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Blood pressure lowering effect of Ficus deltoidea var kunstleri in spontaneously hypertensive rats: possible involvement of renin–angiotensin–aldosterone system, endothelial function and anti-oxidant system

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Abstract

This study investigated the effects of a standardised ethanol and water extract of Ficus deltoidea var. Kunstleri (FDK) on blood pressure, renin–angiotensin–aldosterone system (RAAS), endothelial function and antioxidant system in spontaneously hypertensive rats (SHR). Seven groups of male SHR were administered orally in volumes of 0.5 mL of either FDK at doses of 500, 800, 1000 and 1300 mg kg− 1, or captopril at 50 mg kg− 1 or losartan at 10 mg kg− 1 body weight once daily for 4 weeks or 0.5 mL distilled water. Body weight, systolic blood pressures (SBP) and heart rate (HR) were measured every week. 24-hour urine samples were collected at weeks 0 and 4 for electrolyte analysis. At week 4, sera from rats in the control and 1000 mg kg− 1 of FDK treated groups were analyzed for electrolytes and components of RAAS, endothelial function and anti-oxidant capacity. SBP at week 4 was significantly lower in all treatment groups, including captopril and losartan, when compared to that of the controls. Compared to the controls, ACE activity and concentrations of angiotensin I, angiotensin II and aldosterone were lower whereas concentrations of angiotensinogen and angiotensin converting enzyme 2 were higher in FDK treated rats. Concentration of eNOS and total anti-oxidant capacity were higher in FDK treated rats. Urine calcium excretion was higher in FDK treated rats. In conclusion, it appears that ethanol and water extract of FDK decreases blood pressure in SHR, which might involve mechanisms that include RAAS, anti-oxidant and endothelial system.

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References

  1. Fuchs FD, Fuchs SC, Moreira LB, Gus M (2012) Proof of concept in cardiovascular risk: the paradoxical findings in blood pressure and lipid abnormalities. Vasc Health Risk Manage 8:437–442

    Article  Google Scholar 

  2. Shimbo D, Muntner P, Mann D, Barr RG, Tang W, Post W, Lima J, Burker G, Bluemke D, Shea S (2011) Association of left ventricular hypertrophy with incident hypertension: the multi-ethnic study of atherosclerosis. Am J Epidemiol 173(8):898–905

    Article  PubMed  PubMed Central  Google Scholar 

  3. World Health Organization (2013), World Health Day, A Global Brief on Hypertension, 1–40

  4. Bener A, Al-Ansari A, Afifi M, Krishna V, P (2007) Erectile dysfunction among hypertensive men in a rapidly developing country. Indian J Urol 23(2):109–113

    Article  PubMed  PubMed Central  Google Scholar 

  5. De Carvalho MV, Siqueira LB, Sousa ALL, Jardim PCV (2013) The influence of hypertension on quality of life. Arq Bras De Cardiol 100(2):164–174

    Article  Google Scholar 

  6. World Health Organization (WHO) (2016) Global Health Observatory (GHO) data, Non-communicable disease. http://www.who.int/gho/ncd/en/

  7. Abdul-Razak S, Daher AM, Ramli AS, Ariffin F, Mazapuspavina MY, Ambigga KS, Miskan M, Abdul-Hamid H, Mat-Nasir N, Nor-Ashikin MNK, Ng KK, Nawawi H, Yusoff K, REDISCOVER investigators (2016) Prevalence, awareness, treatment, control and socio demographic determinants of hypertension in Malaysian adults. BMC Public Health 16(1):1–10

    Article  Google Scholar 

  8. Ministry of Health (MOH), Putrajaya M (2013) Health Technology Assessment Section, Medical Development Division Ministry of Health, Malaysia. Clinical Practice Guideline (CPG) on Management of Hypertension

  9. Naing C, Yeoh PN, Wai VN, Win NN, Kuan LP, Aung K (2016) Hypertension in Malaysia. Medicine 95(2):2417

    Article  Google Scholar 

  10. Rende P, Paletta L, Gallelli G, Raffaele G, Natale V, Brissa N, Costa C, Gratteri S, Giofre C, Gallelli L (2013) Retrospective evaluation of adverse drug reactions induced by antihypertensive treatment. J Pharmacol Pharmacother 4(Suppl1):47–50

    Google Scholar 

  11. Shrestha RK, Khan GM, Thapa P, Koju R (2012) Study of the side effects profile of different antihypertensive drugs among the hypertensive patient. Nepalese Heart J 9(1):5–9

