Natural compound fraxinellone ameliorates intestinal fibrosis in mice via direct intervention of HSP47-collagen interaction in the epithelium

Wang, Jie; Bai, Mei; Zhang, Cui; Wan, Li; Wang, Xiaoning; Du, Ronghui; Shen, Yan; Yuan, Zhiyao; Wu, Xudong; Wu, Xue-Feng; Xu, Qiang

doi:10.1038/s41401-023-01143-1

Cited by 3 publications

(3 citation statements)

References 43 publications

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“…A direct binding of (4) to the purified protein has been evidenced by surface plasmon resonance (Kd = 3.542 × 10 −5 M), and a modeling analysis helped to define the location of the binding site with the implication of some key amino acids in the binding process, notably residues Tyr383 and Asp385. This drug interaction inhibits and destroys the complex between the chaperone Hsp47 and collagen, thereby perturbating procollagen folding and collagen processing [102]. The interaction with Hsp47 directly implicates the furan unit of fraxinellone.…”

Section: Potential Molecular Targets Of Prieurianin and Analogsmentioning

confidence: 99%

“…The regulation of Hsp47-collagen's interaction with fraxinellone accounts for the antifibrotic action of the limonoid [102], and it may also contribute to its antimetastatic activity because Hsp47 is a known stimulator of metastasis in solid tumors, notably in breast cancer [103]. These observations prompted us to consider that, by analogy, prieurianin could bind to Hsp47 via its fraxinellone-like moiety.…”

Section: Potential Molecular Targets Of Prieurianin and Analogsmentioning

confidence: 99%

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Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Vergoten,

Bailly

2024

IJMS

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Limonoids are extremely diversified in plants, with many categories of products bearing an intact, rearranged or fragmented oxygenated scaffold. A specific subgroup of fragmented or degraded limonoids derives from the tetranortriterpenoid prieurianin, initially isolated from the tree Trichilia prieuriana but also found in other plants of the Meliaceae family, including the more abundant species Aphanamixis polystachya. Prieurianin-type limonoids include about seventy compounds, among which are dregeanin and rohitukin. Prieurianin and analogs exhibit insecticidal, antimicrobial, antiadipogenic and/or antiparasitic properties but their mechanism of action remains ill-defined at present. Previous studies have shown that prieurianin, initially known as endosidin 1, stabilizes the actin cytoskeleton in plant and mammalian cells via the modulation of the architecture and dynamic of the actin network, most likely via interference with actin-binding proteins. A new mechanistic hypothesis is advanced here based on the recent discovery of the targeting of the chaperone protein Hsp47 by the fragmented limonoid fraxinellone. Molecular modeling suggested that prieurianin and, to a lesser extent dregeanin, can form very stable complexes with Hsp47 at the protein–collagen interface. Hsp-binding may account for the insecticidal action of the product. The present review draws up a new mechanistic portrait of prieurianin and provides an overview of the pharmacological properties of this atypical limonoid and its chemical family.

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Section: Potential Molecular Targets Of Prieurianin and Analogsmentioning

confidence: 99%

Section: Potential Molecular Targets Of Prieurianin and Analogsmentioning

confidence: 99%

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Vergoten,

Bailly

2024

IJMS

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“…In 2023, multiple studies were conducted to assess the effectiveness of existing management strategies and investigate potential new anti‐fibrotic treatments (Table 4 ). 23 , 73 , 74 , 75 , 76 , 77 , 78 , 80 , 81 , 82 , 83 …”

Section: Managementmentioning

confidence: 99%

Intestinal strictures in Crohn's disease: An update from 2023

Liu,

Huang,

Wang

et al. 2024

UEG Journal

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Crohn's disease (CD) is a chronic inflammatory disease that leads to intestinal stricture in nearly 35% of cases within 10 years of initial diagnosis. The unknown pathogenesis, lack of universally accepted criteria, and absence of an effective management approach remain unconquered challenges in structuring CD. The pathogenesis of stricturing CD involves intricate interactions between factors such as immune cell dysbiosis, fibroblast activation, and microecology imbalance. New techniques such as single‐cell sequencing provide a fresh perspective. Non‐invasive diagnostic tools such as serum biomarkers and novel cross‐sectional imaging techniques offer a precise understanding of intestinal fibrostenosis. Here, we provide a timely and comprehensive review of the worthy advancements in intestinal strictures in 2023, aiming to dispense cutting‐edge information regarding fibrosis and to build a cornerstone for researchers and clinicians to make greater progress in the field of intestinal strictures.

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Traditional Chinese Medicine: A Promising Treatment Option for Intestinal Fibrosis

Zhou,

Chen,

Jin

et al. 2024

Am. J. Chin. Med.

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Intestinal fibrosis, a common complication of inflammatory bowel disease, in particular in Crohn’s disease, arises from chronic inflammation, leading to intestinal narrowing, structural damage, and functional impairment that significantly impact patients’ quality of life. Current treatment options for intestinal fibrosis are limited, with surgery being the primary intervention. Traditional Chinese Medicine (TCM) has emerged as a promising approach in preventing and treating intestinal fibrosis. However, there is a scarcity of literature summarizing the mechanisms underlying TCM’s efficacy in this context. To address this gap, we conducted a comprehensive review, uncovering multiple mechanisms through which TCM mitigates intestinal fibrosis. These mechanisms include immune cell balance regulation, suppression of inflammatory responses, reduction of inflammatory mediators, alleviation of colon tissue damage, restoration of intestinal function, modulation of growth factors to inhibit fibroblast activation, dynamic regulation of TIMPs and MMPs to reduce extracellular matrix deposition, inhibition of epithelial–mesenchymal transition and endothelial–mesenchymal transition, autophagy modulation, maintenance of the intestinal mucosal barrier, prevention of tissue damage by harmful factors, and regulation of cell proliferation and apoptosis. This study aims to bridge existing knowledge gaps by presenting recent evidence supporting the utilization of TCM in both clinical and experimental research settings.

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Natural compound fraxinellone ameliorates intestinal fibrosis in mice via direct intervention of HSP47-collagen interaction in the epithelium

Cited by 3 publications

References 43 publications

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Intestinal strictures in Crohn's disease: An update from 2023

Traditional Chinese Medicine: A Promising Treatment Option for Intestinal Fibrosis

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