INTRODUCTION:

Natural and medicinal plants value in treatment strategies:

Natural sources have been already used for adjunct therapy for most of the diseases from ancient time of medicine due to low cost and easily availability, acceptability by our society¹. Herbal medicines and natural products are extensively used in the developed and developing countries for the primary treatment due to easy accessibility and low cost^2-5.

These natural and herbal products/leads are mostly considered due to the better acceptability from many scientific societies, safety profile, potent, inexpensive, and lesser side effects, due to presence of their potent antioxidants, anti-inflammatory, immunomodulatory activity⁶. In current scenario, there is a great need of development of new therapeutic agent with lesser side effects. This problem can be solved by using plants as source of therapeutic agents.

Natural products and medicinal plants: scope and role in antihypertensive therapy:

Plants based natural products have been popular in human healthcare system since from thousands of the years. Plant extracts and phytopharmaceuticals possess a potential of modulating human metabolism in such a way that prevents chronic and metabolic disorders^7-10. Since last few decades, most of the European and Asian countries depends on dietary supplements and nutraceuticals product due to their fewer side effects and economically fit for adjunct therapy. From long back, plant crude extracts as well as pure molecules are exploited for the hypertension treatment. However, in most cases the expected health benefits are not scientifically proven by rigorous clinical trials^11-12. Hence, it is vital to provide robust scientific evidence for clinical efficacy and safety. Cardiovascular disease is a leading cause of mortality and morbidity in the developed and developing countries including low- and middle-income nations Africa, middle east Europe, India, Malaysia, Indonesia etc. and these countries are depending on low and easily accessible drug source and economically fit for treatment and most people are depends on the conventional source of medicine^13-19.

METHODS:

Materials:

A literature search for articles published in peer-reviewed journal articles based on phytoestrogen and hypertension, as well as electronic database searches using PubMed, Scopus, Science Direct, Google Scholar. Were used to gather the information on various plants based lignans and neolignans that have historically been used for pharmacological based hypertension treatment, ethnomedicinal, phytochemical, and the treatment of other cardiovascular disorders²⁰.

Antihypertensive drugs are exhaustively used for the treatment of hypertension and related cardiovascular diseases but, due to increased risk of adverse side effects of these synthetic or semi-synthetic drugs were used, the preferred adjunct and conventional therapy are herbal or natural products or derivatives, which have been shown least side effects as compared to synthetic drugs available in the market²¹. The huge morbidity and mortality burden related to cardiovascular diseases with no end in sight, there is a high interest in the discovery of novel leads/compounds as well as novel pharmacological targets that might be effective in the primary treatment or adjunct therapy and prevention of cardiovascular and/or metabolic disorders. Although drug discovery from natural or herbal product often requires more efficient compared to High Throughput Screening (HTS) and combinatorial chemistry, nature is still considered as the most productive source of potential drug leads for new medicines for the treatment of major metabolic disorders²². In recent years, it has been observed that most of the herbal remedies and natural products have undisputedly attracted many of the researchers due to the context of prevention or treatment of cardiovascular and metabolic disease²³.

Only for this reason most of the researcher focused on the natural products and it’s derivates used as a good source of medicine from early days of human civilization and most of the compounds are comes out from the natural and plant derived sources and used in the different types of diseases. It has been an important source for drug discovery and play an important role for food as well as nutritional supplements and provide potential health benefits for CVDs. And more than half of FDA-approved drugs are coming from naturally or its derivatives²⁴. And these products are widely accepted and most popular due to their accessibility and economically fit for conventional therapy throughout the world. Dietary nutrients present in foods behave as antioxidants that decrease the oxidative stress through the scavenging of free radicals. Growing evidence suggests that oxidative stress plays a significant role in the pathophysiology of CVD, and therefore natural products play a major role for their prevention and control. Besides antioxidant activity, natural products have other biological properties that lead to a reduced risk of CVD²⁵. The present systemic review on the cardioprotective role of the most used natural products, with the emphasis on epidemiological and clinical studies have been cited in parenthesis^26-29. Medicinal plants have been reported to be useful in hypertension worldwide and have been used empirically as antihypertensive, antidiabetic and antihyperlipidemic^30-35. The most common herbal and phytomolecules used in hypertension therapy which are presented in table no. 1.

