Cytotoxic and anti-inflammatory constituents from roots of Hypericum beanii and the antitumor potential under the view of cancer-related inflammation.

Hypericum beanii, a traditional folk medicine plant, has been employed in the treatment of various inflammation-related diseases and has demonstrated promising potential as an herbal remedy for cancer. In this study, we isolated 29 compounds from the roots of H. beanii. We evaluated their cytotoxic effects on five human cancer cell lines, which revealed that the ethanol extract, along with compounds 4 and 14, exhibited significant cytotoxic activity. Additionally, we assessed their anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Our findings showed that the ethanol extract (IC50 = 7.41 ± 0.38 µg/mL), compound 4 (IC50 = 7.82 ± 0.42 µM), and compound 14 (IC50 = 3.05 ± 0.06 µM) displayed substantial anti-inflammatory activity. ELISA assays and qPCR analysis revealed that compounds 4 and 14 may exert their anti-inflammatory and antitumor effects by inhibiting the expression of iNOS, TNF-α, IL-1ß, and IL-6 mRNA, shedding light on their role in cancer-related inflammation.

Vaccarin alleviates cisplatin-induced acute kidney injury via decreasing NOX4-derived ROS.

Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin, a chemical entity of flavonoid glycoside, against cisplatin-induced AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were used as the model of cisplatin-induced AKI. The levels of blood urea nitrogen (BUN) and creatine (Cr) levels and periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which was detected by the ICP-MS 6 h after cisplatin injection. Moreover, vaccarin can significantly alleviate the product of reactive oxygen species and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in cisplatin-induced AKI, both in vivo and in vitro. In addition, vaccarin decreased the receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown by the protein levels of cleaved-caspase3 and flow cytometry) and inflammation (shown by the decreased levels of NLRP3, p-P65 and the mRNA of several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) and NOX4 kowndown by siRNA have equivalent protective effect of vaccarin in vitro. When vaccarin was administered together with GLX or NOX4 siRNA, this protective effect of vaccarin did not further increase, as indicating by the index of oxidative stress, cell viability, necroptosis and apoptosis. In conclusion, vaccarin can alleviate cisplatin-induced AKI via inhibiting NOX4.

Multifunctional polyimide-based femtosecond laser micro/nanostructured films with triple Janus properties.

Flexible multifunctional composite films in which opposing surfaces have two or more distinct physical properties are highly applicable for wearable electronic devices, electrical power systems and biomedical engineering. However, fabrication of such "Janus" films can be time consuming, complex or economically not feasible. In this work, Janus polyimide (PI) films were prepared by femtosecond laser direct writing technology, which generated a honeycomb porous structure (HPS) on one side and a lawn-like structure (LLS) on the other. Deposition of silver nanowires (AGNWs) by drop coating on the LLS side (AGNWs@LLS) resulted in a film in which each face possessed highly distinct triple properties. The HPS side was superhydrophobic with a water contact angle (WCA) of ∼153.3° and electrically non-conductive, while the AGNWs@LLS side was superhydrophilic (WCA ∼7.8°) and highly conductive (∼3.8 Ω). Moreover, the AGNWs@LLS face showed ultra-low thermal radiation performance, almost reaching saturation. On a heating table at ∼100 °C, the temperature of the AGNWs@LLS side remained at ∼44.5 °C, while the HPS side exhibited a temperature of ∼93.9 °C. This "triple Janus film" and lasing techniques developed might be useful for designing new materials for the integration and miniaturization of multifunctional electronic equipment.

Long-term follow-up after discharge witnesses a slow decline of insulin autoantibodies in patients with insulin autoimmune syndrome complicated with Grave's disease: a report of two cases.

BACKGROUND: Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by high levels of blood insulin autoantibodies. It has been documented that drugs containing sulfhydryl groups may result in IAS. In this study, we present two cases of IAS induced by methimazole, along with their corresponding treatments and a long-term follow-up after hospitalization. CASE PRESENTATION: We report two patients with Grave's disease (GD), carrying the HLA-DRB1 04:06 genotype, who experienced hypoglycemic episodes after taking methimazole. Inpatient treatments helped return their blood glucose levels to normal. Although no recurrences of hypoglycemia were present in the two cases studied, insulin autoantibodies remained positive for the previous follow-up sessions, which turned negative only three years after discharge. CONCLUSIONS: GD patients who carry the HLA-DRB1 04:06 genotype are prone to IAS if they take drugs containing sulfhydryl groups. It may take time for the elimination of insulin autoantibodies after the recovery from the hypoglycemic episode in IAS patients.

