INTRODUCTION:

Beta-sitosterol, a naturally occurring phytosterol found in various plants, has been thoroughly investigated for a variety of biological activities. This compound has demonstrated potent anti-inflammatory, anticancer, chemoprotective, and hypocholesterolemic effects, among others. Research has shown that beta-sitosterol can modulate immune responses, inhibit the proliferation of cancer cells, and reduce cholesterol absorption, making it a promising candidate for therapeutic applications. Additionally, its ability to induce apoptosis, enhance antioxidant defenses, and exhibit antimicrobial properties highlights its multifaceted role in promoting health and combating various diseases. Beyond its immunomodulatory effects, BS is reported to possess significant anticancer properties against various types of cancer, including breast, prostate, colon, lung, stomach, ovarian, and leukemia. Studies indicate it can inhibit cancer cell growth, induce apoptosis, affect the cell cycle, and modulate various cell signaling pathways. BS also exhibits other biological effects such as anti-inflammatory, anti-pyretic, anti-ulcer, anti-hypercholesterolemic, antibacterial, and antifungal properties. Despite its potential, particularly as a generally non-toxic compound compared to conventional cancer therapeutics, BS is described as a "Promising but Orphan Nutraceutical" in the context of cancer research, with suggestions for more extensive study into its mechanisms and delivery methods.^1,2

MATERIALS AND METHODS:

The literature survey was conducted on the PUBMED search engine, and literature papers were surveyed, analyzed, and studied for reported pharmacological activities. The literature was searched for " Pharmacological action of Beta-sitosterol", as per the applied search above, data was generated, and the applied statistics for the survey is explained below.

Reported pharmacological properties of beta-sitosterol:

Anti-inflammatory:

A substance called beta-sitosterol, present in many different plants, has demonstrated strong anti-inflammatory effects in rodent experiments. Research has indicated that it can suppress inflammation in both particular and generalized acute inflammatory situations. Tests like the mouse ear edema test, the rat paw edema test, the rat pleurisy assay, and the mouse myeloperoxidase activity assay have all shown the anti-inflammatory properties of beta-sitosterol. It is thought that by regulating the synthesis of inflammatory cytokines, it can modify immune response, inflammation, and pain thresholds. Furthermore, it has been demonstrated that beta-sitosterol inhibits the activity of enzymes that contribute to inflammation, such as myeloperoxidase, which is involved in synthesizing inflammatory mediators and reactive oxygen species. Moreover, beta-sitosterol may interfere with cholesterol absorption in the intestinal tract, which can indirectly impact inflammatory pathways as cholesterol metabolism is linked to inflammation. Furthermore, beta-sitosterol has been reported to affect calcium uptake in activated neutrophils, leading to an anti-inflammatory effect. Overall, the multifaceted mechanisms of beta-sitosterol contribute to its potent anti-inflammatory properties, as observed by the substantial reduction in edema, pleural effusion, and neutrophil activity, highlighting the compound's potential as an effective anti-inflammatory agent. According to the study's findings, beta-sitosterol has a strong anti-inflammatory effect on rodents' acute inflammation in both particular and non-specific forms.^3,4

Apoptosis:

Apoptosis, also known as cellular suicide, is a strictly regulated process of cell self-destruction in multicellular organisms. It is a fundamental biological process that maintains tissue homeostasis, controls development, and eliminates harmed or infected cells. Certain morphological and biochemical alterations in the cell, such as membrane blebbing, chromatin condensation, DNA fragmentation, and cell shrinkage, are indicative of apoptosis. The protease enzymes known as caspases become active during apoptosis due to the activation of certain signaling pathways. Caspases are necessary for executing the cell death process. One important mechanism by which beta-sitosterol induces apoptosis in Michigan Cancer Foundation-7

cells is the activation of caspase. According to the study, beta-sitosterol treatment inhibited MCF-7 in a dose-dependent way. This growth inhibitory effect was associated with an increase in cellular caspase activity, specifically caspases 3, 6, 7, and 8. Caspases are crucial enzymes in the process of apoptosis, a programmed cell death mechanism required to eliminate unhealthy or unwanted cells and maintain tissue homeostasis. Caspases, particularly caspase-3, are activated during apoptosis and cleave a range of cellular substrates to induce cell death. Caspases activate in response to beta-sitosterol-induced apoptosis in MCF-7 cells, initiating an apoptotic cascade that ultimately results in cell death. The potential of beta-sitosterol as a naturally occurring substance with anticancer properties is highlighted by this mechanism, which involves causing programmed cell death in breast carcinoma cells.⁵