Table 1: Natural product and Phytomolecules with their mechanism of action used for antihypertensive activity

Herb	Biol. Activity	Chemical Const.	Mechanism	Antihypertensive Activity
Allium sativum (Garlic)	Anti- Inflammatory, Antioxidant, Antibacterial, Hypocholesteremic, and Anti-Cancer Properties	Garlic’s organo-sulfur constituents such as Allicin, S- allylcysteine (SAC), diallyl disulfides (DADS), diallyl trisulfides (DATS), and methyl thiosulfonate	Increases NO level through activation of eNOS, also inhibits ACE, Significantly Increases H₂S level, and Reduces VCAM-1	In HUVEC cells, Fructose-fed Wistar rats, Rat isolated pulmonary arteries and SD rat aortic rings
Acorus calamus (Sweet Flagor Calamus)	Neuropathic pain, cognitive-enhancing properties, antioxidant	α and β-asarone	Ca²⁺ dependent mechanism	High K⁺ treated rabbit aorta, Normotensive rats
Agelanthusdodoneifolius (Mistletoe)	Antiplasmodial, antimalarial	Dodoneine	Inhibiting carbonic anhydrase and activating calcium-gated potassium (K_Ca) channels, negative ionotropic effect on the rat heart	rat isolated thoracic aorta
Allium cepa (Onion)	Antioxidant, antihypertensive,	Quercetin, quercetin-3-glucoside, isorhamnetin-4-glucoside, organosulfur compounds, allylsulfides	Regulation of extracellular Ca²⁺ levels	Rat mesenteric artery
Alpinia zerumbet (Shel Ginger)	Hypotensive, diuretic and antiulcerogenic properties	5,6-dehydrokawain, dihydro-5,6-dehydrokawain, 8(17),12-labdadiene-15,16-dial (labdadiene)	Inhibition of Ca²⁺ channel	VSMC, DOCA treated hypertensive model, rat thoracic aortic rings
Andrographis paniculata (King of bitter)	Cold, CVDs and fever with anti-bacterial, anti-inflammatory, antioxidant	14-deoxy- 11,12-didehydroandrographolide and 14-deoxyandrographolide	Increases NO level, also inhibited rise in intracellular Ca²⁺ via VDCCs and also reduces ACE level	Isolated rat heart (Langendorff modal) from SD and SHR rats
Apium graveolens (Celery)	Potent antioxidant, antihypertensive	Limonene, sesquiterpenes, β-selinene	Blocking of Ca²⁺ influx via calcium channels (voltage and receptor gated	Rat isolated aortic rings, DOCA induced hypertensive rats
Bidens pilosa L. (Beggar’s tick, black-jack, and broom stick)	Anticancer, Anti-Bacterial, Anti-malarial, Antiinflammatory, and anti-obesity Properties	luteolin (a flavonoid) and ethyl caffeate (ester of hydroxycinnamic acid)	Blockade of intracellular Ca²⁺ channels	KCl-treated rat aorta, SHRs and fructose-fed hypertensive rats
Camellia sinensis (Tea)	Antibacterial, anti-inflammatory, anti-cancer, anti-diabetic, as well as antihypertensive actions	Catechins, the major flavonoids in tea, include (−) – epicatechin (EC), (−)-epicatechin-3-gallate (ECG), (−)- Epigallocatechin (EGC), and (−)-epigallocatechin-3-gallate (EGCG). EGCG constitutes the primary component of tea’s total catechins	Increases flow-mediated vasodilation (FMD), NO level, Inhibition of eNOS uncoupling and blockade of AT₁ receptor	Brachial arteries (elevated cholesterol level and coronary heart disease patients), Healthy male smokers, Diabetic SHR, STZ-fed SD rats
Cassia occidentalis (Coffee weed)	Anti-inflammatory and anti-oxidant	Achrosin, Gallactomannan, aloe-emodin	Inhibition of external Ca²⁺ influx via voltage-dependent channels	In vitro cell (HUVEC),
Coptis chinensis (Goldthread)	Neurodegenerative, anti-atherosclerosis	Berberine, coptisine, epiberberine, berberrubine, palmatine, columbamine	Up regulation of eNOS expression, Decreases EMP and opening of K_ATPchannel and blockade of Ca²⁺ influx	Rat isolated cardiomyocytes (insulin-induced hypertrophy) and Isolated thoracic aorta rings
