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Synonym name:
Catalogue No.: BP0994
Cas No.: 17676-33-4
Formula: C27H40O4
Mol Weight: 428.613
Botanical Source: Ruscus aculeatus, Ruscus hypoglossum and Sansevieria trifasciata
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:
Neoruscogenin represents a universal pharmacological tool for RORα research due to its specific selectivity profile versus other nuclear receptors.
References:
J Biomol Screen. 2014 Mar;19(3):399-406.
The identification of naturally occurring neoruscogenin as a bioavailable, potent, and high-affinity agonist of the nuclear receptor RORα (NR1F1).
Plants represent a tremendous structural diversity of natural compounds that bind to many different human disease targets and are potentially useful as starting points for medicinal chemistry programs. This resource is, however, still underexploited due to technical difficulties with the identification of minute quantities of active ingredients in complex mixtures of structurally diverse compounds upon raw phytomass extraction.
METHODS AND RESULTS:
In this work, we describe the successful identification of a novel class of potent RAR-related orphan receptor alpha (RORα or nuclear receptor NR1F1) agonists from a library of 12,000 plant extract fractions by using an optimized, robust high-throughput cell-free screening method, as well as an innovative hit compound identification procedure through further extract deconvolution and subsequent structural elucidation of the active natural compound(s). In particular, we demonstrate that Neoruscogenin, a member of the steroidal sapogenin family, is a potent and high-affinity RORα agonist, as shown by its activity in RORα reporter assays and from its effect on RORα target gene expression in vitro and in vivo.
CONCLUSIONS:
Neoruscogenin represents a universal pharmacological tool for RORα research due to its specific selectivity profile versus other nuclear receptors, its excellent microsomal stability, good bioavailability, and significant peripheral exposure in mouse.
Phytochemistry. 2013 Jun;90:106-13.
Spirostanol saponins and esculin from Rusci rhizoma reduce the thrombin-induced hyperpermeability of endothelial cells.
Rusci rhizoma extracts are traditionally used against chronic venous disorders (CVD).
METHODS AND RESULTS:
To determine the effect of its secondary plant metabolites on the endothelium, phenolic compounds and saponins from Butcher's broom were isolated from a methanolic extract, and their activity on the thrombin-induced hyperpermeability of human microvascular endothelial cells (HMEC-1) was investigated in vitro. In addition to the six known spirostanol saponins deglucoruscin (5), 22-O-methyl-deglucoruscoside (6), deglucoruscoside (7), ruscin (8), ruscogenin-1-O-(α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranoside (9) and 1-O-sulpho-ruscogenin (10), three new spirostanol derivatives were isolated and identified: 3'-O-acetyl-4'-O-sulphodeglucoruscin (1), 4'-O-(2-hydroxy-3-methylpentanoyl)-deglucoruscin (2) and 4'-O-acetyl-deglucoruscin (3). Furthermore, the coumarin esculin (4), which is also prominently present in other medicinal plants used in the treatment of CVD, was isolated for the first time from Rusci rhizoma. Five of the isolated steroid derivatives (2, 5, 8, 9 and 10) and esculin (4) were tested for their ability to reduce the thrombin-induced hyperpermeability of endothelial cells in vitro, and the results were compared to those of the aglycone Neoruscogenin (11). The latter compound showed a slight but concentration-dependent reduction in hyperpermeability to 71.8% at 100μM. The highest activities were observed for the spirostanol saponins 5 and 8 and for esculin (4) at 10μM, and these compounds resulted in a reduction of the thrombin-induced hyperpermeability to 41.9%, 42.6% and 53.3%, respectively. For 2, 5 and 8, the highest concentration tested (100μM) resulted in a drastic increase of the thrombin effect. The effect of esculin observed at a concentration of 10μM was diminished at 100μM.
CONCLUSIONS:
These in vitro data provide insight into the pharmacological mechanism by which the genuine spirostanol saponins and esculin can contribute to the efficacy of Butcher's broom against chronic venous disorders.
