38 results on '"Masataka Sunagawa"'
Search Results
2. Behavioral and neurological improvement by <scp> Cydonia oblonga </scp> fruit extract in chronic immobilization stress rats
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Mana Tsukada, Fatma Zahra Sakhri, Yusuke Ohashi, Tadashi Hisamitsu, Zahia Kabouche, Naoki Adachi, Sakina Zerizer, Hideshi Ikemoto, and Masataka Sunagawa
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Male ,medicine.medical_specialty ,Doublecortin Protein ,Hippocampus ,Hippocampal formation ,Open field ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Stress, Physiological ,Internal medicine ,medicine ,Animals ,Chronic stress ,Rats, Wistar ,Rosaceae ,Pharmacology ,0303 health sciences ,Plant Extracts ,business.industry ,Dentate gyrus ,030302 biochemistry & molecular biology ,Neurogenesis ,medicine.disease ,Rats ,Endocrinology ,Fruit ,030220 oncology & carcinogenesis ,Chronic Disease ,business ,Behavioural despair test - Abstract
It is known that chronic stress is a contributing factor to several physical and mental diseases. In this study, we examined the effect of hydroethanolic extract of Cydonia oblonga fruit (HECO, 300 mg/kg) in chronically immobilized rats on physiological and behavioral parameters by the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST) and on neurological alterations by analysis of the hippocampal neurogenesis. A daily 6 hr exposure to chronic immobilization stress (CIS) for 21 consecutive days induced anxiety- and depressive-like behaviors in rats' concomitant with decreased weight gain and increased plasma corticosterone (CORT) levels, rats also showed atrophy in the CA3 subregion of the hippocampus and a decreased number of Ki67 and DCX positive cells in the dentate gyrus (DG). Treatment with HECO successfully suppressed the physiological and behavioral markers of the CIS and prevents the structural abnormality and the impaired cell proliferation in the hippocampus. Moreover, the daily administration of HECO improved the mood function in normal rats. Taking together, our findings demonstrate, for the first time, the anti-depressive effect of C. oblonga fruit by enhancing the hippocampal neurogenesis in the rat model of depression.
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- 2020
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3. Analgesic Effect of Boiogito, a Japanese Traditional Kampo Medicine, on Post-Traumatic Knee Osteoarthritis through Inhibition of ERK1/2 Phosphorylation in the Dorsal Horn of the Spinal Cord
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Masataka Sunagawa, Naoki Adachi, Takayuki Okumo, Midori Tanaka, Kanako Yusa, Taro Kimura, Yusuke Kunieda, Koji Kanzaki, and Hideshi Ikemoto
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MAPK/ERK pathway ,Technology ,medicine.drug_class ,QH301-705.5 ,Kampo ,QC1-999 ,Analgesic ,Osteoarthritis ,Pharmacology ,kampo ,destabilization of the medial meniscus (DMM) ,medicine ,General Materials Science ,pain ,Biology (General) ,Instrumentation ,QD1-999 ,Fluid Flow and Transfer Processes ,business.industry ,Process Chemistry and Technology ,Physics ,General Engineering ,boiogito ,Protein kinase inhibitor ,Spinal cord ,medicine.disease ,Engineering (General). Civil engineering (General) ,Computer Science Applications ,Blot ,Chemistry ,osteoarthritis ,ERK ,medicine.anatomical_structure ,Phosphorylation ,TA1-2040 ,business - Abstract
Boiogito (BO), a Japanese traditional herbal medicine, has been proven to be clinically effective against knee osteoarthritis (KOA)-associated pain. However, the therapeutic mechanism of BO remains unclear. Thus, we investigated the analgesic mechanism of BO using a rat KOA model. KOA was induced by destabilization of the medial meniscus (DMM). Rats were allocated into the following four groups: control, sham, DMM, and DMM + BO groups. Rotarod test was performed to evaluate the pain-related locomotive dysfunction. Expression of phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) in the spinal dorsal horn was examined using immunofluorescence staining and Western blotting on days 1 and 28 after DMM surgery. A mitogen-activated protein kinase inhibitor, U0126, was intrathecally injected and rotarod test and Western blotting were performed. The rotarod test revealed hampered locomotive function in the DMM group, which was significantly improved upon BO administration. The number of pERK1/2-positive cells was increased in the DMM group, whereas it was significantly decreased in the DMM + BO group. U0126 significantly inhibited ERK1/2 phosphorylation and increased walking time in the rotarod test, suggesting that the DMM-related pain was associated with ERK1/2 phosphorylation in the spinal dorsal horn. In conclusion, BO administration improved the pain-related locomotive dysfunction by suppressing ERK1/2 phosphorylation.
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- 2021
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4. Influences of Lavender Essential Oil Inhalation on Stress Responses during Short-Duration Sleep Cycles: A Pilot Study
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Takayuki Okumo, Yosuke Sato, Yoshiki Tsunokawa, Takuji Izuno, Mana Tsukada, Tatsuki Inoue, Tadashi Hisamitsu, Masataka Sunagawa, and Wakako Yogi
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Saliva ,Sympathetic nervous system ,endocrine system ,Leadership and Management ,Lavender ,chromogranin A ,Health Informatics ,cortisol ,Article ,03 medical and health sciences ,0302 clinical medicine ,Health Information Management ,aromatherapy ,medicine ,lavender essential oil ,030212 general & internal medicine ,Inhalation ,business.industry ,Health Policy ,Crossover study ,Sleep in non-human animals ,antistress effect ,α-amylase ,Mood ,medicine.anatomical_structure ,Anesthesia ,Medicine ,business ,030217 neurology & neurosurgery ,Aromatherapy - Abstract
Lavender essential oil (LEO) was reported to improve sleep quality. We investigated the influence of aromatherapy by testing the effects of LEO on stress responses during a short-duration sleep in a single-blind, randomized, crossover trial. The subjects were twelve healthy adults who were nonsmokers without any known disease and who were not prescribed medications, and nine of these completed the study. After the subjects had fallen asleep, they were sprayed with LEO using an aroma diffuser. Before and after 90 min of sleep, α-amylase, chromogranin A (CgA), and cortisol levels in saliva were measured as objective stress indicators, and the Japanese version of the UWIST Mood Adjective Checklist was used as a subjective indicator. A comparison of changes before and after sleep, with and without LEO, revealed that the cortisol level did not significantly change, however, α-amylase (p <, 0.05) and CgA (p <, 0.01) levels significantly decreased after LEO inhalation. A mood test indicated no change in mood before and after sleep, with or without LEO. Since α-amylase and CgA reflect the sympathetic nervous system response, these results indicate that LEO aromatherapy during a short-duration sleep cycle suppresses the stress response, especially that of the sympathetic nervous system.
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- 2021
5. Analgesic Effect of Combined Therapy with the Japanese Herbal Medicine 'Yokukansan' and Electroacupuncture in Rats with Acute Inflammatory Pain
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Takayuki Okumo, Nachi Ebihara, Hideshi Ikemoto, Taro Kimura, Naoki Adachi, Tadashi Hisamitsu, Masataka Sunagawa, Kanako Yusa, Atsufumi Manabe, and Satoshi Hattori
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Analgesic effect ,Combination therapy ,Electroacupuncture ,medicine.medical_treatment ,Kampo ,Yokukansan ,Pharmacology ,Article ,03 medical and health sciences ,0302 clinical medicine ,electroacupuncture ,medicine ,Acupuncture ,General Environmental Science ,business.industry ,phosphorylated ERK ,General Engineering ,Inflammatory pain ,formalin ,Kampo medicine ,030220 oncology & carcinogenesis ,General Earth and Planetary Sciences ,Combined therapy ,Medicine ,business ,030217 neurology & neurosurgery - Abstract
Background: Japanese herbal medicine, called Kampo medicine, and acupuncture are mainly used in Japanese traditional medicine. In this experiment, the analgesic effect of Yokukansan (YKS) alone and a combination of YKS and electroacupuncture (EA) on inflammatory pain induced by formalin injection were examined. Methods: Animals were divided into four groups: a control group, formalin injection group (formalin), YKS-treated formalin group (YKS), and YKS- and EA-treated formalin group (YKS + EA). The duration of pain-related behaviors and extracellular signal-regulated protein kinase (ERK) activation in the spinal cord after formalin injection in the right hind paw were determined. Results: The duration of pain-related behaviors was dramatically prolonged in the late phase (10–60 min) in the formalin group. The YKS treatment tended to reduce (p = 0.08), whereas YKS + EA significantly suppressed the pain-related behaviors (p <, 0.01). Immunohistochemical and Western blot analyses revealed that the number of phosphorylated ERK1/2 (pERK1/2)-positive cells and the pERK expression level, which were increased by formalin injection, were significantly inhibited by YKS (p <, 0.05) and YKS + EA (p <, 0.01). Conclusions: The YKS + EA combination therapy elicited an analgesic effect on formalin-induced acute inflammatory pain.
