Product name: Stigmastanol
Synonym name: Fucostanol; Sitostanol; 19466-47-8
Catalogue No.: BP4769
Cas No.: 83-45-4
Formula: C₂₉H₅₂O
Mol Weight: 416.734
Botanical Source:
Type of Compound: Oligoses

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.

HNMR of Stigmastanol

HPLC of Stigmastanol

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

Introduction/Overview

Phytosterols are a type of natural active ingredient widely present in the plant kingdom, with a structure similar to cholesterol in animals, but with differences in the side chains. Stigmastanol, also known as sitosterol, is a member of the plant sterol family and a saturated derivative of Stigmastol. Its CAS number is 83-45-4. For a long time, plant sterols have been widely added to functional foods due to their cholesterol lowering effects. However, recent studies have gradually revealed that plant sterols, represented by stigmasterol, have biological activities far beyond regulating lipid metabolism. Research has shown that stigmasterol can regulate immune cytokines (such as increasing the secretion of IL-2 and IL-10), affect cellular energy metabolism (such as reducing maximum mitochondrial respiration), and exhibit beneficial effects in immune related disease models such as asthma. These findings have expanded the research scope of stigmasterol from nutrition to the fields of immunopharmacology and metabolic regulation, making it a highly promising natural product lead compound. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, potential mechanisms of action, pharmacological evaluation, and clinical application prospects of stigmasterol, in order to provide comprehensive academic references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

The chemical name of stigmastanol is (3 β, 5 α) - stigmastan-3-ol, with a molecular formula of C29H52O and a molecular weight of 416.7340. Structurally speaking, stigmasterol belongs to steroid compounds and has a classical cyclopentane dihydrophenanthrene core. Its core feature is that the A/B ring is trans coupled (5 α - H, where the hydrogen at position 5 is in the α configuration), and a β - configured hydroxyl group is attached to the carbon at position 3, which is the key functional group with biological activity. Compared with unsaturated stigmasterol (which has double bonds at the C5-C6 and C22-C23 positions), the steroid nucleus C5-C6 and side chain C22-C23 positions of stigmasterol are completely saturated. This structural difference significantly affects its physicochemical properties and biological activity.

Based on its chemical structure, stigmasterol exhibits typical physicochemical properties of plant sterols. Its lipophilicity is extremely strong, and the calculated lipid water partition coefficient (LogP) is as high as 8.3735, indicating its high lipophilicity and hydrophobicity. Consistent with this, its theoretical polar surface area (TPSA) is only 20.23 Å ², and its water solubility is extremely low. It is often labeled as 0.0000 mg/mL in databases, which determines its absorption, distribution, and delivery mode in organisms. High lipid solubility also means that it is easy to penetrate the lipid bilayer, and its penetration through the blood-brain barrier (BBB) is predicted to be "high", providing a structural basis for its potential central nervous system activity research. In terms of preliminary safety prediction, the data shows no risk of hERG potassium channel inhibition (hERG inhibition: No), and the Ames mutagenicity test result is 0.0, indicating a low risk of genetic toxicity and a good safety starting point.

Plant sources and extraction methods

Soybean sterols are widely distributed in nature and are secondary metabolites of various plants. The literature clearly states that it can be derived from plants in the family Theaceae Hypericum riparium It was isolated from a plant of the genus Hypericum. In addition, stigmasterol is also commonly found in various grains (such as corn and wheat), vegetable oils (such as corn oil and rapeseed oil), nuts, and legumes, often coexisting with other plant sterols such as stigmasterol and β - sitosterol.

The extraction and purification of sitosterol from plant materials usually follow the general extraction process of plant sterols, and special attention should be paid to its separation from structurally similar compounds. The conventional extraction methods include:
1. Solvent extraction method The most commonly used method. Organic solvents such as n-hexane, chloroform, ethyl acetate, or their mixed solvents are used for Soxhlet extraction, reflux extraction, or ultrasound assisted extraction of dried and crushed plant materials. This method has high efficiency, but poor selectivity, and can simultaneously extract a large amount of fat soluble components such as oils and pigments.
2. saponification To obtain free sterols, crude extracts or plant oils are often subjected to alkaline saponification treatment. Heating and refluxing in an alcoholic potassium hydroxide solution to hydrolyze sterol esters into free sterols, followed by organic solvent extraction and purification. This step can effectively remove triglycerides.
3. Separation and Purification After obtaining the mixture of free sterols, further separation of stigmasterol is required. Due to the highly similar structure of plant sterols, separation is difficult. Traditional methods include recrystallization(Utilizing the difference in solubility in different solvents) and column chromatography(Silica gel column chromatography is most commonly used, with gradient elution using n-hexane/ethyl acetate, etc.). Modern separation technology relies more on High performance liquid chromatography (HPLC)Especially with the use of normal phase silica gel columns or reverse phase C18 columns, efficient separation and quantitative analysis of sitosterol and sitosterol, β - sitosterol, etc. can be achieved.Gas chromatography-mass spectrometry (GC-MS) This is the key technology for identifying and confirming the structure of stigmasterol, as it requires derivatization (such as silanization) of the sample to increase volatility.

