Antihyperglycemic Effect of Crude Extracts of Some Egyptian Plants and Algae

Abstract

Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabetic activity and are considered as promising substitution for antidiabetic drugs. The antihyperglycemic effect of 16 plants and 4 algae, commonly used in Egypt for the treatment of diabetes mellitus, was investigated. A diabetes model was induced by intraperitoneal injection of nicotinamide (120 mg/kg body weight [b.wt.]), then streptozotocin (200 mg/kg b.wt.) after 15 min. Hydroethanolic extracts (80%) of the plants and algae under investigation were prepared. The extracts were orally administered to nicotinamide-streptozotocin–induced diabetic mice by a gastric tube at doses 10 or 50 mg/kg b.wt. for 1 week. The antidiabetic activity was assessed by detection of serum glucose concentrations at the fasting state and after 2 h of oral glucose loading (4.2 mg/kg b.wt.). Extracts prepared from Cassia acutifolia, Fraxinus ornus, Salix aegyptiaca, Cichorium intybus, and Eucalyptus globulus showed the highest antihyperglycemic activity among the tested plants. Extracts prepared from Sonchus oleraceus, Bougainvillea spectabilis (leaves), Plantago psyllium (seeds), Morus nigra (leaves), and Serena repens (fruits) were found to have antihyperglycemic potentials. Extracts prepared from Caulerpa lentillifera and Spirulina versicolor showed the most potent antihyperglycemic activity among the tested algae. However, some of the tested plants have insulinotropic effects, all assessed algae have not. Identification of lead compounds from these plants and algae for novel antidiabetic drug development is recommended.

Introduction

Diabetes mellitus is a group of pancreatic endocrine-based disease state of differing causes and severity.¹ It occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Hyperglycemia, raised blood sugar, is a common effect of uncontrolled diabetes mellitus. The disease is becoming a major public health problem globally.² According to the International Diabetes Federation, it is estimated that 230 million people in the world have diabetes. The World Health Organization (WHO) estimates that this number will exceed 370 million by 2030 and considers the disease as the fifth leading cause of death in the world. Diabetes is associated with many vascular complications leading to blindness, renal failure, cardiovascular diseases, and limb amputations.³ Most cases can be divided into two types: insulin-dependent diabetes mellitus (Type 1) and noninsulin-dependent diabetes mellitus (Type 2). Type 2 diabetes comprises three abnormalities: relative insulin deficiency, insulin resistance involving myocytes and adipocytes, and hepatic insulin resistance resulting in increased gluconeogenesis and impaired glycogen synthesis. Management of type 2 diabetes by oral administration of hypoglycemic agents can be achieved by different mechanisms: increase in insulin secretion, increase in peripheral glucose uptake, decrease in glucose absorption, and decrease in hepatic glucose production. Various plant extracts have proven antidiabetic activity and are considered as promising substitution for antidiabetic drugs.^4,5 The research in this field is driven by an apparent trend to use herbal medicine due to adverse reactions and undesirable side effects of synthetic drugs. The lower cost and high availability of medicinal plants make it a preferable choice especially in rural populations of developing countries.⁶ Unfortunately, most of the plant extracts that have the potential to treat type 2 diabetes have not been studied in depth and usually their active substances are not known.

Recent studies have shown that algae have beneficial effects on type 2 diabetes mellitus.^7
–9 Spirulina, a blue-green alga, is now becoming a health food worldwide. It has a wide range of biological effects such as antidiabetic, antiviral, anticancer, and hypocholesterolemic activities. It is gaining attention as a nutraceutical and a source of potential pharmaceutical.¹⁰ Despite health benefits with algae consumption, it is not widely consumed in East Asian countries such as Korea, Japan, and China.⁷

The main aim of this research is to find novel treatments from plant or marine origin that possess potential therapeutic properties for type 2 diabetes mellitus with no or few side effects.

