Marine-Derived Compounds Applied in Cardiovascular Diseases: Submerged Medicinal Industry

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TL;DR

This review summarizes the cardioprotective potential of marine-derived compounds such as omega-3 fatty acids, xyloketal B, asperlin, and saringosterol for hypertension, atherosclerosis, myocardial infarction, and other cardiovascular diseases. These natural compounds offer advantages over synthetic drugs due to lower toxicity, fewer side effects, and diverse biological activities including antioxidant, anti-inflammatory, and lipid-lowering effects. The paper highlights the need for further mechanistic studies and clinical trials to establish marine drugs as effective therapies for CVDs.

Full summary

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**Background:** Cardiovascular diseases (CVDs) are a leading cause of death globally, accounting for 32% of all deaths (approximately 17.9 million) in 2019, with projections to reach 24 million by 2030. Current synthetic treatments (e.g., ACE inhibitors, beta-blockers, diuretics) are associated with adverse effects such as hypotension, bradycardia, arrhythmia, and electrolyte imbalances. Marine-derived natural compounds offer a promising alternative due to their high safety profile, minimal toxicity, and diverse pharmacological activities. This narrative review focuses on the cardioprotective potential of marine compounds for hypertension, atherosclerosis, myocardial infarction, ischemic heart disease, cardiac stroke, arrhythmia, cardiac dysfunction, and valvular heart disease.

**Methods:** The authors conducted a narrative review of the literature, summarizing findings from in vitro, in vivo, and clinical studies on marine-derived compounds for CVDs. The review covers compounds from marine sources including sponges, tunicates, fish, algae, fungi, and bacteria. Key compounds discussed include omega-3 fatty acids, xyloketal B, asperlin, saringosterol, astaxanthin, fucoxanthin, manzamine A, echinochrome A, tetrodotoxin, botulinum toxin, and zeaxanthin heneicosylate. The review also addresses marine lipid bioactives and the role of reactive oxygen species (ROS) in CVD pathogenesis.

**Key Results:** - **Hypertension:** Marine-derived ACE inhibitory peptides (e.g., FQIN[M(O)]CILR, TGAPCR from *Gracilariopsis lemaneiformis*) significantly reduced systolic and diastolic blood pressure in spontaneously hypertensive rats. Xyloketal B from mangrove fungus decreased blood pressure via the Akt/eNOS pathway. *Spirulina maxima* supplementation reduced systolic blood pressure and improved antioxidant markers in hypertensive patients. - **Atherosclerosis:** Saringosterol from *Sargassum fusiforme* reduced atherosclerotic plaque burden in apoE-deficient mice without liver toxicity. Asperlin from *Aspergillus versicolor* reduced inflammatory cytokines (iNOS, IL-1β, TNF-α) and increased protective cytokines (IL-10, IL-4). Manzamine A from *Acanthostrongylophora ingens* lowered serum total cholesterol, LDL-cholesterol, and triglyceride levels and reduced atherosclerotic lesions in apoE-deficient mice. Astaxanthin reduced total plasma cholesterol and triglycerides and increased LDL receptor expression in apoE(-/-) mice. - **Myocardial Infarction:** Omega-3 polyunsaturated fatty acids (PUFA) and docosahexaenoic acid (DHA) reduced myocardial infarction size in experimental models. Gold nanoparticles synthesized from cyanobacterial extract showed anti-MI activity. - **Ischemic Heart Disease:** Histochrome (echinochrome A) from sea urchins prevented apoptosis in cardiac progenitor cells by downregulating Bax and cleaved caspase-3 and upregulating Bcl-xL and Bcl-2. Alginate from brown seaweed lowered TC, TG, and LDL-C and increased HDL-C. - **Cardiac Stroke:** Fucoxanthin from brown algae and astaxanthin showed protective effects by reducing inflammation and oxidative stress. Xyloketal B protected in a stroke-prone hypertensive model. - **Cardiac Arrhythmia:** Tetrodotoxin from marine sediments and botulinum toxin-chitosan nanoparticles inhibited arrhythmias by blocking sodium, calcium, and potassium channels. Omega-3 fatty acids (EPA and DHA) showed antiarrhythmic effects against various arrhythmic disturbances. - **Cardiac Dysfunction:** Zeaxanthin heneicosylate from *Dunaliella salina* reduced plasma biochemical alterations (AST, ALT, urea, creatinine), pro-inflammatory markers (IL-6, NF-κB, iNOS), and increased SOD in D-galactose-induced cardiac dysfunction rats via retinoid receptor stimulation. - **Valvular Heart Disease:** Fucoxanthin reduced H2O2-induced ROS, DNA damage, and calcification in heart valve interstitial cells and improved left atrium to aortic dimension ratio and E/e' value in dogs.

**Clinical Implications:** Marine-derived compounds show promise as safer alternatives or adjuncts to synthetic drugs for CVDs, with antioxidant, anti-inflammatory, lipid-lowering, and anti-thrombotic properties. However, most evidence comes from preclinical studies; more clinical trials are needed to confirm efficacy and safety in humans. The review emphasizes the need for detailed mechanistic studies and nano-formulation approaches to enhance delivery and reduce side effects. Marine natural products represent a valuable library for developing new therapies that may synergize with standard treatments.