RESUMEN
Currently, prolong use of standard anti-epileptics may cause tolerance and ineffective for about 30% of epileptic patients. Medicinal plants provide an attractive therapeutic effect in preventing and treating seizures in traditional and folk medicine. In this study, we investigate the antiepileptic effects of PTAT decoction on acute and chronic seizure models in mice and explore the potential mechanisms. PTAT decoction dose-dependently protected mice against MES and PTZ induced seizure. Meanwhile, it decreased the seizure severity and reduced seizure-caused anxious behavior in the PTZ-kindling mice, suggesting a significant antiepileptic activity and anxiolytic/anxiogenic potential. PTAT decoction dose-dependently increased the levels of GSH and the activity SOD and CAT, while decreased the level of MDA in the hippocampi of treated mice. Furthermore, a significant decrease in the proinï¬ammatory cytokine levels, including TNF-α, IL-1ß, IL-6 and MCP-1 was found in treated mice compared with the mice in the vehicle + PTZ group. Moreover, PTAT decoction dose-dependently reversed the alterations induced by PTZ in GABA, GABA-T, L-GAD and glutamate levels in kindling mice, showing an effect on the modulation of the GABA neurotransmission. Thus, PTAT decoction has a promising anticonvulsant activity mediated via multiple mechanisms, which might be used as an up-and-coming phytotherapy strategy in the management of epilepsy and its complications.
Asunto(s)
Acorus , Epilepsia , Polygala , Ratones , Animales , Anticonvulsivantes/efectos adversos , Acorus/metabolismo , Polygala/metabolismo , Pentilenotetrazol/toxicidad , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Estrés Oxidativo , Ácido gamma-Aminobutírico/farmacología , Ansiedad/inducido químicamente , Ansiedad/tratamiento farmacológico , Inflamación/tratamiento farmacológicoRESUMEN
Epilepsy is a serious public health problem in the world. At present, over 30% of affected patients remain refractory to currently available treatment. Medicinal plants as pharmaceuticals and healthcare treatments have been frequently used in the management of epilepsy in China for many centuries. Gastrodia elata-Acous tatarinowii (GEAT), as a classic and most commonly used herb pair in traditional Chinese medicine (TCM), has been employed to control seizures for thousands of years. However, the animal experiment data on its anticonvulsant effect is limited in the literature. Thus, this study aimed to reveal the therapeutic actions of GEAT decoction against seizures in mice. UHPLC-MS/MS was performed to analyze the chemical components of GEAT decoction. The mice were given GEAT decoction for 7 days, and MES, PTZ, and 3-MP injection was given 30 min after the last administration. Video monitoring was performed for comparisons. In addition, the PTZ-induced kindling models were conducted to investigate the seizure severity, anxiety and cognitive profile, inflammation, and oxidative stress parameters in mice. The results showed that GEAT decoction dose-dependently protected mice against MES, 3-MP, and PTZ-induced acute seizures. Furthermore, GEAT decoction significantly ameliorated seizure severity, decreased the accumulation of inflammatory mediators TNF-α, IL-1ß, and IL-6, mitigated oxidative stress, as well as alleviated anxious-like behavior and cognitive deficits in PTZ-kindled mice. These results suggest that GEAT decoction possesses certain anticonvulsant properties, which might be clinically useful as phytotherapy alone or as an adjunct therapy for the prevention and treatment of seizures and epilepsy.
Asunto(s)
Acorus , Epilepsia , Gastrodia , Ratones , Animales , Anticonvulsivantes/efectos adversos , Gastrodia/química , Acorus/química , Espectrometría de Masas en Tándem , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Purpose: Inflammation and accompanying pain is a common global health problem that seriously affects human quality of life worldwide. Here, we aimed to investigate the anti-nociceptive and anti-inflammatory activities of the ethyl acetate extract of B. chinensis (EAEBc) along with the underlying mechanisms of action. Methods: The in vitro anti-inflammatory activity of EAEBc was explored using an LPS-induced RAW264.7 cell inflammatory model. Nitric oxide (NO) production, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels were evaluated. In vivo anti-nociceptive and anti-inflammatory activities of EAEBc were assessed with the aid of classical experimental mouse models. In addition, LPS-induced biomarker contents (TNF-α, IL-1ß, IL-6, NO, iNOS, and PGE2) and formalin-induced serum inflammatory factors (NO, PGE2, 5-HT, ß-EP, substance P, and NE) were determined in mice. Results: In vitro, EAEBc significantly reduced LPS-induced NO generation and suppressed the production of TNF-α, IL-1ß, and IL-6 in RAW264.7 cells in a concentration-dependent manner. In vivo, EAEBc downregulated serum TNF-α, IL-1ß, IL-6, NO, iNOS, and PGE2 contents in mice with LPS-induced inflammation in a dose-dependent manner. EAEBc displayed anti-inflammatory activity in carrageenan-induced paw edema and xylene ear edema tests. Intragastric administration of EAEBc at test doses of 100 and 200 mg/kg led to inhibition of nociception and capillary permeability induced by acetic acid to varying degrees. Similarly, EAEBc exerted analgesic effects in the formalin and hot plate tests. In particular, the administration of EAEBc reversed the changes in the levels of inflammatory indicators NO, PGE2, 5-HT, ß-EP, substance P, and NE in a mouse model of formalin-induced pain. Conclusion: Our findings provide considerable evidence to support the extensive application of B. chinensis in traditional medicine and demonstrate the utility of this plant species as an effective candidate for prevention or treatment of various pain and inflammation-related conditions.