Publications by authors named "Chaoran Wang"

54 Publications

Long Noncoding RNA: Shining Stars in the Immune Microenvironment of Gastric Cancer.

Front Oncol 2022 25;12:862337. Epub 2022 Mar 25.

Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Gastric cancer (GC) is a kind of malignant tumor disease that poses a serious threat to human health. The GC immune microenvironment (TIME) is a very complex tumor microenvironment, mainly composed of infiltrating immune cells, extracellular matrix, tumor-associated fibroblasts, cytokines and chemokines, all of which play a key role in inhibiting or promoting tumor development and affecting tumor prognosis. Long non-coding RNA (lncRNA) is a non-coding RNA with a transcript length is more than 200 nucleotides. LncRNAs are expressed in various infiltrating immune cells in TIME and are involved in innate and adaptive immune regulation, which is closely related to immune escape, migration and invasion of tumor cells. LncRNA-targeted therapeutic effect prediction for GC immunotherapy provides a new approach for clinical research on the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2022.862337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989925PMC
March 2022

Integrated hepatic single-cell RNA sequencing and untargeted metabolomics reveals the immune and metabolic modulation of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia.

Phytomedicine 2022 Mar 2;97:153922. Epub 2022 Jan 2.

School of Pharmacy, Second Military Medical University, Shanghai 200433, China; The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosafety, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Background: Although Qing-Fei-Pai-Du decoction (QFPDD) is extensively used clinically to treat COVID-19 patients, the mechanism by which it modulates the immunological and metabolic functions of liver tissue remains unknown.

Purpose: The purpose of this study is to investigate the mechanism of action of QFPDD in the treatment of mice with coronavirus-induced pneumonia by combining integrated hepatic single-cell RNA sequencing and untargeted metabolomics.

Methods: We developed a human coronavirus pneumonia model in BALB/c mice by infecting them with human coronavirus HCoV-229E with stimulating them with cold-damp environment. We initially assessed the status of inflammation and immunity in model mice treated with or without QFPDD by detecting peripheral blood lymphocytes and inflammatory cytokines. Then, single-cell RNA sequencing and untargeted metabolomics were performed on mouse liver tissue.

Results: HCoV-229E infection in combination with exposure to a cold-damp environment significantly decreased the percentage of peripheral blood lymphocytes (CD4 and CD8 T cells, B cells) in mice, which was enhanced by QFPDD therapy. Meanwhile, the levels of inflammatory cytokines such as IL-6, TNF-α, and IFN-γ were significantly increased in mouse models but significantly decreased by QFPDD treatment. Single-cell RNA sequencing analysis showed that QFPDD could attenuate disease-associated alterations in gene expression, core transcriptional regulatory networks, and cell-type composition. Computational predictions indicated that QFPDD rectified the observed aberrant patterns of cell-cell communication. Additionally, the metabolic profiles of liver tissue in the Model group were distinct from mice in the Control group, and QFPDD significantly regulated hepatic purine metabolism.

Conclusion: To the best of our knowledge, this study is the first to integrate hepatic single-cell RNA sequencing and untargeted metabolomics into a TCM formula and these valuable findings indicate that QFPDD can improve immune function and reduce liver injury and inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2021.153922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720382PMC
March 2022

Acupuncture for prostatectomy incontinence: study protocol for a multicenter single-blind randomized parallel controlled trial.

Trials 2022 Jan 4;23(1). Epub 2022 Jan 4.

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Background: Urinary incontinence is a common complication post radical prostatectomy. Acupuncture is considered an effective treatment for post-prostatectomy incontinence (PPI), but the evidence is still limited. We propose to evaluate the effectiveness of acupuncture in a rigorously conducted trial.

Methods: Twenty hospitals will recruit 340 participants with urinary incontinence after radical prostatectomy in China from April 2021 to April 2022. Participants will be randomly allocated to acupuncture or sham acupuncture with a 1:1 ratio using computerized simple random sampling. The study plan consists of 1-week baseline, 6-week treatment, and 18-week follow-up. Eighteen 30-min sessions of acupuncture or sham acupuncture treatment will be provided between weeks 1 and 6. The primary outcome is the change in the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF) score at the week 6 from the baseline. Secondary outcomes include the change in volume of urine leakage at weeks 4 and 6 from a baseline measured using the 1-h pad test; 72-h incontinence episode frequency based on a 72-h voiding diary; change in the Expanded prostate cancer Index Composite scale (EPIC-26); change in the Self-Rating Anxiety Scale; weekly consumption of pads; and the severity of urinary incontinence based on a 72-h bladder diary and self-assessment of the therapeutic effect. The safety of acupuncture will also be assessed.

Discussion: This trial will help to identify whether acupuncture is effective for PPI, and, if so, whether it exerts a therapeutic rather than a placebo effect.

Trial Registration: www.Chictr.org.cn ChiCTR2100042500 . Retrospectively registered on 22 January 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-021-05805-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725553PMC
January 2022

Establishment of Holistic Quality Control Methods for Nelumbinis Folium Containing Alkaloids and Flavonoids with Simple HPLC Conditions.

J Chromatogr Sci 2021 Dec 30. Epub 2021 Dec 30.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 16 Nanxiao Street, Dongzhimen Nei, Beijing 100700, China.

In this study, a positive charged C18 column was used to explore its performance in analysis of herbal medicines containing alkaloids and flavonoids with Nelumbinis Folium (NF) as an example. A chromatographic fingerprint analysis method was established by high performance liquid chromatography-diode array detector with commonly used 0.1% formic acid as mobile phase additive and this method could simultaneously detect both alkaloids and flavonoids with good peak shape. It is noted that the HPLC conditions were directly applied in the HPLC-ESI-Orbitrap-MS/MS analysis, and 12 common peaks were identified. In the quantification method of nuciferine, compared with common C18 column, good performance was observed, including sharp and symmetric peak shape of nuciferine, and no obvious retention time shift in chromatogram. The fingerprint method and quantification method of nuciferine and quercetin-3-O-glucuronic acid could be readily utilized as quality control methods for NF and its related preparations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/chromsci/bmab138DOI Listing
December 2021

Isolated tuberculosis of the lumbar facet joint: A case report.

Medicine (Baltimore) 2021 Dec;100(51):e28268

Department of Spine Surgery, General Hospital of Ningxia Medical University, Yinchuan, China.

Rationale: Spinal tuberculosis (TB) is the most common in bone and joint TB, of which vertebral TB is more common, while accessory TB is rare. The incidence of isolated adnexal lesions in spinal TB is 2% to 3%. It is difficult to distinguish the imaging changes of spinal adnexal TB from other types of spinal infections and spinal tumors, and the pathological diagnosis of spinal TB is often atypical. Here, we report a case of isolated lumbar facet joint TB.

