褪黑素在哮喘防治中的作用

褪黑素是由松果体分泌的一种神经内分泌激素,具有节律调节、应激反应和清除自由基等生物学功能。近年研究发现,在哮喘患者体内存在褪黑素分泌及代谢功能紊乱,褪黑素干预研究显现其在哮喘的抗炎、免疫调节等方面具有一定的作用。     

α-黑素细胞刺激素作用的信号转导机制

α-黑素细胞刺激素(α-MSH)是来源于阿黑皮素原的一种神经内分泌免疫调节肽。本文综述了近年来对α-MSH作用的信号转导机制的研究进展,包括α-MSH在调节黑素生成,保护黑素细胞,抗炎,抑制摄食,介导脱敏,调节B细胞生长及调控皮肤光老化过程中的相关信号转导机制。     

宿主防御肽抗病毒感染机制研究进展

宿主防御肽是一类广泛存在于脊椎动物的小分子多肽,具有广谱的抗菌活性以及抗炎、细胞趋化、促进血管生成和修复损伤等免疫调节功能。以往的研究多集中在宿主防御肽抗细菌和真菌感染的研究上。近年来大量研究发现,宿主防御肽也具有广泛的抗病毒活性,在临床各类病毒病的预防和治疗上具有潜在的应用前景。本文围绕宿主防御肽直接杀伤病毒、调节病毒感染过程和参与宿主抗病毒天然免疫调节这3个方面的作用机制进行综述,为宿主防御肽抗病毒相关研究和相关抗病毒生物药物的研发提供参考和借鉴。     

壳寡糖的制备及生物学活性研究进展

壳寡糖是由壳聚糖水解得到的一类具有抗炎、抗肿瘤、可调节免疫和神经保护等多种生物学活性的化合物,被广泛应用于农业、医药、食品等领域,也是目前国内外研究的热点。本文就壳寡糖的制备方法及生物学活性进行了综述,以期对深入研究壳寡糖提供依据。     

腺苷酸活化蛋白激酶在脂联素心血管保护效应中的作用

脂联素是主要由白色脂肪组织分泌的一种活性多肽,具有调节脂肪酸和葡萄糖代谢、抗炎、减轻动脉粥样硬化等多种生物学功能,血浆脂联素含量降低参与了代谢性疾病及心血管疾病的发生、发展。腺苷酸活化蛋白激酶（AMP．activated protein kinase,AMPK）是脂联素信号通路中的关键信号分子,本文就其在脂联素心血管保护效应中的作用作一综述,介绍脂联素改善糖、脂代谢紊乱、动脉粥样硬化、心力衰竭及心肌缺血,再灌注损伤作用机制的新进展。     

橘皮素生物活性及其对运动性哮喘的潜在功效CSCD

运动性哮喘(exercise-induced asthma,EIA)作为运动员群体的第一大慢性疾病,正日益受到关注。虽然EIA的病理研究及药物治疗研究已取得一定进展,但长期服用EIA治疗药物不仅危害运动员身心健康,而且极易导致兴奋剂阳性问题。因此,亟需寻求一种安全、健康、有效的干预方法以替代药物治疗或降低药物依赖度。橘皮素是一种天然柑橘提取化合物,近年多项研究指出它在治疗EIA方面有巨大潜力。本文归纳、梳理与分析了橘皮素的多种生物活性,如:抗炎、抗氧化、抗肿瘤活性、调节尿酸与皮质醇合成分泌、调节糖脂代谢与抗肥胖、神经保护等,为深入研究和开发橘皮素食品、保健品及药品并用于EIA治疗提供思路与理论支撑。     

白藜芦醇的生理功能及其应用前景

白藜芦醇是广泛存在于葡萄、花生、虎杖、藜芦、决明等植物中的活性物质,也是红葡萄酒的主要保健成分,具有保肝、抗炎、抗肿瘤、调节血脂、抗病原微生物等多种有益于人体的生物学作用。综述了白藜芦醇的生理功能和应用前景。     

乌索酸与齐墩果酸衍生物的合成进展

乌索酸和齐墩果酸在多种植物中均有分布.二者互为同分异构体,均属于五环三萜类化合物,由于其结构多样性而具有广泛的生物活性,包括抗肿瘤、抗氧化、抗艾滋病、抗溃疡、抗炎、免疫调节等功能.有关这两种活性物质的衍生化研究一直为科研人员所关注,本文主要综述了近10年来二者衍生物合成方面的新进展,为寻找活性先导化合物、合理设计药物分子提供依据.     