Chemoprotective

1. Beta-sitosterol, a phytosterol commonly found in plant-based foods, exhibits significant chemoprotective properties. Its mode of action includes:

2. 1. Restriction of Cancer Cell Growth: Beta-sitosterol inhibits the proliferation of various malignant cells, including those of the prostate and colon, through multiple pathways. It interferes with cell proliferation and induces apoptosis, which is the programmed death of cancer cells.

3. 2. Induction of Apoptosis: This compound triggers apoptosis in cancer cells by disrupting mitochondrial function and activating p53, a tumor suppressor protein. This is particularly evident in studies involving A549 lung cancer cells, where beta-sitosterol's action involves reactive oxygen species (ROS) mediated pathways.

4. 3. Anti-inflammatory Effects: Beta-sitosterol has notable anti-inflammatory properties. It reduces inflammation by modulating the immune response and decreasing the levels of inflammatory mediators. This can prevent the chronic inflammation that often leads to cancer development.

5. 4. Antioxidant Activity: Beta-sitosterol acts as an antioxidant, protecting cells from oxidative stress, which It plays a crucial role in the initiation and advancement of cancer. It enhances the activity of enzymatic and non-enzymatic antioxidants within cells, contributing to its chemoprotective effects.

6. 5. Cholesterol Modulation: As a cholesterol analog, beta-sitosterol competes with cholesterol for absorption in the intestines, thereby lowering blood cholesterol levels. This not only benefits cardiovascular health but also reduces the risk of hormone-related cancers, such as breast and prostate cancer, by altering hormone levels in the body.

7. Overall, beta-sitosterol's chemoprotective action is multifaceted, involving the inhibition of cancer cell proliferation, induction of apoptosis, anti-inflammatory effects, and antioxidant activity⁶

Hypocholesterolemia:

Plant sterol beta-sitosterol has shown strong hypocholesterolemic action, which means it can reduce the body's cholesterol levels. In studies involving young male rats, beta-sitosterol and its hydrogenated form, beta-sitostanol, were found to have similar effects on liver cholesterol and triglyceride concentrations, with beta-sitostanol exhibiting a greater hypocholesterolemic effect. Remarkably, the majority of beta-sitosterol was eliminated through feces, with recovery rates varying from 85% to 92%. Dietary supplements containing phytosterols, such as beta-sitosterol, have been demonstrated in human studies to lower plasma and HDL cholesterol concentrations as well as the concentration of apolipoprotein B (apo-B) in LDL Cholesterol. This indicates a potential benefit for patients with primary hyperlipoproteinemia. These findings suggest that beta-sitosterol can be a beneficial dietary supplement for managing cholesterol levels, contributing to cardiovascular health by reducing overall cholesterol and LDL levels in the bloodstream⁷

Anticancer:

The anticancer properties of β-sitosterol in colon, breast, and prostate cancers, among other cancer types. Research has indicated that β-sitosterol suppresses tumor growth and metastasis, induces apoptosis, suppresses cancer cell growth, and alters various signaling pathways that contribute to cancer progression. Furthermore, it has been discovered that β-sitosterol has little effect on normal cells, preserving their viability. Β-sitosterol shows encouraging anticancer qualities by selectively targeting cancer cells while preserving healthy cells⁸

Anti-Pyretic:

Beta-sitosterol, or "BS," has been shown to have an antipyretic effect by some of the following:

impact In line with aspirin: Aspirin and "BS" have similar antipyretic effects. This tells us that "BS" might work to lower fever. Processing and Extractions of Plants: Additionally, antipyretic activity has been demonstrated by preparations and extracts of plants containing "BS." A common antipyretic medication, aspirin, has effects that are comparable to these. Fever may be managed with beta-sitosterol because of its antipyretic qualities. Its safety and effectiveness require more investigation ⁹

Antinociceptive:

