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ORIGINAL ARTICLE
Year : 2021  |  Volume : 12  |  Issue : 4  |  Page : 384-388  

Antihypertensive activity of combination of anredera cordifolia (Ten.) V. Steenis and Sonchus arvensis L. leaves on Epinephrine Induced male Wistar Rat


1 Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Institute Teknologi Bandung, Bandung, Indonesia
2 Department of Pharmacology, Faculty of Pharmacy, University of Jenderal Achmad Yani, Cimahi, Indonesia
3 Department of Pharmaceutical Biology, School of Pharmacy, Institute Teknologi Bandung, Bandung, Indonesia
4 Department of Pharmacology, School of Pharmacy, Institute Teknologi Bandung, Bandung; Department of Pharmacology, Faculty of Pharmacy, University of Jenderal Achmad Yani, Cimahi, Indonesia

Date of Submission10-Apr-2021
Date of Decision07-Jul-2021
Date of Acceptance19-Jul-2021
Date of Web Publication20-Oct-2021

Correspondence Address:
Prof. Dr. Elin Yulinah Sukandar
Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Institute Teknologi Bandung, Bandung, Indonesia; Department of Pharmacology, Faculty of Pharmacy, University of Jenderal Achmad Yani, Cimahi
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/japtr.japtr_91_21

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  Abstract 


In Indonesia, hypertension is a condition that can lead to death through stroke and TB. Herbs have traditionally been used in Indonesia as an alternative medicine for lowering blood pressure. The leaves of Anredera cordifolia and Sonchus arvensis have been investigated for their antihypertensive potential. Based on the number of treatments, rats were randomized into groups. Each group consists of five rats. The test animals were grouping as follows: the positive control group (hypertension induction without treatment), A. cordifolia 50 mg/kg b.w. group, A. cordifolia 100 mg/kg b.w., S. arvensis 50 mg/kg b.w, S. arvensis 100 mg/kg b.w., A. cordifolia 25 mg/kg b.w + S. arvensis 25 mg/kg b.w, A. cordifolia 50 mg/kg b.w + S. arvensis 50 mg/kg b.w, and atenolol 4.5 mg/kg b.w. The rats were given 0.25 mg/kg b.w. of epinephrine intraperitoneally. The initial, after induction, and final blood pressure of the animals were measured using the CODA® noninvasive blood pressure device. All animal test groups at T60 showed a significant difference in systolic and diastolic blood pressures to initial blood pressure (T0), P < 0.05. The combination of A. cordifolia 50 mg/kg b.w and S. arvensis 50 mg/kg b.w showed the highest percent inhibition of systolic and diastolic blood pressure. The combination of A. cordifolia and S. arvensis 50–50 mg/kg b.w showed the best effect of lowering systolic and diastolic blood pressure on the pathway of inhibiting adrenergic receptors.

Keywords: Anredera cordifolia, Antihypertension, epinephrine, Sonchus arvensis


How to cite this article:
Suliska N, Suryani, Insanu M, Sukandar EY. Antihypertensive activity of combination of anredera cordifolia (Ten.) V. Steenis and Sonchus arvensis L. leaves on Epinephrine Induced male Wistar Rat. J Adv Pharm Technol Res 2021;12:384-8

How to cite this URL:
Suliska N, Suryani, Insanu M, Sukandar EY. Antihypertensive activity of combination of anredera cordifolia (Ten.) V. Steenis and Sonchus arvensis L. leaves on Epinephrine Induced male Wistar Rat. J Adv Pharm Technol Res [serial online] 2021 [cited 2021 Nov 29];12:384-8. Available from: https://www.japtr.org/text.asp?2021/12/4/384/328637




  Introduction Top


Hypertension is a disease that can cause death such as stroke and heart failure in Indonesia. Basic Health Research survey in 2018 reported that the prevalence of hypertension increased from 25.8% to 34.1%, and the highest majority occurred in South Kalimantan province with 44.1%.[1] If untreated, hypertension can lead to stroke, coronary heart disease, diabetes, renal failure, and blindness.[2]

