Artificial intelligence analysis to explore synchronize exercise, cobalamin, and magnesium as new actors to therapeutic of migraine symptoms: a randomized, placebo-controlled trial.

INTRODUCTION: Migraine is recognized as a complex neurological disorder that has imposed a social burden. We assessed the signaling pathways and molecular mechanisms based on the in silico analysis and predicted drug candidates by the biomedicine approach. Moreover, we evaluated high-intensity interval training and vitamin B12 + magnesium on women's migraine attacks and inflammatory status. METHODS: This study computed differential gene expression in migraine syndrome and the dimension network parameters visualized by software. Moreover, we proposed the functional mechanism and binding energy of essential micronutrients on macromolecules based on drug discovery. In this clinical trial, 60 cases were randomized to four groups, including applied high-intensity interval training (HIIT), cases consumed supplementation vitamin B12 and magnesium (Supp), cases applied high-intensity interval training, and consumed supplementation (HIIT + Supp), and migraine cases for 2 months. Serum levels of calcitonin gene-related peptide (CGRP) were measured at baseline and at the end of the study. In addition, migraine disability assessment score (MIDAS), frequency, intensity, and duration were recorded before and during interventions. RESULTS: In silico study revealed the association between inflammation signaling pathways and pathogenesis of migraine attacks as a remarkable pathomechanism in this disorder. Furthermore, serum concentrations of CGRP were significantly declined in the HIIT + Supp compared with other groups. In addition, MIDAS, frequency, intensity, and duration were reduced in the HIIT + Supp group compared with the other groups. CONCLUSION: We found that the synergistic effects of cobalamin and magnesium followed by regular exercise could silence the inflammation signaling pathway, and a combination of HIIT + Supp could ameliorate migraine pain. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials; IRCT code: IRCT20170510033909N12. Approval Data: 2021/06/02.

The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial.

BACKGROUND: Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. METHODS: The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. RESULTS: The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). CONCLUSION: According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. TRIAL REGISTRATION: The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.

Identification and quantification of the quality markers and anti-migraine active components in Chuanxiong Rhizoma and Cyperi Rhizoma herbal pair based on chemometric analysis between chemical constituents and pharmacological effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong Rhizoma and Cyperi Rhizoma (CRCR), an ancient and classic herbal pair, has been used in herbal medicines for treating migraine, but its effective components are not clear. AIM OF THE STUDY: The present study aimed to identify and quantify the quality markers and anti-migraine active components in CRCR based on chemometric analysis between chemical constituents and pharmacological effects. MATERIALS AND METHODS: The HPLC fingerprints of eight batches of CRCR samples were obtained, and their characteristic common peaks were identified by HPLC-ESI-Q-TOF-MS/MS. The therapeutic effects of eight batches of CRCR samples on nitroglycerin-induced migraine rats were evaluated by migraine-related neurotransmitters and neuropeptides. Similarity analysis, hierarchical cluster analysis and principal component analysis were applied to screen the quality markers. Artificial neural network and partial least squares regression models were used to screen the anti-migraine compounds by correlating the chemical constituents in HPLC fingerprints and pharmacological indicators. RESULTS: Eighteen characteristic common peaks were found in the HPLC fingerprints, including eleven known compounds and seven unknown compounds. Ferulic acid (FA), senkyunolide I (SI), senkyunolide A (SA), 3-n-butylphthalide (NBP), Z-ligustilide (LIG), Z-3-butylidenephthalide (BDPH), nookatone (NKT), levistilide A (LA), α-cyperone (CYP) and other five unknown compounds (P1, P2, P7, P8 and P9) were identified as quality markers. SA, NBP, LIG, NKT, CYP and other three unknown compounds (P1, P4 and P9) can be considered as anti-migraine prototype compounds. The quality markers and anti-migraine active components were further quantified in CRCR extract, rat serum and cerebral cortex by UPLC-MS/MS, which gives a clue to track the dynamic changes of the contents of the main constituents. CONCLUSIONS: Our study explored the anti-migraine material basis, and could lay a foundation for the improvement of the quality control of CRCR in practice.

Precise and systematic survey of the efficacy of multicomponent drugs against functional dyspepsia.

