Beta sitosterol

5.82K views
beta sitosterol

What is beta sitosterol

Beta-sitosterol (24-ethylcholesterol) is a phytosterol with a chemical structure similar to that of cholesterol 1, widely distributed throughout the plant kingdom and known to be involved in the stabilization of cell membranes. Beta-sitosterol is a natural micronutrient in higher plants and is found in the serum and tissues of healthy individuals at a concentration 800–1000 times lower than that of endogenous cholesterol 2. Beta-sitosterol glycoside, sitosterolin, is also present in serum, but in lower concentration 3. Beta-sitosterol molecules are synthesized in plants; whereas animals obtain them through diet 1. Beta sitosterol could be obtained from different plants, but the total biosynthetic pathway, as well as its exact physiological and structural function in plants, have not been fully understood 2.

Beta sitosterol benefits

Beta sitosterol prostate

Five hundred nineteen men from four randomized, placebo‐controlled, double‐blind trials, (lasting 4 to 26 weeks) were assessed 4. Three trials used non‐glucosidic B‐sitosterols and one utilized a preparation that contained 100% B‐sitosteryl‐B‐D‐glucoside. This 1999 Cochrane review found that beta‐sitosterol treatments were well tolerated and improved urinary symptoms and flow measures in men with mild to moderate benign prostatic hyperplasia (nonmalignant enlargement of the prostate). Furthermore, the review authors added that more research into long‐term effects of beta‐sitosterols is needed 4.

Beta sitosterol hair loss

The results of this pilot study in the treatment of hair loss in men (androgenetic alopecia) 5 showed a positive response to treatment. The blinded investigative staff assessment report showed that 60% of (6/10) study subjects dosed with the active study formulation were rated as improved at the final visit. Apart from that small pilot study, there is still no long-term convincing result regarding the efficacy of beta sitosterol against alopecia or hair loss in men.

Antihyperlipidemic and Anti-Atherosclerosis Effects

Beta sitosterol is recommended for the prevention of different cardiovascular diseases 6 and the FDA has approved beta sitosterol for the treatment of hyperlipidemia 7. It prevents the absorption of cholesterol by displacing it from micelles 8 and thereby decreasing the amount in plasma 9. In combination with other statins, it increases the potency of those statins 10. Still further studies are required to resolve existing debate regarding its role in treating hypercholesterolaemia 11. Study regarding the role of beta sitosterol on the upregulation of paraoxonase-2 needs to be conducted in order to substantiate the claim made by Rosenblat et al. 12 regarding the beneficial effect of simvastatin in combination with beta sitosterol. beta sitosterol has also been related to sitosterolemia but not as a causal agent for the development of coronary heart disease in sitosterolemic patients 13. Further experimental evidence is required.

Central Nervous System

Beta sitosterol containing plants show antinociceptive 14, anxiolytic, and sedative effects 15 in rats, but such findings in humans are not available. Neither the brain region nor the pathway affected by beta sitosterol has been studied extensively yet. It has been shown that the effect of beta sitosterol is somewhat similar to diazepam but whether the mechanism of action is similar or not has not been studied 16. It has been proposed that beta sitosterol is effectual by interacting with GABAA receptor, but there is no confirmatory evidence for this claim 15. beta sitosterol has been shown to potentiate the binding of other compounds to muscarinic receptors 17. However, whether or not beta sitosterol binds to the muscarinic receptor itself is not known. Studies in immortalized mouse hippocampal cell line HT22 showed that beta sitosterol prevents oxidative damage and neurotoxicity 18 and a series of other studies showed the beneficial effect in preventing neuronal damage 19. There is evidence that beta sitosterol crosses the blood brain barrier (BBB), but fundamental studies regarding the efficacy and efficiency of beta sitosterol to cross blood brain barrier have not been undertaken. A comparative study has been done with other phytosterols like campesterol and sitosterol to check the efficiency in passing the brain endothelial monolayer where the reason behind the irreversible passage of the plant sterols across the endothelial monolayer was found to be the molecular complexity of the sterol side chain. A possible explanation for the difference of phytosterols in passing the blood brain barrier may be the different esterification rate within the endothelial cells 20. Recent studies have shown that beta sitosterol alone 21 or as extract 22 increases neural stem cell proliferation. However, further studies are recommended for potential applications in tissue engineering.

Skin

According to the Norwegian Food Safety Authority (Mattilsynet, NFSA, Oslo, Norway), beta sitosterol has a skin conditioning effect and is used in sunscreen, moisturizer, body wash, and anti-aging cosmetic preparations. Skin is one of the paths of beta sitosterol excretion. It has been reported that beta sitosterol inhibits the production and mRNA expression of thymic stromal lymphopoietin through blocking of caspase-1 and nuclear factor-kB (NkB) signal pathways in the stimulated human mast cell line, HMC-1 cells. Even though this study showed the potential therapeutic effect against atopic dermatitis, studies on long-term use of beta sitosterol on the skin need to be conducted 23.

Cardiovascular System

Beta sitosterol has beneficial effects on the cardiovascular system and prevents different cardiovascular diseases except for patients with ABCG5 and ABCG8 mutation 24. However, there is no study regarding its effects on cells within the heart: the cardiomyocytes and the cardiac pacemaker cells. Although some studies point to the possibility that elevated plasma phytosterol concentrations could contribute to the development of premature coronary artery diseases, extensive safety evaluation studies have been conducted for these compounds, and they are considered safe 25.

Liver

Beta sitosterol containing diets change the live ultra-structure and such differences are observed in both young and adult mice fed with beta sitosterol 26. Pathophysiology of the liver is also affected by beta sitosterol. For example, beta sitosterol prevents gallstone formation and decreases serum and liver cholesterol 27, but such preventive effects are observed only at high doses 28. The effect of beta sitosterol on different metabolizing enzymes has not been studied and therefore sufficient information regarding the metabolism of drugs that are affected by beta sitosterol is not available.

Endocrine System

Beta sitosterol possesses a weakly estrogenic effect and alone or in combination with progesterone, it inhibits the expression of intercellular adhesion molecule-1 29 and testosterone propionate induced prostate hyperplasia 30 as well as reducing pregnenolone production 31. Even though the molecular effect of beta sitosterol on the tonicity of the uterus has been studied 32, the long-term effect of beta sitosterol on different hormones has not been studied and therefore further study is required.

