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μ μ μ μ μ μ μ μ μ

α μ μ

β μ α μ

α γ

μ α β

α γ γ μ

μ μ

αα αα α α β

μ α

Diabetic Patients ( 천만 ) 35 30 25 20 15 10 5 0 1985 2003 2010 2025 Year Anual number of Diabetic Patients

α α

μ μ

δ δ δ δ δ δ δ δ δ δ δ δ δ γ γ H H H H H H H H H 1 2 3 H H H CH 3 H H H H 4 5 6

μ μ μ

μ μ μ μ μ

μ α λ ε θ θ α λ ε α λ ε β

α α δ δ δ δ δ

δ δ δ δ δ α δ δ δ δ δ δ δ δ δ δ δ

δ β α δ δ δ δ δ H CH 3 CH 3 CH 3 H 7 H 2 4 H H 1" 3' 4' 1' 5' CH 3 1'" H 7 H 2 4 H 1' 3' 4' H 1" 5' H CH 3 1'" H H H 4' 2' 1' H H H 1" H 3 4 1 b 5 a H H CH 3 1'" H 2 3 6

δ δ δ δ δ δ α β

H 1" H 7 5 2 3' R 2 4' 1"' 5' H CH 3 R 1 1 R 1 = H R 2 = CH 3 2 R 1 = H R 2 = CH 3 4 R 1 = H R 2 = H 5 R 1 = H R 2 = H 3 1" H H 7 H 4' 2' 1' H 1 b a 6 4 CH 3 1"' H 3 C CH 3 H H 8 9 H

μ μ μ μ μ μ

μ μ

α λ ε θ θ θ ν α λ ε θ θ θ θ α λ ε θ θ θ θ

α λ ε θ θ θ α λ ε θ θ θ θ α λ ε θ θ θ α λ ε θ θ θ θ ν α λ ε θ θ θ θ

α λ ε θ θ θ ν α λ ε θ θ θ θ α λ ε θ θ θ ν α λ ε θ θ θ

α δ δ δ α δ δ δ δ δ δ δ δ

δ δ α δ δ δ δ δ δ δ δ δ δ

δ δ δ δ δ δ δ δ δ δ δ δ δ

δ δ δ δ

δ α δ δ

. 2 3 4 5 6 7 8 9 10 1' 2' 3' 4' 5' 6' 2" 3" 4" 5" 6" 1"' 2"' 3"' 4"' 5"' CH 3

H H H H H H H CH 3 H H H 1 2 6 H H H H H H H H H H H H H 7 8 9 H H H H H H H 11 12

H H H CH 3 H H H 3 5 H H H H H 4 10

H 7 5 H R 1 2' 2 3 4 4" 6' 3" R 3 6" 2" R 2 1'" 3'" prenyl 4'" 5'" H R 1 R 5 R 3" 4 4" 2" 2' R 3 R 2 5" 6" 1 R 1 = prenyl, R 2 = H, R 3 = CH 3 2 R 1 = H, R 2 = H, R 3 = CH 2 H 3 R 1 = H, R 2 = CH 3, R 3 = CH 2 H 5 R 1 = R 5 = H, R 2 = R 4 = H, R 3 = prenyl H H 4" 2' 1''' 4 5" 2" 6" 3''' 4''' 2''' 5''' 6 R 1 = R 5 = H, R 2 = R 4 = H, R 3 = CH 3 7 R 1 = R 4 = R 5 = H, R 2 = R 3 = H 8 R 1 = R 4 = R 5 = H, R 2 = H, R 3 = prenyl 9 R 1 = R 4 = R 5 = H, R 2 = prenyl, R 3 = H 10 R 1 = R 3 = H, R 2 = R 5 = H, R 4 = (=) 11 R 1 = R 2 = R 4 = H, R 3 = R 5 = H 12 R 1 = R 2 = H, R 3 = R 4 = R 5 = H

