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Clinical Phytoscience

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Open Access 01.12.2021 | Review

Efficacy, safety and phytochemistry of medicinal plants used for the management of diabetes mellitus in Ethiopia: a systematic review

verfasst von: Serawit Deyno, Kassahun Eneyew, Sisay Seyfe, Elias Wondim

Erschienen in: Clinical Phytoscience | Ausgabe 1/2021

Abstract

Background

Despite tremendous developments in synthetic medicine, medicinal plants are still commonly used for the management of diabetes mellitus. This study synthesized scientific evidence on commonly used medicinal plants for the management of diabetes mellitus (DM) in Ethiopia.

Methods

Databases (PubMed, Cochrane, CINAHL and Google Scholar) have been thoroughly sought and evidence was synthesized.

Results

Thirty studies conducted anti-diabetic activities studies on 19 medicinal plants in Ethiopia. Most of the studies were in vivo studies (25). Others include; clinical study (1), in vitro studies (2), and both in vivo and in vitro study (2). Trigonella foenum-graecum L., clinical study, showed an improved lipid profile in type II diabetic patients. Comparable blood sugar level (BSL) lowering effect to glibenclimide was observed with Persea Americana and Moringa stenopetala. Noteworthy in vitro half maximal inhibitory concentration (IC 50) of Aloe megalacantha B and Aloe monticola R were observed. Animal model studies demonstrated the relative safety of the plants extract and phytochemistry studies showed various components.

Conclusion

Medicinal plants used for management of diabetes mellitus in Ethiopia are worthy for further study for pharmacologically active ingredients and clinical evaluation.

Additional file 1.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s40816-021-00251-x.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

BSl

Blood sugar level

Total cholesterol

Total glyceraldehydes

LDL-C

Low density lipoprotein cholesterol

HDL-C

High density lipoprotein cholesterol

T1DM

Type 1 diabetes mellitus

T2DM

Type 2 diabetes mellitus

STZ

Streptozotocin

Confidence interval

Retention factor

LD₅₀

Median lethal dose

Background

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia due to impaired insulin secretion, defective insulin action or both. Chronic hyperglycemia is associated with long term microvascular complications affecting the cardiovascular, eyes, kidneys, and nerves [1]. The complications include nephropathy, retinopathy, nephropathy, peripheral vascular disease and coronary heart diseases [2]. The complications cause major impact on the lives and well-being of individuals, families and societies.

No successful cure for DM has yet been found but can be managed using insulin, diet modification and oral anti-diabetic agents. Herbal medicines could provide an alternative management. Compromised effectiveness, cost, accessibility, affordability, and tolerability are some of the limitations of current conventional anti-diabetic medicine. African medicinal plants are commonly used in the management of DM and provide an alternative therapy. Research is required on different indigenous plant and herbal formulations. The research will shed light on effectiveness and safety of herbal medicines. The findings will help to discover novel drugs and/or optimize the traditional use.

In Ethiopia, there are numerous medicinal plants used for DM and a number of these were assayed for their anti-diabetic activity. An estimated 80 to 90% of Ethiopians use herbal medicine as a primary form of health care [3] and many rural communities continue to depend on it [4]. There are preliminary studies on the scientific evidence of commonly used medicinal plants in Ethiopia though evidences were not synthesized. With a lack of critical appraisal on the currently evidence studies, this study aimed at reviewing information on the reported scientific evidence for effectiveness of medicinal plans used in Ethiopia in the management of DM.

Methods 1

Study design

This systematic review and meta-Analysis was conducted using databases searches and the reporting adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis [5]. PRISMA checklist was included as additional file (see Supplementary file 1).

Search strategy

Databases, PubMed, CINAHL, the Cochrane Central Register of Controlled Trials and clinical trial.gov and Google scholar, were searched from inception to May 25, 2020. The reference lists of all identified articles were searched for additional studies. Flow diagram was used to summarize the number of studies identified, screened, excluded and finally included in the study. Key words used in the search include (Diabetes mellitus OR T1DM OR type I diabetes mellitus OR T2DM OR type 2 diabetes mellitus) AND (Plant* OR herb* OR dietary supplement* OR traditional medicine*) AND (Ethiopia).

Study selection and data extraction

Three reviewers (SS, KE and EW) independently carried out a literature search and examined relevant studies and sequentially screened their titles and abstracts for eligibility. The full texts of potentially eligible studies were retrieved. Disagreements were resolved on discussion with the fourth author (SD). A screening guide was used to ensure that all review authors reliably apply the selection criteria. Human, animal and in-vitro studies which were conducted to examine anti-diabetic effect of medicinal plants in Ethiopia were included. Data extraction was performed using a pre-designed format. Extracted data include first author, study area, scientific, family and local name, study model used, the animal type used, extraction method used, a component of the extract used, duration of treatment, and change in BSL (from diabetic control, from normal control and standard control). A study is included if the effect on diabetic control is reported, otherwise it is excluded.

Definition of terms

Diabetic control refers animals with DM but no standard or experimental treatment is given which could refer a placebo control. Whereas standard controls are animals with induced DM and treated with standard treatment most commonly glibenclamide. Normal controls are animal being followed and managed in the same was as experimental conduction but no induction of Dm or treatment is given.