Some Indonesian people have consumed certain herbs as an alternative or additional therapy to lower blood pressure, such as Anredera cordifolia and Sonchus arvensis. A. cordifolia and S. arvensis contain flavonoids, tannins, alkaloids, saponins, phenols, steroids/triterpenoids, tannins, quinones, and glycosides.[3] A. cordifolia leaves have antihypertensive activity. The mechanism is vasodilators through the nitric oxide (NO) pathway and adrenergic receptor antagonists. A. cordifolia also has an ACE inhibitory effect (moderate), a diuretic/saluretic effect, and calcium channel inhibition.[4] S. arvensis leaves are reported to have antihypertensive actions through the ACE inhibitor mechanism[5] and have a diuretic effect.[6]


  Materials and Methods Top


Plant materials

Every 3 months, leaves of A. cordifolia and S. arvensis were gathered from the Herbal Jaya Garden in Tawangmangu, Karanganyar, Central Java, and identified at the Herbarium Bandungense, School of Life Sciences and Technology, Institut Teknologi Bandung (No. 652/I1.CO2.2/PL/2018).

Chemical

The chemicals used were epinephrine (PT. Etika), propranolol (PT. Dexa Medica), sodium chloride physiological (PT. Whidatama Bhakti), sodium carboxymethyl cellulose, Dragendorff reagent, aqua dest, FeCl3, AlCl3, ethanol 70%, HCl, KOH, Mayer reagent, and analytical grades of weighing paper. The other chemical materials used for this research were obtained from authorized organizations.

Apparatuses

The apparatuses used were rotary evaporator, reflux apparatus, and CODA noninvasive blood pressure system (a tail-cuff Method, Kent Scientific Corporation), and high-performance liquid chromatography.

Standardization of extract of Anredera cordifolia and Sonchus arvensis

According to the Indonesian Herbal Pharmacopoeia, the determination of water-soluble content, ethanol-soluble content, and water content are all part of the standardization of A. cordifolia and S. arvensis extracts. The result of phytochemical screening shows alkaloids, flavonoids, saponins, steroids, triterpenoids, and tannins.[7]

Total flavonoid level

The total flavonoids level was calculated using Chang et al.[8] The calibration curve was made using vitexin and in various concentrations. About 0.5 mg of vitexin and luteolin were dissolved each in 80% ethanol and then diluted to 10, 20, 40, 60, 80, and 100 μg/mL. About 20 μL standard solutions were mixed with 60 μL of 95% ethanol, add 4 μL potassium acetate 1 M, 4 μL aluminum chloride 10%, and 112 μL of distilled water. The mix solution was incubated for 30 min at 25°C, the absorbance was assessed at 340, and 410 nm with a Tecan Microplate reader (Switzerland). Similarly, 20 μL of ethanol extracts (2500 ppm) was carried out with the same treatment as standard.

High-performance liquid chromatography

A. cordifolia and S. arvensis extracts were diluted with methanol. In the high-performance liquid chromatography system, 10 10 μL samples were injected. A column (5 m; 4.6150 mm, Agilent) with an ultraviolent-visible detector was used to separate the samples. Separation is performed using solvents A (0.05% trifluoroacetic acid) and solvent B (0.038% trifluoroacetic acid in 83% acetonitrile (v/v) with the following gradient: 0–5 min, 15% B in A, 5–10 min, 70% B in A, 10–15 min, and 70% B in A. 1 mL/min was the flow rate. Vitexin and luteolin were used as standard chemicals to measure the amount in the extract. The calibration curves were used to calculate each chemical. All samples were assayed three times.

