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1 ª Ÿ (Korean J. Medicinal Crop Sci.) 19(2) : (2011) ³ z ù x Melatonin Serotonin w e w Jin Ling*Á½ **Á **Á *Á *Á *Á ***Á x *, ** * w œw, ** w Á w, *** l The Effect of Extracts of Berberis koreana Bark by Lactobacillus Fermentation on the Concentration of Serotonin and Melatonin in the Serum of Treated ICR Mice Jin Ling*, Ji Seon Kim**, Yong Chang Seo**, Woon Yong Choi*, Ju Hee Ahn*, Choong Je Ma*, Chang Soon Yoon*** and Hyeon Yong Lee*, ** *College of Bioscience and Biotechnology, Kangwon National University, Chuncheon , Korea. **Medical & Bio-Material Research Center and College of Bioscience and Biotechnology, Kangwon National University, Chuncheon , Korea. ***Shebah Biotech Co., Hallym Business Incubator/Industry-University, Coop Center #301, Chuncheon , Korea. ABSTRACT : This study was to investigate the effect of fermentation extracts on the concentration of serotonin and melatonin in the serum of the ICR mice. The ICR mice were divided into water control group, lactobacillus fermentation solution including (Lactobacillus paracasei and Bifidobacterium longum B6) control group, positive control group (milk and doxylamine succinate), negative control group (caffein) and the groups treated with the extracts of Berberis koreana bark (WE: water extracts, FE-L.P: fermentation extracts of Lactobacillus paracasei, FE-B.L: fermentation extracts of Bifidobacterium longum B6). After ten-day feeding treatment, the mean concentration of serotonin for water control, WE, FE-L.P and FE- B.L group was , , and ng/, respectively. The mean concentration for FE-L.P and FE-B.L group were approximately 66% larger than that for water control group. The mean concentration of melatonin for water control, WE, FE-L.P and FE-B.L group was 76.92, , and pg/, respectively. The mean concentration of melatonin for FE-L.P and FE-B.L group were also larger than that for water control group. Our results indicated that the fermentation extracts of Berberis koreana bark have relatively greater potential to induce secretion of serotonin and melatonin. Therefore, the fermentation extracts have antidepressant effect. Key Words : Berberis koreana bark, Fermentation, Serotonin, Melatonin, Antidepressant ƒ w wù ƒ w ù h ö wš rwš w (Park et al., 2004). 6~17% š û 2 ùkùš (Song and Li, 2002), p z, s» p» ƒ w š š (Kim et al., 2000; Chung, 1996). w wì,,, ƒ,. šm 2 y k k y w ƒ š w (Hong et al., 1998). w yw ³ w wš w,, z w. p norepinephrine, serotonin monoamine v»w ƒ w (Kim and Lee, 2004). x, e w w monoamine w y w tricyclic antidepressants (TCA) monoamine w w monoamine yz monoamine Corresponding author: (Phone) ( ) hyeonl@kangwon.ac.kr Received 2010 November 5 / 1st Revised 2011 April 19 / 2nd Revised 2011 April 21 / Accepted 2011 April