Results

Characteristics of included studies

A total of 17,954 articles were identified through the electronic database search. De-duplication reduced the total number of articles to 6, 090. After titles and abstracts screening, 33 articles remained and further screening left 29 articles for inclusion [6‐28], Fig 1. Among the studies twenty-four were in vivo studies [7, 9, 11‐24, 26‐32, 33], two were in vitro studies [8, 25] and three was both in vivo and in vitro study [10, 34, 35]. Reasons for exclusion include: herbal medicine use prevalence and ethnobotanical survey studies [36, 37]. Ten of the total studies were conducted in the southern nation nationalities region, 9 in Amhara, four in Tigra, 3 in Addis Abab, 3 in Oromia. Seven studies were done in Moringa Stenopetala [7‐9, 11, 17, 19, 23], 2 in Aloe megalacantha B [14, 25], 2 in Bersama abyssinica Fresen [32, 34], 2 in Datura stramonium [12, 31], 2 in Thymus schimperi [26, 29], and 14 in different plants.

Three in vitro studies were conducted on four plants (Terminalia brownie Fresen, Moringa Stenopetala, Aloe megalacantha B, and Aloe monticola R.) (Table 1).

Table 1

Characteristics of included studies

No	Study	Study area	Name of plant (Scientific, family, local)	Model
1.	Amare et al., 2020 [35]	Fiche, oromia region	Aloe pulcherrima Gilbert and Sebsebe (Aloaceae)	Male Swiss albino mice
2.	Alema et al., 2020 [10]	Abiy Addi, Northwest Tigray	Terminalia brownie Fresen, Combretaceae, Abaloweyba (Am)	in vitro and STZ-induced mice
3.	Belayneh et al., 2018 [22]	South Gondar zone	Calpurnia aurea, Fabaceae, digita (Am)	STZ-induced albino mice
4.	Belayneh et al., 2019 [12]	Gondar town	Datura stramonium L. solanaceae, atefaris (Am)	STZ-induced diabetic mice
5.	Birru et al., 2015 [21]	Lake Tana	Indigofera spicata Forssk, Fabaceae, yeayitmisir (Am)	Alloxan-induced albino mice &wistar rats
6.	Gebremeskel et al., 2019 [6]	Mekelle	Trigonellafoenum-graecum, Fenugreek, Abish (Am)	T2DM
7.	Hammeso et al., 2019 [14]	SehartiSamre, Mekelle	Aloe megalacantha B, Aloaceae, Eret (Am)	STZ -induced mice
8.	Kifle & Eneyew, 2020 [34]	South Gondar	Bersama abyssinica Fresen, tena adam (Am)	Male Swiss albino mice
9.	Kifle et al., 2020 [32]	South Gondar	Bersama abyssinica Fresen	Male Swiss albino mice
10.	Makonnen et al., 1997 [17]	Arbaminch area	Moringa stenopetala, Moringaceae, shiferaw (Am), aleko (Welaytegna)	Albino rabbits
11.	Melaku and Amare et al., 2020 [35]	Wollo, Amhara region	Datura stramonium Linn (Solanaceae)	Male Swiss albino mice
12.	Mussa et al., 2008 [11]	Arba Minch	Moringas stenopetalla	Alloxan-induced mice
13.	Nardos, et al., 2011 [23]	Arbaminch town	Moringa stenopetala, Moringaceae,Shiferaw (AM)/Haleko (GM)	Alloxan-induced mice
14.	Rao and Adinew 2011 [33]	Tepi,	Persea Americana, Laurel, Avocado	STZ induced rats
15.	Seifu et al., 2017 [27]	Southern, Ethiopia	Melia azedarachlinn, Meliaceae, Laylak (milya)	Ob/obmice and Rats
16.	Shewamene et al., 2015 [16]	Ayimba, Gondar, Ethiopia	Otostegia integrifolia, Lamiaceae, Tunzut	STZinduced Rat or mice
17.	Shewasinad et al., 2019 [26]	Gudoberet, North Shoa	Thymus schimperi, Lamiaceae, Tosign	STZ induced mice
18.	Sileshi et al 2014 [7]	Arbaminch town	Moringa Stenopetala,Moringaceae “Shiferaw (Am), Halekko (Wolita/gammo).”	Alloxan-induced Swiss albino mice
19.	Tafesse, etal 2017 [20]	Addis Ababa	Ajuga remota, Lamiaceae, Akorarach	Alloxan-induced mice
20.	Tamiru et al. 2012 [28]	Dirre, way from Bishoftu to Ziquala	Caylusea abyssinica (fresen.) fisch. &Mey. Resedaceae	STZ induced Swiss albino mice and Wistar rats
21.	Taye et al., 2020 [29]	Suluta, Oromia Region	Thymus schimperi (Lamiaceae)	Swiss albino mice
22.	Tefera et al., 2020 [30]	Woreta, Amhara region	L. culinaris	Swiss albino mice
23.	Tekulu et al. 2019 [25]	Tigray	Aloe megalacantha B.,Asphodelaceae, Aloe monticola R., Asphodelaceae“yedega ret. (Am)”	in vitro
24.	Tesfaye et al., 2016 [13]	Wolayta soddo, SNNPR	Justicia Schimperia naacanthaceae” Sensel or Simiza”	Normal andSTZ-induced mice
25.	Toma et al., 2012 [19]	Wolaitta zone, SNNPR	Moringa Stenopetala, Moringaceae “shiferaw Am” “HalekkoWo.”	Alloxan Induced mice
26.	Toma et al., 2014 [8]	GamoGofa Zone, SNNPR	Moringa Stenopetala,	in vitro
27.	Toma et al., 2015 [9]	GamoGofa Zone, SNNPR	Moringa Stenopetala	STZ-induced rats
28.	Tsegaye et al., 2008 [18]	Semen Mazegaja, Addis Ababa	UrticasimensisHochst. ex. A. Rich, “Samma”	STZ-induced mice
29.	Yibru et al., 2015 [15]	Addis Ababa	Coriandrum sativum, “dembellal”	STZ-induced mice

Where; STZ streptozotocin, T2DM Type 2 Diabetes mellitus, Ob/ob obese mouse

In vitro studies

In vitro half-maximal carbohydrate digestive enzyme inhibitory concentration (IC 50) of Aloe megalacantha B, Aloe monticola R, Moringa Stenopetala, and Terminalia brownie Fresen were evaluated. The IC50 was less than100 μg/ml except ethanolic extract of Moringa Stenopetala and aqueous extract of Terminalia brownie Fresen. All extract and fractions showed less effect compared to a standard control (acarbose), Table 2.

