Bioactive Constituents and Toxicological Evaluation of Selected Antidiabetic Medicinal Plants of Saudi Arabia

Abstract

The purpose of this review is to summarize the available antidiabetic medicinal plants in the Kingdom of Saudi Arabia with its phytoconstituents and toxicological findings supporting by the latest literature. Required data about medicinal plants having antidiabetic activities and growing in the Kingdom of Saudi Arabia were searched/collected from the online databases including Wiley, Google, PubMed, Google Scholar, ScienceDirect, and Scopus. Keywords used in search are in vivo antidiabetic activities, flora of Saudi Arabia, active ingredients, toxicological evaluations, and medicinal plants. A total of 50 plant species belonging to 27 families were found in the flora of Saudi Arabia. Dominant family was found Lamiaceae with 5 species (highest) followed by Moraceae with 4 species. β-Amyrin, β-sitosterol, stigmasterol, oleanolic acid, ursolic acid, rutin, chlorogenic acid, quercetin, and kaempferol are the very common bioactive constituents of these selected plant species. This paper has presented a list of antidiabetic plants used in the treatment of diabetes mellitus. Bioactive antidiabetic phytoconstituents which showed that these plants have hypoglycemic effects and highly recommended for further pharmacological purposes and to isolate/identify antidiabetes mellitus (anti-DM) active agents also need to investigate the side effects of active ingredients.

Full text

Review Article
Bioactive Constituents and Toxicological Evaluation of Selected
Antidiabetic Medicinal Plants of Saudi Arabia
Ali S. Alqahtani ,
1
,
2
Riaz Ullah ,
1
,
2
and Abdelaaty A. Shahat
1
,
2
1
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
2
Medicinal Aromatic and Poisonous Plants Research Centre, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Correspondence should be addressed to Riaz Ullah; rullah@ksu.edu.sa
Received 13 December 2021; Accepted 30 December 2021; Published 17 January 2022
Academic Editor: Rajadurai Murugan
Copyright ©2022 Ali S. Alqahtani et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
e purpose of this review is to summarize the available antidiabetic medicinal plants in the Kingdom of Saudi Arabia with its
phytoconstituents and toxicological findings supporting by the latest literature. Required data about medicinal plants having
antidiabetic activities and growing in the Kingdom of Saudi Arabia were searched/collected from the online databases including
Wiley, Google, PubMed, Google Scholar, ScienceDirect, and Scopus. Keywords used in search are in vivo antidiabetic activities,
flora of Saudi Arabia, active ingredients, toxicological evaluations, and medicinal plants. A total of 50 plant species belonging to 27
families were found in the flora of Saudi Arabia. Dominant family was found Lamiaceae with 5 species (highest) followed by
Moraceae with 4 species. β-Amyrin, β-sitosterol, stigmasterol, oleanolic acid, ursolic acid, rutin, chlorogenic acid, quercetin, and
kaempferol are the very common bioactive constituents of these selected plant species. is paper has presented a list of an-
tidiabetic plants used in the treatment of diabetes mellitus. Bioactive antidiabetic phytoconstituents which showed that these
plants have hypoglycemic effects and highly recommended for further pharmacological purposes and to isolate/identify anti-
diabetes mellitus (anti-DM) active agents also need to investigate the side effects of active ingredients.
1. Introduction
Medicinal plants are used for the treatment of different in-
fections [1, 2]. ese plants contributed as a source of inspi-
ration for novel therapeutic compounds [3]. e medicinal
value of plants is due to the presence of a wide variety of
secondary metabolites including alkaloids, glycosides, tannins,
volatile oil, and terpenoids [4, 5]. Medicinal plants and their
extracts represent a rich source of crude medications that
possess therapeutic properties. Indeed, the World Health Or-
ganization reports that various plant fractions and their dy-
namic constituents are utilized as traditional medicines by 80%
of the world population [6]. Plants are the primary source for
different pharmaceutical, perfumery, flavor, and cosmetics in-
dustries; the use of modern drugs dramatically resulted into
resistant microorganisms toward different modern drugs; the
researchers are now in search for alternate source of treatment
of various disorders [7, 8]. For this purpose, the medicinal herbs
are the best alternate to various drugs. Most of natural products
possess interesting biological activities and medicinal potential.
Various herbs, fruits, and grains have been found to have
different important biological activities such as antioxidant, [9]
antitumor, antimutagenic, antidiabetes, antianalgesic, [10]
antidementia, inflammation inhibitory effect, [9] antitumor,
[11] anticancer, [12] antimicrobial, antileishmanial, and anti-
malarial properties [13, 14]. e consumption of natural an-
tioxidants will reduce risk of many diseases including cancer,
cardiovascular disease, diabetes, and other diseases allied with
aging [15]. For natural antioxidants, a larger number of me-
dicinal herbs have been evaluated by applying laboratories’
developed procedures. Plants derived substances, collectively
called phytonutrients or phytochemicals, been recognized as
good source of natural antioxidants [16, 17].
e Kingdom of Saudi Arabia is a huge arid land with an
area of about 2,250,000 km
2
covering the major part of the
Arabian Peninsula, characterized by different ecosystems
Hindawi
Evidence-Based Complementary and Alternative Medicine
Volume 2022, Article ID 7123521, 23 pages
https://doi.org/10.1155/2022/7123521

