Tang Yun, Chen Yi-Gang, Huang Hsi-Yuan, Li Shang-Fu, Zuo Hua-Li, Chen Ji-Hang, Li Li-Ping, Mao Run-Bo, Lin Yang-Chi-Dung, Huang Hsien-Da
School of Medicine, The Chinese University of Hong Kong, Shenzhen, Longgang District, Shenzhen, 518172, Guangdong, China.
Warshel Institute for Computational Biology, The Chinese University of Hong Kong, Shenzhen, Longgang District, Shenzhen, 518172, Guangdong, China.
Chin Med. 2023 Jun 20;18(1):74. doi: 10.1186/s13020-023-00768-y.
Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available.
To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved.
Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic β cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1.
This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.
中药三七(SQ),即三七(PNS)的干燥根或茎,据报道具有抗糖尿病和抗肥胖作用,通常作为中药汤剂服用。为了替代使用三七纯化合物进行治疗,我们有动力提出一种非常规方案来研究三七混合物的功能。然而,很少有研究提供基于转录组学的三七信号网络的详细概述。
为了探究三七治疗胰岛素抵抗等代谢紊乱的机制,我们采用基于系统生物学的方法,结合RNA测序(RNA-seq)和miRNA测序数据,以阐明关键途径、基因和miRNA。
功能富集分析显示,三七上调氧化应激相关途径,下调胰岛素和脂肪酸代谢。在三七处理的大鼠胰腺β细胞(INS-1)中测量了超氧化物歧化酶1(SOD1)、过氧化物酶体增殖物激活受体1(PRDX1)、血红素加氧酶-1(Hmox1)和谷氨酸半胱氨酸连接酶(GCLc)的mRNA和蛋白质水平,以及相关miRNA水平。三七处理上调Hmox1、SOD1和GCLc的表达,同时下调miR-24-3p和miR-139-5p以抑制氧化应激。此外,我们验证了miR-139-5p和miR-24-3p与GCLc和SOD1之间的新相互作用。
这项工作揭示了三七在代谢紊乱中调节细胞分子的机制。因此,将组学数据与系统生物学策略相结合可能是探索中药治疗代谢紊乱潜在功能和分子机制的一种实用方法。