# Digitonin **Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/digitonin **Data Source:** Hermetica Superfoods Ingredient Encyclopedia **Updated:** 2026-03-19 **Evidence Score:** 4 / 10 **Category:** Compound **Also Known As:** Digitonin, Steroidal saponin from Digitalis, Foxglove saponin, Digitalis glycoside, Purpurea saponin, Cardiac saponin ## Overview Digitonin is a steroidal saponin compound derived from foxglove plants that demonstrates anti-cancer properties through cell membrane permeabilization and apoptosis induction. Research shows it may inhibit gastric cancer cell proliferation with IC50 values of 1-5 μM in multiple cancer cell lines. ## Health Benefits • May inhibit gastric cancer cell proliferation - Preclinical evidence shows IC50 ~1-5 μM in MKN1, NUGC3, and HGC27 cell lines (PMID: 40206492) • Could reduce tumor growth - Mouse xenograft models demonstrated tumor volume reduction comparable to 5-FU when administered intraperitoneally (PMID: 40206492) • Potential to block cancer cell migration and invasion - In vitro studies using wound healing and transwell assays showed significant inhibition at 0.3125-20 μM (PMID: 40206492) • May target HSP90AA1 and NFKB1 pathways - Network pharmacology and Western blot analysis confirmed downregulation of these cancer-related proteins (PMID: 40206492) • Shows minimal toxicity to normal cells - GES-1 normal gastric cells showed low cytotoxicity at concentrations <1 μM (PMID: 40206492) ## Mechanism of Action Digitonin functions as a membrane-permeabilizing agent that selectively disrupts cholesterol-rich cell membranes, leading to cytotoxicity in cancer cells. It induces apoptosis through [mitochondrial](/ingredients/condition/energy) membrane permeabilization and activation of caspase pathways. The compound's selective toxicity toward cancer cells appears related to altered cholesterol [metabolism](/ingredients/condition/weight-management) in malignant tissues. ## Clinical Summary Current evidence for digitonin is limited to preclinical studies with no human clinical trials available. In vitro studies demonstrate anti-proliferative effects against gastric cancer cell lines (MKN1, NUGC3, HGC27) with IC50 values ranging from 1-5 μM. Mouse xenograft models showed tumor volume reduction comparable to 5-FU chemotherapy when administered intraperitoneally. The evidence remains preliminary and requires human studies to establish therapeutic potential and safety profiles. ## Nutritional Profile Digitonin is not a nutrient or food component; it is a steroidal saponin glycoside (C₅₆H₉₂O₂₉, molecular weight ~1229.3 g/mol) derived primarily from the seeds of Digitalis purpurea (purple foxglove). It consists of a spirostanol agenin (digitogenin) linked to a branched pentasaccharide chain composed of 2 glucose, 2 galactose, and 1 xylose unit. It has no macronutrient value (no protein, fat, carbohydrate, or fiber contribution to diet) and contains no vitamins or minerals. Its primary bioactive property is its ability to complex with membrane cholesterol (binding ratio ~1:1 molar with 3β-hydroxysterols), which underlies both its detergent-like membrane-permeabilizing activity and its pharmacological effects. Digitonin has very low oral bioavailability due to its large molecular size, high hydrophilicity of the sugar moiety, and susceptibility to gastrointestinal degradation; most preclinical anticancer studies utilize intraperitoneal or direct in vitro administration. Critical micelle concentration (CMC) is approximately 0.5 mM (~0.06% w/v) in aqueous solution. At sub-CMC concentrations (~1–5 μM, as used in cancer cell studies), it acts on cholesterol-rich membrane microdomains rather than as a bulk detergent. It is classified as toxic at higher doses (LD₅₀ in mice: ~5.7 mg/kg IV), and it is not approved for human dietary or therapeutic oral consumption. It is used exclusively as a research reagent (membrane permeabilization, cholesterol quantification assays) and as an investigational preclinical compound. No recommended dietary intake, tolerable upper limit, or nutritional reference value exists. ## Dosage & Preparation No clinically studied dosages exist due to lack of human trials. Preclinical in vitro studies used 0.3125-20 μM digitonin for 24-72 hours. In vivo mouse studies used intraperitoneal injections every 2 days for 4 weeks (approximately 10 mg/kg inferred from similar saponin models). Consult a healthcare provider before starting any new supplement. ## Safety & Drug Interactions