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- 2021
6. Regulatory Role of Orexin in the Antistress Effect of 'Press Tack Needle' Acupuncture Treatment
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Tadashi Hisamitsu, Mana Tsukada, Takayuki Okumo, Hideshi Ikemoto, Aki Fujiwara, Takuji Izuno, Masataka Sunagawa, and Satoshi Hattori
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medicine.medical_specialty ,Leadership and Management ,medicine.drug_class ,Health Informatics ,press tack needle ,Article ,03 medical and health sciences ,Orexin-A ,0302 clinical medicine ,Health Information Management ,Internal medicine ,medicine ,Acupuncture ,Receptor ,aggressive behavior ,030304 developmental biology ,orexin receptor ,0303 health sciences ,business.industry ,Health Policy ,Acupuncture treatment ,Receptor antagonist ,Orexin receptor ,antistress effect ,Orexin ,Endocrinology ,orexin ,Needle acupuncture ,Medicine ,business ,030217 neurology & neurosurgery ,acupuncture - Abstract
The aim of this research was to investigate the antistress effect of press tack needle (PTN) acupuncture treatment using rats with social isolation stress (SIS). Rats were divided into non-stress group (Grouped+sham), stress group (SIS+sham), and PTN-treated SIS group (SIS+PTN). Rats in the SIS+PTN and SIS+sham groups were housed alone for eight days. For the SIS+PTN group, a PTN (length, 0.3 or 1.2 mm) was fixed on the GV20 acupoint on day 7. We measured stress behavior based on the time the rats showed aggressive behavior and the levels of plasma corticosterone and orexin A on day 8. In addition, the orexin-1 receptor or orexin-2 receptor antagonist was administered to rats that were exposed to SIS. The duration of aggressive behavior was significantly prolonged in the SIS+sham group, and the prolonged duration was inhibited in the SIS+PTN (1.2 mm) group. The levels of plasma corticosterone and orexin A were significantly increased in the SIS+sham group, however, these increases were inhibited in the SIS+PTN group. The aggressive behavior was significantly reduced after the orexin-2 receptor antagonist was administered. These findings suggest that PTN treatment at GV20 may have an antistress effect, and the control of orexin is a mechanism underlying this phenomenon.
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- 2021
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7. Analgesic effect of voluntary exercise in a rat model of persistent pain via suppression of microglial activation in the spinal cord
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Akiou Nakamura, Satoshi Sakaue, Fatma Zahra Sakhri, Naoki Adachi, Masataka Sunagawa, Hiroyuki Horikawa, Risa Takahara-Yamauchi, Takayuki Okumo, Hideshi Ikemoto, and Mami Kato
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0301 basic medicine ,Male ,medicine.medical_specialty ,Analgesic ,Down-Regulation ,Pain ,Physical exercise ,Tropomyosin receptor kinase B ,Motor Activity ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Neurotrophic factors ,Internal medicine ,Formaldehyde ,Physical Conditioning, Animal ,medicine ,Nociception assay ,Animals ,Rats, Wistar ,Cell Proliferation ,Pain Measurement ,Analgesics ,business.industry ,musculoskeletal, neural, and ocular physiology ,Brain-Derived Neurotrophic Factor ,General Medicine ,Spinal cord ,nervous system diseases ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Allodynia ,Spinal Cord ,Hyperalgesia ,Microglia ,medicine.symptom ,Chronic Pain ,business ,030217 neurology & neurosurgery - Abstract
In this study, we employed a rodent model for persistent allodynia and hyperalgesia to determine whether voluntary exercise could exert analgesic effects on these pain symptoms. Rats were subcutaneously injected with formalin into the plantar surface of the right hind paw to induce mechanical allodynia and hyperalgesia. We assessed the analgesic effects of a voluntary wheel running (VWR) using the von Frey test and investigated microglial proliferation in the dorsal horn of the spinal cord. We also determined the effect of formalin and VWR on the protein expression levels of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and K+-Cl- cotransporter 2 (KCC2), which play a key role in inducing allodynia and hyperalgesia. Rats with access to the running wheels showed beneficial effects on persistent formalin-induced mechanical allodynia and hyperalgesia. The effects of VWR were elicited through the suppression of formalin-induced microglial proliferation, TrkB up-regulation, and KCC2 down-regulation in the spinal cord. BDNF, however, might not contribute to the beneficial effects of VWR. Our results show an analgesic effect of voluntary physical exercise in a rodent model with persistent pain, possibly through the regulation of microglial proliferation and TrkB and KCC2 expression in the spinal cord.
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- 2021
8. Kamikihito, a traditional Japanese Kampo medicine, increases the secretion of oxytocin in rats with acute stress
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Taka-aki Matsuyama, Takayuki Okumo, Hideshi Ikemoto, Mana Tsukada, Tatsuki Inoue, Takashi Takaki, Keita Mizuno, Yoshiki Tsunokawa, Naoko Tsuchiya, Masataka Sunagawa, and Xiao-Pen Lee
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Male ,Restraint, Physical ,Microdialysis ,medicine.medical_specialty ,Kampo ,Administration, Oral ,Oxytocin ,Open field ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adrenocorticotropic Hormone ,Corticosterone ,Stress, Physiological ,Internal medicine ,Drug Discovery ,Medicine ,Animals ,Rats, Wistar ,Defecation ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Behavior, Animal ,business.industry ,Oxytocin secretion ,Oxytocin receptor ,Disease Models, Animal ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,Medicine, Kampo ,business ,Locomotion ,Hormone ,medicine.drug ,Drugs, Chinese Herbal ,Paraventricular Hypothalamic Nucleus - Abstract
Ethnopharmacological relevance 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. Aim of the study This study aimed to evaluate the possible antistress effect of KKT in rats with acute stress and the contribution of oxytocin to the process. Materials and methods 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. Results 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. Conclusions These results suggest that KKT has antistress activity and increased oxytocin secretion may be a mechanism underlying this phenomenon.
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- 2021
9. Analgesic Efficacy of a Combination of Fentanyl and a Japanese Herbal Medicine 'Yokukansan' in Rats with Acute Inflammatory Pain
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Hideshi Ikemoto, Naoki Adachi, Mana Tsukada, Mami Kato, Wakako Yogi, Yuko Akanuma, Takayuki Okumo, Yusuke Ohashi, Masataka Sunagawa, and Yasunori Takayama
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MAPK/ERK pathway ,transient receptor potential ankyrin 1 (TRPA1) channel ,Yokukansan ,Analgesic ,lcsh:Medicine ,Pharmacology ,fentanyl ,Article ,phosphorylated extracellular signal-regulated kinase (pERK) ,Fentanyl ,03 medical and health sciences ,Subcutaneous injection ,0302 clinical medicine ,030202 anesthesiology ,Single high dose ,medicine ,General Environmental Science ,business.industry ,fungi ,lcsh:R ,General Engineering ,food and beverages ,Inflammatory pain ,Hyperalgesia ,herbal medicine ,General Earth and Planetary Sciences ,medicine.symptom ,business ,030217 neurology & neurosurgery ,whole-cell patch-clamp recording ,medicine.drug - Abstract
Background: Fentanyl can induce acute opioid tolerance and postoperative hyperalgesia when administered at a single high dose, thus, this study examined the analgesic efficacy of a combination of fentanyl and Yokukansan (YKS). Methods: Rats were divided into control, formalin-injected (FOR), YKS-treated+FOR (YKS), fentanyl-treated+FOR (FEN), and YKS+FEN+FOR (YKS+FEN) groups. Acute pain was induced via subcutaneous injection of formalin into the paw. The time engaged in pain-related behavior was measured. Results: In the early (0&ndash, 10 min) and intermediate (10&ndash, 20 min) phases, pain-related behavior in the YKS+FEN group was significantly inhibited compared with the FOR group. In the late phase (20&ndash, 60 min), pain-related behavior in the FEN group was the longest and significantly increased compared with the YKS group. We explored the influence on the extracellular signal-regulated kinase (ERK) pathway in the spinal cord, and YKS suppressed the phosphorylated ERK expression, which may be related to the analgesic effect of YKS in the late phase. Conclusions: These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful.
