Gymsyloside F and Gymsyloside G,Two New Pregnane Glycosides From the Leaves of Gymnema sylvestre and Their α-Glucosidase and α-Amylase Inhibitory Activities

Abstract

Two new pregnane glycosides were isolated from the leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. Their chemical structures were determined as (20S)−12β-tigloyloxy-5α-hydroperoxy-3β,8β,14β,17β,20-pentahydroxypregn-6-ene 3-O-β-D-glucopyranosyl-(1→4)‐6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (1) and (20S)−12β-benzoyloxy-5α-hydroperoxy-3β,8β,14β,17β,20-pentahydroxypregn-6-ene 3-O-β-D-glucopyranosyl-(1→4)‐6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside (2) on the basis of the extensive spectroscopic methods, including 1D, 2D NMR, HRESIMS, and in comparison with the reported data. At the concentration of 200 µM, compounds 1 and 2 showed moderate anti α-glucosidase and α-amylase activities with inhibitory percentage of 31.1 ± 1.2 and 42.3 ± 1.7% (for α-glucosidase), and 27.8 ± 1.3 and 34.5 ± 1.5% (for α-amylase), respectively.

Keywords

Apocynaceae pregnane gymsyloside

Gymnema sylvestre (Retz) R. Br. ex. Schult (Apocynaceae) known as “gur-ma” in Indian folklore, means “sugar killer,” have been used as a traditional diabetes medicine all over the world. In addition, methanol and other extracts of the leaves from G. sylvestre exhibit a variety of biological activities such as hypoglycemia, antioxidant, anti-obesity and antimicrobial.^1

-4 The principle chemical component of G. sylvestre are pregnaneglycosides^5
-7 and oleanane saponins.^8

-16 In the previous paper, we reported the isolation and structure elucidation of twelve pregnaneglycosides name gymsylosides A-F and gymnepregosides R-T.^6,7 Continue researching on bioactive compounds from the leave of G. sylvestre, we reported herein the isolation and structural elucidation of two new pregnaneglycosides and their α-glucosidase and α-amylase inhibition activities.

