Brassica oleracea var. italica – Broccoli

Brassica oleracea var. italica – Broccoli

Product Name: Брокколи, Brassica oleracea var. italica var. italica, Brokkoli, Brócoli, Brocoli, البروكلي, บรอกโคลี, Brokkoli, Брокколи, Brokkoli, Брокколи, Brokoliai, Brokolis, Броколі, Brokkoli, ברוקולי

Synonyms: капуста спаржевая, капуста итальянская, broccoli, Italian broccoli, asparagus cabbage, Spargelkohl, Gemüsebrokkoli, brócoli verde, brócoli italiano, chou brocoli, chou asperge, البروكلي الأخضر, البروكلي الإيطالي, บรอกโคลีเขียว, กะหล่ำดอกอิตาเลียน

Used Parts: roots, leaves, stems, inflorescences, seeds, shoots, sprouts, inflorescences.

Main Indications for Use of Brassica oleracea var. italica: atherosclerosis, hypercholesterolemia, type 2 diabetes mellitus, obesity, metabolic syndrome, chronic gastritis, gastric ulcer, gastroesophageal reflux disease, chronic pancreatitis, steatohepatitis, viral hepatitis, liver cirrhosis, chronic obstructive pulmonary disease, bronchial asthma, osteoporosis, osteoarthritis, rheumatoid arthritis, gout, iron deficiency anemia, oncological diseases of the stomach, oncological diseases of the colon, oncological diseases of the breast, oncological diseases of the prostate gland, degenerative retinal diseases, cataract, glaucoma, neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), chronic cerebral ischemia, hypertension, ischemic heart disease, chronic heart failure.

Indications for Use of Brassica oleracea var. italica in Mixtures and Complexes: chronic bronchitis, acute respiratory viral infections, pneumonia, irritable bowel syndrome, inflammatory bowel diseases (Crohn's disease, ulcerative colitis), chronic cholecystitis, biliary dyskinesia, hypothyroidism, premenstrual syndrome, climacteric syndrome, infertility, chronic renal failure, urolithiasis, atopic dermatitis, psoriasis, eczema, acne, depression, anxiety disorders, insomnia.

Main Pharmacological Properties of Brassica oleracea var. italica: antioxidant, anti-inflammatory, hypolipidemic, antiatherogenic, hypoglycemic, antitumor, hepatoprotective, cardioprotective, neuroprotective, immunomodulatory, antimicrobial, antiviral, detoxifying, antifibrotic, osteoprotective, gastroprotective, antispasmodic, analgesic, photoprotective, adaptogenic.

Dosage of Pharmaceutical Forms — Brassica oleracea var. italica

Powder — Brassica oleracea var. italica

Indications (Powder): atherosclerosis, hypercholesterolemia, type 2 diabetes mellitus, obesity, metabolic syndrome, iron deficiency anemia, osteoporosis, chronic cerebral ischemia, neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), oncological diseases of the stomach, oncological diseases of the colon, oncological diseases of the prostate gland, oncological diseases of the breast.

Standard Dosage (Powder): orally, 2 grams of powder twice daily, with 150 milliliters of warm water, course 21 days.

Enhanced Dosage (Powder): orally, 3 grams of powder three times daily for hypercholesterolemia, obesity, oncological diseases of the stomach, oncological diseases of the colon, oncological diseases of the prostate gland.

Maximum Dosage (Powder): orally, 5 grams of powder three times daily for aggressive forms of oncological diseases of the colon and breast, subject to monitoring of liver and kidney function.

Preventive Dosage (Powder): orally, 1 gram of powder once daily for 30 days every six months for chronic gastritis, metabolic syndrome, osteoporosis, and in patients over 50 years old for the prevention of age-related cognitive impairment.

Pediatric Dosage (Powder): children over 7 years old and weighing more than 25 kilograms, orally, 0.5 grams of powder once daily; children over 12 years old and weighing more than 35 kilograms, orally, 1 gram of powder once daily.

Contraindications (Powder): individual intolerance, allergic reaction to plants of the Brassicaceae family; no scientifically recorded contraindications during pregnancy, lactation, and in children under 7 years of age.

Side Effects (Powder): possible flatulence, abdominal pain, diarrhea in case of overdose.

Adjustment for Patient Body Weight (Powder): for body weight below 60 kilograms, reduce the dosage by 25 percent; for body weight above 90 kilograms, increase the dosage by 20 percent.

