Effects of shinbuto and ninjinto on prostaglandin E₂production in lipopolysaccharide-treated human gingival fibroblasts

Abstract

Previously, we revealed that several kampo medicines used for patients with excess and/or medium patterns (kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), and orento (TJ-120)) reduced prostaglandin (PG)E2 levels using LPS-treated human gingival fibroblasts (HGFs). Recently, we examined other kampo medicines used for patients with the deficiency pattern [bakumondoto (TJ-29), shinbuto (TJ-30), ninjinto (TJ-32), and hochuekkito (TJ-41)] and the herbs comprising shinbuto and ninjinto using the same experimental model. Shinbuto and ninjinto concentration-dependently reduced LPS-induced PGE2 production by HGFs, whereas hochuekkito weakly reduced and bakumondoto did not reduce PGE2 production. Shinbuto and ninjinto did not alter cyclooxygenase (COX) activity or the expression of molecules involved in the arachidonic acid cascade. Therefore, we next examined which herbs compromising shinbuto and ninjinto reduce LPS-induced PGE2 production. Among these herbs, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly and concentration-dependently decreased LPS-induced PGE2 production. However, both shokyo and kankyo increased the expression of cytosolic phospholipase (cPL)A2 but did not affect annexin1 or COX-2 expression. These results suggest that shokyo and kankyo suppress cPLA2 activity. We demonstrated that kampo medicines suppress inflammatory responses in patients with the deficiency pattern, and in those with excess or medium patterns. Moreover, kampo medicines that contain shokyo or kankyo are considered to be effective for the treatment of inflammatory diseases.

The Biological Efficacy of Natural Products against Acute and Chronic Inflammatory Diseases in the Oral Region

“…Examples of herbal medicine which have been reported to reduce PGE2 production in in vitro and/or animal models are shown in Table 1. In particular, we reported that kakkonto (TJ-1), shosaikoto (TJ-9), hangeshashinto (TJ-14), shinbuto (TJ-30), ninjinto (TJ-32), and orento (TJ-120) reduced LPS-induced PGE2 production using HGFs [36,37,38,39,40]. Other groups have also demonstrated that several herbal medicines reduced PGE2 production using human periodontal ligament cells [41], human monocytes [42], mouse macrophage RAW264.7 cells [43,44], human oral keratinocytes [7], and animals [45,46,47,48].…”

“…Shinbuto (TJ-30) and ninjinto (TJ-32) enhanced annexin1 expression, but did not alter ERK phosphorylation and COX activity [39]. However, the contribution of enhancement of annexin1 expression is considered to be small because shokyo, which is the main herb in shinbuto to reduce PGE2 production, did not affect annexin1 expression.…”

“…The ingredients in the formula of herbal medicines that were used are shown in Table 2, Table 3, Table 4, Table 5, Table 6 and Table 7. In our experiments at the herb level, shokyo ( Zingiberis Rhizoma ), kankyo ( Zingiberis Processum Rhizoma ), kanzo ( Glycyrrhizae Radix ), and keihi ( Cinnamomi Cortex ) reduced PGE2 production (Figure 3 and Figure 4) [29,39]. We summarized major ingredients in herbs and their mechanism against arachidonic acid cascade in Table 8.…”

Peer Review #1 of "Effects of shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) on prostaglandin E2 production in lipopolysaccharide-treated mouse macrophage RAW264.7 cells (v0.1)"

“…Manuscript to be reviewed Rhizoma) reduced PGE 2 production (Ara and Sogawa, 2017). In particular, shokyo and kankyo strongly reduced LPS-induced PGE production.…”

“…Japanese traditional medicines (kampo medicines) are used for the treatment of several inflammatory diseases. We focused on the inflammatory effects of these kampo medicines, and found that lipopolysaccharide (LPS)-induced PGE 2 production by human gingival fibroblasts (HGFs) were reduced by several kampo medicines, including shosaikoto (TJ-9) (Ara et al, 2008), orento (TJ-120) (Ara et al, 2010), hangeshashinto (TJ-14) (Nakazono et al, 2010), kakkonto (TJ-1) (Kitamura et al, 2014), shinbuto , and ninjinto (TJ-32) (Ara and Sogawa, 2017). Moreover, among the herbs contained in kakkonto, shokyo (Zingiberis Rhizoma), kanzo (Glycyrrhizae Radix), keihi (Cinnamomi Cortex) (Ara and Sogawa, 2016), and kankyo (Zingiberis Processum PeerJ reviewing PDF | (2019:04:36484:2:0:CHECK 19 Aug 2019)…”