[Improvement effect of cinnamaldehyde on reserpine-induced Parkinson's disease rat model].

In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment. The brain was taken and fixed. The positive expression of dopamine receptor D1(DRD1) was detected by TSA, and the changes in neurotransmitters such as dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC) in the brain were detected by enzyme-linked immunosorbent assay(ELISA). The protein and mRNA expression levels of tyrosine hydroxylase(TH) and α-synuclein(α-Syn) in substantia nigra(SN) were detected by RT-PCR and Western blot. The results showed that after the injection of reserpine, the hair color of the model group became yellow and dirty; the arrest behavior was weakened, and the body weight was reduced. The spontaneous movement and exploration behavior were reduced, and the coordination exercise ability was decreased. The number of oral chewing was increased, but the cognitive ability was decreased, and the proportion of DRD1 positive expression area in SN was decreased. The expression of TH protein and mRNA was down-regulated, and that of α-Syn protein and mRNA was up-regulated. After cinnamaldehyde intervention, it had an obvious curative effect on PD model animals. The spontaneous movement behavior, the time of staying in the rod, the time of movement, the distance of movement, and the number of standing times increased, and the number of oral chewing decreased. The proportion of DRD1 positive expression area in SN increased, and the protein and mRNA expression levels of α-Syn were down-regulated. The protein and mRNA expression levels of TH were up-regulated. In addition, the levels of DA, DOPAC, and homovanillic acid(HVA) neurotransmitters in the brain were up-regulated. This study can provide a new experimental basis for clinical treatment and prevention of PD.

Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor ß (TGF-ß) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-ß expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.

A Reliable High-Throughput Screening Model for Antidepressant.

Depression is the most frequent affective disorder and is the leading cause of disability worldwide. In order to screen antidepressants and explore molecular mechanisms, a variety of animal models were used in experiments, but there is no reliable high-throughput screening method. Zebrafish is a common model organism for mental illness such as depression. In our research, we established chronic unpredictable mild stress (CUMS) models in C57BL/6 mice and zebrafish; the similarities in behavior and pathology suggest that zebrafish can replace rodents as high-throughput screening organisms. Stress mice (ip., 1 mg/kg/d, 3 days) and zebrafish (10 mg/L, 20 min) were treated with reserpine. As a result, reserpine caused depression-like behavior in mice, which was consistent with the results of the CUMS mice model. Additionally, reserpine reduced the locomotor ability and exploratory behavior of zebrafish, which was consistent with the results of the CUMS zebrafish model. Further analysis of the metabolic differences showed that the reserpine-induced zebrafish depression model was similar to the reserpine mice model and the CUMS mice model in the tyrosine metabolism pathway. The above results showed that the reserpine-induced depression zebrafish model was similar to the CUMS model from phenotype to internal metabolic changes and can replace the CUMS model for antidepressants screening. Moreover, the results from this model were obtained in a short time, which can shorten the cycle of drug screening and achieve high-throughput screening. Therefore, we believe it is a reliable high-throughput screening model.

Curcumin Ameliorates Reserpine-Induced Gastrointestinal Mucosal Lesions Through Inhibiting IκB-α/NF-κB Pathway and Regulating Expression of Vasoactive Intestinal Peptide and Gastrin in Rats.

The objective of our study was to investigate whether curcumin protects against reserpine-induced gastrointestinal mucosal lesions (GMLs) in rats and to explore the mechanism of curcumin's action. Sprague-Dawley rats were randomly divided into four groups: control group, reserpine-treated group, reserpine treatment group with curcumin at high dose (200 mg/kg), and reserpine treatment group with curcumin at low dose (100 mg/kg). Rats in reserpine-treated group were induced by intraperitoneally administered reserpine (0.5 mg/kg) for 28 days. TUNEL staining and hematoxylin and eosin staining were used to evaluate the apoptotic cells and morphologic changes. In addition, to explore the mechanism of curcumin in protecting GMLs, we used serum of experimental rats to assess the level of vasoactive intestinal peptide (VIP), gastrin, interleukin-6, interleukin-10, tumor necrosis factor-α and interferon-γ by ELISA and radioimmunoassay. The protein levels of NF-κB, p-IκB-α, IκB-α, Bcl-2, Bax, and cleaved-caspase-3 were examined by western blot analysis. Data were analyzed with SPSS 19.0 software package. Curcumin treatment prevented tissue damage and cell death in the reserpine-treated rats and effectively decreased inflammatory response and balanced the expression of VIP and gastrin in the reserpine-treated rats. NF-κB, p-IκB-α, Bax, and cleaved-caspase-3 were increased in the reserpine group, but the curcumin high-dose group inhibited them. Curcumin can target the IκB-α/NF-κB pathway to inhibit inflammatory response and regulate the level of VIP and gastrin in reserpine-induced GML rats.

