Ferulic acid FOOD & COSMETIC FERULIC ACID A Natural Phenolic Compound Extracted from Rice Bran Ferulic acid is a rice polyphenolic compound and interestingly it is a source of vanillin. Ferulic acid is also used as an antioxidant, and an antimicrobial agent. It is also recognized that ferulic acid exhibits a preventive effect on discoloration in various food products and a variety of physiological functions such as suppression of Alzheimer s disease, prevention of muscular fatigue, improvement in hypertension, and antitumor activity of breast, liver, and colon. Among its various benefits, much interest has been focused on the recent study on the clinical trial of Alzheimer s disease. Ferulic acid is also used for cosmetics, because it exhibits UV absorption effect, whitening effect and anti-inflammatory effect. O CH3O OH HO Figure 1: Structure of ferulic acid. Functional characteristic of ferulic acid 1. Prevention of discoloration The preventive effect of ferulic acid on discoloration was investigated as the following experiment: Each ferulic acid solution of 0.02%, 0.05% and 0.1% was added into the mixed fruit juice containing apple, banana and orange, and left at room temperature for one hour. Figure 2 shows that the higher the concentration of ferulic acid, the higher the stability of color. Control 0.02 Ferulic Acid 0.05% Ferulic Acid 0.1% Ferulic Acid Figure 2: Preventive effect of ferulic acid on discoloration of fruit juice. (In-house data) 1
2. Antioxidant effect It is believed that the ferulic acid supplies hydrogen to free radicals with phenolic -OH groups to provide the antioxidation effect. Ferulic acid exhibits radical capture and active oxygen elimination activity as shown in Figure 3. Radical capture was measured in the DPPH (2, 2-diphenyl-1-picrylhydrazyl) method. Figure 3A shows the radical scavenging activities of 15, 30, 45 µm of ferulic acid and α-tocopherol. Moreover, active oxygen elimination was measured in the hemolysis method induced by CuOOH (cuminhydroperoxide). Figure 3B shows the IC 50, 50% inhibition of DPPH radicals. Lower IC 50 value indicates higher antioxidant activity. As this figure indicates, IC 50 value of α-tocopherol was three times as large as that of ferulic acid. Figure 3: Antioxidant effect of ferulic acid. A) The radical scavenging activity of ferulic acid and α- tocopherol using DPPH. B) IC 50, 50% inhibition of DPPH radicals. (In-house data) 3. Effect of ferulic acid on healing of Alzheimer-type disease (AD) It is known that a cranial nerve cell will decrease with age. Reduction of a cranial nerve cell is more significant with brain disease, such as Alzheimer s disease. Control of reduction in a brain cell and activation of a brain cell are required to maintain brain functions. In 2008, Nakamura et al. [1] reported that the preparation ANM176 containing ferulic acid as a principal component showed a suppressive effect on Alzheimer-type Disease (AD). They administered ANM176 containing 100 mg of ferulic acid twice a day for 9 months to 98 AD subjects. AD progressions were estimated with ADAS-Jcog method*. The higher score, the worse the AD symptom. As shown in Figure 4, remarkable suppressive effect was observed in two groups; one was a group of age of onset of older than or equal to 65 years old, another was a group of mild symptom. Since most onset age of AD is older than 65, the finding is epoch making. * Estimation of AD Progression (ADAS-Jcog): ADAS-Jcog (Alzheimer s Disease Assessment Scale-Japanese Cognitive part) used is a Japanese version of a worldwide method of examination for estimation of AD Progression, especially for cognitive dysfunction, and is composed of 11 inspection items for three fields, memory, speech, and apraxia. Higher the score is, worse cognitive dysfunction is. ADAS-Jcog is often used as a sensitive indicator of AD progression and as a judgment method for treatment effect of drugs in many clinical tests. The score described above is a difference of ADAS- Jcog score before administration and 9 months administration. 2
[2] The difference of ADAS-Jcog score before and after 9 months by administration of ferulic acid Figure 4: Effect of ferulic acid on healing of Alzheimer-type disease (AD). (Original data from [1]) 4. Effect of ferulic acid on skin 4.1 UV absorption The UV absorption property of ferulic acid is shown in Figure 5. Ferulic acid (1 mg) was dissolved in 95% ethanol (100 ml). The absorbance was measured in the range of 200-370 nm. UV-B absorption was observed and SPF (Sun Protection Factor) was estimated to be 6.4. (Ref. SPF of octyl 4-methoxycinnamate is 7.1 [3]) 1.500 UV-B UV-A ABS 0.000 200 300 400 [nm] Figure 5: Effect of ferulic acid on UV absorption. (In-house data) 3
