OBJECTIVES: Patients with heart failure with reduced ejection fraction (HFrEF) often require diuretics during hospitalization to alleviate fluid retention and improve prognosis. However, the diuretic efficacy and renal impact of dapagliflozin in this population remain unclear. This study aims to investigate the effects of dapagliflozin on diuresis and renal function in hospitalized patients with HFrEF. METHODS: This retrospective analysis included clinical data from 200 hospitalized HFrEF patients treated at Xiangya Hospital of Central South University between January 2021 and September 2022. Patients were divided into 2 groups based on whether they received dapagliflozin: a standard treatment group (n=120) and a dapagliflozin treatment group (n=80). The following were compared between the 2 groups during hospitalization: The 24-hour average difference of liquid intake and output during the first 5 days, urine output, cumulative urine output, diuretic efficiency, estimated glomerular filtration rate (eGFR), N-terminal pro B-type natriuretic peptide (NT-proBNP), hospitalization costs, drug costs, and cost-effectiveness ratio (C/E). RESULTS: 1) Primary outcome: The 24-hour average difference of liquid intake and output during the first 5 days was significantly higher in the dapagliflozin treatment group than in the standard treatment group (P<0.05). 2) Secondary outcomes: The 24-hour average urine volume, cumulative urine volume and diuretic efficiency in the first 5 days of dapagliflozin treatment group were higher than those in the standard treatment group, and the differences were statistically significant (all P<0.05). Among patients with impaired renal function on admission [eGFR between 45 and 90 mL/(min·1.73 m²)], the change in eGFR after treatment was significantly smaller in the dapagliflozin treatment group (P<0.05). For patients with normal renal function on admission [eGFR >90 mL/(min·1.73 m²)], the difference in eGFR changes between 2 groups was not significant (P>0.05). NT-proBNP decreased more in the dapagliflozin treatment group than in the standard treatment group during hospitalization (P<0.05). 3) Other indicators: The length of hospital stay was longer in the dapagliflozin treatment group. However, discharge systolic blood pressure, drug costs, and hospitalization costs were all higher in the standard group, though differences were not statistically significant (all P>0.05). The C/E was more favorable in the dapagliflozin treatment group (425.36 vs. 476.67). CONCLUSIONS In hospitalized patients with chronic HFrEF, dapagliflozin treatment increased 24-hour average difference of liquid intake and output and total urine output, reduced NT-proBNP levels, and showed a milder decline in eGFR in those with pre-existing renal impairment. Discharge blood pressure, drug costs, and hospital stay were not significantly affected. While standard therapy may offer better short-term clinical benefits, dapagliflozin demonstrated a superior short-term cost-effectiveness profile.
Humans ; Benzhydryl Compounds/pharmacology* ; Glucosides/pharmacology* ; Retrospective Studies ; Male ; Female ; Heart Failure/physiopathology* ; Hospitalization ; Middle Aged ; Aged ; Glomerular Filtration Rate/drug effects* ; Diuretics/therapeutic use* ; Kidney/drug effects* ; Natriuretic Peptide, Brain/blood* ; Stroke Volume ; Peptide Fragments/blood* ; Diuresis/drug effects*

Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae＿ukn. The relative abundance of Desulfovibrio and Streptococcaceae＿ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.
Animals ; Croton ; chemistry ; Diuretics ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Microbiome ; drug effects ; Glycyrrhiza ; chemistry ; Intestines ; Mice ; Plant Roots ; chemistry ; Seeds ; chemistry