Reproductive System

The effect of beta sitosterol on the reproductive system is contradictory. Study on American mink shows increased male fertility due to beta sitosterol intake 33, but other studies in male rats 34 and goats 35 show the opposite effect on reproduction. The level of sex hormones such as testosterone in males and estradiol in females is increased due to beta sitosterol intake in rats 36. Whether or not this increase has any clinical significance has not yet been studied.

Wound Healing

Different plants containing phytosterols like Mimosa tenuiflora have been used for decades as a remedy in the treatment of wounds and burns of the skin. This can be explained by the re-epithelialization process in wounded areas which is believed to be aided by beta sitosterol. So, the ability to heal, together with the anti-inflammatory and antimicrobial activity of beta sitosterol demonstrate its potential in tissue engineering applications 37.

Antioxidant Activity

Several findings suggest that beta sitosterol has antioxidant property 38. It has also been shown to modulate antioxidant enzymes and human estrogen receptor 39. It has been reported from a study that beta sitosterol reduced Oxygen free radical and Hydrogen Peroxide levels in Phorbol myristate acetate (PMA) stimulated RAW 264.7 cells but does not function as a radical scavenger 40. Glutathione peroxidase (GSH) and Mn superoxide dismutase (SOD) activities are decreased significantly by beta sitosterol treatment 41. Beta sitosterol does not affect Cu-Zn SOD activity, but whether beta sitosterol promotes up-regulation of Mn-SOD needs further investigation.

Angiogenic Effect

beta sitosterol plays a role in blood vessel formation and thus possesses potentials in wound healing 42. However, there has been no experimental study on the mechanism of wound healing until now. Choi et al. 43 shows blood vessel formation in ischemia, but further study regarding the feasibility of using beta sitosterol as a therapeutic agent for ischemic stroke has not been conducted.

Antipyretic Activity

A study on rats has shown that the antipyretic effect of beta sitosterol is comparable to that of aspirin 44. The preparations and extracts of plants containing beta sitosterol have also been shown to have antipyretic activity 45. This effect is comparable to that of the standard antipyretic drug, aspirin, but the detailed mechanism has not yet been studied.

Anti-Inflammatory Activity

Beta sitosterol possesses anti-inflammatory activity in human aortic cells 46 as well as in rats 47. Several studies in animals have indicated that beta sitosterol reduces the secretion of pro-inflammatory cytokines, TNF-α as well as edema 48 and increases anti-inflammatory cytokines 49. Chronic treatment with beta sitosterol reduces its anti-inflammatory potential 50 and it does not affect the mast cells in histamine release 51 and the arachidonic acid pathway 52. Whether beta sitosterol inhibits either myeloperoxidase or adenosine deaminase activity or both needs further investigation. Again, whether beta sitosterol inhibits or not IL-1β and TNF-α levels by increasing calcium uptake in activated neutrophils in a concentration- and time-dependent manner through l-type voltage-dependent calcium channels, phosphoinositide kinase-3, intracellular calcium and microtubule modulation, and thus promotes the anti-inflammatory activity as proposed by Liz et al. 53, requires experimental evidence. Even though Mahanjan and Mehta 54 have shown therapeutic potential in allergic asthma by a chronic study in pigs it has not been used for clinical trials in humans.

Anti-Arthritic Activity

It has been reported from a study that the plant extract containing beta sitosterol has significant anti-arthritic activity 55. According to Moreau et al. 56, beta sitosterol decreases the activation of NF-κB transcription factor in PMA-stimulated macrophage cells. However, further investigations are required regarding the therapeutic potential of beta sitosterol to treat arthritis.

Immune Modulation and Anti-HIV Effect

Beta sitosterol has been shown to act as a powerful immune modulator 57. beta sitosterol exhibits immune-modulating activities in HIV-infected patients 58. It has also been reported that beta sitosterol targets specific T-helper (Th) lymphocytes, increasing Th1 activity and improving T-lymphocyte and natural killer (NK) cell activity 59. In another study it was observed that beta sitosterol maintains stable CD 4 cell counts in AIDS, declines apoptosis of CD 4 lymphocytes slightly, thereby slowing HIV. A significant decrease in IL-6 levels in the same study leads to a further claim that there is slowing down of viral replication rates in infected cells thereby decreasing viral load 60. Neurath et al. 61 proposes beta sitosterol as an envelope virus neutralizing compound (EVNC) and thus acting as an HIV-1 entry inhibitor. This claim has been substantiated by the fact that the envelope virus neutralizing compounds in the body fluid neutralize viruses in the blood stream and elicit an immune response to the neutralized authentically folded virus particle 62. Even though the effect of beta sitosterol on entry and exit out of the cell is not available, it is evident that beta sitosterol facilitates the development of a potentially protective immunity against HIV. However, further study for considering beta sitosterol as potential therapeutic agent has not progressed. Therefore, extensive study is suggested.

Anti-Cancer Effect

Experimental and epidemiological studies have shown the efficacy of beta sitosterol in treating different types of cancer via different pathways. One recent review documented in detail regarding this 63. However, most studies have been carried out with different cancer cell lines, where different cellular factors are affected by beta sitosterol, but ultimately cell lines undergo apoptosis. For breast cancer, MDA-MB-231 64, U937 65, HL60, MCF-7; for colon cancer, HT-29 66, HT116, COLO 320 DM, Caco 2; for prostate cancer, LNCaP 64, PC-3, 22Rv1, DU145; for fibrosarcoma MCA-102 67; for uterine cervix cancer, SiHa cells 68; for larynx carcinoma, Heps 69 have been studied. Studies on the antitumor effect of beta sitosterol in animals are relatively few. For colon carcinogenesis, studies were done on rodents and on rat prostate 70. For the former, the result is positive, but for the later the result is negative. These studies with beta sitosterol are extensive and explain the anticancer mechanism of action. For example, several studies have indicated that beta sitosterol inhibits the growth of various cultured cancer cell lines that are associated with the activation of the sphingomyelin cycle 71; cell cycle arrest 72, and the stimulation of apoptotic cell death 73. Beta sitosterol isolated from various plants promotes apoptosis by increasing first apoptosis signal (Fas) levels and caspase-8 activity 74, phosphorylation of extracellular signal-regulating kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) 75, inhibition of cancer cell proliferation, even at low concentrations with no cytotoxic effect on noncancerous cells 68, modulation of antioxidant enzyme levels in pathogenesis 41, arresting of cells at G2/M phase in cancer cells 76, and decreasing free radical generation in vitro [102,162]. beta sitosterol induces a reduction in membrane sphingomyelin and an increase in the ceramide levels in some tumor cells 66. The efficiency of ceramide playing a role in the activation of the extrinsic pathway as suggested by observations of death receptor clustering in ceramide-rich lipid rafts has not been studied for experimental evidence 77. In addition to the negative effect of beta sitosterol on cell growth, beta sitosterol treatment of tumor cells is associated with increased apoptosis 78. Even with these extensive studies, there is still very little translational research for treating different cancers. One possible explanation could be its lower efficacy and another could be fewer chances of patents by pharmaceutical research organizations. Therefore, research in an academic setting is needed.

