gamma oryzanol

GammaGammaGammaGamma----OOOOryzanolryzanolryzanolryzanol | FOOD & COSMETIC

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GammaGammaGammaGamma----OryzanolOryzanolOryzanolOryzanol A Unique Component of Rice Bran

One of the phytochemicals found at high concentration in rice is gamma-oryzanol (-oryzanol), a group of ferulic acid esters of phytosterols and triterpene alcohols. Campesteryl ferulate, -sitosteryl ferulate, cycloartenyl ferulate, 24-methylenecycloartanyl ferulate are the four major components of -oryzanol (Figure 1). -Oryzanol exists mainly in bran layers, and it is a component unique to extracted rice bran oil. -Oryzanol acts as an efficient natural antioxidant in the oil.

Figure 1: Chemical structures of four major components of -oryzanol.

Cycloartenyl ferulate 24-Methylenecycloartanyl ferulate

Campesteryl ferulate -Sitosteryl ferulate


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1. Physiological functions of -oryzanol

-Oryzanol is associated with decreasing plasma cholesterol [1], lowering serum cholesterol [2], decreasing cholesterol absorption [2] and decreasing platelet aggregation [3]. -Oryzanol has also been used to treat hyperlipidemia [4], disorders of menopause [5] and to increase the muscle mass [6].

-Oryzanol exhibits positive effects on stress-related disorders. It also offers variety of benefits to women as it helps improve dry skin, display skin whitening effect, and address menopausal syndrome.

-Oryzanol has been used as medicine in Japan to treat psychosomatic disease. -Oryzanol involves in the metabolism of catecholamines, such as dopamine, adrenalin, and noradrenalin in the hypothalamus. Catecholamines are part of the sympathetic nervous system. Various stimulant drugs are catecholamine analogues [7]. On the other hand, -oryzanol is hydrolyzed almost completely in the process of digestion in the body. In addition, the effect of -oryzanol and ferulic acid on prevention against alcoholic hepatitis was reported as the same degree as curcumin [8]. -Oryzanol has also been reported to be effective for suppression of inflammation, diabetes, and allergy [9].

2. Anti-inflammation, anti-arteriosclerosis, and anti-diabetes

functions of -oryzanol [10]

The effect of -oryzanol on anti-inflammation, anti-arteriosclerosis, and anti-diabetes can be ascribed to the suppression of activation of nuclear factor kappa B (NFB). The NFB dimers are sequestered in the cytoplasm by a family of inhibitors, inhibitory factor kappa B (IB) in unstimulated cells. When activated by signals from the outside of the cell, the IB kinase phosphorylates two serine residues located in an IB regulatory domain. Then IB is separated from NFB, and then NFB is activated. The activated NFB is then freed to enter the nucleus to promote the transcription of inflammatory cytokine. Thus inflammation is amplified (Figure 2). Since -oryzanol prevents the phosphorylation of IB, inflammation is suppressed.

The activation of NFB leads to not only promotion of inflammatory cytokine transcription, but also suppression of adiponectin transcription. Adioponectin is one of the adipo-cytokine, and activates AMP kinase and PPAR. Blocking of activation of NFB by -oryzanol activates adiponectin, AMP kinase, and PPAR.

Accordingly, glucose uptake, fat-burning, and energy consumption increase, and gluconeogenesis decreases, and functions of anti-arteriosclerosis, anti-diabetes, and anti-obesity are activated.


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Figure 2: Mechanism of NFB activation. (Modified from [11])


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3. Antiallergenic action of -oryzanol

Allergens are generally proteins or polysaccharides. Type I allergy typified by pollen allergy, atopy and asthma is closely involved with both IgE antibody and mast cells. The allergen binds to the antigen-binding sites, which are situated on the variable regions of the IgE molecules bound to the receptor of the mast cell surface. It appears that binding of two or more IgE molecules (cross-linking) is required to activate the mast cell. When mast cell is activated by the cross-linkage, the mast cell releases the characteristic granules and various hormonal mediators, such as histamine and prostaglandin into the interstitium. Consequently allergic episodes, such as a runny nose, sneezing, and itch, and furthermore inflammation with eposinophil infiltration are expressed (Figure 3).

Recently it was reported that dietary -oryzanol suppressed type I allergy by binding to IgE antibody, resulting in inhibition of binding of IgE to the receptor of mast cell [12] (Figure 3).

Figure 3: Type I allergy reaction and antiallergenic action by -oryzanol. (Modified from [13])


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4. Improvement effect of -oryzanol on dementia

Hippocampus (HPP) plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Insulin-like growth factor 1 (IGF-1) is deeply involved in neoangiogenesis and neurogenesis for recovery of HPP function and the improvement of dementia.

