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Year 2020, Volume: 24 Issue: 1, 150 - 158, 27.06.2025

Azizah Ugusman , Noor Fazilah Md Fadze Adila A Hamid Zanariyah Asmawi Amilia Aminuddin

https://doi.org/10.35333/jrp.2020.122
Cited By: 5

Abstract

References

  • [1] Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, Alexander L, Estep K, Hassen Abate K, Akinyemiju TF, Ali R, Alvis-Guzman N, Azzopardi P, Banerjee A, Bärnighausen T, Basu A, Bekele T, Bennett DA, Biadgilign S, Catalá-López F, Feigin VL, Fernandes JC, Fischer F, Gebru AA, Gona P, Gupta R, Hankey GJ, Jonas JB, Judd SE, Khang YH, Khosravi A, Kim YJ, Kimokoti RW, Kokubo Y, Kolte D, Lopez A, Lotufo PA, Malekzadeh R, Melaku YA, Mensah GA, Misganaw A, Mokdad AH, Moran AE, Nawaz H, Neal B, Ngalesoni FN, Ohkubo T, Pourmalek F, Rafay A, Rai RK, Rojas-Rueda D, Sampson UK, Santos IS43, Sawhney M, Schutte AE, Sepanlou SG, Shifa GT, Shiue I, Tedla BA, Thrift AG, Tonelli M, Truelsen T, Tsilimparis N, Ukwaja KN, Uthman OA, Vasankari T, Venketasubramanian N, Vlassov VV, Vos T, Westerman R, Yan LL, Yano Y, Yonemoto N, Zaki ME, Murray CJ. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017; 317(2): 165-182. [CrossRef]
  • [2] Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016; 134(6): 441-450. [CrossRef]
  • [3] Tomeleri CM, Marcori AJ, Ribeiro AS, Gerage AM, de Souza Padilha C, Schiavoni D, Souza MF, Mayhew JL, do Nascimento MA, Venturini D, Barbosa DS. Chronic blood pressure reductions and increments in plasma nitric oxide bioavailability. Int J Sports Med. 2017; 38(04): 290-299. [CrossRef]
  • [4] Li Q, Youn JY, Cai H. Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension. J Hypertens. 2015; 33(6): 1128-1136. [CrossRef]
  • [5] Lu Y, Liu H, Bi Y, Yang H, Li Y, Wang J, Zhang Z, Wang Y, Li C, Jia A, Han L, Hu Y, Zhao Y, Wang R, Liu G. Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis. Cell Mol Immunol. 2018; 15(6): 618-629. [CrossRef]
  • [6] Reber LL, Daubeuf F, Plantinga M, De Cauwer L, Gerlo S, Waelput W, Van Calenbergh S, Tavernier J, Haegeman G, Lambrecht BN, Frossard N, De Bosscher K. A dissociated glucocorticoid receptor modulator reduces airway hyperresponsiveness and inflammation in a mouse model of asthma. J Immunol. 2012; 188(7): 3478-3487. [CrossRef]
  • [7] Soto-Piña AE, Franklin C, Rani CSS, Gottlieb H, Hinojosa-Laborde C, Strong R. A novel model of dexamethasoneinduced hypertension: use in investigating the role of tyrosine hydroxylase. J Pharmacol Exp Ther. 2016; 358(3): 528– 536. [CrossRef]
  • [8] Schäfer SC, Wallerath T, Closs EI, Schmidt C, Schwarz PM, Förstermann U, Lehr H. Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles. Am J Physiol Heart Circ Physiol. 2005; 288(1): H436-444. [CrossRef]
  • [9] Thent ZC, Das S. Piper sarmentosum maintains blood pressure and morphological integrity of liver in type 1 diabetic rats. Int J Pharrma Med Biol Sci. 2015; 4: 24-28.
  • [10] Ab Rahman MR, Abdul Razak F, Mohd Bakri M. Evaluation of wound closure activity of nigella sativa, melastoma malabathricum, pluchea indica, and piper sarmentosum extracts on scratched monolayer of human gingival fibroblasts. Evid Based Complement Alternat Med. 2015;2014: 190342. [CrossRef]
