Nitrates, Glucosinolates, and Cancer Protection

How arugula's high nitrate content supports cardiovascular health and how its unique glucosinolate erucin offers anti-inflammatory and cancer-protective effects

Arugula (Eruca sativa, also called rocket) is a peppery leafy green with a nutritional profile that punches well above its weight. It is one of the highest-nitrate vegetables available — gram for gram, comparable to spinach and beets — which means it supports the body's nitric oxide production, lowering blood pressure and improving circulation [4]. At the same time, arugula contains a distinct glucosinolate called glucoerucin that converts into erucin, an isothiocyanate with well-documented anti-inflammatory and cancer-protective properties [1][2]. A large handful of raw arugula also delivers meaningful vitamin K (about 22% of daily needs per 100g), folate, and the antioxidants lutein and zeaxanthin. As a cruciferous green you can eat raw in salads — unlike broccoli or Brussels sprouts — arugula is one of the easiest ways to get this class of compounds regularly.

The Nitrate-to-Nitric Oxide Pathway

Arugula belongs to the group of vegetables — alongside spinach, beets, celery, and lettuce — with exceptionally high inorganic nitrate content, typically ranging from 100 to 490mg of nitrate per 100g of fresh weight. This nitrate is not inherently active. The conversion chain is:

Dietary nitrate is absorbed in the small intestine and concentrated in saliva
Salivary bacteria reduce nitrate to nitrite (this is why chewing matters and why antibacterial mouthwash can blunt the effect)
Nitrite is swallowed and, in the acidic stomach environment and through enzymatic reduction in blood vessels, converted to nitric oxide (NO)
Nitric oxide relaxes vascular smooth muscle (vasodilation), reduces platelet aggregation, and lowers vascular resistance

This is the same mechanism by which beetroot juice improves exercise performance and lowers blood pressure. A 2020 randomized crossover trial in 30 healthy adults found that a week of nitrate-rich vegetable consumption reduced systolic blood pressure by approximately 5 mmHg and diastolic by approximately 5 mmHg, with plasma nitrate levels reaching 277 ± 134 μmol/L — comparable to dedicated beetroot supplementation [4]. Arugula can be used as a practical, whole-food vehicle for this effect in ways that beetroot juice supplements are not.

For people who cannot swallow pills, have borderline-high blood pressure, or simply want to support cardiovascular health through food, eating arugula regularly provides a meaningful and accessible nitrate source.

Glucoerucin and Erucin: Arugula's Distinctive Glucosinolate

All cruciferous vegetables contain glucosinolates, but different species have different profiles. Broccoli and cauliflower are rich in glucoraphanin (the precursor to sulforaphane), while arugula's dominant glucosinolate is glucoerucin, which converts to erucin via the myrosinase enzyme when plant tissue is disrupted.

Erucin is structurally similar to sulforaphane — both are isothiocyanates — but differs in that it also releases hydrogen sulfide (H2S) as a signaling molecule. H2S is now recognized as an endogenous gasotransmitter in the body (alongside nitric oxide and carbon monoxide), with roles in:

Vascular relaxation and blood pressure regulation
Anti-inflammatory signaling
Cytoprotection in the gut and cardiovascular system
Apoptosis induction in cancer cells at pharmacological concentrations

This dual mechanism — isothiocyanate activity plus H2S release — gives erucin a somewhat distinct pharmacological profile compared to sulforaphane alone.

Key mechanisms of erucin:

Activates the Nrf2 pathway (same as sulforaphane), upregulating antioxidant and detoxification gene expression
Inhibits NF-κB signaling, reducing inflammatory cytokine production (TNF-α, IL-6, IL-1β) [2]
Inhibits COX-2 and iNOS expression (prostaglandin and nitric oxide signaling in inflammation) [2]
Suppresses microtubule dynamics in cancer cells, disrupting cell division [1]
Inhibits ERK1/2 phosphorylation in KRAS-mutant cancer cells [3]

Anti-Inflammatory Effects

A 2013 study examined erucin's effects on both murine macrophages (in vitro) and mouse skin inflammation (in vivo) [2]. When macrophages were stimulated with LPS — a bacterial component that triggers a strong inflammatory response via Toll-like receptor 4 — erucin at 2.5–5 μmol/L significantly reduced nitric oxide and prostaglandin E2 production. It suppressed expression of TNF-α, IL-6, IL-1β, iNOS, and COX-2 while restoring the protective cytokine IL-10.