Table 2

In vitro anti-diabetic activity of medicinal plants in Ethiopia

Study	Scientific name	Parts used	Extraction method	Assay method	Active cpd, Fraction / extraction	IC50
Alema et al. 2020 [10]	Terminalia brownii Fresen	stem bark	methanolic extract & solvent fractions	α-Amylase Inhibition (chromogenic DNSA method)	aqueous fraction	> 100 μg/ml
					Butanol fraction	84.69 μg/ml
					chloroform fraction	63.41 μg/ml
					ethyl acetate fraction	> 100 μg/ml
					crude extract	> 100 μg/ml
					Acarbose	~ 12.5 μg/ml
Kifle and Eneyew., 2020 [34]	Bersama abyssinica	leaf	Methanolic Extraction	α-Amylase Inhibition (chromogenic DNSA method)	Chloroform fraction	30.97 + 0.84
					Ethyl acetate fraction	20.34 + 0.67
					Aqueous fraction	13.33 + 0.57
					Crude extract	6.57 + 0.74
					Acarbose	2.26 + 0.53
Toma et al. 2014 [8]	Moringa Stenopetala	powdered leaves	ethanol extract	Pancreatic α-amylase	ethanol extract	> 5 mg/ml
				Maltase		> 5 mg/ml
				Pancreatic C. esterase		> 5 mg/ml
				Pancreatic lipase		> 5 mg/ml
				Sucrase		1.47 ± 0.19 mg/ml
Tekulu et al. 2019 [25]	Aloe megalacantha B Aloe monticola R	leaf	Methanol extract	α-Amylase Inhibition (chromogenic DNSA method)	TLC fraction from A. megalacantha coded as AM1	37.83 ± 3.31 μg/mL
					Leaf latex ofA. megalacantha	74.76 ± 1.98 μg/mL
					TLC fraction from A. megalacantha coded as AM2	96.75 ± 1.98 μg/mL
					Leaf latex ofA. monticola	78.10 ± 1.88 μg/mL
					TLC fraction from A. monticola, AG1	56.95 ± 1.88 μg/mL
					TLC fraction from A. monticola, AG2	64.03 ± 3.60 μg/mL
					Acarbose	16.49 ± 1.91 μg/mL

In vivo studies

There was a significant difference in duration of treatment among in vivo studies, ranges from 4h to 30 days. Fifteen studies used mice, three used rats, and two studies used both rats and mice. In eight of the studies the plant was extracted using methanol, in six ethanol extract and in other six aqueous extract was used, Table 3.