2 Jin LingÁ½ Á Á Á Á Á Á x oxidase inhibitor (MAOI) š,, m, x ƒ š š š (Lee et al., 2003). w ƒ w š. ù (Berberis koreana) ù ù ù z ƒ w p wù,» w û s (Jin et al., 2008; Cho and Kim, 1974). jƒ 2m y q ƒ ƒ ù w x š 2 ƒ š 1 ƒ ƒ ƒ ù. w wš ù, m, w, x, w³, w y, w, z ƒ š (Jin et al., 2009; Qadir et al., 2009). w ù ethanol y e ethanol n ƒ š ƒ w š š š (Cho and Kim, 1974), ù y Majarine (5,6- Dihydro-9,10 dimethoxybenzo [g]-1,3-benzodioxolo [5,6-a] quinolizinium) n x w w e š š š (Kim, 1986). wr, z ƒ» t, t, y t w y š wì w t z x ¾ ƒ š». z t y» t š (Park et al., 2006), p v p (probiotics) ³» x w š. ³ z t p t w w ü y,, ³, g l w, w w wš e w š (Kim et al., 2002). w w ü w p p» w š, ³ z w z w ƒ š š (Yoon et al., 2009). w, ¾ ù z» w ù w z w w. ù w z y wš x mw yw d w serotonin melatonin y d w. w z» w» w z ù w z z y š wz ù» z t w» w w w» w x ww. 1. x x ù w p w, k z w. 100 g ù v y þƒ»ƒ v j 10 w 100æ 12 2z w. z óù z, ù ³ Lactobacillus paracasei (L.P) y Bifidobacterium longum B6 (B.L) 10 CFU/ w % L-cysteine HCl ƒ MRS broth w 37æ x» Gaspak anaerobic system (BBL, Cockeysville, MD, USA) 96 w. ƒƒ w z» (rotary vaccum evaporator N-N series, Evela, Tokyo, Japan) w w w x w. 2. s s x s s s HEK293 (human embryonic kidney cell, ATCC, Manassas, VA, USA) w š Roswell Park Memorial Institute Medium (RPMI 1640) 10% Fetal bovine serum (FBS) ƒw incubator (37æ, 5% CO 2 ) w. 3. s d ù s w» w s HEK293 w sulforhodamine B (SRB) assay (Kim et al., 2007) w s d w. SRB assay s w s ù d w x s HEK293 (in 10% FBS media) 4~ cell/ 96 well plate ƒ well 100 ƒw 24 (37æ, 5% CO 2 )w z ƒƒ 0.2, 0.4, 0.6, 0.8, 1.0 / 100 ƒw 48 w. z wš ƒ 10% (w/v) trichloroacetic acid (TCA) 100 ƒw 4æ 1 ew z 4~5z w TCA wš plate w ƒ well 1% (v/v) acetic acid 0.4% (w/ v) SRB 100 ƒwš 30 g. w w 1% acetic acid 4~5z, k z 10 mm tris buffer 118

3 melatonin serotonin w ù z e w 100 ƒw ü z 540 microplate reader (THERMO max, Molecular Devices, Sunnyvale, CA, USA) w Ÿ d w. 4. x,, 1) x x p (Orient Bio Inc. Seongnam, Korean) f ICR (4, 22~24 g) w w 9 ù w 20 w. 2) 24 ± 1æ 55 ± 10% g, y»z 10~15 z/hr, 12» w. šx w, ³w w. x 10 k z x w. 3) n milk 1, (doxylamine succinate) 10 1 w š caffein w. ù [water extract (WE), fermentation extract by Lactobacillus paracasei (FE-L.P), fermentation extract by Bifidobacterium longum B6 (FE-B.L)] ƒƒ 75 1 w. ³ w š w» w 8log CFU/ z ³ z (L.P B.L) ƒƒ 1 w. w n w. 4) x serotonin melatonin d w Serotonin ELISA kit Melatonin ELISA kit GENWAY (San Diego, USA) l w š doxylamine succinate Boram Pharm (Ansan, Korea) l w w, caffein Samchun pure Chem. (Pyeongtaek, Korea) l w w. 5. x x 2 w n 2 z x w. ƒ 4 kw x tube w (retro-orbital sinus bleeding) x w z, 3000 rpm 15 w x EDTAƒ tube w w. 6. ELISA w serotonin d 1) Sample vr 20 x polystyrene tube z 100 assay buffer š vortexw. 