The diuretic effect of ethyl acetate fractions of Artocarpus altilis, Artocarpus champeden, and Artocarpus heterophyllus leaves in normotensive Wistar rats

Fitrya; Annisa Amriani; Rennie Puspa Novita; Rachel Gabriella; Sherly Violeta Lestari; Adelya Agustina

doi:10.1016/j.jaim.2023.100746

. 2023 Jul 17;14(4):100746. doi: 10.1016/j.jaim.2023.100746

The diuretic effect of ethyl acetate fractions of Artocarpus altilis, Artocarpus champeden, and Artocarpus heterophyllus leaves in normotensive Wistar rats

Fitrya ^1,^∗, Annisa Amriani ¹, Rennie Puspa Novita ¹, Rachel Gabriella ¹, Sherly Violeta Lestari ¹, Adelya Agustina ¹

PMCID: PMC10372390 PMID: 37467570

Abstract

Background

Artocarpus altilis, A. Champeden, and Artocarpus heterophylus are popular species in Indonesia, and are commonly used as traditional medicine.

Objective

This study aims to evaluate the diuretic effects of the ethyl acetate fraction of these three species on normotensive Wistar rats.

Methods

The ethyl acetate fraction was prepared by a liquid–liquid extraction method. To evaluate diuretic effects, the sixty rats were divided into normal (distilled water), negative (4.5% NaCl), positive control (furosemide 5 mg/kg), and the testing groups. The testing groups were orally given the ethyl acetate fraction of A. altilis, Artocarpus champeden, and A. heterophylus at three dose levels of 25, 50, and 100 mg/kg. All animals were orally given 4.5% NaCl at a dose of 2 mL/200 g except the normal group; then the animals were given drugs according to group doses. Urine volume and electrolyte levels produced by the testing groups were compared to those of the control group. The concentration and ratio of ions were calculated to determine the natriuretic and carbonic anhydrase activities. Results: The ethyl acetate fractions of the three Artocarpus species at 100 mg/kg dose were more active than the standard furosemide (p < 0.05) to increase urinary excretion. Furthermore, at doses of 50 and 100 mg/kg, the fraction significantly increased the excretion of Na^+, K⁺, and Cl^- ions more than the standard (p < 0.05). The testing groups showed good natriuretic and carbonic anhydrase activities.

Conclusions

The ethyl acetate fraction of A. altilis, A. champeden, and A. heterophylus leaves performed good diuretic and natriuretic activities. Therefore, the fractions can be considered as potential natural diuretic medicines.

Keywords: Ethyl acetate fraction, Artocarpus altilis, Artocarpus champeden, Artocarpus heterophyllus, Diuretic, Natriuretic

1. Introduction

Hypertension is a major risk factor for various diseases such as congestive heart failure, nephrotic syndrome, cirrhosis, edema, and stroke. The first strategy to treat hypertension is to reduce arterial resistance and cardiac output using diuretics. Diuretics are substances able to increase the formation of urine. They reduce the reabsorption of electrolytes in the renal tubules, manifested by increasing the excretion of water and electrolytes for osmotic balance [1].

In 2019, about 59% of women between 55 and 62-year old and 49% of men aged 46 to 52 had hypertension [2]. According to Basic Health Research data, the prevalence of hypertension in Indonesia was 34.1% in 2018 [3]. Besides diuretics and beta-adrenergic blockers, drugs working on a renin-angiotensin-aldosterone action are commonly used for hypertension treatment. However, in most cases, diuretics are used as a first-line treatment or combined with other medicine classes [4]. Furosemide is the most common loop diuretic used in hypertension treatment. The use of synthetic drugs, such as furosemide, has side effects including hypokalemia, hypercalcemia, impaired-glucose tolerance, and diabetes [1]. Discovering alternative drugs that have a diuretic activity working in different ways and have fewer side effects is a challenge [4]. Alternative treatments using natural ingredients should be explored to reduce side effects. Currently, plants containing flavonoids have been extensively studied because of their ability to increase urine volume and electrolyte excretion [5].

