Synonym name:
Catalogue No.: BP0443
Cas No.: 35730-78-0
Formula: C₁₉H₂₂O₆
Mol Weight: 346.379
Botanical Source: Cynara scolymus, Centaurea canariensis, Amberboa ramosa, Grossheimia macrocephala, Tricholepis glaberrima and others

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

Description:

Cynaropicrin is a potent activator of the AhR-Nrf2-Nqo1 pathway, and could therefore be applied to prevention of UVB-induced photo aging; it may be a potential anticancer agent against some leukocyte cancer cells such as lymphoma or leukemia, through pro-apoptotic activity. Cynaropicrin shows in vivo activity against Trypanosoma brucei. Cynaropicrin possesses immunomodulatory effects on cytokine release, nitric oxide production and immunosuppressive effects. Cynaropicrin also has anti-inflammatory effects, it may participate in the inflammatory response by inhibiting the production of inflammatory mediators and the proliferation of lymphocytes and its inhibitory effect is mediated through conjugation with sulphydryl groups of target protein(s).

References:

Eur J Pharmacol. 2000 Jun 23;398(3):399-407.    

In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa.   

We investigated in vitro anti-inflammatory effects of Cynaropicrin, a sesquiterpene lactone from Saussurea lappa, on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) release, and lymphocyte proliferation. 

METHODS AND RESULTS:

Cynaropicrin strongly inhibited TNF-alpha release from lipopolysaccharide-stimulated murine macrophage, RAW264.7 cells, and differentiated human macrophage, U937 cells, proved to produce notable amount of TNF-alpha. It also potently attenuated the accumulation of NO released from lipopolysaccharide- and interferon-gamma-stimulated RAW264.7 cells in a dose-dependent manner. In addition, the immunosuppressive effects of the compound on lymphocyte proliferation in response to mitogenic stimuli were examined. Cynaropicrin also dose-dependently suppressed the proliferation of lymphocytes from splenocytes and interleukin-2-sensitive cytotoxic T lymphocyte, CTLL-2 cells, stimulated by lipopolysaccharide, concanavalin A, phytohemagglutinin and interleukin-2. However, treatment with sulphydryl compound, L-cysteine, abrogated all these inhibitory effects. 

CONCLUSIONS:

These results suggest that Cynaropicrin may participate in the inflammatory response by inhibiting the production of inflammatory mediators and the proliferation of lymphocytes and its inhibitory effect is mediated through conjugation with sulphydryl groups of target protein(s).    

Planta Med. 2012 Apr;78(6):553-6.    

Cynaropicrin: the first plant natural product with in vivo activity against Trypanosoma brucei.   

A screen of 1800 plant and fungal extracts with subsequent HPLC-based activity profiling was done to identify new antiprotozoal leads from nature. 

METHODS AND RESULTS:

This led to the identification of Cynaropicrin (1) from the herb CENTAUREA SALMANTICA L. (Asteraceae) as a potent IN VITRO inhibitor of TRYPANOSOMA BRUCEI RHODESIENSE. It preferentially inhibited T. B. RHODESIENSE (IC (50) of 0.3 μM) and T. BRUCEI GAMBIENSE (IC (50) of 0.2 μM), compared to TRYPANOSOMA CRUZI (IC (50) of 4.4 μM) and PLASMODIUM FALCIPARUM (IC (50) of 3.0 μM). Testing against melarsoprol- and pentamidine-resistant strains (IC (50)s of 0.3 μM and 0.1 μM, respectively) showed no cross-resistance. Intraperitoneal administration of 2 × 10 mg/kg body weight/day in the T. B. RHODESIENSE STIB 900 acute mouse model led to a 92 % reduction of parasitemia compared to untreated controls on day seven post-infection. Removal of the 2-hydroxymethyl-2-propenoyl moiety of Cynaropicrin led to a loss of toxicity towards T. B. RHODESIENSE. Cytotoxicities against rat myoblasts (L6 cells), human colon adenocarcinoma cells, and murine peritoneal macrophages were measured, and selectivity indices of 7.8, 62, and 9.5 were determined. 

CONCLUSIONS:

This is the first report of a plant natural product with potent IN VIVO activity against TRYPANOSOMA BRUCEI.    