Patient Concerns: A 64-year-old female patient had an 8-month history of low back pain, decreased pinprick sensation in the left anterior middle thigh area, weakening of the patellar tendon reflex of the left lower limb, and enhanced MRI of the lumbar vertebrae showed bone destruction at the left superior and inferior articular process of the lumbar 2 to 3 and the encapsulated calcification containing the lesion around the articular process. The enhanced scan showed solid part and septal enhancement, and the lesion protruded to the left and posterior side of the spinal canal, and the left posterior edge of the dural sac was compressed at the same level. Conservative treatment for 8 months was ineffective.

Diagnoses: L2-3 vertebral lamina, facet joint, and intraspinal space-occupying Lamina TB.

Interventions: The diagnostic treatment scheme for anti-TB drugs was routinely administered before the operation. Isoniazid (300 mg), rifampicin (450 mg), ethambutol (750 mg), and pyrazinamide (1500 mg) were administered orally once daily after breakfast for 1 month, as anti-TB treatment for 1 month. Posterior lumbar total laminectomy and decompression, pedicle screw internal fixation, TB focus debridement, lumbar intertransverse process bone graft fusion was performed 1 month later.

Outcomes: The patient was relieved of symptoms after surgical treatment and anti-tubercular medication.

Lessons: We present a case of isolated TB of the lumbar facet joint, which was initially diagnosed as L2-3 vertebral lamina, facet joint, and intraspinal space-occupying osteochondroma. For patients with long-term low back pain, it is suggested to follow-up with lumbar computed tomography and lumbar magnetic resonance imaging when conventional X-ray examination does not show any lesion. Despite its rarity, isolated TB of the lumbar facet joint should be highly suspected in elderly patients with pulmonary TB, low-grade fever, and waist pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000028268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701758PMC
December 2021

Analysis of alkaloids in Gelsemium elegans Benth using an online heart-cutting + comprehensive RPLC×RPLC system tandem mass spectrometry.

Talanta 2022 Mar 20;239:123069. Epub 2021 Nov 20.

Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China; Ganjiang Chinese Medicine Innovation Center, Nanchang, 330000, China. Electronic address:

Characterization of alkaloids and new compound discovery become increasing challenging for Gelsemium elegans Benth. (G. elegans), due to the lack of an effective separation method. In this study, we developed a new online heart-cutting + comprehensive (HC) RPLC × RPLC system with pH difference, which was coupled to a mass detector to realize the separation and characterization of alkaloids from G. elegans. 18 Gelsemium standards were used to construct the RPLC × RPLC system with pH difference (pH 3 and 11), and good orthogonality (correlation coefficient 0.3) was obtained. A heart-cutting valve was introduced into the traditional online comprehensive RPLC × RPLC system to remove principal components and improve detection of minor components. The online HC RPLC × RPLC system achieved good resolving power (effective peak capacity 687) in condition of optimized practical factors, like the first- and second-dimension flow rates, modulation period and elution gradient et al. Finally, a total of 256 alkaloids were grouped and tentatively identified, among which 156 were unreported, including a new alkaloid type in G. elegans and many dimeric indole alkaloids, which was an important supplement to the study on chemical constituents of G. elegans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2021.123069DOI Listing
March 2022

SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate.

Int J Biol Macromol 2021 Dec 29;193(Pt B):1124-1129. Epub 2021 Oct 29.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address:

Thrombotic complication has been an important symptom in critically ill patients with COVID-19. It has not been clear whether the virus spike (S) protein can directly induce blood coagulation in addition to inflammation. Heparan sulfate (HS)/heparin, a key factor in coagulation process, was found to bind SARS-CoV-2 S protein with high affinity. Herein, we found that the S protein can competitively inhibit the bindings of antithrombin and heparin cofactor II to heparin/HS, causing abnormal increase in thrombin activity. SARS-CoV-2 S protein at a similar concentration (~10 μg/mL) as the viral load in critically ill patients can cause directly blood coagulation and thrombosis in zebrafish model. Furthermore, exogenous heparin/HS can significantly reduce coagulation caused by S protein, pointing to a potential new direction to elucidate the etiology of the virus and provide fundamental support for anticoagulant therapy especially for the COVID-19 critically ill patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.10.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553634PMC
December 2021

Spectral filtering effect-induced temporal rogue waves in a Tm-doped fiber laser.

Opt Express 2021 Sep;29(19):30494-30505

We have experimentally and theoretically investigated optical rogue waves (ORWs) in a net negative dispersion Tm-doped fiber laser with a long cavity, adopting nonlinear polarization evolution as a mode-locker as well as a spectral filter. We obtained a state with numerous pulses bunched in a burst accompanied by perturbation within the burst, in which the spectrum was partially perturbed. After statistical analysis, we found that ORWs have existed in this bunching state. By adjusting the intra-cavity polarization controllers, the perturbed pulse bunching turned into a chaotic pulse bunching state, which gave rise to giant pulses with ultra-high amplitudes, and the giant pulses were a precursor of a broad-spectrum noise-like pulse. The probability of occurrence of ORWs was increased in the chaotic state, which is caused by multi-pulse instability induced by the spectral filtering effect. Simulation results confirm the experimental results and demonstrate that the spectral filter bandwidth (SFB) is directly related to the probability of the emergence of ORWs. When increasing the SFB across the range of multi-pulse instability at a fixed pump power, the frequency with which ORWs appear increases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.434390DOI Listing
September 2021

Symbiotic coexistence of noise-like pulses.

Opt Express 2021 Sep;29(19):30449-30460

Noise-like pulse (NLP) can split and then self-assemble into dynamic bound states, named NLP polymer. Here, we reported the first observation, to the best of our knowledge, of the buildup process of bound NLPs in all-normal-dispersion Yb-doped fiber lasers. By designing two NLP fiber lasers, the distinct autocorrelation trace property for the bound NLPs with a short time interval (around 30 ps), and the high-speed oscilloscope trace characterization for the bound NLPs with a relatively broad time interval (∼500 ps) have all been exhibited. Also, we have demonstrated that it was the Raman effect that mediated the NLP bound states. The experiment results showed that though the inter-interval between the NLPs and the NLP width in the bound states are constantly changing, the envelope of each NLP remained localized and the bound NLPs could maintain within a wide pump range. The dynamics of the experimentally observed bound NLPs have also been discussed with fitting models and numerical simulations. In addition, the experimental test results for the coherence of the NLPs and their bound states further indicated that the NLPs had low temporal coherence characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.432957DOI Listing
September 2021

Kanglaite Combined With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapy for Stage III/IV Non-Small Cell Lung Cancer: A PRISMA-Compliant Meta-Analysis.