Animal experimental design

The male Wistar rats weighed 200–250 g and were 8–10 weeks old. The animals were adapted for 7 days before the experiment was carried out and maintain under laboratory room temperature was 22°C ± 3°C, relative humidity 30%–70%, and lighting was set for 12 h bright and 12 h dark. Animals were provided with suitable laboratory animal food and drink are provided indefinitely. Animals were habituated to CODA noninvasive blood pressure system three times before being given treatment. Healthy and normal male Wistar rats have fasted for 4 h before the experiment while still drinking water. Rats were randomly assigned into eight groups that each consists of five rats.

The groups are (1) the positive control group (hypertension induction without treatment),(2) A. cordifolia 50 mg/kg b.w. group, (3) A. cordifolia 100 mg/kg b.w., (4) S. arvensis 50 mg/kg b.w, (5) S. arvensis 100 mg/kg b.w., (6) A. cordifolia 25 mg/kg b.w + S. arvensis 25 mg/kg b.w, and (7) A. cordifolia 50 mg/kg b.w + S. arvensis 50 mg/kg b.w, (8) atenolol 4.5 mg/kg b.w. Each test animal's systolic and diastole blood pressure was measured using noninvasive blood pressure apparatus and recorded as initial blood pressure. The test sample was then given to the rats orally, according to their group. The rats were given epinephrine 0.25 mg/kg b.w. intraperitoneally 30 min later. After 30 min of induction, the animals' blood pressure was remeasured using noninvasive blood pressure apparatus and recorded as final blood pressure. The Institutional Animal Ethics Committee has accepted all experimental animal procedures that comply with the Committee's recommendations for the Objective of Supervision and Control of Animal Experiments (No. 002b/SK/I1. B03/KP/2019).

The statistical analysis was done to compare systolic and diastolic blood pressure before and after induction using pair t-test and compare test groups against a positive control group at T60 using one-way ANOVA with lysergic acid diethylamide posthoc test. The data were stated to be statistically significant when P < 0.05.


  Results Top


Standardization and phytochemical characterization

A. cordifolia leaves' crude drug was extracted using ethanol 70%, whereas S. arvensis leaves were extracted using aqua dest. The distilled water content, water-soluble content, and ethanol-soluble content of A. cordifolia and S. arvensis leaves, as well as phytochemical screening extract, were used to determine the standardization of the extract. [Table 1] shows the data of extract standardization and phytochemical screening.
Table 1: Characteristics of extract of Anredera cordifolia and Sonchus arvensis leaves

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The results of extracts' characterization showed that extracts met the Indonesian Herbal Pharmacopoeia requirements, i.e. water content was not more than 10%.

Many medicinal plants contain bioactive flavonoids. The total flavonoids content of A. cordifolia and S. arvensis extracts was shown in [Table 2].
Table 2: Total flavonoid compounds of extract of Anredera cordifolia and Sonchus arvensis leaves

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High-performance liquid chromatography quantification of vitexin and luteolin

As described in [Figure 1], A. cordifolia was examined for the presence of flavonoid chemicals, and the presence of vitexin was revealed using integrated peak areas at 350 nm for quantification. In contrast, S. arvensis showed the presence of luteolin [Figure 2]. The concentration of the sample was measured from the regression equation of calibration curves. [Table 3] shows the quantification of these compounds.
Table 3: High performance liquid chromatography quantification of extract of Anredera cordifolia and Sonchus arvensis leaves

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Figure 1: High performance liquid chromatography fingerprints of Anredera cordifolia

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Figure 2: High performance liquid chromatography fingerprints of Sonchus arvensis

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Antihypertensive activity

In this study, epinephrine was used to induce hypertension in test animals. [Table 4] shows the systolic and diastolic blood pressures before and after administering epinephrine. All animal test groups (T60) showed a significant difference in systolic and diastolic blood pressures before induction (T0) P (<0.05) [Table 3].
Table 4: Systolic and diastolic blood pressure of rat before and after epinephrine induction

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A. cordifolia, S. arvensis and their combination test groups could significantly reduce systolic blood pressure than the positive control group (P < 0.05). Meanwhile, A. cordifolia 50 mg/kg b.w and combination 50–50 mg/kg b.w could significantly reduce diastolic blood pressure to the positive control group (P < 0.05). [Figure 3] shows that atenolol has the lowest systolic and diastolic blood pressures of all test groups.
Figure 3: Systolic and diastolic blood pressure elevation after epinephrine administration

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The positive control group showed the highest blood pressure increase, which proved that epinephrine induction successfully induced hypertension in test animals. The combination of A. cordifolia and S. arvensis 50–50 mg/kg b.w group showed the smallest elevated in systolic and diastolic blood pressure than all test groups.

