Cynaropicrin
1. Identity: Chemical Characterization, Botanical Sources, and Forms
1.1 Chemical Identity
Cynaropicrin is a guaianolide-type sesquiterpene lactone primarily derived from plants within the Asteraceae family. Structurally, it features a distinctive 5–7–5 tricyclic framework, four exocyclic double bonds, and two hydroxyl groups. It has a 5-7-5 fused tricyclic skeleton with six stereocenters, four exo-olefins, and two hydroxyl groups. The γ-butyrolactone (GBL) ring is a very important pharmacophore which is implicated in many biological activities of cynaropicrin. Its molecular weight is 346.38. Its CAS number is 35730-78-0.
The absolute stereochemistry of cynaropicrin was determined by chemical relation to α-santonin (Corbella et al., 1972). The researchers who first isolated it encountered difficulties in acquiring cynaropicrin in a crystalline form, which they later found to be caused by its ability to readily polymerize. Cynaropicrin has a 5-7-5 fused tricyclic skeleton and contains two hydroxyl groups on each side of the molecule, allowing it to form a homopolymer.
1.2 Botanical Sources
Cynaropicrin is a sesquiterpene lactone of the guaianolide type found mainly in leaves of artichoke plants. It is one of the compounds that gives the artichoke its characteristic bitterness. It is found in artichoke leaves with an abundance of approximately 87 g/kg, but can hardly be found in other parts of the plant. Cynaropicrin makes up about 0.7% of leaf extracts of the artichoke.
The primary botanical source is Cynara scolymus L. (globe artichoke), but cynaropicrin has also been identified in several other members of the Asteraceae (Compositae) family. Cynaropicrin, a sesquiterpene lactone from Saussurea lappa, has been reported to possess immunomodulatory effects on cytokine release, nitric oxide production and immunosuppressive effects. It has additionally been isolated from Centaurea drabifolia and from the herb Centaurea salmantica L. (Asteraceae). Cynaropicrin has also been isolated from Moquinia kingii, where it was evaluated for trypanocidal activity.
Cynaropicrin is synthesized in the leaves of the artichoke plant and was found to accumulate in the trichomes. While the full mechanism of biosynthesis of cynaropicrin is unknown, it is proposed that biosynthesis starts with three isoprene C5-units, which are processed by the mevalonate pathway to form farnesyl pyrophosphate (FPP). With germacrene A and germacrene A acid as intermediates, FPP is converted into costunolide using two syntheses and a cytochrome P450 oxidase. Multiple yet unknown reactions occur to first form guaianolide and later cynaropicrin.
1.3 Discovery and History of Isolation
Research into the composition of the artichoke started in the first half of the 20th century. In the early 1950s, cynarin was isolated from the leaves and some years later cynaropicrin was discovered. Cynaropicrin was first isolated from the leaves of the Cynara scolymus L. (artichoke) in 1959 by a group of researchers of the Czechoslovak Academy of Sciences in Prague. It was found to be the main compound causing the bitter flavour of the artichoke. In 1960, cynaropicrin was formally reported from artichoke (Cynara scolymus L.) and is now considered a chemotaxonomic marker of artichoke plants.
1.4 Common Forms and Preparations
Cynaropicrin is currently used as part of crude extracts in several nutraceutical formulations, with demonstrated anti-inflammatory, antispasmodic, antitrypanosomal, and proapoptotic properties. The extraction of cynaropicrin is most often performed using conventional and in some cases toxic organic solvents, such as chloroform and dichloromethane. Other cynaropicrin extraction methods and solvents include water at elevated temperatures or supercritical COâ‚‚. Research-grade cynaropicrin is also isolable from artichoke leaf extracts using ionic liquid-based aqueous solutions, with optimized operational conditions leading to a cynaropicrin extraction yield of 3.73 wt%, and with recycling of the biomass and solvent achieving a higher yield of 6.47 wt%.
In standardized artichoke extract preparations investigated for dyslipidaemia, a particularly preferred cultivar specification has a 3.8% content of caffeoylquinic acids, 1.5% luteolin flavonoids, and 3% cynaropicrin.
2. Traditional and Historical Use
The knowledge of the health benefits of the artichoke dates back to the 4th century B.C., but its use was not rediscovered until the 16th century. Artichoke cultivation traces back to ancient Mediterranean civilizations—Greeks, Romans, and Egyptians. The Roman scholar Pliny the Elder described artichokes around 77 CE, praising their digestive virtues.