μ μ

α ν α ν α α ν δ δ

α ν δ δ α ν δ δ

α δ δ δ δ δ δ δ δ δ δ δ α δ δ δ δ δ δ

αα α δ δ αα α α

α α

position 1 2 δ H (J in Hz) a δ C δ H (J in Hz) δ C 1 1.61 m, 1.96 m 35.2 t 1.58 m, 1.93 m 35.1 t 2 1.87 m, 2.76 t (14.1) 28.1 t 1.90 m, 2.75 t (13.0) 28.0 t 3 4.73 br s 71.1 d 4.72 br s 71.0 d 4 48.9 s 48.7 s 5 2.17 m 50.1 d 2.15 m 50.0 d 6 2.02 m 2.36 m 21.3 t 2.13 m 2.39 m 21.2 t 7 1.60 m, 1.89 m 34.8 t 1.60 m, 1.81 m 34.5 t 8 40.9 s 40.9 s 9 2.16 m 47.6 d 2.14 m 47.5 d 10 38.8 s 38.7 s 11 1.82 m, 2.10 m 24.7 t 2.14 m, 2.20 m 24.6 t 12 5.68 br s 129.0 d 5.65 br s 128.7 d 13 140.1 s 140.3 s 14 42.9 s 42.7 s 15 1.40 br d (13.2), 2.80 m 29.7 t 1.35 m, 2.38 m 29.6 t 16 2.18 m, 3.24 m 27.4 t 2.06 m, 3.13 td (13.5, 4.0) 26.8 t 17 48.8 s 48.7 s 18 3.27 s 55.9 d 3.08 s 55.1 d 19 73.4 s 73.1 s 20 157.1 s 1.51 m 42.8 d 21 2.30 m, 3.17 td (12.6, 3.9) 29.4 t 2.10 m, 2.13 m 27.3 t 22 2.16 m, 2.38 m 39.8 t 2.08 m, 2.17 m 38.8 t 23 1.80 s 25.8 q 1.80 s 25.7 q 24 181.2 s 181.1 s 25 1.27 s 14.2 q 1.26 s 14.1 q 26 1.24 s 17.9 q 1.25 s 17.7 q 27 1.76 s 24.4 q 1.72 s 24.9 q 28 180.6 s 181.1 s 29 1.67 s 28.1 q 1.45 s 27.5 q 30 5.02 s, 4.82 s 105.7 t 1.13 d (6.5) 17.1 q 19 H 5.74 s 5.01 s

H H H CH H CH H H HC H H H H H H HC 1 2

12 29 R 4 R 3 20 19 R 3 R 4 19 12 30 29 R 1 1 3 5 8 27 14 17 CH 28 R 1 3 1 5 27 14 CH 28 23 R2 24 23 24 R 2 1 R 1 = a-h, R 2 = CH, R 3 = H, R 4 = CH 2 2 R 1 = a-h, R 2 = CH, R 3 = H, R 4 = a-ch 3 3 R 1 = a-h, R 2 = CH 2 H, R 3 = H, R 4 = CH 2 4 R 1 = a-h, R 2 = CH 2 H, R 3 = H, R 4 = a-ch 3 11 R 1 = a-h, R 2 = H, R 3 = R 4 = H 12 R 1 = a-h, R 2 = R 4 = H, R 3 = H 13 R 1 = b-h, R 2 = R 3 = R 4 = H 14 R 1 = b-h, R 2 = R 3 = H, R 4 = H 5 R 1 = a-h, R 2 = CH 2 H, R 3 = H, R 4 = a-ch 3 6 R 1 = b-h, R 2 = CH 2 H, R 3 = H, R 4 = a-ch 3 7 R 1 = b-h, R 2 = CH 3, R 3 = H, R 4 = a-ch 3 8 R 1 = b-h, R 2 = CH 2 H, R 3 = H, R 4 = a-ch 3 9 R 1 = b-h, R 2 = CH 3, R 3 = H, R 4 = a-ch 3 10 R 1 = (=), R 2 = CH 2 H, R 3 = H, R 4 = a-ch 3

β μ α

α μ

CH 3 CH 3 H 3 C H 3 C H 3 C H 3 C 미리스티신 (myristicin) 엘레미신 (elemicin) 사프롤 (safrole)

μ μ μ μ

μ δ δ δ

실험조건으로용출에사용한용매 화합물질 30% EtH 50% EtH 70% EtH 80% EtH 90% EtH EtH Acetone Nectandrin B 유출유출 meso-dihydroguaia retic acid 유출 유출 Macelignans 유출 Myristicin 유출유출 μ

