[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

In vivo quantification of human aqueous veins by enhanced depth imaging optical coherence tomography and optical coherence tomography angiography images.

AIM: To investigate the aqueous vein in vivo by using enhanced depth imaging optical coherence tomography (EDI-OCT) and optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional comparative study, 30 healthy participants were enrolled. Images of the aqueous and conjunctival veins were captured by EDI-OCT and OCTA before and after water loading. The area, height, width, location depth and blood flow of the aqueous vein and conjunctival vein were measured by Image J software. RESULTS: In the static state, the area of the aqueous vein was 8166.7±3272.7 µm2, which was smaller than that of the conjunctival vein (13 690±7457 µm2, P<0.001). The mean blood flow density of the aqueous vein was 35.3%±12.6%, which was significantly less than that of the conjunctival vein (51.5%±10.6%, P<0.001). After water loading, the area of the aqueous vein decreased significantly from 8725.8±779.4 µm2 (baseline) to 7005.2±566.2 µm2 at 45min but rose to 7863.0±703.2 µm2 at 60min (P=0.032). The blood flow density of the aqueous vein decreased significantly from 41.2%±4.5% (baseline) to 35.4%±3.2% at 30min but returned to 45.6%±3.6% at 60min (P=0.021). CONCLUSION: The structure and blood flow density of the aqueous vein can be effectively evaluated by OCT and OCTA. These may become biological indicators to evaluate aqueous vein changes and aqueous outflow resistance under different interventions in glaucoma patients.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Progression of myopia among undergraduate students in central China.

AIM: To investigate the progression of myopia and risk factors among university students in central China. METHODS: A total of 7359 first-year undergraduate students at Huazhong University of Science and Technology in central China were recruited to the study and invited to a centralized clinic for medical examination, including optometry, and re-examined after one year. Correlation analyses were performed to assess the associations between one-year myopia progression and various parameters. RESULTS: The spherical equivalent refraction for the overall population was -3.14±2.28 D at baseline. The rate of myopia progression over 0.50 D after one year was 41.9%, and the 1-year progression of myopia was -0.47±0.58 D. There was no difference of mean 1-year myopia progression between male and female or difference among age group. The myopia progression of original myopia was severer than progression of new-onset myopia. There was also difference of mean myopia progression among different degrees of myopia at baseline. The under corrected eyes had a higher percentage of myopia progression than well corrected eyes (χ 2=7.90, P<0.01). There was no correlation between myopia progression and height, weight, body mass index, hemoglobin (Spearman correlation, ρ=-0.078, -0.152, -0.170, -0.096, respectively, all P>0.05). CONCLUSION: Myopes still progress in undergraduate students, especially in high myopes.

Imaging characteristics of orbital peripheral nerve sheath tumors: Analysis of 34 cases.

BACKGROUND: Peripheral nerve sheath tumors (PNSTs), a rare group of neoplasms in the orbit, comprise only 4% of all orbital tumors. At present, there are very few studies detailing the features of these tumors identified using imaging technology. AIM: To compare the differences in location, morphology, magnetic resonance imaging (MRI) signal intensity/computed tomography (CT) value, and enhancement degree of tumors of different pathological PNSTs types. METHODS: Clinical, pathological, CT, and MRI data were analyzed retrospectively in 34 patients with periorbital sheath tumors diagnosed using histopathology from January 2013 to August 2021. RESULTS: Among 34 cases of orbital peripheral nerve sheath tumors, 21 were schwannomas, 12 were neurofibromas, and 1 was a plexiform neurofibroma. Common clinical symptoms presented by patients with these types of tumors include eyelid swelling, exophthalmos, and limited eye movement. Schwannomas mostly occur in the intramuscular space with small tumor volume and rare bone involvement. Neurofibromas develop in the extrapyramidal space with larger tumor volume and more bone involvement. Radiologically, schwannomas and neurofibromas are characterized by regular morphology and uneven density and signal. One case of plexiform neurofibroma showed tortuous and diffuse growth along the nerve, with a worm-like appearance on imaging. CONCLUSION: Different pathological types of orbital peripheral nerve sheath tumors have unique imaging characteristics. Comprehensive consideration of the patient's clinical and imaging manifestations is of great value in the diagnosis of orbital peripheral nerve sheath tumors.

[Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway].

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

Changes in Schlemm's canal, trabecular meshwork, and relevant parameters in the early stage after SMILE of myopia patients.

AIM: To observe the changes in Schlemm's canal (SC), trabecular meshwork (TM), and anterior chamber relevant parameters after small incision lenticule extraction (SMILE) of myopia patients. METHODS: A total of 58 eyes from 30 patients who underwent SMILE were divided into a low and moderate myopia group (group A, 32 eyes) and a high myopia group (group B, 26 eyes). The diameter and area of the SC, the width and thickness of TM obtained by CIRRUS HD-OCT5000, and the related anterior chamber parameters obtained by Pentacam anterior segment analysis system, accommodation amplitude (AMP) were observed pre- and postoperatively. The preoperative intraocular pressure (IOP) and postoperative correction of intraocular pressure (IOPcc) were measured. RESULTS: The diameter and area of the SC in the two groups were significantly increased postoperatively (all P<0.01). The TM width of the patients in the two groups were increased at 1mo after surgery (both P<0.01), but the TM thickness did not change (P>0.05). The corneal curvature, central anterior chamber depth, and anterior chamber volume decreased after SMILE surgery (all P<0.01). There was a weak negative correlation between the SC area change and AMP change in group A (r=-0.362, P<0.01). The postoperative IOP decreased after correction by Shah formula (P<0.05). CONCLUSION: SC and TM in myopia patients change in the early postoperative stage of SMILE and the IOP is decline.

Analogs of microgravity: the function of Schlemm's canal, intraocular pressure and autonomic nervous during the head-down tilt test in healthy subjects.

AIM: To evaluate the ocular outcomes and to elucidate possible mechanisms underlying intraocular pressure (IOP) change following the head-down tilt (HDT) test. METHODS: The study included 21 participants at the Department of Ophthalmology of Tongji Hospital. Subjects received the test of I-care tonometry, enhanced depth imaging optical coherence tomography and heart rate variability (HRV) analysis before and after 15min HDT test. The lumen area of Schlemm's canal (SCAR), IOP, HRV were calculated. RESULTS: IOP increased significantly after 20° head down position from 14.0±3.0 to 17.0±3.3 mm Hg (P<0.001). SCAR decreased from 13449.0±5454.9 µm2 at sitting condition to 9576.6±4130.9 µm2 post 15min HDT test. High frequency (HF) indices increased significantly from 1462±865 Hz at baseline to 2128±824 Hz. Heart rate (HR) decreased significantly from 76±11.48 to 70±11.52 bpm after the HDT. The linear regression analysis showed that the difference of HF and SCAR significantly correlated with each other during the HDT (R2 =20%, P=0.04). CONCLUSION: These outcomes perform the first evidence of the activation of autonomic nervous system of HDT may cause the collapse of Schlemm's canal lumen, which in turn leading to the increased IOP.

[Processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae decoction].

On the basis of the previous work of the research group, the orthogonal design method was further used to optimize the processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae Decoction. A total of 9 processed products of T.wilfordii in L.christinae decoction were prepared by four factors and three levels orthogonal design table. The contents of triptolide in T.wilfordii were determined by high performance liquid chromatography(HPLC) before and after processing: 4.27, 3.92, 3.57, 2.75, 2.42, 2.66, 3.51, 1.87, 1.75, 2.03 µg·g~(-1). On this basis, the above processed products were orally given to mice for 28 days. 12 hours after the last administration, food fasting except water was provided, and 24 hours later, the eyeballs were taken for blood and liver tissue. Serum biochemical indexes, liver lipid peroxidation and antioxidant related indexes were detected by kit method. Twenty-eight days after oral administration of raw T.wilfordii, the levels of serum alanine aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and liver malondialdehyde(MDA) in mice increased by 91%(P<0.01), 46%(P<0.05), 73%(P<0.01) and 99%(P<0.01), while the liver antioxidant indexes such as superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GPX) and glutathione-S transferase(GST) significantly decreased(P<0.01). After administration of the processed products, the above indexes were significantly reversed(P<0.01 or P<0.05). Especially, the processing conditions of A_3B_2C_1D_3 had the best detoxification effect on T.wilfordii, which decreased the high levels of AST, ALT, ALP and MDA by 49%(P<0.01), 32%(P<0.01), 42%(P<0.01), and 17%(P<0.05). Therefore, the best processing conditions for T.wilfordii in L.christinae decoction were A_3B_2C_1D_3, namely "15% mass fraction of L.christinae, 1 h moistening time, 160 ℃ frying temperature, and 9 min frying time".