25 acylation reagent (3% acetic acid anhydride in acetone) z vortex k z, tube 37æ 15 g. š 2 assay buffer z vortex k z 1,500 g 10 w e jš û w. 2) Serotonin vr 50 standard acylated control acylated sample ELISA well plate ƒƒ š, 50 serotonin-biotin 50 serotonin arntiseum (wx ) š plate z, plate y 2~8æ 16~20 g. plate y wš 250 wash buffer (phosphate buffer) 3z w z wash buffer w. vr 150 enzyme conjugate ƒw z y incubator (18~25æ, 500 rpm) 60 w. y wš w z 250 wash buffer 3z w. ƒƒ well 200 para-nitrophenylphosphate (PNPP) substrate solution š incubator (18~25æ, 500 rpm) 30 w z, ƒƒ well 50 PNPP stop solution k 405 Ÿ d w (Hong et al., 1999). 7. ELISA w melatonin d 1) Column Melatonin w column methanol (undiluted) g 2z w š,» 2 column g 2z w. 2) Sample Column tube š 0.5 standard, control sample ƒƒ column š 200 g 1 wš, 10% 1 methanol 500 g 1 2z w column w. polystyrene tube column wš column 1 methanol (undiluted) g w. Column wš tube sw methanol k z 0.15 w. 119

4 Jin LingÁ½ Á Á Á Á Á Á x 3) Melatonin vr 50 ELISA well plate standard, control sample š 50 melatonin-biotin 50 melatonin-antiserum (wx ) ƒwš, y w 2~8æ 14~20 g. wš 250 assay buffer 3z w z w. vr secondary antibody enzyme 150 w jš y 120 k z 3z w. ƒƒ well 200 PNPP» z, (18~24æ) orbital shaker 30 g. 3 M PNPP stop solution 50 k 405 Ÿ d w (Hong et al., 1999). 8. HPLC w ù phenolic acids w œ ù phenolic acids w š š j m v (HPLC; High-peroformance Liquid Chromatography) w w. HPLC»» UV absorbance detector (280, 0.05 AUFS)ƒ š j m v (HPLC, Waters M600E, Milfold, MA) w, phenolic acids w» w Waters Spherisord ODS2 Column [ (inside diameter), 5 ] w. œ ù w HPLC water 0.2 syringe filter wš Injection volume 20 d w. A [1 mm trifluoroacetic acid (TFA)ƒ w 10% (V/V) acetonitrile], B [1 mm TFAƒ w 40% methanol 40% acetonitrile] w š (0 min 90% A 10% B; 0~10 min 90% A 10% B; 10~15 min 60% A 40% B; 15~24 min 60% A 40% B; 24~ 40 min 0% A 100% B; 40~45 min 90% A 10% B; 45~50 min 90% A 10% B) w 1.0 / min. Phenolic acids t vanillin, vanillic acid, p-hydroxybenzoic acid, p-hydroxybenzaldehyde, trans-p-coumaric acid, trans-cinnamic acid, trans-ferulic acid 10, 50, 100 / w w (He et al., 2010). 9. Scanning electron microscope (SEM) y z ùkü ù p š ù z œ x (Low Vacuum-Scanning Electron, 1 K) xk w. 3% glutaraldehyde 3 š w z, 0.1 M sodium phosphate buffer (ph ) 15 3z w. 2% aqueous osimium tetroxide w 4æ 26 zš (postfixation) 0.1 M sodium phosphate buffer 15 3z. 30% acetone 10% graded acetone series k eš, k isoamyl acetate 34z z 4æ þ. z Hitachi HCP-2 critical point dryer w liquid CO 2 w (critical point drying, CPD) Hitachi E-1030 sputter e 10 Ì v (Au gold coating) z œ x w image data file z ƒƒ x k wš w (Kim and Lee, 2005). 10. m e mean ± SD ùkþ. x m v SPSS 16.0 w, (ANOVA: analysis of variance) w z α =0.05 Duncan (DMRT: Duncan's multiple range test) w. š 1. s d x ù ƒƒ 0.2, 0.4, 0.6, 0.8, 1.0 / w s HEK293 w s d w. Fig. 1 s w, p WEƒ 0.6 /» s ƒw ùkü. FE-L.Pƒ û s ùkü WE 0.6 / l Fig. 1. Cytotoxicity of Berberis koreana bark on human normal cell line, HEK293. (WE: water extract at 100, control. FE-LP: fermentation extract by Lactobacillus paracasei. FE- B.L: fermentation extract by Bifidobacterium longum B6.). Each value represents the mean±sd. 120

