Repercussions of pathway inhibition response of Panaxginseng fractions ameliorate cardiac dysfunction in hypertensive model rats

Naglaa A. Ali; Al Shimaa Gamal Shalaby; Tamer I. M. Ragab; Medhat M. Menshawy; Noha S. Abdel Latif; Aziza B. Shalby; Abdel-Razik H. Farrag; Safaa H. Mohamed

doi:10.53730/ijhs.v5nS2.12560

Authors

Naglaa A. Ali
na.hamdan@nrc.sci.eg
Department of Hormones, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, 12622, Cairo, Egypt
Al Shimaa Gamal Shalaby Chemistry of Natural and Microbial Products Department, National Research Centre, El-Buhouth St., Dokki, Giza, 12622, Egypt
Tamer I. M. Ragab Chemistry of Natural and Microbial Products Department, National Research Centre, El-Buhouth St., Dokki, Giza, 12622, Egypt
Medhat M. Menshawy Department of Biology, Center of Basic Sciences, College of Pharmacy, Misr University for Science and Technology, 6th October City, Egypt
Noha S. Abdel Latif Assistant Professor of Medical pharmacology, Faculty of Medicine, Cairo University, Egypt
Aziza B. Shalby Department of Hormones, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, 12622, Cairo, Egypt
Abdel-Razik H. Farrag Departments of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, 33 El Bohouth St., Dokki, Giza, 12622, Egypt.
Safaa H. Mohamed Department of Hormones, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, 12622, Cairo, Egypt

Keywords:

Panax ginseng, L-NAME, hypertension, histology, cholesterol, antihypertensive

Abstract

This study examined the preventive and therapeutic benefits of various Panax ginseng fractions against NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension in rats. Rats injected with L-NAME plus vehicle exhibited persistently elevated SBP, serum concentrations of the cardiac injury biomarkers creatine kinase (CK), CK-MB, and troponin, total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), and interleukin (IL)-6, but lower high-density lipoprotein (HDL) compared to the vehicle control group. Furthermore, L-NAME disrupted the normal histological structure and function of rat cardiac tissue. All ginseng fractions and losartan restored SBP to a normal level, reversed the changes in CK, CK-MB, troponin, total cholesterol, TG, HDL, and LDH, and preserved normal myocardial histology, with the WGF demonstrating the greatest cardioprotective and antihypertensive effects. Compounds within multiple ginseng fractions, but especially the aqueous fraction, possess potent and effective antihypertensive, antilipidemic, anti-inflammatory, and cardioprotective properties.

Downloads

Download data is not yet available.

References

Adedara IA, Alake SE, Olajide LO, Adeyemo MO, Ajibade TO, Farombi EO. Taurine Ameliorates Thyroid Hypofunction and Renal Injury in L-NAME-Induced Hypertensive Rats. Drug Res. 2018; 69, 83–92.

Al Saad AMS, Alasmari F, Abuohashish HM, Mohany M, Ahmed M, Al-Rejaie S. Renin angiotensin system blockage by losartan neutralize hypercholesterolemia-induced inflammatory and oxidative injuries, Redox Report, 2020; 25:1, 51-58, DOI: 10.1080/13510002.2020.1763714 .

Aldubayan MA, Ahmed AS, Emara AM, Ahmed AA, Elgharabawy RM. Sinapic Acid Attenuates Cardiovascular Disorders in Rats by Modulating Reactive Oxygen Species and Angiotensin Receptor Expression. Oxid Med Cell Longev. 2020; 2020:1436858. DOI: 10.1155/2020/1436858.

Armitage P, Berry G. Comparison of several groups In: statistical method in medical research2th Ed Blockwell significant Publication Oxford, 1987; pp: 186-213.

Barragán-Zarate GS, Lagunez-Rivera L, Solano R, Pineda-Peña EA, Landa-Juárez AY, Chávez-Piña AE, Carranza-Álvarez C, Hernández-Benavides DM. Prosthechea karwinskii, an orchid used as traditional medicine, exerts anti-inflammatory activity and inhibits ROS. J Ethnopharmacol. 2020; 253:112632. DOI: 10.1016/j.jep.2020.112632

Bhosale, A., Khedkar, S., Khade, S. K., & Reddy, M. M. (2022). Study of serum uric acid levels in essential hypertension. International Journal of Health Sciences, 6(S7), 3528–3536. https://doi.org/10.53730/ijhs

Bilanda DC, Dzeufiet PDD, Kouakep L, Aboubakar BFO, Tedong L, Kamtchouing P, Dimo T. Bidenspilosa Ethylene acetate extract can protect against L-NAME-induced hypertension on rats. BMC Complement Altern Med. 2017; 17(1):479. DOI: 10.1186/s12906-017-1972-0.

