Letters

α-Glucosidase Inhibitory Activities of Isoflavanones, Isoflavones, and Pterocarpans from Mucuna pruriens Tshewang Dendup 1, Vilailak Prachyawarakorn 2, Acharavadee Pansanit 2, Chulabhorn Mahidol 1, 2, Somsak Ruchirawat 1, 2, 3, Prasat Kittakoop 1, 2, 3 1 Chulabhorn Graduate Institute, Chemical Biology Program, Bangkok, Thailand 2 Chulabhorn Research Institute, Bangkok, Thailand 3 Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Bangkok, Thailand

Abstract !

Three new isoflavanones (1–3) and thirteen known compounds (4–16) were isolated from the roots of Mucuna pruriens. The absolute configurations of isoflavanones 1–3 and parvisoflavanone (4), lespedeol C (5), and uncinanone C (6) were addressed by a circular dichroism technique. Isoflavanones, isoflavones, and pterocarpans of M. pruriens were found to be α-glucosidase inhibitors. Medicarpin (7) and parvisoflavone B (9) were potent αglucosidase inhibitors (twofold less active than the standard drug acarbose). The production of bioactive metabolites in M. pruriens seems to be season-dependent.

Key words Mucuna pruriens · Fabaceae · α‑glucosidase inhibitor · isoflavanone · isoflavone · pterocarpan Supporting information available online at http://www.thieme-connect.de/products

Mucuna pruriens L. (Fabaceae) is an annual herbaceous twining legume. In Thailand, seeds of M. pruriens are used as a nerve tonic and diuretic, and also for the treatment of male impotence and fevers. In India, entire parts of M. pruriens have many medicinal properties with more than 200 herbal formulations, especially in the Ayurvedic system of medicine for the treatment of Parkinsonism [1]. Extracts of M. pruriens exhibited various biological activities including sperm protection and improving male fertility [2], a hypoglycemic property [3], anticataleptic and antiepileptic activities [4], and symptomatic and neuroprotective efficacy [5]. Clinical studies demonstrated that the herbal preparation of M. pruriens showed promising effects for the treatment of Parkinsonʼs disease [6]. Although there have been several reports on the biological activities of M. pruriens crude extracts, only a few metabolites, e.g., L-3,4-dihydroxyphenylalanine (L-DOPA) and alkaloids, of this plant have been characterized [7–9]. LDOPA is the only M. pruriens metabolite that was evaluated for biological activity [2, 6], while other metabolites have never been explored for biological activities despite the fact that there have been a number of reports on bioactivities of the crude extracts. The crude extract of M. pruriens was previously reported to exhibit a hypoglycemic property [3], however, the active constituents have never been identified. Here, we report α-glucosidase inhibitory activity of the metabolites from M. pruriens.

