南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (3): 594-604.doi: 10.12122/j.issn.1673-4254.2024.03.22

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连翘配方颗粒与饮片的抗炎、抗肿瘤和抑菌效果的比较研究

郭新邓，郭卓琳，孙冬梅，邹丽芳，区锦莹，余林中，卢子滨，曹惠慧，刘俊珊   

  1. 南方医科大学中医药学院中药药理实验室//广东省中药制剂重点实验室//广东省中药制剂技术工程实验室，广东 广州 510515；广东一方制药有限公司，广东 佛山 528244
  • 出版日期:2024-03-20 发布日期:2024-04-03

Single extract of Forsythia Suspense versus the prepared drug in pieces: comparison of their anti-inflammatory, antitumor and antibacterial effects in zebrafish

GUO Xindeng, GUO Zhuolin, SUN Dongmei, ZOU Lifang, OU Jinying, YU Linzhong, LU Zibin, CAO Huihui, LIU Junshan   

  1. Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparations, Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Laboratory of Ethnopharmacology, School of Chinese Traditional Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong E-fong Pharmaceutical Co., Ltd., Foshan 528244, China
  • Online:2024-03-20 Published:2024-04-03

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摘要： 目的 采用斑马鱼体内模型实验和体外抗菌实验比较连翘配方颗粒和饮片的抗炎、抗肿瘤和抑菌的药效差异。方法 将斑马鱼胚胎分为空白组、模型对照组、10 μg/mL地塞米松处理组、连翘饮片处理组（剂量为400、600、800 μg/mL）和连翘配方颗粒处理组（剂量为400、600、800 μg/mL），分别构建硫酸铜、尾鳍横断和LPS显微注射斑马鱼炎症模型，采用中性粒细胞观察、病理组织切片、生存分析和实时定量荧光PCR实验评价连翘配方颗粒与饮片的抗炎药效差异，并从MAPK和NF-κB信号通路角度探讨其抗炎作用机理差异。将斑马鱼胚胎分为模型对照组、250 nmol/L索拉菲尼处理组、连翘饮片处理组（400、600、800 μg/mL）和连翘配方颗粒处理组（400、600、800 μg/mL），采用斑马鱼异种移植肿瘤细胞模型，通过荧光观察和病理组织切片评价连翘配方颗粒与饮片抗肿瘤的药效差异。将实验分为空白组、连翘饮片处理组（1.95、3.91、7.81、15.63、31.25、62.5、125、250、500 mg/mL）和连翘配方颗粒处理组（1.95、3.91、7.81、15.63、31.25、62.5、125、250、500 mg/mL），采用微量肉汤稀释法评价连翘配方颗粒与饮片的抑菌药效差异。结果 与模型对照组比较，连翘配方颗粒及饮片均可抑制中性粒细胞聚集数量（P<0.001）和Tnfα、Il6、P38、Jnk、Erk和P65的mRNA表达（P<0.05或P<0.01或P<0.001），升高斑马鱼的存活率（P<0.01或P<0.001）；减少人肺腺癌A549细胞、人结直肠癌HCT116细胞、人胰腺癌PANC-1细胞、人肝癌Hep3B细胞和人宫颈癌Hela细胞在卵黄囊内的聚集（P<0.05或P<0.01或P<0.001）；并在15.63 mg/mL时起到抑菌作用。结论 连翘配方颗粒及饮片均具有显著抗炎、抗肿瘤和抑菌作用，两者除在低剂量下抑制Il6、P65、Jnk的mRNA表达和HCT116细胞增殖有显著性差异外，其他作用均无明显差异。

关键词: 连翘；中药配方颗粒；药效等效性；斑马鱼

Abstract: Objective To compare the anti-inflammatory, antitumor and anti-bacterial effects of the single extract (in granules) and the prepared drug in pieces of Forsythia Suspense (Lianqiao, a traditional Chinese herbal medicine). Methods In zebrafish embryo models of CuSO4 exposure, tail transection and LPS microinjection-induced inflammation, the anti-inflammatory effects of 10 μg/mL DEX, single extract of Forsythia Suspense, and the water extract of the prepared drug (400, 600, and 800 μg/mL) were evaluated by observing neutrophil counts, RT- qPCR, HE staining and survival analysis. Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining. The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs. Results In the zebrafish embryo models of inflammation, both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation, reduced the mRNA expressions of TNF-α, IL-6, P38, Jnk, Erk and P65, and increased the survival rate of zebrafish. They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells (HCT116), pancreas adenocarcinoma cells (PANC-1), lung cancer cells (A549), liver cancer cells (Hep3B) and cervical carcinoma cells (Hela) in zebrafish embryos, and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL. Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory, antitumor and antibacterial effects, but their effects for inhibiting IL-6, P65, and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

Key words: Forsythia Suspensa; sing extract of traditional Chinese medicine; pharmacological equivalence; zebrafish