Chen XQ, Zhang DL, Zhang MJ, Guo M, Zhan YY, Liu F, Jiang WF, Zho L, Zhao L, Wang QX, Liu X. TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis. Biochem Biophys Res Commun. 2015; 464(1):100-5. DOI: 10.1016/j.bbrc.2015.05.131.

Christensen LP. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 2009; 55:1-99. DOI: 10.1016/S1043-4526(08)00401-4.

de Gracia MC, Osuna A, O’Valle F, Del Moral RG, Wangensteen R, Del Rio CG, Vargas F. Deoxycorticosterone suppresses the effects of losartan in nitric oxide-deficient hypertensive rats, J. Am. Soc. Nephrol. 2000; 11 (11) () 1995–2000.

Dou L, Lu Y, Shen T, Huang X, Man Y, Wang S, Li J. Panaxnotogingsengsaponins suppress RAGE/MAPK signaling and NF-kappaB activation in mice. Cell. Physiol. Biochem. 2012; 100730, 875–882.

EL Desoky ES, Hassan AKM, Salem SY, Fadil SA, Taha AF. Cardioprotective effect of Losartan alone or in combination with remote ischemic preconditioning on the biochemical changes induced by ischemic/reperfusion injury in a mutual prospective study with a clinical and experimental animal arm. Heart Res Open J., 2017; 4(3): 57-65. doi: 10.17140/HRO

Fan X, Zhang C, Niu S, Fan B, Gu D, Jiang K, Li R, Li S. Ginsenoside Rg1 attenuates hepatic insulin resistance induced by high-fat and high-sugar by inhibiting inflammation .Eur J Pharmacol. 2019; 854:247-255. doi: 10.1016/j.ejphar.2019.04.027.

Han KH, Choe SC, Kim HS, Sohn DW, Nam KY, Oh BH, Lee, M.M., Park YB, Choi YS, Seo JD, et al. Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension. The American journal of Chinese medicine, 1998; 26(2), 199–209. https://doi.org/10.1142/S0192415X98000257

Hong H, Baatar D, Hwang S G. Anticancer Activities of Ginsenosides, the Main Active Components of Ginseng. Evidence-based complementary and alternative medicine. 2021; eCAM, 2021, 8858006. https://doi.org/10.1155/2021/8858006

Jan-On G, Sangartit W, Pakdeechote P, Kukongviriyapan V, Sattayasai J, Senaphan K, Kukongviriyapan U. Virgin rice bran oil alleviates hypertension through the upregulation of eNOS and reduction of oxidative stress and inflammation in L-NAME-induced hypertensive rats. Nutrition. 2020; 69:110575. DOI: 10.1016/j.nut.2019.110575.

John OD, Wanyonyi S, Mouatt P, Panchal SK, Lindsay Brown L. Achacha ( Garciniahumilis) Rind Improves Cardiovascular Function in Rats with Diet-Induced Metabolic Syndrome. Nutrients. 2018; 10(10):1425. DOI: 10.3390/nu10101425.

Jovanovski E, Bateman EA, Bhardwaj J, Fairgrieve C, Mucalo I, Jenkins AL, Vuksan V. Effect of Rg3-enriched Korean red ginseng (Panax ginseng) on arterial stiffness and blood pressure in healthy individuals: A randomized controlled trial. J. Am. Soc. Hypertens. 2014; 8, 537–541.

Kalra J, Dasari D, Bhat A, Mangali S, Goyal SG, Jadhav KB, Dhar A. PKR inhibitor imoxin prevents hypertension, endothelial dysfunction and cardiac and vascular remodelling in L-NAME-treated rats. Life Sci. 2020; 262:118436. DOI: 10.1016/j.lfs.2020.118436.

Kim JS. Investigation of phenolic, flavonoid, and vitamin contents in different parts of Korean ginseng (Panax ginseng C.A. Meyer). Prev. Nutr. Food Sci., 2016; 21, 263–270.

