Elsevier

Phytomedicine

Volume 92, November 2021, 153753
Phytomedicine

Herbs and their bioactive ingredients in cardio-protection: Underlying molecular mechanisms and evidences from clinical studies

https://doi.org/10.1016/j.phymed.2021.153753Get rights and content

Abstract

Background

Medicinal plants or herbs produce a bounty of bioactive phytochemicals. These phytochemicals can influence a variety of physiological events related to cardiovascular health through multiple underlying mechanisms, such as their role as antioxidative, anti-ischemic, anti-proliferative, hypotensive, anti-thrombotic, and anti-hypercholesterolemic agents.

Purpose

The purpose of this review is to summarize and connect evidences supporting the use of phytotherapy in the management of some of the most common cardiovascular impairments, molecular mechanisms underlying cardio-protection mediated by herbs, and clinical studies which are positively linked with the use of herbs in cardiovascular biology. Additionally, we also describe several adverse effects associated with some of the herbal plants and their products to provide a balanced set of studies in favor or against phytotherapy in cardiovascular health that may help global discourses on this matter.

Methods

Studies relating to the use of medicinal plants were mined by strategically searching scientific databases including Google Scholar, PubMed and Science Direct. Investigations involving approximately 175 articles including reviews, research articles, meta-analyses, and cross-sectional and observational studies were retrieved and analyzed in line with the stated purpose of this study.

Results

A positive correlation between the use of medicinal plants and cardiovascular health was observed. While maintaining cardiovascular physiology, medicinal plants and their derivatives seem to govern a variety of cellular mechanisms involved in vasoconstriction and vasorelaxation, which in turn, are important aspects of cardiovascular homeostasis. Furthermore, a variety of studies including clinical trials, cross-sectional studies, and meta-analyses have also supported the anti-hypertensive and thus, cardio-protective effects, of medicinal plants. Apart from this, evidence is also available for the potential drawbacks of several herbs and their products indicating that the unsupervised use of many herbs may lead to severe health issues.

Conclusions

The cardio-protective outcomes of medicinal plants and their derivatives are supported by ever-increasing studies, while evidences exist for the potential drawbacks of some of the herbs. A balanced view about the use of medicinal plants and their derivative in cardiovascular biology thus needs to be outlined by researchers and the medical community. The novelty and exhaustiveness of the present manuscript is reflected by the detailed outline of the molecular basis of “herbal cardio-protection”, active involvement of several herbs in ameliorating the cardiovascular status, adverse effects of medicinal plants, and the clinical studies considering the use of phytotherapy, all on a single platform.

Introduction

Cardiovascular diseases (CVDs) are the umbrella of impairments related to the circulatory system. These impairments are responsible for greater than 17 million annual fatalities. Previously, the World Health Organization acknowledged 31% of fatalities related to CVDs. Therefore, it is not an exaggeration to say that CVDs impart a significant global burden on the economy of developing nations worldwide (WHO Fact Sheet, 2017; Kumar et al., 2020a, b). Despite significant advancements in the management of CVDs, they still account for more deaths than claimed collectively by all type of cancers (Mozaffarian et al., 2015). Moreover, the American Heart Association's statistics sheet also estimated that about 50% of the US population suffer from at least one kind of CVD (Benjamin et al., 2019). The broad umbrella of CVDs spans diverse impairments including coronary heart disease, stroke, dyslipidemias, heart attack or myocardial infarction, and heart failure among several others (Fig. 1) (Toth, 2007, Reiner et al., 2019, Dey et al., 2020).

The major cause underlying the onset and progression of most of the CVDs include sedentary life-style habits, obesity, diabetes, smoking, alcoholism, aging, heredity, and certain dietary factors among others (Al-Shehabi et al., 2016). In addition to these, hypertension and vascular dysfunction are also among the prime cause associated with the manifestation of several CVDs. If undiagnosed, hypertension and endothelial dysfunction, may lead to organ damage (Kumar et al., 2020b). Fortunately, hypertension and endothelial dysfunction are reversible and manageable events, that open avenues for a lot of cardiovascular therapies to be discovered (Kumar et al., 2020b). Some of these therapies consider the use of modern-day interventions, which indeed are major life saviors. However, the fact that in their long-term use, they may have a lot of associated complications, cannot be disregarded (Gholami et al., 2008; Shanmugam et al., 2019).