Anti-Diabetic Effect

Oral treatment with beta sitosterol increases the fasting plasma insulin levels. There is a corresponding decrease in fasting glycemia when beta sitosterol is administered orally. In addition, it improves the oral glucose tolerance test with an increase in glucose-induced insulin secretion 79. These effects are comparable to that of the standard anti-hyperglycemic drug Glibenclamide. However, the hypoglycemic effect manifested by beta sitosterol by increasing circulating insulin levels and the mechanism of this increase need further study. A study has shown that treatment of diabetic rats with beta sitosterol prevents the development of diabetes as well as ameliorating diabetic complications along with other diseases such as arthritis 80. The same study showed that beta sitosterol increases glucose uptake in adipocytes and stimulates adipogenesis in differentiating preadipocytes. Paradoxically, it also induces lipolysis in adipocytes which have not been attenuated by insulin and co-incubation with epinephrine. Like insulin, it down-regulates GLUT4 gene expression, but a confirmatory study is required to ensure that elevation of glucose uptake by beta sitosterol in adipocytes is unrelated to the de novo synthesis of GLUT4 and whether lipolysis is associated with down-regulation of Akt and PI3K genes. Even though due to the unique effects of beta sitosterol on the regulation of glucose uptake, adipogenesis, and lipolysis in adipocytes supports its potential to be utilized in diabetes and weight management 81, no clinical study has yet progressed. Furthermore, a study should be conducted on whether or not beta sitosterol has any role in insulin sensitivity and glucagon secretion.

Anti-Pulmonary Tuberculosis Effect

According to the double-blind, randomized, placebo-controlled trial conducted by Donald et al. 82 on culture-positive pulmonary tuberculosis patients, beta sitosterol has been found to have a significant improvement in weight that is lost due to pulmonary tuberculosis. The same study showed that patients receiving beta sitosterol exhibit notable differences in certain hematological parameters, including increased lymphocyte, eosinophil, and monocyte counts. The detailed mechanism of this effect has not yet been studied. The efficiency of beta sitosterol as immune modulating agent in case of multi-drug-resistant tuberculosis needs further investigation.

Antimicrobial Activity

beta sitosterol obtained from different plants shows antibacterial and antifungal activity without toxicity in brine shrimp lethality assay 83. The formulation or plant extract containing beta sitosterol shows mosquito larvicidal activities 84 and antitrypanosomal activities 85. beta sitosterol has been reported to have antibacterial activity with a comparable zone of inhibition to other standard antimicrobial agents 86. The prime limitation of these studies is the inadequacy in explaining the mechanism of actions. Kanokmedhakul et al. 87 attributed this to the ability of beta sitosterol to inhibit bacterial cell surface protein, “sortase” thus preventing transpeptidation. Betasitosterol-3-O-glucopyranoside, a derivative of beta sitosterol, inhibits bacterial cell adhesion to a fibronectin indicating that modification of beta sitosterol is needed to exert its antibacterial effect 88. However, no study has been conducted regarding the mechanism of anti-protozoal, anti-larvicidal or anti-fungal effects. Again, no study has been run to ensure any effect of beta sitosterol on the ribosome, RNA transcription, DNA replication or the enzymes involved in central dogma. A detailed study is proposed with a hope of obtaining a good alternative to the antimicrobial agent in this current era of antimicrobial resistance.

Beta sitosterol foods

Beta sitosterol is one of the most abundant dietary phytosterols present in many beans, nuts, and seeds 89. Beta sitosterol has been reported to be present in various dietary and non-dietary plants 90. Beta sitosterol exists in different plant parts such as leaves 91, rhizomes 92, and fruits 93. Beta sitosterol has also been reported to be present in different plant tissue cultures 94. Studies have been reported regarding its membrane stabilizing effect on cell membrane 95, but its role in the cytoplasm and chloroplast has not been studied yet 96. Beta sitosterol-derived phytoecdysteroid is higher in plant tissues which are the most important chemical substance for plant survival, but whether or not beta sitosterol has a significant role in plant protection needs further research 97.

Beta sitosterol supplement

Beta-sitosterol has been used to lower cholesterol and improve symptoms in mild to moderate enlarged prostate. Beta-sitosterol has also been investigated for its immune system and anticancer effects.

Beta sitosterol dosage

Beta-sitosterol is added to margarine, yogurt, or other foods to provide a daily intake of 1.5 to 3 g.

Beta sitosterol side effects

Beta-sitosterol may cause gastrointestinal side effects as well as impotence. In 1 study, side effects related to beta-sitosterol use were gas, discoloration of the feces, appetite changes, stomach problems, leg cramps, skin rash, and low white blood cell count. A 1-year study in healthy patients consuming 1.6 g/day of plant sterols in a dietary spread showed cholesterol-lowering effects and long-term tolerance.