To search for the active diuretic fractions of Clematidis Armandii Caulis( CAC) and determine its main active chemical components by using liquid chromatography-mass spectrometry( LC-MS) and diuretic activity evaluation. CAC 75% ethanol extracts and extracts from different polar solvents were orally administered to saline-loaded rats at different doses. 6 h urinary volume,p H and contents of electrolyte Na+,K+and Cl-were measured. The chemical components of the active fractions were separated and identified by ultra performance liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry( UPLC-ESI-Q-TOF-MS/MS) method. As compared with the control group,the urine volume was increased by 44%( P< 0. 01) and 34%( P < 0. 05) in CAC75% ethanol extract 57. 74 and 28. 8 mg·kg-1 groups respectively; the Na+excretion was increased by 52%( P< 0. 01) and 45%( P<0. 05),respectively; while the Cl-excretion was increased by 101%( P<0. 01) and 85%( P<0. 05),respectively. The urine volume,Na+excretion and Cl-excretion were increased by 50%( P< 0. 01),58%( P< 0. 05),and 65%( P< 0. 05) respectively in petroleum ether extract 70. 98 mg·kg-1 group as compared with the control group. While for the n-butanol extract 194. 18 mg·kg-1 group,the urine volume,Na+and Cl-excretion were increased by 42%( P<0. 01),41%( P<0. 05) and 97%( P<0. 01),respectively. The diuretic activity of other fractions was not obvious. There was no statistical difference in K+excretion in all groups. The results of LC-MS analysis showed that six compounds,including two sterols,one chromogen and three fatty acids,were identified from petroleum ether extract.Fourteen compounds,including six triterpenoid saponins,six lignin glycosides,one sterol glycoside and one phenolic glycoside,were identified from the n-butanol extract. All the results suggested that the ethanol extract of CAC had remarkable diuretic activity and its main effective components included sterol,triterpenoid saponin and lignin glycosides.
Animals ; Ascomycota ; chemistry ; Diuretics ; pharmacology ; Materia Medica ; pharmacology ; Rats ; Solvents ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Poria cocos (Schw.) Wolf, an important medicinal and food fungus, is well known in East Asia. Due to growing market demand, long cultivation period, and consumption of pine trunk during cultivation, developing alternative methods for producing P. cocos and/or its active components is of interest. In the present study, the effects of different culture methods on biomass and accumulation of four triterpenoids were investigated. The ethanol extract of fermented mycelium (EFM) was orally administered to rats. Urine output and concentrations of electrolytes (Na, K, and Cl) were measured. Our results showed that mycelia grew better under continuous shaking culture condition (7.5 g DW·L), and higher triterpenoid levels were accumulated in two-stage culture (112 mg·L, 2.03%). The optimal starting time of static culture for triterpenoid yield was 4 d after shaking culture. Single administration of middle and high dose of EFM significantly increased urine output, Na and Cl excretion, and Na/K ratio. These results suggested that ethanol extract of cultured mycelia showed significant diuretic activity in rats and two-stage culture of P. cocos could be an alternative way to produce mycelia and triterpenoids.
Animals ; Biomass ; Diuretics ; pharmacology ; Mycelium ; chemistry ; growth & development ; Rats ; Triterpenes ; metabolism ; Wolfiporia ; chemistry ; growth & development

OBJECTIVEZanthoxylum heitzii is a medicinal plant widely used in central Africa for the treatment of many diseases, especially cardiovascular diseases and hypertension. The diuretic effects of crude stem bark extraction were determined and its safety in rats was evaluated.

METHODSThe diuretic effects of crude stem bark extraction of Z. heitzii 250 g ± 10 g) of both sexes. The crude stem bark extraction of Z. heitzii at the doses of 225, 300 and 375 mg/kg was administered to rats at 5 mL/kg body weight. Urine volume was determined 1, 2, 3, 4, 5, 6 and 24 h after administration of the extract. Kinetics of electrolyte elimination in response to a single oral administration dose of acute treatment was measured. The experiments were performed under the same conditions with two synthetic pharmacological diuretics considered as reference (furosemide and hydrochlorothiazide). Urinary and plasma concentrations of sodium and potassium ions were determined using flame photometry. Concentrations of creatinine, urea, glucose, albumin and electrolytes in the plasma and urine samples were evaluated using a two-way digital bidirectional spectrophotometer. The osmolarity of plasma and urine samples was measured by cytometry using an osmometer. Aldosterone was measured by radioimmunoassay.

RESULTSThe plant extract accelerated the elimination of overloaded fluid and increased urine volume and the excretion of Na+, K+ and Cl- 24 h after administration (P<0.05). The increase in elimination of Na+, K+, and Cl- induced by caused alkalinization of the urine, and showed a strong inhibitory effect on carbonic anhydrase and saluretic. These effects were mainly observed at the dose of 375 mg/kg. At the maximum diuretic response, urinary osmolarity decreased significantly (P<0.05) when compared to controls. The stability of aldosterone level, the absence of correlation with the plasma levels of Na+, and increased clearance of free water in the animals treated with indicated that increased diuresis and natriuresis were tubular in origin. No significant (P>0.05) changes were observed in the body temperature of the animals.