Results and Discussion

Compound 1 was obtained as a white amorphous powder. The molecular formula of 1 was determined to be C₆₀H₉₈O₂₇ base on the quasi-molecular ion peak [M + Na]⁺ at m/z 1273.6193, (calcd for [C₆₀H₉₈O₂₇Na]⁺ 1273.6193, Δ = 0,0 ppm) in the high resolution electron spray ionization mass spectrometry (HRESIMS) (Supplemental Figure S1). The ¹H NMR spectrum of 1 indicated the present of two methyl singlets at δ _H 1.51 and 1.03, one methyl doublet at δ _H 1.04 (J = 6.0 Hz), two olefinic protons at δ _H 5,60 and 5,96 (each, d, J = 10.0 Hz), suggesting the present of the pregnane skeleton having a double bond at C-6/C-7, which is a very typical frame type of the Gymnema species.^17,18 The tigloyl moiety was identified by the methyl signals at δ _H 1.78 (3H, d, J = 7.2 Hz), 1.84 (3H, s), and one olefinic proton at δ _H 6.94 (1H, q, J = 7.2 Hz). In addition, five anomeric protons [δ _H 4.81, 4.77 (each, d, J = 10.0 Hz), δ _H 4.56, 4.69, and 4.32 (each, d, J = 8.0 Hz)], four methoxy groups [δ _H 3.39, 3.41 × 2 and 3.57], and 4 sary methyl groups [δ _H 1.17, 1.19, 1.28, and 1.34 (each, d, J = 6.0 Hz)] suggested the occurrence of five Gymnema sugar units (Supplemental Figure S2).^17,18 In the aglycone ¹³C NMR spectrum of 1, 1 sary (δ _C 18.7), two tertiary methyl groups (δ _C 12.4 and 18.9), four oxygenated quaternary carbons (δ _C 75.1, 83.6, 88.3, and 89.2), and the double bond [δ _C 132.4 (CH) and 132.6 (CH)] were identified. The above data matched with the corresponding data of 5α-hydroperoxy-3β,8β,14β,17β,20-pentahydroxypregn-6-ene part of gymnepregosides A-Q, except for δ _C-5 value of 1 was strong downfield (δ _C-5 83.6), comparing to that of gymnepregosides A-Q [(which had OH group at C-5): δ _C-5 =74.7 ~ 75.1]^17,18 and similar to that of (24S)−24-ethyl-5α-hydroperoxycholesta-6,25-dien-3 β-ol and (24R)−24-ethyl-5α-hydroperoxy-cholest-6-en-3β-ol (δ _C-5 84.3)^19,20 (Supplemental Figure S3). These evidence suggested that compound 1 had one peroxy group at C-5. Furthermore, the positions of the double bond, tigloyl, and hydroxy groups were indicated by the observed HMBC correlations as shown in Figure 1. The sugar moieties was identified as D-cymarose (Cym I, II), D-oleandrose (Ole), 6-deoxy-3-O-methyl-D-allose (All), and D-glucose (Glc) by comparing the NMR data of them with those reported for gymnepregosides B and E,^17,18 and further indicated by HSQC, COSY, and HMBC spectra (Supplemental Figure S4-S6), as well as by acid hydrolysis followed by separation of individual sugars and their specific rotations. The large coupling constant of the anomeric protons (J = 7.6 ~ 9.6 Hz) indicated β-form of the glycosyl linkages. The HMBC correlations from Glc H-1 (δ _H 4.32) to All C-4 (δ _C 83.9), from All H-1 (δ _H 4.69) to Ole C-4 (δ _C 83.9), from Ole H-1 (δ _H 4.56) to Cym II C-4 (δ _C 83.8), from Cym II H-1 (δ _H 4.77) to Cym I C-4 (δ _C 83.9) and from Cym H-1 (δ _H 4.81) to aglycone C-3 (δ _C 75.6) were observed confirming the sugar moiety of 1 was 3-O-β-D-glucopyranosyl-(1→4)‐6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside.^17,18 In addition, HMBC correlation from H-12 (δ _H 4.64) to carbonyl carbon of the tigloyl group (δ _C 169.2) indicated that this group attached to C-12 by an ether linkage. All the NMR assignments of 1 were done by HSQC, HMBC, and COSY spectra (Tables 1 and 2). Furthermore, the configuration of 1 were proven by the similar biogenetic pregnane from Gymnema genus,^21,22 and further confirmed by the ROESY spectrum (Figure 2). The observed ROESY correlations between Hα−9 (δ _H 2.21) and Hα−1 (δ _H 1.57), between Hα−1 and H-3 (δ _H 4.07) suggested H-3 orientation was α. The ROESY cross peaks from Hα−9 to H-12 (δ _H 4.68), from H-12 to H₂-15 (δ _H 2.05), and from H₂-15 to CH₃-20 suggested 2 hoursydroxy groups at C-14 and C-17 were β-orientation (Supplemental Figure S8).^17,18 Based on the above evidence, the structure of 1 was elucidated as (20S)−12β-tigloyloxy-5α-hydroperoxy-3β,8β,14β,17β,20-pentahydroxypregn-6-ene 3-O-β-D-glucopyranosyl-(1→4)‐6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside, a new compound named gymsylosides F (Figure 3).

Figure 1

Important H-H COSY and HMBC correlations of compounds 1 and 2.

Table 1

NMR Spectral Data for the Aglycone Moieties of 1 and 2 in Deuterated Methanol.