δ δ

δ δ δ δ δ δ

No. 1 2 3 4 5 6 7 d H (J in Hz) d H (J in Hz) d H (J in Hz) d H (J in Hz) d H (J in Hz) d H (J in Hz) d H (J in Hz) 1 2 5.12, d, 6.6 4.65, d, 9.6 5.10, d, 9.0 4.53, d, 6.6 4.43, d, 7.8 4.50, d, 7.2 5.45, d, 4.2 3 2.65, m 2.33, m 2.24, m 2.35, m 2.27, m 2.32, m 2.43, m 4 2.65, m 2.33, m 1.78, m 2.35, m 2.27, m 2.34, m 2.43, m 5 5.12, d, 6.6 5.46, d, 4.2 4.36, d, 9.6 4.53, d, 6.6 4.44, d, 7.2 4.52, d, 7.2 4.61, d, 9.6 1 2 6.99, d, 1.8 6.92, d, 2.4 7.07, d, 1.8 6.99, d, 1.8 7.09, br, s 6.67, br, s 6.93, d, 1.8 3 4 5 6.90, d, 8.4 6.77, d, 8.4 6.78, d, 8.4 6.92, d, 8.4 6.92, d, 8.4 6.91, d, 7.8 6.78, d, 8.4 6.92,dd,1.8,8.4 6.80,dd,2.4,8.4 6.98, dd, 1.8, 7.8 6.98, dd, 1.8, 9.0 6.70, br, s 6 6.84,dd,1.8,8.4 1 2 6.99, d, 1.8 6.92, d, 2.4 7.07, d, 1.8 6.99, d, 1.8 7.09, br, s 6.97, d, 1.2 6.93, d, 1.8 3 4 5 6.90, d, 8.4 6.78, d, 8.4 6.91, d, 7.8 6.92, s, 8.4 6.91, d, 7.8 6.78, d, 8.4 6 6.84,dd,1.8,8.4 3 Me 0.61, d, 6.0 1.01, d, 6.6 1.01, d, 6.6 1.05, d, 6.6 1.02, d, 3.6 1.04, d, 6.6 0.97, d, 6.6 4 Me 0.61, d, 6.0 0.63, d, 6.6 0.65, d, 6.6 1.05, d, 6.6 1.00, d, 3.6 1.06, d, 7.2 0.60, d, 7.2 3 Me 3.91, s 3.90, s 3.87 3.85, s 3.80, s 3.88, s 4 H 5.59, br, s 5.65, br, s 5.96, br, s 5.58, br, s 5 Me 3.88, br, s 3 Me 3.91, s 3.92, s 3.87, s 3.85, s 3.82, s 3.88, s 4 H 5.47, br, s 4 Me 3.86, s CH 2 5.93, s 5.94, s

No. 1 2 3 4 5 6 7 d C (ppm) d C (ppm) d C (ppm) d C (ppm) d C (ppm) d C (ppm) 1 2 82.7 84.8 84.6 87.2 88.2 87.2 87.4 3 41.5 43.4 43.5 44.1 45.5 44.0 44.7 4 41.5 47.6 47.8 44.1 45.6 44.5 44.7 5 82.7 85.8 89.0 87.2 88.0 87.5 86.3 1 132.5 132.6 133.0 133.9 136.4 134.0 138.0 2 109.0 108.3 115.7 114.1 115.5 109.2 108.8 3 146.2 146.6 148.6 146.4 150.4 146.9 149.3 4 144.3 146.3 146.8 144.9 146.9 145.1 148.9 5 113.9 113.9 111.9 109.2 111.3 146.9 107.8 6 119.3 119.3 120.9 119.1 111.9 103.1 121.0 1 132.5 135.0 133.8 133.9 135.1 133.5 135.8 2 109.0 108.7 116.1 114.1 112.7 109.2 108.8 3 146.2 145.0 149.0 146.4 149.9 146.9 147.9 4 144.3 144.3 147.5 144.9 148.3 146.4 148.6 5 113.9 114.0 111.6 109.2 110.9 114.1 107.8 6 119.3 118.8 120.7 119.1 120.0 119.3 120.2 3 Me 11.8 9.4 14.8 12.7 13.1 12.9 11.9 4 Me 11.8 11.8 15.2 12.7 13.2 13.1 9.8 3 Me 55.8 56.0 56.3 55.6 56.2 56.3 3 Me 55.8 55.8 56.4 55.6 56.3 55.8 4 Me 56.1 5 Me 56.3 CH 2 102.3 102.5

