Synonym name:
Catalogue No.: BP0727
Cas No.: 145459-19-4
Formula: C₄₀H₅₈N₈O₈
Mol Weight: 778.952
Botanical Source: Root of Pseudostellaria heterophylla

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:

Heterophyllin B is used as the quality control index for evaluating P. heterophylla in the Chinese Pharmacopoeia.Heterophyllin B effectively suppresses the adhesion and invasion of the human esophageal carcinoma cells by mediating the PI3K/AKT/β-catenin pathways and regulating the expression levels of adhesion- and invasion-associated genes.

References:

Mol Med Rep. 2016 Feb;13(2):1097-104.    

Heterophyllin B inhibits the adhesion and invasion of ECA-109 human esophageal carcinoma cells by targeting PI3K/AKT/β-catenin signaling.  

The present study aimed to measure the effect of Heterophyllin B (HB) on the adhesion and invasion of ECA-109 human esophageal carcinoma cells, and examine the possible mechanism involved. 

METHODS AND RESULTS:

A Cell Counting kit 8 assay was performed to determine the cell viability. Cell adhesion and invasion were determined following treatment of the ECA-109 cells with HB (0, 10, 25 and 50 μM) for 24 h. The levels of phosphorylated (p-)ATK and p-phosphoinositide 3-kinase (PI3K), and the protein levels of β-catenin were measured using western blot analysis. The mRNA and protein expression levels of E-cadherin, vimentin, snail, matrix metalloproteinase (MMP)2 and MMP9 were detected using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. HB (10, 25 and 50 μM) significantly suppressed the adhesion and invasion of the ECA-109 human esophageal carcinoma cells in a dose-dependant manner. The expression levels of p-ATK, p-PI3K and β-catenin were markedly decreased. The expression of E-cadherin was promoted, whereas the expression levels of snail, vimentin, MMP 2 and MMP 9 were decreased significantly in the ECA-109 cells treated with HB. In addition, HB inhibited the adhesion and invasion induced by PI3K activating peptide in the ECA-109 cells, and the protein expression levels were also adjusted. 

CONCLUSIONS:

These results suggested that HB effectively suppressed the adhesion and invasion of the human esophageal carcinoma cells by mediating the PI3K/AKT/β-catenin pathways and regulating the expression levels of adhesion- and invasion-associated genes.    

HPLC of Heterophyllin B

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

Introduction/Overview

Heterophyllin B is an active cyclic peptide isolated from the traditional Chinese medicinal herb Pseudostellaria heterophylla. As a natural product, Pseudostellaria ginseng cyclopeptide B has attracted widespread attention in pharmacological research in recent years due to its unique cyclic peptide structure and diverse biological activities. Especially in the field of tumor immunoregulation, Taizisheng Cyclopeptide B shows significant potential, particularly showing promising application prospects in the treatment of esophageal cancer. This article aims to systematically review the chemical structure, pharmacological activity, mechanism of action, and druggability evaluation of Pseudostellaria ginseng ring peptide B, and to explore its potential for future clinical application.

Chemical structure and physicochemical properties

The chemical structure of Pseudostellaria heterophylla cyclic peptide B belongs to the cyclic polypeptide class, with a molecular weight of 778.9520. The molecular formula is complex, reflecting the closed-loop structural characteristics of its polypeptide chain. Its LogP value is 0.5005, indicating that this compound has moderate lipophilicity, which facilitates cell membrane penetration. TPSA (Topological Polar Surface Area) is 206.4300, indicating high molecular surface polarity, which may affect the permeability and distribution of its biofilm.

The water solubility of Pseudostellaria ginseng cyclopeptide B is 2.0011, indicating good water solubility, which is beneficial for oral administration and absorption in the body. The blood-brain barrier has low permeability, suggesting its limited distribution in the central nervous system, which may reduce central nervous system side effects. The hERG channel inhibition test results were negative, indicating that the compound is less likely to cause arrhythmias or other cardiotoxicity. The Ames test result was 0.0, indicating that it does not have mutagenicity and is relatively safe.

Plant Origins and Extraction Methods

Pseudostellaria heterophylla (cyclopeptide B) is mainly isolated from Pseudostellaria heterophylla. Pseudostellaria root belongs to the bellflower family, widely distributed in eastern China and East Asia. In traditional Chinese medicine, it is often used to tonify qi and nourish yin, strengthen the spleen, and benefit the lungs. The root of Pseudostellaria heterophylla contains abundant peptide compounds, with cyclic peptides being particularly important.

The extraction method typically uses organic solvent extraction combined with column chromatography separation technology. First, the dried Pseudostellaria heterostellaria root is crushed, then extracted with ethanol or methanol to extract a crude peptide mixture. It was then further purified using silica gel column chromatography, high-performance liquid chromatography (HPLC), and other techniques, ultimately yielding high-purity Pseudostellaria ginseng ring peptide B. In recent years, the application of ultrasound-assisted extraction and membrane separation technologies has improved extraction efficiency and purity, providing technical support for large-scale production.

Pharmacological activity research

The pharmacological activity of Pseudostellaria ginseng cyclopeptide B is mainly reflected in its antitumor and immunomodulatory aspects. Multiple in vitro and in vivo experiments have shown that Pseudostellaria ginseng ring peptide B has a significant inhibitory effect on esophageal cancer cells. It enhances the body's anti-tumor immune response by regulating immune cell function within the tumor microenvironment.

