Lignans derived from Eucommia ulmoides Oliver (Eucommia lignans) inhibit the progression of inflammatory diseases, while their effect on the progression of diabetic nephropathy (DN) remained unclear. This work was designed to assess the function of Eucommia lignans in DN. The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS. The binding between Eucommia lignans and aldose reductase (AR) was predicted by molecular docking. Eucommia lignans (200, 100, and 50 mg·kg^-1) were used in model animals to evaluate their renal function changes. Rat glomerular mesangial cells (HBZY-1) were transfected with sh-AR, sh-AMPK, and oe-AR in the presence of high glucose (HG) or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis. Eucommia lignans significantly attenuated the progression of DN in vivo. Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury, while downregulating the levels of Cyto c, caspase 9, AR, and NOX4 in HBZY-1 cells. In contrast, HG-induced downregulation of Nrf2, HO-1 and p-AMPKα levels were abolished by Eucommia lignans. Meanwhile, knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression, and AR overexpression reversed the effect of Eucommia lignans. Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis. Thus, these findings might provide evidence for the use of Eucommia lignans in treating DN.
Animals ; Rats ; AMP-Activated Protein Kinases/genetics* ; Diabetes Mellitus ; Diabetic Nephropathies/prevention & control* ; Eucommiaceae/metabolism* ; Lignans/therapeutic use* ; Molecular Docking Simulation ; NF-E2-Related Factor 2/metabolism* ; Tandem Mass Spectrometry

To explore the effects of honokiol (HKL) on pulmonary microvascular endothelial cells in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) and the underlying mechanisms.
 Methods: In animal experiment, a total of 40 C57BL/6J mice were randomly divided into a control group (Con group), a LPS intervention group (LPS group), a LPS+honokiol (HKL) intervention group (HKL group) and a LPS+HKL+nicotinamide (NAM) intervention group (NAM group) (n=10 in each group). In the cell experiment, the experiment cells were divided into a control group (Con group), a LPS intervention group (LPS group), a LPS+HKL intervention group (HKL group), a LPS+HKL+NAM intervention group (NAM group), and a LPS+HKL+compound C (CMC) intervention group (CMC group). The pathological changes of the lung tissues were evaluated by hematoxylin and eosin (HE) staining; the protein concentration, total cells and neutrophils in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissues were detected; the changes of pulmonary microvascular permeability were determined by Evans blue assay; the effect of HKL on the vitality of human pulmonary microvascular endothelial cells were examined by cell counting kit-8 (CCK-8); the inhibitors including NAM and CMC were applied to explore the molecular mechanism of the protective effects of HKL. The expression levels of Sirt3, caspase-3, cleaved caspase-3, Bcl-2, Bax, p-adenosine monophosphate activated protein kinase (p-AMPK) and AMPK in lung tissues or cells were detected by Western blot.
 Results: In animal models, compared with the Con group, the mice in the LPS group displayed typical ARDS pathological changes, and the ratio of lung wet/dry weight (W/D) and MPO activity in the lung tissues, protein concentration, total cells and neutrophils in BALF, Evans blue leaking index (ELI), expression levels of cleaved caspase-3 were significantly increased (all P<0.05), while the expression levels of Sirt3 was obviously decreased (P<0.05). Compared with the LPS group, the above changes in the LPS group were significantly improved in the HKL group (all P<0.05); Compared with the HKL group, the curative effect of HKL intervention could be partly inhibited in the NAM group (P<0.05). In cell experiments, compared with the LPS group, the HPMECs viability in the HKL group was markedly improved (P<0.05), while the expression levels of Bcl-2 and Sirt3 were significantly upregulated (P<0.05), and the expression levels of Bax and cleaved caspase-3 were significantly downregulated (P<0.05), accompanied by the activation of AMPK pathway (P<0.05) in the HKL group. Compared with the HKL group, the curative effect of HKL intervention was partly inhibited in the CMC group (P<0.05).
 Conclusion: HKL can significantly attenuate LPS-induced lung injury and inhibit the apoptosis of pulmonary microvascular endothelial cells through regulation of Sirt3/AMPK pathway.
AMP-Activated Protein Kinases ; metabolism ; Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Biphenyl Compounds ; pharmacology ; therapeutic use ; Humans ; Lignans ; pharmacology ; therapeutic use ; Lipopolysaccharides ; Lung ; Mice ; Mice, Inbred C57BL ; Mitochondria ; drug effects ; metabolism ; Signal Transduction ; drug effects ; Sirtuin 3 ; metabolism

OBJECTIVETo ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum.

