College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China.
Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
Int J Mol Sci. 2022 Oct 6;23(19):11860. doi: 10.3390/ijms231911860.
Gelsemium elegans Benth. (GEB) is a traditional medicinal plant in China, and acts as a growth promoter in pigs and goats. Koumine (KM) is the most abundant alkaloid in GEB and produces analgesic, anti-cancer, and immunomodulatory effects. KM can be used as an aquatic immune stimulant, but its growth-promoting effects and transcriptional mechanisms have not been investigated. Diets containing KM at 0, 0.2, 2, and 20 mg/kg were fed to Cyprinus carpio for 71 days to investigate its effects on growth performance, intestinal morphology, microflora, biochemical indicators, and transcriptional mechanisms. Cyprinus carpio fed with KM as the growth promoter, and the number of intestinal crypts and intestinal microbial populations were influenced by KM concentration. KM increased the abundance of colonies of Afipia, Phyllobacterium, Mesorhizobium, and Labrys, which were associated with compound decomposition and proliferation, and decreased the abundance of colonies of pathogenic bacteria Methylobacterium-Methylorubrum. A total of 376 differentially-expressed genes (DEGs) among the four experimental groups were enriched for transforming growth factor-β1 and small mother against decapentaplegic (TGF-β1/Smad), mitogen-activated protein kinase (MAPK), and janus kinases and signal transducers and activators of transcription (Jak/Stat) signaling pathways. In particular, tgfbr1, acvr1l, rreb-1, stat5b, smad4, cbp, and c-fos were up-regulated and positively correlated with KM dose. KM had a growth-promoting effect that was related to cell proliferation driven by the TGF-β1/Smad, MAPK, and Jak/Stat signaling pathways. KM at 0.2 mg/kg optimized the growth performance of C. carpio, while higher concentrations of KM (2 and 20 mg/kg) may induce apoptosis without significantly damaging the fish intestinal structure. Therefore, KM at low concentration has great potential for development as an aquatic growth promotion additive.
钩吻（GEB）是中国的一种传统药用植物，作为猪和山羊的生长促进剂。钩吻碱（KM）是 GEB 中含量最丰富的生物碱，具有镇痛、抗癌和免疫调节作用。KM 可用作水产免疫刺激剂，但它的促生长作用及其转录机制尚未得到研究。在 71 天的时间里，给鲤鱼投喂含有 0、0.2、2 和 20mg/kg KM 的饮食，以研究其对生长性能、肠道形态、微生物群、生化指标和转录机制的影响。作为生长促进剂的 KM 影响了鲤鱼肠道隐窝数量和肠道微生物种群的数量。KM 增加了与化合物分解和增殖相关的 Afipia、Phyllobacterium、Mesorhizobium 和 Labrys 菌群的丰度，降低了致病性细菌 Methylobacterium-Methylorubrum 菌群的丰度。在这四个实验组中，共富集到 376 个差异表达基因（DEGs），这些基因与转化生长因子-β1 和小母亲对抗 decapentaplegic（TGF-β1/Smad）、丝裂原活化蛋白激酶（MAPK）和 Janus 激酶和信号转导和转录激活物（Jak/Stat）信号通路有关。特别是，tgfbr1、acvr1l、rreb-1、stat5b、smad4、cbp 和 c-fos 上调，并与 KM 剂量呈正相关。KM 具有促生长作用，与 TGF-β1/Smad、MAPK 和 Jak/Stat 信号通路驱动的细胞增殖有关。0.2mg/kg 的 KM 优化了鲤鱼的生长性能，而较高浓度的 KM（2 和 20mg/kg）可能在不显著损害鱼类肠道结构的情况下诱导细胞凋亡。因此，低浓度的 KM 具有作为水产生长促进添加剂开发的巨大潜力。