Numerical simulation of the flow of aqueous humor in the Schlemm's canal.

Schlemm's canal (SC) is a ring structure responsible for maintaining fluid homeostasis in the anterior chamber of the eye by draining aqueous humor (AH) from the trabecular meshwork (TM) into the collecting channel (CC). Obstruction of the AH flow in this conventional pathway leads to an elevation of intraocular pressure in glaucoma, which is internationally recognized as the most common cause of blindness. Although there are obvious morphological differences between patients and healthy individuals, the AH drainage capacity of SC with specific parameters is difficult to quantitatively evaluate due to the limitations of analyses or experimental technologies. In this paper, the AH flow dynamic features under various SC morphological parameters are studied by numerical simulations of 3D models. The axis length of the SC cross-section and the level of openness are chosen as the main morphological factors according to the clinical data. The flow features, including the velocity, streamline and wall shear stress, are analyzed. This study aimed not only to explore the feasibility of 3D numerical modeling in evaluating the SC drainage capacity, but also to reveal the relationship between SC morphological parameters and the dynamic features of AH drainage.

Nestin+/CD31+ cells in the hypoxic perivascular niche regulate glioblastoma chemoresistance by upregulating JAG1 and DLL4.

BACKGROUND: Failure of glioblastoma (GBM) therapy is often ascribed to different types of glioblastoma stem-like cell (GSLC) niche; in particular, a hypoxic perivascular niche (HPVN) is involved in GBM progression. However, the cells responsible for HPVNs remain unclear. METHODS: Immunostaining was performed to determine the cells involved in HPVNs. A hypoxic chamber and 3-dimensional (3D) microfluidic chips were designed to simulate a HPVN based on the pathological features of GBM. The phenotype of GSLCs was evaluated by fluorescence scanning in real time and proliferation and apoptotic assays. The expression of JAG1, DLL4, and Hes1 was determined by immunostaining, ELISA, Western blotting, and quantitative PCR. Their clinical prognostic significance in GBM HPVNs and total tumor tissues were verified by clinical data and The Cancer Genome Atlas databases. RESULTS: Nestin+/CD31+ cells and pericytes constitute the major part of microvessels in the HPVN, and the high ratio of nestin+/CD31+ cells rather than pericytes are responsible for the poor prognosis of GBM. A more real HPVN was simulated by a hypoxic coculture system in vitro, which consisted of 3D microfluidic chips and a hypoxic chamber. Nestin+/CD31+ cells in the HPVN were derived from GSLC transdifferentiation and promoted GSLC chemoresistance by providing more JAG1 and DLL4 to induce downstream Hes1 overexpression. Poor GBM prognosis correlated with Hes1 expression of tumor cells in the GBM HPVN, and not with total Hes1 expression in GBM tissues. CONCLUSIONS: These results highlight the critical role of nestin+/CD31+ cells in HPVNs that acts in GBM chemoresistance and reveal the distinctive prognostic value of these molecular markers in HPVNs.

Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology.

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 µg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 µg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 µg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 µg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.

Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.

