Jian-You Guo

Dissection of placebo analgesia in mice: the conditions for activation of opioid and non-opioid systems

Amanzio and Benedetti (J Neurosci 1999; 19: 484—494) first addressed the conditions necessary for the activation of opioid and non-opioid placebo responses in human. Here, we investigated whether placebo analgesia is subdivided into opioid and non-opioid components in mice by using the model of hot-plate test. Drug conditioning was performed by the combination of the conditioned cue stimulus with the unconditioned drug stimulus, either opioid agonist morphine hydrochloride or non-opioid aspirin. Placebo analgesic responses were evoked by an exposure to a conditioned cue previously paired with drug conditioning. Morphine conditioning produced placebo responses that were completely antagonised by naloxone. By contrast, the conditioned cue after aspirin conditioning elicited a placebo effect that was not blocked by naloxone. Therefore, we first evoked opioid and non-opioid placebo responses in mice that were either naloxone-reversible or naloxone-insensitive, depending on the drug used in conditioning procedure. These findings support that the mechanisms underlying placebo analgesia may depend on the drug conditioning that was originally performed. The present procedure of mice may serve as a model for further understanding of the opioid and non-opioid mechanisms underlying placebo responses.

Effects and mechanisms of aloperine on 2, 4-dinitrofluorobenzene-induced allergic contact dermatitis in BALB/c mice

Allergic contact dermatitis is a prototypic T-cell-mediated cutaneous inflammatory response. Multiple cell types, inflammatory mediators and cytokines are involved in the regulation of immunologic and inflammatory processes in allergic contact dermatitis. Aloperine is an isolated alkaloid found in the plant of Sophora alopecuroides L. It has been clinically proved effective in China for a long time for skin inflammatory diseases such as allergic contact dermatitis. However, the mechanism of aloperine on allergic contact dermatitis is largely unknown. Therefore, the aim of this study was to investigate the effect of aloperine on 2, 4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis in BALB/c mice and the possible underlying mechanisms. The results showed that topical application of DNFB on the ear provoked typical allergic contact dermatitis with ear swelling and ear erythema in BALB/c mice. Treatments with 1% aloperine suppressed DNFB-induced increase in ear thickness and ear erythema. Moreover, 1% aloperine treatment significantly decreased the up-regulated mRNA and protein levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) induced by DNFB in ear biopsy homogenates. Our findings suggest that aloperine greatly improves the DNFB-induced allergic contact dermatitis in mice. The therapeutic mechanism might be related to the reduction of TNF-alpha, IL-1beta and IL-6 production induced by DNFB.

The effects of corn silk on glycaemic metabolism.

BackgroundCorn silk contains proteins, vitamins, carbohydrates, Ca, K, Mg and Na salts, fixed and volatile oils, steroids such as sitosterol and stigmasterol, alkaloids, saponins, tannins, and flavonoids. Base on folk remedies, corn silk has been used as an oral antidiabetic agent in China for decades. However, the hypoglycemic activity of it has not yet been understood in terms of modern pharmacological concepts. The purpose of this study is to investigate the effects of corn silk on glycaemic metabolism.MethodsAlloxan and adrenalin induced hyperglycemic mice were used in the study. The effects of corn silk on blood glucose, glycohemoglobin (HbA1c), insulin secretion, damaged pancreatic β-cells, hepatic glycogen and gluconeogenesis in hyperglycemic mice were studied respectively.ResultsAfter the mice were orally administered with corn silk extract, the blood glucose and the HbA1c were significantly decreased in alloxan-induced hyperglycemic mice (p < 0.05, p < 0.01, respectively), while the level of insulin secretionn was markedly elevated in alloxa-induced hyperglycemic mice (p < 0.05). The alloxan-damaged pancreatic β-cells of the mice were partly recovered gradually after the mice were administered with corn silk extract 15 days later. Also, the body weight of the alloxan-induced hyperglycemic mice was increased gradually. However, ascension of blood glucose induced by adrenalin and gluconeogenesis induced by L-alanine were not inhibited by corn silk extract treatment (p > 0.05). Although corn silk extract increased the level of hepatic glycogen in the alloxan-induced hyperglycemic mice, there was no significant difference between them and that of the control group(p > 0.05).ConclusionCorn silk extract markedly reduced hyperglycemia in alloxan-induced diabetic mice. The action of corn silk extract on glycaemic metabolism is not via increasing glycogen and inhibiting gluconeogenesis but through increasing insulin level as well as recovering the injured β-cells. The results suggest that corn silk extract may be used as a hypoglycemic food or medicine for hyperglycemic people in terms of this modern pharmacological study.

