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Synonym name:
Catalogue No.: BP0939
Cas No.: 54522-52-0
Formula: C52H86O22
Mol Weight: 1063.24
Botanical Source:
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:
Methyl protodioscin has anti-thrombosis, antiosteoporotic, anti-myocardial infarction, and cytotoxic activities. Methyl protodioscin shows strong cytotoxicity against most cell lines from solid tumors with GI50 ≤10.0 microM, but moderate cytotoxicity is shown against leukemia cell lines with GI50 10-30 microM. It potentially increase HDL cholesterol while reducing LDL cholesterol and triglycerides, it also can treat diverse inflammatory pulmonary diseases.
References:
Pharmacogn Mag. 2014 Jul;10(39):318-24.
Methyl protodioscin induces G2/M cell cycle arrest and apoptosis in A549 human lung cancer cells.
Methyl protodioscin (MPD) is a furostanol bisglycoside with antitumor properties. It has been shown to reduce proliferation, cause cell cycle arrest. The present study elucidates the mechanism underlying MPD's apoptotic effects, using the A549 human lung cancer cell line.
METHODS AND RESULTS:
The human pulmonary adenocarcinoma cell line A549 was obtained from the Cell Bank of the Animal Experiment Center, North School Region, Sun Yat-Sen University. All of the cells were grown in RPMI 1640 supplemented with 10% fetal calf serum (Hyclone, Logan, UT, USA), penicillin (10,000 U/l), and streptomycin (100 mg/l) at 37°C in a 5% CO2 humidified atmosphere. The induction of apoptosis was observed in flow cytometry and fluorescent staining experiments. MPD showed growth inhibitory effects in A549 cells in a dose- and time-dependent manner. The significant G2/M cell cycle arrest and apoptotic effect were also seen in A549 cells treated with MPD. MPD-induced apoptosis was accompanied by a significant reduction of mitochondrial membrane potential, release of mitochondrial cytochrome c to cytosol, activation of caspase-3, downregulation of Bcl-2, p-Bad, and upregulation of Bax.
CONCLUSIONS:
Our results show that the induction of apoptosis by MPD involves multiple molecular pathways and strongly suggest that Bcl-2 family proteins signaling pathways. In addition, mitochondrial membrane potential, mitochondrial cytochrome c and caspase-3 were also closely associated with MPD-induced apoptotic process in human A549 cells.
Cancer Invest. 2003 Jun;21(3):389-93.
The cytotoxicity of methyl protodioscin against human cancer cell lines in vitro.
Methyl protodioscin (NSC-698790) was a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of the urinary bladder, and renal tumors for centuries.
METHODS AND RESULTS:
To systematically evaluate its potential anticancer activity, Methyl protodioscin was tested cytotoxicity in vitro against human cancer cell lines by the NCI's (National Cancer Institute) anticancer drug screen. As a result, Methyl protodioscin showed strong cytotoxicity against most cell lines from solid tumors with GI50 < or = 10.0 microM, especially selectively against one colon cancer line (HCT-15) and one breast cancer line (MDA-MB-435) with GI50 < 2.0 microM but moderate cytotoxicity was shown against leukemia cell lines with GI50 10-30 microM.
CONCLUSIONS:
The data are consistent with the fact that the rhizome of D. collettii var. hypoglauca has been employed for the treatment of solid tumors rather than leukemia in China for centuries. Based on an analysis using the COMPARE computer program with Methyl protodioscin as a seed compound, no compounds in the NCI's anticancer drug screen database have cytotoxicity patterns similar to those of Methyl protodioscin, indicating a potential novel mechanism of anticancer action.
Phytomedicine. 2015 May 15;22(5):568-72.
Dioscin and methylprotodioscin isolated from the root of Asparagus cochinchinensis suppressed the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor.
The root of Asparagus cochinchinensis (Lour.) Merr. has been utilized as mucoregulators and expectorants for controlling the airway inflammatory diseases in folk medicine. We investigated whether dioscin and Methyl protodioscin isolated from the root of Asparagus cochinchinensis (Lour.) Merr. suppress the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor.
METHODS AND RESULTS:
Confluent NCI-H292 cells were pretreated with dioscin or Methyl protodioscin for 30 min and then stimulated with EGF or PMA for 24 h. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. (1) Dioscin and Methyl protodioscin suppressed the expression of MUC5AC mucin gene induced by EGF or PMA; (2) dioscin suppressed the production of MUC5AC mucin induced by either EGF at 10(-5) M (p < 0.05) and 10(-6) M (p < 0.05) or PMA at 10(-4) M (p < 0.05), 10(-5) M (p < 0.05) and 10(-6) M (p < 0.05); (3) Methyl protodioscin also suppressed the production of MUC5AC mucin induced by either EGF at 10(-4) M (p < 0.05) or PMA at 10(-4) M (p < 0.05).
