[Movement Control of Striatum Neural Pathway].

Striatum is the central structure controlling movement. It plays a pivotal role in the regulation of voluntary movement, unconscious movement, muscle tone, posture adjustment and fine movement. Dysfunction of striatum causes a variety of movement disorders ranging from the hypokinetic disorders with increased muscle tone, such as Parkinson's disease, to the hyperkinetic disorders with decreased muscle tone, such as Huntington's disease. It is generally recognized that striatum receives the neural movement signals from the motor cortex, and then processes and modifies these signals and subsequently transfers the signals back to the motor cortex via thalamus for execution of the movement through pyramidal system. The movement control function of striatum depends on a complex neural circuit system. In this review, the studies on the movement control function of striatum as well as the striatal neural circuit system are summarized with an emphasis on the progress made during recent years for better understanding the mechanism underlying the movement control function as well as the disease association of striatum.

Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid ß-Mediated Neurotoxicity.

Alzheimer's disease (AD) is characterized by a large number of amyloid-ß (Aß) deposits in the brain. Therefore, inhibiting Aß aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported to exhibit antioxidant and neuroprotective effects. Recent study shows that COS could markedly decrease oligomeric Aß-induced neurotoxicity and oxidative stress in rat hippocampal neurons. However, the potential mechanism that COS reduce Aß-mediated neurotoxicity remains unclear. In the present study, our findings from circular dichroism spectroscopy, transmission electron microscope and thioflavin T fluorescence assay suggested that COS act as an inhibitor of Aß aggregation and this effect shows dose-dependency. Moreover, data from thioflavin T assay indicated that COS could significantly inhibit fibrils formation and disrupt preformed fibrils in a dose-dependent manner. Furthermore, the addition of COS attenuated Aß1-42-induced neurotoxicity in rat cortical neurons. Taken together, our results demonstrated for the first time that COS could inhibit Aß1-42 fibrils formation and disaggregate preformed fibrils, suggesting that COS may have anti-Aß fibrillogenesis and fibril-destabilizing properties. These findings highlight the potential role of COS as novel therapeutic agents for the prevention and treatment of AD.

[Leptin Signalings and Leptin Resistance].

Leptin plays a critical role in the regulation of energy balance and metabolic homeostasis. Impairment of leptin function is closely involved in the pathogenesis of obesity, diabetes mellitus and some other metabolic diseases. Leptin initiates intracellular signal transductions in the leptin-receptor-expressing neurons in the central nervous system to exert its physiological functions. The fact that high circulating levels of leptin partially or completely fail to promote weight loss in obesity has given rise to the notion of "leptin resistance". Recently, the impairment of leptin signalings in the hypothalamus has been regarded as a critical contributor to leptin resistance. In this review, the studies on leptin signaling and leptin resistance are summarized with an emphasis on the progress made during the last five years.

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis.

14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen-glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1.

CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.

Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro. In addition, the effects of CART on ischemia-induced neuronal apoptosis and ER stress were suppressed by tyrosine receptor kinase B (TrkB) IgG, whereas the effects of CART on BDNF transcription, synthesis and secretion were abolished by CREB siRNA. This work suggests that CART is functional in inhibiting the cerebral I/R-induced ER stress and neuronal apoptosis by facilitating the transcription, synthesis and secretion of BDNF in a CREB-dependent way.

Aß-40 Y10F increases ßfibrils formation but attenuates the neurotoxicity of amyloid-ß peptide.

Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid-ß peptide (Aß) in extracellular deposits known as senile plaques. The tyrosine residue (Tyr-10) is believed to be important in Aß-induced neurotoxicity due to the formation of tyrosyl radicals. To reduce the likelihood of cross-linking, here we designed an Aß-40 analogue (Aß-40 Y10F) in which the tyrosine residue was substituted by a structurally similar residue, phenylalanine. The aggregation rate was determined by the Thioflavin T (ThT) assay, in which Aß-40 Y10F populated an ensemble of folded conformations much quicker and stronger than the wild type Aß. Biophysical tests subsequently confirmed the results of the ThT assay, suggesting the measured increase of ß-aggregation may arise predominantly from enhancement of hydrophobicity upon substitution and thus the propensity of intrinsic ß-sheet formation. Nevertheless, Aß-40 Y10F exhibited remarkably decreased neurotoxicity compared to Aß-40 which could be partly due to the reduced generation of hydrogen peroxide. These findings may lead to further understanding of the structural perturbation of Aß to its fibrillation.

High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways.