5 melatonin serotonin w ù z e w s ùkü. š 1.0 / w WE 20.52% s w FE-B.L FE-L.P ƒƒ 17.39%, 15.96% w 3.1%~4.5% z ƒ ùkü. š œ w Spirulina maxima w (Oh et al., 2010) 13.8%~18.6% s w ùkü, š œ Spirulina maxima s 1.7%~4.8% z w w ùk ü. w w ³ z z w in vivo w z z ƒ ƒ û ùkü, z w ùkü p ƒ q, x» š (Yoon et al., 2009). ³ z mw z ù x y q g jš ww y j d.» ³ z mw z w wz ù w» t t ƒ w, w zœ w, j š. 2. Serotonin Monoamine serotonin (5-hydroxytryptamine : 5HT),, m w y (Kwon et al., 2000)w, œ w (Lee et al., 1996), w ƒ š š (Choi et al., 1988). Fig n 2 x w x serotonin d w. ù (WE, FE-LP, FE-B.L) w (water), ³ z (L.P B.L), (milk) (doxylamine succinate) w er (caffein) w w. ú milk, doxylamine succinate, WE, FE-L.P FE-B.L n serotonin w ƒw w, p 10 ƒƒ ng/, ng/, ng/, ng/ ng/ ƒ ùkû. û caffein n serotonin w w ng/ ƒ û. 10 ³ z n w L.P B.L serotonin w water w ùkù l ³ z w e (P < 0.05). Serotonin w y n l w, milk û w ƒw ù water m w ƒ š doxylamine succinate WE ƒƒ 4, 8 l š FE- L.P FE-B.L ƒƒ 2 l water ƒw, caffein 8 ú l (P <0.05). ù z doxylamine succinate z serotonin w e y w. 10 ù»k n x serotonin s³w w water, milk, doxylamine succinate, caffein, L.P Fig. 2. Comparison of serotonin concentration in the serum of ICR mice by different oral administration treatment [water, milk, doxylamine succinate, caffein, lactobacillus fermentation solution (L.P and B.L) and the extracts of Berberis koreana bark (WE, FE- L.P and FE-B.L)]. Each value represents the mean±sd. Means followed by different letters differ significantly (P <0.05). 121

6 Jin LingÁ½ Á Á Á Á Á Á x B.L ƒƒ ng/, ng/, ng/, ng/, ng/ ng/ ùkü. w r ù n WE ng/, FE- L.P ng/, FE-B.L ng/. Doxylamine succinate, WE, FE-L.P FE-B.L n serotonin w water w ƒƒ 44.08%, 35.84%, 72.28% 66.11% m w ƒw š milk n 24.39% ƒw ù ƒ caffein n 25.71% w (P < 0.05). Lee w (~ ), w ( «), ( Œ) y ( Ž) n x serotonin w d w w ƒƒ 52.75%, 47.76%, 31.37% 41.76% ƒw š š (Lee et al., 2000). w x ù z n x serotonin ƒ 66% ƒw ù z serotonin z š š. w FE-L.P FE-B.L w WE w 20% ƒw l z mw ù ƒ» w serotonin z š y w, z mw y ƒw ù y z ù» serotonin ƒ. 3. Melatonin Melatonin (N-acetyl-5-methoxytryptamine) s y,, w y, w,, w ù» w e š w (Kang and Baick, 2008; Na et al., 2008). Table 1 ICR w 10 2 x w x melatonin w d w. ú milk, doxylamines succinate, WE, FE-L.P FE-B.L n melatonin w ƒw w š 10 ƒƒ pg/, pg/, pg/, pg/, pg/ ƒ ùkþ. û caffein n melatonin w w pg/ ƒ û. water ³ z n (L.P B.L ) 10 w yƒ j. Melatonin w y n w 2, 4, 6 milk, doxylamine succinate, FE-L.P FE-B.L n w 4 ƒƒ water ùkü š 8 l L.P B.L w water ùkü (P <0.05). melatonin w n w š w. 10 ù»k n x melatonin s³w w milk doxylamine succinate water (76.92 pg/ ) w ƒƒ ƒw wr, caffein 0.3 (P < 0.05). ù w