We have previously reported cognitive impairments in both young and old mice, particularly in female mice expressing mouse Arg-61 apoE, with a point mutation to mimic the domain interaction feature of human apoE4, as compared to the wildtype mouse (C57BL/6J) apoE. In this study, we further evaluated water maze performance in the female Arg-61 mice at an additional time point and then investigated related hippocampal cyto-architecture in these young female Arg-61 apoE mice vs. the wildtype mice. The results of behavioral performance consistently support our previous report that the young female Arg-61 apoE showed cognitive impairment versus C57BL/6J at the same age. The cyto-architectural results showed that volume of the granular cell layer (GCL) was significantly larger in both 5- and 10-month old Arg-61 apoE mice versus C57BL/6J mice. While the number of newborn calretinin-positive neurons was greater in the sub-granular zone (SGZ) in 5-month old Arg-61 mice, this number dropped significantly in 10-month old Arg-61 mice to a lower level than in age-matched C57BL/6J mice. In addition, the amyloid ß species was significantly higher in 5-month old Arg-61 mice versus age-matched C57BL/6J mice. In conclusion, impaired cognitive functions in female Arg-61 apoE mice appear correlated with larger GCL volume and higher calretinin-positive cell number and suggest a compensatory cellular response that may be related to amyloid beta perturbations early in life. Therefore this study suggests a novel cyto-architectural mechanism of apoE4-dependent pathologies and increased susceptibility of APOEε4 subjects to Alzheimer's disease.

Pharmacokinetics and Tissue Distribution of Gingerols and Shogaols from Ginger (Zingiber officinale Rosc.) in Rats by UPLC⁻Q-Exactive⁻HRMS.

Gingerols and shogaols are recognized as active ingredients in ginger and exhibit diverse pharmacological activities. The preclinical pharmacokinetics and tissue distribution investigations of gingerols and shogaols in rats remain less explored, especially for the simultaneous analysis of multi-components. In this study, a rapid, sensitive, selective, and reliable method using an Ultra-Performance Liquid Chromatography Q-Exactive High-Resolution Mass Spectrometer (UPLC-Q-Exactive⁻HRMS) was established and validated for simultaneous determination of eight compounds, including 6-gingerol, 6-shogaol, 8-gingerol, 8-shogaol, 10-gingerol, 10-shogaol, Zingerone, and 6-isodehydrogingenone in plasma and tissues of rats. The analytes were separated on a Syncronis C18 column (100 × 2.1 mm, 1.7 µm) using a gradient elution of acetonitrile and 0.1% formic acid in water at a flow rate of 0.25 mL/min at 30 °C. The method was linear for each ingredient over the investigated range with all correlation coefficients greater than 0.9910. The lowest Lower Limit of quantitation (LLOQ) was 1.0 ng/mL. The intra- and inter-day precisions (Relative Standard Deviation, RSD%) were less than 12.2% and the accuracy (relative error, RE%) ranged from -8.7% to 8.7%. Extraction recovery was 91.4⁻107.4% and the matrix effect was 86.3⁻113.4%. The validated method was successfully applied to investigate the pharmacokinetics and tissue distribution of eight components after oral administration of ginger extract to rats. These results provide useful information about the pharmacokinetics and biodistribution of the multi-component bioactive ingredients of ginger in rats and will contribute to clinical practice and the evaluation of the safety of a Chinese herbal medicine.

ERß agonist alters RNA splicing factor expression and has a longer window of antidepressant effectiveness than estradiol after long-term ovariectomy

Background: Estrogen therapy (ET), an effective treatment for perimenopausal depression, often fails to ameliorate symptoms when initiated late after the onset of menopause. Our previous work has suggested that alternative splicing of RNA might mediate these differential effects of ET. Methods: Female Sprague­Dawley rats were treated with estradiol (E2) or vehicle 6 days (early ET) or 180 days (late ET) after ovariectomy (OVX). We investigated the differential expression of RNA splicing factors and tryptophan hydroxylase 2 (TPH2) protein using a customized RT2 Profiler PCR Array, reverse-transcription polymerase chain reaction, immunoprecipitation and behaviour changes in clinically relevant early and late ET. Results: Early ET, but not late ET, prolonged swimming time in the forced swim test and reduced anxiety-like behaviours in the elevated plus maze. It reversed OVX-increased (SFRS7 and SFRS16) or OVX-decreased (ZRSR2 and CTNNB1) mRNA levels of splicing factors and ERß splicing changes in the brains of OVX rats. Early ET, but not late ET, also increased the expression of TPH2 and decreased monoamine oxidase A levels in the dorsal raphe in the brains of OVX rats. In late ET, only diarylpropionitrile (an ERß-specific agonist) achieved similar results ­ not E2 (an ERα and ERß agonist) or propylpyrazoletriol (an ERα-specific agonist). Limitations: Our experimental paradigm mimicked early and late ET in the clinical setting, but the contribution of age and OVX might be difficult to distinguish. Conclusion: These findings suggest that ERß alternative splicing and altered responses in the regulatory system for serotonin may mediate the antidepressant efficacy of ET associated with the timing of therapy initiation. It is likely that ERß-specific ligands would be effective estrogen-based antidepressants late after the onset of menopause.