  • [11] Mohd Zainudin M, Zakaria Z, Megat Mohd Nordin NA, MM, Anita N, Othman F. Does oral ingestion of Piper sarmentosum cause toxicity in experimental animals? Evid Based Complement Alternat Med. 2013; 2013: 705950. [CrossRef]
  • [12] Mohd Zainuddin M, Zakaria Z, Megat Mohd Nordin NA. The use of Piper sarmentosum leaves aqueous extract (Kadukmy™) as antihypertensive agent in spontaneous hypertensive rats. BMC Complement Altern Med. 2015; 10;15: 54. [CrossRef]
  • [13] Amran AA, Zakaria Z, Othman F, Das S, Raj S, Nordin NA. Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits. Lipids Health Dis. 2010; 9(1): 44. [CrossRef]
  • [14] Luangpirom AK, Kourchampa W, Somsapt. P. Evaluation of hypoglycemic properties and fertility effect of Piper sarmentosum Roxb. aqueous leaf extract in streptozotocin induced diabetic mice. Int J Phytomed. 2014; 6(3): 448–454.
  • [15] Ugusman A, Zakaria Z, Hui CK, Nordin NA. Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells. Clinics (Sao Paulo). 2010; 65(7): 709-714. [CrossRef]
  • [16] Ong SLH, Zhang Y, Sutton M, Whitworth JA. Hemodynamics of dexamethasone-induced hypertension in the rat. Hypertensi Res. 2009; 32(10): 889. [CrossRef]
  • [17] Wallerath T, Witte K, Schafer SC, Schwarz PM, Prellwitz W, Wohlfart P, Kleinert H, Lehr HA, Lemmer B, Förstermann U. Down-regulation of the expression of endothelial no synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci USA. 1999; 96(23): 13357-13362. [CrossRef]
  • [18] Tobias S, Habermeier A, Siuda D, Reifenberg G, Xia N, Closs EI, Förstermann U, Li H. Dexamethasone, tetrahydrobiopterin and uncoupling of endothelial nitric oxide synthase. J Geriatr Cardiol. 2015; 12(5): 528-539. [CrossRef]
  • [19] Ugusman A, Zakaria Z, Chua KH, Nordin NA, Abdullah Mahdy Z. Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells. ScientificWorldJournal. 2014; 2014: 169370. [CrossRef]
  • [20] Olaleye MT, Crown OO, Akinmoladun AC, Akindahunsi AA. Rutin and quercetin show qreater efficacy than nifedipin in ameliorating hemodynamic, redox, and metabolite imbalances in sodium chloride-induced hypertensive rats. Hum Exp Toxicol. 2014; 33(6): 602-608. [CrossRef]
  • [21] Maneesai P, Prasarttong P, Bunbupha S, Kukongviriyapan U, Kukongviriyapan V, Tangsucharit P, Prachaney P, Pakdeechote P. Synergistic antihypertensive effect of Carthamus tinctorius L. extract and Captopril in L-NAMEinduced hypertensive rats via rRestoration of eNOS and AT(1)R expression. Nutrients. 2016; 8(3): 122. [CrossRef]
  • [22] Ugusman A, Zakaria Z, Hui CK, Nordin NA, Mahdy ZA. Flavonoids of Piper sarmentosum and its cytoprotective effects against oxidative stress. Excli J. 2012; 11: 705-714.
  • [23] Alwi NA, Zakaria Z, Karim AA, Nordin NA, Ugusman A. Antihypertensive effect of Piper sarmentosum in LNAME-Induced hypertensive rats. SAINS MALAYS. 2018; 47(10): 2421-2428. [CrossRef]
  • [24] Ugusman A, Zakaria Z, Hui CK, Nordin NA. Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells. BMC Complement Altern Med. 2011; 11:31. [CrossRef]
  • [25] Valipour Nouroozi R, Valipour Noroozi M, Ahmadizadeh M. Determination of protein concentration using bradford microplate protein quantification assay. Int Elec J Med. 2015; 4(1): 11-17. [CrossRef]