Artichoke (Cynara scolymus L.) and artichoke leaf extracts have a long history as a traditional part of the Mediterranean diet as well as in folk medicine for the treatment of dyspeptic disorders. Artichoke leaf extracts have been widely used in traditional medicine because of their hepatoprotective, cholagogic, hypoglycaemic, hypolipemic and antibacterial properties.
The different pharmacologic properties of plants containing cynaropicrin, especially artichokes, have been known for many centuries. While cynaropicrin itself was only isolated in 1959, its parent plant had been used across many cultures for hepatic, digestive, and choleretic indications for centuries. Artichoke extracts have traditionally been used as a herbal remedy for dyspepsia (indigestion), and research suggests that they may improve digestion by stimulating bile production and improving liver function.
Within the ethnobotanical tradition of Saussurea lappa (costus root, also known as Saussurea costus), which is another plant source of cynaropicrin, the plant is widely used in different traditional medicinal systems, particularly those of India, China, Tibet, and Korea, and is used to treat a variety of conditions including persistent skin diseases, rheumatoid arthritis, dysentery, persistent hiccups, abdominal discomfort, typhoid, osteoarthritis, quartan malaria, and leprosy.
3. Key Constituents, Related Compounds, and Chemical Context
Cynaropicrin belongs to the sesquiterpene lactone class. Sesquiterpene lactones are the most biologically significant class of secondary metabolites. In the artichoke plant, cynaropicrin co-occurs with other sesquiterpene lactones including grosheimin, deacylcynaropicrin, 11β,13-dihydrocynaropicrin, and structurally related guaianolides. Among the constituents of artichoke leaf extract, six sesquiterpene lactones—cynaropicrin, grosheimin, 11β,13-dihydrocynaropicrin, and three other hydroxylated guaianolide derivatives—have been shown to inhibit nitric oxide (NO) production and/or inducible nitric oxide synthase (iNOS) induction.
The broader phytochemical profile of the artichoke includes cynarin (a caffeoylquinic acid that is classically considered the major bioactive component), other caffeoylquinic acids, flavonoids (especially luteolin and its glycosides), polyphenols, inulin, and various terpenes. Other documented "active" chemicals in artichoke leaf include flavonoids, sesquiterpene lactones, polyphenols and caffeoylquinic acids. Cynaropicrin is distinguished as a chemotaxonomic marker and is quantitatively the dominant sesquiterpene lactone in the leaf.
4. Mechanisms of Action
4.1 NF-κB Pathway Inhibition
Beyond its antitumor properties, cynaropicrin exhibits a broad spectrum of bioactivities, including antioxidant, antiviral, antiparasitic, and immunomodulatory effects, primarily via the modulation of signaling pathways like NF-κB. Structure-activity relationship (SAR) studies indicate that the side chain, the hydrophilicity of the OH-3 and OH-19 substituents, and the C17-C18 exo-olefin structure critically influence its NF-κB inhibitory activity.
The acyl group having an α,β-unsaturated carbonyl group at the 8-position and the α-methylene-γ-butyrolactone moiety were identified as important for strong inhibitory activity. The results suggested that these sesquiterpene lactones inhibited LPS-induced iNOS expression via the suppression of the JAK-STAT signaling pathway in addition to the NF-κB signaling pathway.
4.2 Antitumor Mechanisms
Extensive studies have demonstrated that cynaropicrin exhibits remarkable antitumor activities by effectively inhibiting the proliferation of various malignancies. The underlying mechanisms are primarily associated with the regulation of cell cycle progression and apoptosis-related pathways.
Cynaropicrin significantly induced cytotoxicity and autophagy in hepatocellular carcinoma cells, but not in immortalized non-cancerous hepatocytes, which was related to the generation of mitochondrial reactive oxygen species (mtROS) and induction of mitochondrial membrane potential loss. Pretreatment with the ROS scavenger N-acetylcysteine reversed the cytotoxicity induced by cynaropicrin, confirming the centrality of oxidative stress in its cell-killing mechanism.
Cynaropicrin inhibited the growth of colorectal cancer HCT116 and oxaliplatin-resistant HCT116 cells in a dose- and time-dependent manner. It induced apoptosis as identified by Annexin V-FITC/PI staining, and this apoptosis was accompanied by the phosphorylation of JNK and p38 MAPK. Treatment with kinase-specific inhibitors confirmed that this apoptosis was mediated by JNK and p38 MAPK.
