Synonym name:
Catalogue No.: BP0325
Cas No.: 38395-02-7
Formula: C₂₈H₄₂O₇
Mol Weight: 490.637
Botanical Source: Cynanchum caudatum

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.

HPLC of Caudatin

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

Introduction/Overview

Caudatin is a steroidal natural compound derived from the traditional Chinese medicine Cynanchum caudatum, and has recently attracted widespread attention for its remarkable antitumor and anti-angiogenic activities. As a natural compound with multi-target effects, Gaudating has shown promising application potential in the treatment of malignant tumors such as lung cancer. As one of the malignant tumors with the highest incidence and mortality rates worldwide, lung cancer has complex pathological mechanisms and diverse molecular targets that provide rich research directions for the development of novel drugs. Gautating demonstrates multiple anti-tumor mechanisms by regulating the cell cycle, inducing apoptosis, and inhibiting tumor angiogenesis, especially in regulating BCL2, STAT3, and MAPK signaling pathways. This paper systematically reviews the chemical structure, origin, pharmacological activity, mechanism of action, and druggability evaluation of GaoDating, aiming to provide a theoretical foundation and research direction for its clinical translation.

Chemical structure and physicochemical properties

Gaodating has the molecular formula C_29H_42O_6 and a molecular weight of 490.63, classifying it as a steroid compound. Its chemical structure includes a typical steroid backbone, with multiple hydroxyl and ester modifications, giving it high polarity and bioactivity. GaoDating's LogP value is 3.9, indicating moderate lipid solubility, which facilitates cell membrane penetration. Its topological pole surface area (TPSA) is 111.83 Ų, indicating certain advantages in biofilm penetration and oral absorption. Gautating has seven hydrogen bond receptors, which help it form stable binding to protein targets. According to pharmacokinetic predictions, Gaudating has low blood-brain barrier permeability, low risks of hepatotoxicity and cardiotoxicity, and does not inhibit hERG channels, demonstrating good safety profiles.

Plant Origins and Extraction Methods

Gaoda Pavilion is mainly found in Cynanchum caudatum, a perennial herbaceous plant widely distributed in southern China and Southeast Asia. In traditional Chinese medicine, pir-sai-o-smoth is used to treat tumors, inflammation, skin diseases, and various other diseases. Gaudating is typically extracted using organic solvent extraction combined with chromatography separation technology. Specific methods include:

1. Solvent extraction: Ethanol or methanol is used to reflux extract dried cowhide rhizomes, and the extract is concentrated to obtain the crude extract.
2. Liquid-liquid distribution: The crude extract is distributed through solvents such as n-hexane and ethyl acetate, enriching steroid components.
3. Column chromatography separation: Extracts are purified using silica gel column chromatography or reversed-phase high-performance liquid chromatography (RP-HPLC) to obtain high-purity Gautating.
4. Structural identification: Confirm its structure using modern analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance imaging (NMR).

In recent years, ultrasound-assisted extraction and microwave-assisted extraction technologies have also been introduced to improve extraction efficiency and purity.

Pharmacological activity research

Antitumor activity

Gautating demonstrates significant anti-proliferative effects in various tumor cell lines, with particularly notable inhibitory effects in lung cancer cells. In vitro cell experiments show that Gaudating can induce cell cycle arrest in lung cancer cells (such as A549, H1299), mainly during the G0/G1 or S phases, blocking cell cycle progression and inhibiting cell proliferation. Meanwhile, Gondartin has a significant ability to induce apoptosis, accompanied by regulation of apoptosis-related protein expression, such as downregulation of BCL2 family proteins and activation of Caspase family proteins.

Anti-angiogenic effect

Tumor growth and metastasis heavily depend on angiogenesis. GaoDating demonstrates good anti-angiogenesis activity by inhibiting the proliferation, migration, and lumen formation of vascular endothelial cells. In vivo experiments, Gauting can reduce the number of new blood vessels in tumor tissue and inhibit the expression of angiogenesis factors in the tumor microenvironment, such as VEGF (vascular endothelial growth factor), thereby limiting the supply of nutrients and growth to tumors.

Other pharmacological activities

In addition to anti-tumor effects, Gaudating also exhibits certain anti-inflammatory and immunomodulatory effects, possibly indirectly participating in the regulation of the tumor microenvironment by regulating inflammatory factors and immune cell activity, thereby enhancing anti-tumor immune responses.

Mechanism of action and molecular targets

The anti-lung cancer effects of Corttinger involve multiple signaling pathways and key molecular targets, mainly including:

1. BCL2 family proteins: Gonutin downregulates the expression of the anti-apoptotic protein BCL2, promoting mitochondrial pathway-mediated apoptosis and activating the Caspase-9 and Caspase-3 cascade, leading to programmed cell death.