[Table 5] shows the highest percent inhibition of systolic and diastolic blood pressure of the combination 100–100 mg/kg b.w group than to the A. cordifolia 100 mg/kg b.w, S. arvensis 100 mg/kg b.w, and combination 50–50 mg/kb b.w group.
Table 5: Per cent inhibition of blood pressure elevation

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  Discussion Top


Systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were used to classify hypertension. If the blood pressure was >150 mmHg/90 mmHg for age >60 years and >140 mmHg/90 mmHg for 60 years, pharmacological therapy for hypertension was started.[9]

In the circulation system, cardiac output and peripheral resistance will affect blood pressure. Stroke volume and heart rate play a role in the work of cardiac output. The adrenal medulla releases epinephrine and norepinephrine, enhancing cardiac output, heart rate, and contraction force.[10]

The alpha and beta-adrenergic receptors were the targets of epinephrine's pharmacological activities. Epinephrine causes vasoconstriction by activating the enzymes phospholipase-C and protein kinase-C. G-protein coupled binding to epinephrine induces phosphorylation and a rise in calcium influx from the endoplasmic reticulum (positive chronotropic effect).[11],[12],[13] The activity of atenolol was slow the heart rate and decrease myocardial contractility. Atenolol is one of the β adrenergic receptor antagonists. The short-term administration of atenolol will reduce cardiac output. Meanwhile, β-receptor antagonists will reduce the heart rate during exercise or stress.[14]

A. cordifolia and S. arvensis have been reported to lower blood pressure. A. cordifolia has antihypertensive action as the vasodilator. The mechanism is the NO pathway and adrenergic receptor antagonists. A. cordifolia also has a moderate ACE inhibitory effect, a diuretic/saluretic effect, and calcium channel inhibition.[4] S. arvensis leaves are reported to have an antihypertensive impact through the ACE inhibitor mechanism[5] and have a diuretic effect.[6] The combination of A. cordifolia and S. arvensis has been reported to lower systolic and diastolic blood pressure better than a single extract in the ACE inhibitor mechanism.[15]

In this study, the combination of A. cordifolia and S. arvensis 50–50 mg/kg b.w showed the best percent inhibition of systolic and diastolic blood pressure to a combination of A. cordifolia and S. arvensis at 25–25 mg/kg b.w or a single extract in the receptor adrenergic inhibition pathway.

A. cordifolia leaves contained secondary metabolites such as flavonoids, terpenoids, steroids, glycosides, and alkaloids. Apigenin, apigethrin, and vitexin were the secondary metabolites found in the A. cordifolia plant.[16] Vitexin and isovitexin have been reported to have adrenergic receptor (β-blocker) antagonistic effects.[17] S. arvensis leaves contained lactone, sesquiterpenes, glycerates, triterpenoid, steroids, luteolin, and luteolin 7-O glucoside.[18] Luteolin has been reported to lower blood pressure spontaneously in hypertensive rats.[19],[20]


  Conclusion Top


The combination of A. cordifolia and S. arvensis 50–50 mg/kg b.w showed the best effect in lowering systolic and diastolic blood pressure on the pathway of inhibiting adrenergic receptors.

