Experimental Antidiabetic Plants
Various studies have been undertaken in different regions of Morocco in order to
select and classify the main medicinal plants used to treat diabetes. Ziyyat et al. [63]
conducted an ethnomedical study in eastern Morocco on plants used for diabetes
and hypertension and an inventory of 42 plants used has been established. For di-
abetes, 38 species have been reported; the most used were Trigonella foenum-graecum
(Leguminosae), Globularia alypum (Globulariacea), Artemisia herba-alba
(Compositae), Citrullus colocynthis (Cucurbitaceae), and Tetraclinis articulata (Cu-
pressaceae). Three of these species, namely Artemisia herba-alba, Tetraclinis articulata,
and Trigonella foenum-graecum are also used for hypertension, which suggests
a relationship between hypertension and diabetes.
Bnouham et al. [64] examined antidiabetic effect of an aqueous extract of the aer-
ial parts of Urtica dioïca (nettle), a plant used in eastern Morocco for both diabetes
and hypertension, on hyperglycemia induced by oral glucose tolerance test (OGTT)
and on alloxan-induced diabetic rats. The authors showed a strong antihyperglyce-
mic effect of the plant (250 mg kg–1) during the first hour after glucose loading in
rats under OGTT (33% versus control) but a lack of hypoglycemic effect in alloxan-
induced diabetic rats. Furthermore, intestinal glucose absorption was significantly
reduced in situ in jejunum segment, which suggests that the extract may act on glu-
cose homeostasis via an extrapancreatic mechanism.
In another study, continuous perfusion of U. dioica aqueous extract progressive-
ly reduced arterial blood pressure and increased both diuresis and natriuresis pro-
portionally at the same time [65]. The observed acute hypotensive effect was pro-
voked by an important bradycardia, which is independent of cholinergic and 1-ad-
renergic receptors [66]. Preliminary acute toxicity on rats suggested a low toxicity of
the water extract since some people in eastern Morocco use the plant as a supple-
ment with salad without any side effects.
On the other hand, an investigation of 2400 patients with diabetes in the Wilaya
of Marrakech (southern Morocco) [67] demonstrated that the most used plants are
6.2 Ethnobotanic and Ethnopharmacology of Traditional Moroccan Plants 129
Trigonella foenum-graecum (19.11%), Marrubium vulgare (13.42%), Artemisia herba
alba (11.24%), Ammi visnaga (10.09%) , Globularia alypum (9.86%), and Zygophyl-
lum gaetulum (5.21%). Patients (15 men and 15 women) treated with a single dose
of the infusion of Z. gaetulum leaves (Zygophyllaceae), locally known as “Alaa-
gaya”, showed a significant fall in blood glucose levels at 3 h (–13.26%) and at 6 h
(–13.84%), and this fall was maintained at 9 h (–35.97%) [68]. The same authors
have tested the plant but this time on alloxan-induced hyperglycemic rats [69] and
shown that oral treatment with the aqueous extract caused a continuous marked
reduction of blood glucose levels particularly at 6 and 9 h after treatment (–52.82%
and –69.80% respectively). Toxicological assay of an aqueous extract of the plant on
rats (32 g kg–1 body weight) showed mild central nervous system stimulation, slow
respiration, no motor activity, and distending of the stomach [68]. In all doses of
aqueous extract examined (up to 16 g kg–1 body weight) no significant change in
motor activity was observed, skin was found to be normal, with no noticeable
changes in behavior (LD50 = 15.5 g kg–1 body weight). Chemical studies on Z. gaetulum
have been conducted by Safir and Fkih-Tetouani [57] and three new bides-
mosidic triterpene saponins have been isolated and identified, named zygophylo-
side I, L, and M.
Another medicinal plant, Globularia alypum (Globulariacee), known locally as
“ain larnab,” which is frequently used to cure diabetes in eastern and southern Mo-
rocco [63, 67] and is also known to be laxative [3], stomachic, a good purgative, and
sudorific [5], has been evaluated for its antihyperglycemic activity. Skim et al. [70],
working on an infusion of G. alypum leaves, found that the extract exhibited a re-
markable hypoglycemic effect 2 h after oral or intraperitoneal treatment (–69.96%
and –53.29% respectively). The authors speculate that G. alypum activity could be
due to an enhancement of the peripheral metabolism of glucose and an enhance-
ment of insulin glucose levels.
