Phenolic Constituents, Anti-Inflammatory and Antidiabetic Activities of Cyperus Laevigatus L.

Elshamy, El-Shazly, Yassine, El-Bana, Farrag, Nassar, Singab, Noji, and Umeyama: Phenolic Constituents, Anti-Inflammatory and Antidiabetic Activities of Cyperus Laevigatus L.



Cyperaceae is a largest family in the monocotyledons that includes more than 100 genera. Cyperus genus is the largest genus in this family that contains more than 600 species.1 Cyperus species are widely used as weeds in traditional medicines.2 In 1983, Buolus reported that Cyperus species were traditionally used as an emollient to treat analgesic, diuretic, carminative and others.3 Pharmacological studies on Cyperus sp. indicated a myriad of biological effects such as anti-inflammatory, hepatoprotective, gastroprotective, anti-malarial and anti-diabetic activities.4-7 Several secondary metabolites were reported from Cyperus sp. Including quinones, flavonoids, sesquiterpenes, steroids and essential oils.2-8-10 Herein we report the phenolic constituents of the aerial parts of Cyperus laevigatus (Family: Cyperaceae) as well as the pharmacological effects of the different extracts and isolated compounds.


General Experimental procedures

Optical rotation was measured using JASCO P1020 polarimeter (JASCO International Co. Ltd., Tokyo, Japan). NMR spectra were recorded on JEOL AL-400 NMR spectrometer (JEOL Inc., Tokyo, Japan). HR-ESI-MS were recorded by a Shimadzu LC-MS-IT-TOF-MS spectrometer (Shimadzu Inc., Kyoto, Japan). An OMM 7070E Shimadzu visible recording model UV 200 and 240 spectrophotometers (Shimadzu Inc., Kyoto, Japan) were used for UV spectra.

Plant material

Aerial parts of Cyperus laevigatus L., were collected from Baltim, Kafr Elsheikh, Egypt, in April 2013 and kindly identified by Asoc. Prof. Ahmed M. Abdel Gawad. A voucher specimen (PHG-P-CL179) was deposited in Ain Shams University herbarium, Cairo, Egypt.

Extraction and isolation

Air-dried powder aerial parts of C. laevigatus (2.0 kg) were extracted by 70% MeOH, filtered, and dried under vacuum to give dark black gum (85.0 gm). The dry extract was successively fractionated using n-hexane (12.0), CH2Cl2 (10.0), EtOAc (11.0) and MeOH (52.0), respectively. The MeOH fraction was subjected to polyamide CC and eluted with H2O: EtOH in gradient afforded 8 major fractions (CL-1:CL-8). Fraction CL-3 (160.0 mg; 25% MeOH) was subjected to preparative paper chromatography that afforded two subfractions CL-3 (A, 112 mg; Rf: 0.4 AcOH) and (B; 43 mg; Rf: 0.65 AcOH). Subfractions CL-3-B was eluted on Sephadex LH-20 by 40% MeOH afforded compound 1 (8.3 mg). The other seven flavonoids (2-8) were purified using different chromatographic techniques such as preparative paper and Sephadex LH-20 column. Complete acid hydrolysis followed by PC investigation was preceded.11

Spectroscopic data of new flavonoid (1)

Yellow amorphous solid (8 mg), {[α]–16° (c 0.01, MeOH)}, UV λmax nm (MeOH): 208, 266, 347; NaOAc: 213, 260, 348, 368; + Boric acid: 215, 258, 348; AlCl3: 211, 279, 306.6, 355.4; + HCl: 216.2, 277.2, 300.8, 347.4; H3BO3: 209.2, 269.6, 336.6; +NaOAc: 221.8, 270.8, 334.8. HR-ESI-MS m/z: 689.6365 [M+Na]+, ESI-MS m/z [M-H]-: 666.1. 1H- (400 MHz); 13C- (100 MHz; DMSO-d6) NMR (see Table 1).

Table 1

1H- (400 MHz) and 13C-NMR (100 MHz) of compound 1 (DMSO-d6).