    Google Scholar 

  12. Umair Khan M, Shah S, Hameed T (2014) Barriers to and determinants of medication adherence among hypertensive patients attended National Health Service Hospital, Sunderland. J Pharm Bioallied Sci 6(2):104–108

    Article  Google Scholar 

  13. Lobay D (n.d.) (2015) Rauwolfia in the treatment of hypertension. Integr Med 14(3):40–46

    Google Scholar 

  14. Yao Y, Wang W, Li M, Ren H, Chen C, Wang J, Wang WE, Yang J, Zeng C (2016) Curcumin exerts its anti-hypertensive effect by down-regulating the AT1 receptor in vascular smooth muscle cells. Sci Rep 6:25579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jawaid T, Kamal M, Kumar S (2017) Antihypertensive effect of the alcoholic extract of seeds of Phaseoulus Vulgaris Linn. (Fabaceae) on high salt diet induced hypertension in male rats. Int J Pharm Sci Res 8(7):3092–3097

    CAS  Google Scholar 

  16. Jung IH, Kim SE, Lee Y-Ge, Kim DH, Kim H, Kim G-S, Baek N-I, Lee DY (2018) Antihypertensive effect of ethanolic extract from Acanthopanax sessiliflorus Fruits and quality control of active compounds. Oxidative Med Cell Longevity 5158243:14

    Google Scholar 

  17. Cunha GH, Fechine FV, Frota Bezerra FA, Moraes M,O, Silveira E, Canuto K, Moraes E (2016) Comparative study of the antihypertensive effects of hexane, chloroform and methanol fractions of essential oil of Alpinia zerumbet in rats Wistar. Rev Bras PI Med Campinas 18(1):113–124

    Article  Google Scholar 

  18. Al-Qattan KK, Thomson M, Al-Mutawa’a S, Al-Hajeri D, Drobiova H, Ali M (2006) Nitric oxide mediates the blood-pressure lowering effect of garlic in the rat two-kidney, one-clip model of hypertension. J Nutr 136(3):774S–776S

    Article  CAS  PubMed  Google Scholar 

  19. Mohtar M, Mahmood N, N.Z., and Haron N (2016) Herba emas negara. Forest Research Institute Malaysia (FRIM), Malaysia

    Google Scholar 

  20. Ong HC, Zuki RM, Milow P (2011) Traditional knowledge of medicinal plants among the Malay villagers in Kampung Mak Kemas, Terengganu, Malaysia. Ethno-Med 5(3):175–185

    Article  Google Scholar 

  21. Wan Embong WH (2006) Healing herbs of Malaysia. Federal Land Development Authority (FELDA), Malaysia

    Google Scholar 

  22. Ong HC, Lina E, Milow P (2012) Traditional knowledge and usage of medicinal plants among the Semai Orang Asli at Kampung Batu 16, Tapah, Perak, Malaysia Hean. Ethno Med 6(3):207–211

    Article  Google Scholar 

  23. Misbah H, Aziz AA, Aminudin N (2013) Antidiabetic and antioxidant properties of Ficus deltoidea fruit extracts and fractions. BMC Complement Altern Med 13(1):118

    Article  PubMed  PubMed Central  Google Scholar 

  24. Farsi E, Ahmad M, Hor SY, Ahamed MBK, Yam MF (2014) Standardized extract of Ficus deltoidea stimulates insulin secretion and blocks hepatic glucose production by regulating the expression of glucose-metabolic genes in streptozitocin-induced diabetic rats. BMC Complement Altern Med 14(1):1–13

    Article  Google Scholar 

  25. Abdullah Z, Hussain K, Zhari I, Rasadah MA, Mazura P, Jamaludin F, Sahdan R (2009) Evaluation of extracts of leaf of three Ficus deltoidea varieties for antioxidant activities and secondary metabolites. Phcog Res 1(4):216–223

    Google Scholar 

  26. Abdullah Z, Khalid H, Zhari I, Rasadah MA (2009) Anti-inflammatory activity of standardised extracts of leaves of three varieties of Ficus deltoidea. Int J Pharm Clin Res 1(3):100–105

    Google Scholar 

  27. Shafaei A, Syima MN, Nassar ZD, Aisha AFA, Abdul Majid AMS, Ismail Z (2014) Antiangiogenic effect of Ficus deltoidea jack standardised leaf extracts. Trop J Pharm Res 13(5):761–768