Pos.	^a δ _C	^b δ _H (mult., J in Hz)	^a δ _C	^b δ _H (mult., J in Hz)
1	30.1	1.30 (m) 1.57 (m)	30.1	1.32 (m) 1.60 (m)
2	29.0	1.91 (m) 1.60 (m)	29.0	1.91 (m) 1.60 (m)
3	75.6	4.07 (m	75.6	4.08 (m)
4	33.9	1.37 (m) 2.37 (m)	34.0	1.37 (m) 2.37 (m)
5	83.6	-	83.6	-
6	132.6	5.60 (d, 10.0)	132.6	5.60 (d, 10.0)
7	132.4	5.96 (d, 10.0)	132.4	5.96 (d, 10.0)
8	75.1	-	75.1	-
9	38.1	2.21 (m)	38.1	2.27 (m)
10	39.6	-	39.6	-
11	23.3	1.53 (m) 1.87 (m)	23.3	1.67 (m) 1.98 (m)
12	76.5	4.64 (dd, 11.6, 4.0)	76.5	4.84 (*)
13	59.0	-	59.1	-
14	88.3	-	88.3	-
15	33.5	2.05 (m)	33.5	2.05 (m)
16	34.0	1.74 (m) 1.90 (m)	34.0	1.74 (m) 1.90 (m)
17	89.2	-	89.2	-
18	12.4	1.51 (s)	12.4	1.65 (s)
19	18.9	1.03 (s)	18.7	1.05 (s)
20	70.8	3.43 (m)	70.9	3.52 (m)
21	18.7	1.04 (d, 6.0)	19.2	1.02 (d, 6.0)
Tigloyl or benzoyl moiety
1′	169.2	-	131.9	-
2′	130.1	-	130.9	8.08 (d, 7.6)
3′	139.3	6.94 (q, 7.2)	129.5	7.44 (m)
4′	14.5	1.78 (d, 7.2)	134.2	7.57 (m)
5′	12.1	1.84 (s)	129.5	7.44 (m)
6′			130.9	8.08 (d, 7.6)
7′			167.7	-

Abbreviation: NMR, Nuclear magnetic resonance.

Asterisk indicates overlapped signals.

^aMeasured at 100 MHz.

^bMeasured at 400 MHz.

Table 2

NMR Spectral Data for Sugar Moieties of 1 and 2 in Deuterated Methanol.

C-3 sugar		^a δ _C	^b δ _H (mult., J in Hz)	^a δ _C	^b δ _H (mult., J in Hz)
Cym I	1	98.2	4.84 (br d, 9.6)	98.2	4.86 (br d, 9.6)
	2	36.6	1.54 (m)2.08 (m)	36.6	1.54 (m)2.08 (m)
	3	78.6	3.82 (m)	78.6	3.82 (m)
	4	83.9	3.24 (m)	83.9	3.24 (m)
	5	69.8	3.80 (m)	69.8	3.80 (m)
	6	18.5	1.17 (d, 6.0)	18.5	1.18 (d, 6.0)
OMe		58.4	3.41 (s)	58.4	3.41 (s)
Cym II	1	101.2	4.77 (br d, 10.0)	101.2	4.77 (br d, 9,6)
	2	36.4	1.54 (m)/2.08 (m)	36.4	1.54 (m)/2.08 (m)
	3	78.4	3.82 (m)	78.4	3.82 (m)
	4	83.8	3.24 (m)	83.8	3.24 (m)
	5	69.9	3.80 (m)	69.9	3.80 (m)
	6	18.6	1.19 (d, 6.0)	18.6	1.20 (d, 6.0)
OMe		58.5	3.41 (s)	58.5	3.41 (s)
Ole	1	102.6	4.56 (br d, 8.0)	102.6	4.56 (br d, 8.0)
	2	37.6	1.40 (m)2.30 (m)	37.6	1.40 (m)2.32 (m)
	3	80.4	3.35 (m)	80.4	3.36 (m)
	4	83.9	3.17 (m)	83.9	3.18 (m)
	5	72.5	3.34 (m)	72.5	3.35 (m)
	6	19.2	1.34 (d, 6.0)	18.9	1.34 (d, 6.0)
OMe		57.5	3.39 (s)	57.5	3.39 (s)
All	1	102.2	4.69 (d, 8.0)	102.2	4.69 (d, 8.4)
	2	72.9	3.30 (m)	72.9	3.30 (m)
	3	83.2	3.93 (m)	83.2	3.93 (m)
	4	83.9	3.30 (m)	83.9	3.30 (m)
	5	70.2	3.79 (m)	70.2	3.80 (m)
	6	18.1	1.28 (d, 6.0)	18.1	1.28 (d, 6.0)
OMe		62.0	3.57 (s)	62.0	3.57 (s)
Glc	1	106.2	4.33 (d, 8.0)	106.2	4.32 (d, 8.0)
	2	75.5	3.16 (m)	75.5	3.16 (m)
	3	78.1	3.20 (m)	78.1	3.20 (m)
	4	71.8	3.22 (m)	71.9	3.22 (m)
	5	77.9	3.32 (m)	77.9	3.32 (m)
	6	63.1	3.63 (dd, 11.8, 6.0)3.89 (d, 11.8)	63.1	3.63 (dd, 11.8, 6.0)3.89 (d, 11.8)

Abbreviation: NMR, Nuclear magnetic resonance.