中枢神经系统中的心房利钠多肽

放射免疫及免疫组织化学等方法显示:大鼠中枢神经系统广泛存在心房利钠多肽样免疫活性物质,其密度以下丘脑和隔区最高。中枢神经系统中的某些神经元可能在核周体合成心房利钠多肽,参与水、电解质平衡以及心血管活动等多种生理功能的中枢调节过程。提示心房利钠多肽可能既是一种激素,又是中枢神经系统一种新的肽类神经递质或调节因子。     

红枣活性成分及其生物活性研究进展

红枣中的活性成分以多糖、黄酮类、环核苷酸类、多酚类、五环三萜类、生物碱为主,具有抗氧化、免疫调节及抗肿瘤、保护肝脏、降血糖、抗炎等多种生物活性。本文综述了红枣中活性成分及生物活性的研究进展,并对红枣产业的发展进行展望,为红枣中活性成分的开发与利用提供科学依据。     

Neuropeptide FF activates ERK and NF kappa B signal pathways in differentiated SH-SY5Y cells

Neuropeptide FF (NPFF) has been reported to play important roles in regulating diverse biological processes. However, little attention has been focused on the downstream signal transduction pathway of NPFF. Here, we used the differentiated neuroblastoma cell line, dSH-SY5Y, which endogenously expresses hNPFF2 receptor, to investigate the signal transduction downstream of NPFF. In particular we investigated the regulation of the extracellular signal-regulated protein kinase (ERK) and the nuclear factor kappa B (NF-κB) pathways by NPFF in these cells. NPFF rapidly and transiently stimulated ERK. H89, a selective inhibitor of cyclic AMP-dependent protein kinase A (PKA), inhibited the NPFF-activated ERK pathway, indicating the involvement of PKA in the NPFF-induced ERK activation. Down-regulation of nitric oxide synthases also attenuated NPFF-induced ERK activation, suggesting that a nitric oxide synthase-dependent pathway is involved. Moreover, the core upstream components of the NF-κB pathway were also significantly activated in response to NPFF, suggesting that the NF-κB pathway is involved in the signal transduction pathway of NPFF. Collectively, these data demonstrate that nitric oxide synthases are involved in the signal transduction pathway of NPFF, and provide the first evidence for the interaction between NPFF and the NF-κB pathway. These advances in our interpretation of the NPFF pathway mechanism will aid the comprehensive understanding of its function and provide novel molecular insight for further study of the NPFF system.     

Anti-analgesia of a selective NPFF2 agonist depends on opioid activity

NPFF agonists designed to be selective NPFF(2) receptor probes were synthesized. D.Asn-Pro-(N-Me)Ala-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH(2) (dNPA) displays a very high affinity (0.027nM) for NPFF(2) receptors transfected in CHO cells, and a very high selectivity with a discrimination ratio greater than 100 versus NPFF(1) receptors. dNPA acts as a potent and selective agonist in [(35)S]GTPgammaS binding experiments and inhibits intracellular cAMP production with the same efficacy as NPA-NPFF. In SH-SY5Y cells expressing NPFF(2) receptors dNPA, in the presence of carbachol, stimulates Ca(2+) release from the intracellular stores. In vivo, after intracerebroventricular injection dNPA increases body temperature in mice and reverses the morphine-induced analgesia. Also, dNPA displays anti-opioid activity after systemic administration. So far, dNPA exhibits the highest affinity and selectivity for NPFF(2) receptors and reveals that its behavioral anti-opioid activity depends on the degree of opioid-induced analgesia.     