AIM: To investigate whether high glucose stimulates the expression of inflammatory cytokines and the possible mechanisms involved. METHODS: ELISA and real-time PCR were used to determine the expression of the inflammatory factors, and a chemiluminescence assay was used to measure the production of reactive oxygen species (ROS). RESULTS: Compared to low glucose (10 mmol/L), treatment with high glucose (35 mmol/L) increased the secretion of tumor necrosis factor (TNF)α and monocyte chemotactic protein-1 (MCP-1), but not interleukin (IL)-1ß and IL-6, in a time-dependent manner in primary cultured rat microglia. The mRNA expression of TNFα and MCP-1 also increased in response to high glucose. This upregulation was specific to high glucose because it was not observed in the osmotic control. High-glucose treatment stimulated the formation of ROS. Furthermore, treatment with the ROS scavenger NAC significantly reduced the high glucose-induced TNFα and MCP-1 secretion. In addition, the nuclear factor kappa B (NF-κB) inhibitors MG132 and PDTC completely blocked the high glucose-induced TNFα and MCP-1 secretion. CONCLUSION: We found that high glucose induces TNFα and MCP-1 secretion as well as mRNA expression in rat microglia in vitro, and this effect is mediated by the ROS and NF-κB pathways.

Temporospatial effects of acyl-ghrelin on activation of astrocytes after ischaemic brain injury.

The protective mechanisms of astrocyte signalling are based on the release of neurotrophic factors and the clearing of toxic substances in the early stages of cerebral ischaemia. However, astrocytes are also responsible for the detrimental effects that occur during the later stages of ischaemia, in which glial scars are formed, thereby impeding neural recovery. Acyl-ghrelin has been found to be neuroprotective after stroke, although the influence of acyl-ghrelin on astrocytes after ischaemic injury is yet to be clarified. In the present study, we used permanent middle cerebral arterial occlusion to establish a brain ischaemia model in vivo, as well as oxygen and glucose deprivation (OGD) to mimic ischaemic insults in vitro. We found that acyl-ghrelin injection significantly increased the number of activated astrocytes in the peri-infarct area at day 3 after brain ischaemia and decreased the number of activated astrocytes after day 9. Moreover, the expression of fibroblast growth factor 2 (FGF2) in the ischaemic hemisphere increased markedly after day 3, and i.c.v. injection of SU5402, an inhibitor of FGF2 signalling, abolished the suppression effects of acyl-ghrelin on astrocyte activation in the peri-infarct region during the later stages of ischaemia. The results from in vitro studies also showed the dual effect of acyl-ghrelin on astrocyte viability. Acyl-ghrelin increased the viability of uninjured astrocytes in an indirect way by stimulating the secretion from OGD-injured astrocytes. It also inhibited the astrocyte viability in the presence of FGF2 in a dose-dependent manner. Furthermore, the expression of acyl-ghrelin receptors on astrocytes was increased after acyl-ghrelin and FGF2 co-treatment. In conclusion, acyl-ghrelin promoted astrocyte activation in the early stages of ischaemia but suppressed the activation in later stages of ischaemic injury. These later effects were likely to be triggered by the increased expression of endogenous FGF2 after brain ischaemia.

Ghrelin Promotes Cortical Neurites Growth in Late Stage After Oxygen-Glucose Deprivation/Reperfusion Injury.

Acyl ghrelin, a novel brain-gut peptide, is an endogenous ligand for the growth hormone secretagogue receptor. Accumulated research data have shown that acyl ghrelin exercises a significant neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury in animal models and in cultured neurons during the acute phase, usually, 1 day after cerebral ischemia. The chronic effects of acyl ghrelin 1 week after brain ischemia remain largely unknown. In this study, we explored the effects of acyl ghrelin on cultured organotypic brain slices and cortical neurons which were injured by oxygen-glucose deprivation/reperfusion(OGD/R) for 7 days. The underlying molecular mechanisms were deciphered based on label-free proteomic analysis. Acyl ghrelin treatment promoted neurite (axons and dendrites) growth and alleviated the neuronal damage in both cultured brain slices and neurons. Proteomic analysis showed that cell division control protein 42 (Cdc42) mediates the effects of acyl ghrelin on neurite growth. Acyl ghrelin stimulated the expression of Cdc42 and neurite growth in cultured neurons comparing with OGD/R group. Inhibition of Cdc42 attenuated the effects of acyl ghrelin. These results suggest that acyl ghrelin promotes neurite growth during the later stage after OGD/R injury via Cdc42. Our study suggests that acyl ghrelin may be promising to restore the neuronal structure in the late phase after stroke.

Unravel a neuroactive sHA sulfation pattern with neurogenesis activity by a library of defined oligosaccharides.