• Aglycon
36.71 s104.8
66.41 d (J = 2.0 Hz)99.9
86.77 d (J = 2.0 Hz)94.9
2’7.34 s113.8
5’6.9 d (J = 8.0 Hz)116.4
6’7.42 d (J = 8.0 Hz)119.5
OCH33.91 s56.1
• 7-O-Glc
1’’5.11 d (J = 7.2 Hz)99.8
2’’3.21 – 3.6573.2
• 4Glc-O- Glc
1’’’5.08 d (J = 7.2 Hz)100.0
2’’’3.16 – 4.1175.3
OCH33.91 s56.7
• 6```Acetate
COOCH32.15 br s21.1

[i] *All assignments are based on 1D and 2D measurements (HMBC, HSQC, COSY).

Antioxidant activity of C. laevigatus extracts

The antioxidant activity of the different extracts of C. laevigatus aerial parts along with the isolated flavonoids 1-8 were evaluated in terms of DPPH radical-scavenging ability, as described before12 in a comparising with a reference drug, ascorbic acid.

Anti-inflammatory activity of different extracts of C. laevigatus

The anti-inflammatory of total extract, MeOH and EtOAc fractions was evaluated at different concentrations (12.5, 25, 50 and 100 μg/ml) using LPS-stimulated RAW264.7 macrophages model with a reference drug, dexamethasone as described previously.13

Cell culture

Raw murine macrophages (RAW 264.7) were purchased from the American Type Culture collections and cultured in RPMI-1640 supplemented with 10% fetal bovine serum (FBS), 2 mM L-glutamine, containing 100 U/mL penicillin G sodium, 100 U/mL streptomycin sulphate, and 250 ng/ml amphotericin B. Cells were maintained in humidified air containing 5% CO2 at 37 °C (Cambrex BioScience, Copenhagen, Denmark).

MTT cell viability assay

The mitochondrial-dependent reduction of MTT to formazan was used to measure cell respiration as an indicator of cell viability.13 Cells (0.5 × 105 cells/ well) in serum-free media were plated in a flat bottom 96-well microplate, and treated with 20 μL of different concentrations of the tested samples for 24 h at 37 °C, in a humidified 5% CO2 atmosphere. After incubation, the media were removed and 40 μL MTT solution / well was added and incubated for an additional 4 h. MTT crystals were solubilized by adding 180 μL of acidified isopropanol/well and the plate was shacked at room temperature, followed by photometric determination of the absorbance at 570 nm using 96 wells microplate ELISA reader.

Inhibition of nitric oxide (NO) production

Raw murine macrophages (RAW 264.7) were seeded in 96-well plates at 0.5 × 105 cells / well for 2 h in RPMI without phenol red. The cells were stimulated with LPS with final concentrations of 10 μg/mL. The stimulated cells after 2 extra h were treated with serial concentrations of the tested samples, dexamethasone (50 μg/mL) or left with the LPS alone. Untreated cells were used as a negative control.13

Nitrite accumulation was used as an indicator of NO production using a microplate assay based on the Griess reaction. In each well of flat bottom 96 well-microplates, 40 μL of freshly prepared Griess reagent was mixed with 40 μL cell supernatant or different concentrations of sodium nitrite ranging from 0-100 μmol/L. The plate was incubated for 10 min in the dark and the absorbance of the mixture at 540 nm was determined using the microplate ELISA reader. The amount of nitrite in the media was calculated from NO standard curve.

Antidiabetic activity of total alcoholic extract of C. laevigatus Chemicals and animals

Streptozotocin (STZ) was purchased from Sigma Chemical Co. St. Louis, MO, USA. The study was conducted on 60 adult albino rats (200-210 g) (National Research Centre (NRC), Dokki, Giza, Egypt). Rats were performed in accordance with the Ethics Committee of the NRC. Rats were divided into 4 groups (15 rats in each) as follow: control group, rats received intragastric C. laevigatus MeOH fraction (50 mg /kg b.w. day) dissolved in distilled water, Diabetic group, diabetes were induced by single subcutaneous injection of streptozotocin (50 mg/kg b.w.) The animals were considered diabetic if fasting glucose level was 200 mg/dL after 48 hours of the injection, treated group, diabetic rats received intragastric C. laevigatus total extract (50 mg/kg b. w. day).14

