Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model

Abstract

Background Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicine based on ancient Chinese medicine, has been used for treatment of infectious purulent diseases in Japan. In this study, we investigated the protective and therapeutic efficacy of Hainosankyuto against S. pyogenes-skin infection.Methodology/Principal FindingsA broth microdilution method revealed that Hainosankyuto did not show a direct anti-bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survival rate and reduced the size of local skin lesions compared with mice fed PBS. Although we did not find the significant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significant smaller after Hainosankyuto administration compared with mice fed PBS. No difference was observed in the anti-bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed that the survival rate of S. pyogenes using the blood from Hainosankyuto -treated mice was lower than that using the blood from untreated mice. We also found increased levels of IL-12, IFN-γ and a decreased level of TNF-α in the serum of S. pyogenes-infected mice treated with Hainosankyuto. Mouse peritoneal macrophage from Hainosankyuto-treated mice had significant phagocytic activity and increased mRNA levels of IL-12, IFN-γ and decreased mRNA level of TNF-α compared with control macrophage.Conclusions/SignificanceHainosankyuto increased survival rate after S. pyogenes infection and up-regulated both blood bactericidal activity and macrophage phagocytic activity through modulation of inflammatory cytokines. Our data also suggest Hainosankyuto may be useful for the treatment of S. pyogenes infection more prophylactically than therapeutically.

Effect of shin'iseihaito on lung colonization of pneumococcus in murine model

“…Each blood sample was centrifuged, and the resultant serum was stored at −80°C until the day of assay (Minami et al, 2011).…”

“…We determined the levels of serum and BAL cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IgA during the course of infection in pneumococcus-infected mice treated with SSHT as described earlier (Minami et al, 2011). TNF-α, IL-1β, IL-6 (Biolengend Inc. CA.…”

“…Blood bactericidal assays were performed as an evaluation of whole blood bactericidal effect with some modification (Minami et al, 2011). In the SSHT-treated group, mice were force-fed SSHT (0.1 mL/10 g body weight (bw)) on 4 days before collection.…”

“…In such studies, several infectious murine experiments revealed the mechanism of traditional Kampo medicine (Minami et al, 2011;Dan et al, 2013). However, the effects of shin'iseihaito on ameliorating the pneumococcus-infected model have not been previously reported.…”

Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models

“…Prior studies have shown that topical applications of herbal extract prevent acute irritant murine contact dermatitis [1] and that oral administration of Cordyceps sinensis extract prevents cutaneous damages from Streptococcus pyogenes infection in an air pouch murine infection model [2]. Likewise, oral administration of Hainosankyuto reduces skin lesion size and increased survival rate in a Streptococcus pyogenes infected murine model [3]. Similarly, oral administration of the water extract of Astragalus membranaceus inhibits the development of atopic dermatitis-like lesions in a murine model [4].…”