Ninjin-yoeito activates ghrelin-responsive and unresponsive NPY neurons in the arcuate nucleus and counteracts cisplatin-induced anorexia

Goswami, Chayon; Dezaki, Katsuya; Wang, Lei; Inui, Akio; Seino, Yutaka; Yada, Toshihiko

doi:10.1016/j.npep.2019.03.001

Cited by 34 publications

(26 citation statements)

References 34 publications

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“…The klotho mice (KL) and wild-type mice (WT) were fed with (+) or without (-) 0.5% JTT from 3.5 weeks of age until the mice were 7 weeks old. Consistent with our knowledge that Kampo medicine does not have a biological effect on a healthy recipient (Goswami et al, 2019; Shimada et al, 2008), the data for WT fed with and without JTT were essentially the same. Accordingly, the data for WT mice fed with JTT are not shown in the main text, although subsets are shown in the supplementary figures.…”

Section: Resultssupporting

confidence: 86%

Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese multi-herbal medicine

Okada

Oshima

Iwasaki

et al. 2020

Preprint

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Section: Resultssupporting

confidence: 86%

Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese multi-herbal medicine

Okada

Oshima

Iwasaki

et al. 2020

Preprint

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“…Ex vivo whole-cell patch-clamp recordings showed that ghrelin depolarized 40% of GFP-labeled arcuate NPY neurons in brain slices from 8–12 week-old male NPY-humanized Renilla reniformis green fluorescent protein transgenic mice ( 28 ). Ghrelin increased [Ca 2+ ] i in 59% of single ARC NPY neurons ( 9 ) and in 21–41% of single ARC neurons ( 12 , 25 ) in 5–7 week-old male mice. The present study demonstrated that ghrelin-unresponsive neurons occur substantially among NPY neurons of ARC in 5–7 week-old male mice fed normal chow.…”

Section: Discussionmentioning

confidence: 98%

“…We previously reported that Ninjin'yoeito counteracted the anorexigenic and body weight-lowering effects of cisplatin, a chemo-therapy drug, in mice ( 9 ). In parallel, Ninjin'yoeito increased cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in single neurons isolated from ARC, and the majority (79%) of the Ninjin'yoeito-responsive neurons were immunoreactive (IR) to neuropeptide Y (NPY).…”

Section: Introductionmentioning

confidence: 99%

Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus

et al. 2020

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Appetite loss or anorexia substantially deteriorates quality of life in various diseases, and stand upstream of frailty. Neuropeptide Y (NPY) in the hypothalamic arcuate nucleus (ARC) and ghrelin released from stomach are potent inducers of appetite. We previously reported that Ninjin'yoeito, a Japanese kampo medicine comprising twelve herbs, restores food intake, and body weight in cisplatin-treated anorectic mice. Furthermore, Ninjin'yoeito increased cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in not only ghrelin-responsive but ghrelin-unresponsive NPY neurons in ARC. The cellular lineage/differentiation of ghrelin-unresponsive neuron is less defined but might alter along with aging and diet. This study examined the occupancy of ghrelin-unresponsive neurons among ARC NPY neurons in adult mice fed normal chow, and explored the mechanisms underlying Ninjin'yoeito-induced [Ca 2+ ] i increases in ghrelin-unresponsive vs. ghrelin-responsive NPY neurons. Single ARC neurons were subjected to [Ca 2+ ] i measurement and subsequent immunostaining for NPY. Ghrelin failed to increase [Ca 2+ ] i in 42% of ARC NPY neurons. Ninjin'yoeito (10 μg/ml)-induced increases in [Ca 2+ ] i were abolished in Ca 2+ free condition in ghrelin-responsive and ghrelin-unresponsive ARC NPY neurons. Ninjin'yoeito-induced [Ca 2+ ] i increases were inhibited by N-type Ca 2+ channel blocker ω-conotoxin in the majority (17 of 20), while by L-type Ca 2+ channel blocker nitrendipine in the minority (2 of 23), of ghrelin-responsive neurons. In contrast, Ninjin'yoeito-induced [Ca 2+ ] i increases were inhibited by nitrendipine in the majority (14 of 17), while by ω-conotoxin in the minority (8 of 24), of ghrelin-unresponsive neurons. These results indicate that ghrelin-unresponsive neurons occur substantially among NPY neurons of ARC in adult mice fed normal chow. Ninjin'yoeito preferentially target N-type and L-type Ca 2+ channels in the majority of ghrelin-responsive and ghrelin-unresponsive neurons, respectively, to increase [Ca 2+ ] i . We suggest ARC N- and L-type Ca 2+ channels as potential targets for activating, respectively, ghrelin-responsive, and unresponsive NPY neurons to treat anorexia.

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“…In a basic pharmacological study using a bleomycin-induced pulmonary fibrosis model, ninjin'yoeito was reported to have suppressed decreases in food intake and body weight, atrophy of the gastrocnemius, and expression of inflammatory cytokines in the lungs ( 8 ). Regarding the mechanism by which it improves loss of appetite, activation of ghrelin-responsive, and unresponsive neuropeptide Y neurons in the arcuate nucleus of the hypothalamus ( 9 ) and actions mediated by dopamine D 2 receptors ( 10 ) have been reported.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Efficacy of Ninjin'yoeito Treatment for Idiopathic Pulmonary Fibrosis

2021

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Ninjin'yoeito, a Kampo prescription, was administered to two patients with idiopathic pulmonary fibrosis (IPF) over a period of 12 weeks to improve loss of appetite and lassitude. In Case 1, improvements were observed in appetite, lassitude, and breathlessness, as well as increases or increasing tendencies in body weight, blood albumin level, and hemoglobin (Hb) level. Case 2 showed no changes in appetite but improvements in lassitude and no deterioration of breathlessness. His body weight and his blood albumin and Hb levels increased or showed increasing trends. In both cases, a trend for improvement of respiratory function was observed. In summary, ninjin'yoeito trended to improve the subjective symptoms and nutritional status of a patient with pulmonary fibrosis.

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Ninjin-yoeito activates ghrelin-responsive and unresponsive NPY neurons in the arcuate nucleus and counteracts cisplatin-induced anorexia

Cited by 34 publications

References 34 publications

Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese multi-herbal medicine

Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese multi-herbal medicine

Ninjin'yoeito Targets Distinct Ca2+ Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus

Case Report: Efficacy of Ninjin'yoeito Treatment for Idiopathic Pulmonary Fibrosis

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