A Traditional Chinese Remedy for Hepatocellular Carcinoma Functions by Suppressing Exosomal miR-23a-3p/Smad Signaling

Article Information

Title: A Traditional Chinese Remedy for Hepatocellular Carcinoma Functions by Suppressing Exosomal miR-23a-3p/Smad Signaling

Authors: Editorial Staff

Journal: Phytopharmacological Communications (PPC)

HEC Recognition History

Category	From	To
Y	2024-10-01	2025-12-31
Y	2023-07-01	2024-09-30

Publisher: COSMOS Learning Center

Country: Pakistan

Year: 2022

Volume: 2

Issue: 1

Language: English

DOI: 10.55627/ppc.002.01.0087

Abstract

A decoction of Jianpi Huayu (JHP) has been used traditionally in orthodox Chinese medicine to treat tumors such as hepatocellular carcinoma (HCC), however, the mechanism is still a mystery. Intercellular communication in the cancer cell microenvironment points toward a strong role of exosomes, but their contribution to HCC is still not well understood. Xie and colleagues investigated the anti-neoplastic effects of JHD and the possible function of exosomal signaling. Nude mice models with subcutaneous cancer were used to gauge the effects of JHD. Migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT) of cultured HCC cells were mitigated by JHD. From the EMT-induced HCC cells, exosomes increased the invasion, migration, and EMT of other cultured HCC cells, whereas post-treatment of JHD, exosomes from EMT-induced HCC cells had little effect. Exosomal miR-23a-3p which is significantly upregulated in cancer cells as compared to normal cells was reduced in JHD-treated cultured HCC cells. Post hepatectomy, patients with high miR-23a-3p levels had low survival rates. Smad signaling protein expression as well HCC cell proliferation was upregulated by miR-23a-3p. More critically, miR-23a-3p overexpression countered the EMT and Smad signaling inhibition brought about by JHD treatment. In vivo examinations revealed that treatment with JHD additionally diminished the development of HCC-derived tumors in naked mice, and decreased the levels of miR-23a-3p in serum exosomes and the degree of EMT in cancer cells. The authors conclude that the anticancer properties of JHD partially if not completely are due to the downregulation of exosome-mediated intercellular miR-23a-3p transfer and subsequent blockade of Smad signaling. Disrupting this exosomal miR-23a-3p/Smad signaling pathway may be an effective treatment. J Ethnopharmacol. 2022 Aug 10;294:115360.

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Research Objective

To investigate the potential therapeutic effects and underlying mechanisms of various natural compounds and traditional remedies in treating diseases such as ulcerative colitis, hepatocellular carcinoma, wound healing, cognitive impairment in Alzheimer's disease, and liver fibrosis.

Methodology

Studies employed a combination of in-vivo animal models (mice, rabbits), in-vitro cell culture experiments, western blotting, 16sRNA gene sequencing, and analysis of molecular signaling pathways (PI3K/Akt/mTOR, exosomal miR-23a-3p/Smad, Wnt/-catenin, TGF1-SMAD2/3).

Methodology Flowchart

                        graph TD;
    A["Natural Product/Remedy Identification"] --> B["In-vivo/In-vitro Studies"];
    B --> C["Molecular Pathway Analysis"];
    C --> D["Data Interpretation"];
    D --> E["Conclusion on Therapeutic Efficacy and Mechanism"];

Discussion

The findings support the use of natural compounds and traditional remedies for various diseases, elucidating their molecular mechanisms of action. The studies highlight the importance of signaling pathways and intercellular communication (exosomes) in disease progression and therapeutic response.

Key Findings

Rhein alleviated ulcerative colitis symptoms by inhibiting the PI3K/Akt/mTOR pathway and modulating gut microbiota. Jianpi Huayu (JHP) demonstrated anti-neoplastic effects against hepatocellular carcinoma by downregulating exosomal miR-23a-3p and blocking Smad signaling. Oleoresin preparations of Pistacia vera showed significant wound healing properties with no observed toxicity. Icarisid II improved cognition in an Alzheimer's disease mouse model by promoting neurogenesis via the Wnt/-catenin pathway and mitigating mitochondrial fission. Pharbitis nil ethanolic extract (PNE) ameliorated liver fibrosis by downregulating TGF1-induced SMAD2/3 activation.

Conclusion

Natural compounds and traditional remedies hold significant therapeutic potential for a range of diseases, offering novel treatment strategies through modulation of specific molecular pathways and biological processes.

Fact Check

- Rhein administration in mice showed a decrease in TNF-, IL-6, and IL-1 cytokines.
- JHP treatment in nude mice models with subcutaneous cancer mitigated migration, invasion, proliferation, and epithelial-mesenchymal transition (EMT).
- PNE successfully mitigated liver fibrosis, inflammation, and hepatic necrosis in both CCl4-treated mice and mice subjected to a high-fat diet.

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