Effect of &lt;i&gt;Eucommia ulmoides&lt;/i&gt; Leaf Extract on Chronic Dextran Sodium Sulfate-Induced Colitis in Mice

Murakami, Satoshi; Tasaka, Yuichi; Takatori, Shingo; Tanaka, Akihiro; Kawasaki, Hiromu; Araki, Hiroaki

doi:10.1248/bpb.b17-00878

Cited by 15 publications

(8 citation statements)

References 25 publications

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“…Body weight and bloody diarrhea score were evaluated and recorded daily. Bloody stool score was evaluated according to the following standards: normal-colored stool (score 0), brown stool (score 1), reddish stool (score 2), bloody stool (score 3) [ 20 ]. All groups were anesthetized under pentobarbital sodium anesthesia and euthanized by cervical dislocation.…”

Section: Methodsmentioning

confidence: 99%

Pinocembrin alleviates ulcerative colitis in mice via regulating gut microbiota, suppressing TLR4/MD2/NF-κB pathway and promoting intestinal barrier

Yue

Ren

et al. 2020

Bioscience Reports

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Pinocembrin, a plant-derived flavonoid, has a variety of pharmacological activities, including anti-infection, anti-cancer, anti-inflammation, cardiovascular protection, etc. However, the mechanism of pinocembrin on the anti-colitis efficacy remains elusive and needs further investigation. Here, we reported that pinocembrin eased the severity of dextran sulfate sodium (DSS)-induced colitis in mice by suppressing the abnormal activation of toll-like receptor 4 (TLR4) / nuclear factor-kappa B (NF-κB) signal pathway in vivo. In addition, the gut microbiota was disordered in DSS colitis mice, which was associated with a significant decrease in microbiota diversity and a great shift in bacteria profiles; however, pinocembrin treatment improved the imbalance of gut microbiota and made it similar to that in normal mice. On the other hand, in vitro, pinocembrin down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level, pinocembrin competitively inhibited the binding of LPS to myeloid differentiation protein 2 (MD2), thereby blocking the formation of receptor multimer TLR4/MD2·LPS. Furthermore, pinocembrin dose-dependently promoted the expression of tight junction proteins (ZO-1, Claudin-1, Occludin and JAM-A) in Caco-2 cells. In conclusion, our work presented evidence that pinocembrin attenuated DSS-induced colitis in mouse, at least in part, via regulating intestinal microbiota, inhibiting the over-activation of TLR4/MD2/NF-κB signaling pathway, and improving the barriers of intestine.

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Section: Methodsmentioning

confidence: 99%

Pinocembrin alleviates ulcerative colitis in mice via regulating gut microbiota, suppressing TLR4/MD2/NF-κB pathway and promoting intestinal barrier

Yue

Ren

et al. 2020

Bioscience Reports

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“…In recent years, EL extract (ELE) has been found to have beneficial effects on immune regulation, antioxidants, bone injury wound healing, and intestinal health enhancement ( Zhu and Sun, 2018 ). EL extract, for example, has been reported to alleviate intestinal epithelium injury, which induced by obesity in mice ( Murakami et al, 2018 ). Although the potential mechanism of ELE in alleviating IBD remains unclear, the protective effect may be attributed to bioactive components such as polyphenols, flavonoids, and polysaccharides in ELE.…”