[Influence of ferulic acid on the pain-depression dyad induced by reserpine].

This study is to offer a clinical pain-depression dyad therapy of ferulic acid, the pain-depression dyad induced by reserpine was established and the dose-effect relationship of ferulic acid on ameliorating pain-depression dyad was explored. Mice were randomly divided into control group, reserpine + vechile and reserpine + ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)) groups. The reserpine treated mice were tested with thermal hyperalgesia, mechanicial allodynia and forced swimming tests, and the SOD and NO levels of hippocampus and frontal cortex were measured. Moreover, the HPLC-ECD was used to detect the changes of central monoamines concentrations. Compared with control group, reserpine can induce a significant decrease in the nociceptive threshold and increase in the immobility time of the forced swimming test. The results suggested that reserpine significantly increased the level of nitrite in hippocampus and frontal cortex and reduced the levels of SOD, 5-HT and NE in these two brain regions. However, these indexes can be a dose-dependently reversed by ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)). Ferulic acid can reverse pain-depression dyad, especially at the dose of 80 mg x kg(-1). In addition, it can influence oxidative stress and monoamine level.

[Effect of sijunzi decoction on the intestinal glucose absorption in model rats of Pi-qi deficiency syndrome: an experimental research].

OBJECTIVE: To observe the effect of Sijunzi Decoction (SD) on the intestinal absorption of glucose in model rats of Pi-qi deficiency syndrome (PQDS). METHODS: PQDS rat model was established by subcutaneous injection of reserpine from the neck. The body weight and urine D-xylose excretion rates were measured. The glucose uptake rate was measured by jejunum perfusion. The intestinal mucosa was collected. The glucose transporter-2 (GLUT2) protein and mRNA expression levels were detected. RESULTS: Compared with the normal control group, the body weight and D-xylose excretion rates decreased in the model group. Meanwhile, the glucose uptake and GLUT2 protein and mRNA expression levels decreased in the model group. The aforesaid indices were improved in the SD group. CONCLUSION: SD could promote the recovery of glucose uptake in the small intestine of reserpine induced PQDS rats.

[Effect of euodiae fructus on hepatic energy metabolism-related mechanisms of reserpine-induced asthenia cold syndrome rats].

OBJECTIVE: To discuss the effect of Euodiae Fructus on hepatic energy metabolism-related mechanisms of mitochondria of hepatic tissues of asthenia cold syndrome rats. METHOD: Rats were subcutaneously injected with Reserpine to establish the model. After the oral administration with Euodiae Fructus for 12 d, the oxygen electrode method was adopted to determine the respiration efficiency. The expressions of Cox4, Atp5b, Ucp2,Pgc-1alpha, Nrf1, Tfam mRNA were assayed by using RT-PCR method. RESULT: Euodiae Fructus 4.2 g x kg(-1) could obviously increase ST3 and RCR of asthenia cold syndrome rats, and expressions of Cox4, Ucp2 Nrf1 mRNA. It could also increase expressions of Atp5b and Pgc-1alpha mRNA, but with no statistical significance. No obvious change was observed in Tfam mRNA expression. Euodiae Fructus 4.2 g x kg(-1) could significantly increase ST3 and RCR of asthenia cold syndrome rats and Pgc-1alpha mRNA and Nrf1 mRNA expressions, and significantly decrease P/O, with no obvious impact on Cox4, AtpSb, Ucp2, Tfam mRNA expressions. CONCLUSION: Euodiae Fructus can promote mitochondrial respiratory function and oxidative phosphorylation efficiency by improving Pgc-1alpha mRNA and Nrf1 mRNA expressions and regulating Cox4 and Atp5b mRNA in mitochondrial respiratory chain. It can also strengthen mitochondrial uncoupling respiration and add heat production by activating Ucp2 mRNA expression in liver.

Korean ginseng extract attenuates reserpine-induced orofacial dyskinesia and improves cognitive dysfunction in rats.

Reserpine-induced orofacial dyskinesia in rats is an animal model of tardive dyskinesia that has been linked with free radical generation and oxidative stress. In the present study, reserpine (1 mg kg(-1), s.c.) was given to rats on days 1, 3 and 5 to induce orofacial dyskinesia, which is characterised by increased vacuous chewing and tongue protrusion. Sub-chronic treatment with Korean ginseng extract from day 1 to day 21 along with reserpine on days 1, 3 and 5 significantly and dose-dependently (100 and 200 mg kg(-1)) reduced reserpine-induced vacuous chewing movements and tongue protrusions. Reserpine-treated animals also showed poor retention of memory in the elevated plus maze paradigm. The sub-chronic Korean ginseng extract administration significantly reversed reserpine-induced retention deficits. Biochemical analysis revealed that repeated reserpine treatment significantly induced lipid peroxidation and decreased glutathione (GSH) levels in the brains of rats. Reserpine-treated rats also showed decreased levels of antioxidant defence enzymes, superoxide dismutase (SOD), and catalase. Sub-chronic administration of Korean ginseng extract dose-dependently and significantly reduced lipid peroxidation and restored decreased GSH levels by repeated reserpine treatment. It also significantly reversed the reserpine-induced decrease in brain SOD and catalase levels in rats. The present study concludes that oxidative stress might play an important role in reserpine-induced abnormal oral movements, and Korean ginseng extract could be useful in the treatment of drug-induced dyskinesia and amnesia.