Functional dyspepsia (FD) is one of the most prevalent functional gastrointestinal disorders, and more and more multicomponent drugs represented by traditional Chinese medicines have provided a favorable therapeutic effect in its treatment. However, their precise localization in the clinic, as well as corresponding mechanism, is ambiguous, thus hindering their widespread use. To meet this requirement, a precise and systematic approach based on a restriction of special disease-related molecules and the following network pharmacology analysis was developed and applied to a multicomponent conventional drug, XiaoErFuPi (XEFP) granules. Experimental verification of the results indicates that this approach can facilitate the prediction, and the precise and systematic efficacy of XEFP could be easily revealed, which shows that XEFP has an advantage over the positive control drug on lactate, gastrin, interleukin 4 and calcitonin gene-related peptide. Moreover, by the proteomics analysis, its superposition of multi-target effects was revealed and a new candidate target for the treatment of FD, striatin, was obtained and verified. This study provides a practicable precise approach for the investigation of the efficacy of multicomponent drugs against FD and offers a promising alternative for the systematical management of FD.

Hyperbaric oxygen may improve vascular endothelial function in patients undergoing coronary stent implantation.

Background: Hyperbaric oxygen (HBO2) therapy improves myocardial function and reduces clinical restenosis in coronary arteries. This study aims to evaluate whether the HBO2 therapy can improve vascular endothelial dysfunction in patients undergoing coronary stent implantation. Methods: The retrospective study included 115 patients undergoing coronary stent implantation. Patients receiving HBO2 therapy were included in the HBO2 group (n=55) and those without HBO2 therapy were included as controls (n=60). The levels of brachial artery endothelial-dependent flow-mediated dilation (FMD), endothelial-independent nitrate-mediated dilatation (NMD), nitric oxide (NO), endothelin-1(ET-1), calcitonin gene-related peptide (CGRP) and high-sensitivity C-reactive protein (hs-CRP) were used to evaluate vascular endothelial function. Results: There were no significant differences with regard to the above parameters at baseline in either group (p⟩0.05). In both the HBO2 and control groups the levels of FMD, NO and CGRP after treatment were significantly higher than those before treatment (p⟨0.05). The levels of hs-CRP and ET-1 after treatment were significantly lower than those before treatment (p⟨0.05). After treatment, the levels of FMD, NO and CGRP in the HBO2 group were significantly higher than those of the control group (p⟨0.05), whereas the hs-CRP and ET-1 levels were significantly lower than those of the control group (p⟨0.05). Conclusion: Using HBO2 therapy as an adjunct treatment in patients undergoing coronary stent implantation may significantly improve vascular endothelial function. HBO2 therapy may have the potential to alter the course of coronary artery disease in the future. Further randomized, multicenter, prospective studies are needed.

Effect of Transcutaneous Electrical Stimulation of Nerves on Blood Pressure and Blood Content of Neuropeptide CGRP and Nitric Oxide in Hypertensive Rats with Metabolic Disturbances.

The development of arterial hypertension in male Wistar rats with fructose-induced metabolic syndrome (12.5% of fructose solution as the only drinking source for 10 weeks) along with impaired glucose tolerance and increased serum concentration of triglycerides and LPO products caused a decrease in the content of serum blood calcitonin gene-related peptide (CGRP). Low-frequency transcutaneous electrical nerve stimulation (1 mA, 2 Hz, 10 min daily for 2 weeks) performed in 8 weeks after the beginning of fructose treatment reduced systolic BP and serum concentration of triglycerides and LPO produces and improved glucose tolerance. After stimulation, CGRP content in rats maintained on fructose diet returned to normal values and the content of nitric oxide metabolites increased. We hypothesize that CGRP and nitric oxide are involved in mechanisms mediating the therapeutic effect of low-frequency transcutaneous electrical nerve stimulation on arterial hypertension developing in metabolic syndrome.

Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix.