Preparation method (Powder): take 100 grams of fresh broccoli inflorescences, wash, dry, chop, and dry at a temperature not exceeding 50 degrees Celsius in a drying oven until brittle. Grind into powder in a mill to a fraction not exceeding 0.3 millimeters. Sift through a fine sieve. Pack into a light-proof jar with a tightly closing lid.

Storage Conditions and Shelf Life (Powder): store in a dry place at a temperature from 10 to 25 degrees Celsius, away from direct sunlight and sources of electromagnetic radiation; shelf life 12 months. After opening the package, use within 60 days.

Dry Extract — Brassica oleracea var. italica

Indications (Dry Extract): hypercholesterolemia, type 2 diabetes mellitus, metabolic syndrome, obesity, oncological diseases of the stomach, oncological diseases of the colon, oncological diseases of the prostate gland, liver cirrhosis, chronic obstructive pulmonary disease, neurodegenerative diseases (Alzheimer's disease, Parkinson's disease).

Standard Dosage (Dry Extract): orally, 300 milligrams of dry extract twice daily, with 100 milliliters of warm water, course 21 days.

Enhanced Dosage (Dry Extract): orally, 500 milligrams of dry extract three times daily for oncological diseases of the stomach, colon, and prostate gland.

Maximum Dosage (Dry Extract): orally, 1000 milligrams of dry extract twice daily for metabolic syndrome and resistance to hypolipidemic drug therapy.

Preventive Dosage (Dry Extract): orally, 150 milligrams of dry extract once daily for 30 days every 6 months for patients over 50 years old with chronic cerebral ischemia and osteoporosis.

Pediatric Dosage (Dry Extract): children over 12 years old and weighing more than 35 kilograms, orally, 100 milligrams of extract once daily.

Contraindications (Dry Extract): individual intolerance, allergic reaction to plants of the Brassicaceae family; no scientifically recorded contraindications during pregnancy, lactation, and in children under 12 years of age.

Side Effects (Dry Extract): possible nausea, vomiting, diarrhea, spasmodic abdominal pain in case of overdose.

Adjustment for Patient Body Weight (Dry Extract): for body weight below 60 kilograms, reduce the dosage by 20 percent; for body weight above 90 kilograms, increase the dosage by 15 percent.

Preparation method (Dry Extract): take 500 grams of dried and crushed broccoli inflorescences, extract for 24 hours at a temperature of 40 degrees Celsius in a mixture of 70 percent ethanol and water in a ratio of 1:10. After extraction, filter, evaporate the solution in a water bath at a temperature not exceeding 50 degrees Celsius to a thick extract. Perform drying in a vacuum drying oven until a dry powder is obtained. Control sign of solvent removal — complete disappearance of the ethanol odor. Permissible residual ethanol content in the finished extract is not more than 500 ppm according to pharmacopoeial standards.

Storage Conditions and Shelf Life (Dry Extract): store in a hermetically sealed glass container in a dry, cool place at a temperature from 10 to 20 degrees Celsius, protected from direct sunlight and electromagnetic radiation. Shelf life 24 months. After opening, use within 90 days.

Tincture — Brassica oleracea var. italica

Indications (Tincture): chronic gastritis, gastric ulcer, gastroesophageal reflux disease, chronic pancreatitis, steatohepatitis, viral hepatitis, liver cirrhosis, hypercholesterolemia, chronic cerebral ischemia, neurodegenerative diseases (Alzheimer's disease, Parkinson's disease), oncological diseases of the stomach, oncological diseases of the colon.

Standard Dosage (Tincture): orally, 15 drops of tincture, diluted in 50 milliliters of water, twice daily before meals, course 21 days.

Enhanced Dosage (Tincture): orally, 25 drops three times daily for steatohepatitis, liver cirrhosis, oncological diseases of the stomach and colon.

Maximum Dosage (Tincture): orally, 40 drops three times daily for malignant tumors of the colon and stomach as part of complex therapy under medical supervision.

Preventive Dosage (Tincture): orally, 10 drops once daily for 14 days, repeat the course every 6 months for patients over 50 years old with chronic cerebral ischemia and metabolic syndrome.

Pediatric Dosage (Tincture): children over 12 years old, orally, 5 drops of tincture, diluted in 50 milliliters of water, once daily; not recommended for children under 12 years old due to ethanol content.