Crataegus spp. Hawthorns (hawberry or thorn apple)	Expresses numerous bioactive functions including anti- oxidant, anti-inflammatory, and vasorelaxant effects.	flavonoids (hyperoside, quercetin, rutin, and vitexin) and oligomeric proanthocyanidins (OPCs, epicatechin, procyanidin, and procyanidin B-2	Activation of eNOS, ROS, decline concentrations of NF-kB,TNF-α, CAT, SOD	L-NAME induced hypertensive rats, Wistar Rat isolated aortic rings
Crocus sativus (Saffron)	antihypertensive, anticonvulsant, antitussive, antigenototoxic and cytotoxic effects	Saffron’s main components include crocin, picrocrocin, safranal, and crocetin	Potassium channel opener and antagonizing β-adrenoceptors, Activation of eNOS and blockade of Ca²⁺ channels,	ischemia-reperfusion (IR) in rats and Guinea pig Isolated heart, DOCA induced hypertensive model
Cymbopogon citratus (Lemongrass)	Antiinflammatory and antihypertensive, perfume purpose, insecticidal	Citronellol, an acyclic monoterpenoid	Increases NO level and blockade of Ca²⁺ influx through VOCCs, also suppress ROS activity, anti-inflammatory pathways by inhibiting NF-kB and iNOS activity	Isolated aorta from SHR, WKR
Cinnamomum zeylanicum (Cinnamon)	Antioxidant, antimicrobial, antibacterial, anti-candida	cinnamyl acetate, and cinnamyl alcohol, and other volatile substances	NO and K_ATP channels	L-NAME-induced hypertension model, Isolated rat aorta
Gentiana floribunda	antioxidant and antimicrobial	swertiamarin, gentiopicroside, sweroside, isoorientin, and isovitexin	Blocking of Ca²⁺ channels	Isolated rat aorta, L-NAME-induced hypertension model,
Hibiscus sabdariffa (Roselle)	Antiinflammatory, antiproliferative, antihypertensive and antioxidant	neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeoylshikimic acid and flavonoid compounds such as quercetin, kaempferol	Increases NO level, blockade of Ca²⁺ channels, Opening of K_ATP channel, also inhibit cardiac hypertrophy and decrease heart rates in rats and Reduces ACE	SHR isolated aorta, Male Wistar rat thoracic aorta, Stage 1 and 2 hypertensive humans
Nigella sativa (Black Cumin; Seed of Blessing)	Antihypertensive role, black cumin is also effective against diabetes and gastrointestinal diseases	Thymoquinone (TQ), one of the most abundant and bioactive components in seeds	Blockade of Ca²⁺ channels(voltage-gated and ligand-gated), Inhibits the generation of TNF-α and NF-kB	Rat isolated aorta, L-NAME induced hypertensive model,
Panax (Ginseng)	Anti-hypertensive, anti-carcinogenic, anti-proliferative, anti-atherosclerotic and antidiabetic	Heterogeneous triterpenoid saponins and steroid glycosides or ginsenosides (or panaxosides) are the active principle components of ginseng, Ginsenoside Rg3	Increases eNOS via activation of NO, cGMP production, activate Ca²⁺-gated potassium channels	SHR adrenal medulla, VSMC
Salviaemiltiorrhizae (Danshen or red/Chinese sage traditional herbs)	Antioxidative, antiinflammatory, antiproliferative and antihypertensive	salvianolic acid A (SalA), salvianolic acid B (SalB), danshensu, and tanshinones, dihydrotanshinone (lipophilic constituent of danshen)	Increases NO level, Opening of K_ATP channels, Reduces ACE activity, blockade of Ca²⁺ channels, and Inhibits VCAM-1	Rabbit thoracic aortic rings, SHR aorta, Rat and Porcine coronary rings, Isolated Rat heart, HUVEC cells
Zingiber officinale (Ginger)	Antioxidative, antiinflammatory, antiproliferative and antihypertensive	two bioactive constituents of ginger, namely (6)-gingerol and (6)-shogoal, zingerone, another active compound	Ang-II type 1 receptor antagonist, inhibit lipid peroxidation, potently scavenge oxidant molecules, reduces total cholesterol, triglyceride, LDL, and vLDL, but it can also inhibit ACE-1 activity	Rat heart, VSMC