CONCLUSIONS:
These results suggest that dioscin and Methyl protodioscin isolated from the root of Asparagus cochinchinensis suppress the gene expression and production of MUC5AC mucin, by directly acting on airway epithelial cells, and the results are consistent with the traditional use of Asparagus cochinchinensis as remedy for diverse inflammatory pulmonary diseases.
HPLC of Methyl protodioscin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
335.0600
1.7162
1.7160
.2032
.4880
.3851
Low
64.7533
6.8407
No
No
No
No
No
No
0.0
Yes
No
No
No
Methyl protodioscin (CAS No.: 54522-52-0), also known as NSC-698790 or Smilax saponin B, is an important active component in a class of steroid saponins and is widely found in plants of the Dioscoreaceae family. As a multi-target sterosaccharide-type inhibitor, methyl prodiosgenin has attracted significant attention in natural product pharmacology due to its remarkable anti-tumor, anti-inflammatory, and anti-vascular restenosis activity. In recent years, with further research into its mechanism of action, the therapeutic potential of methylprodiosgenin in various tumors such as lung cancer, prostate cancer, and pancreatic cancer, as well as inflammatory diseases like airway inflammation and enteritis, has gradually become an important candidate for natural drug development.
This review aims to systematically summarize the chemical structure and physicochemical properties, plant origin, and extraction methods of methyl prodiosgenin, focusing on analyzing its pharmacological activity and molecular mechanisms, evaluating its druggability and pharmacokinetic characteristics, and exploring its clinical application prospects and future research directions, providing scientific basis for natural product pharmacology and new drug development.
Methyl prodiosgenin belongs to the steroid saponin class of compounds, with a molecular formula of C51H84O22 and a molecular weight of 1063.2380. Its structural core is a steroid backbone, connected to multiple glycosyl residues, forming a disaccharide-type structure. The compound has a LogP value of 1.7162, indicating moderate lipid solubility, which facilitates penetration of cell membranes. The total polar surface area (TPSA) was 335.0600, indicating high polarity that may affect oral absorption and bioavailability.
Water solubility is 0.2032, which is moderately low in water solubility, suggesting that there may be some solubility limitations when distributed in vivo. The low permeability of the blood-brain barrier indicates its limited distribution in the central nervous system, which helps reduce the risk of central toxicity. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames-induced mutagenic test was 0.0, indicating a low genotoxicity risk and meeting safety requirements.
Chemically, the steroid framework of methyl diosgenin gives it stable chemical properties, while the presence of sugar groups enhances its water solubility and biological activity. Its complex glycoside linkage provides the molecular basis for its multi-target action.
Methyl prodioscoreins are mainly found in plants of the Dioscoreaceae family, especially in the rhizomes and tubers of Dioscorea spp. and Smilax spp. Common source plants include Dioscorea nipponica, Clematis chinensis, and Smilax glabra. In traditional Chinese medicine, these plants are widely used to treat tumors, inflammation, and immune-related diseases.
The extraction method typically uses alcohols (such as methanol, ethanol) or water-alcohol mixtures to extract dried plant tubers by reflux or ultrasound. After concentration, separation, and multi-step chromatographic separation (such as silica gel column and reversed-phase C18 column chromatography), the extract was purified and identified using high-performance liquid chromatography (HPLC) and mass spectrometry (MS) technologies. In recent years, the application of supercritical CO2 extraction and membrane separation technologies has improved extraction efficiency and purity.
Optimization of the extraction process not only improves the yield of methyl prodiosgenin but also lays the foundation for large-scale production and drug development.
Methylprodiosgenin exhibits broad-spectrum antitumor activity, significantly inhibiting the proliferation, migration, and invasion of various cancer cell lines, and inducing apoptosis. Its anti-tumor effects cover lung, prostate, pancreatic, and breast cancers, demonstrating strong tumor suppression potential.
In vitro experiments have shown that methyl prodiosgenin can induce cell cycle blockade during the G2/M phase of cancer cells, blocking cell division and thereby inhibiting tumor cell proliferation. The apoptosis induced by this is closely related to the regulation of Bcl-2 family proteins, manifested as downregulation of Bcl-2 expression and upregulation of Bax expression, promoting mitochondrial pathway-mediated apoptosis. Additionally, methylprodiosenosides regulate tumor cell growth and metabolism by inhibiting the Akt1/c-Myc signaling axis and the MAPK/ERK pathway.
Animal experiments further confirmed its antitumor effect, showing that methyl prodiosgenin can significantly inhibit tumor volume growth, prolong survival in tumor model animals, and has relatively low toxicity and side effects.
Methyl prodiosgenin demonstrates good anti-inflammatory effects in models of inflammatory diseases. Its mechanism mainly involves inhibiting the JNK/c-Jun signaling pathway, reducing the expression of pro-inflammatory cytokines IL-6 and TNF-α, thereby alleviating inflammatory responses. This action is of great significance for alleviating diseases such as airway inflammation and enteritis.