Front Pharmacol 2021 13;12:739843. Epub 2021 Sep 13.

Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Kanglaite(KLT), a type of Chinese medicine preparation, is considered as an adjuvant therapeutic option for malignant cancer treatment. This study aimed to systematically investigate the efficacy and safety of the combination of KLT and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for the treatment of stage III/IV non-small cell lung cancer. Randomized controlled trials (RCTs) that compared KLT plus EGFR-TKI with EGFR-TKI alone for the treatment of stage III/IV non-small cell lung cancer were reviewed. Literature searches (up to July 10, 2021) were performed on PubMed, Web of Science, Cochrane Library, Embase, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), Wanfang Database, and the Chinese Scientific Journal Database. Two researchers independently assessed the risk of bias with the tool of Cochrane Collaboration. RevMan 5.3.0 was used in the analysis of the included trial data. 12 RCTs recruiting 1,046 patients with stage III/IV NSCLC were included. Results showed that compared with EGFR-TKI alone, KLT plus EGFR-TKI significantly increased the disease control rate (DCR) (odds ratio [OR]=3.26; 95% confidence interval [CI]:2.22-4.77; < 0.00001), the objective response rate (ORR) (OR=2.59; 95% CI:1.87-3.58; < 0.00001) and Karnofsky performance status (KPS) (OR = 2.76; 95% CI:1.73-4.39; < 0.00001). Furthermore, patient immunity was enhanced with KLT plus EGFR-TKI. The combined treatment increased the percentage of CD4 + T cells (weighted mean difference [WMD]=5.36; 95% CI:3.60-7.13; < 0.00001),the CD4+/CD8 + ratio (WMD = 0.18; 95% CI: 0.08-0.27; = 0.004), and percentage of NK cells (WMD=4.84; 95% CI: 3.66-6.02; < 0.00001).With regard to drug toxicity, the occurrence rate of nausea and vomiting was significantly reduced by KLT plus EGFR-TKI (OR=0.37; 95% CI: 0.16-0.86; = 0.02). KLT plus EGFR-TKI was effective in treating stage III/IV non-small cell lung cancer. Thus, its application in these patients is worth promoting. Additional double-blind, well-designed and multicenter RCTs are required to confirm the efficacy and safety of this treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.739843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473705PMC
September 2021

[Quality analysis of extracts based on high performance liquid chromatography quantitative fingerprint and ultra-high performance liquid chromatography-tandem mass spectrometry quantification].

Se Pu 2021 Sep;39(9):989-997

Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

is the dried seeds of Mill. var. (Bunge) Hu ex H. F. Chou, and its extract has broad application prospects in the development of sleep-aid functional foods. However, the quality parameters of extracts currently available in the market are not uniform and there is a lack of unified standards. Therefore, it is important to establish an accurate and comprehensive method for quality evaluation. In view of the problems that the UV responses of flavonoids and saponins in the extracts vary dramatically and the saponin content in water extract is very low, high performance liquid chromatography (HPLC) was used to establish the fingerprint and quantify spinosin. The separation was carried out on a Waters XSelect HSS C18 column (250 mm×4.6 mm, 5 μm), and the mobile phase was acetonitrile-0.1% (v/v) phosphoric acid aqueous solution for gradient elution. The eight common peaks in the fingerprint of the extracts, identified by HPLC-quadrupole time-of-flight mass spectrometry, were attributed to flavonoids by reference substance identification, literature comparison, and high-resolution mass spectrometry data analysis. Semi-quantitative analysis of seven flavonoids and quantitative analysis of spinosin were conducted using the established HPLC quantitative fingerprint. The contents of jujuboside A and jujuboside B were determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7 μm) by gradient elution using a mobile phase of acetonitrile-0.1%(v/v) formic acid aqueous solution. The target compounds were analyzed in multiple reaction monitoring mode with positive electrospray ionization. The semi-quantitative and quantitative data of the above-mentioned 10 components are displayed in the form of radar. Using the above methods, three batches of water extracts prepared in the laboratory and 15 batches of extract samples obtained from 15 suppliers were analyzed and compared. The results showed that although the raw materials of three batches water extracts prepared in the laboratory were from different enterprises, the overall difference was not significant. However, the component contents of the samples provided by different manufacturers were greatly different, suggesting that there are some problems associated with the different manufacturers, such as dilution of excipients, adulteration of , alcohol extraction, purification, and enrichment. For example, the representative composition contents in the extracts obtained from manufacturers B, C, E, F, G, H, I, and O were low, which were approximately 1/10 of corresponding contents in the normal water extracts prepared in the laboratory. It is speculated that to reduce the unit price of the product, the manufacturer used fewer raw materials or a large number of auxiliary materials to dilute the extracts. The contents of some flavonoids in the extract from manufacturer N were slightly higher than that in the self-preparation water extract, but it did not contain jujuboside A; thus, it was speculated that the might be used for extraction. The contents of 10 components in the extract obtained from manufacturer D were all higher than the corresponding ones in the self-preparation water extract. Combined with the quality label of total saponin content > 20% and poor water solubility, it was speculated that the product might be prepared by alcohol extraction or purified and enriched by using resin. These results provided the basis for the enterprise to establish internal control quality standards for extracts and to select qualified suppliers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3724/SP.J.1123.2021.06019DOI Listing
September 2021

Probiotic fermentation of Ganoderma lucidum fruiting body extracts promoted its immunostimulatory activity in mice with dexamethasone-induced immunosuppression.

Biomed Pharmacother 2021 Sep 10;141:111909. Epub 2021 Jul 10.

College of Basic Medical Science, Dalian Medical University, Dalian, China. Electronic address:

Ganoderma lucidum is a legendary traditional Chinese medicine with various bioactivities. This study was conducted (a) to explore the in vitro fermentation of the water extracts of G. lucidum fruiting body with Lactobacillus acidophilus and Bifidobacterium breve and (b) to investigate the effect of fermentation broth (GLFB) on dexamethasone (DEX)-induced immunosuppressed mice. Our results demonstrated that probiotic fermentation of G. lucidum fruiting body extracts underwent structural changing of major ganoderic acid components, such as ganoderic acid A (GA) into GC2, and this fermentation process involves changing of several metabolic pathways in the probiotic strains. GLFB could significantly improve the immunity, intestinal integrity, and gut microbiota dysbiosis in DEX-treated mice, and the immunostimulatory activity of GLFB was found closely related to its direct regulation on the expansion of CD4 T cells in Peyer's patches of mice. These data implied that probiotic fermentation of G. lucidum fruiting body extracts promoted its immunostimulatory activity via biotransformation of components such as GA. This research provides a theoretical support for the development and application of G. lucidum fermentation by probiotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2021.111909DOI Listing
September 2021

The dysfunction of parvalbumin interneurons mediated by microglia contributes to cognitive impairment induced by lipopolysaccharide challenge.