Adult Wistar albino rats (150-200g) and young Swiss albino mice (25-35g) were used. was administered beta-sitosterol, and the antinociceptive effects were assessed using the hot plate analgesia test for central activity and the acetic acid-induced pain test for peripheral activity. The opioid antagonist naloxone counteracted the pain-relieving effect of beta-sitosterol, suggesting the involvement of opioid receptors. Beta-sitosterol 10 and 20 mg/kg demonstrated dose-dependent antinociceptive activity. The hot plate analgesic test indicates the central antinociceptive effect of beta-sitosterol, and the acetic acid-induced pain test confirms the peripheral antinociceptive activity of beta-sitosterol. However, in the acetic acid writing test, beta-sitosterol significantly inhibited the response induced by acetic acid. The inhibition was dose-dependent and comparable to the reference drug acetaminophen (50 mg/kg). ¹⁰

Alzheimer

By lowering beta-amyloid synthesis, blocking acetylcholinesterase, and boosting antioxidant defenses, beta-sitosterol demonstrates a multifaceted strategy to treat Alzheimer's disease. Given its capacity to traverse the blood-brain barrier and enhance cognitive and motor abilities, it presents a favorable prospect for additional investigation and possible therapeutic application in the management of AD ¹¹

Improve growth performance and intestinal barrier function¹²

The research explored the impact of beta-sitosterol (BS). The addition of supplements to development, performance, and gut barrier function in broiler chickens was examined.

1. Growth Performance: During 1 to 14 days and 1 to 21 days, BS supplementation at various levels (0.025, 0.050, 0.075, and 0.10 g/kg) demonstrated a quadratic decrease in feed conversion ratio, with effects being more pronounced at 25 or 50 mg/kg. According to the findings, broiler chicken growth performance was positively impacted by BS, especially in terms of feed conversion efficiency.

2. Intestinal Barrier Function: Elevations of D-lactate and changes in plasma diamine oxidase activity showed that BS supplementation improved intestinal barrier function. In particular, at 14 days, BS decreased plasma diamine oxidase activity and D-lactate levels in a linear and quadratic fashion; at 25 or 50 mg/kg supplementation, more notable effects were seen. These results imply that in young broiler chickens, BS may help improve intestinal barrier integrity and function. Overall, the study emphasizes the role that beta-sitosterol plays in promoting overall health and well-being in poultry production and the potential advantages of supplementing with the nutrient for enhancing development, performance and intestinal barrier function in broiler chickens.

Antimalarial:

Dihydrofolate reductase (DHFR), a crucial enzyme in the metabolism of folate and a confirmed target for anti-malarial medications, was found to interact with beta-sitosterol. Strong binding interaction with a binding score indicating significant potential was found during docking studies using the HDOCK server. The binding of beta-sitosterol to the DHFR enzyme was dependent on certain amino acids, including serine. Using Discovery Studio software, the interaction's hydrogen bonds and van der Waals forces were shown. When beta-sitosterol binds to the DHFR_2 domain, it may cause targeted inhibition of this important enzyme, which could stop the parasite from synthesizing nucleotides. The disruption may impede the Plasmodium falciparum parasite's ability to survive and reproduce ¹³

Healing Activity:

The study aimed to determine whether β-sitosterol and naringenin together could heal scratches. Comparing the combination of β-sitosterol and naringenin to the negative control, the outcomes demonstrated a significant improvement in wound closure rates. Superoxide dismutase (SOD) activity was also elevated by this combination, suggesting improved antioxidant defense systems. Additionally, in comparison to wounds that were left untreated, the combination decreased the amount of pro-inflammatory cytokine interleukin-1β (IL-1β). Crucially, the MTT test verified that the mixture was not harmful to fibroblasts. Overall, by increasing the antioxidant response and decreasing inflammation, the synergistic effect of β-sitosterol and naringenin showed promising potential in promoting wound healing ¹⁴

Anti-Arthritic Activity:

Significant anti-arthritic effects are shown by the plant extract containing beta-sitosterol. When PMA stimulates macrophage cells, beta-sitosterol reduces the transcription factor NF-kB's activation. To investigate beta-sitosterol as a possible arthritis treatment, more research is required ⁹

Antibacterial:

