Product name: Beta-Sitosterol
Synonym name:
Catalogue No.: BP0237
Cas No.: 83-46-5
Formula: C₂₉H₅₀O
Mol Weight: 414.718
Botanical Source: Widely distributed in plants; the commonest sterol of higher plants. Also occurs in marine organisms, incl. the scallop Placopecten magellanicus, the sponge Reniera sp. and the alga Cladophora densa
Physical Description: Cryst.
Type of Compound: Steroids

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, up to kilograms
Inquire for bulk scale.

Descriptions:
Beta-Sitosterol a main dietary phytosterol found in plants, may have the potential for prevention and therapy for human cancer, β-sitosterol induces apoptosis in HT116 cells is associated with a decreased expression of the anti-apototic Bcl-2 protein and mRNA and a concomitant increase of the pro-apototic Bax protein and mRNA, and with release of cytochrome c from the mitochondria into the cytosol. [1]
Beta-Sitosterol (LD50>3 g/kg i.p. in mice, minimum ulcerogenic dose was 600 mg/kg i.p. in rats)has potent anti-inflammatory activity , similar to hydrocortisone and oxyphenbutazone when administered intraperitoneally; possesses antipyretic activity, similar to acetylsalicylic acid.[2]
Beta-Sitosterol shows a potent angiogenic activity in the chorioallantoic membrane (CAM) assay, it stimulates neovascularization in the mouse Matrigel plug assay and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay in the presence of heparin, thus β-sitosterol is a novel plant-derived angiogenic factor which may have potential pharmaceutical applications for the management of chronic wounds.[3]
Beta-Sitosterol can inhibit proliferation and induce apoptosis in human solid tumors such as colon and breast cancers, it potently induces apoptosis in U937 cells and induces apoptosis is related to the selective activation of caspase-3 and induction of Bax/Bcl-2 ratio.[4]

References:
[1] Choi Y H, Kong K R, Kim Y A, et al. Int J Oncol, 2003, 23(6):1657-62.
[2] Gupta MB, Nath R, et al. Srivastava Planta Medica, 1980, 39(2):157-63
[3] Moon E J, You M L, Lee O H, et al. Angiogenesis, 1999, 3(2):117-123.
[4] Park C, Moon D O, Rhu C H, et al. Biol Pharm Bull, 2007, 30(7):1317-23.
[5] Nair V D, Kanfer I, Hoogmartens J. J Pharmaceut Biomed , 2006, 41(3):731-7.

HPLC of Beta-Sitosterol

HNMR of β-Sitosterol

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

Introduction/Overview

β-Sitosterol (Beta-Sitosterol, CAS No.: 83-46-5), a plant sterol widely found in plants, has attracted significant attention in recent years in the field of natural product pharmacology due to its diverse bioactivity and good safety. β-Sitosterol exhibits significant anti-inflammatory and anticancer, antioxidant, antibacterial, antidiabetic, and analgesic effects, and can regulate cellular function through multiple signaling pathways, demonstrating promising therapeutic potential. This paper will systematically review the chemical structure and physicochemical properties of β-sitosterol, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and explore its clinical application prospects and research prospects.

Chemical structure and physicochemical properties

β-Sitosterol is a typical plant sterol with a molecular formula of C29H50O and a molecular weight of 414.7. Its structural features include a tetracyclic steroid framework and a side chain with a hydroxyl group (-OH) located at the C-3 position, making it a sterol compound. The LogP value of β-sitosterol reached as high as 9.29, indicating strong lipid solubility, TPSA (topological polar surface area) of 20.23, and a hydrogen bond receptor count of 1, reflecting its low polarity and difficulty crossing the blood-brain barrier (BBB permeability). Oral bioavailability is about 10%, indicating limited oral absorption. Toxicological data indicate that β-sitosterol LD50 reaches as high as 5000 mg/kg, with no significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition. The Ames mutagenic test was negative, indicating good safety.

Plant Origins and Extraction Methods

β-Sitosterol is widely found in various vegetable oils, nuts, seeds, and vegetables, with particularly high levels found in corn oil, soybean oil, peanut oil, sesame oil, and pumpkin seed oil. Its extraction usually uses solvent extraction methods, with commonly used solvents including ethanol, methanol, and hexane. Modern extraction technologies such as ultrasonic-assisted extraction and supercritical CO2 extraction are also applied to improve extraction efficiency and purity. After extraction, purification is often performed by silica gel column chromatography, recrystallization, or high-performance liquid chromatography (HPLC), ultimately yielding β-sitosterol products with a purity ≥80%.

Pharmacological activity research

Anti-inflammatory effects

β-Sitosterol demonstrated significant anti-inflammatory activity across various inflammation models. Its mechanism mainly involves inhibiting the expression of pro-inflammatory cytokines such as TNF-α and IL-1β, lowering reactive oxygen species (ROS) levels and suppressing activation of the nuclear factor κB (NF-κB p65) signaling pathway, thereby alleviating inflammatory responses. In the bovine mammary gland epithelial cell inflammation model, β-sitosterol inhibits adipoietic disorders by restoring the activity of the HIF-1α/mTOR signaling pathway, further alleviating inflammatory damage. Additionally, β-sitosterol can regulate macrophage polarization, promote the formation of the M2 anti-inflammatory phenotype, and reduce the inflammatory response in rheumatoid arthritis in mice.