Cynaropicrin disrupts microtubule- and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma. Confocal microscopy revealed that cynaropicrin disrupted the microtubule network in cells stably expressing α-tubulin-GFP. Furthermore, cynaropicrin promoted DNA damage in multiple myeloma cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently a novel form of cell death, parthanatos.
Western blotting results suggested that the antitumor effects of cynaropicrin in colorectal cancer cells may be mediated by inhibition of the LIFR/STATs axis. Cynaropicrin reduced the formation of STAT3/STAT4 heterodimers and blocked their entry into the nucleus.
Cynaropicrin significantly enhances the efficacy of chemotherapeutic agents including temozolomide, cisplatin, and docetaxel, suggesting promising potential for combination therapy.
4.3 Antiparasitic Mechanisms
The antitrypanosomal activity of cynaropicrin is mediated by the depletion of intracellular glutathione (GSH) and trypanothione (T(SH)₂)—which the trypanosomes depend on for redox regulation—as well as the inhibition of trypanosomal ornithine decarboxylase. This action is mediated by the cynaropicrin α,β-unsaturated methylene moiety which acts as a Michael acceptor for GSH and trypanothione.
4.4 Antiviral Mechanisms (HCV)
In vitro studies showed that cynaropicrin has potent and broad spectrum activity as a cell-entry inhibitor against all genotypes of HCV with ECâ‚…â‚€ in the low micromolar range. Cynaropicrin acts during the early steps of the HCV lifecycle, including cell-free and cell-cell infection inhibition. Time-of-addition experiments revealed that cynaropicrin inhibited HCV virus at a time-point during entry.
4.5 Anti-inflammatory and Antioxidant Mechanisms
Cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. Cynaropicrin is a potent inhibitor of TNF-α action, which is a major mediator of the inflammatory process in HCV patients. Serum levels of TNF-α have been correlated with elevated alanine aminotransferase (ALT) and increased severity of fibrosis in HCV patients.
Cynaropicrin inhibits the activation of major adhesion molecules CD29 and CD98 involved in inflammation, but not CD43, indicating that it might be a specific immunopharmacological effect.
4.6 Anti-hyperlipidemic Mechanisms
Cynaropicrin shows anti-hyperlipidemic activity. The oxygen functional groups and the methylene of the GBL ring were found to help in anti-hyperlipidemic activity. Inhibition of gastric emptying also plays a minor role in this property. The cynaropicrin present in artichoke extracts also acts at the hepatic level on the enzymes that regulate HDL biosynthesis.
4.7 Target Protein Interactions
With regard to the target molecules of the sesquiterpene lactones, high-affinity proteins of cynaropicrin were purified from cell extract. ATP/ADP translocase 2 and tubulin were identified and suggested as molecular targets. In silico docking has also demonstrated the potential for cynaropicrin to bind the DNA-binding domain of NF-κB.
5. Scientific Evidence by Area of Use
Important caveat: With the exception of epidemiological data on artichoke as a dietary constituent, essentially all direct evidence for cynaropicrin as an isolate comes from in vitro (cell culture) and in vivo (animal model) studies. As of the available literature, no published human clinical trials have directly tested isolated cynaropicrin as a therapeutic agent. The evidence reviewed below should be understood in that context.
5.1 Antiviral Activity: Hepatitis C Virus (HCV)
For the first time, performed in vitro studies showed that cynaropicrin has potent and broad spectrum activity as a cell-entry inhibitor against all genotypes of HCV with ECâ‚…â‚€ in the low micromolar range. Cynaropicrin efficiently inhibited cell-cell transmission, which was confirmed by using a co-culture of two different cell types: Huh7/Scr cells infected with the Jc1 virus acting as HCV donor cells while Huh7.5/EGFP-NLS-IPS cells act as acceptor cells. Furthermore, the antiviral activity of cynaropicrin was pan-genotypic as HCV genotypes 1a, 1b, 2b, 3a, 4a, 5a, 6a, and 7a were inhibited.
The effect of cynaropicrin on all affected HCV genotypes has been shown to be generally strong, with EC₅₀ values in low micromolar ranges: 0.4–1.4 μM, with an average of 0.8 μM. Structurally, cynaropicrin might be considered a potential drug candidate, since it has no violations for Lipinski's rule of five and its water-solubility could allow formulation as therapeutic injections.
