# Targeting hypertension through natural phenolics: The multifaceted role of cinnamic acid and its derivatives

**Authors:** Samuel S. P. de Araujo, Brenda L. B. dos Santos, Waldilleny R. A. de Moura, Leonardo G. Rodrigues, Luiz G. S. Branco, Helio C. Salgado, Renato N. Soriano, Marina de T. Durand, João Paulo J. Sabino

PMC · DOI: 10.1007/s00424-026-03163-2 · Pflugers Archiv · 2026-03-26

## TL;DR

This review explores how natural compounds like cinnamic acid and its derivatives may help treat hypertension by reducing inflammation, oxidative stress, and blood pressure.

## Contribution

The paper highlights the antihypertensive, anti-inflammatory, and antioxidant potential of cinnamic acid and its derivatives as promising natural therapeutic agents.

## Key findings

- Cinnamic acid and ferulic acid showed strong angiotensin-converting enzyme inhibition.
- Phenolic acids reduced pro-inflammatory cytokines and increased anti-inflammatory IL-10.
- Cinnamic acid derivatives improved antioxidant markers and scavenged free radicals effectively.

## Abstract

Hypertension is a serious global public health problem that significantly increases the risk of cardiovascular diseases. Its etiology involves inflammatory processes, oxidative stress, and imbalances in blood pressure (BP) regulatory systems. In this context, the search for new therapeutic agents remains a major challenge, highlighting natural compounds such as cinnamic acid (CA) and its derivatives, including caffeic acid (CAF) and ferulic acid (FA). This review aimed to investigate the antihypertensive, anti-inflammatory, and antioxidant potential of CA and its derivatives. The phenolic acids analyzed, particularly CA and FA, exhibited greater inhibitory activity on angiotensin-converting enzyme (ACE), whereas CAF showed lower activity. Furthermore, cinnamic acid and its derivatives increased nitric oxide (NO) production, contributing to vasodilation. Regarding the inflammatory response, studies on phenolic acids demonstrated a reduction in the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α, accompanied by an increase in the anti-inflammatory cytokine IL-10, indicating a relevant anti-inflammatory effect. Similarly, in the antioxidant system, increased levels of superoxide dismutase (SOD) and glutathione (GSH) were observed, along with a reduction in the pro-oxidant marker malondialdehyde (MDA). Additionally, the DPPH and ABTS assays demonstrated greater free radical scavenging activity for CA, CAF, and FA derivatives. Taken together, these findings suggest that phenolic acids are promising candidates for the treatment of hypertension due to their favorable safety profile, with CA standing out as the main compound with hypotensive effects.

## Linked entities

- **Chemicals:** cinnamic acid (PubChem CID 444539), caffeic acid (PubChem CID 689043), ferulic acid (PubChem CID 445858), nitric oxide (PubChem CID 145068), IL-6 (PubChem CID 165368475), IL-8 (PubChem CID 169410440), IL-10 (PubChem CID 146070), glutathione (PubChem CID 124886), malondialdehyde (PubChem CID 10964)