Detoxication mechanisms of Radix Tripterygium wilfordii via compatibility with Herba Lysimachia christinae in S180-bearing mice by involving Nrf2.

The combined administration between Radix Tripterygium wilfordii Hook F (LGT) and Herba Lysimachia christinae Hance (JQC) belongs to mutual detoxication compatibility of seven emotions in traditional Chinese medicine (TCM) theory. However, until now, the compatibility detoxication mechanisms remain unknown. The present study was undertaken to observe detoxication mechanisms of LGT through compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2 (Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on antitumor activity was also investigated here. Our results demonstrated that compatibility with JQC administration significantly reversed LGT-elevated serum alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes' swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the strongest detoxication effect. Besides, compatibility with JQC administration reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) but also the LGT lowered GSH, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and interleukin (IL)-10 levels. Furthermore, compatibility with JQC administration significantly up-regulated protein expression of Nrf2 and mRNA expression of it regulated downstream antioxidant genes such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase catalytic subunit (GCLC). In addition, compatibility with JQC further decreased LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the strongest synergistic effect. Collectively, through compatibility with JQC exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms could be at least partly attributed to up-regulation of Nrf2 and its downstream signals, thereby enhancing antioxidant defenses, and inhibiting lipid peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1 (LGT/JQC) exerted the strongest effects on both detoxication and synergism.

Ethanol extract of Rehmannia glutinosa exerts antidepressant-like effects on a rat chronic unpredictable mild stress model by involving monoamines and BDNF.

The dried roots of Rehmannia glutinosa Libosch. (Scrophulariaceae) are of both medicinal and nutritional importance. Our previous study has found that the 80% ethanol extract of R. glutinosa (RGEE) produced antidepressant-like activities in mouse behavioral despair depression models. However, its mechanisms are still unclear. The present study aimed to observe the antidepressant-like mechanisms of RGEE on a rat chronic unpredictable mild stress (CUMS) model by involving monoaminergic neurotransmitters and brain-derived neurotrophic factor (BDNF). CUMS-stressed rats were orally given RGEE daily (150, 300, and 600 mg/kg) or fluoxetine hydrochloride (FH) for 3 weeks after starting the CUMS procedure. Sucrose preference test was carried out to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. Results demonstrated that CUMS induced depression-like behavior, whereas RGEE and FH administration inhibited this symptom. Furthermore, CUMS caused excessively elevated levels of serum corticosterone (CORT), an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, in a manner attenuated by RGEE and FH administration. RGEE administration also further elevated monoamine neurotransmitters and BDNF levels, up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB) in hippocampus of rats suffering CUMS. Together, our findings suggest that RGEE can improve CUMS-evoked depression-like behavior, and indicate its mechanisms may partially be associated with restoring HPA axis dysfunctions, enhancing monoamineergic nervous systems, and up-regulating BDNF and TrkB expression.

Structure-Activity Relationship of Xanthones as Inhibitors of Xanthine Oxidase.