Piper sarmentosum attenuates dexamethasone-induced hypertension by stimulating endothelial nitric oxide synthase

Year 2020, Volume: 24 Issue: 1, 150 - 158, 27.06.2025

Azizah Ugusman , Noor Fazilah Md Fadze Adila A Hamid Zanariyah Asmawi Amilia Aminuddin

https://doi.org/10.35333/jrp.2020.122
Cited By: 5

Abstract

Reduced endothelial nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) in the vasculature is a feature of endothelial dysfunction. Dexamethasone causes secondary hypertension by inhibiting eNOS activity. Piper sarmentosum is an herb with anti-hypertensive effect. The aim of this study was to evaluate the antihypertensive effect of aqueous extract of P. sarmentosum (AEPS) in dexamethasone (Dex)-induced hypertensive rats. A total of 30 male Sprague Dawley rats were divided into five groups including control, AEPS (500 mg/kg/day, orally), Dex (20 μg/kg/day, subcutaneously), Dex (20 μg/kg/day) + AEPS (500 mg/kg/day) and Dex (20 μg/kg/day) + captopril (40 mg/kg/day, orally). Blood pressure was measured using tail-cuff method at baseline and fortnightly thereafter. The rats were sacrificed and the serum was collected to quantify the amount of NO after 28 days of treatment. Aortic samples were homogenized for measurement of eNOS mRNA expression, protein level and activity. Treatment of Dex-induced hypertensive rats with AEPS lowered systolic blood pressure (P < 0.001) and diastolic blood pressure (P < 0.01), increased eNOS mRNA expression (P < 0.01), eNOS protein (P < 0.01), eNOS activity (P < 0.05) and NO level (P < 0.05). In conclusion, AEPS reduces the blood pressure of Dex-induced hypertensive rats as it shows positive effects on eNOS and NO production.

Keywords

Dexamethasone endothelial nitric oxide synthase hypertension nitric oxide Piper sarmentosum