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- 2020
10. Preventive Effect of the Japanese Traditional Herbal Medicine Boiogito on Posttraumatic Osteoarthritis in Rats
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Koji Kanzaki, Takayuki Okumo, Haruka Takemura, Yusuke Kunieda, Jun Oike, Hideshi Ikemoto, Hiroshi Takagi, Masataka Sunagawa, and Shingo Nakai
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Kampo ,lcsh:Medicine ,Osteoarthritis ,Right knee ,Article ,knee osteoarthritis ,Sham group ,03 medical and health sciences ,0302 clinical medicine ,Oral administration ,Medicine ,rat ,General Environmental Science ,030203 arthritis & rheumatology ,business.industry ,lcsh:R ,Therapeutic effect ,General Engineering ,boiogito ,medicine.disease ,Walking time ,medicine.anatomical_structure ,Anesthesia ,General Earth and Planetary Sciences ,business ,Medial meniscus ,030217 neurology & neurosurgery - Abstract
Background: Considering the anti-inflammatory properties of the Japanese traditional Kampo medicine Boiogito (BO), we aimed to investigate the therapeutic effect of BO to prevent the development of knee osteoarthritis (KOA) in rats with surgically induced KOA. Methods: Destabilization of the medial meniscus (DMM) was performed to induce osteoarthritis in the right knees of 12-week-old Wistar rats under general anesthesia. The rats were orally administered 3% BO in standard powder chow for 4 weeks after surgery (controls: n = 6, sham group: n = 6, DMM group: n = 5, DMM + BO group: n = 5). During this period, the rotarod test was performed to monitor locomotive function. After 4 weeks, histological assessment was performed on the right knee. Results: Oral administration of BO improved locomotive function in the rotarod test. Walking time on postoperative days 1, 14, or later was significantly longer in the DMM + BO group than in the DMM group. Histologically, the DMM group showed significant progression of KOA, which, in the DMM + BO group, was strongly suppressed, as assessed by the Osteoarthritis Research Society International score. Conclusions: Our results showed that oral administration of BO had a clinically preventive effect on early stage posttraumatic KOA.
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- 2020
11. Kamikihito rescued depressive-like behaviors and hippocampus neurogenesis in chronic restraint stress rats
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Tadashi Hisamitsu, Mami Kato, Tatsuki Inoue, Hideshi Ikemoto, Naoki Adachi, Masataka Sunagawa, Yusuke Ohashi, and Fatma Zahra Sakhri
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medicine.medical_specialty ,Adrenal gland ,business.industry ,Kampo ,Neurogenesis ,Hippocampal formation ,Open field ,medicine.anatomical_structure ,Endocrinology ,Complementary and alternative medicine ,Internal medicine ,medicine ,Hippocampus (mythology) ,Anxiety ,medicine.symptom ,business ,Behavioural despair test - Abstract
Background and aim 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. Experimental procedure 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. Results and conclusion 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.
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- 2020
12. Corrigendum to 'Huachansu capsule inhibits the proliferation of human gastric cancer cells via Akt/mTOR pathway' [Biomed. Pharmacother. 118 (2019) 109241]
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Jun Feng, Haibo Wang, Dan Li, Feng Jin, Li Tao, Masataka Sunagawa, Yanqing Liu, Weimin Wang, Mengying Lv, Yayun Qian, and Tengyang Ni
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Pharmacology ,business.industry ,Cancer cell ,Cancer research ,Medicine ,Capsule ,General Medicine ,HuaChanSu ,Therapeutics. Pharmacology ,RM1-950 ,business ,Protein kinase B ,PI3K/AKT/mTOR pathway - Published
- 2020
13. Yokukansan (Kampo medicinal formula) prevents the development of morphine tolerance by inhibiting the secretion of orexin A
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Mana Tsukada, Yasuaki Kanada, Hiroki Suga, Haruka Takemura, Hitoshi Mera, Masataka Sunagawa, Ayami Katayama, Yuko Akanuma, Tadashi Hisamitsu, and Takahiro Ono
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0301 basic medicine ,Kampo ,Analgesic ,Yokukansan ,Pharmacology ,03 medical and health sciences ,Subcutaneous injection ,Orexin-A ,0302 clinical medicine ,Medicine ,Hot plate test ,lcsh:Miscellaneous systems and treatments ,Orexin A ,business.industry ,lcsh:RZ409.7-999 ,Morphine tolerance ,030104 developmental biology ,Nociception ,Complementary and alternative medicine ,nervous system ,Kampo medicine ,Morphine ,Original Article ,business ,Astrocyte ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: 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. Keywords: Astrocyte, Kampo medicine, Morphine tolerance, Orexin A, Yokukansan
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- 2018
14. Efficacy of Juzentaihoto for Tumor Immunotherapy in B16 Melanoma Metastasis Model
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Masataka Sunagawa, Chiaki Tezuka, Takako Ishikawa, Kazuhito Asano, Shintaro Ishikawa, and Tadashi Hisamitsu
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0301 basic medicine ,Article Subject ,business.industry ,medicine.medical_treatment ,Melanoma ,Cell ,Interleukin ,Cancer ,lcsh:Other systems of medicine ,Immunotherapy ,lcsh:RZ201-999 ,medicine.disease ,Metastasis ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Complementary and alternative medicine ,In vivo ,Immunology ,medicine ,Cancer research ,business ,neoplasms ,Ex vivo ,Research Article - Abstract
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-)γlevels 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.
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- 2017
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15. Development of a Highly Sensitive Technique for Capturing Renal Cell Cancer Circulating Tumor Cells
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Michio Naoe, Kazuhiko Oshinomi, Masataka Sunagawa, Mana Tsukada, Chiho Kusaka, Jun Morita, Hideaki Shimoyama, Yoshio Ogawa, Mika Ohta, Yuki Hasebe, Kohzo Fuji, Hikaru Ishii, Tsutomu Unoki, and Takehiko Nakasato
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,renal cell carcinoma ,Clinical Biochemistry ,Cell ,circulating tumor cells ,G250 antigen ,urologic and male genital diseases ,Article ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Renal cell carcinoma ,Internal medicine ,medicine ,Liquid biopsy ,neoplasms ,lcsh:R5-920 ,biology ,business.industry ,medicine.disease ,female genital diseases and pregnancy complications ,Highly sensitive ,Clinical trial ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Cell cancer ,Antibody ,business ,lcsh:Medicine (General) - Abstract
purpose: Liquid biopsy is becoming increasingly important as a guide for selecting new drugs and determining their efficacy. In urological cancer, serum markers for renal cell and urothelial cancers has made the development of liquid biopsy for these cancers strongly desirable. Liquid biopsy is less invasive than conventional tissue biopsy is, enabling frequent biopsies and, therefore, is considered effective for monitoring the treatment course. Circulating tumor cells (CTCs) are a representative liquid biopsy specimen. In the present study, we focused on developing our novel technology for capturing renal cell cancer (RCC)-CTCs using an anti-G250 antibody combined with new devices. Basic experiments of our technology showed that it was possible to detect RCC-CTC with a fairly high accuracy of about 95%. Also, RCC-CTC was identified in the peripheral blood of actual RCC patients. Additionally, during the treatment course of the RCC patient, change in the number of RCC-CTC was confirmed in one case. We believe that the technology we developed will be useful for determining the treatment efficacy and drug selection for the treatment of renal cell cancer (RCC). In order to solve issues such as thresholds setting of this technology, large-scale clinical trials are expected.
