Studies on Shokyo, Kanzo, and Keihi in Kakkonto Medicine on Prostaglandin E₂ Production in Lipopolysaccharide-Treated Human Gingival Fibroblasts

Abstract

We previously demonstrated that a kampo medicine, kakkonto, decreases lipopolysaccharide- (LPS-) induced prostaglandin E2 (PGE2) production by human gingival fibroblasts. In this study, we examined the herbs constituting kakkonto that exhibit this effect. Shokyo strongly and concentration dependently and kanzo and keihi moderately decreased LPS-induced PGE2 production. Shokyo did not alter cyclooxygenase-2 (COX-2) activity, cytosolic phospholipase A2 (cPLA2), annexin 1 and COX-2 expression, and LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Kanzo inhibited COX-2 activity but increased annexin 1 and COX-2 expression and did not alter LPS-induced ERK phosphorylation. Keihi inhibited COX-2 activity and LPS-induced ERK phosphorylation but slightly increased COX-2 expression and did not alter cPLA2 and annexin 1 expression. These results suggest that the mechanism of shokyo is through the inhibition of cPLA2 activity, and that of kanzo and keihi is through the inhibition of COX-2 activity and indirect inhibition of cPLA2 activity. Therefore, it is possible that shokyo and kakkonto are clinically useful for the improvement of inflammatory responses.

Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

“…Shokyo is the powdered rhizome of ginger (Zingiber offinale Roscoe), whereas, kankyo is the steamed and powdered rhizome of ginger. Many reports demonstrated that ginger has anti-inflammatory effects in human (Afzal et al, 2001;Lakhan et al, 2015), animal (Thomson et al, 2002;Aimbire et al, 2007;El-Abhar et al, 2008), and in vitro models (Ara and Sogawa, 2016;Podlogar and Verspohl, 2012). Shokyo contains gingerols such as 6-, 8-, and 10-gingerols.…”

A Novel Peptide from <i>Vespa ducalis</i> Induces Apoptosis in Osteosarcoma Cells by Activating the p38 MAPK and JNK Signaling Pathways

“…After treatment with peptide for 12 h, the cells were collected and washed twice with iced PBS. Then, cells were resuspended in 150 µL of extraction lysis buffer 21) for 30 min at 4°C. Thereafter, the supernatant was collected and frozen after discarding cell debris.…”

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“…Previously, we reported that several kampo medicines, shosaikoto (TJ-9) (Ara et al, 2008b), orento (TJ-120) (Ara et al, 2010), hangeshashinto (TJ-14) (Nakazono et al, 2010), and kakkonto (TJ-1) (Kitamura et al, 2014), suppress lipopolysaccharide (LPS)-induced PGE 2 production by human gingival fibroblasts (HGFs). Moreover, we found that shokyo, kanzo, and keihi, which are herbs contained in kakkonto, reduce PGE 2 production (Ara and Sogawa, 2016). These results suggested that these kampo medicines and herbs have anti-inflammatory effects in periodontal disease.…”

“…In our previous studies, we reported the importance of HGFs in the study of periodontal disease (Kamemoto et al, 2009;Ara et al, 2010;Nakazono et al, 2010;Ara et al, 2012;Kitamura et al, 2014;Ara and Sogawa, 2016), because HGFs are the most prominent cells in periodontal tissue. Moreover, LPS-treated HGFs produce inflammatory chemical mediators, such as PGE 2 and inflammatory cytokines such as IL-6 and IL-8 (Sismey-Durrant and Hopps, 1991; Bartold and Haynes, 1991;Tamura et al, 1992).…”

“…Shokyo is the powdered rhizome of ginger (Zingiber offinale Roscoe), whereas, kankyo is the steamed and powdered rhizome of ginger. Many reports demonstrated that ginger has anti-inflammatory effects in human (Afzal et al, 2001;Lakhan et al, 2015), animal (Thomson et al, 2002Aimbire et al, 2007;El-Abhar et al, 2008), and in vitro models (Ara and Sogawa, 2016;Podlogar and Verspohl, 2012). Shokyo contains gingerols such as 6-, 8-, and 10-gingerols.…”