ABSTRACT
Carpesabrolide A (1), featuring an unprecedented fumaric acid-guaiane sesquiterpenoid hybrid, has been isolated from the folk medicinal plant Carpesium abrotanoides. The structure with absolute configuration has been established by spectroscopic methods and single crystal X-ray diffraction analysis. The plausible biosynthetic pathway for 1 is proposed. Compound 1 shows significant anti-inflammatory activity by inhibiting NO production with an IC50 value of 2.7 µM.
ABSTRACT
Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.
Subject(s)
C-Reactive Protein , Lupus Nephritis , MAP Kinase Signaling System , Sapogenins , Serum Amyloid P-Component , Lupus Nephritis/drug therapy , Lupus Nephritis/metabolism , Animals , Sapogenins/pharmacology , C-Reactive Protein/metabolism , Mice , Humans , MAP Kinase Signaling System/drug effects , Female , Serum Amyloid P-Component/metabolism , Cell Proliferation/drug effects , Adult , Male , Mice, Inbred MRL lpr , Kidney/drug effects , Kidney/metabolism , Kidney/pathologyABSTRACT
Two new quinoline alkaloids with an α, ß-unsaturated amide side chain, xylarinines A and B (1 and 2), were isolated from the ethyl acetate extracts of Xylaria longipes solid fermentation. The structures of these were primarily determined though NMR and HRESIMS data analysis. The absolute configuration of compound 1 was assigned using experimental and calculated ECD data. The neuroprotective effects of compounds 1 and 2 against glutamate-induced damage in PC12 cells were evaluated in vitro bioassay. The results demonstrated that both compounds significantly improved cell viability, inhibited apoptosis, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced intracellular reactive oxygen species (ROS) accumulation. These findings suggested that these mechanisms contribute to the neuroprotective effects of the compounds.
Subject(s)
Alkaloids , Apoptosis , Neuroprotective Agents , Quinolines , Reactive Oxygen Species , Xylariales , PC12 Cells , Neuroprotective Agents/pharmacology , Neuroprotective Agents/isolation & purification , Animals , Rats , Quinolines/pharmacology , Quinolines/isolation & purification , Molecular Structure , Alkaloids/pharmacology , Alkaloids/isolation & purification , Reactive Oxygen Species/metabolism , Xylariales/chemistry , Apoptosis/drug effects , Superoxide Dismutase/metabolism , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Malondialdehyde/metabolism , Glutathione/metabolism , Cell Survival/drug effects , China , Glutamic AcidABSTRACT
OBJECTIVES: This study aims to explore the analgesic mechanism of fire needle on peripheral sensitization in rats with neuropathic pain(NP) induced by oxaliplatin, so as to investigate its mechanism in improving peri-pheral sensitization. METHODS: Male SD rats aged 8 weeks were randomly divided into 4 groupsï¼normal group(n=6), model group(n=6), fire needle group(n=6), and medication group(n=6). NP rat model was established by intraperitoneal injection of oxaliplatin(4 mg/kg) on days 1, 2, 8, 9, 15, 16, 22, and 23. For rats in the fire needle group, fire needle treatment was performed at the "Jiaji"(EX-B2) acupoints of the L4-L6 segments on days 24, 26, and 28, ie. 1 day, 3 and 5 days after modeling. The medication group received intraperitoneal injection of pregabalin(100 mg/kg). Mechanical pain thresholds of the rats were measured before modeling, after modeling and intervention. Serum contents of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and chemokine ligand 12(CXCL12) were detected by ELISA. Skin histopathology changes in the acupoint area were observed using HE staining. The number of mast cells in the skin of the acupoints was observed using toluidine blue staining. Immunohistochemical staining was performed to detect the postive expressions of transient receptor potential vanilloid 1(TRPV1), protease-activated receptor 2(PAR2) and tryptase(TPS) in the skin of the acupoint area. Western blot was used to detect the protein expressions of TRPV1 and PAR2 in the dorsal root ganglia(DRG). RESULTS: Compared with the normal group, the model group had decreased paw withdrawal threshold(PWT) after modeling(P<0.05), increased serum contents of IL-6, TNF-α, and CXCL12(P<0.05), increased number of mast cells in the acupoint area(P<0.05), and increased positive protein expressions of TPS, TRPV1, and PAR2 in the skin of the acupoint area(P<0.05). Compared with the model group, the fire needle group and medication group had increased PWT after intervention(P<0.05), decreased serum contents of IL-6, TNF-α, and CXCL12, and postive protein expressions of TPS, TRPV1, and PAR2 in the skin of the acupoint area(P<0.05)ï¼while the medication group had decreased protein expressions of TRPV1 and PAR2 in DRG(P<0.05). HE staining showed thickened epidermis, disordered cellular arrangement, significant intercellular edema, and inflammatory cell infiltration in the model group. In the medication and fire needle groups, the epidermis was thinner, cellular arrangement was clearer, and the extent of tissue edema and inflammatory cell infiltration was reduced compared to the model group. CONCLUSIONS: Fire needle can improve mechanical pain threshold and reduce the contents of peripheral inflammatory factors in rats with oxaliplatin-induced NP. This effect may be related to the inhibition of mast cell activation and the inhibition of TPS, TRPV1 and PAR2 protein expressions, in the local areas of acupoints.
