Effect of Hangeshashinto on calprotectin expression in human oral epithelial cells

Hiroshima, Yuka; Bando, Mika; Inagaki, Yuji; Kido, Reiko; Kataoka, Masatoshi; Nagata, Toshihiko; Kido, Jun‐ichi

doi:10.1007/s10266-015-0196-3

Cited by 13 publications

(7 citation statements)

References 43 publications

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“…23 On the other hand, antibacterial peptide production involves 3,4-dihydroxybenzaldehyde, baicalin, and ginsenoside Rb1, which act on oral mucosal epithelial cells and are considered to protect them against bacterial infection by enhancing the production of the antimicrobial peptide calprotectin. 35 The present results revealed markedly lower numbers of bacteria in the TJ-14 group, suggesting antibacterial activity in the mucosa of anticancer drug-induced stomatitis. No significant differences were observed in body weight changes or food intake on Days 9 and 11 between the three groups.…”

Section: Discussionsupporting

confidence: 52%

<p>Effects of Topical Hangeshashinto (TJ-14) on Chemotherapy-Induced Oral Mucositis</p>

Ozawa¹,

Onda²,

Hayashi³

et al. 2020

CMAR

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Purpose: Hangeshashinto (TJ-14), a Kampo medicine comprising seven types of herbs, has been used in Japan to alleviate the side effects associated with anticancer drug treatments. However, the pharmacological effects of this medicine currently remain unclear. The present study aimed to demonstrate the efficacy of TJ-14 against anticancer drug-induced stomatitis, the pain associated with which may have a negative impact on mastication and swallowing. Methods: Mucositis was induced in Sprague-Dawley rats by cancer chemotherapy. Changes in body weight, stomatitis grades, histopathological scores, and oral bacterial counts were examined among TJ-14-treated, saline-treated, and Control (no treatment) rats. In vitro studies, including cell proliferation and wound healing assays, using epidermal keratinocyte and fibroblast cell lines were conducted. Results: The local application of TJ-14 exerted strong antibacterial effects and attenuated oral chemotherapy-induced stomatitis in rats. TJ-14 also increased the viability and invasion of epidermal keratinocytes and fibroblasts. Conclusion: The present results demonstrated the potential of TJ-14 to attenuate chemotherapy-induced stomatitis.

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Section: Discussionsupporting

confidence: 52%

<p>Effects of Topical Hangeshashinto (TJ-14) on Chemotherapy-Induced Oral Mucositis</p>

Ozawa¹,

Onda²,

Hayashi³

et al. 2020

CMAR

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“…HST thus constitutes a promising therapy, the efficacy of which has been demonstrated via a clinical study with a high evidence level 22,44 . Basic research findings have indicated that HST enhances OUM healing through multiple pharmacological actions (e.g., anti-oxidant, anti-inflammatory, anti-bacterial, and analgesic activities) [23][24][25] . With regard to anti-inflammatory effects, we have shown that various ingredients in HST decrease the interleukin 1β-induced prostaglandin E2 (PGE2) production www.nature.com/scientificreports www.nature.com/scientificreports/ in HOKs with multi-targeting effects, such as dual suppression of cyclooxygenase-2 expression and PGE2 metabolic activity 26 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, double-blind, placebo-controlled, randomized studies have reported that repetitive mouth-washing with HST was effective for the improvement of chemotherapy-induced OUM in patients with colorectal or gastric cancer 22 . Several in vitro studies also reported that HST induced antibacterial and antioxidant effects, suggesting that these effects were involved in the mechanisms of HST with respect to the improvement of OUM [23][24][25] . Moreover, our previous studies in vitro and in vivo revealed additional mechanisms of HST in OUM, including both anti-inflammatory and analgesic effects [26][27][28] .…”

mentioning

confidence: 92%

The Japanese herbal medicine Hangeshashinto enhances oral keratinocyte migration to facilitate healing of chemotherapy-induced oral ulcerative mucositis

