Jiao-tai-wan inhibits inflammation of the gut-brain-axis and attenuates cognitive impairment in insomnic rats.
Su Hao,Zhang Chu,Zou Xin,Lu Fuer,Zeng Yong,Guan Hongwei,Ren Yanlin,Yuan Fen,Xu Lijun,Zhang Mingmin,Dong Hui
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Jiao-tai-wan is a well-known traditional Chinese herbal medicine formula that is used to treat insomnia and systemic inflammation. Studies indicate chronic insomnia might contribute to the prevalence of cognitive impairment. The role of systemic inflammation and intestinal permeability in the progression of neurodegenerative diseases attracts much attention. AIM OF THE STUDY:This study aimed to investigate if Jiao-tai-wan plays a role in promoting the repair of the intestinal epithelial barrier to suppress systemic inflammation and cognitive impairment in sleep-deprived (SD) rats. MATERIALS AND METHODS:Male obesity-resistant SD rats were partially sleep-deprived for 16 weeks. During the last 8 weeks, they were treated with Jiao-tai-wan. A Morris water maze was used to analyze their cognitive ability. Aβ42 and proinflammation cytokines in the cerebrospinal fluid, tissue, or serum were determined using enzyme-linked immunosorbent assay or polymerase chain reaction. Intestinal permeability was detected using the fluorescein isothiocyanate-dextran perfusion assay method. Plasma lipopolysaccharide (LPS) levels were detected with Tachypleus Amebocyte Lysate. Western bolt was used in the signaling pathway analysis. RESULTS:Sleep deprivation deteriorated the performance of rats in the Morris water maze and increased the Aβ42, caspase3, IL-6, and TNF-α levels in their brains. The intestinal TLR4/NF-κB pathway was activated with an increase in the expression of IL-6 and TNF-α. The expression of tight junction proteins was also decreased in the intestinal tissue. This increased the intestinal permeability and circulation of LPS, LPS binding protein, IL-6, and TNF-α. Treatment with Jiao-tai-wan could partly reverse these changes. CONCLUSION:Jiao-tai-wan has the potential to attenuate systemic inflammation and cognitive impairment in partially sleep-deprived rats. The possible underlying mechanism is by preventing an inflammation trigger being transferred through the gut-brain-axis.
10.1016/j.jep.2019.112478
Decreased alertness due to sleep loss increases pain sensitivity in mice.
Alexandre Chloe,Latremoliere Alban,Ferreira Ashley,Miracca Giulia,Yamamoto Mihoko,Scammell Thomas E,Woolf Clifford J
Nature medicine
Extended daytime and nighttime activities are major contributors to the growing sleep deficiency epidemic, as is the high prevalence of sleep disorders like insomnia. The consequences of chronic insufficient sleep for health remain uncertain. Sleep quality and duration predict presence of pain the next day in healthy subjects, suggesting that sleep disturbances alone may worsen pain, and experimental sleep deprivation in humans supports this claim. We demonstrate that sleep loss, but not sleep fragmentation, in healthy mice increases sensitivity to noxious stimuli (referred to as 'pain') without general sensory hyper-responsiveness. Moderate daily repeated sleep loss leads to a progressive accumulation of sleep debt and also to exaggerated pain responses, both of which are rescued after restoration of normal sleep. Caffeine and modafinil, two wake-promoting agents that have no analgesic activity in rested mice, immediately normalize pain sensitivity in sleep-deprived animals, without affecting sleep debt. The reversibility of mild sleep-loss-induced pain by wake-promoting agents reveals an unsuspected role for alertness in setting pain sensitivity. Clinically, insufficient or poor-quality sleep may worsen pain and this enhanced pain may be reduced not by analgesics, whose effectiveness is reduced, but by increasing alertness or providing better sleep.
10.1038/nm.4329
Effect of Jiaotai Pill () on intestinal damage in partially sleep deprived rats.
Huang Wen-Ya,Zou Xin,Lu Fu-Er,Zhang Chu,Ren Yan-Lin,Xu Li-Jun,Wang Kai-Fu,Dong Hui
Chinese journal of integrative medicine
OBJECTIVE:To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD). METHODS:Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined. RESULTS:The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. CONCLUSIONS:JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.
10.1007/s11655-017-2969-8
[Effect of Acupuncture at Points in Heel Vessel for Circadian Genes of 1 and 2 mRNAs in the Suprachiasmatic Nucleus in Insomnia Rats].