Neurosci Lett 2021 09 23;762:136133. Epub 2021 Jul 23.

Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China. Electronic address:

Background: The mechanisms underlying cognitive impairments induced by systemic inflammation remain unclear. Increasing evidence has suggested that parvalbumin (PV) interneurons play an important role in regulating cognitive behaviors and its dysfunction is implicated in many neurological disorders. Thus, the present study was aimed to detect whether the destruction of PV interneurons mediates cognitive impairment associated with systemic inflammation.

Methods: Male wild-type C57BL/6J mice (12-14 weeks old) received lipopolysaccharide (LPS 2 mg/kg i.p.) injection to establish the systemic inflammation model. For the suppression of microglial activation, minocycline (50 mg/kg i.p.) was applied. Animal behavior tests were conducted on day 3 post-LPS injection including the open field test, fear conditioning test and Y maze test. The PV expression in hippocampus was detected by Western blot and immunofluorescence. The number of perisomatic boutons around the NeuN-positive cells and microglia in hippocampus was detected by immunofluorescence.

Results: LPS induced hippocampus-dependent memory and working memory impairment, coinciding with decreased PV expression, reduced perisomatic boutons around the NeuN-positive cells and activated microglia in the hippocampus. Notably, the treatment of minocycline suppressed the microglial activation and rescued the PV expression as well as the perisomatic boutons around the NeuN-positive cells in the hippocampus, contributing to improved cognitive function.

Conclusion: Our study suggests that the dysfunction of parvalbumin interneurons mediated by microglia plays a key role in LPS-induced cognitive impairments, which may serve a therapeutic strategy for cognitive disorders associated with systemic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2021.136133DOI Listing
September 2021

[Hydrophilic interaction liquid chromatography for removal of pesticide residues in ginseng extracts].

Se Pu 2021 Apr;39(4):444-452

Hubei Minzu University, Enshi 445000, China.

Ginseng extracts are rich in a variety of ginseng monomer saponins, which have pharmacological functions of retarding aging, enhancing immunity, stimulating blood circulation, and lowering blood pressure. Ginseng is widely used in health products and dietary supplements in the domestic and foreign market. However, the amount of pesticide residues is an important index for measuring the quality of ginseng and ginseng extracts. Therefore, studies focused on methods for the removal of pesticide residues in ginseng extract are of great significance. Hydrophilic interaction liquid chromatography (HILIC) is used to improve the retention and separation selectivity of strongly polar substances, and it is widely employed in drug analysis, metabolomics, proteomics, etc. In this study, a method for the removal of pesticide residues was developed based on the difference in the retention behavior of pesticide residues and ginsenosides on the HILIC column. Using commercially available ginsenoside extracts, the retention behaviors of pesticide residues and ginsenosides on reverse chromatography and hydrophilic chromatographic columns were evaluated by high performance liquid chromatography. The results proved that on the reversed-phase liquid chromatography (RPLC) stationary phase, in addition to the strong retentions of quintozene and pentachloroaniline, which could be clearly separated from the saponins, the retentions of the other five pesticide residues including carbendazim, azoxystrobin, procymidone, iprodione and propiconazole were similar to total ginsenosides. The seven ginsenosides showed strong retention due to the formation of hydrogen bonds between the hydroxyl groups on the sugar chain and the carboxyl groups on the HILIC stationary phase. However, the pesticide residues were not well retained because of their poor hydrophilicity and small molecular weights. For this reason, the pesticide residues and ginsenosides could be completely separated on the HILIC column. Thus, enrichment of the seven ginsenosides and removal of the 14 pesticide residues was realized in one step on the HILIC column. In addition, the effects of loading amount, loading volume, and washing volume on the removal of pesticide residues in ginsenosides were investigated using the Click XIon SPE column. Then, taking the ginsenoside recoveries and pesticide residue removal rates into account, we confirmed the following: the ratio of the maximum sample loading mass to the filler mass was 1∶10; the optimal elution volume was twice the column volume; and the optimal loading volume was twice the column volume. The ginseng extracts were solvated with a 95% ethanol solution and loaded onto an HILIC column. The sample was subjected to pesticide residue removal, and ginsenoside purification and enrichment under the optimum removal conditions. Gradient elution was carried out using ethanol and water as the mobile phases. The total ginsenoside content in the final extracts was increased to 69.61%. The recovery of the total ginsenosides was 94.4%. The pesticide residues in the samples were quantitatively detected by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) in the multiple reaction monitoring (MRM) mode. The 14 pesticide residues in the original ginsenoside extracts were effectively removed. The amounts of five residues were reduced to below 0.05 mg/kg, while the other nine residues were completely eliminated. This study demonstrates the application of HILIC to pesticide residue removal in traditional Chinese medicine extracts and reveals a new technique for the purification of natural products. The proposed method shows a high removal rate of pesticide residues and a high recovery of total ginsenosides. It is safe, efficient, and environment-friendly, and can aid the development of high-quality ginsenoside extracts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3724/SP.J.1123.2020.08017DOI Listing
April 2021

Discovery of eight alkaloids with D1 and D2 antagonist activity in leaves of Nelumbo nucifera Gaertn. Using FLIPR assays.

J Ethnopharmacol 2021 Oct 15;278:114335. Epub 2021 Jun 15.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

Ethnopharmacological Relevance: Dopamine receptors are long-standing primary targets in the treatment of mental diseases and there is growing evidence that suggests relationships between obesity and the dopamine system, especially dopamine D1 and D2 receptors. Leaves of Nelumbo nucifera Gaertn. (lotus leaves) have been medically used for helping long-term maintenance of weight loss. Whether and how components of lotus leaves function through the dopamine receptors remains unclear.

Aim Of The Study: This work aimed to discover dopamine receptor-active alkaloids isolated from the lotus leaves, to evaluate their potencies and to analyze their structure activity relationship.

Materials And Methods: Dried lotus leaves were prepared and total extract was divided into alkaloids and flavones. Eight alkaloids were separated and characterized by a combination of high-performance liquid chromatography, quadrupole time-of-flight mass spectrometry and nuclear magnetic resonance, and assayed by a fluorometric imaging plate reader platform. Human embryonic kidney 239 cell lines expressing dopamine D1, D2 and serotonin 2A (5-HT2A) receptors, respectively, were cultured and used in the assay.