DISCUSSION:

Plant extracts and phytopharmaceuticals possess a potential of modulating human metabolism in such a way that prevents chronic and metabolic disorders. Since last few decades, most of the European and Asian countries depends on dietary supplements and nutraceuticals product due to their fewer side effects and economically fit for adjunct therapy³⁶. From long back, plant crude extracts as well as pure molecules are exploited for the hypertension treatment. However, in most cases the expected health benefits are not scientifically proven by rigorous clinical trials. Hence, it is vital to provide robust scientific evidence for clinical efficacy and safety. Cardiovascular disease is a leading cause of mortality and morbidity in the developed and developing countries including low- and middle-income nations Africa, middle east Europe, India, Malaysia, Indonesia etc. and these countries are depending on low and easily accessible drug source and economically fit for treatment and most people are depends on the conventional source of medicine.

CONCLUSION:

Dietary nutrients present in foods behave as antioxidants that decrease the oxidative stress through the scavenging of free radicals. Growing evidence suggests that oxidative stress plays a significant role in the pathophysiology of CVD, and therefore natural products play a major role for their prevention and control. Besides antioxidant activity, natural products have other biological properties that lead to a reduced risk of CVD. The present systemic review on the cardioprotective role of the most used natural products, with the emphasis on epidemiological and clinical studies have been cited in parenthesis. Medicinal plants have been reported to be useful in hypertension worldwide and have been used empirically as antihypertensive, antidiabetic and antihyperlipidemic.

CONFLICT OF INTEREST:

The author has no conflicts of interest.

ACKNOWLEDGMENTS:

The author would like to thank NCBI, PubMed and Web of Science for the free database services for their kind support during this study.

REFERENCES:

1. World Health Organization. WHO traditional medicine strategy: 2014-2023. World Health Organization, 2013.

2. World Health Organization. WHO global report on traditional and complementary medicine 2019. World Health Organization, 2019.

3. World Health Organization. "The regional strategy for traditional medicine in the Western Pacific (2011-2020)." (2012).

4. World Health Organization. Regional strategy for traditional medicine in the Western Pacific. Manila: WHO Regional Office for the Western Pacific, 2002.

5. Gautam, Y., Dwivedi, S., Srivastava, A., Hamidullah, Singh, A., Chanda, D., Singh, J., Rai, S., Konwar, R., Negi, A.S., 2016. 2-(3′,4′-Dimethoxybenzylidene) tetralone induces anti-breast cancer activity through microtubule stabilization and activation of reactive oxygen species. RSC Adv. 6, 33369–33379.

6. Hamid, A.A., Hasanain, M., Singh, A., Bhukya, B., Omprakash, Vasudev, P.G., Sarkar, J., Chanda, D., Khan, F., Aiyelaagbe, O.O., Negi, A.S., 2014. Synthesis of novel anticancer agents through opening of spiroacetal ring of diosgenin. Steroids 87, 108–118.

7. Hamid, A.A., Kaushal, T., Ashraf, R., Singh, A., Chand Gupta, A., Prakash, O., Sarkar, J., Chanda, D., Bawankule, D.U., Khan, F., Shanker, K., Aiyelaagbe, O.O., Negi, A.S., 2017. (22β,25R)-3β-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway. Steroids 119, 43–52.

8. Jain, S., Singh, A., Khare, P., Chanda, D., Mishra, D., Shanker, K., Karak, T., 2017. Toxicity assessment of Bacopa monnieri L. grown in biochar amended extremely acidic coal mine spoils. Ecological Engineering 108, 211–219.