Subject(s)
Neuralgia , Tumor Necrosis Factor-alpha , Rats , Male , Animals , Rats, Sprague-Dawley , Oxaliplatin/adverse effects , Tumor Necrosis Factor-alpha/genetics , Interleukin-6/genetics , Neuralgia/etiology , Neuralgia/genetics , EdemaABSTRACT
Chemical investigation of medicinal plant Glycosmis lucida Wall. ex C. C. Huang leaves led to the production of ten compounds (1-10), including two previously unreported geranylated sulfur-containing amides (1 and 2) and eight known ones (3-10). Structural characterization was carried out using comprehensive spectroscopic methods including NMR, MS and CD. The inhibitory effects of all isolates on Th17 differentiation were evaluated, of which compounds 1 and 6 significantly inhibited Th17 differentiation with IC50 values of 0.36 and 1.30⠵M, respectively, while both 1 and 6 failed to bind to retinoic acid-related orphan receptor gamma t (RORγt), suggesting that their inhibition of Th17 differentiation is independent of RORγt.
Subject(s)
Amides , Nuclear Receptor Subfamily 1, Group F, Member 3 , Amides/pharmacology , Amides/chemistry , Sulfur , Cell DifferentiationABSTRACT
The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I (1-9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the Rf values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC50 values of 37.5, 38.8, and 42.8 µM (L-NMMA was used as a positive control, IC50 39.3 µM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.
Subject(s)
Marsdenia , Plants, Medicinal , Humans , Plants, Medicinal/chemistry , Marsdenia/chemistry , China , Pregnanes/chemistry , Glycosides/chemistryABSTRACT
A series of oxygenated yohimbane alkaloids, including three new compounds, ophiorrhines H-J (1-3), and seven known compounds, were isolated from the aerial parts of Ophiorrhiza japonica. The structures with absolute configurations were elucidated by extensive MS and NMR spectroscopic methods, as well as the single crystal X-ray diffraction and ECD calculations. Ophiorrhines H (1) and I (2) represent key oxygenated intermediates in the formation of aromatic ring E in the demethoxycarbonyl-3,14-dihydrogambirtannine (10). Ophiorrhine J (3) is a highly oxidized yohimbane derivative with the planar superconjugated system. The cytotoxic activities of all alkaloids against five human cancer cell lines were evaluated.
Subject(s)
Alkaloids , Rubiaceae , Humans , Molecular Structure , Indole Alkaloids , Alkaloids/pharmacology , Alkaloids/chemistryABSTRACT
The ethanol precipitation process of Nauclea officinalis extract was optimized based on the concept of quality by design(QbD). Single factor tests were carried out to determine the levels of test factors. The ethanol volume fraction, pre-ethanol precipitation drug concentration, and ethanol precipitation time were taken as critical process parameters(CPPs). With the comprehensive scores of strictosamide transfer rate and solid removal rate as the critical quality attributes(CQAs), Box-Behnken design was employed to establish the mathematical models and space design between CPPs and CQAs, and the obtained optimal operating space was validated. The optimal operating space included ethanol volume fraction of 65%-70%, pre-ethanol precipitation drug concentration of 22-27 mg·mL~(-1), and ethanol precipitation time of 12 h. Based on the concept of QbD, this study adopted the design space to optimize the ethanol precipitation process of N. officinalis extract, which provided a reliable theoretical basis for the quality control in the production process of N. officinalis preparations. Moroever, this study provided a reference value for guiding the research and industrial production of traditional Chinese medicines.