The study has emphasized the pharmacological actions of beta-sitosterol, a phytosterol that is present in a variety of plants and marine organisms, especially in relation to its antibacterial qualities. Important details about its ability to fight bacteria include. Many bacterial strains, such as Pseudomonas aeruginosa, Enterococcus faecalis, and golden staph, are likelihood to the antibacterial effects of beta-sitosterol. According to the study, beta-sitosterol is a compound that warrants more investigation because its derivatives have demonstrated encouraging antibacterial effects. Beta-sitosterol is thought to damage bacterial cell membranes, increasing permeability and ultimately causing cell death, though the precise mechanisms are still being investigated. When combined with other antibiotics, this action can increase their efficacy. This was demonstrated in a study where the beta-sitosterol-rich EAF of Neopetrosia exigua showed notable antibiotic-potentiating effects. The results of the study indicate that beta-sitosterol-rich extracts may help overcome antibiotic resistance by increasing bacterial susceptibility to treatment. They may also synergistically enhance the activity of antibiotics such as ampicillin. In conclusion, beta-sitosterol is a useful substance in the hunt for novel antimicrobial agents because of its proven strong antibacterial activity and ability to increase the effectiveness of antibiotics ¹⁵

Antiviral:

Of the 15 tested herbal extracts, beta-sitosterol was found to be the main active ingredient in Pinellia ternata and to have the strongest inhibitory effect on WSSV. The white spot syndrome virus (WSSV) study on beta-sitosterol's antiviral activity provides important new information about pharmacological principles and experimental procedures. Action Mechanism: By regulating immune factor expression, altering innate immune pathways, causing apoptosis during early antiviral responses, supporting viral suppression, and normalizing protein levels impacted by WSSV, beta-sitosterol inhibits the replication of white blood cell white blood cells (WSSV). This lowers oxidative stress and inflammation. There were two mechanisms used in the experimentation. Dose-Dependent Inhibition: The antiviral effect is dose-dependent, with higher concentrations yielding greater inhibition rates (e.g., 96.44% at 6.25 mg/kg and 42.45% at 0.1 g/kg), The highest constraint rate was observed at concentration of 50 mg/kg, reducing WSSV genomic DNA copy numbers by 95.79% at 24 hours post-infection. In Vivo and In Vitro Effects: Antiviral effects were confirmed in both crayfish (in vivo) and cell cultures (in vitro). Co-incubation with WSSV did not affect viral infectivity, indicating that beta-sitosterol's efficacy is primarily in vivo. Beta-sitosterol significantly inhibited the transcription of key viral genes (immediate early gene 1 (ie1), DNA polymerase (DNApol), and envelope protein 28 (VP28)). The inhibition of these genes was both dose- and time-dependent, contributing to the overall reduction in viral replication. Beta-sitosterol interfered with WSSV's ability to hijack the host's innate immune signaling pathways, including the immune deficiency (IMD), the Toll and the Janus kinase/Signal Transducers, and Activators. These findings underscore beta-sitosterol's potential as an effective agent against WSSV in crustacean aquaculture, paving the way for future research and large-scale applications. Beta-sitosterol is a potent antiviral agent against WSSV, demonstrating significant inhibitory effects on viral replication and enhancing the survival rates of infected crayfish. This study supports the potential of beta-sitosterol as a practical and effective antiviral treatment in crustacean aquaculture ⁴

Fig 1.Various Pharmacological Properties of Beta-sitosterol

CONCLUSION:

Beta-sitosterol (BS) exhibits a broad spectrum of pharmacological activities, highlighting its significant therapeutic potential. From anti-inflammatory and anticancer effects to hypocholesterolemic, antiviral, and neuroprotective actions, BS demonstrates efficacy through multiple biological mechanisms such as immune modulation, apoptosis induction, and antioxidant activity. Its non-toxic profile, combined with selective cytotoxicity toward cancer cells and promising effects in managing chronic diseases and infections, supports its role as a multifunctional nutraceutical. Additionally, its potential in promoting wound healing, intestinal health, and combating microbial resistance further enhances its biomedical relevance. Continued research is essential to exploit BS in clinical and therapeutic applications fully.

CONFLICT OF INTEREST:

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGMENT:

The gratitude of Thanks to Dr. Lalita Shashikant Nemade, Professor, HOD, Govindrao Nikam College of Pharmacy, Chiplun, Ratnagiri for the support.

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Received on 15.04.2025 Revised on 20.05.2025

Accepted on 19.06.2025 Published on 20.06.2025

Available online from June 30, 2025

International Journal of Technology. 2025; 15(1):37-42.

DOI: 10.52711/2231-3915.2025.00007

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