## Full-text entities

- **Genes:** Ren (renin) [NCBI Gene 24715] {aka RATRENAA, RENAA, Ren1}, Prkaa2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 78975] {aka Ampk, Ampka2}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Nppb (natriuretic peptide B) [NCBI Gene 25105] {aka BNP, Bnf}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Nos3 (nitric oxide synthase 3) [NCBI Gene 24600] {aka eNos}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Hmox1 (heme oxygenase 1) [NCBI Gene 24451] {aka HEOXG, Heox, Hmox, Ho-1, Ho1, hsp32}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Caf (caffeine susceptibility) [NCBI Gene 104272], Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 287362] {aka Cias1}, KAT2B (lysine acetyltransferase 2B) [NCBI Gene 8850] {aka CAF, P/CAF, PCAF}, Ache (acetylcholinesterase) [NCBI Gene 83817], Crp (C-reactive protein) [NCBI Gene 25419] {aka Aa1249, Ab1-341, Ab2-196, Ac1-114, Ac1262, Ac2-069}, Agt (angiotensinogen) [NCBI Gene 24179] {aka ANRT, Ang, AngII, PAT}, Keap1 (Kelch-like ECH-associated protein 1) [NCBI Gene 117519] {aka Inrf2}, Map3k5 (mitogen-activated protein kinase kinase kinase 5) [NCBI Gene 365057] {aka Ask1, RGD1306565}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Mapk14 (mitogen activated protein kinase 14) [NCBI Gene 81649] {aka CRK1, CSBP, CSPB1, Csbp1, Csbp2, Exip}, Agt (angiotensinogen) [NCBI Gene 11606] {aka AngI, AngII, Aogen, Serpina8}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], Nos3 (nitric oxide synthase 3, endothelial cell) [NCBI Gene 18127] {aka 2310065A03Rik, Nos-3, eNOS, ecNOS}, Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, Nqo1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 24314] {aka Dia4}, Ace (angiotensin I converting enzyme) [NCBI Gene 24310] {aka CD143, Dcp1, StsRR92}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, Ppard (peroxisome proliferator-activated receptor delta) [NCBI Gene 25682] {aka Pparb}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 24770] {aka MCP-1, MCP1, Scya2, Sigje}, Calm1 (calmodulin 1) [NCBI Gene 24242] {aka CaMI, Calm, Cam1}, Mpo (myeloperoxidase) [NCBI Gene 303413], Bche (butyrylcholinesterase) [NCBI Gene 65036], Tac1 (tachykinin, precursor 1) [NCBI Gene 24806] {aka PPTA3, Ppt5fl, RATPPTA3, TAC}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Gpx1 (glutathione peroxidase 1) [NCBI Gene 24404] {aka GSHPx, GSHPx-1}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}
- **Diseases:** hemolysis (MESH:D006461), metabolic diseases (MESH:D008659), left ventricular hypertrophy (MESH:D017379), AH (MESH:D000081029), cardiac fibrosis (MESH:D005355), Diabetic nephropathy (MESH:D003928), diabetic cardiomyopathy (MESH:D058065), cardiotoxic (MESH:D066126), heart failure (MESH:D006333), infectious (MESH:D003141), hypertrophy (MESH:D006984), Hypertension (MESH:D006973), endothelial dysfunction (MESH:D014652), fatty liver disease (MESH:D005234), Inflammation (MESH:D007249), cardiomyocyte injury (MESH:D014947), insulin resistance (MESH:D007333), cardiac hypertrophy (MESH:D006332), CA (MESH:D011015), kidney injury (MESH:D007674), deaths (MESH:D003643), obese (MESH:D009765), type 2 diabetes (MESH:D003924), non-alcoholic fatty liver disease (MESH:D065626), hypotensive (MESH:D007022), Toxicity (MESH:D064420), cardiovascular and metabolic diseases (MESH:D002318), acute pancreatitis (MESH:D010195), Type I diabetes (MESH:D003922), hepatocellular carcinoma (MESH:D006528), mitochondrial impairment (MESH:D028361), reperfusion (MESH:D015427), diabetes (MESH:D003920), DBP (MESH:D006337), ischemia (MESH:D007511), sympathetic hyperactivity (MESH:D006948), OS (MESH:D000079225)
- **Chemicals:** 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MESH:C022616), p-coumaroyl malate (MESH:C521941), sodium (MESH:D012964), diterpenoids (MESH:D004224), apigenin (MESH:D047310), GSSG (MESH:D019803), orlistat (MESH:D000077403), uric acid (MESH:D014527), ROS (MESH:D017382), rosmarinic acid (MESH:C041376), methanol (MESH:D000432), salt (MESH:D012492), H2O2 (MESH:D006861), olive oil (MESH:D000069463), fructose (MESH:D005632), acetylcholine (MESH:D000109), ethyl acetate (MESH:C007650), GSH (MESH:D005978), ethyl ferulate (MESH:C099085), flavonoids (MESH:D005419), Polyphenols (MESH:D059808), LPS (MESH:D008070), 2,2-diphenyl-1-picrylhydrazyl (MESH:C004931), chicoric acid (MESH:C100435), acrylic acid (MESH:C036658), ascorbic acid (MESH:D001205), carbohydrate (MESH:D002241), MTT (MESH:C070243), p-coumaric acid (MESH:C495469), isoproterenol (MESH:D007545), chlorogenic acid (MESH:D002726), kukoamine A (MESH:C096274), valsartan (MESH:D000068756), NaCl (MESH:D012965), GLUC (MESH:D005947), flavonols (MESH:D044948), quercetin (MESH:D011794), Calcium (MESH:D002118), vanillic acid (MESH:D014641), captopril (MESH:D002216), streptozotocin (MESH:D013311), CA (MESH:C029010), citric acid (MESH:D019343), coumaric acid (MESH:D003373), O2- (-), gallic acid (MESH:D005707), NO (MESH:D009569), Phenolic acids (MESH:C017616), carbon (MESH:D002244), 4-hydroxybenzoic acid (MESH:C038193), anthocyanins (MESH:D000872), Oxygen (MESH:D010100), MDA (MESH:D008315), Thiobarbituric Acid Reactive Substances (MESH:D017392), superoxide (MESH:D013481), Sulfhydryl (MESH:D013438), FA (MESH:C004999), polyamines (MESH:D011073), alloxan (MESH:D000496), syringic acid (MESH:C001945)
- **Species:** Cynara cardunculus (artichoke thistle, species) [taxon 4265], Rattus norvegicus (brown rat, species) [taxon 10116], Ocimum gratissimum (species) [taxon 204144], Malus domestica (apple, species) [taxon 3750], Laetiporus sulphureus (chicken-of-the-woods, species) [taxon 5630], Solanum lycopersicum (tomato, species) [taxon 4081], Cynara cardunculus var. scolymus (artichoke, varietas) [taxon 59895], Morchella elata (species) [taxon 39930], Plectranthus barbatus (species) [taxon 41228], Coprinopsis atramentaria (species) [taxon 71694], Mus musculus (house mouse, species) [taxon 10090], Amaranthus cruentus (blood amaranth, species) [taxon 117272], Salvia rosmarinus (rosemary, species) [taxon 39367], Citrullus colocynthis (alhandal, species) [taxon 252529], Mangifera indica (mango, species) [taxon 29780], Aronia melanocarpa (black chokeberry, species) [taxon 661339], Homo sapiens (human, species) [taxon 9606], Ipomoea batatas (batate, species) [taxon 4120], Thymus vulgaris (common thyme, species) [taxon 49992], Panax ginseng (Asiatic ginseng, species) [taxon 4054], Agaricus bisporus (common mushroom, species) [taxon 5341], Cinnamomum verum (Ceylon cinnamon, species) [taxon 128608]
- **Cell lines:** /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797), CRL-1446 — Homo sapiens (Human), Transformed cell line (CVCL_2H16), L6 — Mus musculus (Mouse), Hybridoma (CVCL_XK50), ATCC HB-8065 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123), H9c2 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0286)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13021695/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC13021695/full.md

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Source: https://tomesphere.com/paper/PMC13021695