The molecular mechanism involved blocking the degradation of IκBα and preventing the NF-κB p65 subunit from translocating to the nucleus — the same NF-κB inhibitory mechanism that many plant compounds share, but here specifically activated by erucin.

In the in vivo skin inflammation model, topical erucin application at 100–300 nmol reduced edema significantly compared to control (n=4 animals per group). These findings have relevance not just for cancer biology but for understanding why regular intake of arugula might support the management of chronic low-grade inflammation.

See our Broccoli page and Sulforaphane page for related coverage of the broader cruciferous vegetable and isothiocyanate family.

Cancer Cell Research

Breast cancer: A 2014 study at the University of California, Santa Barbara examined erucin's effects on MCF7 breast cancer cells [1]. Erucin inhibited cell proliferation with an IC50 of 28 μM and induced cell cycle arrest at mitosis at an IC50 of 13 μM. The mechanism was suppression of microtubule dynamics — erucin reduced the rates at which microtubules grew, shortened, and transitioned between these states, and reduced overall dynamicity. Microtubule dynamics are essential for chromosome segregation during cell division; drugs that target this mechanism (taxanes, vinca alkaloids) are established chemotherapy agents. Erucin's mechanism is similar, though its potency and delivery via food versus concentrated drug are not comparable.

Pancreatic cancer: A 2019 study tested erucin on AsPC-1 pancreatic adenocarcinoma cells — a particularly aggressive cell line with a KRAS mutation [3]. Erucin inhibited cell viability, suppressed cancer cell migration, disrupted the cell cycle, and induced apoptosis. The mechanism included inhibition of ERK1/2 phosphorylation, a signaling node frequently activated downstream of mutant KRAS. The researchers also confirmed erucin's role as an H2S donor in this context, suggesting the H2S release contributes to its pro-apoptotic effects in cancer cells.

Neuroprotection: A 2018 study on Eruca sativa seed extract found it protected motor neurons exposed to inflammatory conditions [5]. The extract eliminated COX-2 and NLRP3 inflammasome expression, prevented apoptotic cell death in neurons, and restored IL-10 expression. This extends erucin's anti-inflammatory action into the neurological context.

Nutrition Profile and Preparation

Per 100g raw arugula (approximate):

Calories: 25
Protein: 2.6g
Fiber: 1.6g
Vitamin K: 109mcg (~91% RDA)
Folate: 97mcg (~24% RDA)
Vitamin C: 15mg (~17% RDA)
Calcium: 160mg (~16% RDA)
Nitrates: 100–490mg (highly variable by growing conditions)
Glucoerucin: 30–70mg

For maximum glucosinolate activity:

Eat raw when possible, or only very lightly dressed with acid (lemon, vinegar) — no heat required
Chop or tear before eating and let rest briefly — allows myrosinase to begin conversion
Combining raw arugula with cooked cruciferous vegetables (broccoli, cauliflower) provides active myrosinase from the arugula to supplement conversion from the cooked vegetables, where the enzyme has been denatured by heat

For nitrate benefits:

Avoid antibacterial mouthwash before eating, as it kills the oral bacteria needed to convert nitrate to nitrite
Chew thoroughly to maximize saliva contact
Eating arugula alongside other high-nitrate vegetables (beets, spinach, celery) compounds the effect

Evidence Review

Erucin and Breast Cancer Microtubule Dynamics — Azarenko et al. (2014)

Azarenko O, Jordan MA, and Wilson L published in PLoS One (PMID 24950293) a detailed mechanistic analysis of erucin's effects on MCF7 human breast cancer cell proliferation [1]. The study used live-cell imaging and biochemical assays to characterize how erucin affects microtubule dynamics — the continuous cycles of polymerization and depolymerization that are essential for mitotic spindle function and chromosome segregation.