[Effect and mechanism of reserpine for changing salivary protein secretion in Pi-deficient rats].

OBJECTIVE: To study the effect of reserpine (RSP) for changing salivary protein secretion in Pi-deficient rats and to explore its possible mechanism. METHODS: Twenty rats allocated in the RSP group were given subcutaneous injection of RSP [0.4 mg/(kg x d)] for 9 successive days, while the other 20 rats in the control group were injected with same volume of saline instead. On the 10th day, ten rats randomly selected from each group were subjected for extracting saliva to detect salivary amylase activity (sAA) before and after an acid stimulation; and drawing blood from the orbital vein to measure the contents of vasoactive intestinal peptide (VIP) and cyclic adenosine monophosphate (cAMP). Then they were sacrificed and their parotids were taken out for pathological examination with HE staining, as well as for VIP and cAMP measuring, and zymogen granules counting under a transmission electron microscope. The remainder animals were stopped injecting and normally fed to 40 days, then subjected to be detected as above-mentioned. RESULTS: Food intake and body weight reduction were more significantly in the RSP group than in the control group. On the 10th day, the ratio of sAA before/after stimulation in the RSP group was 0.39 +/- 0.18, significantly lower than that in the control group (0.80 +/- 0.21, P < 0.01), but it was restored rapidly, reaching the normal range on the 25th day, on the 40th day, it became significantly different to the level on the 10th day (P < 0.05) and approached the level in the control group (P > 0.05). No significant pathological change of parotid was found in both groups; but the number of zymogen granules in the RSP group was remarkably more than that in the control group (41.4 +/- 4.9 vs 34.6 +/- 5.2, P < 0.01). Serum level of VIP in the RSP group was significantly less while that of cAMP was higher than that in the control group (22.5 +/- 13.1 mg/L vs 38.5 +/- 14.1 mg/L, and 125.8 +/- 15.5 micromol/L vs 105.3 +/- 16.7 micromol/L, both P < 0.05), but no inter-group difference was found in parotid tissue contents of both VIP and cAMP. All the indices detected became equivalent in the two groups on the 40th day. CONCLUSION: The reduction of salivary protein in Pi-deficient rats induced by RSP may be related to the regulatory pathway of VIP and cAMP.

Different concepts in first-line treatment of essential hypertension. Comparison of a low-dose reserpine-thiazide combination with nitrendipine monotherapy. German Reserpine in Hypertension Study Group.

Low-dose combination therapy has been proposed as a rational first-line approach to hypertension treatment. We compared the efficacy and tolerability of the fixed combination of reserpine (0.1 mg) plus the thiazide clopamid (5 mg) with its single components and the calcium-antagonist nitrendipine (20 mg) in a randomized, double-blind, parallel study of 273 hypertensive patients with diastolic blood pressure (BP) between 100 and 114 mm Hg. The four groups did not differ regarding baseline characteristics (mean age, 58 years; 51% men; mean BP after a 2-week placebo period, 158 to 160/103 to 104 mm Hg). After 6 weeks of treatment with one capsule daily, mean reductions in sitting BP from baseline at 24 hours after dosing in the reserpine-clopamid combination, reserpine, clopamid, and nitrendipine groups were -23.0/-17.1, -14.0/-11.7, -13.6/-11.9, and -11.6/-12.3 mm Hg, respectively (2P < .01). The corresponding normalization rates (diastolic BP < 90 mm Hg) were 55%, 40%, 36%, and 33% (2P = .11). All patients whose BP had not been normalized at this point received two capsules of the respective medication once daily from weeks 7 to 12. At week 12, mean BP reductions were -25.7/-18.1, -14.6/-12.2, -17.7/-13.4, and -14.9/-15.3 mm Hg in the four groups, respectively (2P < .01). The respective normalization rates were 69%, 35%, 39%, and 45% (2P < .0001). Linear regression modeling indicated that reserpine and clopamid combined acted more than additively. As regards tolerability, adverse experiences were observed in 27%, 28%, 29%, and 48% of patients, respectively (2P < .05). The respective rates of premature discontinuation because of adverse effects were 3%, 3%, 7%, and 13% (2P = .06). In conclusion, a low-dose combination of reserpine and clopamid lowered BP significantly more than both the components alone and nitrendipine. Moreover, the combination was tolerated as well as its components and significantly better than nitrendipine. Thus, the use of this low-dose reserpine-thiazide combination appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.