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- 2019
16. Inhibition of Angiogenic Factor Productions by Quercetin In Vitro and In Vivo
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Masataka Sunagawa, Takayuki Okumo, Atsuko Furuta, Kanako Yusa, Tarou Kimura, and Kazuhito Asano
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Angiogenesis ,Basic fibroblast growth factor ,Pharmacology ,Immunoglobulin E ,Article ,quercetin ,angiogenic factor ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,heterocyclic compounds ,030304 developmental biology ,General Environmental Science ,0303 health sciences ,allergic rhinitis ,biology ,business.industry ,General Engineering ,in vitro ,suppression ,Mast cell ,Vascular endothelial growth factor ,in vivo ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Medicine ,General Earth and Planetary Sciences ,Nasal administration ,Nasal Lavage Fluid ,mast cell ,Quercetin ,business - Abstract
Background: Angiogenesis is well known to be an important event in the tissue remodeling observed in allergic diseases. Although there is much evidence that quercetin, one of the most abundant dietary flavonoids, exerts anti-allergic effects in both human and experimental animal models of allergic diseases, the action of quercetin on angiogenesis has not been defined. Therefore, in this study, we first examined the action of quercetin on the secretion of angiogenic factors from murine mast cells in vitro. We also examined the action of quercetin on angiogenic factor secretion in the murine allergic rhinitis model in vivo. Methods: Mast cells (1 × 105 cells/mL) sensitized with ovalbumin (OVA)-specific murine IgE were stimulated with 10.0 ng/mL OVA in the presence or the absence of quercetin for 24 h. The concentrations of angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-α, IL-6 and IL-8 in the supernatants were examined by ELISA. BALB/c male mice immunized with OVA were challenged intranasally with OVA every other day, starting seven days after the final immunization. These mice were then orally administered quercetin once a day for five days, starting seven days after the final immunization. Clinical symptoms were assessed by counting the number of sneezes and nasal rubbing behaviors during the 10 min period just after OVA nasal provocation. The angiogenic factor concentrations in the nasal lavage fluids obtained 6 h after nasal antigenic provocation were examined by ELISA. Results: Quercetin significantly inhibited the production of angiogenetic factors induced by IgE-dependent mechanisms at 5.0 µM or more. Oral administration of 25.0 mg/kg quercetin into the mice also suppressed the appearance of angiogenetic factors in nasal lavage fluids, along with the attenuation of nasal symptoms. Conclusions: These results strongly suggest that the inhibitory action of quercetin on angiogenic factor secretion may be implicated in the therapeutic action of quercetin on allergic diseases, especially allergic rhinitis.
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- 2021
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17. Yokukansan, a Kampo medicine, prevents the development of morphine tolerance through the inhibition of spinal glial cell activation in rats
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Mayumi Okada, Ayami Katayama, Mariko Takemoto, Masataka Sunagawa, Hideshi Ikemoto, Tadashi Hisamitsu, Hiroshi Otake, and Hiroki Suga
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0301 basic medicine ,Kampo ,Yokukansan ,microglia ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,astrocyte ,morphine tolerance ,medicine ,lcsh:Miscellaneous systems and treatments ,Microglia ,business.industry ,Chronic pain ,medicine.disease ,lcsh:RZ409.7-999 ,030104 developmental biology ,Nociception ,medicine.anatomical_structure ,nervous system ,Complementary and alternative medicine ,Kampo medicine ,Anesthesia ,Morphine ,Original Article ,business ,Cell activation ,030217 neurology & neurosurgery ,Astrocyte ,medicine.drug - Abstract
Background: Animal models have shown that glial cells (microglia and astrocytes) in the spinal cord undergo activation following peripheral injury associated with chronic pain, suggesting the involvement of these cells in pain diseases. We have previously reported that Yokukansan (YKS), a Japanese traditional herbal (Kampo) medicine, is effective against chronic pain through the suppression of spinal glial cell activation. Morphine is a widely-used opioid analgesic for relieving severe pain, but its repeated administration leads to the development of antinociceptive tolerance. The development of morphine tolerance is also reported to be caused by spinal glial cells activation. In the present study, we investigated the inhibitory effects of YKS on the development of morphine tolerance and the activation of the spinal microglia and astrocytes using a rat model. Methods: Male Wistar rats received a subcutaneous injection of morphine hydrochloride (10 mg/kg/d) for 7 days, and the withdrawal latency to thermal stimulation was measured daily using a hot plate test. Thereafter, the appearance of activated microglia and astrocyte in the spinal cord (L5) was examined by immunofluorescence staining. Ionized calcium binding adapter molecule-1 (Iba-1) staining was used to label microglia and glial fibrillary acidic protein (GFAP) staining was performed to label astrocytes. YKS was administered mixed with powdered rodent chow at a concentration of 3%. Results: The preadministration of YKS (started 3 d before the morphine injection) prevented the development of morphine tolerance. The repeated administration of morphine increased Iba-1 and GFAP immune reactivities in the spinal cord; however, these activations were inhibited by the preadministration of YKS. Conclusion: These results suggest that the preadministration of YKS attenuates the development of antinociceptive morphine tolerance, and the suppression of spinal glial cell activation may be one mechanism underlying this phenomenon.
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- 2016
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18. Kampo (Traditional Japanese Herbal) Formulae for Treatment of Stomatitis and Oral Mucositis
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Mana Tsukada, Hideshi Ikemoto, Nachi Ebihara, Masataka Sunagawa, Tadashi Hisamitsu, and Kojiro Yamaguchi
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0301 basic medicine ,medicine.medical_specialty ,Kampo ,medicine.medical_treatment ,lcsh:Medicine ,Review ,03 medical and health sciences ,0302 clinical medicine ,Basic research ,traditional Japanese herbal medicine ,Hochuekkito ,medicine ,Mucositis ,In patient ,Stomatitis ,General Environmental Science ,Chemotherapy ,business.industry ,lcsh:R ,General Engineering ,medicine.disease ,Dermatology ,Juzentaihoto ,stomatitis ,Hangeshashinto ,030104 developmental biology ,mucositis ,030220 oncology & carcinogenesis ,kampo formula ,General Earth and Planetary Sciences ,business - Abstract
Stomatitis is occasionally multiple, recurrent, and refractory. Currently, mucositis induced by chemotherapy and radiation therapy in patients with cancer has become a significant clinical problem. Effective treatments have not been established and the treatment of numerous cases remains a challenge for physicians. Traditional Japanese herbal medicines termed Kampo formulae (i.e., Hangeshashinto, Orengedokuto, Inchinkoto, Orento, Byakkokaninjinto, Juzentaihoto, Hochuekkito, and Shosaikoto) are used for treating various types of stomatitis and mucositis. Its use has been based on the Kampo medical theories—empirical rules established over thousands of years. However, recently, clinical and basic research studies investigating these formulae have been conducted to obtain scientific evidence. Clinical studies investigating efficacies of Shosaikoto and Orento for the treatment of cryptogenic stomatitis and acute aphthous stomatitis and those investigating the effects of Hangeshashinto, Orengedokuto, and Juzentaihoto on chemotherapy- or radiotherapy-induced mucositis have been conducted. The Kampo formulae comprise several crude drugs, whose mechanisms of action are gradually being clarified. Most of these drugs that are used for the treatment of stomatitis possess anti-inflammatory, analgesic, and antioxidative properties. In this review, we introduce the clinical applications and summarize the available evidence on the Kampo formulae for the treatment of stomatitis and oral mucositis.