Recently such an improvement effect of -oryzanol on dementia and its mechanism were reported [14]. According to the report, IGF-1 in HPP increases by the information of binding of -oryzanol to the vanilloid receptor 1 via sensory neuron in gastrointestinal tract.

5. Improvement in hyperlipidemia

-Oryzanol is also considered effective in the treatment of hyperlipidemia because of its potential to decrease cholesterol and triglyceride levels, as well as boost the ratio of high-density lipoprotein (HDL) level. Cholesterol-lowering action of -oryzanol appears to involve a combination of the following effects: -oryzanol increases the conversion of cholesterol to bile acids, increases bile acid excretion, and inhibits the absorption of cholesterol.

Table 1 shows lipid metabolism action of -oryzanol. Male rats were fed the following diets for 7 weeks: 1) control diet, 2) control + 1% cholesterol +0.15% bile salts (high cholesterol diet, HCD), 3) HCD + 0.5% oryzanol. The result in Table 1 reports a 20% decrease in serum total cholesterol for rats fed with oryzanol. HDL-cholesterol has a tendency to increase (statistically insignificant) in rats on the HCD + oryzanol diet. Oryzanol significantly decreases liver total cholesterol (by 26%). Table 1: Effect of -oryzanol on serum lipids and liver lipids of rats. (Original data from [15])

Serum lipid (mg/dL) Liver lipid (mg/dL) TC HDL LDL+VLDL TC

Control 65.1 3.0 29.9 1.5 35.2 2.1 3.05 0. 13 HCD* 311.3 19.7 12.4 1.0 299.4 20.1 107.7 4.8

HCD+0.5% Oryzanol 248.9 10.9 16.0 1.0 232.9 9.1

79.2 5.7 (*HCD: High Cholesterol Diet)

Several studies indicate that -oryzanol is quite effective in lowering blood cholesterol and triglyceride levels as follows.

Cheng et al. [16] reported that palm oil (PO) markedly increased plasma low-density-lipoprotein cholesterol, plasma triglycerides, and hepatic triglyceride levels, but did not reduce the area under the curve for glucose and insulin significantly, compared with the control group. Adding -oryzanol to PO improved the negative influence of PO on lipid


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metabolism in T2DM rats. In addition, -oryzanol tended to increase insulin sensitivity in T2DM rats compared to control and PO groups.

Hata et al. [17] reported that -oryzanol decreased 62.7% of serum cholesterol and 51 % of serum triglyceride by administration of 300 mg per day for 4 months.

Goto et al. [18] reported that -oryzanol decreased 6 to 38% of serum cholesterol and 14 to 39% of serum triglyceride by administration of 75 mg per day for 4 months, and decreased 24 to 64% of serum cholesterol and 23 to 61% of serum triglyceride by administration of 300 mg per day for 4 months.

Ayukawa, [19] reported that -oryzanol decreased arteriosclerosis index, apoprotein B, and apoprotein B/A-I index by administration of 300 mg per day for 2 months.

6. Improvement in menopausal symptoms

-Oryzanol is used primarily in the treatment of menopause, including hot flashes, in the early 1960s [20]. Subsequent studies have further documented its effectiveness in menopause. Its primary action is to reduce the secretion of leutinizing hormone (LH) by the pituitary and promote endorphin release by the hypothalamus.

There are a number of clinical studies report that -oryzanol is beneficial in the treatment of relieving menopausal symptoms.

As shown in Table 2, Okawa et al. [21] reported that -oryzanol improved about 77% of headache, stiff shoulder, insomnia, and uneasiness by administration of 30 mg per day for 2 weeks. Ishihara et al. [22] reported that -oryzanol improved a glow on face, nervousness, depression, headache, palpitation and trouble getting to sleep by administration of 300 mg per day for 4 to 8 weeks.

Table 2: Clinical data of -oryzanol for improvement in menopausal symptoms.

Target illness Administration Effects

Menopausal syndrome subjects [21]

30 mg per day, for 2 weeks

Improvement in headache, stiff shoulder, insomnia, uneasiness, etc. (about 77%)

Menopausal syndrome subjects [22]

300 mg per day, for 4 to 8 weeks

Improvement in glow on face (about 81%) Nervousness (about 83%) Depression (about 77%) Headache (about 78%) Palpitation (about 82%) Trouble getting to sleep (about 80%)


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7. Antioxidant effect

Active Oxygen Method (AOM) is one of the widely used methods for evaluating antioxidant activity. The higher the AOM value indicates the higher the antioxidant effect. The antioxidant action of -oryzanol was shown in the Figure 4.