Acknowledgment

This study was supported by the 2019 Innovative Research Productive İnvitations of Educational Fund Management İnstitutions (RISPRO Invitasi LPDP 2019), Indonesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Health Research and Development of Ministry of Health Republic of Indonesia. Riset Kesehatan Dasar 2018. Jakarta: Ministry of Health Republic of Indonesia; 2018. p. 152-163.  Back to cited text no. 1
    
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Garmana AN, Sukandar ES, Fidrianny I. Preliminary study of blood pressure lowering effect of Anredera cordifolia (Ten.) steenis on wistar rats. Int J Pharmacogn Phytochem Res 2016;8:300-4.  Back to cited text no. 4
    
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Suryani Y, Sukandar EY, Sutjiatmo AB, dan Vikasari SN. Angiotensin Converting Enzyme Inhibitor Activity of Ethanol Extract of Sonchus arvensis (Lin.) Leaves, Conference: The 6th International Conference; 2017. p. 124-8.  Back to cited text no. 5
    
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Muhtadi WN, Sutrisna EM, Suhendi A, Anggoro BK. Efek Diuresis dari Kombinasi Ektrak Salam (Syzygium polyanthum Wight.) dan Tempuyung (Sonchus arvensis L.) pada Mencit Hiperurisemia, The 4th University Research Coloquium; 2016. p. 22-7.  Back to cited text no. 6
    
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Directorate General of Pharmaceutical and Medical Devices. Farmakope Herbal Indonesia. 2nd ed. Jakarta: Ministry of Health Republic of Indonesia; 2017. p. 71-72, 480-481.  Back to cited text no. 7
    
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Chang CC, Yang MH, Wen HM, Chern JC. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal 2002;10:178-82.  Back to cited text no. 8
    
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James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20.  Back to cited text no. 9
    
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Wachter SB, Gilbert EM. Beta-adrenergic receptors, from their discovery and characterization through their manipulation to beneficial clinical application. Cardiology 2012;122:104-12.  Back to cited text no. 11
    
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Authentia S, Merlin LK, George AK, Kwesi PT, Richmond A, Yakubu J, et al. Hypotensive and antihypertensive properties and safety for use of Annona muricata and Persea americana and their combination products. Evid Based Complement Alternat Med 2020;2020:1-13.  Back to cited text no. 13
    
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Laurence LB, editor. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 12th ed. New York: The McGraw-Hill Companies Inc.; 2011. p. 312-4, 677, 765-6.  Back to cited text no. 14
    
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Sukandar EY, Garmana AN, Aidasari AU, Crystalia AA. Antihypertensive activity of ethanol extract combination of Anredera cordifolia (Ten.) v. Steenis and Sonchus arvensis L. leaves on angiotensin II- induced male wistar rat. J Res Pharm 2019;23:1090-7.  Back to cited text no. 15
    
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Sukandar EY, Ridwan A, Sukmawan YP. Vasodilatation effect of oleanolic acid and apigenin as metabolite compound of Anredera cordifolia (Ten) stennis on isolated rabbit aortic and frog heart. Int J Res Ayurveda Pharm 2016;7:82-4.  Back to cited text no. 16
    
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Vasant OK, Vijay BG, Virbhadrappa SR, Dilip NT, Ramahari MV, Laxamanrao BS. Antihypertensive and diuretic effects of the aqueous extract of Colocasia esculenta Linn. leaves in experimental paradigms. Iran J Pharm Res 2012;11:621-34.  Back to cited text no. 17
    
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Li XM, Yang PL. Research progress of Sonchus species. Int J Food Prop 2018;21:147-57.  Back to cited text no. 18
    
19.
Bramwell D, Dakshini KM. Luteoline 7-O glucoside and hydroxycoumarins in canary island Sonchus species. Phytochemistry 1971;10:2245-6.  Back to cited text no. 19
    
20.
Ichimura T, Yamanaka A, Ichiba T, Toyokawa T, Kamada Y, Tamamura T, et al. Antihypertensive effect of an extract of Passiflora edulis rind in spontaneously hypertensive rats. Biosci Biotechnol Biochem 2006;70:718-21.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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