Section: Introductionmentioning

confidence: 99%

The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity

et al. 2021

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Eucommia ulmoides leaves (EL) are rich in phenolic acids and flavonoids, showing enhancing intestinal health effects. The intestinal microbiota-bile acid axis plays important roles in the occurrence and recovery of inflammatory bowel disease (IBD). However, whether EL extract (ELE) has regulatory effects on the intestinal microbiota, bile acid metabolism, and IBD is still unclear. To fill this gap, 2% dextran sulfate sodium (DSS)-induced mild IBD in a C57BL/6J mouse model that was treated with 200 or 400 mg/kg (intake dose/body weight) ELE was used. Oral ELE supplementation alleviated DSS-induced shortening of colon and colonic epithelial injury. Compared with the DSS group, ELE supplementation significantly decreased Toll-like receptor 4 (TLR4) and interlukin-6 (IL-6) and increased occludin and claudin-1 mRNA expression level in the colon (p < 0.05). Combined 16S rRNA gene sequencing and targeted metabolomic analyses demonstrated that ELE significantly improved the diversity and richness of the intestinal microbiota, decreased the abundance of Bacteroidaceae, and increased Akkermansiaceae and Ruminococcaceae abundance (p < 0.05) compared with DSS-induced IBD mice. Moreover, ELE significantly increased the serum contents of deoxycholic acid (DCA) and tauroursodeoxycholic acid (TUDCA), which were highly positively correlated with Akkermansia and unidentified_Ruminococccaceae relative to the DSS group. We then found that ELE increased Takeda G-protein coupled receptor 5 (TGR5), claudin-1, and occludin mRNA expression levels in the colon. In the Caco-2 cell model, we confirmed that activation of TGR5 improved the reduction in transepithelial electoral resistance (TEER) and decreased the permeability of FITC-dextran on monolayer cells induced by LPS (p < 0.05). siRNA interference assays showed that the decrease in TGR5 expression led to the decrease in TEER, an increase in FITC-dextran permeability, and a decrease in claudin-1 protein expression in Caco-2 cells. In summary, ELE alleviated IBD by influencing the intestinal microbiota structure and composition of bile acids, which in turn activated the colonic TGR5 gene expression in the colon and promoted the expression of tight junction proteins. These findings provide new insight for using ELE as a functional food with adjuvant therapeutic effects in IBD.

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“…Ulcerative colitis (UC) is a common refractory and life-long disease (Sedghi, 2016;Murakami et al, 2018). The common presenting symptoms include gastroenteritis, fever, diarrhea, rectal bleeding, mucus in stools, sense of urgency for bowel movements, and abdominal pain (Xu et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat

et al. 2019

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Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease with a high incidence rate and a difficult treatment regimen. Recently, significant advances in the treatment of intestinal diseases, particularly UC, have been made with the use of the drugs baicalin and baicalein, separately or in combination. However, the therapeutic efficacy and mechanism of action of baicalin, baicalein, and their combination therapy, in the treatment of UC has not been fully elucidated.Materials and Methods: we constructed a UC rat model that encompassed a variety of complex factors, including a high-sugar and high-fat diet, a high temperature and humidity environment (HTHE), excess drinking, and infection of Escherichia coli. Model rats were then treated with baicalin, baicalein, or a combination of the two. Results:The results showed significant differences in the therapeutic effects of baicalin, baicalein, and the combination therapy, in the treatment of UC, as well as differences in the inhibition of inflammation via the nuclear factor-κB and MAPK pathways. The rat model of UC was established as described above. Then, the rats were treated for 7 days with baicalin (100 mg kg -1 ), baicalein (100 mg kg -1 ), or both (100 mg kg -1 , baicalin: baicalein = 4:1/1:1). Clinical symptoms and signs, body temperature, organ indices, histopathology, blood biochemistry, and metabolites were examined to compare treatment effects and indicators of UC. Baicalin, YSR (Young Scutellaria baicalensis ratio of baicalin and baicalein), baicalein, and WSR (Withered Scutellaria baicalensis ratio of baicalin and baicalein) had significantly different effects in terms of clinical symptoms and signs, body temperature, organ indices, serum inflammatory cytokine levels, blood biochemistry, and histopathology changes in the main organs; YSR exhibited the best treatment effects. LC-MS/MS was used to detect the conversion of baicalin, baicalein, or both, into the six types of metabolites: baicalin, wogonoside, oroxin A, baicalein, wogonin, and oroxylin A. The levels of the six metabolites under the different treatment Frontiers in Pharmacology | www.frontiersin.org Baicalin, Baicalein and Their Combinations on UC Liang et al.conditions were significantly different in the large intestine, small intestine, and lungs, but not in the blood. The levels of the six metabolites were significantly different in the large intestine, small intestine, and lung, but not in the serum.Conclusion: All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in Scutellaria baicalensis (Tiaoqin) should be preferred in treatment of UC.

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Effect of <i>Eucommia ulmoides</i> Leaf Extract on Chronic Dextran Sodium Sulfate-Induced Colitis in Mice

Cited by 15 publications

References 25 publications

Pinocembrin alleviates ulcerative colitis in mice via regulating gut microbiota, suppressing TLR4/MD2/NF-κB pathway and promoting intestinal barrier

Pinocembrin alleviates ulcerative colitis in mice via regulating gut microbiota, suppressing TLR4/MD2/NF-κB pathway and promoting intestinal barrier

The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat

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