Product name: Chikusaikoside II
Synonym name:
Catalogue No.: BP5077
Cas No.: 166338-14-3
Formula: C₄₈H₇₈O₁₈
Mol Weight: 943.134
Botanical Source:
Type of Compound: Triterpenoids

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

Chikusaikoside II is a natural triterpene saponin compound isolated from Bupleurum longeradiatum, a plant of the Bupleurum genus. Bupleurum plants are widely used in traditional Chinese medicine, especially renowned for their effects in releasing the exterior, soothing the liver, and harmonizing the nutritive and defensive qi. In recent years, with the development of natural product pharmacology, bupleurum saponin compounds have attracted widespread attention due to their diverse bioactivities. As an important member, Bupleurum Saponin II demonstrates significant anti-inflammatory activity, involving multiple inflammation-related molecular targets, providing a theoretical basis for its potential applications in the treatment of inflammatory diseases.

This paper systematically reviews the chemical structure and physicochemical properties of Bupleurum Saponin II, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and finally explores its clinical application prospects and research prospects, aiming to provide scientific reference for further research and drug development of this compound.

Chemical structure and physicochemical properties

The chemical structure of Bupleurum Saponin II belongs to the triterpene saponin class, with a complex molecular formula and a molecular weight of 943.1340. Its structural core is a pentacyclic triterpene backbone, connecting multiple sugar groups to form a typical saponin structure. The compound has a LogP value of 2.3399, indicating moderate lipid solubility, which facilitates membrane penetration without being overly hydrophobic. The topological pole surface area (TPSA) is 287.1400, indicating high polarity, and the presence of sugar groups significantly increases its polarity and hydration capacity.

Water solubility is relatively low, about 0.0566 mg/mL, indicating limited solubility in water and possibly affecting oral bioavailability. The blood-brain barrier has low permeability, indicating limited distribution in the central nervous system and potentially reducing central side effects. The hERG channel inhibition test results were 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

Bupleurum longadiatum is mainly isolated from Bupleurum longeradiatum, a plant of the Bupleurum genus. Bupleurum large-leaf is widely distributed in northern China and East Asia, and has traditionally been used in traditional Chinese medicine formulas such as releasing the exterior, dissipating heat, soothing the liver, and regulating qi. The root of the plant is the main medicinal part and also the site where saponin compounds are enriched.

The extraction process usually uses alcohol extraction, using 70%-95% ethanol or methanol for reflux or ultrasonic extraction of the dried and crushed roots. After concentration, the extract is separated using multi-stage liquid-liquid distribution (such as ethyl acetate, n-butanol, etc.) to separate saponin components. Further purification was performed using commonly used techniques such as silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC), combined with mass spectrometry (MS) and nuclear magnetic resonance (NMR) methods to confirm the structure.

In recent years, the application of supercritical CO₂ extraction and membrane separation technologies has provided new ideas for improving extraction efficiency and purity, and is more in line with green chemistry principles. Optimizing the extraction process not only affects yield but also holds significant importance for subsequent pharmacological activity research and formulation development.

Pharmacological activity research

The main pharmacological activity of Saponin II is its anti-inflammatory effect, but it also involves immune regulation, antioxidant effects, and cell protection. Numerous in vitro and in vivo studies have shown that this compound can significantly inhibit the expression and release of various inflammatory mediators, reducing inflammatory responses.

In cell models, Saponin II can inhibit the production of inflammatory factors IL-6 and TNF-α, reduce the activity of inflammation-related enzymes such as PTGS1 (COX-1), PTGS2 (COX-2), and NOS2 (iNOS), and alleviate oxidative stress and apoptosis. Its regulation of the inflammasome-related protein CASP1 helps inhibit the maturation and release of inflammatory mediators.

Animal model studies show that large-leaf bupleurum saponin II can relieve symptoms of various inflammatory diseases such as arthritis, hepatitis, and pneumonia, improve histopathological markers, and reduce infiltration of inflammatory cells. Its anti-inflammatory effect is similar to traditional bupleurum saponins, but its specific regulation of certain inflammatory targets is more pronounced.

Additionally, Bupleurum saponin II has a regulatory effect on TRPV1 and TRPA1 plasma channels, which play key roles in pain and inflammation signaling, suggesting potential application value in inflammatory pain management.

Mechanism of action and molecular targets

The anti-inflammatory mechanism of Saponin II involves the coordinated regulation of multiple signaling pathways and molecular targets. Core targets include inflammatory factor IL-6, transcription factor STAT3, inflammasome component CASP1, inflammatory mediator synthase PTGS1/PTGS2, pro-inflammatory cytokine TNF, and oxidative stress-related enzyme NOS2.

1. IL-6/STAT3 signaling pathway: IL-6 is a pro-inflammatory cytokine that promotes inflammation and cell proliferation by activating the STAT3 signaling pathway. Saponin II can inhibit IL-6 expression and STAT3 phosphorylation, block signal transduction, and reduce transcription of inflammatory genes.