Biochemical Analysis

Serum glucose was performed according to the method of Passing, 1983.15 Serum glucagon and insulin were performed according to previous reported methods.15,16 NO was determined according to the reported method17 where nitrite, stable end product of nitric oxide radical, is mostly used as indicator for the production of NO. The activity of paraoxonase was measured spectrophotometrically in supernatants using phenyl acetate as the substrate. In this assay, aryl esterase/paraoxonase catalyzes the cleavage of phenyl acetate, resulting in phenol formation. The rate of phenol formation is measured by monitoring the increase in absorbance at 270 nm at 25 °C. Absorbance at 270 nm was taken every 15 s for 120 s using UV Spectrophotometer.18

Histopathological evaluation

The pancreatic tissues were dissected out immediately, fixed in 10% normal formalin dehydrated in series of alcohol and then to xylene each for 1 h followed by embedding in wax at 60°C. Paraffin blocks of the tissues were sectioned to 5 μm thickness. The sections were then stained with hematoxylin and eosin for histopathological evaluation.19

Statistical analysis

All data were expressed as mean ± standard error. Data were analyzed using one-way ANOVA using SPSS (Version 16). Duncan’s new multiple-range test was used to assess differences between means. A significant difference was considered at the level of P < 0.05.


A new acylated flavone diglucoside namely, chrysoeriol 7-O-β-(6‴-O-acetyl-β-D-glucopyranosyl)-(1→4) glucopyranoside (1) and seven knowns, apigenin (2), apigenin 7-O-β-glucopyranoside (3), luteolin (4), luteolin 7-O-β-glucopyranoside (5), chrysoeriol (6), chrysoeriol 7-O-β-glucopyranoside (7), and tricin (8)20,21 were isolated for the first time from the aerial parts of C. laevigatus (Figure 1A). The structures of isolated compounds were established using spectroscopic methods, including UV, 1D, 2D-NMR and HR-ESI-MS.

Figure 1A

Isolated flavonoids from C. laevigatus.

UV spectroscopic data of compound (1) indicated a flavone with free 5 and 4’-hydroxyl groups.11 HR-ESI-MS spectrum showed a molecular ion peak [M+Na]+ at m/z 689.6365, corresponding to the molecular formula of C30H34O17. The 1H-NMR spectral data (Table 1) showed a downfield shift of H-6 at δH 6.41 (d, J = 2.0), H-8 at 6.77 (d, J = 2.0 Hz) suggested the presence of C-7-O-substitution. A characteristic signal of methoxy group at δH 3.91 s was detected. Additionally, the spectrum showed two anomeric protons at δH 5.11 (d, J = 7.2) and at δH 5.08 (d, J = 7.2). The signals appeared at δH 3.16 – 4.11 were attributed to the protons of the remaining sugar. A characteristic proton signal of one methyl for acetyl group was observed at δH 2.15 s. 13C-NMR spectrum showed 30 carbon resonances (Table 1), two of which were carbonyls which appeared at δC 182.3 for C-4 and at δC 172.3 for characteristic for an acetoxy group. Dept-145 experiment suggested the presence of two methylene, sixteen methine signals, one metyl of methoxy group (at δC 56.1); ome methyl for acetoxy group (at δC 21.1) and ten quaternary carbon signals. The C-7-O-sabstitution was suggested by the downfield shift carbon signal of C-7 at δC 163.4. Ten carbon signals for two glucosyl moieties were showed at δC 73.2 (C-2’’), 73.5 (C-3’’), 79.5 (C-4’’), 74.2 (C-5’’), 62.3 (C-6’’), 75.3 (C-2’’’), 76.6 (C-3’’’), 72.1 (C-4’’’), 73.5 (C-5’’’), 63.3 (C-6’’’), two anomeric carbons at δC 99.8 (C-1’’), δC 100.0 (C-1’’’). The assignment of the protonated carbons was established by HSQC experiment. The 7-O-glucosidic linkage was confirmed by HMBC correlation of the anomeric proton at δH 5.11 (d, J = 7.20, H-1’’) and C-7 at 163.4 (J3). The very clear downfield shieft of C-4’’ at δC 79.5 in addition to the HMBC correlation of the anomeric proton at δH 5.08 (d, J = 7.20, 1’’’) with the C-4’’ (J3) deduced the 4’’ → 1’’’ diglucoside linkage 22. Also the downfield shieft of the C-6’’’ by approximately 1 ppm at δC 63.3 suggested the acetylated C-6’’’ that supported by HMBC correlation of H-6’’’ at δH 3.16 m with the acetyl carbonyl group at δC 172.3 (J3). Moreover, a correlation between the methyl proton signal at δH 2.15 s and the carbonyl group at δC 172.3 (J2) was observed. Also the HMBC correlation between the methyl proton at δH 3.91 s and C-3’ at δC 148.6 (J3) indicated methoxylation of C-3’ (Figure 1B). The β orientation of the glucosidic linkage was confirmed was by the large coupling constant of the anomeric proton (7.2 ppm).22,23 The structure of this compound was confirmed by mass fragments; at m/z 367.1056 characteristic to 6’’’-O-acetyl-β-D-diglucopyranoside; at m/z 301.1413 characteristic to chrysoeriol and at m/z 461.2 in the negative mode ESI-MS characteristic to chrysoeriol-7-O-glucoside. The acid hydrolysis of 1 afforded an aglycone and a sugar moiety, which was composed of chrysoeriol and glucose. From the above mentioned data, the structure of 1 was characterized as chrysoeriol 7-O-β-(6‴-O-acetyl-β-D-glucopyranosyl)-(1→4) glucopyranoside (1)

