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Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

ABSTRACT: Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system. The extracts identified as autophagy activators were administered to mice with 2% dextran sodium sulfate (DSS). Among the autophagy inducers, Sanguisorba officinalis L. (SO) suppressed DSS-induced colitis. To identify the mechanism by which SO ameliorates colitis, epithelial cell and innate myeloid cells-specific Atg7-deficient mice (Villin-cre; Atg7^f/f and LysM-cre; Atg7^f/f mice, respectively) were analyzed. SO-mediated inhibition of colitis was observed in Villin-cre; Atg7^f/f mice. However, SO and a mixture of its components including catechin acid, ellagic acid, gallic acid, and ziyuglycoside II (Mix₄) did not suppressed colitis in LysM-cre; Atg7^f/f mice. In large intestinal macrophages (M?) of Atg7^f/f mice, SO and Mix₄ upregulated the expression of marker genes of anti-inflammatory M? including Arg1, Cd206, and Relma. However, these alterations were not induced in LysM-cre; Atg7^f/f mice. These findings indicate that SO and its active components ameliorate DSS-induced colitis by providing intestinal M? with anti-inflammatory profiles via promotion of Atg7-dependent autophagy.

SUBMITTER: Yasueda A

PROVIDER: S-EPMC7305163 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

Yasueda Asuka A Kayama Hisako H Murohashi Michiko M Nishimura Junichi J Wakame Koji K Komatsu Ken-Ichi KI Ogino Takayuki T Miyoshi Norikatsu N Takahashi Hidekazu H Uemura Mamoru M Matsuda Chu C Kitagawa Toru T Takeda Kiyoshi K Ito Toshinori T Doki Yuichiro Y Eguchi Hidetoshi H Shimizu Shigeomi S Mizushima Tsunekazu T

Scientific reports 20200619 1

Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system. The extracts identified as autophagy activators were administered to mice with 2% dextran sodium sulfate (DSS). Among the autophagy inducers, Sanguisorba officinalis L. (S ...[more]

PMID: 32561763

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Project description:Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. In vitro findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was via regulation of autophagy. Further experiments-including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection-validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis via Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy in vivo, which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.

Project description:BackgroundMaternal asthma is a risk factor for asthma in offspring; however, transmission of the risk for allergic asthma without direct offspring sensitization has not been explored.ObjectiveTo determine whether offspring from mothers with ovalbumin (OVA)-sensitized asthma would develop airway disease at first-ever exposure to OVA and whether preconception maternal treatment with the Antiasthma Simplified Herbal Medicine Intervention (ASHMI) or dexamethasone (DEX) could modify this risk in offspring.MethodsFemale BALB/c mice (F0) with OVA-induced asthma were generated using established protocols. Mice with asthma were treated with ASHMI, DEX, or water for 6 to 7 weeks. Naive mice served as controls. Subsequently, mice were mated. Twelve-day-old F1 offspring received 3 consecutive intranasal low- or high-dose OVA exposures without sensitization. Forty-eight hours later, airway inflammation, mucus hypersecretion, serum antibodies, and cytokines were evaluated.ResultsOffspring from OVA-sensitized mothers, but not naive mothers, showed eosinophilic and neutrophilic airway inflammation, and mucus hyperplasia after OVA exposure and he presence of OVA-specific IgG1 and IgG2a. Offspring of ASHMI- and DEX-treated mothers showed decreased airway inflammation and mucus hypersecretion after low-dose OVA (P < .05-.001 for the 2 comparisons vs offspring of OVA/Sham mothers). Offspring of ASHMI-treated, but not DEX-treated, mothers were protected after the high-dose OVA challenge (P < .05-.01 vs offspring OVA/Sham). Maternal ASHMI therapy was associated with increased IgG2a (P < .01 vs offspring of OVA/Sham mothers) and decreased bronchoalveolar lavage fluid CXCL-1 and eotaxin-1 levels (P < .01 and P < .05, respectively, vs offspring of OVA/Sham mothers).ConclusionOffspring of mothers with OVA-induced asthma developed airway inflammation and mucus to first-ever OVA exposure without prior sensitization. Maternal therapy with ASHMI was superior to DEX in decreasing offspring susceptibility to airway disease and could be a strategy to lower asthma prevalence.

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Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

Publications

Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

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