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Objective: We aimed to analyze the mechanisms underlying spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction derived from the trimethylamine N-oxide (TMAO) metabolic pathway of intestinal microbiota in the treatment of macrovascular lesions caused by type 2 diabetes mellitus (T2DM). Methods: Hartley-guinea pigs were randomly divided into 3 groups-the blank, model, and intervention groups. The T2DM combined with atherosclerosis guinea pig models were established in the model and intervention groups. After successful modeling, spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction were administered intragastrically to the intervention group, while the same volume of normal saline was administered via gavage to the blank and model groups. After 6 weeks of continuous gavage, guinea pigs were sacrificed in all groups, the colon contents were obtained, and the diversity and structural differences of intestinal microbiota were analyzed via bioinformatics. Serum was collected to detect differences in lipids, TMAO, oxidative stress, and inflammation markers between groups. Results: Compared to the blank group, the species diversity of the intestinal microbiota in the model and intervention groups was significantly reduced. Based on the results of Analysis of Similarities and Multiple Response Permutation Procedure, the microbiota structure of the intervention group was closer to that of the blank group. After modeling, the blood lipid levels of guinea pigs increased significantly, and drug intervention significantly reduced the levels of TC, TG, and LDL-C (P < 0.05). TMAO expression was significantly increased after modeling (P < 0.05), while drug intervention reduced TMAO expression (P < 0.05). Compared to the model group, drug intervention significantly increased the concentrations of SOD while decreasing the concentrations of MDA, ICAM-1, VCAM-1, IL-6, and hs-CRP. Conclusion: Spleen-and-stomach-tonifying, yin-fire-purging, and yang-raising decoction can reduce the risk of macrovascular lesions in T2DM, and its mechanism may be associated with its ability to regulate the TMAO metabolic pathway of intestinal microbiota.
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Mercury is a highly toxic heavy metal with definite cardiotoxic properties and can affect the health of humans and animals through diet. Selenium (Se) is a heart-healthy trace element and dietary Se has the potential to attenuate heavy metal-induced myocardial damage in humans and animals. This study was designed to explore antagonistic effect of Se on the cardiotoxicity of mercuric chloride (HgCl2) in chickens. Hyline brown hens received a normal diet, a diet containing 250 mg/L HgCl2, or a diet containing 250 mg/L HgCl2 and 10 mg/kg Na2SeO3 for 7 weeks, respectively. Histopathological observations demonstrated that Se attenuated HgCl2-induced myocardial injury, which was further confirmed by the results of serum creatine kinase and lactate dehydrogenase levels assay and myocardial tissues oxidative stress indexes assessment. The results showed that Se prevented HgCl2-induced cytoplasmic calcium ion (Ca2+) overload and endoplasmic reticulum (ER) Ca2+ depletion mediated by Ca2+-regulatory dysfunction of ER. Importantly, ER Ca2+ depletion led to unfolded protein response and endoplasmic reticulum stress (ERS), resulting in apoptosis of cardiomyocytes via PERK/ATF4/CHOP pathway. In addition, heat shock protein expression was activated by HgCl2 through these stress responses, which was reversed by Se. Moreover, Se supplementation partially eliminated the effects of HgCl2 on the expression of several ER-settled selenoproteins, including selenoprotein K (SELENOK), SELENOM, SELENON, and SELENOS. In conclusion, these results suggested that Se alleviated ER Ca2+ depletion and oxidative stress-induced ERS-dependent apoptosis in chicken myocardium after HgCl2 exposure.
Subject(s)
Selenium , Humans , Animals , Female , Selenium/pharmacology , Selenium/metabolism , Chickens , Calcium/metabolism , Mercuric Chloride/toxicity , Mercuric Chloride/metabolism , Apoptosis , Myocardium , Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Cardiotoxicity/metabolismABSTRACT
To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.
