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| Capsaicin is a chemical compound that gives chili peppers their spicy flavor and heat. Biological activity, capsaicin has been reported to exhibit a range of effects, including: Pain relief: 10-50 μM Anti-inflammatory activity: 20-50 μM Antioxidant activity: 10-100 μM Anti-cancer activity: 50-100 μM Cardiovascular health: 20-50 μM Approximate μM concentrations of capsaicin, the active compound in chili peppers, that can be achieved with different amounts of chili peppers: 1 teaspoon of dried chili pepper flakes (5g):~10-50 μM of capsaicin 1 tablespoon of dried chili pepper flakes (15g): ~30-150 μM of capsaicin 1 cup of fresh chili peppers (100g): ~100-500 μM of capsaicin 1 teaspoon of chili pepper extract (5g): ~100-500 μM of capsaicin 1 tablespoon of chili pepper extract (15g): ~300-1500 μM of capsaicin Approximate μM concentrations of capsaicin in various foods that contain capsaicin: Jalapeño peppers: 1 pepper (20g): ~20-100 μM of capsaicin 2–8 mg/100g of fresh Jalapeño Serrano peppers: 1 pepper (10g): ~10-50 μM of capsaicin 5–15 mg/100g Cayenne peppers: 1 pepper (10g): ~50-200 μM of capsaicin Habanero peppers: 1 pepper (20g): ~100-500 μM of capsaicin 15–30 mg/100g Ghost peppers: 1 pepper (20g): ~200-1000 μM of capsaicin Hot sauce: 1 teaspoon (5g): ~10-50 μM of capsaicin Chili flakes: 1 teaspoon (5g): ~10-50 μM of capsaicin Spicy sauces and marinades: 1 tablespoon (15g): ~10-50 μM of capsaicin Cayenne Pepper Powder – Approximate capsaicin content: roughly 5–20 mg/g (15-30g human for 100uM?) -IC50 in Cancer Cell Lines: Approximately 50–300 µM (consume 150mg of capsaican not possible?) -IC50 in Normal Cell Lines: Generally higher—often 2–3 times greater Pathways: -disrupting mitochondrial membrane potential, leading to cytochrome c release and subsequent activation of caspases -Activation of TRPV1: resulting in increased intracellular calcium levels -capsaicin can lead to increased production of ROS within cancer cells -Inhibition of NF-κB -Inhibit PI3K/AKT/mTOR signaling -STAT3 Inhibition -Cell Cycle Arrest -reduce the expression of vascular endothelial growth factor (VEGF) -COX-2 -capsaicin is a natural ADAM10 activator and shows potential to attenuate amyloid pathology and protect against AD Capsaicin — capsaicin is a pungent vanilloid alkaloid phytochemical from Capsicum peppers and the principal TRPV1 agonist responsible for chili heat. It is best classified as a natural product / small-molecule vanilloid with approved topical analgesic use but no established anticancer indication. Standard abbreviations include CAP and CAPS. In cancer literature it is a pleiotropic stressor whose dominant preclinical effects usually converge on Ca2+ influx, mitochondrial dysfunction, ROS generation, suppression of pro-survival signaling, and apoptosis, but its biology is context- and concentration-dependent, with occasional low-dose pro-migratory / pro-metastatic signaling reported. Primary mechanisms (ranked):
Bioavailability / PK relevance: Capsaicin is lipophilic, rapidly absorbed, and rapidly metabolized, with substantial first-pass limitation after oral exposure. Human oral PK from a capsicum preparation containing 26.6 mg capsaicin produced a Cmax of about 2.47 ng/mL at ~47 minutes, while the FDA-approved 8% topical system produced transient systemic exposure usually below 5 ng/mL, with a highest detected plasma level of 4.6 ng/mL. Delivery is therefore a major translation constraint for anticancer use, and formulation-based approaches are often invoked to overcome short half-life, irritancy, and exposure limits. In-vitro vs systemic exposure relevance: This is a major limitation. Many anticancer cell studies use roughly 10–300 µM, whereas reported human plasma exposures from oral or approved topical use are in the low ng/mL range, approximately ~0.008–0.015 µM, i.e., orders of magnitude lower than many cytotoxic in-vitro concentrations. Accordingly, direct systemic tumoricidal translation from standard dietary or approved topical exposure is weak unless local delivery, sustained-release systems, or substantially altered formulations are used. Clinical evidence status: Anticancer evidence is predominantly preclinical, with in-vitro and some in-vivo support across several tumor types. There is no regulatory approval for cancer treatment. Human oncology use is currently much more credible as supportive care for neuropathic pain, especially chemotherapy-induced peripheral neuropathy, where topical high-concentration capsaicin patches are being studied and used off-label / investigationally, rather than as a direct antitumor therapy. Mechanistic Table
P: 0–30 min R: 30 min–3 hr G: >3 hr |
| Source: TCGA |
| Type: Antiapoptotic |
| Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response. -One way to estimate Nrf2 induction is through the expression of NQO1. NQO1, the most potent inducer: SFN 0.2 μM, quercetin (2.5 μM), curcumin (2.7 μM), Silymarin (3.6 μM), tamoxifen (5.9 μM), genistein (6.2 μM ), beta-carotene (7.2μM), lutein (17 μM), resveratrol (21 μM), indol-3-carbinol (50 μM), chlorophyll (250 μM), alpha-cryptoxanthin (1.8 mM), and zeaxanthin (2.2 mM) 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. 3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress -In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. -Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic. -Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer - "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1. Nrf2 Inhibitors and Activators Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api - potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue. – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. – While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS). -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent . -Oridonin: -Wogonin: although its effects might be cell‑ and dose‑specific. - Withaferin A |
| 5859- | CAP, | Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain? |
| - | Review, | Var, | NA |
| 5847- | CAP, | An updated review on molecular mechanisms underlying the anticancer effects of capsaicin |
| - | in-vitro, | Liver, | HepG2 |
| 2394- | CAP, | Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction |
| - | in-vitro, | Nor, | GES-1 |
Query results interpretion may depend on "conditions" listed in the research papers. Such Conditions may include : -low or high Dose -format for product, such as nano of lipid formations -different cell line effects -synergies with other products -if effect was for normal or cancerous cells
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