Hejie Zhitong prescription promotes sleep and inhibits nociceptive transmission-associated neurotransmitter activity in a rodent migraine model

Abstract

Background Migraine is painful disease in which neurotransmitters related to pain transmission play an important role. Hejie Zhitong prescription (HJZT) has been used in the clinic as an effective prescription for the treatment of migraine for many years. Our team aimed to further explore its antimigraine mechanism based on previous research results and to explore the inhibitory effect of HJZT on the transmission of pain related to nitroglycerine (NTG)-induced migraine as well as the synergistic effect of HJZT with pentobarbital sodium on promoting sleep. Methods Sixty mice were randomly assigned to groups and received the corresponding interventions. Sleep latency and sleep time were recorded to calculate the incidence of sleep. Forty-eight Wistar rats were randomly assigned and administered an intervention corresponding to their group. Calcitonin gene-related peptide (CGRP), serotonin (5-HT), substance P (SP), and cholecystokinin (CCK) levels were measured using ELISAs. Levels of the cannabinoid receptor type 1 (CB1R) and cyclooxygenase-2 (COX-2) protein were assessed using immunohistochemistry. The expression of the CGRP and CCK mRNAs in the midbrain and trigeminal ganglion (TG) were measured using real-time quantitative PCR. Results HJZT promoted the occurrence of sleep in mice. HJZT downregulated COX-2 expression in the midbrain and TG of rats but upregulated the expression of the CB1R, and decreased the plasma level of the CGRP protein and expression of its mRNA in the midbrain and TG. It also downregulated the expression of the CCK mRNA in the midbrain and TG. The high-dose HJZT treatment increased plasma 5-HT levels, but did not induce changes in the plasma levels of the SP or CCK protein. Conclusions HJZT exerts a synergistic effect with pentobarbital sodium on promoting sleep. As for anti-migraine, HJZT can inhibits the expression of nociceptive transmission-associated neurotransmitters, including 5-HT, CGRP and CCK, which may be related to its upregulation of CB1R and downregulation of COX-2.

A role of NLRP3 and MMP9 in migraine progression: a systematic review of translational study

“…Across the research included in this review, a variety of outcome measures were observed, such as behavioral tests ( n = 9; 40.09%) ( 30 , 70 , 74–76 ), Sensory sensitivity testing ( 28 ), von Frey Testing ( 27 , 77 ), Light/dark test ( 27 ), Von frey test ( 27 ). To check the specific biomarker estimation ELISA ( n = 8; 36.36%) ( 30 , 31 , 72 , 74 , 75 , 77–79 ), Western blot analysis ( n = 9; 40.09%) ( 28 , 70 , 73–75 , 79–83 ), immunohistochemistry ( n = 4; 18.18%) ( 72 , 73 , 75 , 77 , 78 , 81 , 82 ), Histopathology ( 27 ), Immunofuorescence staining ( n = 9; 40.09%) ( 27 , 28 , 30 , 31 , 70 , 76 , 78 ), and for gene expression used qRT PCR ( n = 7; 31.81%) ( 27 , 28 , 31 , 70 , 74 , 77 , 78 , 80 , 81 , 83 ). The majority of researchers, around 60–70%, neglect to validate their experiments using behavioral tests, Western blotting, Immunofluorescence, and Immunohistochemistry, despite these tests being crucial for experimental validation.…”

Role of herbal medicine for prevention and treatment of migraine

“…Six major ingredients (baicalin, arginine, proline, oroxindin, galactinol, and choline) were detected in this prescription after HPLC-MS/MS analysis, but their contents were not provided (X. Wang et al, 2020). pain intensity for a treatment period of 16 weeks (Fu et al, 2012).…”

“…Hejie Zhitong prescription (i.g., 2.34, 4.68, and 9.36 g/kg/day, for 1 week) exerted antimigraine activities through the extension of sleep latency and time in mice and the restriction of nociceptive transmission by dose‐dependently downregulating neurotransmitters like 5‐HT, CGRP, and CCK in migraine rats, which might be related to the elevated CB1R and reduced COX‐2 expressions. Six major ingredients (baicalin, arginine, proline, oroxindin, galactinol, and choline) were detected in this prescription after HPLC–MS/MS analysis, but their contents were not provided (X. Wang et al, 2020).…”

Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions

“…Studies have shown that as a supplementary treatment of modern medicine, TCM improved the therapeutic effect of modern medicine. For example, after intraperitoneal injection of pentobarbital sodium, rats were given He jie Zhitong prescription by gavage, the sleep latency of rats was significantly decreased, and the sleep time was prolonged, suggesting that Hejie Zhitong prescription exerted a synergistic effect with pentobarbital sodium [ 19 ]. Shufeng Jiedu Capsule enhanced doxorubicin therapeutic efficacy in hepatocellular carcinoma by inhibiting migration and invasion [ 20 ].…”