Subject(s)
Animals , Mice , Bile Acids and Salts , Chromatography, Liquid , Drugs, Chinese Herbal , Ileum , Liver , Sleep Initiation and Maintenance Disorders/drug therapy , Tandem Mass SpectrometryABSTRACT
BACKGROUND: The intensity of electrical acupoint stimulation such as electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS) is regulated by the observation of skin shivering or the participant's comfort response. However, the specific intensity and spatial scope following EA or TENS stimulation are unclear. OBJECTIVE: This study aimed to test the stimulatory current intensities of lower and upper sensation thresholds in TENS- and EA-based treatment of Bell's palsy patients. Also, the spatial scope of the stimulation at these current intensities was simulated and measured quantitatively. METHODS: A total of 19 Bell's palsy patients were recruited. Six acupoints on the affected side of the face were stimulated by TENS and EA successively at 30-min intervals. During the stimulation, the current intensity was regulated gradually from 0 to 20 mA, and we simultaneously measured the lower (sensory) and upper (tolerability) sensations. After the treatment by TENS and EA, the modified Chinese version of the Massachusetts General Hospital Acupuncture Sensation Scales (C-MMASS) was applied to survey the de-qi sensations during stimulation. Additionally, we analyzed the correlation between current intensities and C-MMASS and comfort scores. Finite element models were established to depict the spatial distribution of electric field gradients at the lower and upper thresholds. RESULTS: The mean sensory and tolerability thresholds of TENS were 3.91-4.37 mA and 12.33-16.35 mA, respectively. The median sensory and tolerability thresholds of EA were 0.2 mA and 2.0-3.2 mA, respectively. We found a significant correlation between total C-MMASS scores and the current intensities at the tolerability threshold of TENS. The finite element model showed that the activated depths of TENS and EA at the lower threshold were 3.8 and 7 mm, respectively, whereas those at the upper threshold were both 13.8 mm. The cross-sectional diameter of the activated area during TENS was 2.5-4 times larger than that during EA. CONCLUSION: This pilot study provided a method for exploring the current intensity at which the de-qi sensations can be elicited by TENS or EA. The finite element analysis potentially revealed the spatial scope of the electrical stimulation at a specific current intensity.
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To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.
Subject(s)
Animals , Mice , Bile Acids and Salts , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Mice, Inbred ICR , Reproducibility of Results , Sleep , Tandem Mass SpectrometryABSTRACT
To determine if the effect of manipulative acupuncture monitored by laser speckle contrast imaging (LSCI) can improve facial blood perfusion in patients with severe Bell's palsy. This randomized, single-blind, controlled trial included 120 newly diagnosed patients (within 14 days) with severe Bell's palsy (House-Brackmann grading system (HBGS) ≥ grade IV). The patients were randomized (1 : 1) to receive either acupoints acupuncture combined with manipulations of twirling, lifting, and thrusting treatments (manipulative acupuncture) or acupoints acupuncture therapy alone (simple acupuncture). These treatments consisted of a total of 24 sessions, three times per week, and each treatment lasted for 30 min. Following 8 weeks of treatment and 6 months after the initial onset of facial palsy, facial nerve functioning was scored (HBGS) and clinical efficacy was measured. The patients' facial blood perfusion significantly improved following manipulative acupuncture assisted by LSCI compared with that at baseline (P < 0.01). At the conclusion of the 8-week treatment, both groups showed improvement; however, the recovery rate was significantly different (manipulative acupuncture 53.3% vs. simple acupuncture 33.9%, P < 0.05). Follow-up analysis at 6 months after the onset of facial palsy revealed a significantly higher recovery rate (91.7% vs. 78.0%; P < 0.05). In addition, the number of treatments in the observation group was less than that in the simple acupuncture therapy group (P < 0.05). Compared with simple acupuncture therapy, manipulative acupuncture therapy led to a more significant recovery rate in the treatment of severe Bell's palsy and required a shorter course of treatment. This trial was registered with ChiCTR1800019463.