Magnetically Actuated Superhydrophilic Robot Sphere Fabricated by a Femtosecond Laser for Droplet Steering.

Droplet steering has important applications in biomedical detection, local chemical reactions, liquid collection, and microfluidic control. Presently, droplet steering methods typically require specific paths and can be challenging to operate, involving complex fabrications for the operating systems. Here, we show a magnetically actuated superhydrophilic robot sphere (MSR) based on femtosecond laser direct writing technology for droplet steering. Through femtosecond laser treatment, uniform micro-/nanostructures are constructed on the surface of a MSR. Additionally, the contactless magnetic actuator makes it possible to remotely steer the MSR to transport droplets. After preliminary exploration of the mechanism by which MSR drives the droplet movement, the ability of MSR to control the droplet movement was systematically tested and analyzed. Moreover, the applications of the MSR in complex path liquid collection and transport, three-dimensional space transport, self-cleaning, etc., are further verified. This strategy provides a novel and reliable path for droplet manipulation and broadens its application.

Norlignans and phenolics from genus Curculigo protect corticosterone-injured neuroblastoma cells SH-SY5Y by inhibiting endoplasmic reticulum stress-mitochondria pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of genus Curculigo are divided into the Section Curculigo and the Section Capitulata, which are mainly distributed in southeastern and southwestern China. Various ancient chinese books record that these plants were used as an important herb for tonifying kidney yang. Traditional Chinese medicine often draws on this property to treat depression syndrome. Thus genus Curculigo has potential for the treatment of neurodegenerative diseases (ND). The study showed that phenolics were the main characteristic components of plants in the Section Curculigo, represented by orcinol glucoside and curculigoside; the norlignans, with Ph-C5-Ph as the basic backbone, were the main characteristic components of the Section Capitulata. However, there is a lack of sufficient scientific evidence as to whether these two types of ingredients have neuroprotective effects. AIM OF THE STUDY: To determine the neuroprotective effects of phenolics and norlignans in genus Curculigo on human neuroblastoma cells SH-SY5Y. To discuss their structure-activity relationship and screen for compounds with high activity and neuroprotective effects. To reveal that the amelioration of endoplasmic reticulum (ER) stress by two classes of compounds is mediated by the PERK/eIF2α/ATF4 pathway. MATERIALS AND METHODS: The cytotoxicity of 17 compounds was assayed by MTT. SH-SY5Y cells were damaged by corticosterone (Cort) (200 µM) for 24 h and then co-administered with 17 compounds (0.1-100 µM) and Cort (200 µM) for 24 h. Cell survival was determined by MTT assay. Apoptosis rate, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels were detected using flow cytometry. Intracellular Ca2+ levels were detected using a fluorescent probe. Cellular mitochondrial and ER damage was observed using transmission electron microscopy (TEM). ER stress and apoptotic pathway-related proteins (BiP, CHOP, cleaved caspase-3, cleaved caspase-9, Bax/Bcl-2), and the expression level of PERK/eIF2α/ATF4 pathway was measured via western blot (WB). RESULTS: The experimental data showed that Cort treatment of SH-SY5Y cells resulted in decreased cell survival and increased apoptosis, mitochondrial depolarization, ROS, and intracellular Ca2+ levels. The co-action of 17 compounds and Cort for a period of time significantly increased cell survival. Compounds 3, 7, 12, 13 also reduced apoptosis rate, mitochondrial depolarization, ROS and intracellular Ca2+ levels in the subsequent experiments. In addition, TEM observed that Cort caused mitochondrial and ER damage, and the damage was improved after treatment. WB analysis obtained that Cort increased the expression of apoptotic and ER stress-related proteins and activated pathway expression. However, in the presence of compounds 3, 7, 12, 13, the expression of BiP, CHOP, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 was significantly reduced, and the phosphorylation of PERK and eIF2α and the expression of ATF4 were inhibited. CONCLUSION: This study found that one phenolic (3) and three norlignans (7, 12, 13) from genus Curculigo have significant neuroprotective effects. The results of the structure-activity relationship indicated that the glucosyl polymeric norlignans and the phenolics with benzoic acid as the parent nucleus were more active. The neuroprotective effect of three norlignans is the latest discovery. This finding has important research value in the field of prevention and treatment of neurodegenerative diseases.

Facile fabrication of hierarchical textures for substrate-independent and durable superhydrophobic surfaces.