Materials and Methods

Collection of plants and algae

Plants under investigation in this study were collected from the Beni-Suef region from April to June 2010. Fraxinus ornus, Plantago psyllium, Lepidium sativum, Cassia acutifolia, Serenoa repens, and Tamarindus indica were obtained from the Harraz Medicinal Plant Company, Cairo, Egypt. The plants were identified by Dr. Abdelhalim Mohamed (Flora and Phytotaxonomy Department, Horticulture Research Institute, Agricultural Research Center, Ministry of Agriculture, Giza, Egypt) and Dr. Mohamed Abd Allah Fadl (Botany Department, Faculty of Science, Beni Suef University). Voucher specimens were deposited at the Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University. Green marine algae were obtained from El-Koseir, Egypt. Spirulina versicolor (blue-green microalga) was obtained from the Harraz Medicinal Plant Company. Algae were authenticated by Dr. Khalid Nageh Yameni, Botany Department, Faculty of Science, Beni-Suef University.

Extract preparation for biological screening

Collected plants and algae were air-dried in the shade and separately pulverized to a fine powder using a mechanical grinder. The powdered materials were extracted (×2) by maceration in double volume of 80% aqueous ethanol at room temperature for 12 h. After filtration, the filtrate was concentrated under reduced pressure in a rotary evaporator (Buchi, Flawil, Switzerland) at 50°C. The residues were stored at −20°C till use in biological evaluation. Table 1 shows the yield obtained for different extracts (extract weight/plant or alga on dry weight basis).

Table 1.

Part Used, Extract Yield, and Antihyperglycemic Effect of Hydroethanolic Extracts of Plants and Algae Under Investigation

	Part used	Extract yield (w/w)	Dose (mg/kg)	Fasting glucose concentration (mg/dL)	2-h glucose concentration (mg/dL)
Normal				83.39±11.08	123.99±0.51
Diabetic control				228.00±30.86⁺⁺	274.02±27.90⁺⁺⁺
Plants
Bauhinia variegata L.	L	0.12	10	205.89±20.76	206.00±19.68
(Leguminosae)			50	142.83±28.72	190.00±61.73
Bougainvillaea spectabilis	L	0.12	10	213.07±5.65	177.13±6.84^**
Willd. (Nyctaginaceae)			50	110.33±5.98^**	91.39±17.45^***
	F	0.16	10	205.79±7.71	339.64±33.87
			50	224.73±19.13	279.82±13.20
Cassia acutifolia Delile.	L	0.03	10	73.75±9.51^***	126.25±5.03^***
(Fabaceae)			50	41.00±4.92^***	50.00±2.58^***
Cichorium intybus L.	L	0.08	10	105.17±2.70^**	116.00±4.83^***
(Asteraceae)			50	60.17±8.59^***	80.69±8.58^***
Cucurbita pepo L.	Fr	0.14	10	212.38±28.57	291.25±38.58
(Cucurbitaceae)			50	198.75±47.26	174.50±23.64^*
	P		10	115.92±15.73^**	185.08±19.62^*
			50	173.13±26.87	204.50±30.45
Eucalyptus globulus	L	0.05	10	105.66±20.08^**	169.00±26.66^*
Labill. (Myrtaceae)			50	94.31±20.52^**	37.00±37.00^***
Fraxinus ornus L.	S	0.05	10	31.50±2.91^***	124.00±15.34^***
(Oleaceae)			50	28.67±3.58^***	79.33±7.81^***
Lepidium sativum L.	S	0.05	10	261.66±24.78	291.25±27.39
(Cruciferae)			50	215.83±38.16	196.67±32.59
Mangifera indica L.	L	0.07	10	193.33±47.81	206.67±16.57
(Anacardiaceae)			50	255.50±29.75	254.32±28.45
Morus nigra L.	L	0.08	10	189.16±50.95	255.00±12.78
(Moraceae)			50	107.50±32.58^*	100.00±28.51^**
Opuntia ficus indica Mill.	P	0.06	10	188.00±1.79	342.85±46.93
(Cactaceae)			50	298.50±35.11	330.65±74.44
Plantago psyllium L.	Mu	0.23	10	119.42±21.81^*	140.39±15.54^**
(Plantaginaceae)			50	70.66±0.17^***	105.65±0.11^***
Salix aegyptiaca L.	L	0.07	10	121.25±34.24^*	145.83±26.35^**
(Salicaceae)			50	38.75±10.23^***	91.25±31.49^**
Serenoa repens (Bartr.) Small	F	0.03	10	96.66±31.07^*	139.17±30.31^**
(Arecaceae)			50	210.00±38.35	207.5±21.00
Sonchus oleraceus L.	L	0.06	10	111.67±0.55^**	111.00±1.32^***
(Asteraceae)			50	106.33±0.56^**	108.00±2.28^***
Tamarindus indica L.	Fr	0.42	10	238.00±51.91	310.00±48.30
(Fabaceae)			50	242.50±1.12	287.50±48.36
Algae
Caulerpa lentillifera		0.02	10	141.58±20.40^*	172.50±8.11^**
			50	63.75±7.27^***	144.24±10.07^**
Enteromorpha intestinalis		0.04	10	72.73±4.95^**	182.00±30.01^*
			50	139.19±1.16^*	218.00±44.68
Spirulina versicolor		2.4	10	121.65±6.42^**	172.45±4.53^*
			50	49.94±7.70^***	184.97±22.01^*
Ulva lactuca		0.002	10	156.67±43.83	147.50±31.08^*
			50	202.50±0.91	116.57±22.64^**