Dendup T et al. α-Glucosidase Inhibitory Activities …

Roots of M. pruriens were collected in rainy and winter seasons, and their CH2Cl2 extracts were individually separated by chromatographic techniques. The sample collected in the rainy season gave compounds 1, 2, 6, 13, and 14, while that collected in the " Fig. 1). Compounds 1– winter provided 3–5, 7–12, 15, and 16 (l 3 were new isoflavanones. Thirteen known compounds including three isoflavanones (4–6), two pterocarpans (7 and 8), five isoflavones (9, 13–16), and three isoflavans (10–12) were obtained from M. pruriens. Known compounds, parvisoflavanone (4), lespedeol C (5), uncinanone C (6), (6aR,11aR)-medicarpin (7), maackiain (8), parvisoflavone B (9), (3R)-vestitol (10), (3R)-4′,7dihydroxy-2′,3′-dimethoxyisoflavan or (3R)-laxifloran (11), 8methoxyvestitol (12), formononetin (13), afrormosin (14), 8-Omethylretusin (15), and derrone (16) had identical spectroscopic data to those reported in the literature [10–20]. Compound 1, namely mucunone A (1), had a molecular formula of C20H18O6, and IR spectrum showed the presence of hydroxyl (3349 cm−1) and conjugated carbonyl (1640 cm−1) functionalities. 1 H NMR spectrum of 1 showed the presence of 1,2,4-trisubstituted and pentasubstituted benzene rings, a 2,2-dimethylchromene moiety, a chelated hydroxyl group, an sp3 methine, and a nonequivalent oxygenated methylene. The 1H-1H COSY data showed the coupling between H2-2 and H-3, while the HMBC spectrum exhibited correlations from H2-2 to C-4, C-1′, and C-9; H-3 to C-4, C-1′, C-2′, and C-6′; H-8 to C-9 and C-10; and H-6′ to C-1′ and C-3. Chemical shifts of non-protonated carbons, C-2′ (δC 156.9) and C-4′ (δC 158.9), suggested that these carbons were attached to a hydroxyl group (OH). The HMBC correlations from H-3 to C-1′, C-2′, and C-6′; 2′-OH (δH 8.61, s) to C-1′, C-2′, and C-3′; and 4′-OH (δH 8.28, s) to C-3′, C-4′, and C-5′ allowed the assignment of C-2′ and C-6′ and the positions of the two OHs on the 1,2,4-trisubstituted aromatic ring. The downfield resonance (δH 12.73, s) of 5-OH implied that it had a hydrogen bonding with C-4 ketone. The HMBC correlations from H-4′′ to C-5, C-6, and C7; H-8 to C-6, C-9, and C-10; H2-2 to C-9; and 5-OH to C-5, C-6, and C-10 assigned the substituents on the pentasubstituted ben" Fig. 2. Upon zene ring. Selected HMBC correlations of 1 are in l these spectroscopic data, the structure of 1 was established. The optical rotation of 1 was close to zero, [α]29 D − 2.53, suggesting that it might exist as a racemic mixture. The insignificant Cotton effect in a CD spectrum supported the racemic nature of 1. Compound 2, namely mucunone B (2), exhibited a molecular formula of C21H20O6. The 1H and 13C NMR spectra of 2 and 1 were nearly superimposed, except for an additional methoxy group (δH 3.76; δC 55.5) in 2. HMBC correlations from 2′-OMe to C-2′ and from H-3 to C-1′, C-2′ and C-6′ established the 2′-OMe position in 2. Key HMBC correlations for 2 were observed from H2-2 to C-1′, C-4, and C-9; H-3 to C-1′, C-2′, C-6′, and C-4; 5-OH to C-5, C-6, and C-10; H-8 to C-6, C-7, C-9, and C-10; H-3′ to C-1′, C-2′, C4′, and C-5′; H-5′ to C-1′, C-3′, and C-4′; H-6′ to C-3, C-2′, and C-4′; H-3′′ to C-2′′, C-6, and 2′′-Me; and H-4′′ to C-2′′, C-5, C-6, and C-7. " Fig. 2. These data established the HMBC correlations of 2 are in l structure of 2. The absolute configuration of 2 was addressed by the CD technique. At the region of 320–352 nm, (3S)-isoflavanones exhibit a negative Cotton effect, whereas (3R)-isoflavanones have a positive Cotton effect [21]. The negative Cotton effect at 328 nm was observed for 2, indicating the 3S-configuration. Compound 3, namely mucunone C (3), had a molecular formula of C16H14O5. Again, NMR data revealed an isoflavanone skeleton in 3. The 1H NMR spectrum of 3 showed signals of para-disubstituted and 1,2,3,4-tetrasubstituted benzene rings, and a methoxy

Planta Med 2014; 80: 604–608

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

604

Letters

605

Fig. 2 Selected HMBC correlations of isoflavanones 1–3. (Color figure available online only.)