Even though the United States National Toxicology Program reviewed toxicological effects of beta sitosterol about 18 years ago 2, many study results need to be re-evaluated based on the latest findings. A high level of beta sitosterol concentrations in blood has also been correlated with increased severity of heart disease in men who have previously been suffering from heart attacks 98. There are drug interactions of beta sitosterol with Ezetimibe and atorvastatin, pravastatin, simvastatin, and lovastatin or fluvastatin 99. Ezetimibe inhibits the uptake of beta sitosterol which provides the molecular basis for the treatment of sitosterolemia with ezetimibe 100. Short-term repeated administration of beta sitosterol in rats has been reported not to produce gross or microscopic lesions in liver or kidney 34 but such a report on humans taking beta sitosterol for a long time has not been produced. An extensive toxicological study has shown high LD50 (lethal dose 50 is the amount of an ingested substance that kills 50 percent of a test subjects) in rats (>2 gm/kg) 38. According to Joint FAO/WHO Expert Committee on Food Additives (JECFA) (2009), acceptable daily intake (ADI) is 40 mg/kg body weight per day; No-Observed-Adverse-Effect-Level (NOAEL) is 4200 mg/kg body weight per day; Margin of Safety (MOS) is 210 mg/kg body weight per day and 8.3 mg/kg body weight per day for systemic and cosmetic products respectively. These values are calculated approximately from phytosterol mixtures, not directly from beta sitosterol solely and therefore values based on beta sitosterol are highly recommended. Beta sitosterol inhibits mutagenicity 101, prevents chromosomal breaks 102, and shows no genotoxic effects 103. Even though one study found its potentially harmful effect on the reproductive system 104, later study found that it does not have an effect on the reproductive system 105. However, there is no study regarding the long-term effect of beta sitosterol in the human reproductive system. In a recent study, it was shown that high exposure of beta sitosterol is related to impaired hepatic and intestinal ATP-binding cassette transporters G5/8 and possesses potential risks of blood-brain barrier integrity in diabetic rats 106. Another main limitation of beta sitosterol toxicity study is the unavailability of its readily oxidized products.

