Both Senkyunolide I and Ligustrazine Suppress Retinal Spreading Depression

Research Article

Austin J Pharmacol Ther. 2017; 5(1).1091.

Both Senkyunolide I and Ligustrazine Suppress Retinal Spreading Depression

Li YL¹, Wang Y¹ and Wang M1,2*

¹Centre for Neuroscience, Xi’an Jiaotong- Liverpool University (XJTLU), Suzhou, China

²Department of Biological Sciences, XJTLU, Suzhou, China

*Corresponding author: Minyan Wang, Department of Biological Sciences, Xi’an Jiaotong-Liverpool University, Suzhou, 215123, China;

Received: March 13, 2017; Accepted: April 04, 2017; Published: April 10, 2017


Senkyunolide I (SEI) and ligustrazine are two active components of Chuanxiong Rhizoma that is commonly prescribed for migraine therapy; However their actions in early stage of migraine are not fully understood. This study aimed to investigate effects of these two compounds in a chick migraine model and to explore their possible mechanism of action. An in vitro chick retinal spreading depression (RSD) was induced by KCl and intrinsic optical imaging was used for RSD recording. Enzyme-linked immunosorbent activity assay was used to quantify retinal Calcitonin Gene-Related Peptide (CGRP) level. The results show that SEI concentration-dependently suppressed both the magnitude and propagation rate of RSD in the chick retina. Similarly, but to a lesser extent, the magnitude of RSD was also suppressed by ligustrazine. ELISA data further shows that the retinal CGRP level during RSD was slightly reduced by SEI but this reduction did not reach significance. This data demonstrates that both SEI and ligustrazine had the ability in suppressing RSD, suggesting these two active components of Chuanxiong Rhizoma may perform similar function for migraine prophylaxis and their activity is of neuronal mechanism.

Keywords: Senkyunolide I; Ligustrazine; Retinal spreading depression; Migraine


RSD: Retinal Spreading Depression; CGRP: Calcitonin Gene- Related Peptide; NO: Nitric Oxide; SEI: Senkyunolide I; CSD: Cortical Spreading Depression; MDA: Methylenedioxyamphetamine; SOD: Superoxide Dismutase; NMDAR: N-Methyl-D-Aspartate Receptor; ROS: Reactive Oxidative Stress; AOI: Area of Interest; AUC: Area Under the Curve


Chuanxiong Rhizoma is the most commonly prescribed traditional Chinese medicine for migraine therapy [1] and ischemia [2]. The herb contains many active ingredients, which are classified into phthalide compounds, organic acids, phenols, ferulic acid, essential oil and alkaloid tetramethylpyrazine, also termed ligustrazine [3]. These active ingredients can exert distinct functions, either possessing neuroprotective role by elevating vasoactive molecules such as Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP) [4,5], or regulating anti-inflammatory activity such as cytokines [6,7]. However, the role of these active ingredients in migraine and the associated mechanism are still not fully understood. Among these ingredients, phthalide compounds are regarded to have great therapeutic potential for treating migraine [7-9], in which Senkyunolide I (SEI, Figure 1) is a key component and shows effectiveness in migraine models. Oral administration of SEI can decrease pain threshold in a nitroglycerin-induced migraine model of rats [9]. When injected intraperitoneally in rats [10], the drug also suppresses the amplitude and frequency of Cortical Spreading Depression (CSD), the pathophysiological basis of migraine [11- 13]. The effectiveness of SEI on migraine models is associated with its vascular action in that the drug not only has the ability in regulating plasma 5-HIAA/5HT monoamine turnover rate [9], but also in reducing the elevated plasma concentrations of NO [9,10] and CGRP induced by CSD in rats [10]. Whether SEI has neuronal action is still controversial. On one hand, SEI is unable to alter the elevated NO level in the nitroglycerin-induced migraine model of rats [9]. On the other hand, SEI attenuates oxygen-glucose deprivation/ reoxygenation-induced inflammation in microglial cells [7], which suggests a neuronal action. In light of these observations, it is worth clarifying if the mechanism of action of SEI in a migraine model is neuronal. Ligustrazine (Figure 1) is another active component of Chuanxiong Rhizoma. This component can strengthen antioxidative function by lowering methylenedioxyamphetamine (MDA) content and elevating Superoxide Dismutase (SOD) activity [14]. Ligustrazine also alleviates N-Methyl-D-Aspartate (NMDA) receptor-elicited injury of rat retinal ganglion cells both morphologically and functionally by reducing reactive oxidative stress (ROS) level, Ca2+ response to NMDA and inhibiting the L-type calcium channel [15], signals of which are key in migraine pathophysiology [16,17]. Given that both ROS and NMDA receptor are key in migraine mechanism as ROS can be induced by CSD in the trigeminal nociceptive system [18] and inhibition of NMDA receptor can block CSD in various migraine models [16,19,20], we reason that ligustrazine may be also effective in suppressing CSD.