Role of Herbal Active Compound in Cardiac Failure Treatment

Jyotsna Upadhyay; Amle Vandana Sonaji; Khonde Shital Trimbak; Chapke Seema Ganesh; Kisan Vivek Pawar; Anamika; Roshan Kumar

doi:10.55544/jrasb.3.2.16

Authors

Jyotsna Upadhyay Assistant Professor, Department of Pharmacy, Shree Dev Bhoomi Institute of Education Science and Technology, Dehradun, 248007, Dehradun, Uttarakhand, INDIA.
Amle Vandana Sonaji Shri Bhairavnath Nisarg Mandal, S.R.T.M. University, Hingoli, Maharashtra, INDIA.
Khonde Shital Trimbak Shri Bhairavnath Nisarg Mandal, S.R.T.M. University, Hingoli, Maharashtra, INDIA.
Chapke Seema Ganesh Shri Bhairavnath Nisarg Mandal's Diploma in Pharmacy Institute, Hingoli, Maharashtra, INDIA.
Kisan Vivek Pawar Shri Bhairavnath Nisarg Mandal, S.R.T.M. University, Hingoli, Maharashtra, INDIA.
Anamika Assistant Professor, Department of Pharmacy, Shree Dev Bhoomi Institute of Education Science and Technology, Dehradun, 248007, Dehradun, Uttarakhand, INDIA.
Roshan Kumar Assistant Professor, Department of Pharmacy, Shree Dev Bhoomi Institute of Education Science and Technology, Dehradun, 248007, Dehradun, Uttarakhand, INDIA.

DOI:

https://doi.org/10.55544/jrasb.3.2.16

Keywords:

Plants, medicinal herbs, diseases, toxicity, heart disease

Abstract

The prevalence of cardiovascular diseases (CVDs) is constantly rising, making them a major health burden. In terms of global mortality and morbidity, they are still at the top. An alternate method of treating many illnesses, including CVDs, is the use of medicinal herbs. There is a current, unprecedented push to include herbal remedies into contemporary healthcare systems. The widespread conviction in their safety and the fact that they offer more effective treatment at a lower cost than conventional modern medicines are two of the main factors propelling this movement. However, there has not been enough testing of the purported safety of herbal remedies. As a result, people need to know that medical herbs can be toxic, have possibly fatal side effects, and can interact negatively with other drugs. Experimental evidence suggests that medicinal herbs may be useful in the treatment of cardiovascular diseases (CVDs) due to their ability to inhibit multiple risk factors for these conditions. So, in order to successfully use herbs in CVD therapy, there have been numerous initiatives to transition medicinal herb research from the lab to the clinic. Presented below are cardiovascular diseases (CVDs) and the variables that put people at risk for developing them. Next, we provide a synopsis of herbal medicine's role in the treatment of disease, with a focus on cardiovascular diseases. In addition, information is compiled and examined about the ethnopharmacological therapeutic possibilities and medicinal qualities against cardiovascular diseases of four commonly used plants: ginseng, gingko biloba, ganoderma lucidum, and gymnostemma pentaphyllum. The use of these four plants in the treatment of cardiovascular diseases (CVDs) including myocardial infarction, hypertension, peripheral vascular disorders, coronary heart disease, cardiomyopathies, and dyslipidemias has been well examined. We are also making an effort to describe the current in vitro and in vivo investigations that have attempted to examine the cellular and molecular underpinnings of the four plants' cardio-protective effects. Lastly, we highlighted the effectiveness, safety, and toxicity of these four medicinal herbs by reviewing and reporting the results of current clinical trials.

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References

Gérard, A., Woolfe, A., Mottet, G., Reichen, M., Castrillon, C., Menrath, V., ... & Brenan, C. (2020). High-throughput single-cell activity-based screening and sequencing of antibodies using droplet microfluidics. Nature biotechnology, 38(6), 715-721.

Awuchi, C. G., Amagwula, I. O., Priya, P., Kumar, R., Yezdani, U., & Khan, M. G. (2020). Aflatoxins in foods and feeds: A review on health implications, detection, and control. Bull. Environ. Pharmacol. Life Sci, 9, 149-155.

Kaur, R. P., Vasudeva, K., Kumar, R., & Munshi, A. (2018). Role of p53 gene in breast cancer: focus on mutation spectrum and therapeutic strategies. Current pharmaceutical design, 24(30), 3566-3575.

Kumar, R., Saha, P., Lokare, P., Datta, K., Selvakumar, P., & Chourasia, A. (2022). A Systemic Review of Ocimum sanctum (Tulsi): Morphological Characteristics, Phytoconstituents and Therapeutic Applications. International Journal for Research in Applied Sciences and Biotechnology, 9(2), 221-226.

Kumar, R., Saha, P., Kumar, Y., Sahana, S., Dubey, A., & Prakash, O. (2020). A Review on Diabetes Mellitus: Type1 & Type2. World Journal of Pharmacy and Pharmaceutical Sciences, 9(10), 838-850.

Kumar, R., Sood, U., Gupta, V., Singh, M., Scaria, J., & Lal, R. (2020). Recent advancements in the development of modern probiotics for restoring human gut microbiome dysbiosis. Indian journal of microbiology, 60, 12-25.

Kumar, R., & Saha, P. (2022). A review on artificial intelligence and machine learning to improve cancer management and drug discovery. International Journal for Research in Applied Sciences and Biotechnology, 9(3), 149-156.

Dubey, A., Yadav, P., Verma, P., & Kumar, R. (2022). Investigation of proapoptotic potential of ipomoea carnea leaf extract on breast cancer cell line. Journal of Drug Delivery and Therapeutics, 12(1), 51-55.

Bind, A., Das, S., Singh, V. D., Kumar, R., Chourasia, A., & Saha, P. (2020). Natural bioactives for the potential management of gastric ulceration. Turkish Journal of Physiotherapy and Rehabilitation, 32(3), 221-226.

Umama, Y., Venkatajah, G., Shourabh, R., Kumar, R., Verma, A., Kumar, A., & Gayoor, M. K. (2019). Topic-The scenario of pharmaceuticals and development of microwave as; sisted extraction technique. World J Pharm Pharm Sci, 8(7), 1260-1271.

Daharia, A., Jaiswal, V. K., Royal, K. P., Sharma, H., Joginath, A. K., Kumar, R., & Saha, P. (2022). A Comparative review on ginger and garlic with their pharmacological Action. Asian Journal of Pharmaceutical Research and Development, 10(3), 65-69.

Saha, P. (2020). Evolution of tolbutamide in the treatment of diabetes mellitus. Diabetes, 2(10).

Saha, P., Nyarko, R. O., Lokare, P., Kahwa, I., Boateng, P. O., & Asum, C. (2022). Effect of Covid-19 in Management of Lung Cancer Disease: A Review. Asian Journal of Pharmaceutical Research and Development, 10(3), 58-64.

Nalimu, F., Oloro, J., Kahwa, I., & Ogwang, P. E. (2021). Review on the phytochemistry and toxicological profiles of Aloe vera and Aloe ferox. Future Journal of Pharmaceutical Sciences, 7, 1-21.