Polygala plants contain a large number of xanthones with good physiological activities. In our previous work, 18 xanthones were isolated from Polygala crotalarioides. Extented study of the chemical composition of the other species Polygala sibirica led to the separation of two new xanthones-3-hydroxy-1,2,6,7,8-pentamethoxy xanthone (A) and 6-O-ß-d-glucopyranosyl-1,7-dimethoxy xanthone (C)-together with 14 known xanthones. Among them, some xanthones have a certain xanthine oxidase (XO) inhibitory activity. Furthemore, 14 xanthones as XO inhibitors were selected to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The CoMFA model predicted a q² value of 0.613 and an r² value of 0.997. The best CoMSIA model predicted a q² value of 0.608 and an r² value of 0.997 based on a combination of steric, electrostatic, and hydrophobic effects. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active XO inhibitors.

In vivo protective effects of chlorogenic acid against triptolide-induced hepatotoxicity and its mechanism.

CONTEXT: Triptolide (TP) has outstanding biological activities, but it induces toxicities, particular hepatotoxicity, severely limiting its clinical application. Chlorogenic acid (CGA) has prominently medicinal and nutritional values. However, until now, it is not known whether CGA could mitigate TP-induced hepatotoxicity. OBJECTIVE: This study explored the possible protection of CGA against TP-induced hepatotoxicity and its potential mechanisms, for the first time. MATERIAL AND METHODS: KM mice were treated orally with TP at a single dose of 1 mg/kg at 4 h after being treated with CGA (10, 20 and 40 mg/kg) for seven continuous days. Blood samples were collected at 24 h after TP administration for measurement of serum biomarkers, and hepatic tissues for analysis of potential mechanisms. RESULTS: TP treatment-induced acute hepatotoxicity manifested by the significant elevation in serum alanine transaminase (93.9 U/L), aspartate transaminase (185.8 U/L) and hepatic malondialdehyde (0.637 µmol/mg protein), and the remarkable reduction in hepatic glutathione (1.425 µg/mg protein), glutathione S-transferase, glutathione peroxidase, superoxide dismutase and catalase (91.7, 320.7, 360.6 and 140.7 U/mg protein, respectively). In contrast, pretreatment with CGA for 7 days effectively attenuated acute liver injury and oxidative stress caused by TP with each ED50 of 44.4, 57.1, 46.6, 22.2, 40.9, 58.1, 86.4 and 61.0 mg/kg, respectively. Furthermore, pretreatment with CGA promoted the accumulation of Nrf2 into the nucleus, and up-regulated mRNA expression of Nrf2-target downstream genes. DISCUSSION AND CONCLUSIONS: Combined CGA medication may probably reduce the risk of TP poisoning, and in-depth mechanisms can be developed around the signal molecules of Nrf2.

Diurnal macular choroidal area fluctuation in normal and primary open angle glaucoma groups.

AIM: To assess and compare the diurnal macular choroidal area fluctuation in normal and primary open angle glaucoma (POAG) groups using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: Twenty-eight normal and 27 POAG eyes were enrolled in this study. EDI-OCT was used to measure the macular choroidal area every 3h from 9:00 a.m. to 21:00 p.m. RESULTS: Significant diurnal fluctuations of macular choroidal area were observed in both normal (P=0.003) and POAG groups (P<0.001). But no significant macular choroidal area difference has been found between the two groups at all the five measurement time-points (512778±166242 vs 455079±207278 µm2, P=0.195 at 9:00 a.m.; 501526±168953 vs 447846±211147 µm2, P=0.245 at 12:00 a.m.; 501982±173158 vs 448024±206653 µm2, P=0.239 at 15:00 p.m.; 508912±174589 vs 457783±207081 µm2, P=0.252 at 18:00 p.m.; 503787±171241 vs 453230±205955 µm2, P=0.274 at 21:00 p.m.; respectively). Furthermore, neither the fluctuation manners nor the change in macular choroidal area between the two adjacent measurement time points showed significant difference between normal and POAG groups (all P>0.05). In the meantime, significant diurnal intraocular pressure fluctuations were also observed in normal and POAG groups (both P<0.001). CONCLUSION: In diurnal time, the macular choroidal area in both normal and POAG groups fluctuated significantly; moreover, neither the value of macular choroidal area, nor the fluctuation of macular choroidal area in POAG group is significantly different from that in normal group.