Table 3

In vivo anti-diabetic activity of medicinal plat in Ethiopia

Study	Plant	Animal type	Extraction method/ component	Duration of treatment	From diabetic Control	From standard control
Amare et al., 2020 [35]	Terminalia brownii Fresen	Normoglycemic Mice	Methanol E	14 Days	–	200 mg/kg = 16.74 ± 2.57 400 mg/kg = 6.9 ± 2.33 600 mg/kg = 5.36 ± 2.20
		Mice Loaded with Oral Glucose		14 Days		200 mg/kg = 16.30 ± 1.11 400 mg/kg = 7.14 ± 0.46 600 mg/kg = 3.25 ± 0.96
		STZ -induced Mice			200 mg/kg = − 22.48 ± 4.66 400 mg/kg = − 26.6 ± 5.89 600 mg/kg = − 29.54 ± 4.29	200 mg/kg = 7.94 ± 2.72 400 mg/kg = 3.82 ± 4.51 600 mg/kg = 0.88 ± 2.02
Alema et al., 2020 [10]	Terminalia brownii Fresen	Normoglycemic Mice	Methanolic E.	15 days	–	250 mg/kg = − 43.5 ± 6.21500 mg/kg = − 41 ± 7.12 750 mg/kg = − 32.5 ± 9.37
		Mice Loaded with Oral Glucose	Methanolic E.		–	250 mg/kg = − 40 ± 7.3 500 mg/kg = − 46.5 ± 7.67 750 mg/kg = − 44.67 ± 8.38
		STZ -induced Mice	Methanolic E.		250 mg/kg = 151.5 ± 59.14 500 mg/kg = 196.5 ± 61.86 750 mg/kg = 264.33 ± 53.5	250 mg/kg = − 123.67 ± 43.02 500 mg/kg = − 78.67 ± 46.61 750 mg/kg = − 11. 5 ± 34.84
			aqueous F.		500 mg/kg = 324.84 ± 40.14	500 mg/kg = − 11.16 ± 30.22
			Ethyl acetate F.		500 mg/kg = 278.5 ± 51.65	500 mg/kg = − 57.5 ± 37.85
			Butanol F.		500 mg/kg = 68.67 ± 62.71	500 mg/kg = − 267.33 ± 51.93
Belayneh et al., 2018 [22]	Calpurnia aurea	Normoglycemic Mice Loaded with Oral Glucose	Methanol E	14 Days	100 mg/kg = 4.06 ± 8.88 200 mg/kg = 11.73 ± 9.38 400 mg/kg = 0.67 ± 10.36	100 mg/kg = − 26.33 ± 4.56 200 mg/kg = − 18.66 ± 5.47 400 mg/kg = − 29.72 ± 7.03
		Normoglycemic Mice Loaded with Oral Glucose			100 mg/kg = 28.12 ± 14.9 200 mg/kg = 18.95 ± 14.5 400 mg/kg = 30.51 ± 13.93	100 mg/kg = − 22.55 ± 11.04 200 mg/kg = − 31.72 ± 10.47 400 mg/kg = − 20.16 ± 9.55
		STZ -induced Mice			100 mg/kg = 144.94 ± 52.94 200 mg/kg = 153.11 ± 60.64 400 mg/kg = 134.89 ± 23.25	100 mg/kg = − 98.95 ± 50.04 200 mg/kg = − 90.78 ± 58.12 400 mg/kg = − 109 ± 58.48
Belaynehet al., 2019 [12]	Datura stramonium L.	Normoglycemic mice	Ethanol E	14 days	100 mg/kg = 16.72 ± 7.87 200 mg/kg = 20.11 ± 5.76 400 mg/kg = 15.39 ± 5.30	100 mg/kg = − 23.39 ± 8.10 200 mg/kg = − 20 ± 6.08 400 mg/kg = − 24.72 ± 5.66
Belaynehet al., 2019 [12]	Datura stramonium L.	Diabetic mice	Ethanol E	14 days	100 mg/kg = 38.12 ± 11.30 200 mg/kg = 38.62 ± 11.25 400 mg/kg = 42.89 ± 11.35	100 mg/kg = − 23 .71 ± 2.75 200 mg/kg = − 23.27 ± 2.51 400 mg/kg = − 19 ± 5.30
Birru et al., 2015 [21]	Indigofera spicata Forssk	Normoglycemic rat	Methanol E	10 h	100 mg/kg = − 6.66 ± 7.67 200 mg/kg = 10.48 ± 7.11 400 mg/kg = − 2.5 ± 6.45	100 mg/kg = − 17 ± 6.85 200 mg/kg = 0.5 ± 6.22 400 mg/kg = − 12.48 ± 5.51
Birru et al., 2015 [21]	Indigofera spicata Forssk	Normoglycemic rat Loaded with Oral Glucose	Methanol E	10 h	100 mg/kg = 3.17 ± 10.08 200 mg/kg = 5.5 ± 8.17 400 mg/kg = 10.17 ± 6.73	100 mg/kg = − 26.67 ± 10.22 200 mg/kg = − 24.83 ± 8.33 400 mg/kg = − 20.17 ± 6.93
		alloxan induced mice			100 mg/kg = 179.67 ± 30.71 200 mg/kg = 196 ± 26.86 400 mg/kg = 196.67 ± 24.73	100 mg/kg = − 30.33 ± 23.22 200 mg/kg = − 14 ± 17.80 400 mg/kg = − 13.33 ± 14.41
Hammeso, et al., 2019 [14]	Aloe megalacantha B.	Normoglycemic mice	Aqueous E	14 days	100 mg/kg = 55.53 ± 12.65 200 mg/kg = 55.66 ± 13.98 400 mg/kg = 57.61 ± 13.32	100 mg/kg = − 20.16 ± 8.18 200 mg/kg = − 20 ± 10.13 400 mg/kg = − 18.05 ± 9.19
		Postprandial Normoglycemic mice			100 mg/kg = 32.05 ± 8.49 200 mg/kg = 39.83 ± 5.60 400 mg/kg = 30.83 ± 5.54	100 mg/kg = − 8.11 ± 8.07 200 mg/kg = − 0.33 ± 4.94 400 mg/kg = − 9.33 ± 4.87
		STZ-induced diabetic mice			100 mg/kg = 65 ± 5.57 200 mg/kg = 64.83 ± 5.42 400 mg/kg = 66.83 ± 5.39	100 mg/kg = − 12.16 ± 2.83 200 mg/kg = − 12.33 ± 2.52 400 mg/kg = − 10.33 ± 2.46
Kifle and Eneyew., 2020 [34]	Bersama abyssinica Fresen	Normoglycemic Mice	Methanolic E.	8 h		100 mg/kg = 25.67 ± 3.07 200 mg/kg = 14.17 ± 2.39 400 mg/kg = 8.83 ± 3.43
Kifle and Eneyew., 2020 [34]	Bersama abyssinica Fresen	Mice Loaded with Oral Glucose	Methanolic E.	8 h		100 mg/kg = 14.34 ± 10.30 200 mg/kg = 10.17 ± 6.38 400 mg/kg = 2.50 ± 2.65