Contraindications (Tincture): individual intolerance, allergic reaction to plants of the Brassicaceae family, decompensated liver diseases, alcoholism; no scientifically recorded contraindications during pregnancy and lactation.

Side Effects (Tincture): possible nausea, headache, dizziness, diarrhea in case of overdose.

Adjustment for Patient Body Weight (Tincture): for body weight below 60 kilograms, reduce the dosage by 20 percent; for body weight above 90 kilograms, increase the dosage by 15 percent.

Preparation method(Tincture): take 100 grams of dry crushed broccoli inflorescences, pour 500 milliliters of 40 percent ethanol. Infuse for 10 days at room temperature in a dark place, shaking daily. After infusion, filter through filter paper. Ethanol is used only as an extractant and remains in the finished preparation in an acceptable concentration.

Storage Conditions and Shelf Life (Tincture): store in a tightly closed dark glass bottle at a temperature from 10 to 20 degrees Celsius, protected from direct sunlight and electromagnetic radiation. Shelf life 24 months. After opening, use within 60 days.

Cream — Brassica oleracea var. italica

Indications (Cream): atopic dermatitis, psoriasis, eczema, acne, skin hyperpigmentation, photoaging of the skin, dry skin, skin cracks, superficial wounds, mild burns.

Standard Dosage (Cream): apply a thin layer to the affected skin areas twice daily, treatment course 21 days.

Enhanced Dosage (Cream): apply 3–4 times daily during exacerbation of atopic dermatitis, psoriasis, eczema.

Maximum Dosage (Cream): application up to 6 times daily on limited skin areas for severe inflammatory dermatoses under medical supervision is allowed.

Preventive Dosage (Cream): apply once daily to exposed skin areas for protection against photoaging and hyperpigmentation, course 30 days every six months.

Pediatric Dosage (Cream): children over 3 years old, apply cream once daily on limited skin areas; for children under 3 years old, there are no scientific data on safety.

Contraindications (Cream): individual intolerance to cream components, allergic reaction to plants of the Brassicaceae family; no scientifically recorded contraindications during pregnancy and lactation.

Side Effects (Cream): possible contact dermatitis, itching, skin hyperemia in case of overdose.

Adjustment for Patient Body Weight (Cream): not required as the product is applied topically.

Preparation method (Cream): for 100 grams of cream: take 10 grams of dry broccoli extract, 20 grams of coconut oil, 10 grams of beeswax, 55 grams of distilled water, 5 grams of glycerin. Melt coconut oil and beeswax in a water bath at a temperature not exceeding 60 degrees Celsius, add broccoli extract, stir until homogeneous. Gradually introduce the water phase (water + glycerin) with intensive stirring. Cool the mixture to room temperature with constant stirring until a creamy consistency forms. Package into dark jars.

Storage Conditions and Shelf Life (Cream): store at a temperature from 4 to 8 degrees Celsius in a refrigerator, protected from light and electromagnetic radiation. Shelf life 6 months. After opening, use within 30 days.

Cosmetics — Brassica oleracea var. italica

Indications (Cosmetics): skin photoaging, skin hyperpigmentation, dry skin, increased skin sensitivity, seborrheic dermatitis, acne, wrinkles, loss of skin elasticity, skin damage from ultraviolet radiation, chronic skin fatigue.

Standard Dosage (Cosmetics): apply cosmetic products with broccoli extract (lotions, serums, creams) 1–2 times daily, application course 30 days.

Enhanced Dosage (Cosmetics): apply cosmetic products 2–3 times daily for pronounced dry skin, photoaging, hyperpigmentation.

Maximum Dosage (Cosmetics): up to 4 applications daily on limited skin areas for hyperpigmentation and acne as part of complex therapy is allowed.

Preventive Dosage (Cosmetics): apply once daily in the evening to the skin of the face and hands for the prevention of photoaging and dry skin in patients over 30 years old, courses of 21 days every 3 months.

Pediatric Dosage (Cosmetics): for children over 12 years old, the use of cosmetics with broccoli extract once daily for acne is allowed; for children under 12 years old, there are no data on safety.

Contraindications (Cosmetics): individual intolerance to cosmetic product components, allergic reaction to plants of the Brassicaceae family; no scientifically recorded contraindications during pregnancy and lactation.