One of the potential tropical plants to be examined is the genus Artocarpus (Moraceae). There are three popular species of this Artocarpus in Indonesia, namely jackfruit (Artocarpus heterophyllus), cempedak (Artocarpus champeden), and breadfruit (Artocarpus altilis). They are rich in flavonoids, including prenylated flavonoids, prenylated chromones, prenylated aurons, chalcones, geranyl flavonoids, geranyl dihydrochalcones, and flavanones. These compounds exhibit antioxidant, antiviral, antifungal, antiarthritis, antidiabetic, antibacterial, and anti-inflammatory activities [[6], [7], [8], [9]]. Artocarpus has traditionally been used in treating various diseases in Indonesia. A. altilis leaves are used to treat hypertension and diabetes, and to repair kidney damage and A. heterophyllus leaves are used to treat diabetes, hypertension, diarrhea, cough, burns, and asthma. It is thus important to investigate the potential efficacy of these plants as diuretic agents [4]. This study aims to evaluate the diuretic effects of the ethyl acetate fraction of A. altilis, A. champeden, and A. heterophyllus leaves on Wistar rats.

2. Material and methods

2.1. Chemicals and plant material

The chemicals used in this study were NaCl (Merck®), gallic acid (Merck®), aquadest, furosemide (Lasix®), tween 80 (Merck®), n-hexane (Brataco®), ethyl acetate (Brataco®), absolute ethanol (Merck®), and Folin-Ciocalteau reagent (Merck®). The fresh leaves of A. altilis, A. champeden, and A. heterophyllus were collected in January 2019 from the Ogan Ilir district of South Sumatra, Indonesia. The plant specimens were identified and stored at the Indonesian Institute of Sciences with registration No.: 165/IPH.06/HM/I/2019.

2.2. Preparation of ethyl acetate fraction

The ethyl acetate fraction was prepared using a liquid–liquid extraction method. The previous study used maceration in the extraction of crude ethanol extract [10]. Fifty grams of the ethanol extract was suspended in 200 mL of ethanolic water (1:1). Hereafter, the extract was fractionated with 200 mL of n-hexane in a separating funnel, and was shaken consecutively. It was then allowed to stand until it forms two layers. The n-hexane fraction in the lower layer was separated into Erlenmeyer. This process was repeated three times to produce a colorless n-hexane fraction. Furthermore, the ethanol residue was re-fractionated using ethyl acetate solvent in the same way as the n-hexane. The fractions were combined and concentrated using a rotary evaporator (Yamato® RE301) to obtain n-hexane, ethyl acetate, and ethanol fractions [11]. Finally, the ethyl acetate fraction was used to test diuretic activity.

2.3. Determination of total phenolic content

The total phenolic content was determined using a Pontis method (2014). A 10 mg ethyl acetate fraction was dissolved in 10 mL absolute ethanol. Afterward, 0.1 mL of each test sample was put into a test tube, which added 7.9 mL of distilled water and 1.5 mL of Folin Ciocalteau reagent. They were vortexed for 1 min. The vortexed solution was added Na₂CO₃ (concentration of 20%) until the volume reached 10 mL, and it was incubated for 2 h. The absorbance of the phenolic compound was spectrophotometrically measured at a wavelength of 744 nm. The total phenolic content was calculated using a curve of standard gallic acid at concentrations of 10 ppm, 20 ppm, 30 ppm, 40 ppm, 50 ppm, and 60 ppm, consecutively. Finally, the total phenolic content is expressed in the mg GAE/g [12].

2.4. Diuretic effect test

This study used healthy male Wistar rats aged 2–3 months old and 180 g–200 g weight. Test animal use has received approval from the Ahmad Dahlan University Research Ethics Committee (No. 0221111048). The sixty animals were divided into 12 groups, i.e., one normal group (distilled water), one positive control group (Furosemide 5 mg/kg), one negative control group (NaCl 4.5%), and 9 testing groups. The testing groups were orally given the ethyl acetate fraction of breadfruit leaves (ES), jackfruit leaves (EN), and Cempedak leaves (EC) at doses of 25, 50, and 100 mg/kg, respectively. Furthermore, the testing group was orally treated with the drug according to the dose groups after 3 h of 4.5% NaCl administration at a dose of 2 mL/200 g. All rats were individually then put in a metabolite cage. The urine volume of these rats was measured after 1 h, 2 h, 4 h, 6 h, and 24 h. The concentrations of Na⁺, K⁺, and Cl⁻ ions were analyzed using the Ion Selective Electrode method (EasyLyte®, USA) [13]. Finally, the diuretic action and activity (diuretic index) were calculated using Equations (1), (2)) [11,14].

