Synonym name:
Catalogue No.: BP0502
Cas No.: 20086-06-0
Formula: C₁₉H₂₀O₆
Mol Weight: 344.363
Botanical Source: Dioscorea bulbifera (air potato)

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:

Diosbulbin B has potential anti-tumor effects which may be related to influencing the immune system for the first time, it also exhibits potential hepatotoxicity.

References:

J Zhejiang Univ Sci B. 2014 Jun;15(6):540-7.    

Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo.    

METHODS AND RESULTS:

The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by Diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments Diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases Diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in Diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in Diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of Diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in Diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments Diosbulbin B-induced tumor growth inhibition compared with Diosbulbin B alone. 

CONCLUSIONS:

Taken together, the present study shows that ferulic acid prevents Diosbulbin B-induced liver injury via ameliorating Diosbulbin B-induced liver oxidative stress injury and augments Diosbulbin B-induced anti-tumor activity.    

Hum Exp Toxicol. 2014 Jul;33(7):729-36.    

Diosbulbin B-induced liver injury in mice and its mechanism.   

Dioscorea bulbifera L., a commonly used medicinal plant in China, is reported to induce hepatotoxicity. The present study is undertaken to investigate the hepatotoxicity induced by Diosbulbin B(DB), a diterpene lactone isolated from D. bulbifera L., and to further explore its underlying mechanism. 

METHODS AND RESULTS:

DB was administered to mice at the doses of 0, 16, 32, and 64 mg/kg once daily for 12 consecutive days. Liver injury induced by Diosbulbin B was evidenced by the increased activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver histological evaluation showed that the mice treated with Diosbulbin B exhibited liver damage with the swelling of hepatocytes. Further results showed that the amount of malondialdehyde (MDA) in the liver was increased in mice treated with Diosbulbin B, while the glutathione amount and the enzymatic activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), copper/zinc-superoxide dismutase (CuZn-SOD), manganese-SOD (Mn-SOD), and catalase (CAT) were all decreased. Diosbulbin B also decreased the gene expression of CuZn-SOD and CAT. 

CONCLUSIONS:

Taken together, our results indicate that oral administration of Diosbulbin B for 12 consecutive days can lead to the oxidative stress liver injury in mice.    

HPLC of Diosbulbin B

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

Introduction/Overview

Diosbulbin B is a natural diterpene lactone derived from the traditional Chinese medicinal material Dioscorea bulbifera L., and has attracted widespread attention due to its unique biological activity. As the main hepatotoxic component of Huangduzhong, Huangdusu B not only holds an important position in traditional Chinese medicine toxicology research but its anti-tumor potential has also been gradually confirmed by modern pharmacology. In recent years, xandoxin B has demonstrated significant cell proliferation inhibition and pro-apoptosis in the field of anti-cancer treatment, especially in non-small cell lung cancer (NSCLC) research, becoming a hot topic in natural product pharmacology and cancer treatment research. This paper systematically reviews the chemical structure and physicochemical properties of xanthoxin B, plant origin and extraction methods, pharmacological activity, mechanism of action and molecular targets, druggability evaluation, and pharmacokinetic characteristics, and looks ahead to its clinical application prospects, aiming to provide theoretical basis and reference for subsequent drug development and mechanistic studies.

Chemical structure and physicochemical properties

Xanthoxin B is a diterpene lactone compound, with a molecular formula of C20H24O6 and a molecular weight of 344.3630. Its structural features include a typical diterpene framework and lactone rings, giving it unique biological activity. The LogP value of xanthoxin B is 1.8222, indicating moderate lipid solubility that facilitates cell membrane penetration. The polar surface area (TPSA) is 74.97 Ų, reflecting its polar characteristics in drug absorption and distribution. Its low water solubility (0.0394 mg/mL) suggests limited solubility in the aqueous phase, which may affect its bioavailability. Xandoxin B can cross the blood-brain barrier, suggesting its potential value in treating central nervous system diseases or brain tumors. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. Ames mutagenic test scored 0.9, indicating a low genotoxicity risk and meeting drug safety requirements.

Plant Origins and Extraction Methods

Xanthosin B is mainly found in the tubers and tuber nodules of Dioscorea bulbifera L. Huangdu belongs to the dioscorea family, widely distributed in tropical and subtropical Asia, and is commonly used in traditional Chinese medicine to treat digestive system diseases and tumors. Huangdu contains various diterpene lactone compounds, among which Huangduxin B serves as the main active ingredient and has significant biological effects.

Common methods for extracting xantoxin B include organic solvent extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. The typical process is: after drying and crushing Huangdu, reflux extraction is performed with ethanol or methanol, concentration is performed by silica gel column chromatography, and the target components are separated using solvent systems of different polarities. Finally, high-purity xanthoxin B is obtained by HPLC purification. In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity, reduced solvent usage, and aligned with green chemistry principles.

Pharmacological activity research

The pharmacological activity of xantoxin B mainly focuses on two main aspects: antitumor and hepatotoxicity. Numerous in vitro cell experiments and some in vivo animal model studies have shown that xantoxin B can significantly inhibit the proliferation of various cancer cell lines, especially non-small cell lung cancer (NSCLC) cells. Its anticancer activity manifests as multiple mechanisms such as inducing cell cycle arrest, promoting apoptosis, and activating autophagy.

