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Cardenolides: Insights from chemical structure and pharmacological utility

El-Seedi HR, Khalifa SAM, Taher EA, Farag MA, Saeed A, Gamal M, et al.

Pharmacol Res, 2019 03;141:123-175.
PMID: 30579976 DOI: 10.1016/j.phrs.2018.12.015

Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na+/K+-ATPase enzyme, and they are regarded as an effective treatment for congestive heart failure (CHF), cardiac arrhythmia and atrial fibrillation. Furthermore, increasing evidence has indicated the potential cytotoxic effects of CGs against various types of cancer. In this review, we highlight some of the structural features of this class of natural products that are crucial for their efficacy, some methods of isolating these compounds from natural resources, and the structural elucidation tools that have been used. We also describe their physicochemical properties and several modern biotechnological approaches for preparing CGs that do not require plant sources.

Matched MeSH terms: Diuretics/pharmacology
Fulltext Diuretic activity of Boswellia serrata Roxb. oleo gum extract in albino rats

Asif M, Jabeen Q, Abdul-Majid AM, Atif M

Pak J Pharm Sci, 2014 Nov;27(6):1811-7.
PMID: 25362605

The aim of the study was to evaluate the effect of crude aqueous extract of Boswellia serrata Roxb. oleo gum on urinary electrolytes, pH and diuretic activity in normal albino rats. Moreover, acute toxicity of the gum extract was assessed using mice. Albino rats were divided into five groups. Control group received normal saline (10 mg/kg), reference group received furosemide (10 mg/kg) and test groups were given different doses of crude extract (10, 30 and 50 mg/kg) by intra-peritoneal route, respectively. The Graph Pad Prism was used for the statistical analysis and p < 0.05 was considered statistically significant. Significant diuretic, kaliuretic and natriuretic effects were observed in the treated groups in a dose dependent manner. Diuretic index showed good diuretic activity of the crude extract. Lipschitz values indicated that the crude extract, at the dose of 50 mg/kg, showed 44 % diuretic activity compared to the reference drug. No lethal effects were observed among albino mice even at the higher dose of 3000 mg/kg. It is concluded that aqueous extract of Boswellia serrata oleo gum, at the dose of 50 mg/kg showed significant effects on urinary volume and concentration of urinary electrolytes with no signs of toxicity.

Matched MeSH terms: Diuretics/pharmacology*
Studies on diuretic and hypouricemic effects of Orthosiphon stamineus methanol extracts in rats

Arafat OM, Tham SY, Sadikun A, Zhari I, Haughton PJ, Asmawi MZ

J Ethnopharmacol, 2008 Aug 13;118(3):354-60.
PMID: 18602231 DOI: 10.1016/j.jep.2008.04.015

AIM OF THE STUDY: Orthosiphon stamineus (Labiatae) is a traditional folk medicine widely used in Southeast Asia for the treatment of several kidney disorders, gout and as a diuretic. This study was conducted to examine the diuretic and hypouricemic effects of Orthosiphon stamineus leaf extracts.
MATERIALS AND METHODS: The diuretic effect of different methanol extracts was examined by treating different groups of Sprague-Dawley rats with single (2g/kg) oral doses of methanol and methanol:water (1:1) extracts. Hydrochlorothiazide (10mg/kg) was used as positive control in acute study. Methanol and methanol water (1:1) extracts at 0.5 g/kg were administered for a period of 7 consecutive days. Cumulative urine volume and electrolytes (Na+ and K+) concentrations at different time intervals were measured. On the other hand, hypouricemic activity of methanol:water extract (1:1) was experimented using different oral single doses (0.25, 0.5, 1 and 2g/kg). Allopurinol was used as positive control. Uric acid concentration in serum was analyzed by using RP-HPLC at 280 nm.
RESULTS: Sodium and potassium excretion increased significantly (p<0.05 and <0.01) in the first 8h of treatment with a single dose (2g/kg) of the extracts in a pattern comparable to that of the known diuretic hydrochlorothiazide. Meanwhile, repeated administration of 0.5 g/kg methanol:water (1:1) extract showed a significant increase in urine volume (from day 3 to day 7) (p<0.01) and electrolytes excretion (Na+ and K+) from day 2 to day 7 (p<0.05 and <0.01). On the other hand, 0.5, 1 and 2g/kg of methanol:water (1:1) extract and the standard allopurinol reduced the serum urate level in hyperuricemic rats at hour 6.
CONCLUSION: These results provided an evidence of the high tendency of methanol:water (1:1) extract of Orthosiphon stamineus towards diuretic and hypouricemic effects in rats.

Matched MeSH terms: Diuretics/pharmacology*
Outcomes of diuretic use in pre-dialysis CKD patients with moderate renal deterioration attending tertiary care referral center

Khan YH, Sarriff A, Adnan AS, Khan AH, Mallhi TH

Clin Exp Nephrol, 2017 Dec;21(6):1011-1023.
PMID: 28271257 DOI: 10.1007/s10157-017-1397-6

INTRODUCTION: Diuretic therapy has been the mainstay of treatment in chronic kidney disease (CKD) patients, primarily for hypertension and fluid overload. Apart from their beneficial effects, diuretic use is associated with adverse renal outcomes. The current study is aimed to determine the outcomes of diuretic therapy.
METHODOLOGY: A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by Bioimpedance analysis (BIA).
RESULTS: A total 312 patients (mean age 64.5 ± 6.43) were enrolled. Among 144 (46.1%) diuretic users, furosemide and hydrochlorothiazide (HCTZ) were prescribed in 69 (48%) and 39 (27%) patients, respectively, while 36 (25%) were prescribed with combination therapy (furosemide plus HCTZ). Changes in BP, fluid compartments, eGFR decline and progression to RRT were assessed over a follow-up period of 1 year. Maximum BP control was observed with combination therapy (-19.3 mmHg, p

Matched MeSH terms: Diuretics/pharmacology
Diuretic properties of Orthosiphon stamineus Benth

Adam Y, Somchit MN, Sulaiman MR, Nasaruddin AA, Zuraini A, Bustamam AA, et al.

J Ethnopharmacol, 2009 Jul 6;124(1):154-8.
PMID: 19375494 DOI: 10.1016/j.jep.2009.04.014

Orthosiphon stamineus has been used in traditional medicine for centuries especially to treat diseases of the urinary system.

Matched MeSH terms: Diuretics/pharmacology*
Fulltext Chronic Kidney Disease, Fluid Overload and Diuretics: A Complicated Triangle

Khan YH, Sarriff A, Adnan AS, Khan AH, Mallhi TH

PLoS One, 2016;11(7):e0159335.
PMID: 27442587 DOI: 10.1371/journal.pone.0159335

BACKGROUND: Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy.
METHODS: A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation.
RESULTS: Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users.
CONCLUSIONS: The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

Matched MeSH terms: Diuretics/pharmacology