Erucin suppressed individual parameters of microtubule dynamics: growth rates, shortening rates, the frequencies of transitions between growth and shortening (catastrophes and rescues), and overall dynamicity. IC50 values for proliferation inhibition (28 μM) and mitotic arrest (13 μM) were determined from independent experiments (n=3–4 replicates per condition). The authors noted the similarity to established microtubule-targeting chemotherapy drugs, while acknowledging that clinical concentrations achievable from dietary sources are far lower than those used in culture.

Limitations: In vitro only; MCF7 is a hormone receptor-positive cell line, so findings may not generalize to other breast cancer subtypes; concentrations used in culture (micromolar range) likely exceed plasma erucin levels achievable from food consumption; no animal or human data. Grade: C+ (mechanistically consistent with other isothiocyanates; hypothesis-generating).

Erucin Anti-inflammatory via NF-κB Inhibition — Cho et al. (2013)

Cho HJ, Lee KW, and Park YH published in International Journal of Molecular Sciences (PMID 24132147) a combined in vitro and in vivo study of erucin's anti-inflammatory mechanisms [2]. RAW 264.7 macrophages were used as the in vitro model; LPS-stimulated mouse skin edema was the in vivo model.

In macrophages, erucin reduced LPS-induced nitric oxide production and prostaglandin E2 at 2.5–5 μmol/L, with corresponding reductions in iNOS and COX-2 expression. Western blotting confirmed that erucin prevented IκBα phosphorylation and degradation, thus blocking NF-κB p65 nuclear translocation. Inflammatory cytokines TNF-α, IL-6, and IL-1β were reduced; protective IL-10 was preserved. In mouse skin, 100–300 nmol topical erucin significantly reduced edema versus vehicle control.

Limitations: RAW 264.7 macrophages are a standard but simplified model; topical skin application is mechanistically different from dietary ingestion; small animal group sizes (n=4); no human data. Grade: C+ (specific molecular mechanism identified; relevant signaling pathway; translational relevance unclear).

Erucin and Pancreatic Cancer — Citi et al. (2019)

Citi V et al. published in Phytotherapy Research (PMID 30632211) a study of erucin on AsPC-1 cells — a KRAS-mutant human pancreatic adenocarcinoma cell line representing one of the most treatment-resistant cancer types [3]. The investigators tested multiple biological endpoints: cell viability, migration (scratch assay), cell cycle distribution, and apoptosis.

Erucin reduced AsPC-1 viability at 30–100 μM, suppressed migration, induced G2/M cell cycle arrest, and increased the proportion of apoptotic cells. ERK1/2 phosphorylation — a downstream effector of KRAS oncogenic signaling — was inhibited. The paper also confirmed erucin's activity as an H2S donor and proposed that H2S release contributes independently to its anti-cancer effects alongside the isothiocyanate pharmacophore.

Limitations: Single cell line (KRAS-mutant); no animal model; pharmacological concentrations (30–100 μM) far exceed typical plasma erucin levels from dietary intake; no assessment of erucin bioavailability in the pancreatic microenvironment. Grade: C (mechanistically interesting; KRAS pathway relevance noteworthy; very early-stage evidence).

Nitrate-Rich Vegetables and Blood Pressure — van der Avoort et al. (2020)

Van der Avoort CMT et al. published a randomized crossover trial in the Journal of the Academy of Nutrition and Dietetics (PMID 32386891) in 30 healthy young adults (15 men, 15 women; mean age 24±6 years) [4]. Participants consumed either nitrate-rich vegetables or a low-nitrate control diet for one week each, with a washout period between.

The nitrate intervention increased fasting plasma nitrate to 277 ± 134 μmol/L and significantly elevated plasma nitrite post-meal. Systolic blood pressure was reduced by approximately 5 mmHg and diastolic by approximately 5 mmHg measured approximately 2.5 hours post-meal on day 1 (P<0.05 for both). Effects were most pronounced acutely after consumption rather than as a sustained fasting change, consistent with the nitrate-nitrite-NO pathway's acute dynamics. Blood pressure reductions were comparable in magnitude to those observed in beetroot juice supplementation trials.

