Keigairengyoto's effects on the accumulation of F4/80-positive cells at the lesion site. (A) The ears injected with FITC-conjugated S. aureus were cut off 2, 6, and 24 h later and subjected to immunofluorescence staining for F4/80. Representative images of F4/80-positive cells are shown at 2 h after the injection. Arrows and areas surround by white dotted lines indicate F4/80-positive cells and clumps of bacteria, respectively. Yellow bars indicate 50 μm. (B) F4/80-positive cells were counted as the number of positive cells per unit area around the clump of bacteria or abscess in the ears at 2, 6, and 24 h after the injection. Yellow bars indicate 50 μm. N = 7 or 8. *: P < 0.05; **: P < 0.01 (Tukey-Kramer test). 

Keigairengyoto's effects on the accumulation of F4/80-positive cells at the lesion site. (A) The ears injected with FITC-conjugated S. aureus were cut off 2, 6, and 24 h later and subjected to immunofluorescence staining for F4/80. Representative images of F4/80-positive cells are shown at 2 h after the injection. Arrows and areas surround by white dotted lines indicate F4/80-positive cells and clumps of bacteria, respectively. Yellow bars indicate 50 μm. (B) F4/80-positive cells were counted as the number of positive cells per unit area around the clump of bacteria or abscess in the ears at 2, 6, and 24 h after the injection. Yellow bars indicate 50 μm. N = 7 or 8. *: P < 0.05; **: P < 0.01 (Tukey-Kramer test). 

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Prompt elimination of pathogens including bacteria and dead cells prevents the expansion of secondary and prolonged inflammations and tissue damage. Keigairengyoto (KRT) is a traditional Japanese medicine prescribed for dermatoses such as purulent inflammations. Our aim is to clarify the actions of KRT in bacterial clearance and to examine the cell...