Results: Alkaloids in the lotus leaves were the bioactive phytochemicals and inhibited dopamine from accessing the D1 and D2 receptors. All eight compounds functioned as D1-receptor antagonists and except N-nornuciferine, seven alkaloids functioned as D2-receptor antagonists. (S)-coclaurine and (R)-coclaurine are optical isomers and antagonized both D1 and D2 with equivalent potencies, suggesting that the optical rotation of the methylene linker in the monobenzyl isoquinoline backbone did not influence their activity. Among the eight alkaloids, O-nornuciferine was the potent antagonist to both receptors (the lowest IC values, D1: 2.09 ± 0.65 μM and D2: 1.14 ± 0.10 μM) while N-nornuciferine was found to be the least potent as it moderately antagonized D1 and was inactive on D2. O-nornuciferine was also a 5-HT2A antagonist (IC~20 μM) while N-nornuciferine had no activity. These hinted the importance of a methyl group attached to the nitrogen atom in the aporphine backbone. Armepavine showed a nearly 10-fold selectivity to D2.

Conclusions: In this work, eight alkaloids were isolated from the leaves of Nelumbo nucifera Gaertn. and assayed on the D1 and D2 receptors. They were D1/D2 antagonists with IC values in the mid- to low-micromolar range and O-nornuciferine was the most potent alkaloid among the eight. This family of alkaloids was biochemically evaluated on the dopamine receptors by the same platform for the first time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114335DOI Listing
October 2021

Identification and target-pathway deconvolution of FFA4 agonists with anti-diabetic activity from Arnebia euchroma (Royle) Johnst.

Pharmacol Res 2021 01 4;163:105173. Epub 2020 Oct 4.

Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. Electronic address:

FFA4 is a novel therapeutic target for the treatment of metabolic diseases, such as type II diabetes. However, there are still few ligands with structural diversity, selectivity and high potency, and the signaling pathway downstream of FFA4 remains to be poorly characterized. In this study, a high performance liquid chromatography-corona charged aerosol detector (HPLC-CAD) combined with label-free dynamic mass redistribution (DMR) method was introduced to guide the discovery of FFA4 agonists from Arnebia euchroma (Royle) Johnst. Ten compounds were identified as FFA4 agonists and structure-activity relationship was obtained. Among them, shikonin displayed the most potent activity with pEC value of 6.02 ± 0.19. The activity of shikonin was confirmed by FLIPR (fluorometric imaging plate reader) assay. Signaling pathways of FFA4 were explored in HT-29 cells endogenously expressing FFA4 using shikonin and known FFA4 agonists α-linolenic acid (ALA) and TUG891. Multiple pathways included Gq/11-PLC-Ca-PKC, RohA, JNK, p38 MAPK, Gi/o and PI3K signaling but may not involve Gs signaling triggered by shikonin, ALA and TUG891. Besides, shikonin, TUG891 and ALA could induce ERK1/2 and AKT phosphorylation in HT-29 cells. Moreover, anti-diabetes effects of shikonin were evaluated on the glucose intolerance in diabetic db/db mice. Shikonin reduced plasma glucose level, suggesting that it had the potential in treatment of type II diabetes. The agonists identified in this study provided structure guidance for FFA4 drug design. This study was also useful for understanding FFA4 pharmacology and its biological function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.105173DOI Listing
January 2021

P-STAT3 Inhibition Activates Endoplasmic Reticulum Stress-Induced Splenocyte Apoptosis in Chronic Stress.

Front Physiol 2020 30;11:680. Epub 2020 Jun 30.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Chronic stress leads to immunosuppression and induces splenocyte apoptosis. STAT3 is a transcription factor that regulates immunity and apoptosis; however, it is unclear whether the increased expression of phosphorylated STAT3 (p-STAT3) observed in chronic stress is related to splenocyte apoptosis. To explore the relationship between splenocyte apoptosis and STAT3 in chronic stress, we treated rats undergoing a 21-day chronic restraint stress program with the STAT3 inhibitor S3I-201. This chronic stress model was verified by observing rats' behavior and measuring their serum corticosterone levels. Chronic stress led to increased expression of anti-inflammatory cytokines, and p-STAT3 inhibition enhanced splenocyte apoptosis in chronic stress. We detected key proteins in three apoptotic pathways to determine which pathway mediated increasing splenocyte apoptosis and found that the death receptor pathway was the main apoptotic pathway that occurred in the spleen during chronic stress. The unfolded protein response (UPR) was also activated, but the Bcl-2 family was not involved in chronic stress. P-STAT3 inhibition had no influence on the Bcl-2 family and the death receptor pathway; however, p-STAT3 inhibition disrupted the pro-survival function of the UPR by decreasing the expression of ATF6α and p-IRE1α. Furthermore, p-STAT3 inhibition activated endoplasmic reticulum stress by promoting the expression of CHOP, p-JNK, and procaspase-12. Collectively, these findings indicate that the increased p-STAT3 expression during chronic stress may promote splenocyte survival by activating the UPR. Consequently, STAT3 and the UPR may be considered as potential therapeutic targets for chronic stress in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340136PMC
June 2020

Dexmedetomidine Protects Against Lipopolysaccharide-Induced Acute Kidney Injury by Enhancing Autophagy Through Inhibition of the PI3K/AKT/mTOR Pathway.

Front Pharmacol 2020 25;11:128. Epub 2020 Feb 25.

Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Background: Acute kidney injury (AKI) is often secondary to sepsis. Previous studies suggest that damaged mitochondria and the inhibition of autophagy results in AKI during sepsis, but dexmedetomidine (DEX) alleviates lipopolysaccharide (LPS)-induced AKI. However, it is uncertain whether the renoprotection of DEX is related to autophagy or the clearance of damaged mitochondria in sepsis-induced AKI.

Methods: In this study, AKI was induced in rats by injecting 10 mg/kg of LPS intraperitoneally (i.p.). The rats were also pretreated with DEX (30 μg/kg, i.p.) 30 min before the injection of LPS. The structure and function of kidneys harvested from the rats were evaluated, and the protein levels of autophagy-related proteins, oxidative stress levels, and apoptosis levels were measured. Further, atipamezole (Atip) and 3-Methyladenine (3-MA), which are inhibitors of DEX and autophagy, respectively, were administered before the injection of DEX to examine the protective mechanism of DEX.

Results: Pretreatment with DEX ameliorated kidney structure and function. DEX decreased the levels of blood urea nitrogen (BUN) and creatinine (Cre), urine kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), reactive oxygen species (ROS), and apoptosis proteins (such as cleaved caspase-9 and cleaved caspase-3). However, DEX upregulated the levels of autophagy and mitophagy proteins, such as Beclin-1, LC3 II and PINK1. These results suggest that DEX ameliorated LPS-induced AKI by reducing oxidative stress and apoptosis and enhancing autophagy. To promote autophagy, DEX inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Furthermore, the administration of Atip and 3-MA inhibitors blocked the renoprotection effects of DEX.