Sulfated hyaluronic acid (sHA) is chemically synthetic mimetic of glycosaminoglycan (GAG) presenting promising biological functions. Specific sulfation pattern, termed as sulfation code plays critical roles in regulating the binding mode between GAG and proteins. As a structural analogue of chondroitin sulfate (CS), sHA bears much higher molecular weight and is nearly free of other proteoglycan contaminants. These properties make sHA a better bioscaffold to build safer and more functionalized material. However, chemical sulfonation process on naked HA polysaccharide produces random sulfation patterns which makes it difficult in disclosing the SAR. Herein, we utilized sHA and CS oligosaccharides with defined sulfation pattern to unravel the SAR between sHA and neurogenesis. We demonstrate sHA tetrasaccharide bearing 6-O-sulfation (sHA-6S) but not other sulfation patterns bind to growth factors at nanomolar range and promote the neurite outgrowth of rat E18 hippocampal neurons in vitro. Furthermore, synthetic sHA polysaccharide enriched in 6-O-sulfation also promote the hippocampal neurite outgrowth in vitro. Our work provides an effective method to disclose the bioactive sulfation pattern of sHA. Our results indicate that a specific sHA sulfation pattern could direct important physiological processes and open the way for the application of sHA-6S in neuroscience and medicine.

Activation of the Nuclear Receptor Fxr Improves Intestinal Cell Tolerance to Ischemia-Reperfusion Injury.

The farnesoid X receptor (FXR) plays an important role in bile acid metabolism, intestinal homeostasis, and intestinal ischemia-reperfusion (I/R) injury. We aimed to clarify the potential effects of FXR on intestinal epithelial cell tolerance to intestinal I/R injury and reveal the underlying mechanisms. An intestinal I/R injury model was established by the occlusion of the superior mesenteric artery for ischemia for 1 h, followed by reperfusion for 4 h in C57BL/6 (wild type [WT]) and FXR mice. The small intestine injury was assessed by histological analysis. Diamine oxidase and TNF-α levels in the serum were measured. Expressions of Bcl-2, Bax, caspase-3, and cystathionine-γ-lyase (CSE) were determined by immunohostochemical staining. Oxygen-glucose deprivation/reperfusion (OGD/R) was used to make injury in cultured Caco-2 cells pretreated with FXR agonist (INT-747) or DL-propargylglycine (PAG) for 24 h. Cell viability and the expressions of NF-κB, TNF-α, and IL-6 were assessed. Compared with WT I/R mice, FXR knockout mice exacerbated intestinal I/R injury, intestinal epithelial apoptosis, and inflammatory response. The I/R injury in WT mice was alleviated with INT-747 pretreatment. CSE expression increased after intestinal I/R injury in WT but not in FXR mice. INT-747 enhanced Caco-2 cell viability and inhibited inflammatory response by blocking the NF-κB pathway after OGD/R injury, which was diminished by a CSE-specific inhibitor (PAG). Thus, we demonstrated that FXR activation enhances intestinal epithelial cell tolerance to I/R by suppressing the inflammatory response and NF-κB pathway via CSE mediation.

Ghrelin-containing neuron in cerebral cortex and hypothalamus linked with the DVC of brainstem in rat.

Ghrelin is a newly discovered brain-gut peptide and an endogenous ligand for growth hormone secretagogues receptor (GHS-R). Ghrelin and GHS-R present extensively in central and peripheral tissues such as stomach, brain and other organs of rodent and human, which suggest it has multiple biological effects. It has been reported that ghrelin has significant role in the regulation of energy homeostasis, food intake and appetite. The organization of central circuitry appears to play an important role in integrating orexigenic effects of ghrelin, but the detail is not fully clear. In this study, we examined the expression of ghrelin, ghrelin mRNA and GHS-R mRNA in cerebrum and brainstem by RT-PCR and immunofluorescence histochemistry, and analyzed the connection among the cerebral cortex, hypothalamus, dorsal vagal complex (DVC). The results showed that the positive staining of ghrelin was found on the pyramidal neuron of layer V in the sensorimotor area of cerebral cortex, cingulate gyrus, as well as in the neuron of lateral hypothalamus (LH), PVN and ARC. The expression of ghrelin mRNA and GHS-R mRNA were also found in the sensorimotor cortex and hypothalamus by method of RT-PCR. The GHS-R mRNA was also found in the DVC of medulla oblongata. Other finding is that the FG/ghrelin dual labeled neurons were found in LH of hypothalamus (not in cortex). The ghrelin-containing neuron in the LH projects its axon to the DVC with the method of retrograde tracing. In conclusion, the ghrelin neurons are located not only in hypothalamus (LH, PVN, ARC), but also in the cortex (sensorimotor area, cingular gyrus), and the fibers of ghrelin neurons in hypothalamus projected directly to the DVC. It suggests that ghrelin plays its role from hypothalamus to brainstem as a neurotransmitter or neuromodulator to regulate function of vagal nuclei in brainstem.