and diversity of plant species. e climate in Saudi Arabia
differs greatly between the coast and the interior. High
humidity coupled with more moderate temperatures is
prevalent along the coast, whereas aridity and extreme
temperatures characterize the interior. e flora of Saudi
Arabia is one of the richest biodiversities in the Arabian
Peninsula and comprises very important genetic resources of
crops and medicinal plants. Saudi Arabia contains 97 trees,
564 shrubs, and about 1620 herbs, which cover, respectively,
4.25%, 24.73%, and 71.02% of higher plant diversity of the
country [18].
Diabetes mellitus is one of the most prevalent diseases in
endocrine gland system with an increasing incidence in
human community [19]. Type I diabetes is caused by insulin
secretion deficit, while type II diabetes is accompanied with
progressive rate of insulin resistance in liver and peripheral
tissues, reducing β-cell mass, and deficient insulin secretion
[20, 21]. is disease brings about acute metabolic side ef-
fects including ketoacidosis, hyperosmolar coma accom-
panied with chronic disorders, and long term, adverse side
effects such as retinopathy, renal failure, neuropathy, skin
complications, as well as increasing cardiovascular com-
plication risks [22, 23]. Also, common symptoms of diabetes
are frequent urine, thirsty, and overeating [24]. Diabetes
inflicts 100 million people yearly and is recognized as the
seventh cause of death in the world [25]. It has been esti-
mated that the number of diabetic people will increase from
150 million individuals in 2003 to 300 million by 2025 [26].
e essential and effective drugs for diabetes mellitus are
insulin injection and hypoglycemic agents, but these com-
pounds possess several adverse effects and have no effects on
diabetes complications in long term. erefore, it is im-
portant to find effective compounds with lower side effects in
treating diabetes [27]. Medicinal plants are good sources as
alternative or complementary treatments for this and other
diseases [28–30]. Although various plants have been tra-
ditionally used throughout history to reduce blood glucose
and improve diabetes complications, there is not enough
scientific information about some of them. Herbal medicines
are commonly prescribed throughout the world because of
low side effects, availability, roughly low cost, and also its
effectiveness [31, 32].
In Saudi Arabia, the number of people who suffer from
DM increased from 890,000 in 2000 to a staggering pro-
jection of 2,523,000 in 2030. In 2011, Saudi Arabia reported a
prevalence of DM at 30% of the total population, with a rate
of 27.6% in women and 34.1% in men [33]. According to
2010 data from several sources (WHO, World Bank,
UNESCO, CIA, and individual country databases), DM is
the number three disease-related cause of death in Saudi
Arabia [34].
In the present situation, herbal medicines’ usage has
significantly increased and published studies from developed
countries emphasize that a paramount proportion of
medicines supplied by them have herbal origins, so growing
and producing the herbal medicines could be helpful to both
economic development and community’s health [35].
Keeping in mind the importance of medicinal plants, in the
current review various medicinal plants used for antidiabetic
treatment around the world, native to or cultivated in Saudi
Arabia, are documented for the purpose to provide up-to-
date insight on medicinal plant used for DM, so that re-
searcher easily selects plant for bioscreening and active
constituents’ identification purposes. erefore, we invite
researchers’ attention to carry out detailed ethno-
pharmacological and toxicological studies on unexplored
antidiabetic plants in order to provide reliable knowledge to
the patients and develop novel antidiabetic drugs.
2. Methods
Required data about medicinal plants having antidiabetic
activities and growing in the Kingdom of Saudi Arabia were
searched/collected from the online databases including
Wiley, Google, PubMed, Google Scholar, ScienceDirect, and
Scopus. Keywords used in search are in vivo antidiabetic
activities, flora of Saudi Arabia, active ingredients, toxico-
logical evaluations, and medicinal plants. Latest published
data approximately in the last ten years with the key outcome
of change in blood glucose level in animal model were in-
cluded. One or two articles are selected as references for each
plant’s species on priority basis from the journals found in
web of science and latest years.
3. Results
e names, families, used parts, location, and antidiabetic
properties in animal model of the native/cultivated Saudi
medicinal plants are summarized in Table 1. e active
ingredients and toxicological effect of these plants in animal
model are given in Table 2. A total of 50 plant species belong
from 27 families were found in the flora of Saudi Arabia.
Dominant family was found Lamiaceae with 5 species
(highest) followed by Moraceae with 4 species.
4. Discussion
e majority of the experiments confirmed the benefits of
medicinal plants with hypoglycemic effects in the man-
agement of diabetes mellitus. From Table 1, it can be
concluded that among the plants used for the treatment of
diabetes, H. salicornicum, T. oliverianum, A. cepa, A. herba-
alba, Teucrium polium, Sesamum indicum, Z. spina-christi,
and U. dioica seem to be most common plants used to treat
diabetes and are available everywhere in the world. e
leaves were most commonly used plant part, and other parts
(root, stem, bark, flower, seed, and whole plant) were also
useful for curing. e most common diabetic model that was
used was the streptozotocin and alloxan-induced diabetic
mouse or rat as diabetic models. e most commonly in-
volved active constituents are flavonoid, alkaloid, saponin,
carbohydrate, vitamins, amino acid and its derivatives,
phenol and its derivatives, and benzoic acid derivatives. e
very common phytoconstituents, targeted metabolic path-
ways, and its structure are given in Table 3 [194, 195]. e
native to or cultivated plant species of the kingdom given in
Table 1 are selected from the published literature about
ethnobotanical value and antidiabetic potential of medicinal
2Evidence-Based Complementary and Alternative Medicine

Table 1: Antidiabetic medicinal plants growing in Saudi Arabia.
S.
no. Names of plants Family Part used location Antidiabetes Activities
1. Allium cepa Liliaceae Bulb Central Saudi Arabia
[36]
Ethanol extract of A. cepa in STZ-induced diabetic
rats causes 66% decreased at 200 mg/kg after 24 h
in blood glucose level [37].
0.4 g/100gbw of A. cepa reduced 50% the fasting
glucose levels of diabetic rats [38]. Similar results
reported by other researchers [39].
2. Anthemis herba-
alba
Compositae/
Asteraceae Aerial parts Farasan Island of Red
Sea [40]
72% plasma glucose levels decreased in albino
mice by ethyl alcohol extract of Artemisia herba-
alba [41]
3. Cichorium intybus Asteraceae Seeds Qassim region [42]
C. intybus leaf powder, ethanol, aqueous seed
extracts, and hexane extracts led to a decrease in
blood glucose levels to near normal value.
Hypoglycemic effects of C. intybus were observed
in diabetic rats, and a dose of 125 mg of plant
extract/kg body weight exhibited the most potent
hypoglycemic effect [43–45]
4. Clitoria ternatea Fabaceae Aerial parts Cultivated throughout
Saudi Arabia [46]
e aqueous extract of Clitoria ternatea leaves and
flower administered for 84 days to diabetic rats
significantly decreased blood glucose [46–48]
5. Ficus carica Moraceae Leaves Southwest of Saudi
Arabia [49]
Different extracts and fractions of F. carica showed
a clear hypoglycemic effect in diabetic rats.
F. carica leaves exerted significant effect on
carbohydrate metabolism enzymes with promising
hypoglycemic and hypolipidemic activities in type
2 diabetic rats [50, 51]
6. Ficus
benghalensis Moraceae Bark Riyadh [52]
In streptozotocin-induced diabetic rats, bark
aqueous extract, and an isolated compound,
α-amyrin acetate exhibited antidiabetic activity by
decreasing the blood glucose level and increasing
the HDL level [53]
7. Ficus religiosa Moraceae
Root bark,
stem bark,
aerial roots
Riyadh [52]
e aqueous extract of bark and ethanol extract of
leaves and fruits had a promising antidiabetic
effect in streptozotocin-induced diabetic rats by
decreasing the blood glucose, serum triglyceride,
and total cholesterol levels and increasing serum
insulin, body weight, and glycogen content in the
liver and skeletal muscle [53]
8. Ficus microcarpa Moraceae Leaves Riyadh [52]
F. microcarpa leaves showed protective effect
against alloxan-induced diabetic rats by reducing
blood glucose, cholesterol and triglyceride levels,
and increased insulin level [53]
9. Hypericum
perforatum Hypericaceae Leaves Western Saudi Arabia
[54]
H. perforatum ethyl acetate extract possesses
potent antihyperglycemic activity in STZ-induced
diabetic rats [55].
10 Anethum
graveolens Apiaceae Seeds Makka [56]
Different extracts and tablets of Anethum
graveolens possess potent antihyperglycemic
activity in alloxan-induced diabetic mice [57]
11 Cuminum
cyminum L.
Apiaceae or
Umbelliferae Seeds Makka [56]
Oral administration of cumin seeds crude ethanol
extract and glibenclamide to diabetic rats
significantly and progressively restored toward
normal. Cumin seeds crude ethanol extract and
glibenclamide reduced plasma glucose levels by
38.34 and 37.73%, respectively, compared with
diabetic control [58]. Other studies also reported
similar results [59].
12 Marrubium
vulgare Lamiaceae Whole plant Widely distributed in
Saudi Arabia [60]
M. vulgare extracts lower blood glucose level 30 to
60% in dose-dependent manner in streptozotocin-
induced diabetic rats [60].
Evidence-Based Complementary and Alternative Medicine 3