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INTRODUCTION: Preliminary evidence from clinical observations suggests that Tai Chi exercise may offer potential benefits for patients with chronic coronary syndrom (CCS). However, the advantages for CCS patients to practice Tai Chi exercise as rehabilitation have not been rigorously tested and there is a lack of consensus on its benefits. This study aims to develop an innovative Tai Chi Cardiac Rehabilitation Program (TCCRP) for CCS patients and to assess the efficacy, safety and acceptability of the programme. METHODS AND ANALYSIS: We propose to conduct a multicentre randomised controlled clinical trial comprising of 150 participants with CCS. The patients will be randomly assigned in a 1:1 ratio into two groups. The intervention group will participate in a supervised TCCRP held three times a week for 3 months. The control group will receive supervised conventional exercise rehabilitation held three times a week for 3 months. The primary and secondary outcomes will be assessed at baseline, 1 month, 3 months after intervention and after an additional 3-month follow-up period. Primary outcome measures will include a score of 36-Item Short Form Survey and Chinese Perceived Stress Scale. The secondary outcome measures will include body composition, cardiopulmonary exercise test, respiratory muscle function, locomotor skills, echocardiogram, New York Heart Association classification, heart rate recovery time and laboratory examination. Other measures also include Seattle Angina Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 and Berg Balance Scale. All adverse events will be recorded and analysed. ETHICS AND DISSEMINATION: This study conforms to the principles of the Declaration of Helsinki and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of Chinese People's Libration Army General Hospital (approval number: S2019-060-02). Findings from this study will be published and presented at conferences for widespread dissemination of the results. TRIAL REGISTRATION NUMBER: NCT03936504.
Subject(s)
Cardiac Rehabilitation/methods , Coronary Disease/rehabilitation , Tai Ji , Adolescent , Adult , Aged , Aged, 80 and over , Angina Pectoris/etiology , Anxiety/etiology , Chronic Disease/psychology , Chronic Disease/rehabilitation , Coronary Disease/complications , Coronary Disease/physiopathology , Coronary Disease/psychology , Exercise Therapy , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Patient Acceptance of Health Care , Quality of Life , Randomized Controlled Trials as Topic , Research Design , Stress, Psychological/etiology , Tai Ji/adverse effects , Young AdultABSTRACT
Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is an anthraquinone compound mainly isolated from the herbal medicine rhubarb. It possesses a wide spectrum of pharmacological effects. However, the lack of sustained release properties and the poor bioavailability hinder clinical transformation. Hydrogel-based drug delivery system provides an ideal carrier to improve the release control and the therapeutic efficacy of drugs. Herein, we present a chitosan hydrogel for the delivery of rhein. This rhein-chitosan hydrogel (CS-Rh gel) exhibited superior characteristics including mechanical strength, sustained release, and low toxicity. For medical application, the enzyme-linked immunosorbent assay and Western blot analyses indicated that CS-Rh gel significantly suppressed the production of proinflammatory cytokines including TNF-α and IL-1ß in lipopolysaccharide-induced BV2 cells. Additionally, CS-Rh gel blocked the neuroinflammation-related mitogen-activated protein kinase (JNK, ERK, and p38)-signaling pathways. Interestingly, these inhibitory effects at 48 h outperformed the pharmacologic actions at 24 h, showing that the CS-Rh gel exerted optimal sustained antineuroinflammation. This study highlights a novel chitosan hydrogel containing rhein used as a potential antineuroinflammatory agent.
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OBJECTIVE: To evaluate the effect of Buyang Huanwu Decoction (, BYHWD) on glial scar after intracerebral hemorrhage (ICH) and investigate the underlying mechanism. METHODS: Collagenase type VII (0.5 U) was injected stereotaxically into right globus pallidus to induce ICH model. One hundred and twenty Sprague-Dawley rats were randomly divided into 3 groups according to a random number table, including normal group (n=40), ICH model group (n=40) and BYHWD group (n=40), respectively. After ICH, the rats in the BYHWD group were intragastrically administered with BYHWD (4.36 g/kg) once a day for 21 days, while the rats in ICH group were administered with equal volume of distilled water for 21 days, respectively. Double immunolabeling was performed for proliferating cell nuclear antigen (PCNA)+/glial fibrillary acidic protein (GFAP)+ nuclei. The expression of GFAP and leukemia inhibitory factor (LIF) was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The astrocytes with hypertrophied morphology around the hematoma was observed on day 3 after ICH. The number of GFAP positive cells and GFAP mRNA levels increased notably on day 3 and reached the peak on day 14 post-ICH (P<0.01). PCNA+/GFAP+ nuclei were observed around the hematoma and reached the peak on day 14 post-ICH (P<0.01). In addition, LIF-positive astrocytes and LIF mRNA level in the hemorrhagic region increased significantly till day 14 post-ICH (P<0.01). However, BYHWD not only reduced the number of PCNA+/GFAP+ nuclei, but also decreased GFAP and LIF levels (P<0.05). CONCLUSIONS: BYHWD could attenuate ICH-induced glial scar by downregulating the expression of LIF in the rats.