Gastroprotective activity of ginger zingiber officinale rosc., in albino rats.

The cytoprotective and gastric anti-ulcer studies of ginger have been carried out in albino rats. Cytodestruction was produced by 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl. Whereas gastric ulcers were produced by ulcerogenic agents including indomethacin, aspirin and reserpine, beside hypothermic restraint stress and by pylorus ligated Shay rat technique. The results of this study demonstrate that the extract in the dose of 500 mg/kg orally exert highly significant cytoprotection against 80% ethanol, 0.6M HC1, 0.2M NaOH and 25% NaCl induced gastric lesions. The extract also prevented the occurrence of gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) and hypothermic restraint stress. These observations suggest cytoprotective and anti-ulcerogenic effect of the ginger.

Gastric cytoprotective properties of SCH 32651, a novel antiulcer agent.

The antisecretory activity of SCH 32651 (3-amino-2-methyl-8-phenylmethoxyimidazo[1,2-a] pyrazine HCl . 1/3 H2O) has been described in a preceding paper. This report describes its gastric cytoprotective properties. SCH 32651 inhibited the gastric lesions due to ethanol in a dose-dependent manner (ID50 = 5 mg/kg p.o.) and exerted its maximal effect when given 30 min before ethanol and had a duration of at least 90 min at 30 mg/kg p.o. The activity of SCH 32651 against ethanol was unaffected by indomethacin pretreatment. Furthermore, SCH 32651 produced significant increases in gastric mucus release (10-100 mg/kg p.o.) and rapidly reversed ethanol-induced (30-100 mg/kg p.o.) fall in gastric potential difference (PD). SCH 32651 displayed significant antiulcer activity in indomethacin-(30-100 mg/kg p.o.), aspirin - (30-100 mg/kg p.o.), "aspirin + acid" - (10-100 mg/kg p.o.), reserpine - (10-100 mg/kg p.o.), stress - (30-100 mg/kg p.o.), and cysteamine (10-100 mg/kg p.o.) ulcers. The present data in conjunction with those reported in a preceding paper indicate that SCH 32651 is an orally effective novel antiulcer drug with both gastric antisecretory and cytoprotective properties.

Pharmacology of nomifensine: a review of animal studies.

Nomifensine has demonstrated efficacy in several animal models that have been found to be predictive of clinical antidepressant activity, and has also been found to have a low potential for both cardiovascular and anticholinergic side effects. A comparison of nomifensine's profile with those of standard antidepressant agents shows this drug to possess clear advantages which may make it an attractive choice for the treatment of endogenous depression.

Reserpine and breast cancer. A community-based longitudinal study of 2,000 hypertensive women.

To supplement several case-control studies questioning whether use of reserpine is associated with occurrence of breast cancer, we conducted a longitudinal study of nearly 2,000 hypertensive women residing in Rochester, Minn. Exposure to antihypertensive agents and subsequent incidence of breast cancer were ascertained. Expected numbers of cases, derived from local population data and from the Connecticut Tumor Registry, were compared with the numbers of cases observed in exposure groups of interest. No evidence was found of any association of reserpine use, thiazide use, or untreated hypertension with subsequent occurrence of breast cancer in these hypertensive women. In addition, several issues were investigated that warrant consideration in evaluating reports published to date, especially before conclusions are drawn as to the questionable contention that reserpine has caused breast cancer in women.

Side effects in the neonate from psychotropic agents excreted through breast-feeding.

Neuroleptics, antidepressants, lithium, anxiolytics, and hypnotics may be excreted in breast milk. Because of the danger to the neonate, drugs such as diazepam, lithium, bromides, reserpine, and opium alkaloids should not be given to lactating women, and barbiturates, haloperidol, and penfluridol should be administered with caution. The side effects produced as a result of breast-feeding of the infant by mothers consuming psychotropic drugs are reviewed and possible preventive measures are discussed.

A basis for migraine therapy- the autonomic theory reappraised.

The concept that migraine results from an initial vasoconstriction due to increased release of noradrenaline from the sympathetic nerves to cranial blood vessels has been reappraised in the light of recently acquired knowledge of the mechanisms of action of drugs used in the treatment of migraine, physiological and pharmacological evidence implicating noradrenaline, and the observations by others that several migraine variants may be associated with some degree of sympathetic overactivity. If the theory is correct, it suggests that both prophylaxis and management of the acute condition should be possible by means of selective alpha-adrenoceptor antagonism. The use of drugs with potentially dangerous vasoconstrictor properties appears to be unnecessary. The suggestion is made that the increased adrenergic activity might result from changes within the hypothalamus.