Evidence strength: Preliminary; in vitro only. No clinical trials in HCV-infected humans have been reported.
5.2 Anticancer Activity
Multiple Myeloma
Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, was investigated against multiple myeloma (MM) cells in vitro and its in vivo effectiveness assessed in a xenograft tumor zebrafish model. Cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines, with AMO1 being the most sensitive cell line (IC₅₀ = 1.8 ± 0.3 μM). Cynaropicrin (0.8, 1.9, 3.6 μM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells, associated with significant downregulation of STAT3, AKT, and ERK1/2.
Colorectal Cancer
In vivo efficacy of cynaropicrin was evaluated by a xenotransplantation model in nude mice. Cynaropicrin significantly reduced the survival ability of human colorectal cancer (CRC) cells and promoted apoptosis in a dose-dependent manner. Intraperitoneal administration of cynaropicrin at doses of 2.5 and 5 mg/kg resulted in decreased tumor volume and weight compared to the vehicle group and a reference comparator (Napabucasin, 10 mg/kg) group. The study put forward for the first time that cynaropicrin can inhibit the proliferation of CRC and induce its apoptosis by targeting the LIFR/STATs axis in vitro and in vivo.
Flow cytometry with propidium iodide staining and western blot analysis indicated that cynaropicrin induced cell cycle arrest at the G2/M phase by modulating cell cycle regulators, and western blot analysis revealed that cynaropicrin altered the balance of Bcl-2 family proteins. Flow cytometry also showed cynaropicrin activated multiple caspases.
Glioblastoma
Cynaropicrin showed an inhibitory effect on human glioblastoma cell U-87 MG growth. At IC₅₀ values, cynaropicrin at 4, 8, and 10 μM displayed significant cytotoxicity as confirmed by cell count and MTT assay. Furthermore, cynaropicrin completely abolished the ability of U-87 MG cells to form colonies and induced drastic morphological changes.
Hepatocellular Carcinoma
Cynaropicrin exerts cytotoxic effects against hepatocellular carcinoma (HCC) cells by inducing mitochondrial autophagy through the activation of the p38 MAPK-ROS pathway, indicating that cynaropicrin could be a potential therapeutic agent for liver cancer treatment. The results demonstrated that cynaropicrin significantly induced cytotoxicity and autophagy in HCC cells, but not in immortalized non-cancerous hepatocytes, which was related to the generation of mitochondrial reactive oxygen species (mtROS) and induction of mitochondrial membrane potential loss.
Pancreatic Cancer
Using sulforhodamine B and trypan blue assays, cynaropicrin was measured for cell viability following treatment in PANC-1 cells. Cynaropicrin reduced cell viability in a concentration-dependent manner (IC₅₀ = 5.29 μM) and significantly decreased free thiol levels. In silico docking demonstrated the potential for cynaropicrin to bind the DNA-binding domain of NF-κB. These data support further investigation of cynaropicrin as a potential therapeutic candidate in pancreatic cancer.
Leukemia
The cytotoxic effect of cynaropicrin was examined against several types of cell lines such as macrophages, eosinophils, fibroblasts, and lymphocytes. Cynaropicrin potently inhibited the proliferation of leukocyte cancer cell lines, such as U937, Eol-1, and Jurkat T cells, but some other cells such as Chang liver cells and human fibroblast cell lines were not strongly suppressed by cynaropicrin treatment.
Evidence strength for anticancer activity: Predominantly in vitro and animal (xenograft, zebrafish) models. Evidence is promising but preliminary. No human oncology clinical trials for isolated cynaropicrin have been reported.
5.3 Antiparasitic Activity
African Trypanosomiasis (Trypanosoma brucei)
Cynaropicrin has anti-parasitic activities for various organisms (trypanosoma) both in vitro and in vivo. The compound is the first natural product that has in vivo potential against T. brucei. Administration of 2 × 10 mg/kg body weight/day in the T. b. rhodesiense STIB 900 acute mouse model (which mimics the first stage of human African trypanosomiasis) resulted in a 92% reduction of parasitemia compared to untreated controls.
Chagas Disease (Trypanosoma cruzi)
In vitro and in vivo activities against Trypanosoma cruzi were evaluated for cynaropicrin. Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo. In vitro data showed that cynaropicrin was more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive of parasite autophagy.
Although cynaropicrin presented quite considerable trypanocidal effects in vitro (as effective as the control drug benznidazole), the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. This discrepancy between in vitro and in vivo activity against T. cruzi specifically contrasts with the more compelling in vivo results against T. brucei.
