Abstract
Hochuekkito (HET), Juzentaihoto (JTT), and Ninjin'yoeito (NYT) have been used as Hozai, a group of traditional Japanese herbal medicines, to treat physically and mentally weak cancer patients. Their compositions are quite different, and Japanese pharmaceutical companies have been using different types or quantities of herbs for formulations with the same name. Here, we compared the immunological differences between HET, JTT, and NYT with respect to the induced T cell subsets and cytokines. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and treated with 0 (control), 25, 50, 100, 200, or 400 μg/mL HET, JTT, or NYT (manufactured by Tsumura [TJ], Kracie [KR], and Kotaro [KO]). PBMC proliferation, CD4+ T cell, CD8+ T cell, and regulatory T cell (Treg) proportions and interleukin (IL) concentrations (IL-6, IL-10, IL-17A, interferon-γ, tumor necrosis factor-α, and transforming growth factor (TGF)-β) secreted by PBMCs were measured using Cell Counting Kit-8 or flow cytometry bead analysis. PBMC proliferation and CD4+ T cell percentages were similar in the HET, JTT, NYT, and control groups; however, the percentage of CD8+ T cells tended to increase after treatments. Tregs were suppressed by HET, JTT, and NYT, and TJ-JTT significantly decreased Treg numbers (compared with control). The concentrations of all cytokines except TGF-β were increased in a concentration-dependent manner (p < 0.05); particularly, KR-HET induced IL-6 secretion (compared with the control, TJ-HET, and KO-HET; 37-, 7-, and 17-fold, respectively; p < 0.05). The TGF-β concentration was decreased in a concentration-dependent manner by HET, JTT, and NYT (compared with the control). These results suggest that, compared with TJ-HET and KO-HET, KR-HET should be administered with caution. Although HET, JTT, and NYT belong to the same Hozai group and have the same names among companies, their differing effects on immune activity must be considered and they must be administered with caution.
Highlights
Hozai, a group of Japanese traditional herbal medicines (Kampo), has been used to treat patients with fatigue, including patients with cancer who are physically and mentally weakened [1, 2]
We aimed to investigate the immunological differences in human peripheral blood mononuclear cells (PBMCs) treated with HET, JTT, and NYT manufactured by different pharmaceutical companies to provide evidence for their appropriate use in patients
400 μg/mL Kracie Pharma Ltd. (KR)-JTT and KO-JTT significantly decreased Peripheral blood mononuclear cells (PBMCs) proliferation compared with the control (∗p 0.0231 and ∗∗p 0.0052, respectively; Figure 1(b)), there were no significant differences among groups treated with different concentrations of Hozai from TJ, KR, and KO (Figure 1(b))
Summary
A group of Japanese traditional herbal medicines (Kampo), has been used to treat patients with fatigue, including patients with cancer who are physically and mentally weakened [1, 2]. Hochuekkito (HET), Juzentaihoto (JTT), and Ninjin’yoeito (NYT) are representative of Hozai and are marketed by several companies in Japan; their formulations contain different types and amounts of herbs, they have been given the same name by different companies (Table 1). Mori et al [4] reported that HET inhibits influenza virus infection by enhancing host immune responses in mice. HET has been shown to reduce cancer-related fatigue [5] and prevent chemically induced cancer [6]. JTT improves the function of natural killer cells and suppresses the immune inhibitory system, Evidence-Based Complementary and Alternative Medicine Volume (g) TJ(a) HET KR(b) KO(c) JTT KR(d) KO(e) TJ(f ) NYT KR(g) KO(h)
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