Conclusions: Here, we demonstrate a novel mechanism in which DEX protects against LPS-induced AKI. DEX enhances autophagy, which results in the removal of damaged mitochondria and reduces oxidative stress and apoptosis in LPS-induced AKI through the α-AR and inhibition of the PI3K/AKT/mTOR pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.00128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052304PMC
February 2020

Therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis.

J Int Med Res 2020 Mar 16;48(3):300060519873461. Epub 2019 Dec 16.

Department of Orthopedics, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.

Objective: To study the therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis (OA).

Methods: The OA rat model was established by intra-articular injection of papain. Changes in knee diameter, toe volume and histopathology were measured. Levels of interleukin (IL)-β and tumor necrosis factor (TNF)-α were assessed by ELISA. Relative expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was evaluated by western blotting.

Results: Compared with rats treated with papain alone, changes in knee diameter, toe volume and Makin' s score were less apparent in OA rats treated with quercetin. Levels of serum IL-1β and TNF-α were also reduced in quercetin-treated OA rats. Expression of TLR-4 and NF-κB was significantly suppressed in a dose-dependent manner in quercetin-treated OA rats.

Conclusion: Quercetin exhibited a therapeutic effect in OA rats, which may be related to inhibition of IL-1β and TNF-α production via the TLR-4/NF-κB pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060519873461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607207PMC
March 2020

Aromatic rosane diterpenoids from the roots of Euphorbia ebracteolata and their inhibitory effects against lipase.

Bioorg Chem 2020 01 16;94:103360. Epub 2019 Oct 16.

College of Pharmacy, Academy of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian 116044, China. Electronic address:

The bioactive chemical constituents of Euphorbia ebracteolata have been investigated in the present work using various techniques. On the basis of chromatographic methods, such as silica gel, RP C-18 column chromatography, five novel rosane type diterpenoids with an aromatic A-ring (1-5) have been isolated from the roots of Euphorbia ebracteolata. Their structures were elucidated by widely spectroscopic data, including HRESI-MS, 1D and 2D NMR. Additionally, the inhibitory effects on lipase of these isolated diterpenoids were evaluated in vitro. Compound 1 as a new diterpenoid displayed significant inhibitory effect on lipase (IC = 1.0 μM). And, the inhibitory kinetics has been studied fully, which determined a competitive inhibition model for compound 1 on the enzymatic activity of lipase (K = 1.8 μM).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2019.103360DOI Listing
January 2020

Glucocorticoid-Driven NLRP3 Inflammasome Activation in Hippocampal Microglia Mediates Chronic Stress-Induced Depressive-Like Behaviors.

Front Mol Neurosci 2019 29;12:210. Epub 2019 Aug 29.

Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Chronic stress is a key risk factor for depression, and microglia have been implicated in the pathogenesis of the disease. Recent studies show that the Nod-like receptor protein 3 (NLRP3) inflammasome is expressed in microglia and may play a crucial role in depression. However, the mechanism of NLRP3 inflammasome activation in hippocampal microglia and its role in depressive-like behaviors remain poorly understood. In this study, rats were subjected to 6 h of restraint stress per day for 21 days to produce a model of stress-induced depression. Behavioral tests and serum corticosterone were used to assess the success of the model. Furthermore, HAPI cells were pretreated with dexamethasone (5 × 10 M) to assess stress-induced changes in microglial cells in culture. The microglial marker Iba-1, reactive oxygen species (ROS), nuclear factor kappa B (NF-κB) and key components of the NLRP3 inflammasome and its downstream inflammatory effectors (IL-1β and IL-18) were measured. Chronic stress induced depressive-like behavior, increased serum corticosterone levels and produced hippocampal structural changes. Chronic stress and dexamethasone both increased Iba-1 expression and ROS formation and also elevated levels of NF-κB, NLRP3, cleaved caspase-1, IL-1β and IL-18. After use of the NF-κB inhibitor BAY 117082 and knocked out NLRP3 decreased ROS formation and the expression of Iba-1, NF-κB and NLRP3 as well as levels of cleaved caspase-1, IL-1β and IL-18. These findings suggest that activation of the glucocorticoid receptor-NF-κB-NLRP3 pathway in hippocampal microglia mediates chronic stress-induced hippocampal neuroinflammation and depression-like behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnmol.2019.00210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727781PMC
August 2019

A Natural Product with High Affinity to Sigma and 5-HT Receptors as Novel Therapeutic Drug for Negative and Cognitive Symptoms of Schizophrenia.

Neurochem Res 2019 Nov 16;44(11):2536-2545. Epub 2019 Sep 16.

Department of Pharmacology, University of California, Irvine, CA, 92697, USA.

Dehydrocorybulbine (DHCB), an alkaloid from Corydalis yanhusuo. W.T, has been identified as a dopamine receptor antagonist. We extended our assessment of its pharmacological profile and found that DHCB exhibits high to moderate binding affinities to sigma 1 and 2 receptors, serotonin 5-HT receptor, and histamine H2 receptors. This led us to evaluate DHCB properties in pharmacological (apomorphine and MK-801) animal models of schizophrenia in mice. The pharmacological profile of DHCB was screened through radioligand receptor binding assays. Single dose of DHCB reversed the locomotor hyperactivity, stereotypy, and prepulse inhibition deficits induced by the dopaminergic agonist apomorphine. DHCB also reversed the depressive-like behavior and memory deficit induced by the glutamatergic antagonist MK-801 in the forced swim and the novel object recognition assays, respectively. These results indicate that DHCB effectively improves schizophrenia-like behavioral deficits that are induced by the disruption of dopaminergic and glutamatergic systems. The effectiveness of DHCB in reversing responses that mimic negative and cognitive deficits of schizophrenia might suggest that its anti-schizophrenia effects are mediated through modulating the activities of several receptor particularly sigma 1, sigma 2, 5-HT and dopamine receptors. Our study casts DHCB as a promising lead for therapeutic treatment of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-019-02873-7DOI Listing
November 2019

[Arthroscopic Twin Tail TightRope combined with distal joint capsule repair technique for acute acromioclavicular dislocation].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Aug;33(8):970-975

Department of Orthopedics, the Second Affiliated Hospital of Kunming Medical University, Kunming Yunnan, 650101, P.R.China.

Objective: To investigate arthroscopic treatment for acute acromioclavicular dislocation by using Twin Tail TightRope combined with distal joint capsular repair.