Figure 1B

Isolated flavonoids from C. laevigatus.

Antioxidant activity

The total extract and MeOH fractions showed moderate DPPH radical scavenging activity with IC50 23.39±0.72 and 24.28±0.56, respectively but EtOAc, and n-hexane showed weak activity with IC50 57.89±0.71, and 76.98±0.73, respectively. Also the isolated flavonoids exhibited from moderate to weak antioxidant activity by the order of compound 4>2>5>6>3>7>8>1 (Table 2). The moderate antioxidant activity of both the total extract and MeOH fraction was attributed to the high flavonoid content. It was reported that flavonoids possess antioxidant activity especially luteolin derivatives and methoxylated flavonoids.24 The DPPH reaction mechanism with the compounds that exhibited activity depending upon the free OH groups in B-ring, so the flavons exhibited more activity that the flavons 7-O-glycosides.25

Table 2

Antioxidant activity of C. laevigatus extracts and isolated flavonoids (1-8).

Tested sampleDPPH assay IC50 (μg/ml)
n-hexane fraction76.98±2.69
EtOAc fraction57.58±1.93
MeOH fraction24.28±0.67
Compd 165.93±1.57
Compd 228.78±1.21
Compd 334.12±0.98
Compd 426.54±1.03
Compd 531.19±1.14
Compd 633.76±0.87
Compd 752.62±0.65
Compd 858.44±1.74
Ascorbic acid1.85±0.12

Anti-inflammatory activity

Cytotoxicity results confirmed that the tested extracts are safe on RAW264.7 macrophages with different concentrations (12.5, 25, 50 and 100 μg/ml). The total extract (12.5, 25, 50, and 100 μg/ml) and MeOH fraction (12.5, 25, and 50 μg/ml) decreased NO% accumulation as the concentration increased reaching 76 - 66% and 84 - 67%, respectively. Also, the EtOAc fraction (12.5, 25, and 50 mg) decreased the NO% accumulation with concentration increased with values ranging from 77 - 66%. The results of the anti-inflammatory assay suggested that the total, MeOH and EtOAc extracts exhibited potent activity at different concentrations and the results were comparable with the reference drug, dexamethasone (Figure 2). A strong correlation has been always noticed between chemical constituents and herbal biological activities. By the same analogy, the anti-inflammatory activity of C. laevigatus can be correlated to its chemical constituents. The phytochemical study of this plant elucidated that it is rich with bioactive compounds. Luteolin, its methoxylated and glycosides derivatives inhibited the NO production and iNOS expression in LPS-stimulated BV-2 microglial cells.26

Figure 2

NO% accumulation in response to; B) total extract; C) MeOH fraction and D) EtOAC fraction of C. laevigatus. The results were compared with the results of LPS stimulated cells, non-treated cells and dexamethasone (50 μg/ml) treated cells. a P ≤ 0.005, b P ≤ 0.0005 compared to LPS stimulated cells.