Equation 1.

(1)

Equation 2.

(2)

Saluretic activities were obtained from the electrolyte ratio of the testing groups to the control group. While natriuretic and inhibitory activities of carbonic anhydrase (CAI) were respectively calculated by the ratio of Na⁺/K⁺ and Cl⁻/[K⁺+Na⁺] [11,15]. The research flow chart can be shown in Fig. 1.

Fig. 1 — The flow chart of experimental design.

2.5. Data analysis

This study utilized SPSS 16.0 program for data analysis. The normality of data distribution was assessed through Shapiro–Wilk analysis. If the data is normally distributed (p > 0.05) the test was continued with the one-way ANOVA test. In addition, differences among groups were analyzed by Duncan's Post hoc test (p < 0.05 was considered statistically significant). Data that were not normally distributed were analyzed with the Kruskal–Wallis test and then continued with the Mann–Whitney test.

3. Results

3.1. Total phenolic content of ethyl acetate fraction

The total phenolic contents of the ethyl acetate fractions of Artocarpus heterophylus (EN), A. altilis (ES), and A. champeden (EC) were 51 mg GAE/g, 59 mg GAE/g, and 99.67 mgGAE/g, respectively.

3.2. Diuretic activity of ethyl acetate extract

In Table 1, the ethyl acetate fraction increased urine excretion from the 1st to the 24th hour.

Table 1.

Ethylacetate fraction effects of A. altilis, A. champeden, and A. heterophylus on rat's urine volume.

Groups	Urine Volume (mL)
Groups	1st hr	2nd hr	4th hr	6th hr	24st hr	Diuretic action	Diuretic activity
Normal	0.25 ± 0.12^b^,^c	0.3 ± 0.21^c	0.47 ± 0.09^b^,^c	0.52 ± 0.09^b^,^c	0.9 ± 0.08^c	1.00	–
Negative	0.47 ± 0.09^a^,^c	0.5 ± 0.35^c	0.67 ± 0.20^a^,^c	0.87 0.35^a^,^c	1.05 ± 0.12^c	1.51	–
Positive	1.27 ± 0.09^a^,^b	1.15 ± 0.12^a^,^b	1.25 ± 0.12^a^,^b	1.45 0.12^a^,^b	1.7 ± 1.08^a^,^b	2.87	1.00
EN 25	0.62 ± 0.10^a^,^c	0.65 ± 0.12^a^,^c	0.85 ± 0.12^a^,^c	1.12 ± 0.09^a^,^b^,^c	1.35 ± 0.05^a^,^b^,^c	1.93	0.67
ES 25	0.6 ± 0.08^a^,^c	0.65 ± 0.12^a^,^c	0.9 ± 0.08^a^,^b^,^c	1.25 ± 0.05^a^,^b	1.32 ± 0.09^a^,^b^,^cc	2.00	0.70
EC 25	0.83 ± 0.10^a^,^b^,^c	0.85 ± 0.13^a^,^b^,^c	1.05 ± 0.13^a^,^b^,^c	0.95 ± 0.1^a3^a^,^c	1.5 ± 0.08^a^,^b	2.07	0.72
EN 50	0.97 ± 0.09^a^,^b^,^c	0.92 ± 0.09^a^,^b	1.12 ± 0.09^a^,^b	1.27 ± 0.09^a^,^b	1.5 ± 0.08^a^,^b	2.49	0.87
ES 50	0.92 ± 0.18^a^,^b^,^c	0.95 ± 0.12^a^,^b	1.17 ± 0.12^a^,^b	1.32 ± 0.09^a^,^b	1.47 ± 0.09^a^,^b^,^c	2.50	0.87
EC 50	1.00 ± 0.14^a^,^b^,^c	0.93 ± 0.14^a^,^b	1.68 ± 0.17^a^,^b^,^c	1.18 ± 0.13^a^,^b^,^c	1.98 ± 0.34^a^,^b^,^cc	2.56	0.89
EN 100	1.45 ± 0.12^a^,^b^,^c	1.55 ± 0.12^a^,^b^,^c	1.8 ± 0.08^a^,^b^,^c	2.15 ± 0.12^a^,^b^,^c	2.45 ± 0.12^a^,^b^,^c	4.09	1.42
ES 100	1.47 ± 0.09^a^,^b^,^c	1.5 ± 0.08^a^,^b^,^c	1.82 ± 0.09^a^,^b^,^c	2.22 ± 0.09^a^,^b^,^c	2.55 ± 0.12^a^,^b^,^c	4.15	1.44
EC 100	1.63 ± 0.10^a^,^b^,^c	1.5 ± 0.08^a^,^b^,^c	1.8 ± 0.08^a^,^b^,^c	2.25 ± 0.13^a^,^b^,^c	2.83 ± 0.10^a^,^b^,^c	4.22	1.47