group. The HMBC spectrum established the structure of 3, showing the correlations of H2-2 to C-1′, C-4, and C-9; H-3 to C-1′, C-4, and C-2′ (or C-6′); H-5 to C-4, C-7, and C-9; H-6 to C-7, C-8, and C10; H-3′ (or H-5′) to C-1′ and C-4′; H-2′ (or H-6′) to C-1′, C-3, and C-4′; and 8-OMe to C-8. Selected HMBC correlations of 3 are in " Fig. 2. The CD spectrum of 3 displayed a positive Cotton effect l at 327 nm, indicating the 3R-configuration. Parvisoflavanone (4), lespedeol C (5), and uncinanone C (6) were previously isolated from plants [10–12], however, their absolute configuration has not yet been clarified. In the present work, 4 showed a positive Cotton effect at 337 nm, indicating the 3R-configuration. Compounds 5 and 6 exhibited a negative Cotton effect at 324 nm and 322 nm, respectively, revealing the 3S-configuration. This is the first report on the absolute configurations of 4– 6. It should be noted that isoflavanones obtained from M. pruriens have either a 3S- (i.e., 2, 5, and 6) or 3R-configuration (i.e., 3 and 4). The presence of the two configurations within the same plant could be due to (i) the enzymatic nature of this plant that catalyzes the formation of both R and S configurations at C-3 or (ii) racemization of isoflavanones leading to the presence of only the stable enantiomer. The latter is supported by the fact that isoflavanones can undergo racemization during extraction and pu-

rification procedures [22, 23]. Moreover, isoflavanone 1 was isolated as a racemate, supporting the idea that isomerization might also occur for isoflavanones obtained from M. pruriens. Compounds 1, 2, 7, 9, 10, and 12 displayed α-glucosidase inhibitory activity with respective IC50 values of 58.43, 115.01, 13.62, 12.19, 32.96, and 51.88 µM, while compounds 4, 5, 8, 14, and 15 were inactive (Table 1S, Supporting Information). The standard drug acarbose exhibited an IC50 value of 7.96 µM, therefore, 7 and 9 were considered potent α-glucosidase inhibitors (IC50 of 13.62 and 12.19 µM, respectively; twofold less active than acarbose). Previously, medicarpin (7) was reported as a potent α-glucosidase inhibitor [24]. It should be noted that compound 1 (IC50 58.43 µM) was twofold more active than its corresponding 2′OMe derivative 2 (IC50 115.01 µM). Therefore, the 2′-OH group of isoflavanones was important for the inhibition of α-glucosidase. Isoflavanones 10 (IC50 32.96 µM) and 12 (IC50 51.88 µM) with the 2′-OH group exhibited relatively the same activity as that of 1, supporting the importance of the 2′-OH for enzyme inhibition. It is possible that the inhibition of α-glucosidase is partly due to the hydrogen bonding between the 2′-OH and an enzyme active site. Moreover, isoflavanones 4 and 5 had both 2′-OMe and 3′-OMe, and their α-glucosidase inhibitory activities were completely diminished. While medicarpin (7) exhibited potent activity, its corresponding methylenedioxy derivative, maackiain (8),

Dendup T et al. α-Glucosidase Inhibitory Activities …

Planta Med 2014; 80: 604–608

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

Fig. 1 Structures of the isolated compounds 1–16.

Letters

was inactive, implying that the 4′-OMe was critically important for the α-glucosidase inhibitory activity. Compounds 1, 2, and 9 exhibited only weak cytotoxic activity against A549 and HuCCA1 cell lines with IC50 values of 53.1 to 73.2 µM, while 4, 5, 7, 8, 10– 12, 14, and 15 were inactive. The crude extract of M. pruriens was formerly reported to have hypoglycemic activity [3]; therefore, the activity is possibly due to isoflavanones, isoflavones, and pterocarpans described here. Plant flavonoids apigenin and chrysin are also sources of α-glucosidase inhibitors. Recently it was found that derivatives of apigenin and chrysin displayed more potent inhibitory activity toward α-glucosidase than the standard drugs acarbose and 1-deoxynojirimycin [25]. It is worth mentioning that the metabolites profile in M. pruriens seems to be season-dependent. M. pruriens is rich in bioactive metabolites (e.g., compounds 3–5, 7–12, 15, and 16) in winter, particularly with a relatively large amount (108 mg) of medicarpin (7), an α-glucosidase inhibitor. M. pruriens produces few metabolites (1, 2, 6, 13, and 14) in monsoon (rainy) season. M. pruriens is an annual plant (growing for only one season) that starts growing in monsoon season, reaches maturity in winter, and dies by the end of winter. Therefore, M. pruriens collected in monsoon season has less maturity than that collected in winter, and this could be the reason that it produces only a few metabolites during monsoon season, while that collected in winter produces many compounds because of its maturity. Season-dependent metabolite production in M. pruriens suggests that the collection time (period) for herbal medicines is important and may significantly affect the remedies.