^aMeasured at 100 MHz.

^bMeasured at 400 MHz.

Figure 2

Observed ROESY couplings of compounds 1 and 2.

Figure 3

Chemical structures of compounds 1 and 2.

Compound 2 was obtained as a white amorphous powder. Its molecular formula (C₆₂H₉₆O₂₇) was deduced by the HRESIMS (found m/z: 1295.6051 [M + Na]⁺ (calcd for [C₆₂H₉₆O₂₇Na]⁺, 1295.6037, Δ = 1.1 ppm) (Supplemental Figure S9). The NMR spectra of 2 were very similar to those of 1 except the tigloyl signals disappeared and were replaced by the signals of one benzoyl group [δ _H 7.44 ~ 8.08 (5H)/ δ _C 129.5 (2CH), 130.9 (2CH), 131.9 (C), 134.2 (CH)]. All the other signals appeared at almost the same positions between 1 and 2 (Supplemental Figure S10-S14).^17,18 The benzoyl group was linked to C-12 by an ether linkage by the HMBC correlation from H-12 (δ _H 4.85) and carbonyl carbon (δ _C 167.7). The relative configuration of 2 was indicated by ROESY spectrum as shown in Figure 2 (Supplemental Figures S15 and S16). Consequently, compound 2 was elucidated as (20S)−12β-benzoyloxy-5α-hydroperoxy-3β,8β,14β,17β,20-pentahydroxypregn-6-ene 3-O-β-D-glucopyranosyl-(1→4)‐6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside, a new compound named gymsylosides G (Figure 3).

Compounds 1 and 2 were evaluated for both anti α-glucosidase and α-amylase activities at the concentration of 200 µM (Table 3). Acarbose, an antidiabetic drug was used as a positive control in both tests. All the experiments were performed in triplicate and the biological results were described in the percentage of inhibition. Compounds 1 and 2 showed moderate anti α-glucosidase and α-amylase activity with inhibitory percentage of 31.1 ± 1.2 and 42.3 ± 1.7% (for α-glucosidase), and 27.8 ± 1.3 and 34.5 ± 1.5% (for α-amylase), respectively.

Table 3

Α-Glucosidase and Α-Amylase Inhibitory Effects of Compounds 1 and 2 (200 µM).

Compd.	Inhibition (%)
Compd.	α-glucosidase	α-amylase
1	31.1 ± 1.2	27.8 ± 1.3
2	42.3 ± 1.7	34.5 ± 1.5
Acarbose^a	57.8 ± 3.2^b	91.2 ± 1.31^c

^aAcarbose was used as a positive control.

^b500 µg/mL.

^c100 µg/mL.

Material and Methods

General Experimental Procedures

All NMR spectra were recorded on an Agilent 400-MR-NMR spectrometer operated at 400 and 100 MHz for ¹H and ¹³C, respectively. Data processing was carried out with the MestReNova ver.6.0.2 program. HRESIMS spectra were obtained using an AGILENT 6550 iFunnel Q-TOF LC/MS system. Optical rotations were determined on a Jasco DIP-370 automatic polarimeter. Preparative HPLC was carried out using an AGILENT 1200 HPLC system. Column chromatography was performed on silica-gel (Kieselgel 60, 70‐230 mesh and 230‐400 mesh, Merck) or YMC RP-18 resins (30, 50 μm, Fujisilisa Chemical Ltd.). For TLC, a pre-coated silica-gel 60 F₂₅₄ (0.25 mm, Merck) and RP-18 F_254S plates (0.25 mm, Merck) were used.

Plant Material

The leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. were collected in Hai Loc, Hai Hau, Nam

Dinh in November 2015, and identified by Dr. Nguyen The Cuong, Institute of Ecology and Biological Resources. A voucher specimen (NCCT-P20) was deposited at the Herbarium Institute of Marine Biochemistry, VAST.