    Article  CAS  Google Scholar 

  28. Ahmad VN, Mohd Amin I (2017) Anti-oral ulcer activity of Ficus deltoidea leaves extract on animal model. Pertanika J Sci Technol 25(S):41–52

    Google Scholar 

  29. Che A, Tantowi NA, Lau SF, Mohamed S (2018) Calcified Tissue International, Ficus deltoidea prevented bone loss in preclinical osteoporosis/osteoarthritis model by suppressing inflammation. Calcif Tissue Int 103(4), 388–399

    Article  CAS  Google Scholar 

  30. Abdullah NAH, Karsani SA, Aminudin N (2008) Effects of Ficus Deltoidea Extract on the Serum Protein Profile of Simultaneously Hypertensive Rats (SHR). Proceedings of The Joint 2nd Pacific Rim International Conference on Protein Science and 4th Asian-Oceania Human Proteome Organization,Cairns-Australia, 22–26

  31. Adam Z, Hamid M, Ismail A, Khamis S (2007) Effect of Ficus deltoidea aqueous extract on blood glucose level in normal and mild diabetic rats. Jurnal Sains Kesihatan Malaysia 5(2):9–16

    Google Scholar 

  32. Samsulrizal N, Awang Z, Mohd Najib MLH, Idzham M, Zarin A (2011) Effect of Ficus deltoidea leaves extracts on sperm quality, LDH-C 4 activity and testosterone level in alloxan-induced male diabetic rats. IEEE Colloquium Humanit Sci Eng (1):888–891 13)

  33. Razali N, Manshor N,M, Dewa A, Asmawi MZ, Ismail Z, Hassan Z (2013) Vascular reactivity on aortic ring of spontaneously hypertensive rats with methanolic and water extracts of Ficus deltoidea. Int J Vasc Med 3(2):93–102

    Google Scholar 

  34. Miguel M, Gomez-Ruiz JA, Recio I, Aleixandre A (2010) Changes in arterial blood pressure after single oral administration of milk casein-derived peptides in spontaneously hypertensive rats. Mol Nutr Food Res 54(10):1422–1427

    Article  CAS  PubMed  Google Scholar 

  35. Farsi E, Shafaei A, Hor SY, Ahamed MBK, Yam MF, Asmawi MZ, Ismail Z (2013) Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves. Clinics 68(6):865–875

    Article  PubMed  PubMed Central  Google Scholar 

  36. Md Jamal NA, Ahmad K, Nafiah MA (2017) Phytochemical studies of Fcus deltoidea var Kunstleri. Asian J Chem 29(7):1451–1454

    Article  CAS  Google Scholar 

  37. Mustapha Z, Harun H (2014) Phytochemical Constituents in leaves and callus of Ficus deltoidea Jack var. Kunstleri (King) Corner. Agric Technol Biol Sci 12(5):471–479

    Google Scholar 

  38. Dzolin S, Ahmad R, Mat Zain M, Aris S (2012) Inhibition of free radical and neuroprotective effect of four varieties of Ficus deltoidea. Adv Mater Res, 554:554–556

    Google Scholar 

  39. Yahaya N, Dom M, Adam Z, Hamid M (2018) Insulinotropic activity of standardized methanolic extract of Ficus deltoidea from seven varieties. Evidence-Based Complement Altern Med, 2018

  40. Sharifi N, Souri E, Ziai SA, Amin G, Amanlou M (2013) Discovery of new angiotensin converting enzyme (ACE) inhibitors from medicinal plants to treat hypertension using an in vitro assay. DARU J Pharm Sci 21(74):1–8

    Google Scholar 

  41. Hakiman M, Syed MA, Syahida A, Maziah M (2012) Total antioxidant, polyphenol, phenolic acid and flavanoid content in Ficus deltoidea varieties. J Med Plant Res 6(33):4776–4784

    Article  CAS  Google Scholar 

  42. Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Peter L, Stanley D, Stein PE, Pipkin FB, Read RJ (2010) A redox switch in angiotensinogen modulates angiotensin release. Int J Sci 468:108–111

    CAS  Google Scholar 

  43. Kleinsasser A, Pircher I, Treml B, Schwienbacher M, Schuster M, Janzek E, Loibner H, Penninger JM, Loeckinger A (2012) Recombinant angiotensin-converting enzyme 2 suppresses pulmonary vasoconstriction in acute hypoxia. Wilderness Environ Med 23(1):24–30

    Article  PubMed  Google Scholar 

  44. Silva ACS, Silviera KD, Ferreira AJ, Teixeira MM (2013) ACE2, angiotensin-(1–7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol 169(3):477–492