Subject(s)
Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/genetics , Cicatrix/drug therapy , Down-Regulation , Drugs, Chinese Herbal/therapeutic use , Leukemia Inhibitory Factor/genetics , Neuroglia/pathology , Animals , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Leukemia Inhibitory Factor/metabolism , Male , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: Sarcopenia, an age-related decline of muscle mass, strength, and physical function, was associated with falls, frailty, and poor quality of life. The aim of the current study is to examine the effect of nutritional supplement containing whey protein, vitamin D and E on measures of sarcopenia. METHODS: A total of 60 sarcopenic older adult subjects participated in the current randomized, double-blind, placebo-controlled (iso-caloric control product) trial for 6 months. Muscle mass [Relative skeletal mass index (RSMI) measured by bioimpedance analysis (BIA)], muscle strength (handgrip strength), physical function (6-m gait speed, chair stand test, and timed-up-and-go test, TUG), quality of life (measured by Short-Form 36-Item Health Survey, SF-36), and blood biochemical indexes were measured before and after the 6-month intervention. RESULTS: Compared to placebo group, nutritional supplementation improves RSMI (mean difference: 0.18 kg/m2, 95%CI: 0.01-0.35, P = 0.040), handgrip strength (mean difference: 2.68 kg, 95%CI: 0.71-4.65, P = 0.009), SF-36 mental component summary (SF-36 MCS) (mean difference: 11.26, 95%CI: 3.86-18.65, P = 0.004), SF-36 physical component summary (SF-36 PCS) (mean difference: 20.21, 95%CI: 11.30-29.12, P < 0.001), serum IGF-1 (mean difference: 14.34 ng/mL, 95%CI: 2.06-26.73), IL-2 (mean difference: -575.32 pg/mL, 95%CI: -1116.94 â¼ -33.70, P = 0.038), serum vitamin D3 (mean difference: 11.01 ng/mL, 95%CI: 6.44-15,58, P < 0.001), and serum vitamin E (mean difference: 4.17 ng/L, 95%CI: 1.89-6.45, P = 0.001). CONCLUSION: The current study demonstrated that the combined supplementation of whey protein, vitamin D and E can significantly improve RSMI, muscle strength, and anabolic markers such as IGF-I and IL-2 in older adults with sarcopenia. Further larger well-designed studies are warranted to evaluate whether long-term whey protein supplementation can blunt the declines of muscle function and mass in older adults with sarcopenia.
Subject(s)
Dietary Supplements , Muscle Strength/drug effects , Quality of Life , Sarcopenia/diet therapy , Vitamin D/therapeutic use , Vitamin E/therapeutic use , Whey Proteins/therapeutic use , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Muscle, Skeletal/drug effects , Vitamins/therapeutic useABSTRACT
Nitrogen (N) is an essential macronutrient for plant development and growth, and the deposition of N has increased in recent decades. Legumes that fix N can also provide N for nearby species. However, N in soil inhibits N fixation. We tested the effects of N fertilisation on one N-fixing (Robinia pseudoacacia) and two non-N-fixing (Sophora japonica and Senna surattensis) woody legume species, which were subjected to five different N levels (0, 1.5, 2.9, 5.9 and 11.4 mg N per plant day-1) under greenhouse conditions. The growth of the two non-N-fixing species was promoted by N supply, while that of R. pseudoacacia was unaffected. Among the three species, R. pseudoacacia had the largest specific leaf area and chlorophyll concentration, S. japonica had the largest root-to-shoot ratio and main root-to-lateral root ratio, and S. surattensis had the largest leaf N and phosphorus concentrations. The N-fixing species was mostly unaffected by N supply. The growth, leaf chlorophyll concentration, and leaf number in the non-N-fixing species were promoted by N supply. The N-fixing species showed better growth in low-N environments, while under increased N deposition, its growth was similar to that of the non-N-fixing species.