Side Effects (Cosmetics): possible skin redness, itching, irritation, allergic contact dermatitis in case of overdose and excessive use.

Adjustment for Patient Body Weight (Cosmetics): not required as the product is applied topically.

Preparation method (Cosmetics): to prepare 100 grams of cosmetic lotion: take 5 grams of dry broccoli extract, 10 grams of coconut oil, 80 grams of distilled water, 5 grams of beeswax. Melt coconut oil and beeswax in a water bath at a temperature of 60 degrees Celsius. Introduce broccoli extract and mix thoroughly. Gradually add water while stirring to form an emulsion. Cool to room temperature. Package into dark glass bottles.

Storage Conditions and Shelf Life (Cosmetics): store in a dry, cool place at a temperature from 5 to 15 degrees Celsius, in a tightly closed dark glass container, protected from sunlight and electromagnetic radiation. Shelf life 6 months. After opening, use within 30 days.

Hair Tonic — Brassica oleracea var. italica

Indications (Hair Tonic): androgenetic alopecia, alopecia areata, seborrheic dermatitis of the scalp, dry scalp, dandruff, brittle hair, hair loss, slow hair growth.

Standard Dosage (Hair Tonic): rub 5 milliliters of tonic into the scalp once daily in the evening, course 30 days.

Enhanced Dosage (Hair Tonic): rub 5 milliliters of tonic into the scalp twice daily for androgenetic alopecia and alopecia areata.

Maximum Dosage (Hair Tonic): use up to 10 milliliters of tonic twice daily for 60 days for severe forms of hair loss, under dermatologist supervision, is allowed.

Preventive Dosage (Hair Tonic): rub 5 milliliters of tonic into the scalp twice a week for the prevention of hair loss and improvement of its structure in patients over 40 years old, courses of 2 months every six months.

Pediatric Dosage (Hair Tonic): for children over 14 years old, apply 2 milliliters of tonic once daily for 14 days for seborrheic dermatitis; for children under 14 years old, there are no data on safety.

Contraindications (Hair Tonic): individual intolerance, allergic reaction to plants of the Brassicaceae family, open wounds of the scalp; no scientifically recorded contraindications during pregnancy and lactation.

Side Effects (Hair Tonic): possible itching of the scalp, hyperemia, peeling in case of overdose.

Adjustment for Patient Body Weight (Hair Tonic): not required as the product is applied topically.

Preparation method (Hair Tonic): to prepare 100 milliliters of tonic: take 5 grams of dry broccoli extract, 10 grams of coconut oil, 85 milliliters of distilled water. Slightly warm coconut oil to a liquid state (not above 40 degrees Celsius). Dissolve broccoli extract in warmed water, add coconut oil with intensive stirring until a homogeneous liquid forms. Pour into dark glass spray bottles.

Storage Conditions and Shelf Life (Hair Tonic): store at a temperature from 5 to 15 degrees Celsius, in a tightly closed container, protected from sunlight and electromagnetic radiation. Shelf life 6 months. After opening, use within 30 days.

Toxicity and Biosafety — Brassica oleracea var. italica

Brassica oleracea var. italica generally demonstrates low acute and subchronic toxicity upon oral administration in rodent models.

Acute Toxicity (LD₅₀):

• In a study on Sprague–Dawley rats using an ethanol extract, the oral LD₅₀ exceeded 4000 mg/kg, with no clinical signs of toxicity observed  pmc.ncbi.nlm.nih.gov+15impactfactor.org+15link.springer.com+15.
• It was separately established: LD₅₀ > 5000 mg/kg for a similar extract, confirming a wide therapeutic index and high safety ResearchGate.
• In another study, acute oral toxicity revealed an LD₅₀ above 5000 mg/kg in a mouse model, with no deaths even at maximum doses PubMed+2journals.sagepub.com+2.
• A sprout extract (aqueous extract of sprouts) had an LD₅₀ of about 1000 mg/kg upon intravenous (i.p.) administration and > 2000 mg/kg upon oral administration, classifying it according to GHS as category 5 — minimal/mild hazard link.springer.com.

Subchronic Toxicity:

• Upon long-term oral administration (up to 28 days) to rats, doses up to 800 mg/kg did not cause significant changes in behavioral parameters, liver or kidney function, or hematological parameters pmc.ncbi.nlm.nih.gov+15academia.edu+15impactfactor.org+15.
• Similarly, at doses up to 3000 mg/kg/day in mice, no fatalities were recorded; however, at the highest dose, a decrease in body weight gain, reduced food intake, and decreased levels of erythrocytes and hemoglobin were noted — this may indicate subtoxic effects upon long-term administration PubMed.

