Effects of Banxia Shumi Decoction on 5-hydroxytryptamine receptor, 5-HT, and 5-HIAA of chronic insomnia rats with internal obstruction of phlegm-dampness / 国际中医中药杂志

Objective:To observe the effects of Banxia Shumi Decoction on 5-HT 1AR, 5-HT 2AR, 5-HT, and 5-HIAA of chronic insomnia (CI) rats with internal obstruction of phlegm-damp (IOPD) type, to investigate the mechanisms of Banxia Shumi Decoction on resolving and draining dampness, guiding yang into yin and tranquilizing mind. Methods:A total of 48 Wistar rats were divided into control group, model group, Banxia Shumi Decoction low-dosage group, medium-dosage group, high-dosage group, and diazepam group according to random number table method, with 8 rats in each group. Except the control group, the CI with IOPD rats model were prepared by the method of "high-fat diet + single-platform water environment" in other groups. The rats in the Banxia Shumi Decoction low-, medium-, high-dosage group were treated with Banxia Shumi Decoction by gavage at the dose of 4.69, 9.38 and 18.75 g/kg respectively, the rats in the diazepam group were given 0.52 mg/kg diazepam aqueous solution by gavage, and the rats in the control group and model group were given the equal volume normal saline, once a day for consecutive 2 weeks. The mRNA expressions of 5-HT 1AR, 5-HT 2AR in rat brain stem were detected by qPCR, the protein expressions of 5-HT 1AR, 5-HT 2AR in rat brain raphe nucleus were detected by Western blot, and the contents of 5-HT and 5-HIAA in rat brain stem were determined by HPLC-MS. Results:Compared with model group, the expression of 5-HT 1AR mRNA significantly increased in the Banxia Shumi Decoction low-, medium-, high-dosage group, and diazepam group ( P<0.01); the expression of 5-HT 2AR mRNA significantly decreased in the Banxia Shumi Decoction high-dosage group and diazepam group ( P<0.05), and the expression of 5-HT 1AR and 5-HT 2AR significantly increased in the Banxia Shumi Decoction high-dosage group and diazepam group ( P<0.05 or P<0.01); 5-HT content significantly increased in the Banxia Shumi Decoction medium-, high-dosage group and diazepam group ( P<0.05 or P<0.01); 5-HIAA content significantly increased in the Banxia Shumi Decoction low-, medium-, high-dosage group, and diazepam group ( P<0.05 or P<0.01). Conclusion:Banxia Shumi Decoction may intervene CI with IOPD type and perform the actions of resolving and draining dampness, guiding yang into yin and tranquilizing mind by regulating the expressions of 5-HT 1AR, 5-HT 2AR, 5-HT and 5-HIAA.

Dissecting the novel abilities of aripiprazole: The generation of anti-colorectal cancer effects by targeting Gαq via HTR2B

Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo, but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (Gαq) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of Gαq to HTR2B was decreased after Ari treatment. Knockdown of Gαq not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and Gαq was found in that the mutation at amino acid 190 of Gαq reduced the efficacy of Ari. Thus, these results confirm that Gαq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.

Down-regulation effects of IFN-alpha on p11, 5-htr1b and 5-HTR4 protein levels were affected by NH4CL or MG132 treatment in SH-sy5y cells

Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed aftertreatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterallyovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX?OA control, OVX?OA ? diclofenac (5 mg/kg) (positive control), OVX?OA ? LP leaf extract (150 and300 mg/kg) and healthy sham control. After 8 weeks’ treatment, their conditions were evaluated via serum biomarkers,knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilageerosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenacand the non-treated OA. The cartilage catabolic markers’ (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa,CASP3 and HIF-2a) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased byLP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilageprotective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondralbone restoration. The cartilage ERa over-expression showed a strong positive correlation with MMP-13, COL10a1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.

Progress of mechanism of 5-HT on bone metabolism / 医学研究生学报

5-HT as an important neurotransmitter which takes part in the development of many diseases, including bronchial asthma,schizophrenia and bone metabolism as reported in literatures in recent years. Central 5-HT can inhibit sympathetic excitations and promote bone formation through Tph2. Lrp5 can reduce the level of peripheral 5-HT and act on Tph1 to promote bone formation. Peripheral 5-HT blocks the association between transcription factor FOXO1 and CREB and inhibits bone formation. Peripheral 5-HT can also promote IL-6 expression and induce bone reabsorption. LP533401 as a Tph1 inhibitor could effectively reduce the level of peripheral 5-HT and induce bone formation as reported. In this paper, we try to summarize the effect of 5-HT on bone metabolism and its mechanism, and further using 5-HT to regulate bone quantity effectively.

Effect of Acupuncture Combined with Antidepressant on Behavioral Changes, and mRNA Expression of 5-Hydroxytryptamine Receptors in Nucleus Raphes Dorsalis of Sleep Deprivation Depression Rats / 广州中医药大学学报