References

  • [1] Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, Alexander L, Estep K, Hassen Abate K, Akinyemiju TF, Ali R, Alvis-Guzman N, Azzopardi P, Banerjee A, Bärnighausen T, Basu A, Bekele T, Bennett DA, Biadgilign S, Catalá-López F, Feigin VL, Fernandes JC, Fischer F, Gebru AA, Gona P, Gupta R, Hankey GJ, Jonas JB, Judd SE, Khang YH, Khosravi A, Kim YJ, Kimokoti RW, Kokubo Y, Kolte D, Lopez A, Lotufo PA, Malekzadeh R, Melaku YA, Mensah GA, Misganaw A, Mokdad AH, Moran AE, Nawaz H, Neal B, Ngalesoni FN, Ohkubo T, Pourmalek F, Rafay A, Rai RK, Rojas-Rueda D, Sampson UK, Santos IS43, Sawhney M, Schutte AE, Sepanlou SG, Shifa GT, Shiue I, Tedla BA, Thrift AG, Tonelli M, Truelsen T, Tsilimparis N, Ukwaja KN, Uthman OA, Vasankari T, Venketasubramanian N, Vlassov VV, Vos T, Westerman R, Yan LL, Yano Y, Yonemoto N, Zaki ME, Murray CJ. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015. JAMA. 2017; 317(2): 165-182. [CrossRef]
  • [2] Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016; 134(6): 441-450. [CrossRef]
  • [3] Tomeleri CM, Marcori AJ, Ribeiro AS, Gerage AM, de Souza Padilha C, Schiavoni D, Souza MF, Mayhew JL, do Nascimento MA, Venturini D, Barbosa DS. Chronic blood pressure reductions and increments in plasma nitric oxide bioavailability. Int J Sports Med. 2017; 38(04): 290-299. [CrossRef]
  • [4] Li Q, Youn JY, Cai H. Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension. J Hypertens. 2015; 33(6): 1128-1136. [CrossRef]
  • [5] Lu Y, Liu H, Bi Y, Yang H, Li Y, Wang J, Zhang Z, Wang Y, Li C, Jia A, Han L, Hu Y, Zhao Y, Wang R, Liu G. Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis. Cell Mol Immunol. 2018; 15(6): 618-629. [CrossRef]
  • [6] Reber LL, Daubeuf F, Plantinga M, De Cauwer L, Gerlo S, Waelput W, Van Calenbergh S, Tavernier J, Haegeman G, Lambrecht BN, Frossard N, De Bosscher K. A dissociated glucocorticoid receptor modulator reduces airway hyperresponsiveness and inflammation in a mouse model of asthma. J Immunol. 2012; 188(7): 3478-3487. [CrossRef]
  • [7] Soto-Piña AE, Franklin C, Rani CSS, Gottlieb H, Hinojosa-Laborde C, Strong R. A novel model of dexamethasoneinduced hypertension: use in investigating the role of tyrosine hydroxylase. J Pharmacol Exp Ther. 2016; 358(3): 528– 536. [CrossRef]
  • [8] Schäfer SC, Wallerath T, Closs EI, Schmidt C, Schwarz PM, Förstermann U, Lehr H. Dexamethasone suppresses eNOS and CAT-1 and induces oxidative stress in mouse resistance arterioles. Am J Physiol Heart Circ Physiol. 2005; 288(1): H436-444. [CrossRef]
  • [9] Thent ZC, Das S. Piper sarmentosum maintains blood pressure and morphological integrity of liver in type 1 diabetic rats. Int J Pharrma Med Biol Sci. 2015; 4: 24-28.
  • [10] Ab Rahman MR, Abdul Razak F, Mohd Bakri M. Evaluation of wound closure activity of nigella sativa, melastoma malabathricum, pluchea indica, and piper sarmentosum extracts on scratched monolayer of human gingival fibroblasts. Evid Based Complement Alternat Med. 2015;2014: 190342. [CrossRef]
  • [11] Mohd Zainudin M, Zakaria Z, Megat Mohd Nordin NA, MM, Anita N, Othman F. Does oral ingestion of Piper sarmentosum cause toxicity in experimental animals? Evid Based Complement Alternat Med. 2013; 2013: 705950. [CrossRef]
  • [12] Mohd Zainuddin M, Zakaria Z, Megat Mohd Nordin NA. The use of Piper sarmentosum leaves aqueous extract (Kadukmy™) as antihypertensive agent in spontaneous hypertensive rats. BMC Complement Altern Med. 2015; 10;15: 54. [CrossRef]
  • [13] Amran AA, Zakaria Z, Othman F, Das S, Raj S, Nordin NA. Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits. Lipids Health Dis. 2010; 9(1): 44. [CrossRef]
  • [14] Luangpirom AK, Kourchampa W, Somsapt. P. Evaluation of hypoglycemic properties and fertility effect of Piper sarmentosum Roxb. aqueous leaf extract in streptozotocin induced diabetic mice. Int J Phytomed. 2014; 6(3): 448–454.
  • [15] Ugusman A, Zakaria Z, Hui CK, Nordin NA. Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells. Clinics (Sao Paulo). 2010; 65(7): 709-714. [CrossRef]
  • [16] Ong SLH, Zhang Y, Sutton M, Whitworth JA. Hemodynamics of dexamethasone-induced hypertension in the rat. Hypertensi Res. 2009; 32(10): 889. [CrossRef]
  • [17] Wallerath T, Witte K, Schafer SC, Schwarz PM, Prellwitz W, Wohlfart P, Kleinert H, Lehr HA, Lemmer B, Förstermann U. Down-regulation of the expression of endothelial no synthase is likely to contribute to glucocorticoid-mediated hypertension. Proc Natl Acad Sci USA. 1999; 96(23): 13357-13362. [CrossRef]
  • [18] Tobias S, Habermeier A, Siuda D, Reifenberg G, Xia N, Closs EI, Förstermann U, Li H. Dexamethasone, tetrahydrobiopterin and uncoupling of endothelial nitric oxide synthase. J Geriatr Cardiol. 2015; 12(5): 528-539. [CrossRef]
  • [19] Ugusman A, Zakaria Z, Chua KH, Nordin NA, Abdullah Mahdy Z. Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells. ScientificWorldJournal. 2014; 2014: 169370. [CrossRef]
  • [20] Olaleye MT, Crown OO, Akinmoladun AC, Akindahunsi AA. Rutin and quercetin show qreater efficacy than nifedipin in ameliorating hemodynamic, redox, and metabolite imbalances in sodium chloride-induced hypertensive rats. Hum Exp Toxicol. 2014; 33(6): 602-608. [CrossRef]
  • [21] Maneesai P, Prasarttong P, Bunbupha S, Kukongviriyapan U, Kukongviriyapan V, Tangsucharit P, Prachaney P, Pakdeechote P. Synergistic antihypertensive effect of Carthamus tinctorius L. extract and Captopril in L-NAMEinduced hypertensive rats via rRestoration of eNOS and AT(1)R expression. Nutrients. 2016; 8(3): 122. [CrossRef]
  • [22] Ugusman A, Zakaria Z, Hui CK, Nordin NA, Mahdy ZA. Flavonoids of Piper sarmentosum and its cytoprotective effects against oxidative stress. Excli J. 2012; 11: 705-714.
  • [23] Alwi NA, Zakaria Z, Karim AA, Nordin NA, Ugusman A. Antihypertensive effect of Piper sarmentosum in LNAME-Induced hypertensive rats. SAINS MALAYS. 2018; 47(10): 2421-2428. [CrossRef]
  • [24] Ugusman A, Zakaria Z, Hui CK, Nordin NA. Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells. BMC Complement Altern Med. 2011; 11:31. [CrossRef]
  • [25] Valipour Nouroozi R, Valipour Noroozi M, Ahmadizadeh M. Determination of protein concentration using bradford microplate protein quantification assay. Int Elec J Med. 2015; 4(1): 11-17. [CrossRef]
There are 25 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Azizah Ugusman

