Dicaffeoyl spermidine derivative glycosides and use thereof

Abstract

The present invention relates to dicaffeoyl spermidine derivative glycosides, a preparation method and a use thereof. The biological activity experiments show that the dicaffeoyl spermidine derivative glycosides of the present invention have anti-oxidative activity and antiviral activity, and their activity are even better than that of a positive control drug, thus can be used as an antioxidant for the prevention and/or treatment of neurodegenerative diseases such as Senile dementia, and as an antiviral agent for the prevention and/or treatment of viral infections.

Claims

1. A method of treating a neurodegenerative disease, comprising administering to a subject in need of treatment a therapeutically effective amount of dicaffeoyl spermidine derivative glycosides of formula (I) or the pharmaceutically acceptable salts thereof, ##STR00003## wherein, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are hydroxy, methoxy, or optionally substituted glycosyl, and at least one of R.sub.1, R.sub.2, R.sub.3 and R.sub.4 is an optionally substituted glycosyl, R.sub.5 and R.sub.6 are both —CH═ or —CH.sub.2—, wherein the optionally substituted glycosyl is optionally substituted with one or more of the following monosaccharide groups and disaccharide groups or polysaccharide groups formed by the following monosaccharides selected from the group consisting of: glucosyl, glucuronyl, mannosyl, galactosyl, allosyl, fructosyl, sorbosyl, furanosyl, rhamnosyl, quinovosyl, arabinosyl, lyxosyl, xylosyl, ribosyl; wherein the dicaffeoyl spermidine derivative glycosides or the pharmaceutically acceptable salts thereof further comprises pharmaceutically acceptable excipients to provide a pharmaceutical composition, wherein the content of the dicaffeoyl spermidine derivative glycosides or the pharmaceutically acceptable salts thereof is 1% to 90% by weight of the pharmaceutical composition.

2. The method according to claim 1, wherein the neurodegenerative disease is one or more of senile dementia, Parkinson's disease, multiple sclerosis and Huntington's disease, and the senile dementia is Alzheimer's disease, vascular dementia, dementia with Lewy body or frontotemporal dementia.

3. The method according to claim 1, wherein the pharmaceutically acceptable salts are salts formed by the dicaffeoyl spermidine derivative glycosides of formula (I) with an inorganic acid or an organic acid.

4. The method according to claim 3, wherein the inorganic acid is hydrochloric acid, hydrobromic acid, sulfuric acid, or nitric acid, and the organic acid is trifluoroacetic acid, acetic acid, propionic acid, malonic acid, butyric acid, lactic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, maleic acid, benzoic acid, succinic acid, picric acid, tartaric acid, citric acid, or fumaric acid.

5. The method according to claim 1, wherein the compound of formula (I) is: ##STR00004##

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The following examples are intended to illustrate the present invention without limiting it further. The present invention can be implemented in any of the ways described in the Summary of the Invention.

(2) In the following examples, the mass spectrometer was a LCQ Advantage MAX mass spectrometer manufactured by Finnigan, Germany. The superconducting NMR spectrometers were Bruker AV-300, Bruker AV-400 and Bruker AV-600. Column chromatography HP-20 macroporous resin is a product of Japan's Mitsubishi Corporation. Thin-layer chromatography silica gel GF254 and column chromatography silica gel (200-300 mesh) are both products of Qingdao Ocean Chemical Factory. The reversed phase ODS filler (50 μm) is a product of YMC Japan. The low-medium pressure liquid chromatography is a product of Shanghai Lisui Electronic Technology Co., Ltd. The preparative column used for the liquid phase separation was a Phenomex Gemini C18 column (21.2×250 mm, 5 μm) or a Cosmosil Packed C18 column (20.0×250 mm, 5 μm). The acetonitrile or methanol for liquid chromatography is chromatographic grade, the water is double distilled water, and the other reagents are analytical grade.

Example 1 Preparation of Compounds of Formula (II)—Formula (XIV)

(3) The 19.5 kg fructus lycii was extracted 3 times for 2 hours each time by heating under reflux with 100 L ethanol-water (60:40, v/v). After filtration, the filtrate was concentrated under reduced pressure to obtain a concentrated solution. The concentrated solution was chromatographed through a macroporous resin column, and eluted successively with ethanol-water having the volume ratios of 0:100, 30:70, 50:50, 70:30, and 95:5, and 5 fractions of F1, F2, F3, F4, F5 were obtained. Then the fraction F2, obtained by the elution with ethanol-water having the volume ratio of 30:70, was subjected to a silica gel column chromatography under normal pressure by using 70.0 g of F2, and eluted successively with chloroform-methanol-water having the volume ratios of 95:5:0, 90:10:1, 85:15:1.5, 80:20:2, 70:30:3, 60:40:4, 50:50:5, 40:60:6 and 0:100:0, a total of 10 sub-fractions of F2.1, F2.2, F2.3, F2.4, F2.5, F2.6, F2.7, F2.8, F2.9 and F2.10 were obtained. Subsequently, the sub-fraction F2.8 (10.1 g), obtained by the elution with chloroform-methanol-water having the volume ratio of 50:50:5, was subjected to a low-medium pressure liquid phase ODS column chromatography, and eluted successively with methanol-water-trifluoroacetic acid having the volume ratios of 10:90:0.1, 15:85:0.1, 20:80:0.1, 25:75:0.1, 30:70:0.1, 40:60:0.1 and 100:0:0, a total of 8 sub-fractions of F2.8.1, F2.8.2, F2.8.3, F2.8.4, F2.8.5, F2.8.6, F2.8.7, and F2.8.8 were obtained. The sub-fraction F2.8.1 (0.5 g), obtained by the elution with methanol-water-trifluoroacetic acid having the volume ratio of 10:90:0.1, was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), eluted with methanol-water-trifluoroacetic acid at a flow rate of 8 mL/min (20:80:0.1, v/v/v), and a total of 5 sub-fractions of F2.8.1.1, F2.8.1.2, F2.8.1.3, F2.8.1.4 and F2.8.1.5 were obtained. The sub-fraction F2.8.1.3 (48.3 mg) was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with acetonitrile-water-trifluoroacetic acid (10:90:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salt of the compound of formula (XI) (t.sub.R: 75.8 min, 10.0 mg, purity 95%) was obtained. The sub-fraction F2.8.1.4 (153.5 mg) was subjected to a reversed phase preparative HPLC (Phenomex Gemini C18 column), and eluted with methanol-water-trifluoroacetic acid (20:80:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salt of the compound of formula (II) (t.sub.R: 104.5 min, 129.9 mg, purity 95%) was obtained. The sub-fraction F2.8.1.5 (87.6 mg) was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with acetonitrile-water-trifluoroacetic acid (10:90:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salts of the compound of formula (III) (t.sub.R: 117.7 min, 44.6 mg, purity 95%) and the compound of formula (IV) (t.sub.R: 131.5 min, 6.0 mg, purity 95%) were obtained.