9. Khwaja, S., Fatima, K., Hasanain, M., Behera, C., Kour, A., Singh, A., Luqman, S., Sarkar, J., Chanda, D., Shanker, K., Gupta, A.K., Mondhe, D.M., Negi, A.S., 2018. Antiproliferative efficacy of curcumin mimics through microtubule destabilization. European Journal of Medicinal Chemistry 151, 51–61.

10. Kumar, B.S., Ravi, K., Verma, A.K., Fatima, K., Hasanain, M., Singh, A., Sarkar, J., Luqman, S., Chanda, D., Negi, A.S., 2017. Synthesis of pharmacologically important naphthoquinones and anticancer activity of 2-benzyllawsone through DNA topoisomerase-II inhibition. Bioorganic & Medicinal Chemistry 25, 1364–1373.

11. Mishra, D., Jyotshna, Singh, A., Chanda, D., Shanker, K., Khare, P., 2019. Potential of di-aldehyde cellulose for sustained release of oxytetracycline: A pharmacokinetic study. International Journal of Biological Macromolecules 136, 97–105.

12. Sathish Kumar, B., Kumar, A., Singh, J., Hasanain, M., Singh, A., Fatima, K., Yadav, D.K., Shukla, V., Luqman, S., Khan, F., Chanda, D., Sarkar, J., Konwar, R., Dwivedi, A., Negi, A.S., 2014a. Synthesis of 2-alkoxy and 2-benzyloxy analogues of estradiol as anti-breast cancer agents through microtubule stabilization. European Journal of Medicinal Chemistry 86, 740–751.

13. Sathish Kumar, B., Singh, Aastha, Kumar, A., Singh, J., Hasanain, M., Singh, Arjun, Masood, N., Yadav, D.K., Konwar, R., Mitra, K., Sarkar, J., Luqman, S., Pal, A., Khan, F., Chanda, D., Negi, A.S., 2014b. Synthesis of neolignans as microtubule stabilisers. Bioorganic & Medicinal Chemistry 22, 1342–1354.

14. Singh, A., Mohanty, I., Singh, J., Rattan, S., 2020. BDNF augments rat internal anal sphincter smooth muscle tone via RhoA/ROCK signaling and nonadrenergic noncholinergic relaxation via increased NO release. American Journal of Physiology-Gastrointestinal and Liver Physiology 318, G23–G33.

15. Singh, A., Rattan, S., 2021. BDNF rescues aging-associated internal anal sphincter dysfunction. American Journal of Physiology-Gastrointestinal and Liver Physiology 321, G87–G97.

16. Singh, A., Singh, J., Rattan, S., 2021. Evidence for the presence and release of BDNF in the neuronal and non‐neuronal structures of the internal anal sphincter. Neurogastroenterology& Motility.

17. Singh, Aastha, Fatima, K., Singh, Arjun, Behl, A., Mintoo, M.J., Hasanain, M., Ashraf, R., Luqman, S., Shanker, K., Mondhe, D.M., Sarkar, J., Chanda, D., Negi, A.S., 2015. Anticancer activity and toxicity profiles of 2-benzylidene indanone lead molecule. European Journal of Pharmaceutical Sciences 76, 57–67.

18. Singh, Aastha, Fatima, K., Srivastava, A., Khwaja, S., Priya, D., Singh, Arjun, Mahajan, G., Alam, S., Saxena, A.K., Mondhe, D.M., Luqman, S., Chanda, D., Khan, F., Negi, A.S., 2016. Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer. Chem Biol Drug Des 88, 625–634.

19. Manmohan, S., Arjun, S., Khan, S. P., Eram, S., &Sachan, N. K., 2012. Green chemistry potential for past, present and future perspectives. International Research Journal of Pharmacy, 3, 31-36.

20. Singh, A., R. Sharma, K. M. Anand, S. P. Khan, and N. K. Sachan. "Food-drug interaction." International Journal of Pharmaceutical & Chemical Science 1, no. 1 (2012): 264-279.

21. Thanh-Hoang, N.-V.; Loc, N.; Nguyet, D.; Thien-Ngan, N.; Khang, T.; Cao, H.; Le, L. Plant Metabolite Databases: From Herbal Medicines to Modern Drug Discovery. J. Chem. Inf. Model. 2020, 60, 1101–1110.