In the experiment, 0.002 g of -oryzanol was added to 5 g of oleic acid to compare with 0.002 g of -tocopherol in 5 g of oleic acids, and a control sample. All samples were heated to 90C, then the oxidation stability was measured. The result shows a level of AOM for -oryzanol sample to be comparable to the AOM level of -tocopherol (positive control). The result also suggests that -oryzanol has equivalent antioxidant effect to that of -tocopherol.

Figure 4: Antioxidant effect of -oryzanol. Control is oleic acid. (In-house data)

8. -Oryzanol for improvement on skin

-Oryzanol is considered to impede the progress of melanin pigmentation by restraining the erythema activity of tyrosinase as it intercepts the ultraviolet rays at the skin's surface and hinders its (ultraviolet rays) transmission. It improves microcirculation, and helps protect the skin against freckles and aging.

Because -oryzanol is oil soluble, easily absorbed into the skin and has the effect of stimulating blood circulation under the skin, it is recognized as an effective nutrient for the skin.

8.1 Effect on skin temperature

Kamimura et al. [23] reported that -oryzanol improved vascular resistance, skin temperature and amount of blood on the skin for healthy subjects by oral administration of 30 mg x 2 per days for a week.


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Hayakawa et al. [24] reported that -oryzanol improved amount of skin surface lipid for ill subject by administration of 100 mg per day for a month. 8.2 UV absorption

-Oryzanol has a protective role in UV-light induced lipid peroxidation and hence it is used as a sunscreen agent.

Figure 5 shows the UV absorption property of 1 mg of -oryzanol dissolved into 100 mL of n-heptane. From the result, UV-B absorption was observed. SPF (Sun Protection Factor) of 1% oryzanol cream was estimated to be 1.7.

Figure 5: The UV absorption property of -oryzanol. (In-house data)

8.3 Anti-inflammatory effect on skin

Table 3 shows a summary of clinical data of -oryzanol for anti-inflammatory effect on skin.

Table 3: Clinical data of -oryzanol for anti-inflammatory effect on skin.

Test subject Dose and administration Effect on skin

Healthy individual [25] 6 mg once a day for 3 months

Improvement of inflammation of skin eczema

Guinea pig [26] 0.05, 0.1, 0.15 mg/cm2 Suppression of erythema as UV irradiation is prevented by high

density of -oryzanol

In vitro [27] IC50: 25 M IC50: 38 M Lipoxygenase activity inhibition

Cyclooxygenase 2 activity inhibition


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Recommended dosage

According to the prescription of the medical drug in Japan, the dosage against hyperlipemia is 300 mg per day for adult, and against menopausal symptoms and mild anxiety is 10 to 50 mg per day for adult (Table 4).

Table 4: Recommended dosage of -oryzanol.

Symptoms Dosage

Hyperlipemia 300 mg/day

Menopausal symptoms 10 50 mg/day

Mild anxiety 10 50 mg/day

Applications

For pharmaceutical products such as tablets, capsules, and so on. For cosmetics such as soap, cream, skin lotion, shampoo, conditioner, and so on.

Properties

Product : Gamma-Oryzanol (-Oryzanol) INCI name : ORYZANOL Appearance : White or yellowish white, odorless crystalline powder Solubility : Freely soluble in chloroform, slightly soluble in ethanol and

insoluble in water Stability : Stable at 30C up to 80 days

Note: All Tsuno's products are extracted naturally from rice bran and are GMO free, BSE/TSE free and non-allergy. We obtained bulk GMP in Japan and Halal and Kosher certified products are also available.

References

[1] Yoshino, G., Kazumi, T., Amano, M., Tateiwa, M., Yamasaki, T., Takashima, S., Iwai, M., Hatanaka, H., and Baba, S. (1989). Effects of gamma-oryzanol and probucol on hyperlipidemia. Curr. Ther. Res., 45(6), 975-982.

[2] Gerhardt, A.L., and Gallo, N.B. (1998). Full fat rice bran and oat bran similarly reduced Hypercholesterolemia in humans. J. Nutr., 128, 865-869.

[3] Seetharamaiah, G.S., Krishnakantha, T.P., and Chandrasekhara, N. (1990). Influence of oryzanol on platelet aggregation in rats. J. Nutr. Sci. Vitaminol., 36(3), 291-297.


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[4] Nakayama, S., Manabe, A., Suzuki, J., Sakamoto, K., and Inagaki, T. (1987).Comparative effects of two forms of gamma-oryzanol in different sterol compositions on hyperlipidemia induced by cholesterol diet in rats. Jpn. J. Pharmacol., 44, 135-143.