Guo Bao-Jun,Yu Si-Yi,Shen Zhi-Fu,Hu You-Ping
Zhen ci yan jiu = Acupuncture research
OBJECTIVE:To investigate the influence and mechanism of acupuncture at the points in Heel Vessel for the circadian clock genes of Period () 1 and 2 mRNAs in the suprachiasmatic nucleus (SCN) in insomnia rats. METHODS:Thirty male SD rats were randomly divided into blank, model, acupuncture groups, 10 rats in each group. Insomnia model was established by intraperitoneal injection of PCPA (suspension, 1 mL/100 g). Acupuncture at "Shenmai" (BL 62) and "Zhaohai" (KI 6) was used in the acupuncture group for continuous 7 days, 15 min/day and once daily. The circadian rhythm was observed; the expressions of 1 and 2 mRNAs in SCN were examined with real time-PCR. RESULTS:The activity in the model group in rest period everyday increased compared with that in the blank group, and the expressions of 1 and 2 mRNAs in SCN decreased (<0.05). Compared with the model group, the activity in the acupuncture group in rest period decreased and the expressions of 1 and 2 mRNAs in the SCN increased (<0.05). CONCLUSIONS:Acupuncture at BL 62 and KI 6 can increase the expressions of 1 and 2 mRNAs in the SCN, so as to decrease the activity in rest period, and improve the quality of sleep in insomnia rats.
10.13702/j.1000-0607.2017.06.007
[Effects of Acupuncture at "Shenmen" (HT 7) on Brainwaves and Cognitive Ability in Rats with Sleep Deprivation].
Li Jia,Liu Jiao-Ping
Zhen ci yan jiu = Acupuncture research
OBJECTIVE:To observe the effects of acupuncture at "Shenmen" (HT 7) on brainwaves and cognitive ability in rats with sleep deprivation. METHODS:SD rats were randomly divided into control group, model group, acupuncture group and sham acupuncture group, 15 rats in each group. Insomnia model rats were established by sleep deprivation for 72 hours. Acupuncture was applied to acupuncture group at bilateral "Shenmen" (HT 7) for 20 min, once daily for 7 days. Rats in the sham acupuncture group received superficial insertion of 1 mm and without retaining needle. The learning and memory abilities of rats were eva-luated by Hexagonal maze. The BL-420 F physiological recorder was used to record EEG for 30 min on the 1, 4, 7 and 10 day respectively, and the frequency of each wave was analyzed. RESULTS:After sleep deprivation, the frequency of searching the exits of Hexagonal maze in the model group was obviously increased, the searching time was shortened, the number of searching errors was increased obviously, and the cognitive rate was decreased (<0.01). Compared with the model group and the sham acupuncture group, the frequency of searching the exits in the acupuncture group was obviously decreased, the searching time was longer, the number of seeking errors was decreased, and the cognitive rate was increased (<0.05). Compared with the control group, the EEG of δ wave in the model group was decreased while β wave increased with statistical significance (<0.01). Compared with the model group, the δ wave of rats in the acupuncture group was significantly increased and the β wave was significantly decreased (<0.05). There were no statistically significant differences between the sham acupuncture group and the model group (>0.05). CONCLUSIONS:Acupuncture at HT 7 can effectively improve the cognitive abilities and brainwaves in sleep deprived rats.
10.13702/j.1000-0607.2017.06.006
Natural Products from Single Plants as Sleep Aids: A Systematic Review.
Kim Jungyoon,Lee Suji L,Kang Ilhyang,Song Youme A,Ma Jiyoung,Hong Young Sun,Park Shinwon,Moon Seog In,Kim Soojeong,Jeong Semi,Kim Jieun E
Journal of medicinal food
Insufficient sleep, insomnia, and sleep-related problems are important health issues, as their overall prevalence accounts for about 30% of the general population. The aim of this study was to systematically review previous studies investigating the effects of orally administered single plant-derived extracts on sleep-related outcomes in humans. Data sources were PubMed, Google Scholar, and Cochrane Library. The data search was conducted in two steps: step 1, names of plants which have been studied as sleep aids in humans were searched and retrieved; and step 2, each ingredient listed in step 1 was then added into the search term. Only original articles or reviews were applicable to the scope of this review. Studies on human subjects, with or without sleep-related disorders, were included. Sleep-related disorders refer to not only insomnia or sleep behavior disorders but also diseases with sleep-related symptoms. Studies were considered eligible for this review when the plant extracts were administered orally. Outcome measures relevant to sleep quality, duration, or other sleep-related problems were included. Twenty-one plants were listed in the first step of the search as potential candidates for natural sleep aids. Seventy-nine articles using these single plant-derived natural products were included in the final review. Although valerian was most frequently studied, conflicting results were reported, possibly due to the various outcome measures of each study. Other plants were not as rigorously tested in human studies. There was limited evidence with inconclusive results regarding the effects of single plant-derived natural products on sleep, warranting further studies.
