Product name: Triptolide
Synonym name:
Catalogue No.: BP1411
Cas No.: 38748-32-2
Formula: C₂₀H₂₄O₆
Mol Weight: 360.406
Botanical Source: Tripterygium wilfordii Hook.f.
Physical Description:
Type of Compound: Diterpenoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

The product could be supplied from milligrams to grams, upto kiloframs.
Inquire for bulk scale.

Triptolide is a diterpenoid epoxide which is produced by the thunder god vine, Tripterygium wilfordii. It has in vitro and in vivo activities against mouse models of polycystic kidney disease and pancreatic cancer, but its physical properties and severe toxicity limit its therapeutic potential.

Consequently, a synthetic water-soluble prodrug, minnelide, is being studied clinically instead.

Several putative target proteins of triptolide have been reported, including polycystin-2, ADAM10,DCTPP1, TAB1, and XPB. Multiple triptolide-resistant mutations exist in XPB (ERCC3) and its partner protein GTF2H4. However, no triptolide-resistant mutations were found in polycystin-2, ADAM10, DCTPP1 and TAB1. Cys342 of XPB was identified as the residue that undergoes covalent modification by the 12,13-epoxide group of triptolide, and the XPB-C342T mutant rendered the T7115 cell line nearly completely resistant to triptolide. The level of resistance conferred by the C342T mutation is about 100-fold higher than the most triptolide-resistant mutants previously identified. Together, these results validate XPB as a target responsible for the antiproliferative activity of triptolide.

Triptolide has been used to treat a variety of ailments, including rheumatoid arthritis, nephritic syndrome and Lupus erythematosus. It is also a strong antitumor agent. Several angiogenesis assays in numerous research studies have shown that triptolide is an angiogenesis inhibitor. Numerous preclinical studies have shown that TPL inhibits cell proliferation, induces apoptosis and limits tumor metastasis. TPL also has a synergistic action with other treatment methods whereby, it enhances the effects of other antitumor treatments, as studied in various cancer cell lines. This review summarizes the recent developments and discussion of antiangiogenic mechanisms of TPL in cancer, brief outline of its clinical trials and its future in cancer therapeutics.

HPLC of Triptolide

HNMR of Triptolide

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

Introduction/Overview

Triptolide, CAS number 38748-32-2, is a diterpene tricyclic oxide extracted from the root of the traditional Chinese medicinal material Tripterygium wilfordii Hook.f.. As one of the main active ingredients of Trigonos, Trigondox Glycosis has attracted widespread attention in recent years in the fields of natural product pharmacology and new drug development due to its remarkable immunosuppressive, anti-inflammatory, anti-proliferative, and anti-tumor activities. Thunder Godzine is not only used in traditional Chinese medicine to treat autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, but its inhibitory effects on various malignant tumor cells—especially its potential therapeutic value in solid tumors like breast cancer—have made it a hot topic in modern pharmacological research.

This paper aims to systematically review the chemical structure and physicochemical properties, plant origin, and extraction methods of Tripontotengjia, explore its pharmacological activity and mechanism of action in depth, focus on analyzing its molecular targets in breast cancer treatment, evaluate its druggability and pharmacokinetic characteristics, and finally look ahead to its clinical application prospects and future research directions, providing a theoretical foundation and practical guidance for drug development.

Chemical structure and physicochemical properties

Trigon Tengformin is a typical diterpene tricyclic oxide, with a molecular formula of C20H24O6 and a molecular weight of 360.4060. Its chemical structure consists of a complex tricyclic framework with multiple epoxy groups and lactone rings, structural features that give it high bioactivity. The LogP value of Trigongtengformin is 1.7323, indicating moderate lipid solubility, which is beneficial for cell membrane penetration. Its topological pole surface area (TPSA) is 84.12 Ų, indicating certain polarity that facilitates binding with biological macromolecules such as proteins.

Low water solubility (0.0929 mg/mL) limits its solubility in the aqueous phase and affects bioavailability. Notably, Trigon Tengjia has a high blood-brain barrier penetration ability, which opens up potential applications in central nervous system diseases. Additionally, the hERG channel inhibition test results were negative, indicating a low risk of cardiotoxicity. The Ames test result was 2.1, indicating a low genotoxicity risk, but further safety evaluation is still needed.

Plant Origins and Extraction Methods

Tripterygium wilfordii Hook.f. mainly comes from the root of Tripterygium wilfordii Hook.f.. Lycopodium is a plant of the Eumyceae family, genus Lycogonus, widely distributed in southern China and East Asia. In traditional Chinese medicine, Trigodratia is used to treat various inflammatory and immune-related diseases. Its roots are rich in active diterpenoids, with Trigonidium being particularly high in methyl hormone.

Traditional methods for extracting Trigongteng Methyl mainly include solvent extraction, ultrasound-assisted extraction, and high-performance liquid chromatography separation. Generally, ethanol or methanol is used as the extraction solvent, followed by multi-step solvent separation and column chromatography purification to obtain high-purity Trigon Teng methyl extract. In recent years, the application of supercritical CO2 extraction technology and microwave-assisted extraction technology has improved extraction efficiency and purity, reduced the use of organic solvents, and aligned with the concept of green chemistry.

Pharmacological activity research

Trigon Tengjia exhibits a variety of pharmacological activities, covering immunomodulatory, anti-inflammatory, anti-proliferative properties, and anti-tumor effects.

1. Immunosuppressive effects
   Triptogra Tengjia exerts significant immunosuppressive effects by inhibiting the activation of T cells and B cells, reducing the release of inflammatory mediators. Its mechanism involves inhibition of the NF-κB signaling pathway, reducing the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and alleviating immune-mediated tissue damage.

