Objective. This study was designed to evaluate the clinical efficacy of combined traditional Chinese medicine (TCM) and conventional chemotherapy versus conventional chemotherapy in patients with stage II‐IIIA non‐small‐cell lung cancer (NSCLC) after radical surgery. Methods. A retrospective cohort study was conducted in patients with stage II‐IIIA NSCLC from Subei People′s Hospital and Yangzhou Traditional Chinese Medicine Hospital in Yangzhou City of Jiangsu Province from 2012 to 2016. Patients were divided into two groups: the TCM user group (patients receiving treatment with integrated TCM and conventional chemotherapy) and the non‐TCM user group (patients receiving conventional chemotherapy only). The two groups were compared for their median disease‐free survival (DFS) and median overall survival (OS). Results. A total of 67 patients with stage II‐IIIA NSCLC were enrolled between January 2012 and December 2016. The median DFS for the non‐TCM user group was 601 days (95% confidence interval [CI], 375.7‐826.3). The median DFS for TCM user group could not be calculated. However, log‐rank analysis showed that the median survival time in the TCM user group was significantly longer than that of the non‐TCM user group (P < 0.05). In addition, several significant risk factors were detected for predicting disease prognosis in patients with NSCLC, such as age, ECOG, lymphatic metastasis, and body mass index (BMI). For patients harboring these independent risk factors, the DFS of TCM user group was much longer than that of non‐TCM user group (P < 0.05). Conclusion. Adjuvant therapy with TCM may reduce the rate of tumor recurrence and metastasis and prolong DFS of patients with stage II‐IIIA NSCLC.

Introduction. Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence. In this study, we examined the effects of JTT on natural killer (NK) cell activity and metastasis in combined treatments with anti‐PD‐1 antibody in a mouse model of melanoma metastasis. Methods. C57BL/6 male mice were intravenously injected with B16 melanoma cells (B16 cell) and were given chow containing 3% JTT. In subsequent in vivo experiments, we assessed serum cytokine levels and tumor colony formation in the lungs. Additionally, we assessed NK cell activity in ex vivo experiments. Results. JTT significantly suppressed B16 cell metastasis, whereas injection of anti‐asialo‐GM1 antibody into mice abrogated the inhibitory actions of JTT. JTT significantly increased interleukin‐ (IL‐) 12 and interferon‐ (IFN‐) γ levels in serum and induced NK cell activity. It increased the inhibitory actions of the anti‐PD‐1 antibody on B16 cell metastasis. Discussion. These data suggest that JTT inhibits B16 cell metastasis by inducing NK cell activity. Additionally, combination therapy with JTT and anti‐PD‐1 antibody increased treatment response rates for B16 melanoma.

Substantial evidence suggests the effectiveness of plant-based medicine in stress-related diseases. Kamikihito (KKT), a Japanese traditional herbal medicine (Kampo), has been used for anemia, insomnia, and anxiety. Recent studies revealed its ameliorating effect on cognitive and memory dysfunction in several animal models. We, therefore, determined whether daily supplementation of KKT has an antidepressant-like effect on the stress-induced behavioral and neurological changes in rats. The effect of KKT against the stress-induced changes in anxiety- and depressive-like behaviors and hippocampal neurogenesis were determined using a rat model of chronic restraint stress (CRS). KKT was orally administered daily at 300 or 1000 mg/kg during 21 consecutive days of CRS (6 h/day). The effect of CRS and KKT on physiological parameters, including body weight gain, food/water consumptions, plasma corticosterone (CORT) levels, and percentage of adrenal gland weight to body weight, were firstly measured. Anxiety- and depressive-like behaviors in rats were assessed in the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Hippocampal neurogenesis was determined by immunohistochemistry. CRS for 21 days caused a significant decrease in body weight gain and increase in plasma CORT levels and percentage of adrenal gland weight to body weight, which were rescued by KKT treatment. KKT also suppressed the CRS-induced anxiety- and depressive-like behaviors and impairment of hippocampal neurogenesis. These results suggest that daily treatment of KKT has a protective effect against physiological, neurological, and behavioral changes in a rat model of depression.

