The effect of Hangeshashinto on Oral Mucositis Caused by Induction Chemotherapy in Patients with Head and Neck Cancer

Taira, Kenkichiro; Fujiwara, Kazunori; Fukuhara, Takahiro; Koyama, Satoshi; Takeuchi, Hiromi

doi:10.33160/yam.2020.08.007

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…In the no treatment control group, the animals were not treated with any ointment. To mimic clinical studies by mouthwashes with TJ-14 solution [ 16 – 21 ], 5% TJ-14 solution or water (200 μL) was applied using a syringe in the left cheek pouch twice per day from day 1 to day 12. Hence, in the groups treated with 12% HST oral ointment (50 μg) and 5% TJ-14 solution (200 μL), the same amount of HST extract (6 μg) was applied to the mucositis area, although the former was less frequent (once per day) that the later (twice per day) for the same period.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, several clinical studies showed that repetitive use of mouthwashes with 5% HST solution (as a medical product, TSUMURA Hangeshashinto Extract Granules, TJ-14) reduces the duration of COM in patients with gastric and colorectal cancers [ 16 – 18 ]. Similarly, mouthwashes with 2.5% or 6.25% TJ-14 solution improve the rate of chemoradiation completion and the nutritional status of patients with head and neck cancer [ 19 – 21 ]. However, these effects are insufficient to prevent COM because the treatment did not affect the incidence of COM, which was set as a primary endpoint, in these clinical studies.…”

Section: Introductionmentioning

confidence: 99%

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Preparation and pharmaceutical properties of Hangeshashinto oral ointment and its safety and efficacy in Syrian hamsters with 5-fluorouracil-induced oral mucositis

et al. 2022

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Chemotherapy-induced oral mucositis (COM) is a common adverse effect of cancer chemotherapy. Several clinical studies reported that repetitive use of mouthwashes containing 2.5–6.25% Hangeshashinto (HST), a Kampo formula, relieves COM, but the effect is insufficient. To solve this problem, we produced an oral ointment of 12% HST extract (considered quantitatively equivalent to 20% commercially available HST), which will increase the local concentrations of its active ingredients and prolong the contact time with COM. In this study, we evaluated the pharmaceutical properties (spreadability and stability) of HST oral ointment. In addition, its safety (oral mucosal irritation) and therapeutic effects on 5-fluorouracil-induced oral mucositis were evaluated in male Syrian hamsters. The HST ointment showed good spreadability and stability for more than 8 weeks at 4 °C. In the oral mucosal irritation test, topical application of HST ointment (0.2 g) three times per day for 14 days had no adverse effect on the oral mucosa of hamsters. In hamsters treated with 5-fluorouracil (60 mg/kg) twice, COM was induced by a submucosal injection of 5% acetic acid into the cheek pouch. When HST ointment (50 µg) was topically applied to the mucositis area once per day for 12 days, the area and macroscopic score of mucositis were significantly decreased, and the depth of the wound tended to be reduced compared with the lactose ointment-treated control animals. These findings suggest that HST oral ointment shows good properties in spreadability, stability, and safety, and elicits a therapeutic effect in an animal model of COM. Graphical abstract

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preparation and pharmaceutical properties of Hangeshashinto oral ointment and its safety and efficacy in Syrian hamsters with 5-fluorouracil-induced oral mucositis

et al. 2022

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“…The present study demonstrated that frozen Hangeshashinto treatment significantly (p<0.01) alleviated radiation-induced stomatitis (Figure 2A). Frozen Hangeshashinto suppressed the aggravation of radiationinduced stomatitis, possibly due to the anti-inflammation activity of Hangeshashinto (8,10,11) and vasoconstriction induced by cooling (1,15). Frozen Hangeshashinto significantly prolonged the expression time of oral mucositis by 41% (from 9.5 to 16.1 days) (Figure 2B), indicating that it delayed the onset of radiation stomatitis.…”

Section: Discussionmentioning

confidence: 91%

Efficacy of Cryotherapy and Hangeshashinto for Radiation-induced Oral Stomatitis: Preliminary Study

