YES-10, A Combination of Extracts from Clematis mandshurica RUPR. and Erigeron annuus (L.) PERS., Prevents Ischemic Brain Injury in A Gerbil Model of Transient Forebrain Ischemia

Abstract

Clematis mandshurica RUPR. (CMR) and Erigeron annuus (L.) PERS. (EALP) have pharmacological effects including anti-inflammatory activity and been used in traditional medicines in Asia. However, neuroprotective effects of CMR and/or EALP extracts against brain ischemic insults have never been addressed. Thus, the aim of this study was to examine neuroprotective effects of YES-10, a combination of extracts from CMR and EALP (combination ratio, 1:1), in the hippocampus following ischemia/reperfusion in gerbils. Protection of neurons was investigated by cresyl violet staining, fluoro-jade B histofluorescence staining and immunohistochemistry for neuronal nuclei. In addition, attenuation of gliosis was studied by immunohistochemistry for astrocytic and microglial markers. Treatments with 50 or 100 mg/kg YES-10 failed to protect neurons in the hippocampus after ischemia/reperfusion injury. However, administration of 200 mg/kg YES-10 protected neurons from ischemia/reperfusion injury and attenuated reactive gliosis. These findings strongly suggest that a combination of extracts from CMR and EALP can be used as a prevention approach/drug against brain ischemic damage.

Experimental pretreatment with YES‑10®, a plant extract rich in scutellarin and chlorogenic acid, protects hippocampal neurons from ischemia/reperfusion injury via antioxidant role

“…YES-10 ® was prepared as previously described in our published paper ( 5 , 30 ). Briefly, CMR and EALP were cultivated in Metro-Mix potting soil with a slow releasing fertilizer (Osmocote Plus).…”

“…The administration of the vehicle or YES-10 ® was orally given with a feeding needle once/day for 7 days because extracts from natural products have orally been ingested in traditional medicine. The dose of YES-10 ® (200 mg/kg) was chosen on the basis of our published paper, in which pretreatment with 200 mg/kg of YES-10 ® strongly protected the pyramidal neurons located in the hippocampal CA1 field after TI ( 5 ). We applied 7 days for YES-10 ® administration according to previous studies with plant extracts, and since data regarding to ADME properties of YES-10 ® had been rarely reported ( 18 , 31 ).…”

“…The neuroprotective mechanisms of YES-10 ® against brain ischemic injury have been poorly investigated, although we reported neuroprotective effects in a gerbil model of 5-min transient forebrain ischemia ( 5 ). In addition, it has been demonstrated that plants belonging to the genus Clematis , specifically Clematis chinensis , contains scutellarin, a flavonoid glycoside compound ( 20 , 21 ).…”

“…In this regard, we recently published a paper that showed that pretreatment with YES-10 ® , a combination of extracts from Erigeron annuus (L.) PERS (EALP) and Clematis mandshurica RUPR. (CMR), protected cornu ammonis 1 (CA1) pyramidal neurons and attenuated gliosis (astrogliosis and microgliosis) in the hippocampus of a gerbil model of 5-min transient forebrain ischemia ( 5 ).…”

Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

“…In addition, it has been reported that a severer aspect of neuronal loss/death in the hippocampus is shown following 15 min of TFI than that in 5 min TFI in gerbils [ 2 ]. Furthermore, a rat model of focal brain ischemia induced by MCAO for over 1 h develops infarct lesion (necrotic tissue) which is easily visualized by 2, 3, 5-triphenyltetrazolium chloride (TTC) assay, but infarction does not occur in the brain induced by TFI for 5–15 min in gerbils when the TTC assay is applied, in which selective neuronal death only occurs [ 1 , 15 , 30 , 31 , 32 , 33 ].…”