CONCLUSIONThe significant increase in urine volume 24 h after treatment followed a dose-response pattern. The excretion of Na+, K+ and Cl- caused a decrease in urine osmolarity. The stability of aldosterone, the absence of correlation with the plasma levels of sodium, and increased clearance of free water in animals treated with aqueous extract suggest that increased diuresis and moderate natriuresis elevation were of tubular origin.

Animals ; Carbonic Anhydrase Inhibitors ; pharmacology ; Diuretics ; pharmacology ; Electrolytes ; metabolism ; Female ; Furosemide ; pharmacology ; Hydrochlorothiazide ; pharmacology ; Kidney ; drug effects ; physiology ; Male ; Plant Bark ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Zanthoxylum ; chemistry

In recent years, the discovery and studies on aquaporin have made us have a more in-depth understanding about the physiological and pathological processes of water metabolism. Over years, however, there has been no quantitative study on the target sites of diuretic traditional Chinese medicines at the molecular level. In that case, aquaporin was found to been a new target molecule to explain the efficacy exertion of diuretic traditional Chinese medicines. By studying aquaporin, researchers can understand the implicit meaning of the diuretic effect of traditional Chinese medicines and conduct quantitative studies on the diuretic effect. So far, many scholars have conducted a series of studies in the traditional Chinese medicine field by using the findings on aquaporin and made certain advances. This article provides a summary about the efficacy exertion of diuretic traditional Chinese medicines through target molecule aquaporin.
Animals ; Aquaporins ; genetics ; metabolism ; Diuretics ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Water ; metabolism

OBJECTIVETo observe the effect of Gansui Banxia Tang plus-minus Gansui and Gancao anti-drug combination on hepatic and renal functions in malignant ascites rats to explore whether the efficacy or toxicity associated with the anti-drug combination.

METHODThe male wistar rats were randomly divided into a blank group, model group, furosemide group, Gansui Banxia Tang group, Gansui Banxia Tang removed Zhigancao group, Gansui Banxia Tang removed Cugansui group, Gansui Banxia Tang removed Zhigancao and Cugansui group. In addition to normal feeding, every morning except for the blank group and model group, the rest of the group was given drugs, the control group and the model group was given distilled water, the volume is 10 mL x kg(-1). Administered five days, all rats were fasted but except water for 24 hours to collect urine. Administered nine days all rats were fasted but except water for 12 hours, we need to weigh weight of rats. When we remove the ascites, we also need to weigh weight of rats. We use the weight before removing ascites minus weight after removing ascites to indirectly measure the amount of ascites. When we remove the ascites, we need to abdominal aortic blood, centrifuge testing renin, angiotensin II, aldosterone, antidiuretic hormone and other indicators.

RESULTThe effect of Gansui Banixa Tang on increasing the net weight, lowering abdominal circumference and body weight ratio, lowering renin, angiotensin, aldosterone, antidiuretic hormone is better than the other treatment group.

CONCLUSIONIn diuresis party, the group of Gansui Banxia Tang is better than the group of Gansui Banxia Tang remove Zhigancao or Cugansui or Zhigancao and Cugansui, renin-angiotensin-aldosterone system may play a diuretic effect of its one way.

Aldosterone ; metabolism ; Angiotensin II ; metabolism ; Animals ; Ascites ; drug therapy ; metabolism ; physiopathology ; Body Weight ; drug effects ; Diuretics ; pharmacology ; therapeutic use ; Dose-Response Relationship, Drug ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Wistar ; Renin-Angiotensin System ; drug effects

OBJECTIVETo investigate effects of the furosemide, antisterone and hydrochlorothiazide on expression of kidney aquaporin-2 (AQP(2)) gene and urine aquaporin-2 excretion in rats.