The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio. The optimal conditions for CO2 supercritical fluid extraction of EOAD, as determined by orthogonal test [L9(34)], were as follows: 2 h extraction time, 20 MPa pressure, 40°C temperature, and 30 mesh. The yield of EOAD was 1.8%. On gas chromatography-mass spectrometry, 45 peaks were found in EOAD, and 22 compounds were identified and quantified. The main constituents of EOAD were 1-dodecanol (13.71%), elemene (7.54%), palmitic acid ethyl ester (7.32%), α-pinene (6.25%), and 1-pentadecanol (6.08%). Compared with rat migraine model controls, EOAD (35, 70, and 140 mg/kg) significantly reduced the number of head shaking, head scratching, and hind leg shooting events, decreased serum and brain NO levels, decreased plasma CGRP, and increased ET levels in rats. ET/NO ratio was elevated to 28.68 in the EOAD high-dose group. EOAD ameliorates NTG-induced migraine in rats likely by modulating the levels of vasoactive substances.

Chemical profiles and pharmacological activities of Chang-Kang-Fang, a multi-herb Chinese medicinal formula, for treating irritable bowel syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown. AIM OF THE STUDY: To investigate the chemical profiles and effects of CKF on IBS model. MATERIALS AND METHODS: The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated. RESULTS: 80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0g/kg/d. CONCLUSIONS: CKF could alleviate the symptoms of IBS by modulating the brain-gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF.

Thyroid volume and serum calcitonin changes during pregnancy.

BACKGROUND: Pregnancy has a profound impact on thyroid homeostasis which results in change of thyroid function and thyroid volume (TV). Moreover, calcitonin (CT), and its gene-related peptide have been demonstrated to play an important role in the implantation process. PURPOSE: To evaluate changes in TV and serum CT levels during pregnancy. METHODS: One hundred and fifty-five pregnant women were consecutively enrolled at the first trimester of gestation and underwent clinical, biochemical and sonographic assessment at enrollment, at the second and third trimesters and at 6 months after delivery. RESULTS: Throughout gestation serum TSH exceeded the upper specific first trimester cut-off in 5% of patients. TV significantly increased at the third trimester of gestation and returned to baseline levels at 6 months after delivery, while serum CT levels did not show significant changes. TV directly correlated with BMI or gestational weight gain at each trimester of pregnancy, while no significant association between serum CT levels and either weight or TV were found. Finally, in none of the patients with nodular goiter an increase in the volume of the nodules was noted. The appearance of a nodule was recorded during the second trimester in one patient. CONCLUSION: This study confirms a prevalence of thyroid autoimmunity/hypertropinemia in 3-5% of pregnant women and shows that serum CT does not change in relation to the transient increase in TV occurring during gestation. An adequate daily iodine supplementation might be particularly useful during pregnancy to limit the TSH increase and the resulting thyroid gland and nodule enlargement.

Pharmacodynamic action and mechanism of Du Liang soft capsule, a traditional Chinese medicine capsule, on treating nitroglycerin-induced migraine.

ETHNOPHARMACOLOGICAL RELEVANCE: Du Liang soft capsule (DL) is a traditional Chinese medicine for treating migraines; it is made from two Chinese herbs, including LigusticumstriatumDC., root; Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., root. AIM OF THE STUDY: In the present study, we aimed to elucidate the pharmacodynamic action of DL and its mechanism in an animal model of migraines induced by glyceryl trinitrate (GTN). MATERIALS AND METHODS: Sixty rats were randomly divided into six groups, including a normal control group, model control group, positive group (Sumatriptan 0.006gkg-1), and three DL groups (0.44, 1.31 and 3.93gkg-1). All rats were intragastrically treated with the corresponding treatment for 7 consecutive days, and they were subcutaneously injected with GTN (10mgkg-1) 30min after the last treatment, except in the normal control group. After model establishment, the behaviors of all rats, including head scratching, cage climbing, and the development of red ears were observed continuously by digital camera every 30min for 3h. Four hours after GTN treatment, all rats were anaesthetized and the blood and tissue samples were collected. Plasma calcitonin gene related to peptide (CGRP) and endothelin (ET) levels were measured using the radioimmunoassay method, and serum NO was determined by the colorimetric method. Afterwards, the brainstem tissues were dissected and washed with physiological saline, and divided evenly into two parts. One part was used to test the monoamine levels, including levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA), by the fluorometric method, and the other part was used to determine the nuclear factor kappaB (NF-κB) p65, nuclear c-fos, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß (IL-1ß), and cyclooxygenase-2 (COX-2) levels by Western blot analysis. RESULTS: In the pharmacodynamic action assay, DL (1.31 and 3.93gkg-1) greatly improved the abnormal behaviors of migraine rats, including head scratching and cage climbing, and the development of red ears. In the mechanism assay, compared with the control group, the plasma CGRP and serum NO levels and the brainstem 5-HT, NE and DA levels in the DL administration groups were significantly decreased; and the plasma ET levels were remarkably increased. Moreover, down-regulation of NF-κB p65, c-fos and pro-inflammatory cytokines, including iNOS, IL-1ß and COX-2 in the brainstem in the DL administration groups were observed by Western blot analysis. CONCLUSIONS: The above results suggested that DL has a therapeutic effect on migraines, and its mechanism may be related to adjusting the level of neurotransmitters and vasoactive substances, consequently relieving neurogenic inflammation.

