Curcumin attenuates morphine dependence by modulating µ-opioid receptors and glial cell-activated neuroinflammation in rat.

In recent years, the association between neuroinflammation and opioid dependence has attracted considerable attention. Curcumin, a component of the Curcuma longa, has been shown to act as a suppressor of glial cells and inflammatory cytokines. The main goal of this study was to explore the attenuating effects of curcumin on morphine dependence with a focus on neuroinflammation and µ-opioid receptors in the rat prefrontal cortex. To induce morphine dependence in male Wistar rats, morphine was administered i.p. once daily for 18 days in an escalating dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Immunofluorescence staining and ELISA methods were used to evaluate glial cells activity and inflammatory cytokines levels, respectively. Western blotting was used to evaluate the expression of µ-opioid receptors. The administration of curcumin (2.5, 5, and 10 mg/kg) for 9 days significantly attenuated the symptoms of morphine withdrawal syndrome. The prefrontal cortex concentration of TNF-α and IL-6 was also reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Furthermore, curcumin decreased the number of Iba1 and GFAP positive cells in morphine-dependent rats. Moreover, the expression of µ-opioid receptors was significantly reduced by curcumin (10 mg/kg). The results of this study demonstrate that curcumin attenuates morphine dependence in rats through an inhibitory effect on neuroinflammation and a decrease in the expression of µ-opioid receptors in the prefrontal cortex.

The effect of microglial inhibition on the expression of BDNF, KCC2, and GABAA receptor before and after the establishment of CCI-induced neuropathic pain model.

Damage to the peripheral or central nervous system results in neuropathic pain. Based on a complicated mechanism, neuropathic pain has no efficient treatment so far. It has been well-known that the expression of some proteins (BDNF, KCC2, GABA-A) during neuropathic pain changes. Microglial cell activation is considered as a trigger to alter the expression of these proteins. In the current study, the effect of minocycline as a potent microglial activation inhibitor on the gene and protein expression of these neuropathic pain mediators was investigated. This experiment was done in two paradigms, preinjury and postinjury administration of minocycline. In each paradigm, male Wistar rats (weight 150-200 g, n = 6) were allocated to sham, control, and drug groups. Minocycline (30 mg/kg, i.p.) was injected 1 h before or at day seven after nerve injury and continued till day 14 in the preemptive or postinjury part of the study, respectively. After the last injection, the animals were decapitated and the lumbar part of the spinal cord was isolated to assess the expression of genes and proteins of interest. In the preventive study, minocycline increased the expression of KCC2 and GABA-A/γ2 proteins and decreased BDNF expression. On the other hand, the target gene expression and protein expression were not changed when minocycline was administered after nerve injury. It seems that minocycline was able to change the expression of proteins of interest merely when used before nerve damage.

Paroxetine effects on morphine analgesic tolerance in rats.

OBJECTIVES: To alleviate different pain intensities, morphine administration has been extensively used. However, prolonged administration of morphine leads to a progressive decline of its analgesic effect which limits their overall utility. Morphine tolerance is considered as a challenging issue for the treatment of both acute and chronic pain. We conducted this study in rats to investigate the effect of paroxetine on morphine tolerance when used preemptively or after morphine tolerance had developed. METHODS: Male Wistar rats (weight 250-300 g, n=10) were used to evaluate the effects of paroxetine on tolerance to morphine. In order to induce tolerance, daily intraperitoneal injection of morphine (7 mg/kg) was done. After tolerance induction, a group of animals received intraperitoneal injection of 10 mg/kg paroxetine 30 min prior to each morphine dose. In another trial, to investigate the potential of paroxetine to prevent tolerance to morphine, animals were pretreated with 10 mg/kg paroxetine 30 min before morphine administration. In the control groups, 10 mL/kg of saline was injected. The behavioral test (tail-flick test) was done for all groups. RESULTS: Our data showed that paroxetine significantly reversed tolerance to morphine when used after tolerance induction (p<0.001). However, administration of paroxetine before occurrence of tolerance had no effect. CONCLUSIONS: We conclude that paroxetine could decrease tolerance to morphine when used after the occurrence of morphine tolerance, while it was not able to prevent morphine tolerance when administered preemptively. ETHICAL COMMITTEE NUMBER: IRIB.SBMU.MSP.REC.1394.098.

