Effect and mechanism of Magnolia officinalis in colorectal cancer: multi-component-multi-target approach.

Ethnopharmacological relevance: Colorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. Traditional Chinese medicine (TCM) has a long history of treating CRC, with advantages such as effectiveness, multi-target, multi-pathway, and minimal side effects. TCM Magnolia officinalis (M. officinalis) refers to the dried bark, root bark, and branch bark of either Magnolia officinalis Rehd.et Wils. or Magnolia officinalis Rehd.et Wils. var. biloba Rehd.et Wils.. It is commonly utilized to alleviate the side effects of chemotherapy for CRC, owing to its anti-inflammatory and anti-tumor properties. However, current research primarily focuses on the individual components and does not take into consideration the characteristics of multi-component-multi-target action.

Aim of the study: Our aim is to study the new action characteristics of M. officinalis in the treatment of CRC.

Materials and methods: Utilizing network pharmacology to identify potential active ingredients, key targets, and main signaling pathways of M. officinalis for the treatment of CRC. The binding effect was further validated through molecular docking analysis. Furthermore, the aforementioned components were identified using liquid chromatography-mass spectrometry (LC-MS), and the cleavage pathways of the main components were analyzed. Subsequently, both in vitro and in vivo experiments were carried out to investigate the anti-CRC effect of the active ingredients of M. officinalis and its potential mechanism.

Results: Network pharmacology and Molecular docking identified 5 main active ingredients and 6 core targets of M. officinalis for the treatment of CRC. Then, LC-MS identified the active components of M. officinalis. At the same time, both in vitro and in vivo experiments have confirmed the ability of Eucalyptol (Euc) and Obovatol (Obo)to inhibit inflammation and tumor cell proliferation. The possible mechanism involved is that Euc and Obo counteract CRC by inhibiting the over-activation of NF-κBp65/JAK and Bcl-2/Caspase signaling pathways, respectively. They also play a role in the anti-CRC effect of M. officinalis.

Conclusion: Magnolol (MAG), Honokiol (HK), Euc, Obo, and Neohesperidin (NHP) in M. officinalis may be the pharmacological substance basis for its anti-cancer effect on CRC. The treatment of CRC with M. officinalis is characterized by its multi-component, multi-target, and multi-pathway approach. These findings provide a theoretical basis for further inspiring the clinical application of M. officinalis and the development of efficacy targets.