Nitric oxide (NO) is known to play pivotal roles as one of the final effector molecules in the development of allergic diseases, including allergic rhinitis (AR). Although quercetin has been reported to attenuate the clinical conditions of AR, its influence on NO production is not well defined. The present study aimed to examine the influence of quercetin onin vitroNO production from nasal epithelial cells after interleukin‐ (IL‐) 4 stimulation. Human nasal epithelial cells (HNEpCs) at a concentration of 1 x 10⁵cells/ml were stimulated with 10.0 ng/ml of IL‐4 in the presence and absence of quercetin. After 48 hours, the culture supernatants were collected and assayed for NO (NO₂and NO₃) using the Griess method. The influences of quercetin on the transcription factor, STAT6, activation, and iNOS mRNA expression were also examined using ELISA and real‐time quantitative RT‐PCR, respectively. Addition of quercetin to cell cultures caused suppression of NO production from HNEpCs after IL‐4 stimulation. The minimum concentration of quercetin that caused significant suppression was 1.0 nM. Treatment of cells with quercetin at more than 1.0 nM suppressed STAT6 activation and iNOS mRNA expression induced by IL‐4 stimulation. The present results strongly suggested that quercetin favorably modified the clinical condition of AR through the suppression of NO production from nasal epithelial cells after IL‐4 stimulation.

Kamikihito (KKT) is a Kampo medicine that is prescribed in Japan for the treatment of anemia, insomnia and mental anxiety in Japan. However, its precise mechanism of action remains unclear. This study aimed to evaluate the possible antistress effect of KKT in rats with acute stress and the contribution of oxytocin to the process. Acute immobilization stress (AIS; for 90 min) was used to assess the effect of KKT on acute stress. Male Wistar rats were orally treated with KKT. Parameters of stress were evaluated, and concentrations of oxytocin in plasma and cerebrospinal fluid (CSF) were measured. AIS-induced defecation and fecal weight were significantly decreased because of treatment with KKT. The plasma levels of stress-related hormones following AIS were investigated. The pre-administration of KKT significantly increased adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) levels following AIS. Conversely, there was no significant change in the plasma oxytocin level. Microdialysis and hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) were used to monitor the oxytocin secretion in CSF. Oxytocin level increased during AIS following the treatment of KKT. At 30 min after AIS, the level remained higher than before AIS. Furthermore, using an open field test, the locomotion (exploratory behavior) immediately after AIS was examined. The total traveled distance decreased after AIS; however, the decrease was significantly inhibited by the treatment of KKT. However, the effect of KKT was obstructed by the pre-administration of the oxytocin receptor antagonist. These results suggest that KKT has antistress activity and increased oxytocin secretion may be a mechanism underlying this phenomenon.

Yokukansan (YKS), a traditional herbal (Kampo) medicine consisting of seven herbs, is effective in the treatment of pain disorders, such as headache, postherpetic neuralgia, fibromyalgia, and trigeminal neuralgia, and we have previously shown it to be effective against morphine analgesic tolerance in rats. It has been reported that orexin receptor antagonists prevent the development of morphine tolerance and that YKS inhibits the secretion of orexin A in the hypothalamus. This study examined whether the inhibition of the secretion of orexin A by YKS is one mechanism underlying its effect against morphine analgesic tolerance. Male Wistar rats were administered a subcutaneous injection of morphine hydrochloride (10 mg/kg/day) for 5 days. One group was preadministered YKS, starting 3 days before the morphine. The withdrawal latency following thermal stimulation was measured daily using a hot plate test. On day 5, the levels of orexin A in the plasma and the midbrain were measured, and the appearance of activated astrocytes in the midbrain was examined by immunofluorescence staining. The preadministration of YKS prevented the development of morphine tolerance. The repeated administration of morphine significantly increased the plasma and midbrain levels of orexin A and the activation of astrocytes. These increases were significantly inhibited by the preadministration of YKS. These results suggest that the preadministration of YKS attenuated the development of antinociceptive morphine tolerance and that the inhibition of orexin A secretion may be one mechanism underlying this phenomenon.