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- 2018
19. Inhibitory effect of the Kampo medicinal formula Yokukansan on acute stress-induced defecation in rats
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Yasuaki Kanada, Ayami Katayama, Kana Takahashi, Masataka Sunagawa, Mana Tsukada, Hideshi Ikemoto, Akio Nakamura, Shogo Ishino, and Tadashi Hisamitsu
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0301 basic medicine ,acute stress ,Neuropsychiatric Disease and Treatment ,medicine.drug_class ,Kampo ,Yokukansan ,Peptide hormone ,Pharmacology ,Anxiolytic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Corticosterone ,oxytocin ,Medicine ,Original Research ,irritable bowel syndrome ,business.industry ,corticosterone ,Atosiban ,030104 developmental biology ,Oxytocin ,chemistry ,Kampo medicine ,Defecation ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Yasuaki Kanada, Ayami Katayama, Hideshi Ikemoto, Kana Takahashi, Mana Tsukada, Akio Nakamura, Shogo Ishino, Tadashi Hisamitsu, Masataka Sunagawa Department of Physiology, School of Medicine, Showa University, Shinagawa-ku, Tokyo, Japan Objectives: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with symptoms of abnormal defecation and abdominal discomfort. Psychological factors are well known to be involved in onset and exacerbation of IBS. A few studies have reported effectiveness of traditional herbal (Kampo) medicines in IBS treatment. Yokukansan (YKS) has been shown to have anti-stress and anxiolytic effects. We investigated the effect of YKS on defecation induced by stress and involvement of oxytocin (OT), a peptide hormone produced by the hypothalamus, in order to elucidate the mechanism of YKS action. Methods and results: Male Wistar rats were divided into four groups; control, YKS (300 mg/kg PO)-treated non-stress (YKS), acute stress (Stress), and YKS (300 mg/kg PO)-treated acute stress (Stress+YKS) groups. Rats in the Stress and Stress+YKS groups were exposed to a 15-min psychological stress procedure involving novel environmental stress. Levels of plasma OT in the YKS group were significantly higher compared with those in the Control group (P < 0.05), and OT levels in the Stress+YKS group were remarkably higher than those in the other groups (P < 0.01). Next, rats were divided into four groups; Stress, Stress+YKS, Atosiban (OT receptor antagonist; 1 mg/kg IP)-treated Stress+YKS (Stress+YKS+B), and OT (0.04 mg/kg IP)-treated acute stress (Stress+OT) groups. Rats were exposed to acute stress as in the previous experiment, and defecation during the stress load was measured. Administration of YKS or OT significantly inhibited defecation; however, administration of Atosiban partially abolished the inhibitory effect of YKS. Finally, direct action of YKS on motility of isolated colon was assessed. YKS (1 mg/mL, 5 mg/mL) did not inhibit spontaneous contraction. Conclusion: These results suggested that YKS influences stress-induced defecation and that increased OT secretion may be a mechanism underlying this phenomenon. Keywords: Yokukansan, oxytocin, irritable bowel syndrome, acute stress, corticosterone, Kampo medicine
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- 2018
20. Traditional Chinese Medicine Integrated with Chemotherapy for Stage II-IIIA Patients with Non-Small-Cell Lung Cancer after Radical Surgery: A Retrospective Clinical Analysis with Small Sample Size
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Xiaochun Zhang, Xiaojun Dai, Jun Feng, Guang Zhu, Yanqing Liu, Yan Yan, Ting Yang, Xueyu Zhao, Masataka Sunagawa, Bo Pan, Shanshan Wang, and Yayun Qian
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Article Subject ,medicine.medical_treatment ,Traditional Chinese medicine ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Adjuvant therapy ,Radical surgery ,Stage (cooking) ,Lung cancer ,Chemotherapy ,business.industry ,Retrospective cohort study ,lcsh:Other systems of medicine ,medicine.disease ,lcsh:RZ201-999 ,030104 developmental biology ,Complementary and alternative medicine ,030220 oncology & carcinogenesis ,business ,Research Article - Abstract
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.
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- 2018
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21. Urinary bladder mucosal responses to ischemia
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Tadashi Hisamitsu, Amanda Wolf-Johnston, Karl-Erik Andersson, Lori A. Birder, Masanori Nomiya, Norifumi Sawada, and Masataka Sunagawa
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Male ,Nephrology ,medicine.medical_specialty ,Urology ,Urinary Bladder ,Ischemia ,Vimentin ,urologic and male genital diseases ,Connexins ,Article ,Rats, Sprague-Dawley ,Internal medicine ,medicine ,Animals ,Urothelium ,Lamina propria ,Mucous Membrane ,Urinary bladder ,biology ,business.industry ,Mucous membrane ,Rat Urinary Bladder ,medicine.disease ,female genital diseases and pregnancy complications ,Rats ,Connexin 26 ,Disease Models, Animal ,medicine.anatomical_structure ,Connexin 43 ,Chronic Disease ,biology.protein ,business - Abstract
The objectives of this study were to examine the expression of various cellular proteins within the urothelium (UT) and lamina propria (LP) following chronic bladder ischemia in the rat urinary bladder.Urinary bladders were removed from adult Sprague-Dawley rats 8 weeks after creation of bladder ischemia and from sham controls. Immunocytochemistry was used to examine distribution of LP-vimentin-immunoreactive (IR) cells and connexins (Cx26; Cx43), and western immunoblotting or ELISA for proteins involved in UT barrier and sensory functions.Ischemia was associated with a significant increase in LP-vimentin-IR cells and increased expression of the gap junction proteins Cx26 and Cx43 within the bladder UT as compared to sham control. Ischemia also resulted in an increased (p 0.05) expression level of the junctional marker (ZO-1) and non-significantly increased expressions of the trophic factor nerve growth factor as well as norepinephrine.Our findings reveal that chronic ischemia alters a number of proteins within the UT and underlying LP. These proteins are involved in barrier function, remodeling, repair as well as intercellular communication. The increased expression of LP-vimentin-IR cells suggests that changes in cell-cell interactions could play a role in ischemia-induced changes in bladder activity.
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- 2014
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22. Evaluation of restriction of movement and hyperalgesia in an only–ankle–immobilization rat model
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Takako Nakanishi–Ueda, Masataka Sunagawa, Tadashi Hisamitsu, Takeshi Kijima, Yuuri Yoshida, Norio Yoshida, and Noriyuki Serada
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medicine.anatomical_structure ,business.industry ,Anesthesia ,Hyperalgesia ,Rat model ,medicine ,Ankle ,medicine.symptom ,business - Published
- 2014
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23. Analgesic and Anti-stress Effects of Yokukansan in Rats with Adjuvant Arthritis
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Takako Nakanishi, Tadashi Hisamitsu, Masataka Sunagawa, Hiroki Suga, Sanae Yoneyama, Shintaro Ishikawa, Shogo Ishino, Yutaka Honda, Hideshi Ikemoto, and Hiroaki Iwanami
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business.industry ,Crying ,medicine.medical_treatment ,Kampo ,Analgesic ,Yokukansan ,Chronic pain ,Pharmacology ,medicine.disease ,Irritability ,Anesthesia ,Threshold of pain ,medicine ,medicine.symptom ,business ,Adjuvant - Abstract
Yokukansan (YKS), one of the traditional Japanese “Kampo” medicines, is a mixture of extract powders from seven kinds of medicinal herbs (Atractylodis Lanceae Rhizoma, Hoelen, Cnidii Rhizoma, Uncariae Uncis Cum Ramulus, Angelicae Radix, Bupleuri Radix, and Glycyrrhizae Radix). YKS has been administered to fragile habitus patients who show symptoms such as emotional irritability, neurosis and insomnia, and to infants who suffer from night crying and convulsions. In recent years, YKS has been reported to be effective against pain disorders such as headache and chronic pain, but the mechanism underlying these beneficial effects is still unclear. In this study, the effect of YKS on chronic inflammatory pain and stress caused by pain were investigated using rats with adjuvant arthritis. Male Wistar rats were injected with complete Freund’s adjuvant into the plantar surface of the right hindpaw, and then pain thresholds and stress markers were measured. The thermal pain threshold measured with the plantar test significantly decreased, and the level of salivary chromogranin A (CgA), which is used as a mental stress marker, was significantly increased in this model. The administration of YKS controlled the activation of spinal microglia involved in the expression of chronic pain, and significantly reduced a decrease in the pain threshold. Moreover, an increase in the level of salivary CgA was significantly inhibited. The authors concluded that YKS has effects in reducing chronic inflammatory pain and the stress caused by pain.
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- 2013
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24. Inductive Effect of Palmatine on Apoptosis in RAW 264.7 Cells
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Yui Ogawa, Meng Zhang, Kiyomi Kaneki, Shintaro Ishikawa, Tadashi Hisamitsu, Masataka Sunagawa, and Misako Tamaki
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0301 basic medicine ,musculoskeletal diseases ,Article Subject ,business.industry ,Palmatine ,Osteoblast ,lcsh:Other systems of medicine ,Pharmacology ,lcsh:RZ201-999 ,Bone resorption ,Resorption ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,medicine.anatomical_structure ,Complementary and alternative medicine ,chemistry ,Osteoclast ,Apoptosis ,Cell culture ,Medicine ,Viability assay ,business ,Research Article - Abstract
Osteoporosis is a serious public health problem characterized by low bone density and deterioration of the bone microarchitecture. Current treatment options target either osteoclast resorption or osteoblast formation. It has been reported that berberine, a close structural analog of palmatine, inhibited bone loss in an osteoporosis model. In this study, osseous metabolism was observedin vitrowith osteoclast bone resorbing cells. We proved that mouse preosteoclastic cell line (RAW 264.7) has a higher sensitivity to palmatine than mouse osteoblastic cell line (MC3T3-E1); the cell survival rates significantly decreased at 40 μM palmatine. TheNO2-level, a metabolic product of nitric monoxide (NO), and iNOS mRNA expression, an osteoclast with NO induced enzyme, also increased with higher dosage of palmatine. Furthermore, it was recognized that the cell viability decrease from palmatine was caused by apoptosis rather than necrosis. Additionally, osteoclast apoptosis from palmatine did not occur when iNOS was inhibited withNG-nitro-L-arginine methyl ester hydrochloride (pan NOS inhibitor). These results indicate that palmatine plays an important role in osteoclast apoptosis via the NOS system. Hence, palmatine could be considered as a viable pharmaceutical candidate for osteoporosis bone resorption inhibitor.