Materials and Methods !

Plant material: Roots of M. pruriens were collected in two different seasons, monsoon (June 2011) and winter (February 2012), from Nakhonsawan Province, Thailand. M. pruriens was identified by P. Kittakoop, and a voucher specimen (no. CRI 679/56) was deposited at the Chulabhorn Research Institute, Thailand. Extraction and isolation: The first batch in monsoon season: Roots (1 kg) were air-dried, ground, and extracted sequentially with CH2Cl2 (10 L) and MeOH (8 L). The extracts were filtered and evaporated to yield CH2Cl2 (9.3 g) and MeOH extracts (28.8 g). A CH2Cl2 extract was subjected to silica gel vacuum column chromatography (10 × 6 cm) and eluted with a gradient system of hexane-CH2Cl2 (100 : 0 to 0 : 100, 1.5 L), then with a gradient system of CH2Cl2-MeOH (100 : 0 to 0 : 100, 1.5 L) to obtain fractions 1-F1 to 1-F15. Fraction 1-F11 (1.7 g) was separated by Sephadex LH-20 (3 × 115 cm) column chromatography (CC) and eluted with CH2Cl2-MeOH (1 : 1, 1.5 L) to yield 4 fractions (4-F1 to 4-F4). Fraction 4-F4 (0.13 g) was separated with silica gel CC (1 × 30 cm) and eluted with a stepwise gradient of EtOAc-hexane (1–20% of EtOAc, 200 mL) to yield 13 (10 mg) along with 5 fractions (5-F1 to 5-F5). Fraction 5-F4 (66.2 mg) was separated by preparative TLC, developed with 4 % MeOH in CH2Cl2, to give bands 6-B1 and 6-B2. The purification of 6-B2 (37.7 mg) was achieved by reversed-phase HPLC (Cosmosil C18 column, 20 × 250 mm), with MeCN‑H2O (48 : 52, flow rate 12 mL/min) as an eluent, to furnish 1 (16 mg). Fraction 5-F2 (73 mg) was separated on preparative TLC, developed with 27 % EtOAc in hexane, to afford 4 bands (7B1 to 7-B4). Fraction 7-B1 (19.6 mg) was purified by reversedphase HPLC (Sunfire C18 column, 19 × 250 mm), eluted with MeOH‑H2O (72 : 28, flow rate 12 mL/min), to yield 2 (8 mg). Fraction 7-B2 (18.6 mg) was purified by reversed-phase HPLC (Hichrom C18 column, 21.2 × 250 mm), eluted with a gradient sysDendup T et al. α-Glucosidase Inhibitory Activities …