1. Inhibits cell proliferation
   Xanthoxin B can effectively inhibit cancer cell proliferation, mainly by blocking the cell cycle progression, especially by inducing arrest during the G0/G1 phase, reducing the entry of cells into S and M phases, and lowering the rate of cell division.

2. Induces apoptosis
   The mechanism by which xanthoxin B induces cancer cell apoptosis involves mitochondrial pathways, manifesting as a decrease in mitochondrial membrane potential, upregulation of pro-apoptosis protein expression (such as Caspase-9 activation), and downregulation of anti-apoptotic protein BCL2, ultimately triggering programmed cell death.

3. Autophagy activated
   Xanthoxin B can induce cellular autophagy, regulating intracellular metabolic balance and damage repair as part of cellular stress responses. The activation of autophagy is to some extent related to its anti-tumor effects, but the specific mechanisms still require further exploration.

4. Hepatotoxicity
   Huangdoxin B, as the main hepatotoxic component of Huangdu, can induce hepatocyte damage, manifesting as abnormal liver function and histopathological changes. The mechanisms of hepatotoxicity may be closely related to mitochondrial dysfunction, oxidative stress, and inflammatory responses, posing safety challenges for its clinical application.

Mechanism of action and molecular targets

The antitumor effects of xanthoxydronin B involve multiple signaling pathways and key molecular targets, forming a complex regulatory network. Through molecular biology techniques and network pharmacological analysis, several important targets have been identified:

• BCL2: Xanthoxin B downregulates the expression of the anti-apoptotic protein BCL2, promoting apoptosis.
• ABCA1: Regulates lipid metabolism in cell membranes and affects cell signal transduction.
• STAT3: Inhibits the STAT3 signaling pathway, blocking tumor cell proliferation and survival signals.
• ESR2 (estrogen receptor β): regulates hormone-dependent growth of tumor cells.
• MAPT (microtubule-associated protein Tau): affects cytoskeletal stability and interferes with cell division.
• PIK3CG: Inhibits the PI3K/Akt signaling pathway, blocking cell proliferation and survival.
• RELA (NF-κB p65 subunit): Inhibits the NF-κB signaling pathway, reducing inflammation and tumor promoter expression.
• MAPK1 and MAPK8: regulate cellular stress responses and apoptosis signals.
• CASP9: Activates key apoptotic enzymes in the mitochondrial pathway, promoting programmed cell death.

Through the synergistic regulation of these targets, xantoxin B achieves a multi-layered attack on tumor cells, inhibiting their proliferation, promoting apoptosis and autophagy, and blocking tumor progression.

Druggability evaluation and pharmacokinetics

The druggability evaluation of huangdozin B indicates that it has certain potential for drug development. Both molecular weight and LogP value comply with the Lipinski rule, which is beneficial for oral absorption. Lower water solubility may limit its bioavailability, but it can be improved through modern formulation technologies such as nanocarriers and liposomes. High blood-brain barrier penetration offers potential in the treatment of brain tumors and neurological diseases.

In terms of safety, xantoxin B does not significantly inhibit hERG channels, reducing the risk of cardiotoxicity. Ames test results indicate that it carries a low genotoxicity risk and meets drug safety requirements. However, the hepatotoxicity of xantoxin B still requires close attention. Before clinical application, further optimization of dosage and administration regimens, or structural modification to reduce toxicity, is necessary.

Pharmacokinetic research is still in its early stages, and the characteristics of absorption, distribution, metabolism, and excretion (ADME) in vivo require further systematic study. Data suggest that it may be metabolized in the liver in the body, and the activity and toxicity of these metabolites require in-depth evaluation.

Prospects and outlooks for clinical applications

Huangdozin B, a natural product with multi-target anticancer activity, shows promising application prospects in the treatment of solid tumors such as non-small cell lung cancer. Its multiple mechanisms make it promising as an adjunct to combination chemotherapy or targeted therapy, enhancing treatment efficacy and reducing resistance risk.

Future research directions include:

1. Structural optimization and derivative development
   Chemical modification reduces liver toxicity, improves water solubility and bioavailability, and develops safer and more effective xanthoxin B derivatives.

2. Innovation in drug delivery systems
   Using nanotechnology, liposomes, polymer carriers, and other methods, the pharmacokinetic properties of xantoxin B are improved to achieve targeted release and sustained release.

3. In-depth analysis of mechanisms
   Using multi-omics technology and high-throughput screening, the molecular networks and signaling pathways involved in xantoxin B are further revealed, and new targets and biomarkers are discovered.

4. Preclinical and clinical research
   Systematic animal model experiments and safety evaluations are being conducted, and clinical trials are gradually advanced to verify efficacy and safety.

5. Mechanisms of hepatotoxicity and protective strategies
   In-depth research on the molecular mechanisms of xendoxin B hepatotoxicity, exploring combination or adjunctive therapies to reduce liver injury risk.

Conclusion

As the main active ingredient in Huangdu Zhong, Huangdusu B possesses both significant anticancer activity and potential hepatotoxicity, reflecting the complexity and challenges of natural product pharmacology. Its multi-target, multi-mechanism antitumor effects provide new ideas and candidate drugs for the treatment of malignant tumors such as non-small cell lung cancer. In the future, through structural optimization, formulation innovation, and in-depth mechanistic research, it is expected that its toxicity limitations will be overcome, promoting the translation of xantoxin B into clinical applications to benefit patients. The continued development of natural product pharmacology will provide a solid foundation for the development of xanthoxin B and similar compounds, promoting the modernization of traditional Chinese medicine and advances in precision medicine.