Significant, ⁺⁺highly significant, and ⁺⁺⁺very highly significant as compared with normal control.

Significant, ^**highly significant, and ^***very highly significant, as compared with diabetic control.

F, flowers; Fr, fruits; L, leaves; Mu, mucilage; P, pulp; S, seeds.

Preparation of mucilage from P. psyllium seeds

The swelling index of P. psyllium seeds was determined according to the WHO reported method.¹¹ One gram of whole seeds was accurately weighed and introduced into a 25-mL glass stoppered measuring cylinder. Twenty-five milliliters of water were added and the mixture was shaken thoroughly every 10 min for 1 h. The mixture was allowed to stand for 3 h at room temperature and the swelling index was calculated. Three determinations were carried out simultaneously. To prepare the mucilage fraction, P. psyllium seeds were extracted according to a reported method.¹² Ten grams of the dried seeds was heated to boiling with 100 mL of 0.1 M HCl. After boiling, the solution was filtered through a muslin cloth while hot. The filtrate was mixed with double volume of 95% ethanol, stirred, and allowed to stand for 2 h. The supernatant was decanted and the precipitate was dried in an oven at 50°C. The mass of the precipitate represented the total mucilage content.

Phytochemical screening

Dried plant material was ground to fine powder and extracted by 100 mL of 70% ethanol for 45 min, filtered, and then divided into three parts. One part was tested for alkaloids using the Dragendorff's reagent.¹³ A second part was tested for anthraquinones.¹⁴ A third part of the extract was tested for cardenolides/bufadienolides.¹⁴ One gram of the powdered plant material was shaken with 10 mL of 1% HCl for 5 min, filtered, and tested for flavonoids.¹⁵

Experimental animals

Male albino mice weighing 25–30 g were used as experimental animals in this study. They were obtained from the animal house of the Ophthalmology Research Institute, Giza, Egypt. They were kept under observation to exclude any intercurrent infection. They were fed a standard diet ad libitium and free access to drinking water. All animal procedures were performed upon approval from the Ethics Committee of the Beni-Suef University and in accordance with the recommendations of proper care and use of laboratory animals.

Toxicity screening

Dried extracts of plants or algae were dissolved in 10 mL of 1% carboxymethyl cellulose (CMC) and were orally administered once to the mice by a gastric tube between 9 and 10 a.m. The control group was given the respective volume of 1% CMC. Each group consisted of six mice. The animals were kept under observation and the toxic symptoms as well as the rate of mortality in each group were recorded during 48 h after the extract administration. The hydroethanolic extract of all plants and algae included in the study produced no mortality with increasing doses to 2000 mg/kg body weight (b.wt.) except for the Cichorium intybus hydroethanolic extract, which caused mortality of one animal out of the six. Thus, LD₅₀ of C. intybus hydroethanolic extract was determined according to the reported method.¹⁶ Nine groups each of six male albino mice weighing 20–25 g were used. One group served as control and the other groups were orally administered the tested extract by a gastric tube in gradual increasing doses (500, 1000, 1500, 2000, 2500, 3000, 3500, and 4000 mg/kg b.wt.). After 48 h, the number of dead animals in each group, the mean of dead animals in two successive doses (z), and the constant factor between two successive doses (d) were recorded and LD₅₀ was calculated as follows:

LD₅₀=the lowest dose that killed all animals – [Σ(z·d)]/n

where n is the number of animals in each group (six animals in each group).

LD₅₀ of albino rats was calculated from that of mice (Table 2) by using the conversion table of Paget and Barnes and the therapeutic dose used for the subsequent studies was chosen based on the obtained LD₅₀.¹⁷

Table 2.

