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OBJECTIVE@#To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac rats.@*METHODS@#The insomniac model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). In behavioral experiments, rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and diazepam [4 mg/(kg•d)] groups. The treatment effect of JTP was evaluated by weight measurement (increasement of body weight), open field test (number of crossings) and forced swimming test (immobility time). A high performance liquid chromatography-electrochemical detection (HPLC-ECD) method was built to determine the concentration of monoamine transmitters in hypothalamus and peripheral organs from normal, model, JTP, citalopram [30 mg/(kg•d)], maprotiline [40 mg/(kg•d)] and bupropion [40 mg/(kg•d)] groups. Expressions of serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) were analyzed by quantitative polymerase chain reaction (qPCR) and Western blot in normal, model and JTP groups. A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method was established to determine the pharmacokinetics, urine cumulative excretion of metformin in vivo, and tissue slice uptake in vitro, which were applied to assess the activity of organic cation transporters (OCTs) in hypothalamus and peripheral organs.@*RESULTS@#Compared with the insomniac model group, the body weight and spontaneous locomotor were increased, and the immobility time was decreased after treatment with JTP (P<0.01). Both serotonin and dopamine contents in hypothalamus and peripheral organs were increased (P<0.01). The norepinephrine content was increased in peripheral organs and decreased in hypothalamus (P<0.05 or P<0.01). At the same time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in hypothalamus and peripheral organs was inhibited (P<0.05).@*CONCLUSION@#JTP alleviates insomnia through regulation of monoaminergic system and OCTs in hypothalamus and peripheral organs.
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OBJECTIVE To explore the efficacy of Jiaotai pill (JTW) and JTW modified prescriptions (JTW+) plus benzodiazepines (BDZ) for insomnia in China by systematic review and network meta-analysis, especially optimization ratio (m:n) between Coptis chinensis and Cinnamo. METHODS Randomized controlled trials (RCTs) regarding JTW and JTW++BDZ for insomina were comprehensively searched in CNKI, VIP, Wanfang, and PubMed, Cochrane Library, OVID, Embase databases from their inception to December 2017. The risk of bias was assessed by the Cochrane collab?oration's tool and Jadad scale. Systematic review and network meta-analysis were performed to evaluate the relative risk (RR) plus 95％confidence interval (95％CI) or prediction interval (95％PrI), and draw surface under the cumulative rank?ing curves (SUCRA) by Stata 14.0 and RevMan 5.0 software. RESULTS A total of 13 RCTs (1 RCT was omitted by sen?sitivity analysis) with 1040 patients were included. Overall heterogeneity was acceptable, except publication bias. Based on classical meta-analysis, JTW and JTWm:n++BDZ, such as JTW2:1++BDZ, JTW5:1++BDZ, JTW6:1++BDZ, JTW10:1++BDZ, had more efficacy than BDZ. Based on network meta-analysis, JTW and JTWm:n++BDZ, such as JTW2:1++BDZ, JTW6:1++BDZ, JTW10:1++BDZ, had more efficacy than BDZ; meanwhile, SUCRA showed the best rank of JTW/JTW+ (BDZ<JTWm:n++BDZ<JTW) for insomina, as same as that of JTWm:n+(BDZ<JTW5:1++BDZ<JTW10:1++BDZ<JTW2:1++BDZ<JTW6:1++BDZ). CONCLUSION Based on the existing clinical evidence, JTW has efficacy for insomnia, but the optimization ratio between Coptis chinensis and cinnamo of JTWm:n++BDZ for insomnia needs more supports.
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This study was aimed to explore the pharmacokinetics of epiberberine, jatrorrhizine, coptisine, palmatine, berberine of Jiaotai pill in the normal and depressed rats. According to ‘Katz’ method, the model of chronic unpredictable mild stress (CUMS) was established. The extract of Jiaotai pill was orally administered to rats, and the blood samples were collected via the the oculi chorioideae vein according to the time schedule. The concentrations of epiberberine, jatrorrhizine, coptisine, palmatine, berberine in rat plasma were determined by LC-MS/MS, and the pharmacokinetic parameters were calculated by DAS1.0 software. Compared with normal rats, the Cmax of palmatine, coptisine, berberine and jatrorrhizine in Jiaotai pill in depressed rats were 1.99, 2.14, 2.3, 1.82 times than the normal group, while the AUC0−t were 1.23, 1.25, 1.29, 1.46 times and the AUC0−∞ were 1.21, 1.25, 1.30, 1.43 times, which were significantly different.
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Objective: To study the mechanism of Jiaotai Pill on inflammation and anti-inflammatory cytokines in mice with chronic unpredictable mild stress (CUMS) depression. Methods: Mice were treated with CUMS depression model, then the weight comparison, sugar test, opening experiment was conducted; The levels of IL-1β, IL-6 and TNF-α, IL-4, and IL-10 in the serum and hippocampus of rats were measured by enzyme-linked immunosorbent assay (ELISA), and rat hippocampal neuron morphology was observed by Nissl's staining. Results: Compared with the blank group, the consumption of sugar, the number of crosses and the number of vertical bars in the model group were significantly decreased; The levels of IL-1β, IL-6, TNF-α, and IL-4 in serum and hippocampus were significantly higher than those in the blank group, and IL-10 significantly reduced; Hippocampal neurons stratified unclear, arranged disorder, Nissie shallow staining or disappear. Compared with the model group, the consumption of sugar, the number of crosses and the number of vertical bars in Jiaotai Pill administration group were significantly increased; The levels of IL-1β, IL-6, and TNF-α in serum and hippocampus were significantly decreased, and the levels of IL-4 and IL-10 was significantly increased; Hippocampal neuronal stratification was more obvious, Nissl shallow staining. Conclusion: Jiaotai Pill can significantly improve the behavior of rat depression and hippocampal neuronal injury whose mechanism may be related to down-regulation of serum and hippocampus proinflammatory cytokines IL-1β, IL-6, TNF-α, up-regulation of anti-inflammatory cytokines IL-4 and IL-10.