A Contemporary Treatment Approach to Both Diabetes and Depression by Cordyceps sinensis, Rich in Vanadium

Diabetes mellitus is accompanied by hormonal and neurochemical changes that can be associated with anxiety and depression. Both diabetes and depression negatively interact, in that depression leads to poor metabolic control and hyperglycemia exacerbates depression. We hypothesize one novel vanadium complex of vanadium-enriched Cordyceps sinensis (VECS), which is beneficial in preventing depression in diabetes, and influences the long-term course of glycemic control. Vanadium compounds have the ability to imitate the action of insulin, and this mimicry may have further favorable effects on the level of treatment satisfaction and mood. C. sinensis has an antidepressant-like activity, and attenuates the diabetes-induced increase in blood glucose concentrations. We suggest that the VECS may be a potential strategy for contemporary treatment of depression and diabetes through the co-effect of C. sinensis and vanadium. The validity of the hypothesis can most simply be tested by examining blood glucose levels, and swimming and climbing behavior in streptozotocin-induced hyperglycemic rats.

Acupuncture Activates ERK-CREB Pathway in Rats Exposed to Chronic Unpredictable Mild Stress

Extracellular signal-regulated kinase (ERK)-cAMP response element binding protein (CREB) signal pathway has been implicated in the pathogenesis of depression. There is growing evidence that acupuncture in traditional Chinese medicine has antidepressant-like effect. However, the effect of acupuncture on ERK-CREB pathway remains unknown. In our study, the antidepressant-like effect of acupuncture treatment was measured by sucrose intake test and open field test in rats exposed to chronic unpredictable mild stress (CUMS) for 4 weeks. The protein levels of ERK1/2, CREB, phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated CREB (p-CREB) in the hippocampus (HP) and prefrontal cortex (PFC) were examined by Western blot analysis. Our results showed that CUMS rats exhibited the reduction in behavioral activities, whereas acupuncture stimulation at acupoints Baihui (Du20) and Neiguan (PC6) reversed the behavioral deficit. In addition, exposure to CUMS resulted in the decrease of p-ERK1/2 and p-CREB in the HP and PFC. Acupuncture increased the ratio of p-ERK1/2 to ERK1/2 and the ratio of p-CREB to CREB in the HP and PFC. Our study suggested that one potential way, by which acupuncture had antidepressant-like effect, might be mediated by activating the ERK-CREB pathway in the brain.

Anti-inflammation and antioxidant effect of Cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis, in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

Cordymin is a peptide purified from the medicinal mushroom Cordyceps sinensis. The present study investigated the effects of Cordymin in prevention of focal cerebral ischemic/reperfusion (IR) injury. The right middle cerebral artery occlusion model was used in the study. The effects of Cordymin on mortality rate, neurobehavior, grip strength, glutathione content, lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity glutathione S transferase activity and on the regulation of C3 and C4 protein level, polymorphonuclear cells, interleukin-1β and tumor necrosis factor-α in a rat model were studied respectively. Treatment (orally) of Cordymin significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Moreover, Cordymin significantly inhibited infiltration of polymorphonuclear cells and IR-induced up-regulation of the brain production of C3 protein level, interleukin-1β and tumor necrosis factor-α. Cordymin significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. Our findings suggest that cordymin have a neuroprotective effect in the ischemic brain, which is due to the inhibition of inflammation and increase of antioxidants activity related to lesion pathogenesis. Cordymin can be used as potential preventive agent against cerebral ischemia-reperfusion injury.