Subject(s)
Drugs, Chinese Herbal , Ethanol , Medicine, Chinese Traditional , Quality Control , Models, TheoreticalABSTRACT
Chemical investigation on the fruiting bodies of the mushroom Geoglossum fallax led to the isolation of two carboxamides, geoglamides A and B (1 and 2), one meroterpenoid, geoglol A (3), together with seven known metabolites (4-10). Their structures were identified by spectroscopic analyses as well as ECD calculations. Compounds 1 and 2 are rare long chain fatty amides containing a 4-oxo-1,4-dihydropyridine moiety, while compound 3 is a rare C6-C5 type meroterpenoid. Compound 1 displayed cytotoxic activity against human MCF-7 cells with an IC50 value of 25.9 ± 0.51 µM. compounds 2 and 8 showed weak pancreatic lipase inhibition activity. To our best knowledge, this is the first report of the chemical constituents in the genera Geoglossum and their bioactive activity.
Subject(s)
Agaricales , Antineoplastic Agents , Ascomycota , Humans , Agaricales/chemistry , Molecular Structure , Antineoplastic Agents/chemistryABSTRACT
Eight undescribed phenylpropanoid-dihydrochalcone hybrids, namely (+)- and (-)-malahupin A, (+)- and (-)-malahupin B, (±)-malahupin C, malahupinosides A and B, 7â´-epi-malahupinoside B, together with two known compounds, phloretin and phlorizin, were isolated from the leaves of the folk medicinal plant Malus hupehensis. Their structures were elucidated by extensive NMR and MS spectroscopic methods, chiral-phase analysis, and ECD calculations. Compounds (+)-malahupin B and malahupinoside B showed weak inhibition activities against the nitric oxide production in liposaccharide-induced murine RAW264.7 macrophages with IC50 values of 36.7 and 27.0 µM, respectively. Compounds (+)- and (-)-malahupin A, (+)- and (-)-malahupin B exhibited significant α-glucosidase inhibitory activity, with IC50 values of 22.5, 19.1, 19.2, and 17.4 µM, respectively. The postulated biosynthetic pathways to these hybrid compounds were proposed. This work represents the first report of the natural phenylpropanoid-dihydrochalcone hybrid compound, and lays foundation for the study on the bioactive principles of the ethnic hypoglycemic medicinal plant.
ABSTRACT
The current study aimed to establish simple and quick quality evaluation method of Chishao based on QAMS. Oxypaeoniflorin is used as a marker in the Chishao root. Based on it, the content of other components could be obtained by establishing the mathematical relationship. UPLC method was used to collect data, and the detection wavelengths were 230nm (benzoic acid, paeoniflorin), 263nm (hydroxy paeoniflorin) 274nm (gallic acid, paeoniflorin, catechin), respectively. The stationary phase was an Agilent ZORBAX SB-C18 and the mobile phase was acetonitrile -0.1% formic acid-water. The gradient elution method was adopted at the certain flow rate (0.3 mL/min). The column temperature set 40oC, and the injection volume was 1µL. Multiple reaction monitoring mode was selected for data collection. The linear ranges of benzoic acid, paeoniflorin, hydroxy-paeoniflorin, gallic acid, catechin and paeoniflorinhad good linearity (r ≥0.9995). The UPLC method was established to determine the content of paeoniflorin, benzoic acid, catechin, gallic acid, paeoniflorin, andhydroxy-paeoniflorin in Radix Paeoniae Rubra. In the current study, the method for the chemical components in Radix Paeoniae Rubra to provide the evaluation basis of medicinal effects.
