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Identification of Erzhu Jiedu Recipe and its molecular mechanism underlying inhibited human hepatoma cells by UHPLC-Q-Exactive Orbitrap HRMS and network pharmacology.
- Source :
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Journal of Ethnopharmacology . May2024, Vol. 325, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- Erzhu Jiedu Recipe (EZJDR) is a formula of traditional Chinese medicine (TCM) for treating hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). However, its effective components and the mechanism of action remain unclear. To explain how the active compounds of EZJDR suppress the growth of hepatoma cells. UHPLC-Q-Exactive Orbitrap HRMS was used to identify the chemical constituents of EZJDR and their distribution in the serum and liver of mice. Together with experimental investigations, network pharmacology unraveled the molecular mechanism of components of EZJDR underlying the inhibited Hep3B cells. A total of 138 compounds which can be divided into 18 kinds of components (such as sesquiterpenoids, diterpenoids, anthraquinones, flavonoids and so on) were found in the aqueous extract of EZJDR. Of these components, the tricyclic-diterpenoids exhibited a highest exposure in the serum (74.5%) and liver (94.7%) of mice. The network pharmacology revealed that multiple components of EZJDR interacted with key node genes involved in apoptosis, proliferation, migration and metabolism through various signaling pathways, including ligand binding and protein phosphorylation. In vitro experiments demonstrated that 6 tricyclic-diterpenoids, 2 anthraquinones and 1 flavonoid inhibited the viability of Hep3B cells, with IC 50 values ranging from 3.81 μM to 37.72 μM. Dihydrotanshinone I had the most potent bioactivity, arresting the S phase of cell cycle and inducing apoptosis. This compound changed the expression of proteins, including Bad, Bax, Bcl-2, Bal-x, caspase3 and catalase, which were associated with mitochondria-mediated apoptotic pathways. Moreover, dihydrotanshinone I increased the levels of p21 proteins, but decreased the phosphorylated p53, suggesting accumulation of p53 protein prevented cell cycle progression of Hep3B cells with damaged DNA. These results suggested that multiple components of EZJDR—diterpenoid, anthraquinone and flavonoid—could be the effective material for the treatment of HBV-HCC. This research provided valuable insights into the molecular mechanism of action underlying the therapeutic effects of EZJDR. [Display omitted] • A total of 138 compounds of EZJDR, and 48 absorbed in the liver and serum of mice were identified. • The diterpenoid, flavonoid and anthraquinone components showed effective suppression of growth of human hepatoma cells. • Network pharmacology unraveled the complexity of action mechanism of EZJDR, involving multiple biological processes. • These potential compounds displayed anti-cancer activity by inducing apoptosis and arresting cell cycle. • Dihydrotanshinine I induced Hep3B cell death involved caspase-dependent apoptosis and p53 pathways. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BLOOD serum analysis
*LIVER analysis
*CELL metabolism
*EXPERIMENTAL design
*PROTEINS
*IN vitro studies
*HEPATITIS B
*MEDICINAL plants
*HEMATOMA
*HIGH performance liquid chromatography
*DNA
*FLAVONOIDS
*ANIMAL experimentation
*APOPTOSIS
*ANTINEOPLASTIC agents
*CELLULAR signal transduction
*CELL cycle
*TREATMENT effectiveness
*MASS spectrometry
*DESCRIPTIVE statistics
*GENES
*CELL proliferation
*PLANT extracts
*PHARMACEUTICAL chemistry
*CHINESE medicine
*MICE
*PHOSPHORYLATION
*HEPATOCELLULAR carcinoma
Subjects
Details
- Language :
- English
- ISSN :
- 03788741
- Volume :
- 325
- Database :
- Academic Search Index
- Journal :
- Journal of Ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 175603016
- Full Text :
- https://doi.org/10.1016/j.jep.2024.117893