Kumar, R., Jangir, D. K., Verma, G., Shekhar, S., Hanpude, P., Kumar, S., ... & Kanti Maiti, T. (2017). S-nitrosylation of UCHL1 induces its structural instability and promotes α-synuclein aggregation. Scientific reports, 7(1), 44558.

Talwar, C., Nagar, S., Kumar, R., Scaria, J., Lal, R., & Negi, R. K. (2020). Defining the environmental adaptations of genus Devosia: insights into its expansive short peptide transport system and positively selected genes. Scientific reports, 10(1), 1151.

Roshan, K. (2020). Priya damwani, Shivam kumar, Adarsh suman, Suthar Usha. An overview on health benefits and risk factor associated with coffee. International Journal Research and Analytical Review, 7(2), 237-249.

Sahana, S. (2020). Purabi saha, Roshan kumar, Pradipta das, Indranil Chatterjee, Prasit Roy, Sk Abdur Rahamat. A Review of the 2019 Corona virus (COVID-19) World Journal of Pharmacy and Pharmaceutical science, 9(9), 2367-2381.

Saha, P., Kumar, R., Nyarko, R. O., Kahwa, I., & Owusu, P. (2021). Herbal Secondary Metabolite For Gastro-Protective Ulcer Activity With Api Structures.

Sahana, S., Kumar, R., Nag, S., Paul, R., Chatterjee, I., & Guha, N. (2020). A Review On Alzheimer Disease And Future Prospects.

Kumar, S., Jangir, D. K., Kumar, R., Kumari, M., Bhavesh, N. S., & Maiti, T. K. (2018). Role of sporadic Parkinson disease associated mutations A18T and A29S in enhanced α-Synuclein fibrillation and cytotoxicity. ACS Chemical Neuroscience, 9(2), 230-240.

Kumar, R., Kumari, R., Kumar, S., Jangir, D. K., & Maiti, T. K. (2018). Extracellular α-synuclein disrupts membrane nanostructure and promotes S-nitrosylation-induced neuronal cell death. Biomacromolecules, 19(4), 1118-1129.

Kumari, R., Kumar, R., Kumar, S., Singh, A. K., Hanpude, P., Jangir, D., & Maiti, T. K. (2020). Amyloid aggregates of the deubiquitinase OTUB1 are neurotoxic, suggesting that they contribute to the development of Parkinson's disease. Journal of Biological Chemistry, 295(11), 3466-3484.

Nyarko, R. O., Kumar, R., Sharma, S., & Chourasia, A. (2022). Ayushmann Roy, and Purabi Saha.". Antibacterial Activity Of Herbal Plant-Tinospora Cordifolia And Catharnthus Roseus, 10-24.

Kumar, R., Saha, P., Kahwa, I., Boateng, E. A., Boateng, P. O., & Nyarko, R. O. (2022). Biological Mode of Action of Phospholipase A and the Signalling and Pro and Anti Inflammatory Cytokines: A Review. Journal of Advances in Medicine and Medical Research, 34(9), 1-10

Singhal, A. K. V., Giri, S., & Kumar, R. (2022). Investigation of in-vitro anti-oxidant & anti-ulcer activity of angiogenesis latifolia roxb (dhava). NeuroQuantology, 20(11), 5680-5686.

Afzaal, M., Saeed, F., Ateeq, H., Akhtar, M. N., Imran, A., Ahmed, A., ... & Awuchi, C. G. (2023). Probiotics encapsulated gastroprotective cross‐linked microgels: Enhanced viability under stressed conditions with dried apple carrier. Food Science & Nutrition, 11(2), 817-827.

Gupta, V., Haider, S., Verma, M., Singhvi, N., Ponnusamy, K., Malik, M. Z., ... & Lal, R. (2021). Comparative genomics and integrated network approach unveiled undirected phylogeny patterns, co-mutational hot spots, functional cross talk, and regulatory interactions in SARS-CoV-2. MSystems, 6(1), 10-1128.

Mishra, A., Singh, Y., Singh, R., Kumar, R., Shukla, S., Prajapati, R. K., ... & Sagar, L. P. (2022). Ethano-pharmacology activity & Antioxidant activity of Centella asiatica Plant Parts. Neuroquantology, 20(11), 7562.

Keshamma, E., Kumar, A., Jha, R., Amle, V. S., Dudhate, G. S., Patel, D., ... & Kumar, R. (2022). Breast cancer treatment relying on herbal bioactive components. Journal for Research in Applied Sciences and Biotechnology, 1(4), 105-115.

Kumar, S., Keshamma, E., Trivedi, U., Janjua, D., Shaw, P., Kumar, R., ... & Saha, P. (2022). A meta analysis of different herbs (leaves, roots, stems) used in treatment of cancer cells. Journal for Research in Applied Sciences and Biotechnology, 1(3), 92-101.

Nyarko, R. O., Prakash, A., Kumar, N., Saha, P., & Kumar, R. (2021). Tuberculosis a globalized disease. Asian Journal of Pharmaceutical Research and Development, 9(1), 198-201.

Kumar, R., Saha, P., Nyarko, R. O., Kahwn, I., Boateng, E. A., Boateng, P. O., ... & Bertram, A. (2021). Role of Cytokines and Vaccines in Break through COVID 19 Infections. Journal of Pharmaceutical Research International, 33(60B), 2544-2549.

Kumar, R., Jain, A., Tripathi, A. K., & Tyagi, S. (2021, January). Covid-19 outbreak: An epidemic analysis using time series prediction model. In 2021 11th international conference on cloud computing, data science & engineering (Confluence) (pp. 1090-1094). IEEE.

Kumar, R., & Dubey, A. (2020). Phytochemical investication and heptoprotective evalution acacia rubica extract isonized and paracetamol indused animal toxicity. Turkish Journal of Physiotherapy and Rehabilitation, 32(3), 65-69.

Nyarko, R. O., Kumar, R., Sharma, S., Chourasia, A., Roy, A., & Saha, P. (2022). Antibacterial Activity of Herbal Plant-Tinospora Cordifolia And Catharnthus Roseus.

Kumar, R., Verma, H., Singhvi, N., Sood, U., Gupta, V., Singh, M., ... & Lal, R. (2020). Comparative genomic analysis of rapidly evolving SARS-CoV-2 reveals mosaic pattern of phylogeographical distribution. Msystems, 5(4), 10-1128.

Raj, A. R. J. E. S. H., Tyagi, S., Kumar, R., Dubey, A., & Hourasia, A. C. (2021). Effect of isoproterenol and thyroxine in herbal drug used as cardiac hypertrophy. Journal of Cardiovascular Disease Research, 204-217.

Purabisaha, R. K., Rawat, S. S. N., & Prakash, A. (2021). A Review On Novel Drug Delivery System.