Subject(s)
Catechin , Drugs, Chinese Herbal , Paeonia , Benzoic Acid , Bridged-Ring Compounds , Chromatography, High Pressure Liquid/methods , Gallic Acid , Monoterpenes , Paeonia/chemistry , SnailsABSTRACT
Excessive alcohol consumption has long been identified as a risk factor for adverse atrial remodeling and atrial fibrillation (AF). Icariin is a principal active component from traditional Chinese medicine Herba Epimedii and has been demonstrated to exert potential antiarrhythmic effect. The present study was designed to evaluate the effect of icariin against alcohol-induced atrial remodeling and disruption of mitochondrial dynamics and furthermore, to elucidate the underlying mechanisms. Excessive alcohol-treated C57BL/6 J mice were infected with serotype 9 adeno-associated virus (AAV9) carrying mouse SIRT3 gene or negative control virus. Meanwhile, icariin (50 mg/kg/d) was administered to the animals in the presence or absence of AAV9 carrying SIRT3 shRNA. We noted that 8 weeks of icariin treatment effectively attenuated alcohol consumption-induced atrial structural and electrical remodeling as evidenced by reduced AF inducibility and reversed atrial electrical conduction pattern as well as atrial enlargement. Furthermore, icariin-treated group exhibited significantly enhanced atrial SIRT3-AMPK signaling, decreased atrial mitoSOX fluorescence and mitochondrial fission markers, elevated mitochondrial fusion markers (MFN1, MFN2) as well as NRF-1-Tfam-mediated mitochondrial biogenesis. Importantly, these beneficial effects were mimicked by SIRT3 overexpression while abolished by SIRT3 knockdown. These data revealed that targeting atrial SIRT3-AMPK signaling and preserving mitochondrial dynamics might serve as the novel therapeutic strategy against alcohol-induced AF genesis. Additionally, icariin ameliorated atrial remodeling and mitochondrial dysfunction by activating SIRT3-AMPK signaling, highlighting the use of icariin as a promising antiarrhythmic agent in this circumstance.
Subject(s)
Atrial Fibrillation , Atrial Remodeling , Flavonoids , Sirtuin 3 , AMP-Activated Protein Kinases/genetics , Alcohol Drinking/adverse effects , Animals , Atrial Fibrillation/chemically induced , Atrial Fibrillation/drug therapy , Flavonoids/pharmacology , Mice , Mice, Inbred C57BL , Sirtuin 3/geneticsABSTRACT
Alpinia hainanensis is an important food spice and ethnic medicine in Southwest China. In this study, we found that the EtOAc-soluble fraction (AHE) of the A. hainanensis rhizome ethanol extract could ameliorate dextran sulfate sodium-induced ulcerative colitis (UC). To explore active constituents, five pairs of previously unreported enantiomers (1-5), together with nine known ones (6-14), were obtained. Structural characterization was achieved by comprehensive spectroscopic methods. Compounds 1 and 2 were new curcumin-butyrovanillone hybrids featuring a rare structural fragment of 2,3-dihyrofuran. The anti-inflammatory activities of isolates were evaluated, and the results indicated that compounds (-)-1, (-)-3, 6, 9, 11, and 12 significantly inhibited the nuclear factor-κB signaling pathway. These findings indicate the major active fraction of the A. hainanensis rhizome ethanol extract enriched with diarylheptanoids, flavonoids, phenolics, and their hybrid mixtures, which could be developed as a nutritional and dietary supplement for treating UC.
Subject(s)
Alpinia , Colitis, Ulcerative , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Dextran Sulfate/adverse effects , Disease Models, Animal , Humans , NF-kappa B/metabolism , Plant Extracts/chemistry , RhizomeABSTRACT
Three new pyrrole alkaloids albifipyrrols A-C (1-3), were isolated from the endophytic fungus Albifimbria viridis collected from the Chinese medicinal plant. Their structures were elucidated by extensive NMR and HRESIMS spectrometric analyses. All compounds were evaluated for immunosuppressive activity. Fortunately, compound 2 exhibits certain inhibition specifically against the LPS-induced proliferation of B lymphocyte cells with IC50 value 16.16 µM.
ABSTRACT
Mitochondrial reactive oxygen species (ROS) damage and atrial remodeling serve as the crucial substrates for the genesis of atrial fibrillation (AF). Branched-chain amino acids (BCAAs) catabolic defect plays critical roles in multiple cardiovascular diseases. However, the alteration of atrial BCAA catabolism and its role in AF remain largely unknown. This study aimed to explore the role of BCAA catabolism in the pathogenesis of AF and to further evaluate the therapeutic effect of melatonin with a focus on protein kinase G (PKG)-cAMP response element binding protein (CREB)-Krüppel-like factor 15 (KLF15) signaling. We found that angiotensin II-treated atria exhibited significantly elevated BCAA level, reduced BCAA catabolic enzyme activity, increased AF vulnerability, aggravated atrial electrical and structural remodeling, and enhanced mitochondrial ROS damage. These deleterious effects were attenuated by melatonin co-administration while exacerbated by BCAA oral supplementation. Melatonin treatment ameliorated BCAA-induced atrial damage and reversed BCAA-induced down-regulation of atrial PKGIα expression, CREB phosphorylation as well as KLF15 expression. However, inhibition of PKG partly abolished melatonin-induced beneficial actions. In summary, these data demonstrated that atrial BCAA catabolic defect contributed to the pathogenesis of AF by aggravating tissue fibrosis and mitochondrial ROS damage. Melatonin treatment ameliorated Ang II-induced atrial structural as well as electrical remodeling by activating PKG-CREB-KLF15. The present study reveals additional mechanisms contributing to AF genesis and highlights the opportunity of a novel therapy for AF by targeting BCAA catabolism. Melatonin may serve as a potential therapeutic agent for AF intervention.
