pharmacological and analytical aspects of bergenin: a concise report 张 慧 2012213034 asian...
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Pharmacological and analytical aspects of bergenin: a concise report
张 慧2012213034
Asian Pacific Journal of Tropical Disease (2012) 163–167
Abstracts
Present review described the pharmacological activity, analytical methods and isolation techniques of bergenin, which give an idea about the nature and activity of bergenin.
This review could be helpful to the researchers in the future for the development of new drugs for the treatment of various types of illness.
The data in the present review were collected from the available literature sources.
Contents
1. Introduction
2. Pharmacological activity
3. Physicochemical properties of bergenin
4. Chemical derivative of bergenin
5. Isolation of bergenin
6. Analytical techniques
7. Discussion
Structure of bergenin.
1. Introduction
O
HO
OH
H3CO
O
HOH
O
HOH
OH
1 2 3
44a
566a
78
9
10 10a10b
COOH
HO
O
HO
H3C
1. Introduction
OHO
HOOH
OH
OH
O
HO
OH
H3CO
COOH
HOH
HOH
OH
1 23
44a
66a78
9
10 10a10b
OH
O
HO
OH
H3CO
O
HOH
O
HOH
OH
1 23
44a
566a78
9
10 10a10b
O
HO
OH
H3CO
O
HOH
O
HOH
OH
1 23
44a
566a78
9
10 10a10b
1. Introduction
a colourless crystalline polyphenol It is hydrolyzable tannin and an isocoumarin derivative with three hydroxyl (OH) groups and two phenolic OH groups
O
HO
OH
H3CO
O
HOH
O
HOH
OH
1 23
44a
566a78
9
10 10a10b
Bergenial crassifoliaMallotus philippinensisCorylopsis spicataCaesalpinia digynaMallotus japonicus
•Isolated from
2. Pharmacological activity2.1 Antiinflammatory activity
2.2 Antimicrobial activity
Bergenin
modulation of Th1/Th2 cytokine balance
show anti-arthritic activity.
Norbergenin
inhibits the growth of the yeasts C. albicans, C.tropicalis, but presents lower activity against filamentous fungi Aspergillus flavus.
O
HO
OH
HO
O
HOH
O
HOH
OH
norbergenin
showed antioxidant activity in lipid peroxidation, superoxide and DPPH radical assays.
2.3 Antioxidant activity
Bergenin showed antiviral activity against herpes simplex virus type-1 in non cytotoxic concentrations.
2.4 Cytotoxic activity
2. Pharmacological activity
2.5 Effect of bergenin on bioavailability
bergenin-phospholipid complex(BPC)
extensive use
Bergenin exhibits various biological activities such as antiulcer, antifungal, immunomodulatory and burn wound healing.
in humanthe lack of a sensitive assay for its determination in biological fluids
2. Pharmacological activity
solid state characteristics
solution stability
dissociation constant
solubility
Physicochemical properties
octanol/water partition coefficient (Log P)
3. Physicochemical properties of bergenin
O
HO
OH
H3CO
O
HOH
O
HOH
OH
1 23
44a
566a78
9
10 10a10b
RAE-1
Properties:
White granular crystal, easily soluble in DMSO, pyridine, soluble in MeOH,
insoluble in P. ether, CH2Cl2 and EtOAc.
A dark spot under UV254 nm, no fluorescence under UV365 nm on silica gel
TLC. Turn gray-blue in 2% FeCl3-EtOH, and drab yellow in 5% PMA-EtOH.
Purity test:
GF254 silica gel TLCEtOAc: MeOH: H2O: HAc = 95: 5: 4: 5 Rf = 0.51
EtOAc: Me2CO: H2O: HAc = 7: 3: 0.3: 0.5 Rf = 0.51
CH2Cl2: MeOH: H2O: HAc = 82: 18: 1: 5 Rf = 0.47
RAE-1, 11.06 mg, 1H-NMR, in DMSO-d6 .
2.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
1.3
26
1.1
16
1.1
05
1.0
94
2.8
35
0.9
88
1.0
28
1.0
26
0.9
81
1.0
00
0.9
58
1.0
46
1.0
82
1.0
63
2.5
06
3.1
66
3.1
79
3.1
91
3.2
06
3.3
35
3.5
50
3.5
70
3.6
43
3.6
57
3.7
75
3.8
27
3.8
35
3.9
71
3.9
96
4.0
20
4.8
94
4.9
07
4.9
21
4.9
68
4.9
95
5.4
24
5.4
39
5.6
42
5.6
55
6.9
93
8.4
50
9.7
50
RAE-1
O
O
OH
HO
H
HOH
O
HO
O
OH
16
1114
2
7
15
49
12
solvent peak
water peak
6. 46. 66. 87. 07. 27. 47. 67. 88. 08. 28. 48. 68. 89. 09. 29. 49. 69. 810. 010. 210. 410. 6f1 (ppm)
1.04
6
1.08
2
1.06
3
6.9
93
8.4
50
9.7
50
H-4,s7-OH,s5-OH,s
RAE-1
O
O
OH
HO
H
HOH
O
HO
O
OH
16
1114
2
7
15
49
12
4.754.854.955.055.155.255.355.455.555.655.755.85f1 (ppm)
1.0
26
0.9
81
1.0
00
0.9
58
4.8
94
4.9
07
4.9
21
4.9
68
4.9
95
5.4
24
5.4
39
5.6
42
5.6
55
13-OH,d,5.3Hz
12-OH,d,5 Hz 16-OH,t
H-9,d,10.8 Hz
RAE-1
O
O
OH
HO
H
HOH
O
HO
O
OH
16
1114
2
7
15
49
12
RAE-1
H-14,dd,9.8 Hz,9.8 Hz
16-Hb,dd,11.6Hz,4.4HzOMe
O
O
OH
HO
H
HOH
O
HO
O
OH
16
1114
2
7
15
49
12
H-13,ddd,8.8 Hz,5.6 Hz,5.6 Hz
H-11,br t,8.8 Hz
16-Ha,ddd,12.4 Hz,6.8 Hz,6.8 Hz
H-12,ddd,8.8 Hz,6 Hz,6 Hz
No. Obs. (400 MHz, DMSO-d6) Ref. (400 MHz, DMSO-d6) Difference
H-4 6.99 (1H, s) 6.98 (s) 0.01
H-9 4.98 (1H, d, J = 10.8 Hz) 4.96 ( d, J = 10.4 Hz) 0.02
H-14 4.00 (1H, dd, J = 10, 9.6 Hz) 4.00 (dd, J = 10.4, 9.5 Hz) 0.00
H-16b 3.84 (1H, dd, J = 11.6, 4.4 Hz) 3.85 (dd, J = 10.9, 3.2 Hz) -0.01
H-15 3.78 (3H, s) 3.78 0.00
H-13 3.65 (1H, ddd, J = 8.8, 5.6, 5.6 Hz) 3.65 (ddd, J = 9.5, 8.8, 5.3 Hz) 0.00
H-11 3.57 (1H, t, J = 8.8 Hz) 3.58 (ddd, J = 7.6, 3.2, 1.9 Hz) -0.01
H 3.44 (1H, ddd, J = 12.4, 6.8, 6.8
Hz)
3.44 (ddd, J = 10.9, 8.1, 1.9
Hz)
0.00
H-12 3.20 (1H, ddd, J = 8.8, 6.6 Hz) 3.20 (ddd, J = 8.8, 7.6, 5.0 Hz) 0.00
5-OH 9.75 (1H, s) 9.76 (s) -0.01
7-OH 8.45 (1H, s) 8.45 (s) 0.00
13-OH 5.65 (1H, d, J = 5.2 Hz) 5.64 ( d, J = 5.3 Hz) 0.01
12-OH 5.43 (1H, d, J = 6 Hz) 5.42 ( d, J = 5 Hz) 0.01
16-OH 4.91 (1H, t) 4.91 (m) 0.00
Table 2-2 1H-NMR spectroscopic data for RAE-1 (400 MHz, DMSO-d6)
and compared with literature
Abreu H A, Lago I A, Souza G P et al. Antioxidant activity of (+)-bergenin—a phy- toconstituent isolated from the bark of Sacoglottis uchi Huber (Humireaceae) [J]. Organic and Biomolecular Chemistry, 2008, 6: 2713-2718.
4. Chemical derivative of bergenin
O
HO
OH
H3CO
O
HOH
O
HOH
OH
1 23
44a
566a78
9
10 10a10b
using .H, .OH, .CH3,and .CCl3
Frontier molecular orbital analysis
DFT thermodynamic calculations
RAE-13
Properties:
White amorphous powder, easily soluble in MeOH, insoluble in CH2Cl2.
A dark spot under UV254 nm, no fluorescence under UV365 nm on silica gel
TLC. Turn blue-black in 2% FeCl3-EtOH, light gray-blue in 5% PMA-EtOH, and
light red in 5% H2SO4-EtOH.
Purity test:
GF254 silica gel TLC
CH2Cl2 : MeOH : H2O : HAc = 8:2:2d:10d Rf = 0.45
CH2Cl2 : Me2CO : H2O : HAc = 5:5:2d:10d Rf = 0.39
Polyamide TLC
CH2Cl2 : MeOH : H2O : HAc = 6:4:3d:10d Rf = 0.44
Me2CO : MeOH : H2O : HAc = 7:3:4d:10d Rf = 0.60
EtOAc : MeOH : H2O : HAc = 6:4:7d:10d Rf = 0.48
RAE-13, 7 mg, 1H-NMR, in CD3OD .
RAE-13, 30 mg, 13C-NMR, in CD3OD .
O
HO
OH
H3CO
O
HOH
O
HO
OH
OH
OH
OHO
1 23
44a
566a78
9
10 10a10b 7' 1'2' 3'
4'
5'6'solvent peak water peak
RAE-13
O
HO
OH
H3CO
O
HOH
O
HO
OH
OH
OH
OHO
1 23
44a
566a78
9
10 10a10b 7' 1'2' 3'
4'
5'6'
H-2’, H-6’, s
H-7, s
H-4,dd,9 Hz,9.6 Hz
H-10b,d,10.8Hz
RAE-13
O
HO
OH
H3CO
O
HOH
O
HO
OH
OH
OH
OHO
1 23
44a
566a78
9
10 10a10b 7' 1'2' 3'
4'
5'6'
s, -OCH3
H-4a,t,10.2 Hz
H-3,dd,12 Hz
H-2,H-11,m,overlapped
RAE-13
O
HO
OH
H3CO
O
HOH
O
HO
OH
OH
OH
OHO
1 23
44a
566a78
9
10 10a10b 7' 1'2' 3'
4'
5'6'
solvent peak
RAE-13
O
HO
OH
H3CO
O
HOH
O
HO
OH
OH
OH
OHO
1 23
44a
566a78
9
10 10a10b 7' 1'2' 3'
4'
5'6'
7’ 4’
3’,5’
2’,6’
1’
OMe
112
34
4a
66a 78
91010a
10b
RAE-13
Table 1 13C-NMR spectroscopic data for RAE-13(600 MHz, CD3OD)
and compared with literature No. Obs. (600 MHz, CD3OD) Ref. (22.6 MHz,
MeOH-d4-DMSO-d6 (15: 1))
Difference
C-2 81.7 83.3 -1.6
C-3 68.7 70.3 -1.6
C-4 74.8 76.6 -1.8
C-4a 77.7 79.3 -1.6
C-6 164 166.1 -2.1
C-6a 117.9 119.7 -1.8
C-7 109.9 111.9 -2
C-8 151.0 152.9 -1.9
C-9 141.0 143.1 -2.1
C-10 148.0 150.0 -2
C-10a 115.6 117.5 -1.9
C-10b
C-11
OMe
72.9 74.5 -1.6
61 62.6 -1.6
60 61.4 -1.4
Takashi Y, Kaoru S, Yukiko T et al. Bergenin derivatives from Mallotus japonicus [J]. Phytochemistry, 1982, 21(5): 1180-1182.
No. Obs. (600 MHz, CD3OD) Ref. (22.6 MHz,
MeOH-d4-DMSO-d6 (15: 1))
Difference
C-1’ 119.9 121.9 -2
C-2’, C-6’ 109.1 111.2 -2.1
C-3’, C-5’ 145.1 147.2 -2.1
C-4’ 138.6 140.7 -2.1
C-7’ 166.4 168.6 -2.2
Table 1(continue) 13C-NMR spectroscopic data for RAE-13(600 MHz, CD3OD)
and compared with literature
Takashi Y, Kaoru S, Yukiko T et al. Bergenin derivatives from Mallotus japonicus [J]. Phytochemistry, 1982, 21(5): 1180-1182.
5. Isolation of bergenin
5. Isolation of bergenin
11-O-(4'-O-methylgalloyl)-bergenin
O
HO
OH
H3CO
O
HOH
O
HOH
HO
H3CO
OH
O
O
O
HO
OH
H3CO
O
HOH
O
HOH
OH
O
HO
OH
H3CO
O
HOH
O
HOH
OH
a dimer of bergenin
11-O-(3'-O-methylgalloyl)-bergenin
O
HO
OH
H3CO
O
HOH
O
HOH
OH
OHH3CO
O
O
4-O-galloylbergenin
O
HO
OH
H3CO
O
HOH
O
HO
OH
OH
OH
OHO
1
11-O-caf feoylbergenin
O
HO
OH
H3CO
O
HOH
O
HOH
O
O
OH
OH
11-O-acetylbergenin
O
HO
OH
H3CO
O
HOH
O
HOH
O
O
CH3
rivebergenin A(1) and B(2)
O
R2
R1
H3CO
O
HOH
O
HO
R3
R4 R5
OH
OH
OHO
1 R1=R2=OMe,R3=R5=H,R4=CH2OH2 R2=R3=OH,R1=R4=R5=CH2OH
O
HO
OH
HO
O
HOH
O
HOH
OH
norbergenin
6. Analytical techniquesPlant/Source method
Rodgersia HPLC ： Agilent Zorbax XDB-C18 columnmobile phase ： acetonitrile-0.2% phosphoric acid solution flow rate ： 1.0 mL/min
Bergenia purpurascens
HPLC
Bergenia ciliata Bergenia ligulata
TLC：toluene: ethyl acetate: formic acid (4:6:1, v/ v)
Bergenia ligulata Bergenia ciliataBergenia stracheyi
RP-HPLC method coupled with photodiode-array detection
Caesalpinia digyna LC-MS
Highest: Rodgersia sambucifolia Hemsl Lowest: Rodgersia aesculifolia Batalin
bergenin in human plasma after oral administration
high-performance liquid chromatography-tandem mass spectrometry
bergenin in human plasma after oral administration
liquid chromatography/tandem mass spectrometry
bergenin in rabbit plasma after intravenous administration
HPLC
bergenin in rat plasma after intravenous administration
reversed-phase HPLC
bergenin content in dicha kechuan oral liquid
HPLC
Bergenia species contain
most bergenin, so the most
potent plant species is used
in herbal formulations and
has the strongest desired
effect.
7. Discussion
Bergenia species are important medicinal plants distributed in South and East Asia and European countries. In India these plants grow at high altitudes in the Himalayas usually in rocky areas and on cliffs.
This review gives an idea about the nature and activity of bergenin which might be used in the future for the development of new drugs for the treatment of various type of illness.
Thank you！