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<p><b>OBJECTIVE</b>To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
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Objective: To study the effects of Jiaotai Pill on the behavior and monoamine neurotransmitters of chronic mild unpredictable stress (CUMS) depression rat model and to investigate the anti-depression effect and mechanism of Jiaotai Pill. Methods: A total of 72 SD rats were divided into six groups randomly, namely control, model, positive drug (fluoxetine hydrochloride, 7.5 mg/kg), low-, mid-, and high-doses of Jiaotai Pill (crude drug 0.75, 1.5, and 3 g/kg) groups (n = 12), which were reared in cage and execpt the control group, the other five groups of rats were given CUMS to stimulate the production of CUMS depression model, then ig given Jiaotai Pill for 14 d. Rats in each group were measured the body weight and the rate of sucrose preference once a week to observe the open-field activity behavior (through the horizontal grid and the number of vertical changes) at the 5th week. All the animals were killed to get the blood and brain cortex to test the levels of NE, 5-HT, and 5-HIAA in hippocampus, cortex, and hypothalamus by high performance liquid chromatography (HPLC). Results: Compared with the model group, the test indexes of rat body weight, sucrose water consumption, and the open-field activity behavior were significantly increased in the low-, mid-, and high-dose of Jiaotai Pill groups. And the contents of NE and 5-HT increased, while the content of 5-HIAA decreased obviously in the hippocampus, cortex, and hypothalamus in all Jiaotai Pill groups (P < 0.05 or 0.01). Conclusion: Jiaotai Pill has a better antidepressant effect whose mechanism is related to increasing the level of monoamine neurotransmitters in the cerebral cortex.
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<p><b>OBJECTIVE</b>To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells.</p><p><b>METHODS</b>Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction.</p><p><b>RESULTS</b>PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study.</p><p><b>CONCLUSION</b>It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.</p>
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Animals , Mice , AMP-Activated Protein Kinases , Metabolism , Berberine , Chemistry , Pharmacology , Cell Line , Cinnamates , Chemistry , Pharmacology , Fatty Acids , Metabolism , Gene Expression Regulation , Insulin-Secreting Cells , Metabolism , Intracellular Space , Metabolism , Lipogenesis , Genetics , Oxidation-Reduction , Palmitic Acid , Toxicity , Triglycerides , MetabolismABSTRACT
Objective To discuss the sedative and hypnotic effect of Jiaotai Pills on insomnia in PCPA rat model .Methods The PCPA ( PCPA acid) rats insomnia model was established, and the rats were divided into the model group, high, middle and low dosage of Jiaotai Pills group, and diazepam positive control group.The high performance liquid detective method was adopted to observe the effect of Jiaotai Pills on rat insomnia and hypothalamus neurotransmitters 5-HT and GABA.Results Compared with the model group, there existed significant difference in the insomnia state of rats and the central neurotransmitters 5 -HT in the high and middle dosages of Jiaotai Pill group and diazepam group.However, in the comparison of the high and middle dosages of Jiaotai Pill group and the model group, there was no significant difference in GABA in the central nervous system .Conclusion Jiaotai Pills has sedative and hypnotic efficacy.Its mechanism may be related to the effects of central neurotransmitter 5 -HT.Its relationship with GABA in the central nervous system is not obvious.The research has significant influence on the further development of Jiaotai Pills.
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Objective To explore the therapeutic mechanism of Jiaotai Pill(JP) for restoring normal coordination between the heart and the kidney.Methods Fifty SD rats were equally randomized into normal group,model group,Huanglian(Rhizoma Coptidis,15g) group,Rougui(Cortex Cinnamomi,1.5g) group,and JP group(the ratio of Huanglian and Ruigui being 15∶1.5).Insomnia rat models were induced by intraperitoneal injection of one-dose para-chloroamphetamine acid(PCPA,300mg/kg),and the serum interleukin-1(IL-1) and tumor necrosis factor(TNF-?) levels were detected by enzyme-linked immunosorbent assay(ELISA).Results In the model group,the serum levels of IL-1 and TNF-? were decreased(P0.05 compared with the model group),and increased in JP group(P
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WAE. Conclusion SBE method is better than the other three methods in the extraction of Jiaotai Pill components.
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Objective:To optimize the extraction condtions in the modification of the formula of Jiaotai Pill. Methods: The semi bionic extraction (SBE) conditions were optimized through homogeneous design while berberine, cinnamic acid, total alkaloids, volatile oil and dry extract were adopted as markers. Results: PH in first extraction was adjusted to 2.20 by the use of HCL solution. And then PH in second and third extraction adjusted to 6.50 and 7.80 , duration of run was 170 min, 80 min and 40 min, respectively. Conclusion: Semi bionic extraction in Jiaotai Pill is approximated to theoretical extraction value.
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AB; and there is not obvious difference in the TLC of 2 kinds of extraction liquid, but there is difference in the GC of volatile oil in them. Conclusion: It is the best combination to extract Rhizoma Coptidis and Cortex Cinnamomi seperately.