Choi J., Kim T. H., Choi T. Y., Lee M. S. (2013). Ginseng for health care: a systematic review of randomized controlled trials in Korean literature. PloS One 8 (4), e59978. 10.1371/journal.pone.0059978

Choi E. K., Won Y. H., Kim S. Y., Noh S. O., Park S. H., Jung S. J., et al. (2019). Supplementation with extract of Gynostemma pentaphyllum leaves reduces anxiety in healthy subjects with chronic psychological stress: A randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 52, 198–205. 10.1016/j.phymed.2018.05.002

Chou T. C., Yen M. H., Li C. Y., Ding Y. A. (1998). Alterations of nitric oxide synthase expression with aging and hypertension in rats. Hypertension 31 (2), 643–648. 10.1161/01.hyp.31.2.643

Chu T. T., Benzie I. F., Lam C. W., Fok B. S., Lee K. K., Tomlinson B. (2012). Study of potential cardioprotective effects of Ganoderma lucidum (Lingzhi): results of a controlled human intervention trial. Br. J. Nutr. 107 (7), 1017–1027. 10.1017/s0007114511003795

Chua Y. T., Ang X. L., Zhong X. M., Khoo K. S. (2015). Interaction between warfarin and Chinese herbal medicines. Singapore Med. J. 56 (1), 11–18. 10.11622/smedj.2015004 Cianfrocca C., Pelliccia F., Auriti A., Santini M. (2002). Ginkgo biloba-induced frequent ventricular arrhythmia. Ital. Heart J. 3 (11), 689–691.

Cong W.-n., Tao R.-y., Tian J.-y., Zhao J., Liu Q., Ye F. (2011). EGb761, an extract of Ginkgo biloba leaves, reduces insulin resistance in a high-fat-fed mouse model. Acta Pharm. Sin. B 1 (1), 14–20. 10.1016/j.apsb.2011.04.006

Coon J. T., Ernst E. (2002). Panax ginseng: a systematic review of adverse effects and drug interactions. Drug Saf. 25 (5), 323–344. 10.2165/00002018-200225050-00003

Cooper R. S., Kaufman J. S., Bovet P. (2017). Global Burden of Disease Attributable to Hypertension. JAMA 317 (19), 2017–2018. 10.1001/jama.2017.4213

Couto G. K., Britto L. R., Mill J. G., Rossoni L. V. (2015). Enhanced nitric oxide bioavailability in coronary arteries prevents the onset of heart failure in rats with myocardial infarction. J. Mol. Cell Cardiol. 86, 110–120. 10.1016/j.yjmcc.2015.07.017

Cragg G. M., Newman D. J. (2013). Natural products: a continuing source of novel drug leads. Biochim. Biophys. Acta 1830 (6), 3670–3695. 10.1016/j.bbagen.2013.02.008

uong V. T., Chen W., Shi J., Zhang M., Yang H., Wang N., et al. (2019). The anti-oxidation and anti-aging effects of Ganoderma lucidum in Caenorhabditis elegans. Exp. Gerontol. 117, 99–105. 10.1016/j.exger.2018.11.016

Davies M. J., Gordon J. L., Gearing A. J., Pigott R., Woolf N., Katz D., et al. (1993). The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J. Pathol. 171 (3), 223–229. 10.1002/path.1711710311

Davison E. K., Brimble M. A. (2019). Natural product derived privileged scaffolds in drug discovery. Curr. Opin. Chem. Biol. 52, 1–8. 10.1016/j.cbpa.2018.12.00

DeKosky S. T., Williamson J. D., Fitzpatrick A. L., Kronmal R. A., Ives D. G., Saxton J. A., et al. (2008). Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA 300 (19), 2253–2262. 10.1001/jama.2008.68

Deng Z., Wang Y., Jiang K., Liu X., Wu W., Gao S., et al. (2006). Molecular cloning and characterization of a novel dehydrin gene from Ginkgo biloba. Biosci. Rep. 26 (3), 203–215. 10.1007/s10540-006-9016-x

Deng J., Liu Y., Duan Z., Zhu C., Hui J., Mi Y., et al. (2017). Protopanaxadiol and protopanaxatriol-type saponins ameliorate glucose and lipid metabolism in type 2 diabetes mellitus in high-fat diet/streptozocin-induced mice. Front. Pharmacol. 8, 506. 10.3389/fphar.2017.00506

Diamond B. J., Bailey M. R. (2013). Ginkgo biloba: indications, mechanisms, and safety. Psychiatr. Clin. North Am. 36 (1), 73–83. 10.1016/j.psc.2012.12.006

DiBona G. F. (2013). Sympathetic nervous system and hypertension. Hypertension 61 (3), 556–560. 10.1161/hypertensionaha.111.00633

Dodge H. H., Zitzelberger T., Oken B. S., Howieson D., Kaye J. (2008). A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline. Neurology 70 (19 Pt 2), 1809–1817. 10.1212/01.wnl.0000303814.13509.db

Dokken B. B. (2008). The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond Blood Pressure and Lipids. Diabetes Spectr. 21 (3), 160–165. 10.2337/diaspect.21.3.160

Dong H., Ma J., Li T., Xiao Y., Zheng N., Liu J., et al. (2017). Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng-warfarin interaction. Sci. Rep. 7 (1), 5813. 10.1038/s41598-017-05825-9

Douglas G., Channon K. M. (2014). The pathogenesis of atherosclerosis. Medicine 42 (9), 480–484. 10.1016/j.mpmed.2014.06.011

Dugoua J. J., Mills E., Perri D., Koren G. (2006). Safety and efficacy of ginkgo (Ginkgo biloba) during pregnancy and lactation. Can. J. Clin. Pharmacol. 13 (3), e277–e284.

Egan B. M., Kjeldsen S. E., Grassi G., Esler M., Mancia G. (2019). The global burden of hypertension exceeds 1.4 billion people: should a systolic blood pressure target below 130 become the universal standard? J. Hypertens. 37 (6), 1148–1153. 10.1097/HJH.0000000000002021

Eisenberg D. M., Davis R. B., Ettner S. L., Appel S., Wilkey S., Van Rompay M., et al. (1998). Trends in alternative medicine use in the United States 1990-1997: results of a follow-up national survey. JAMA 280 (18), 1569–1575. 10.1001/jama.280.18.1569

Fabricant D. S., Farnsworth N. R. (2001). The value of plants used in traditional medicine for drug discovery. Environ. Health Perspect. 109 (Suppl 1), 69–75. 10.1289/ehp.01109s169

Fan A. Z., Strine T. W., Jiles R., Mokdad A. H. (2008). Depression and anxiety associated with cardiovascular disease among persons aged 45 years and older in 38 states of the United States 2006. Prev. Med. 46 (5), 445–450. 10.1016/j.ypmed.2008.02.016

Fan X., Zhu M., Chi C., Yu S., Xiong J., Lu Y., et al. (2017). Association of arteriosclerosis and/or atherosclerosis with hypertensive target organ damage in the community-dwelling elderly Chinese: the Northern Shanghai Study. Clin. Interv. Aging 12, 929–936. 10.2147/cia.S133691

Farnsworth N. R., Akerele O., Bingel A. S., Soejarto D. D., Guo Z. (1985). Medicinal plants in therapy. Bull. World Health Organ. 63 (6), 965–981.