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- 2016
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25. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial–mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis
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Hua Zhang, Masataka Sunagawa, Yayun Qian, Dan Liu, Shiyu Guo, Yanqing Liu, Yu Zhang, Guoqing Li, and Tadashi Hisamitsu
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medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,Knee Joint ,Morpholines ,Clinical Biochemistry ,Arthritis ,Inflammation ,Arthritis, Rheumatoid ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Cell Movement ,Internal medicine ,Synovial Fluid ,medicine ,Animals ,Humans ,LY294002 ,Epithelial–mesenchymal transition ,RNA, Small Interfering ,Rats, Wistar ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Phosphoinositide-3 Kinase Inhibitors ,business.industry ,Cell migration ,Cell Biology ,General Medicine ,Fibroblasts ,Hypoxia (medical) ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Arthritis, Experimental ,Genistein ,Cell Hypoxia ,Rats ,Enzyme Activation ,Endocrinology ,chemistry ,Chromones ,Gene Knockdown Techniques ,Cancer research ,Female ,medicine.symptom ,business ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Migration and invasion of fibroblast-like synoviocytes (FLSs) are critical in the pathogenesis of rheumatoid arthritis (RA). Hypoxic conditions are present in RA joints, and hypoxia has been extensively studied in angiogenesis and inflammation. However, its effect on the migration and invasion of RA-FLSs remains unknown. In this study, we observed that RA-FLSs exposed to hypoxic conditions experienced epithelial-mesenchymal transition (EMT), with increased cell migration and invasion. We demonstrated that hypoxia-induced EMT was accompanied by increased hypoxia-inducible factor (HIF)-1α expression and activation of Akt. After knockdown or inhibition of HIF-1α in hypoxia by small interfering RNA or genistein (Gen) treatment, the EMT transformation and invasion ability of FLSs were regained. HIF-1α could be blocked by phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, indicating that HIF-1α activation was regulated by the PI3K/Akt pathway. Administration of LY294002 (20 mg/kg, intra-peritoneally) twice weekly and Gen (25 mg/kg, by gavage) daily for 3 weeks from day 20 after primary immunization in a collagen-induced arthritis rat model, markedly alleviated the clinical signs, radiology progression, synovial hyperplasia, and inflammatory cells infiltration of joints. Thus, results of this study suggest that activation of the PI3K/Akt/HIF-1α pathway plays a pivotal role in mediating hypoxia-induced EMT transformation and invasion of RA-FLSs under hypoxia.
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- 2012
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26. Suppressive Effect of Juzentaihoto on Vascularization Induced by B16 Melanoma CellsIn VitroandIn Vivo
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Takako Ishikawa, Shintaro Ishikawa, Hiroshi Fujiwara, Kazuhito Asano, Mayumi Okada, Masataka Sunagawa, and Tadashi Hisamitsu
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medicine.medical_specialty ,Article Subject ,business.industry ,Cell ,Cancer ,lcsh:Other systems of medicine ,Pharmacology ,lcsh:RZ201-999 ,medicine.disease ,In vitro ,Metastasis ,Surgery ,Vascular endothelial growth factor ,Subcutaneous injection ,chemistry.chemical_compound ,medicine.anatomical_structure ,Complementary and alternative medicine ,chemistry ,In vivo ,Oral administration ,medicine ,business ,Research Article - Abstract
Juzentaihoto (JTT) is well known to be one of Japanese herbal medicines, and used for the supplemental therapy of cancer patients with remarkable success. The present study, therefore, was undertaken to examine the possible therapeutic mechanisms of JTT on cancer using B16 melanoma cell (B16 cell)/experimental mouse system. JTT was well mixed with rodent chow at 3.0% concentrations, and was administered orally ad libitum. Administration of JTT was started one week before tumor cell injection and continued throughout the experiment. Administration of JTT into mice significantly inhibited tumor metastasis in lungs after intravenous injection of2×105B16 cells in a volume of 50 μL. JTT also significantly suppressed enlargement of tumor size in hind footpad after the subcutaneous injection of2×105(50 μL) B16 cells. In the second part of experiments, the chamber that containing B16 cells was buried in the murine back. In JTT administrated group, vascular endothelial growth factor (VEGF) of chamber internal fluid significantly decreased, and vascularization of chamber circumference was also inhibited. These results strongly suggest that oral administration of JTT caused decrease in the generation of VEGF, which is responsible for vascularization, and results in inhibition of B16 cell metastasis.
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- 2012
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27. Detection of circulating tumor cells and the importance of their measurement in urological cancers
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Hironori Osawa, Yuki Matsui, Masataka Sunagawa, Mika Ohta, Tsutomu Unoki, Yuki Hasebe, Takehiko Nakasato, Yoshio Ogawa, Michio Naoe, Hideaki Shimoyama, Hikaru Ishii, Masaharu Matuzaki, Masayuki Ishige, and Mana Tsukada
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Urology ,Immune checkpoint inhibitors ,lcsh:RC870-923 ,Disease course ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Internal medicine ,medicine ,Liquid biopsy ,liquid biopsy ,business.industry ,urological cancer ,Circulating tumor cells ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Urological cancers ,Microvesicles ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,Kidney cancer ,Serum markers - Abstract
In recent years, various new drugs such as molecularly targeted drugs and immune checkpoint inhibitors have been developed. Liquid biopsy is becoming increasingly important as a guide for selecting these new drugs and determining their efficacy. In urological cancers, given the lack of serum markers for kidney cancer or urothelial cancers, the development of liquid biopsy is strongly desired. Liquid biopsy is less invasive than conventional tissue biopsy, enabling frequent biopsies, and is therefore considered effective for monitoring of the treatment course. Liquid biopsy is largely divided into three types: circulating tumor cells (CTCs), cell-free DNA, and exosomes, each of which has its own set of advantages and disadvantages with regard to the identification method and utility. In the present article, we focus on CTCs and discuss issues in their identification method as well as recent findings.
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- 2018
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28. The Effects of Adrenergic Receptor Agonists and Antagonists on Blood Fluidity in Rats
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Tokuko Ishino, Shintaro Ishikawa, Erika Tokita, Tadashi Hisamitsu, Hiroto Tanigawa, Masataka Sunagawa, Steven K. H. Aung, and Takao Sato
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Beta-1 adrenergic receptor ,Beta-3 adrenergic receptor ,medicine.medical_specialty ,Adrenergic receptor agonists ,Endocrinology ,business.industry ,Internal medicine ,Adrenergic receptor antagonists ,medicine ,Blood fluidity ,Pharmacology ,business ,Alpha-1A adrenergic receptor - Published
- 2010
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29. The Effects of Electrical Shock Stress on Blood Fluidity in Rats
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Tokuko Ishino, Shintaro Ishikawa, Masataka Sunagawa, Takao Sato, Skh Aung, Hlaing Thein, and Tadashi Hisamitsu
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Stress (mechanics) ,medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,medicine ,Blood fluidity ,Electrical shock ,business - Published
- 2009
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30. Anti-invasive effects of celastrol in hypoxia-induced fibroblast-like synoviocyte through suppressing of HIF-1α/CXCR4 signaling pathway
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Shiyu Guo, Guoqing Li, Yaodong Zhu, Dan Liu, Tadashi Hisamitsu, Yanqing Liu, Yu Zhang, Masataka Sunagawa, and Yayun Qian
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Fibroblast-like synoviocyte ,Receptors, CXCR4 ,Cell Survival ,Immunology ,Anti-Inflammatory Agents ,CXCR4 ,Pathogenesis ,Arthritis, Rheumatoid ,chemistry.chemical_compound ,Downregulation and upregulation ,Cell Movement ,medicine ,Immunology and Allergy ,Humans ,CXC chemokine receptors ,RNA, Small Interfering ,Hypoxia ,Cells, Cultured ,Pharmacology ,Messenger RNA ,business.industry ,Cell Cycle ,Synovial Membrane ,Hypoxia (medical) ,Fibroblasts ,Hypoxia-Inducible Factor 1, alpha Subunit ,Triterpenes ,chemistry ,Celastrol ,Cancer research ,medicine.symptom ,business ,Pentacyclic Triterpenes - Abstract
Rheumatoid arthritis (RA) joints are in a hypoxic condition. Hypoxia-induced migration and invasion of fibroblast-like synoviocytes (FLSs) are considered to play a critical role in the pathogenesis of RA. Among the key genes upregulated by hypoxia-inducible factor-1α (HIF-1α), CXC chemokine receptor 4 (CXCR4) plays an important role in FLS migration and invasion. Our previous studies have shown that celastrol exerts anti-arthritic effects by inhibiting FLS migration and invasion under normoxic conditions. However, the effect and molecular mechanisms underlying the effect of celastrol on hypoxia-induced FLS migration and invasion are poorly understood. In the present study, we assessed the effect of celastrol on hypoxia-induced FLS migration and invasion. Results showed that celastrol suppressed hypoxia-induced FLS migration and invasion. In addition, we also found that celastrol inhibited hypoxia-induced CXCR4 expression at both the mRNA and the protein levels in RA-FLSs. Meanwhile, it is revealed that celastrol inhibited the transcriptional activity of CXCR4 under hypoxic conditions by suppressing the binding activity of HIF-1α in the CXCR4 promoter, and blocked hypoxia-induced accumulation of nuclear HIF-1α. Furthermore, treatment with HIF-1α inhibitor reduced the hypoxia-induced expression and transcriptional activity of CXCR4. In conclusion, our results indicate that celastrol inhibits hypoxia-induced migration and invasion via suppression of HIF-1α mediated CXCR4 expression in FLSs under hypoxic conditions. These results provide a strong rationale for further testing and validation of the use of celastrol as a new alternative for using in the treatment of RA.
