Berberine increases stromal production of Wnt molecules and activates Lgr5+ stem cells to promote epithelial restitution in experimental colitis.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%. RESULTS: Here we show that berberine, a natural plant product, is more effective than the frontline drug sulfasalazine in treating DSS (dextran sulfate sodium)-induced colitis in mice, and that berberine not only suppresses macrophage and granulocyte activation but also promotes epithelial restitution by activating Lgr5+ intestinal stem cells (ISCs). Mechanistically, berberine increases the expression of Wnt genes in resident mesenchymal stromal cells, an ISC niche, and inhibiting Wnt secretion diminishes the therapeutic effects of berberine. We further show that berberine controls the expression of many circadian rhythm genes in stromal cells, which in turn regulate the expression of Wnt molecules. CONCLUSIONS: Our findings suggest that berberine acts on the resident stromal cells and ISCs to promote epithelial repair in experimental colitis and that Wnt-ß-Catenin signaling may be a potential target for colitis treatment.

A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF-EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Effects of Periplaneta americana extracts on the growth and proliferation of cutaneous interstitial cells in cutaneous-wound healing.

Cutaneous-wound healing requires a coordinated reaction of multiple cells, including interstitial cells. Impaired recovery of cutaneous wounds can lead to various adverse health outcomes. Kangfuxin (KFX), an extract obtained from Periplaneta americana, is beneficial in cutaneous-wound healing. In this study, we isolated dermal cells from suckling mice and established a mouse model of cutaneous injury to evaluate the therapeutic effects of KFX. Cell biology experiments indicated that treatment with KFX improved cell proliferation and migration and also repaired cutaneous wounds in the animal model. Activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway was the core molecular mechanism of KFX. Our study provides a theoretical and practical basis for the clinical application of KFX in cutaneous-wound healing.

Bavachin inhibits IL-4 expression by downregulating STAT6 phosphorylation and GATA-3 expression and ameliorates asthma inflammation in an animal model.

IL-4 plays a key role in many human diseases, including allergic asthma, autoimmunity, allergies, and cancer. Therefore, the investigation of small compounds that regulate IL-4 secretion is of great interest for fighting these diseases. Natural flavonoids are useful compounds reported to have therapeutic effects in diseases involving IL-4. This study aimed to investigate small compounds that inhibit the effect of IL-4 with the lowest cell toxicity. We found that Bavachin had the greatest ability to downregulate IL-4 in the spleen of T cells from 4get IL-4-GFP mice. To identify the underlying molecular mechanisms, we found that Bavachin could decrease the IL-4 levels by downregulating the level of Gata-3 expression and STAT6 phosphorylation. These findings reveal the potential use of Bavachin as a tool for selectively controlling diseases involving IL-4 and, more generally, STAT6-dependent responses.