Kyvelou SM, Vyssoulis GP, Karpanou EA, Adamopoulos DN, Zervoudaki AI, Pietri PG, Stefanadis CI. Effects of antihypertensive treatment with angiotensin II receptor blockers on lipid profile: an open multi-drug comparison trial. Hellenic J Cardiol. 2006;47(1):21-8. PMID: 16532712.

Lee HJ, Kim BM, Lee SH, Sohn JT, Choi JW, Cho CW, Hong HD, Rhee YK, Kim HJ. Ginseng-Induced Changes to Blood Vessel Dilation and the Metabolome of Rats. Nutrients. 2020 Jul 27;12(8):2238. doi: 10.3390/nu12082238. PMID: 32727012; PMCID: PMC7468881.

Lee S, Rhee D K. Effects of ginseng on stress-related depression, anxiety, and the hypothalamic-pituitary-adrenal axis. J. Ginseng Res. 2017; 41, 589–594. doi: 10.1016/j.jgr.2017.01.010

Li F, Wu Z, Sui X. Biotransformation of ginsenoside Rb1 with wild Cordycepssinensis and Ascomycota sp. and its antihyperlipidemic effects on the diet-induced cholesterol of zebrafish. J Food Biochem. 2020; 44(6):e13192. doi: 10.1111/jfbc.13192.

Lu S, Luo Y, Zhou P, Yang K, Sun G, Sun X. Ginsenoside compound K protects human umbilical vein endothelial cells against oxidized low-density lipoprotein-induced injury via inhibition of nuclear factor-κB, p38, and JNK MAPK pathways. J Ginseng Res. 2019; 43(1):95-104. doi: 10.1016/j.jgr.2017.09.004.

Ma F, Li Y, Jia L, Han Y, Cheng J, Li H, Qi Y, Du J. Macrophage-stimulated cardiac fibroblast production of IL-6 is essential for TGF β/Smad activation and cardiac fibrosis induced by angiotensin II . PLOS ONE. 2012; 7(5):e35144. doi: 10.1371/journal.pone.0035144.

Mahmoudabady M, Kazemi N, Niazmand S. The effect of angiotensin-converting enzyme inhibition on inflammatory and angiogenic factors in hypercholesterolemia. Pharmacol Rep. 2015; 67(5):837–841. doi: 10.1016/j.pharep.2015.01.008.

Miguel-Carrasco JL, Mate A, Monserrat MT, Arias JL, Aramburu O, Vázquez CM. The role of inflammatory markers in the cardioprotective effect of L-carnitine in L-NAME-induced hypertension. Am J Hypertens. 2008;21(11):1231-7. DOI: 10.1038/ajh.2008.271.

Miller LG. Herbal medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998; 158, 2200-2211.

Murphy AM, Wong AL, Bezuhly M. Modulation of angiotensin II signaling in the prevention of fibrosis. Fibrogenesis& Tissue Repair. 2015; 8:7. DOI 10.1186/s13069-015-0023-z.

Nagar H, Choi S, Jung S, Jeon BH, Kim CS. Rg3-enriched Korean red ginseng enhances blood pressure stability in spontaneously hypertensive rats. Integr. Med. Res. 2016; 5, 223–229. [CrossRef] [PubMed]

Nunes DO, Marques VB, Almenara CCP, Marcarini WD, Júnior RFR, Padilha AS. Linoleic acid reduces vascular reactivity and improves the vascular dysfunction of the small mesentery in hypertension. J Nutr Biochem. 2018; 62:18-27.DOI: 10.1016/j.jnutbio.2018.07.016.

Opie LH, Cammerford PJ, Gerch BJ, Pfeffer MA. Controversies in cardiology 4. Controversies in ventricular remodeling, Lancet, 2006; 367 (2006) 356–376.

Patel S, Rauf A. Adaptogenic herb ginseng (Panax) as medical food: Status quo and future prospects. Biomed. Pharmacother. 2017; 85, 120–127.