METHODSThe 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum (chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione (HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid (BLA), blood urea nitrogen (BUN), malondialdehyde (MDA), hepatic glycogen (HG), lactic dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) determined following the recommended procedures provided by the commercial kits.

RESULTSCompared with the control group, the lignans extract (ethyl acetate fraction) of Herpetospermum caudigerum and HPE could signifificantly prolonged the exhaustive swimming time (P<0.05 or P<0.01), and also increased the HG levels (P<0.05 or P<0.01) and the activities of antioxidant enzymes (SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups (P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group (P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters.

CONCLUSIONSThe lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.

Animals ; Body Weight ; drug effects ; Cucurbitaceae ; chemistry ; Fatigue ; blood ; drug therapy ; Glycogen ; metabolism ; Lignans ; pharmacology ; therapeutic use ; Liver ; drug effects ; metabolism ; Male ; Mice ; Plant Extracts ; pharmacology ; therapeutic use ; Swimming ; Time Factors

A new γ-alkylated-γ-butyrolactone, named melongenolide A (1), along with nine known compounds were obtained from the roots of Solanum melongena, and their structures were identified as melongenolide A (1), (+)-syringaresinol (2), (+)-lyoniresinol (3), 5,5'-dimethoxy lariciresinol (4), (+)-(7R,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7, 9-diol-7'-aldehyde (5), kaempferol-3-O-(2″,6″-di-O-p-trans-coumaroyl)-β-glucoside (6), arjunolic acid (7), vanillic acid (8), scoparone (9), and β-sitosterol (10). Compounds 2, 6, and 7 showed potent inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages, with IC50 values being 5.62 ± 0.86, 11.47 ± 0.98, and 27.75 ± 1.26 μmol·L(-1), respectively.
4-Butyrolactone ; analogs & derivatives ; isolation & purification ; Animals ; Furans ; isolation & purification ; pharmacology ; Inflammation ; drug therapy ; metabolism ; Inhibitory Concentration 50 ; Kaempferols ; isolation & purification ; pharmacology ; Lignans ; isolation & purification ; pharmacology ; Macrophages ; drug effects ; metabolism ; Mice ; Nitric Oxide ; metabolism ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Plant Roots ; chemistry ; RAW 264.7 Cells ; Solanum melongena ; chemistry ; Triterpenes ; isolation & purification ; pharmacology

In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.
Animals ; Antibiotics, Antineoplastic ; adverse effects ; Antioxidants ; metabolism ; Cardiomyopathies ; chemically induced ; drug therapy ; Cardiotoxicity ; drug therapy ; Cyclooctanes ; therapeutic use ; Dexrazoxane ; therapeutic use ; Doxorubicin ; adverse effects ; Heart ; physiopathology ; Lignans ; therapeutic use ; Myocardium ; enzymology ; Polycyclic Compounds ; therapeutic use ; Rats ; Rats, Sprague-Dawley

Honokiol (HNK) is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma (OSCC) cells is unknown. We investigated the antitumor activities of HNK on OSCC cells in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide (PI) assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling (TUNEL), and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 microg x mL(-1) or 20 microg x mL(-1) of HNK were more stronger compared with those of 20 microg x mL(-1) 5-fluorouracil (5-Fu, the control) applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.
Antineoplastic Agents ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; therapeutic use ; Apoptosis ; Biphenyl Compounds ; pharmacology ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Flow Cytometry ; Fluorouracil ; pharmacology ; therapeutic use ; Humans ; In Situ Nick-End Labeling ; Lignans ; pharmacology ; therapeutic use ; Magnolia ; Mouth Neoplasms ; drug therapy ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use

OBJECTIVETo investigate the effects of Tiangou Jiangya capsule on blood pressure of spontaneous hypertensive rats.