		STZ -induced Diabetic Mice	Methanolic E.			400 mg/kg = 21.17 ± 12.47
			chloroform F.			400 mg/kg = 104.0 ± 11.07
			Ethyl acetate F.			400 mg/kg = 69.67 ± 15.32
			aqueous F.			400 mg/kg = 54.5 ± 9.51
Kifle, et al., 2020 [32]	Abyssinica Fresen.	Normoglycemic mice	Aqueous F	14 days		100 mg/kg = 26.67 ± 2.28 200 mg/kg = 15.17 ± 2.72 400 mg/kg = 11. 5 ± 5.47
	Abyssinica Fresen.	Normoglycemic mice	Ethyl acetate F			100 mg/kg = 29.5 ± 6.28 200 mg/kg = 18.00 ± 3.13 400 mg/kg = 16.33 ± 2.31
		Mice Loaded with Oral Glucose	Aqueous F			100 mg/kg = 21.5 ± 6.24 200 mg/kg = 13.67 ± 6.11 400 mg/kg = 5.67 ± 6.67
			Ethyl acetate F			100 mg/kg = 19.5 ± 7.33 200 mg/kg = 14.67 ± 6.83 400 mg/kg = 9.5 ± 6.31
		STZ-induced mice	Aqueous F		100 mg/kg = − 119.5 ± 14.22 200 mg/kg = − 142.83 ± 16.98 400 mg/kg = − 180.0 ± 12.56	100 mg/kg = 95.33 ± 11.82 200 mg/kg = 72.0 ± 15.02 400 mg/kg = 34.83 ± 9.75
Makonnenet al., 1997 [17]	Moringa stenopetala,	Albino rabbits	Aqueous E	6 h	10 g/kg = 5.5 ± 1.48 15 g/kg = 9.8 ± 1.04	10 g/kg = − 37.7 ± 1.48 15 g/kg = − 33.4 ± 1.04
Melaku and Amare et al., 2020 [35]	Datura stramonium Linn	Normoglycemic mice	Methanolic E	14 days		100 mg/kg = 17.64 ± 2.13 200 mg/kg = 17.11 ± 2.91 400 mg/kg = 15.66 ± 3.40
Melaku and Amare et al., 2020 [35]	Datura stramonium Linn	Diabetic Mice	Methanolic E	14 days		100 mg/kg = 10.04 ± 1.66 200 mg/kg = 8.37 ± 1.94 400 mg/kg = 6.99 ± 1.65
Mussa. et al., 2008 [11]	Moringa stenopetalla,	Non-diabetic Mice	Aqueous E.	6 h	20.10 ± 10.02	− 23.60 ± 8.13
			Chloroform F.		21.50 ± 10.70	−22.20 ± 8.96
			Butanol F.		15.50 ± 8.39	− 28.20 ± 5.98
			Aqueous R.		12.50 ± 10.38	− 31.20 ± 8.58
		Alloxan-induced mice	Aqueous E.		12.60 ± 10.16	−44.70 ± 9.24
			Chloroform F.		16.00 ± 7.71	−41.30 ± 6.44
			Butanol F.		41.40 ± 10.56	−15.90 ± 9.67
			Aqueous R.		37.80 ± 7.29	−19.50 ± 5.94
Nardos, et al., 2011 [23]	Moringa stenopetala	Alloxan-induced diabetic mice (Repeated doses)	Aqueous E	8 days	55.4 ± 4.55	−8.6 ± 4.78
			Ethanol E		59.2 ± 3.26	−4.8 ± 3.58
			Chloroform F		47.9 ± 2.26	−16.1 ± 2.70
			Butanol F		46 ± 3.53	−18 ± 3.82
		Normoglycemic mice (Effects of a single dose)	Aqueous E		23.2 ± 7.53	−14.8 ± 5.50
			Ethanol E		24.8 ± 8.8	−13.2 ± 7.14
			Petroleum F		2.2 ± 7.49	−35.8 ± 5.46
			Chloroform F		20.6 ± 7.75	−17.4 ± 5.79
			Butanol F		24.4 ± 7.78	−13.6 ± 5.85
			Aqueous R		13.2 ± 7.83	−24.6 ± 5.90
		Alloxan induced mice (single dose)	Aqueous E		50.8 ± 4.48	−27.4 ± 4.3
			Ethanol E		54.2 ± 6.08	−24 ± 5.95
			Petroleum F		5.2 ± 3.44	−73 ± 3.20
			Chloroform F		59.2 ± 6.26	−19 ± 6.13
			Butanol F		55.2 ± 4.10	−23 ± 3.90
			Aqueous R		18.8 ± 3.33	−59.4 ± 3.08
Rao and Adinew 2011 [33]	Persea Americaca	STZ-induced rats	Ethanol E	30 days	145.18 ± 18.89	−6.84 ± 7.14
Seifu, et al., 2017 [27]	Melia azedarach Lin,	Ob/ob mice and rat	Aqueous E	20 days	Decreased at 200mgg/kg and 400 mg/kg	Similar at 200mgg/kg and 400 mg/kg
Shewamene, et al., 2015 [16]	Otostegiainte grifolia,	Normoglycemic mice	Methanol E	4 h	At 100 mg/kg = 25.61 ± 5.76 At 200 mg/kg = 33.77 ± 4.44 At 400 mg/kg = 1.48 ± 7.03	100 mg/kg = − 9.16 ± 4.18 200 mg/kg = − 1.00 ± 2.06 400 mg/kg = − 36.25 ± 5.81
		Streptozotocin induced mice	Methanol E	4 h	100 mg/kg =183.67 ± 51.36 200 mg/kg =215.67 ± 74.96 400 mg/kg = 168 ± 50.20	100 mg/kg = − 52.45 ± 47.08 200 mg/kg = − 20.45 ± 71. 400 mg/kg = − 67.62 ± 45.84
		Oral Glucose Tolerance Test in rats	Methanol E	4 h	100 mg/kg = 33.39 ± 5.02 200 mg/dl = 50.39 ± 4.37 400 mg/kg = − 22.19 ± 15.82	100 mg/kg = − 40.11 ± 6.64 200 mg/kg = − 23.11 ± 3.93 400 mg/kg = − 95.69 ± 15.71
Shewasinad, et al., 2019 [26]	Thymus schimperi	Normoglycemic mice or rat	Methanol E	Day 15	250 mg/kg = −11.8 ± 8.93 500 mg/kg = − 19.6 ± 7.49750 mg/kg = 1.6 ± 8.48	250 mg/kg = − 75.0 ± 7.16 500 mg/kg = − 82.8 ± 5.26 750 mg/kg = − 61.6 ± 6.60
		Streptozotocin induced rat or mice	Methanol E	Day 15	250 mg/kg = 109.83 ± 11.42 500 mg/kg = 125.27 ± 51.21 750 mg/kg =146.17 ± 45.45	250 mg/kg = − 112.84 ± 35.52 500 mg/kg = − 97.4 ± 50.81 750 mg/kg = − 76.5 ± 45.08
