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

Miyano, Kanako; Ohshima, Kaori; Suzuki, Nozomi; Furuya, Saho; Yoshida, Yuki; Nonaka, Miki; Higami, Yoshikazu; Yoshizawa, Kazumi; Fujii, H.; Uezono, Yasuhito

doi:10.3389/fnut.2020.00005

Cited by 18 publications

(13 citation statements)

References 62 publications

(83 reference statements)

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“…The antioxidant effect of NYT on the brain is mediated by its constituents, including cinnamon bark, polygala root, and citrus unshiu peel [ 69 ]. A recent report showed that cinnamaldehyde (present in cinnamon bark) has potent neuroprotective effects against oxidative stress and apoptosis induced by glutamate in the rat pheochromocytoma PC12 cell line (a neuron model) [ 70 ]. In addition, Sedighi et al reported that an extract of cinnamon bark prepared with ethanol could protect heart tissue against ischemia/reperfusion injury through an antioxidant mechanism [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Effects of Ninjin’yoeito on Physical Frailty in Mice

Otsuka

Fukumaru

Tani

et al. 2022

IJMS

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Physical frailty is an aging-related clinical syndrome involving decreases in body weight, mobility, activity, and walking speed that occurs in individuals with sarcopenia and is accelerated by increased oxidative stress. Ninjin’yoeito, a traditional Japanese Kampo medicine, is used for treating conditions, including anemia and physical weakness. Here, we investigated whether ninjin’yoeito could improve physical frailty by controlling oxidative stress in the senescence-accelerated mouse prone 8 (SAMP8) model. First, SAMP8 mice were divided into two groups, ninjin’yoeito treated and untreated, with the former consuming a diet containing 3% ninjin’yoeito from 3 months of age. At 7 months of age, body weight, motor function, locomotor activity, and mean walking speed were measured. Subsequently, mice were euthanized and measured for muscle weight, 8-hydroxy-2′-deoxyguanosine levels in muscle and brain, and cleaved caspase-3 expression in brain. The results showed reductions in weight, locomotor function, locomotion, and average walking speed in the untreated group, which were significantly improved by ninjin’yoeito. Furthermore, 8-hydroxy-2′-deoxyguanosine levels were reduced in muscle and brain from ninjin’yoeito-treated mice, compared with the levels in untreated mice; cleaved caspase-3 expression was similarly reduced in brain from the treated mice, indicating reduced apoptosis. Our findings suggest that ninjin’yoeito inhibits sarcopenia-based physical frailty through its antioxidant effects.

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Section: Discussionmentioning

confidence: 99%

Analysis of the Effects of Ninjin’yoeito on Physical Frailty in Mice

Otsuka

Fukumaru

Tani

et al. 2022

IJMS

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“…A review of RCTs of NYT demonstrated the usefulness of NYT in the treatment of cancer and related conditions ( Takayama et al, 2019 ). Other studies have reported increased food intake via the activation of orexigenic OX1R-expressing neurons in the hypothalamus ( Miyano et al, 2020 ), maintenance of nutritional status in patients with wasting conditions ( Sasatani et al, 2020 ), and the activation of both ghrelin-responsive and ghrelin-unresponsive neuropeptide Y pathways for the treatment of anorectic conditions, which are associated with cancer or frailty ( Goswami et al, 2019 ). These studies support the potential of NYT in cancer patients with anorexia, malnutrition, and mental disorders.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Prolonged Anorexia With Nausea Caused by Immune Checkpoint Inhibitors for Malignant Melanoma Treated Using Kampo Medicines Bukuryoingohangekobokuto and Ninjin’yoeito

2022

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Immune checkpoint inhibitors (ICIs) are indicated for several cancers, including malignant melanoma. Anorexia and nausea resulting in malnutrition are side effects of ICIs. In such cases, conventional drugs are used for symptom relief, but the symptoms may persist. We report a case of advanced malignant melanoma with prolonged anorexia and nausea, which occurred after nivolumab administration, and was successfully treated using Kampo medicines. A 75-year-old man with nasal bleeding visited our hospital. A nasal scope revealed an obstructive tumor in the left nasal concha. Tissue biopsy showed malignant melanoma, and computed tomography showed metastasis to the liver and bone. Thus, the patient was diagnosed with stage IV malignant melanoma. He received radiotherapy (30 Gy) and nivolumab with ipilimumab four times, followed by nivolumab administration alone. During the administration of nivolumab, he complained of severe anorexia and nausea, with a numeric rating scale (no symptoms, 0; severe symptoms, 10) score of 10. He could not consume food because of these symptoms, even after nivolumab administration was discontinued. His blood pressure was 92/59 mmHg, his performance status (PS; no fatigue, 0; bedridden or disabled, 4) was 4, and his body weight gradually decreased from 60 to 39 kg in a month. The patient showed malnutrition and dehydration and experienced anxiety and depression. Nivolumab was terminated, and conventional symptomatic drugs were prescribed, but the symptoms persisted. We then prescribed 9.0 g/day of ninjin’yoeito (TJ-108, Tsumura and Co.) to allow recovery from anorexia and subsequently added bukuryoingohangekobokuto (TJ-116, Tsumura and Co.) to treat the persistent nausea. After treatment with these two Kampo medicines, the patient’s appetite gradually recovered. Along with the recovery of nutritional status, his PS improved to 0, his anxiety and depressive state improved, and his body weight increased to 60 kg. The patient remained in good condition without cancer recurrence. The patient’s clinical course shows the usefulness of Kampo medicine as supportive care for symptom relief and maintenance of nutritional and mental status during cancer treatment.

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“…The mechanisms of action of ninjin'yoeito in chemotherapy-induced anorexia include the activation of neuropeptide Y neurons 56 and orexin-1 receptor. 57 A clinical study is now underway to validate the efficacy of ninjin'yoeito in preventing the progression of malnutrition and cachexia in patients with advanced or recurrent colorectal cancer. 58…”

Section: Kampo Medicines For Cancer Cachexiamentioning

confidence: 99%