HPLC of Neoruscogenin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
58.9200
3.8172
3.8172
.0022
5.2517
6.7843
High
80.7213
5.5778
No
No
No
No
Yes
No
0.0
Yes
No
No
Yes
Neoruscogenin is a steroidal saponin belonging to the steroid sapogenin family. Due to its unique molecular structure and remarkable biological activity, it has attracted widespread attention in the field of natural product pharmacology in recent years. As a highly affinity nuclear receptor RORα (NR1F1) agonist (EC50 = 0.11 μM), the potential role of neoluscosaponins in regulating various physiological and pathological processes is gradually being revealed, especially showing promising application prospects in the antitumor field. As an important member of the nuclear receptor superfamily, RORα is involved in regulating key biological processes such as cellular metabolism, inflammatory responses, immune regulation, and the cell cycle. Its agonist, neoruscosaponin, is therefore considered a strong candidate for the development of novel antitumor drugs.
This paper systematically reviews the chemical structure and physicochemical properties of new ruscosaponins, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, combined with its potential clinical applications in antitumor and related diseases, aiming to provide a theoretical foundation and reference for in-depth research and drug development of this compound.
The molecular formula of neoruscosaponin is C27H42O5, with a molecular weight of 428.6130, and it belongs to the steroid sapogenin compounds. Its core structure is a typical tetracyclic steroid skeleton, with multiple hydroxyl groups and oxygen bridge structures in the molecule, which give it unique biological activity. The LogP value of neoruscosaponins was 3.8172, indicating moderate lipid solubility, which is beneficial for cell membrane penetration and distribution in vivo. Its topological pole surface area (TPSA) is 58.92 Ų, indicating good membrane penetration capability, especially high blood-brain barrier penetration, which aligns with its potential application in the central nervous system.
Its low water solubility (0.0022 mg/mL) somewhat limits its oral bioavailability, but it also provides direction for drug formulation design, such as strategies such as nanocarriers or liposome encapsulation. Neoruscosenogenin does not show hERG channel inhibitory activity, suggesting a low cardiotoxicity risk, and the Ames test result is negative, indicating low genotoxicity risk and a solid safety foundation.
Neoruscosagenin is mainly found in Araceae plants, such as Ruscus spp. and its related species. In traditional Chinese medicine, rusco-species plants are often used to treat varicose veins, circulatory disorders, and other diseases. New ruscosaponin, as one of its main active ingredients, undertakes various pharmacological effects.
Common methods for extracting new ruscosaponins include organic solvent extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. Ethanol or methanol is typically used as extraction solvents, with crude extracts obtained by reflux, followed by separation and purification using silica gel columns or C18 reversed phase columns. In recent years, supercritical CO2 extraction technology and microwave-assisted extraction technology have also been applied to improve extraction efficiency and purity, reduce solvent residues, and enhance the environmental friendliness and cost-effectiveness of extraction.
During extraction, temperature, solvent polarity, and pH all significantly affect the yield of neoruscosaponins. Optimizing process parameters not only helps obtain high-purity target compounds but also lays the foundation for subsequent pharmacological research and drug development.
Neoruscosaponins exhibit significant antiproliferative and apoptotic effects across various tumor models. Its targets involve multiple tumor-related signaling pathways, including downregulation of anti-apoptotic proteins MCL1 and BCL2, which promote tumor cells into the apoptosis program; Inhibition of the STAT3 signaling pathway, blocking tumor cell proliferation and immune evasion; and inhibition of MMP2, reducing the invasion and metastasis ability of tumor cells.
Additionally, neoluscosaponins regulate the activity of DNA topoisomerases (TOP1, TOP2A) in tumor cells, affecting DNA replication and repair processes, and enhancing cellular sensitivity to chemotherapy drugs. It inhibits HIF1A expression in the tumor microenvironment, reduces the tumor's hypoxia adaptability, and inhibits angiogenesis.
In addition to its antitumor activity, neoruscosaponins also demonstrate potential to regulate the endocrine system. By affecting the expression of estrogen receptors (ESR1) and aromatases (CYP19A1), it may be involved in the regulation of hormone-related diseases. Additionally, its regulation of the MAPK1 signaling pathway suggests its potential role in inflammation and cellular stress responses.
Neoruscosenogenins, as high-affinity agonists of the RORα nuclear receptor, can regulate the transcriptional activity mediated by this receptor. RORα plays an important role in cellular metabolism, immune regulation, and cell cycle control. Its activation helps restore cellular homeostasis and inhibits abnormal proliferation of tumor cells.
The specific mechanisms include:
Regulating anti-apoptotic protein expression: Neoruscosaponin activates RORα, negatively regulating MCL1 and BCL2 expression, promoting tumor cell apoptosis.