			Ethyl acetate F	Day 15	250 mg/kg = 69 ± 35.29 500 mg/kg = 67 ± 32.80	250 mg/kg = − 167.6 ± 23.83 500 mg/kg = − 169.6 ± 19.99
			n-butanol F	Day 15	250 mg/kg = 132 ± 31.57 500 mg/kg = 143.8 ± 40.38	250 mg/kg = − 104.6 ± 17.91 500 mg/kg = − 92.8 ± 30.91
			Aqueous F	Day 15	250 mg/kg = 104.8 ± 33.16 500 mg/kg = 109 ± 33.46	250 mg/kg = − 131.8 ± 20.58 500 mg/kg = − 127.6 ± 21.06
		In glucose loaded mice	Methanol E	Day 15	250 mg/kg = 80.2 ± 17.6 500 mg/kg = 61.2 ± 16.74 750 mg/kg = 54.4 ± 14.54	250 mg/kg = − 31.8 ± 11.17500 mg/kg = − 51.4 ± 71 At 750 mg/kg = − 60.2 ± 6. 67
Sileshi et al., 2014 [7]	Moringa Stenopetala,	Alloxan induced swiss albino mice	Ethanol E	6 h	− 14.29 ± 6.65	34.77 ± 7.54
			Hexane F	6 h	− 25.50 ± 6.32	23.56 ± 7.24
			Dichloromethane F	6 h	−36.56 ± 7.91	12.50 ± 8.67
			Butanol F	6 h	− 22.76 ± 12.17	26.30 ± 12.68
			Aqueous R	6 h	− 23.31 ± 7.82	25.30 ± 8.41
Tafesse et al., 2017 [20]	Ajuga remota,	Alloxan-induced mice	Aqueous E	14 days	300 mg/kg = − 18.73 ± 3.32 500 mg/kg = − 29.88 ± 1.64	300 mg/kg = 23.27 ± 4.18 500 mg/kg = 12.12 ± 3.03
Tafesse et al., 2017 [20]	Ajuga remota,	Alloxan-induced mice	Ethanol E	14 days	300 mg/kg = − 18.84 ± 2.44 500 mg/kg = − 19.16 ± 2.36	300 mg/kg = 23.16 ± 3.52 500 mg/kg = 22.84 ± 3.45
Tamiru et al., 2012 [28]	Caylusea abyssinica (fresen.) fisch. &Mey.	normalmice	Methanolic E	4 h	100 mg/kg = 9 ± 5.33 200 mg/kg = 8 ± 4.25 300 mg/kg = 10 ± 4.30	100 mg/kg = 11 ± 7.62 200 mg/kg =10 ± 6.91 300 mg/kg =12 ± 6.94
		streptozotocin induced mice			100 mg/kg = 111.67 ± 53.44 200 mg/kg = 149 ± 41.58 300 mg/kg = 105.78 ± 51.61	100 mg/kg = − 33.7 ± 43.36200 mg/kg = 3.56 ± 27.45 300 mg/kg = − 39.66 ± 41.89
		Oral glucose loaded rat			100 mg/kg = 3.83 ± 6.14 200 mg/kg = 8.17 ± 4.86 300 mg/kg = − 9.5 ± 12.18	100 mg/kg = − 14 ± 10.54 200 mg/kg = − 9.66 ± 9.85 300 mg/kg = − 27.33 ± 14.89
Taye et al., 2020 [29]	Thymus schimperi	alloxan induced diabetic mice	Aqueous E	4 h	250 mg/kg = − 128.6 ± 60.97 500 mg/kg = − 155 ± 35.71	250 mg/kg = 76.4 ± 65.45 500 mg/kg = 49.8 ± 42.4
Taye et al., 2020 [29]	Thymus schimperi	alloxan induced diabetic mice	Methanol E	4 h	250 mg/kg = − 145.6 ± 56.11 500 mg/kg = − 171.2 ± 28.91	250 mg/kg = 59.2 ± 60.59 500 mg/kg = 33.6 ± 36.86
Tefera et al., 2020 [30]	L. culinaris	Diabetic mice	Methanol E	21 days	100 mg/kg = − 61.34 ± 4.24 200 mg/kg = − 71.34 ± 4.79 400 mg/kg = − 82.25 ± 4.17	100 mg/kg = 49.66 ± 2.17 200 mg/kg = 39.66 ± 3.11 400 mg/kg = 28.75 ± 2.03
Tesfaye et al., 2016 [13]	Justicia Schimperiana	Normal mice	Aqueous extract	4 h	200 mg/kg = − 1 ± 3.81 400 mg/kg = 10.17 ± 2.74	200 mg/kg = − 13.33 ± 4.19 400 mg/kg = − 2.16 ± 3.26
Tesfaye et al., 2016 [13]	Justicia Schimperiana	Streptozocin-induced mice	Aqueous extract	4 h	200 mg/kg = 2.5 ± 11.70 400 mg/kg = 39 ± 11.13	200 mg/kg = − 46.66 ± 9.33 400 mg/kg = − 10.16 ± 8.60
Toma et al., 2012 [19]	Moringa Stenopetala	Normal	Butanol f. of Ethanol extract	28 days		500 mg/kg = − 2 ± 18.9
Toma et al., 2012 [19]	Moringa Stenopetala	Alloxan Induced Mice	Butanol f. of Ethanol extract	28 days	500 mg/kg = 77.6 ± 24.11	500 mg/kg = −2 ± 18.9
Tomaet al., 2015 [9]	Moringa Stenopetala	streptozocin-induced rats	Ethanol fraction	14 days	at 500 mg/kg = 15.77 ± 3.66	at 500 mg/kg = − 2.5 ± 3.77
Tomaet al., 2015 [9]	Moringa Stenopetala	streptozocin-induced rats	Butanol fraction	14 days	at 500 mg/kg = 13.1 ± 3.18	at 500 mg/kg = − 5.17 ± 3.61
Tsegayeet al., 2008 [18]	Urtica simensis Hochst. ex. A. Rich At 300 mg/kg Unit mg/dl	STZ-induced diabetic mice	Methanol E	4 h	152 ± 8.36	−131 ± 19.5
			Aqueous E		147.9 ± 33.94	− 135.6 ± 38.33
			Petroleum ether F.		10.5 ± 9.19	− 273 ± 20.05
			Chloroform F.		−14.1 ± 13.95	− 297.6 ± 22.63
			Acetone F.		13.7 ± 21.72	− 269.8 ± 28.09
			Methanol F.		105.5 ± 19.56	− 178 ± 26.31
			Aqueous R		201.7 ± 40.03	−81.8 ± 44.75
Yibruet al., 2015 [15]	Coriandrum Sativum	STZI nduced T2DM Mice	Ethanol	21 days	Increased at 300, 400 and 500 mg/kg	Decreased at 300, 400 and 500 mg/kg