Anti-cancer effects

The anticancer activity of β-sitosterol has been validated in various cancer types, including breast, lung, colorectal cancer, and others. Its anti-cancer mechanism involves inducing apoptosis in cancer cells and inhibiting tumor cell proliferation and migration. β-Sitosterol activates the p53 signaling pathway through ROS-mediated mitochondrial dysfunction, promoting apoptosis. It also activates caspase-3, caspase-8, and caspase-9, mediates PARAP inactivation, regulates the Bcl-2/Bax ratio, promotes cytochrome c release, and ultimately triggers apoptosis. Additionally, β-sitosterol inhibits matrix metalloproteinase (MMP) activity, blocking tumor cell invasion and metastasis. Multiple animal studies have shown that β-sitosterol significantly inhibits tumor growth and has good anti-tumor potential.

Antioxidant and antidiabetic effects

β-Sitosterol enhances antioxidant enzyme activity by scavenging free radicals and lowering ROS levels, protecting cells from oxidative stress damage. In diabetes models, β-sitosterol improves insulin sensitivity, regulates lipid metabolism, and lowers blood sugar levels. It regulates lipid metabolism disorders-related targets such as NOTCH1, ABCB1, HIF1A, SIRT1, MAPK1, GSK3B, NR1H3, and NPC1L1, improving metabolic disorders.

Other pharmacological effects

β-Sitosterol also exhibits certain antibacterial and analgesic activities, inhibiting the growth of various pathogenic bacteria and relieving inflammation-related pain. Additionally, it has potential effects on immune regulation, promoting the maintenance of immune homeostasis.

Mechanism of action and molecular targets

The multi-target mechanism of β-sitosterol forms the basis for its various pharmacological activities. By regulating ROS levels, it affects intracellular redox states, thereby modulating multiple signaling pathways:

• NF-κB signaling pathway: β-sitosterol inhibits nuclear translocation of NF-κB p65 subunits, reducing pro-inflammatory factor expression and alleviating inflammatory responses.
• HIF-1α/mTOR pathway: By restoring this pathway's activity, β-sitosterol regulates cellular metabolism and adipogeney, alleviating inflammation and metabolic disorders.
• p53 pathway: activates p53, induces cell cycle arrest and apoptosis, exerting anticancer effects.
• Caspase cascade: activates caspase-3, -8, and -9, promoting the initiation of apoptosis processes.
• Bcl-2 family protein regulation: modulates the Bcl-2/Bax ratio, promotes changes in mitochondrial membrane permeability, and releases cytochrome c.
• MMP inhibition: Reduces matrix metalloproteinase activity, preventing tumor cell invasion and metastasis.
• Regulation of macrophage polarization: Promotes the polarization of M2-type macrophages and reduces inflammatory responses.

Additionally, β-sitosterol regulates lipid metabolism and energy homeostasis by targeting lipid metabolism-related targets such as NOTCH1, ABCB1, and SIRT1, thereby improving metabolic disease states.

Druggability evaluation and pharmacokinetics

β-Sitosterol has high lipid solubility (LogP=9.29), but its oral bioavailability is low (about 10%), possibly limited by intestinal absorption and first-pass effects. Its extremely low polarity and large molecular weight limit its ability to cross the blood-brain barrier, suggesting its application in central nervous system diseases is limited. Toxicological evaluation showed that β-sitosterol is safe, with no significant hepatic or cardiac toxicity, nor does it inhibit hERG channels, resulting in a negative mutagenic test and meeting favorable pharmacological safety profiles.

Pharmacokinetic studies show that β-sitosterol is widely distributed in the body, with liver metabolism as its main metabolic pathway and excretion mainly through bile and feces. Its low water solubility and bioavailability limit its clinical application, and there is an urgent need to improve its pharmacokinetic performance through drug formulation techniques such as nanocarriers and liposomal encapsulation.

Prospects and outlooks for clinical applications

Due to its multiple pharmacological activities and good safety profile, β-sitosterol shows broad clinical application prospects across various disease fields. Especially in anti-inflammatory, anti-cancer, and metabolic diseases (such as diabetes and lipid metabolism disorders), β-sitosterol has potential therapeutic value. Currently, β-sitosterol is widely used as a dietary supplement and functional food ingredient, but clinical research as a drug is still in its early stages.

Future research should focus on:

1. Pharmacokinetic optimization: Improving oral bioavailability and targeting through novel formulation technologies.
2. In-depth mechanism analysis: By combining multi-omics techniques, systematically revealing its molecular action network and key targets.
3. Clinical trial conduct: Designing scientific and reasonable clinical trials to verify efficacy and safety in inflammatory diseases, tumors, and metabolic diseases.
4. Combination Therapy Strategy: Explore the synergistic effects of β-sitosterol with existing drugs to enhance treatment outcomes.
5. Structural modification and derivative development: Chemical modification improves pharmacokinetics and pharmacodynamic properties to develop novel, highly efficient derivatives.

Conclusion

As a natural plant sterol, β-sitosterol demonstrates broad application potential in anti-inflammatory, anti-cancer, antioxidant, and metabolic regulation fields due to its multi-target and multi-mechanism pharmacological properties. Its excellent safety and diverse biological activities make it an important subject for pharmacological research of natural products. Although its clinical applications still face challenges such as low bioavailability and pharmacokinetic limitations, advances in formulation technology and molecular pharmacology make β-sitosterol a key candidate for future natural drug development. Systematic and in-depth mechanistic research and clinical validation will provide a solid foundation for its translational application, promoting its widespread use in the treatment of various diseases.