tem of MeOH‑H2O (60–80% of MeOH over 60 min, flow rate 12 mL/min), to afford 6 (2.4 mg). Fraction 7-B4 (8.7 mg) was purified by reversed-phase HPLC, eluted with MeOH‑H2O (52 : 48, flow rate 12 mL/min), to yield 14 (2.3 mg). The second batch in winter: The air-dried roots of M. pruriens (1 kg) were ground and extracted sequentially with CH2Cl2 (10 L) and MeOH (8 L) to give CH2Cl2 (9.3 g) and MeOH extracts (81 g). A CH2Cl2 extract was fractionated by Sephadex LH-20 CC (4 × 58 cm), eluted with CH2Cl2-MeOH (50 : 50, 1 L; 0 : 100, 0.5 L), to obtain fractions 1-F1 to 1-F3. Fraction 1-F3 (3.8 g) was separated by MPLC (silica gel, 2.6 × 46 cm), eluted with a gradient system of CH2Cl2-hexane (from 50–100% of CH2Cl2, over 250 min), to afford 13 fractions (2-F1 to 2-F13). Fraction 2-F13 (1.5 g) was separated by MPLC using a gradient system of MeOH‑CH2Cl2 (from 2–10% of MeOH) to yield 15 fractions (3-F1 to 3-F15). Fraction 3-F2 (372 mg) was separated by preparative TLC, developed with 1% MeOH in CH2Cl2, to afford 3 bands (4-B1 to 4-B3). The fractionation of 4-B2 (199 mg) by Sephadex LH-20 CC (1 × 50 cm), using CH2Cl2-MeOH (1 : 1, 250 mL) as an eluent, furnished 4 fractions (5-F1 to 5-F4). Fraction 5-F4 (132 mg) was purified by reversed-phase HPLC (Symmetry C18 column, 30 cm × 19 mm), using MeOH‑H2O (60 : 40, flow rate 12 mL/min) as an eluent, to afford 7 (108 mg) and 8 (9.7 mg). Fraction 3-F3 (60 mg) was purified by reversed-phase HPLC (Hichrom C18 column, 25 cm × 21.2 mm), eluted with a gradient system of MeOH‑H2O (40–90 % of MeOH over 85 min, flow rate 12 mL/min), to afford 11 (22.5 mg) and 16 (3.5 mg). Fraction 3-F4 (67 mg) was purified by reversed-phase HPLC (Hichrom C18 column, 25 cm × 21.2 mm), eluted with a gradient system of MeOH‑H2O (55–60 % of MeOH over 40 min, flow rate 12 mL/min), to yield 12 (4 mg) and 15 (10.5 mg). Fraction 3-F5 (262 mg) was separated by preparative TLC, developed with 5 % acetone in CH2Cl2, to give 5 bands (9-B1 to 9-B5). Fraction 9-B3 (71.9 mg) was purified by reversed-phase HPLC (Hichrom C18 column, 25 cm × 21.2 mm), eluted with a gradient system of MeOH‑H2O (50–100 % of MeOH, flow rate 12 mL/min), to yield 4 (43.0 mg) and 9 (3.4 mg). Band 9B5 (26 mg) was purified by reversed-phase HPLC, eluted with a gradient system of MeOH‑H2O (50–100 % of MeOH over 60 min, flow rate 12 mL/min), to give 3 (2.1 mg). Likewise, the purification of 9-B4 (20 mg) by reversed-phase HPLC, eluted with MeOH‑H2O (60 : 40, flow rate 12 mL/min), afforded 10 (4.6 mg). Fraction 3-F6 (79 mg) was purified by reversed-phase HPLC, eluted with a gradient system of MeOH‑H2O (50–85 % of MeOH, flow rate 12 mL/min), to obtain 5 (6.8 mg). Mucunone A (1): Pale yellow oil; [α]29 D − 2.53 (c 1.11 in MeOH); UV (MeOH) λmax nm (log ε): 272 (5.19), 288 (4.66), 293 (4.73), 355 (3.86); FTIR (UATR) νmax · cm−1: 3349, 2976, 2926, 1640, 1624, 1570, 1460, 1443, 1386, 1282, 1155, 1117, 976, 830, 737; APCI‑TOF MS m/z: 355.1178 [M + H]+ (calcd. for C20H19O6, " Table 1. 355.1176); 1H and 13C NMR data (acetone-d6), see l Mucunone B (2): Pale yellow oil; [α]30 − 43.41 (c 0.67 in CHCl3); CD D (MeOH): 328 nm (Δε − 0.473), 261 nm (Δε − 1.919); UV (MeOH) λmax nm (log ε): 233 (3.44), 272 (3.97), 294 (3.47), 306 (3.38), 357 (2.62); FTIR (UATR) νmax · cm−1: 3380, 2973, 2928, 1645, 1463, 1386, 1280, 1155, 1119, 1034, 957, 829; APCI‑TOF MS m/ z: 369.1337 [M + H]+ (calcd. for C21H21O6, 369.1333); 1H and 13C " Table 1. NMR data (CDCl3), see l Mucunone C (3): Yellow amorphous solid; [α]25 D + 14.05 (c 0.21 in MeOH); CD (MeOH): 327 nm (Δε + 0.270), 299 nm (Δε + 0.358), 279 nm (Δε + 0.509), 239 nm (Δε + 0.309), 228 nm (Δε − 0.633), 225 nm (Δε + 1.716), 220 nm (Δε − 2.090); UV (MeOH) λmax nm (log ε): 283 (2.75), 482 (4.16); FTIR (UATR) νmax · cm−1: 3361,