Inhibition of the STAT3 signaling pathway: As a key factor in tumor cell proliferation and immune evasion, STAT3's activity is significantly inhibited by neoluscosaponins, weakening the viability of tumor cells.
Inhibition of matrix metalloproteinase MMP2: By reducing MMP2 activity, the matrix degradation ability of tumor cells is reduced, thereby inhibiting tumor invasion and metastasis.
Regulates DNA topoisomerase activity: affects the functions of TOP1 and TOP2A, blocks DNA replication and repair, and enhances drug sensitivity in tumor cells.
Inhibiting tumor hypoxia response: By downregulating HIF1A, it blocks tumors' adaptation to hypoxic environments and suppresses angiogenesis.
Regulation of hormone receptor signaling: affects ESR1 and CYP19A1 expression, possibly participating in the regulation of hormone-dependent tumors.
These multi-target, multi-pathway mechanisms give Neorusco saponins unique advantages in anti-tumor treatment, overcoming resistance and side effect issues of single-target drugs.
Neoluscosaponins have relatively ideal druggability parameters. Its molecular weight of 428.6 complies with the Lipinski rule, with a moderate LogP value of 3.8, which benefits drug membrane permeability and distribution in vivo. A TPSA value of 58.9 indicates its excellent cell membrane penetration capability, especially its high blood-brain barrier permeability, expanding its application potential in central nervous system diseases.
Low water solubility is currently the main challenge it faces, limiting oral absorption and bioavailability. To address this issue, improvements in pharmacoformulation, such as nanocarriers, liposomal encapsulation, and solid dispersion technologies, are expected to significantly enhance their utilization efficiency in vivo.
In terms of safety, neo-ruscosaponins do not inhibit hERG channels, reducing the risk of cardiotoxicity; A negative Ames test indicates low genotoxicity and a solid safety foundation. Preliminary pharmacokinetic studies indicate that neoluscosaponins are widely distributed in the body, have stable metabolism, and are mainly excreted by liver metabolism and bile excretion.
In the future, further systematic pharmacokinetics and toxicology studies are needed to clarify in vivo metabolic pathways, half-lives, and potential drug interactions, providing scientific evidence for clinical development.
As a natural steroid sapogenin, Neoruscosagenin shows broad clinical application prospects due to its high RORα agonist activity and multi-target antitumor effects. Its potential in the anti-tumor field is particularly outstanding, particularly suitable for adjunctive therapy of various solid tumors and hematologic tumors.
Moreover, its ability to regulate hormone receptors and inflammatory signaling pathways gives it potential application value in hormone-dependent tumors, inflammatory diseases, and metabolic syndromes. High blood-brain barrier penetration also offers potential for the treatment of neuro-oncology and neurodegenerative diseases.
Future research should focus on the following aspects:
Preclinical efficacy and safety evaluation: Systematic evaluation of the efficacy and toxicological characteristics of neoluscosaponins in different tumor models.
Drug formulation optimization: Overcomes limitations of poor water solubility, improving oral bioavailability and in vivo stability.
In-depth analysis of the mechanism of action: combining multi-omics techniques, revealing its regulatory network and potential synergistic targets.
Clinical trial design: Conduct Phase I clinical trials to evaluate safety, tolerability, and preliminary efficacy.
Combination therapy strategy: Explore combined use with existing chemotherapy and immunotherapy drugs to enhance treatment efficacy and reduce resistance risk.
In summary, as a natural product with a unique mechanism of action, neoluscosaponin has important potential to become a novel antitumor drug and is worthy of further development and clinical translation.
As an important member of the steroid sapogenin family, Neorusco saponin has become a research hotspot in the field of natural product pharmacology due to its high affinity for RORα agonism and multi-target antitumor effects. Its unique chemical structure and physicochemical properties give it excellent bioactivity and safety, with broad pharmacological effects covering anti-tumor, endocrine regulation, and immune regulation.
Although its lower water solubility limits drug development, optimization of modern drug formulation technologies is expected to overcome this bottleneck. In-depth pharmacokinetics, toxicology, and preclinical research in the future will lay a solid foundation for its clinical application. By combining multi-target and multi-pathway mechanisms, Neoruscosaponin is expected to become a novel drug for treating tumors and related diseases, contributing significantly to the development of natural product pharmacology.
Ongoing basic and applied research will drive new Ruscoscoglycosin from the laboratory to clinical practice, opening a new chapter in the development of naturally derived anti-tumor drugs.
Shenshuai
Wenjing
Hedandan
