN

A new skeleton of diterpenoid, 1,2,3,4,4α,9,10,10α-octahydro-(4α-hydroxyymethyl) -1,1-dimethyl-9-(1-methylethyl)-(2S,3S,4αR,9R,10αS)-2,3,5,7-phenanthrenetertrol, named plebeianiol A (1), along with four known diterpenoids (2-5), were isolated from Salvia plebeia R. Br. Their structures were determined on the basis of spectral analysis. In the bioactivity tests, compounds 1, 2 and 5 showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities with IC50 values of 20.0-29.6 µM. In addition, these three compounds had significant inhibitory effects on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-induced macrophages. Compounds 1-3 inhibited nitric oxide (NO) production in LPS-induced macrophages with IC50 values of 18.0-23.6 µM. These results showed that compounds 1, 2 had significant antioxidant and anti-inflammatory activities and might provide basis for the treatment of diseases associated with oxidative lesions and inflammation.


Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Diterpenos/farmacología , Salvia/química , Animales , Antiinflamatorios/química , Antioxidantes/química , Vías Biosintéticas/efectos de los fármacos , Compuestos de Bifenilo/química , Espectroscopía de Resonancia Magnética con Carbono-13 , Supervivencia Celular/efectos de los fármacos , Diterpenos/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Óxido Nítrico/biosíntesis , Picratos/química , Espectroscopía de Protones por Resonancia Magnética , Células RAW 264.7
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