Extraction and isolation

The dried powders of G. sylvestre leaves (4.0 kg) were sonicated with hot methanol (3 times × 10 L, each 3 hours) to give MeOH extract (450 g) after evaporation of the solvent. The MeOH extract was suspended in water and successively partitioned with hexane, CH₂Cl₂ and EtOAc to obtain the hexane (GS1, 47.0 g), CH₂Cl₂ (GS2, 60.0 g), EtOAc extracts (GS3, 27.0 g) and H₂O layer (GS4). GS2 was chromatographed on a silica gel column eluting with gradient solvent of hexane: acetone (40:1, 20:1, 10:1, 5:1, 1:1, and 0:1, v/v) to give seven fractions, GS2A-GS2G. Fraction GS2G was chromatographed on an RP-18 column eluting with MeOH:H₂O (4:1, v/v) to give 4 smaller fractions, GS2G1-GS2G4. GS2G4 was chromatographed on a J’sphere H-80 column (150 × 20 mm), solvent condition of 35% CH₃CN in H₂O to give to yield 1 (18.2 mg) and 2 (20.0 mg).

Gymsyloside F (1)

White amorphous powder; ${[α]}_{D}^{25}$ + 180.0 (c 0.1, MeOH); C₆₀H₉₈O₂₇, HRESIMS m/z: 1273.6193 [M + Na]⁺ (calcd for [C₆₀H₉₈O₂₇Na]⁺, 1273.6193, Δ = 0 ppm); ¹H (CD₃OD, 400 MHz) and ¹³C NMR (CD₃OD, 100 MHz) data, see Tables 1 and 2.

Gymsyloside G (2)

White amorphous powder; ${[α]}_{D}^{25}$ + 245.0 (c 0.1, MeOH); C₆₂H₉₆O₂₇, HRESIMS m/z: 1295.6051 [M + Na]⁺ (calcd for [C₆₂H₉₆O₂₇Na]⁺, 1295.6037, Δ = 1.1 ppm); ¹H (CD₃OD, 400 MHz) and ¹³C NMR (CD₃OD, 100 MHz) data, see Tables 1 and 2.

Acid hydrolysis of compounds 1 and 2

Each compound (1 and 2, 10.0 mg) was separately dissolved in 1.0 M HCl (dioxane−H₂O, 1:1, v/v, 1.0 ml) and heated to 80 °C in a water bath for 3 hours. The acidic solution was dried under N₂ overnight. After extraction with CHCl₃, the aqueous layer was dried using N₂ to give aqueous residue (A). The aqueous residue (A) was separated by silica gel CC eluting with CH₂Cl₂–MeOH (10:1, v/v) and then further fractionated by RP-18 CC using a solvent gradient of MeOH–H₂O (6:4, 7:3, and 8:2, v/v) to give the saccharides. The specific rotations of these sugars were determined. The specific rotations ( ${[α]}_{D}^{25}$ ) of sugars was determined after dissolving in H₂O for 24 hours and compared to the literature (lit): D-cymarose (1.2 mg): found +51.0 (c 0.04, H₂O), lit +51.8²³; D-oleandrose (0.5 mg): found +11.5 (c 0.04, H₂O), lit +11.7²³; 6-deoxy-3-O-methyl-D-allose (0.6 mg): found +10.5 (c 0.04, H₂O); lit +10.0²⁴; D-glucose (0.7 mg): found +50.0 (c 0.04, H₂O); lit +48.0.²⁴ Based on the above evident, sugar components were found in: compounds 1 and 2: D-cymarose, D-oleandrose, 6-deoxy-3-O-methyl-D-allose, and D-glucose.

α-Glucosidase inhibitory assay

The α-glucosidase (G0660-750UN, Sigma-Aldrich, St. Louis, MO) enzyme inhibition assay was performed according to the previously described method.²⁵ The sample solution (2 ml dissolved in dimethyl sulfoxide (DMSO) and 0.5 U/mL α-glucosidase (40 ml) were mixed in 120 ml of 0.1 M phosphate buffer (pH 7.0). After 5 minutes pre-incubation, 5 mM p-nitrophenyl-α-D-glucopyranoside solution (40 ml) was added, and the solution was incubated at 37 °C for 30 minutes. The absorbance of released 4-nitrophenol was measured at 405 nm by using a microplate reader (Molecular Devices, Sunnyvale, CA).