Figure. 85 Chemical structures of compounds 1 7 isolated from M. fragrans. 3 4 2' 2 5 Me 3' 1' 1'' 6' H 4' 6'' 5' 2'' 5'' Me 3'' 4'' H Me H Me H 1 2 Me Me R 1 R 3 H 3 H H R 2 R 4 4 R 1 = R 3 = Me, R 2 = R 4 = H 5 R 1 = R 3 = Me, R 2 = H, R 4 = Me 6 R 1 = R 2 = R 3 = Me, R 4 = H 7

Figure. 86 l l l Stimu atory effects of iso ated ignans 1 7 on AMPK activity. A B l l 7 (A ) The stimu atory effects of iso ated compounds 1 the concentration of 20 μg/ml. (B ) The l on AMPK activity at stimu atory effects 7 on AMPK activity at the concentration of 5 μg/ml. compounds 1 152 of l iso ated

μ H H H H H H H H H H H H H H H H 1 2

Morus sp. ( 500 g) Extracted with MeH The extract was dried, suspened in H 2, partitioned with n-hexane, EtAc, and BuH, successively. n-hexane EtAc BuH H 2 C 18 -Silica gel Vacum Liquid Column Chromatography MeH/H 2 gradient Fr.#5 Fr. #6 Silica gel Vacum Liquid Column Chromatography RP HPLC CH 2 Cl 2 /MeH gradient CH 3 CN/H 2 gradient Fr.#57 Fr.#58 2 Sanggenon G and C 5 Moracin 6 Moracin P 4 Kuwanon L 혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 상백피 - 중국 (150 mg/kg, n=6) 90 70 50 대조군 (Vehicle, n=6) 상백피 - 중국 (150 mg/kg, n=6) 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w 10 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks) Time (weeks)

혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 상백피 - 한국 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 상백피 - 한국 (150 mg/kg, n=6) 50 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w 10 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks) Time (weeks)

H H H H TN567-2 (13.3 mg) H TN567-3 (13.2 mg) H H H TN-3-7 (4.0 mg) TN-3-5 (3.8 mg)

Torreya nucifera (Seeds, 500 g) Extracted with MeH The extract was dried, suspened in H 2, partitioned with n-hexane, EtAc, and BuH, successively. n-hexane EtAc BuH H 2 Sephadex LH-20 Column Chromatography 3:2:1 hexane:toluene:meh Fr.#3 RP HPLC CH 3 CN Fr. #5-7 RP HPLC CH 3 CN TN-3-5 TN-3-7 1 2 혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 비자 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 비자 (150 mg/kg, n=6) * 50 200 100 0 w 1 w 2 w 3 w 4 w Time (weeks) * 30 10 0 w 1 w 2 w 3 w 4 w Time (weeks)

5 3' 4 2' 1' 3 2'' 12'' 1'' (CH 2 ) 10 CH 3 (CH 2 ) 12 CH 3 H 1 H 1 2 (CH 2 ) 10 CH 3 (CH 2 ) 10 CH 3 H H 3 4 H H (CH 2 ) 11 CH 3 (CH 2 ) 12 CH 3 H 5 H 6

Siegesbeckia glabrescens ( 500 g) Extracted with MeH The extract was dried, suspened in H 2, partitioned with n-hexane, EtAc, and BuH, successively. n-hexane EtAc BuH H 2 Sephadex LH-20 column chromatography 3:2:1 hexane-toluene-meh Fr. #3 Fr. #8 RP HPLC CH 3 CN/H2 gradient SH-359-4 SH-34-5 SH-343-4 SH-343-3 SHF-8-9 SHF-8-10 혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 희첨 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 희첨 (150 mg/kg, n=6) 50 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w 10 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks) Time (weeks)