Table 1: Continued.
S.
no. Names of plants Family Part used location Antidiabetes Activities
13 Mentha longifolia Lamiaceae Whole plant Madinah [61]
Remarkable antidiabetic, anticholinesterase, and
antityrosinase effects were recorded for the mint
oil [61, 62]. Still need to investigate in vivo
antidiabetic potential.
14 Origanum
syriacum Lamiaceae Leaves Saudi Desert [63]
e whole plant extract of O. syriacum at 100 and
400 mg/kg significantly lowers glucose level in
diabetic induced rats [64].
15 Teucrium
oliverianum Lamiaceae Aerial parts roughout Saudi
Arabia [65,66]
Aqueous and ethanol extract of Teucrium
oliverianum were tested for antidiabetic activity in
alloxan-induced diabetic mice. Both extracts
significantly reduced blood sugar levels [65]
16 Teucrium polium Lamiaceae Leaves Madinah [67]
Infusion orally (64% decrease glucose level) and
intraperitoneal of different extracts of T. polium
caused significant reductions in blood glucose
concentration in STZ hyperglycemic rats [68]
17 Achyranthes
aspera Amaranthaceae Whole plant Al Hada Road Taif [69]
e methanolic and ethanolic extract of A. aspera
exhibited significant hypoglycemic activity in
streptozotocin-induced diabetic rats [70]
18 Aerva lanata Amaranthaceae Leaves Southwest region of
Saudi Arabia [71, 72]
Extracts of Aerva lanata and glibenclamide were
found to significantly (P<0.01 and P<0.05)
reduce the blood glucose level and lipid profile in
streptozotocin-induced diabetic rats [73]
19 Alternanthera
sessilis Amaranthaceae Whole plant Hail region, Saudi
Arabia [74]
In diabetic mice at doses of 50, 100, 200, and
400 mg per kg body weight, the extract reduced
blood sugar levels by 22.9, 30.7, 45.4, and 46.1%,
respectively, compared to control animals. By
comparison, a standard antihyperglycemic drug,
glibenclamide, when administered at a dose of
10 mg per kg body weight, reduced blood glucose
level by 48.9% [75]
20 Carissa edulis Apocynaceae Leaves Southern region of
Saudi Arabia [76]
Oral administration of C. edulis extracts of the
leaves significantly reduced the blood glucose level
in STZ diabetic rats [77].
21 Catharanthus
roseus Apocynaceae
Flower,
leaves, stem,
and root
Western Saudi Arabia
[78]
C. roseus (100 mg/kg BW) lowered the glucose
level more than metformin-treated group (100 mg/
kg BW) in STZ-induced hyperglycemia rats.
C. roseus 200 mg/kg dose was found to be more
effective in reducing fasting blood glucose levels
[79]
22 Rhazya stricta Apocynaceae Leaves, seeds
Middle and western
region of Saudi Arabia
[80]
Extracts Rhazya stricta lowered 37.9% blood
glucose level in the streptozotocin-induced
diabetic rats. Serum cholesterol and triglyceride
levels were significantly (P<0.05) reduced in the
treated diabetic group compared to the untreated
diabetic group [81]
23 Calotropis procera Asclepiadaceae Latex Al-Kharj [82]
Different extracts of C. procera at dose of 250 mg/
kg were orally administered as single dose per day
to diabetes-induced rats for the period of 15 days
significantly decreases blood glucose level to the
level of standard drug glibenclamide [83]
24 Opuntia dillenii Cactaceae Fruit Jazan Region [84]
Researcher observed the significant hypoglycemic
activity of Opuntia dillenii extract in
streptozotocin-induced diabetic mice and rabbits
[85]
4Evidence-Based Complementary and Alternative Medicine

Table 1: Continued.
S.
no. Names of plants Family Part used location Antidiabetes Activities
25 Opuntia ficus-
indica Cactaceae Stem Jazan Region [84]
Powder and water extract of O. ficus-indica
significantly (in comparison with control group)
returned blood glucose level to the initial level,
180 min after administration in STZ-induced
diabetic rats [86]. Many studies confirmed the
hypoglycemic activities of O. ficus-indica [87]
26 Capparis decidua Capparaceae Fruits, seeds Jazan Region [84]
C. decidua extracts at dose level of 200 and 800 mg/
kg significantly reduce sugar level (in a dose-
dependent manner) compared to standard drug in
STZ-induced diabetic and normal rats [88].
27 Beta vulgaris Chenopodiaceae Root bark
North Hejaz and
Eastern Najd region of
Saudi Arabia [89]
Extract of B. vulgaris at does level 50, 100, and
200 mg/kg of significantly reduced sugar level and
increased in insulin level (in a dose-dependent
manner) in streptozotocin or alloxan-induced
diabetic mice [90]. Other researchers also
concluded similar finding in STZ-induced diabetic
rats [91].
28
Haloxylon
salicornicum
Bunge
Chenopodiaceae Whole plant Wadi-Hafr-Al-Batin,
Saudi Arabia [92]
Ethanol extract (100 and 200 mg/kg of bw) of
H. salicornicum (oral administration) exhibited
persistent hypoglycemic effects in STZ-induced
diabetic rats [93]
29 Evolvulus
alsinoides Convolvulaceae Whole plant Jazan Region [84]
E. alsinoides ethanol extract at dose level (150 mg/
kg bw) in normal and streptozotocin-induced
diabetic rats leads to hyperglycemia in
experimental diabetic rats that decreased
utilization of glucose by insulin-dependent
pathways [94, 95]
30 Ipomea aquatica Convolvulaceae Whole plant Jazan Region [96]
I. aquatica ethanol extract at dose level (10, 100,
and 1000 µg/ml in streptozotocin-induced diabetic
rats significantly (P<.05) exhibited the ability to
enhance insulin-mediated glucose uptake into
3T3F442A adipocytes cells compared to insulin
alone [97]. Another study confirmed that doses
(200 mg/kg and 400 mg/kg) reduced blood glucose
level, and it was statistically highly significant
(P<0.001) in comparison with control group [98].
31 Citrullus
colocynthis Cucurbitaceae Fruits Jazan Region [84]
1 ml/kg and 2 ml/kg of C. colocynthis extract
(orally administered) stabilized animal body
weight and ameliorated hyperglycemia in a dose-
and time-dependent manner in alloxan-induced
diabetic rats [99]
32 Citrullus lanatus Cucurbitaceae Seed Wadi Lajab, Saudi
Arabia [100]
C. lanatus seed extract (2, 4 g/kg) treatment
significantly lowers glucose level which suggested
that C. lanatus had antidiabetic property in STZ-
induced diabetes mice [101]. Other researcher also
concluded similar finding in STZ-induced diabetic
rats [102]
33 Coccinia grandis Cucurbitaceae Whole plant Jazan Region [84]
e C. grandis extract (0.75 mg/kg, orally) showed
remarkable glycemic effect which confirmed
antidiabetic potential in streptozotocin-induced
diabetic rats [103].
34 Jatropha curcas Euphorbiaceae Leaves Jazan Region [84]
Ethanolic extract of J. curcas leaves at doses of (250
and 500 mg ml
−1
bw by administered orally)
reduced glucose level from 219.5 to 116.5 and 237
to 98.8, respectively, in alloxan-induced diabetic
rats. e results were comparable to reduction in
rats treated with the standard glibenclamide
232–94.5 at 600 μg kg
−1
[104].
Evidence-Based Complementary and Alternative Medicine 5