Impact of Food Components on in vitro Calcitonin Gene-Related Peptide Secretion-A Potential Mechanism for Dietary Influence on Migraine.

Calcitonin gene-related peptide (CGRP) is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine-related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL) and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL) extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 µM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S-petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further.

[Effect of Tanshinone IIA in Preventing and Treating Oxaliplatin Induced Peripheral Neuropathy].

OBJECTIVE: To observe preventive and therapeutic effects of Tanshinone IIA (T II A) on oxaliplatin induced peripheral neuropathy (OlPN) and to explore its effects on the expression of calcitonin gene related peptide (CGRP) and never growth factor (NGF). METHODS: Totally 36 phase II - III patients with malignant tumor of digestive tract undergoing chemotherapy program with oxaliplatin, were equally assigned to the T II A group (using THA at 80 mg/day 1 day before oxaliplatin chemotherapy for 3 successive days) and the control group (using chemotherapy program with oxaliplatin alone) by segmented randomization. After 4 cycles of chemotherapy, the incidence degree and incidence of OlPN were evaluated. Sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity ( MNCV) were tested by EMG evoked potential device. Serum levels of CGRP and NGF were also detected in the two groups before and after chemotherapy. The correlation of serum levels of CGRP and NGF to OIPN was assessed using linear correlation analysis. RESULTS: After chemotherapy the OlPN incidence was 27.8% (5/18 cases) in the T II A group, obviously lower than that in the control group (55.6%, 10/18 cases; P < 0.05). Compared with before treatment in the same group, SNCV and MNCV of common peroneal nerve were slowed down, serum NGF levels decreased, and serum CGRP levels obviously increased in the two groups (all P < 0.05). Compared with the control group after treatment, SNCV and MNCV of common peroneal nerve were obviously accelerated, serum NGF levels increased, and serum CGRP levels obviously decreased in the THA group (all P < 0.05). Results of linear correlation analysis indicated serum NGF level was negatively correlated with peripheral neuropathy (PN), serum CGRP expression was positively correlated with neurotoxicity (P < 0.05). CONCLUSION: T II A could reduce the incidence of OlPN, which might be associated with inhibiting the expression of CGRP and up-regulating NGF activities.

Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns.

BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) may increase the future health risks of women and their offspring. The aim of this study was to determine the effect of capsaicin supplementation on blood glucose, lipid metabolism and pregnancy outcomes in women with GDM. METHODS: Forty-four pregnant women with GDM at 22-33 gestational weeks were randomly assigned to the capsaicin group (5 mg/d of capsaicin) or to the placebo group (0 mg/d of capsaicin) for 4 weeks in a randomized, double-blind, placebo-controlled trial. The concentrations of fasting plasma glucose and serum insulin, 2-h postprandial plasma glucose (2-h PG) and serum insulin (2-h INS), and fasting serum lipids, liver and kidney function parameters, and calcitonin gene-related peptide (CGRP) were measured at 0 and 4 weeks. The maternal and neonatal outcomes were also recorded. RESULTS: Forty-two women completed the trial. Compared to the placebo group, 2-h PG and 2-h INS concentrations and 2-h postprandial HOMA-IR (2-h HOMA-IR) levels, and the fasting serum total cholesterol and triglycerides concentrations significantly decreased in the capsaicin group after treatment (P < 0.05). Moreover, the fasting serum apolipoprotein B and CGRP concentrations significantly increased in the capsaicin group (P < 0.05). The changes in the 2-h PG and 2-h INS concentrations and in the 2-h HOMA-IR were negatively correlated with the change in the serum CGRP concentration (P < 0.05). Furthermore, the incidence of large-for-gestational-age (LGA) newborns was significantly lower in the capsaicin group than in the placebo group (P = 0.022). CONCLUSIONS: Capsaicin-containing chili supplementation regularly improved postprandial hyperglycemia and hyperinsulinemia as well as fasting lipid metabolic disorders in women with GDM, and it decreased the incidence of LGA newborns.