In Tafilalet (south-eastern Morocco), G. alypum was also found among the most
frequently used plants for diabetes, along with Ammi visnaga, A. herba alba, T. foenum-
graecum, Marrubium vulgare, Nigella sativa, Allium sativum, Olea europea, C.
colocynthis, Aloe succotrina, and Rosmarinus officinalis [71]. In this study 16 plants
used for diabetes were also used to treat hypertension and cardiac diseases and we
can note some used plants known for their toxicity such as Peganum harmala and
Nerium oleander. Globularia alypum was also evaluated by Jouad et al. [72] together
with Rubus fructicosis (Rosaceae), traditionally used as a depurative and an astrin-
gent. The aqueous extracts of these two plants produced a significant decrease of
plasma glucose. In contrast, the mechanism of action stipulated was different from
that suggested by Skim and workers [70] and was found to be independent of ele-
vation of insulin secretion. This could be due to the difference in the method of
preparation, in the doses used, and in the origins of the plants used. However, the
authors are in agreement in considering that G. alypum leaves extract are free of
toxic compounds at the dose tested [70, 72, 73]. The decoction of Rubus fructicosis
was more potent that metformin [72]. It was also demonstrated in another study
that a 20% dried leaves infusion of Rubus ulmifolius caused a significant decrease
of plasma glucose in streptozotocin rats [74].
130 6 Biological and Toxicological Properties of Moroccan Plant Extracts: Advances in Research
In the central northern region of Morocco (Fez-Boulemane), about 90 plants
were recorded as traditional remedies for treating diabetes, cardiac, and renal dis-
eases [75], 54 of which were cited for diabetes (over 100 citations). Two of the cited
plants have been studied scientifically to confirm the traditional claims that they
cure diabetes. Jouad et al. [76] undertook a survey of an aqueous extract of Spergu-
laria purpurea (Caryophyllaceae) and found evidence of a plasma glucose lowering
effect but no effect on plasma insulin concentration, suggesting that S. purpurea
extract acts via an insulin-independent mechanism, possibly by stimulating glu-
cose utilization in peripheral tissues. On the other hand, the extract had a low acute
toxicity in rats (LD50 = 10.75 g kg–1) and can be considered free of side effects.
Various studies have been undertaken in different regions of Morocco in order to
select and classify the main medicinal plants used to treat diabetes. Ziyyat et al. [63]
conducted an ethnomedical study in eastern Morocco on plants used for diabetes
and hypertension and an inventory of 42 plants used has been established. For di-
abetes, 38 species have been reported; the most used were Trigonella foenum-graecum
(Leguminosae), Globularia alypum (Globulariacea), Artemisia herba-alba
(Compositae), Citrullus colocynthis (Cucurbitaceae), and Tetraclinis articulata (Cu-
pressaceae). Three of these species, namely Artemisia herba-alba, Tetraclinis articulata,
and Trigonella foenum-graecum are also used for hypertension, which suggests
a relationship between hypertension and diabetes.
Bnouham et al. [64] examined antidiabetic effect of an aqueous extract of the aer-
ial parts of Urtica dioïca (nettle), a plant used in eastern Morocco for both diabetes
and hypertension, on hyperglycemia induced by oral glucose tolerance test (OGTT)
and on alloxan-induced diabetic rats. The authors showed a strong antihyperglyce-
mic effect of the plant (250 mg kg–1) during the first hour after glucose loading in
rats under OGTT (33% versus control) but a lack of hypoglycemic effect in alloxan-
induced diabetic rats. Furthermore, intestinal glucose absorption was significantly
reduced in situ in jejunum segment, which suggests that the extract may act on glu-
cose homeostasis via an extrapancreatic mechanism.
In another study, continuous perfusion of U. dioica aqueous extract progressive-
ly reduced arterial blood pressure and increased both diuresis and natriuresis pro-
portionally at the same time [65]. The observed acute hypotensive effect was pro-
voked by an important bradycardia, which is independent of cholinergic and 1-ad-
renergic receptors [66]. Preliminary acute toxicity on rats suggested a low toxicity of
the water extract since some people in eastern Morocco use the plant as a supple-
ment with salad without any side effects.