Kato

Sakagami

2023

In Vivo

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Background/Aim: Radiation-induced stomatitis is one of the main acute disorders in patients with head and neck cancer. Since its treatment is often delayed or discontinued, the control of perioperative oral function is necessary. It has been reported that Hangeshashinto (Japanese traditional herbal medicine) and cryotherapy (known as frozen therapy) alleviate oral stomatitis and the accompanying pain. In the present study, the combination effect of Hangeshashinto and cryotherapy on radiationinduced stomatitis in patients with head and neck cancers was investigated for the first time. Patients and Methods: Fifty patients with head and neck cancer were subjected to radiation therapy with concomitant administration of anticancer drugs. They were separated into two groups, matched according to age, stage of cancer progression, total radiation dose, and type of concomitant anticancer drugs. One group was orally administrated frozen Hangeshashinto, while another group was not. Oral mucosal damage was assessed by the grade classification CTCAE v4.0 of the National Cancer Institute of the United States (Japanese JCOG version). Duration time of radiation-induced stomatitis was determined by the appearance of grade 1 redness to its disappearance. Results: Frozen Hangeshashinto significantly alleviated, delayed the onset, and reduced the duration time of the radiation-induced stomatitis. Conclusion: Cryotherapy in combination withHangeshashinto can be used for the treatment of radiationinduced oral stomatitis.Head and neck cancer is one of the most common cancer types with an incidence of more than 5 million cases per year, approximately 90% of which are accounted by oral, pharyngeal, and laryngeal squamous cell carcinoma (SCC). As treatments, surgical resection, and radiation therapy, alone or combined, have been used over the past few decades (1, 2).Radiation therapy improves clinical, morphological, and functional outcomes in cancer patients. Currently, nearly 75% of head and neck cancer patients benefit from radiation therapy, regardless of getting primary or adjuvant therapy after surgical resection. In the early stages of cancer, radiation therapy can replace surgical resection (3-5). Cancer patients can be treated with chemoradiotherapy for locally advanced cancer or surgical resection followed by adjuvant radiation therapy (6). Therefore, it is important to complete the treatment of radiation therapy. Stomatitis caused by radiation therapy is one of the main acute disorders, and treatment is often delayed or discontinued (6). Since radiation-induced stomatitis is inevitable, it is important to control the perioperative oral function in cancer therapy (7). However, despite many approaches tried so far, it has been difficult to control oral function in most cases.Hangeshashinto is a traditional Japanese medicine composed of seven herbal crude extracts: pinelliae tuber, Scutellariae Radix, Glycyrrhizae Radix, Zizyphi fructus, Ginseng Radix, Zingiberis Processum Rhizoma, and Coptidis Rhizoma. Hangeshashinto has been rep...

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“…In recent years, we conducted a randomized double-blind placebo-controlled trial of hangeshashinto in 16 patients with head and neck cancer who developed oral mucositis due to chemical radiation therapy. The trial demonstrated that gargling with hangeshashinto shortened the healing time of oral mucositis and reduced the severity of mucositis grade [ 24 ]. In addition, a study involving 22 terminally ill cancer patients reported that hangeshashinto improved oral dryness and may prevent the development of oral mucositis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Hangeshashinto Inhibits Porphyromonas gingivalis Pathogen-Associated Molecular Patterns-Mediated IL-6 and IL-8 Production through Toll-Like Receptors in CAL27 Cells

Oh,

Makita,

Masuno

et al. 2024

Evidence-Based Complementary and Alternative Medicine

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While previous reports have established the anti-inflammatory effects of hangeshashinto, the intracellular signal transduction pathways involved have yet to be elucidated. We aim to employ an experimental system using oral cancer cells to assess the impact of hangeshashinto on intracellular signal transduction pathways in response to stimulation by Porphyromonas gingivalis pathogen-associated molecular patterns (PAMP). Hangeshashinto demonstrated the ability to inhibit the production of interleukin (IL)-6 and IL-8 induced by P. gingivalis PAMP. Furthermore, hangeshashinto suppressed the activation of the IL-6 promoter stimulated by PAMP. Hangeshashinto, like Toll-like receptor (TLR) signaling inhibitors (resatorvid and C29) and an immunosuppressant (dexamethasone), exhibited the ability to suppress TLR-mediated activation of the transcription factor nuclear factor-κB (NF-κB) in response to PAMP stimulation. This study suggests that the anti-inflammatory effects of hangeshashinto may be attributed to the inhibition of TLR signal transduction pathways including NF-κB activation, thereby suppressing NF-κB-dependent gene expression.

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The effect of Hangeshashinto on Oral Mucositis Caused by Induction Chemotherapy in Patients with Head and Neck Cancer

Cited by 6 publications

References 21 publications

Preparation and pharmaceutical properties of Hangeshashinto oral ointment and its safety and efficacy in Syrian hamsters with 5-fluorouracil-induced oral mucositis

Preparation and pharmaceutical properties of Hangeshashinto oral ointment and its safety and efficacy in Syrian hamsters with 5-fluorouracil-induced oral mucositis

Efficacy of Cryotherapy and Hangeshashinto for Radiation-induced Oral Stomatitis: Preliminary Study

Hangeshashinto Inhibits Porphyromonas gingivalis Pathogen-Associated Molecular Patterns-Mediated IL-6 and IL-8 Production through Toll-Like Receptors in CAL27 Cells

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