Subject(s)
Atrial Fibrillation , Melatonin , Amino Acids, Branched-Chain , Angiotensin II , Atrial Fibrillation/chemically induced , Atrial Fibrillation/drug therapy , Atrial Fibrillation/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic GMP-Dependent Protein Kinases/genetics , Humans , Kruppel-Like Transcription Factors , Melatonin/pharmacologyABSTRACT
Kiwi (Actinidia chinensis) plants are severely destroyed by canker disease which is caused by the bacterium Pseudomonas syringae pv. actinidiae (Psa). This program tries to find anti-Psa agents among secondary metabolites of endophytic fungi from kiwi plant itself. The chemical investigation on one kiwi endophytic fungi, Fusarium tricinctum, resulted in the isolation of nine new imidazole alkaloids, fusaritricines A-I (1-9) together with seven known analogues (10-16). The structures of new compounds were established by extensive spectroscopic methods. Compounds 2, 3, 9, and 13 showed good antibacterial activity against Psa with MIC values between 25 and 50 µg/mL. It is suggested that imidazole alkaloids should be potential anti-Psa agents.
Subject(s)
Actinidia/microbiology , Alkaloids/pharmacology , Anti-Bacterial Agents/pharmacology , Fusarium/chemistry , Imidazoles/pharmacology , Pseudomonas syringae/drug effects , Alkaloids/chemistry , Alkaloids/isolation & purification , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/isolation & purification , Fourier Analysis , Fruit/microbiology , Imidazoles/chemistry , Imidazoles/isolation & purification , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Pseudomonas syringae/isolation & purification , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
Four new limonoids, named as trichiconlide G (1), 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), 21-oxo-23-hydroxyltrijugin F (4), along with sixteen known analogues (5-20) were isolated from the leaves and twigs of Trichilia connaroides. Their structures and absolute configurations were determined by spectroscopic analyses, X-ray diffraction analysis, and TD-DFT-ECD calculations. Trichiconlide G (1) is one rare naturally occurring 1,2-seco phragmalin-type limonoid bearing a C-7/28 δ-lactone ring. Additionally, 2-hydroxyltrijugin F (2), 23-oxo-21-hydroxyltrijugin F (3), and 21-oxo-23-hydroxyltrijugin F (4) are three naturally occurring limonoids with a rare C-16/8 δ-lactone ring. All isolates were evaluated for their cytotoxic and anti-inflammatory activities. None of compounds exhibited cytotoxicity against five human cancer cell lines A-549, HepG2, 5-8F, Siha, and SCC-4 at the concentration of 40 µM. Compounds 16 and 17 showed moderate anti-inflammatory activity with IC50 values of 28.45 ± 2.51 and 22.66 ± 2.01 µM, respectively.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Limonins/pharmacology , Meliaceae/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Cell Line, Tumor , China , Humans , Limonins/isolation & purification , Mice , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Leaves/chemistry , RAW 264.7 CellsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Salvianolic acid A (SAA) is extracted from traditional Chinese medicine Salvia miltiorrhiza and is the main water-soluble and the biologically active ingredient. SAA possesses a variety of pharmacological activities and has an excellent protective effect on kidney disease, especially steroid resistant nephrotic syndrome (SRNS), and has advantages in improving the efficacy of glucocorticoids, but its mechanism needs to be further explored. PURPOSE: The study was designed to explore the effect of suPAR and uPAR in SRNS patients and evaluate the potential effect of SAA in improving podocyte steroid resistance and explore its mechanism. METHODS AND MATERIALS: The ELISA kits were used to detect the levels of suPAR in the blood and urine of subjects. The levels of uPAR, GRα, and GRß expression in renal tissues of SRNS patients was detected by immunohistochemistry and analyzed using the Pearson method. In vitro studies, steroid resistance model was induced by the TNF-α and IFN-γ. The protein and mRNA expression of Nephrin, GR, GRα and GRß were analyzed using western blot and qRT-PCR. The activity of GR-DNA binding was detected by using TransAM™ GR kits. Adriamycin further induced steroid resistance