Guchang Zhixie Wan protects mice against dextran sulfate sodium-induced colitis through modulating the gut microbiota in colon.
Guchang Zhixie Wan (GC) is a traditional Chinese patent medicine used in the treatment of colitis in clinical trials. Though the notable effect of GC on colitis, the concrete mechanism of GC remain elusive. Emerging evidence showed that the imbalances of inflammatory cytokines and gut microbiota were both closely related to the initiation and progression of colitis.
To elucidate the relationship between the protective effects of GC on colitis and gut microbiota.
Male Kunming (KM) mice were enrolled in our work to establish colitis model induced by dextran sulfate sodium (DSS). The colitis mice were randomly divided into different groups and treated orally with 125 mg/kg of sulfasalazine (positive control) and 25, 50, 100 mg/kg of GC for 7 days, respectively. Inflammation cytokines of IL-1β, IL-4, IL-6, IL-8, IL-11, IL-12 and TNF-α were detected by ELISA analysis and the histological changes were detected by H&E staining. Gut microbiota diversity was analyzed by 16S rDNA sequencing. Metagenomes analysis were also conducted to reflect the protective effects of GC on colitis.
The results of CAS (Clinical Activity Score) confirmed the protective effects of GC on colitis. After administration of GC, the levels of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-11, IL-12 and TNF-α were all decreased while the anti-inflammatory cytokines IL-4 was slightly increased, indicating that GC could down regulate pro-inflammatory cytokines. H&E staining revealed that GC could improve the histopathological structure of the colon tissue. The results of 16S rDNA sequences analysis showed that GC could decrease the relative abundance of Turicibacter and increase the relative abundance of Ruminococcaceae_UCG-005.
GC greatly improve the health condition of colitis mice induced by DSS through improving the imbalances of inflammatory cytokines and gut microbiota.
Wang Z
，Liang Y
，Yu J
，Zhang D
，Ren L
，Zhang Z
，Liu Y
，Wu X
，Liu L
，Tang Z
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2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside, a major bioactive component from Polygoni multiflori Radix (Heshouwu) suppresses DSS induced acute colitis in BALb/c mice by modulating gut microbiota.
Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), which is a common idiopathic digestive disease without a specific cure or treatment for improvement. Because Polygoni multiflori Radix has a traditional medicinal use to treat intestinal diseases, and the water extract of this herbal medicine had a positive influence on dextran sulfate sodium (DSS) induced UC model in our study. Meanwhile 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) as the major component of the water extract of Polygoni multiflori Radix with yield of more than 10% exhibited the remarkable anti-inflammatory activity in vivo and in vitro, we predicted that TSG may contribute to benefit intestinal tract presented by the water extract of Polygoni multiflori Radix. Therefore, the present study aims to explore the pharmacological effect of this compound on UC model and its possible mechanism to regulate intestinal function through gut microbiota.
Ulcerative colitis model was established in BALb/c mice by continuously administrating 3% (w/v) DSS aqueous solution for one week. The disease activity index (DAI), colon length, histopathological examination by H&E and the levels of tight junction proteins (TJP) by immunofluorescence staining were performed in ulcerative colitis model following the protocol. Furthermore, the levels of main inflammatory factors like TNF-α, IL-β, IL-6, and IL-10 were analyzed by the ELIZA kits for the further confirmation of anti-inflammatory activity of TSG on ulcerative colitis model. Finally, 16S rDNA sequencing technology was conducted to explore the composition and relative abundance of gut microbiota of different treatment groups.
TSG treatments effectively increased body weight about 5% of those in DSS group (p < 0.001) as well remarkably reduced the DAI scores to the 50% of those in DSS group (p < 0.001) in the UC model. TSG treatments of either 25 mg/kg (TSG-25) or 100 mg/kg (TSG-100) dosage restored epithelial barrier structure and exhibited obviously intact colon histology with reduced signs of inflammatory cells infiltration, preserved epithelia barrier, restored crypt structure, and increased numbers of goblet cells. TSG treatments could markedly lessen the histopathologic score two or three times than those in DSS group (p < 0.001). Especially for TSG-100 treatment, the fluorescence intensity of ZO-1 and Occludin were nearly back to 80% of those in normal group, and were 1.5 times more than those in the DSS group (p < 0.001). Additionally, direct evidence pointed to TSG as a therapeutically active molecule in the prevention and treatment of UC by significantly reducing the production of these pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 (p < 0.05-0.001) and increasing the levels of anti-inflammatory cytokine IL-10 (p < 0.05-0.001). Finally, it was found TSG treatments significantly raised the relative abundances of Firmicutes and Bacteroidetes with a dose-dependently and improved the homeostasis of the gut microbiota composition which disrupted by DSS through increasing genus level Lachnospiraceae_NK4A136 and decreasing genus level of Helicobacter, Bacteroides, Parabacteroides.
The present results suggested that TSG treatments had a desirable pharmacological effect on acute colitis induced by DSS in the mice as well showed the possible mechanism relate to improve the intestinal function through balancing the gut microbiota of intestinal flora.
He X
，Liu J
，Long G
，Xia XH
，Liu M
... -
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Ethanol extract of Centella asiatica alleviated dextran sulfate sodium-induced colitis: Restoration on mucosa barrier and gut microbiota homeostasis.
Ulcerative colitis (UC) is a relapsing inflammatory disease that still demands for effective remedies due to various adverse effects of the current principal treatments. Centella asiatica is a traditional medical herb with long application history in anti-inflammation.
To explore the anti-inflammatory effect and possible mechanism of C. asiatica ethanol extract (CA) in a murine colitis model induced by dextran sulfate sodium (DSS).
CA was analyzed by high performance liquid chromatograph (HPLC). The colitis model was induced by free access to 3% DSS in distilled water for 7 days. CA (100, 200, and 400 mg/kg) and 5-aminosalicylic acid (5-ASA, 400 mg/kg) were administrated by gavage during the 7-day DSS challenge. At the end of experiment, mice were sacrificed and the brain, colon and cecum contents were harvested for analysis. Colitis was evaluated by disease activity index (DAI), colon length and colon lesion macroscopic score with hematoxylin-eosin staining. Myeloperoxidase (MPO) activity in colon and 5-hydroxytryptamine (5-HT) in brain were determined by ELISA. Tight junction protein expressions (ZO-1, E-Cadherin, Claudin-1) and c-Kit in colon were assessed by western blot and immunohistochemistry, respectively. Microbiota of cecum content was analyzed by 16S rRNA sequencing.
Data showed that with recovery on the colon length and histological structure, CA prominently decreased DAI and macroscopic score for lesion in the suffering mice. CA relieved the colitis by suppressing inflammatory cell infiltration with decreased MPO activity in the colon, and up-regulated the expression of tight junction protein (ZO-1, E-cadherin) to enhance the permeability of intestinal mucosa. Moreover, CA restored intestinal motility by promoting c-Kit expression in the colon and 5-HT in the brain. Moreover, CA was able to reshape the gut microbiota in the suffering mice. It increased the α-diversity and shifted the community by depleting the colitis-associated genera, Helicobacter, Jeotgalicoccus and Staphylococcus, with impact on several metabolism signaling pathways, which possibly contributes to the renovation on the impaired intestinal mucosal barrier.
CA displayed the anti-inflammatory activity against the DSS-induced colitis, which would possibly rely on the restoration on mucosa barrier and gut microbiota homeostasis, highlights a promising application of C. asiatica in the clinical treatment of UC.
Li H
，Chen X
，Liu J
，Chen M
，Huang M
，Huang G
，Chen X
，Du Q
，Su J
，Lin R
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