Pharmacological activity research

In recent years, pharmacological research has broken through the traditional understanding of the lipid-lowering function of sitosterol, revealing its multiple activities in immune regulation and cellular metabolism.

1. Immune regulatory activity：

   • Cytokine regulation Research has shown that stigmasterol can significantly affect the cytokine secretion profile of immune cells. It can Increase the secretion of interleukin-2 (IL-2) and interleukin-10 (IL-10)IL-2 is a key factor in T cell growth and proliferation, and is crucial for initiating and maintaining adaptive immune responses; IL-10 is an important anti-inflammatory cytokine that can inhibit excessive inflammatory responses and maintain immune homeostasis. Doustanol simultaneously promotes the secretion of these two seemingly contradictory factors, suggesting that it may have complex, environment dependent immune regulatory abilities that can enhance specific immune responses while preventing immune overactivation.
   • The benefits of asthma models Based on the above immune regulatory characteristics, stigmasterol has shown potential in immune imbalance disease models such as asthma. The characteristics of asthma are an overactive Th2 immune response and chronic airway inflammation. Doustanol has been reported to regulate the cytokine network by potentially increasing IL-10 to inhibit inflammation Weakened immune function in asthma has beneficial effects The term 'weakened immune function' here may refer to the correction of immune suppression or immune imbalance, indicating that it may alleviate the pathological process of asthma by restoring immune balance.

2. Cellular metabolic regulation activity：

   • Effects on mitochondrial function An important study has found that stigmasterol can Reduce the maximum mitochondrial respiration of cells Mitochondrial respiration is the core process by which cells produce ATP (energy currency). The maximum respiratory capacity reflects the metabolic potential of cells under energy demand pressure. The inhibition of this ability by stigmasterol suggests that it may directly or indirectly affect the complex function of mitochondrial electron transfer chain (ETC), substrate utilization, or mitochondrial membrane permeability. This metabolic reprogramming effect may be closely related to cell proliferation, differentiation, apoptosis, and functional polarization of immune cells (such as the transition of macrophages from pro-inflammatory M1 type to anti-inflammatory M2 type), providing a potential metabolic mechanism explanation for their immunomodulatory effects.

3. Other potential activities：
   Although the information provided in this article is limited, based on the widespread research on plant sterols, it is possible that stigmasterol may also have antioxidant, anti-inflammatory (independent of the IL-10 pathway), and classic lipid-lowering effects through competitive inhibition of cholesterol absorption.

Mechanism of action and molecular targets

The exact molecular targets and detailed mechanisms of action of stigmasterol are still in the exploratory stage, but existing research has outlined a possible network of action for it.

1. Possible mechanisms of immune regulation：

   • Through membrane receptors or nuclear receptors Steroid compounds often exert their effects by binding to receptors on the cell membrane or nucleus. Doustanol may interact with certain G protein coupled receptors or lipid raft microdomains on the membrane of immune cells (such as T cells, macrophages) similar to other sterols, thereby initiating downstream signaling pathways (such as MAPK, NF - κ B, STAT pathways), ultimately affecting the transcription of genes such as IL-2 and IL-10. It may also act as a weak ligand for certain nuclear receptors, such as liver X receptor LXR and estrogen receptor ER, indirectly regulating immune responses.
   • Metabolic Immune Cross Dialogue: Its Reduce maximum mitochondrial respiration The role is a key clue. In immune cells, metabolic status determines their function. For example, activated effector T cells and M1 macrophages rely on glycolysis and higher mitochondrial respiration, while regulatory T cells (Treg) and M2 macrophages rely more on oxidative phosphorylation. Doustanol inhibits maximal respiration, which may promote a shift in immune cell metabolic patterns towards a more anti-inflammatory/regulatory phenotype, thereby promoting IL-10 secretion and indirectly affecting the production environment of IL-2.

2. Potential targets affecting mitochondrial function：

   • Doustanol may directly embed into the inner membrane of mitochondria, affecting membrane fluidity and the assembly or function of electron transfer chain (ETC) complexes (such as complexes I and III).
   • It may affect proton leakage and ATP synthesis efficiency by regulating the activity of mitochondrial uncoupling proteins (UCPs) or adenylate transporters (ANT).
   • It is also possible that the upstream regulates the AMPK signaling pathway that perceives cellular energy status, or the key regulatory factor PGC-1 α that affects mitochondrial biosynthesis.

3. The integrated mechanism of beneficial effects on asthma：
   In asthma models, sitosterol may exert its effects through the following comprehensive pathways: ① upregulation of IL-10, directly inhibiting airway inflammation and Th2 response; ② Inhibiting the function of overactive immune cells (such as eosinophils and activated Th2 cells) through metabolic reprogramming; ③ It may stabilize the cell membrane and reduce degranulation of mast cells through its steroid structure. These effects collectively contribute to its correction of the state of "weakened immune function" (i.e. Th2/Treg imbalance).