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Significantly different from the normal group (p < 0.05).

Significantly different from the negative control group (p < 0.05).

Significantly different from the positive control group (p < 0.05).

The effect of the fractions of EN, ES, and EC at the dose of 25 mg is less than that of furosemide (p < 0.05) on increasing urinary excretion, but it is better than that of the negative control group (p < 0.05) (Table 1). Furthermore, at a dose of 50 mg, the EN, ES, and EC fractions affected an increase in urine volume that was insignificantly different from the standard furosemide (p > 0.05). However, at a dose of 100 mg, all fractions increased much more in urinary excretion than the standard furosemide (p < 0.05). Higher doses of the fraction have more increase in the diuretic activity. So, these fractions have a dose-dependent activity.

3.3. Analysis of Na⁺, Cl⁻ and K⁺ ion contents

The effect of the ethyl acetate fraction on increasing urine volume was accompanied by a rise in the excretion of Na⁺, K⁺, and Cl⁻ ions in the test group with a higher dose.

Sodium-ion excretion increases for all testing groups treated with all doses were much better than those for the normal, negative, and positive control groups (p < 0.05) (Table 2). While, the low-dose group did not show a different effect on the excretion of potassium ions from the negative group (p > 0.05), and the middle and high doses treatment groups showed different effects from others (p < 0.05). This difference could be an early indication that the extract increased the excretion of sodium ions more than that of potassium. Besides diuretics, the saluretic and natriuretics also have dose-dependent activity. The 50 mg and 100 mg testing groups also showed a better increase in Cl⁻ ion excretion than the positive-control group (p < 0.05).

Table 2.

Effect of ethyl acetate fraction of A. altilis, A. champeden, and A. heterophylus on ion excretion.

Group	Urine electrolyte (mmol/L ± SD)			Saluretic Index			Na⁺/K⁺	CAI
Group	Na⁺	K⁺	Cl^-	Na⁺	K⁺	Cl^-	Na⁺/K⁺	CAI
Normal	37.64 ± 0.67^b^,^c	21.18 ± 0.67^b^,^c	32.17 ± 0.45^b^,^c	–	–	–	1.78	0.55
Negative	104.18 ± 0.39^a^,^c	46.88 ± 1.05^a^,^c	113.48 ± 0.83^a^,^c	2.76	2.21	3.52	2.22	0.75
Positive	157.14 ± 1.39^a^,^b	57.67 ± 1.28^a^,^c	205.43 ± 1.63^a^,^b	4.17	2.72	6.38	2.72	0.96
EEN 25	190.66 ± 0.88^a^,^b^,^c	46.81 ± 0.85^a^,^c	151.08 ± 0.68^a^,^b^,^c	5.06	2.21	4.69	4.07	0.64
EES 25	192.36 ± 0.98^a^,^b^,^c	46.97 ± 0.90^a^,^c	151.17 ± 0.77^a^,^b^,^c	5.11	2.21	4.69	4.10	0.63
EEC 25	197.69 ± 0.95^a^,^b^,^c	47.67 ± 1.28^a^,^c	152.83 ± 1.91^a^,^b^,^c	5.25	2.25	4.75	4.15	0.62
EEN 50	296.42 ± 1.26^a^,^b^,^c	66.99 ± 0.57^a^,^b^,^c	252.93 ± 0.81^a^,^b^,^c	7.87	3.16	7.86	4.42	0.70
EES 50	298.33 ± 0.77^a^,^b^,^c	67.28 ± 0.52^a^,^b^,^c	253.35 ± 0.61^a^,^b^,^c	7.92	3.17	7.87	4.43	0.69
EEC 50	303.87 ± 3.21^a^,^b^,^c	67.49 ± 1.97^a^,^b^,^c	257.99 ± 1.07^a^,^b^,^c	8.07	3.16	8.01	4.50	0.69
EEN 100	324.01 ± 0.55^a^,^b^,^c	72.75 ± 0.80^a^,^b^,^c	306.21 ± 0.88^a^,^b^,^c	8.6	3.43	9.51	4.45	0.77
EES 100	326.99 ± 0.81^a^,^b^,^c	73.19 ± 0.25^a^,^b^,^c	307.29 ± 0.92^a^,^b^,^c	8.68	3.45	9.55	4.47	0.77
EEC 100	333.83 ± 2.63^a^,^b^,^c	73.19 ± 1.28^a^,^b^,^c	313.95 ± 2.60^a^,^b^,^c	8.86	3.45	9.75	4.56	0.77

