Entrapment of Macrophage-Target Nanoparticles by Yeast Microparticles for Rhein Delivery in Ulcerative Colitis Treatment

Chen, Qiyan; Luo, Rui; Han, Xiaoqin; Zhang, Jinming; He, Yao; Qi, Shanshan; Pu, Xiulan; Nie, Wenbiao; Dong, Lingling; Xu, Haiting; Liu, Fang; Lin, Meisi; Zhong, Heng; Fu, Chaomei; Gao, Fei

doi:10.1021/acs.biomac.1c00425

Cited by 40 publications

(30 citation statements)

References 41 publications

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“…The maximum dose of Rhein in this study was significantly lower than that in Yang's study (Jones‐Hall et al, 2015). On the other hand, nano‐drug delivery system was reported to have advantages of increase in target distribution of drugs in the lesions and decrease in the non‐target distribution in other organs from the perspective of pharmaceutics (Chen et al, 2021; Luo et al, 2021). Hence, a nano‐drug delivery system for oral delivery of Rhein has the potential to become a novel and safety strategy for the treatment of UC.…”

Section: Discussionmentioning

confidence: 99%

“…Anthraquinones have been recognized as the active compounds of Rhei Radix et Rhizoma. In our existing study, Rhein, one of the main anthraquinones, was reported to exert anti‐UC effect by regulating the NF‐κB signaling pathway (Chen et al, 2021). However, whether Rhein could regulate the PI3K/Akt/mTOR signaling pathway in UC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Anti‐inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota

Dong

Zhang

et al. 2022

Phytotherapy Research

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110

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This study aimed to analyze the therapeutic effect of Rhein on ulcerative colitis (UC) in mice and its possible mechanism. LPS‐induced UC cell model and DSS‐induced UC mouse model were used to analyze the antiinflammatory effect of Rhein on UC in vitro and in vivo, respectively. Network pharmacology analysis was conducted to identify potential signaling pathways involved in Rhein treating UC, and the results were further confirmed through western blotting assay. 16sRNA sequencing was performed to study the regulatory effect of Rhein on gut microbiota in UC mice. As indicated by the results, Rhein could significantly inhibit the production of pro‐inflammatory cytokines (e.g., TNF‐α, IL‐6 and IL‐1β) in vivo and in vitro, and alleviate DSS‐induced UC‐associated symptoms in mice (e.g., colon shortening, weight loss, diarrhea and hematochezia). The PI3K/Akt/mTOR signaling pathway was predicted as the potential interacting protein of Rhein in the treatment of UC through network pharmacology analysis. It was found through western blotting assay that the Rhein treatment could significantly inhibit the PI3K/Akt/mTOR signaling pathway by decreasing the phosphorylated protein levels of PI3K, Akt, mTOR and p70S6K1. By 16sRNA gene sequencing analysis, Rhein administration could partially reverse the gut dysbacteriosis of mice induced by DSS and decrease pathogenic bacteria (e.g., Enterobacteriaceae and Turicibacter). It was positively correlated with the production of pro‐inflammatory cytokines above, whereas the increase in probiotics (e.g., Unspecified‐S24‐7 and Rikenellaceae) was negatively correlated with the production of pro‐inflammatory cytokines. In conclusion, Rhine had anti‐UC efficacy, which was demonstrated by mitigating the UC symptoms and reducing intestinal inflammation by inhibiting the PI3K/Akt/mTOR signaling pathway and modulating gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti‐inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota

Dong

Zhang

et al. 2022

Phytotherapy Research

Self Cite

110

View full text Add to dashboard Cite

show abstract

“…7 However, as its pathogenesis is complex, including the interaction of host response and gene and immune influence caused by exogenous substances, 8 the therapeutic outcomes are greatly limited. 9 Moreover, these agents are apt to result in some unpredictable side-effects 10 including cardiac complications 11 and non-asthmatic eosinophilic bronchitis. 12 Nowadays, epidemiological investigations suggest that some functional foods such as green tea, coffee, polysaccharides 69 and yogurt possessing antioxidant, anti-inflammatory and gut microbiota regulation properties exhibit prevention capability for UC.…”