Feng Z., Yang X., Zhang L., Ansari I. A., Khan M. S., Han S., et al. (2018). Ginkgolide B ameliorates oxidized low-density lipoprotein-induced endothelial dysfunction via modulating Lectin-like ox-LDL-receptor-1 and NADPH oxidase 4 expression and inflammatory cascades. Phytother. Res. 32 (12), 2417–2427. 10.1002/ptr.6177

Fleming R. M. (2002). The effect of high-, moderate-, and low-fat diets on weight loss and cardiovascular disease risk factors. Prev. Cardiol. 5 (3), 110–118. 10.1111/j.1520-037X.2002.01231.x

Forstermann U., Munzel T. (2006). Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 113 (13), 1708–1714. 10.1161/CIRCULATIONAHA.105.602532

Fox C. S., Pencina M. J., Wilson P. W., Paynter N. P., Vasan R. S., D'Agostino R. B. (2008). Lifetime risk of cardiovascular disease among individuals with and without diabetes stratified by obesity status in the Framingham heart study. Diabetes Care 31 (8), 1582–1584. 10.2337/dc08-002

Franceschi C., Bonafe M., Valensin S., Olivieri F., De Luca M., Ottaviani E., et al. (2000). Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 908, 244–254. 10.1111/j.1749-6632.2000.tb06651.x

Frishman W. H., Beravol P., Carosella C. (2009). Alternative and complementary medicine for preventing and treating cardiovascular disease. Dis. Mon. 55 (3), 121–192. 10.1016/j.disamonth.2008.12.002

Fu Y., Ji L. L. (2003). Chronic ginseng consumption attenuates age-associated oxidative stress in rats. J. Nutr. 133 (11), 3603–3609. 10.1093/jn/133.11.3603

Fulton D. J., Barman S. A. (2016). Clarity on the Isoform-Specific Roles of NADPH Oxidases and NADPH Oxidase-4 in Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 36 (4), 579–581. 10.1161/ATVBAHA.116.307096

Gao Y., Chen G., Dai X., Ye J., Zhou S. (2004). A phase I/II study of ling zhi mushroom Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae) extract in patients with coronary heart disease. Int. J. Med. Mushrooms 6 (4).

Gao S., Liu Z., Li H., Little P. J., Liu P., Xu S. (2012). Cardiovascular actions and therapeutic potential of tanshinone IIA. Atherosclerosis 220 (1), 3–10. 10.1615/IntJMedMushr.v6.i1.20

Gardner C. D., Taylor-Piliae R. E., Kiazand A., Nicholus J., Rigby A. J., Farquhar J. W. (2008). Effect of Ginkgo biloba (EGb 761) on treadmill walking time among adults with peripheral artery disease: a randomized clinical trial. J. Cardiopulm. Rehabil. Prev. 28 (4), 258–265. 10.1097/01.HCR.0000327184.51992.b8

Gauhar R., Hwang S.-L., Jeong S.-S., Kim J.-E., Song H., Park D. C., et al. (2012). Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol. Lett. 34 (9), 1607–1616. 10.1007/s10529-012-0944-1

Gerry C. J., Schreiber S. L. (2018). Chemical probes and drug leads from advances in synthetic planning and methodology. Nat. Rev. Drug Discov. 17 (5), 333–352. 10.1038/nrd.2018.53

Gou S. H., Huang H. F., Chen X. Y., Liu J., He M., Ma Y. Y., et al. (2016). Lipid-lowering, hepatoprotective, and atheroprotective effects of the mixture Hong-Qu and gypenosides in hyperlipidemia with NAFLD rats. J. Chin. Med. Assoc. 79 (3), 111–121. 10.1016/j.jcma.2015.09.002

Gou S. H., Liu B. J., Han X. F., Wang L., Zhong C., Liang S., et al. (2018). Anti-atherosclerotic effect of Fermentum Rubrum and Gynostemma pentaphyllum mixture in high-fat emulsion- and vitamin D3-induced atherosclerotic rats. J. Chin. Med. Assoc. 81 (5), 398–408. 10.1016/j.jcma.2017.08.018

Grosse Y., Loomis D., Lauby-Secretan B., El Ghissassi F., Bouvard V., Benbrahim-Tallaa L., et al. (2013). Carcinogenicity of some drugs and herbal products. Lancet Oncol. 14 (9), 807–808. 10.1016/S1470-2045(13)70329-2

Guerrero-Garcia C., Rubio-Guerra A. F. (2018). Combination therapy in the treatment of hypertension. Drugs Context 7, 212531. 10.7573/dic.212531

Gui Q. F., Xu Z. R., Xu K. Y., Yang Y. M. (2016). The Efficacy of Ginseng-Related Therapies in Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-analysis. Medicine (Baltimore) 95 (6), e2584. 10.1097/MD.0000000000002584

Gurovic M. S. V., Viceconte F. R., Pereyra M. T., Bidegain M. A., Cubitto M. A. (2018). DNA damaging potential of Ganoderma lucidum extracts. J. Ethnopharmacol. 217, 83–88. 10.1016/j.jep.2018.02.005

Harvey A. (2000). Strategies for discovering drugs from previously unexplored natural products. Drug Discovery Today 5 (7), 294–300. 10.1016/S1359-6446(00)01511-7

Hashiguchi M., Ohta Y., Shimizu M., Maruyama J., Mochizuki M. (2015). Meta-analysis of the efficacy and safety of Ginkgo biloba extract for the treatment of dementia. J. Pharm. Health Care Sci. 1, 14. 10.1186/s40780-015-0014-7

He M., Pan H., Chang R. C., So K. F., Brecha N. C., Pu M. (2014). Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage. PloS One 9 (1), e84800. 10.1371/journal.pone.0084800

Heleno S. A., Barros L., Martins A., Queiroz M. J. R., Santos-Buelga C., Ferreira I. (2012). Fruiting body, spores and in vitro produced mycelium of Ganoderma lucidum from Northeast Portugal: A comparative study of the antioxidant potential of phenolic and polysaccharidic extracts. Food Res. Int. 46 (1), 135–140. 10.1016/j.foodres.2011.12.009

Heriansyah T., Nurwidyaningtyas W., Sargowo D., Tjahjono C. T., Wihastuti T. A. (2019). Polysaccharide peptide (PsP) Ganoderma lucidum: a potential inducer for vascular repair in type 2 diabetes mellitus model. Vasc. Health Risk Manage. 15, 419. 10.2147/VHRM.S205996

Hikino H., Konno C., Mirin Y., Hayashi T. (1985). Isolation and Hypoglycemic Activity of Ganoderans A and B, Glycans of Ganoderma lucidum Fruit Bodies1. Planta Med. 51 (4), 339–340. 10.1055/s-2007-969507

Hong S. Y., Kim J. Y., Ahn H. Y., Shin J. H., Kwon O. (2012). Panax ginseng extract rich in ginsenoside protopanaxatriol attenuates blood pressure elevation in spontaneously hypertensive rats by affecting the Akt-dependent phosphorylation of endothelial nitric oxide synthase. J. Agric. Food Chem. 60 (12), 3086–3091. 10.1021/jf20444

Hong J. M., Shin D. H., Lim Y. A., Lee J. S., Joo I. S. (2013). Ticlopidine with Ginkgo Biloba extract: a feasible combination for patients with acute cerebral ischemia. Thromb. Res. 131 (4), e147–e153. 10.1016/j.thromres.2013.01.026

Hori T., Ridge R. W., Tulecke W., Del Tredici P., Tremouillaux-Guiller J., Tobe H. (1997). Ginkgo biloba: a global treasure: from biology to medicine (Japan: Springer; ).