Noteworthy glycemic control was observed with Terminalia brownie Fresen for 14 days, better BSL control compared to a diabetic control. Three studies [22, 24, 26] also showed better reductions in BSL compared to a diabetic control. These studies were conducted respectively for 30, 14 and 15 days in Persea Americana, Calpurnia aurea, and Thymus schimperi. Comparable effect to a standard control (glibenclimide) was observed in Persea Americana and Moringa stenopetala [9, 19, 23, 24]. Better acute glycaemia control was observed in Indigofera spicata Forssk, Thymus schimperi and Urtica simensis Hochst.ex. A. Rich [16, 18, 21].

Clinical studies

Trigonella foenum-graecum L. showed noteworthy effect on lipid profile of newly diagnosed type II diabetic patients [6]. Out of 114, 95 completed the study, 49 in the treatment group and 46 in the control group. Both treatment and control groups had abnormal FBG (≥180 mg/dL) and abnormal lipid profile (TC, TG, HDL-C, and LDL-C) at baseline. Trigonella foenum-graecum administered (25 mg seed powder solution for 30 consecutive days) showed a significant reduction (13.6%) in serum TC level as compared to baseline TC level. Yet, no significant difference in TC level in the control group. The treatment group showed a statistically significant decrease (23.53%) in serum TG level compared to baseline TG level but the control group had no significant difference in TG level. HDL-C level was significantly increased in the treatment group by 21.7% as compared to the baseline HDL-C level within the group. LDL-C level had a significantly reduced by 23.4% as compared to the baseline LDL-C level. Trigonella foenum-graecum produced a significant reduction in TC, TG, and LDL-C levels and an increase in HDL-C level compared to baseline.

Toxicology

Acute toxicity studies in animal model demonstrated the relative safety of the plants extract. Seven plants, Terminalia brownie, Calpurnia aurea, Datura stramonium, Indigofera spicata Forssk, Aloe megalacantha, Thymus schimperi, Caylusea abyssinica, Justicia Schimperiana, and Coriandrum Sativum, showed LD₅₀ greater than 2000 mg/kg [10, 12‐15, 21, 22, 26, 28]. Other plants showed LD₅₀ greater than 5000 mg/kg [11, 16, 19, 20, 23]. The LD50 of Moringa stenopetalla were 50.6 g/kg [11] and 50 g/kg [23]. The LD₅₀ of Persea Americana was greater 1000 mg/kg [23]. The sub-chronic toxicity of Moringa Stenopetala showed normal hematological, significantly higher platelet counts compared to controls, significant changes were observed in the clinical chemistry parameters (urea, creatinine, CA125, TSH, FT3, ALT, TGs, and cholesterol), FT4 significantly reduced, and AST were significantly higher in the mice received the treatment [7].

Phytochemistry

Preliminary phytochemical investigation were given in Table 4 and Tekulu et al, 2019 [25] further studied TLC isolates, AM1 and AG1, separated from leaves latexes of A. megalacantha and A. monticola respectively. AM1 and AG1are considered to be more polar compounds than AM2 and AG2 as they have small Rf values during isolation using silica gel coated TLC plate with chloroform: methanol (80:20) solvent system [25]. They could be assigned as glycosides of anthraquinones or its derivatives as they have similar Rf with previously isolated anthraquinone glycosides from leaf latex and root extracts of different Aloe species [38‐40].