Subject(s)
Fabaceae/drug effects , Fabaceae/growth & development , Nitrogen Fixation/drug effects , Nitrogen/pharmacology , Robinia/drug effects , Robinia/growth & development , Wood/drug effects , Wood/growth & development , Ecosystem , Environment , Plant Leaves/drug effects , Plant Leaves/growth & development , Plant Roots/drug effects , Plant Roots/growth & development , Plant Shoots/drug effects , Plant Shoots/growth & development , Soil/chemistryABSTRACT
The aim of the present study was to compare the different effects of berberine (Ber) and Coptischinensis extract (CCE) on a rat model of type 2 diabetes mellitus (T2DM), and the islet Rin5f cell line was used to examine the differences between Ber and CCE and the underlying mechanisms. CCE was extracted and purified prior to analysis. Male SpragueDawley rats were provided with a highfat diet to induce insulin resistance prior to injecting with streptozotocinto establish the T2DM model, the T2DM rats were treated with Ber and CCE, and blood samples and pancreatic tissues were obtained and compared to examine T2DM metabolic syndromes among the groups of rats, which included healthy rats, model rats, and model rats treated with Ber and CCE at different doses between 0 and 8 weeks. The protective effects of Ber and CCE on the Rin5f islet cell line were also evaluated. The effects on Rin5f cell proliferation and cell cycle, glucosestimulated insulin release test (GSIS), the antiapoptotic effects caused by fat induction, and protein expression levels of poly ADPribose polymerase (PARP1) were evaluated. The results showed that the content of the prepared CCE was 96.07% for five alkaloids. When it was used for treatment of the T2DM rats, compared with Ber, metformin and rosiglitazone, the fasting blood glucose, glucosylated serum protein (GSP) and glucose infusion rate indicesin the fasting rats were ameliorated, compared with those in the T2MD rats, with no significant differences between treatment with Ber or CCE and metformin or rosiglitazone. The indices of mean optical density and fasting ßcell function index (FBCI) were different following treatment with Ber and CCE, compared with those in the model rats, which may have stimulated the pancreatic secretion of insulin. When Ber and CCE were used to examine the protective effects on Rin5F cells, it was found that the Rin5f cell GSIS, cell cycle, lipotoxic islet cell proliferation and protein expression of PARP1 were altered and improved, which may have protected pancreatic islet ßcells by improving islet ßcell proliferation and the protein expression of PARP1. CCE and Ber exerted similar effects when used for the treatment of T2MD rats, and may have stimulated the pancreatic secretion of insulin through the protective effect on islet ßcells via improving islet ßcell proliferation and the protein expression of PARP1.
Subject(s)
Berberine/pharmacology , Cell Proliferation/drug effects , Diabetes Mellitus, Type 2/pathology , Plant Extracts/pharmacology , Protective Agents/pharmacology , Animals , Blood Glucose/analysis , Cell Cycle Checkpoints/drug effects , Cell Line , Cell Survival/drug effects , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/veterinary , Diet, High-Fat , Glucose/metabolism , Glycation End Products, Advanced/analysis , Insulin/metabolism , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Male , Pancreas/metabolism , Pancreas/pathology , Plant Extracts/chemistry , Ranunculaceae/chemistry , Ranunculaceae/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: Hyperbaric oxygen (HBO) is widely used in treating various neurological diseases. However, HBO for treatment of intracerebral haemorrhage (ICH) remains controversial, in either animal or clinical studies. Therefore, we conducted this systematic review and meta-analysis on studies describing the efficacy of HBO in animal models of ICH. METHODS: Studies were identified by searching mainstream databases through November 2015. The efficacy of HBO in animal models of ICH was assessed by changes in the brain water content (BWC), neurobehavioural outcome (NO) or both. Subgroup analyses were performed according to different design characteristics. RESULTS: In total 15 studies met our inclusion criteria. HBO can reduce the BWC (-0.982, 95% CI, -1.148 to -0.817; P < 0.01; 57 comparisons), and improve NO (-0.767, 95% CI, -1.376 to -0.159; P < 0.01; eight comparisons). HBO was most effective in reducing BWC when given 72 h after ICH for a 4- to 5-day consecutive treatment at the chamber pressure of 3.0 atmosphere absolute. Efficacy was higher with phenobarbital anaesthesia, the blood infusion model and in rabbits. CONCLUSION: Although HBO was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality and the limited number of studies conducting clinical trials.