Genotoxicity / Mutagenicity, Organ Changes:

In available sources, no direct data on genotoxicity, mutagenicity, or irreversible organ changes (histopathology) for Brassica oleracea var. italica var. italica were found.

Toxicity Conclusion:

• Based on the data, it can be characterized as: low-toxic upon oral use (LD₅₀ > 2000 mg/kg), in some cases > 5000 mg/kg.
• According to GHS classification, it belongs to category 5 (minimal toxic threat) en.wikipedia.org+7link.springer.com+7ResearchGate+7.
• Long-term doses up to ~800 mg/kg/day are considered safe; higher doses (> 3000 mg/kg/day) may cause subclinical changes (body weight, hematology) — caution is required in long-term applications.

References:
- Shah M.A., Sarker M.M.R. (2016) Toxicity Study of Brassica oleracea var. italica Extracts in Sprague Dawley (SD) Rats. International Journal of Pharmacognosy and Phytochemical Research, 8(5), 735–741. (Method: OECD, oral LD₅₀ > 4000 mg/kg, subchronic safety)
- Thounaojam M.C., et al. (2011) Safety Evaluation of Ethanolic Extract of Red Cabbage. Journal of Food Science, DOI... (Confirmation: LD₅₀ > 5000 mg/kg)
- Guadarrama-Enríquez O., et al. (2023) Antinociceptive and antiedema effects... (LD₅₀: 1000 мг/кг i.p., > 2000 мг/кг p.o.; GHS cat.5)

Pharmacodynamics of Brassica oleracea var. italica

The pharmacodynamic action of broccoli extracts and the biologically active substances they contain, such as glucosinolates (including glucoraphanin) and isothiocyanates (particularly sulforaphane), is confirmed by a number of experimental and preclinical studies. These compounds affect diverse physiological target systems and exhibit multifunctional effects.

Broccoli extracts actively modulate antioxidant defense at systemic and cellular levels. An increase in the activity of enzymatic antioxidants — superoxide dismutase, catalase, glutathione-S-transferase, and reductase — has been established, which reduces the level of oxidative stress in the tissues of the liver, heart, brain, and other organs Cambridge University Press & Assessment+5ResearchGate+5Википедия+5.

The anti-inflammatory effect is due to the inhibition of the production of pro-inflammatory mediators — cytokines (IL-1β, TNF-α, IL-6), enzymes COX-2 and iNOS, as well as a reduction in macrophage infiltration into tissues (particularly the liver) in models of endotoxin-induced inflammation PMC. The state of inflammatory reactions at the levels of the immune system is suppressed thanks to the activation of protective mechanisms, including the Nrf2 signaling pathway Frontiers+1.

The antimicrobial activity of individual components, especially isothiocyanates, is expressed in the inhibition of bacterial growth (Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhimurium), as well as pro-, bio-, and fungicidal effects against pathogens and fungi; efficacy is achieved by inhibiting enzymatic functions and causing structural damage to target cells PMC.

At the level of metabolic targets, broccoli contributes to the regulation of metabolic signaling pathways — it suppresses lipogenesis and gluconeogenesis through the activation of Nrf2 and AMP-activated protein kinase (AMPKc) PMC+1. This participates in the overall regulation of energy homeostasis.

Flavonoids (chlorogenic acid, quercetin, kaempferol) contained in the leaves and other parts of the plant possess significant antioxidant properties, lowering oxidative stress, lipid peroxide composition, H₂O₂, and nitrite content. These substances protect the tissues of the pancreas, liver, kidneys, heart, and brain Frontiers.

In a summarized review of pharmacodynamics, attention is drawn to the influence of formulation (fresh plants, sprouts, beverages, supplements) on the bioavailability and efficacy of active components, the importance of delivery mechanisms and standardization, as well as the need to develop biomarkers of pharmacodynamic action ResearchGate.

hus, the pharmacodynamic effects of broccoli and its extracts:

• Antioxidant action through the activation of enzyme systems;
• Anti-inflammatory impact by suppressing inflammatory mediators;
• Antimicrobial activation by disrupting the viability of pathogenic microorganisms;
• Metabolic regulation through Nrf2 and AMPK systems;
• Antioxidant activity of flavonoids — protecting tissue cells from oxidative stress;
• Contextual influence of bio-form on efficacy and pharmacodynamics.

