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J Ethnopharmacol ; 249: 112437, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794788


ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is a disabling neurovascular disorder, which increases risk of cardiovascular events and is a social burden worldwide. The present first-line anti-migraine medications can cause overwhelming side-effects, of which one includes the onset of cardiovascular disease. As one of the marketed Tibetan drugs, Ru-yi-Zhen-bao Pills (RYZBP) have been clinically used to treat cardiovascular disorders and as anti-migraine medication. However, there is currently no research exploring the anti-migraine actions of RYZBP. AIM OF THE STUDY: The current research was designed to assess the anti-migraine roles of RYZBP and explore the underlying mechanisms in a nitroglycerin (NTG)-induced migraine rat model trial. MATERIALS AND METHODS: 120 rats were randomly divided into the following six groups of 20 rats each: normal control group, model control group, positive control group, and RYZBP high/medium/low-dose groups (Ru-yi-Zhen-bao Pills; TH 1.00 g/kg, TM 0.50 g/kg and TL 0.25 g/kg). All rats were administered intragastrically for 7 consecutive days, which were subcutaneously injected with the NTG (10 mg/kg) after the last gavage (except in the normal control group). 3min after NTG treatment, 30 rats (5 rats from each group) were anesthetized and devoted to electroencephalogram(EEG) testing, which was used to evaluate the analgesic effect of RYZBP. One hour after NTG treatment, the rest of the 90 rats (15 rats from each group) were anesthetized and midbrain tissue sample was dissected. The dissection was then washed with physiological saline and collected. The histopathological changes in the periaqueductal gray(PAG) of 5 tissue samples were determined by aematoxylin-eosin (H&E) staining, as well as an estimation of substance P (SP) and neurokinin 1 receptor (NK1R) expression through immunohistochemically staining(IHC). Another 5 midbrain preparations were carried out to evaluate calcitonin gene-related peptide (CGRP), proenkephalin (PENK), SP, and cholecystokinin (CCK) expressions by real-time quantitative polymerase chain reaction (RT-qPCR). The rest of the 5 brainstem tissues were then used to measure CCK, CGRP, and opioid peptide receptor (DORR) levels by western blotting(WB). RESULTS: In the EEG test, RYZBP (TM 0.50 g / kg) treatment transformed the EEG pain-wave of the NTG-induced migraine model rats in different time period. In the mechanism assay, compared with the model control group, RYZBP pretreatment reduced inflammatory cell infiltration, fibrosis and vacuolation of neuronal cells of PAG tissue seen by HE staining. IHC experiments further showed that RYZBPTM up-regulated SP expression levels and enhanced NK1R levels in the NTG-induced migraine rats (P < 0.05). Therapeutic administration of RYZBP also increased PENK mRNA expression and DORR protein level. Both RT-qPCR and western blotting trials indicated that RYZBP treatment significantly decreased CCK and CGRP expression levels (P < 0.01 or P < 0.05) in the NTG-induced migraine rats. CONCLUSIONS: RYZBP has the potential to be an effective anti-migraine treatment through suppressing the EEG pain-wave, increasing the levels of SP, PENK, DORR and reducing expression of CCK and CGRP. Mediating the PAG anti-nociceptive channel and inhibiting central sensitization were the two potential mechanisms, which offers further evidence for clinical therapy.

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 16(3): 151-4, 2004 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-15009961


OBJECTIVE: To study ultrastructured change and neuron apoptosis after focal cerebral ischemia/reperfusion (I/R) in the aged rats. METHODS: The aged SD rats (20-21 months) and the young (4-5 months) were subjected to 3 hours of middle cerebral artery occulsion with the intraluminal filament technique, followed by reperfusion for 3 hours, 6 hours, 12 hours, 24 hours, 72 hours. The ultrastructure of brain, infarct zone and neuron apoptosis were observed. RESULTS: The cerebral infarct zone increased in the aged rats with ischemia for 3 hours and I/R for 12 hours compared with those in the young. The brain injury was obviously deteriorated with I/R time longer, which was serious in the aged than that in the young. The neuron apoptosis increase with I/R time longer, and showed earlier and lasted longer in the aged. CONCLUSION: The cerebral injury is serious and neuron apoptosis increase shows early and lasts longer.

Apoptose , Isquemia Encefálica/fisiopatologia , Neurônios/patologia , Traumatismo por Reperfusão/fisiopatologia , Fatores Etários , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos Sprague-Dawley
Zhongguo Zhong Yao Za Zhi ; 29(1): 66-70, 2004 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15709387


OBJECTIVE: To study neuro-protective effect of naomaitong on brain damage after focal cerebral ischemia reperfusion (I/R) in the aged rats. METHOD: 11 groups of 20-22-month old SD rats were subjected to 3 hours of middle cerebral artery occlusion with the intraluminal filament technique, followed by 12 hours of reperfusion. Nervous symptom, oedema of brain, infarct size, morphology and superfine structure of brain, etc were monitored thoughout cerebral ischemia and reperfusion. RESULT: Infarct size of brain in ischemia and reperfusion groups were significantly greater. Oedema of it was higher, nervous symptom of it was more serious, and morphology and superfine structure brain were more obvious than those of sham-operated group. Nervous symptom, oedema of brain, infarct size, morphology and superfine structure of brain in treated groups were ligher than those of untreated groups (P < 0.001). CONCLUSION: Naomaitong can protect brain damage after focal cerebral I/R in the aged rats.

Encéfalo/patologia , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Plantas Medicinais , Traumatismo por Reperfusão/patologia , Fatores Etários , Animais , Comportamento Animal/efeitos dos fármacos , Isquemia Encefálica/complicações , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Masculino , Panax/química , Plantas Medicinais/química , Pueraria/química , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia , Rheum/química