  1. Bouic P., Clark A., Lamprecht J., Freestone M., Pool E., Liebenberg R., Kotze D., van Jaarsveld P. The effects of B-sitosterol (BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: Inhibition of post marathon immune suppression and inflammation. Int. J. Sports Med. 1999;20:258–262. doi: 10.1055/s-2007-971127[↩][↩]
  2. Bin Sayeed MS, Karim SMR, Sharmin T, Morshed MM. Critical Analysis on Characterization, Systemic Effect, and Therapeutic Potential of Beta-Sitosterol: A Plant-Derived Orphan Phytosterol. Medicines (Basel). 2016;3(4):29. Published 2016 Nov 15. doi:10.3390/medicines3040029 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456237[↩][↩][↩]
  3. Pegel K.H. The importance of sitosterol and sitosterolin in human and animal nutrition. S. Afr. J. Sci. 1997;93:263–268.[↩]
  4. Wilt TJ, Ishani A, MacDonald R, Stark G, Mulrow CD, Lau J. Beta‐sitosterols for benign prostatic hyperplasia. Cochrane Database of Systematic Reviews 1999, Issue 3. Art. No.: CD001043. DOI: 10.1002/14651858.CD001043 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001043/full[↩][↩]
  5. A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. J Altern Complement Med. 2002 Apr;8(2):143-52. https://doi.org/10.1089/acm.2002.8.143[↩]
  6. Retelny V.S., Neuendorf A., Roth J.L. Nutrition protocols for the prevention of cardiovascular disease. Nutr. Clin. Pract. 2008;23:468–476. doi: 10.1177/0884533608323425[↩]
  7. Yeshurun D., Gotto A. Drug treatment of hyperlipidemia. Am. J. Med. 1976;60:379–396. doi: 10.1016/0002-9343(76)90755-5[↩]
  8. Jesch E.D., Carr T.P. Sitosterol reduces micellar cholesterol solubility in model bile. Nutr. Res. 2006;26:579–584. doi: 10.1016/j.nutres.2006.08.006[↩]
  9. Ellegard L.H., Andersson S.W., Normén A.L., Andersson H.A. Dietary plant sterols and cholesterol metabolism. Nutr. Rev. 2007;65:39. doi: 10.1111/j.1753-4887.2007.tb00266.x[↩]
  10. Richter W.O., Geiss H.C., Sönnichsen A.C., Schwandt P. Treatment of severe hypercholesterolemia with a combination of beta-sitosterol and lovastatin. Curr. Ther. Res. 1996;57:497–505. doi: 10.1016/S0011-393X(96)80059-2[↩]
  11. Weingärtner O., Böhm M., Laufs U. Controversial role of plant sterol esters in the management of hypercholesterolaemia. Eur. Heart J. 2009;30:404–409. doi: 10.1093/eurheartj/ehn580[↩]
  12. Rosenblat M., Volkova N., Aviram M. Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis. 2013;226:110–117. doi: 10.1016/j.atherosclerosis.2012.10.054[↩]
  13. Wilund K.R., Yu L., Xu F., Vega G.L., Grundy S.M., Cohen J.C., Hobbs H.H. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler. Thromb. Vasc. Biol. 2004;24:2326–2332. doi: 10.1161/01.ATV.0000149140.00499.92[↩]
  14. Santos A., Niero R., Yunes R., Pizzolatti M., Delle Monache F., Calixto J. Antinociceptive properties of steroids isolated from Phyllanthus corcovadensis in mice. Planta Medica. 1995;61:329–332. doi: 10.1055/s-2006-958093[↩]
  15. López-Rubalcava C., Piña-Medina B., Estrada-Reyes R., Heinze G., Martínez-Vázquez M. Anxiolytic-like actions of the hexane extract from leaves of Annona cherimolia in two anxiety paradigms: Possible involvement of the GABA/benzodiazepine receptor complex. Life Sci. 2006;78:730–737. doi: 10.1016/j.lfs.2005.05.078[↩][↩]
  16. Aguirre-Hernández E., Rosas-Acevedo H., Soto-Hernández M., Martínez A.L., Moreno J., González-Trujano M.E. Bioactivity-guided isolation of beta-sitosterol and some fatty acids as active compounds in the anxiolytic and sedative effects of Tilia americana var. Mexicana. Planta Medica. 2007;73:1148–1155. doi: 10.1055/s-2007-981593[↩]
  17. Zhu M. CNS active principles from Alangium plantanifolium. Planta Medica. 1998;64:8–11. doi: 10.1055/s-2006-957356[↩]
  18. Brimson J.M., Brimson S.J., Brimson C.A., Rakkhitawatthana V., Tencomnao T. Rhinacanthus nasutus extracts prevent glutamate and amyloid-β neurotoxicity in ht-22 mouse hippocampal cells: Possible active compounds include lupeol, stigmasterol and β-sitosterol. Int. J. Mol. Sci. 2012;13:5074–5097. doi: 10.3390/ijms13045074[↩]
  19. Shi C., Wu F., Xu J. Incorporation of β-sitosterol into mitochondrial membrane enhances mitochondrial function by promoting inner mitochondrial membrane fluidity. J. Bioenerg. Biomembr. 2013;45:301–305. doi: 10.1007/s10863-012-9495-3[↩]
  20. Vanmierlo T., Weingärtner O., Pol S., Husche C., Kerksiek A., Friedrichs S., Sijbrands E., Steinbusch H., Grimm M., Hartmann T., et al. Dietary intake of plant sterols stably increases plant sterol levels in the murine brain. J. Lipid Res. 2012;53:726–735. doi: 10.1194/jlr.M017244[↩]
  21. Hamedi A., Ghanbari A., Saeidi V., Razavipour R., Azari H. Effects of β-sitosterol oral administration on the proliferation and differentiation of neural stem cells. J. Funct. Foods. 2014;8:252–258. doi: 10.1016/j.jff.2014.03.021[↩]
  22. Hamedi A., Ghanbari A., Razavipour R., Saeidi V., Zarshenas M.M., Sohrabpour M., Azari H. Alyssum homolocarpum seeds: Phytochemical analysis and effects of the seed oil on neural stem cell proliferation and differentiation. J. Nat. Med. 2015;69:1–10. doi: 10.1007/s11418-015-0905-9[↩]
  23. Han N.-R., Kim H.-M., Jeong H.-J. The β-sitosterol attenuates atopic dermatitis-like skin lesions through down-regulation of TSLP. Exp. Biol. Med. 2014;239:454–464. doi: 10.1177/1535370213520111[↩]
  24. Su Y., Wang Z., Yang H., Cao L., Liu F., Bai X., Ruan C. Clinical and molecular genetic analysis of a family with sitosterolemia and co-existing erythrocyte and platelet abnormalities. Haematologica. 2006;91:1392–1395[↩]
  25. Brufaua G., Canelab M.A., Rafecas M. Phytosterols: Physiologic and metabolic aspects related to cholesterol-lowering properties. Nutr. Res. 2008;28:217–225. doi: 10.1016/j.nutres.2008.02.003[↩]
  26. Tamura M., Suzuki H., Itoh K. Effect of beta-sitosterol on ultrastructure of liver cells in young and aged mice. Int. J. Vitam. Nutr. Res. 1997;68:146–148[↩]
