GAMMA ORYZANOL-A THERAPEUTIC AGENT

Anshu Sharma. Gamma oryzanol is a combination of ferulate, esters of fatty acid and triterpene alcohol which acts as an antioxidant against free radicals. It is present in rice bran oil however it also occurs in corn and barley oils. It also possesses several properties which play an important role in lowering plasma and serum cholesterol by decreasing its absorption to the blood from intestinal tract, alleviate postmenopausal syndrome, improve insulin sensitivity, reduce the skin related problems and growth of cancerous cells. It also increases testosterone levels, thus stimulate secretion of endorphins and also promote the growth of lean muscle tissue, hence find applications in body building aid and health supplements for athletes or sport persons. It also stimulates immune system. It is widely used in cosmoceutical, nutraceutical and pharmaceutical products due to all these health related properties.


Therapeutic roles of gamma oryzanol:-
Due to its unique composition and nutritional properties, gamma oryzanol finds many roles in different health conditions. These are:  Role in Immunity: The Nuclear Factor kappa-light-chain-enhancer of activated β-cells (NF-kβ) translocation in lipopolysaccaride-stimulated (LPS) macrophages was prevented at a 10ng/ml concentration by gamma oryzanol (specifically β-sitosteryl ferulate, Cycloartenyl ferulate and 24-methylenecycloartenyl ferulate). The translocation of NF-kβ was reduced to below 20% by gamma oryzanol with cycloartenyl ferulate at 10ng/ml and with other components between 20-40 % (Islam et al., 2009). This inhibition has also been seen in endothelial cells, the LPS-induced NF-kβ translocation was reduced at 30µM gamma oryzanol to 12.5%, compared to Pyrrolidine dithiocarbamate (PDTC) (Sakai et al., 2012). In a study of rats with implanted colonic tumors, an increase by 130%, 170% and 220% in NK cell activity above control by feeding orally either 0.2, 0.5 or 1 % gamma oryzanol for two weeks while evaluating splenic natural killer (NK) cell activity . At oral doses of 0.2, 0.5, or 1% of the diet containing gamma oryzanol for 2 weeks was able to increase the activity of macrophages that suppressed by the presence of a colonic tumor. The activity seen in tumor planted mice (50% or so) was increased to 80% of control by 1% of diet (when nitric oxide release while evaluating) and phagocytosis normalization (  Role in Postmenopausal Syndrome: In menopause, the immature eggcells in the ovaries give less response resulted in FSH (Follicle Stimulating Hormone) and LH (Luteinizing Hormone) oversecretion by the pituitary, which is responsible to start the another ovulatory cycle which contributes to the onset of hot flashes and menopausal symptoms (profuse sweating, mood changes) (Murray, 1996).The supplementation of 150 mg gamma oryzanol twice daily has beenshown to reduce the luteinizing hormone (LH) secretion by the pituitary gland and also promote the release of endorphin by the hypothalamus (Murray, 1996). In clinical trials of menopausal women and women whose ovaries were surgicallyremoved, around 67-85 % women experienced a significant reduction in the symptoms of menopause by treating with gamma oryzanol (Murray, 1996;Fujiwara et al., 1982). During menopause, the decline in circulating estrogenlevels lead to the rise in blood cholesterol and thedevelopment of atherosclerosis in postmenopausal women. This is due to the fact that cholesterol was not efficiently removed from blood as the number of low density lipoprotein cholesterol receptors on body cells increases by estrogen (Murray, 1996;Fujiwara et al., 1982). Studies on gamma oryzanol in Japan revealed that it is beneficial in the treatment of menopausal syndromes, elevated cholesterol and various gastrointestinal conditions (Ishihara et al., 1982).
 Role in Cancer: The gamma oryzanol was able to regulate angiogenesis, suppressing 61% of blood vessel formation in tumor implanted mice was suppresses at the diet of 1% . It was also able to reduce melanin concentration by 13% at 3µM and 38% at 30µM in B16F1 Melanoma cells; as there is a correlation with a reduction in protein kinase A (PKA) activity that reduced melanin synthesis by decreasing microphthalmia-associated transcription factor (MTIF) (Jun et al., 2012). There was also a Tyrosinase protein content and mRNA downregulation . In a study of rats after implantation of colonic tumor, evaluated the components of rice bran (Gamma Oryzanol, Ferulic Acid, Phytic Acid and Tocotrienols) at 0.2% that tumor size was reduced slightly by all components but gamma oryzanol and somewhat phytic acid was more effective (Kim et al., 2012). The dose-dependent reductions in colonic tumor size at 0.2%, 0.5% and 1% of diet was found in these rats, with 1% reducing the tumor size by 44% yet 10% rice bran (used as an active control) reduced size by 7% .
 Role in Interaction with Hormones:-Testosterone: The supercritical carbon extraction of rice bran itself showed to suppress the 5α reductase type I enzyme (Ruksiriwanich et al., 2011), investigated the increment in the concentrations of testosterone and reduced dihydrotestosterone (DHT) in the body. In healthy male athletes alongwith a weight training program, 500 mg gamma oryzanol was failed to influence the concentrations of testosterone (Fry et al., 1997). Thus, gamma oryzanol do not caused an increment in the concentration of testosterone.

Cortisol, Estrogen and Growth Hormone:-
In 22 healthy male athletes, 500 mg of gamma oryzanol daily for 9 weeks constitute with a resistance training program significantly failed to affect the circulating levels of cortisol, estrogen and growth hormone (Fry et al., 1997). In rats study, there was a reduction in the circulating levels of adiponectin with palmitate (a fatty acid) and beef tallow fed to these rats noted that at 0.025 mmol gamma oryzanol was able to preserve adiponectin levels under the influence of palmitate and acted to increase circulating adiponectin in control (corn oil) (Nagasaka et al., 2011). As palmitate activates NF-kβ (Cacicedo et al., 2005) which then acts to suppress adiponectin secretion from mouse 3T3-L1 adipocytes (Ohara et al., 2009) secondary to binding to Peroxisome Proliferator-Activator Receptor Gamma (PPARγ) and inhibiting its genomic actions (Suzawa et al., 2003),it is possible that these observed effects are secondary to gamma oryzanol inhibiting NF-kB. It was later confirmed that gamma oryzanol (290mcg/kg) was able to increase adiponectin levels, and alongside Gamma Amino Butyric Acid (GABA) (also found in rice bran, 600mcg/kg) there appeared to be slightly better effects, but did not appear to be significantly synergistic . In animals, gamma oryzanol showed to increase adiponectin levels.

Conclusion:-
Gamma oryzanol contains several components which are known for their potential role in reducing the risk of cardiovascular disease by controlling blood cholesterol and fat absorption, enhancing insulin sensitivity, reducing cancer risk, alleviating menopausal disorders, providing gastrointestinal health. It also serves as a natural source of antioxidant. Thus, it is known for several applications in cosmoceutical, nutraceutical and pharmaceutical industries.