Table 1: Continued.
S.
no. Names of plants Family Part used location Antidiabetes Activities
35 Ricinus communis Euphorbiaceae Leaves Jazan Region [84]
R. communis extracts at doses of 300 and 600 mg/
kg/BW administered orally caused hyperglycemia
in a dose-dependent manner in streptozotocin-
induced diabetic rats [105].
36 Ficus carica Moraceae Leaves Jazan Region [84]
A review article focusing on antidiabetic potential
of F. carica confirmed that different extracts and
fractions of F. carica and different doses
significantly reducing hyperglycemia in
streptozotocin-induced diabetic rats compared to
standard drug [106].
37 Ficus sycomorus Moraceae Leaves Jazan Region [84]
Alloxan-induced type 2 diabetic albino Wistar rats
treated with 250, 500, and 1000 mg/kg (body
weight) of the extract of F. sycomorus
intraperitoneally reduced glucose level in diabetic
rats almost to the normal as compared to diabetic
control [107]
38 Sesamum indicum Pedaliaceae Seeds Jazan Region [84]
Alloxan-induced diabetic rats treated with 5% and
10% of Sesamum indicum seed powder
significantly decreased blood glucose and
increased insulin levels as compared with the
positive (diabetic) control group [108]
39 Plantago ovata Plantaginaceae Husk
Northern border
region of Saudi Arabia
[18]
In intravenous administration of alloxan-induced
diabetic rabbits glucose level lowering effect
observed (time dependent manner) with P. ovata
husk extract of dose level (300 mg/kg, orally
administered) [109]
40 Polygala erioptera Polygalaceae Aerial part Jazan Region [84]
0.7 g/kg of P. erioptera extract showed significant
antidiabetic effect compared to standard drug
metformin and glibenclamide in normal and
alloxan-induced diabetic rats [110]
41 Polygonum
aviculare LPolygonaceae Aerial parts Taif Region [111, 112]
Many ethnopharmacological investigations
reported its antidiabetic potential but still need to
study its in vivo and in vitro antidiabetic potential
[113, 114]
42 Ziziphus spina-
christi Rhamnaceae Leaves Eastern region of Saudi
Arabia [84, 112]
e strongest (P<0.001) antidiabetic activity
(25.59 and 39.48% after 7 and 15 days,
respectively) was found following treatment with
dose level of 500 mg/kg of Z. spina-christi extract
in streptozotocin-induced diabetes mice [115].
43 Bacopa monnieri Scrophulariaceae Aerial parts Jazan Region [84]
B. monnieri extract at dose level of 50, 100, 200,
and 400 mg/kg significantly inhibited (33.3, 34.2,
42.1, and 44.2%, respectively) the increase in
serum glucose concentration in a dose-dependent
manner compared to standard drug [116].
44 Lycium shawii Solanaceae Aerial parts Taif Region [112]
e strongest (P<0.001) antidiabetic activity of
L. shawii extract of 250 and 500 mg/kg bw was
found in a dose-dependent manner in
streptozotocin-induced diabetes rats [117].
45 Solanum nigrum Solanaceae Whole plant Jazan Region [84]
S. nigrum extract was given orally in the dose level
of 200 and 400 mg/kg/day (7 days) significantly
lowering the blood glucose level in fasting
compared to standard drug in alloxan-induced
diabetic albino Wistar rats [118].
6Evidence-Based Complementary and Alternative Medicine

plants around the world. e ethnobotanical information
reports about 800 plants that may possess antidiabetic po-
tential [196, 197]. Jeeva and Anlin also reported 177 plants
belonging to 156 genera and 76 families used traditionally
for antidiabetic treatment [198]. In the Middle East coun-
tries, there are 129 plant species still in use in traditional
Arabic medicine. is indicates that the medicinal plant
species require preservation as well as the ethnobotanical
and ethnopharmacological knowledge. e preservation of
the herbs is an essential requirement for maintaining tra-
ditional Arabic medicine as a medicinal and cultural re-
source [199]. e selected plant species H. salicornicum,
T. oliverianum, A. cepa, A. herba-alba, Teucrium polium,
Sesamum indicum, Z. spina-christi, and F. religiosa are the
native Saudi medicinal plants traditionally used for the
treatment of DM [200]. Similarly published data showed that
20 medicinal plants are traditionally used in Tabuk region of
Saudi Arabia [201]. Anisotes trisulcus, Artemisia judaica, and
Moringa peregrine are used in Al Khobah village, Saudi
Arabia, for DM treatment [202]. O. europaea is used in Al
Bahah region of KSA for DM treatment [203]. C. roseus,
A. cepa, U. dioica, A. aspera, C. intybus, C. cyminum,
F. bengalensis, C. colocynthis, and T. polium are the highly
investigated medicinal plants for antidiabetic potential
[204–206].
Desiring to contribute to the conservation priorities of
traditional medicine knowledge of various medicinal plants
native to or cultivated in Saudi Arabia and to make it easy
and familiarized with disease treatment, the present com-
pilation was conducted. According to the International
Union for Conservation of Nature and the World Wildlife
Fund, there about 15,000 medicinal plant species are
threatened with extinction from overharvesting and habitat
destruction and 20% of their wild resources have already
been nearly exhausted with the increasing human pop-
ulation and plant consumption [207]. Each plant species lost
due to extinction phenomena could represent not only the
loss of healthcare saving cures for special diseases but also
the loss of probable primary metabolite liker protein- or
vitamin-rich foods [208]. Medicinal plants have been cited as
a potential source of heavy metal toxicity to both man and
animals. e most common heavy metals implicated in
human toxicity include lead, mercury, arsenic, and cad-
mium, although aluminum and cobalt may also cause
Table 1: Continued.
S.
no. Names of plants Family Part used location Antidiabetes Activities
46 Withania
somnifera Solanaceae Leaves Jazan Region [84]
W. somnifera extract oral administration at two
doses (200 and 400 mg/kg) reduced the blood
glucose level significantly (P<0.001) in a dose-
dependent manner in streptozotocin-induced
diabetes rats. Only WS treatment did not register
any significant change in the blood glucose level
when compared to citrate control rats [119].
Another study also confirmed similar results in
alloxan-induced diabetic rats [120]
47 Lantana camara Verbenaceae Leaves Jazan Region [84]
Literature survey showed that L. camara leaf
extract oral administration (200, 250, and 500 mg/
kg of bw) showed antidiabetic potential in alloxan-
induced diabetic rats [121]
48 Peganum harmala Zygophyllaceae Seeds Taif Region [112]
P. harmala seed extract at dose level of (30, 60, and
120 mg/kg, orally administered for four weeks)
significantly decreases in blood glucose (in all
doses, P<0.001), in comparison with diabetic
group [122].
49 Tribulus terrestris Zygophyllaceae Stem, leaves Jazan Region [84]
Taif Region [112]
T. terrestris extract at (2 g/kg body weight)
produced protective effect in streptozotocin-
induced diabetic rats by inhibiting oxidative stress
[123].
T. terrestris L. extract (250 mg/kg of bw orally
administered) significantly lowers glucose level to
normal compared to standard drug in glucose-
loaded normal rabbits [124]
50 Urtica dioica Urticaceae Leaves Wild plant, Tanhat,
Saudi Arabia [125]
Urtica dioica extract at 100 mg/kg (P<0.01) and
200 mg/kg (P<0.001) significantly decreased
serum glucose fructose-induced insulin resistance
rats [126].e aqueous extract
of U. dioica significantly (P<0.001; 67.92%)
reduced the blood glucose level at dose of 300 mg/
kg, IP) in streptozotocin-induced diabetes rats
[127]
Evidence-Based Complementary and Alternative Medicine 7