Section: Introductionmentioning

confidence: 99%

Protective mechanisms of Zanthoxylum bungeanum essential oil on DSS-induced ulcerative colitis in mice based on a colonic mucosal transcriptomic approach

et al. 2022

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“…Based on our preliminary research and previous relevant experimental research, RH has been shown to have multiple therapeutic effects on UC . Indeed, the available evidence indicates that RH can alleviate UC symptoms by regulating multiple inflammatory pathways (including TLR4/MyD 88 /NF-κB, and PI3K/Akt/mTOR signaling pathway). , In particular, the TLR4/NF-κB pathway is a key signaling pathway involved in colon inflammation . Meanwhile, some studies have shown that RH can alleviate symptoms of UC by activating the Nrf2/HO-1-mediated oxidative stress pathway .…”

Section: Introductionmentioning

confidence: 86%

“…Next, the RH release profiles from RH-F/C-NPs were examined using a dialysis method. 10 Briefly, 3 mL RH-F/C-NPs and free RH (RH concentration: 45 μg/mL) were added to separate the dialysis bags (MWCO 3000, Millipore). Meanwhile, Tween-80 (1% (w/v)) was supplemented into the releasing medium to maintain the RH solubility in the aqueous phase.…”

Section: Ph/ros Dual Sensitivity and Releasementioning

confidence: 99%

pH/ROS Dual-Sensitive Natural Polysaccharide Nanoparticles Enhance “One Stone Four Birds” Effect of Rhein on Ulcerative Colitis

Luo

Han

et al. 2022

ACS Appl. Mater. Interfaces

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Rhein (RH), a natural anthraquinone compound, is considered an effective treatment candidate for ulcerative colitis (UC), whose multiple biological activities contribute to UC, including anti-inflammation, antioxidation, intestinal barrier repair, and microflora regulation. However, the application of RH is severely limited by its low water solubility, low bioavailability, and poor colonic targeting. Although some nanoparticles have been developed for the oral delivery of RH, most of them mainly highlighted only one effect of some drug delivery strategies but the above multiple biological activities. Therefore, a multiple polysaccharide-based nanodelivery system, comprising chitosan (CS) and fucoidan (FU), with pH/reactive oxygen species (ROS) sensitivity and mucosal adhesion, was developed and first used to load RH as a comprehensive treatment for UC. Briefly, RH-F/C-NPs were prepared using the polyelectrolyte self-assembly method; the average size of RH-F/C-NPs was 233.1 ± 5.7 nm, and the encapsulation rate of RH was 93.67 ± 1.60%. And it could maintain gastric stability and release RH in the colon with the designed pH/ROS sensitivity contributed by the polysaccharide-based structures. Cellular uptake experiments showed that both NCM 460 cells and RAW 264.7 cells had a good uptake of RH-F/C-NPs. Importantly, the effects of RH were highlighted in in vivo experiments, the results of which showed that RH-F/C-NPs could significantly reduce DSS-induced inflammation by inhibiting the TLR4/NF-κB-mediated anti-inflammatory pathway, the Nrf2/HO-1-mediated antioxidant pathway, colonic mucosal barrier repair, and intestinal microflora regulation. In addition, pharmacokinetic studies have shown that F/C-NPs contribute to the increase in the plasma concentration and the accumulation of RH in the colon to some extent. In short, this study is the first to develop an oral multiple polysaccharide-based nanosystem with pH/ROS dual sensitivity to study the "one stone four birds" therapeutic effect of RH on UC.

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Entrapment of Macrophage-Target Nanoparticles by Yeast Microparticles for Rhein Delivery in Ulcerative Colitis Treatment

Cited by 40 publications

References 41 publications

Anti‐inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota

Anti‐inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota

Protective mechanisms of Zanthoxylum bungeanum essential oil on DSS-induced ulcerative colitis in mice based on a colonic mucosal transcriptomic approach

pH/ROS Dual-Sensitive Natural Polysaccharide Nanoparticles Enhance “One Stone Four Birds” Effect of Rhein on Ulcerative Colitis

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