2. Anti-inflammatory effects
   Triptophyllaine can inhibit key enzymes and signaling pathways in inflammatory responses, reducing infiltration of inflammatory cells and the release of inflammatory mediators. Its anti-inflammatory activity has been validated in various inflammatory models, such as rheumatoid arthritis and inflammatory bowel disease.

3. Antiproliferative and anti-tumor effects
   Trigongtosterin exhibits strong inhibitory effects on various cancer cell lines, especially demonstrating significant cell cycle inhibition and apoptosis induction abilities in breast cancer cells. Its antitumor mechanism involves regulation of multiple signaling pathways, including activation of apoptosis-related proteins, transcription factor inhibition, and downregulation of multidrug resistance proteins.

Mechanism of action and molecular targets

The pharmacological effects of Trigongteng Methoraxin are closely related to its multi-target regulation, especially in breast cancer treatment, where several key molecular targets have been confirmed to be involved in its anti-tumor effects.

• AMPK（PRKAA1）
  Thunder Gongteng Methyl activates the AMPK signaling pathway, promotes cellular energy metabolism regulation, and inhibits cancer cell proliferation and migration. AMPK activation can also induce autophagy, promoting apoptosis of cancer cells.

• BCL2
  As an anti-apoptotic protein, BCL2 is highly expressed in breast cancer cells. Trigongteng methyl hormone disrupts mitochondrial membrane potentials by downregulating BCL2 expression and activates endogenous apoptosis pathways.

• STAT3
  The STAT3 signaling pathway plays a central role in tumor cell proliferation and immune evasion. Trigongteng methorin inhibits STAT3 phosphorylation and nuclear translocation, blocking its transcriptional activity and inhibiting tumor growth.

• ESR2
  Triptosterin regulates estrogen receptor β (ESR2) expression and interferes with signaling in hormone-dependent breast cancer.

• ABCB1 and ABCG2
  These two multidrug-resistant transporters are important reasons for chemotherapy failure in breast cancer. Triptoplasma can inhibit the expression and function of ABCB1 and ABCG2, reverse multidrug resistance, and improve the sensitivity of chemotherapy drugs.

• MAPT
  The microtubule-associated protein Tau (MAPT) is involved in cytoskeletal stabilization, and Trigongtengformin influences cell division and migration by regulating MAPT.

• TOP1 and TOP2A
  Topoisomerase I (TOP1) and IIα (TOP2A) are key enzymes for DNA replication and transcription. Triptosterin inhibits its activity, blocking DNA metabolism in tumor cells.

• SIRT1
  The deacetylase SIRT1 plays a role in cellular stress responses and metabolic regulation. Trigmatin regulates SIRT1 activity, affecting cell apoptosis and metabolic homeostasis.

Additionally, as an inhibitor of NF-κB activation, Trigongteng Metoxin blocks the key role of this transcription factor in inflammation and tumors, further enhancing its anti-inflammatory and antitumor effects.

Druggability evaluation and pharmacokinetics

The druggability evaluation of Trigongteng Jiasu shows it has certain potential for drug development, but there are also challenges.

• Physical and chemical properties
  Moderate molecular weight and LogP values facilitate drug absorption and distribution in the body. Its low water solubility limits its oral bioavailability, requiring improvements in dosage form or nanocarrier technology to enhance solubility and stability.

• The blood-brain barrier was breached
  Trigongtosterin has high blood-brain barrier permeability, suggesting its potential for use in central nervous system diseases, but neurotoxicity risks should also be considered.

• Security
  Negative inhibition of hERG channels reduces the risk of cardiotoxicity, while Ames test results show low genotoxicity, but preclinical toxicology studies still need to be systematically conducted, with particular attention to hepatorenal toxicity and immunosuppressive side effects.

• Pharmacokinetics
  Existing studies show that Triptophyllin metabolizes rapidly in the body, has a short half-life, and limited bioavailability. Its main metabolic pathways include hepatic enzyme-mediated oxidation and hydrolysis, and the activity and safety of these metabolites need further clarification. Nanoformulations and liposomal loading technologies have been attempted to improve their pharmacokinetic properties.

Prospects and outlooks for clinical applications

With its multi-target and multi-mechanism pharmacological activity, especially its therapeutic potential for solid tumors such as breast cancer, Thunder Godeng Pharmacosin has become an important candidate for the development of natural anti-tumor drugs. Its immunomodulatory and anti-inflammatory effects also offer new ideas for the treatment of autoimmune diseases.

However, the clinical application of Trigon Tengjia still faces issues such as a narrow dosage window, significant toxic side effects, and suboptimal pharmacokinetics. Future research should focus on:

1. Innovative dosage forms
   Develop nanocarriers, liposomes, and sustained-release formulations to improve bioavailability and reduce toxicity.

2. Structural decoration
   Chemical modification improves water solubility and selectivity, enhancing efficacy and reducing side effects.

3. Combination therapy
   Combined with chemotherapy or targeted drugs, it overcomes multidrug resistance and improves treatment outcomes.

4. Clinical trials
   Conduct systematic clinical studies to evaluate safety, efficacy, and optimal administration regimens.

5. Mechanism research
   Deeply analyze its molecular action network to discover new therapeutic targets and biomarkers.

Conclusion

As a natural diterpenoid tricyclic oxide with multiple pharmacological activities, Triptosterin demonstrates broad immunosuppressive, anti-inflammatory, and anti-tumor potential, especially playing an important role in molecular target regulation in breast cancer treatment. Although its druggability is somewhat limited, through modern drug design and dosage form improvements, Tripontosterin is expected to become an important source of next-generation anti-tumor and immunomodulatory drugs. Future research needs to integrate pharmacology, pharmacokinetics, and clinical science to move Triptocophylium from the laboratory to clinical practice, bringing greater benefits to patients.