(4) Similarly, the sub-fraction F2.9 (3.8 g), obtained by the elution with chloroform-methanol-water having the volume ratio of 40:60:6, was subjected to a low-medium pressure liquid phase ODS column chromatography, and eluted successively with methanol-water-trifluoroacetic acid having the volume ratios of 5:95:0.1, 10:90:0.1, 15:85:0.1, 20:80:0.1, 25:75:0.1, 30:70:0.1, 40:60:0.1 and 100:0:0, a total of 9 sub-fractions of F2.9.1, F2.9.2, F2.9.3, F2.9.4, F2.9.5, F2.9.6, F2.9.7, F2.9.8 and F2.9.9 were obtained. The sub-fraction F2.9.2 (170.6 g), obtained by the elution with methanol-water-trifluoroacetic acid having the volume ratio of 10:90:0.1, was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), eluted with methanol-water-trifluoroacetic acid (18:82:0.1, v/v/v) at a flow rate of 8 mL/min, and a total of 6 sub-fractions of F2.9.2.1, F2.9.2.2, F2.9.2.3, F2.9.2.4 F2.9.2.5 and F2.9.2.6 were obtained. The sub-fraction F2.9.2.4 (41.0 mg) was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with acetonitrile-water-trifluoroacetic acid (10:90:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salt of the compound of formula (XIII) (t.sub.R: 32.0 min, 29.7 mg, purity 95%) was obtained. The sub-fraction F2.9.2.5 (97.3 mg) was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with acetonitrile-water-trifluoroacetic acid (12:88:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salt of the compound of formula (VIII) (t.sub.R: 19.3 min, 30.4 mg, purity 95%) was obtained. The sub-fraction F2.9.3 (239.0 mg), obtained by the elution with methanol-water-trifluoroacetic acid having the volume ratio of 10:90:0.1, was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with methanol-water-trifluoroacetic acid (18:82:0.1, v/v/v) at a flow rate of 8 mL/min, a total of 6 sub-fractions of F2.9.3.1, F2.9.3.2, F2.9.3.3, F2.9.3.4 F2.9.3.5 and F2.9.3.6 were obtained. The sub-fraction F2.9.3.3 (40.1 mg) was subjected to a reversed phase preparative HPLC (Phenomex Gemini C18 column), and eluted with methanol-water-ammonia (15:85:0.1, v/v/v) at a flow rate of 8 mL/min, the compound of formula (XIV) (t.sub.R: 59.0 min, 23.9 mg, purity 95%) was obtained.

(5) The sub-fraction F2.9.3.5 (32.0 mg) was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with acetonitrile-water-trifluoroacetic acid (10:90:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salt of the compound of formula (XII) (t.sub.R: 44.3 min, 17.6 mg, purity 95%) was obtained. The sub-fraction F2.9.3.6 (103.8 mg) was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with acetonitrile-water-trifluoroacetic acid (12:88:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salt of the mixture of the compound of formula (IX) and the compound of formula (X) (t.sub.R: 25.8 min, 69.2 mg, purity 95%) was obtained. The sub-fraction F2.9.5 (344.6 mg), obtained by the elution with methanol-water-trifluoroacetic acid having the volume ratio of 15:85:0.1, was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with methanol-water-trifluoroacetic acid (20:80:0.1, v/v/v) at a flow rate of 8 mL/min, a total of 4 sub-fractions of F2.9.5.1, F2.9.5.2, F2.9.5.3 and F2.9.5.4 were obtained. The sub-fraction F2.9.5.1 (31.8 mg) was subjected to a reversed phase preparative HPLC (Cosmosil Packed C18 column), and eluted with acetonitrile-water-trifluoroacetic acid (10:90:0.1, v/v/v) at a flow rate of 8 mL/min, the trifluoroacetate salts of the compound of formula (V) (t.sub.R: 53.0 min, 7.2 mg, purity 95%) and compound of formula (VI) (t.sub.R: 49.5 min, 8.0 mg, purity 95%) were obtained. The sub-fraction F2.9.5.2 (159.5 mg) was subjected to a reversed phase preparative HPLC (Phenomex Gemini C18 column), and eluted with methanol-water-ammonia (15:85:0.1, v/v/v) at a flow rate of 8 mL/min, the compound of formula (VII) (t.sub.R: 44.3 min, 122.0 mg, purity 95%) was obtained.

(6) The physicochemical constants are as follows:

(7) The trifluoroacetate salt of the compound of formula (II): green oily liquid; [α].sub.D.sup.27 −25.1 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.54), 219 (4.28), 287 (4.06), 290 (4.06), 325 (4.13) nm; IR (KBr) v.sub.max 3219, 2948, 1678, 1509, 1437, 1284, 1205, 1132, 1074, 801, 723 cm.sup.−1; ESIMS (positive) m/z 634.4; ESIMS (negative) m/z 632.5; HRESIMS (positive) m/z 634.2978 (calcd. for C.sub.31H.sub.44N.sub.3O.sub.11, 634.2976), and the molecular formula of this compound was identified as C.sub.31H.sub.43N.sub.3O.sub.11; .sup.13C and .sup.1H NMR are shown in Table 1.

(8) The trifluoroacetate salt of the compound of formula (III): green oily liquid; [α].sub.D.sup.27 −25.6 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.52), 232, (4.25), 292 (4.23), 315 (4.25) nm; IR (KBr) v.sub.max 3283, 2870, 1687, 1508, 1281, 1200, 1137, 1068, 860, 724 cm.sup.−1; ESIMS (positive) m/z 634.5; ESIMS (negative) m/z 632.6; HRESIMS (positive) m/z 634.2969 (calcd. for C.sub.31H.sub.44N.sub.3O.sub.11, 634.2976), and the molecular formula of this compound was identified as C.sub.37H.sub.43N.sub.3O.sub.11; .sup.13C and .sup.1H NMR are shown in Table 1.