Other Protozoa
Cynaropicrin showed strong protozoacidal activity in vitro (active at 0.24–7.8 μg/mL) against Entamoeba histolytica and Trichomonas vaginalis.
Evidence strength for antiparasitic activity: In vitro and animal model data available; results for T. brucei are promising (in vivo efficacy in mouse model), while results for T. cruzi show a gap between in vitro and in vivo efficacy. No human clinical trials reported.
5.4 Anti-inflammatory Activity
Cynaropicrin has demonstrated anti-inflammatory activity associated with the suppression of the key proinflammatory NF-κB pathway. It also showed a strong inhibitory effect on colorectal cancer in vitro and in vivo, and a potent cytotoxic effect on human melanoma cells A375 and the HeLa cervical cancer cell line.
Evidence strength: In vitro and animal model data. No human clinical trials testing anti-inflammatory endpoints for isolated cynaropicrin have been reported.
5.5 Anti-hyperlipidemic Activity
Several biological mechanisms of action have been suggested for artichoke leaf extract in lipid management, including increased biliary secretion leading to increased cholesterol elimination and/or inhibition of HMG-CoA reductase activity resulting in decreased cholesterol biosynthesis; however, convincing and conclusive human studies investigating the blood cholesterol-lowering properties of artichoke or artichoke leaf extract are currently limited. Cynaropicrin itself is one of the active contributors to this lipid-modulating effect within whole artichoke extracts, though human trials have not isolated its specific contribution.
5.6 Anti-photoaging Activity
Due to its antioxidant and anti-inflammatory activities, artichoke has been used as folk medicine to treat various diseases. Cynaropicrin is a major bioactive phytochemical in the artichoke. Research has investigated whether cynaropicrin activates the AhR–Nrf2–Nqo1 pathway, which some phytochemicals use to exert antioxidant activity. These findings indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. Evidence is currently limited to in vitro cell-based assays.
5.7 Anti-malarial Activity
Cynaropicrin has demonstrated in vitro activity against Plasmodium falciparum. IC₅₀ values against Trypanosoma cruzi and Plasmodium falciparum were determined at 4.4 and 3.0 μM, respectively. Evidence for anti-malarial activity remains limited to in vitro data with no in vivo animal studies or human clinical trials reported.
6. Body Systems and Health Areas Associated with Cynaropicrin
- Hepatic system: Antitumor activity in hepatocellular carcinoma (in vitro/animal), anti-hyperlipidemic effects relevant to liver lipid metabolism, anti-HCV activity (in vitro), and involvement in bile metabolism through artichoke extracts.
- Immune system: Immunomodulatory effects on cytokine release, NO production, and adhesion molecule expression; inhibition of TNF-α and NF-κB.
- Hematologic/oncologic system: Cytotoxic and pro-apoptotic activity demonstrated in multiple myeloma, leukemia (U937, Eol-1, Jurkat T), colorectal cancer, glioblastoma, hepatocellular carcinoma, pancreatic cancer, and cervical cancer cell lines.
- Parasitology: Demonstrated anti-trypanosomal (African and American), anti-malarial, anti-amebic, and anti-trichomonas activity in vitro and, for T. brucei, in vivo.
- Cardiovascular/metabolic system: Anti-hyperlipidemic activity; involvement in HDL biosynthesis regulation at the hepatic level.
- Integumentary system (skin): Anti-photoaging activity via NF-κB inhibition; contact allergen causing dermatitis in susceptible individuals.
- Gastrointestinal system: Activation of bitter sensory receptors; antispasmodic effects; contribution to artichoke's traditional use in dyspepsia and digestive support.
7. Dosages Reported in Studies
No standardized human therapeutic dose of isolated cynaropicrin has been established. The following doses appear in the cited scientific literature:
- In glioblastoma (U-87 MG) cell studies, cynaropicrin at 4, 8, and 10 μM displayed significant cytotoxicity as confirmed by cell count and MTT assay.
- In pancreatic cancer PANC-1 cell studies, cynaropicrin reduced cell viability in a concentration-dependent manner with an IC₅₀ of 5.29 μM.
- In multiple myeloma cell line studies, cynaropicrin exerted potent cytotoxicity against nine MM cell lines, with AMO1 being the most sensitive (IC₅₀ = 1.8 ± 0.3 μM).