  27. Goswami S.K., Frey C.F. Effect of beta-sitosterol on cholesterol-cholic acid-induced gallstone formation in mice. Am. J. Gastroenterol. 1976;65:305–310[↩]
  28. Singhal A.K., Cohen B.I., Finver-Sadowsky J., McSherry C.K., Mosbach E.H. Role of hydrophilic bile acids and of sterols on cholelithiasis in the hamster. J. Lipid Res. 1984;25:564–570[↩]
  29. Bustos P., Duffau C., Pacheco C., Ulloa N. Β-sitosterol modulation of monocyte-endothelial cell interaction: A comparison to female hormones. Maturitas. 2008;60:202–208. doi: 10.1016/j.maturitas.2008.06.002[↩]
  30. Wu G.-X., Lin Y.-X., Ou M.-R., Tan D.-F. An experimental study (II) on the inhibition of prostatic hyperplasia by extract of seeds of Brassica alba. Zhongguo Zhong Yao Za Zhi. 2003;28:643–646.[↩]
  31. Leusch F.D., MacLatchy D.L. In vivo implants of β-sitosterol cause reductions of reactive cholesterol pools in mitochondria isolated from gonads of male goldfish (Carassius auratus) Gen. Comp. Endocrinol. 2003;134:255–263. doi: 10.1016/S0016-6480(03)00265-X[↩]
  32. Promprom W., Kupittayanant P., Indrapichate K., Wray S., Kupittayanant S. The effects of pomegranate seed extract and β-sitosterol on rat uterine contractions. Reprod. Sci. 2010;17:288–296. doi: 10.1177/1933719109352687[↩]
  33. Nieminen P., Pölönen I., Mustonen A.-M. Increased reproductive success in the white American mink (Neovison vison) with chronic dietary β-sitosterol supplement. Anim. Reprod. Sci. 2010;119:287–292. doi: 10.1016/j.anireprosci.2010.01.008[↩]
  34. Malini T., Vanithakumari G. Rat toxicity studies with β-sitosterol. J. Ethnopharmacol. 1990;28:221–234. doi: 10.1016/0378-8741(90)90032-O[↩][↩]
  35. Chattopadhyay D., Dungdung S.R., Mandal A.B., Majumder G.C. A potent sperm motility-inhibiting activity of bioflavonoids from an ethnomedicine of onge, Alstonia macrophylla Wall ex A. Dc, leaf extract. Contraception. 2005;71:372–378. doi: 10.1016/j.contraception.2004.11.006[↩]
  36. Ryökkynen A., Käyhkö U.-R., Mustonen A.-M., Kukkonen J.V., Nieminen P. Multigenerational exposure to phytosterols in the mouse. Reprod. Toxicol. 2005;19:535–540. doi: 10.1016/j.reprotox.2004.09.003[↩]
  37. Martel-Estrada S.A., Rodríguez-Espinoza B., Santos-Rodríguez E., Jiménez-Vega F., García-Casillas P.E., Martínez-Pérez C.A., Armendáriz I.O. Biocompatibility of chitosan/Mimosa tenuiflora scaffolds for tissue engineering. J. Alloy. Compd. 2015;643:119–123. doi: 10.1016/j.jallcom.2015.01.034[↩]
  38. Paniagua-Pérez R., Madrigal-Bujaidar E., Reyes-Cadena S., Molina-Jasso D., Gallaga J.P., Silva-Miranda A., Velazco O., Hernández N., Chamorro G. Genotoxic and cytotoxic studies of beta-sitosterol and pteropodine in mouse. BioMed Res. Int. 2005;2005:242–247. doi: 10.1155/JBB.2005.242[↩][↩]
  39. Song Y.S., Jin C., Park E.-H. Identification of metabolites of phytosterols in rat feces using GC/MS. Arch. Pharm. Res. 2000;23:599–604. doi: 10.1007/BF02975248[↩]
  40. Moreno J.J., Mitjavila M.T. The degree of unsaturation of dietary fatty acids and the development of atherosclerosis (review) J. Nutr. Biochem. 2003;14:182–195. doi: 10.1016/S0955-2863(02)00294-2[↩]
  41. Vivancos M., Moreno J.J. Β-sitosterol modulates antioxidant enzyme response in raw 264.7 macrophages. Free Radic. Biol. Med. 2005;39:91–97. doi: 10.1016/j.freeradbiomed.2005.02.025[↩][↩]
  42. Moon E.-J., Lee Y.M., Lee O.-H., Lee M.-J., Lee S.-K., Chung M.-H., Park Y.-I., Sung C.-K., Choi J.-S., Kim K.-W. A ncovel angiogenic factor derived from aloe vera gel: Β-sitosterol, a plant sterol. Angiogenesis. 1999;3:117–123. doi: 10.1023/A:1009058232389[↩]
  43. Choi Y.H., Kong K.R., Kim Y., Jung K.-O., Kil J.-H., Rhee S.-H., Park K.-Y. Induction of bax and activation of caspases during β-sitosterol-mediated apoptosis in human colon cancer cells. Int. J. Oncol. 2003;23:1657–1662. doi: 10.3892/ijo.23.6.1657[↩]
  44. Gupta M., Nath R., Srivastava N., Shanker K., Kishor K., Bhargava K. Anti-inflammatory and antipyretic activities of beta-sitosterol (Cyperus) Planta Medica. 1980;39:157–163. doi: 10.1055/s-2008-1074919[↩]
  45. Begum T.N., Ilyas M.H.M., Anand A.V. Antipyretic activity of Azima tetracantha in experimental animals. Int. J. Curr. Biomed. Pharm. Res. 2011;1:41–44[↩]
  46. Loizou S., Lekakis I., Chrousos G.P., Moutsatsou P. Β-sitosterol exhibits anti-inflammatory activity in human aortic endothelial cells. Mol. Nutr. Food Res. 2010;54:551–558. doi: 10.1002/mnfr.200900012[↩]
  47. Nirmal S.A., Pal S.C., Mandal S.C., Patil A.N. Analgesic and anti-inflammatory activity of β-sitosterol isolated from Nyctanthes arbortristis leaves. Inflammopharmacology. 2012;20:219–224. doi: 10.1007/s10787-011-0110-8[↩]
  48. Bouic P., Etsebeth S., Liebenberg R., Albrecht C., Pegel K., Van Jaarsveld P. Beta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: Implications for their use as an immunomodulatory vitamin combination. Int. J. Immunopharmacol. 1996;18:693–700. doi: 10.1016/S0192-0561(97)85551-8[↩]
  49. Valerio M., Awad A.B. Β-sitosterol down-regulates some pro-inflammatory signal transduction pathways by increasing the activity of tyrosine phosphatase SHP-1 in J774A. 1 murine macrophages. Int. Immunopharmacol. 2011;11:1012–1017. doi: 10.1016/j.intimp.2011.02.018[↩]
  50. Gomez M., Saenz M., Garcia M., Fernandez M. Study of the topical anti-inflammatory activity of Achillea ageratum on chronic and acute inflammation models. Z. Naturforschung C. 1999;54:937–941. doi: 10.1515/znc-1999-1113[↩]
  51. Navarro A., De Las Heras B., Villar A. Anti-inflammatory and immunomodulating properties of a sterol fraction from Sideritis foetens Clem. Biol. Pharm. Bull. 2001;24:470–473. doi: 10.1248/bpb.24.470[↩]
  52. Breu W., Hagenlocher M., Redl K., Stadler F., Wagner H. Anti-inflammatory activity of sabal fruit extracts prepared with supercritical carbon dioxide. In vitro antagonists of cyclooxygenase and 5-lipoxygenase metabolism. Arzneim.-Forsch. 1992;42:547–551.[↩]
