To systematically evaluate the efficacy and superiority of Flunarizine Hydrochloride when combined with Traditional Chinese Medicine (TCM) Decoctions in treating migraine headaches.
The authors conducted a comprehensive search for clinical Randomized Controlled Trials (RCTs) investigating the combination of Flunarizine Hydrochloride with Chinese herbal decoctions in treating migraines. The databases searched included CNKI, VIP, Wanfang, PubMed, WOI, Cochrane Library, and Embase, covering the period from January 1, 2019, to November 10, 2023. Two independent researchers meticulously screened, extracted, and assessed the relevant data, employing the Revman 5.3 software for meta-analysis.
The meta-analysis revealed that, in comparison to Flunarizine Hydrochloride used in isolation, the combination with Chinese herbal decoctions markedly enhanced the effective rate (RR = 1.26, 95 % CI [1.18, 1.34], p < 0.0001). Moreover, significant improvements were observed in the TCM symptom score (MD = 4.97, 95 % CI [-6.74, -3.19], p < 0.00001). The observation group demonstrated a statistically significant improvement in endothelin levels compared to the control group (I2 = 85 %, MD = -13.66, 95 % CI [-17.87, -9.45], p = 0.0001). The observation group showed a significant reduction in NRS scores compared to the control group, indicating better outcomes (I2 = 95 %, MD = -2.11, 95 % CI [-3.09, -1.12], p < 0.0001). The observation group was superior to the control group in terms of the reduction in the number of episodes (I2 = 63 %, MD = -1.16, 95 % CI [-1.45, -0.87], p = 0.007).
The confluence of Flunarizine Hydrochloride with traditional Chinese medicine decoctions in treating migraine patients demonstrated substantial clinical efficacy and improvement in TCM symptom score over the use of Flunarizine Hydrochloride alone.

OBJECTIVE: Intraocular administration was a commonly route of administration in clinic, but most of the intraocular administration was only used to treat local ocular diseases. Based on the particularity of the ocular structure, this article mainly explored the feasibility of flunarizine hydrochloride in the treatment of ischemic cerebral vascular diseases (ICVD) by intraocular administration.
METHODS: A total of 150 SD rats were randomly divided into 3 groups with intraocular, intragastric, and intravenous administration, respectively. The doses were 14 mg/kg for intraocular and intragastric groups and 5 mg/kg for intravenous group. The plasma and brain concentration of flunarizine hydrochloride were analyzed by high performance liquid chromatography (HPLC). Main pharmacokinetic parameters and absolute bioavailability were evaluated. Brain targeting of flunarizine hydrochloride through intraocular administration was studied by drug targeting index of brain (DTIbrain).
RESULTS: Maximum contentration (Cmax) and area under the time-concentration curve from o to t (AUC0-t) of plasma after intraocular administration were significantly higher than those of plasma after intragastric administration (both P<0.05). Cmax and AUC0-t of brain after intraocular administration were significantly higher than those of brain after intragastric administration (both P<0.05). The bioavailability of plasma and brain after intraocular administration was 18.67% and 34.67%, respectively, which was higher than 14.32% and 21.56% of plasma and brain after intragastric administration. The DTIbrain of intraocular administration was 1.84, and the DTIbrain of intragastric administration was 1.48.
CONCLUSIONS: Flunarizine hydrochloride could be absorbed into the systemic circulation after intraocular administration. Not only the absolute bioavailability but also the brain targeting index of intraocular administration is higher than that of intragastric administration.
目的: 眼部给药是临床上常用的一种给药途径，但大多只用于治疗眼局部性疾病。基于眼部结构的特殊性，本文主要探索盐酸氟桂利嗪经眼部给药治疗缺血性脑血管疾病的可行性。方法: 150只健康雄性SD大鼠随机分为滴眼组、灌胃组和注射组。滴眼组和灌胃组均以14 mg/kg的剂量给药，注射组剂量为5 mg/kg。采用高效液相色谱法(high performance liquid chromatography，HPLC)测定大鼠血浆和脑组织中的盐酸氟桂利嗪的含量，评价主要药代动力学参数和生物利用度，并通过药物脑靶向指数(drug targeting index of brain，DTIbrain)研究盐酸氟桂利嗪眼部给药的脑靶向性。结果: 盐酸氟桂利嗪经眼部给药后血浆Cmax和AUC0-t，脑组织Cmax和AUC0-t均高于经灌胃给药，差异有统计学意义(均P<0.05)。经眼部给药血浆和脑组织的生物利用度分别为18.67%和34.67%，均高于经灌胃给药的14.32%和21.56%。滴眼和灌胃两种给药途径的DTIbrain分别为1.84和1.48。结论: 盐酸氟桂利嗪经眼部给药后能吸收进入血液和脑组织，眼部给药的生物利用度和DTIbrain高于灌胃给药。.