- In multiple myeloma AMO1 cells, doses of 0.8, 1.9, and 3.6 μM were used to demonstrate dose-dependent c-Myc suppression.
- In a colorectal cancer xenograft mouse model, intraperitoneal administration at doses of 2.5 and 5 mg/kg resulted in decreased tumor volume and weight.
- In the T. b. rhodesiense acute mouse model, i.p. administration of 2 × 10 mg/kg body weight/day on day seven post-infection resulted in a 92% reduction of parasitemia.
- In mice, doses of 25 mg/kg/day increased mortality and induced toxic effects such as ataxia and tremors. At higher doses (≥200 mg/kg), the liver was also affected, with increases in ALT levels and effects of mononuclear cell infiltration, necrosis, and hepatocyte regeneration.
Structurally, cynaropicrin might be considered a potential drug candidate, since it has no violations for Lipinski's rule of five and its water-solubility could allow formulation as therapeutic injections. Moreover, cynaropicrin is a small molecule that can be easily synthesized and, as the major constituent of the edible plant artichoke, has a history of safe dietary use.
8. Safety Considerations and Toxicology
8.1 Human Toxicity
In humans, there have been no proven toxicological effects at normal dietary intake. However, when taken in pure form in large quantities, cynaropicrin is acutely toxic. People who come into contact with the compound due to their profession sometimes develop the allergic reaction contact dermatitis or local eczema.
8.2 Contact Allergy and Dermatitis
The contact allergen in artichoke is cynaropicrin, which is released when the plant is cut. This is a sesquiterpene lactone known to cause allergic contact dermatitis. Artichoke is most commonly eaten in Western Europe but is not considered to cause allergy very frequently from ingestion. Most of the case studies of allergic reactions due to artichoke are after occupational exposure, affecting those who grow, pick, or process the vegetable.
Contact with artichoke and other plants of the Asteraceae family (daisy, chrysanthemum, marigold, Echinacea, and ragweed) has caused allergic reactions in sensitive individuals; cynaropicrin and other sesquiterpene lactones may be the responsible chemical constituents.
8.3 Systemic Allergic Reactions
Patients with Compositae sensitization are routinely warned against the ingestion of vegetables, spices, teas, and herbal remedies from this family of plants. The evidence for the occurrence of systemic allergic dermatitis caused by sesquiterpene lactone-containing plants is mostly anecdotal and based on statements from patients rather than scientific data. However, a few clinical reports on accidental sensitization and exposure and oral challenge prove the existence of this kind of reaction. Other Compositae species suspected of causing systemic reactions include artichoke, mugwort, yarrow, dandelion, feverfew, and elecampane.
8.4 Animal Toxicity Data
Ultrastructural alterations induced by cynaropicrin in parasites included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies suggesting parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body weight given intraperitoneally. Although no major plasma biochemical alterations could be detected at lower doses, histopathology demonstrated that the liver was the most affected organ in cynaropicrin-treated animals.
In a colorectal cancer xenograft model at doses of 2.5 and 5 mg/kg i.p., no significant loss of body weight occurred in any of the treatment groups. Evaluation by hematoxylin-eosin staining in the hearts, livers, lungs, and kidneys of treated mice showed no obvious cellular inflammatory changes, edema, or necrosis, demonstrating an acceptable safety profile at those doses.
8.5 Cross-Reactivity
Sesquiterpene lactone is found in many plants from the Asteraceae family (the daisy, aster, or sunflower family). Patients allergic to sesquiterpene lactone mix may react to the plant or pollen, as well as cosmetics, ointments, creams, lotions, and topical medicaments that use these plant extracts. Individuals with known Asteraceae/Compositae allergies should therefore exercise caution with artichoke leaf extract preparations containing cynaropicrin.
8.6 Drug Interaction Considerations
Cynaropicrin's demonstrated inhibition of NF-κB and TNF-α, as well as its modulation of multiple signaling pathways (STAT3, AKT, ERK1/2, p38 MAPK), raises theoretical considerations about interactions with immunosuppressive therapies, chemotherapeutic agents, and anti-inflammatory drugs. Cynaropicrin significantly enhances the efficacy of chemotherapeutic agents including temozolomide, cisplatin, and docetaxel, suggesting that combination with these agents could alter their pharmacodynamic profile. These observations are entirely preclinical, and no formal pharmacokinetic or drug-interaction studies in humans have been published.
References
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