Effect of Paroxetine on the Neuropathic Pain: A Molecular Study.

Background: Neuropathic pain, due to peripheral nerve damage, has influenced millions of people living all over the world. It has been shown that paroxetine can relieve neuropathic pain. Recently, the role of certain proteins like brain-derived neurotrophic factor (BDNF), GABAA receptor, and K+-Cl- cotransporter 2 (KCC2) transporter in the occurrence of neuropathic pain has been documented. In the current study, the expression of these proteins affected by paroxetine was evaluated. Methods: Male Wistar rats were allocated into two main groups of pre- and post-injury. Rats in each main group received paroxetine before nerve injury and at day seven after nerve damage till day 14, respectively. The lumbar spinal cord of animals was extracted to assess the expression of target genes and proteins. Results: In the preventive study, paroxetine decreased BDNF and increased KCC2 and GABAA gene and protein expression, while in the post-injury paradigm, it decreased BDNF and increased KCC2 genes and protein expression. In this regard, an increase in the protein expression of GABAA was observed. Conclusion: It seems that paroxetine with a change in the expression of three significant proteins involved in neuropathic pain could attenuate this type of chronic pain.

The Attenuating Effect of Curcumin on Morphine Dependence in Rats: The Involvement of Spinal Microglial Cells and Inflammatory Cytokines.

New evidence suggests an important role for spinal glial cells in the development of opioid dependence. Curcumin, a component of the Curcuma Longa, has shown to act as a suppressor of microglial cells. The main goal of this study was to explore the attenuating effects of curcumin on morphine dependence with a focus on spinal microglial cells and inflammatory cytokines. In order to induce morphine dependence in male Wistar rats, morphine was administered intraperitoneally (i.p.) once daily for 9 days in an increasing dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Naloxone-precipitated abstinence syndrome was used to assess the behavioral symptoms of morphine dependence. Immunofluorescence staining of Iba1 and ELISA test were used to measure spinal microglial activity and inflammatory cytokines levels, respectively. The results showed that curcumin (2.5, 5, and 10 mg/kg) significantly decreased jumping, leaning, and diarrhea in morphine-dependent rats. In addition, the spinal concentration of TNF-α and IL-6 was reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Moreover, curcumin showed a potent attenuating effect on the number of Iba1 positive cells in rats which were subjected to morphine dependence. The results of this study demonstrated that curcumin exerts a remarkable reducing effect on morphine dependence in rats. The findings showed that the therapeutic effect of curcumin on morphine dependence is mediated through the suppression of activated microglial cells and reduction of inflammatory cytokines levels in the spinal cord.

Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats.

OBJECTIVES: Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fully clarified. The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP channel pathway in the central and peripheral antinociceptive effect of thymoquinone in rats. MATERIALS AND METHODS: Rats were pretreated intraplantarly (IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l-NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl cyclase inhibitor), glibenclamide (the blocker of KATP channel), and tetraethylammonium (TEA, a Kv channel blocker) before the injection of thymoquinone. RESULTS: Local ipsilateral (20 and 40 µg, IPL) but not contralateral and ICV (4 and 8 µg) administration of thymoquinone caused a dose-dependent and significant antinociception in both early and late phases of the formalin test. Pretreatment of rats with L-arginine (100 µg, IPL or ICV) and SNAP (200 µg, IPL or ICV) increased while l-NAME (100 µg, IPL or 1 µg, ICV) and methylene blue (400 µg, IPL or ICV) decreased the antinociceptive effects of thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not modify but glibenclamide (50 µg, IPL or ICV) significantly abolished the peripheral and central antinociceptive effects of thymoquinone in both phases of the formalin test. CONCLUSION: The results of the present study indicate that L-arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral antinociceptive effect of thymoquinone.

Neuroprotective Effect of Paroxetine on Memory Deficit Induced by Cerebral Ischemia after Transient Bilateral Occlusion of Common Carotid Arteries in Rat.