Qin Q, Lin N, Huang H, Zhang X, Cao X, Wang Y, Peng L. Ginsenoside Rg1 ameliorates cardiac oxidative stress and inflammation in streptozotocin-induced diabetic rats. Diabetes Metab Syndr Obes. 2019; 12:1091-1103. DOI: 10.2147/DMSO.S208989

Ragab TIM, Ali NA, El Gendy ANG, Mohamed SH, Shalby AB, Farrag ARH, Shalaby ASG. Renoprotective and therapeutic effects of newly water, ethanol, and butanol ginseng fractions in hypertensive and chronic kidney disease with L-NAME. Biomedicine and Pharmacotherapy, 2021; 142, 111978

Ramanathan V, Thekkumalai M. Role of chrysin on hepatic and renal activities of Nω-nitro-l-arginine-methylester induced hypertensive rats, Int. J. Nutr. Pharmacol. Neurol. Dis. 2014; 4 (1): 58–63. DOI: 10.4103/2231-0738.124615.

Rosa AC, Rattazzi L, Miglio G, Collino M, Fantozzi R. Angiotensin II induces tumor necrosis factor-α expression and release from cultured human podocytes. Inflamm Res. 2012;61(4):311-7. doi: 10.1007/s00011-011-0412-8. Epub 2012 Jan 6. PMID: 22223068.

Rossoni G, Manfredi B, De Gennaro Colonna V, Berti M, Guazzi M, Berti F. Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia-reperfusion damage in the rat. Br J Pharmacol. 2007; 150(5):567-76. DOI: 10.1038/sj.bjp.0707131.

Sivasubramaniam S, Kumarasamy B. Pleiotropic Effects of Losartan in Hypertensive Patients with Dyslipidemia, 2017;11(9), FC05 FC08. https://www.doi.org/10.7860/JCDR/2017/30909/10638.

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). Get vaccinated when it is your turn and follow the local guidelines. International Journal of Health Sciences, 5(3), x-xv. https://doi.org/10.53730/ijhs.v5n3.2938

Torres-Narváez JC, Pérez-Torres I, Castrejón-Tellez V, Varela-López E, Oidor-Chan VH, Guarner-Lans V, Vargas-González Á, Memije RM, Flores-Chávez P, Cervantes-Yañez EZ. The Role of the Activation of the TRPV1 Receptor and of Nitric Oxide in Changes in Endothelial and CardiacFunction and Biomarker Levels in Hypertensive Rats. Int. J. Environ. Res. Public Health, 2019; 16, 3576.

Veerappan R, Senthilkumar R. Chrysin enhances antioxidants and oxidative stress in L-NAME-induced hypertensive rats, 2015; 5 ( 1) 20–27.

Velasquez, C. A. L., Perez, G. L. R., Landa, A. F. C., Velasquez, R. M. L., & Ortiz, D. J. Z. (2018). Occupational health and safety prevention plan in water treatment plant. International Journal of Life Sciences, 2(3), 1–12. https://doi.org/10.29332/ijls.v2n3.196

Wang X, Meng H, Wang Q, Shao M, Lu W, Chen X, Jiang Y, Li C, Wang Y, Tu P. Baoyuan decoction ameliorates apoptosis via AT1-CARP signaling pathway in H9C2 cells and heart failure post-acute myocardial infarction rats. J Ethnopharmacol. 2020; 252:112536. DOI: 10.1016/j.jep.2019.112536.

Wu Y, Pan N, An Y, Xu M, Tan L, Zhang L. Diagnostic and Prognostic Biomarkers for Myocardial Infarction. Front. Cardiovasc. Med. 2021; 7:617277. doi: 10.3389/fcvm.2020.617277.

Wunpathe C, Maneesai P, Rattanakanokchai S, Bunbupha S, Kukongviriyapan U, Tong-Un T, Pakdeechote P. Tangeretin mitigates l-NAME-induced ventricular dysfunction and remodeling through the AT 1 R/pERK1/2/pJNK signaling pathway in rats. Food Funct. 2020; 11(2):1322-1333.DOI: 10.1039/c9fo02365h.

Yang G, Zhuo J, Lin Y, Zhang M, Liu L, Chen X, Gao R. Ginsenoside Rb1 Prevents Dysfunction of Endothelial Cells by Suppressing Inflammatory Response and Apoptosis in the High-Fat Diet Plus Balloon Catheter-Injured Rabbit Model via the G Protein-Coupled Estrogen Receptor-Mediated Phosphatidylinositol 3-Kinases (PI3K)/Akt Pathway. Med SciMonit. 2019; 25:7407-7417. doi: 10.12659/MSM.912986.