Noor Fazilah Md Fadze

Adila A Hamid

Zanariyah Asmawi

Amilia Aminuddin

Publication Date June 27, 2025
Published in Issue Year 2020 Volume: 24 Issue: 1

Cite

APA Ugusman, A., Md Fadze, N. F., A Hamid, A., Asmawi, Z., et al. (2025). Piper sarmentosum attenuates dexamethasone-induced hypertension by stimulating endothelial nitric oxide synthase. Journal of Research in Pharmacy, 24(1), 150-158. https://doi.org/10.35333/jrp.2020.122
AMA Ugusman A, Md Fadze NF, A Hamid A, Asmawi Z, Aminuddin A. Piper sarmentosum attenuates dexamethasone-induced hypertension by stimulating endothelial nitric oxide synthase. J. Res. Pharm. June 2025;24(1):150-158. doi:10.35333/jrp.2020.122
Chicago Ugusman, Azizah, Noor Fazilah Md Fadze, Adila A Hamid, Zanariyah Asmawi, and Amilia Aminuddin. “Piper Sarmentosum Attenuates Dexamethasone-Induced Hypertension by Stimulating Endothelial Nitric Oxide Synthase”. Journal of Research in Pharmacy 24, no. 1 (June 2025): 150-58. https://doi.org/10.35333/jrp.2020.122.
EndNote Ugusman A, Md Fadze NF, A Hamid A, Asmawi Z, Aminuddin A (June 1, 2025) Piper sarmentosum attenuates dexamethasone-induced hypertension by stimulating endothelial nitric oxide synthase. Journal of Research in Pharmacy 24 1 150–158.
IEEE A. Ugusman, N. F. Md Fadze, A. A Hamid, Z. Asmawi, and A. Aminuddin, “Piper sarmentosum attenuates dexamethasone-induced hypertension by stimulating endothelial nitric oxide synthase”, J. Res. Pharm., vol. 24, no. 1, pp. 150–158, 2025, doi: 10.35333/jrp.2020.122.
ISNAD Ugusman, Azizah et al. “Piper Sarmentosum Attenuates Dexamethasone-Induced Hypertension by Stimulating Endothelial Nitric Oxide Synthase”. Journal of Research in Pharmacy 24/1 (June 2025), 150-158. https://doi.org/10.35333/jrp.2020.122.
JAMA Ugusman A, Md Fadze NF, A Hamid A, Asmawi Z, Aminuddin A. Piper sarmentosum attenuates dexamethasone-induced hypertension by stimulating endothelial nitric oxide synthase. J. Res. Pharm. 2025;24:150–158.
MLA Ugusman, Azizah et al. “Piper Sarmentosum Attenuates Dexamethasone-Induced Hypertension by Stimulating Endothelial Nitric Oxide Synthase”. Journal of Research in Pharmacy, vol. 24, no. 1, 2025, pp. 150-8, doi:10.35333/jrp.2020.122.
Vancouver Ugusman A, Md Fadze NF, A Hamid A, Asmawi Z, Aminuddin A. Piper sarmentosum attenuates dexamethasone-induced hypertension by stimulating endothelial nitric oxide synthase. J. Res. Pharm. 2025;24(1):150-8.

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