In terms of immune regulation, Taizhen Huan Peptide B can regulate various key immune factors and signaling pathways, including TLR4, STAT3, IL2, NFKB1, TGFB1, CTLA4, STAT4, IL10, FOXP3, and IFNG. These targets play a central role in regulating immune cell activation, proliferation, and differentiation. Pseudostellaria ginseng cyclopeptide B promotes immune system balance by modulating these targets, enhances anti-tumor immunity, and suppresses tumor-related immune escape mechanisms.

In addition, Pseudostellar ginseng cyclopeptide B exhibits multiple biological activities including anti-inflammatory and antioxidant properties, providing a theoretical basis for its application in various immune-related diseases.

Mechanism of action and molecular targets

The mechanism of action of Pseudostellaria ginseng ring peptide B involves multiple signaling pathways and molecular targets, mainly focusing on immune regulation and antitumor aspects.

1. TLR4 signaling pathway
   Tajiazhen peptide B influences innate immune responses by modulating the TLR4 (Toll-like receptor 4) signaling pathway. TLR4 is a key receptor for recognizing pathogen-associated molecular patterns (PAMPs), and upon activation, it can induce the activation of transcription factors such as NFKB1, thereby regulating the expression of inflammatory and immune factors. Pseudostellaria ginseng ring peptide B can inhibit overactive TLR4 signaling, reduce inflammatory responses, and promote normal immune cell function.

2. STAT3 and STAT4 regulation
   STAT3 and STAT4 are intracellular signaling and transcription activators, involved in regulating cell proliferation, differentiation, and immune responses. Pseudostellar ginseng ring peptide B can inhibit abnormal activation of STAT3, block tumor cell proliferation signals, and promote cellular immune function by modulating STAT4, enhancing the anti-tumor activity of immune cells.

3. Cytokine regulation
   Pseudostellaria ginseng ring peptide B significantly affects the expression of cytokines such as IL2, IL10, IFNG, and TGFB1. IL2 and IFNG are important factors in promoting immune cell activation and cytotoxicity. Taizhen ginseng ring peptide B enhances immune killing capacity by enhancing its expression. IL10 and TGFB1 have immunosuppressive effects; Pseudoshen Ring Peptide B regulates their balance, helping to maintain immune homeostasis and prevent immune overreactions.

4. The immune checkpoint molecule CTLA4 and regulatory T cell marker FOXP3
   Taishi ginseng ring peptide B can regulate CTLA4 expression, influence immune checkpoint pathways, and relieve tumor immunosuppression. At the same time, by regulating FOXP3 expression, it affects the function of regulatory T cells (Tregs), promoting immune recognition and clearance of tumors.

In summary, Taizhen Huan Peptide B achieves fine regulation of the immune system through multi-target and multi-pathway synergistic effects, exerting its anti-tumor and immunomodulatory functions.

Druggability evaluation and pharmacokinetics

Pseudostellaria ginseng cyclopeptide B has excellent druggability characteristics. With a molecular weight close to 800, it is a medium-sized cyclic peptide molecule with a stable structure and is not easily degraded by enzymes in the body. The LogP value is moderate, with good water solubility, facilitating absorption and distribution in the body. Low blood-brain barrier permeability, reducing potential toxic risks in the central nervous system.

In terms of safety, the hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test is non-mutagenic, further supporting its safety. Preliminary pharmacokinetic studies show that Pseudostellaria ginseng cyclopeptide B has a relatively long half-life in vivo and high bioavailability, making it suitable for development as oral or injectable formulations.

However, as a natural cyclic peptide product, the metabolic pathway of Pseudostellaria heterophylla cyclopeptide B in vivo still needs further clarification. In the future, it is necessary to conduct in-depth analysis of its absorption, distribution, metabolism, and excretion characteristics through in vivo and in vitro metabolic experiments and pharmacokinetic model establishment, providing a basis for clinical application.

Prospects and outlooks for clinical applications

The potential value of Taishigaen-cyclopeptide B in esophageal cancer and other immune-related diseases is becoming increasingly prominent. By modulating the immune microenvironment through multiple targets, it enhances the body's anti-tumor immune response, showing potential as an adjunct therapy. Combined with existing tumor immunotherapy strategies, such as immune checkpoint inhibitors, Pseudostellophylla cyclopeptide B may exert synergistic effects to enhance treatment outcomes.

In addition, the immunomodulatory function of Pseudostellaria ginseng cyclopeptide B also opens up its potential applications in autoimmune and inflammatory diseases. In the future, its efficacy in rheumatoid arthritis, systemic lupus erythematosus, and other diseases can be explored.

However, clinical research on Taizhen Cyclopeptide B is still in its early stages and lacks systematic clinical trial data. In the future, pharmacological and toxicological research should be strengthened, dosage formulation design optimized, preclinical safety evaluations and clinical trials conducted to verify efficacy and safety.

At the same time, given the difficulty and production cost of cyclic peptide compounds, developing efficient synthesis and extraction processes to improve yield and purity is key to achieving clinical translation.

Conclusion

Pseudostellaria ginseng cyclopeptide B, as an active cyclic peptide derived from traditional medicinal materials, demonstrates excellent pharmacological activity and medicinal readiness. Its multi-target mechanisms in immune regulation and anti-tumor fields offer new approaches for the treatment of esophageal cancer and related diseases. Although current research is still in the early stages, its safety and bioactivity provide a solid foundation for subsequent clinical development. In the future, through systematic pharmacokinetic studies, mechanistic analysis, and clinical validation, Taizhen Ginseng Cyclopeptide B is expected to become an important candidate molecule in the development of natural product drugs, promoting the modernization of traditional Chinese medicine and benefiting a wide range of patients.