On account of their wide range of applications in self-cleaning, anti-icing, frost suppression, etc., superhydrophobic surfaces have attracted considerate attention. However, most of the superhydrophobic surfaces can only be prepared on the surfaces of specific materials and are easily damaged in the case of friction. In this work, we propose a facile method to achieve superhydrophobicity on various substrate surfaces. By femtosecond laser direct processing, micron-level grooves and protrusions are constructed on substrates to form a protective layer. Then, the substrates covered by polytetrafluoroethylene (PTFE) were scanned to make the surfaces of the substrates superhydrophobic. Since the PTFE micro-nano-particles are evenly distributed on the grooves and protrusions, the surfaces exhibit robust superhydrophobicity with excellent anti-friction performance that is independent of the substrate properties. This work provides an efficient and environmentally friendly path for achieving robust superhydrophobic surfaces on various substrates.

The protective effect of rabeprazole on cisplatin-induced apoptosis and necroptosis of renal proximal tubular cells.

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis.

Nanoparticulate Carriers Used as Vaccine Adjuvant Delivery Systems.

Vaccination plays a crucial role in the control of infectious diseases, but often fails to eradicate certain refractory infections for which the development of an effective vaccine is eagerly desired but elusive. In many cases, failure in developing a vaccine is attributed to the inability of the candidates, especially among subunit vaccines, to evoke appropriate immuno-responses for establishing humoral as well as cellular immunity. In past decades, nanoparticles (NPs) sizing from 10 to 500 nm, such as liposomes, inorganic or metal NPs (iNPs), viruslike particles (VLPs), emulsions, immune-stimulating complexes (ISCOMs), and polymeric NPs, have been developed a potential carrier for vaccines to stabilize and deliver the adjuvant and antigens, thus forming proper vaccine adjuvant-delivery systems (VADSs). In particular, many NPs are rationally designed according to distinct cellular features and, therefore, are specifically engineered with functional materials so that they can deliver vaccine ingredients to target antigen-presenting cells (APCs) while directing immunoresponses against antigens along a specific Th1 (T helper type 1) and/or Th2 pathway to establish robust cellular and antibody immunity. In addition, a variety of NP-based VADSs are suitable for mucosal immunization, which contributes to systemic and, particularly, topical immunity, thus forming a dual barrier to pathogen invasion. This paper describes different NP-based VADSs designed for delivering vaccines, and evaluates their potential in the preparation of new products that can be used for prophylaxis against pathogens via different immunization routes.

Preparation of curcumin-hydroxypropyl-ß-cyclodextrin inclusion complex by cosolvency-lyophilization procedure to enhance oral bioavailability of the drug.

The curcumin (CUR)-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex (CUR-HP-ß-CD) was prepared to erase its therapeutic restrictions of poor aqueous solubility and low oral bioavailability. CUR-HP-ß-CD was prepared by a simple procedure of water-ethanol cosolvent incubation-lyophilization which may be suitable for scale up production, and characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), phase solubility method and dissolution study; the in vitro cytotoxicity was assayed by MTT, whereas the in vivo pharmacokinetics was tested by HPLC in rats receiving formulations via intravenous and oral administration, respectively. CUR was successfully encapsulated in HP-ß-CD with a loading capacity of about 1:7 of CUR to HP-ß-CD mole ratio, which remarkably enhanced drug water solubility and maintained well the antitumour activity of CUR. The CUR-HP-ß-CD and free CUR have a similar pharmacokinetic behaviour in rats after intravenous administration; however, the oral bioavailability of CUR was enhanced to 2.77-fold by the HP-ß-CD. The CUR-HP-ß-CD can be successfully prepared by a simple method, which may be feasible for industrial scaling up, to remarkably increase drug water solubility and oral bioavailability while maintaining its bioactivity and may be a promising therapeutic preparation.

Targetted inhibition of CD74 attenuates adipose COX-2-MIF-mediated M1 macrophage polarization and retards obesity-related adipose tissue inflammation and insulin resistance.

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targetted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-dependent increases in CD74 gene expression and MIF release in M1-polarized macrophages facilitated the expression of COX-2 and MIF in co-cultured SGBS adipocytes. CD74 shRNA intravenous injection suppressed HF-induced AT M1 macrophage polarization and inflammation as well as insulin resistance in mice. The present study suggested that COX-2-mediated MIF secretion through NF-κB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity.

Determination and comparative analysis of 13 nucleosides and nucleobases in natural fruiting body of Ophiocordyceps sinensis and its substitutes.