Neuropeptide FF receptor antagonist, RF9, attenuates the fever induced by central injection of LPS in mice

The endogenous opioid system has been found to be involved in the fever caused by lipopolysaccharide (LPS). Neuropeptide FF (NPFF, FLFQPQRF-NH₂) is an endogenous peptide known to modulate opioid activity, mainly in the central nervous system. Therefore, those data suggested a link between LPS-induced fever and NPFF systems. Using a model of acute neuroinflammation, we sought to determine the effects of NPFF systems on the fever induced by i.c.v. injection of LPS. Coinjected with different doses of NPFF (10 and 30 nmol), the fever of LPS (125 ng) was not modified. Interestingly, the selective NPFF receptors antagonist RF9 (30 nmol) injected into the third ventricle failed to induce significant effect, but it decreased the fever of LPS (125 ng) after cerebral administration in mice. These results suggest that NPFF receptors activation is required for LPS to produce fever. This interaction is the first evidence that NPFF systems participate in the control of acute neuroinflammation in conscious animals.     

Modulatory roles of the NPFF system in pain mechanisms at the spinal level

The possible roles of the NPFF system in pain processing are summarized from the viewpoints of (1) biological activities of NPFF, (2) anatomical distribution of NPFF and its receptor(s) and (3) the regulation of NPFF and receptor(s) in animal models of pain. NPFF and NPFF analogues were found to have analgesic, pronociceptive and morphine modulating activities. Since the isolation of NPFF, several other RF-NH2 peptides have been identified and some of them were found to have nociceptive or morphine modulating activity. Depending on the pharmacological doses and locations of administration, NPFF may exhibit the biological activities of other structurally related RF-NH2 peptides thus complicating NPFF bioactivity studies and their interpretation. Acid sensing ion channels were found to respond to RF-NH2 peptides including NPFF, raising the possibility that interaction of NPFF and acid sensing ion channels can modulate nociceptive activity. NPFF and NPFF receptor mRNAs are highly expressed and localized in the superficial layers of the dorsal cord, the two genes are also in dorsal root ganglia though at much lower level. The spinal NPFF system is up-regulated by peripheral inflammation in the rat. Furthermore, immunohistochemically, NPFF receptor 2-protein was demonstrated to be increased in the primary afferents in the spinal cord of rats with peripheral inflammation. Regulation and localization of spinal NPFF systems, taken together with the analgesic bioactivity of intrathecally administered NPFF, strongly suggest involvement of spinal NPFF system in pain processing.     

Assessing activation of the human neuropeptide FF2 receptor with a non-radioactive GTP binding assay

We have evaluated a novel, time-resolved fluorometric GTP binding assay for its suitability for functional screening of neuropeptide FF (NPFF) receptor ligands. Our results suggest that this assay, which relies on the use of a europium-labeled GTP analogue, Eu-GTP, provides a powerful alternative to the [³⁵S]guanosine-5′-O-(3-thio)triphosphate binding assay for assessing the functional properties of NPFF analogs. Further, we demonstrate that the tetrapeptide PMRF-NH₂ exhibited high agonist potency at the NPFF2 receptor, and that the efficacies of this peptide and another shortened NPFF analog were greater than that of NPFF.     

Regulation of endogenous human NPFF2 receptor by neuropeptide FF in SK-N-MC neuroblastoma cell line

Neuropeptide FF has many functions both in the CNS and periphery. Two G protein-coupled receptors (NPFF1 and NPFF2 receptors) have been identified for neuropeptide FF. The expression analysis of the peptide and receptors, together with pharmacological and physiological data, imply that NPFF2 receptor would be the primary receptor for neuropeptide FF. Here, we report for the first time a cell line endogenously expressing hNPFF2 receptor. These SK-N-MC neuroblastoma cells also express neuropeptide FF. We used the cells to investigate the hNPFF2 receptor function. The pertussis toxin-sensitive inhibition of adenylate cyclase activity upon receptor activation indicated coupling to Gi/o proteins. Upon agonist exposure, the receptors were internalized and the mitogen-activated protein kinase cascade was activated. Upon neuropeptide FF treatment, the actin cytoskeleton was reorganized in the cells. The expression of hNPFF2 receptor mRNA was up-regulated by neuropeptide FF. Concomitant with the receptor mRNA, the receptor protein expression was increased. The homologous regulation of hNPFF2 receptor correlates with our previous results in vivo showing that during inflammation, the up-regulation of neuropeptide FF mRNA precedes that of NPFF2 receptor. The regulation of hNPFF2 receptor by NPFF could also be important in the periphery where neuropeptide FF has been suggested to function as a hormone.     