Role of the central interleukin-1 in stress responses.

The molecules of interleukin-1 (IL-1) system are widely distributed in central nervous system. As a classical pro-inflammatory factor, central IL-1 has diverse biological functions and plays a pivotal role in a number of important physiological and pathophysiological processes. During the past few years, particular attentions have been directed to the stress mediator actions of central IL-1. This paper reviews some recent findings in the studies of central IL-1 functions in stress responses, including the effects of stress on central IL-1, the roles of IL-1 in the initiation of stress responses, the neural circuitries and intracellular signal transduction pathways involved in the central IL-1 mediated stress responses, as well as the actions of central IL-1 on brain high function and behavior under stressful conditions.

Effects of ghrelin on the proliferation and secretion of splenic T lymphocytes in mice.

Ghrelin, a novel gut--brain peptide predominantly produced by the stomach, displays strong growth hormone (GH)-releasing activity mediated by the hypothalamus-pituitary GH secretagogue receptor (GHS-R). Recently, the ghrelin receptor has also been detected in peripheral systems including immune tissues, suggesting that ghrelin may play an important role in the regulation of immune function. In this paper, we assessed the presence and function of the ghrelin receptor in murine splenic T cells. The enriched T cells express the mRNA of ghrelin and ghrelin receptor mRNA, and there is a significantly positive correlation between them. Moreover, we showed that ghrelin dose-dependently inhibits proliferation of splenic T cells when they are costimulated by anti-CD3. In addition, ghrelin suppressed Th(1) (IL-2 and IFN-gamma) and Th(2) (IL-4 and IL-10) cytokines mRNA expression. These results demonstrate the presence of the ghrelin receptor in murine spleen T lymphocytes and a functional role of ghrelin as a modulator of lymphocyte function. This function of ghrelin may have some relevance to the pathophysiology of immunologic alterations related to metabolism.

[Central interleukin-1beta involved in modulation of motor behavior in novelty stress rats].

OBJECTIVE: To investigate the effect of central interleukin-1beta (IL-1beta) on motor behavioral responses in novelty stress rats. METHODS: The novelty stress was elicited by novel environmental stimuli with novelty stress box. The intracerebrolventricular (ICV) cannula and microinjection were performed with rat brain stereotaxic system. Movement behaviors of rats were monitored by behavioral radio-telemetry system. As behavior index, mean percent immobility (MPI) was used to assess immobility of rats. RESULTS: The decrease of MPI was remarkably elicited by novel environmental stimuli. In non-stressful condition, ICV anti-IL-1beta antibody did not influence the MPI. The decrease of MPI induced by novel environmental stimuli was significantly blocked by ICV pretreatment with anti-IL-1beta antibody. In novel stress, MPI of rats was not affected by ICV injection of non specific IgG. CONCLUSION: Central interleukin-1beta plays an important role in modulation of motor behavioral response to novelty stress.

[Progress in central interleukin-1 system and its signaling pathway].

Central interleukin-1 (IL-1 ) system is a relatively independent system which is composed of IL-1 and other molecules associated with IL-1 in functions or structures. The knowledge of central IL-1 system in the constitution and function have been extended with the discovery of new members and its function, the extensive and intensive research on intracellular signaling pathways, as well as the relationship among those molecules. This paper reviews the recent findings in the study of central IL-1 system, which comprises the new members, new signaling molecules, new biological functions, and the effects in the processes of physiology and pathophysiology.

Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Ab42-induced neurodegeneration.

The outer mitochondrial membrane (OMM) protein, the translocator protein 18 kDa (TSPO), formerly named the peripheral benzodiazepine receptor (PBR), has been proposed to participate in the pathogenesis of neurodegenerative diseases. To clarify the TSPO function, we identified the Drosophila homolog, CG2789/dTSPO, and studied the effects of its inactivation by P-element insertion, RNAi knockdown, and inhibition by ligands (PK11195, Ro5-4864). Inhibition of dTSPO inhibited wing disk apoptosis in response to γ-irradiation or H2O2 exposure, as well as extended male fly lifespan and inhibited Aß42-induced neurodegeneration in association with decreased caspase activation. Therefore, dTSPO is an essential mediator of apoptosis in Drosophila and plays a central role in controlling longevity and neurodegenerative disease, making it a promising drug target.