Nucleosides and nucleobases are one of the most important indicators of quality control. A sensitive and reliable high performance liquid chromatography-ultraviolet method was applied to analyse 13 nucleosides and nucleobases simultaneously in 15 batches of nine Ophiocordyceps species and its allies in China. Principal component analysis (PCA) and cluster analysis were conducted by SPSS 22.0 software (IBM Corp., Armonk, NY, USA). The 15 samples of Cordyceps were differentiated successfully based on their nucleoside and nucleobase content. Total nucleosides content in mycelium was significantly higher than that in the natural fruiting bodies of Ophiocordyceps sinensis (NFOS). Five nucleosides or nucleobases - adenine (A), guanosine (Gu), uracil (U), uridine (Ur) and guanine (G) - were the major components contributed to the total variance according to PCA. The profiles of the 13 tested nucleosides and nucleobases (including adenosine, cytidine, guanosine, inosine, thymidine, uridine, cordycepin, adenine, cytosine, guanine, thymine, uracil and hypoxanthine) can discriminate different samples and can be candidate indicators applied for the quality control of Ophiocordyceps and its allies.

Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis.

Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. Adrenocorticotropic hormone (ACTH) and corticosterone (CORT) serum levels, adrenal gland index and hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression were measured to assess the activity of hypothalamus-pituitary-adrenal (HPA) axis. Hypothalamic glucocorticoid receptor α (GRα) mRNA expression and GRα protein expression in hypothalamic paraventricular nucleus (PVN) were also determined by real-time PCR and immunohistochemistry, respectively. We found that geniposide (25, 50, 100mg/kg) treatment reversed the CUMS-induced behavioral abnormalities, as suggested by increased sucrose intake, improved crossing and rearing behavior in OFT, shortened immobility and prolonged swimming time in FST. Additionally, geniposide treatment normalized the CUMS-induced hyperactivity of HPA axis, as evidenced by reduced CORT serum level, adrenal gland index and hypothalamic CRH mRNA expression, with no significant effect on ACTH serum level. Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis.

Expression of hedgehog signal pathway in articular cartilage is associated with the severity of cartilage damage in rats with adjuvant-induced arthritis.

BACKGROUND: Cartilage damage is a crucial step in rheumatoid arthritis (RA) disease progress while its molecular mechanisms are not fully understood. Here we investigated the expression of hedgehog (Hh) signal pathway in articular cartilage of adjuvant-induced arthritis (AIA) rats and its possible pathological role in cartilage damage. METHODS: 30 rats were divided into sham and AIA group (n = 15). Complete Freund's adjuvant was used to induce AIA. Secondary paw swelling was measured on day 10, 14, 18, 22 and 26 after induction. Rats were sacrificed on day 26 and knee joints and cartilage tissues were collected. Paw swelling, cartilage histopathologic changes and OARSI scores were used to evaluate AIA in rats. The protein expression of Hh signal related genes (Shh, Ptch1, Smo and Gli1) in cartilage were assayed by immunohistochemistry. The mRNA levels of Shh, Ptch1, Smo, Gli1, type-II collagen (COII) and aggrecan in cartilage were assayed by real-time PCR. In vitro study, cultured AIA chondrocytes were treated with cyclopamine (a specific inhibitor of Hh signal) and the mRNA levels of Hh signal and ECM components (COII and aggrecan) were measured by real-time PCR. RESULTS: Immunohistochemical results revealed that Shh, Ptch1, Smo and Gli1 proteins showed higher expression in the articular cartilage of AIA rats than those of sham rats. Real-time PCR results confirmed that Shh, Ptch1, Smo and Gli1 mRNA levels in cartilage tissues of AIA rats were significantly increased compared with those of sham rats (1.6, 1.4, 1.6, 2.0 fold, respectively). The mRNA levels of Shh, Ptch1, Smo, and Gli1 were associated with the severity of cartilage damage (indicated by OARSI scores, COII and aggrecan mRNA levels in cartilage). In vitro, cyclopamine effectively decreased the mRNA levels of Shh, Ptch1, Smo and Gli1, and increased the mRNA levels of COII and aggrecan in AIA chondrocytes, suggesting Hh signal inhibition might directly promote ECM production. CONCLUSIONS: Our findings present certain experimental evidence that Hh signal pathway is involved in the pathogenesis of cartilage damage in RA.

Inhibition of hedgehog signal pathway by cyclopamine attenuates inflammation and articular cartilage damage in rats with adjuvant-induced arthritis.

