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Table 5 Acute toxicity profiles of some MPs employed in the treatment of epilepsy and related symptoms

From: Medicinal plants utilized in the management of epilepsy in Ethiopia: ethnobotany, pharmacology and phytochemistry

No.

Scientific name

PU

Extract

Animal models

Acute toxicity studies

Refs.

Doses (mg/kg)

LD50 (mg/kg)

Treatment outcomes

1

Ajuga integrifolia

R

HME

Swiss albino male mice (20–30 g)

2000

 > 2000

Neither mortality of mice nor any signs of toxicity (behavioral, neurological, autonomic, or physical changes) was observed at 2000 mg/kg of body weight

[189]

2

Allium sativum

Bu

AQ

Wistar rats (⁓115–126 g)

100, 1000, 2500 & 5000

 > 5000

No death was recorded at all doses. The rats treated with 5000 mg/kg of body weight experienced cardiac problem and disorientation

[190]

3

Artemisia abyssinica

Ar

ET

Swiss albino mice (25–30 g)

500, 1000 & 3000

 > 3000

The mice did not show visible toxicity, although at 3000 mg/kg a decreased in locomotor activity was observed

[191]

4

Artemisia afra

L

AQ

Female adult Swiss albino mice (25–30 g)

200, 700, 1200, 2200, 3200, 4200 &5000

 > 5000

Mild toxicities like anxiety and piloerection were observed at higher doses (≥ 3200 mg/kg) that disappear in the wash out periods. No mortality in mice was recorded at all doses

[175]

  

L

ET, DCM & HX

Swiss albino mice (20–22 g)

1000, 2000 and 2500

 > 2500

Loss of appetite, hypoactivity, lethargic, dizziness that disappeared in the washout period was noticed in mouse treated with DCM extract at 2500 mg/kg

[192]

5

Asparagus africanus

R

HET & BU

Swiss albino mice (20–25 g)

1000, 3000 & 5000

 > 5000

There was no dose-dependent behavioral change, weight change and mortality in mice treated single dose BUT fraction orally

[182]

6

Azadirachta indica

L

AQ

Female BALB/c mice (average mass of 30 g)

1250, 2500 & 5000

 > 5000

The mice treated with the extract were devoid of weight/hair loss, allergy, or other symptoms of discomfort

[176]

7

Balanites aegyptiaca

SB

AQ

Fishes

17.5, 20, 22.5 & 25a

⁓18.99–20.72a

B. nurse, L. intermedius and L. bynni fish species treated with the extract suffered from the debilitating toxic effect

[193]

8

Biophytum umbraculum

R

AQ, BU & CH

Female Swiss Albion mice (22–30 g)

2000

 > 2000

There was no behavioral change, weight change and mortality in mice treated single dose of all fractions

[183]

9

Brucea antidysenterica

L

AQ, ME & CH

Swiss albino mice (27–36 g)

500, 1000 & 2000

The extracts lack visible signs of acute toxicity and mice fatality till the dose of 1000 mg/kg. But, at the dose of 2000 mg/kg it caused mortality in all mice with in 24 h

[194]

10

Buddleja polystachya

L

HME

Female Sprague–Dawley rats (150–200 g)

2000

There was no visible sign of skin reaction, inflammation, erythema, irritation or redness, and any adverse reaction in rats

[177]

11

Calpurnia aurea

L

AQ & HME

Female Swiss albino mice

5000

 > 5000

The mice were devoid of gross behavioral or physical changes and signs of overt toxicity such as lacrimation, urination, muscle weakness and convulsions

[186]

12

Capparis tomentosa

R

HME

Male Swiss Albino mice (25–38 g)

2000, 3000 & 5000

 > 2000

The mice showed signs of slight rigidity and sleepy activity at higher doses of extract (3000 and 5000 mg/kg). No mortality was recorded at all doses

[184]

13

Carissa edulis

L

AQ

Wistar albino rats of either sex

2000

 > 2000

The rats showed no gross behavioral or physical changes and signs of overt toxicity

[195]

  

RB

ET

Wistar albino rats (124–220 g) & Swiss mice (16–35 g)

10, 100 & 1000

⁓3808

None of the mice and rats orally treated with the extract manifested signs of toxicity except death at the dose of 5000 mg/kg (in both species)

[187]

14

Caylusea abyssinica

L

HME

Male Swiss albino mice (20–30 g)

2000

 > 2000

The mice didn’t experience any behavioral, neurological, autonomic or physical changes

[196]

15

Clerodendrum myricoides

R

AQ

Swiss albino mice of either sex (25–30 g)

1134

Behavioral changes such as horripilation, difficulty in breathing, grooming, and asthenia followed by death was noticed in mice treated with 1134 mg/kg

[197]

16

Croton macrostachyus

R

HME

Female Swiss Albino mice (25–28 g)

2000 & 5000

 > 5000

The mice showed no visible signs of lacrimation, loss of appetite, tremors, hair erection, salivation, diarrhea and convulsion

[198]

  