Pharmacological characterization of a novel gastrodin derivative as a potential anti-migraine agent.

Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis.

Clinical study of Butylphthalide combined with Xue Shuan Tong on serum inflammatory factors and prognosis effect of patients with cerebral infarction.

To investigate the effect of Butylphthalide and Xue Shuan Tong on serum inflammatory factors and prognosis of patients with cerebral infarction. One hundred and twenty patients with acute cerebral infarction were randomly divided into control group, Butylphthalide group and Xue Shuan Tong group, with 40 patients in each group. Conventional therapy was performed in the control group; On the basis of conventional therapy, 100ml Butylphthalide intravenously twice a day was administrated among patients in Butylphthalide group; On the basis of conventional therapy, 250ml 0.9% NaCl intravenously once a day was conducted among patients in Xue Shuan Tong group. A treatment course of continuous 7 days was taken in the three groups. The serum levels of IL-2 and CGRP were detected for patients in the three groups before and after treatment. Carotid plaque thickness and size as well as intima-media thickness were detected by ultrasonic testing for patients in three groups before treatment and 90 days after follow-up. The NIHSS, Barthel and MRS scoring were performed for all the patients after 90-day follow-up to evaluate the prognosis. After treatment, differences in the levels of IL-2 and CGRP for patients in the three groups showed statistical significance (P<0.05), while the levels of IL-2 and CGRP in Xue Shuan Tong group were significantly higher than those in the other two groups (P<0.05). After 7-day treatment, plaque size and thickness in Xue Shuan Tong group and Butylphthalide group were significantly reduced, compared with those before treatment (P<0.05), but no significant differences was shown in the plaque size and thickness between Xue Shuan Tong group and Butylphthalide group (P>0.05) .The CA-IMT in Xue Shuan Tong group and Butylphthalide group was significantly reduced after treatment, and that in Butylphthalide group was significantly larger than that in Xue Shuan Tong group (P<0.05). After 90-day follow-up, NIHSS scores in Butylphthalide group were significantly less than those in the other two groups (P<0.05). After 90-day follow-up, Barthel scores in Butylphthalide group and Xue Shuan Tong group were significantly larger than those in control group (P<0.05), while differences between Butylphthalide group and Xue Shuan Tong group indicated no statistical significance (P>0.05). There were significant differences in MRS scores among patients in the three groups after 90-day follow-up (P<0.05). Butylphthalide and Xue Shuan Tong are clinically effective in treating acute cerebral infarction. Butylphthalide has significant efficacy in inhibiting inflammation and improving prognosis of neurological function, while Xue Shuan Tong has obvious effect in improving carotid intima-media thickness.

Fasting serum CGRP levels are related to calcium concentrations, but cannot be elevated by short-term calcium/vitamin D supplementation.