Table 2: Active ingredients and toxicological evaluation of the medicinal plants given in Table 1.
S.
No Names Active ingredients Toxicological evaluation
1Allium cepa
Quercetin, N-acetylcysteine, alliuocide, cycloalliin, S-
methyl-L-cysteine, S-propyl-L-cysteine, sulfoxide, dimethyl
trisulfide, S-methyl-L-cysteine sulfoxide [128]
e animals tested were found healthy with no sign
of toxicity up to the dose of 2 500 mg/kg. However,
at 5 000 mg/kg, animals were weak and had intense
extreme tachycardia and disorientation but no
death was recorded. us, LD
50
was more than
5 000 mg/kg [129].
2Anthemis herba
alba
Guainalides, eudesmanolide, pseudogua inolides,
xanthonolides, flavone, flavonol glycosides, hispidulin,
cirsilineol, vicenin-2, schaftoside, isoschaftoside, 5′,4-
dihydroxy-6,7,3-trimethoxyflavone, quercetin-3-
rutinoside, patuletin 3-rutinoside, patuletin 3-glucoside
[130]
e available toxicological investigations have
shown generally that Anthemis herba-alba is free
from toxic effects at the different doses used in the
studies [130]
3Cichorium intybus
Chicoric acid, inulin, cichoralexin, cichoriin, esculetin,
isochlorogenic acid, chlorogenic acid, caffeic acid,
dicaffeoylquinic acid, aesculin, arginine, histidine,
isoleucine, leucine, lysine, methionine, cysteine,
phenylalanine, tyrosine, threonine, valine, serine, glutamic
acid, glycine, alanine, aspartic acid, and proline [44, 45]
ere were no treatment-related toxic effects from
chicory extract administered orally at 70, 350, or
1000 mg/kg/day. ere were no observed adverse
effects of chicory extract in these studies [45]
4Clitoria ternatea
Kaempferol, quercetin, myricetin, taxaxerol, tannic acid, 3-
monoglucoside, β-sitosterol, delphinidin-3,5-diglucoside,
anthoxanthin glucoside, p-hydroxycinnamic acid,
kaempferol 3-neohesperidoside, myricetin 3-rutinoside,
hexacosanol [48]
Ethanolic extract of aerial parts and root of CT led
to lethargy in mice at the doses of 1500 mg/kg and
above, orally [31]. Ptosis was seen above 2000 mg/
kg dose in mice. rough intraperitoneal route,
2900 mg/kg dose was lethal within 6 hr due to
severe CNS depression [47].
5Ficus carica
Over 100 bioactive compounds have been identified in fig
such as rutin, arabinose, chlorogenic acid, β-amyrins,
syringic acid, β-carotenes, glycosides, β-sitosterols, and
xanthotoxol [131]
e rats tested were found healthy with no sign of
toxicity up to the dose of 5000, 5500, and 6000 mg/
kg. However, at 5 000 mg/kg, animals were weak
and had intense extreme tachycardia
and disorientation but no death was recorded.
us, LD
50
was more than 6000 mg/kg [132]
6Ficus
benghalensis
Leucopelargonidin-3-0-α-L rhamnoside, eucodelphinidin,
leucoanthocyanidia, leucoanthocyanin, α-amyrin acetate
[53]
In acute toxicity studies, no mortality and signs of
toxicity were observed at the dose of 2000 and
5000 mg/kg body weight for aqueous and ethanol
extracts, respectively [53]
7Ficus religiosa
Lupeol, β-sitosterol, β-sitosterol-d-glucoside, stigmasterol,
lanosterol, campesterol, octacosanol, methyl oleonate,
lupen-3-one, bergapten, and bergaptol [53]
Acute toxicity reported up to dose level 2000 mg/kg
showed no mortality [53]
8Ficus microcarpa
Polyphenols, organic acids, alkaloids, polysaccharides,
megastigmanes, pheophytins, catechin, epicatechin,
isovitexin, phenolic acids [53]
e oral administration of a single dose of 2000 mg/
kg ethanol or methanol extract of leaves showed no
mortality or behavioral alterations in the tested
animals [53]
9Hypericum
perforatum
Quercitrin, rutin, hypericin, kaempferol, biapigenin,
hyperforin [133]
Acute toxicity studies revealed the nontoxic nature
of the H. perforatum [55]
10 Anethum
graveolens
Carvone, α-phellandrene, limonene, dill ether, myristicin
coumarins, flavonoids, phenolic acids, steroids [134]
e mice treated with AG of different doses of 1000,
2000, 3000, 4000, and 5000 mg/kg of body showed
no toxicity [135]
11 Cuminum
cyminum
Cuminaldehyde, limonene, α- and β-pinene, 1, 8-cineole, o-
and p-cymene, α- and c-terpinene, safranal, and linalool
[58, 59]
e acute lethal toxicity test revealed that cumin
crude extract was very safe [58]
12 Marrubium
vulgare
Furanic labdane diterpenes, marrubenol, marrubiin,
ladanein [60]
An acute toxicity study of M. vulgare (1 g/kg)
extract orally administered at a dose of 1 g/kg body
weight to the mice and treated mice showed
tachycardia 1 h after intake of the infusion and loss
of appetite 3 h after intake of the infusion. In
another experiment, a single dose of 2000 mg/kg
extract of M. vulgare for an acute toxicity study
showed no toxicity [60].
8Evidence-Based Complementary and Alternative Medicine

Table 2: Continued.
S.
No Names Active ingredients Toxicological evaluation
13 Mentha longifolia
Lucenin-1, lucenin-2, camphelinone, camphene, carveol,
carvone, carvone oxide, limonene, linalool, menthatriene,
menthofuran, menthol, menthone, myrcene, p-cymene,
piperitenone, piperitone, sabinene, α-pinene, α-terpinene,
α-terpineol, longifone, pulegone, longifoamide-A,
longifoamide-B, longiside-A, longiside-B, eugenol,
salvianolic acid, eriodictyol-7-rutinoside, apigenin-7-O-
glucoside, hypolaetin, longitin, luteolin, etc. [136]
M. longifolia extract was safe, and no toxicity or
mortality was observed in both the oral (3200 mg/
kg) and intraperitoneal (1730 mg/kg)
administration in rats. Fourteen days of oral
administration of the essential oil (125, 250, 375,
and 500 µL/kg) resulted in the reduction of red
blood cells and lymphocytes and elevation of
neutrophils and monocytes compared with normal
animals [136].
14 Origanum
syriacum Carvacrol, thymol, thymoquinone [137] Not available
15 Teucrium
oliverianum
8-O-acetylharpagide, 12-O-methylteucrolin A, teucrolivin
A, eupatorin, teucrolivin B, μ24(S)-stigmasta-5,22,25-trin-
3β-ol [66]
Not available
16 Teucrium polium
Apigenin, luteolin, rutin, cirsiliol, cirsimaritin, salvigenin,
and eupatorin in the roots, aerial parts, and inflorescences,
teucardoside, b-sitosterol, stigmasterol, campesterol,
brassicasterol, and clerosterol [68]
All rats treated with different concentrations of the
total extract of TP were alive during the 14 days of
observation. e animals did not show visible signs
of acute toxicity. It suggested that the LD50 of the
total extract was higher than 8 g/kg [138]
17 Achyranthes
aspera
Aliphatic acid, betaine, achyranthine, β-ecdysterone,
achyranthes saponins A, B, C, D, oleonolic acid, glycosides,
triacontanol, E-sitosterol and spinasterol, triacontanol,
hydroquinone, eugenol [70]
In acute oral toxicity studies, there was no increase
or decrease in any of the parameters studied, in
comparison with control animals [139]
18 Aerva lanata
Quercetin, betulin, aervine, ervoside, methylervine, aervine,
lupeol, kaempferol, aervolanine, aervolanine, ervoside,
methylaervine, persinosides A and B, tannic acid, lupeol
acetate, benzoic acid, methyl grevillate [140]
e LD
50
of the extract of AL for oral and IP acute
toxicity tests were 22.62 g/kg and 0.432 g/kg,
respectively. e extract produced apparent
changes in body weights of both male and female
rats and increased the weights of lung, brain, and
pancreas of female rats while reducing the weight of
testes in male rats. Hematological parameters were
also altered [72]
19 Alternanthera
sessilis
Stigmasterol, β-sitosterol, β-carotene, ricinoleic acid,
myristic, palmitic, stearic, oleic, and linoleic acids,
α-spiraterol, uronic acid, cyclo eucalenol, choline, oleanolic
acid, lupeol [141]
e crude extract did not show any toxicity in mice
even at the highest dose tested [75]
20 Carissa edulis
Β-Amyrin, (+)-carissone, 2α-carissanol, 6α-carissanol,
dehydrocarissone, pinene, myrcene, limonene, sabanene,
rutin, epicatechin gallate, carinol, lariciresinol, β-sitosterol,
sitosterol glucoside, stigmasterol glucoside, scopoletin,
isofraxidin, pinitol [77]
Lethal effects were not observed after the oral
administration of the standardized ethanol extract
at doses of 1600, 2900, and 5000 mg/kg. No
behavioral changes were observed during the
observation period. e oral LD50 of the extract
was estimated to be greater than 5000 mg/kg. [142].
21 Catharanthus
roseus
Vinblastine, vincristine, vindesine, vindeline tabersonine,
ajmalicine, vinceine, vineamine, raubasin, reserpine,
catharanthine, rosindin [143]
No mortality, but dose level higher than 300 mg of
C. roseus extract can produce signs of biochemical
and histopathological toxicity in liver, kidney, and
heart. It is recommended that lower doses than the
studied ones should be used for treatment [144]
22 Rhazya stricta
Polyneuridine, stemmadenine, strictanol, rhazimine,
rhazinilam, rhazimanine, sewarine, vallesiachotamine,
tetrahydrosecamine [145]
Daily oral dosing of R. stricta extract (0.25 g/kg) for
42 days was not fatal to sheep [145].
Evidence-Based Complementary and Alternative Medicine 9