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- 2013
31. Urothelial‐Neural Responses to Chronic Bladder Ischemia
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Masanori Nomiya, Kark‐Erik Andersson, Masataka Sunagawa, Norifumi Sawada, Tadashi Hisamitsu, Lori A. Birder, and Amanda Wolf-Johnston
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medicine.medical_specialty ,business.industry ,Genetics ,Urology ,medicine ,Ischemia ,medicine.disease ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2013
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32. Celastrol inhibits lipopolysaccharide-stimulated rheumatoid fibroblast-like synoviocyte invasion through suppression of TLR4/NF-κB-mediated matrix metalloproteinase-9 expression
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Yanqing Liu, Guoqing Li, Hua Zhang, Tadashi Hisamitsu, Shiyu Guo, Masataka Sunagawa, Yayun Qian, Yu Zhang, and Dan Liu
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Fibroblast-like synoviocyte ,Lipopolysaccharides ,Phytochemistry ,Lipopolysaccharide ,Phytopharmacology ,Phytochemicals ,Arthritis ,lcsh:Medicine ,Matrix metalloproteinase ,Arthritis, Rheumatoid ,chemistry.chemical_compound ,Cell Movement ,lcsh:Science ,Multidisciplinary ,Anti-Inflammatory Agents, Non-Steroidal ,Cell Cycle ,NF-kappa B ,Animal Models ,Chemistry ,Matrix Metalloproteinase 9 ,Celastrol ,Medicine ,Female ,Signal transduction ,Pentacyclic Triterpenes ,Research Article ,Signal Transduction ,medicine.medical_specialty ,Cell Survival ,Primary Cell Culture ,Rheumatoid Arthritis ,Model Organisms ,Complementary and Alternative Medicine ,Rheumatology ,Internal medicine ,medicine ,Animals ,Humans ,Rats, Wistar ,Biology ,Collagen Type II ,business.industry ,lcsh:R ,medicine.disease ,NFKB1 ,Arthritis, Experimental ,Triterpenes ,Rats ,Toll-Like Receptor 4 ,Endocrinology ,chemistry ,Gene Expression Regulation ,Cancer research ,TLR4 ,Rat ,lcsh:Q ,business ,Joint Capsule - Abstract
Invasion of fibroblast-like synoviocytes (FLSs) is critical in the pathogenesis of rheumatoid arthritis (RA). The metalloproteinases (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasive activity of celastrol on LPS-stimulated human RA-FLSs, and to elucidate the mechanism involved. We investigated the effect of celastrol on LPS-induced FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that celastrol suppressed LPS-stimulated FLS migration and invasion by inhibiting MMP-9 expression and activity. Furthermore, our results revealed that celastrol inhibited the transcriptional activity of MMP-9 by suppressing the binding activity of NF-κB in the MMP-9 promoter, and suppressed the TLR4/MyD88/NF-κB pathway. Administration of celastrol (0.5 mg/kg and 1 mg/kg, intraperitoneally) daily for 3 weeks in a collagen-induced arthritis rat model markedly alleviated the clinical signs, synovial hyperplasia and inflammatory cell infiltration of joints. In conclusion, celastrol might inhibit FLS migration and invasion induced by LPS by suppressing TLR4/NF-κB-mediated MMP-9 expression, providing a theoretical foundation for the clinical treatment of RA with celastrol.
- Published
- 2013
33. Celastrol inhibits interleukin-17A-stimulated rheumatoid fibroblast-like synoviocyte migration and invasion through suppression of NF-κB-mediated matrix metalloproteinase-9 expression
- Author
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Tadashi Hisamitsu, Hua Zhang, Shiyu Guo, Yayun Qian, Dan Liu, Guoqing Li, Yanqing Liu, Masataka Sunagawa, and Yu Zhang
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Fibroblast-like synoviocyte ,RNA Folding ,Immunology ,Arthritis ,Matrix metalloproteinase ,Real-Time Polymerase Chain Reaction ,Gene Expression Regulation, Enzymologic ,Arthritis, Rheumatoid ,chemistry.chemical_compound ,Cell Movement ,Synovial Fluid ,Immunology and Allergy ,Medicine ,Humans ,RNA, Messenger ,Cells, Cultured ,Pharmacology ,Regulation of gene expression ,Molecular Structure ,business.industry ,Interleukin-17 ,NF-kappa B ,NF-κB ,Fibroblasts ,medicine.disease ,Triterpenes ,IκBα ,chemistry ,Matrix Metalloproteinase 9 ,Celastrol ,Cancer research ,Interleukin 17 ,business ,Pentacyclic Triterpenes - Abstract
Interleukin-17A (IL-17A)-induced migration and invasion of fibroblast-like synoviocytes (FLSs) is critical for the pathogenesis of rheumatoid arthritis (RA). More than 30% of RA patients are resistant to available therapies, despite the introduction of novel biologic agents. Therefore, it is necessary to develop new anti-arthritic agents. Recent studies have demonstrated that celastrol has anti-arthritic activity in an adjuvant-induced arthritis (AIA) model. However, the effect and molecular mechanisms of celastrol on the migration and invasion of RA-FLSs are not yet understood. Results showed that treatment of RA-FLSs with celastrol suppressed the IL-17A-induced migration and invasion abilities of the cells. In addition, celastrol inhibited IL-17A-induced matrix metalloproteinase (MMP)-9 mRNA and protein expression, and the proteolytic activity of MMP-9 in RA-FLSs. Furthermore, our results revealed that celastrol inhibited the transcriptional activity of MMP-9 by suppression of the binding activity of nuclear factor-κB (NF-κB) in the MMP-9 promoter, and inhibited IκBα phosphorylation and nuclear translocation of NF-κB. In conclusion, celastrol can inhibit IL-17A-induced migration and invasion by suppressing NF-κB-mediated MMP-9 expression in RA-FLSs. These results provide a strong rationale for further testing and validation of celastrol as an adjunct with conventional drugs for the treatment of RA in humans.