μ H H H H 1 2 3 Seed of Psoralea corylifolia ( 보골지 ) : 260 g EtH extract (36.1 g) Suspended in H 2 Partitioned with EtAc EtAc Fraction (30.5 g) Silica gel column (4.8 * 50 cm) n-hexane/etac stepwise gradient 30% MeH in CHCl 3 Collect 300 ml Fr.2 (7.06 g) Fr.4 (2.5 g) Fr.5 (1.05 g) Silica gel column (4.8 * 34 cm) n-hexane : CH 2 Cl 2 = 1 : 3 Sephadex LH-20 column (3 * 30 cm) n-hexane : CHCl 3 : MeH = 4: 3 : 1 Sephadex LH-20 column (2.5 * 30 cm) n-hexane : CHCl 3 : MeH = 4: 3 : 1 Bakuchiol (6.13 g) IC 50 = 20.8 ± 1.9 um Psoralidin (313.2 mg) IC 50 = 20.8 ± 1.9 um Corylin (39.4 mg) Inactive

혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 보골지 -1 (150 mg/kg, n=6) 90 70 50 대조군 (Vehicle, n=6) 보골지 -1 (150 mg/kg, n=6) 200 30 100 10 0 w 1 w 2 w 3 w 4 w 5 w 6 w 0 w 1 w 2 w 3 w 4 w 5 w 6 w Time (weeks) Time (weeks) 체중변화 400 300 혈당변화 대조군 (Vehicle, n=6) 보골지 -2 (150 mg/kg, n=6) 90 70 50 대조군 (Vehicle, n=6) 보골지 -2 (150 mg/kg, n=6) 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w 10 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks) Time (weeks)

PL-2-1819-2 (9.3 mg) N H PL-2-1819-3 (6.6 mg) N N H N PL-2-1819-4 (9.2 mg) PL-2-1819-6 (4.5 mg) PL-2-1819-7 (2.3 mg) N H 혈당변화 체중변화 400 300 90 70 대조군 (Vehicle, n=6) 필발 (150 mg/kg, n=6) 50 200 100 대조군 (Vehicle, n=6) 필발 (150 mg/kg, n=6) 0 w 1 w 2 w 3 w 4 w 30 10 0 w 1 w 2 w 3 w 4 w Time (weeks) Time (weeks)

Comps. PTP1B VHR PPase1 1 11.4 ± 0.6 > 100 > 500 1 2 2 3 RK-682 22.4 ± 0.6 56.1 ± 6.3 5.0 > 100 > 100 NT > 500 > 100 NT (IC 50 = μm) 3

체중변화 혈당변화 400 300 대조군 (Vehicle, n=6) 단삼 (150 mg/kg, n=6) 90 70 50 대조군 (Vehicle, n=6) 단삼 (150 mg/kg, n=6) 200 30 100 10 0 w 1 w 2 w 3 w 4 w 0 w 1 w 2 w 3 w 4 w Time (weeks) Time (weeks) Comps. PTP1B VHR PPase1 H H 1 38.0 ± 1.5 3.0 ± 0.2 > 200 H 3 C CH 3 H 3 C H 2 > 200 > 200 > 200 1 2 (IC 50 = μm)

혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 석곡 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 석곡 (150 mg/kg, n=6) 50 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w 6 w 10 0 w 1 w 2 w 3 w 4 w 5 w 6 w Time (weeks) Time (weeks)

μ H H H H H H H ST-EA-2-11-2 H ST-EA-2-12-4-1 H H H H H H 3 C H H H H H H ST-EA-2-12-4-2 ST-EA-4-9

혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 권백 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 권백 (150 mg/kg, n=6) 50 200 30 100 10 0 w 1 w 2 w 3 w 4 w 0 w 1 w 2 w 3 w 4 w Time (weeks) Time (weeks)

혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 자초 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 자초 (150 mg/kg, n=6) 200 50 30 100 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks) 10 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks)

μ H H H H H H H 1 2 H H H H

S. flavescens Extracted with MeH Th wit n-hexane EtAc BuH Silica gel Col Hexane/aceto Hexane/acetone = 15/1 혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 고삼 (150 mg/kg, n=6) 90 70 50 대조군 (Vehicle, n=6) 고삼 (150 mg/kg, n=6) 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks) 10 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks)