(9) The trifluoroacetate salt of the compound of formula (IV): green oily liquid; [α].sub.D.sup.27 −21.4 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 203 (4.43), 288 (3.95), 325 (4.02) nm; IR (KBr) v.sub.max 3314, 2935, 2868, 1680, 1517, 1439, 1283, 1204, 1137, 1075, 802, 722 cm.sup.−1; ESIMS (positive) m/z 634.6; ESIMS (negative) m/z 632.5; HRESIMS (positive) m/z 634.2966 (calcd. for C.sub.31H.sub.44N.sub.3O.sub.11, 634.2976), and the molecular formula of this compound was identified as C.sub.31H.sub.43N.sub.3O.sub.11; .sup.13C and .sup.1H NMR are shown in Table 1.

(10) The trifluoroacetate salt of the compound of formula (V): green oily liquid; [α].sub.D.sup.27 −21.0 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.50), 218 (4.24), 233 (4.11), 287 (4.21), 316 (4.06) nm; IR (KBr) v.sub.max 3344, 2933, 2871, 1675, 1515, 1439, 1269, 1199, 1137, 1070, 802, 722 cm.sup.−1; ESIMS (positive) m/z 634.5; ESIMS (negative) m/z 632.4; HRESIMS (positive) m/z 634.2979 (calcd. for C.sub.31H.sub.44N.sub.3O.sub.11, 634.2976), and the molecular formula of this compound was identified as C.sub.31H.sub.43N.sub.3O.sub.11; .sup.13C and .sup.1H NMR are shown in Table 1.

(11) The trifluoroacetate salt of the compound of formula (VI): green oily liquid; [α].sub.D.sup.27 −33.6 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.52), 294 (4.10), 315 (4.13) nm; IR (KBr) v.sub.max 3314, 2931, 2876, 1677, 1509, 1437, 1280, 1205, 1136, 1077, 801, 722 cm.sup.−1; ESIMS (positive) m/z 796.7; ESIMS (negative) m/z 794.6; HRESIMS (positive) m/z 796.3482 (calcd. for C.sub.37H.sub.54N.sub.3O.sub.16, 796.3504), and the molecular formula of this compound was identified as C.sub.37H.sub.53N.sub.3O.sub.16; .sup.13C and .sup.1H NMR are shown in Table 1.

(12) The compound of formula (VII): green oily liquid; [α].sub.D.sup.27 −18.7 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.17), 288 (3.62), 313 (3.62) nm; IR (KBr) v.sub.max 3295, 2928, 2876, 1649, 1496, 1438, 1282, 1231, 1063, 825, 722 cm.sup.−1; ESIMS (positive) m/z 796.6; ESIMS (negative) m/z 794.7; HRESIMS (positive) m/z 796.3517 (calcd. for C.sub.37H.sub.54N.sub.3O.sub.16, 796.3504), and the molecular formula of this compound was identified as C.sub.37H.sub.53N.sub.3O.sub.16; .sup.13C and .sup.1H NMR are shown in Table 2.

(13) The trifluoroacetate salt of the compound of formula (VIII): green oily liquid; [α].sub.D.sup.27 −25.0 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.42), 281 (3.83), 314 (3.71) nm; IR (KBr) v.sub.max 3329, 2930, 2874, 1681, 1509, 1435, 1283, 1206, 1132, 1071, 802, 722 cm.sup.−1; ESIMS (positive) m/z 796.4; HRESIMS (positive) m/z 796.3517 (calcd. for C.sub.37H.sub.54N.sub.3O.sub.16, 796.3504), and the molecular formula of this compound was identified as C.sub.37H.sub.53N.sub.3O.sub.16; .sup.13C and .sup.1H NMR are shown in Table 2.

(14) The trifluoroacetate salts of the compounds of formula (IX) and formula (X): green oily liquid; [α].sub.D.sup.27 −19.0 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 205 (4.59), 281 (3.66) nm; IR (KBr) v.sub.max 3311, 2934, 2867, 1681, 1509, 1438, 1283, 1206, 1134, 1075, 801, 723 cm.sup.−1; ESIMS (positive) m/z 636.5; HRESIMS (positive) m/z 636.3129 (calcd. for C.sub.31H.sub.46N.sub.3O.sub.11, 636.3132), and the molecular formula of the compound was identified as C.sub.31H.sub.45N.sub.3O.sub.11; .sup.13C and .sup.1H NMR are shown in Table 2.

(15) The trifluoroacetate salt of the compound of formula (XI): green oily liquid; [α].sub.D.sup.27 −22.6 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.49), 224 (3.97), 282 (3.60) nm; IR (KBr) v.sub.max 3302, 2931, 2871, 1681, 1511, 1436, 1206, 1140, 1076, 801, 723 cm.sup.−1; ESIMS (positive) m/z 636.5; ESIMS (negative) m/z 634.7; HRESIMS (positive) m/z 636.3128 (calcd. for C.sub.31H.sub.46N.sub.3O.sub.11, 636.3132), and the molecular formula of this compound was identified as C.sub.31H.sub.45N.sub.3O.sub.11; .sup.13C and .sup.1H NMR are shown in Table 2.

(16) The trifluoroacetate salt of the compound of formula (XII): green oily liquid; [α].sub.D.sup.27 −17.3 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.68), 280 (3.68) nm; IR (KBr) v.sub.max 3341, 2933, 2881, 1675, 1516, 1440, 1283, 1194, 1064, 801, 723 cm.sup.−1; ESIMS (positive) m/z 798.5; HRESIMS (positive) m/z 798.3661 (calcd. for C.sub.37H.sub.56N.sub.3O.sub.16, 798.3661), and the molecular formula of this compound was identified as C.sub.37H.sub.55N.sub.3O.sub.16; .sup.13C and .sup.1H NMR are shown in Table 3.

(17) The trifluoroacetate salt of the compound of formula (XIII): green oily liquid; [α].sub.D.sup.27 −28.5 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 204 (4.51), 279 (3.52) nm; IR (KBr) v.sub.max 3342, 2930, 2874, 1682, 1508, 1436, 1281, 1207, 1133, 1071, 801, 722 cm.sup.−1; ESIMS (positive) m/z 798.6; HRESIMS (positive) m/z 798.3664 (calcd. for C.sub.37H.sub.56N.sub.3O.sub.16, 798.3661), and the molecular formula of this compound was identified as C.sub.37H.sub.55N.sub.3O.sub.16; .sup.13C and .sup.1H NMR are shown in Table 3.

(18) The compound of formula (XIV): green oily liquid; [α].sub.D.sup.27 −25.5 (c 0.50, MeOH); UV (MeOH) λ.sub.max (log ε) 205 (4.68), 279 (3.74) nm; IR (KBr) v.sub.max 3353, 2928, 2868, 1648, 1508, 1283, 1076, 815 cm.sup.−1; ESIMS (positive) m/z 798.7; ESIMS (negative) m/z 796.7; HRESIMS (positive) m/z 798.3632 (calcd. for C.sub.37H.sub.56N.sub.3O.sub.16, 798.3661), and the molecular formula of this compound was identified as C.sub.37H.sub.55N.sub.3O.sub.16; .sup.13C and .sup.1H NMR are shown in Table 3.