Determination of Mediam Lethal Dose of Cichorium intybus Hydroethanolic Extract in Albino Mice

Dose (mg/kg b.wt.)	Total no. of animals	No. of dead animals	z	d	Σ(z·d)
500	6	0	0	0	0
1000	6	0	0	500	0
1500	6	0	0	500	0
2000	6	1	0.5	500	250
2500	6	3	2	500	1000
3000	6	4	3.5	500	1750
3500	6	5	4.5	500	2250
4000	6	6	5.5	500	2750

LD₅₀=the lowest dose that killed all animals – [Σ(z·d)]/n=4000 – (8000/6)=2666.6 mg/kg b.wt. By using the conversion table of Paget and Barnes,¹⁷ half-maximal lethal dose (LD₅₀) for rats was calculated from that of mice and was found to be 1866.62 mg/kg b.wt.

z, mean number of dead animals in two successive doses; d, constant factor between two successive doses; LD₅₀, mediam lethal dose.

Antidiabetic screening

Evaluating the antihyperglycemic effect of the tested plants and algae was carried out using nicotinamide-streptozotocin (NA-STZ) type 2 diabetic mice. This model of diabetes was induced by intraperitoneal injection of nicotinamide (120 mg/kg b.wt.) dissolved in saline 15 min before intraperitoneal injection of STZ (200 mg/kg b.wt.) dissolved in the citrate buffer at pH 4.5.^18,19 Ten days after NA-STZ injection, blood samples were obtained from the lateral tail vein of overnight food deprived animals at a fasting state and after 2 h of oral glucose loading (4.2 g/kg b.wt.). The serum glucose concentration was determined. Animals that have a 2-h serum glucose concentration higher than 180 mg/kg b.wt. were considered diabetic and included in the experiment. Hydroethanolic extract of each plant and alga under investigation was orally administered to STZ-NA–induced diabetic mice by a gastric tube at doses of 10 and 50 mg/kg b.wt. for 1 week. These doses were further far from LD₅₀ or from the higher tested doses, which cause no mortality in an acute toxicity study.

Statistical analysis

The data were analyzed using the t test using PC-STAT.²⁰ The results are expressed as mean±standard error and values of P>.05 are not significantly different, while values of P<.05, P<.01, and P<.001 are significant, highly significant, and very highly significant, respectively.

Results

Hydroethanolic extracts (80%) were prepared from dried and grounded plants and algae under investigation. The yield of the extract ranged from 0.03 to 0.23 for the selected plants (Table 1). Algae showed lesser yield than plants probably due to their high water content. The mucliage fraction was prepared from P. psyllium seeds. It was previously demonstrated that mucilage prepared from this species showed significant reduction in the fasting plasma glucose level when used as an adjunct to dietary therapy.²¹ The swelling index, defined as the volume in mL taken up by the swellling of 1 g of plant material after addition of water to the whole P. psyllium seeds, was 5.10±0.05.

Extracts prepared from the collected plants and algae were separately subjected to tests for the presence of major classes of phytochemicals. The plants and algae were screened for the presence of alkaloids and/or basic nitrogenous compounds, tannins, flavonoids, saponins. F. ornus extract showed the presence of alkaloids. F. ornus, Eucalyptus globulus, Morus nigra, L. sativum, Sonchus olreaceus, S. repens, Opuntia tuna, and Bougainvillea spectabilis extracts showed the presence of tannins. All extracts under investigation in this study tested positive for the presence of flavonoids except T. indica. F. ornus, B. spectabilis, C. intybus, P. psyllium, M. nigra, S. oleraceus, S. repens, T. indica, and O. ficus indica tested positive for the presence of saponins. All of the tested algae extracts showed the presence of saponins except U. lactuca. E. intestinalis showed the presence of tannins. S. versicolor showed the presence of flavonoids.

Acute toxicity testing was performed to determine LD₅₀ of the extracts of tested plants and algae and to ensure the use of safe doses in screening the antihyperglycemic effect. The hydroethanolic extracts of plants and algae produced no mortality with increasing doses up to 2000 mg/kg b.wt. except for C. intybus. The hydroethanolic extract of this species caused mortality of one animal out of six. The LD₅₀ of C. intybus hydroethanolic extract was determined and the results are shown in Table 2.