Objective To investigate the effect of acupuncture combined with antidepressant on behavioral changes and 5-hydroxytryptamine 1A and 2A receptor ( 5-HT1AR and 5-HT2AR) mRNA expression in nucleus raphes dorsalis (NRD) of sleep deprivation depression (SDD) rats. Methods Eight normal Sprague Dawley (SD) rats were caged together without any stimulus or treatment, serving as the normal group. Thirty-two SD rats were given solitary raise for 21 days, together with chronic unpredictable mild stress ( CUMS) and rapid eye movement ( REM) sleep deprivation to establish the model. Twenty-eight rats completed the modeling successfully, and were divided into model group, acupuncture group, medicine group, and combination group, 7 rats in each group. Rats in the model group were given modeling treatment but without any intervention. Rats in the acupuncture group were given acupuncture on acupoint Yintang, Shenting and bilateral Taichong, acupuncture stimulation lasting 15 s every 10 min and acupuncture retention for 20 min in each day. Rats in the medicine group were given gastric gavage of Zoloft solution (0.83 mg·kg-1·d-1) and Alprazolam solution (0.067 mg· kg-1·d-1) , and rats in the combination group were given both acupuncture and medicine intervention. The intervention for the three intervention groups lasted for 7 days. Results Compared with the normal group, body weight, Open-field scores and sucrose preference of the model rats were significantly decreased on modeling day 7, 14, 21 (P<0.05). On modeling day 28, body weight and Open-field scores of each intervention group were significantly increased compared with those of the model group (P<0.05), and Open-field scores of combination group differed from those of acupuncture group and medicine group ( P<0.05). Only sucrose preference of combination group was improved significantly compared with the model group (P<0.05). Compared with the model group, NRD 5-HT1AR mRNA expression level was increased in the combination group (P<0.05), and NRD 5-HT2AR mRNA expression level was down-regulated in all of the three intervention groups ( P<0.05). Conclusion Acupuncture and antidepressant treatment covering 7 days can evoke rapid effect on SDD rats, which can improve the slow effect of antidepressant.

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

Lorcaserin: a selective serotonin receptor (5-HT2C) agonist for the treatment of obesity.

Lorcaserin is a selective serotonin receptor (5-HT2C) agonist that recently received the U.S. Food and Drug Administration (FDA) approval for chronic weight management. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in three phase-3 clinical trials. The available evidence indicates that this drug does not show heart valve abnormalities, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. However, the drug’s manufacturer will be required to conduct postmarketing studies, including a long-term cardiovascular outcomes trial to assess the effect of Lorcaserin on the risk for major adverse cardiac events such as heart attack and stroke.

Preventive effect of ramosetron on patient-controlled analgesia-related nausea and vomiting after laparoscopic hysterectomy / 대한산부인과내시경학회지

OBJECTIVE: Patient-controlled-analgesia (PCA) using intravenous (IV) opioids is recognized a safe and effective method for pain control. However, postoperative analgesia with opioids is associated with a high incidence of postoperative nausea and vomiting (PONV) exceeding 30%. The 5-hydroxytryptamine receptor 3 (5-HT3) antagonists alleviate nausea and vomiting. This study aims to compare the effectiveness of ramosetron and ondansetron in preventing PONV following laparoscopic hysterectomy for benign uterine diseases under general anesthesia. METHODS: The medical records of 1483 patients who underwent laparoscopic hysterectomy between January 2005 and May 2009 were reviewed. Of the 1483 patients, 1184 patients who received IVPCA with ramosetron 0.3 mg (n=761) or ondansetron 8 mg (n=423) were analyzed. Fentanyl-based IVPCA was administered for 48 hours after surgery. The overall incidence of postoperative nausea and vomiting, bowel ileus, Levin tube insertion for severe bowel ileus, additional usage of pain killers and discontinuation of the IVPCA infusion with PCA-related severe nausea and vomiting were assessed for 48 hours after surgery. The amount of time until bowel gas passage resumption after surgery was measured. RESULTS: There was a significant difference between the two groups regarding the duration until post-operative bowel gas passage resumption (1.78+/-0.79 days in the ramosetron group, and 2.23+/-0.83 days in the ondansetron group; p=0.005); however, there were no significant differences found in other aspects. CONCLUSION: Ramosetron is superior to ondansetron in terms of faster recovery in bowel mobility, with similar effects in preventing the incidence of PONV.

The antiemetic effect of magnetotherapy in chemotherapy patients / 中华物理医学与康复杂志

Objective To observe and compare the antiemetic effectiveness and adverse effects of magnetotherapy plus the 5 -hydroxytryptamine (5-HT3 ) receptor inhibitor granisetron hydrochloride with that of granisetron hydrochloride alone with chemotherapy patients. Methods Sixty-four patients were randomized to receive either granisetron hydrochloride alone ( control group: granisetron hydrochloride 3 mg intravenous infusion before chemotherapy, from the 1st day of chemotherapy until the day after the chemotherapy course was completed) or magnetotherapy plus granisetron hydrochloride ( treatment group: the same granisetron hydrochloride regimen plus rotatory magnetotherapy of 1 h/time every day after chemotherapy). The baseline characteristics of the two groups were similar. The patients' emesia was evaluated according to the WHO's criteria. The density of 5-HT, in serum was detected by enzyme-linked immunosorbent assay ( ELISA). Results In terms of acute vomiting, there was no significant difference between the two groups, but in terms of tardive vomiting, the effectiveness in the treatment group was significantly better than in the control group. The densities of S-HT, in serum in the treatment and the control group were (225.32±57.29 ) ng/ml vs (213.00±53.29 ) ng/ml before chemotherapy and (273.88±5.42) ng/ml vs ( 313.17±76.36 ) ng/ml after chemotherapy, a significant difference. The rates of adverse events were 36.36% and 48.39% respectively in the treatment group and control group, a difference which was not significant. Conclusions Magnetotherapy plus granisetron hydrochloride is more effective than granisetron hydrochloride alone, and the two therapies have a synergistic effect. Adverse events didn't rise in the treatment group.