Methods: The clinical data of 40 patients with acromioclavicular dislocation treated between February 2016 and December 2017 were retrospectively analyzed. The patients were divided into arthroscopic group (20 cases, using arthroscopic Twin Tail TightRope combined with distal joint capsular repair for anatomical repair of stable structure of acromioclavicular joint) and control group (20 cases, treated with clavicular hook plate internal fixation) according to different surgical methods. There was no significant difference in gender, age, cause of injury, Rockwood classification, time from injury to operation, preoperative visual analogue scale (VAS) score and Constant score between the two groups ( >0.05), which were comparable. Postoperative VAS score and Constant score were used to assess shoulder function and re-dislocation was also observed.

Results: The incisions of the two groups healed by first intention, and no early postoperative complications occurred. All patients were followed up 12-18 months (mean, 13.5 months). Postoperative X-ray films showed good anatomical reduction in both groups, but the clavicular hook had a presense in the subacromial space in control group. All patients in arthroscopic group achieved satisfactory shoulder function and returned to work after operation; there was no obvious pain, no complications such as exposure of implant after operation, and no need to remove the implant. In the control group, 4 patients had obvious subacromial impingement pain after operation, and 1 patient had re-dislocation after removal of internal fixator at 1 year after operation; the rest had no complications related to internal fixation, and the internal fixators were removed at 1.0-1.5 years after operation, without re-dislocation. The VAS score and Constant score at 3 months and 1 year after operation in both groups significantly improved when compared with those before operation, and further improved at 1 year after operation ( <0.05). The VAS score and Constant score at 3 months and 1 year after operation in arthroscopic group were significantly better than those in control group ( <0.05).

Conclusion: Arthroscopic treatment for acute acromioclavicular joint dislocation by using Twin Tail TightRope combined with distal capsular repair is more effective than traditional incision surgery and can obtain more satisfactory results in patient compliance and function recovery because of minimally invasive surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7507/1002-1892.201903019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337892PMC
August 2019

Purification of tertiary and quaternary alkaloids from Rhizoma Corydalis using reversed-phase/weak cation-exchange mixed-mode class separation combined with preparative C18 and silica based strong cation-exchange chromatography.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Sep 31;1126-1127:121742. Epub 2019 Jul 31.

Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; DICP-CMC Innovation Institute of Medicine, Taizhou 225300, China. Electronic address:

A new optimization strategy for purification of alkaloids from Rhizoma Corydalis using preparative liquid chromatography was developed, featuring a selective separation of different types of alkaloids into different parts by a reversed-phase/weak cation-exchange mixed-mode column (named C18WCX) at first. The total alkaloids of Rhizoma Corydalis were divided into four fractions with fraction III and IV corresponding to the tertiary type medium bases and the quaternary type strong bases, respectively. For fraction III, a conventional C18 column was used to isolate tertiary alkaloids using acetonitrile and 0.1% phosphoric acid (adjusted with triethylamine to pH 6.0) as mobile phases. High selectivity and symmetrical peak shapes of tertiary alkaloids were obtained, resulting in six main tertiary alkaloids isolated in a single run. As strong bases, quaternary alkaloids often suffer from serious peak tailing problem on conventional C18 columns. Therefore, a silica-based strong cation-exchange (SCX) column was used for purification of fraction IV. On the SCX column, good peak shapes in high sample loading were achieved. Five main quaternary alkaloids were isolated and identified from the fraction in one-step. The procedures presented effective for the preparative isolation and purification of alkaloids from Rhizoma Corydalis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2019.121742DOI Listing
September 2019

Dexmedetomidine alleviates lipopolysaccharide-induced acute kidney injury by inhibiting the NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway.

J Cell Biochem 2019 10 26;120(10):18509-18523. Epub 2019 Jun 26.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Dexmedetomidine (DEX) prevents kidney damage caused by sepsis, but the mechanism of this effect remains unclear. In this study, the protective molecular mechanism of DEX in lipopolysaccharide (LPS)-induced acute kidney injury was investigated and its potential pharmacological targets from the perspective of inhibiting oxidative stress damage and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Intraperitoneal injection of DEX (30 μg/kg) significantly improved LPS (10 mg/kg) induced renal pathological damage and renal dysfunction. DEX also ameliorated oxidative stress damage by reducing the contents of reactive oxygen species, malondialdehyde and hydrogen peroxide, and increasing the level of glutathione, as well as the activity of superoxide dismutase and catalase. In addition, DEX prevented nuclear factor-kappa B (NF-κB) activation and I-kappa B (IκB) phosphorylation, as well as the expressions of NLRP3 inflammasome-associated protein and downstream IL-18 and IL-1β. The messengerRNA (mRNA) and protein expressions of toll-like receptor 4 (TLR4), NADPH oxidase-4 (NOX4), NF-κB, and NLRP3 were also significantly reduced by DEX. Their expressions were further evaluated by immunohistochemistry, yielding results were consistent with the results of mRNA and protein detection. Interestingly, the protective effects of DEX were reversed by atipamezole-an alpha 2 adrenal receptor (α AR) inhibitor, whereas idazoxan-an imidazoline receptor (IR) inhibitor failed to reverse this change. In conclusion, DEX attenuated LPS-induced AKI by inhibiting oxidative stress damage and NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway, mainly acting on the α AR rather than IR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.29173DOI Listing
October 2019

Dexmedetomidine ameliorates lipopolysaccharide-induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK-3β/Nrf2 signaling pathway.

J Cell Physiol 2019 08 28;234(10):18994-19009. Epub 2019 Mar 28.

Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, People's Republic of China.

Acute kidney injury (AKI) is a frequent and serious complication of sepsis; however, there are currently no effective therapies. Inflammation and oxidative stress are the major mechanisms implicated in lipopolysaccharide (LPS)-induced AKI. Dexmedetomidine (DEX) has been reported to have remarkable anti-inflammatory and antioxidant effects. Here, we examined the renoprotective effects of DEX and potential underlying mechanisms in rats with LPS-induced AKI. We analyzed renal function and structure; serum inflammatory cytokine; renal oxidant and antioxidant levels; and renal expression of glycogen synthase kinase-3β (GSK-3β)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins in rats 4 hr after administration of LPS. Pretreatment with DEX improved renal function and significantly reduced the levels of inflammatory cytokines and oxidative stress markers. Treatment with DEX and the GSK-3β inhibitor SB216367 promoted phosphorylation of GSK-3β, induced Nrf2 nuclear translocation, and increased transcription of the Nrf2 target genes heme oxygenase-1 and NAD(P)H quinone oxidoreductase-1, primarily in renal tubules. Alpha-2-adrenergic receptor (α2-AR) antagonist atipamezole and imidazoline I receptor (I R) antagonist idazoxan reversed the effects of DEX. These results suggest that the renoprotective effects of DEX are mediated via α2-AR and I R-dependent pathways that reduce inflammation and oxidative stress through GSK-3β/Nrf2 signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.28539DOI Listing
August 2019

Dexmedetomidine protects against lipopolysaccharide-induced early acute kidney injury by inhibiting the iNOS/NO signaling pathway in rats.