  53. Liz R., Zanatta L., dos Reis G.O., Horst H., Pizzolatti M.G., Silva F.R.M.B., Fröde T.S. Acute effect of β-sitosterol on calcium uptake mediates anti-inflammatory effect in murine activated neutrophils. J. Pharm. Pharmacol. 2013;65:115–122. doi: 10.1111/j.2042-7158.2012.01568.x[↩]
  54. Mahajan S.G., Mehta A.A. Suppression of ovalbumin-induced Th2-driven airway inflammation by β-sitosterol in a guinea pig model of asthma. Eur. J. Pharmacol. 2011;650:458–464. doi: 10.1016/j.ejphar.2010.09.075[↩]
  55. Tatiya A.U., Saluja A.K. Further studies on membrane stabilizing, anti-inflammatory and FCA induced arthritic activity of various fractions of bark of Machilus macrantha in rats. Rev. Bras. Farmacogn. 2011;21:1052–1064. doi: 10.1590/S0102-695X2011005000152[↩]
  56. Moreau R.A., Whitaker B.D., Hicks K.B. Phytosterols, phytostanols, and their conjugates in foods: Structural diversity, quantitative analysis, and health-promoting uses. Prog. Lipid Res. 2002;41:457–500. doi: 10.1016/S0163-7827(02)00006-1[↩]
  57. Fraile L., Crisci E., Córdoba L., Navarro M.A., Osada J., Montoya M. Immunomodulatory properties of beta-sitosterol in pig immune responses. Int. Immunopharmacol. 2012;13:316–321. doi: 10.1016/j.intimp.2012.04.017[↩]
  58. Bouic P.J. The role of phytosterols and phytosterolins in immune modulation: A review of the past 10 years. Curr. Opin. Clin. Nutr. Metab. Care. 2001;4:471–475. doi: 10.1097/00075197-200111000-00001[↩]
  59. Breytenbach U., Clark A., Lamprecht J., Bouic P. Flow cytometric analysis of the Th1–Th2 balance in healthy individuals and patients infected with the human immunodeficiency virus (HIV) receiving a plant sterol/sterolin mixture. Cell Biol. Int. 2001;25:43–49. doi: 10.1006/cbir.2000.0676[↩]
  60. Bouic P.J. Immunomodulation in HIV/AIDS: The Tygerberg/Stellenbosch University Experience. AIDS Bull. 1997;6:18–20[↩]
  61. Neurath A.R., Strick N., Li Y.Y., Debnath A.K. Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide. Ann. N. Y. Acad. Sci. 2005;1056:311–327. doi: 10.1196/annals.1352.015[↩]
  62. Kotwal G.J., Kulkarni A.P. Antigenic variation in microbial evasion of immune responses. eLS. 2013 doi: 10.1002/9780470015902.a0001207.pub3[↩]
  63. Bin Sayeed M.S., Ameen S.S. Beta-sitosterol: A promising but orphan nutraceutical to fight against cancer. Nutr. Cancer. 2015;67:1–7. doi: 10.1080/01635581.2015.1087042[↩]
  64. Awad A., Downie A.C., Fink C.S. Inhibition of growth and stimulation of apoptosis by beta-sitosterol treatment of MDA-MB-231 human breast cancer cells in culture. Int. J. Mol. Med. 2000;5:541–546. doi: 10.3892/ijmm.5.5.541[↩][↩]
  65. Park C., Moon D.-O., Rhu C.-H., Choi B.T., Lee W.H., Kim G.-Y., Choi Y.H. Beta-sitosterol induces anti-proliferation and apoptosis in human leukemic U937 cells through activation of caspase-3 and induction of Bax/Bcl-2 ratio. Biol. Pharm. Bull. 2007;30:1317–1323. doi: 10.1248/bpb.30.1317[↩]
  66. Awad A., Von Holtz R., Cone J., Fink C., Chen Y. Beta-sitosterol inhibits growth of HT-29 human colon cancer cells by activating the sphingomyelin cycle. Anticancer Res. 1997;18:471–473[↩][↩]
  67. Jayaprakasha G., Mandadi K., Poulose S.M., Jadegoud Y., Gowda G.N., Patil B.S. Inhibition of colon cancer cell growth and antioxidant activity of bioactive compounds from Poncirus trifoliata (L.) Raf. Bioorg. Med. Chem. 2007;15:4923–4932. doi: 10.1016/j.bmc.2007.04.044[↩]
  68. Wang L., Yang Y., Chen S., Ge X., Xu C., Gui S. Effects of beta-sitosterol on microtubular systems in cervical cancer cells. Zhonghua Yi Xue Za Zhi. 2006;86:2771–2775[↩][↩]
  69. Matos M., Leite L., Brustolim D., De Siqueira J., Carollo C., Hellmann A., Pereira N., da Silva D. Antineoplastic activity of selected constituents of Duguetia glabriuscula. Fitoterapia. 2006;77:227–229. doi: 10.1016/j.fitote.2006.01.013[↩]
  70. Nair P.P., Turjman N., Kessie G., Calkins B., Goodman G.T., Davidovitz H., Nimmagadda G. Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Dietary cholesterol, beta-sitosterol, and stigmasterol. Am. J. Clin. Nutr. 1984;40:927–930[↩]
  71. Awad A.B., Fink C.S. Phytosterols as anticancer dietary components: Evidence and mechanism of action. J. Nutr. 2000;130:2127–2130.[↩]
  72. Awad A.B., Williams H., Fink C.S. Phytosterols reduce in vitro metastatic ability of MDA-MB-231 human breast cancer cells. Nutr. Cancer. 2001;40:157–164. doi: 10.1207/S15327914NC402_12[↩]
  73. Awad A.B., Roy R., Fink C.S. Β-sitosterol, a plant sterol, induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells. Oncol. Rep. 2003;10:497–500. doi: 10.3892/or.10.2.497[↩]
  74. Awad A., Chinnam M., Fink C., Bradford P. Β-sitosterol activates fas signaling in human breast cancer cells. Phytomedicine. 2007;14:747–754. doi: 10.1016/j.phymed.2007.01.003[↩]
  75. Moon D.-O., Lee K.-J., Choi Y.H., Kim G.-Y. Β-sitosterol-induced-apoptosis is mediated by the activation of ERK and the downregulation of Akt in MCA-102 murine fibrosarcoma cells. Int. Immunopharmacol. 2007;7:1044–1053. doi: 10.1016/j.intimp.2007.03.010[↩]
  76. Awad A.B., Burr A.T., Fink C.S. Effect of resveratrol and β-sitosterol in combination on reactive oxygen species and prostaglandin release by PC-3 cells. Prostaglandins Leukot. Essent. Fatty Acids. 2005;72:219–226. doi: 10.1016/j.plefa.2004.11.005[↩]
  77. Hueber A. Role of membrane microdomain rafts in TNFR-mediated signal transduction. Cell Death Differ. 2003;10:7–9. doi: 10.1038/sj.cdd.4401155[↩]
  78. Awad A., Chinnam M., Fink C., Bradford P. Targeting ceramide by dietary means to stimulate apoptosis in tumor cells. Curr. Top. Nutraceutical Res. 2004;2:93–100[↩]
  79. Ivorra M., D’ocon M., Paya M., Villar A. Antihyperglycemic and insulin-releasing effects of beta-sitosterol 3-beta-d-glucoside and its aglycone, beta-sitosterol. Arch. Int. Pharmacodyn. Thér. 1987;296:224–231[↩]
  80. Gupta R., Sharma A.K., Dobhal M., Sharma M., Gupta R. Antidiabetic and antioxidant potential of β-sitosterol in streptozotocin-induced experimental hyperglycemia. J. Diabetes. 2011;3:29–37. doi: 10.1111/j.1753-0407.2010.00107.x[↩]