    Article  CAS  Google Scholar 

  45. Simoes e, Silva AC, Santos RA, Maric C, Silva DMR, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T (2003) Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas. PNAS 100(14):8258–8263

    Article  CAS  Google Scholar 

  46. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P (2002) Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 277(17):14838–14843

    Article  CAS  PubMed  Google Scholar 

  47. Shumei M, Chengde L (2015) Hypotensive and angiotensin-converting enzyme inhibitory activities of Eisenia fetida extract in spontaneously hypertensive rats. Evid-Based Complement Altern Med 349721:7 pages

    Google Scholar 

  48. Ruzicka M, Coletta E, White R, Davies R, Haddad H, Leenen FH (2010) Effects of ACE inhibitors on cardiac angiotensin II and aldosterone in humans: relevance of lipophilicity and affinity for ACE. Am J Hypertens 23(11):1179–1182

    Article  CAS  PubMed  Google Scholar 

  49. Brunce AS (1986) Regulation by adrenal corticosteroids of sodium and potassium transport in loop of Henle and distal tubule of rat kidney. J Clin Investig 78(6):1612–1620

    Article  Google Scholar 

  50. Piluzza G, Bullitta S (2011) Correlations between phenolic content and antioxidant properties in twenty-four plant species of traditional ethnoveterinary use in the Mediterranean area. Pharm Biol 49(3):240–247

    Article  CAS  PubMed  Google Scholar 

  51. Yunusa AK, Rashid ZM, Mat N, Bakar CAA, Ali AM (2018) Chemicals and Bioactivity Discrimination of Syconia of Seven Varieties of Ficus deltoidea Jack via ATR-IR Spectroscopic-Based Metabolomics. Pharm J, 10(6), Suppl: s147-s151

  52. Hakiman M, Syed MA, Syahida A, Maziah M (2012) Total antioxidant, polyphenol, phenolic acid, and flavonoid content in Ficus deltoidea varieties. J Med Plant Res 6(33):4776–4784

    Article  CAS  Google Scholar 

  53. Lee SK, Sirajudeen KNS, Sundaram A, Zakaria R, Singh HJ (2011) Effects of antenatal, postpartum and post-weaning melatonin supplementation on blood pressure and renal antioxidant enzyme activities in spontaneously hypertensive rats. J Physiol Biochem 67(2):249–257

    Article  CAS  PubMed  Google Scholar 

  54. Treasure CB, Manoukian SV, Klein JL, Vita JA, Nabel EG, Renwick GH, Selwyn AP, Alexander RW, Ganz P (1992) Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients. Circ Res 71(4):776–781

    Article  CAS  PubMed  Google Scholar 

  55. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1993) Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 87(5):1468–1474

    Article  CAS  PubMed  Google Scholar 

  56. Berenyiova A, Drobna M, Cebova M, Kristek F, Cacanyiova S (2018) Changes in the vasoactive effects of nitric oxide, hydrogen sulfide and the structure of the rate thoracic aorta: the role of age and essential hypertension. J Physiol Pharmacol, 69(4)

  57. Fu J, Han Y, Wang J, Liu Y, Zheng S, Zhou L, Jose PA, Zeng C (2016) Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK-Akt-eNOS-NO Pathway in the Spontaneously Hypertensive Rat. J American Heart Assoc, 5(11):e003433

    Article  Google Scholar 

  58. Arora S, Das N, Srivastava K (2009) Nitric oxide and eNOS gene in essential hypertension. Int J Collab Res Intern Med Public Health 1(2):56–71

    Google Scholar 

  59. Mohammad N, Kar WY, Abu Bakar NF (2012) Determination of mineral content in the Ficus deltoidea leaves. Jurnal Sains Kesihatan Malaysia 10(2):25–29

    Google Scholar 

  60. Shafik I, Green R (1989) Effect of magnesium infusion on calcium handling in the rat kidney. J Exp Physiol 74:19–26

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the Ministry of Agriculture (MOA) (100-RMI/MOA/ 16/62).

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Correspondence to Harbindar Jeet Singh.

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Azis, N.A., Agarwal, R., Ismail, N.M. et al. Blood pressure lowering effect of Ficus deltoidea var kunstleri in spontaneously hypertensive rats: possible involvement of renin–angiotensin–aldosterone system, endothelial function and anti-oxidant system. Mol Biol Rep 46, 2841–2849 (2019). https://doi.org/10.1007/s11033-019-04730-w

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