Calcitonin gene-related peptide (CGRP) is an important cardioprotective neuropeptide. Few studies have shown that calcium supplementation may increase CGRP levels transiently. However, the relationship between CGRP and calcium is poorly known. This study was to explore the correlation between serum calcium and CGRP in coronary artery disease (CAD), and observe whether short-term calcium/vitamin D supplementation would increase fasting serum CGRP. A randomized, placebo-controlled and double-blind clinical trial, and a supplementary study for further analysis of the correlations were conducted. The results showed that the correlation between serum calcium and CGRP was positive in CAD without myocardial infarction (MI) (r = 0.487, P = 0.029), but negative in acute and healing MI (r = -0.382, P = 0.003). Moreover, we found a positive correlation between lg (amino-terminal pro-B-type natriuretic peptide, NT-proBNP) and CGRP (r = 0.312, P = 0.027), but a negative correlation between lg (NT-proBNP) and serum calcium (r = -0.316, P = 0.025) in acute and healing MI. As to the clinical trial, participants subjected to CAD but without evolving or acute MI, together with blood calcium ≤ 2.4 mmol/L, were randomized into three groups. Among the groups of placebo, caltrate (600 mg elemental calcium; 125 IU vitamin D3, per tablet) 1 tablet/d and caltrate 2 tablets/d, there were no significant differences in baseline characteristics. After short-term (5 days) treatments, the results indicated that the effect of grouping was not statistically significant (P = 0.915). In conclusion, the correlations between serum calcium and CGRP in different types of CAD are inconsistent, and the main reason may be associated with elevated natriuretic peptides after acute MI. Further, our study shows that short-term calcium/vitamin D supplementation cannot significantly increase fasting serum CGRP levels.

Effect of qilongtoutong granule on calcitonin gene-related peptide, beta-endorphin, serotonin, dopamine, and noradrenalin in migraine model rats and mice.

OBJECTIVE: To study the effect of Qilongtoutong granule (QLTT) on plasma calcitonin gene-related peptide (CGRP), beta-endorphin (beta-EP), 5-HT, dopamine (DA), noradrenalin (NE), and blood viscosity in migraine model rats and mice. METHODS: Both the acute blood stasis model group and nitroglycerin-induced migraine model group included 60 Sprague-Dawley rats. The reserpine-reduced model group had 60 Kunming mice. Rats from each test were grouped into normal control group, model group, Zhengtian pill (ZTP) group, and high, moderate, or low-dose QLTT groups. In the acute blood stasis model test, after gavage for 7 days, rats were given 0.8 mL/kg adrenaline hydrochloride subcutaneously twice, and kept in ice water for 5 min. After fasting for 12 h, rats were anesthetized and blood samples were collected for detection of blood viscosity. In the nitroglycerin-induced migraine group, after gavage for 7 days, rats were intraperitoneally injected nitroglycerin (10 mg/kg), and 4 h later, blood samples were collected from postcava for measuring the plasma CGRP and beta-EP levels. In the reserpine-reduced model test, except the normal control group, mice were administered reserpine (0.25 mg/ kg, i.h.) for 9 days. Mice received intragastric administration from the third day to the ninth day. One hour after the last gavage, blood and brain tissue samples were obtained. Then, blood clotting time and the contents of neurotransmitters were determined. RESULTS: QLTT- (3.6, 1.8, and 0.9 g/kg) and ZTP-treated rats had lower blood viscosity than that in model rats under different shear rates (P < 0.01). QLTT- (3.6, 1.8 g/kg) and ZTP-treated rats had significantly lower plasma CGRP levels and higher plasma beta-EP levels than those in model rats (P < 0.01). QLTT treatment at dose of 0.9 g/kg had lower plasma CGRP levels as well (P < 0.05). QLTT- (5.2, 2.6 g/kg) and ZTP-treated mice had longer blood clotting time than that in model mice (P < 0.01). QLTT- (2.6 g/kg) and ZTP-treated mice had higher plasma serotonin (5-HT) levels than those in model mice (P < 0.05). CONCLUSION: QLTT-treated animals had lower plasma CGRP level, higher plasma beta-EP, 5-HT, higher brain tissue 5-HT, NE, DA levels, and lower blood viscosity than those in the migraine model animals.

Catalpol provides protective effects against cerebral ischaemia/reperfusion injury in gerbils.

OBJECTIVES: To investigate the protective effect of catalpol on cerebral ischaemia/reperfusion (CI/R) injury in gerbils and further explore the underlying mechanism. METHODS: A gerbil model of CI/R was prepared by bilateral common carotid occlusion for 10 min followed by 6 h reperfusion. Catalpol (5, 10 or 20 mg/kg per day) was injected intraperitoneally for 3 days before the carotid occlusion. Stroke index was measured during the reperfusion. The contents of endogenous neuropeptides, endothelin-1 (ET-1) and calcitonin gene-related peptide in plasma were evaluated by radioimmunoassay. Superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissue homogenate were also examined. KEY FINDINGS: The results showed that catalpol significantly improved the stroke index compared with CI/R control group (P < 0.05 or P < 0.01). Catalpol significantly increased the activity of SOD at the doses of 10 and 20 mg/kg (P ≤ 0.05), decreased the brain MDA content and the plasma level of ET-1 at the doses of 10 and 20 mg/kg (P ≤ 0.01). CONCLUSIONS: These data suggested that the efficacy of catalpol pretreatment on CI/R injury may be attributed to reduction of free radicals and inhibition of lipid peroxidation and ET-1 production.

Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP).

Various approaches have been offered to alleviate chronic pain resulting from spinal cord injuries (SCIs). Application of herbs and natural products, with potentially lower adverse effects, to cure diseases has been recommended in both traditional and modern medicines. Here, the effect of crocin on chronic pain induced by spinal cord contusion was investigated in an animal model. Female Wistar rats were randomly divided into five groups (5 rats in each); three groups were contused at the L1 level. One group was treated with crocin (150mg/kg) two weeks after spinal cord injury; the second group, control, was treated with vehicle only; and the third group was treated with ketoprofen. Two normal groups were also considered with or without crocin treatment. The mechanical behavioral test, the locomotor recovery test and the thermal behavioral test were applied weekly to evaluate the injury and recovery of rats. Significant improvements (p<0.05) in mechanical behavioral and locomotor recovery tests were seen in the rats treated with crocin. Thermal behavioral test did not show any significant changes due to crocin treatment. Plasma concentration of calcitonin-gene related peptide (CGRP) changed from 780.2±2.3 to 1140.3±4.5pg/ml due to SCI and reached 789.1±2.7pg/ml after crocin treatment. These changes were significant at the level of p<0.05. The present study shows the beneficial effects of crocin treatment on chronic pain induced by SCI, through decreasing CGRP as an important mediator of inflammation and pain.

Measurement of calcitonin and calcitonin gene-related peptide mRNA refines the management of patients with medullary thyroid cancer and may replace calcitonin-stimulation tests.

BACKGROUND: Serum calcitonin (sCT) is the main tumor marker for medullary thyroid cancer (MTC), but it has certain limitations. Various sCT assays may have important intra-assay or interassay variation and may yield different and sometimes conflicting results. A pentagastrin- or calcium-stimulation calcitonin (CT) test may be desirable in some situations. Alternatively, or in the absence of the stimulation test, mRNA detection offers the advantages of being more comfortable and less invasive; it only requires blood collection and has no side effects. The objective of this study was to investigate the applicability of measuring calcitonin-related polypeptide alpha (CALCA) gene transcripts (CT-CALCA and calcitonin gene-related peptide [CGRP]-CALCA) in patients with MTC and in relatives diagnosed with a RET mutation and to test mRNA as an alternative diagnostic tool for the calcitonin-stimulation test. METHODS: Twenty-three healthy controls and 26 individuals evaluated for MTC were selected, including patients with sporadic or hereditary MTC and RET mutation-carrying relatives. For molecular analysis, RNA was extracted from peripheral blood, followed by cDNA synthesis using 3.5 µg of total RNA. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed with SYBR Green and 200 nM of each primer for the two specific mRNA targets (CT-CALCA or CGRP-CALCA) and normalized with the ribosomal protein S8 as the reference gene. RESULTS: We detected CALCA transcripts in the blood samples and observed a positive correlation between them (r=0.946, p<0.0001). Both mRNAs also correlated with sCT (CT-CALCA, r=0.713, p<0.0001; CGRP-CALCA, r=0.714, p<0.0001). The relative expression of CT-CALCA and CGRP-CALCA presented higher clinical sensitivity (86.67 and 100, respectively), specificity (97.06 and 97.06), positive predictive value (92.86 and 93.75), and negative predictive value (94.29 and 100), than did sCT (73.33, 82.35, 64.71, and 87.50, respectively). In addition, the CALCA transcript measurement mirrored the response to the pentagastrin test. CONCLUSION: We demonstrate that the measurement of CALCA gene transcripts in the bloodstream is feasible and may refine the management of patients with MTC and RET mutation-carrying relatives. We propose considering the application of this diagnostic tool as an alternative to the calcitonin-stimulation test.