Reversing Declines in Testosterone Levels with Age
o Apigenin Revitalizing Leydig Cell Testosterone Production
Age-related declines in testosterone is a normal process in most men. However, with decrease levels of testosterone comes a decrease in libido, energy and increases in cardiovascular dysfunction. Recent studies indicate that decreases in testosterone due to aging are associated with diminished levels of a protein (the steroidogenic acute regulatory (StAR) protein) that is considered to be a critical part of the testosterone biosynthesis process. StAR is an important transport protein, which takes cholesterol (an important raw material for steroid hormone synthesis) and transports it into the inner mitochondria of the leydig cells (in the testicles), where testosterone is produced. The StAR protein is genetically expressed in the leydig cells. In addition to aging, StAR activity is reduced by alcohol consumption, explaining why excessive amounts of alcohol can lower testosterone. In studies conducted on mouse leydig cells, apigenin enhanced StAR gene expression, thereby increasing levels of this important protein. Apigenin was able to revitalize the testosterone production of the aging leydig cells by increasing StAR protein production. (1)
Protecting Testicular Function from Environmental Factors
o Curcumin Protects Against Cadmium Toxicity of Testes.
Cadmium is a common environmental toxic metal, which plants readily absorb from contaminated soil. In fact, it is prevalent in many commercial fertilizers (in particular phosphate fertilizers), thereby making it a widespread food contaminate. Cadmium effects many parts of the body, and is considered a carcinogen. Of particular importance to men, is toxicity to the testes, resulting in cell death and reduced production of testosterone. Experiments with rats showed that administration of curcumin to cadmium treated rats significantly improved the detrimental histological cadmium changes to rat testes, and significantly raised serum testosterone levels.(2)
Prostate: Anti-Cancer Properties of Yellow
o Apigenin, Curcumin, EGCG, Luteolin, Fisetin, Pterostilbene and Prostate Cancer
In experiments with mice, apigenin, curcumin and EGCG were able to either delay or reduce the development of prostate cancer in these mice. Specifically, in vitro studies, using human and mouse prostate carcinoma cell cultures, each of these natural compounds were able to inhibit the growth of cancer cells.(3) Apigenin has been shown to be a powerful inhibitor of the cellular growth cycle and cellular death of human prostate cancer cells - both in vitro and in vivo (10). In other studies, luteolin has been shown to significantly inhibit prostate cancer cells both in animals and in cell cultures.(4,5) In cell culture studies, fisetin has demonstrated multi-antitumor mechanisms in the inihibition of prostate cancer cells.(6,7) Furthermore, researchers have also identifiedpterostilbene as a potentially powerful agent against prostate cancer.(8)
o Apigenin Inhibition of Prostate Cancer Cell Motility and Metastasis
Prostate cancer mortality is due primarily to the motility and invasiveness into other organs. Hence, because of this, many researchers believe that targeting the metastasis of the disease is the most effective approach against prostate cancer. Apigenin has been shown (in lab studies) to have anti-cancer effects against many different types of cancer. Utilizing live cell studies, tests on prostate carcinoma cells showed that apigenin inhibited the motility and invasiveness of the carcinoma cells.(9)
(1) Li W, et al. Effects of apigenin on steroidogenesis and steroidogenic acute regulatory gene expression in mouse Leydig cells. J Nutr Biochem. 2011 Mar;22(3):212-8.
(2) Aktas C, et al. Anti-apoptotic effects of curcumin on cadmium-induced apoptosis in rat testes. Toxicol Ind Health. 2011 Jun 1.
(3) Slusarz A, et al. Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer. Cancer Res. 2010 Apr 15;70(8):3382-90. J Steroid Biochem Mol Biol. 2010 Jan;118(1-2):41-50.
(4) Shoulars K, et al. Regulation of cell cycle and RNA transcription genes identified by microarray analysis of PC-3 human prostate cancer cells treated with luteolin. J Steroid Biochem Mol Biol. 2010 Jan;118(1-2):41-50.
(5) Markaverich BM, et al. Luteolin and gefitinib regulation of EGF signaling pathway and cell cycle pathway genes in PC-3 human prostate cancer cells. J Steroid Biochem Mol Biol. 2010 Oct;122(4):219-31.
(6) Haddad AQ, et al. Antiproliferative mechanisms of the flavonoids 2,2'-dihydroxychalcone and fisetin in human prostate cancer cells. Nutr Cancer. 2010;62(5):668-81.
(7) Suh Y, et al. Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells. Carcinogenesis. 2010 Aug;31(8):1424-33.
(8) Chakraborty A, et al. In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from Pterocarpus marsupium. Toxicol In Vitro. 2010 Jun;24(4):1215-28.
(9) Franzen CA, et al. The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism. Cancer Prev Res (Phila). 2009 Sep;2(9):830-41.
(10) Pandey M, et al. Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study. Mol Carcinog. 2011 Oct 17. doi: 10.1002