The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema

Isago, Hideaki; Mitani, Akihisa; Kohno, Shiho; Nagoshi, Saki; Ishimori, Taro; Saito, Minako; Tamiya, Hiroyuki; Miyashita, Naoya; Ishii, Takashi; Matsuzaki, Hirotaka; Yatomi, Yutaka; Nagase, Takahide; Jo, Taisuke

doi:10.1248/bpb.b20-00556

Cited by 9 publications

(11 citation statements)

References 22 publications

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“…Clinical studies have also demonstrated that HET has beneficial effects on fatigue, nutritional status, chronic wounds, and quality of life in elderly patients with malnutrition (Satoh et al, 2005;Hamada et al, 2018;Akita et al, 2019). Its clinical efficacy has also been supported by studies using animal models (Park et al, 2017;Cai and Yang, 2019;Isago et al, 2021). Previously, we demonstrated that HET enhances gluconeogenesis and thermogenesis by promoting amino acid utility, which is related to the activation of hepatic autophagy and mitophagy, in aged mice with excessively restricted amount of daily food intake as a model of malnutrition (Nahata et al, 2021).…”

Section: Introductionmentioning

confidence: 96%

Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition

et al. 2022

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Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a food restricted (FR) mouse, we aimed to evaluate the effect of aging on locomotor activity and liver metabolic function. Further, we also investigated the involvement of hepatic mitochondria in liver metabolic function during aging, as well as the therapeutic benefit of the traditional Japanese medicine, hochuekkito (HET). Our findings indicated that following food restriction provided as 30% of ad libitum intake for 5 days, the locomotor activity was lower in 23–26-month-old (aged) mice than in 9-week-old (young) mice. Further, compared with young mice, aged mice exhibited significant decreases in the levels of metabolites related to the urea cycle, mitochondrial function, and anti-oxidative stress. The livers of the aged mice also showed a greater decrease in mitochondrial DNA copy number than young mice. Furthermore, the gene expression levels of sirtuin 1 (SIRT1) and mitochondrial biogenesis-related regulators were attenuated in aged mice. However, these changes were partially restored by HET treatment, which also improved locomotor activity, and combined treatment with alanine resulted in more significant effects in this regard. Therefore, our findings suggested that the decrease in locomotor activity in aged FR mice was associated with a decline in the metabolic function of hepatic mitochondria via decreased SIRT1 expression, which was restored by HET treatment. This implies that enhancing the metabolic function of liver mitochondria can contribute to alleviating energy deficiency in the elderly.

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Section: Introductionmentioning

confidence: 96%

Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition

et al. 2022

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“… 12 In mice having intestinal mucositis, the TNF‐ α, and IL‐1β also reduced after HET treatment. 13 Furthermore, HET downregulated the expression of TNF‐α in lung tissue, 35 the expression of IL‐1β, IL‐6, and IFN‐γ in the hippocampus in chronic fatigue syndrome mice, 36 and the expression of IFN‐ γ in bleomycin‐induced lung injury mice. 22 These earlier studies revealed that HET treatment suppressed the production of these inflammatory cytokines from the macrophages and T‐lymphocyte in several inflammation conditions.…”

Section: Discussionmentioning

confidence: 99%

“…22 These earlier studies revealed that HET treatment suppressed the production of these inflammatory cytokines from the macrophages and T-lymphocyte in several inflammation conditions. 22,35,37 In aging mouse ovaries, the NLRP3 inflammasome is activated in macrophages and lymphocytes, leading to an increase in pro-inflammatory cytokines including IL-6, TNFα, IL-1β, and IFNγ regardless of the ovulation process. [3][4][5] Thus, in addition to the suppression of inflammaging in ovaries, similar actions of HET to other organs might decline In conclusion, this is the first work identifying the impact of traditional Japanese herbal medicine, HET, on female aging infertility.…”

Section: Ilmentioning

confidence: 99%

Effects of Hochuekkito, a traditional Japanese medicine (Kampo), on reproduction of aging female mice

Sato

Kawagoe

et al. 2021

Reprod Medicine & Biology

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Purpose To determine the potentials of Hochuekkito (HET) treatment for aging infertility. Methods Mice at 36 weeks of age were fed without (control, n = 40) or with low (100 mg/kg/day, n = 24) and high (1000 mg/kg/day, n = 38) doses of HET for 12 weeks. Aging animals at 48 weeks of age were used for in vitro fertilization‐embryo transfer (IVF‐ET), and their ovaries were subjected to histological and quantitative inflammation analyses. Results HET administration decreased transcript levels of ovarian inflammatory markers, interleukin 6 (IL‐6), IL‐1β, tumor necrosis factor (TNF)‐α, and interferon‐gamma (IFN‐γ) but suppressed ovulation rates and the number of ovulated oocytes in aging mice. Furthermore, HET treatment decreased the rates of oocytes maturation and fertilization and the cumulus‐cell expression of TNF‐α‐induced protein 6 and epidermal growth factor receptor. After IVF‐ET, no improvement of declined live offspring rate by aging was achieved by HET administration, although there were no adverse effects on embryo development and implantation as well as gross morphology and bodyweight of pups. Conclusion Present study indicated HET treatment interfered with ovulation and fertilization in aging mice without affecting ovarian follicle development. No improvement on the age‐associated decline of live offspring rate and follicle development was achieved after HET treatment.

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“…Inflammatory cytokines have also been reported to decrease dopaminergic function [ 25 ]. The anti-inflammatory effect of TJ-41 may improve dopaminergic function [ 26 , 27 ]. Further studies are needed to clarify the mechanism by which TJ-41 improves apathy symptoms in patients with COPD.…”

Section: Discussionmentioning

confidence: 99%

Hochuekkito Combined with Pulmonary Rehabilitation in Apathetic Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Pilot Trial

Hamada

Sekikawa

Okusaki³

et al. 2022

JCM

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The main treatment goals for chronic obstructive pulmonary disease (COPD) are the reduction of its symptoms and future risks. The addition of the traditional herbal medicine Hochuekkito (TJ-41) treatment to pulmonary rehabilitation (PR) has been reported to improve dyspnea and health-related quality of life (HRQOL) in patients with COPD. However, the reason for this improvement is not sufficiently understood. The purpose of the present study was to investigate whether the addition of TJ-41 treatment to PR improves symptoms of apathy, dyspnea, and HRQOL and increases physical activity among apathetic patients with COPD. Apathetic patients with COPD were randomly assigned to receive low-intensity exercise with (TJ-41 group) or without (control group) TJ-41 treatment for 12 weeks. A total of 29.9% of COPD patients had apathetic symptoms without severe depression. After the 12-week treatment, Apathy Scale, Patient Health Questionnaire-9, visual analog scale for dyspnea, and COPD assessment test energy scores decreased significantly in the TJ-41 group (p < 0.05), but not in the control group. Additionally, the total number of steps taken was significantly higher in the TJ-41 group than in the control group. TJ-41 combined with PR may benefit apathetic patients with COPD with respect to apathy, dyspnea, HRQOL, and physical activity, but larger randomized placebo-controlled trials are required to validate the findings because of the small sample size and lack of placebo controls in this study.

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The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema

Cited by 9 publications

References 22 publications

Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition

Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition

Effects of Hochuekkito, a traditional Japanese medicine (Kampo), on reproduction of aging female mice

Hochuekkito Combined with Pulmonary Rehabilitation in Apathetic Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Pilot Trial

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