RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Lonicera japonica Thunberg is a traditional herbal medicine widely used in East Asia as an anti-bacterial, anti-inflammatory, and antiviral agent. This study was designed to investigate the effects of HS-23, ethanol extract of the dried flower buds of Lonicera japonica, in experimental models of sepsis and elucidate the mechanisms of action of HS-23. MATERIALS AND METHODS: Male ICR mice were intravenously administered HS-23 (20 and 40 mg/kg) for 0 (immediately) and 24 h after cecal ligation and puncture (CLP) for survival tests, and HS-23 (40 mg/kg) immediately after CLP for biochemical assays. RESULTS: HS-23 improved sepsis-induced mortality, enhanced bacterial clearance, and attenuated multiple organ failure. The mechanisms of action of HS-23 included attenuation of increased toll-like receptor (TLR)4 protein and mRNA expression. HS-23 suppressed sepsis-induced increases in protein expression of myeloid differentiation primary response protein 88, p38 and c-Jun N-terminal kinase in both liver and lung, as well as TIR-domain-containing adapter-inducing interferon-ß and interferon regulatory transcription factor 3 protein expression in liver. CONCLUSION: The results of this study revealed that HS-23 attenuated sepsis through suppression of TLR signaling pathways. Therefore, our findings suggest that HS-23 might be useful as a potential therapeutic agent for treatment of sepsis.
Asunto(s)
Lonicera/química , Extractos Vegetales/farmacología , Sepsis/tratamiento farmacológico , Receptor Toll-Like 4/metabolismo , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hígado/efectos de los fármacos , Hígado/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , ARN Mensajero/metabolismo , Sepsis/mortalidad , Transducción de Señal/efectos de los fármacosRESUMEN
This study examined the hepatoprotective effects of Agrimonia eupatoria water extract (AE) against chronic ethanol-induced liver injury. Rats were fed a Lieber-DeCarli liquid diet for 8 weeks. Animals were treated orally with AE at 10, 30, 100, and 300 mg/kg/day. After chronic consumption of ethanol, serum aminotransferase activities and pro-inflammatory cytokines markedly increased, and those increases were attenuated by AE. The cytochrome P450 2E1 activity and lipid peroxidation increased after chronic ethanol consumption, while reduced glutathione concentration decreased. Those changes were attenuated by AE. Chronic ethanol consumption increased the levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expression, inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression, and nuclear translocation of nuclear factor-kappa B, which was attenuated by AE. Our results suggest that AE ameliorates chronic ethanol-induced liver injury, and that protection is likely due to the suppression of oxidative stress and TLR-mediated inflammatory signaling.
Asunto(s)
Agrimonia/química , Etanol/toxicidad , Hepatopatías Alcohólicas/prevención & control , Extractos Vegetales/farmacología , Animales , Secuencia de Bases , Peso Corporal , Citocromo P-450 CYP2E1/metabolismo , Citocinas/sangre , Cartilla de ADN , Relación Dosis-Respuesta a Droga , Mediadores de Inflamación/sangre , Peroxidación de Lípido , Masculino , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptor Toll-Like 4/metabolismo , Transaminasas/sangreRESUMEN
AIM OF THE STUDY: GCSB-5 (traditional name: Chungpa-Juhn), an herbal medicine composed of 6 crude herbs (Saposhnikovia divaricata Schiskin, Achyranthis bidentata Blume, Acanthopanax sessiliflorum Seem, Cibotium baromets J. Smith, Glycine max Meriill, and Eucommia ulmoides Oliver), has been widely used in Asia for treatment of neuropathic and inflammatory diseases. This study investigated the protective effect of GCSB-5 against peripheral nerve injury in vitro and in vivo. MATERIALS AND METHODS: After left sciatic nerve transection, rats received oral administration of GCSB-5 (30, 100, 300, and 600 mg/kg), or saline (vehicle), respectively, once daily for 8 weeks. Motor functional recovery and axonal nerve regeneration were evaluated by measurement of sciatic functional index (SFI), sensory regeneration distance, and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. In the in vitro study, the effects of GCSB-5 on H(2)O(2)-induced oxidative damage in SH-SY5Y cells were investigated by measurement of cell viability, production of reactive oxygen species (ROS), lipid peroxidation, release of lactate dehydrogenease (LDH), and cellular glutathione contents. Neurite outgrowth was also determined. RESULTS: After 8 weeks of nerve transection, SFI, regeneration distance, and gastrocnemius muscle mass ratio and myelinated axon number showed a significant decrease and these decreases were attenuated by GCSB-5. GCSB-5 significantly inhibited H(2)O(2)-induced cell death and oxidative stress, as evidenced by decreases in production of ROS and lipid peroxidation and release of LDH, and by increase in total GSH content. CONCLUSIONS: The neuroprotective effect afforded by GCSB-5 is due in part to reduced oxidative stress.