Results of testing the antihyperglycemic effect revealed that NA-STZ type 2 diabetic animals exhibited highly (P<.01) and very highly (P<.001) significant elevation of serum glucose concentrations at the fasting state and 2 h postglucose loading, respectively. The percentage increases of serum glucose concentrations were 173.41% and 121.00% at the fasting state and 2 h postoral glucose loading compared with control. The hydroethanolic extract of C. acutifolia leaflets showed the highest antihyperglycemic effect at fasting state and 2 h postglucose loading at dose levels 10 and 50 mg/kg b.wt. The hydroethanolic extract of F. ornus fruits showed a significantly high antihyperglycemic effect at fasting state at the same dose levels. The tested hydroethanolic plant extracts are arranged according to their antihyperglycemic potency as follows: C. acutifolia > F. ornus > E. globulus > C. intybus > Salis aegyptiaca > P. psyllium > S. oleraceus > B. spectabilis (leaves) > S. repens > M. nigra. The hydroethanolic extracts of Bauhinia variegata, B. spectabilis (flowers), Cucurbita pepo (fruits and pulp), L. sativum, Mangifera indica, O. ficus indica, and T. indica did not show any antihyperglycemic activity (Table 2).

The hydroethanolic extracts of the tested algae produced potent antihyperglycemic effects in NA-STZ–induced type 2 diabetic rats. Caulerpa lentillifera (sea grape) and S. versicolor extracts were the most potent and induced significant antihyperglycemic effects at fasting state and 2 h postglucose loading in a dose-dependent manner. On the other hand, U. lactuca extract produced significant antihyperglycemic effects only after 2 h of oral glucose loading; the effect was significant (P<.05) and highly significant (P<.05) as a result of administration of 10 and 50 mg/kg b.wt., respectively. The lower dose of E. intestinalis hydroethanolic extract was more effective than the higher dose; the lower dose produced percentage decreases (68.10 and 33.40) that were greater than those of higher dose (38.95 and 20.26) at fasting state and 2 h postglucose loading, respectively (Table 1).

The serum insulin level exhibited a significant decrease (P<.001) in NA-STZ type 2 diabetic animals (3.026±0.299 μIU/mL) as compared with normal mice (7.072±0.605 μIU/mL). The treatment of diabetic mice with the tested hydroethanolic extracts of plants produced a nonsignificant (P>.05) effect on serum insulin concentrations except for the treatment with the lower dose of E. globulus (7.544±0.129 μIU/mL; P<.001), C. pepo (4.620±0.130 μIU/mL; P<.001), M. nigra (4.488±0.140 μIU/mL; P<.01), the high dose of C. intybus (5.369±0.183 μIU/mL; P<.001) and S. oleraceus (5.413±0.172 μIU/mL; P<.001), and both the low (5.154±0.138 μIU/mL; P<.001) and high (4.026±0.129 μIU/mL; P<.05) doses of O. ficus indica, which induced a significant increase of the lowered diabetic value (3.026±0.299 μIU/mL). On the other hand, all hydroethanolic extracts of macroalgae and microalgae produced no significant effect on the diminished serum insulin level of NA-STZ type 2 diabetic mice.

Discussion

Many plant extracts are used in Egyptian folklore medicine as therapeutic remedies for diabetes. Some of these extracts have a proven antihyperglycemic activity, which make them an attractive substitution for traditional antidiabetic drugs. In this study, C. acutifolia showed the highest potential as herbal treatment for diabetes although it had no significant effect on the lowered serum insulin level of NA-STZ diabetic mice. There is no previous research about the potential use of this particular Cassia species for treatment of diabetes. C. angustifolia, a closely allied species, has been clinically investigated for its effect on fasting blood sugar levels in patients with type 2 diabetes mellitus.²² A daily dose of 200 mg of the macerate of the leaves decreased the blood sugar level by 14.3%. C. occidentalis did not significantly altered blood glucose or insulin concentration in streptozotocin diabetic mice.²³ C. auriculata aqueous leaf extracts at doses of 400 mg/kg for 15 days of oral administration significantly reduced fasting blood glucose.²⁴ The aqueous extract of the leaves and bark of Ca. glauca at a dose of 500 mg/kg p.o. for 21 days of treatment significantly increased serum insulin and decreased fasting blood glucose.²⁵ Methanolic extract of C. siamea leaves at doses of 250 and 500 mg/kg for 3 weeks significantly decreased blood glucose levels.²⁶ C. fistula, C. skinneri, and C. tomentosa are commonly used plants in Mexico for the treatment of diabetes.²⁷ Chrysophanol, an anthraquinone isolated from the leaflets of C. acutifolia, showed mild antidiabetic properties in cell culture.²⁸ The activity was proposed to be mediated through affecting glucose transport and tyrosine phosphorylation of insulin receptor.