Dynamic Changes in Brain Activations and Functional Connectivity during Affectively Different Tactile Stimuli

In the present study, we compared brain activations produced by pleasant, neutral and unpleasant touch, to the anterior lateral surface of lower leg of human subjects. It was found that several brain regions, including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), as well as contralateral middle and posterior insula cortex were commonly activated under the three touch conditions. In addition, pleasant and unpleasant touch conditions shared a few brain regions including the contralateral posterior parietal cortex (PPC) and bilateral premotor cortex (PMC). Unpleasant touch specifically activated a set of pain-related brain regions such as contralateral supplementary motor area (SMA) and dorsal parts of bilateral anterior cingulated cortex, etc. Brain regions specifically activated by pleasant touch comprised bilateral lateral orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), intraparietal cortex and left dorsal lateral prefrontal cortex (DLPFC). Using a novel functional connectivity model based on graph theory, we showed that a series of brain regions related to affectively different touch had significant functional connectivity during the resting state. Furthermore, it was found that such a network can be modulated between affectively different touch conditions.

The opioid placebo analgesia is mediated exclusively through μ-opioid receptor in rat.

Placebo analgesia is one of the most robust and best-studied placebo effects. Recent researches suggest that placebo analgesia activated the μ-opioid receptor signalling in the human brain. However, whether other opioid receptors are involved in the placebo analgesia remains unclear. We have previously evoked placebo responses in mice (Guo et al. 2010, 2011) and these mice may serve as a model for investigating placebo analgesia. In the present study, we tried to explore the site of action and types of opioid receptors involved in placebo response. Male Sprague-Dawley rats were trained with 10 mg/kg morphine for 4 d to establish the placebo analgesia model. This placebo analgesia can be blocked by injection of 5 mg/kg dose naloxone or by microinjection with naloxone (1, 3 or 10 μg/rat) into rostral anterior cingulate cortex (rACC). Then, animals were tested after intra-rACC microinjection of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP, a selective μ-opioid receptor antagonist) or naltrindole (NTI, a highly selective δ-opioid receptor antagonist) or nor-binaltorphimine (nor-BNI, a highly selective κ-opioid receptor antagonist). Our results showed that CTOP, but not NTI or nor-BNI, could reduce the pain threshold in placebo analgesia rats. It may be concluded that rACC is the key brain region involved in placebo analgesia and the opioid placebo analgesia is mediated exclusively through μ-opioid receptor in rat.

Beta-asarone, a major component of Acorus tatarinowii Schott, attenuates focal cerebral ischemia induced by middle cerebral artery occlusion in rats

BackgroundIschemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. β-Asarone, which has significant pharmacological effects on the central nervous system (CNS), was used in the prevention of cerebral ischemia in this paper.MethodsThe right middle cerebral artery occlusion model was used in the study. The effects of β-Asarone on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+-K+-ATPase activity and glutathione S transferase activity in a rat model were studied respectively.Resultsβ-Asarone significantly improved the neurological outcome after cerebral ischemia and reperfusion in terms of neurobehavioral function in rats. Meanwhile, supplementation of β-Asarone significantly boosted the defense mechanism against cerebral ischemia via increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may help the brain recover from ischemic injury.ConclusionsThese experimental results suggest that complement β-Asarone is protective against cerebral ischemia in specific way. The administration of β-Asarone could reduce focal cerebral ischemic/reperfusion injury. The Mechanism of β-Asarone in protection of cerebral ischemia was via increasing antioxidants activity related to lesion pathogenesis.

Topical application of aloperine improves 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice

Aloperine has been shown to inhibit 2,4-dinitrofluorobenzene (DNFB) induced allergic contact dermatitis in BALB/c mice. In the present study, we further investigated the effect of aloperine on DNFB-induced atopic dermatitis-like skin lesions in NC/Nga mice. NC/Nga mice elicited atopic dermatitis-like skin lesions after the topical application of DNFB. Aloperine treatment significantly inhibited dermatitis index and ear thickness in DNFB-treated NC/Nga mice in a dose-dependent manner. Eosinophils, mast cells infiltration into the ears and plasma level of immunoglobulin (Ig) E were also suppressed by aloperine treatment. Finally, cytokine (interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-13, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) productions in ear biopsies homogenates were significantly elevated after DNFB challenge. Topical application of aloperine increased the immunosuppressive cytokine IL-10 level, while it reduced other cytokines production in a dose-dependent manner. Taken together, these data suggest that aloperine may be one of the effective therapeutic agents for the treatment of atopic dermatitis.