On the other hand, an investigation of 2400 patients with diabetes in the Wilaya
of Marrakech (southern Morocco) [67] demonstrated that the most used plants are
6.2 Ethnobotanic and Ethnopharmacology of Traditional Moroccan Plants 129
Trigonella foenum-graecum (19.11%), Marrubium vulgare (13.42%), Artemisia herba
alba (11.24%), Ammi visnaga (10.09%) , Globularia alypum (9.86%), and Zygophyl-
lum gaetulum (5.21%). Patients (15 men and 15 women) treated with a single dose
of the infusion of Z. gaetulum leaves (Zygophyllaceae), locally known as “Alaa-
gaya”, showed a significant fall in blood glucose levels at 3 h (–13.26%) and at 6 h
(–13.84%), and this fall was maintained at 9 h (–35.97%) [68]. The same authors
have tested the plant but this time on alloxan-induced hyperglycemic rats [69] and
shown that oral treatment with the aqueous extract caused a continuous marked
reduction of blood glucose levels particularly at 6 and 9 h after treatment (–52.82%
and –69.80% respectively). Toxicological assay of an aqueous extract of the plant on
rats (32 g kg–1 body weight) showed mild central nervous system stimulation, slow
respiration, no motor activity, and distending of the stomach [68]. In all doses of
aqueous extract examined (up to 16 g kg–1 body weight) no significant change in
motor activity was observed, skin was found to be normal, with no noticeable
changes in behavior (LD50 = 15.5 g kg–1 body weight). Chemical studies on Z. gaetulum
have been conducted by Safir and Fkih-Tetouani [57] and three new bides-
mosidic triterpene saponins have been isolated and identified, named zygophylo-
side I, L, and M.
Another medicinal plant, Globularia alypum (Globulariacee), known locally as
“ain larnab,” which is frequently used to cure diabetes in eastern and southern Mo-
rocco [63, 67] and is also known to be laxative [3], stomachic, a good purgative, and
sudorific [5], has been evaluated for its antihyperglycemic activity. Skim et al. [70],
working on an infusion of G. alypum leaves, found that the extract exhibited a re-
markable hypoglycemic effect 2 h after oral or intraperitoneal treatment (–69.96%
and –53.29% respectively). The authors speculate that G. alypum activity could be
due to an enhancement of the peripheral metabolism of glucose and an enhance-
ment of insulin glucose levels.
In Tafilalet (south-eastern Morocco), G. alypum was also found among the most
frequently used plants for diabetes, along with Ammi visnaga, A. herba alba, T. foenum-
graecum, Marrubium vulgare, Nigella sativa, Allium sativum, Olea europea, C.
colocynthis, Aloe succotrina, and Rosmarinus officinalis [71]. In this study 16 plants
used for diabetes were also used to treat hypertension and cardiac diseases and we
can note some used plants known for their toxicity such as Peganum harmala and
Nerium oleander. Globularia alypum was also evaluated by Jouad et al. [72] together
with Rubus fructicosis (Rosaceae), traditionally used as a depurative and an astrin-
gent. The aqueous extracts of these two plants produced a significant decrease of
plasma glucose. In contrast, the mechanism of action stipulated was different from
that suggested by Skim and workers [70] and was found to be independent of ele-
vation of insulin secretion. This could be due to the difference in the method of
preparation, in the doses used, and in the origins of the plants used. However, the
authors are in agreement in considering that G. alypum leaves extract are free of
toxic compounds at the dose tested [70, 72, 73]. The decoction of Rubus fructicosis
was more potent that metformin [72]. It was also demonstrated in another study
that a 20% dried leaves infusion of Rubus ulmifolius caused a significant decrease
of plasma glucose in streptozotocin rats [74].
130 6 Biological and Toxicological Properties of Moroccan Plant Extracts: Advances in Research
In the central northern region of Morocco (Fez-Boulemane), about 90 plants
were recorded as traditional remedies for treating diabetes, cardiac, and renal dis-
eases [75], 54 of which were cited for diabetes (over 100 citations). Two of the cited
plants have been studied scientifically to confirm the traditional claims that they
cure diabetes. Jouad et al. [76] undertook a survey of an aqueous extract of Spergu-
laria purpurea (Caryophyllaceae) and found evidence of a plasma glucose lowering
effect but no effect on plasma insulin concentration, suggesting that S. purpurea
extract acts via an insulin-independent mechanism, possibly by stimulating glu-
cose utilization in peripheral tissues. On the other hand, the extract had a low acute
toxicity in rats (LD50 = 10.75 g kg–1) and can be considered free of side effects.
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