12 13 12' 13' H H H 5 5' R 1 9-11 3 1 1' 3' 7 R 1 R 2 H HH 1 CH 2CH 3 CH 2CH 3 2 CH 2CH 3 4 CH 3 12 13 CH 2CH 2CH 3 CH 2CH 3 12' R 3 H 5 H R 1 9-11 3 5 1 H H 7 5' 1' 3' H H 3 C H H R 1 3 CH 2CH 2CH 3 6 CH 3 7 CH 2CH 3 8 CH 3 R 2 CH 3 H H H R CH CH CH H

EtAc fr. (91 g) Si CC Hex-CHCl 3 (2:1 1:1) Hex-CHCl 3 -EtH (10:10:1 9:9:2) Fr. 1 inhibition at 30 mg/ml Fr. 2 98% inhibition at 30 mg/ml Fr. 3 91% inhibition at 30 mg/ml Fr. 4 92% inhibition at 30 mg/ml Fr. 5 92% inhibition at 30 mg/ml Fr. 6 97% inhibition at 30 mg/ml Fr. 7 inhibition at 30 mg/ml Fr. 8 inhibition at 30 mg/ml 1. Si CC: Cyclohex-iPrH-MeH (2:2:1) 2. LH-20: MeH 6, 7, 8, 9 and 10 혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 관중 -F5 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 관중 -F5 (150 mg/kg, n=6) 50 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w 10 0 w 1 w 2 w 3 w 4 w 5 w Time (weeks) Time (weeks)

Sugar fraction Panax ginseng (MeH ext., 5 kg) H 2 layer Partitioned with CHCl 3 and EtAc BuH layer Partitioned with BuH MeH/H Eluated with MeH/H 2 (2/1) HP-20 column chmatography with Saponin fraction 혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 미삼 (150 m g/kg, n=6) 90 70 50 대조군 (Vehicle, n=6) 미삼 (150 m g/kg, n=6) 200 30 100 0 w 1 w 2 w 3 w 4 w 10 0 w 1 w 2 w 3 w 4 w Time (weeks) Time (weeks)

혈당변화 체중변화 400 300 대조군 (Vehicle, n=6) 육두구 (150 mg/kg, n=6) 90 70 대조군 (Vehicle, n=6) 육두구 (150 mg/kg, n=6) 50 200 30 100 0 w 1 w 2 w 3 w 4 w 5 w 6 w 10 0 w 1 w 2 w 3 w 4 w 5 w 6 w Time (weeks) Time (weeks)

1 2 3 4 5 6 7 8 9

Body weights Control 57 1 (125 mg/ml) 47 2 (125 mg/ml) d d d 37 3 d 6 d 9 d 2 d 5 d 8 d Treatment days 1 d 3 d 6 d 9 d 2 d 3 (125 mg/ml) 4 (50 mg/ml) Blood glucose 500 Control 1 (125 mg/ml) 300 2 (125 mg/ml) 3 (125 mg/ml) 4 (50 mg/ml) 100 0 d 5 d 8 d 13 d 16 d 19 d 22 d 25 d 28 d 31 d 33 d 36 d 39 d 42 d Treatment days

T G 2 주차 6 주차 250 200 150 100 50 0 Cont r ol 1 2 3 4 G L U 2 주차 600 6 주차 500 400 300 200 Cont r ol 1 2 3 4 C H 2 주차 6 주차 250 200 150 100 Cont r ol

GT GPT 600 500 400 300 200 100 0 600 500 400 300 200 100 0 Control Contr ol 1 2 3 4 BUN CK 50 40 30 20 10 0 Contr ol 1 2 3 4 1000 800 600 400 200 0 1 2 3 4 Contr ol CRE HDL 0. 8 0. 6 150 0. 4 100 0. 2 50 0 Contr ol 1 2 3 4 0 Contr ol 1 2 3 4

GTT 550 450 350 250 150 50 0 분 10 분 30 분 60 분 120 분 Time

분석시간 100% 메탄올 (%) 0.1% formic acid (%) 0 -> 25 min 72 25 25 -> 45 min 90 10 45 -> 55 min 100 0 55 -> 75 min 100 0 75 -> 85 min 72 28 85 -> 90 min 72 28

분석시간 100% 메탄올 (%) 3 차증류수 (%) 0 min 59 41 0 -> 70 min 65 35 70 -> 90 min 100 0 90 -> 100min 59 41 100-> 105min 59 41

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