w FE-L.P ( pg/ )>FE-B.L ( pg/ )>WE ( pg/ ) ùkü, water w 38% w ƒ. Hong w melatonin w ƒ ùkù k (20.4%) ƒ ù ƒ melatonin {wš y w (Hong et al., 1999). FE-L.P melatonin w Table 1. Melatonin concentration in the serum of ICR mice by different oral administration treatment [water, milk, doxylamine succinate, caffein, lactobacillus fermentation solution (L.P and B.L) and the extracts of Berberis koreana bark (WE, FE-L.P and FE-B.L)]. Samples Melatonin concentration (pg/ ) 2 day 4 day 6 day 8 day 10 day Water ±8.33 de ±5.59 de ±4.79 de ±4.85 d ±3.33 e* Milk ±7.95 ab ±14.57 bc ±7.22 bc ±23.53 b ±16.60 c Doxylamine succinate ±15.66 a ±28.39 a ±18.36 a ±12.08 a ±21.07 a Caffein ±6.15 e ±4.39 e ±4.24 e ±3.75 f ±3.61 f L.P ±5.36 cde ±9.80 d ±15.73 cd ±11.91 cd ±12.56 de B.L ±10.49 bcde ±9.67 de ±9.16 de ±9.44 cd ±12.98 de WE ±9.82 ad ±19.83 cd ±15.61 cd ±21.47 bc ±19.66 d FE-L.P ±18.09 a ±19.47 ab ±24.11 bc ±18.26 a ±21.33 ab FE-B.L ±7.82 ac ±11.07 cd ±28.96 b ±21.43 b ±16.67 bc * Mean±SD with different capital superscripts in the same column are significantly different at P <

7 melatonin serotonin w ù z e w Fig. 3. Typical HPLC chromatogram of phenolic acid standards (A: p- hydroxybenzoic acid. B: vanillic acid. C: p-hydroxybenzaldehyde. D: vanillin. E: trans-p-coumaric acid. F: trans-ferulic acid. G: trans-cinnamic acid.). Table 2. Comparison of phenolic acids in the extracts of Berberis koreana bark according to different extraction processes. ( /100 g) Sample p-hydroxybenzoic acid vanillic acid p-hydroxybenzaldehyde vanillin trans-p-coumaric acid trans-ferulic acid FE-L.P FE-B.L FE-LP: fermentation extract by Lactobacillus paracasei. FE-B.L: fermentation extract by Bifidobacterium longum B6. pg/ ù ƒ doxylamine succinate pg/ ¾ w w. ù FE-L.P doxylamine succinate m ƒ ùkù l melatonin w z š (P <0.05). l ù z serotonin melatonin w e y w š p z» w ù z ƒ, w n w y w. wz ù w w w ù z y w v w. 4. HPLC w ù z phenolic acids w ù v phenolic acids w w» w p-hydroxybenzoic acid, vanillic acid, p- hydroxybenzaldehyde, vanillin, trans-p-coumaric acid, transferulic acid, trans-cinnamic acid 7ƒ t w š HPLC w d w ƒƒ 9.95, 11.34, 13.52, 16.65, 20.02, 21.00, (Fig. 3). Table 2 ù z phenolic acids w w. z ù phenolic acids vanillic acid w ƒ ùkù trans-cinnamic acid w. P- hydroxybenzoic acid, vanillin, trans-p-coumaric acid FE- L.Pƒ ƒƒ /100 g, /100 g, /100 g FE-B.L w ƒƒ 44.5%, 59.0%, 49.3% w ƒw. Vanillic acid trans-ferulic acid FE-B.L w ƒƒ /100 g, /100 g FE-L.P w ƒƒ 13.9%, 24.2% ƒ. P-hydroxybenzaldehyde FE-L.P š FE-B.L w.» l ù ³ z phenolic acids w yƒ y w wz ù phenolic acids w ¾ ƒ v w. 5. Scanning electron microscope (SEM) ù v xk y w» w œ x w w (Fig. 4). A xk j û 123

