Corrigendum: The Extracts of Morinda officinalis and Its Hairy Roots Attenuate Dextran Sodium Sulfate-Induced Chronic Ulcerative Colitis in Mice by Regulating Inflammation and Lymphocyte Apoptosis.

[This corrects the article DOI: 10.3389/fimmu.2017.00905.].

Recombinant ling zhi-8 enhances Tregs function to restore glycemic control in streptozocin-induced diabetic rats.

OBJECTIVES: To explore the effect of recombinant LZ-8 (rLZ-8) on streptozocin (STZ)-induced diabetic rats and further illustrate its underlying mechanism. METHODS: Rats were intraperitoneally injected with single-dose STZ 50 mg/kg for induction of type 1 diabetes (T1D), and then, the diabetic rats were treated with rLZ-8 for 3 months. The clinical symptoms, fasting blood glucose, insulin, cytokines, histopathology, flow cytometry and immunofluorescence were used to evaluate the therapeutic effect and underlying mechanism of rLZ-8 on alleviating diabetes mellitus (DM). KEY FINDINGS: Treatment with rLZ-8 obviously alleviated the clinical symptoms of T1D and dose-dependently reduced the levels of blood glucose, blood lipid and haemoglobin A1c (HbA1c) in diabetic rat model. Meanwhile, rLZ-8 markedly increased insulin secretion and protected against STZ-induced pancreatic tissue injury. Additionally, rLZ-8 dramatically inhibited the levels of TNF-α and IL-1ß, and obviously increased the level of IL-10 in serum and pancreas. Further investigation indicated that rLZ-8 treatment significantly increased the number of regulatory T cells (Tregs) and up-regulated the expression of Foxp3 to restore balance between anti-inflammatory and inflammatory cytokines. CONCLUSIONS: These data suggest that rLZ-8 can antagonize STZ-induced T1D, and its mechanism may be related to inhibit inflammation and enhance Tregs generation.

A recombinant protein rLZ-8, originally extracted from Ganoderma lucidum, ameliorates OVA-induced lung inflammation by regulating Th17/Treg balance.

Asthma is one of the most common chronic and inflammatory respiratory diseases, which is estimated to affect 1-10% of the population in different regions across the world. Previous studies have shown that recombinant Ling-Zhi 8 (rLZ-8), an immunoregulatory protein originally extracted from Ganoderma lucidum, plays multiple roles in regulating murine immune cells, including T cells. Here, we examined whether rLZ-8 would ameliorate pulmonary inflammation in a model of asthma-like mice. We found that rLZ-8 significantly inhibited the lung inflammation and reduced infiltration of inflammatory cells, including dendritic cells and eosinophils, in OVA-induced asthmatic mice. It also deceased IL-17A level but increased IL-10 level in bronchoalveolar lavage fluid (BALF) while reducing RORγt mRNA expression and enhancing Foxp3 mRNA level in the lung tissue. Flow cytometry studies demonstrated that rLZ-8 remarkably down-regulated Th17 cells but upregulated Foxp3+ regulatory T (Treg) cells, rather than influencing Th1 versus Th2 cells. Experiments in vitro also showed that rLZ-8 suppressed murine CD3+ T cell proliferation and reduced the frequency of Th17 cells while promoting the differentiation of CD4+ Foxp3+ Tregs. Moreover, rIL-8 similarly altered human Th17/Treg generation or their balance in vitro. Finally, we found that rLZ-8 suppressed signaling pathways of both STAT3 and NF-κB (P100/P52) in murine lung tissue as well as cultured T cells. Thus, we have demonstrated that rLZ-8 attenuates pulmonary inflammation through regulating the balance of Th17/Treg cells in OVA-induced asthmatic mice and that rLZ-8 may be a potential therapeutic agent for the treatment of asthma in clinic.

The Extracts of Morinda officinalis and Its Hairy Roots Attenuate Dextran Sodium Sulfate-Induced Chronic Ulcerative Colitis in Mice by Regulating Inflammation and Lymphocyte Apoptosis.

Morinda officinalis is beneficial for the treatment of inflammatory bowel disease (IBD). The hairy root with higher genetic and biochemical stability cultured from M. officinalis might have similar effects to treat IBD. In this study, the main chemical composition of the root extracts of M. officinalis (MORE) native plant and the hairy root extract of M. officinalis (MOHRE) was compared by quantitative HPLC. The difference of their therapeutic effects and potential mechanism was evaluated using 3% dextran sodium sulfate-induced chronic colitis in mice and T lymphocytes in vitro. The results found that MOHRE possesses many specific peaks unobserved in the chromatogram of native plant. The content of iridoids in the MORE (3.10%) and MOHRE (3.01%) is somewhat similar but quite different for their anthraquinones's content (0.14 and 0.66%, respectively). Despite all this, treatment with both MORE and MOHRE significantly attenuated the symptoms of colitis, including diarrhea, body weight loss, colon shortening, histological damage, and decreased inflammatory cytokine levels. In addition, they dose-dependently increased the apoptosis of T lymphocyte in vivo and in vitro. And, the differences for treatment effects on ulcerative colitis (UC) between them both in this study were mostly insignificant. The results demonstrated that the effects of MORE and MOHRE for the treatment of UC are similar, although there are a few difference on their chemical composition, indicating the hairy root cultured from M. officinalis might be able to replace its native plant on treatment of UC. The successful derivation of a sustainable hairy root culture provides a model system to study the synthetic pathways for bioactive metabolites, which will make the use of bioreactors to largely produce traditional medicine become reality.