METHODThe 13-14 week SPF rats were selected and randomly divided into model groups, the low, middle, high dose of Tiangou Jiangya capsule groups, positive control group administrated with captopril. Drugs were intragastric administrated once per day, lasting four weeks. The blood pressure, heart rate, heart ventricle indexes, urinary volume and the level of PRA,angiotensing II (Ang II), aldosterone (ALD) of rats were observed.

RESULTThe low, middle, high dose of Tiangou Jiangya capsule can remarkably reduce the systolic pressure, diastolic pressure and mean arterial pressure of spontaneous hypertensive rats (P < 0.05 or P < 0.01). The low, middle dose can reduce the heart rate of rats (P < 0.01). The low dose can effectively inhibit the left ventricle indexes (P < 0.05). The Tiangou Jiangya capsule has no markedly effects on the renin-angiotensin-aldosterone system (RAAS) activity and urinary output of rats.

CONCLUSIONThe results indicate that the Tiangou Jiangya capsule has evident effect of lowering blood pressure of rats, which is related to reducing heart rate, heart ventricle indexes, and has no effect on the RAAS and diuresis.

Animals ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Benzyl Alcohols ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Disease Models, Animal ; Diuresis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Flavonoids ; pharmacology ; therapeutic use ; Furans ; pharmacology ; therapeutic use ; Glucosides ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Hypertension ; drug therapy ; Lignans ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Inbred SHR ; Renin-Angiotensin System ; drug effects ; Ventricular Function, Left ; drug effects

OBJECTIVETo observe the effect of Tiangou Jiangya capsule (TJC) on blood pressure in renovascular hypertension rats and explore its possible mechanism.

METHODSeventy-two Wistar rats were randomly divided into normal control group, model group, captopril group, TJC small, medium and high dose groups. Non-invasive blood pressure measurement was used to detect the arterial blood pressure of rat tails. PRA, Ang II , ALD, 6-Keto-PGF1alpha, ET and TXB2 content in blood was measured by radioimmunoassay. NO content in blood was determined by method of nitrate reductase.

RESULTThe systolic, diastolic and mean pressure significantly increased, serum PRA, Ang II , ALD decreased, ET levels significantly increased in model group rats. TJC significantly reduced blood pressure, improved the plasma renin activity, decreased ET levels and increased NO content of model rats.

CONCLUSIONTJC can reduce blood pressure of renovascular hypertention rats, and the mechanism may be related to its regulating lower blood pressure regulation of the secretion of RAAS system and improving vascular endothelial function.

Angiotensin II ; blood ; Animals ; Antihypertensive Agents ; administration & dosage ; pharmacology ; therapeutic use ; Benzyl Alcohols ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Flavonoids ; pharmacology ; therapeutic use ; Furans ; pharmacology ; therapeutic use ; Glucosides ; pharmacology ; therapeutic use ; Hypertension, Renovascular ; blood ; drug therapy ; Lignans ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Renin ; blood ; Renin-Angiotensin System ; drug effects

OBJECTIVETo evaluate the effects of Tiangou Jiangya capsule on blood pressure and hemodynamics in anesthetized Beagle dogs.

METHODAnesthetized dogs were divided into five groups: Tiangou Jiangya capsule 3-dose groups as 1.6, 3.2, 6.4 g x kg(-1), positive control group was giving captopril, negative control was giving 0.5% CMC-Na, duodenal administration. The blood pressure and hemodynamic changes were observed.