8 Jin Ling 김지선 서용창 최운용 안주희 마충제 윤창순 이현용 Fig. 4. Morphology observation of Berberis koreana bark by SEM (A: water extract at 100, control. B: fermentation extract by Lactobacillus paracasei. C: fermentation extract by Bifidobacterium longum B6.). 반면 발효 추출물인 B와 C의 표면 조직이 파괴되어 작은 절 편으로 조각나 있었으며 다공성 조직이 형성되어 있음을 확인 할 수 있다. 이는 발효과정에서 생성된 유산 및 유기산으로 매자나무 조직을 느슨하게 함으로써 조직이 파괴되어 절편이 쉽게 형성되거나 혹은 발효과정에서 생성된 가스가 국부 조직 을 파괴하여 다공조직이 형성된 것으로 사료된다. SEM 사진 을 통해 유산균 발효가 매자나무 내부까지 영향을 주어 세포 벽이 깨지면서 조직 및 구조가 변형, 파괴된 것을 확인할 수 있는데, 이는 매자나무의 생리활성이 증가한 원인중의 하나로 사료된다. 또한 유산균 및 대사산물이 독성감소 및 활성증진 의 원인일 가능성도 높아 향후 유산균과 이의 대사산물에 대 한 연구가 더 필요하다고 사료된다. depression and menopausal syndroms in women at midlife. Korean Journal of Women Health Nursing. 3: Cho SH and Kim CI. (1974). Effects of Berberis koreana palibin on sleep duration and rectal temperature in mouse. Korean Journal of Pharmacology. 10: Choi BS, Jeoung HY and Han SH. (1988). Low platelet serotonin level in lnsomnia. Journal of the Korean Neuropsychiatry Association. 27: Hong SC, Han JH, Lee SP and Bang SK. (1998). The effect of tricyclic antidepressant (Dothiepin) on sleep in depressed patients. Journal of the Korean Neuropsychiatry Association. 37: Hong YY, Moon IS, Kom DI and Lee TK. (1999). A study on melatonin, serotonin secretion change and behavior in the rats treated with Yiseontang, Gammakdaejotang, Sanjointang and Sanjogammaktang. The Journal of Oriental Gynecology. 12: 감사의 글 He X, Kim SS, Park SJ, Seong DH, Yoon WB, Lee HY, Park DS and Ahn J. (2010). Combined effects of probiotic fermentation and high-pressure extraction on the antioxidant, antimicrobial, and antimutagenic activities of Deodeok (Codonopsis lanceolata). Journal of Agricultural and Food Chemistry. 58: 본 결과물은 2011년 교육과학기술부로부터 지원받아 수행된 연구 (지역거점연구단육성사업/의료 바이오신소재융복합연구 사업단)로 이에 감사를 드립니다. Jin L, Han JG, Ha JH, Jeong HS, Kwon MC, Ahn J, Kim JC, Choi GP, Chung EK and Lee HY. (2008). Effect of immune LITERATURE CITED activity on Berberis koreana palibin by ultra high pressure low temperature process. Korean Journal of Medicinal Crop Science. 16: Chung ES. (1996). An analysis of th relationship between 124

9 melatonin serotonin w ù z e w Jin L, Ha JH, Jeong MH, Chung EK, Chung AR, Kim JC, Ahn JH and Lee HY. (2009). Enhancenment of the antioxidant and anticancer activities of Berberis koreana bark by using a low temperature and high-pressure extraction process. Korean Journal of Food Science and Technology. 41: Kang SH and Baick SC. (2008). The effects of milking time and dairy processes on melatonin contents in milk. Journal of the Korean of Dairy Science and Technology. 26:1-4. Kim IJ and Lee DW. (2004). Experimental study on the antidepressant effect of Ginseng Radix Alba and Cyperi Rhizoma. Journal of Oriental Neuropsychiatry. 15: Kim HT, Kim JW, Lim MK, Jin TW, Yeo SG, Jang KH, Oh TH and Lee KW. (2007). Cytotoxic effect of Artemisia capillaris extracts on the cancer cells on in vitro. Journal of Veterinary Clinics. 