2. Regulation of inflammasomes: CASP1, as a key enzyme in inflammasomes, participates in the maturation of inflammatory factors such as IL-1β. Large-leaf Bupleurum Saponin II reduces the release of pro-inflammatory cytokines by inhibiting CASP1 activity, thereby alleviating inflammatory responses.

3. Cyclooxygenase (PTGS1/PTGS2) inhibits :P catalytic prostaglandin synthesis of TGS1 and PTGS2, serving as an important mediator of inflammatory responses. This compound inhibits both enzymes, reducing the formation of inflammatory mediators.

4. Pro-inflammatory cytokine TNF inhibition: TNF-α is one of the core factors in inflammatory responses. Saponin II can significantly reduce TNF-α expression and alleviate inflammatory cascade reactions.

5. Oxidative stress regulation: By inhibiting NOS2, it reduces excessive nitric oxide (NO) formation, thereby decreasing oxidative stress damage.

6. TRPV1/TRPA1 regulation: These two ion channels play important roles in inflammatory pain and neuroinflammation. Large-leaf Bupleurum Saponin II regulates its activity to relieve pain and inflammation symptoms.

7. NF-κB signaling pathway inhibition: NF-κB is a key transcription factor regulating the expression of inflammatory genes. Large-leaf Bupleurum Saponin II can inhibit NF-κB activation and reduce the transcription of inflammatory genes.

In summary, large-leaf buprourin saponin II effectively regulates inflammatory responses through multi-target and multi-pathway synergistic effects, demonstrating its advantages as a candidate for anti-inflammatory drugs.

Druggability evaluation and pharmacokinetics

From the perspective of druggability, large-leaf bupleurum saponin II shows certain advantages and challenges. Its molecular weight is relatively large (943.1340), exceeding the ideal range for traditional small molecule drugs, which may affect oral absorption and bioavailability. A higher TPSA value (287.1400) and lower water solubility (0.0566 mg/mL) suggest strong polarity, limited solubility and membrane permeability.

The LogP value is 2.3399, indicating moderate lipid solubility and facilitating membrane penetration, but the complexity of the overall molecular structure and the presence of glycogroups may limit its transmembrane transport. The low permeability of the blood-brain barrier reduces the risk of central nervous system side effects, but also limits its application in central inflammatory diseases.

In terms of safety, the hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0, indicating low genotoxicity risk and good safety.

In terms of pharmacokinetics, current research is relatively limited. Due to its large molecular weight and low water solubility, oral absorption may be limited, and further bioavailability is needed through pharmacological methods (such as nanocarriers, liposomes, etc.). The metabolic pathways in the body remain unclear and require further research. The role and excretion pathways of hepatic metabolic enzymes are key areas of future research.

Prospects and outlooks for clinical applications

With its significant anti-inflammatory activity and multi-target regulatory advantages, large-leaf Bupleurum Saponin II has broad application prospects in the treatment of inflammatory diseases. Its targets cover a variety of inflammation-related factors, making it suitable for rheumatoid arthritis, hepatitis, pneumonia, and inflammatory pain.

Currently, the main challenge in developing natural product drugs is optimizing bioavailability and pharmacokinetic performance. Future research on large-leaf bupleurum saponin II may focus on:

1. Pharmaceutical improvements: Enhancing solubility and absorption rates through nanotechnology, liposomes, and solid dispersions.

2. Structural modification: Chemical modification based on molecular structure optimizes drug properties to enhance targeting and biological activity.

3. In-depth Mechanism Research: Using multi-omics techniques, further elucidating its mechanism of action and target network to uncover potential synergistic effects.

4. Preclinical safety evaluation: Systematic toxicological studies are conducted to assess the safety and tolerability of long-term medication.

5. Clinical trial design: Based on pharmacological and pharmacokinetic data, design reasonable clinical trials to verify efficacy and safety.

In addition, by integrating modern drug design concepts, developing derivatives or compound formulations of Bupleurum Saponin II may achieve better therapeutic outcomes. Its low blood-brain barrier permeability also provides safety for peripheral inflammatory diseases.

Conclusion

Bupleurum Saponin II, as an important triterpene saponin in Bupleurum species, possesses significant anti-inflammatory activity and multi-target regulatory ability, demonstrating good pharmacological potential. Its complex chemical structure and physicochemical properties pose challenges for drug development, but also provide abundant opportunities for transformation. In the future, through in-depth mechanistic research, pharmaceutical optimization, and preclinical evaluation, it is expected to promote clinical application and become a novel natural drug candidate molecule for treating inflammatory diseases.

In summary, large-leaf bupleurum saponin II not only enriches the research system for natural products of bupleurum saponins, but also provides new ideas and directions for the development of anti-inflammatory drugs, making it worthy of continued attention and in-depth exploration in the field of natural product pharmacology.