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... [29] According to a different report, flavonoid glycosides influenced the immune response by boosting macrophage cells' phagocytic activity during the infection phase. [30] The internalization of P. aeruginosa depends heavily on the increase in macrophage phagocytosis activity. As a means of eradicating pathogens, controlling the inflammatory response, preventing the overproduction of the inflammatory response, and averting negative effects, the internalization process of bacteria is crucial. ...
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Thermal burns produce tissue damage, which eliminates the protective role of tissue. Due to the extensive tissue damage from severe burns, an overactive immune response occurs. Furthermore, this raises the possibility of getting sepsis, a condition in which a bacterial infection spreads throughout the body rather than only in the area of the injury or localized infection. To determine the compounds of Ajwa dates have the potential as an anti-inflammatory and antibacterial agent in infectious thermal burns. The research method used the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Various references were collected from the online database Google Scholar and PubMed including reports, journals, and all references mostly published no more than the past 10 years. This systematic review revealed 16 research articles that were pertinent. Polyphenolic substances such as flavonoids, glycosides, and phenolic acids were found in ajwa dates. Specified polyphenol chemicals have the ability to interact with one or more immune cell receptors, moving intracellular messages and influencing the host's immunological response. Ajwa dates' polyphenol acts as an anti-inflammatory agent in severe burns by inhibiting the expression of pathogen-associated molecular pattern receptors, controlling transcription factors, and changing the phenotype of macrophage cells, among other ways. The bacterial activity and immune response regulation of Ajwa dates, on the other hand, also serve as an antibacterial agent directly. The polyphenol compounds in Ajwa dates have the potential to operate as an anti-inflammatory and antibacterial agent in infected thermal burns.
... KRT includes large amounts of various types of medicinal ingredients such as alkaloids, flavonoids, and triterpenoids, which exhibit antimicrobial, anti-inflammatory, antilipogenesis, and antioxidant effects [8][9][10][11][12][13][14]. It was recently reported that KRT suppressed development of bacteria-induced dermatitis in an experimental model, through enhancing bacterial clearance in innate immune cells [15]. However, no published clinical study has shown the efficacy of KRT. ...
... KRT exhibited the strongest effect in an antimicrobial assay using P. acnes among 10 kinds of kampo drugs that were evaluated [22]. According to a recent report, KRT drastically reduced the number of inoculated bacteria in a mouse cutaneous infection model using live Staphylococcus aureus [15]. It is unclear whether the antibacterial effect of KRT could be involved in clinical effects to ameliorate acne, but KRT may have the potential to affect an antibacterial spectrum in a manner that is different from the antibiotics used in the present study and/or to enhance the effects of the other drugs combined with KRT therapy. ...
... A recent report showed that KRT's flavonoids, genistein and liquiritigenin, function as agonists for the nuclear estrogen receptor in macrophages, leading to enhancement of bacterial clearance by macrophages in both in vivo and in vitro assays [13]. KRT is reported to suppress bacteriainduced skin edema and enhanced bacteria phagocytosis by resident macrophages in a model of abscess-forming dermatitis induced by heat-killed Staphylococcus aureus [15]. Some flavonoids such as genistein and liquiritigenin were thought to contribute to the adjuvant effects of KRT. ...
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Several traditional Japanese medicines including Keigairengyoto (KRT) are used to treat acne vulgaris, but there is no robust evidence of their effectiveness. In this study, we examined the effectiveness and safety of KRT in treating acne vulgaris. An open-label, randomized, parallel control group comparison was conducted with a conventional treatment group (adapalene and topical antibiotics; control group) and a KRT group (control treatment plus KRT). The test drugs were administered for 12 weeks to patients (15 to 64 years, outpatient) with inflammatory acne on their face, and the amount of acne at 2, 4, 8, and 12 weeks was measured. Sixty-four patients were enrolled; 29 patients in each group were included in the analysis. Twenty-eight patients in the control group and 24 patients in the KRT group were included in the efficacy analysis. The number of inflammatory skin rashes at 4 and 8 weeks in the KRT group was significantly decreased compared with the control group. There was no significant difference between the two groups in noninflammatory eruptions and general rashes. There were no serious adverse events in both groups. KRT may be a useful agent in patients with inflammatory acne in combination with conventional treatments. This trial is registered with UMIN 000014831 .
... The three-dimensional high-performance liquid chromatograph (3D-HPLC) profile of KRT provided by Tsumura & Co., shows that KRT includes various compounds, especially flavonoids, triterpenoids, and isoquinoline alkaloids (Figure 1). We previously reported that oral administration of KRT suppressed microbe-induced dermatosis in mice and enhanced bacterial clearance through modulation of the immune system [18]. It is likely that bioactive flavonoids derived from KRT mediate the adjuvanticity against microbes. ...
... The threedimensional high-performance liquid chromatograph (3D-HPLC) profile of KRT provided by Tsumura & Co., shows that KRT includes various compounds, especially flavonoids, triterpenoids, and isoquinoline alkaloids ( Figure 1). We previously reported that oral administration of KRT suppressed microbe-induced dermatosis in mice and enhanced bacterial clearance through modulation of the immune system [18]. It is likely that bioactive flavonoids derived from KRT mediate the adjuvanticity against microbes. ...
... Second, KRT may exert antimicrobial effects by enhancing immune system activity, such as macrophage phagocytosis. We previously examined the effects of KRT in a pseudo-infection model using heat-killed S. aureus in order to eliminate the possibility of direct bactericidal effects and observed augmented bacteria clearance as evidenced by biochemical, histological, and immunological methods [18]. Moreover, macrophage activation was promoted by treatment with phytoestrogen flavonoids [23][24][25][26][27][28][29]. ...
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Recent studies have demonstrated that flavonoid glucuronides can be deconjugated to the active form aglycone by β-glucuronidase-expressing macrophages. Keigairengyoto (KRT) is a flavonoid-rich traditional Japanese medicine reported to enhance bacterial clearance through immune modulation. Our aims are to examine the pharmacokinetics of KRT flavonoids and to identify active flavonoids contributing to the adjuvant effects of KRT. KRT was evaluated at pharmacokinetic analysis to quantify absorbed flavonoids, and cutaneous infection assay induced in mice by inoculation of Staphylococcus aureus. Preventive or therapeutic KRT administration reduced the number of bacteria in the infection site as well as macroscopic and microscopic lesion scores with efficacies similar to antibiotics. Pharmacokinetic study revealed low plasma levels of flavonoid aglycones after KRT administration; however, plasma concentrations were enhanced markedly by β-glucuronidase treatment, with baicalein the most abundant (Cmax, 1.32 µg/mL). In random screening assays, flavonoids such as bacalein, genistein, and apigenin enhanced bacteria phagocytosis by macrophages. Glucuronide bacalin was converted to aglycone baicalein by incubation with living macrophages, macrophage lysate, or skin homogenate. Taken together, the adjuvant effect of KRT may be due to some blood-absorbed flavonoids which enhance macrophage functions in host defense. Flavonoid-rich KRT may be a beneficial treatment for infectious skin inflammation.