Elsevier

Phytomedicine

Volume 95, January 2022, 153859
Phytomedicine

Cardioprotective effects of phytopigments via multiple signaling pathways

https://doi.org/10.1016/j.phymed.2021.153859Get rights and content

Abstract

Background

Cardiovascular diseases (CVDs) are among the deadliest non-communicable diseases, and millions of dollars are spent every year to combat CVDs. Unfortunately, the multifactorial etiology of CVDs complicates the development of efficient therapeutics. Interestingly, phytopigments show significant pleiotropic cardioprotective effects both in vitro and in vivo.

Purpose

This review gives an overview of the cardioprotective effects of phytopigments based on in vitro and in vivo studies as well as clinical trials.

Methods

A literature-based survey was performed to collect the available data on cardioprotective activities of phytopigments via electronic search engines such as PubMed, Google Scholar, and Scopus.

Results

Different classes of phytopigments such as carotenoids, xanthophylls, flavonoids, anthocyanins, anthraquinones alleviate major CVDs (e.g., cardiac hypertrophy, atherosclerosis, hypertension, cardiotoxicities) via acting on signaling pathways related to AMPK, NF-κB, NRF2, PPARs, AKT, TLRs, MAPK, JAK/STAT, NLRP3, TNF-α, and RA.

Conclusion

Phytopigments represent promising candidates to develop novel and effective CVD therapeutics. More randomized, placebo-controlled clinical studies are recommended to establish the clinical efficacy of phytopigments.

Introduction

Cardiovascular diseases (CVDs) are chronic disorders with a high risk of morbidity and mortality. According to the latest reports, the alarming and dismaying fact is that around 17.9 million CVD deaths occurred globally (WHO, 2021). Amidst the corona pandemic and unhealthy situations, a panicking upsurge in CVD deaths could be expected in upcoming years (Askin et al., 2020). The rising cases of CVDs and the devastating side effects of available therapeutics underline the neediness for a novel, potent alleviating medication. However, the perplexing fact is that CVDs develop from more than one factor involving different signaling pathways.

Moreover, CVDs leverage and exhibit imperceptible physiological symptoms. Pathological conditions in CVDs such as inflammation, elevated cholesterol level, cell death, rise in blood pressure are multifaceted and could not be alleviated by one drug alone. Safe and novel alternatives should be established, which can combat this complex pathophysiology of CVDs.

In this scenario, it is worth mentioning that plant therapeutics have recently gained much attention because of their effectiveness, mostly minor side effects, low costs, and eco-friendly nature. The secondary metabolites from plants, specifically pigments, have opened up many natural treatment strategies for ameliorating various health disorders, including CVDs (Anantharaman et al., 2016; Bendokas et al., 2020; Siva et al., 2011). Successive formulations of phytopigments possessing anti-inflammatory, antiapoptotic, antioxidant characters will certainly promote the alleviation of multifaceted CVDs via modulating multiple pathogenic pathways. Prominently, defensive efforts of pigments in cardiovascular health have been corroborated both in vitro and in vivo. Inquests with pigments proved their relieving effects on CVDs such as atherosclerosis, cardiac hypertrophy, myocardial infarction, cardiotoxicity, diabetic cardiomyopathy, stroke via moderating signaling pathways, e.g., nuclear factor (erythroid-derived 2)-like 2 (NRF2), nuclear factor-kappa light chain enhancer in B cells (NF-κB), etc. The cumulating pieces of evidence suggested that plant pigments are promising candidates for developing efficient CVD therapeutics. This review reports the pleiotropic protective effects of phytopigments on various CVDs for the first time. The molecular pathways, in which the phytopigments exert their action along with targeted receptors for attenuating CVDs, are also elaborated in detail. Successful clinical trials employing humans are also critically reviewed to highlight the leeway of using natural pigments in alleviating cardiovascular diseases.

Section snippets

CVDs: The need for novel therapeutics

It is a prerequisite to appraise the risk factors involved in the pathophysiology of CVDs before delving into its types and probable therapeutic strategies. Among the long-established risk factors are smoking, insulin resistance, diabetes, hypertension, obesity, and hyperlipidemia, while age, genetic factors, lifestyle, and a high-fat diet are also attributed to the pathogenesis of CVDs. The risk factors such as susceptible C-reactive protein (CRP), homocysteine, and lipoprotein-α (6) are new

Cardiovascular diseases and alleviating plant pigments

Research on cardiovascular diseases was initiated decades ago. However, we are still in quest for some unanswered queries about therapeutics. Millions of dollars have been used up every year to find a perpetual solution for this chronic disorder. An asymptomatic stage is characteristic of CVDs, which is synonymous with an iceberg immersed in the blue ocean. The severity is experienced, only if the iceberg reaches above the waterline, which requires an extended period. Likely, CVDs commence

Signaling pathways and targeted molecules

The etiology of CVDs is multifactorial. Interestingly, pigments simultaneously target multiple pathways for ameliorating CVDs in most cases. This makes them pertinent and reliable candidates for developing CVD therapeutics. Cell lines (e.g., H9c2 and 3T3-L1 adipocytes) and animal models (e.g., Kunming mice, Wistar mice, and Sprague–Dawley rats) have been extensively employed to unearth the signaling pathways, where pigments exert their action. Phytopigments and their effects on signaling

Clinical trials

Studies were conducted on human subjects to evaluate the cardioprotective effects of carotenoids. Fifty-nine patients with acute coronay syndrome and 34 patients with stable angina (SA) were selected to examine the correlation between plasma carotenoid levels and inflammatory cytokines. Lutein was pinpointed as the most anti-inflammatory carotenoid on comparing α-carotene, β-carotene zeaxanthin, β-cryptoxanthin, and lycopene (Chung et al., 2017). Investigations on CVD patients proved that

Conclusion and perspectives

CVDs are deadly silent killers with an escalating rate of mortality. Many risk factors such as obesity, lifestyle etc. foster the development of CVDs. The limited effectiveness and considerable side effects of chemotherapeutics considerably raised the bar of plant secondary metabolite pigments. Numerous in vitro and in vivo investigations have been performed to substantiate the cardiovascular properties of phytopigments. Pigments ameliorate atherosclerosis, cardiac hypertrophy, myocardial

CRediT authorship contribution statement

Ressin Varghese: Writing – original draft. C. George Priya Doss: Writing – review & editing. Raju Suresh Kumar: Writing – review & editing. Abdulrahman I. Almansour: Writing – review & editing. Natarajan Arumugam: Writing – review & editing. Thomas Efferth: Writing – review & editing. Siva Ramamoorthy: Conceptualization, Supervision.

Declaration of Competing Interest

The authors declare that there is no conflict of interest.

Acknowledgment

RV, CGPD, and SR thank the VIT management for the support and encouragement to carry out this work. RSK, AIA and NA thank for the project supported by Researchers Supporting Project number (RSP-2021/142), King Saud University, Riyadh, Saudi Arabia. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.

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