Memory deficit is the most visible symptom of cerebral ischemia. The hippocampus is sensitive against cerebral ischemia. Oxidative stress and inflammation are involved in the pathological process after cerebral ischemic injury. Paroxetine has anti-oxidative and anti-inflammatory effects. In this study, the effect of paroxetine on memory deficit after cerebral ischemia was investigated. Cerebral ischemia/reperfusion (I/R) injury model was established using the bilateral occlusion of common carotid artery method. Paroxetine (10 mg/kg) was intraperitoneally injected into rats, 24 h before surgery or once a day for 7 days after surgery. Learning and memory were evaluated using the Morris water maze task, then the brain tissue was fixed and hippocampal CA1 pyramidal cells damage was analyzed using the Nissl staining method. In the ischemia group the escape latency time (ELT) and the swimming path length (SPL) were significantly increased and the time spent in target quadrant (TSTQ) was significantly decreased compared with the control group. The ELT and the SPL were significantly shortened and the TSTQ was significantly increased compared with the ischemia group after Pre- or post-ischemic administration of paroxetine. The percentage of viable pyramidal cells in the ischemia group was significantly decreased compared with the control group. The percentage of viable cells was significantly increased following pre-or post-ischemic administration of paroxetine compared with the ischemia group. Memory deficit due to I/R was improved and the percentage of viable cells in CA1 region was increased after administration of paroxetine. Therefore, paroxetine may have a neuroprotective effect against cerebral ischemia.

Carbamazepine effects on pain management and serum IL-6, IL-10 evaluation in addicted patients undergoing surgery.

Postoperative pain control remains an important issue in the field of surgery. Assessing and managing patients with acute pain who are addicted to opioids are often challenging. It has been shown that, addicted patients are less tolerant to pain. There is limited evidence to guide the management of acute pain in these patients. Here we studied the effect of preemptive use of carbamazepine on pain behavior and serum IL-6, IL-10 levels in the addicted patients. 90 male patients (25-45 years, BMI 20-27), were divided into 3 group of 30 patients: 1- control, 2- addicted, 3- addicted patients receiving carbamazepine 400mg before surgery. The visual analog pain scale and serum levels of IL-6 and IL-10 were evaluated at time 0 (before surgery), 1 and 12h postoperatively. Compared with control and carbamazepine groups, addicted patients exhibited exaggerated pain behavior before and after surgery, however, postoperatively, a significant increase in pain behavior was seen in control compared to carbamazepine group. A decrease in serum IL-10 and an increase in IL-6 concentrations were observed in addicted patients. In the morphine abuser, a decrease in pain threshold, an increase in IL-6 and a decrease in IL-10 levels were evident compared with non-abuser subjects. Addition of carbamazepine improved pain sensation and serum IL-6 levels and a reduction in serum IL-10 level in control patients was paralleled to their recovery. It seems that, preemptive use of low dose of carbamazepine can improve postoperative pain and cytokine activities in the addicted patients.

Paradoxical effect of minocycline on established neuropathic pain in rat.

Neuropathic pain occurs after peripheral nerve damage, inflammation or infection. In this situation, microglial cells become activated and play a key role in producing pain. Minocycline (microglia inhibitor), was reported to reduce pain when used preventively. However, it seems that, when used after nerve injury, results in its pain reducing effects are different. In this regard, to assess the pain reducing differences of minocycline, neuropathic pain was induced by the ligation of the sciatic nerve in the rat which is recognized as chronic constriction injury (CCI) and minocycline was administered before and after sciatic nerve injury. Wistar male rats (200-250 g, n=6) were used in these experiments. Rats were distributed in various groups: vehicle-treated CCI (control), sham-operated and minocycline-treated CCI groups. In the first part of the experiment (pre-injury study), minocycline (10, 20, 30 and 40 mg/kg,) was injected one hour before surgery and then daily for two weeks. In the second part (post injury study), minocycline was administered: 1: at day one after nerve damage once a day to day 14, 2: at day seven after surgery and continued daily until day 14. Analgesimeter for thermal hyperalgesia and von Frey hairs for mechanical allodynia were used to evaluate pain behavior. Thermal hyperalgesia and mechanical allodynia were attenuated significantly, when minocycline used before surgery, while it was not able to reduce pain behavior administered after surgery. It seems that, in spite of what some previous studies have reported, here, minocycline is not able to attenuate established neuropathic pain.