HPLC of Cynaropicrin

HNMR of Cynaropicrin

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Cynaropicrin, CAS number 35730-78-0, is a natural sesquiterpene lactone compound, originally isolated from the plant Cynara scolymus L. in the Asteraceae family. As a natural compound with multiple biological activities, thistle has attracted attention for its remarkable anti-inflammatory, anti-tumor, and liver-protective effects. In recent years, with in-depth research into the molecular mechanisms of chronic inflammation, tumors, and liver diseases, the role of thistle in regulating key inflammatory factors and signaling pathways has gradually been revealed, demonstrating its tremendous value as a potential drug candidate.

This review systematically summarizes the chemical structure and physicochemical properties of thistle quasarin, plant origin and extraction methods, pharmacological activity, and mechanism of action, with a focus on its regulatory effects on tumor necrosis factor (TNF-α), chondrodegradation factor (MMP13), and nuclear factor κB (NF-κB) signaling pathways. At the same time, combining druggability parameters and safety evaluations, it explores its clinical application prospects and future research directions, aiming to provide researchers in the field of natural product pharmacology with comprehensive and authoritative reference materials.

Chemical structure and physicochemical properties

Thistle kosphenol is a typical sesquiterpene lactone with a molecular formula of C20H26O5 and a molecular weight of 346.37. Structurally, thistle quarin contains an lactone ring and multiple unsaturated double bonds, exhibiting high reactivity. Its physical and chemical properties are as follows:

• Molecular weight: 346.3700
• LogP: 0.1900, indicating a relatively balanced hydrophilicity and hydrophobicity, which facilitates cell membrane penetration
• TPSA (Topological Polar Surface Area): 103.83 Ų, indicating moderate polarity, which is favorable for binding with biological macromolecules
• Number of hydrogen bond receptors: 6, reflecting its potential in intermolecular interactions

Additionally, the structure of thistle matin contains multiple active groups, such as α and β-unsaturated lactone rings, which are key to its biological activity. This structure enables it to covalently bind to the sulfhydryl groups of proteins, thereby regulating multiple signaling pathways.

Plant Origins and Extraction Methods

Thistle bitter is mainly found in the leaves of thistle (Cynara scolymus L.), a perennial herbaceous plant of the Asteraceae family, widely distributed in the Mediterranean region and commonly cultivated as a vegetable and medicinal plant. Traditionally, thistle leaves have been used to promote liver and gallbladder function and as an adjunct treatment for digestive system diseases.

The process for extracting thistle matin mainly includes the following steps:

1. Raw material preparation: Collect mature thistle leaves, dry them, and crush them into powder.
2. Solvent extraction: Using ethanol or methanol as the extraction solvent, with reflux or ultrasonic-assisted extraction, extraction time generally takes 2-4 hours.
3. Separation and purification: The crude extract is separated by liquid-liquid distribution and column chromatography (silica gel or C18 reversed-phase column), combined with high-performance liquid chromatography (HPLC) purification to obtain high-purity thistle mamarin.
4. Structural identification: Confirm the structure using technologies such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

In recent years, the introduction of supercritical CO2 extraction and membrane separation technologies has improved extraction efficiency and purity, reduced the use of organic solvents, and aligned with the concept of green chemistry.

Pharmacological activity research

Thischitin demonstrates broad pharmacological activity across various in vitro and in vivo models, with notable results in anti-inflammation, anti-tumor, and liver protection.

Anti-inflammatory effects

Thisin can significantly inhibit the release of tumor necrosis factor α (TNF-α). The study showed that in mouse and human macrophages, the IC50 inhibition of TNF-α by thischi is 8.24 μM and 3.18 μM, indicating strong anti-inflammatory potential. In addition, thischima can inhibit the expression of other pro-inflammatory cytokines such as IL-1β and IL-6, reducing inflammatory responses.

Antitumor effects

Thistle bitter blocks tumor cell proliferation and migration by inhibiting the NF-κB signaling pathway. NF-κB is a key regulator of survival and drug resistance in various tumor cells, and reduced activity helps induce tumor cell apoptosis. Related studies have shown that thistle tosin can induce cell cycle arrest and apoptosis in various tumor cell lines, with low toxicity to normal cells.

Hepatoprotective effects

As a key organ for metabolism and detoxification, the liver is prone to oxidative stress and inflammatory damage. Thisthisin quantin enhances the liver's antioxidant defense capacity by regulating the expression of various antioxidant enzymes (such as SOD1, SOD2, CAT, GPX1) and detoxifying enzymes (NQO1, HMOX1). At the same time, thistle bitter inhibits matrix metalloproteinase 9 (MMP9) and transforming growth factor β1 (TGFB1), reducing liver fibrosis progression and protecting the structure and function of liver cells.