- Published
- 2012
34. Moxibustion at mingmen reduces inflammation and decreases IL-6 in a collagen-induced arthritis mouse model
- Author
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Morihiro Kogure, Naomi Mimura, Shintaro Ishikawa, Hideshi Ikemoto, Masataka Sunagawa, Takako Nakanishi-Ueda, and Tadashi Hisamitsu
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Male ,medicine.medical_specialty ,Moxibustion ,medicine.medical_treatment ,Type II collagen ,Arthritis ,Inflammation ,collagen-induced arthritis ,chemistry.chemical_compound ,Mice ,Corticosterone ,Internal medicine ,medicine ,Animals ,Interleukin 6 ,Collagen Type II ,IL-6 ,biology ,business.industry ,Interleukin-6 ,Interleukin ,General Medicine ,mingmen (GV4) ,medicine.disease ,Arthritis, Experimental ,Disease Models, Animal ,Endocrinology ,Anesthesiology and Pain Medicine ,chemistry ,Complementary and alternative medicine ,Mice, Inbred DBA ,biology.protein ,Cattle ,Immunization ,medicine.symptom ,business ,Acupuncture Points ,Collagen-induced arthritis - Abstract
The purpose of this study was to compare the effectiveness of moxibustion (MOX) treatment at the GV4 and CV12 acupoints, and to determine the correlations between MOX treatment and interleukin (IL)-6 and corticosterone levels in a collagen-induced arthritis (CIA) mouse model. CIA mice were immunized twice intradermally over a 3-week interval with bovine type II collagen. After the second immunization (day 21), MOX was applied to the mouse equivalent of the GV4 and CV12 acupoints with a 1mg moxa cone five times/day. Clinical symptoms of CIA were observed three times/week until day 35. The concentrations of IL-6 and corticosterone in the blood samples were measured by immunoassay kits. At day 35, the incidence of CIA was significantly decreased in mice treated with MOX at the GV4 acupoint (78%, n=23, p
- Published
- 2011
35. Blood fluidity enhancement by electrical acupuncture stimulation is related to an adrenergic mechanism
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Shintaro Ishikawa, Masaya Fukushima, Hiroki Suga, Yuri Yoshida, Atsuhiro Yoshida, Tadashi Hisamitsu, and Masataka Sunagawa
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laser scattering platelet aggregometer ,Male ,medicine.medical_specialty ,Platelet Aggregation ,Narcotic Antagonists ,Adrenergic ,Endogeny ,Vena Cava, Inferior ,Zusanli ,Stimulus (physiology) ,Inferior vena cava ,Platelet Adhesiveness ,Internal medicine ,Acupuncture ,Medicine ,Animals ,Platelet ,Micro Channel Array Flow Analyzer ,Rats, Wistar ,Muscle, Skeletal ,Blood Coagulation ,business.industry ,Naloxone ,General Medicine ,Blood flow ,Adrenergic beta-Agonists ,Electric Stimulation ,Rats ,electrical acupuncture ,Endocrinology ,Anesthesiology and Pain Medicine ,Electroacupuncture ,medicine.vein ,Complementary and alternative medicine ,endogenous adrenergic mechanism ,blood fluidity ,business ,Acupuncture Points - Abstract
We have reported that electrical acupuncture stimulation (ACU) increases blood fluidity by decreasing platelet aggregation. In this study, we investigated the mechanism causing the increase of blood fluidity. The effects of ACU on blood fluidity and platelet adhesion were examined using a Micro Channel Array Flow Analyzer (MC-FAN) and a laser scattering platelet aggregometer (PA-20). Male Wistar rats (7–8 weeks old) were used in the study. ACU (1 or 100Hz, 3–5V), which causes slight muscle twitching, was applied to the ZuSanli (ST-36) acupoint for 15 or 60 minutes once/day. Blood samples were collected from the inferior vena cava. ACU applied to ST-36 revealed significant increases in blood fluidity, while platelet adhesion activity decreased, regardless of the difference of stimulus time. The acupuncture had an immediate effect. Even if naloxone was administered during acupuncture stimulus, the blood flow time shortened in a similar way, as in the only acupuncture stimulus group. In addition, the effect of acupuncture on blood fluidity was inhibited by a β-antagonist. The results indicate that ACU affects blood fluidity depending on the acupoints, and that the effect of ACU might involve an endogenous adrenergic mechanism.
- Published
- 2011
36. Chinese Herbal Medicine TJ-10(SAIKO-KEISHI-TO) attenuated the reducton of NK cell activity in chronic pain model rats
- Author
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Mayumi Okada, Masataka Sunagawa, Tadashi Hisamitsu, and Shiyu Guo
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Cell activity ,Traditional medicine ,business.industry ,Chronic pain ,Medicine ,Pharmacology ,business ,medicine.disease - Published
- 2003
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37. Promotion of Blood Fluidity by Inhibition of Platelet Adhesion Using Electroacupuncture Stimulation
- Author
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Steven K.H. Aung, Tadashi Hisamitsu, Masataka Sunagawa, Takao Sato, Kazuhito Asano, Shintaro Ishikawa, Erika Tokita, and Makoto Murai
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Blood Platelets ,Male ,laser scattering platelet aggregometer ,medicine.medical_specialty ,Platelet Function Tests ,Electroacupuncture ,medicine.medical_treatment ,Platelet adhesion ,Blood fluidity ,Stimulation ,Zusanli ,Platelet Adhesiveness ,Stress, Physiological ,Internal medicine ,Platelet adhesiveness ,medicine ,Acupuncture ,Animals ,Platelet ,Rats, Wistar ,business.industry ,General Medicine ,Blood Physiological Phenomena ,Electric Stimulation ,Rats ,micro channel array flow analyzer ,Anesthesiology and Pain Medicine ,Endocrinology ,electrical acupuncture ,Complementary and alternative medicine ,platelet aggregation ,Anesthesia ,blood fluidity ,business ,Acupuncture Points - Abstract
Stress applied to rats is known to result in a quick decrease in blood fluidity. Although electrical acupuncture stimulation (ACU) attenuates stress responses, the influence of ACU on blood fluidity has not been well examined. In the present study, the effect of ACU on blood fluidity and platelet adhesion was examined using a Micro Channel Array Flow Analyzer and a laser scattering platelet aggregometer (PA-20), respectively. Male Wistar rats (7-8 weeks old) were used. ACU (1 Hz, 3-5 V), which causes slight muscle twitching, was applied to acupoints for 60 minutes/day once or on 2 consecutive days. Stimulated acupoints were as follows: ZuSanli (ST-36), Sanyinjiao (SP-6), Hegu (L-I4), Neiguan (P-6), and Shenshu (BL-23). ACU applied to ST-36, SP-6, and L-14 revealed significant increases in blood fluidity while platelet adhesion activity decreased. No significant changes were observed when ACU was applied to P-6 and BL-23. Results indicate that ACU affects blood fluidity depending on the acupoints. Blood fluidity changed with ACU within 1 day. In other words, the effect of acupuncture has an immediate effect. In addition, platelet aggregation decreased with ACU, suggesting that an increase in blood fluidity is associated with platelet aggregation ability.
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38. Anti-invasive effects of Celastrus Orbiculatus extract on interleukin-1 beta and tumour necrosis factor-alpha combination-stimulated fibroblast-like synoviocytes
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Shiyu Guo, Yanqing Liu, Guoqing Li, Tadashi Hisamitsu, Dan Liu, and Masataka Sunagawa
- Subjects
Fibroblast-like synoviocyte ,Interleukin-1beta ,Celastrus orbiculatus ,Arthritis, Rheumatoid ,Invasion ,NF-KappaB Inhibitor alpha ,Medicine ,Humans ,Rheumatoid arthritis ,Cells, Cultured ,biology ,MMP ,business.industry ,Activator (genetics) ,Plant Extracts ,Tumor Necrosis Factor-alpha ,Synovial Membrane ,NF-kappa B ,General Medicine ,Celastrus ,Fibroblasts ,biology.organism_classification ,NFKB1 ,IκBα ,Matrix Metalloproteinase 9 ,Complementary and alternative medicine ,Antirheumatic Agents ,Immunology ,Cancer research ,Tumor necrosis factor alpha ,I-kappa B Proteins ,Signal transduction ,business ,Research Article ,Phytotherapy ,Signal Transduction - Abstract
Background Invasion of fibroblast-like synoviocytes (FLSs) is critical in the pathogenesis of rheumatoid arthritis (RA). The metalloproteinases (MMPs) and activator of nuclear factor-kappa B (NF-κB) pathway play a critical role in RA-FLS invasion induced by interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α). The present study aimed to explore the anti-invasive activity and mechanism of Celastrus orbiculatus extract (COE) on IL-1β and TNF-α combination-stimulated human RA-FLSs. Methods We investigated the effect of COE on IL-1β and TNF-α combination-induced FLS invasion as well as MMP expression and explored upstream signal transduction. Results COE suppressed IL-1β and TNF-α combination-stimulated FLSs invasion by inhibiting MMP-9 expression and activity. Furthermore, our results revealed that COE inhibited the transcriptional activity of MMP-9 by suppression of the binding activity of NF-κB in the MMP-9 promoter, and inhibited IκBα phosphorylation and nuclear translocation of NF-κB. Conclusions COE inhibits IL-1β and TNF-α combination-induced FLSs invasion by suppressing NF-κB-mediated MMP-9 expression.
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- View/download PDF
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