Interference-free Determination of Carbamazepine in Human Serum Using High Performance Liquid Chromatography: A Comprehensive Research with Three-way Calibration Methods.

In the present study, a comprehensive and systematic strategy was described to evaluate the performance of several three-way calibration methods on a bio-analytical problem. Parallel factor analysis (PARAFAC), alternating trilinear decomposition (ATLD), self-weighted alternating trilinear decomposition (SWATLD), alternating penalty trilinear decomposition (APTLD), and unfolded partial least squares combined with the residual bilinearization procedure (U-PLS/RBL) were applied on high performance liquid chromatography with photodiode-array detection (HPLC-DAD) data to quantify carbamazepine (CBZ) in different serum samples. Using the proposed approach, successfully quantification of CBZ in human plasma, even in the presence of diverse uncalibrated serious interfering components was achieved. Moreover, the accuracy and precision of each algorithm for analyzing CBZ in serum samples were compared using root mean square error of prediction (RMSEP), the recovery values and figures of merits and reproducibility of the analysis. Satisfying recovery values for the analyte of interest were obtained by HPLC-DAD on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH = 7.5) buffer solution (45:55) coupled with second-order calibrations. Decreas of the analysis time and less solvent consumption are some of the pluses of this method. The analysis of real samples showed that the modeling of complex chromatographic profiles containing CBZ as the target drug using any of the mentioned algorithms can be potentially benefit drug monitoring in therapeutic research.

Neuroprotective effect of minocycline on cognitive impairments induced by transient cerebral ischemia/reperfusion through its anti-inflammatory and anti-oxidant properties in male rat.

Memory deficit is the most visible symptom of cerebral ischemia that is associated with loss of pyramidal cells in CA1 region of the hippocampus. Oxidative stress and inflammation may be involved in the pathogenesis of ischemia/reperfusion (I/R) damage. Minocycline, a semi-synthetic tetracycline derived antibiotic, has anti-inflammatory and antioxidant properties. We evaluated the neuroprotective effect of minocycline on memory deficit induced by cerebral I/R in rat. I/R was induced by occlusion of common carotid arteries for 20min. Minocycline (40mg/kg, i.p.) was administered once daily for 7days after I/R. Learning and memory were assessed using the Morris water maze test. Nissl staining was used to evaluate the viability of CA1 pyramidal cells. The effects of minocycline on the microglial activation was also investigated by Iba1 (Ionized calcium binding adapter molecule 1) immunostaining. The content of malondialdehyde (MDA) and pro-inflammatory cytokines (IL-1ß and TNF-α) in the hippocampus were measured by thiobarbituric acid reaction substances method and ELISA, respectively. Minocycline reduced the increase in escape latency time and in swimming path length induced by cerebral I/R. Furthermore, the ischemia-induced reduction in time spent in the target quadrant during the probe trial was increased by treatment with minocycline. Histopathological results indicated that minocycline prevented pyramidal cells death and microglial activation induced by I/R. Minocycline also reduced the levels of MDA and pro-inflammatory cytokines in the hippocampus in rats subjected to I/R. Minocycline has neuroprotective effects on memory deficit induced by cerebral I/R in rat, probably via its anti-inflammatory and antioxidant properties.

Neuroprotective effects of pretreatment with minocycline on memory impairment following cerebral ischemia in rats.