SB

AQ & HME

Female Swiss albino mice

5000

 > 5000

The mice were devoid of gross behavioral or physical changes and signs of overt toxicity such as lacrimation, urination, muscle weakness and convulsions

[186]

  

SB

HME, AQ & ETAc

Female Swiss albino mice

2000

 > 2000

None of the mice treated with crude extract or solvent fractions showed problems in breathing, alertness, motor activity, restlessness, diarrhea and convulsions

[199]

17

Cucumis ficifolius

R

HME & CH

Swiss albino mice (25–30 g)

125, 250, 500 & 2000

 > 2000

There were no mortality and signs of overt toxicities at a dose of 2000 mg/kg of body weight

[200]

18

Echinops kebericho

Tu

EO

Swiss albino mice (18–26 g)

300 & 2000

 > 2000

Though the mice showed piloerection, muscle spasm and apathy immediately after administration, there were no significant treatment-related morbidities

[201]

  

Tu

AQ

Wistar albino rats (250–350 g)

300, 2000 & 5000

 > 5000

The rats experienced piloerection, muscle twinge, and lethargy after the treatment with the extract (5000 mg/kg) which disappeared after 5 h. But, there were no treatment related morbidity and mortality at 5000 mg/kg

[202]

19

Embelia schimperi

Fr

HET

Female Wistar rats (180–210 g)

400, 1000, 2000, 3000, 4000 & 5000

 > 5000

The extract didn’t elicit prominent signs of toxicity and any mortality in rats in the study period

[203]

20

Eucalyptus Globulus

L

EO

Swiss albino mice of either sex (23–30 g)

2, 2.5, 3 & 3.5b

2.5b

The mice treated with the essential oil showed restlessness, debilitation, reduced food and water intake and piloerection which disappeared in the washout period after treatment with ≥ 2.5 mL/kg

[178]

21

Fagaropsis angolensis

SB

HME, AQ, BU & CH

Adult male Swiss albino mice (25–30 g)

2000

 ≥ 2000

Neither mortality nor any signs of toxicity were observed in mice treated with both extracts at 2000 mg/kg body weight

[204]

22

Foeniculum vulgare

Fr

ET

Swiss labial mice (25–28 g)

500, 1000 & 3000

 ≥ 3000

The extract didn’t trigger mortality of mice and overt toxicity except reduced locotmotor activity and piloerection at 3000 mg/kg of body weight

[205]

23

Gloriosa superba

L

AQ

White male Wistar rats (200–250 g)

⁓121, 364, 1091 & 3274

 > 1500

The rats experienced treated with colchicine of standardized Gloriosa superba extract showed no visible sign of overt toxicity

[206]

  

L

HME

Non-pregnant Wistar rats (120–140 g)

200 & 5000

 > 5000

There were no visible overt signs of toxicity at 5000 mg/kg. No morbidity or mortality was observed in the rats treated groups at both doses

[179]

24

Justicia schimperiana

L

HME

Swiss albino mice (18–30 g)

2000

 > 2000

The extract didn’t trigger signs of overt toxicity. Moreover, no mortality of mice was recorded in the study period

[207]

  

L

HME

Female adult Wistar rats (180–200 g)

2000

 > 2000

Rats showed no formation of edema or erythema. No signs of toxicity as well as no mortality were noted during the study period

[208]

25

Maytenus heterophylla

L

HET

Male CD-6 mice (35–40 g)

1200

 > 1200

The mice treated with the extract were devoid of physical and behavioral changes at 1200 mg/kg

[180]

26

Maytenus senegalensis

RB

ET

Swiss albino mice (18–22 g)

200, 300, 400, 800 & 1600

 > 1600

The mice treated with the extract were devoid of physical and behavioral changes at 1600 mg/kg

[209]

  

SB

HET

Theiller’s albino mice of either sex

1000, 2000, 3000, 4000 & 5000

 > 5000

The mice treated with the extract were devoid of physical and behavioral changes at 5000 mg/kg

[210]

  

L & S

HET

Male CD-6 mice (35–40 g)

1200

The mice treated with leaf extract exhibited some signs of overt toxicity. In addition, the stem extract caused pronounced toxicity at 1200 mg/kg

[180]

27

Myrica salicifolia

R

HME

Non-pregnant female mice

2000

 > 2000

There are no visible signs of overt toxicity and mortality in mice treated with the extract at 2000 mg/kg

[211]

28

Nicotiana tabacum

L

Bio-oil

Female Wistar rats (130–140 g)

5000

 > 5000

The rats exhibited no significant change in the body weight and behavior. In addition, there was no mortality of rats in the study period

[181]

29

Ocimum lamiifolium

L

ME

Swiss albino mice (27–36 g)

500, 1000 & 2000

 ≥ 2000

The crude extract didn’t trigger gross visible signs of acute toxicity such as urination, hair erection, lacrimation, and reduction in feeding activity

[194]

30

Olea europaea

L

ET

Wistar rats of either sex (150–200 g)

2000

 ≥ 2000

Oral administration of the extract didn’t cause any mortality or sign of toxicity at 2000 mg/kg of body weight during the study period