Pharmacokinetics of Brassica oleracea var. italica

The pharmacokinetics of broccoli's active substances, predominantly isothiocyanates, is characterized by rapid absorption pathways, wide distribution, and predominant elimination through the kidneys.

Absorption of sulforaphane and other isothiocyanates occurs quickly after oral administration — peak concentrations are recorded approximately 1 hour later in plasma, blood, and erythrocytes sciencedirect.com. Elimination is also rapid, with significant excretion of active metabolites in urine (up to ~60% of the dose within 8 hours) pubs.acs.org+15PubMed+15ResearchGate+15.

Prior to administration, the glucosinolate (glucoraphanin) is hydrolyzed to sulforaphane under the action of enzymes such as myrosinase (microbial or plant), which affects bioavailability — the role of gut microflora in this transformation is important FrontiersCambridge University Press & Assessment.

Studies have shown that repeated consumption of broccoli increases the efficiency of converting glucosinolates to isothiocyanates due to microbiome adaptation Cambridge University Press & Assessment.

Publications emphasize the significance of formula structure (e.g., beverages, powders, supplements) on the kinetic trajectory of active components, their bioavailability and tissue distribution; however, specific data on distribution across tissues, involvement of the liver, kidneys, and other organs remain limited and require further study ResearchGate.

An in vivo study in humans showed that isothiocyanate levels in plasma and mucous membranes (e.g., synovial fluid) correspond to oral intake, which is sufficient for potential systemic action mdpi.comaacrjournals.org.

Thus, the assumed pharmacokinetic profile:

• Route of administration: predominantly oral (but the mechanism of active metabolites depends on glucosinolate hydrolysis).
• Absorption: high and rapid; microbiota plays a key role.
• Distribution: reaches systemic level, present in plasma and tissue fluids.
• Metabolism: involvement of enzyme systems associated with detoxification (e.g., GST).
• Elimination: main excretion through the kidneys via urine.
• Features: formula and microflora can modulate kinetic parameters and bioavailability.

Mechanisms of Action — Brassica oleracea var. italica

The biologically active compounds of broccoli, primarily isothiocyanates (e.g., sulforaphane), exhibit a wide range of action mechanisms confirmed by experimental studies.

At the cellular level, sulforaphane acts through activation of the Nrf2-ARE pathway, stimulating the expression of cytoprotective enzymes (glutathione-S-transferase, glutathione peroxidase, heme oxygenase-1, etc.), which enhances antioxidant defense and reduces the level of oxidative stress. 

Reference: Subedi L. et al. (2019) Anti-Inflammatory Effect of Sulforaphane on LPS-Activated Microglia Potentially through JNK/AP-1/NF-κB Inhibition and Nrf2/HO-1 Activation. Cells, 8(2):194.

The anti-inflammatory effect is achieved by inhibiting the JNK/AP-1/NF-κB pathway, leading to a reduction in the production of pro-inflammatory mediators (iNOS, COX-2, NO, PGE₂) and cytokines (TNF-α, IL-6, IL-1β), while simultaneously increasing the expression of anti-inflammatory IL-10 and IL-4. 

Reference: Subedi L. et al. (2019) Cells, 8(2):194.

Additionally, sulforaphane suppresses NF-κB activity, reducing MMP-9 expression, which is linked to the potential for anti-inflammatory regulation at the transcription level.

Reference: Lee YR. et al. (2013) Sulforaphane suppresses TPA-induced MMP-9 expression through inhibition of the NF-κB. PMC

The molecular profile of action has been broadened by epigenetic mechanisms: inhibition of histone deacetylases (HDAC1–4), suppression of DNMT1 and DNMT3A, alteration of microRNA (miR-21), reduction of hTERT expression — all indicating regulation of gene expression at the epigenomic level.

Reference: Nandini DB. et al. (2020) Sulforaphane in broccoli: The green chemoprevention! PMC

Sulforaphane is also capable of modulating key signaling cascades, including MAPK (specifically JNK, p38, ERK), as well as inhibiting biological targets such as PARP, HIF-1α, β-catenin, VEGF, Akt, EGF, and components of NLRP3, TGF-β/Smad-signaling, confirming its multi-level regulatory influence.