Nitric Oxide 2019 04 17;85:1-9. Epub 2019 Jan 17.

College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, PR China. Electronic address:

Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early acute kidney injury (AKI) from the perspective of antioxidant stress. We found that DEX (30 μg/kg, i.p.) ameliorated the renal dysfunction and histopathological damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory cells and cast formation) induced by LPS (10 mg/kg). DEX also attenuated renal oxidative stress remarkably in LPS-induced early AKI, as evidenced by reduction in production of reactive nitrogen species, decreasing malondialdehyde levels, as well as increasing superoxide dismutase activity and glutathione content. DEX prevented activator protein-1 translocation, inhibited phosphorylation of I-kappa B (IκB) and activation of nuclear factor kappa B (NF-κB) in LPS-induced early AKI, as assessed by real-time quantitative polymerase chain reaction and protein levels of c-Jun, c-Fos, IκB and NF-κB. Notably, DEX pretreatment had the same effect as intraperitoneal injection of an inhibitor of inducible nitric oxide synthase inhibitor (1400W; 15 mg/kg), and inhibited the activity of renal inducible nitric oxide synthase (iNOS) and decreased the expression of iNOS mRNA and NO production. However, the protective effect of DEX on LPS-induced early AKI was reversed by the alpha 2 adrenal receptor (α-AR) inhibitor atipamezole, whereas the imidazoline receptor inhibitor idazoxan did not. Taken together, DEX protects against LPS-induced early AKI in rats by inhibiting the iNOS/NO signaling pathway, mainly by acting on α-ARs instead of IRs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.niox.2019.01.009DOI Listing
April 2019

Dexmedetomidine attenuates lipopolysaccharide-induced liver oxidative stress and cell apoptosis in rats by increasing GSK-3β/MKP-1/Nrf2 pathway activity via the α2 adrenergic receptor.

Toxicol Appl Pharmacol 2019 02 28;364:144-152. Epub 2018 Dec 28.

Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Dexmedetomidine (DEX) protects against liver damage caused by sepsis. The purpose of this study was to confirm the regulatory effects of DEX on glycogen synthase kinase 3 beta (GSK-3β) via the α2 adrenergic receptor (α2AR) and evaluate the role of GSK-3β in lipopolysaccharide (LPS)-induced liver injury. Sprague-Dawley (SD) rats were administered an intraperitoneal injection of DEX (30 μg/kg) 30 min before an intraperitoneal injection of LPS (10 mg/kg). HE staining and serum biochemical test results indicated that DEX significantly improved liver histopathological damage and liver function indices. Furthermore, DEX increased super oxide dismutase (SOD) activity and L-glutathione (GSH) levels, and inhibited malondialdehyde (MDA) production. Western blot (WB) analysis demonstrated that treatment with the GSK-3β inhibitor SB216763 increased antioxidant-related protein mitogen-activated protein kinase phosphatase 1 (MKP-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. In addition, anti-apoptosis-related proteins were up-regulated and pro-apoptosis-related proteins were down-regulated by SB21676 administration. WB analysis also showed that DEX increased anti-apoptosis-related protein levels and decreased pro-apoptotic protein levels in LPS-induced liver injury. Nrf2, p53, and activated caspase-3 levels were further evaluated using immunohistochemistry (IHC), producing results consistent with WB results. The α2AR antagonist atipamezole (AT) significantly reversed the protective effects of DEX, as shown by WB analysis. Our data suggested that α2AR plays an important role in reversing the effects of liver oxidative stress and apoptosis via DEX, and that DEX exerts antioxidant and anti-apoptosis effects through regulation of the GSK-3β/MKP-1/Nrf2 pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2018.12.017DOI Listing
February 2019

Strong electrostatic repulsive interaction used for fast and effective alkaloid enrichment from plants.

J Chromatogr B Analyt Technol Biomed Life Sci 2019 Jan 19;1105:148-155. Epub 2018 Dec 19.

Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.

Since the content of alkaloids is usually low in plants and they are easily co-eluted with other constituents, enrichment of alkaloids is essential in the discovery of bioactive lead compounds from natural products. In this paper, an easy SPE enrichment method was developed in a buffer-free solvent system based on electrostatic repulsion mechanism. The feasibility of the new method was verified by successful enrichment of alkaloids from Scopolia tangutica (S. tangutica) with an optimized eluting condition. Then this developed method was applied to other representative plants in different families, including Przewalskia tangutica and Peganum harmala L, Lycoris radiata and Menispermum dauricum DC, which enlarged the scope of applicability. Additionally, the new SPE procedure avoided possible structural change destruction caused by pH change. Simple solvent system, including formic acid (FA) and methanol, would benefit subsequent mass analysis, quantity determination and bioactivity screening, and so on.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2018.12.024DOI Listing
January 2019

Identification of Alkaloids from W. T. Wang as Dopamine D₁ Receptor Antagonists by Using CRE-Luciferase Reporter Gene Assay.

Molecules 2018 Oct 10;23(10). Epub 2018 Oct 10.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

W. T. Wang () has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of blocks dopamine receptors, demonstrating that its pharmacological activities are mostly due to the antagonistic effects of some of its components at dopamine receptors. As part of our ongoing project on , the aim of the present study is to establish a high-throughput and low-cost screening assay system and test the abilities of the isolated alkaloids from to inhibit dopamine-induced dopamine D₁ receptor activity. By using our established cyclic adenosine monophosphate (cAMP)-response element (CRE)-luciferase reporter gene assay system, we identified eight alkaloids from with D₁ receptor antagonistic activities. We next validated the activities of these compounds using fluorometric imaging plate reader (FLIPR) assay by measuring the intracellular Ca change. Six out of eight compounds, including tetrahydropalmatine, corydaline, 13-methyldehydrocorydalmine, dehydrocorybubine, dehydrocorydaline, and columbamine, can be confirmed for their inhibitory activities. The dopamine-receptor-antagonistic effects of four compounds, including 13-methyldehydrocorydalmine, dehydrocorydaline, columbamine, and corydaline, are reported for the first time. The present study provides an important pharmacological basis to support the traditional use of in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules23102585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222624PMC
October 2018
-->