Subject(s)
Cerebral Hemorrhage/metabolism , Cerebral Hemorrhage/therapy , Disease Models, Animal , Hyperbaric Oxygenation/methods , Animals , Brain/metabolism , Brain/pathology , Cerebral Hemorrhage/pathology , HumansABSTRACT
OBJECTIVE: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. METHODS: Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT). RESULTS: The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p < 0.01), but not with mental arithmetic efficiency or recognition memory (p > 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)-not working memory (p = 0.113). CONCLUSION: n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made.
Subject(s)
Cognition/drug effects , Cognitive Dysfunction/drug therapy , Dietary Supplements , Fatty Acids, Omega-3/administration & dosage , Aged , Asian People , China , Cognitive Dysfunction/blood , Diet , Docosahexaenoic Acids/administration & dosage , Docosahexaenoic Acids/blood , Double-Blind Method , Eicosapentaenoic Acid/administration & dosage , Eicosapentaenoic Acid/blood , Fatty Acids, Omega-3/blood , Female , Humans , Interleukin-6/blood , Lipoxygenase/blood , Male , Phospholipases A2/blood , Prostaglandin-Endoperoxide Synthases/blood , Treatment Outcome , Tumor Necrosis Factor-alpha/bloodABSTRACT
OBJECTIVES: To evaluate the effectiveness and safety of Guipi Decoction (, GPD) as an adjunctive in the treatment of depression. METHODS: A review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction: Excerpt Medica Database (EMBASE), PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database. Papers published until February 2013 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.1. RESULTS: Nine randomized controlled trials involving 620 patients with depression were included in this review. The meta-analysis revealed that compared with antidepressant therapy alone, treatment with a combination of GPD and an antidepressant drug signifificantly improved the symptoms of depression [weighted mean difference (WMD):-3.09; 95% confifidence interval (CI):-4.11 to-2.07] and increased the rates of effectiveness (OR: 4.75; 95% CI: 2.66-8.51) as well as recovery (OR: 1.73; 95% CI: 1.17-2.56). The adverse effects of GPD were not found to be signifificant in these studies. CONCLUSIONS: The fifindings of this meta-analysis were in keeping with the notion that GPD formulations were effective in the treatment of depression without causing any serious adverse effects. However, currently available evidence was of low quality and therefore inadequate to justify a strong recommendation of using GPD formulations in the management of depression.
Subject(s)
Depression/drug therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Randomized Controlled Trials as Topic , Antidepressive Agents/administration & dosage , Antidepressive Agents/adverse effects , Antidepressive Agents/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Humans , Medicine, Chinese Traditional/adverse effects , Publication Bias , Treatment OutcomeABSTRACT
Coptidis rhizoma (Coptis) and its alkaloids exert various pharmacological functions in cells and tissues; however, the oral absorption of these alkaloids requires further elucidation. The present study aimed to examine the mechanism underlying the poor absorption of alkaloids, including berberine (BER), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT). An ultraperformance liquid chromatography (UPLC) method was validated for the determination of BER, COP, PAL and JAT in the above experimental medium. In addition, the apparent oilwater partition coefficient (Po/w); apparent permeability coefficient (Papp), determined using a parallel artificial membrane permeability assay (PAMPA) plate; membrane retention coefficient (R %); and effect of Pglycoprotein (Pgp) inhibitor on the Papp of the four alkaloids were investigated. The intestinal absorption rate constant (Ka) and absorption percentage (A %) of the four alkaloids were also determined. The results of the present study demonstrated that the Po/w of the four alkaloids in 0.1 mol·l1 HCl medium was significantly higher (P<0.01), compared with those of the alkaloids in phosphate buffer (pH 7.4). The Papp of BER was 1.01.2x106 cm·s1, determined using a PAMPA plate, and the Papp of BER, COP, PAL and JAT decreased sequentially. The concentrations of the four alkaloids on the apicaltobasolateral (APBL) surface and the basolateraltoapical (BLAP) surface increased in a linear manner, with increasing concentrations between 10 and 100 µmol. In addition, the transportation of BER on the BLAP surface was significantly faster (P<0.01), compared with that on the APBL surface and, following the addition of verpamil (a Pgp inhibitor), the Papp (APBL) of the four alkaloids increased, whereas the Papp (BLAP) was significantly decreased (P<0.01). The rat intestinal perfusion experiment demonstrated that the four alkaloids were poorly absorbed; however, the Ka of BER was significantly higher, compared with the three other alkaloids. Furthermore, the A % and Ka provided evidence that the absorption of BER was increased in the jejunum, compared with in the ileum. In conclusion, the four alkaloids from Coptis appeared to be poorly absorbed, determined using a shake flask, precoated PAMPA plates, a Caco2 cell monolayer model and intestinal perfusion; however, absorption was higher in the jejunum than in the ileum. Among the four alkaloids, the permeability of BER was markedly higher than the others, and Pgp efflux had a significant effect on the absorption of those alkaloids.