22. Kumar, S.; Malhotra, R.; Kumar, D. Euphorbia hirta: Its chemistry, traditional and medicinal uses, and pharmacological activities. Pharmacogn. Rev. 2010, 4, 58–61.

23. Arjun Singh. A Review of various aspects of the Ethnopharmacological, Phytochemical, Pharmacognostical, and Clinical significance of selected Medicinal plants. Asian Journal of Pharmacy and Technology; 12(4):349-0. doi: 10.52711/2231-5713.2022.00055

24. M. Girija, N. Kokilavani. Effectiveness of Structured Teaching Programme on Knowledge, Attitude and Practice among Patients with Hypertension. Asian J. Nur. Edu. & Research 4(1): Jan.-March 2014; Page 136-139.

25. Devi. S, L N Samaga. Effect of transcendental meditation on stress and blood pressure among patients with systemic hypertension. Asian J. Nur. Edu. and Research 5(1): Jan.-March 2015; Page151-156.

26. Kavitha. T. A Study to Evaluate the Effectiveness of Structured Teaching Program on Modification of Daily Life Patterns Among Hypertensive Clients Attending OPD at Selected Hospital, Bangalore. Asian J. Nur. Edu. and Research 2016; 6(1): 93-95.

27. Preethi Jazna.B, ReetaJebakumari, Nalini JeyavanthaSantha. A Study to Assess the Effectiveness of Benson Relaxation Therapy on Blood Pressure and Stress among Women with Pregnancy Induced Hypertension in Selected Hospitals, Madurai. Asian J. Nur. Edu. and Research. 2016; 6(2): 167-170.

28. John Shine. Effectiveness of Individual Teaching Programme on Knowledge and Practice Regarding Lifestyle Modification Among Patients With Hypertension In Selected Urban Community At Mangalore. Asian J. Nur. Edu. and Research.2017; 7(2): 139-146.

29. Gehan. H.Soliman, Seham Mohamed Abd Elalem, Samah Mohamed Elhomosy. The Effect of Relaxation Techniques on Blood Pressure and Stress among Pregnant Women with Mild Pregnancy Induced Hypertension. Asian J. Nur. Edu. and Research.2017; 7(3): 321-329.

30. Neha Abhishek Sharma. Esophageal Varices: A Case Study. Asian J. Nursing Education and Research. 2020; 10(3): 321-322.

31. G. Kalaiselvi, K. Savithri. Effectiveness of Yoga Therapy on Mild Pregnancy Induced Hypertension. Asian J. Nursing Education and Research. 2021; 11(1):11-14.

32. Mohd. Yaqub Khan, Poonam Gupta, Bipin Bihari, Vikas Kumar Verma. A Review on Diabetes and Its Management. Asian J. Pharm. Res. 3(1): Jan.-Mar. 2013; Page 27-32.

33. Indu Sharma, Bharat Parashar, Hitesh Kumar Dhamija, Ritusharma. An Ayurvedic Arena for Hypertension Treatment. Asian J. Pharm. Res. 2(2): April-June 2012; Page 54-58.

34. Suraj V. Bondre, Rushikesh S. Chavan, Indrayani D. Raut, Shrinivas K. Mohite, Chandrakant S. Magdum. An Overview of Survey on Antihypertensive Drugs. Asian J. Pharm. Res. 2020; 10(3):160-162.

35. Sonam Soni, Pravin Kumar, Vinay Sagar Verma, Mukesh Sharma. Significance of Indian Medicinal Plants used for Treatment of Dementia. Asian J. Res. Pharm. Sci. 4(4): Oct.-Dec. 2014; Page 202-205.

36. Virani Paras, Virani Kinjal. A Review on New Antihypertensive Agent: Irbesartan. Asian J. Res. Pharm. Sci. 6(1): Jan.-Mar., 2016; Page 34-36.

Received on 21.12.2022 Modified on 31.01.2023

Asian J. Nursing Education and Research. 2023; 13(2):162-166.

DOI: 10.52711/2349-2996.2023.00035