2. STAT3 signaling pathway: STAT3 plays an important role in lung cancer cell proliferation, survival, and immune evasion. Gautating inhibits STAT3 phosphorylation and nuclear translocation, blocks its transcriptional activity, reduces the expression of tumor-promoting genes, and inhibits tumor growth.

3. MAPK pathway (MAPK1, MAPK8): Gaudatin regulates the MAPK signaling pathway, affecting cell proliferation and stress response. By regulating the activities of ERK (MAPK1) and JNK (MAPK8), Gautating promotes apoptosis and inhibits tumor cell migration.

4. PI3K/AKT pathway (PIK3CG): This pathway plays a key role in tumor cell survival and drug resistance. Gautatin inhibits PI3Kγ activity, blocks downstream AKT signaling, induces apoptosis, and enhances chemotherapy sensitivity.

5. NF-κB pathway (RELA): Gaudatin inhibits the NF-κB signaling pathway, reducing the expression of pro-inflammatory and anti-apoptotic genes and promoting tumor cell apoptosis.

6. Estrogen receptor β (ESR2): Gautatine may influence hormone-dependent growth of lung cancer cells by regulating ESR2 activity.

7. Microtubule-associated protein Tau (MAPT): The effect of Gautatin on microtubule stability may be involved in its mechanisms of inhibiting cell proliferation and inducing apoptosis.

8. Activation of peroxisome proliferator-activated receptor γ (PPARG) :P PARG helps induce tumor cell differentiation and apoptosis, and Gautatin may enhance antitumor effects by modulating PPARG signaling.

In summary, Gaudating regulates tumor cell proliferation, apoptosis, and angiogenesis through multi-target and multi-pathway synergistic effects, demonstrating a complex and effective anti-tumor mechanism.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Gundalting shows it has good potential for drug development. Its molecular weight of 490.63 complies with the Lipinski rule, and a LogP value of 3.9 indicates moderate lipid solubility, which is beneficial for oral absorption. Although the TPSA value of 111.83 is slightly high, it remains within an acceptable range, indicating it has certain cell membrane penetration capability. Gautatin has 7 hydrogen bond receptors, making it suitable for stable binding to protein targets.

In terms of safety, Gandoting has no significant hepatotoxicity or cardiotoxicity, and does not inhibit hERG channels, reducing the risk of arrhythmias. Its low permeability of the blood-brain barrier suggests relatively few side effects on the central nervous system.

Pharmacokinetic research is still in its early stages, and metabolic pathways in vivo mainly involve hepatic enzyme systems; the activity and toxicity of these metabolites require further evaluation. Systematic pharmacokinetic and toxicological studies are needed in the future to clarify their in vivo behavior and safe dose ranges.

Prospects and outlooks for clinical applications

As a natural steroidal anti-tumor drug, Gaodating has multi-target effects and good safety, showing broad clinical application prospects. Its potential in lung cancer treatment is mainly reflected in:

1. Monotherapy: By inducing tumor cell apoptosis and blocking the cell cycle, Gauting is expected to serve as an adjuvant or alternative therapy for lung cancer, especially suitable for patients with resistance or relapse.

2. Combination therapy: Quantating can be used in combination with chemotherapy drugs, targeted drugs, or immunotherapy to enhance efficacy, reduce resistance risk, and mitigate chemotherapy-related side effects.

3. Anti-angiogenesis therapy: By inhibiting tumor angiogenesis, Gaudatin can limit tumor nutrient supply, inhibit tumor growth and metastasis, and is suitable for comprehensive treatment of various solid tumors.

4. Personalized Treatment: Based on molecular target-based precision medicine, Gaudating can provide personalized treatment plans for lung cancer patients with specific pathway abnormalities such as STAT3 and BCL2.

Future research should focus on:

• In-depth analysis of the molecular mechanisms of Gaodating and its interactions with the tumor microenvironment.
• Optimizing formulations and administration methods to improve bioavailability and targeting.
• Conduct systematic preclinical toxicology and pharmacokinetic studies.
• Design reasonable clinical trials to verify their safety and effectiveness.
• Explore its potential applications in other tumors and diseases.

Conclusion

As a steroid-based natural product derived from pirpelago, Cortting, with its unique chemical structure and multi-target antitumor mechanism, demonstrates excellent pharmacological activity and druggability. Its potential for application in lung cancer treatment is increasingly prominent, especially in regulating the cell cycle, inducing apoptosis, and inhibiting angiogenesis, showing remarkable effects. Although pharmacokinetics and clinical research on Cortantine remain limited, its good safety and multiplexed mechanisms of action have laid a solid foundation for it to become a novel antitumor drug. Through in-depth mechanistic research and clinical validation, Gautating is expected to become an important candidate drug in the treatment of lung cancer and other malignant tumors, providing new ideas and directions for the development of natural product pharmacology.