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夏枯草和白花蛇舌草粗提取物通过调节 circRNA 表达抑制乙型肝炎病毒相关肝细胞癌生长。

Scutellaria barbata D.Don and Oldenlandia diffusa (Willd.) Roxb crude extracts inhibit hepatitis-B-virus-associated hepatocellular carcinoma growth through regulating circRNA expression.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, Henan, China.

Department of Pathology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Medicine, Shanghai, 200437, Shanghai, China.

出版信息

J Ethnopharmacol. 2021 Jul 15;275:114110. doi: 10.1016/j.jep.2021.114110. Epub 2021 Apr 14.

DOI:10.1016/j.jep.2021.114110
PMID:33864890
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Scutellaria barbata D.Don (SB) and Oldenlandia diffusa (Willd.) Roxb are commonly known as Ban Zhi Lian and Bai Hua She Cao in Chinese herbal medicines, respectively. As a pair of herbs, they have traditionally been used as ethnomedicines for clearing away heat and toxins, removing blood stasis, and promoting blood circulation, diuresis, and detumescence.

AIM OF THE STUDY

The aim of the present study was to determine the active ingredients in SB and OD extracts and to investigate whether these extracts can inhibit the growth of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines (HepG2.2.15 and Hep3B) in vitro and in vivo, as well as to explore their mechanisms of action.

MATERIALS AND METHODS

We determined the levels of total flavonoids, luteolin, and apigenin in SB and OD extracts via ultraviolet-visible spectrophotometry and high-performance liquid chromatography. The effects of SB and OD extracts on HBV-associated HCC cell growth were assessed by HepG2.2.15 and Hep3B cells phenotype and RNA sequencing of Hep3B cells in vitro, and xenograft models in vivo.

RESULTS

The extracts of SB and OD contained total flavonoids. There were active ingredients of luteolin and apigenin in SB, but not in OD. The extracts of SB and OD significantly inhibited HCC growth, migration, invasion, and HBV activity in vitro and in vivo, as well as altered circRNA expression in Hep3B cells. Moreover, we constructed a circRNA-miRNA-mRNA co-expression network.

CONCLUSIONS

The extracts of SB and OD may inhibit HCC cell growth and HBV activity in vitro and in vivo through altering circRNA-miRNA-gene expression and that the efficacies of these extracts may be related to the presence of luteolin and apigenin.

摘要

草药学相关性

黄芩(SB)和白花蛇舌草(OD)在中国草药学中分别被称为板兰根和白花蛇舌草。作为一对草药,它们传统上被用作清除热毒素、活血化瘀、促进血液循环、利尿和消肿的民族药物。

研究目的

本研究旨在确定 SB 和 OD 提取物中的活性成分,并研究这些提取物是否能在体外和体内抑制乙型肝炎病毒(HBV)相关肝癌(HCC)细胞系(HepG2.2.15 和 Hep3B)的生长,并探讨其作用机制。

材料和方法

我们通过紫外可见分光光度法和高效液相色谱法测定了 SB 和 OD 提取物中的总黄酮、木犀草素和芹菜素的含量。通过 HepG2.2.15 和 Hep3B 细胞表型和 Hep3B 细胞的 RNA 测序,以及体内异种移植模型,评估了 SB 和 OD 提取物对 HBV 相关 HCC 细胞生长的影响。

结果

SB 和 OD 的提取物均含有总黄酮。SB 中含有木犀草素和芹菜素等活性成分,但 OD 中没有。SB 和 OD 的提取物在体外和体内均显著抑制 HCC 的生长、迁移、侵袭和 HBV 活性,并改变了 Hep3B 细胞中的 circRNA 表达。此外,我们构建了一个 circRNA-miRNA-mRNA 共表达网络。

结论

SB 和 OD 的提取物可能通过改变 circRNA-miRNA-基因表达,在体外和体内抑制 HCC 细胞生长和 HBV 活性,而这些提取物的疗效可能与木犀草素和芹菜素的存在有关。

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