Digitonin is highly cytotoxic and can cause severe membrane damage at higher concentrations, making it unsuitable for oral supplementation. No human safety data exists, and the compound may interact dangerously with cardiac medications due to its structural similarity to cardiac glycosides. Pregnancy and breastfeeding safety is unknown, and the compound should be avoided outside of research settings. Potential for serious adverse effects including hemolysis and cellular toxicity exists at therapeutic doses. ## Scientific Research No human clinical trials, RCTs, or meta-analyses have been conducted on digitonin as a therapeutic agent. A 2025 network pharmacology and experimental validation study (PMID: 40206492) evaluated digitonin in vitro using gastric cancer cell lines and in vivo using BALB/c nude mouse xenograft models with 5×10⁶ MKN1 cells per mouse (n=6-8 per group). ## Historical & Cultural Context Digitonin has no documented historical use in traditional medicine systems as a distinct compound. While Digitalis species were used in 18th-century European folk medicine for heart conditions due to cardiac glycosides, digitonin was isolated later in the 19th century specifically for laboratory use, not therapeutic applications. ## Synergistic Combinations 5-Fluorouracil (5-FU), HSP90 inhibitors, PI3K inhibitors, HIF-1α inhibitors, [NF-κB](/ingredients/condition/inflammation) inhibitors ## Frequently Asked Questions ### What is digitonin's IC50 value against cancer cells? Digitonin shows IC50 values of 1-5 μM against gastric cancer cell lines including MKN1, NUGC3, and HGC27. This indicates relatively potent anti-proliferative activity in preclinical studies. ### Is digitonin safe for human consumption? No human safety data exists for digitonin, and it demonstrates significant cytotoxicity in laboratory studies. The compound is not approved for dietary supplementation and may cause severe cellular damage. ### How does digitonin compare to chemotherapy drugs? In mouse models, digitonin showed tumor reduction effects comparable to 5-FU chemotherapy when administered intraperitoneally. However, this comparison is limited to preclinical studies with no human data available. ### What plant contains digitonin? Digitonin is naturally found in foxglove plants (Digitalis species). It belongs to the steroidal saponin class of compounds and is structurally related to cardiac glycosides. ### Can digitonin be taken as a supplement? Digitonin is not available as a dietary supplement due to its high toxicity and lack of human safety studies. It remains a research compound studied only in laboratory settings for potential therapeutic applications. ### What does clinical research show about digitonin's effectiveness against cancer? Preclinical studies demonstrate that digitonin inhibits gastric cancer cell proliferation with IC50 values ranging from 1–5 μM in multiple cell lines (MKN1, NUGC3, HGC27), and mouse xenograft models show tumor volume reduction comparable to the chemotherapy drug 5-FU when administered intraperitoneally. However, all current evidence is from laboratory and animal studies; human clinical trials are not yet available. These results suggest potential anticancer properties but do not establish safety or efficacy in humans. ### Does digitonin interact with common medications? Digitonin is structurally related to cardiac glycosides and may interact with drugs metabolized through similar pathways or those affecting electrolyte balance, particularly given its potential cardiac effects. Specific drug interaction data in humans is limited due to the lack of clinical trials and limited supplement use. Anyone considering digitonin supplementation should consult a healthcare provider about potential interactions with their current medications. ### Who should avoid digitonin supplementation? Individuals with cardiac conditions, electrolyte imbalances, or those taking cardiac medications should avoid digitonin due to its relationship to cardiac glycosides and potential to affect heart function and ion balance. Pregnant and nursing women, children, and the elderly lack safety data and should not use digitonin supplements. Given that digitonin is not an approved pharmaceutical or well-established dietary supplement, medical supervision is essential for anyone considering its use. --- *Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com* *License: CC BY-NC-SA 4.0 — Attribution required. 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