Evaluation of drug properties and pharmacokinetics

Based on its physicochemical properties and preliminary data, a preliminary evaluation of the pharmacological properties of stigmasterol is conducted

1. Absorption, distribution, metabolism, excretion (ADME) prediction：

   • absorb Extremely low water solubility and high LogP value indicate that its oral absorption may be poor and variable. In the intestine, it may rely on the solubilization effect of bile micelles to be absorbed in a manner similar to cholesterol. Its absorption efficiency is usually lower than that of its unsaturated analogues (such as β - sitosterol).
   • distribution High lipid solubility and predicted high blood-brain barrier penetration mean that once absorbed, it may be widely distributed in lipid rich areas such as adipose tissue and the nervous system, with potential central activity, but may also pose a risk of accumulation.
   • Metabolism Plant sterols are mainly metabolized by the liver in the body, and may undergo phase II metabolic reactions such as hydroxylation, oxidation, and binding with glucuronic acid or sulfuric acid, forming more polar products that are excreted through bile.
   • excretion The main excretion pathway is through bile and feces, with very little excretion by the kidneys. This is consistent with its lipid solubility characteristics.

2. Advantages and challenges of pharmaceutical properties：

   • Advantage① Natural products with good safety foundation, Ames negative and no hERG inhibition indicate low early safety risk; ② Structural stability (saturated steroid nucleus); ③ Has clear multiple pharmacological activities in immune and metabolic regulation.
   • challenge：① Extremely low water solubility This is its main development obstacle, seriously affecting its oral bioavailability and formulation development. ② High lipid solubility may lead to Organizational Accumulation Long term toxicity assessment is required. ③ The specific molecular targets are unclear, and the mechanism of action still needs to be further elucidated. ④ As an endogenous steroid analogue, its pharmacokinetic studies are complex, and the detection method requires high sensitivity (such as LC-MS/MS).

3. Formulation strategy：
   Future formulation research is crucial to improve its bioavailability. Possible strategies include: ① Lipid preparations(such as self microemulsions, liposomes, nanoemulsions); ② Solid dispersion；③ Cyclodextrin inclusion complex；④ Nanocrystal technology These techniques aim to increase its solubility and dissolution rate, promoting intestinal absorption.

Clinical application prospects and prospects

The unique pharmacological activity of sitosterol has brought potential application prospects in multiple therapeutic fields:

1. Immune inflammatory diseases：

   • Adjuvant treatment for asthma and allergic diseases As a natural product with immunomodulatory effects, it can be explored as an adjuvant therapy for existing glucocorticoids or bronchodilators, aiming to reduce hormone dosage and improve immune homeostasis.
   • Autoimmune diseases Its ability to induce IL-10 and potential immune regulatory phenotypes is worth exploring in autoimmune disease models such as rheumatoid arthritis and inflammatory bowel disease.
   • Metabolic inflammation The chronic low-grade inflammation (metabolic inflammation) associated with obesity and type 2 diabetes may also be the target of intervention.

2. Metabolic related diseases：

   • In addition to the classic cholesterol lowering application, its regulatory effect on mitochondrial function serves as an intervention Mitochondrial dysfunction related diseases(such as certain neurodegenerative diseases and metabolic syndrome) provide new ideas.

3. Functional foods and dietary supplements：
   As a natural plant component, stigmasterol can be further developed to target Immune Support or Metabolic health Functional foods or high-end dietary supplements with high market acceptance.

4. Future research directions and challenges：

   • Target discovery Identifying the molecular targets directly affected by it using chemical biology methods such as photoaffinity labeled probes and proteomics is key to understanding its mechanism and optimizing its activity.
   • structural optimization Based on the parent nucleus of stigmasterol, structural modifications (such as introducing polar groups to improve solubility, or modifying side chains to enhance target affinity) are carried out to develop derivatives with stronger activity and better drug properties.
   • In depth preclinical research It is necessary to validate its efficacy in more comprehensive animal models of diseases and systematically complete pharmacokinetic and toxicological studies.
   • Research on Composite Preparations Explore synergistic effects with other natural products or drugs and develop multi-target compound formulations.

Conclusion

As a naturally occurring plant sterol, stigmasterol has evolved from a traditional nutritional component to a pharmacological active molecule with unique immune and cellular metabolic regulatory activities. It can promote the secretion of IL-2 and IL-10, inhibit the maximum mitochondrial respiration of cells, and show the potential to correct immune imbalance in asthma models, revealing its important value in the cross domain of immune metabolism. Although its extremely low water solubility and unclear mechanism of action are the main challenges in current development, its good preliminary safety and clear multiple biological activities have laid a solid foundation for its subsequent research. In the future, through the cross fusion of modern medicinal chemistry, formulation, and molecular pharmacology methods, the molecular action network of sitosterol will be deeply revealed, and the delivery difficulties caused by its physicochemical properties will be overcome. This natural molecule is expected to be developed into a new therapeutic agent or functional health product for immune inflammatory and metabolic diseases, fully tapping into its natural medicinal potential.