[5] Murase, Y., and Iishima, H. (1963). Clinical studies of oral administration of gamma-oryzanol on climacteric complaints and its syndrome. Obstet. Gynecol. Prac., 12, 147-149.

[6] Bonner, B., Warren, B., and Bucci, L. (1990). Influence of ferulate supplementation on postexercise stress hormone levels after repeated exercise stress. J. Appl. Sport Sci. Res., 4, 110.

[7] Ieiri, T., Kase, N., Hashigami, Y., Kobori, H., Nakamura, T., and Shimoda, S. (1982). Effects of gamma-oryzanol on the hypothalamo-pituitary axis in the rat. Nippon Naibunpi Gakkai Zasshi., 58(10), 1350-1356. (in Japanese)

[8] Chotimarkorn, C., and Ushio, H. (2008). The effect of trans-ferulic acid and gamma-oryzanol on ethanol-induced liver injury in C57BL mouse. Phytomedicine, 15, 951-958.

[9] Islam, S., Reiko, N., Kazuyuki, O., Takamitsu, H., Hiroshi, O., Hideki, U., and Masatoshi H. (2011). Biological Abilities of Rice Bran-Derived Antioxidant Phytochemicals for Medical Therapy. Curr. Top. Med. Chem., 11(14), 1847-1853.

[10] Imagawa, S. (2007). Seikatsusyuukanbyou no Bunsiseibutugaku (Molecular biology of lifestyle disease) Sankyoshuppan, Japan. (in Japanese)

[11] Lentsch, A.B., and Ward, P.A. (1999). Understanding the Pathogenesis of Inflammation Using Rodent Models: Identification of a Transcription Factor (NFkappaB) Necessary for Development of Inflammatory Injury. ILAR J., 40(4), 151-156.

[12] Oka, T., Fujimoto, M., Nagasaka, R., Ushio, H., Hori, M., and Ozaki, H. (2010). Cycloartenyl ferulate, a component of rice bran oil-derived [gamma] - oryzanol, attenuates mast cell degranulation. Phytomedicine, 17, 152-156.

[13] Allergy, Antiallergic Drugs. Antiasthma Drugs [14] Okajima, K., and Harada, N. (2008). Second International Symposium on Rice and Disease Prevention.

Wakayama, Japan, pp 44. [15] Seetharamaiah, G.S., and Chandrasekhara, N. (1993). Comparative hypocholesterolemic activities of

oryzanol, curcumin and ferulic acid in rats. J. Food. Sci. Technol., 30(4), 249-252. [16] Cheng, H.H., Ma, C.Y., Chou, T.W., Chen, Y.Y., and Lai, M.H. (2010). Gamma-oryzanol ameliorates

insulin resistance and hyperlipidemia in rats with streptozotocin/nicotinamide-induced type 2 diabetes. Int. J. Vitam. Nutr. Res., 80(1), 45-53.

[17] Hata, A., Koga, S., Shigematsu, H., Kato, S., et al. (1981). Study on Effects of Gamma-Oryzanol on Hyperlipemia: Multicenter Cooperative Pilot Study for Dosage Finding. Geriat. Med., 19, 1813-1840. (in Japanese)

[18] Goto, Y., et al. (1983). Geriat. Med., 21, 2039-2057. (in Japanese) [19] Ayukawa, K. (1995). Ther. Res., 16(6), 381-385. (in Japanese) [20] Murase, Y., and Iishima, H. (1963). Clinical studies of oral administration of gamma-oryzanol on

climacteric complaints and its syndrome. Obstet. Gynecol. Prac., 12, 147-149. [21] Okawa, T., et al. (1965). Sanfujinka-no-Sekai (The world of obstetrics & Gynecology), 17(2), 65-69. (in

Japanese) [22] Ishihara, M., et al. (1982). Nipon Sanka-Fujinka Gakkaishi (Japan Society of Obstetrics and

Gynecology), 34(2), 243-251. (in Japanese) [23] Kamimura, M., Takahashi, S., and Sato, S. (1964). Influence of -oryzanol on the skin microcirculation.

Vitamins, 30(5), 341-344. (in Japanese) [24] Hayakawa R., et al. (1994). Hifukakiyo, 89(1), 115-119. (in Japanese) [25] Oshida, K. et al. (1985). Kateiyaku-Kenkyu, 4, 34-44. (in Japanese) [26] Ando, Y. (1982). Fragrance J., 53, 125-126. (in Japanese) [27] Terada, S. et al. (2003). Nat. Med., 57, 3, 95-99.

gamma oryzanol

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