Cerebral ischemia leads to memory impairment that is associated with loss of hippocampal CA1 pyramidal neurons. Neuroinflammation and oxidative stress may be implicated in the pathogenesis of ischemia/reperfusion damage. Minocycline has anti-inflammatory and antioxidant properties. We investigated the neuroprotective effects of minocycline in rats subjected to cerebral ischemia/reperfusion injury. Thirty male rats were divided into three groups: control, sham, and minocycline-pretreated group. Minocycline (40 mg/kg) was injected intraperitoneally immediately before surgery, and then ischemia was induced by occlusion of common carotid arteries for 20 min. Seven days after reperfusion, the Morris water-maze task was used to evaluate memory. Nissl staining was also performed to analyze pyramidal cell damage. We measured the contents of malondialdehyde and proinflammatory cytokines in the hippocampus by the thiobarbituric acid method and enzyme-linked immunosorbent assay, respectively. Microglial activation was also investigated by Iba1 immunostaining. The results showed that pretreatment with minocycline prevented memory impairment induced by cerebral ischemia/reperfusion. Minocycline pretreatment also significantly attenuated ischemia-induced pyramidal cell death and microglial activation in the CA1 region and reduced the levels of malondialdehyde and proinflammatory cytokines (interleukin-1ß and tumor necrosis factor-α) in the hippocampus of ischemic rats. Minocycline showed neuroprotective effects on cerebral ischemia-induced memory deficit probably through its anti-inflammatory and antioxidant activities.

Minocycline Effects on IL-6 Concentration in Macrophage and Microglial Cells in a Rat Model of Neuropathic Pain.

BACKGROUND: Evidence indicates that neuropathic pain pathogenesis is not confined to changes in the activity of neuronal systems but involves interactions between neurons, inflammatory immune and immune-like glial cells. Substances released from immune cells during inflammation play an important role in development and maintenance of neuropathic pain. It has been found that minocycline suppresses the development of neuropathic pain. Here, we evaluated the analgesic effect of minocycline in a chronic constriction injury (CCI) model of neuropathic pain in rat and assessed IL-6 concentration from cultured macrophage and microglia cells. METHODS: Male Wistar rat (n=6, 150-200 g) were divided into three different groups: 1) CCI+vehicle, 2) sham+vehicle, and 3) CCI+drug. Minocycline (10, 20, and 40 mg/kg) was injected one hour before surgery and continued daily to day 14 post ligation. Von Frey filaments and acetone, as pain behavioral tests, were used for mechanical allodynia and cold allodynia, respectively. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7, 10, and 14 post -injury. At day 14, rats were killed and monocyte-derived macrophage from right ventricle and microglia from lumbar part of the spinal cord were isolated and cultured in RPMI and Leibovitz's media, respectively. IL-6 concentration was evaluated in cell culture supernatant after 24 h. RESULTS: Minocycline (10, 20, and 40 mg/kg) attenuated pain behavior, and a decrease in IL-6 concentration was observed in immune cells compared to CCI vehicle-treated animals. CONCLUSION: Minocycline reduced pain behavior and decreased IL-6 concentration in macrophage and microglial cells.

Comparison of Anticancer Effects of Carbamazepine and Valproic Acid.

BACKGROUND: Valproic acid (VPA) and carbamazepine (CBZ), two widely used antiepileptic drugs, have recently been found to inhibit histone deacetylases (HDAC). HDAC inhibitors (HDACIs) have various effects on cancer cells. OBJECTIVES: The aim of this study was to compare the anticancer activity of these drugs on SW480 colon cancer cell lines. METHODS: In the present experimental study, implemented during 2014 - 2015 in Iran, after incubation of cells into 96-well plates with 5,500 cells/well, the tested drugs were added, and cytotoxic effects were assessed by MTT. Moreover, after incubation of 8×106 cells in 75 cm² flasks to obtain ß-catenin levels and 106 cells in a six-well plate to obtain vascular endothelial growth factor (VEGF) levels , these levels were estimated using enzyme-linked immunosorbent assay (ELISA) analysis. RESULTS: Through MTT assay, we found that the inhibitory concentration of 50% (IC50) values for VPA and CBZ were 2.5 mM and 5 µM, respectively in comparison to controls in terms of total concentration and times evaluated (P < 0.0001). We also found that treatments with these drugs decreased levels of ß-catenin (P < 0.0001) and VEGF (P < 0.0001) significantly more than controls. CONCLUSIONS: VPA and CBZ treatments caused a decrease in ß-Catenin and VEGF levels in SW480 colon cancer cell lines. These results suggest that CBZ can be considered a potential antitumor drug with potencies different from VPA.

