Ulcer-healing effects of jumihaidokuto extract in a mouse model of methicillin-resistant Staphylococcus aureus causing skin infection

Aim: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogenic bacterium that causes severe skin diseases with ulceration. Since MRSA are not susceptible to multiple antibiotics, novel therapeutic agents are desired. Jumihaidokuto, a combination of 10 crude drugs, is a Japanese traditional Kampo medicine that is used for the treatment of skin diseases. In this study, we investigated the effects of jumihaidokuto extract (JHT) on MRSA-infected mice. Methods: Mice infected subcutaneously with MRSA FPR3757 were administered JHT orally to analyze mouse survival, the condition of the mouse skin ulcer area, and transforming growth factor (TGF)-beta levels in the ulcer tissue. To evaluate the role of crude drug components, modified JHTs were prepared by removing one crude drug component at a time from the formula and the same experiment was conducted. Results: JHT treatment significantly increased the survival rate. Ulcerated areas on the skin of MRSA-infected mice were observed to be significantly reduced in size following JHT treatment. Furthermore, MRSA was not detected at the site of the ulcer in the JHT-treated group. Additionally, TGF-beta levels decreased in the mouse skin ulcer tissues on treatment with JHT. All the crude drug components in JHT were found to partially contribute to the survival rate and healing of skin ulcers. Among the 10 crude drugs, Bupleurum root, cherry bark, Aralia rhizome, ginger, and Schizonepeta spike exhibited higher contribution than the other crude drugs. Conclusion: Our findings indicate the efficacy of JHT in promoting the healing of MRSA-induced murine skin ulcers.