(19) TABLE-US-00001 TABLE 1 .sup.13C NMR and .sup.1H NMR data and attributions of compounds of formula (II)-formula (VI). formula II formula III formula IV formula V formula VI No. δ.sub.C.sup.a δ.sub.H.sup.a δ.sub.C.sup.a δ.sub.H.sup.a δ.sub.C.sup.a δ.sub.H.sup.a δ.sub.C.sup.a δ.sub.H.sup.a δ.sub.C.sup.a δ.sub.H.sup.a 1 8.21, t (5.7) 8.14, t (5.9) 8.17, t (5.3) 8.22, br s 8.10, t (5.8) 2 35.8 3.23, q (6.4) 35.8 3.24, q (6.5) 35.7 3.23, q (6.4) 35.8 3.24, q (5.7) 35.8 3.24, m 3 26.2 1.78, quint 26.2 1.78, quint 26.2 1.77, quint (7.1) 26.2 1.77, quint (6.8) 26.2 1.77, quint (6.8) (6.7) (6.8) 4 44.8 2.90, m 44.7 2.89, m 44.7 2.89 m 44.7 2.90, m 44.7 2.89, m 5 8.46, br s 8.47, br s 8.34, br s 8.34, br s 8.35, br s 6 46.6 2.88, m 46.5 2.88, m 46.5 2.89, m 46.5 2.89, m 46.5 2.89, m 7 23.1 1.53, quint 23.1 1.53, quint 23.1 1.51, quint (6.8) 23.1 1.53, quint (6.7) 23.1 1.53, quint (7.1) (7.1) (7.1) 8 26.3 1.42, quint 26.2 1.41, quint 26.2 1.41, quint (7.4) 26.2 1.42, quint (6.7) 26.2 1.42, quint (7.0) (6.8) (7.3) 9 37.8 3.04, q (6.5) 37.7 3.04, q (6.1) 37.7 3.04, q (6.1) 37.7 3.04, q (6.5) 37.7 3.04, q (6.1) 10 7.86, t (5.6) 7.83 t (5.6) 7.81, t (5.5) 7.82, t (5.5) 7.84, t (5.7) 1′ 126.3 126.4 126.2 129.4 126.4 2′ 113.9 6.95, d (1.9) 115.8 7.35, d (1.7) 113.8 6.94, m 114.1 7.02, d (1.6) 115.8 7.35, d (1.9) 3′ 145.6 145.5 145.5 146.9 145.5 4′ 147.5 148.5 147.4 146.7 148.5 5′ 115.8 6.75, d (8.1) 116.2 6.84, d (8.2) 115.7 6.75, d (8.1) 116.3 7.11, d (8.4) 116.2 6.84, d (8.2) 6′ 120.5 6.84, dd (8.2, 123 7.10, dd (8.2, 120.5 6.84, dd (8.2, 119.9 6.96, dd (8.5, 1.8) 122.9 7.11, dd (8.4, 1.9) 1.9) 1.6) 1.9) 7′ 139.5 7.26, d (15.7) 139.2 7.32, d (15.7) 139.5 7.26, d (15.6) 138.9 7.31, d (15.7) 139.3 7.32, d (15.7) 8′ 118 6.32, d (15.7) 118.8 6.41, d (15.8) 118 6.31, d (15.7) 119.9 6.43, d (15.5) 118.8 6.39, d (15.7) 9′ 166 165.9 166 165.7 165.9 1″ 136.3 132.1 132.2 132.1 136.2 2″ 115.8 6.65, d (2.0) 115.6 6.56, d (1.9) 116.8 6.95, m 115.6 6.55, d (1.9) 115.8 6.64, d (2.1) 3″ 146.7 145 145 144.9 146.6 4″ 143.6 143.3 144.9 143.3 143.6 5″ 117 6.99, d (8.2) 115.4 6.61, d (8.0) 115.6 6.70, d (8.1) 115.4 6.60, d (7.9) 116.9 6.99, d (8.3) 6″ 118.9 6.54, dd (8.3, 118.7 6.41, m 122.4 6.68, dd (8.2, 118.7 6.41, dd (7.9, 2.0) 118.9 6.54, dd (8.2, 2.0) 1.9) 1.6) 7″ 30.6 2.68, t (7.4) 30.6 2.61, t (7.5) 30.5 2.68, td (7.5, 30.6 2.62, t (7.4) 30.6 2.68, t (7.4) 2.9) 8″ 37.2 2.30, t (7.5) 37.6 2.26, t (7.4) 37.1 2.31, t (7.8) 37.6 2.26, t (7.5) 37.2 2.30, t (7.4) 9″ 171.4 171.5 171.4 171.5 171.3 1′″ 102.8 4.59, d (7.3) 102.1 4.74, d (7.3) 102.4 4.62, d (7.3) 101.7 4.75, d (7.3) 102.1 4.74, d (7.4) 2′″ 73.4 3.27, m 73.3 3.31, m 73.3 3.28, m 73.2 3.30, m 73.3 3.28, m 3′″ 75.9 3.27, m 76 3.29, m 75.9 3.27, m 75.8 3.28, m 76.0*.sup.1 3.28, m 4′″ 69.9 3.16, m 69.9 3.18, m 69.8 3.16, m 69.8 3.17, m 69.8 3.17, m 5′″ 77.2 3.28, m 77.3 3.36, m 77.3 3.30, m 77.2 3.34, m 77.3*.sup.2 3.36, m*.sup.4 6′″ 60.8 3.71, dd (11.8, 60.7 3.76, dd (11.8, 60.8 3.73, m, Ha 60.7 3.72, ddd (11.6, 60.8*.sup.3 3.76, ddd (11.8, 1.7), Ha 1.6), Ha 5.3, 1.9), Ha 5.1, 2.0), Ha*.sup.5 3.47, dd (11.9, 3.49, dd (11.9, 3.49, dt (11.8, 3.47, dt (11.8, 3.49, dt (11.9, 5.9), Hb 6.1), Hb 5.9), Hb 6.0), Hb 6.2), Hb*.sup.6 1″″ 102.7 4.58, d (7.5) 2″″ 73.3 3.28, m 3″″ 75.8*.sup.1 3.28, m 4″″ 69.8 3.17, m 5″″ 77.2*.sup.2 3.28, m*.sup.4 6″″ 60.7*.sup.3 3.71, ddd (11.8, 5.2, 1.9), Ha*.sup.5 3.47, dt (11.9, 6.0), Hb*.sup.6 3′-OH 9.12, s 8.79, br s* 4′-OH 9.41, br s* 9.06, br s 3″-OH 8.63, br s 8.43, br s 4″-OH 8.34, br s* 8.69, br s* 2″′-OH 5.53, br s 5.42, br s 5.53, br s*.sup.7 3″′-OH 5.10, d (4.3) 5.10, d (4.3) 5.11, d (4.6)*.sup.8 4″′-OH 5.06, d (5.2) 5.06, d (5.2) 5.08, d (5.3)*.sup.9 6″′-OH 4.66, t (5.7) 4.59, t (5.6) 4.64, t (5.9)*.sup.10 2″″-OH 5.49, br s*.sup.7 3″″-OH 5.08, d (5.3)*.sup.8 4″″-OH 5.04, d (5.3)*.sup.9 6″″-OH 4.59, t (5.8)*.sup.10 .sup.aMeasured in DMSO-d.sub.6 (.sup.1H NMR for 600 MHz, .sup.13C NMR for 150 MHz). *Assignment may be interchanged.

