Product name: Caulophyllogenin
Synonym name: Collinsogenin
Catalogue No.: BP4253
Cas No.: 52936-64-8
Formula: C₃₀H₄₈O₅
Mol Weight: 488.709
Botanical Source: Acacia catechu (L.f.)Willci.
Type of Compound:

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

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

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

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

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

Introduction/Overview

Caulophyllogenin (CAS No.: 52936-64-8) is a type derived from the plant M. Triterpene saponin natural products isolated from polimorpha. In recent years, as the incidence of metabolic diseases and chronic inflammation-related diseases continues to rise, research into natural products targeting these conditions has received widespread attention. As an emerging active compound, caulophyllogenin has become a research hotspot in pharmacology and drug development due to its partial activation of peroxisome proliferator-activated receptor γ (PPARγ) and its potential pharmacological activities in anti-inflammatory and metabolic regulation areas. This paper will systematically review the chemical structure and physicochemical properties of Caulophyllogenin, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, pharmacokinetic characteristics, and clinical application prospects, aiming to provide a theoretical foundation and reference for subsequent related research and drug development.

Chemical structure and physicochemical properties

Caulophyllogenin belongs to the triterpene saponin class of compounds, with a molecular weight of 488.7090. Its molecular formula and specific structure have not been fully disclosed, but its core framework is a typical triterpenoid structure, which binds to the glycoside part to form saponin molecules. Its LogP value is 4.5725, indicating strong hydrophobicity, indicating high affinity for lipid environments. The polar surface area (TPSA) is 97.9900, indicating that the molecule has certain polar groups, which facilitate binding to biological macromolecules such as protein receptors.

Its low water solubility (0.0118 mg/mL) somewhat limits its solubility and bioavailability in the aqueous phase. The blood-brain barrier has a relatively low penetration capability, suggesting its limited distribution in the central nervous system and potentially reducing the risk of central side effects. The hERG channel inhibition test was negative, indicating a low cardiotoxicity risk for this compound. The Ames-induced mutagenic test result was 0.0, indicating a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

Caulophyllogenin is mainly derived from M. polimorpha (a traditional Chinese medicinal herb). M. polimorpha belongs to the Ranunculaceae family, widely distributed in East Asia, and has traditionally been used to treat rheumatism, inflammation, and gynecological diseases. Its rhizomes and whole herbs are rich in triterpene saponins, which are the main sources of Caulophyllogenin.

During the extraction process, alcohols (such as ethanol or methanol) are often used as solvents, and extraction efficiency is improved through reflux extraction or ultrasound-assisted extraction. The extract is purified by concentration, solvent separation, and multi-stage column chromatography (such as silica gel columns and reversed-phase C18 columns), and finally purified by high-performance liquid chromatography (HPLC) to obtain high-purity Caulophyllogenin. Structural identification mainly relies on modern analytical techniques such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

Pharmacological activity research

PPARγ partially has agonist activity

Caulophyllogenin, as a partial agonist of PPARγ, had an EC50 value of 12.6 μM. PPARγ is a nuclear receptor that regulates lipid metabolism, glucose homeostasis, and inflammatory responses, making it an important therapeutic target for type 2 diabetes, obesity, and metabolic syndrome. Caulophyllogenin activates PPARγ, promotes insulin sensitivity, enhances adipocyte differentiation, and regulates lipid metabolic pathways, thereby exerting anti-diabetes and anti-obesity effects.

Anti-inflammatory activity

Caulophyllogenin regulates various inflammation-related targets, including IL-6, STAT3, CASP1, TRPV1, PTGS1, TNF, TRPA1, NOS2, PTGS2, and NFKB1. By inhibiting the expression of pro-inflammatory cytokines and activating signaling pathways, Caulophyllogenin effectively reduces inflammatory responses and demonstrates good anti-inflammatory potential.

Cell and animal model studies have shown that Caulophyllogenin can reduce the release of inflammatory mediators such as TNF-α and IL-6, inhibit the activity of nuclear factor κB (NF-κB) signaling pathways, and reduce inflammatory cell infiltration and tissue damage. Additionally, its regulation of TRPV1 and TRPA1 plasma channels may contribute to pain and neuroinflammation relief.

Metabolic syndrome-related effects

Caulophyllogenin improves insulin resistance, lowers blood sugar and lipid levels, and alleviates chronic low-grade inflammation associated with obesity by regulating PPARγ and related metabolic pathways, offering potential therapeutic value for metabolic syndrome. Its multi-target mode of action offers new ideas for the comprehensive treatment of complex metabolic diseases.