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Significantly different from the normal group (p < 0.05).

Significantly different from the negative control group (p < 0.05).

Significantly different from the positive control group (p < 0.05).

4. Discussion

The diuretic drug is the first line in treating hypertension and symptomatic heart failure. As the importance of the therapeutic effect of diuretics, exploration of its agents from plants becomes popular. Phenolic-rich plants exhibit pharmacological activity in a kidney area of using their diuretic, vasorelaxant, and antioxidant potential [4,16]. We are interested in the exploration of the diuretic potential of several Artocarpus species due to their high flavonoid content. The ethyl acetate fraction was selected because most of the flavonoid compound from the Artocarpus plants is free flavonoids [[17], [18], [19]]; hence, it is more soluble in ethyl acetate.

Administration of 4.5% NaCl to testing animals before treatment aims to balance the water and salt load and to increase the urination rate in rats [20,21]. The excessive ingestion of the NaCl increased the sodium concentration in the extracellular fluid, thus enlarging the extracellular fluid volume. In turn, blood volume was increased. Furthermore, the heart needs harder pumping to push much blood through the vessel, causing hypertension [22]. Table 1 shows that the effect of the ethyl acetate fraction on increasing urine volume depends on doses and the interval time. The testing group indicates a significant increase in urine volume for 4 h. For an hour and 2 h, there was a different increase in urine volume for the testing group compared to the normal and negative groups, but this difference was insignificant compared to that for the standard furosemide group. The testing group has a similar pattern of urine volume increase as furosemide. The onset time of furosemide is 1 h after administration and a peak of the activity after 3 h [23]. A delay of the volume increase in the test group occurring in 4 h implies that its diuretic activity was mediated through secondary metabolites [15].

The diuretic action value indicates the diuretic potential of a substance [24]. The fraction has the lowest diuretic action of 1.93 produced by EN 25 mg/kg, and the highest value of 4.22 produced by EC100 mg/kg. In addition, the ethyl acetate fractions of EN, ES, and EC have diuretic action values greater than 1.5 in all doses for the testing group. A substance has several levels of diuretic potency, i.e., good, moderate, mild, and nil, when their values are >1.50, 1.00–1.50, 0.72–1.00, and <0.72, respectively [23,24]. Based on the levels, the ethyl acetate fractions of EN, ES, and EC have good diuretic potency at all treatment doses. However, the diuretic action (>4) of the 100 mg/kg dose group is better than that of furosemide, and its potency percentage is more than 100%. A substance potency is considered good when the potential diuretic value of the treatment group is greater than the positive control [25]. A diuretic activity value was calculated to compare the diuretic effect of the test group to that of the standard furosemide [24]. Furthermore, the testing group at a 100 mg/kg dose has diuretic activity values better than the standard furosemide. It indicates that the ethyl acetate fractions of EN, ES, and EC at a dose of 100 mg/kg are more potential than standard furosemide in increased urinary excretion.

Electrolyte abnormalities, such as sodium, potassium, and chloride retention, play an essential role in the pathogenesis of hypertension, heart failure, or renal dysfunction [23,26]. Therefore, in these disease treatments, electrolytes excretion is as important as water excretion [15]. The excretion value of sodium and potassium ions is used as an indicator of the saluretic activity [24].