α-Amylase inhibitory assay

The α-amylase (A8220, Sigma-Aldrich, St. Louis, MO) enzyme inhibitory activity was measured using the reported method.²⁵ Substrate was prepared by boiling 100 mg potato starch in 5 ml phosphate buffer (pH 7.0) for 5 minutes, then cooling to room temperature. The samples (2 ml dissolved in DMSO) and substrate (50 ml) were mixed in 30 ml of 0.1 M phosphate buffer (pH 7.0). After 5 minutes pre-incubation, 5 mg/mL α-amylase solution (20 ml) was added, and the solution was incubated at 37 °C for 15 minutes. The reaction was stopped by adding 50 ml 1 M HCl and then 50 ml iodine solution was added. The absorbances were measured at 650 nm by a microplate reader.

Conclusions

Two new pregnane glycosides, gymsyloside F (1) and gymsyloside G (2), were isolated from the leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR, HRESIMS, and in comparison, with the reported data. At the concentration of 200 µM, 1 and 2 showed moderate anti α-glucosidase and α-amylase activity with inhibitory percentage of 31.1 ± 1.2 and 42.3 ± 1.7% (for α-glucosidase), and 27.8 ± 1.3 and 34.5 ± 1.5% (for α-amylase), respectively.

Supplemental Material

Online supplementary file 1 - Supplemental material for Gymsyloside F and Gymsyloside G, Two New Pregnane Glycosides From the Leaves of Gymnema sylvestre and Their α-Glucosidase and α-Amylase Inhibitory Activities

Supplemental material, Online supplementary file 1, for Gymsyloside F and Gymsyloside G, Two New Pregnane Glycosides From the Leaves of Gymnema sylvestre and Their α-Glucosidase and α-Amylase Inhibitory Activities by Pham Hai Yen, Duong Thi Hai Yen, Nguyen Thi Viet Thanh, Nguyen Anh Hung, Ngo Anh Bang, Bui Huu Tai, Nguyen Xuan Nhiem and Phan Van Kiem in Natural Product Communications

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research is funded by Vietnam Academy of Science and Technology under grant number: UDSXTN.04/20-21.

Supplemental Material

Supplemental material for this article is available online.

References

Solanki

Gupta

. In vitro shoot multiplication of Gymnema sylvestre R.Br. Advances in Plant Sciences. 2013;26:321-323.

Ahmed

ABA.

Rao

AS.

Rao

. Role of in vivo leaf and in vitro callus of Gymnema sylvestre in maintaining the normal levels of blood glucose and lipid profile in diabetic Wistar rats. Biomedicine. 2008;28:134-138.

Ahmed

ABA.

Rao

AS.

Rao

. In vitro callus and in vivo leaf extract of Gymnema sylvestre stimulate β-cells regeneration and anti-diabetic activity in Wistar rats. Phytomedicine. 2010;17(13):1033-1039.doi:10.1016/j.phymed.2010.03.019

20537514

Al-Romaiyan

Liu

Asare-Anane

et al. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro . Phytother Res. 2010;24(9):1370-1376.doi:10.1002/ptr.3125

20812281

Yang

Zhang

et al. New pregnane glycosides from Gymnema sylvestre . Molecules. 2015;20(2):3050-3066.doi:10.3390/molecules20023050

25685911

Kiem

PV.

Yen

DTH.

Hung

et al. The anti-glycative potentials of pregnane glycosides from Gymnema sylvestre . Phytochem Lett. 2020;38:19-24.doi:10.1016/j.phytol.2020.04.012

Kiem

PV.

Yen

DTH.

Hung

et al. Five new pregnane glycosides from Gymnema sylvestre and their α-glucosidase and α-amylase inhibitory activities. Molecules. 2020;25(11):2525.doi:10.3390/molecules25112525

Zarrelli

DellaGreca

Ladhari

Haouala

Previtera

. New triterpenes from Gymnema sylvestre . Helv Chim Acta. 2013;96(6):1036-1045.doi:10.1002/hlca.201200331

Peng

SL.

Zhu

XM.

Wang

MK.

Ding

. A novel triterpenic acid from Gymnema sylvestre . Chin Chem Lett. 2005;16:223-224.

10.