(20) TABLE-US-00002 TABLE 2 .sup.13C NMR and .sup.1H NMR data and attributions of compounds of formula (VII)- formula (XI). formula VII formula VIII formula IX formula X formula XI No. δ.sub.C.sup.a δ.sub.H.sup.a δ.sub.C.sup.c δ.sub.H.sup.c δ.sub.C.sup.a δ.sub.H.sup.a δ.sub.C.sup.a δ.sub.H.sup.a δ.sub.C.sup.b δ.sub.H.sup.b 1 7.88, br s 8.25, t (5.5) 8.01/7.98, t (5.8) 8.01/7.98, t (5.8) 2 36.9 3.18, m 35.8 3.17, q (4.8) 35.5 3.10, q (6.1) 35.5 3.10, q (6.1) 36.7 3.20, m 3 29.5 1.58, quint 25.9 1.76, quint 26.1 1.68, quint (6.6) 26.1 1.68, quint 27.5 1.71, quint (6.6) (5.8) (6.6) (7.0) 4 46.8 2.51, t (6.5) 44.9 2.86, m 44.6 2.78, m 44.6 2.78, m 46.1 2.58, m 5 8.47, br s 8.37, br s 8.37, br s 6 48.9 2.46, t (6.6) 46.6 2.86, m 46.6 2.84, m 46.6 2.84, m 48.6 2.79, m 7 26.8 1.35, m 23.1 1.52, quint 23.1 1.52, quint (7.1) 23.1 1.52, quint 24.6 1.49, m (6.4) (7.1) 8 27.1 1.37, m 26.3 1.40, quint 26.3 1.41, quint (6.9) 26.3 1.41, quint 27.5 1.49, m (6.9) (6.9) 9 38.4 3.01, q (5.8) 37.8 3.03, q (5.8) 37.8/37.6 3.04, q (6.1) 37.8/37.6 3.04, q (6.1) 39.3 3.16 t (5.9) 10 7.74, t (5.1) 7.89, t (5.4) 7.86/7.84, t (5.7) 7.86/7.84, t (5.7) 1′ 125.1 126.9 136.2/136.1 132.1/132.0 133.4 2′ 116.2 7.30, d (1.2) 119 7.81, d (1.7) 115.8 6.65, d (2.2) 115.7 6.56, m 117.8 7.04, br s 3′ 146 144.7 146.7 145 146.4 4′ 150.8 147.7 143.6 143.3 146.3 5′ 116.8 6.76, d (8.3) 115.4 6.77, d (8.3) 116.9 6.99, d (8.2) 115.4 6.61, d (8.0) 117.1 6.77, s 6′ 123.3 7.06, dd (8.3, 126.1 7.24, dd 118.9 6.55/6.54, dd 118.7 6.42/6.41, 124.6 6.77, s 1.3) (8.4, 1.6) (8.3, 2.3) dd (8.0, 2.3) 7′ 139 7.27, d (15.5) 137.4 6.52, d 30.6/30.5 2.69, t (7.4) 30.6/30.5 2.63, t (7.9) 31.8 2.84, t (7.1) (13.2) 8′ 118.3 6.34, d (15.7) 120.9 5.80, d 37 2.32, m 37.4/37.2 2.28, m 38 2.51, m (12.9) 9′ 165.5 166.6 172.2/172.1 172.2/172.1 176.3 1″ 132.2 136.2 132.1/132.0 136.2/136.1 133.7 2″ 116.9 6.96, br s 115.9 6.64, d (1.8) 115.7 6.56, m 115.8 6.65, d (2.2) 116.8 6.63, d (2.0) 3″ 145.1 146.7 145 146.7 146.1 4″ 145.1 143.7 143.3 143.6 144.5 5″ 115.7 6.68,s 116.9 6.99, d (8.2) 115.4 6.61, d (8.0) 116.9 6.99, d (8.2) 116.4 6.67, d (8.0) 6″ 122.5 6.68,s 119 6.54, dd 118.7 6.42/6.41, dd 118.9 6.55/6.54, 120.8 6.52, dd (8.0, (8.2, 1.7) (8.0, 2.3) dd (8.3, 2.3) 2.1) 7″ 30.6 2.67, td (8.2, 30.7 2.67, t (7.3) 30.6/30.5 2.61, t (7.9) 30.6/30.5 2.68, t (7.9) 32.4 2.76, t (7.4) 2.9) 8″ 37.2 2.30, t (7.7) 37.3 2.29, t (7.1) 37.4/37.2 2.28, m 37 2.32, m 39.3 2.41, t (7.5) 9″ 171.3 171.5 171.6/171.4 171.6/171.4 175.7 1′″ 102.6 4.69, d (7.1) 102.4 4.65, d (7.1) 102.7 4.58, d (6.8) 102.7 4.58, d (6.8) 103.6 4.80, d (7.8) 2′″ 73.4 3.29, m 73.3*.sup.1 3.29, m 73.3 3.26, m 73.3 3.26, m 74.9 3.47, m 3′″ 76.2*.sup.1 3.29, m 75.9*.sup.2 3.29, m 75.9 3.26, m 75.9 3.26, m 77.6 3.47, m 4′″ 69.9 3.18, m 69.6*.sup.3 3.20, m 69.9 3.15, m 69.9 3.15, m 71.3 3.38, m 5′″ 77.3 3.33, m*.sup.3 77.2*.sup.4 3.29, m 77.2 3.28, m 77.2 3.28, m 78.6 3.47, m 6′″ 60.9*.sup.2 3.76, br d 60.8 3.75, d 60.8 3.71, d (11.2), 60.8 3.71, d 62.4 3.97, dd (12.0), Ha*.sup.4 (11.7), Ha*.sup.5 Ha (11.2), Ha (12.0, 2.0), Ha 3.49, dd 3.48, m, Hb 3.47, dd (11.9, 3.47, dd 3.72, dd (11.8, 5.9), 6.0), Hb (11.9, 6.0), (12.0, 5.8), Hb Hb Hb 1″″ 102.5 4.62, d (7.2) 102.7 4.59, d (7.1) 2″″ 73.4 3.29, m 73.4*.sup.1 3.29, m 3″″ 76.0*.sup.1 3.29, m 76.0*.sup.2 3.29, m 4″″ 69.9 3.18, m 69.9*.sup.3 3.20, m 5″″ 77.3 3.29, m*.sup.3 77.3*.sup.4 3.29, m 6″″ 60.8*.sup.2 3.74, br d 60.8 3.71, d (11.2), Ha*.sup.4 (11.9), Ha*.sup.5 3.49, dd 3.48, m, Hb (11.8, 5.9), Hb 4′-OH 8.99, br s*.sup.6 3″-OH 8.47, br s*.sup.6 .sup.aMeasured in DMSO-d.sub.6 (.sup.1H NMR for 600 MHz, .sup.13C NMR for 150 MHz). .sup.bMeasured in CD.sub.3OD (.sup.1H NMR for 300 MHz, .sup.13C NMR for 75 MHz). .sup.cMeasured in DMSO-d.sub.6 (.sup.1H NMR for 300 MHz, .sup.13C NMR for 75 MHz). *Assignment may be interchanged.