  81. Chai J.-W., Lim S.-L., Kanthimathi M., Kuppusamy U.R. Gene regulation in β-sitosterol-mediated stimulation of adipogenesis, glucose uptake, and lipid mobilization in rat primary adipocytes. Genes Nutr. 2011;6:181–188. doi: 10.1007/s12263-010-0196-4[↩]
  82. Donald P., Lamprecht J., Freestone M., Albrecht C., Bouic P., Kotze D., Van Jaarsveld P. A randomised placebo-controlled trial of the efficacy of beta-sitosterol and its glucoside as adjuvants in the treatment of pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 1997;1:518–522[↩]
  83. Mishra G., Singh P., Verma R., Kumar S., Srivastav S., Jha K., Khosa R. Traditional uses, phytochemistry and pharmacological properties of Moringa oleifera plant: An overview. Der Pham. Lett. 2011;3:141–164.[↩]
  84. Rahuman A.A., Gopalakrishnan G., Venkatesan P., Geetha K. Isolation and identification of mosquito larvicidal compound from Abutilon indicum (Linn.) sweet. Parasitol. Res. 2008;102:981–988. doi: 10.1007/s00436-007-0864-5[↩]
  85. Nweze N.E. In vitro anti-trypanosomal activity of Morinda lucida leaves. Afr. J. Biotechnol. 2011;11:1812–1817[↩]
  86. Bumrela S., Naik S. Hepato protective activity of methanolic extract of Dipteracanthus patulus (Jacq) Nees: Possible involvement of antioxidant and membrane stabilization property. Int. J. Pharm. Pharm. Sci. 2012;4:685–690.[↩]
  87. Kanokmedhakul K., Kanokmedhakul S., Phatchana R. Biological activity of anthraquinones and triterpenoids from Prismatomeris fragrans. J. Ethnopharmacol. 2005;100:284–288. doi: 10.1016/j.jep.2005.03.018[↩]
  88. Oh K.-B., Oh M.-N., Kim J.-G., Shin D.-S., Shin J. Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors. Appl. Microbiol. Biotechnol. 2006;70:102–106. doi: 10.1007/s00253-005-0040-8[↩]
  89. Lomenick B, Shi H, Huang J, Chen C. Identification and characterization of β-sitosterol target proteins. Bioorg Med Chem Lett. 2015;25(21):4976-4979 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567552/[↩]
  90. An Evidence-Based Systematic Review of Beta-Sitosterol, Sitosterol (22,23- dihydrostigmasterol, 24-ethylcholesterol) by the Natural Standard Research Collaboration. J Diet Suppl. 2016;13(1):35-92. Epub 2015 Aug 13. https://www.ncbi.nlm.nih.gov/pubmed/26268617[↩]
  91. Khan A., Rahman M., Islam S. Antipyretic activity of Peperomia pellucida leaves in rabbit. Turk. J. Biol. 2008;32:37–41[↩]
  92. Pateh U., Haruna A., Garba M., Iliya I., Sule I., Abubakar M., Ambi A. Isolation of stigmasterol, β-sitosterol and 2-hydroxyhexadecanoic acid methyl ester from the rhizomes of Stylochiton lancifolius Pyer and Kotchy (Araceae) Niger. J. Pharm. Sci. 2009;7:19–25.[↩]
  93. Khanam S., Sultana R. Isolation of β-sitosterol & stigmasterol as active immunomodulatory constituents from fruits of Solanum xanthocarpum (Solanaceae) IJPSR. 2012;3:1057–1060.[↩]
  94. Sarin R., Bansal N. Phytosterol from in vivo and in vitro cultures of two medicinal plants viz. Adhatoda Vasica. 2011;2:927–930.[↩]
  95. Kongduang D., Wungsintaweekul J., de-Eknamkul W. Biosynthesis of β-sitosterol and stigmasterol proceeds exclusively via the mevalonate pathway in cell suspension cultures of Croton stellatopilosus. Tetrahedron Lett. 2008;49:4067–4072. doi: 10.1016/j.tetlet.2008.04.049[↩]
  96. De-Eknamkul W., Potduang B. Biosynthesis of β-sitosterol and stigmasterol in Croton sublyratus proceeds via a mixed origin of isoprene units. Phytochemistry. 2003;62:389–398. doi: 10.1016/S0031-9422(02)00555-1[↩]
  97. Klein R. Phytoecdysteroids. J. Am. Herbalists Guild. 2004;5:18–28.[↩]
  98. Assmann G., Cullen P., Erbey J., Ramey D.R., Kannenberg F., Schulte H. Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: Results of a nested case-control analysis of the prospective cardiovascular münster (PROCAM) study. Nutr. Metab. Cardiovasc. Dis. 2006;16:13–21. doi: 10.1016/j.numecd.2005.04.001[↩]
  99. Thongtang N., Lin J., Schaefer E.J., Lowe R.S., Tomassini J.E., Shah A.K., Tershakovec A.M. Effects of ezetimibe added to statin therapy on markers of cholesterol absorption and synthesis and LDL-C lowering in hyperlipidemic patients. Atherosclerosis. 2012;225:388–396. doi: 10.1016/j.atherosclerosis.2012.09.001[↩]
  100. Yamanashi Y., Takada T., Suzuki H. Niemann-Pick C1-like 1 overexpression facilitates ezetimibe-sensitive cholesterol and β-sitosterol uptake in Caco-2 cells. J. Pharmacol. Exp. Ther. 2007;320:559–564. doi: 10.1124/jpet.106.114181[↩]
  101. Villaseñor I.M., Angelada J., Canlas A.P., Echegoyen D. Bioactivity studies on β-sitosterol and its glucoside. Phytother. Res. 2002;16:417–421. doi: 10.1002/ptr.910[↩]
  102. Raj A., Katz M. Corn oil and its minor constituents as inhibitors of DMBA-induced chromosomal breaks in vivo. Mutation Res. 1984;136:247–253. doi: 10.1016/0165-1218(84)90058-2[↩]
  103. Maguire L., Konoplyannikov M., Ford A., Maguire A.R., O’Brien N.M. Comparison of the cytotoxic effects of β-sitosterol oxides and a cholesterol oxide, 7β-hydroxycholesterol, in cultured mammalian cells. Br. J. Nutr. 2003;90:767–775. doi: 10.1079/BJN2003956[↩]
  104. MacLatchy D., Peters L., Nickle J., van Der Kraak G. Exposure to β-sitosterol alters the endocrine status of goldfish differently than 17β-estradiol. Environ. Toxicol. Chem. 1997;16:1895–1904. doi: 10.1002/etc.5620160919[↩]
  105. Nieminen P., Pölönen I., Ikonen K., Määttänen M., Mustonen A.-M. Evaluation of reproductive safety of β-sitosterol on the American mink (neovison vison) Chemosphere. 2008;71:493–499. doi: 10.1016/j.chemosphere.2007.10.011[↩]
  106. Li J., Wang X., Liu H., Guo H., Zhang M., Mei D., Liu C., He L., Liu L., Liu X. Impaired hepatic and intestinal ATP-binding cassette transporter G5/8 was associated with high exposure of β-sitosterol and the potential risks to blood–brain barrier integrity in diabetic rats. J. Pharm. Pharmacol. 2014;66:428–436. doi: 10.1111/jphp.12178[↩]

you might also like

Health Jade