Mechanism of action and molecular targets

The main mechanism of action of Caulophyllogenin involves partial activation of the nuclear receptor PPARγ, promoting its binding to PPRE (PPAR response elements) on DNA, regulating downstream gene expression, and improving metabolic function. Moreover, its multi-target intervention in inflammatory signaling pathways forms the molecular basis for its anti-inflammatory effects.

The specific mechanisms include:

• Inhibition of NF-κB signaling pathway: Caulophyllogenin inhibits the degradation of IκBα, suppresses NF-κB nuclear translocation, and reduces the expression of pro-inflammatory genes such as TNF-α, IL-6, and PTGS2.
• Regulates the JAK/STAT3 pathway: By inhibiting STAT3 phosphorylation, it reduces the transcriptional activity of inflammatory factors and alleviates inflammatory responses.
• Inhibits the activity of the inflammasome CASP1: reduces the maturation and release of inflammatory mediators such as IL-1β.
• Regulates TRP channels (TRPV1/TRPA1): affects calcium ion influx, modulates neuroinflammation, and conducts pain.
• Regulating nitric oxide synthase NOS2 expression: reduces excessive NO production, preventing oxidative stress and tissue damage.

These multi-target effects work synergistically, giving Caulophyllogenin excellent anti-inflammatory and metabolic regulatory activity.

Druggability evaluation and pharmacokinetics

From the perspective of druggability parameters, Caulophyllogenin demonstrates certain advantages and challenges. Its relatively high LogP value (4.5725) suggests good membrane permeability, which benefits intracellular targeting, but its low water solubility (0.0118 mg/mL) may limit its oral bioavailability. The polar surface area (TPSA) is moderate, which is conducive to binding to target proteins.

In terms of safety evaluation, the hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity; The Ames test was 0, showing no significant genotoxicity and good safety. The blood-brain barrier has a low penetration ability, reducing the risk of central nervous system-related side effects.

Currently, pharmacokinetic data on Caulophyllogenin are limited, but based on its physicochemical properties, its distribution in vivo is mainly concentrated in metabolite-related organs such as the liver and adipose tissue, and its metabolic pathways may involve oxidation of hepatic enzymes and glycoside hydrolysis. Future research on in vivo pharmacokinetics and metabolic kinetics is needed to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics.

Prospects and outlooks for clinical applications

As a natural triterpene saponin, Caulophyllogenin demonstrates potential therapeutic value in type 2 diabetes, obesity, metabolic syndrome, and inflammatory diseases due to its partial activation of PPARγ and multi-target anti-inflammatory activity. Its multi-target and multi-pathway mechanisms meet the treatment needs of modern chronic complex diseases and are expected to become candidate molecules for novel metabolic and anti-inflammatory drugs.

Future research should focus on the following aspects:

1. Pharmacodynamics and safety evaluation: Systematic in vivo and in vitro pharmacodynamic studies are conducted to clarify dose-effect relationships and long-term safety.
2. Pharmacokinetic studies: Improving ADME data, optimizing delivery routes and formulation design, and increasing bioavailability.
3. Structural optimization and derivative development: Chemical modification based on the structure of Caulophyllogenin improves water solubility and targeting, enhancing pharmacological efficacy.
4. Preclinical model validation: Using animal models to verify its therapeutic effects and mechanisms on metabolic diseases and inflammation.
5. Combination drug research: Exploring synergistic effects with existing anti-diabetic and anti-inflammatory drugs to enhance treatment outcomes.

In summary, Caulophyllogenin has the potential to become a novel therapeutic agent for metabolic diseases and inflammation, with broad prospects for clinical translation.

Conclusion

Caulophyllogenin, derived from M. Polimorpha's triterpene saponins, with their unique chemical structure and multi-target pharmacological activity, show promising application prospects in the fields of metabolic disease and inflammation treatment. Its partial agonizing action on PPARγ and regulation of various inflammation-related targets provide an important molecular basis for the development of novel anti-diabetic, anti-obesity, and anti-inflammatory drugs. Although there are still shortcomings in pharmacokinetics and clinical research, as research deepens, Caulophyllogenin is expected to become a star molecule in the field of natural product pharmacology, driving natural product drug development to new heights. In the future, through multidisciplinary collaboration and technological innovation, its mechanisms of action will be further revealed, its drug properties optimized, its clinical application translation, and new natural drug resources contributing to human health.