Anemoside B4 ameliorates experimental autoimmune encephalomyelitis in mice by modulating inflammatory responses and the gut microbiota.

BACKGROUND: Anemoside B4 (AB4) is a representative component of Pulsatilla decoction that is used in traditional Chinese medicine for treating inflammatory conditions. It is not known whether AB4 has beneficial effects on multiple sclerosis (MS). METHODS: In the present study, we examined the preventative and therapeutic effects of AB4, and the possible mechanism by which it protects female mice against experimental autoimmune encephalomyelitis (EAE). RESULTS: Preventative treatment with AB4 (given orally at 100 and 200 mg/kg for 18 days) reduced the clinical severity of EAE significantly (from 3.6 ± 1.3 to 1.8 ± 1.5 and 1.6 ± 0.6, respectively), and inhibited demyelination and inflammatory infiltration of the spinal cord. In the therapeutic protocol, oral administration of 200 mg/kg AB4 for 21 days after initiation of EAE significantly alleviated disease severity (from 2.6 ± 1.3 to 0.9 ± 0.6) and was as effective as the clinically used drug fingolimod (0.3 ± 0.6). Furthermore, both doses of AB4 significantly inhibited mRNA expression of TNF-α, IL-6, and IL-17, and STAT3 activation, in the spinal cord; and the ex vivo and iv vitro AB4 treatment markedly inhibited secretion of the three cytokines from lymphocytes of EAE mice upon in vitro restimulation. In addition, AB4 reversed the changes in the composition of the intestinal microbiome observed in EAE mice. CONCLUSION: We reveal for the first time that AB4 protects against EAE by modulating inflammatory responses and the gut microbiota, demonstrating that AB4 may have potential as a therapeutic agent for treating MS in humans.

Infection against infection: parasite antagonism against parasites, viruses and bacteria.

BACKGROUND: Infectious diseases encompass a large spectrum of diseases that threaten human health, and coinfection is of particular importance because pathogen species can interact within the host. Currently, the antagonistic relationship between different pathogens during concurrent coinfections is defined as one in which one pathogen either manages to inhibit the invasion, development and reproduction of the other pathogen or biologically modulates the vector density. In this review, we provide an overview of the phenomenon and mechanisms of antagonism of coinfecting pathogens involving parasites. MAIN BODY: This review summarizes the antagonistic interaction between parasites and parasites, parasites and viruses, and parasites and bacteria. At present, relatively clear mechanisms explaining polyparasitism include apparent competition, exploitation competition, interference competition, biological control of intermediate hosts or vectors and suppressive effect on transmission. In particular, immunomodulation, including the suppression of dendritic cell (DC) responses, activation of basophils and mononuclear macrophages and adjuvant effects of the complement system, is described in detail. CONCLUSIONS: In this review, we summarize antagonistic concurrent infections involving parasites and provide a functional framework for in-depth studies of the underlying mechanisms of coinfection with different microorganisms, which will hasten the development of promising antimicrobial alternatives, such as novel antibacterial vaccines or biological methods of controlling infectious diseases, thus relieving the overwhelming burden of ever-increasing antimicrobial resistance.