Table 2: Continued.
S.
No Names Active ingredients Toxicological evaluation
23 Calotropis procera
Calotropin, calotoxin, calactin, uscharin, voruscharin,
uzarigenin, syriogenin, proceroside, calotropagenin,
calotropain enzymes, α-amyrin, β-amyrin, lupeol,
β-sitosterol, ursolic acid, calotropin, gigantin, giganteol
[146]
2000 mg/kg body weight in single oral
administration of aqueous and hydroalcoholic
extract did not cause any death after 72 h post-
treatment in male and female mice. Daily
administration of aqueous extract to male and
female Wistar rats during 3 and 6 weeks at the dose
of 20 mg/kg/day induced no mortality in either sex
[147]. Whoever C. procera is a toxic plant that is
avoided by grazing animals. Its latex is used by
tribes to poison arrows used for hunting. If in
contact with human eye, it could cause ocular
toxicity, causing loss of vision and photophobia
[146]
24 Opuntia dillenii
Betanin, betanidin, kaempferol, kaempferide, quercetin,
isorhamnetin, β-sitosterol, C29-5β-sterols, taraxerol,
friedelin, methyl linoleate, 7-oxositosterol, 6β-
hydroxystigmast-4-ene-3-one, daucosterol, methyl
eucomate, eucomic acid [85]
During the oral toxicity study of the crude drug in
rats, given doses up to 50 ml/kg exhibited no
symptoms of toxicity [85]
25 Opuntia ficus
indica
Quercetin, isorhamnetin, kaempferol, luteolin,
isorhamnetin, isorhamnetin glycosides, gallic acid,
coumaric, narcissin, rutin, nicotiflorin, isoquercetin, ferulic
acid [87].
In vivo toxicity study suggests that the oral
administration of Opuntia ficus indica extract at
levels up to 2000 mg/kg/day does not cause adverse
effects in male and female rats [148].
26 Capparis decidua
n-Triacontane, n-pentacosane, β-carotene, n-triacontanol,
kaempferol, quercetin, isodulcite, nanocosane, capric acid,
glucocapparin, capparine, capparinine, cappariline,
codonocarpin, β-sitosterol [88]
e oral administration of C. decidua extract (500,
1000, 2000, and 4000 mg/kg) did not provoke any
gross behavioral changes or manifestations of toxic
symptoms in male rats [149].
27 Beta vulgaris Betaine, betacyanins, betaxanthins, oxalic acid, and
ascorbic acid [89]
In acute oral toxicity studies, the BVBF did not
show any sign and symptoms of toxicity and
mortality up to 2000 mg/kg dose, considered
relatively safe [150]
28
Haloxylon
salicorlicum
Bunge
Kaempferol, quercetin, betaine chloride, piperidine,
anabasine, aldotripiperideine, haloxine, halosaline,
oxedrine, tyramine, N-methyltyramine, scopoletin,
scopolin, umbelliferone, xanthotoxol, isooxyimperatorin,
esculetin, β-sitosterol, ursolic acid, β-amyrin [93].
H. salicorlicum extract at doses 0.1, 0.2, 0.3, 0.4, and
0.5 mL/kg orally administered in rats was safe and
showed no mortality or adverse effect [92].
29 Evolvulus
alsinoides
β-Sitosterol, betaine, shankpushpin, evolvine, caffeic acid,
6-methoxy-7-O-β-glucopyranoside coumarin, 2-C-methyl
erythritol, kaempferol-7-O-β-glucopyranoside,
kaempferol-3-O-β-glucopyranoside, quercetin-3-O-
β-glucopyranoside, scopoletin, scopolin [151]
e Evolvulus alsinoides extract did not cause any
mortality up to a dose of 1500 mg/kg body weight
and no behavioral, neurological, and autonomic
profiles and was found to be safe [151].
30 Ipomea aquatica
Caffeic acid, chlorogenic acid, quercetin glucoside,
quercetin malonyl glucoside, quercetin diglucoside,
catechin, isochlorogenic acid A, C, aspartic acid, glycine,
alanine and leucine, 7-O-β-D-
glucopyranosyldihydroquercetin-3-O-α-D-
glucopyranoside [97, 98]
In acute toxicity studies, I. aquatica extract was
found to be safe up to 2g to 5 g/kg in mice. No
mortality or toxic symptoms were observed during
the entire duration of the study [152, 153].
31 Citrullus
colocynthis
Cucurbitane, gallic acid, kaempferol, cucurbitacin A-E, I-L,
chlorogenic acid, caffeic acid, colocynthoside A,B,C;
choline, almitic acid, stearic acid, linoleic acid, oleic acids,
catechin, myricetin, α-tocopherol, c-tocopherol, β-carotene
[153]
C. colocynthis plant is safe to use. Studies showed
that lethal dose (LD
50
) to be 200 mg/kg, which
indicate that the studied plant is not toxic when
comparing the LD
50
values of most bioactive
pharmaceuticals currently used in therapeutics
[154]
32 Citrullus lanatus
Lycopene, vitamin A, cucurbitacin E, citrulline arginine,
glutamine and aspartic acid, pectin, vitamin b-complex and
minerals [155, 156]
In acute toxicity study, there was no mortality
observed up to the maximum dose level of
2000 mg/kg body weight of the extract after
administered orally [102]
10 Evidence-Based Complementary and Alternative Medicine