Planta Med 2014; 80: 604–608

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

606

Letters

1

H (600 MHz) and 13C NMR (150 MHz) spectroscopic data of compounds 1–3. 1 (in acetone-d6) δC, type

2 3 4 5 6 7 8 9 10 1′ 2′ 3′ 4′ 5′ 6′ 2′′ 3′′ 4′′ 5-OH 8-OMe 2′-OH 2′-OMe 4′-OH 2′′-Me 2′′-Me

71.1, CH2 47.4, CH 198.9, C 159.5, C 103.3, C 162.2, C 96.2, CH 163.8, C 103.8, C 113.5, C 156.9, C 103.7, CH 158.9, C 107.8, CH 131.7, CH 78.8, C 127.1, CH 115.7, CH – – – – – 28.40, CH3* 28.44, CH3*

2 (in CDCl3) δH (J in Hz) 4.46, dd (11.0, 5.5) 4.61, t (11.0) 4.27, dd (11.0, 5.5) – – – – 5.87, s – – – – 6.44, d (2.4) 6.33, dd (8.3, 2.4) 6.93, d (8.3) 5.61, d (10.0) 6.57, d (10.0) 12.73, s – 8.61, s – 8.28, s 1.42, s* 1.41, s*

δC, type

3 (in CD3OD) δH (J in Hz)

70.4, CH2 46.7, CH 197.6, C 158.8, C 103.0, C 161.8, C 95.9, CH 162.8, C 103.2, C 115.0, C 158.6, C 99.7, CH 156.8, C 107.5, CH 130.8, CH 78.2, C 126.1, CH 115.4, CH – – – 55.5, CH3 – 28.43, CH3* 28.45, CH3*

4.40, dd (11.1, 5.5) 4.51, t (11.1) 4.28, dd (11.1, 5.5) – – – – 5.93, s – – – – 6.41, br s – 6.35, br d (7.4) 6.92, d (8.1) – 5.50, d (10.0) 6.63, d (10.0) 12.50, s – – 3.76, s – 1.45, s 1.45, s

δC, type 73.5, CH2 52.4, CH 194.0, C 124.5, CH 112.1, CH 159.3, C 136.6, C 157.7, C 116.0, C 128.0, C 130.7, CH 116.5, CH 158.0, C 116.5, CH 130.7, CH – – – – 61.3, CH3 – – – –

δH (J in Hz) 4.65, m 3.87, dd (8.0, 5.3) – 7.54, d (8.8) 6.57, d (8.8) – – – – 7.09, d (8.6) 6.75, d (8.6) – 6.75, d (8.6) 7.09, d (8.6) – – – – 3.83, s – – – –

* Assignments may be interchangeable in each column

2922, 2850, 1663, 1594, 1515, 1337, 1307, 1230, 1194, 1098, 835; APCI‑TOF MS m/z: 285.0761 [M – H]− (calcd. for C16H13O5, " Table 1. 285.0769); 1H and 13C NMR data (CD3OD), see l Optical rotation and CD data of 4, 5, and 6: Parvisoflavanone (4): [α]28 D + 16.60 (c 1.03 in MeOH); CD (MeOH): 337 nm (Δε + 0.675), 305 nm (Δε − 2.312), 282 nm (Δε + 3.375), 224 nm (Δε − 8.172), 218 nm (Δε + 0.764); lespedeol C (5): [α]25 D + 15.00 (c 0.14 in MeOH); CD (MeOH): 324 nm (Δε − 2.081), 270 nm (Δε + 2.288), 236 nm (Δε + 1.854), 225 nm (Δε − 4.379), 212 nm (Δε − 3.574), 205 nm (Δε + 7.885); uncinanone C (6): [α]25 D + 57.22 (c 0.27 in CHCl3); CD (MeOH): 322 nm (Δε − 1.132), 286 nm (Δε + 6.395), 221 nm (Δε − 4.929), 206 nm (Δε + 5.273). Assays for inhibition of α-glucosidase and cytotoxicity: An assay for α-glucosidase (Sigma, G5003 from Saccharomyces cerevisiae) was performed using a modified method described by Wu and coworkers [26]. Acarbose (Sigma; purity ≥ 95%) was used as a reference drug (IC50 value of 7.96 µM). Cytotoxic activity was assessed using the MTT method [27]. Doxorubicin (Sigma; purity > 98%) exhibited respective IC50 values of 1.10 and 0.90 µM for HuCCA-1 and A549 cell lines.