Antidiabetic activity of total extract

Cyperus laevigatus aerial parts total extract did not exhibit any obvious toxic symptoms or mortality in rats up to 5000 mg/kg b.w. after 14 days. Biochemical markers in the present work exhibited that the diabetic group treated with C. laevigatus extract showed a decrease in the glucose, glucagon, and NO serum levels and promote serum insulin and paraoxonase levels. Zhang et al. 201027 reported that flavonoids exhibited antidiabetic activity by decreasing fasting blood glucose (FBG) and glucagon serum levels while increasing insulin serum levels (Figure 3). Histological examination of the pancreas of the control and extract treated rats indicated normal architecture (Figure 4-A; B). The islets of Langerhans found in the pancreatic tissue were round in shape with normal cell lining. On the other hand, the acini were arranged in a well-organized manner. The interlobular ducts were surrounded with the supporting tissue. These results were consistent with Jarral et al. 201328 that found that beta-cells comprise the major of islets’ cells of rat’s pancreas.

Figure 3

Mean serum glucose, glucagon and NO levels were significantly high and serum insulin and serum praoxnase activity level were significantly low in diabetic group compared to normal group. Mean serum glucose, glucagon and NO levels were significantly low and serum insulin and serum praoxnase activity level were significantly high in treated group compared to diabetic group.
Figure 4

Section of pancreas of A) control group shows the normal structure of exocrine (dense-staining acinar cells) and endocrine pancreas (light-staining islet of Langerhans), B) rat treated with C. laevigatus extract (50 mg/kg b.w./day) shows the normal structure of exocrine and endocrine pancreas, C): diabetic rat shows decrease in pancreatic islet size, atrophy and vacuolation, and connective tissue invasion in the parenchyma of pancreas islet (black arrow) is shown. A reduction in the pancreatic b-cell (blue arrow) numbers compared to the control group, D): diabetic rat received intragastric C. laevigatus extract (50 mg/kg b.w./day) shows normal structure of the pancreas. Few degenerative cells (black arrow) are seen in the islet (H & E stain, Scale Bar: 20 μm).

In the diabetic rats, the pancreas showed a decrease in the pancreatic islet size, atrophy, vacuolation, and connective tissue invasion in the parenchyma of the pancreas islets. The sections revealed a reduced pancreatic β-cell numbers compared to the control group (Figure 4-C). STZ-induced diabetes may be due to the selective destroying of pancreatic β-cells, which is responsible for the insulin production from endocrine cells.29 The pancreas of the diabetic rats treated with C. laevigatus extract showed dramatic suppression of all abnormal histological changes as compared to the diabetic group (Figure 4-D).

The pancreas of the diabetic rats treated with C. laevigatus extract showed dramatic suppression of all abnormal histological changes. Regarding the mechanism by which C. laevigatus can improve β-cells, researchers found that flavonoids, flavonoid glycosides and phenolic acids exhibited a strong contribution as antioxidant agents that can regenerate the changes in the morphology of β-cells.24-30-31


A new flavonoid, chrysoeriol 7-O-β-(6‴-O-acetyl-β-D-glucopyranosyl)-(1→4) glucopyranoside (1), and seven knowns (2-8) were isolated and identified from aerial parts of C. laevigatus alcoholic extract. The different extracts and isolated compounds exhibited from moderate to low antioxidant activity. The total acoholic extract, MeOH and EtOAC fractions exhibited significant anti-inflammatory activity using by decreasing of NO accumulation in comparison with dexamethasone as a reference drug using LPS-stimulated RAW 264.7 macrophages model. The MeOH fraction exhibited antidiabetic activity by decreasing levels of glucose, glucagon and NO along with increasing level of insulin and promoted paraoxonase activity in streptozotocin-induced diabetic rats.