podocyte. Flow cytometry was used to detect the effect of SAA on podocyte apoptosis. ELISA assay was used to detect the suPAR expression in the podocyte supernatant. Western blot and qRT-PCR were used to detect the protein and mRNA expression of uPAR and Nephrin in podocytes. RESULTS: The serum and urine levels of suPAR were conspicuously higher in SRNS patients than healthy volunteers and SSNS patients, and the expression of uPAR in renal tissue of SRNS patients is negatively correlated with GRα, but positively correlated with GRß. The combination of TNF-α and IFN-γ could conspicuously increase the GRß expression and reduce GRα/GRß, and induce steroid resistance in podocytes. Moreover, we found that SAA could reduce the apoptosis of podocytes and suppress the expression of suPAR/uPAR, and increase the expression of Nephrin. CONCLUSION: The level of suPAR and uPAR expression may have important value in predicting glucocorticoids resistance in patients with idiopathic nephrotic syndrome (INS). The combination of TNF-α and IFN-γ induce podocytes can establish steroid resistance model in vitro. SAA could improve glucocorticoids resistance of podocyte which can be attributed in part to regulate the suPAR/uPAR-αvß3 signaling pathway.
Subject(s)
Caffeic Acids/pharmacology , Glucocorticoids/pharmacology , Lactates/pharmacology , Nephrotic Syndrome/drug therapy , Receptors, Urokinase Plasminogen Activator/genetics , Adult , Caffeic Acids/isolation & purification , Case-Control Studies , Female , Humans , Lactates/isolation & purification , Male , Membrane Proteins/genetics , Middle Aged , Nephrotic Syndrome/genetics , Nephrotic Syndrome/physiopathology , Podocytes/drug effects , Podocytes/metabolism , Receptors, Glucocorticoid/genetics , Salvia miltiorrhiza/chemistry , Signal Transduction/drug effects , Young AdultABSTRACT
Seven previously undescribed trichothecenes, named trichothecrotocins M-S (1-7), along with five known compounds, were isolated from rice cultures of the potato-associated fungus Trichothecium crotocinigenum. Their structures and absolute configurations were determined through spectroscopic methods, single-crystal X-ray diffraction, and quantum chemistry calculations on ECD. Compound 1 possesses a rare 6,11-epoxy moiety in the trichothecene family. Compound 6 exhibited strong cytotoxic activity against MCF-7 cancer cell lines with an IC50 value of 2.34 ± 0.45 µM. It promoted apoptosis induction in MCF-7 cells. Moreover, cell cycle analysis showed cell cycle arrest caused by compound 6 at the G2/M phase which resulted to cell proliferation inhibition and pro-apoptotic activity. Further quantitative real-time PCR (qRT-PCR) analysis confirmed that the G2/M arrest was accompanied by upregulation of p21 and down regulation of cyclins B1 in 6-treated MCF-7 cells.
Subject(s)
Antineoplastic Agents/pharmacology , Hypocreales/chemistry , Solanum tuberosum/chemistry , Trichothecenes/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Hypocreales/metabolism , MCF-7 Cells , Molecular Docking Simulation , Molecular Structure , Solanum tuberosum/metabolism , Structure-Activity Relationship , Trichothecenes/chemistry , Trichothecenes/metabolismABSTRACT
Tujia is a national minority, inhabiting in the mountainous Wuling area in China. Since 1978, Tujia medicine has been studied, summarized and developed, leading to numerous achievements by Chinese researchers, such as the publishing of approximately 30 monographs of Tujia medicine. These publications are focused on summarizing and improving the theory of Tujia medicine and developing clinical therapies from this system of medicine. The shortage of natural medicinal plants used in Tujia medicine has created the need to discover new resources to replace them and protect endangered natural plant species. Endophytic fungi are one of the conservation options, are considered a source of new bioactive natural products, and are a renewable and inexhaustible source of new drugs and agrochemicals. This review summarizes 260 compounds from endophytic fungi that have been previously isolated from the medicinal plants of Tujia. These compounds include steroids, terpenoids, meroterpenoids, polyketides, alkaloids, peptides, aliphatic compounds, aromatic compounds, and heterocyclic compounds.