Subject(s)
Alkaloids/metabolism , Coptis/chemistry , Plant Extracts/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Alkaloids/isolation & purification , Alkaloids/pharmacokinetics , Animals , Caco-2 Cells , Humans , Intestinal Absorption , Jejunum/metabolism , Male , Permeability , Plant Extracts/isolation & purification , Plant Extracts/pharmacokinetics , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Intracerebral hemorrhage (ICH) is a fatal subtype of stroke that lacks effective treatments. Angiogenesis following ICH is an important response mediating brain recovery and repair. Phosphorylation of vascular endothelial growth factor receptor 2 (pVEGFR2) via PI3K/Akt signaling plays a key role in mediating cellular processes involved in repair, such as mitogenesis, angiogenesis, and vascular permeability. This study aimed to investigate the potential effects of Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula, on angiogenesis by VEGFR2 activation through the phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway in a mouse model of ICH. METHODS: Adult male Kunming mice (n = 50) were randomly assigned into sham and ICH-operated groups and treated with one of the followings SU5416 (VEGFR2 inhibitor), BYHWT and BYHWT + SU5416. ICH was induced in mice by injecting collagenase (type VII) into the right globus pallidus of the mouse brain. BYHWD (4.36 g/kg) was administrated in mice by intragastric infusion. Neurological function was evaluated in mice by a modified Neurological Severity Scores (mNSS) as well as corner turn and foot-fault tests. Angiogenesis was examined by intraperitoneal injection of 5-bromodeoxyuridine (BrdU) in mice to quantify new brain vessel growth. SU5416 treatment and assessment of VEGFR2 phosphorylation as well as alterations in PI3K/Akt signaling were performed to determine whether the effect of BYHWD on angiogenesis was partly mediated by phosphorylation of VEGFR2 via the PI3K/Akt signaling pathway. RESULTS: We show that BYHWD treated mice exhibited (i) significantly better recovery from neurological dysfunction, (ii) increased BrdU(+) nuclei in vWF(+) dilated brain vessels and (iii) higher VEGFR2 phosphorylation immunoreactivity in brain microvessels (P <0.05), (iv) higher expression of PI3K and pAkt at the protein level (P <0.05) when compared to untreated ICH mice. These beneficial effects were reversed by SU5416 (P <0.05). CONCLUSIONS: BYHWD promoted neurological recovery and angiogenesis after ICH in mice by enhancing VEGFR2 phosphorylation through the PI3K/Akt signaling pathway.
Subject(s)
Brain/drug effects , Cerebral Hemorrhage/drug therapy , Drugs, Chinese Herbal/therapeutic use , Neovascularization, Physiologic/drug effects , Phosphatidylinositol 3-Kinase/metabolism , Phytotherapy , Vascular Endothelial Growth Factor Receptor-2/metabolism , Animals , Astragalus Plant , Brain/blood supply , Cell Proliferation , Cerebral Hemorrhage/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Male , Mice , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Signal Transduction/drug effects , Stroke/drug therapy , Stroke/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Berberine (BER) and BER-original herbal medicines have a variety of pharmacological functions and have been widely used in clinical. However, its effect of enzyme induction on cytochrome P450 (CYP) in human hepatocytes is unknown. MATERIAL AND METHOD: Metabolism of berberine and its effect on main metabolic enzymes in HepG2 cell in vitro was investigated. Cocktail probe drugs, mRNA expression and protein expression were used to evaluate the metabolism potency. Meanwhile, an UPLC-MS/MS method was validated for the analysis of BER and four probe drugs in HepG2 cell. RESULT: BER significantly increased the metabolism of midazolam, phenacetin and tolbutamide by inducing the CYP1A2 and 3A4 enzyme in a dose-dependent manner, the mRNA and protein expression of CYP1A2 and 3A4 were increased by berberine at 1000ng·mL(-1). The activity of CYP1A2 and 3A4 could be induced by BER more than 500ng·mL(-1) in HepG2 cell, which was confirmed by the increase of its mRNA and protein expression. CONCLUSION: BER increases the metabolism of cocktail drugs such as midazolam, phenacetin and tolbutamide by increasing the mRNA and protein expression of CYP1A2 and 3A4.