[212]

31

Opuntia ficus-indica

S

HET

White Sprague Dawley rats either sex

500, 1000 & 2000

The rats exhibited no genotoxicity at all treatments regimens even at the maximum dose of 2000 mg/kg

[213]

  

Se

HX (fixed oil)

Mus musculus mice (20–30 g)

10, 20, 30, 40, 50, 60 & 70b

43b

The mice suffered from immediate agitation and behavioral perturbations with temporary writhing, followed by a quiet attitude period and sedation

[214]

32

Pentas schimperiana

L

AQ & HME

Swiss Albino mice of either sex (20–33 g)

1000, 2000 & 5000

 > 4000

The mice experienced no visible change in behavior such as restlessness, motor activity, breathing and diarrhea. Moreover, there was no mortality recorded at 5000 mg/kg

[215]

33

Podocarpus falcactus

Ap

AQ

Female Sprague Dawley rats (260–300 g)

2000

 > 2000

The rats showed neither mortality nor gross behavioral changes and mortality at 2000 mg/kg of body weight

[216]

34

Ruta chalepensis

Ar

ET

Male Swiss albino mice (25–30 g)

1600, 3000 & 5000

 > 5000

The extract didn’t trigger mortality nor macroscopic tissue injury or weight loss at 5000 mg/kg per body weight

[164]

35

Rhus vulgaris

SB

AQ,

Female Swiss albino mice (18–26 g)

50, 300 & 2000

 > 2000

The mice were devoid of changes in general appearance and behavioral patterns. In addition, there was no mortality or gross pathology in any organ at necropsy

[217]

36

Securidaca longepedunculata

L, S & R

AQ & ME/CH (1:1)

Swiss female mice (20–22 g)

50, 300 & 2000

 > 2000

The AQ total extracts of leaves and stembark did not show any change in behavior following administration of the crude extracts at 2000 mg/kg of body weight

[218]

37

Sida rhombifolia

Ar

ET

Adult male Wistar albino rats (180–220 g)

2000

 > 2000

There were no visible overt signs of toxicity and mortality in rats treated with 2000 mg/kg of the extract

[219]

  

Ar

HME

Albino Wistar rats (102–134 g)

4000, 8000, 12000 & 1600

 > 8000

The rats exhibited slight changes in general behavior such as sow response to external stimuli, stretching and sluggishness

[220]

  

R

AQ

Sprague Dawley rats of either sex (130–190 g)

5000

 > 5000

The rats experienced neither overt toxicity signs nor mortality at a single dose of 5000 mg/kg

[221]

38

Syzygium

guineense

L

HME

Wistar rats of either sex (120–140 g)

2000 & 5000

 > 5000

In the acute toxicity study, rats treated with 2000 mg/kg and 5000 mg/kg showed no toxicological signs observed on behavior, gross pathology, and body weight of rats

[179]

39

Teclea nobilis

Wh

HME & AQ

Male Swiss mice (⁓20 g)

1000, 2000, 3000, 4000 & 5000

 > 5000

The extract was devoid of any overt toxicities at 5000 mg/kg of body weight. Moreover, there was no mortality recorded in the study period

[222]

40

Vernonia amygdalina

L

AQ & HME

Female Swiss albino mice

5000

 > 5000

The mice exhibited no signs of overt toxicity such as lacrimation, urination, muscle weakness, sedation and convulsions at 5000 mg/kg

[186]

  

L

AQ & ET

Albino Wistar rats (200–250 g)

2000

 > 2000

The extracts triggered no significant effect on the biochemical and hematological parameters of treated rats (no lesions were also observed in the liver and kidneys histologically)

[223]

41

Withania somnifera

R

ME

Wistar rats

5000, 1000 & 2000

 > 2000

The rats didn’t experience any organ atrophy, hypertrophy, and degenerative or infiltrative lesions even at 2000 mg/kg

[185]

42

Zingiber officinale

R

HX (fixed oil), EO

Swiss albino mice (23–26 g) and Wistar rats (150–170 g)

0.02, 0.04, 0.06, 0.08 and 0.1b mL/kg for fixed oil; 0.2, 0.4, 0.6, 0.8, 1.0, 2.0, 4, 6, 8 and 10b for EO

Observed cardinal signs of toxicity for both oils were decreased motor activity, convulsion and paralysis. In addition, mortality of experimental animals was noticed in both fixed-oil (0.2 mL/kg) and EO treated group

[224]

  1. PU plant parts used, Ap apex, L leaf, S stem, Se seeds, SB stembark, R root, RB rootbark, Ar Aerial part, Bu bulbs, Tu tuber and Rh rhizome, Extraction solvents, AQ aqueous, CH chloroform, BU butanol, DCM dichloromethane, ET ethanolic, ETAc ethyl acetate, HX hexane, HET hydroalcoholic/hydroethanolic, ME methanolic, HME hydromethanolic, PE petroleum ether and EO essential oil
  2. aand brepresented the plant extract doses and LD50 values are given in mg/L and mL/kg, respectively