Limitations: Small sample (n=30); young healthy adults — effects may differ in older or hypertensive populations; mixed vegetable intervention (not arugula-specific); acute BP reduction rather than long-term hypertension management; no adverse events recorded but population was healthy. Grade: B (well-designed crossover RCT; clinically meaningful BP effect; relevant mechanistic pathway; population generalizability limited).

Eruca Sativa Seed Extract and Neuroinflammation — Gugliandolo et al. (2018)

Gugliandolo A et al. published in Molecular Medicine Reports (PMID 29512782) a laboratory study testing whether Eruca sativa seed extract protects motor neurons from inflammatory damage [5]. Neurons were exposed to inflammatory conditions (LPS stimulation) with and without ESE treatment.

ESE treatment reduced expression of COX-2, TLR4, and the NLRP3 inflammasome — a key innate immune sensing complex implicated in chronic inflammatory conditions. It prevented apoptotic cell death in motor neurons and restored IL-10 levels. The authors proposed that arugula-derived compounds could contribute to neuroprotection by attenuating neuroinflammation through multiple pathways simultaneously.

Limitations: In vitro neuron model; seed extract contains many compounds beyond erucin (including glucosinolates, flavonoids, polyphenols) so attributing effects to any single compound is not possible; no animal or human neurological data. Grade: C (hypothesis-generating; extends anti-inflammatory evidence into neurological context; mechanism not attributed to specific compound).

Overall Evidence Assessment

Cardiovascular/blood pressure via nitrates: Good evidence from a well-designed RCT that nitrate-rich vegetable consumption meaningfully reduces blood pressure in the same magnitude as dedicated beetroot supplementation [4]. Arugula is among the highest-nitrate leafy greens available and provides a practical whole-food delivery vehicle for this effect. Grade: B.

Anti-inflammatory effects (erucin/NF-κB): Consistent molecular evidence across multiple cell systems; specific inhibitory mechanism on IκBα/NF-κB p65 identified; in vivo skin model supports tissue-level effects [2][5]. Translation to systemic human anti-inflammatory benefit from dietary arugula intake is plausible but not yet clinically demonstrated. Grade: C+ to B.

Cancer protection (erucin): Early-stage but mechanistically coherent across multiple cancer types [1][3]. Concentrations used in lab studies exceed what dietary consumption achieves, but the same caveat applies to most food-based cancer research. The H2S-releasing property of erucin is a distinctive pharmacological angle with growing scientific support. Grade: C+ (mechanistic; not clinical).

Nutrient density: Well-established. Among the highest vitamin K, folate, and nitrate content of raw leafy greens, at essentially zero caloric cost. Grade: A.

References

Erucin, the major isothiocyanate in arugula (Eruca sativa), inhibits proliferation of MCF7 tumor cells by suppressing microtubule dynamicsAzarenko O, Jordan MA, Wilson L. PLoS One, 2014. PubMed 24950293 →
Erucin exerts anti-inflammatory properties in murine macrophages and mouse skin: possible mediation through the inhibition of NFκB signalingCho HJ, Lee KW, Park YH. International Journal of Molecular Sciences, 2013. PubMed 24132147 →
Anticancer properties of erucin, an H2S-releasing isothiocyanate, on human pancreatic adenocarcinoma cells (AsPC-1)Citi V, Piragine E, Pagnotta E, Ugolini L, Di Cesare Mannelli L, Testai L, Ghelardini C, Lazzeri L, Calderone V, Martelli A. Phytotherapy Research, 2019. PubMed 30632211 →
A Nitrate-Rich Vegetable Intervention Elevates Plasma Nitrate and Nitrite Concentrations and Reduces Blood Pressure in Healthy Young Adultsvan der Avoort CMT, Jonvik KL, Nyakayiru J, van Loon LJC, Hopman MTE, Verdijk LB. Journal of the Academy of Nutrition and Dietetics, 2020. PubMed 32386891 →
Eruca sativa seed extract: A novel natural product able to counteract neuroinflammationGugliandolo A, Giacoppo S, Ficicchia M, Aliquò A, Bramanti P, Mazzon E. Molecular Medicine Reports, 2018. PubMed 29512782 →