RESULTThe systolic blood pressure of middle-dose Tiangou Jiangya capsule group was significantly reduced at 30 min after administration. The systolic blood pressure (SAP) and diastolic blood pressure (DAP) of high-dose group of Tiangou Jiangya capsule was significantly reduced at 15 min to 90 min after administration. High-dose Tiangou Jiangya capsule can also significantly reduce cardiac work (LVW) and total peripheral resistance (TPR). Tiangou Jiangya capsule had no significant effect on the other hemodynamic parameters and myocardial oxygen consumption.

CONCLUSIONTiangou Jiangya capsule has a significant effect on reducing blood pressure, which is related to the reducing total peripheral resistance and reducing cardiac work. The result can provide a reference to further clarify the Tiangou Jiangya capsule mechanism on reducing blood pressure.

Animals ; Antihypertensive Agents ; administration & dosage ; pharmacology ; therapeutic use ; Benzyl Alcohols ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Disease Models, Animal ; Dogs ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Flavonoids ; pharmacology ; therapeutic use ; Furans ; pharmacology ; therapeutic use ; Glucosides ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Hypertension ; drug therapy ; Lignans ; pharmacology ; therapeutic use ; Male ; Oxygen Consumption ; drug effects ; Vascular Resistance ; drug effects

OBJECTIVETo observe the effects of schizandrins on the learning and memory disorder in mice, and explore its mechanism.

METHODThe memory impairment model was established by using the pentobarbital sodium (20 mg x kg(-1)) intraperitoneally injected in mice. Schizandrins (0.5, 1.0, 2.0 g x kg(-1)) were administered through intragavage for consecutive 14 days. Morris Water Maze test was used to evaluate the impairment of learning and memory. The energy of superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT) of brain tissue were measured. And the positive expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65), caspase-3 in the hippocampus CA1 region were determined by immunohistochemical analysis. At the cellular level, 24 h after schizandrins (0.062 5, 0.125, 0.25 g x L(-1)) were pre-administered, the apoptosis model of PC12 cell was induced by H2O2, and activity of PC12 cell was detected by MTT colorimetric assay, the energy of NO in cell serum were measured. The expression of Bcl-2 was determined by the combination of immunocytochemical staining and image analysis software.

RESULTMorris Water Maze test showed that the model group mice took shorter searching time and distance on the previous flat area than those in the control group (P < 0.05), which could be prolonged after schizandrins treatment (P < 0.05, P < 0.01). Compared with the control group, the level of NO increased while the activity of SOD, CAT decreased in the model group (both P < 0.01). After treated with schizandrins, the level of NO significantly decreased (P < 0.01), while the activity of SOD increased (P < 0.01). Immunohistochemistry analysis showed that the protein expression of NF-kappaB p65, Caspase-3 in the hippocampal CA1 region significantly increased after modeling, while schizandrins (1.0 g x kg(-1)) can significantly inhibit the protein expression of NF-kappaB p65, Caspase-3 (P < 0.05, P < 0.01). Compared with the H2O2, model group, schizandrins (0.125, 0.25 g x L(-1)) can significantly increased PC12 cell activity and decreased the NO level (P < 0.05, P < 0.01), the expression of Bcl-2 in the schizandrins group (0.125, 0.25 g x L(-1)) was up-regulated.

CONCLUSIONSchizandrins could improve the learning-memory dysfunction induced by the sodium pentobarbital in mice, and its protective mechanism is related to the lowering oxidative damage and inhibiting the cell apoptosis through up-regulating the expression of Bcl-2.

Animals ; Apoptosis ; drug effects ; Behavior, Animal ; drug effects ; CA1 Region, Hippocampal ; metabolism ; Caspase 3 ; metabolism ; Cell Line ; Cyclooctanes ; pharmacology ; therapeutic use ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Learning Disorders ; chemically induced ; drug therapy ; metabolism ; Lignans ; pharmacology ; therapeutic use ; Male ; Memory Disorders ; chemically induced ; drug therapy ; metabolism ; Mice ; Nitric Oxide ; metabolism ; Oxidative Stress ; PC12 Cells ; Polycyclic Compounds ; pharmacology ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Superoxide Dismutase ; metabolism ; Transcription Factor RelA ; metabolism