The effects of seeds with hot and cold temperaments on serum thyroid hormones, corticosterone and urine vanillylmandelic acid concentrations of healthy rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hot and cold temperaments are the basic concepts of Iranian traditional medicine (ITM). Nevertheless, studies on the functional mechanisms of medicinal herbs based on hot and cold temperaments are not very extensive. This study aimed to evaluate the effects of diets containing hot or cold temperament seeds according to ITM on some hormonal and neuromediator parameters with a regulatory role in thermogenesis and energy metabolism in acute (24 hr) and subacute (7-day) experiments that were performed on rats. MATERIALS AND METHODS: Each experiment was performed on 42 male Wistar rats, which were randomly divided into 7 groups. while 1 group received usual diet (controls), 6 other groups were fed with a diet containing 10% seeds, namely, anise, fennel, or ajowan (hot temperament groups) or cucumber, pumpkin, or watermelon (cold temperament groups), respectively. The levels of the rats׳ serum free thyroxin (FT4), free triiodothyronin (FT3), triiodothyronin (T3), thyroxin (T4), corticosterone and urine vanillylmandelic acid (VMA) were analyzed. RESULTS: After 24 hours, a significant decrease in FT3 was observed in groups that were fed anise or fennel seeds. However, a significant increase in T3 was observed in the ajowan seed-fed group, and no changes in other parameters were observed in this group. On the 7th day, FT4 was significantly increased in fennel seed-fed group; T3 was significantly increased in the anise, fennel, ajowan and watermelon seed-fed groups; corticosterone was significantly increased in the watermelon and pumpkin seed-fed groups; and VMA was significantly increased in the fennel seed-fed group and significantly decreased in the cucumber seed-fed group. CONCLUSION: Alterations induced by hot and cold temperament seeds in measured hormonal and neuromediator levels that have a regulatory role in thermogenesis and the body׳s energy metabolism revealed that hot and cold temperament characteristics of studied seeds may most likely be related to their intervention in the body׳s energy metabolism, in that hot temperament seeds may increase energy metabolism and cold temperament ones may decrease it.

The Attenuation of Pain Behavior and Serum COX-2 Concentration by Curcumin in a Rat Model of Neuropathic Pain.

BACKGROUND: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. METHODS: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. RESULTS: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). CONCLUSIONS: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

The effects of selected hot and cold temperament herbs based on Iranian traditional medicine on some metabolic parameters in normal rats.

This study was aimed to evaluate the effects of diets containing some hot and cold temperament herb seeds according to Iranian traditional medicine (ITM) on some metabolic parameters in acute (24 h) and sub-acute (7 day) experiments that were performed on rats. For each experiment, effects of diets containing 10% herb seeds in category of hot (anise, fennel, ajowan) and cold (cucumber, watermelon, pumpkin) temperaments were analyzed on body weight gain, food intake, water consumption, urine output, serum glucose (SG) and insulin levels of rats. In the acute experiment, anise or fennel fed groups showed a significant decrease in food intake and there were not any changes in other parameters. The hot temperament groups in comparison with the cold temperament ones showed a significant decrease in food intake and a significant increase in SG level. In the sub-acute experiment, anise and fennel fed groups had a significant decrease in body weight gain on the 4thday. On the 7th day, the anise fed group experienced a significant decrease in body weight gain and a significant increase in SG levels. The groups that were fed hot temperament diets compared to the ones that consumed cold temperament diets showed a significant decrease in body weight gain and food intake rates and a considerable increase in SG levels. Considering the findings of this study, one can conclude that it is possible that hot temperament herbs such as anise and fennel be useful for humans for certain conditions such as weight control.

Paroxetine attenuates the development and existing pain in a rat model of neurophatic pain.