Supporting Information NMR spectra of compounds 1–3, general experimental procedures, and a table showing α-glucosidase inhibitory activity are available as Supporting Information.

Acknowledgements !

P. K. is supported by The Thailand Research Fund and the Center of Excellence on Environmental Health and Toxicology, Science & Technology Postgraduate Education and Research Development

Office (PERDO), Ministry of Education. T. D. is grateful to the Thailand International Development Cooperation Agency (TICA) for a student grant.

Conflict of Interest !

The authors declare no competing financial interest.

References 1 Warrier PK, Nambiar VPK, Ramankutty C. Indian medicinal plants: a compendium of 500 species, Vol. IV. Andhra Pradesh, India: Orient BlackSwan; 1995: 128–250 2 Singh AP, Sarkar S, Tripathi M, Rajender S. Mucuna pruriens and its major constituent L-DOPA recover spermatogenic loss by combating ROS, loss of mitochondrial membrane potential and apoptosis. PloS one 2013; 8: e54655 3 Gulati V, Harding IH, Palombo EA. Enzyme inhibitory and antioxidant activities of traditional medicinal plants: potential application in the management of hyperglycemia. BMC Complement Altern Med 2012; 12: 77 4 Champatisingh D, Sahu PK, Pal A, Nanda GS. Anticataleptic and antiepileptic activity of ethanolic extract of leaves of Mucuna pruriens: A study on role of dopaminergic system in epilepsy in albino rats. Indian J Pharmacol 2011; 43: 197–199 5 Kasture S, Pontis S, Pinna A, Schintu N, Spina L, Longoni R, Simola N, Ballero M, Morelli M. Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinsonʼs disease. Neurotox Res 2009; 15: 111–122 6 Katzenschlager R, Evans A, Manson A, Patsalos PN, Ratnaraj N, Watt H, Timmermann L, Van der Giessen R, Lees AJ. Mucuna pruriens in Parkinsonʼs disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry 2004; 75: 1672–1677 7 Misra L, Wagner H. Alkaloidal constituents of Mucuna pruriens seeds. Phytochemistry 2004; 65: 2565–2567