Urinary excretion increase of electrolytes (Na⁺, K⁺, and Cl⁻) is important to indicate the diuretic activity of EN, ES, and EC ethyl acetate fractions. The saluretic index of the test substance also depends on doses. This characteristic of loop diuretics acts by inhibiting the Na⁺, K⁺, and Cl⁻ symporter in the loop of Henle [27]. The ethyl acetate fraction of EN, ES, and EC at moderate and high doses increased the excretion of Na⁺, K⁺, and Cl⁻ more than furosemide. In addition, the Na⁺/K⁺ ratio is a biomarker showing a natriuretic activity and predicting a diuretic mechanism of a substance [23,28]. The Na⁺/K⁺ ratio is related to an aldosterone secretory index or mineralocorticoid receptor antagonism. The natriuretic effect is beneficial when the Na⁺/K⁺ ratio is more than 2.0 [23]. Furthermore, this value also indicates that a substance's ability to excrete Na⁺ is greater than K⁺. This is a characteristic of a good diuretic agent [15]. The Na⁺/K⁺ ratio shown in Table 2 indicates that the ethyl acetate fractions of EN, ES, and EC are beneficial diuretic agents. However, they cannot be considered as potassium-sparing diuretics because they do not produce a Na⁺/K⁺ ratio greater than 10 [15,24]. Overall, the natriuretic effects of EN, ES, and EC ethyl acetate fractions were more significant than those of the kaluretic. The fractions at the dose of 100 mg can increase higher K⁺ excretion (126%) than furosemide. This value is smaller than the Na⁺ excretion increase (208%). Thus, this shows that the ethyl acetate fraction of Artocarpus species is a good diuretic agent without much loss of K⁺.

The ratio of Cl⁻/(Na⁺ + K⁺) is an indicator of carbonate anhydrase inhibitory (CAI) activity [24]. This enzyme plays a role in maintaining acid-base balance, reabsorbing bicarbonate, and excreting NH4⁺ kidneys [29]. A substance is considered to have strong carbonic anhydrase activity when the CAI value is less than 0.8 [11]. The fraction of EN, ES, and EC shows the CAI values, indicating a strong carbonic anhydrase inhibitory effect from plant flavonoid compounds [23].

Thiago Buno (2016) mentioned that plants rich in polyphenols, especially free flavonoids and their glycosylated derivatives, can provide diuretic and antihypertensive effects [30]. A. altilis, A. champeden, and A. heterophyllus were reported to be rich in flavonoid compounds [[31], [32], [33]]. Flavonoid is one of the natural antagonist ligands for adenosine A1 receptors, while receptor antagonist activity is known to be related to diuretic activity. The A1 adenosine receptor is responsible for the reabsorption of filtered sodium and water in the proximal tubules. A1 adenosine receptor antagonists induce a diuretic without reducing the glomerular filtration rate through vasodilatation of the renal afferent arteries, stimulating renal blood flow and causing natriuresis and diuresis [15].

Diuretic activity is often associated with antioxidant activity, ACE inhibition, endothelial NO release, and PGE2 regulation. Furthermore, oxidative stress is a main factor affecting an increase in renal medulla ROS and endothelial NO reduction, which predisposes to cardiovascular diseases, including hypertension and heart failure. NO causes natriuresis and diuresis and inhibits fluid reabsorption in the renal tubules [34]. Flavonoid and phenolic compounds, with their antioxidant activity, work to increase endothelial NO levels. The levels induce a diuretic and assist cardioprotective effects [16,35]. Flavonoid compounds and extracts of A. altilis were proved having antioxidant activity through in vitro and in vivo tests [8,36,37], as well as with A. heterophylus [38] and A. champeden [39].

The diuretic effect is often associated with an ACE inhibitory activity. Polyphenol compounds release endothelial NO through ACE inhibitory mechanisms [16,30]. Sidesha (2011) reported that the ethyl acetate extract of A. altilis leaves is a potential ACE inhibitor with an IC₅₀ value of 85.44 ± 0.85 g/mL [40]. The ethyl acetate extract of A. heterophyllus leaves also showed a better ACE inhibitory effect (48%) than the methanol extract (43%) [41]. This scientific evidence supports the results of this study showing the diuretic activity of the ethyl acetate fractions.