In light of the above, herbs and their products have emerged as an alternative approach to counter the onset and progression of several CVDs. Considering this notion, in this extensive review, we emphasize the role of phytotherapy in combating CVDs. We also discuss the mechanistic insights that allow herbs and their bioactive products to counter CVDs. Additionally, this review also provides glimpses of several in vivo studies and clinical trials relating to the use of herbs or medicinal plants and their adverse effects on a single platform.

Section snippets

Why herbs are preferred?

The concept of complementary and alternative medicines dealing with the use of herbs in the treatment of a variety of CVDs including hypertension, dyslipidemias, and diabetes is gaining global acceptance. There are several reasons that prompted the use of herbal products as therapeutics against CVDs. One of them might just be a belief system, which complements the conventional therapy being used as a primary therapeutic linage in many CVDs (Yeh et al., 2006; Barnes et al., 2008; Brook et al.,

Evidences supporting the use of herbs in the management of CVDs

Since ancient times, medicinal plants and their products have been used in the treatment of patients suffering from angina pectoris, atherosclerosis, arrhythmia, systolic hypertension, and several other CVDs (Mashour et al., 1998; Lu et al., 2018; Fardoun et al., 2020; Ajebli and Eddouks, 2020). For example, some of the most common drugs such are aspirin (derived from Salix alba), reserpine (derived from Rauwolfia serpentina), tetrandrine (derived from Stephania tetradra), and many others, used

In vivo studies supporting the cardio-protective potential of medicinal plants

It is clear that medicinal plants and their products have enormous potential to treat a plethora of diseases (Kumar et al., 2016). The protection against a variety of CVDs governed by medicinal plants is thus not an exception. Indeed, pronounced amount of biological data has established a positive correlation between medicinal plants and cardio-protection (Liperoti et al., 2017). For example, in vivo cardio-protective outcome of intraperitoneally administered total flavonoids of Astragalus

Evidences from clinical trials

The evidences outlined in above sections supportthe cardio-protective potential of herbs and medicinal plants. A variety of clinical trials have also supported the capabilities of medicinal plants in improving the cardiovascular status (Chrysant and Chrysant, 2017). Recently, a group of authors reported cardio-protective effects of saffron. Subjects administered with 500 mg of saffron on daily basis (twice for 2 weeks) demonstrated significant decrement in the viscosity of plasma (

Adverse effects of herbs

The evidence given above clearly support the cardio-protective potential of herbal or medicinal plants and their derivatives. Despite these facts, the benefits of cardio-protective effects of herbs may often hide their damaging outcomes, that sometimes, may exceed the beneficial effects. Herbs and their products indeed have a significant impact on the biological mechanisms involved in cardiovascular biology, but robust clinical studies of their affirmative effects are still to be performed in

Concluding remarks and perspectives

CVDs account for more deaths than any other diseases. Indeed, a plethora of anti-hypertensive therapeutics are available in the market, which certainly reduce cardiovascular mortality. However, their long-term use is often associated with severe adverse effects. In such a scenario, plant-derived products or their derivatives offer ample opportunities in the battle against CVDs including hypertension. Evidences discussed in this review also support the beneficial effects of plant-derived

Authors' contribution

The authors of this manuscript contributed in following ways:

Gaurav Kumar: Conceptualization, data curation, compilation, writing, and drafting the manuscript

Sanjay Kumar Dey: Formal analysis, methodology, editing and proofreading of the manuscript

Suman Kundu: Formal analysis, fund acquisition, methodology, editing, proof reading, language corrections, and critical analysis by giving scientific inputs in the manuscript.

All data were generated in-house, and no paper mill was used. All authors

Funding

SK is grateful to the Department of Biotechnology, Government of India, for financial assistance [BT/PR13531/MED/30/1523/2015, BT/PR8391/BRB/10/1231/2013, BT/01/COE/07/UDSC/2008]. SK appreciates financial support over the years from the University of Delhi (R&D and Institution of Eminence), University Grants Commission, Defense Research and Development Organization and Department of Science and Technology, Government of India. GK acknowledges the Council of Scientific and Industrial Research,

Declaration of Competing Interest

None declared.

Acknowledgment

The authors are thankful to the Department of Biochemistry, University of Delhi, South Campus, New Delhi, India, for providing the necessary facilities to conduct this study. Pixabay is acknowledged for kindly providing the images for graphical abstract. Dharmender Singh is acknowledged for his assistance in the laboratory.

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