OBJECTIVE: To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver yang hyperactivity.
METHODS: A total of 110 patients with migraine of liver yang hyperactivity were randomly divided into an electroacupuncture group (55 cases, 2 cases dropped off) and a western medication group (55 cases, 2 cases dropped off). In the electroacupuncture group, electroacupuncture was applied at Siguan points (Hegu [LI 4] and Taichong [LR 3]), with disperse-dense wave of 2 Hz/100 Hz in frequency and current intensity of 0.1-1 mA, 30 min each time, once a day, 5 times per week for 4 weeks. Flunarizine hydrochloride capsule was given orally in the western medication group, 10 mg a day for 4 weeks. The visual analogue scale (VAS) score and the migraine attack days were observed before and after treatment, during follow-up of 1, 3 and 6 months, and the migraine symptom score was observed before and after treatment in the two groups.
RESULTS: After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (Ｐ<0.05), and above indexes in the electroacupuncture group were lower than the western medication group (Ｐ<0.05). After treatment, the migraine symptom scores in the two groups were decreased (Ｐ<0.05), the change in the electroacupuncture group was greater than the western medication group (Ｐ<0.05).
CONCLUSIONS: Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver yang hyperactivity, and the efficacy is superior to oral flunarizine hydrochloride capsules.
目的：比较电针四关穴与口服盐酸氟桂利嗪胶囊治疗肝阳上亢型偏头痛的临床疗效。方法：将110例肝阳上亢型偏头痛患者随机分为电针组（55例，脱落2例）和西药组（55例，脱落2例）。电针组予电针四关穴（合谷、太冲）治疗，疏密波，频率2 Hz/100 Hz，电流强度0.1~1 mA，每次30 min，每天1次，每周5次，连续治疗4周。西药组口服盐酸氟桂利嗪胶囊，每次10 mg，每天1次，连续服用4周。观察两组治疗前、治疗后及随访1、3、6个月的疼痛视觉模拟量表（VAS）评分、头痛发作天数以及治疗前后偏头痛症状评分。结果：治疗后及随访1、3、6个月时，两组VAS评分和头痛发作天数均较治疗前降低（Ｐ<0.05），且电针组均低于西药组（Ｐ<0.05）。治疗后，两组偏头痛症状评分均较治疗前降低（Ｐ<0.05），且电针组降低幅度大于西药组（Ｐ<0.05）。结论：电针四关穴治疗肝阳上亢型偏头痛疗效优于口服盐酸氟桂利嗪胶囊，在降低头痛强度、减少头痛发作天数及改善偏头痛症状方面疗效更佳。.

We developed a safe and efficacious drug delivery system for treatment of brain diseases. A novel in-situ gel system was prepared using soybean oil, stearic acid and N-methyl-2-pyrrolidinone (NMP) (10:1:3, v/w/v). This system had low viscosity as a sol in vitro and turned into a solid or semi-solid gel in situ after administration. The poorly water-soluble drug flunarizine hydrochloride (FNZ) was incorporated into this \"organogel\" system. Organogel-FNZ was characterized by light microscopy, differential scanning calorimetry (DSC) and rheology. Drug release in vitro was investigated. The initial \"burst\" effect did not occur in organogel-FNZ, which is different from other gels formed in situ. Pharmacokinetic studies were undertaken in rats using gel administration (14 mg kg-1), intravenous administration (5 mg kg-1) and administration using drops (14 mg kg-1). Organogel-FNZ could reduce the clearance rate and prolong the duration of action, in the plasma and brain tissues of rats. The peak serum concentration, area under the curve and absolute bioavailability of the organogel-FNZ group were higher than those of the intraocular- drops group. Organogel-FNZ is a promising drug-delivery system for treatment of brain diseases by intraocular administration.

This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood-brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.