Zarrelli

Ladhari

Haouala

Di Fabio

Previtera

DellaGreca

. New acylated oleanane and lupane triterpenes from Gymnema sylvestre . Helv Chim Acta. 2013;96(12):2200-2206.doi:10.1002/hlca.201300047

11.

Malik

JK.

Manvi

FV.

Nanjware

BR.

Dwivedi

DK.

Purohit

Chouhan

. Anti-arthritic activity of leaves of Gymnema sylvestre R.Br. leaves in rats. Der Pharm Lett. 2010;2(1):336-341.

12.

Yoshikawa

Amimoto

Arihara

Matsuura

. Structure studies of new antisweet constituents from Gymnema sylvestre . Tetrahedron Lett. 1989;30(9):1103-1106.doi:10.1016/S0040-4039(01)80371-3

13.

Yoshikawa

Amimoto

Arihara

Matsuura

. Gymnemic acid V, VI and VII from gur-ma, the leaves of Gymnema sylvestre R. Br. Chem Pharm Bull. 1989;37(3):852-854.doi:10.1248/cpb.37.852

14.

Yoshikawa

Nakagawa

Yamamoto

Arihara

Matsuura

. Antisweet natural products. V. structures of gymnemic acids VIII-XII from Gymnema sylvestre R. Br. Chem Pharm Bull. 1992;40(7):1779-1782.doi:10.1248/cpb.40.1779

15.

Yoshikawa

Kondo

Arihara

Matsuura

. Antisweet natural products. IX. Structures of gymnemic acids XV-XVIII from Gymnema sylvestre R. Br. V. Chem Pharm Bull. 1993;41(10):1730-1732.doi:10.1248/cpb.41.1730

16.

Pham

HTT.

Hoang

MC.

TKQ

et al. Discrimination of different geographic varieties of Gymnema sylvestre, an anti-sweet plant used for the treatment of type 2 diabetes. Phytochemistry. 2018;150:12-22.doi:10.1016/j.phytochem.2018.02.013

29529525

17.

Yoshikawa

Matsuchika

Takahashi

et al. Pregnane glycosides, gymnepregosides G-Q from the roots of Gymnema alternifolium . Chem Pharm Bull. 1999;47(6):798-804.doi:10.1248/cpb.47.798

10399837

18.

Yoshikawa

Matsuchika

Arihara

Chang

HC.

Wang

. Pregnane glycosides, gymnepregosides A-F from the roots of Gymnema alternifolium . Chem Pharm Bull. 1998;46(8):1239-1243.doi:10.1248/cpb.46.1239

9734311

19.

Sheu

J-H.

Liaw

C-C.

Duh

C-Y

. Oxygenated clerosterols isolated from the marine alga Codium arabicum . J Nat Prod. 1995;58(10):1521-1526.doi:10.1021/np50124a007

20.

Greca

MD.

Fiorentino

Molinaro

Monaco

Previtera

. Hydroperoxysterols in Arum italicum . Nat Prod Lett. 1994;5(1):7-14.doi:10.1080/10575639408043928

21.

Aquino

Peluso

De Tommasi

De Simone

Pizza

. New polyoxypregnane ester derivatives from Leptadenia hastata . J Nat Prod. 1996;59(6):555-564.doi:10.1021/np960251e

8786361

22.

Trang

DT.

Yen

DTH.

Cuong

et al. Pregnane glycosides from Gymnema inodorum and their α-glucosidase inhibitory activity. Nat Prod Res. 2019:1-7.doi:10.1080/14786419.2019.1663517

23.

Warashina

Noro

. Steroidal glycosides from the aerial part of Asclepias incarnata . Phytochemistry. 2000;53(4):485-498.doi:10.1016/S0031-9422(99)00560-9

10731028

24.

Abe

Okabe

Yamauchi

Honda

Hayashi

. Pregnane glycosides from Marsdenia tomentosa . Chem Pharm Bull. 1999;47(6):869-875.doi:10.1248/cpb.47.869

25.

Tran

HHT.

Nguyen

MC.

et al. Inhibitors of α-glucosidase and α-amylase from Cyperus rotundus . Pharm Biol. 2014;52(1):74-77.doi:10.3109/13880209.2013.814692

24044731

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