(21) TABLE-US-00003 TABLE 3 .sup.13C NMR and .sup.1H NMR data and attributions of compounds of formula (XII) formula (XIV). formula XII formula XIII formula XIV No. δ.sub.C.sup.b δ.sub.H.sup.b δ.sub.C.sup.b δ.sub.H.sup.b δ.sub.C.sup.a δ.sub.H.sup.a 1 7.97, t (5.8) 8.01, t (5.8) 7.79, t (5.6) 2 35.5 3.09, q (6.4) 35.5 3.10, q (6.2) 36.8 3.04, q (5.9) 3 26 1.67, quint (6.8) 26.1 1.68, quint (7.4) 29.5 1.48, quint (6.8) 4 44.6 2.76, m 44.6 2.79, m 46.9 2.42, t (7.0) 5 8.36, br s 8.40, br s 6 46.6 2.82, m 46.6 2.85, m 49 2.41, t (7.0) 7 23.1 1.50, quint (7.0) 23.1 1.52, quint (7.1) 27 1.30, quint (6.8) 8 26.2 1.40, quint (6.9) 26.2 1.41, quint (7.5) 27.1 1.36, quint (6.6) 9 37.8 3.04, q (6.6) 37.8 3.04, q (6.1) 38.5 2.99, q (6.1) 10 7.83, t (5.6) 7.86, t (5.6) 7.74, t (5.5) 1′ 132 136.2 136.4 2′ 116.8*.sup.1 6.95, m 115.8 6.65, d (2.2) 116.8 6.55, br d (2.0) 3′ 145.1 146.9 150.2 4′ 144.9 143.6 144.5 5′ 115.6 6.70, d (8.1) 117 6.99, d (8.2) 117.8 6.91, d (8.2) 6′ 122.5 6.68, dd (8.2, 1.9) 118.9 6.55, dd (8.2, 2.4) 116.5 6.37, dd (8.2, 1.7) 7′ 30.5 2.70, m 30.6* 2.69, t (7.5) 30.9 2.63, m 8′ 36.9 2.34, t (7.7) 37 2.33, t (7.5) 37.4 2.27, t (7.3) 9′ 172.1 172 171.5 1″ 132.2 136.2 130.4 2″ 116.9*.sup.1 6.95, m 115.8 6.65, d (2.2) 117.4 6.90, br s 3″ 145.1 146.9 145.7 4″ 144.9 143.6 147.3 5″ 115.6 6.70, d (8.1) 117 6.99, d (8.2) 116.3 6.62, s 6″ 122.5 6.68, dd (8.2, 1.9) 118.9 6.55, dd (8.2, 2.4) 122.7 6.62, s 7″ 30.6 2.67, m 30.5* 2.68, t (7.9) 30.6 2.65, m 8″ 37.2 2.31, t (7.8) 37.2 2.30, t (7.4) 37.3 2.28, t (7.5) 9″ 171.5 171.4 171.4 1′″ 102.4 4.63, d (7.3)*.sup.2 102.7 4.58, d (6.6) 103.6 4.52, d (7.3) 2′″ 73.3 3.27, m 73.3 3.27, m 73.5*.sup.1 3.25, m 3′″ 75.9 3.27, m 75.9 3.27, m 76.2 3.25, m 4′″ 69.8 3.16, m 69.9 3.15, m 69.9 3.15, m 5′″ 77.3 3.31, m 77.2 3.27, m 77.3 3.25, m 6′″ 60.8 3.74, dd (11.8, 1.7), Ha*.sup.3 60.8 3.71, d (11.2), Ha 60.9 3.70, dd (11.5, 1.3), Ha*.sup.2 3.49, m, Hb 3.47, dd (11.8, 5.9), Hb 3.47, dd (12.4, 5.9), Hb*.sup.3 1″″ 102.4 4.62, d (7.3)*.sup.2 102.7 4.58, d (6.6) 103.1 4.58, d (7.4) 2″″ 73.3 3.27, m 73.3 3.27, m 73.4*.sup.1 3.25, m 3″″ 75.9 3.27, m 75.9 3.27, m 76.2 3.25, m 4″″ 69.8 3.16, m 69.9 3.15, m 69.9 3.15, m 5″″ 77.3 3.31, m 77.2 3.27, m 77.3 3.25, m 6″″ 60.8 3.74, dd (11.9, 1.9), Ha*.sup.3 60.8 3.71, d (11.2), Ha 60.9 3.73, dd (11.6, 1.4), Ha*.sup.2 3.49, m Hb 3.47, dd (11.8, 5.9), Hb 3.49, dd (12.3, 5.9), Hb*.sup.3 .sup.aMeasured in DMSO-d.sub.6 (.sup.1H NMR for 600 MHz, .sup.13C NMR for 150 MHz). .sup.bMeasured in DMSO-d.sub.6 (.sup.1H NMR for 600 MHz, .sup.13C NMR for 100 MHz). *Assignment may be interchanged.