Neuropeptide FF receptors antagonist, RF9, attenuates opioid-evoked hypothermia in mice

The present study used the endpoint of hypothermia to investigate opioid and neuropeptide FF (NPFF) interactions in conscious animals. Both opioid and NPFF systems played important roles in thermoregulation, which suggested a link between opioid receptors and NPFF receptors in the production of hypothermia. Therefore, we designed a study to investigate the relationship between opioid and NPFF in control of thermoregulation in mice. The selective NPFF receptors antagonist RF9 (30nmol) injected into the third ventricle failed to induce significant effect, but it completely antagonized the hypothermia of NPFF (45 nmol) after cerebral administration in mice. In addition, RF9 (30 nmol) co-injected i.c.v. in the third ventricle reduced the hypothermia induced by morphine (5nmol,) or nociceptin/orphanin FQ (N/OFQ) (2 nmol). Neither the classical opioid receptors antagonist naloxone (10 nmol) nor NOP receptor antagonist [Nphe(1)]NC(1-13)NH(2) (7.5 nmol) reduced the hypothermia induced by the central injection of NPFF at dose of 45 nmol. Co-injected with a low dose of NPFF (5 nmol), the hypothermia of morphine (5 nmol) or N/OFQ (2 nmol) was not modified. These results suggest that NPFF receptors activation is required for opioid to produce hypothermia. In contrast, NPFF-induced hypothermia is mainly mediated by its own receptors, independent of opioid receptors in the mouse brain. This interaction, quantitated in the present study, is the first evidence that NPFF receptors mediate opioid-induced hypothermia in conscious animals.     

Neuropeptide FF (NPFF) reduces the expression of cocaine-induced conditioned place preference and cocaine-induced sensitization in animals

The endogenous brain opioid system is believed to play an important role in mediating reward mechanisms. Opioid innervation is high in many limbic regions and reinforcing actions of many drugs of abuse, including cocaine, are thought to be mediated via endogenous opioid system. The aim of the present study was to indicate whether the anti-opioid peptide, neuropeptide FF (NPFF; FLFQPQRF-NH₂) was able to modify the rewarding effect of cocaine (5 mg/kg) measured in the expression of conditioned place preference (CPP) test in rats and the expression of sensitization to hyperlocomotor effect of cocaine (10 mg/kg) in mice. Our results indicate that NPFF (5, 10, and 20 nmol) given intracerebroventricularly (i.c.v.) inhibited the expression of cocaine-induced CPP at the dose of 10 nmol (P < 0.01) and 20 nmol (P < 0.001). Moreover, NPFF inhibited the expression of cocaine-induced sensitization to its hyperlocomotor effect at the dose of 20 nmol (P < 0.05) and acute hyperlocomotor effect of cocaine at doses of 5 nmol (P < 0.01), 10 nmol (P < 0.01), and 20 nmol (P < 0.05). Our study suggests that NPFF may participate in a rewarding effect of cocaine measured in the CPP paradigm. On the other hand, our experiments indicate that NPFF is involved in the mechanism of expression of sensitization to cocaine hyperlocomotion but this effect seems to be non-specific because NPFF also inhibited the acute hyperlocomotor effect of cocaine.     

Inhibition of neuropeptide FF (NPFF)-induced hypothermia and anti-morphine analgesia by RF9, a new selective NPFF receptors antagonist

Neuropeptide FF (NPFF) belongs to a neuropeptide family including two precursors (pro-NPFF_A and pro-NPFF_B) and two receptors (NPFF₁ and NPFF₂). Very recently, the novel compound RF9 was reported as the truly selective antagonist on NPFF receptors. The present study examined the effects of RF9 on the hypothermia and anti-morphine action induced by NPFF in mice. (1) RF9 injected into the third ventricle was devoid of any residual agonist activity, but it completely antagonized the hypothermic effects of NPFF (30 or 45 nmol) after cerebral administration in mice; (2) RF9 did not alter the tail-flick latency and morphine analgesia in nociceptive test, however, co-administration of RF9 prevented the anti-morphine action of intracerebroventricularly applied NPFF (10 nmol, i.c.v.) in the mouse tail-flick assay. Collectively, our data indicate that RF9, behaving as a truly pure NPFF receptors antagonist, prevents NPFF-induced drops of the body temperature and morphine analgesia in mice. In addition, it further confirms that the hypothermia and anti-morphine action of NPFF are mediated directly by NPFF receptors.