Chitosan oligosaccharides protect rat primary hippocampal neurons from oligomeric ß-amyloid 1-42-induced neurotoxicity.

ß-Amyloid peptide (Aß), the major component of senile plaques in patients with Alzheimer's disease (AD), is believed to facilitate the progressive neurodegeneration that occurs in this disease. Mounting natural compounds are proved to be potential candidates for the prevention and treatment of AD. Chitosan oligosaccharides (COSs), the enzymatic hydrolysates of chitosan, have been reported to possess diverse biological activities. Here we investigated the effect of COSs on oligomeric Aß-mediated toxicity in rat primary hippocampal neurons. Pretreatment with COSs markedly inhibited cell death induced by Aß exposure as determined by cell viability assay and lactate dehydrogenase release assay. In parallel, the generation of reactive oxygen species and lipid peroxidation were attenuated by COSs. Furthermore, our results indicated that COSs remarkably prevented Aß-induced cell apoptosis as manifested by depressing the elevation of Bax/Bcl-2 ratio and caspase-3 activation, suggesting that the neuroprotective effect of COSs could be partially due to apoptosis regulation. In addition, pretreatment with COSs significantly blocked Aß-induced phosphorylation of c-Jun N-terminal kinase. Taken together, these findings may shed light on the role of COSs as a potential therapeutic agent for AD.

Influence of fasting, insulin and glucose on ghrelin in the dorsal vagal complex in rats.

The dorsal vagal complex (DVC) is an important site in which ghrelin plays an orexigenic role. However, the relationship between ghrelin expression in DVC and the energy status of the organism is unclear, as well as the role of the vagus nerve in this process. In this study, ghrelin expression in DVC neurons of rats was detected, then levels of ghrelin expression were observed under the conditions of regular diet, fasting, high blood glucose, low blood glucose, and following subdiaphragmatic vagotomy and vagus nerve electrostimulation. The results showed the following: 1) there was positive staining of ghrelin neurons in DVC; 2) ghrelin protein and mRNA levels in DVC increased under fasting condition; 3) Hyperglycemia, induced by glucose production, decreased DVC ghrelin levels and levels did not increase under hypoglycemia induced by insulin injection; 4) the dorsal trunk of the subdiaphragmatic vagus transmits a stimulatory signal to increase DVC ghrelin levels, whereas the ventral trunk transmits inhibitory information; and 5) DVC ghrelin levels decreased with 20 Hz stimulation on the ventral or dorsal trunk of subdiaphragmatic vagus nerves but increased with 1 Hz stimulation on the dorsal trunk. These results indicate that endogenous ghrelin is synthesized in DVC neurons. Conditions such as fasting, hyperglycemia, and hypoglycemia result in changes in DVC ghrelin levels in which the dorsal and ventral trunks of subdiaphragmatic vagus play different modulation roles.

Kirenol upregulates nuclear annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Kirenol is a diterpenoid compound purified from the Chinese Herba Siegesbeckiae. Siegesbeckiae has been employed for the treatment of arthritis for centuries, its safety and efficacy are documented through a long history of human use. AIM OF THE STUDY: To investigate the effects on collagen-induced arthritis (CIA) and anti-inflammatory mechanism of kirenol. MATERIALS AND METHODS: Kirenol was administrated intragastrically in rats after the onset of CIA. Pathological changes were evaluated by paw swelling and histopathology. Concentration of IL-1ß in synovial fluid and adrenal corticotropin (ACTH) in plasma were determined by Elisa. Western blot was performed to detect the expression of annexin-1 and glucocorticoid receptor alpha (GRα) in synovium. NF-κB DNA binding activity was assessed by electrophoretic mobility shift assays (EMSA). RESULTS: Kirenol (1, 2, and 4 mg/kg) and prednisolone depressed paw swelling and reduced IL-1ß of synovial fluid in the CIA rats (p<0.05 or p<0.01). Kirenol and prednisolone upregulated nuclear annexin-1 and inhibited NF-κB activity in synovium of CIA. The inhibitory effect of kirenol and prednisolone on NF-κB activity was enhanced by anti-annexin-1 Ab. Prednisolone, but not kirenol, downregulated plasma ACTH and GRα expression significantly (p<0.01). CONCLUSION: Kirenol and prednisolone can upregulate nuclear annexin-1 which interacts with NF-κB to inhibit NF-κB activity, reduce cytokines expression and thereby attenuate inflammation of CIA joints. Kirenol does not lead to ACTH or GR downregulation, which is in contrast to classic glucocorticoid prednisolone. Kirenol shares with GCs similar anti-inflammatory mechanism but bypass the considerable limitation of GCs treatment.