Subject(s)
Berberine/metabolism , Cytochrome P-450 CYP1A2/biosynthesis , Cytochrome P-450 CYP3A/biosynthesis , Enzyme Induction/drug effects , Base Sequence , Berberine/pharmacology , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , DNA Primers , Hep G2 Cells , Humans , In Vitro Techniques , Polymerase Chain Reaction , RNA, Messenger/genetics , Tandem Mass SpectrometryABSTRACT
BACKGROUND: Angiopoietin (Ang) is one of the major effectors of angiogenesis, playing a critical role in neurovascular remodeling after stroke. Acupuncture has been widely used for treating stroke in China for a long time. Recently, we have demonstrated that electroacupuncture (EA) can accelerate intracerebral hemorrhage (ICH)-induced angiogenesis in rats. In the present study, we investigated the effect of EA on the expression of Ang-1 and Ang-2 in the brain after ICH. METHODS: ICH was induced by stereotactic injection of collagenase type VII into the right globus pallidus. Adult male Sprague-Dawley rats were randomized into the following four groups: sham-operation (SHAM), stroke-no electroacupuncture (SNE), stroke-EA at the Zusanli acupoint (SEZ), and stroke-EA at a nonacupoint (SEN). EA was applied to the bilateral Zusanli (ST36) acupoint in the SEZ group and a nonacupoint in the SEN group. The expression of Ang-1 and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Some Ang-1 and Ang-2 immunoreactive microvessels with a dilated outline were detected in the perihematomal tissues after ICH, and the vessels extended into the clot from the surrounding area since day 7. The expression of Ang-1 increased notably as long as 2 weeks after ICH, while Ang-2 immunoreactivity declined at about 7 days following a striking upregulation at 3 days. EA at the Zusanli (ST36) acupoint upregulated the expression of Ang-1 and Ang-2 at both the protein and mRNA levels. However, EA at a nonacupoint had little effect on the expression of Ang-1 and Ang-2. CONCLUSIONS: Our data suggest that EA at the Zusanli (ST36) acupoint exerts neuroprotective effects on hemorrhagic stroke by upregulation of Ang-1 and Ang-2.
Subject(s)
Angiopoietin-1/genetics , Angiopoietin-2/genetics , Brain Injuries/therapy , Electroacupuncture , Acupuncture Points , Angiopoietin-1/metabolism , Angiopoietin-2/metabolism , Animals , Brain/metabolism , Brain Injuries/genetics , Brain Injuries/metabolism , Brain Injuries/physiopathology , China , Humans , Male , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction (, KJD) by investigating the effects of KJD on behavior, monoamine neurotransmitter levels, and serotonin (5-HT) receptor subtype expression in the brain in a rat model of depression. METHODS: The rat depression model was established using chronic unpredictable mild stress (CUMS). Forty-eight Sprague Dawley rats were randomly divided into control, depression model (CUMS), CUMS+KJD (7.7 g/kg(-1)·d(-1) of crude drug), and CUMS+fluoxetine (2.4 mg/kg(-1)·d(-1)) groups (n=12 in each group), and the treatments lasted for 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine (NE), and dopamine (DA) and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptor mRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction. RESULTS: Compared with the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression. In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expression was higher than in the control group (P<0.05 or P<0.01). Treatment with KJD or fluoxetine partially attenuated these changes (P<0.05 or P<0.01). CONCLUSION: KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT1A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms of antidepressant effects of KJD.