This work was supported by the research project of the National Research Centre (Project ID: 10010303) and the Faculty of Pharmaceutical Science; Tokushima Bunri University.


[2] Conflicts of interest CONFLICT OF INTEREST The authors declare no conflict of interests.




RAW 264.7

Mouse RAW-264.7 Cell lines

1D, 2D-NMR

one and two dimensional nuclear magnetic resonance


Nitric Oxide


Paper Chromatography


(3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide.



Simpson DA, Inglis CA. Cyperaceae of economic, ethnobotanical and horticultural importance. Kew Bull. 2001;56:257–360


Vilhena KS, Guilhon SM, Zoghbi M, Santos L, Filho A. Chemical investigation of Cyperus distans L. and inhibitory activity of scabequinone in seed germination and seedling growth bioassays. Nat Prod Res. 2014;28(23):2128–33


Buolus L. Medicinal Plants of North Africa. Reference Publications Inc. 1983;Egypt.


Kumar SVS, Mishra H. Hepatoprotective activity of rhizomes of Cyperus rotundus linn against carbon tetrachloride-induced hepatotoxicity. Ind J of pharm Sci. 2005;67(1):84–8


Kumari CS, Govindasamy S, Sukumar E. Lipid lowering activity of Eclipta prostrata in experimental hyperlipidemia. Journal of Ethnopharmacology. 2006;105(3):332–5


Thebtaranonth C, Thebtaranonth Y, Wanauppathamkul S, Yuthavong Y. Antimalarial sesquiterpenes from tubers of Cyperus rotundus: structure of 10,12-Peroxycalamenene, a sesquiterpene endoperoxide. Phytochem. 1995;40(1):125–8


Raut NA, Gaikwad NJ. Antidiabetic activity of hydro-ethanolic extract of Cyperus rotundus in alloxan induced diabetes in rats. Fitoterapia. 2006;77(7–8):585–88


Abdel-Razik AF, Nassar MI, El-Khrisy ED, Dawidar AA, Mabry TJ. New prenylflavans from Cyperus conglomeratus. Fitoterapia. 2005 Dec 31;76(7):762–4


Nassar MI, Yassine YM, Elshamy AI, El-Beih A, El-Shazly M, Singab A. Essential oil and antimicrobial activity of aerial parts of Cyperus leavigatus L. (Family: Cyperaceae). J of Ess Oil Bearing Plants. 2015;18(2):416–422


Xu Y, Zhang HW, Yu CY, Lu Y, Chang Y, Zou ZM. Norcyperone, a novel skeleton norsesquiterpene from Cyperus rotundus L. Molecules. 2008;13(10):2474–81


Mabry T, Markham K, Thomas M. The Systematic Identification of Flavonoids. Publ. 1970;New York.


Hyun TK, Kim HC, Kim JS. Antioxidant and antidiabetic activity of Thymus quinquecostatus Celak. Industrial Crops and Products. 2014;52:611–6


Hyun TK, Ko YJ, Kim EH, Chung IM, Kim JS. Anti-inflammatory activity and phenolic composition of Dendropanax morbifera leaf extracts. Industrial Crops and Products. 2015;74:263–70


Simeonova R, Vitcheva V, Krasteva I, Zdraveva P, Konstantinov S, Ionkova I. Antidiabetic and antioxidant effects of saponarin from Gypsophila trichotoma on streptozotocin-induced diabetic normotensive and hypertensive rats. Phytomedicine. 2016;23(5):483–90


Passing H, Bablok PH. A new biometrical procedure for testing the equality of measurements from two different analytical methods. Application of linear regression procedures for method comparison studies in clinical chemistry, Part I. J Clin Chem Clin Biochem. 1983;21(11):709–20


Judzewitsch RG, Pfeifer MA, Best JD, Beard JC, Halter JB, Porte D Jr. Chronic chlorpropamide therapy of noninsulin-dependent diabetes augments basal and stimulated insulin secretion by increasing islet sensitivity to glucose. J Clin Endocrinol Metab. 1982;55(2):321–8