Huang T. H., Li Y., Razmovski-Naumovski V., Tran V. H., Li G. Q., Duke C. C., et al. (2006). Gypenoside XLIX isolated from Gynostemma pentaphyllum inhibits nuclear factor-kappaB activation via a PPAR-alpha-dependent pathway. J. Biomed. Sci. 13 (4), 535–548. 10.1007/s11373-006-9076-8

Huang P., Zhang L., Chai C., Qian X. C., Li W., Li J. S., et al. (2014). Effects of food and gender on the pharmacokinetics of ginkgolides A, B, C and bilobalide in rats after oral dosing with ginkgo terpene lactones extract. J. Pharm. Biomed. Anal. 100, 138–144. 10.1016/j.jpba.2014.07.030

Huang W. C., Chen Y. L., Liu H. C., Wu S. J., Liou C. J. (2018). Ginkgolide C reduced oleic acid-induced lipid accumulation in HepG2 cells. Saudi Pharm. J. 26 (8), 1178–1184. 10.1016/j.jsps.2018.07.006

Huyen V., Phan D., Thang P., Hoa N., Östenson C. (2010). Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients. Horm. Metab. Res. 42 (05), 353–357. 10.1055/s-0030-1248298

Huyen V. T., Phan D. V., Thang P., Ky P. T., Hoa N. K., Ostenson C. G. (2012). Antidiabetic Effects of Add-On Gynostemma pentaphyllum Extract Therapy with Sulfonylureas in Type 2 Diabetic Patients. Evid. Based Complement. Alternat. Med. 2012, 452313. 10.1155/2012/452313

Huyen V., Phan D., Thang P., Hoa N., Östenson C. (2013). Gynostemma pentaphyllum tea improves insulin sensitivity in type 2 diabetic patients. J. Nutr. Metab. 2013, 765383. 10.1155/2013/765383

Hwang S. Y., Son D. J., Kim I. W., Kim D. M., Sohn S. H., Lee J. J., et al. (2008). Korean red ginseng attenuates hypercholesterolemia-enhanced platelet aggregation through suppression of diacylglycerol liberation in high-cholesterol-diet-fed rabbits. Phytother. Res. 22 (6), 778–783. 10.1002/ptr.2363

Isah T. (2015). Rethinking Ginkgo biloba L.: Medicinal uses and conservation. Pharmacogn. Rev. 9 (18), 140–148. 10.4103/0973-7847.162137

Izzo A. A., Ernst E. (2009). Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 69 (13), 1777–1798. 10.2165/11317010-000000000-00000

Jaggy H., Koch E. (1997). Chemistry and biology of alkylphenols from Ginkgo biloba L. Pharmazie 52 (10), 735–738.

Jang S. J., Lim H. J., Lim D. Y. (2011). Inhibitory Effects of Total Ginseng Saponin on Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs. J. Ginseng Res. 35 (2), 176–190. 10.5142/jgr.2011.35.2.176

Jeong Y. Y., Ryu J. H., Shin J. H., Kang M. J., Kang J. R., Han J., et al. (2016). Comparison of Anti-Oxidant and Anti-Inflammatory Effects between Fresh and Aged Black Garlic Extracts. Molecules 21 (4), 430. 10.3390/molecules21040430

Jia Y., Li Z. Y., Zhang H. G., Li H. B., Liu Y., Li X. H. (2010). Panax notoginseng saponins decrease cholesterol ester via up-regulating ATP-binding cassette transporter A1 in foam cells. J. Ethnopharmacol. 132 (1), 297–302. 10.1016/j.jep.2010.08.033

Johansson B. B. (1999). Hypertension mechanisms causing stroke. Clin. Exp. Pharmacol. Physiol. 26 (7), 563–565. 10.1046/j.1440-1681.1999.03081.x

Jovanovski E., Bateman E. A., Bhardwaj J., Fairgrieve C., Mucalo I., Jenkins A. L., et al. (2014). 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. 8 (8), 537–541. 10.1016/j.jash.2014.04.004

Juan Y., Shanzhang Y. (1995). Observation of Effects of Gynostemma Pentaphyllum on Platelet Disaggregation in Human. J. Fujian Med. Univ. (1995) (3), 03.

Kearney P. M., Whelton M., Reynolds K., Muntner P., Whelton P. K., He J. (2005). Global burden of hypertension: analysis of worldwide data. Lancet 365 (9455), 217–223. 10.1016/S0140-6736(05)17741-1

Keilhoff G., Esser T., Titze M., Ebmeyer U., Schild L. (2017). Gynostemma pentaphyllum is neuroprotective in a rat model of cardiopulmonary resuscitation. Exp. Ther. Med. 14 (6), 6034–6046. 10.3892/etm.2017.5315

Keum Y. S., Han S. S., Chun K. S., Park K. K., Park J. H., Lee S. K., et al. (2003). Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat. Res., 523–524, 75-85. 10.1016/s0027-5107(02)00323-8

Kiefer D., Pantuso T. (2003). Panax ginseng. Am. Fam. Physician 68 (8), 1539–1542.

Kim J. H., Han Y. N. (2011). Dammarane-type saponins from Gynostemma pentaphyllum. Phytochemistry 72 (11-12), 1453–1459. 10.1016/j.phytochem.2011.04

Kim S. H., Park K. S. (2003). Effects of Panax ginseng extract on lipid metabolism in humans. Pharmacol. Res. 48 (5), 511–513. 10.1016/S1043-6618(03)00189-0

Kim N. D., Kang S. Y., Kim M. J., Park J. H., Schini-Kerth V. B. (1999. a). The ginsenoside Rg3 evokes endothelium-independent relaxation in rat aortic rings: role of K+ channels. Eur. J. Pharmacol. 367 (1), 51–57. 10.1016/s0014-2999(98)00899-1

Kim N. D., Kang S. Y., Park J. H., Schini-Kerth V. B. (1999. b). Ginsenoside Rg3 mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of K+ channels. Eur. J. Pharmacol. 367 (1), 41–49. 10.1016/s0014-2999(98)00898-x

Kim W. Y., Kim J. M., Han S. B., Lee S. K., Kim N. D., Park M. K., et al. (2000). Steaming of ginseng at high temperature enhances biological activity. J. Nat. Prod. 63 (12), 1702–1704. 10.1021/np990152b

Kim J. H. (2012). Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications. J. Ginseng Res. 36 (1), 16–26. 10.5142/jgr.2012.36.1.16

Kimbel K. H. (1992). Ginkgo biloba. Lancet 340 (8833), 1474. 10.1016/0140-6736(92)92668-6

Kitts D. D., Wijewickreme A. N., Hu C. (2000). Antioxidant properties of a North American ginseng extract. Mol. Cell. Biochem. 203 (1-2), 1–10. 10.1023/a:1007078414639

Kleijnen J., Knipschild P. (1992). Ginkgo biloba. Lancet 340 (8828), 1136–1139. 10.1016/0140-6736(92)93158-j

Klein B. E., Klein R., Lee K. E. (2002). Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam. Diabetes Care 25 (10), 1790–1794. 10.2337/diacare.25.10.1790

Klupp N. L., Chang D., Hawke F., Kiat H., Cao H., Grant S. J., et al. (2015). Ganoderma lucidum mushroom for the treatment of cardiovascular risk factors. Cochrane Database Syst. Rev. (2), CD007259. 10.1002/14651858.CD007259.