Table 2: Continued.
S.
No Names Active ingredients Toxicological evaluation
33 Coccinia grandis
Cephalandrol, β-sitosterol, cephalandrins A and B,
β-amyrin acetate, lupeol, cucurbitacin B, taraxerone,
taraxerol, β-carotene, lycopene, cryptoxanthin, xyloglucan,
carotenoids, β-sitosterol, stigma-7-en-3-one, lupeol,
β-amyrin, β-sitosterol, taraxerol [157]
e acute toxicity study indicated that treatment of
C. grandis is safe up to 2 g/kg tested on animal
[158].
34 Jatropha curcas
Jatrophol, jatropha factor C1, C2, C3,C4, C5, C6,
jatropholones A, B,palmarumycin CP1, JC1,JCV2,curcin,
curcacycline A, curcain, β-amyrin, β-sitosterol,
stigmasterol, friedelin, taraxasterol, diamide, pyrimidine-
2,4-dione, nobiletin, tomentin [103]
Many researchers have confirmed that J. curcas is
highly toxic for animal as well as human. All parts
of J. curcas are toxic and toxic compound reported
from this plant like lectins, curcin, phorbol esters,
phytate, protease inhibitors [103]
35 Ricinus communis
Rutin, quercetin, gallic acid, ricin, ricin A, kaempferol-3-O-
βrutinoside, gentistic acid, linolenic acid, α-pinene,
α-thujone, stigmasterol, ricinine, β-sitosterol, lupeol, castor
oil [159, 160]
R. communis extracts given by oral route were safe
up to a dose of 2,000 mg/kg/BW and did not show
any mortality and toxic effects in the behavior of
the treated animals [104].
36 Ficus carica
Ferulic acid, quercetin-3-O-glucoside, quercetin-3-O-
rutinoside, psoralen, bergapten, coumarin, oleanolic acid,
eugenol, angelicin, germacrene D, menthol, α-pinene,
β-pinene [161]
Toxicity of 70% methanolic extract of Ficus carica
leaves showed LD
50
value of brine shrimp assay was
0.158 mg/ml [162]
37 Ficus sycomorus Tannins, saponins, flavones, aglycones, anthraquinone
glycosides, and flavonoid glycosides [53]
F. sycomorus methanol extract of stem bark is
nontoxic up to the dose of 5000 mg/kg [53]
38 Sesamum indicum
elignans, sesamolin, sesamin, pinoresinol, lariciresinol,
α-globulin, β-globulin, triacylglycerols, oleic, linoleic acids,
sesamol, c-tocopherol, 2-furfurylthiol, 2-phenylethylthiol,
2-methoxyphenol, 2-pentylpyridine, vitamin E, quinone,
sesangolin [163, 164]
S. indicum ethanol extract is safe, up to dose level of
2000 mg/kg in acute toxicity studies in tested
animals [165]
39 Plantago ovata
Hemicellulose,D-xylose, L-arabinose, D-glucose, D-
galactose, and L-rhamnose, 5, 6,8-epiloganic acid,
gardoside, plantamajoside [166]
4,5 Gram seed husk one to four times a day soaked
in 150 ml of warm water recommend by WHO.
Studies confirmed its side effect like bloating, gas,
and allergy. No mortality reported [167]
40 Polygala erioptera
Helioxanthin [168]. No literature available. Recommended
for natural products, isolation, biological and toxicological
evaluation.
No literature available. Recommended for
pharmacological and toxicological evaluation.
41 Polygonum
aviculare L
Protocatechuic acid, catechin, myricitrin, epicatechin-3-O-
gallate, avicularin, quercetin, juglanin, kaempferol,
myricetin 3-0-(3′-0-galloyl-rhamnopyranoside, cinaroside,
liquiritin, rutin [169, 170]
No data available
42 Ziziphus spina-
christi
Jujuboside B1, christinin A, christinin A1 and A2, lotoside
II, catechin, epicatechin, kaempferol 3-O-(6-O-rhamnosyl-
galactoside), quercetin 7-O-(6-O-rhamnosyl-glucoside),
quercetin 3-O-glucoside, kaempferol 3-O-glucoside
[171, 172]
Butanol and water extract of Ziziphus spina-christi
up to 100 mg/kg and 5g/kg, respectively, in animal
model produced no functional or structural
disturbances in liver and kidney and no
hematological changes [173, 174]
43 Bacopa monnieri
Bromine, β-sitosterol, betulinic acid, stigmasterol
nicotinine, herpestine, bacosides A, bacopasides (I, II, III,
IV, V), pseudojujubogenin glycoside, saponins (A, B, C)
[175]
B. monnieri extract at the dose of 5,000 mg/kg did
not cause any side effects. Similarly doses of 30, 60,
300, and 1,500 mg/kg given for 270 days did not
produce any toxicity in rats [176].
44 Lycium shawii
Lyciumate, cyclopentapyrrolidine, imidazole, piperidine,
nortropane, tropane, pyrrole, spermine, costunolide,
catechin, lyciumaside, emodin, betulinic acid, β-sitosterol
glucopyranoside, quercetin, gallic acid, rutin, ρ-coumaric
acid, ferulic acid [177, 178]
Reported data revealed that LD
50
of the L. shawii
extract was greater than 2000 mg/kg b.w in animal
model [179].
45 Solanum nigrum
Chlorogenic acid, quercetin, naringenin, solasodine,
solamargine, solasonine, α-solanigrine, β-solanigrine,
ascorbic acid, nigrumnins I and II [180]
S. nigrum extract at a dose of 2000 mg/kg p.o. was
safe and showed no changes/alteration in normal
behavior in animal model. No mortality was
observed [181]
Evidence-Based Complementary and Alternative Medicine 11

Table 2: Continued.
S.
No Names Active ingredients Toxicological evaluation
46 Withania
somnifera
Withanolides, withaferin, withaferin A, withanone,
withanolide A, withanolide IV, withanolide V, withanolide
D [182].
LD
50
value of W. somnifera extract in rates was
greater than 2000 mg/kg body weight. Compared to
the control group in subacute toxicity study,
administration of extract did not show any
toxicologically significant treatment-related
changes in clinical observations, and the
toxicological studies revealed that the reasonable
doses of W. somnifera are nontoxic and safe
[182, 183]
47 Lantana camara
Eicosane, squalene, β-ionone, caryophyllene oxide,
β-caryophyllene, hexanoic acid, tiglic acid, lantanilic acid,
camaric acid, lantadene B, oleanolic acid, lantadene A,
lantaninilic acid, lantoic acid, ursolic acid, betulinic acid
[184]
L. camara extracts at dose level of 2000 mg/kg and
5000 mg.kg body weight in mice and rats,
respectively, showed no significant toxic signs or
mortality [185, 186]
48 Peganum harmala
Harmine, harmaline, harmalol, harman, vasicine and
vasicinone, pegamine, acacetin 7-O-rhamnoside, 7-O-6″-
O-glucosyl-2 ″-O-(3‴-acetylrhamnosyl) glucoside, 7-0-
(2‴-0-rhamnosyl-2″-O-glucosylglucoside), peganone 1
and 2, p-cymene, limonene, eugenol, thujico acid,
β-cubebene [187–189]
P. harmala different doses of different extracts in
animal and human clinical studies confirmed that
this plant showed side effect like intoxications,
abdominal writhing, body tremors, and toxic at
high does level causing paralysis, liver
degeneration, euphoria, convulsions, nausea,
vomiting, hypothermia. However, therapeutic
doses have been reported to be safe in a rodent
model [189]
49 Tribulus terrestris
Naringin, rutin, hyperoside, quercitrin, naringenin,
quercetin, hesperetin, kaempferol, apigenin, pyrogallol,
gallic acid, catechin, catechol, chlorogenic acid, caffeic acid,
vanillic acid, ferulic acid, salicylic acid, ellagic acid,
coumaric acid, cinnamic acid [190]
T. terrestris extract showed no mortality/or toxicity
at a dose up to 1 g kg
−1
of bw in mice [190]
50 Urtica dioica
β-Amyrin, β-sitosterol, stigmasterol, oleanolic acid, ursolic
acid, quercetin, rutin, chlorogenic, and 2-O-caffeoyl malic
acid expressed as caffeic acid, isoquercetin, kaempferol 3-
O-rutinoside [191–193].
U. dioica extracts up to dose level of 2000 mg/kg
body weight in animal model showed no mortality
or changes/alteration in normal behavior [127].
Table 3: Selected antidiabetic phytoconstituents and its targeted metabolic pathway.
Phytoconstituents Targeted metabolic pathways Structures
Catharanthine
Free radical; our body has a defense system containing
several enzymes, which are catalase, superoxide
dismutase, and glutathione-S transferases and reduced
glutathione. Catharanthine activates these free radical
scavenging enzymes and prevents our body from their
adverse effects.
NH
O
O
H
Harmine Insulin secretion and β-cell regeneration
O
N
H
N
Betaine
Achyranthine
β-ecdysone
Carbohydrate digestion and absorption
H3C
H3C
H3C
N
O
O⊝
O
OH
N
HO
HO
H
H
H
O
OH
OH
OH
12 Evidence-Based Complementary and Alternative Medicine

