Multitargeted Effects of Hangeshashinto for Treatment of Chemotherapy-Induced Oral Mucositis on Inducible Prostaglandin E2 Production in Human Oral Keratinocytes

Kono, Toru; Kaneko, Atsushi; Matsumoto, Chinami; Miyagi, Chika; Ohbuchi, Katsuya; Mizuhara, Yasuharu; Miyano, Kanako; Uezono, Yasuhito

doi:10.1177/1534735413520035

Cited by 66 publications

(77 citation statements)

References 43 publications

(71 reference statements)

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“…A randomized placebo-controlled trial showed that prophylactic systemic administration of indomethacin, a COX-2 inhibitor, significantly lowered the severity and delayed the onset of RIOM (165). In addition, PG E1 and E2 showed improvement in OM induced by RT and CT in few studies; however, their application is still controversial (166–172). …”

Section: Symptomatic Treatment Of Riommentioning

confidence: 99%

Radiation-Induced Oral Mucositis

2017

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Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients. In the United Sates, its economic cost was estimated to reach 17,000.00 USD per patient with head and neck cancers. This review will discuss RIOM definition, epidemiology, impact and side effects, pathogenesis, scoring scales, diagnosis, differential diagnosis, prevention, and treatment.

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Section: Symptomatic Treatment Of Riommentioning

confidence: 99%

Radiation-Induced Oral Mucositis

2017

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“…There have been some reports of the favorable effects of Hangeshashinto on chemotherapy and chemoradiotherapy-induced stomatitis (11)(12)(13)(14). As regards EGFR-TKIinduced stomatitis, to the best of our knowledge, there have no reports evaluating oral care in the management of stomatitis to date.…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the management of stomatitis, oral care with a mouthwash and gargle liquid containing Azunol was administered to patients treated with afatinib, a second-generation epidermal growth factor receptor (EGFR)-TKI. With regard to Hangeshashinto, a traditional herbal (Kampo) medicine, there have been previous reports of its favorable effects on chemotherapy-and chemoradiotherapy-induced stomatitis (11)(12)(13)(14). Patients who developed stomatitis were treated with a mouthwash containing Hangeshashinto, which has been found to reduce CPT-11induced gastrointestinal tract complications (15,16).…”

Section: Introductionmentioning

confidence: 99%

Management of afatinib-induced stomatitis

Kato

Saito

Matsuda

et al. 2017

Molecular and Clinical Oncology

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Abstract. Severe stomatitis may lead to the need to interrupt or discontinue cancer therapy and, thus, may affect control of the primary disease. Stomatitis may also increase the risk of local and systemic infection and significantly affects the quality of life and the cost of care. The present study was conducted to evaluate the efficacy of two traditional herbal medicines in controlling treatment-induced stomatitis in a small cohort of lung cancer patients treated with afatinib. All patients who were treated with afatinib for epidermal growth factor receptor (EGFR) mutated nonsmallcell lung cancer (NSCLC) between January, 2015 and March, 2016, were included in this study. During the study period, a total of 14 NSCLC patients were treated with afatinib, an EGFR-tyrosine kinase inhibitor (TKI). Two patients already had stomatitis at the time of initiation of afatinib therapy; among the remaining 12 NSCLC patients, 2 (16.7%) developed stomatitis. All the lesions in the 4 patients who developed stomatitis were completely alleviated after 2 weeks of therapy with Aznol mouthwash, a chamomile extract with anti-inflammatory effects, and Hangeshashinto, a traditional herbal (Kampo) medicine. Afatinib therapy was re-initiated, but none of the patients developed stomatitis thereafter. To the best of our knowledge, this is the first report evaluating oral care and management of stomatitis. This type of care and treatment may reduce the incidence of complications associated with EGFR-TKI therapy.

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“…16) As the concentration of baicalin, berberine, baicalein, wogonin, 6-gingerol and 6-shogaol exceeded 0.1 µM in 300 µg/mL HST. 16) We therefore used these six ingredients and examined their effects at concentrations equal (20 µM baicalin, 3.4 µM berberin, 1 µM baicalein, 0.6 µM wogonin, 0.4 µM 6-gingerol and 0.18 µM 6-shogaol) to 300 µg/mL HST 16) on 5-FU-induced upregulation of CXCL1 gene expression. This was significantly attenuated by 1 µM baicalein or 0.4 µM 6-gingerol (Fig.…”

Section: Resultsmentioning

confidence: 99%

Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5-Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea Development

Sakai

Tabata

Kimura

et al. 2017

Biological & Pharmaceutical Bulletin

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5-Fluorouracil (5-FU)is widely used as an anti cancer drug and is known to cause severe diarrhea. Recently we suggested that levels of chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophil recruitment in the colonic mucosa were drastically increased by the 5-FU administration in mice. Hange-shashin-to (HST) is prescribed in Japan for treat gastritis, stomatitis, and inflammatory diarrhea. We therefore examined the effects of HST and its active ingredients on 5-FU-induced CXCL1 upregulation in cultured colon tissue, and also examined the effects of HST on 5-FU-induced diarrhea development in the mouse. The distal colon isolated from the mouse was incubated with 5-FU and HST. Mice were given 5-FU (50 mg/kg, intraperitoneally (i.p.)) daily for four days. HST (300 mg/kg, per os ( p.o.)) was administered 30 min before mice received 5-FU. mRNA levels of CXCL1 in the colon were examined using quantitative RT-PCR. 5-FU enhanced CXCL1 mRNA in the colon but the effect by 5-FU was markedly suppressed by application of HST and its active ingredients, baicalein and 6-gingerol. Nuclear factor kappa B (NF-κB) was activated by 5-FU treatment in cultured colon tissue, which was also suppressed by HST and the combination of baicalein and 6-gingerol. Furthermore, HST reduced 5-FU-induced diarrhea development. Under such experimental condition, CXCL1 gene, protein levels of neutrophil elastase and myeloperoxidase upregulation induced by 5-FU in the colon was attenuated by HST. These findings suggest that HST, especially baicalein and 6-gingerol, prevent the development of neutrophil recruitment and diarrhea by the inhibition of NF-κB activity.

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Multitargeted Effects of Hangeshashinto for Treatment of Chemotherapy-Induced Oral Mucositis on Inducible Prostaglandin E2 Production in Human Oral Keratinocytes

Cited by 66 publications

References 43 publications

Radiation-Induced Oral Mucositis

Radiation-Induced Oral Mucositis

Management of afatinib-induced stomatitis

Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5-Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea Development

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