Klupp N. L., Kiat H., Bensoussan A., Steiner G. Z., Chang D. H. (2016). A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome. Sci. Rep. 2 (6), 29540.

Komishon A. M., Shishtar E., Ha V., Sievenpiper J. L., de Souza R. J., Jovanovski E., et al. (2016). The effect of ginseng (genus Panax) on blood pressure: a systematic review and meta-analysis of randomized controlled clinical trials. J. Hum. Hypertens. 30 (10), 619–626. 10.1038/jhh.2016.18

Kressmann S., Muller W. E., Blume H. H. (2002). Pharmaceutical quality of different Ginkgo biloba brands. J. Pharm. Pharmacol. 54 (5), 661–669. 10.1211/0022357021778970

Kudolo G. B. (2000). The effect of 3-month ingestion of Ginkgo biloba extract on pancreatic beta-cell function in response to glucose loading in normal glucose tolerant individuals. J. Clin. Pharmacol. 40 (6), 647–654. 10.1002/j.1552-4604.2000.tb05991.x

Kuller L. H., Ives D. G., Fitzpatrick A. L., Carlson M. C., Mercado C., Lopez O. L., et al. (2010). Does Ginkgo biloba reduce the risk of cardiovascular events? Circ. Cardiovasc. Qual. Outcomes 3 (1), 41–47. 10.1161/circoutcomes.109.871640

Kwok Y., Ng K. F., Li C. C., Lam C. C., Man R. Y. (2005). A prospective, randomized, double-blind, placebo-controlled study of the platelet and global hemostatic effects of Ganoderma lucidum (Ling-Zhi) in healthy volunteers. Anesth. Analg. 101 (2), 423–426. 10.1213/01.ANE.0000155286.2046

la Cour B., Molgaard P., Yi Z. (1995). Traditional Chinese medicine in treatment of hyperlipidaemia. J. Ethnopharmacol. 46 (2), 125–129. 10.1016/0378-8741(95)01234-5

Lacour M., Ez-Zaher L., Raymond J. (1991). Plasticity mechanisms in vestibular compensation in the cat are improved by an extract of Ginkgo biloba (EGb 761). Pharmacol. Biochem. Behav. 40 (2), 367–379. 10.1016/0091-3057(91)90568-m

Lakatta E. G., Levy D. (2003). Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease. Circulation 107 (2), 346–354. 10.1161/01.cir.0000048893.62841.f7

Lasukova T. V., Arbuzov A. G., Maslov L. N., Burkova V. N. (2008). [Ganoderma lucidum extract in cardiac diastolic dysfunction and irreversible cardiomyocytic damage in ischemia and reperfusion of the isolated heart]. Patol. Fiziol. Eksp. Ter. (1), 22–25.

Lasukova T., Maslov L., Arbuzov A., Burkova V., Inisheva L. (2015). Cardioprotective activity of Ganoderma lucidum extract during total ischemia and reperfusion of isolated heart. Bull. Exp. Biol. Med. 158 (6), 739–741. 10.1007/s10517-015-2851-7

Lay S., Chiu J.-H., Shiao M.-S., Lui W.-Y., Wu C.-W. (2003). Crude extract of Salvia miltiorrhiza and salvianolic acid B enhance in vitro angiogenesis in murine SVR endothelial cell line. Planta Med. 69 (01), 26–32. 10.1055/s-2003-37034

Le L., Gao X. L., Ding B. X., Yuan B. X. (2007). [Effect of total flaveos of Gymostemma pentaphyllum on protein expression of Fas/FasL genes and TNF-alpha concentration in cultured neonatal rat cardiomyocytes with hypoxia-reoxygenation]. Zhongguo Zhong Yao Za Zhi 32 (18), 1925–1927. Lee C. H., Kim J. H. (2014). A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J. Ginseng Res. 38 (3), 161–166. 10.1016/j.jgr.2014.03.001

Lee W. M., Kim S. D., Park M. H., Cho J. Y., Park H. J., Seo G. S., et al. (2008). Inhibitory mechanisms of dihydroginsenoside Rg3 in platelet aggregation: critical roles of ERK2 and cAMP. J. Pharm. Pharmacol. 60 (11), 1531–1536. 10.1211/jpp/60.11.0015

Lee N. H., Yoo S. R., Kim H. G., Cho J. H., Son C. G. (2012). Safety and tolerability of Panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers. J. Altern. Complement. Med. 18 (11), 1061–1069. 10.1089/acm.2011.0591

Lee H., Choi J., Shin S. S., Yoon M. (2016). Effects of Korean red ginseng (Panax ginseng) on obesity and adipose inflammation in ovariectomized mice. J. Ethnopharmacol. 178, 229–237. 10.1016/j.jep.2015.12.017 [

Lee K. H., Bae I. Y., Park S. I., Park J. D., Lee H. G. (2016). Antihypertensive effect of Korean Red Ginseng by enrichment of ginsenoside Rg3 and arginine-fructose. J. Ginseng Res. 40 (3), 237–244. 10.1016/j.jgr.2015.08.

Lee Y. H., Kim J. H., Song C. H., Jang K. J., Kim C. H., Kang J. S., et al. (2016). Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1. J. Pharmacopuncture 19 (1), 59–69. 10.3831/KPI.2016.19.008

Lee H., Hong Y., Tran Q., Cho H., Kim M., Kim C., et al. (2019. a). A new role for the ginsenoside RG3 in antiaging via mitochondria function in ultraviolet-irradiated human dermal fibroblasts. J. Ginseng Res. 43 (3), 431–441. 10.1016/j.jgr.2018.07

J. I., Kim S. M., Lee J. K., Kim Y. H., et al. (2019. b). Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1. Nutrients 11 (10), 431–441. 10.3390/nu11102475

Li L., Lau B. H. (1993). Protection of vascular endothelial cells from hydrogen peroxide-induced oxidant injury by gypenosides, saponins of Gynostemma pentaphyllum. Phytother. Res. 7 (4), 299–304. 10.1002/ptr.2650070408

Li Y., Lin W., Huang J., Xie Y., Ma W. (2016). Anti-cancer effects of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan). Chin. Med. 11, 43. 10.1186/s13020-016-0114-9

Liang Z., Yuan Z., Li G., Fu F., Shan Y. (2018). Hypolipidemic, antioxidant, and antiapoptotic effects of polysaccharides extracted from Reishi Mushroom, Ganoderma lucidum (Leysser: Fr) Karst, in mice fed a high-fat diet. J. Med. Food 21 (12), 1218–1227. 10.1089/jmf.2018.4182

Liao W. I., Lin Y. Y., Chu S. J., Hsu C. W., Tsai S. H. (2010). Bradyarrhythmia caused by ginseng in a patient with chronic kidney disease. Am. J. Emerg. Med. 28 (4), 538.e535–536. 10.1016/j.ajem.2009.08.006

Lim L. M., Tsai N. C., Lin M. Y., Hwang D. Y., Lin H. Y., Lee J. J., et al. (2016). Hyponatremia is Associated with Fluid Imbalance and Adverse Renal Outcome in Chronic Kidney Disease Patients Treated with Diuretics. Sci. Rep. 6, 36817. 10.1038/srep36817