Additionally, methyl prodiosgenin can induce FOXO1 expression, inhibit cholesterol synthesis, indirectly regulate the inflammatory microenvironment, and demonstrate multi-layered anti-inflammatory regulatory capabilities.
Vascular restenosis is a common complication after vascular interventional therapy. Methylprodiostenin regulates the proliferation and migration of vascular smooth muscle cells and inhibits ADAM15 expression, thereby effectively reducing the occurrence of vascular restenosis and offering potential cardiovascular protection.
The multi-target mechanism of methyl prodiosgenin is the basis of its pharmacological diversity. The main targets involved are the following signaling pathways and molecular targets:
Cell cycle regulation
Methylprodiosgenin induces G2/M phase cell cycle arrest and blocks cell division, mainly by regulating cyclin and its kinase activity.
Apoptotic pathway regulation
By downregulating the anti-apoptotic protein Bcl-2 and upregulating the pro-apoptotic protein Bax, mitochondria-dependent apoptosis signals are activated, promoting programmed death of cancer cells.
Akt1/c-Myc signal axis suppression
Inhibits Akt1 kinase activity, reduces c-Myc expression, blocks cell metabolism and proliferation signals, and inhibits tumor growth.
MAPK/ERK signaling path regulation
Inhibits the MAPK/ERK pathway, reduces cell proliferation and migration capacity, and blocks tumor metastasis.
JNK/c-Jun pathway inhibition
Lowers the expression of pro-inflammatory factors IL-6 and TNF-α, alleviating inflammatory responses.
FOXO1 inducement
Promotes FOXO1 expression, regulates cholesterol metabolism, and improves the inflammatory microenvironment.
ADAM15 has been reduced
Inhibits the proliferation and migration of vascular smooth muscle cells, preventing restenosis.
In tumors such as breast cancer, methyl prodiosgenin also acts on multiple targets including AMPK, STAT3, ESR2, ABCB1, ABCG2, PRKCA, MAPT, MMP2, and LCK, demonstrating its complex multi-target synergistic regulatory properties.
Methyl prodiosgenin has moderate lipid solubility (LogP 1.7162) and high polarity (TPSA 335.0600), which poses challenges for oral absorption and internal distribution. Its low water solubility (0.2032) suggests that appropriate solubilization or nanocarrier technologies should be adopted in drug formulation design to improve bioavailability.
The low permeability of the blood-brain barrier reduces the potential toxic risk of the central nervous system. hERG channels have no inhibitory effects, reducing the risk of cardiotoxicity. A negative Ames test indicates a low genotoxicity risk and meets safety requirements.
Currently, pharmacokinetic research on methyl prodiosgenin is relatively limited, and in vivo metabolic pathways, half-life, tissue distribution, and excretion modes require further systematic study. Preliminary data suggest that it is metabolized in the liver through enzymatic metabolism and may involve the CYP450 enzyme lineage.
Based on drug development, methyl prodiosgenin has a solid safety foundation, but its in vivo stability and bioavailability need to be improved through formulation optimization and structural modification to meet clinical application needs.
Methyl prodiosgenin, as a multi-target natural product, demonstrates broad antitumor and anti-inflammatory potential, and holds promising clinical development prospects. In the field of tumor treatment, especially in refractory tumors such as lung cancer, prostate cancer, pancreatic cancer, and breast cancer, methylprodiosgenin is expected to become a candidate molecule for novel anticancer drugs through multi-pathway synergistic effects.
Moreover, its anti-inflammatory and anti-restenosis activities offer new ideas for the treatment of chronic inflammatory diseases and cardiovascular diseases. In the future, it can be explored in combination with existing chemotherapy drugs or immunomodulators to achieve synergistic effects.
However, the clinical translation of methyl prodiosgenin still faces many challenges, including low bioavailability, complex metabolism in vivo, and insufficient evaluation of efficacy and safety. It is necessary to strengthen pharmacokinetics, toxicology, and preclinical research, optimize dosage forms and administration routes, and conduct systematic clinical trials to verify efficacy and safety.
Additionally, based on its multi-target characteristics and combined with modern molecular docking, network pharmacology, and systems biology methods, in-depth analysis of its network of action helps guide precise medication and personalized treatment strategies.
Methyl prodiosgenin, as a typical natural steroid saponin product, demonstrates broad application potential in anti-tumor, anti-inflammatory, and anti-vascular restenosis fields due to its multi-target and multi-mechanism pharmacological activity. Its complex mechanism of action and good safety provide a solid foundation for new drug development.
Future research should focus on optimizing its pharmacokinetic properties, deepening mechanistic studies, expanding indications, and promoting clinical translational progress. Through multidisciplinary integration, methyl prodiosgenin is expected to become a star molecule in the field of natural product pharmacology, contributing new strength to human disease treatment.
Shenshuai
Wenjing
Hedandan