Moshage H, Kok B, Huizenga JR, Jansen PL. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem. 1995;41(6 Pt 1):892–6


Hussein J, Abdel L, El-Bana M, Medhat D, Morsy S, El-Toukhy S, et al. New approach in treatment of brain injury: Neurotrophic effects of Apigenin. J of Chem and Pharmac Res. 2015;7(5):996–1004


Drury RAB, Wallington EA. Preparation and fixation of tissues Drury RAB, Wallington EA , editors. Carleton’s Histological Technique. 5. Oxford: Oxford University Press; 1980. p. 41–54


Deng Y, Song A, Wang H. Chemical Components of Seriphidium Santolium Poljak. J Chin Chem Soc. 2004;51(3):629–36


Huang W, Wu S-B, Wang Y, Guo Z-Y, Kennelly E, Long C. Chemical constituents from Striga asiatica and its chemotaxonomic study. Biochem System and Ecol. 2013;48:100–6


Hasan A, Ahmed I, Jay M, Voirin B. Flavonoid glycosides and an anthraquinone from Rumex chalepensis. Phytochem. 1995;39(5):1211–13


Delazar A, Celik S, Gokturk RS, Unal O, Nahar L, Sarker SD. Two acylated flavonoid glycosides from Stachys bombycina, and their free radical scavenging activity. Pharmazie. 2005;60(11):878–80


Akimanya A, Midiwo J, Matasyoh J, Okanga F, Masila V, Walker L, et al. Two polymethoxylated flavonoids with antioxidant activities and a rearranged clerodane diterpenoid from the leaf exudates of Microglossa pyrifolia. Phytochem Lett. 2015;11:183–7


Hammad H, Albu C, Matar S, Litescu S-C, Jaber H, Abualraghib A, et al. Biological activities of the hydro-alchoholic and aqueous extracts of Achillea biebersteinii Afan. (Asteraceae) grown in Jordan = Afr. J. Pharm. Pharmacol. 2013;7(25):1686–94


Choi J, Nurul M, Yousof M, Kim E, Kim Y, Jung H. Effects of C-glycosylation on anti-diabetic, anti-Alzheimer’s disease and anti-inflammatory potential of apigenin. Food Chem Toxic. 2014;64:27–33


Zhang L, Yang J, Chen X, Zan K, Wen X, Chen H, Wang Q, Lai M. Antidiabetic and antioxidant effects of extracts from Potentilla discolor Bunge on diabetic rats induced by high fat diet and streptozotocin. J Ethnopharm. 2010;132(2):518–24


Jarral S, Tahir M, Lone K. Postnatal Histogenesis of Islets of Langerhans in Rat. Pakistan J Zool. 2013;45(2):323–9


Kavalali G, Tuncel H, Goksel S, Hatemi H. Hypoglycemic activity of Urtica pilulifera in streptozotocin-diabetic rats. J Ethnopharm. 2003;84:241–5


Das S, Barman S. Antidiabetic and antihyperlipidemic effects of ethanolic extract of leaves of Punica granatum in alloxan-induced non-insulin-dependent diabetes mellitus albino rats. Indian J Pharmacol. 2012;44(2):219–24


Verma VK, Sarwa KK, Zaman KMD. Antihyperglycemic activity of swertia chirayita and andrographis paniculata plant extracts in streptozotocin induced diabetic rats. Intern J of Pharm and Pharmac Sci. 2013;55(3):305–11


Yomna M. Yassine is a doctoral researcher at National Research Centre, Egypt. She finished her Msc in 2016 from Faculty of Pharmacy; Ain Shams University; Egypt. Her research topic is isolation and identification of bioactive constituents from natural resources

Prof. Dr. Abdel-Razik H. Farrag is a professor of Pathology, Pathology Department, National Research Centre, Egypt. His research topic is study of histological and histochemical effects of natural products from plants and marine soft corals.

Prof. Dr. Mahmoud I. Nassar; is a professor of Natural Product Chemistry, Natural Compounds Chemistry Department, National Research Centre, Egypt. His research topic is isolation and structure elucidation of bioactive constituents from medicinal plants and marine soft coral such as flavonoids, steroids, ceramides and volatile oil.