Lin C. C., Huang P. C., Lin J. M. (2000). Antioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum. Am. J. Chin. Med. 28 (1), 87–96. 10.1142/S0192415X00000118

Lin F. Y., Chen Y. H., Chen Y. L., Wu T. C., Li C. Y., Chen J. W., et al. (2007). Ginkgo biloba extract inhibits endotoxin-induced human aortic smooth muscle cell proliferation via suppression of toll-like receptor 4 expression and NADPH oxidase activation. J. Agric. Food Chem. 55 (5), 1977–1984. 10.1021/jf062945r

Lin M., Wang Y. R., Zhai X. F., Xing S. F., Piao X. L. (2019). [Protective effects of flavonoids from Gynostemma pentaphyllum on oxidative damage in LLC-PK1 cells]. Zhongguo Zhong Yao Za Zhi 44 (6), 1193–1200. 10.19540/j.cnki.cjcmm.20181226.019

Liou C. J., Lai X. Y., Chen Y. L., Wang C. L., Wei C. H., Huang W. C. (2015). Ginkgolide C suppresses adipogenesis in 3T3-L1 adipocytes via the AMPK signaling pathway. Evid. Based Complement. Alternat. Med. 2015, 298635. 10.1155/2015/298635

Liu A. H., Bao Y. M., Wang X. Y., Zhang Z. X. (2013). Cardio-protection by Ginkgo biloba extract 50 in rats with acute myocardial infarction is related to Na(+)-Ca(2)(+) exchanger. Am. J. Chin. Med. 41 (4), 789–800. 10.1142/S0192415X13500535

Liu L., Wu J., Kennedy D. J. (2016). Regulation of Cardiac Remodeling by Cardiac Na(+)/K(+)-ATPase Isoforms. Front. Physiol. 7, 382. 10.3389/fphys.2016.00382

Lu J. M., Weakley S. M., Yang Z., Hu M., Yao Q., Chen C. (2012). Ginsenoside Rb1 directly scavenges hydroxyl radical and hypochlorous acid. Curr. Pharm. Des. 18 (38), 6339–6347. 10.2174/138161212803832254

Luo H. M., Dai R. H., Li Y. (1995). [Nuclear cardiology study on effective ingredients of Astragalus membranaceus in treating heart failure]. Zhongguo Zhong Xi Yi Jie He Za Zhi 15 (12), 707–709.

Ma X., Zhang K., Li H., Han S., Ma Z., Tu P. (2013). Extracts from Astragalus membranaceus limit myocardial cell death and improve cardiac function in a rat model of myocardial ischemia. J. Ethnopharmacol. 149 (3), 720–728. 10.1016/j.jep.2013.07.036

Maguire E. M., Pearce S. W. A., Xiao Q. (2019). Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease. Vascul. Pharmacol. 112, 54–71. 10.1016/j.vph.2018.08.

Mahady G. B., Gyllenhaal C., Fong H. H., Farnsworth N. R. (2000). Ginsengs: a review of safety and efficacy. Nutr. Clin. Care 3 (2), 90–101. 10.1046/j.1523-5408.2000.00020.x

Mahdy H. M., Tadros M. G., Mohamed M. R., Karim A. M., Khalifa A. E. (2011). The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats. Neurochem. Int. 59 (6), 770–778. 10.1016/j.neuint.2011.07.012

Mahmoudian-Sani M. R., Hashemzadeh-Chaleshtori M., Asadi-Samani M., Yang Q. (2017). Ginkgo biloba in the treatment of tinnitus: An updated literature review. Int. Tinnitus J. 21 (1), 58–62. 10.5935/0946-5448.20170011

Malek M. A., Hoang M. H., Jia Y., Lee J. H., Jun H. J., Lee D. H., et al. (2013). Ombuin-3-O-beta-D-glucopyranoside from Gynostemma pentaphyllum is a dual agonistic ligand of peroxisome proliferator-activated receptors alpha and delta/beta. Biochem. Biophys. Res. Commun. 430 (4), 1322–1328. 10.1016/j.bbrc.2012.12.020

Mansour S. M., Bahgat A. K., El-Khatib A. S., Khayyal M. T. (2011). Ginkgo biloba extract (EGb 761) normalizes hypertension in 2K, 1C hypertensive rats: role of antioxidant mechanisms, ACE inhibiting activity and improvement of endothelial dysfunction. Phytomedicine 18 (8-9), 641–647. 10.1016/j.phymed.2011.01.014

Mao X.-q., Yu F., Wang N., Wu Y., Zou F., Wu K., et al. (2009). Hypoglycemic effect of polysaccharide enriched extract of Astragalus membranaceus in diet induced insulin resistant C57BL/6J mice and its potential mechanism. Phytomedicine 16 (5), 416–425. 10.1016/j.phymed.2008.12.011

Martinet W., Coornaert I., Puylaert P., De Meyer G. R. Y. (2019). Macrophage Death as a Pharmacological Target in Atherosclerosis. Front. Pharmacol. 10, 306. 10.3389/fphar.2019.00306

Mashayekh A., Pham D. L., Yousem D. M., Dizon M., Barker P. B., Lin D. D. (2011). Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study. Neuroradiology 53 (3), 185–191. 10.1007/s00234-010-0790-6

Matthews M. K., Jr. (1998). Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 50 (6), 1933–1934. 10.1212/wnl.50.6.1933

Megalli S., Aktan F., Davies N. M., Roufogalis B. D. (2005). Phytopreventative anti-hyperlipidemic effects of Gynostemma pentaphyllum in rats. J. Pharm. Pharm. Sci. 8 (3), 507–515.

Megalli S., Davies N. M., Roufogalis B. D. (2006). Anti-hyperlipidemic and hypoglycemic effects of Gynostemma pentaphyllum in the Zucker fatty rat. J. Pharm. Pharm. Sci. 9 (3), 281–291.

Mehlsen J., Drabaek H., Wiinberg N., Winther K. (2002). Effects of a Ginkgo biloba extract on forearm haemodynamics in healthy volunteers. Clin. Physiol. Funct. Imaging 22 (6), 375–378. 10.1046/j.1475-097X.2002.00445.x

Mei N., Guo X., Ren Z., Kobayashi D., Wada K., Guo L. (2017). Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 35 (1), 1–28. 10.1080/10590501.2016.1278298

Mensah G. A. (2016). Hypertension and Target Organ Damage: Don't Believe Everything You Think! Ethnicity Dis. 26 (3), 275–278. 10.18865/ed.26.3.275

Mesquita T. R. R., de Jesus I. C. G., Dos Santos J. F., de Almeida G. K. M., de Vasconcelos C. M. L., Guatimosim S., et al. (2017). Cardioprotective Action of Ginkgo biloba Extract against Sustained beta-Adrenergic Stimulation Occurs via Activation of M2/NO Pathway. Front. Pharmacol. 8, 220. 10.3389/fphar.2017

Miller M. (2009). Dyslipidemia and cardiovascular risk: the importance of early prevention. QJM 102 (9), 657–667. 10.1093/qjmed/hcp065

Moens A. L., Claeys M. J., Timmermans J. P., Vrints C. J. (2005). Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. Int. J. Cardiol. 100 (2), 179–190. 10.1016/j.ijcard.2004.04.013

