# Cycloastragenol in inflammation-related diseases: mechanisms, pharmacokinetics, and translational prospects

## TL;DR

Cycloastragenol shows promise as a treatment for inflammation-related diseases by targeting key inflammatory pathways and reducing oxidative stress.

## Contribution

This study systematically evaluates the molecular mechanisms and therapeutic potential of Cycloastragenol for inflammation-related diseases.

## Key findings

- Cycloastragenol modulates inflammatory pathways like NF-κB, Nrf2, and the NLRP3 inflammasome.
- It demonstrates therapeutic potential in cancer, neurological disorders, asthma, and fibrosis.
- Improving bioavailability and verifying safety in human trials are critical next steps.

## Abstract

Chronic inflammation, driven by dysregulated immune responses and oxidative stress, underlies the pathogenesis of numerous diseases, from neurodegeneration to cancer. Cycloastragenol (CAG), a bioactive triterpenoid derived from Astragalus membranaceus, has emerged as a multifaceted therapeutic candidate due to its unique ability to simultaneously modulate inflammatory signaling networks, while exhibiting a favorable safety profile in preclinical models. This study aims to systematically evaluate the molecular mechanisms of CAG, including its coordinated anti-inflammatory, immune-regulatory, and tissue-protective effects. By integrating evidence from pharmacology, metabolomics, and clinical studies, our aim is to elucidate the therapeutic potential of CAG and identify strategies to overcome its pharmacokinetic limitations for clinical translation. A comprehensive literature review was conducted using databases such as PubMed, Web of Science, and Science Direct, employing target keywords related to cycloastragenol, inflammation, and disease treatment. Our analysis reveals that CAG exerts multidimensional and networked anti-inflammatory effects by synergistically regulating key inflammatory nodes such as NF-κB, Nrf2, and the NLRP3 inflammasome, as well as by alleviating oxidative stress. It has demonstrated therapeutic potential in diseases such as cancer, neurological disorders, asthma, and visceral fibrosis. CAG exerts significant anti-inflammatory effects by targeting the axis associated with inflammation, oxidative stress, and immune dysregulation. However, future efforts need to focus on improving its bioavailability and verifying its safety in human trials to develop a new generation of anti-inflammatory therapies.

Graphical abstract: Cycloastragenol exerts multidimensional and networked anti-inflammatory effects by modulating multiple inflammatory nodes such as NF-κB, Nrf2, and the NLRP3 inflammasome, and by alleviating oxidative stress. It has shown therapeutic potential in diseases such as cancer, neurological disorders, asthma, and visceral fibrosis.Diagram illustrating the anti-inflammatory properties and mechanisms of Cycloastragenol. Central section highlights anti-inflammatory effects against diseases like degenerative diseases, asthma, various cancers, cerebral ischemia, fibrosis, and abdominal aortic aneurysm. Anti-inflammatory mechanisms include inhibiting the NLRP3 inflammasome, reducing oxidative stress via Nrf2 pathways, and regulating inflammation through NF-kB and TGF-beta factors. The diagram also shows biosynthesis, toxicology, and pharmacokinetics aspects, noting no observed toxicity and emphasizing first intestinal metabolism.

Graphical abstract: Cycloastragenol exerts multidimensional and networked anti-inflammatory effects by modulating multiple inflammatory nodes such as NF-κB, Nrf2, and the NLRP3 inflammasome, and by alleviating oxidative stress. It has shown therapeutic potential in diseases such as cancer, neurological disorders, asthma, and visceral fibrosis.