Another mechanism of reported diuretic effect is through the formation of prostaglandin E2 (PGE₂), which regulates kidney function in the distal nephron by increasing renal blood flow and reducing vascular tone [42]. The normal renal blood flow and function during physiologic stress highly depends on endogenous prostaglandin synthesis. PGE₂ can have opposing effects on several processes, mediated by different E-prostanoid (EP) receptors. Depending on the setting, its effect could either increase or decrease vascular tone [43]. Thus, the ethyl acetate fractions is indicated able to increase PGE₂ excretion in the nephron.

Another study revealed that aqueous extract of A. altilis has antihypertensive activity through antagonism of Ca²⁺ channels [32] and has protective functions in myocardial injury [44]. Meanwhile, the ethyl acetate extract of A. heterophyllus leaves has a heart-protective effect on cardiac arrhythmias [45]. These results support previous study using A. altilis, A. champeden, and A. heterophyllus as diuretic agents in the treatment of hypertension. A. champeden has the best diuretic activity compared to the three tested species of Artocarpus because it has higher total phenolic content than A. altilis and A. heterophyllus.

5. Conclusion

This study firmly suggests that the ethyl acetate fractions of A. altilis, A. champeden, and A. heterophyllus at a dose of 100 mg/kg have good diuretic, natriuretic and carbonic anhydrase effects. This diuretic activity has been tested using normotensive animals. Thus they are suitable to be natural medicines for diuretic and antihypertensive drugs. Further studies should be conducted to examine the effects of the diuretic activity on hypertension animal models and the protective effects of the extract on the kidneys.

Authors contribution

Fitrya: Concept, design, literature sstudy, data acquisition, statistical analysis and manuscript writing. Annisa Amriani and Rennie Puspa Novita: literature study, experimental studies, data analysis and manuscript editing. Rachel Gabriella Sherly Violeta Lestari Adelya Agustina: Literature studies, experimental analysis data acquisition and statistical analysis.

Declaration of competing interest

None.

Acknowledgement

The authors are grateful to the DIPA Budget of the Sriwijaya University Public Service Agency for the 2022 Fiscal Year No. 023.17.2.677515/2022 dated 13 November 2021, following the Dean's Decree 0245/UN.9FMIPA/TU.SK/2022 dated 18 May 2022 for funding this research.

Footnotes

Peer review under responsibility of Transdisciplinary University, Bangalore.

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The diuretic effect of ethyl acetate fractions of Artocarpus altilis, Artocarpus champeden, and Artocarpus heterophyllus leaves in normotensive Wistar rats

Fitrya

Annisa Amriani

Rennie Puspa Novita

Rachel Gabriella

Sherly Violeta Lestari

Adelya Agustina

Abstract

Background

Objective

Methods

Conclusions

1. Introduction

2. Material and methods

2.1. Chemicals and plant material

2.2. Preparation of ethyl acetate fraction

2.3. Determination of total phenolic content

2.4. Diuretic effect test

Fig. 1.

2.5. Data analysis

3. Results

3.1. Total phenolic content of ethyl acetate fraction

3.2. Diuretic activity of ethyl acetate extract

Table 1.

3.3. Analysis of Na⁺, Cl⁻ and K⁺ ion contents

Table 2.

4. Discussion

5. Conclusion

Authors contribution

Declaration of competing interest

Acknowledgement

Footnotes

References

ACTIONS

PERMALINK

RESOURCES

Cite

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PERMALINK

The diuretic effect of ethyl acetate fractions of Artocarpus altilis, Artocarpus champeden, and Artocarpus heterophyllus leaves in normotensive Wistar rats

Fitrya

Annisa Amriani

Rennie Puspa Novita

Rachel Gabriella

Sherly Violeta Lestari

Adelya Agustina

Abstract

Background

Objective

Methods

Conclusions

1. Introduction

2. Material and methods

2.1. Chemicals and plant material

2.2. Preparation of ethyl acetate fraction

2.3. Determination of total phenolic content

2.4. Diuretic effect test

Fig. 1.

2.5. Data analysis

3. Results

3.1. Total phenolic content of ethyl acetate fraction

3.2. Diuretic activity of ethyl acetate extract

Table 1.

3.3. Analysis of Na+, Cl− and K+ ion contents

Table 2.

4. Discussion

5. Conclusion

Authors contribution

Declaration of competing interest

Acknowledgement

Footnotes

References

ACTIONS

PERMALINK

RESOURCES

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3.3. Analysis of Na⁺, Cl⁻ and K⁺ ion contents