Example 2 Antioxidant Activity Results of the Dicaffeoyl Spermidine Derivative Glycosides

(22) The antioxidant activity of the compounds was evaluated by using the oxygen radical absorbance capacity (ORAC) experiment. The detailed experimental procedure is as follows. 0.248 g of AAPH (2,2′-azobisisobutylamidine dihydrochloride) was added to a 50 mL phosphate buffer system to formulate a 18.3 mM AAPH stock solution. 20 μL of phosphate buffer, 20 μL solution of sample to be tested or standard substance Trolox (concentration of 6.25 μM) and 20 μL of fluorescent substance of disodium fluorescein (FL, concentration of 630 nM) were added to the wells of a 96-well plate in order. Then, 140 μL of AAPH (concentration of 18.3 mM) was quickly added to the wells of the 96-well plate, which was immediately placed in a GENios Luciferase-based microplate reader manufactured by Tecan, Switzerland, the excitation wavelength was set as 485 nm and the emission wavelength was set as 527 nm. The fluorescence intensity was measured every 2 minutes and recorded for a total of 100 min.

(23) The antioxidant capacity of the active substance is calculated as follows: Relative ORAC value=(AUC.sub.sample−AUC.sub.blank)/(AUC.sub.trolox−AUC.sub.blank). Wherein, AUC.sub.sample refers to the integral area under the fluorescence decay curve of the test sample, AUC.sub.trolox refers to the integral area under the fluorescence decay curve of the standard substance Trolox, and AUC.sub.blank refers to the integral area under the fluorescence decay curve when the test sample or the standard substance Trolox is not added. The detailed results are shown in Table 4:

(24) TABLE-US-00004 TABLE 4 Antioxidant activity results of dicaffolyl spermidine derivative glycosides ORAC value compound (μmol TE/μmol) formula II 2.04 ± 0.04 formula III 1.87 ± 0.04 formula IV 1.73 ± 0.04 formula V 2.96 ± 0.03 formula VI 2.71 ± 0.03 formula VII 1.02 ± 0.02 formula VIII 3.07 ± 0.02 formula IX and formula X 2.25 ± 0.02 formula XI 2.07 ± 0.03 formula XII 1.23 ± 0.04 formula XIII 2.06 ± 0.04 formula XIV 1.81 ± 0.05 EGCG 1.48 ± 0.02 EGCG (epigallocatechin gallate) represents a positive control drug treatment group.

(25) The experimental results in Table 4 show that the dicaffolyl spermidine derivative glycosides of the present invention have significant antioxidant activity, wherein most of these compounds have stronger antioxidant capacity than the positive control EGCG. Therefore, the compound of the present invention can be used as an antioxidant for the prevention and treatment of the corresponding diseases.

Example 3 Test Method for the Compounds in Improving the Activity of Learning and Memory of Senile Dementia Fruit Fly

(26) (1) Cultivation of Senile Dementia Fruit Fly

(27) W.sup.1118 (isoCJ1), as a background fruit fly of control group in the experiment, was abbreviated as “2U”. The fruit flies that successfully introduced with the pathogenic Aβ.sub.42 protein were (UAS-Aβ.sub.42; abbreviated as “H29.3”). This strain of fruit flies was hybridized with the fruit fly expressing the Gal4 promoter in whole brain, and the fruit fly strain carrying elav-GAL4.sup.c155 (P35) and Aβ.sub.42 was obtained.

(28) (2) Administration of Senile Dementia Fruit Fly

(29) Three groups of drug-free control of healthy fruit fly, drug-free control of disease fruit fly, and dose disease fruit fly were set in the experiment.

(30) All parents of tested fruit flies were housed and propagated at a constant temperature of 24° C. and a humidity of 42% RH (Relative humidity). On the first day after the emergence of the fruit flies, the fruit flies of control group and disease group, as well as the fruit flies to be administered were anesthetized with carbon dioxide, and then the fruit flies of the correct characters were selected into the glass tube containing food. During the dosing period, all tested fruit flies were kept in an incubator with a constant temperature of 28° C. and a constant humidity of 42% to ensure the drug taking efficiency of the fruit flies. Each day the fruit flies were administered for 4 hours, and the drug was administered from the second day after the fruit flies were selected until the 8th day.

(31) The drugs administered were prepared on the second day after the fruit fly selection, and were administered to the fruit flies on the day of preparation. The drugs were dissolved by 100% DMSO to a concentration of 10 mM. When preparing the working solution, the 10 mM stock solution was diluted to 100 μM with 4% sucrose. In addition, the fruit flies of control group were fed sucrose water containing 1% DMSO. For each Performance Index, two tubes of fruit fly groups are required, each tube containing about 100 fruit flies.

(32) Experiments were conducted in a light proof behavior room with constant temperature of 25° C., constant humidity of 70%. The method can be found in references.sup.[1-3].

(33) 1) During the training stage, about 100 flies were loaded into a training tube provided with a copper mesh cross electrode. Two kinds of odors of octanol (OCT) and methylcyclohexanol (MCH) were successively introduced for each 60 s with an intervals for 45 s of fresh air. 60 V pulsed electrical shock stimulation (US, pulse duration 1.5 s, interval 3.5 s) was applied to the fruit flies while introducing the 1.sup.st odor. No electrical shock was applied when the second odor (CS−) was introduced. Thereby one training cycle was completed.

(34) 2) In the transient memory (learning) ability test, the fruit flies that completed one training cycle were immediately transferred to the selection point of T-Maze, while CS+ and CS− were introduced from the opposite two directions. After two minutes of selection, the fruit flies on both sides were collected separately and counted after anesthesia or sacrifice. The calculation formula for the performance index (PI) is as follows: PI=[(CS−)−(CS+)]/[(CS−)+(CS+)]×100.

(35) Using OCT and MCH as CS+ for training and testing respectively, the average of the two PIs obtained was used as PI for one experiment. PI=0 indicates that the selection of the fruit flies for the two odors in the test was 50:50, i.e., no memory was formed; PI=100 indicated that the fruit flies in the test all escaped the odor accompanying the electrical shock, i.e., perfect memory. When performing the activity test, the short-term memory deficit tests for the olfactory sensation of the non-administered healthy flies with the same genetic background (2U*H29.3), non-administered Senile dementia disease flies (P35*H29.3), and test drug administered Senile dementia disease flies were also conducted, and their total learning and memory performance indexes (PIs) was calculated respectively. The learning and memory performance index of the test drug administered Senile dementia disease flies was compared with the performance index of the non-administered healthy flies with the same genetic background (2U*H29.3), and the performance index of the non-administered Senile dementia disease flies (P35*H29.3), to evaluate effect of the test drugs against Senile dementia. The relatively higher learning and memory performance index of the test drug administered Senile dementia disease flies indicates stronger effect of the test samples against Senile dementia. One-way analysis of variance (ANOVA) was used for the comparison. As for the learning and memory performance index of the test drug administered Senile dementia disease flies and the learning and memory performance index of the non-administered (only solvent without drug sample was administered) Senile dementia disease flies, P<0.05 means a significant difference, P<0.01 means a very significant difference, P<0.001 means an extremely significant difference.

(36) The data analysis and graphical display were processed by GraphPad Prism 5.01; see Table 5 for detailed results.

(37) TABLE-US-00005 TABLE 5 The result for the dicaffeoyl spermidine derivative glycosides in improving the activity of learning and memory of Senile dementia fruit flies a b c Genotype/drug PI (100 μM) Genotype/drug PI (100 μM) Genotype/drug PI (100 μM) 2U*H29.3 51.0 ± 1.3   2U*H29.3 50.1 ± 1.0   2U*H29.3 50.2 ± 1.2 P35*H29.3 27.2 ± 1.6.sup.#   P35*H29.3 22.4 ± 2.7.sup.#   P35*H29.3 23.3 ± 3.4.sup.# Memantine 43.1 ± 0.9*** Memantine 42.7 ± 0.9*** Memantine 44.2 ± 2.1*** formula II 35.5 ± 3.8*  formula VII 44.6 ± 2.5*** formula XIV 44.6 ± 1.2*** formula III 42.9 ± 1.6*** formula VIII 32.2 ± 2.3*  formula IV 42.2 ± 2.1*** formula IX 39.8 ± 2.4*** and formula X formula V 35.0 ± 1.3*  formula XI 37.2 ± 2.9*** formula VI 40.2 ± 3.1*** formula XII 33.5 ± 3.0**  formula XIII 42.5 ± 3.0*** 2U*H29.3 represents a healthy fruit fly; P35*H29.3 represents a disease fruit fly; memantine represents a positive control drug treatment group. The drug treatment group was administered at a concentration of 100 μM. Compared with 2U*H29.3 group, .sup.#P < 0.001; compared with P35*H29.3 group, **P < 0.01, ***P < 0.001; n = 6, One-way analysis of variance (ANOVA).

(38) The experimental results in Table 5 show that all the compounds of the present invention can improve the learning and memory function of Senile dementia fruit fly, and the effects of most of the compounds are superior to that of the positive control drug memantine or equivalent to that of the positive control drug.

Example 4 Anti-Respiratory Syncytial Virus (RSV) Activity Results of Dicaffeoyl Spermidine Derivative Glycosides

(39) (1) Cytotoxicity Assay

(40) 1) HEp-2 cells were seeded in 96-well cell culture plates at 100 μL/well and the cell density was 2.5×10.sup.5/mL. The cells were cultured in a 37° C., 5% CO.sub.2 incubator and grown into a cell single layer over about 20 h.

(41) 2) The culture fluid in the 96-well plate was discarded and the sample to be tested was half diluted into different concentrations by using maintenance solution. For each dilution, 3 replicate wells were set at 100 μL/well, and cell control wells were also set at the same time. Then they were placed in the incubator to continue the culture.

(42) 3) The cytopathic effect caused by sample toxicity was observed every day. After 72 hours, the culture solution was discarded, and according to the MTT method, 30 μL of 5 mg/mL MTT solution was added into each well. They were placed in the incubator to continue the incubation for 4 h in dark.

(43) (2) Cytopathic Effect Assay (CPE)

(44) 1) HEp-2 cells were seeded in 96-well cell culture plates at 100 μL/well and the cell density was 2.5×10.sup.5/mL. The cells were cultured in a 37° C., 5% CO.sub.2 incubator and grown into a cell single layer over about 20 h.

(45) 2) The culture fluid in the 96-well plate was discarded and the sample to be tested was half diluted by using maintenance solution with the starting concentration of the monomeric compound being 50 μM, and 50 μL of sample and 50 μL of 100×TCID50 of virus dilution being added into each well. The positive control drug Ribavirin group, virus control group and cell control group were set and placed in a 37° C., 5% CO.sub.2 incubator for culture.

(46) 3) The culture was continued for 60-72 hours, and the viral lesions in each group were recorded when the lesions were completely developed in the virus control group.

(47) 4) The virus-induced cytopathic effect was recorded as follows: no cellular lesion was recorded as “−”, 0 to 25% cellular lesions was recorded as “+”, 25% to 50% cellular lesion was recorded as “++”, 50%˜75% of cellular lesion was recorded as “+++”, and 75% to 100% of cellular lesion was recorded as “++++”. The sample concentration corresponding to the “++” lesion level is the half inhibitory concentration IC.sub.50 of the sample against the virus.

(48) 5) Three replicates were performed independently for each experiment.

(49) The detailed results were shown in Table 6.

(50) TABLE-US-00006 TABLE 6 Anti-respiratory syncytial virus (RSV) activity results of dicaffeoyl spermidine derivative glycosides Compound MNCC (μM) CC.sub.50 (μM) IC.sub.50 (μM) SI = CC.sub.50/IC.sub.50 formula II >100 >100 25 >4 formula III >100 >100 25 >4 formula IV >100 >100 25 >4 formula V >100 >100 25 >4 formula VI >100 >100 25 >4 formula VII >100 >100 50 >2 formula VIII >100 >100 50 >2 formula IX >100 >100 25 >4 and formula X formula XI >100 >100 25 >4 formula XII >100 >100 50 >2 formula XIII >100 >100 25 >4 formula XIV >100 >100 50 >2 Ribavirin 15.32 ± 4.31 37.88 ± 3.82 2.5 15

(51) The experimental results in Table 6 show that the compounds II-XIV of the present invention all have an anti-respiratory syncytial virus effect and are useful as antiviral agents.

(52) The present disclosure merely illustrates some of the claimed embodiments, wherein the technical features recited in one or more technical solutions may be combined with any one or more technical solutions, and these technical solutions obtained by combination are also within the claimed scope of the present application, it is as same as these technical solutions obtained by combination have been specifically described in the present disclosure.

REFERENCES

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