24: Kim IS and Lee SH. (2005). Trichome type and development in leaves of Althaea rosea. Korean Journal of Electron Microscopy. 35: Kim JH, Shin KS and Lee H. (2002). Characterization and action mode of anti-complementary substance prepared from Lactobacillus plantarum. Korean Journal of Food Science and Technology. 34: Kim L, Kim S and Kwon B. (2000). A clinical study on the postpartum depression. Journal of Oriental Neuropsychiatry. 11: Kim YS. (1986). The central action of Maja (Berberis koreana Palibin) and its constituents. The Journal of Soonchunhyang University. 9: Kwon YH, Lee YW and Kim H. (2000). A study on the serotonin metabolism and the morphine-related analgesic mechanism in mice fed tryptophan supplemented diet. The Journal of Applied Pharmacology. 8: Lee DK, Gwak DG and Park SD. (2003). Antidepressant effect of Licium chinense Mill. and its influence on indoleamine and its metabolite of depression model rats. The Koreana Journal of Oriental Medical Prescription. 11: Lee HC, Lee DK, Kim DI and Lee TK. (2000). Effects of Glycyrrhiza uralensis FISCH., Eugenia caryo-phyllata Thunb., Anemarrhena sphodeloides BGE., and Phellodendron chinense SCHNEID. on serotonin, melatonin concentration and activity of rats. The Journal of Oriental Gynecology. 13: Lee JM, Kim KS and Lee WJ. (1996). Effects of brain serotonin on kidney function and hormone release in water-deprived rats. Kyungpook Univrsity of Medicine Journal. 37: Na KA, Kim ES, Eum JH, Kim JH, Yoon SI and Lee DR. (2008). Effect of melatonin on the maturation of mouse germinal vesicle (GV)-stage oocytes and apoptosis of cumulus cells in vitro. Development and Reproduction. 12: Oh SH, Kang H, Choi WY, Seo YC, Heo SJ, Abu AM, Jeong KH and Lee HY. (2010). Enhancement of skin immune activities of Spirulina maxima by high pressure extraction process. Ocean and Polar Research. 32: Park S, Kim DH, Paek NS and Kim SS. (2006). Preparation and quality characteristics of the fermentation product of ginseng by lactic acid bacteris (FGL). Journal of Ginseng Research. 30: Park SJ, Hwang UW, Kim JW, Kim HT, Chi SE and Kim WR. (2004). The effects of bambusae caulis and St. John's Wort in the chronic mild stress model of depression in rats. Journal of Oriental Neuropsychiatry. 15: Qadir SA, Kwon MC, Han JG, Ha JH, Chung HS, Ahn J and Lee HY. (2009). Effect of different extraction protocols on anticancer and antioxidant activities of Berberis koreana bark extracts. Journal of Bioscience and Bioengineering. 107: Song JY and Li GZ. (2002). Why the depression is prevalent in women? Kyung Hee of Medicine. 18: Yoon TJ. Yang WS. Park SM, Jung HY, Lee AN, Jung JH, Kang TB, Yoo YC and Kim JB. (2009). In vivo toxicity and immunoadjuvant activity of korean mistletoe (Viscum album coloratum) extract fermented with Lactobacillus. Korean Journal of Food Science and Technology. 41: