Академический Документы
Профессиональный Документы
Культура Документы
Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jep
Ethnopharmacological communication
art ic l e i nf o
a b s t r a c t
Article history:
Received 14 May 2014
Received in revised form
7 October 2014
Accepted 21 October 2014
Available online 4 November 2014
Ethnopharmacological relevance: Derris indica (Lamk.) Bennet has been used in traditional medicine in
many countries for the treatment of bronchitis, whooping cough, rheumatic joints and dipsia in diabetes.
In addition, several studies have revealed that this plant displayed various pharmacological activities
including anti-diabetic. The present study was designed to isolate the active compounds from its stem
bark and evaluate their inhibitory activity on the formation of advanced glycation end products.
Material and methods: The EtOAc extract of the stem bark of Derris indica was isolated by column
chromatographic techniques. The structures of isolated compounds were established on the basis of
extensive spectroscopic methods. All compounds were assayed for their inhibitory effects on advanced
glycation end products formation using BSAmethylglyoxal assay.
Results: Chromatographic fractionation of the EtOAc extract of Derris indica stem bark led to the isolation
of two new pyranoavonoids, derrisins A and B (12), along with 11 known avonoids (313). The
inhibitory activities of the compounds on the formation of advanced glycation end products were
evaluated. Derrisin B (2) was the most active compound with IC50 value of 18.0 mM, and displayed
stronger inhibitory activity compared with positive control aminoguanidine.
Conclusions: This study provided the possibility that a pyranoavonoid (2) found in Derris indica might
have therapeutic potential as an inhibitor against the formation of advanced glycation end products.
& 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords:
Derris indica
Flavonoid
Pyranoavonoid
Advanced glycation end products
Antiglycation
1. Introduction
Advanced glycation end products (AGEs) are unstable and
irreversible substances generated in the glycation process, a nonenzymatic reaction that initiates from a complex cascade of several
reactions between reducing sugars and free amino groups. AGEs can
react with other free amino groups leading to protein modication
such as alternative protein half-life, immune system, and enzyme
function. Thus they contribute to the pathophysiology of age-related
diseases, including diabetes, atherosclerosis, end-stage renal disease,
and neurodegenerative disease (Brownlee, 1995). More particularly,
the presence and accumulation of AGEs play an important role in the
development and complications of diabetes (Ahmed, 2005; Goldin
et al., 2006). Due to the emerging evidence about the adverse effects
of AGEs on the patients with diabetes, the use of anti-AGEs therapy
http://dx.doi.org/10.1016/j.jep.2014.10.053
0378-8741/& 2014 Elsevier Ireland Ltd. All rights reserved.
438
13
H (mult, J in Hz)
5.10 d (12.4)
4.58 dd (2.0, 12.4)
83.9
72.8
192.1
129.2
112.7
161.9
107.3
160.6
111.9
136.1
127.3
129.3
128.5
129.3
127.3
77.5
70.7
61.0
25.6
21.9
20.6
169.8
20.4
169.5
2
3
4
5
6
7
8
9
10
10
20
30
40
50
60
2
3
4
2-Me
2-Me
3-OAc
5.17 d (4.8)
6.26 d (4.8)
1.41 s
1.45 s
2.05 s
4-OAc
1.94 s
3-OH
3-OMe
3-OH
4-OH
3.70 d (1.6)
7.85 d (8.8)
6.63 d (8.8)
7.46m
7.39 m
7.40 m
7.39 m
7.46 m
H (mult, J in Hz)
7.93 d (8.8)
6.83 d (8.8)
8.10 m
7.48 m
7.46 m
7.48 m
8.10 m
3.90 dd (5.2, 6.4)
5.20 dd (5.2, 5.2)
1.44 s
1.55 s
3.80 s
3.28 d (5.6)
3.54 d (5.6)
C
154.8
141.3
174.5
126.9
116.2
155.6
110.0
157.5
118.1
130.8
128.3
130.7
128.7
130.7
128.3
79.2
71.5
62.0
25.0
22.0
60.1
439
et al., 1988; Tanaka et al., 1992; Das et al., 1994; Yoshioka et al.,
2004; Koysomboon et al., 2006; Lee and Park, 2012 ).
Compound 1 was isolated as colorless needle-like crystals and its
molecular formula C24H24O8 was deduced from HR-ESI-MS at mz
441.1598 [M H] (calcd 441.1544), implying 13 degrees of unsaturation. The 1H NMR data, taken in conjunction with the UV absorption
maxima at 254 and 316 nm, were indicative of a avanone skeleton.
The 1H NMR spectrum of 1 (Table 1) displayed characteristic signals
for two tertiary methyls (H 1.41 s, 1.45 s), two acetyl methyls (H 1.94
s, 2.05 s), and one unsubstituted phenyl ring (H 7.39 m, 2H; 7.40 m,
1H; 7.46 m, 2H). In addition, signals for ortho-coupled aromatic
protons at H 6.63 and 7.85 (each d, J8.8 Hz) were observed,
attributable for an additional aromatic ring. Analysis of 13C NMR
and HSQC data further revealed the presence of two tertiary methyls,
two acetyl methyls, four oxygenated methines, one oxygenated
quaternary carbon, 12 aromatic carbons (two oxygenated), and three
carbonyls (two esters and one ketone). On the basis of the above NMR
data, compound 1 had a tetracyclic skeleton due to nine units of the
13 unsaturations coming from three carbonyl groups and six carbon
carbon double bonds of two aromatic rings. The existence of a 2,2dimethyl-3,4-diacetyl-3,4-dihydro-2H-pyran moiety was corroborated by strong COSY correlations between H-3 and H-4, and HMBC
correlations from both tertiary methyls (2-Me 2) to oxygenated
C-2 and C-3 (Fig. 2). The location of two acetyl groups at C-3 and
C-4 was conrmed by HMBC correlations from H-3 and H-4 to
their carbonyl carbons. Indeed, the NMR data of 1 were very similar to
those of 3-methoxy-(3,4-dihydro-3,4-diacetoxy)-2,2-dimethylpyrano-(7,8:5,6)-avone (Koysomboon et al., 2006), except for the
replacement of the 2,3 double bond by the CH(2)CH(OH)(3) unit
in 1. Finally, a single-crystal X-ray diffraction study conrmed the
gross structure of 1 and allowed the determination of its relative
Fig. 1. Structures of compounds 113 isolated from the stem bark of Derris indica.
440
the methoxyl protons and the double bond carbon C-3 conrmed its
location at the C-3 position. The relative conguration at C-3 and C-4
was deduced from the NOESY interactions to be the same as that of 1,
due to the correlations of H-3H-4 and OH-3 and OH-4 (Fig. 4b).
Therefore compound 2 was identied as a new pyranoavone and was
named derrisin B.
Fig. 4. (a) 1H1H COSY and selected HMBC correlations of compound 2. (b) Diagnostic NOESY correlations of compound 2.
441
Brownlee, M.M., 1995. Advanced protein glycation in diabetes and aging. Annual
Review of Medicine 46, 223234.
Das, B., Chakravarty, A.K., Masuda, K., Suzuki, H., Ageta, H., 1994. A diterpenoid from
roots of Gelonium multiorum. Phytochemistry 37, 13631366.
Garcez, F.R., Scramin, S., Nascimento, M.C.D., Mors, W.B., 1988. Prenylated avonoids as evolutionary indicators in the genus Dahlstedtia. Phytochemistry 27,
10791083.
Gupta, S.C., Singh, F.P., Cook, I.B., Ternai, B., 1982. 13C NMR studies of some complex
natural oxygen heterocycles. V13C NMR spectra of furanoavones. Organic
Magnetic Resonance 20, 221223.
Koysomboon, S., Altena, I., Kato, S., Chantrapromma, K., 2006. Antimicrobacterial
avonoids from Derris indica. Phytochemistry 67, 10341040.
Lee, J.I., Park, S.B., 2012. An effective synthesis of 3-methoxyavones via 1-(2hydroxyphenyl)-2-methoxy-3-phenyl-1,3-propanediones. The Bulletin of the
Korean Chemical Society 33, 13791382.
Nohara, Y., Ususi, T., Kinoshita, T., Watanabe, M., 2002. Generation of superoxide
anions during the reaction of guanidine compounds with methylglyoxal.
Chemical and Pharmaceutical Bulletin 50, 179184.
Peng, X., Zheng, Z., Cheng, K.-W., Shan, F., Ren, G.-X., Chen, F., Wang, M., 2007.
Inhibitory effect of mung bean extract and its constituents vitexin and
isovitexin on the formation of advanced glycation end products. Food Chemistry 106, 475481.
Punitha, R., Manoharan, S., 2006. Antihyperglycemic and antilipidperoxidative
effects of Pongamia pinnata (Linn.) Pierre owers in alloxan induced diabetic
rats. Journal of Ethnopharmacology 105, 3946.
Rao, R.R., Tiwari, A.K., Reddy, P.P., Babu, K.S., Ali, A.Z., Madhusdana, K., Rao, J.M.,
2009. New furanoavanoids, intestinal alpha-glucosidase inhibitory and freeradical (DPPH) scavenging, activity from antihyperglycemic root extract of
Derris indica (Lam.). Bioorganic & Medicinal Chemistry 17, 51705175.
Semalty, A., Semalty, M., Kumar, P., Mir, S.R., Ali, M., Amin, S., 2012. Isolation and
hypoglycemic activity of a novel pongamiaavonylavonol from Pongamia
pinnata pods. International Journal of Pharmacology 8, 265270.
Sikarwar, M.S., Patil, M.B., 2012. Antidiabetic activity of Pongamia pinnata leaf
extracts in alloxan-induced diabetic rats. International Journal of Ayurveda
Research 1, 199204.
Talapatra, S.K., Mallik, A.K., Talapatra, B., 1980. Pongaglabol, a new hydroxyfuranoavone, and aurantiamide acetate, a dipeptide from the owers of Pongamia
glabra. Phytochemistry 19, 11991202.
Talapatra, S.K., Mallik, A.K., Talapatra, B., 1982. Isopongaglabol and 6-methoxyisopongaglabol, two new hydroxyfuranoavones from Pongamia glabra. Phytochemistry 21, 761766.
Tanaka, T., Iinuma, M., Yuki, K., Fujii, Y., Mizuno, M., 1992. Flavonoids in root bark of
Pongamia pinnata. Phytochemistry 31, 993998.
Thornelly, P.J., Langborg, A., Minhas, H.S., 1999. Formation of glyoxal, methylglyoxal
and 3-deoxyglucosone in the glycation of proteins by glucose. Biochemical
Journal 344, 109116.
Yadav, P.P., Ahmad, G., Maurya, R., 2004. Furanoavonoids from Pongamia pinnata
fruits. Phytochemistry 65, 439443.
Yoshioka, T., Inokuchi, T., Fujioka, S., Kimura, Y., 2004. Phenolic compounds and
avonoids as plant growth regulators from fruit and leaf of Vitex rotundifolia.
Zeitschrift fr Naturforschung C 59, 509514.