Mechanism of action and molecular targets

The pharmacological effects of thischirins are mainly achieved through coordinated regulation of multiple targets and pathways, with the following mechanisms:

Inhibits TNF-α release

Thisin can directly inhibit the synthesis and secretion of TNF-α in macrophages, reducing the release of inflammatory mediators and alleviating inflammatory responses. Its mechanism of action is closely related to the covalent modification of key proteins by α,β-unsaturated carbonyl structures in lactone rings.

Inhibits the NF-κB signaling pathway

NF-κB is a core transcription factor regulating inflammation and immune responses. Thisin inhibits the phosphorylation and degradation of IκBα, inhibits the translocation of NF-κB from the cytoplasm to the nucleus, reduces the transcriptional activity of pro-inflammatory genes, and achieves anti-inflammatory and antitumor effects.

Regulates the cartilage degradation factor MMP13

Thistle kosin inhibits MMP13 expression, reduces extracellular matrix degradation, and protects tissue structural integrity. This role is of great significance for the prevention and treatment of diseases such as arthritis and liver fibrosis.

Regulates the antioxidant enzyme system

Thisin activates the nuclear factor 2-related factor 2 (NRF2) signaling pathway, promotes the expression of antioxidant enzymes (SOD1, SOD2, CAT, GPX1) and detoxifying enzymes (NQO1, HMOX1), enhances cellular resistance to oxidative stress, and reduces liver cell damage.

Inhibits fibrosis-related factors

By downregulating growth factor β1 (TGFB1) and actin α2 (ACTA2), thistlein inhibits hepatic stellate cell activation, slows liver fibrosis, and promotes liver tissue repair.

Druggability evaluation and pharmacokinetics

The druggability parameters of thistle and kosin indicate that it has good potential for drug development:

• Lipophilic (LogP=0.19): Moderate lipophilic properties facilitate drug distribution and cell membrane penetration in the body.
• Polar surface area (TPSA=103.83 Ų): the ideal range for oral drug absorption.
• Number of hydrogen bond receptors (6): Facilitate stable binding with target proteins.
• Low blood-brain barrier permeability: reduces the risk of central nervous system side effects.
• Safety indicators: No hepatotoxicity, cardiotoxicity, or hERG channel inhibition; Ames mutagenic test negative, indicating high safety.

Although pharmacokinetic studies on thischid are currently limited, preliminary data indicate that its oral bioavailability is moderate, metabolism in the body is stable, and it is mainly processed by hepatic metabolic enzyme systems, with excretion primarily via bile and urine. In the future, further systematic pharmacokinetic and toxicological studies are needed to provide a basis for clinical application.

Prospects and outlooks for clinical applications

Based on the multi-target effects of thischinosin in anti-inflammation, anti-tumor, and liver protection, its clinical application prospects are broad:

1. Treatment of chronic liver disease: By regulating oxidative stress and fibrosis-related factors, thisthistle bitter is expected to become an adjunctive therapy for hepatitis, liver fibrosis, and cirrhosis.
2. Inflammatory diseases: Inhibits the TNF-α and NF-κB signaling pathways, giving them potential application value in chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.
3. Tumor adjuvant therapy: By inducing tumor cell apoptosis and inhibiting pro-inflammatory factors in the tumor microenvironment, thischi bitter can serve as an adjunct to anti-tumor drugs, enhancing efficacy and reducing side effects.

Future research directions should focus on:

• Optimize extraction and synthesis processes to increase yield and purity.
• In-depth analysis of its molecular mechanisms, especially the structural basis of interactions with target proteins.
• Systematically assess pharmacokinetics and safety, conduct preclinical animal models, and conduct early clinical trials.
• Exploring synergies with other drugs to develop compound formulations.

Conclusion

Thistle bitter, as a natural sesquiterpene lactone derived from thistle, has become a hot topic in natural product pharmacology research due to its multi-target and multi-mechanism pharmacological activity, especially its outstanding performance in anti-inflammation, anti-tumor, and liver protection. Its excellent druggability and safety have laid a solid foundation for clinical translation. In the future, with continuous advances in modern drug development technology, thistle bitter acid is expected to develop into an important natural medicine for treating various chronic diseases, contributing new strength to human health.