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Rhein Inhibits PI3K/Akt/mTOR Signaling Pathway to Show Efficacy in an Ulcerative Colitis Mice Model


Article Information

Title: Rhein Inhibits PI3K/Akt/mTOR Signaling Pathway to Show Efficacy in an Ulcerative Colitis Mice Model

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.002.01.0086

Categories

Abstract

Dong and his associates investigated the potential therapeutic effect of Rhein on ulcerative colitis (UC) and its mechanism in mouse models of human disease. Their results showed a decrease in the levels of TNF-α, IL-6, IL-1β, and other cytokines responsible for promoting inflammation. Moreover, both in-vivo and in-vitro mitigation of UC-associated symptoms such as colon shortening, weight loss, diarrhea, and hematochezia stimulated by dextran sodium sulfate was seen. Through western blotting, decreasing phosphorylated protein levels of PI3K, Akt, mTOR, and p70S6K1 by Rhein was evident which indicates inhibition of the PI3K/Akt/mTOR signaling pathway. Rhein administration also partially reversed the gut dysbacteriosis of mice induced by dextran sulfate sodium. A decrease in pathogenic bacteria (e.g., Enterobacteriaceae and Turicibacter) as revealed by 16sRNA gene sequencing was also observed. The authors conclude that Rhein possesses anti-UC activity as exhibited by alleviating the signs and symptoms of UC and diminishing gastrointestinal inflammation by blocking the PI3K/Akt/mTOR signaling pathway and modulating stomach microbiota. Phytother Res. 2022 May;36(5):2081-2094.


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 models, and liver fibrosis.


Methodology

The studies employed a combination of in vivo (mouse models) and in vitro (cell culture) experimental designs. Techniques included 16sRNA gene sequencing, western blotting, exosome isolation and analysis, wound healing models, histological analysis, and the use of specific pathway inhibitors. Animal models included those for ulcerative colitis induced by dextran sodium sulfate, subcutaneous cancer models for hepatocellular carcinoma, wound healing models, APP/PS1 mice for Alzheimer's disease, and CCl4-treated or high-fat diet-induced liver fibrosis models.

Methodology Flowchart
                        graph TD;
    A["Disease Model Establishment"] --> B["Treatment Administration"];
    B --> C["In Vivo/In Vitro Analysis"];
    C --> D["Mechanism Investigation"];
    D --> E["Data Interpretation"];
    E --> F["Conclusion"];                    

Discussion

The findings suggest that natural compounds and traditional remedies can offer effective therapeutic strategies for various diseases by targeting specific molecular pathways and cellular processes. The research highlights the importance of understanding the mechanisms of action, including signaling pathways and exosomal communication, to develop novel treatments. The studies also validate traditional medicinal practices with scientific evidence.


Key Findings

Rhein alleviated ulcerative colitis symptoms by inhibiting the PI3K/Akt/mTOR signaling pathway and modulating gut microbiota. Jianpi Huayu (JHP) demonstrated anti-neoplastic effects against hepatocellular carcinoma by suppressing exosomal miR-23a-3p transfer and blocking Smad signaling. Oleoresin preparations of Pistacia vera showed significant wound healing properties, comparable to a standard drug, with no observed toxicity. Icarisid II improved cognition in an Alzheimer's disease mouse model by activating 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 products and traditional Chinese remedies hold significant therapeutic potential for a range of diseases. Targeting pathways such as PI3K/Akt/mTOR, exosomal miR-23a-3p/Smad, Wnt/-catenin, and TGF1-SMAD2/3 offers promising avenues for developing new treatments for ulcerative colitis, hepatocellular carcinoma, cognitive decline, and liver fibrosis.


Fact Check

- Rhein administration partially reversed gut dysbacteriosis in mice induced by dextran sulfate sodium. (Confirmed by text)
- Post hepatectomy, patients with high miR-23a-3p levels had low survival rates. (Confirmed by text)
- From day 8 to day 16 significant wound contraction was seen upon application of Algerian and Italian oleoresin ointment preparation. (Confirmed by text)


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