School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Naval Medical University, Shanghai, China.
Pharm Biol. 2023 Dec;61(1):345-355. doi: 10.1080/13880209.2023.2173249.
L (Rutaceae) (Au) and Blanco (Rutaceae) (Ci) are commonly used as couplet prokinetics and DC. (Umbelliferae) (Bup) is an herbal antidepressant in traditional Chinese medicine.
This study evaluates the synergistic prokinetic effects of Bup with Au and Ci in mice suffering from multistress-induced delayed gastric emptying (DGE).
Kunming mice were divided into four groups: control, DGE, AuCi and AuCiBup. Mice were gavaged with AuCi (14.25 g/kg) or AuCiBup (22.13 g/kg) extract for 12 days. Gastric reminder rate, intestinal driving ratio, sucrose preference and open field test were examined, and serotonin (5-HT), motilin (MTL), substance P (SP), 5-HTR and c-kit were assayed. Intracellular Ca levels in primary cultured gastric smooth muscle cells (GSMCs) were determined.
Both AuCi and AuCiBup treatment significantly reduced gastric residual rate (39.5% and 67.7%, < 0.01). Higher serum levels of 5-HT, MTL and SP were observed in treatment groups (AuCi: 0.060 mg/L, AuCiBup: 0.089 mg/L, DGE: 0.025 mg/L, < 0.01). The expression of 5-HTR and c-kit in the antrum and duodenum was upregulated after treatment (AuCi and AuCiBup, 4.3-times, 2.8-times to DGE, < 0.01). Medicated serums of AuCi and AuCiBup effectively increased the influx of Ca into GSMCs (1.8-times, < 0.01). In terms of 5-HTR expression, circulatory contents of 5-HT and SP and Ca influx, AuCiBup demonstrated better prokinetic effects than AuCi.
These findings indicate the potential for developing combination therapy with antidepressants and prokinetics in gastrointestinal dysmotility management.
L(芸香科)(Au)和 Blanco(芸香科)(Ci)通常被用作双联促动力药,而 DC.(伞形科)(Bup)是传统中药中的一种草药抗抑郁药。
本研究评估 Bup 与 Au 和 Ci 联合应用于多发性应激诱导的胃排空延迟(DGE)小鼠的协同促动力作用。
昆明小鼠分为对照组、DGE 组、AuCi 组和 AuCiBup 组。小鼠灌胃 AuCi(14.25g/kg)或 AuCiBup(22.13g/kg)提取物 12 天。检测胃排空率、肠动力比、蔗糖偏好和旷场试验,并测定血清 5-羟色胺(5-HT)、胃动素(MTL)、P 物质(SP)、5-HT 受体和 c-kit。测定原代培养胃平滑肌细胞(GSMCs)内 Ca 水平。
AuCi 和 AuCiBup 治疗均显著降低胃残留率(39.5%和 67.7%, < 0.01)。治疗组血清 5-HT、MTL 和 SP 水平升高(AuCi:0.060mg/L,AuCiBup:0.089mg/L,DGE:0.025mg/L, < 0.01)。治疗后胃窦和十二指肠 5-HTR 和 c-kit 表达上调(AuCi 和 AuCiBup,分别为 DGE 的 4.3 倍和 2.8 倍, < 0.01)。AuCi 和 AuCiBup 的含药血清有效增加 GSMCs 内 Ca 内流(1.8 倍, < 0.01)。就 5-HTR 表达、循环 5-HT 和 SP 含量以及 Ca 内流而言,AuCiBup 显示出比 AuCi 更好的促动力作用。
这些发现表明,在胃肠道动力障碍管理中,开发抗抑郁药和促动力药联合治疗的潜力。