Table 3: Continued.
Phytoconstituents Targeted metabolic pathways Structures
Apigenin Cholesterol synthesis, glycogen synthesis
OH
O
O
OH
HO
Betaine choline Regeneration of pancreatic βcells and insulin secretion
OH
N+X-
Ferulic acid Free radical scavenging activity, insulin secretion
O
OH
H3CO
HO
Leucine, isoleucine, alanine Insulin secretion
O
O
O
OH
OH
OH
NH2
NH2
NH2
H3C
H3C
CH3
Chlorogenic acid Krebs cycle
HO
HO
OH
O
O
OH
OH
CO2H
Emodin, cinnamic acid Insulin secretion
OH OH
OH
OH
O
O
O
H3C
Eugenol, α-pinene, limonene, p-
cymene thujone Insulin secretion, regeneration of pancreatic βcells
O
HO
H3C
H3C
CH3
H3CCH3
CH3
CH3
CH3
H3C
HO
Pectin Glucose transport, carbohydrate metabolism, stabilizing
agents
O
OH
HO
OH
OH
CO2H
Evidence-Based Complementary and Alternative Medicine 13

Table 3: Continued.
Phytoconstituents Targeted metabolic pathways Structures
Inulin Glucose transport, carbohydrate digestion and
absorption
HO
O
HO
OH OH
OH
HO
OH
O
O
O
O
O
HO
n
OH
6
4
HO 3
5
2
OH
1
1
2
3
O
HO
4
5
6
OH
OH
Cucurbitacin B Insulin secretion, glycogen synthesis
CH3
CH3
CH3
CH3
CH3
CH3
CH3
O
O
O
Cucurbitacin-B
OH
HH
HO
HO
O
H3C
H3C
H
O
Catechin
Epicatechin
Scavenging activity
Insulinomematic
HO O
OH
OH
OH
OH
Cucurbitacin-B
OH
OH
OH
OH
HO O
Naringin Glycogen synthesis, glycolysis, gluconeogenesis
HO
HO
OH
OH
OH
OH
OH
OO
O
O
O
HO
H3C
O
Flavones Insulin secretion
O
O
Quercetin, quercitrin, apigenin,
rutin, apigenin-7-O-glucoside Insulin secretion
OOO
O
OH
OH
OH
HO
HO
OH
HO O
OO
O
O
OOH
OH
HO
OH OH
OH
OH
HO
HO
H3C
HO
OH O
O
OH
HO
OH O
O
HO
OH
OH
OH
OH
O
O
O
O
OH
OH
OH
HO
HO
Naringenin Insulin secretion
O
O
HO
OH
OH
14 Evidence-Based Complementary and Alternative Medicine

toxicity. From the study, the levels of these metals differed in
the same plant collected from different geographical loca-
tions. A study conducted showed that the levels of lead in
Cassia alata varied from 17.7 to 4.45 μg/g for the 5 collection
sites. Similarly for Cassia occidentalis and Rauvolfia vomi-
toria, the level is varied between 7.85-4.35 and 9.25–1.55 μg/
g, respectively. Similarly, that of aluminum varied between
105.53 and 23.3 for Rauvolfia vomitoria and 104.25–12.4 μg/
Table 3: Continued.
Phytoconstituents Targeted metabolic pathways Structures
α-Terpineol Insulin secretion
OH
Kaempferol, isorhamnetin,
caffeic acid, p-coumaric acid
Free radical scavenging activity
Carbohydrate digestion and absorption, insulin
secretion
HO
HO
O
OH
HO
O
OH
HO O
O
OH
OH
OH
OCH3
O
O
OH
OH
OH
HO
Vitamin A, E Free radical scavenging activity
OH
HO
H3C
CH3
CH3
CH3
CH3CH3
CH3
CH3
O
HH
Ellagic acid Carbohydrate digestion and absorption, insulin
secretion
OH
OH
O
O
O
O
HO
HO
Carvacrol, linalool Insulin secretion, carbohydrate digestion and
absorption
OH
HO
Stigmasterol Regeneration of pancreatic βcells, insulin secretion
HO
H
H
H
H
Ursolic acid Regeneration of pancreatic βcells and insulin secretion
O
H
H
H
OH
HO
β-Sitosterol Insulin receptor (IR) and glucose transporter 4
H
HH
H
HO
Evidence-Based Complementary and Alternative Medicine 15

g for Paullinia pinnata. e levels of heavy metals also varied
for different plants collected from the same location. Uptake
of metals by plants is influenced by a number of factors
including metal concentrations in soils, cation exchange
capacity, soil pH, organic matter content, types and varieties
of plants, and plant age. However, the prevailing factor is the
concentration of the metal in the soil and thus the existing
environmental conditions [209]. Another study conducted
on onion bulb showed that the concentrations of Cr in onion
bulb and Fe in onion leaf were above the permissible level
(2.3 mg/kg, 425.5 mg/kg) set by FAO/WHO at Mojo
(4.87 mg/kg, 1090.40 mg/kg), Meki (4.13 mg/kg, 1836.47 mg/
kg), and Ziway (3.33 mg/kg, 764.33 mg/kg), respectively. e
results generally indicate that the consumption of these
onion bulbs could be the health risk respective to Cr [210].
erefore, it is suggested that the medicinal plant source for
the treatment of diabetes must not be taken from heavy
metal contaminated areas to avoid their uptake by the plants
because migration of these contaminants into non-
contaminated areas (or leaching through the soil and
spreading of heavy metal contaminated sewage sludge) are a
few examples of events contributing to contamination of the
ecosystem.
5. Conclusion and Recommendations
e present review provides a picture of medicinal plants
that have been studied as anti-DM drugs, which can be
grown either in combination with other medicinal plants or
alone as treatment for diabetes and drawbacks should be
properly addressed so that medicinal plants can be effectively
utilized as anti-DM drugs. Diabetes is a metabolic disorder
which can be considered as a major cause of high economic
loss which can in turn impede the development of nations.
Moreover, uncontrolled diabetes leads to many chronic
complications such as blindness, heart failure, and renal
failure. In order to prevent this alarming health problem, the
development of research into new hypoglycemic and po-
tentially antidiabetic agents is of great interest. In conclu-
sion, this paper has presented a list of anti-DM plants used in
the treatment of diabetes mellitus. Bioactive antidiabetic
phytoconstituents which showed that these plants have
hypoglycemic effects and highly recommended for further
pharmacological purposes and to isolate/identify anti-DM
active agents also need to investigate the side effects of active
ingredients.
Data Availability
is is a review article. All data are taken from published
research papers and available online.
Conflicts of Interest
e authors declare no conflicts of interest.
Authors’ Contributions
All three authors contributed equally.
Acknowledgments
e authors wish to thank Research Center College of
Pharmacy at King Saud University, Riyadh, Saudi Arabia for
their financial support and for providing free access to digital
library and laboratory.
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