F. ornus (Arabic name Hab Elderdar) grows wild in the Mediterranean region and south central Europe.²⁹ Coumarins, secoiridoids, and phenylethanoids are common in the Fraxinus species. The infusion prepared from F. ornus is prescribed in the morning and at night as an antidiabetic agent in Egyptian folklore medicine. Biological studies on this species reveal significant antimicrobial, antioxidant, and anti-inflammatory activities.^30
–32 Fraxin, a coumarin isolated from F. ornus, showed the free radical scavenging effect and cell protective effect against H₂O₂-mediated oxidative stress.³³ To our knowledge, this is the first report about the antidiabetic effect of F. ornus extract. In our opinion, the potent antihyperglycemic effect of hydroethanolic extracts associated with a nonsignificant increase in serum insulin levels in the present study led us to suggest that F. ornus (seeds), C. acutifolia (leaves), S. aegyptiaca (leaves), P. psyllium (seeds), S. repens (fruits), and B. spectabilis (leaves) may produce their antihyperglycemic effects by improving insulin action or insulin independent effects rather than their effects on the insulin secretory response. In contrast, hydroethanolic extracts of many other tested plants, including E. globulus, C. pepo, M. nigra, C. intybus, and S. oleraceus have antihyperglycemic effects assosciated with a potential improvement of serum insulin levels. Thus, the hydroethanolic extracts of tested plants may have potent insulinotropic actions. In agreement with this suggestion, many previous publications stated that E. globulus, S. oleraceus, C. intybus, and M. nigrum leaf extracts have insulinotropic effects in addition to the extrapancreatic action.^34
–36 However, in discordance with the results of the present study, it was found that C. intybus seed water extract produced a decrease in serum glucose concentrations associated with no change in serum insulin concentrations in STZ-induced diabetic rats.³⁷

Hydroethanolic extracts of L. sativum and T. indica did not show a significant antihyperglycemic activity. This result is contradictory to a previously published report showing that L. sativum aqueous extract at doses of 20 mg/kg b.wt. produced a significant decrease on blood glucose levels in STZ-induced diabetic rats after an acute or chronic oral treatment.³⁸ T. indica aqueous seed extract was reported to reduce blood sugar levels in STZ-induced diabetic rats at doses of 80 mg/0.5 mL distilled water/100 g b.wt. per day after 7 days.³⁹

C. lentillifera, a green macroalga, was effective in lowering plant cholesterol levels in rats.⁴⁰ Methanolic extract of C. lentillifera showed a significant radical scavenging and reducing power ability.⁴¹ In accordance with the results of the present study, U. lactuca was reported to have potential antihyperglycemic, antihyperlipidemic, and antioxidant effects in NA-STZ–induced diabetic rats.^8,9 In parallel with the present study, Layam and Reddy found that spirulina significantly lowered the elevated blood glucose level in a dose-dependent manner in STZ-induced diabetic Wistar rats.¹⁰ In the present study, all tested algae have antihyperglycemic effects at various degrees without a significant increase in serum insulin concentrations of NA/STZ type 2 diabetic mice. This effect proved that these algae may improve insulin sensitivity or may have insulin independent action rather than their effects on insulin secretagogue responses.

In conclusion, the antidiabetic effect of 16 plants and 4 algae commonly used in Egypt for treatment of type 2 diabetes mellitus was evaluated. A potential antidiabetic effect was demonstrated for C. acutifolia, F. ornus, C. lentillifera, and S. versicolor that was previously unknown. Further studies are needed for identification of lead compounds from these plants and algae for the development of novel antidiabetic drugs and understanding their modes of action.

Footnotes

Acknowledgment

The authors acknowledge the Science and Technology Development Fund (STDF) (ID 152), Ministry of Scientific Research, Egypt, for funding and following up the project.

Author Disclosure Statement

The authors declare no competing financial interests.

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