10.1089/jmf.2017.4064
The investigation of immunoprotective and sedative hypnotic effect of total polysaccharide from Suanzaoren decoction by serum metabonomics approach.
Niu Xiaoyi,He Bosai,Du Yiyang,Sui Zhenyu,Rong Weiwei,Wang Xiaotong,Li Qing,Bi Kaishun
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
Suanzaoren decoction, as one of the traditional Chinese medicine prescriptions, has been most commonly used in Asian countries and reported to inhibit the process of immunodeficiency insomnia. Polysaccharide is important component which also contributes to the role of immunoprotective and sedative hypnotic effects. This study was aimed to explore the immunoprotective and sedative hypnotic mechanisms of polysaccharide from Suanzaoren decoction by serum metabonomics approach. With this purpose, complex physical and chemical immunodeficiency insomnia models were firstly established according to its multi-target property. Serum samples were analyzed using UHPLC/Q-TOF-MS spectrometry approach to determine endogenous metabolites. Then, principal component analysis was used to distinguish the groups, and partial least squares discriminate analysis was carried out to confirm the important variables. The serum metabolic profiling was identified and pathway analysis was performed after the total polysaccharide administration. The twenty-one potential biomarkers were screened, and the levels were all reversed to different degrees in the total polysaccharide treated groups. These potential biomarkers were mainly related to vitamin, sphingolipid, bile acid, phospholipid and acylcarnitine metabolisms. The result has indicated that total polysaccharide could inhibit insomnia triggered by immunodeficiency stimulation through regulating those metabolic pathways. This study provides a useful approach for exploring the mechanism and evaluating the efficacy of total polysaccharide from Suanzaoren decoction.
10.1016/j.jchromb.2018.04.004
[Manual Acupuncture Stimulation of Paired Acupoints Can Relieve Sleep Disorder Possibly by Upregulating Pineal Melatonin Protein and Its Receptor mRNA Levels in the Suprachiasmatic Nucleus in Insomnia Rats].
Zheng Xue-Na,Wu Xue-Fen,Guo Xin,Xie Li-Na,Xie Zhi-Qiang,Wei Xin-Ran,Liu Li,Chen Xiao-Li,Yue Zeng-Hui
Zhen ci yan jiu = Acupuncture research
OBJECTIVE:To observe the effect of manual acupuncture stimulation of paired "Baihui" (GV 20)+ "Shenmen" (HT 7), GV 20+ "Sanyinjiao" (SP 6), and GV 20+ non-acupoint on expression of melatonine (MT) and suprachiasmatic melatonin receptor 1 (MT) and melatonin receptor 2 (MT) mRNAs in insomnia rats, so as to explore their action difference and the underlying mechanism in improving insomnia. METHODS:Male SD rats were randomly divided into normal control (=12), mo-del (=8), GV 20+HT 7(=12), GV 20+SP 6(=11), and GV 20+ non-acupoint (=10) groups. The insomnia model was established by intraperitoneal injection of Para-chlorophenylalanine suspension (50 mg/mL, 50 mg/100 g), once daily for 2 days. The abovementioned acupoints GV 20, bilateral HT 7, SP 6 and non-acupoints (the midpoint between the elbow-tip and armpit on the medial side of the upper-arm) were punctured with filiform needles and manipulated by rotating the needle for about 1 min which was repeated once again every 10 min during 30 minutes' needle-retaining. The treatment was conducted once daily for 7 days. The expression levels of MT immunoactivity in the conarium tissue, and MT and MT mRNAs of the suprachiasmatic nucleus (SCN) region were detected using immunohistochemistry and fluorescence quantitative real time-PCR, respectively. RESULTS:After modeling, the expression levels of pineal MT (an increase of gray value means a decrease of immunoactivity), SCN MT and MT mRNAs were notably down-regulated in the model group relevant to the normal control group (<0.05, <0.01). Following the treatment, the down-regulated expression levels of MT protein, and MT and MT mRNAs were obviously reversed in the GV 20 + HT 7, GV 20 + SP 6 groups relevant to the model group (<0.05, <0.01). The therapeutic effect of GV 20+ HT 7 was superior to that of GV 20+ non-acupoint in up-regulating the expression of MT mRNA (<0.01), and markedly superior to that of GV 20+ SP 6 and GV 20+ non-acupoint in increasing the sleep duration and in up-regulating the expression of MT mRNA (<0.01). No significant differences were found among the 3 treatment groups in up-regulating the expression of MT (>0.05). CONCLUSION:Manual acupuncture stimulation of GV 20+ HT 7 and GV 20+ SP 6 can improve the sleep disorder in insomnia rats, which may be related to its effects in increasing the levels of pineal MT protein, and MT and MT mRNAs in hypothalamic SCN.
10.13702/j.1000-0607.170409