Dendup T et al. α-Glucosidase Inhibitory Activities …

Planta Med 2014; 80: 604–608

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

Table 1

607

Letters 8 Ghosal S, Singh S, Bhattacharya SK. Alkaloids of Mucuna pruriens chemistry and pharmacology. Planta Med 1971; 19: 280–284 9 Daxenbichler ME, Kleiman R, Weisleder D, VanEtten CH, Carlson KD. A new amino acid, (−)-1-methyl-3-carboxy-6, 7-dihydroxy-1, 2, 3, 4tetrahydroisoquinoline, from velvet beans. Tetrahedron Lett 1972; 13: 1801–1802 10 Assumpção RMV, Gottlieb OR. Flavonoids from Poecilanthe parviflora. Phytochemistry 1973; 12: 1188–1191 11 Miyase T, Ueno A, Noro T, Fukushima S. Studies on the constituents of Lespedeza cyrtobotrya M(IQ). II. The structures of haginin C, haginin D and lespedeol C. Chem Pharm Bull 1981; 29: 2205–2209 12 Tsanuo MK, Hassanali A, Hooper AM, Khan Z, Kaberia F, Pickett JA, Wadhams LJ. Isoflavanones from the allelopathic aqueous root exudate of Desmodium uncinatum. Phytochemistry 2003; 64: 265–273 13 Yoon JS, Sung SH, Park JH, Kim YC. Flavonoids from Spatholobus suberectus. Arch Pharm Res 2004; 27: 589–592 14 Hashidoko Y, Tahara S, Mizutani J. New complex isoflavones in the roots of yellow lupin: Lupinus luteus L., cv. Barpine. Agric Biol Chem 1986; 50: 1797–1807 15 Yahara S, Ogata T, Saijo R, Konishi R, Yamahara J, Miyahara K, Nohara T. Isoflavan and related compounds from Dalbergia odorifera. I. Chem Pharm Bull 1989; 37: 979–987 16 Rao CP, Krupadnam GLD. An isoflavan from Millettia racemosa. Phytochemistry 1994; 35: 1597–1599 17 El-Sebakhy NA, Asaad AM, Abdallah RM, Toaima SM, Abdel-Kader MS, Stermitz FR. Antimicrobial isoflavans from Astragalus species. Phytochemistry 1994; 36: 1387–1389 18 de Rijke E, de Kanter F, Ariese F, Brinkman UAT, Gooijer C. Liquid chromatography coupled to nuclear magnetic resonance spectroscopy for the identification of isoflavone glucoside malonates in T. pratense L. leaves. J Sep Sci 2004; 27: 1061–1070 19 Herath HMTB, Dassanayake RS, Priyadarshani AMA, De Silva S, Wannigama GP, Jamie J. Isoflavonoids and a pterocarpan from Gliricidia sepium. Phytochemistry 1998; 47: 117–119 20 Máximo P, Lourenço A, Feio SS, Roseiro JC. A new prenylisoflavone from Ulex jussiaei. Z Naturforsch C 2002; 57: 609–613 21 Slade D, Ferreira D, Marais JP. Circular dichroism, a powerful tool for the assessment of absolute configuration of flavonoids. Phytochemistry 2005; 66: 2177–2215

Dendup T et al. α-Glucosidase Inhibitory Activities …

22 Zhao M, Duan JA, Che CT. Isoflavanones and their O-glycosides from Desmodium styracifolium. Phytochemistry 2007; 68: 1471–1479 23 Tanaka H, Hirata M, Etoh H, Sako M, Sato M, Murata J, Murata H, Darnaedi D, Fukai T. Six new constituents from the roots of Erythrina variegata. Chem Biodivers 2004; 1: 1101–1108 24 Choi CW, Choi YH, Cha MR, Yoo DS, Kim YS, Yon GH, Hong KS, Kim YH, Ryu SY. Yeast α-glucosidase inhibition by isoflavones from plants of Leguminosae as an in vitro alternative to acarbose. J Agric Food Chem 2010; 58: 9988–9993 25 Wang QQ, Cheng N, Yi WB, Peng SM, Zou XQ. Synthesis, nitric oxide release, and α-glucosidase inhibition of nitric oxide donating apigenin and chrysin derivatives. Bioorg Med Chem 2014; 22: 1515–1521 26 Wu Y, Yang JH, Dai GF, Liu CJ, Tian GQ, Ma WY, Tao JC. Stereoselective synthesis of bioactive isosteviol derivatives as α-glucosidase inhibitors. Bioorg Med Chem 2009; 17: 1464–1473 27 Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 1987; 47: 936–942 received revised accepted

September 5, 2013 March 7, 2014 March 20, 2014

Bibliography DOI http://dx.doi.org/10.1055/s-0034-1368427 Published online April 29, 2014 Planta Med 2014; 80: 604–608 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0032‑0943 Correspondence Dr. Prasat Kittakoop Chulabhorn Research Institute Kamphaeng Phet 6 Road, Laksi Bangkok 10210 Thailand Phone: + 6 68 69 75 57 77 Fax: + 66 25 53 85 45 [email protected]

Planta Med 2014; 80: 604–608

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

608

Copyright of Planta Medica is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.

α-Glucosidase inhibitory activities of isoflavanones, isoflavones, and pterocarpans from Mucuna pruriens.

Three new isoflavanones (1-3) and thirteen known compounds (4-16) were isolated from the roots of Mucuna pruriens. The absolute configurations of isof...
183KB Sizes 0 Downloads 3 Views