Alkaloids from the rhizomes of Ligusticum striatum exert antimigraine effects through regulating 5-HT1B receptor and c-Jun.
J Ethnopharmacol. 2019 Mar 14;:
Authors: Pu ZH, Peng C, Xie XF, Luo M, Zhu H, Feng R, Xiong L
ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is a prevalent, complex, painful, and disabling neurovascular disorder that places an enormous social and economic burden on patients. Rhizome Chuanxiong (RCX), the dried rhizomes of Ligusticum striatum DC., has been widely used in the clinic for the treatment of migraine for centuries in China. Total alkaloids (TAs) are considered to be important effective ingredients of L. striatum, especially for cardiovascular and cerebrovascular diseases. However, there has been no study published, to date, reporting the antimigraine effects of TAs from RCX (RCXTAs).
AIM OF THE STUDY: The present study was designed to evaluate the antimigraine effects of RCXTAs and explore the underlying mechanisms in an experimental migraine rat model.
MATERIALS AND METHODS: RCXTAs were prepared in accordance with our previous optimized preparation process. A nitroglycerin-induced migraine model in rats and a reserpine-induced migraine model in mice were established to investigate the effects of RCXTAs on monoamine neurotransmitters in brain tissue, including 5-hydroxytryptamine (5-HT) and its metabolite (5-HIAA). Migraine rats or mice were divided into six groups as follows: control; model; zolmitriptan (1.67 mg/kg); and low-, medium-, and high-dose RCXTAs (12.5, 25, and 50 mg/kg, respectively). The levels of 5-HT and 5-HIAA in the brains of rats and mice were determined by using the enzyme-linked immunosorbent assay method. Pathological changes in the brains of migraine rats were examined by immunohistochemistry. The protein expression of 5-HT1B receptor, c-Fos, and c-Jun in the periaqueductal gray (PAG) of migraine rats was measured by Western blot.
RESULTS: After preventive administration of RCXTAs to the nitroglycerin-induced migraine rats, the levels of 5-HT and 5-HIAA in the brain tissue were generally upregulated in all three RCXTA dose groups, a finding that was similar to that observed in the control group. Additionally, the 5-HT and 5-HIAA levels were significantly increased in the medium- and high-dose RCXTA groups when compared with the model group (p < 0.01). Therapeutical administration of RCXTAs to reserpine-induced migraine mice also inhibited the reduction of 5-HT and 5-HIAA in the brain (p < 0.01). Both immunohistochemistry and Western blot tests showed that RCXTAs pretreatment has significantly upregulated 5-HT1B receptor expression and downregulated c-Jun expression in the nitroglycerin-induced migraine rats.
CONCLUSIONS: RCXTAs exerted significant preventive and therapeutic effects on migraine. RCXTAs showed an antimigraine effect via regulating the levels of 5-HT and 5-HIAA. Upregulation of the expression of monoamine neurotransmitter 5-HT1B receptor and downregulation of the expression of c-Jun were the possible mechanisms.
PMID: 30880256 [PubMed – as supplied by publisher]