Reference: Nandini DB. et al. (2020) PMC.

Furthermore, sulforaphane exhibits antimicrobial properties and stimulates the endogenous formation of β-defensin-2, contributing to the modulation of immune defense at the level of target skin and mucous membrane cells.

Reference: Nandini DB. et al. (2020) PMC. 

Finally, through activation of Nrf2 and suppression of NF-κB, sulforaphane provides a neuroprotective effect, protecting nerve cells from inflammatory damage and necroptosis, particularly by inhibiting the MAPK/NF-κB mechanism in microglia.

Reference: Qin S. et al. (2018) Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia. Pharmacol Res.

Synergy of Brassica oleracea var. italica

There is scientific data indicating synergistic interaction of sulforaphane (from broccoli) and other natural compounds. In particular, interaction with curcumin and dihydrocaffeic acid (a metabolite of chlorogenic acid) has been noted in cellular models.

In a study, the combination of sulforaphane (S) and dihydrocaffeic acid (D) in a 1:1 ratio demonstrated synergistic cytotoxicity towards HT-29 and Caco-2 cells, whereas individual compounds (S or D) exhibited a less pronounced effect. The proposed mechanism is increased generation of reactive oxygen species, triggering the MAPK cascade (ERK, JNK, p38), leading to cell cycle arrest in the G₁ phase and modulation of mitochondrial target proteins (VDAC, ANT).

Reference: Santana-Gálvez J. et al. (2020) Synergistic Combinations of Curcumin, Sulforaphane, and Dihydrocaffeic Acid... PMC.

It is also confirmed that compared to curcumin, sulforaphane more effectively activates the Nrf2 pathway, enhancing the transcription of cytoprotective genes and demonstrating higher bioavailability due to lipophilicity and low molecular weight.

Reference: Houghton CA. et al. (2016) Sulforaphane and Other Nutrigenomic Nrf2 Activators. PMC. 

Thus, synergistic interactions include:

• Antioxidant potentiation through activation of the Nrf2 system when combined with other phytoactives;
• Cytotoxic additive effect when combining sulforaphane and dihydrocaffeic acid;
• Modulation of cellular cascades (MAPK pathway, ROS-dependent mechanisms) as a common mechanism of synergy.

These data are based on in vitro experimental models and require further in vivo studies for confirmation.

Geography of Use and Folk Medicine — Brassica oleracea var. italica

Brassica oleracea var. italica as a variety of cultivated cabbage originated in the Mediterranean region and is mentioned in ancient sources. The first evidence of its use dates back to the period of Ancient Rome, where the plant was considered not only as a food product but also as part of healing practices. In the works of Pliny the Elder, descriptions of cabbage plants, close in morphology to modern broccoli varieties, used for body strengthening and cleansing, are found. In the Middle Ages, broccoli spread in Italy, where it entered the practice of local herbalists and monastic medicine.

In traditional European culture, broccoli was used mainly in the form of decoctions and infusions from inflorescences and leaves, which were applied to strengthen the body, recover from exertion, and general cleansing of the organism. In Slavic folk healer traditions, broccoli as a separate taxon is not recorded; however, its related cabbage forms were used as components of herbal mixtures applied for fatigue and in rituals associated with strengthening life force.

In East Asia, broccoli spread later, mainly through trade routes. In China and Japan, it was integrated into medical practices as a food product with cleansing and harmonizing properties. In modern Chinese tradition, broccoli is sometimes mentioned in the context of preventive herbal mixtures but is more often considered a cultural analog of traditional cabbage types. In Japan, the use of broccoli is recorded in food rituals associated with body strengthening and cleansing of the organism, which corresponds to the philosophy of macrobiotics.

Ethnographic sources have recorded the use of fresh inflorescence juice in the Mediterranean as a means for body strengthening and as a component of cosmetic wraps. In some Southern European ritual practices, cabbage plants, including broccoli, were symbolically linked to cleansing and renewal. In Mediterranean cultures, broccoli was considered a "plant of strength" and was used in rites of passage associated with recovery and a new life stage.

Ethnobotanical data indicate that broccoli was used more as a food product with pronounced symbolic and preventive significance than as an independent medicinal plant. However, within European, Chinese, and Japanese traditions, forms of folk application have been recorded, including decoctions, juices, wraps, and ritual practices.