OBJECTIVES: We investigated whether inhibition of hedgehog (Hh) signal by cyclopamine attenuated inflammation and cartilage damage in adjuvant-induced arthritis (AIA) rats. METHODS: Cyclopamine (2.5, 5, 10 mg/kg) was given by intraperitoneal injection once daily from day 12 to 21 after AIA induction. Paw swelling (volume changes), serum pro-inflammatory cytokines levels (ELISA), histological analysis of joint damage (H&E staining), proteoglycans expression (Alcian blue staining), mRNA levels of sonic Hh (Shh), glioma-associated oncogene homologue 1 (Gli1), type II collagen (COII) and aggrecan in cartilage (real-time PCR) and articular chondrocyte apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) were measured respectively. KEY FINDINGS: Cyclopamine effectively attenuated inflammation and cartilage damage of AIA rats, as evidenced by reduced paw swelling, serum levels of tumor necrosis factors (TNF)-α, IL-1ß, IL-6 and histological scores of joint damage, increased proteoglycans expression and mRNA levels of COII and aggrecan in articular cartilage. Shh or Gli1 mRNA level was correlated negatively with COII and aggrecan mRNA levels, suggesting Hh signal inhibition was associated with promotion of cartilage extracellular matrix production. Furthermore, cyclopamine decreased the number of apoptotic articular chondrocytes of AIA rats, which might be partly related to its mechanisms on relieving cartilage damage. CONCLUSIONS: Our findings present some experimental evidence that Hh signal inhibition might be of potential clinical interest in rheumatoid arthritis treatment.

[Effect of hesperidin on behavior and HPA axis of rat model of chronic stress-induced depression].

OBJECTIVE: To observe the effect of hesperidin on behavior and hypothalamic-pituitary-adrenal (HPA) axis of ratmodel of chronic stress-induced depression. METHOD: Chronic unpredictable mild stress (CUMS) was used to establish the rat depression model. Sixty male SD rats were divided randomly into six groups: the normal group, the model group, the hesperidin (40, 80, 160 mg x kg(-1)) group and the positive fluoxetine (10 mg x kg(-1)) group. They were orally administered with drugs for three weeks. The sucrose preference test and the forced swimming test (FST) were assayed to detect animal behavior. The levels of corticosterone (CORT) in serum, mRNA of corticotropin release factor (CRF) in hypothalamus as well as protein expression of glucocorticoid receptor (GR) in paraventricular nucleus (PVN) were determined to clarify the anti-depression effect and mechanism of hesperidin. RESULT: Compared with the model group, rats in the hesperidin (40, 80, 160 mg x kg(-1)) treatment group showed significant increase in the sucrose consumption and decrease in the immobility time in FST to varying degrees. Meanwhile, the excessively high serum CORT and adrenal index of CUMS rats were reversed by treatment with hesperidin. In addition, hesperidin inhibited CRF mRNA expression in hypothalamus and up-regulated GR protein expression in PVN among CUMS rats. CONCLUSION: Hesperidin could effectively improve the behavior of CUMS rats and show the anti-depression effect. Its mechanisms may be related to the function of regulating HPA axis.

7,3'-dimethoxy hesperetin inhibits inflammation by inducing synovial apoptosis in rats with adjuvant-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by pronounced inflammation and excessive synovial hyperplasia within affected joint. We previously reported 7, 3'-dimethoxy hesperetin (DMHP) as a highly anti-inflammatory active derivative of hesperidin showed apparent pro-apoptotic effect in vitro on fibroblast-like synoviocytes of rats with adjuvant arthritis (AA), an animal model of RA. Here, we investigated the therapeutic effects of DMHP on inflammation and synovial apoptosis in rats with AA in vivo. Paw swelling, arthritis index, TNF-α and IL-1ß serum levels were measured to evaluate the effect of DMHP on inflammation in AA rats. DNA ladder detection and TUNEL assay were used to investigate the pro-apoptotic effect of DMHP on synovial apoptosis in vivo. Bcl-2, Bax mRNA and protein expressions in synovium were determined by real-time Q-PCR and western blot, respectively. We found DMHP inhibited secondary hind paw swelling and arthritis index, and decreased TNF-α and IL-1ß serum levels in AA rats. Typical DNA ladder formation was found in DNA extraction of synovium from DMHP treated groups. The number of apoptotic synovial cells was elevated with DMHP treatment in TUNEL assay. DMHP markedly decreased Bcl-2 expression whereas increased Bax expression in synovium of AA rats at both transcription and protein levels. Moreover, DMHP treatment on AA rats significantly decreased the protein ratio of Bcl-2/Bax in synovium. In conclusion, DMHP has an apparent therapeutic effect on inflammation in rats with AA. Mechanisms of this effect are partly related to induction of synovial apoptosis through modulation of Bcl-2 and Bax expression.