Miyano¹,

Eto

Hitomi

et al. 2020

Sci Rep

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chemotherapy often induces oral ulcerative mucositis (oUM) in patients with cancer, characterized by severe painful inflammation. Mouth-washing with the Japanese herbal medicine hangeshashinto (HST) ameliorates chemotherapy-induced OUM in patients with colorectal cancer. Previously, we demonstrated that HST decreased interleukin 1β-induced prostaglandin E2 production in human oral keratinocytes (HOKs) and OUM-induced mechanical or spontaneous pain in rats. However, HST effects on tissue repair functions in HOKs remain unclear. Here, we examined the effects of HST on scratchinduced wound healing in vitro and in vivo. In vitro, HSt enhanced wound healing mainly through scratch-induced HOK migration. Screening of the seven constituent medicinal herbs and their major components revealed that Scutellaria root, processed ginger, and Glycyrrhiza components mainly induced the scratch-induced HOK migration. Pharmacokinetic analyses indicated that the active ingredient concentrations in rat plasma following oral HST administration were below the effective doses for HOK migration, suggesting direct effects of HST in OUM. Mitogen-activated protein kinase and C-X-C chemokine receptor 4 inhibitors significantly suppressed HST-induced HOK migration. Moreover, HST enhanced tissue repair in our OUM rat model. Thus, HST likely enhanced OUM tissue repair through oral keratinocyte migration upon MAPK and CXCR4 activation and may be useful in patients with cancer-associated OUM. Patients with cancer receiving chemotherapy, radiotherapy, hematopoietic stem cell transplant, and terminal care often present with severe oral ulcerative mucositis (OUM), which evokes painful inflammation and limits fundamental life behaviours such as 'eating, drinking, and talking' 1-15. In addition, OUM increases the risk of systemic infection via opportunistic microorganisms, which may lead to the extension of hospitalization 5,15-19. OUM also often induces patients with cancer to discontinue/modify their therapy regimen, which adversely affects patient prognosis 13,15,16,20. Therefore, the effective management of OUM is indispensable for improving both the quality of life and prognosis for the patient 15 .

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“…However, the level of increase in Z induced by NYT or citrus unshiu peel [NYT (% of control): 433.3 ± 19.5, citrus unshiu peel: 207.4 ± 28.0] was considerably smaller than that caused by OXA (% of control: 9,781.5 ± 252.9). Theoretically, kampo medicine comprises several medical herbal crude drugs; thus, it is considered to exert multiple actions (11,(44)(45)(46)(47)(48)(49)(50)(51). Furthermore, each action of kampo medicine is considered milder than that of a drug composed of only one component, such as western drugs.…”

Section: Discussionmentioning

confidence: 99%

Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors

Miyano¹,

Ohshima

Suzuki

et al. 2020

Front. Nutr.

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Cancer cachexia is highly prevalent in patients with progressive cancer and is characterized by decreased food consumption, and body weight. Japanese herbal medicine Ninjinyoeito (NYT), composed of 12 herbal crude drugs, is prescribed in Asian countries to improve several symptoms such as anorexia and fatigue, which are commonly observed in patients with cancer cachexia. However, the action mechanisms of NYT in improving anorexia or fatigue in patients with cancer are not clear. Therefore, in the present study, we examined the effects of NYT on the activities of several G-protein-coupled receptors (GPCRs), which activate hyperphagia signaling in the central nervous system, using an in vitro assay with the CellKey TM system, which detects the activation of GPCRs as a change in intracellular impedance ( Z). NYT increased the Z of human embryonic kidney 293 (HEK293) cells expressing orexin 1 receptor (OX1R) and those expressing neuropeptide Y1 receptor (NPY1R) in a dose-dependent manner. On the contrary, NYT did not significantly increase the Z of HEK293A cells expressing growth hormone secretagogue receptor (GHSR) and those expressing NPY5R. The selective OX1R antagonist SB674042 significantly decreased the NYT-induced increase in Z in OX1R-expressing cells. Contrarily, the selective NPY1R antagonist BIBO3340 failed to inhibit the NPY-induced increase in Z in NPY1R-expressing cells. Additionally, we prepared modified NYT excluding each one of the 12 herbal crude drugs in NYT and investigated the effects on the activity of OX1R. Among the 12 modified NYT formulations, the one without citrus unshiu peel failed to activate OX1R. A screening of each of the 12 herbal crude drugs showed that citrus unshiu peel significantly activated OX1R, which was significantly suppressed by SB674042. These finding suggest that NYT and citrus unshiu peel could increase food intake via activation of orexigenic OX1R-expressing neurons in the hypothalamus. This study provides scientific evidence to support the potential of NYT for cancer patients with anorexia.

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Effect of Hangeshashinto on calprotectin expression in human oral epithelial cells

Cited by 13 publications

References 43 publications

<p>Effects of Topical Hangeshashinto (TJ-14) on Chemotherapy-Induced Oral Mucositis</p>

<p>Effects of Topical Hangeshashinto (TJ-14) on Chemotherapy-Induced Oral Mucositis</p>

The Japanese herbal medicine Hangeshashinto enhances oral keratinocyte migration to facilitate healing of chemotherapy-induced oral ulcerative mucositis

Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors

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