Mohammadi H., Hadi A., Kord-Varkaneh H., Arab A., Afshari M., Ferguson A. J. R., et al. (2019). Effects of ginseng supplementation on selected markers of inflammation: A systematic review and meta-analysis. Phytother. Res. 33 (8), 1991–2001. 10.1002/ptr.6399

Mollah M. L., Kim G. S., Moon H. K., Chung S. K., Cheon Y. P., Kim J. K., et al. (2009). Antiobesity effects of wild ginseng (Panax ginseng CA Meyer) mediated by PPAR-γ, GLUT4 and LPL in ob/ob mice. Phytother. Res. 23 (2), 220–225. 10.1002/ptr.2593

Moore K. J., Tabas I. (2011). Macrophages in the pathogenesis of atherosclerosis. Cell 145 (3), 341–355. 10.1016/j.cell.2011.04.005

Morigiwa A., Kitabatake K., Fujimoto Y., Ikekawa N. (1986). Angiotensin converting enzyme-inhibitory triterpenes from Ganoderma lucidum. Chem. Pharm. Bull. 34 (7), 3025–3028. 10.1248/cpb.34.3025

Mozaffarian D., Benjamin E. J., Go A. S., Arnett D. K., Blaha M. J., Cushman M., et al. (2015). Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation 131 (4), e29–322. 10.1161/cir.0000000000000152

Mucalo I., Jovanovski E., Rahelic D., Bozikov V., Romic Z., Vuksan V. (2013). Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension. J. Ethnopharmacol. 150 (1), 148–153. 10.1016/j.jep.2013.08.015

Muller C., Gardemann A., Keilhoff G., Peter D., Wiswedel I., Schild L. (2012). Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract. Phytomedicine 19 (5), 395–401. 10.1016/j.phymed.2011.12.002

Munoz-Durango N., Fuentes C. A., Castillo A. E., Gonzalez-Gomez L. M., Vecchiola A., Fardella C. E., et al. (2016). Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension. Int. J. Mol. Sci. 17 (7), E797. 10.3390/ijms17070797

Muntner P., Carey R. M., Gidding S., Jones D. W., Taler S. J., Wright J. T., Jr., et al. (2018). Potential U.S. Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline. J. Am. Coll. Cardiol. 71 (2), 109–118. 10.1016/j.jacc.2017.10.073

Murthy H. N., Dandin V. S., Park S. Y., Paek K. Y. (2018). Quality, safety and efficacy profiling of ginseng adventitious roots produced in vitro. Appl. Microbiol. Biotechnol. 102 (17), 7309–7317. 10.1007/s00253-018-9188-x

Nadar S. (2011). “Target organ damage in hypertension,” in Hypertension (Oxford Cardiology Library). Eds. Nadar S., Lip G. (London: Oxford University Press;

National Toxicology Program (2013). Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (Gavage studies). Natl. Toxicol. Program Tech. Rep. Ser. (578), 1–183.

NCD Risk Factor Collaboration (NCD-RisC) (2017). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet 389 (10064), 37–55. 10.1016/s0140-6736(16)31919-5

Newman D. J., Cragg G. M. (2016). Natural Products as Sources of New Drugs from 1981 to 2014. J. Nat. Prod. 79 (3), 629–661. 10.1021/acs.jnatprod.5b01055

Ng C., Koon C., Cheung D., Lam M., Leung P., Lau C., et al. (2011). The anti-hypertensive effect of Danshen (Salvia miltiorrhiza) and Gegen (Pueraria lobata) formula in rats and its underlying mechanisms of vasorelaxation. J. Ethnopharmacol. 137 (3), 1366–1372. 10.1016/j.jep.2011.08.006

Nookabkaew S., Rangkadilok N., Satayavivad J. (2006). Determination of trace elements in herbal tea products and their infusions consumed in Thailand. J. Agric. Food Chem. 54 (18), 6939–6944. 10.1021

Noubiap J. J., Nansseu J. R., Nyaga U. F., Sime P. S., Francis I., Bigna J. J.(2019). Global prevalence of resistant hypertension: a meta-analysis of data from 3.2 million patients. Heart 105 (2), 98–105. 10.1136/heartjnl-2018-313599

Oh J., Lee H., Park D., Ahn J., Shin S. S., Yoon M. (2012). Ginseng and its active components ginsenosides inhibit adipogenesis in 3T3-L1 cells by regulating MMP-2 and MMP-9. Evid. Based Complement. Alternat. Med. 2012, 265023. 10.1155/2012/265023

Ojeda D., Jimenez-Ferrer E., Zamilpa A., Herrera-Arellano A., Tortoriello J., Alvarez L. (2010). Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa. J. Ethnopharmacol. 127 (1), 7–10. 10.1016/j.jep.2009.09.059

Omboni S., Volpe M. (2018). Management of arterial hypertension with angiotensin receptor blockers: Current evidence and the role of olmesartan. Cardiovasc. Ther. 36 (6), e12471. 10.1111/1755-5922.12471

Oparil S., Zaman M. A., Calhoun D. A. (2003). Pathogenesis of hypertension. Ann. Intern. Med. 139 (9), 761–776. 10.7326/0003-4819-139-9-200311040-00011

Orekhov A. N., Sobenin I. A., Korneev N. V., Kirichenko T. V., Myasoedova V. A., Melnichenko A. A., et al. (2013). Anti-atherosclerotic therapy based on botanicals. Recent Pat. Cardiovasc. Drug Discov. 8 (1), 56–66. 10.2174/18722083113079990008

Otvos R. A., Still K. B. M., Somsen G. W., Smit A. B., Kool J. (2019). Drug Discovery on Natural Products: From Ion Channels to nAChRs, from Nature to Libraries, from Analytics to Assays. SLAS Discov. 24 (3), 362–385. 10.1177/2472555218822098

Oyama Y., Chikahisa L., Ueha T., Kanemaru K., Noda K. (1996). Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Brain Res. 712 (2), 349–352. 10.1016/0006-8993(95)01440-3

Ozaki M., Kawashima S., Yamashita T., Hirase T., Ohashi Y., Inoue N., et al. (2002). Overexpression of endothelial nitric oxide synthase attenuates cardiac hypertrophy induced by chronic isoproterenol infusion. Circ. J. 66 (9), 851–856. 10.1253/circj.66.851

Paik D. J., Lee C. H. (2015). Review of cases of patient risk associated with ginseng abuse and misuse. J. Ginseng Res. 39 (2), 89–93. 10.1016/j.jgr.2014.11.005

Pan S. Y., Zhou S. F., Gao S. H., Yu Z. L., Zhang S. F., Tang M. K., et al. (2013). New Perspectives on How to Discover Drugs from Herbal Medicines: CAM's Outstanding Contribution to Modern Therapeutics. Evid. Based Complement. Alternat. Med. 2013, 627375. 10.1155/2013/627375

Park M. Y., Lee K. S., Sung M. K. (2005). Effects of dietary mulberry, Korean red ginseng, and banaba on glucose homeostasis in relation to PPAR-alpha, PPAR-gamma, and LPL mRNA expressions. Life Sci. 77 (26), 3344–3354. 10.1016/j.lfs.2005.05.043