METHODSForty SD rats were randomized into 4 groups, namely the control group, furosemide group, antisterone group and hydrochlorothiazide group with corresponding treatment. Blood and urine samples were collected from the rats for measurement of serum Na(+), urine volume and urine osmolality during medication. Semi-quantitative RT-PCR was performed to measure kidney inner medullary AQP(2) and vasopressin V(2)-R mRNA. Western blotting was employed to detect kidney inner medullary AQP(2) protein expression. Urine AQP(2) concentration was measured by enzyme-linked immunosorbent assay (ELISA).

RESULTUrine volume and urinary AQP(2) excretion were both increased in rats treated with the 3 drugs as compared with that of the control group. However, urine osmolality was lower in furosemide group but higher inhydrochlorothiazide and antisterone groups than in the control group (P<0.05). The kidney inner medullary AQP(2) mRNA, V(2)-R mRNA and AQP(2) protein expression of furosemide group increased in comparison with that of the control group (Plt;0.05). In hydrochlorothiazide group, however, the above parameters were all decreased (Plt;0.05).

CONCLUSIONThe three classes of diuretics can all increase the excretion of the urinary AQP(2) but have different effects on the inner medullary AQP(2) mRNA and protein expression in normal rats. Hydrochlorothiazide reduces kidney AQP(2) mRNA and protein expression, while furosemide increased kidney AQP(2) gene expression.

Animals ; Aquaporin 2 ; genetics ; metabolism ; urine ; Blotting, Western ; Diuretics ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Furosemide ; pharmacology ; Gene Expression ; drug effects ; Hydrochlorothiazide ; pharmacology ; Kidney ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

The progress in the studies on chemical constituents, quality control and pharmacological activity of Akebia plants is summarized in recent years. These plants contain various chemical constituents and have broad bioactivities such as diuresis, anti-tumor and antibacteria and should be further investigated.
Animals ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Cell Line, Tumor ; drug effects ; Diuretics ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; toxicity ; Fruit ; chemistry ; Humans ; Magnoliopsida ; chemistry ; classification ; Oleanolic Acid ; analogs & derivatives ; isolation & purification ; pharmacology ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Quality Control ; Saponins ; chemistry ; isolation & purification ; pharmacology ; Triterpenes ; chemistry ; isolation & purification ; pharmacology

OBJECTIVETo observe the effects of conventional therapy combined with Kanlijian (KLJ) on exercise tolerance, quality of life and frequency of heart failure aggravation in patients with chronic heart failure (CHF).

METHODSSixty CHF patients differentiated as sufferring from the syndrome of Xin-Shen Yang deficiency were included in the study and randomly assigned at the ratio of 2:1 into the KLJ group (n = 39) and the control group (n = 21). All the patients were treated with conventional therapy of Western medicine, but to those in the KLJ group, KLJ was medicated additionally one dose daily with 24 wks as one therapeutic course. The efficacy on TCM syndrome and changes of scores on TCM syndrome were observed after treatment. The indexes, including 6-minute walking distance (6MWD), quality of life (QOL, accessed by LHFQ scoring), NYHA grade, hemodynamic indexes and reducing/withdrawal rate of diuretic and digoxin before and after treatment were recorded and compared. Also the frequency of re-admission due to aggravation of heart failure in one year's time were observed.

RESULTS(1) The efficacy on TCM syndrome, improvement on scores of TCM syndrome, therapeutic effects on 6MWD, QOL, and NYHA grade in the KLJ group were superior to those in the control group. (2) Hemodynamic indexes after treatment, left ventricular fractional shortening (LVFS) and E peak/A peak (E/A), between the two groups had no significant difference, while left ventricular ejection fraction (LVEF) was increased significantly in the KLJ group, but with no obvious change in the control group. (3) The reducing/withdrawal rate of diuretic and digoxin in the KLJ group was significantly higher than that in the control group. (4) The 1-year frequency of re-admission significantly decreased in the KLJ group.

CONCLUSIONThe adjuvant treatment of KLJ on the basis of Western conventional therapy can significantly improve CHF patients' exercise tolerance, quality of life and cardiac function, reduce the dosage of diuretic and digoxin needed, and decrease the re-admission frequency due to aggravation of heart failure.

Digoxin ; administration & dosage ; Diuretics ; administration & dosage ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Exercise Tolerance ; drug effects ; Female ; Heart Failure ; drug therapy ; physiopathology ; Humans ; Male ; Middle Aged ; Quality of Life ; Stroke Volume ; drug effects