4.2 Whitening activity Anti-tyrosinase activity It is well-known that melanogenesis is induced by UV light and catalyzed by tyrosinase. Ferulic acid is not only effective UV absorbers, but also tyrosinase inhibitors. Ferulic acid is suggested to suppress melanin generation by antagonizing tyrosine because its chemical structure is similar to tyrosine [4]. Ferulic acid decreased tyrosine activity as shown in Figure 6. Tyrosinase activity was assayed using tyrosine as a substrate. The ratio of tyrosinase inhibition of ferulic acid was higher than that of kojic acid. Moreover, ferulic acid suppressed dark-color pigmentation in the integument of red sea breams [5]. Figure 6: The anti-tyrosinase activity of ferulic acid compare to kojic acid. (In-house data) Prevention of erythema The effect of ferulic acid on prevention of erythema is shown in Figure 7. Erythema generated in response to UV irradiation from 1 to 5x MED (Minimal Erythema Dose) in skin treated with 0.5 to 1% test solutions and mixed solution of ferulic acid (C + E + Ferulic acid). Erythema was significantly reduced when skin was treated with C +E + ferulic acid compared to the control, the other antioxidant solutions, and the commercial creams [6]. 4
Figure 7: The photoprotective effect of ferulic acid in pig skin. (C+E+ferulic acid is a solution containing 15% L-ascorbic acid, 1% α-tocopherol, and 0.5% ferulic acid). (Original data from [6]) 4.3 Anti-inflammatory effect Clinical data of ferulic acid for anti-inflammatory effect on skin is summarized in the Table below. Table 1: Clinical data of ferulic acid concerning anti-inflammatory effect on skin. Author (year published) Test subject Dose and Administration Skin efficacy Saija, et al., (2000) [7] In vitro (Healthy Skin) Healthy individual at ph 3 and 7.2 Ferulic acid dissolved in saturated aqueous solution at ph 7.2 (0.7%) showed a significant protection to the skin against UVB-induced erythema. Shinoda, (1995) [8] Mouse 1 mol/kg Intraperitoneal administration Nakadate, et al.,(1985) [9] in vitro 10 µm Survival effect after X-ray irradiating and protective potencies on skin injury induced by soft X-ray irradiation were observed. Cyclooxygenase 2 activity was inhibited 5
Recommended dosage A recommended dosage for supplement for AD healing is 200 mg per day, and that for prevention of discoloration of fruit juice and ham are 0.001 to 0.1%, and 0.05 to 0.1%, respectively (Table 2). Table 2: Recommended dosage of ferulic acid. Applications Supplement Dosage 200 mg/day Fruit juice 0.001 0.1% Ham 0.05 0.1% Applications in foods The main applications are summarized as follows. Antioxidant Discoloration inhibitor (Confectionery; ferulic acid can prevent a discoloration of red color such as strawberry.) Healthy foods, Supplement Applications in cosmetics Hair wax, skin cream and lotion, soap, etc. Radical scavengers UV absorber (Sun Screens) Whitening agent Antimicrobial agent Anti-inflammatory agent Properties Product : Ferulic acid INCI name : FERULIC ACID Appearance : White or light yellow crystalline powder, odorless or faint characteristic odor Solubility : Freely soluble in ethanol, and slightly soluble in hot water Stability : Heat stable at 50 C for at least 20 hours Light irradiation stable at 10,200 lux at 25 C for at least 20 hours 6
Note: All Tsuno's products are extracted 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] Nakamura, S., et al. (2008). Geriat. Med., 46, 1511-1519. (in Japanese) [2] Caro, J.J., Getsios, D., Migliaccio-Walle K., Raggio, G., and Ward, A. (2001). AHEAD Study group; Assessment of health economics in Alzheimer s disease (AHEAD) based on need for full-time care. Neurology, 57(6), 964-971. [3] Anselmi, C., Centini, M., Andreassi, M., Carini, M., and Facino, R.M. (2001). Biological activities and cosmetic applications of ferulic acid and its derivatives. Yushi, 54(8), 53-59. (in Japanese) [4] Ibata, Y. (1980). Fragrance J., 45, 92. (in Japanese) [5] Maoka, T., Tanimoto, F., Sano, M., Tsurukawa, K., Tsuno, T., Tsujiwaki, S., Ishimaru, K., and Takii, K. (2008). Effects of dietary supplementation of ferulic acid and gamma-oryzanol on integument color and suppression of oxidative stress in cultured red sea bream, Pagrus major. J. Oleo Sci., 57, 133-137. [6] Tournas, J.A., Lin, F.H., Burch, J.A., Selim, M.A., Monterio-Riviere, N.A., Zielinski, J.E., and Pinnell, S.R. (2006). Ubiquinone, idebenone, and kinetin provide ineffective photoprotection to skin when compared to a topical antioxidant combination of vitamin C and E with ferulic acid. J. Invest. Dermatol., 126, 1185-1187. [7] Saija, A., Tomaino, A., Trombetta, D., De Pasquale, D., Uccella, N., Barbuzzi, T., Paolino, D., and Bonina, F. (2000). In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents. Int. J. Pharm., 199, 39-47. [8] Shinoda, M. (1995). Studies on chemical radioprotectors against X-irradiation used by soft X-ray accelerator. Yakugaku zasshi J. Pharm. Soc. Jpn., 115(1), 24-41. [9] Nakadate, T., Aizu, E., Yamamoto, S., and Kato, R. (1985). Effects of chalcone derivatives on lipoxygenase and cyclooxygenase activities of mouse epidermis. Prostaglandins, 30(3), 357-368. 7