BACKGROUND: P2X4 receptor (P2X4R), a purinoceptor expressed in activated spinal microglia, plays a key role in the pathogenesis of neuropathic pain. Spinal nerve injury induces up-regulation of P2X4R on activated microglia in the spinal cord, and blockade of this receptor can reduce neuropathic pain. The present study was undertaken to determine whether paroxetine, an inhibitor of P2X4R, could attenuate allodynia and hyperalgesia in chronic constriction injury (CCI) model of neuropathic pain when used preemptively or after the sciatic nerve injury. METHODS: Male Wistar rats (150-200 g, n = 6) were divided into 3 different groups: 1- CCI vehicle-treated group, 2- Sham group, and 3- CCI paroxetine-treated group. Paroxetine (10 mg/kg, i.p.) was administered 1 h before surgery and continued daily until day 14. In other part of the study, paroxetine (10 mg/kg, i.p.) was administered at day 7 post injury and continued daily until day 14. von Frey filaments for mechanical allodynia and analgesia meter for thermal hyperalgesia were used to assay pain behavior. RESULTS: In a preventive paradigm, paroxetine significantly attenuated both mechanical allodynia and thermal hyperalgesia (P<0.001). A significant decrease in pain behavior was seen with paroxetine on existing allodynia (P<0.001) and hyperalgesia (P<0.01) when initiated at day 7 post injury. CONCLUSION: It seems that paroxetine can attenuate pain behavior when administered before and also after sciatic nerve injury in CCI model of neuropathic pain.

Chemometrics enhanced HPLC-DAD performance for rapid quantification of carbamazepine and phenobarbital in human serum samples.

This paper describes development and validation of a simple and efficient bioanalytical procedure for simultaneous determination of phenobarbital and carbamazepine in human serum samples using high performance liquid chromatography with photodiode-array detection (HPLC-DAD) regarding a fast elution methodology in less than 5 min. Briefly, this method consisted of a simple deproteinization step of serum samples followed by HPLC analysis on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH=7.5) buffer solution (45:55). Due to the presence of serum endogenous components as non-calibrated components in the sample, second-order calibration based on multivariate curve resolution-alternating least squares (MCR-ALS), has been applied on a set of absorbance matrices collected as a function of retention time and wavelengths. Acceptable resolution and quantification results were achieved in the presence of matrix interferences and the second-order advantage was fully exploited. The average recoveries for carbamazepine and phenobarbital were 89.7% and 86.1% and relative standard deviation values were lower than 9%. Additionally, computed elliptical joint confidence region (EJCR) confirmed the accuracy of the proposed method and indicated the absence of both constant and proportional errors in the predicted concentrations. The developed method enabled the determination of the analytes in different serum samples in the presence of overlapped profiles, while keeping experimental time and extraction steps at minimum. Finally, the serum concentration levels of carbamazepine in three time intervals were reported for morphine-dependents who had received carbamazepine for treating their neuropathic pain.

Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression.

OBJECTIVE: Zinc is found in abundance in the human brain. Patients with depression may have decreased consumption of food sources rich in zinc, and zinc supplementation may have a potential influence on depressive symptoms. However, clinical trials on the effect of zinc supplementation in depression are limited. The objective of the present study was to determine the effect of zinc supplementation on efficacy of antidepressant therapy. Furthermore, the effect of zinc on plasma levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and brain-derived neurotrophic factor-a (BDNF-a) were assessed. DESIGN: A single-center, randomized, double-blind, placebo-controlled trial of zinc supplementation was conducted in patients with DSM-IV major depression. Forty-four patients of both sexes aged 18-55 years were recruited for this study from a university hospital. The zinc-supplemented group received zinc sulfate (25 mg elemental Zn/day) orally in addition to their selective serotonin reuptake inhibitor antidepressants for 12 weeks. Symptoms were evaluated using the Hamilton Depression Rating Scale (HDRS) on arrival, weeks 6 and 12. Plasma levels of IL-6, TNF-α and BDNF-a were measured at baseline and at the end of study. RESULTS: Twenty patients in zinc group and 17 patients in placebo groups completed the study. At baseline, there were no significant differences in any variable between the patients allocated to receive placebo and those taking zinc supplement. Zinc supplementation significantly reduced HDRS compared to placebo (P < 0.01 at 12th week). No significant differences were observed in plasma levels of IL-6, TNF-α, and BDNF-a between zinc-supplemented and placebo-supplemented group. CONCLUSION: Zinc supplementation in conjunction with antidepressant drugs might be beneficial for reducing depressive symptoms. However, its effect does not appear to be mediated through impact of zinc on inflammatory processes.