Table 4

Preliminary qualitative phytochemical screening of the studied plants

Test	Alema et al., 2020 [10]	Belayneh et al 2019 [12]	Birru et al 2015 [21]	Hammeso et al 2015	Shewamene et al 2015 [16]	Tafesse et al 2017 [20]	Tamiru et al 2012 [28]	Tekulu et al 2019 [25]	Toma et al 2014 [8]	Amare et al., 2020 [35]	Melaku and Amare et al., 2020 [35]
Plant	Terminalia brownii Fresen	Datura stramonium L	Indigofera spicata Forssk	Aloe megalacantha Baker	Otostegia integrifolia Benth	Ajuga remota Benth	Caylusea abyssinica	Aloe megalacanta and Aloe monticola	Moringa stenopetala	Aloe pulcherrima	Datura stramonium Linn
Flavonoids	+	+	+	+	+	+	+		+	+	+
Phenols	+	+	–	+	+	+	+		+	+	+
Tannins	+	+	+	+	–	+	+		+	+	+
Saponins	+	^a	+	+	+	+	+		^a	+	+
Alkaloids	^a	+	+	+	–	–	+		^a	+	+
Terpenoids	+	–	+	+	^a	^a	^a		^a	^a	+
Glycosides	^a	+	+	+	^a	^a	+		^a	+	+
Steroids	+	+	+	–	–	+	+		^a	–	+
Anthraquinones	^a	+	^a	+	^a	–	–		^a	+	–

Abbreviations: +, present; −, absent; ^a not tested

Discussion

This study reviewed twenty three articles on plants with anti-diabetic activity. Most of the studies (20) were conducted in an animal model, in vitro studies (2) and both in vitro and in vivo study (1). Noteworthy glycemic control was observed with T. brownie Fresen compared to a diabetic control. Carbohydrate digestion inhibitory effect was demonstrated in in vitro studies. The possible mechanism for hypoglycemic effect could be decreasing the absorption of ingested sugars as shown in in vitro α-amylase/α-glucosidase inhibitory activity. The human study was primarily focused on the effect of body weight and lipid profile in patients with type 2 diabetes mellitus [6]. Numbers of studies conducted on anti-diabetic activity of Ethiopian medicinal plants were lower compared to studies conducted in many African countries. For example, a systematic review in Nigeria showed 103 plants have experimental evaluation of their blood sugar reducing effects, either in vivo or in vitro [41].

Several medicinal plants are being used traditionally for treatment of diabetes mellitus in Ethiopia for a long period of time but the number of plants studied is limited. This review summarized studies conducted so far and highlighting the need for further studies. Moringa stenopetala is the most commonly studied plant and other plants remain scantly studied. Inhibition of α-amylase, a potential target to control diabetes mellitus for more than 30 years is considered a strategy for the treatment of diabetes mellitus [42].

The effect exerted by Moringa stenopetala could most probably be carbohydrate absorption inhibition resulting in hypoglycemia which could give an insight into the mechanism of the hypoglycemic activity of the anti-diabetic plants. Herbal medicines are often complex mixtures of various phytochemicals that work synergistically to achieve a desired therapeutic outcome [43] and therefore several mechanisms of action could be expected including protecting and repairing cells. The mechanism of lowering BSL could also be stimulating insulin secretion and action.

Natural products are promising lead candidates for discovering and also easily available, affordable and tolerable [44, 45]. Plants provide a rich source of bioactive molecules and possess diverse pharmacological actions including anti-diabetic activity. The activity is attributed to either a single component or mixture of phytochemicals. The phytochemicals responsible for anti-diabetic properties could mainly be alkaloids, phenolics, flavonoids, glycosides, saponins, polysaccharides, stilbenes, and tannins [46] and phytochemical investigation of current study showed the presence of this component in most studied plants. Several animal studies reported a wide variation in composition between the extraction methods. Phytochemical compositions are also highly dependent on several endogenous and exogenous factors, environment, genetics, and plant part used, growing, drying, and storing conditions [47].

Investigations of phytochemicals responsible for the anti-diabetic activity have progressed in the last few decades and treating diabetes mellitus with plant-derived compound seems highly attractive as they are accessible and do not require laborious pharmaceutical synthesis.

Strengths and limitation of the studies

The evidence synthesized from in vitro/ in vivo studies will have paramount for further studies in human studies. It will show directions of further the studies and promote the traditional use. The limitation of this study arises from the limitation of the included primary studies. The methods used for the induction of diabetic mellitus were streptozotocin or alloxan which mostly induces type 1 diabetes mellitus. The methodological challenge in an animal model study is as induction method mostly induces type 2 diabetes mellitus. With its limitation this study provides preliminary activity assay showed further study direction in other plants, identification and isolation of most active components that could join the adventure of modern drug discovery.

It is also worth noting that only one plant has been studied for efficacy in humans in Ethiopia. No clinical trials were conducted and also no clearly defined preparation for clinical trials in Ethiopia. Furthermore, majority of studies did not report the composition of the formulation, standardization protocols and preparation procedures.

Conclusion

This review demonstrated medicinal plants used for management of diabetes mellitus in Ethiopia are worthy for further investigation of pharmacologically active ingredients and clinical study. Further in vitro, in vivo and clinical studies are warranted to confirm the claimed activity of commonly used medicinal plant species. Studies should also focus on the identification of the active ingredient(s) of potent plant species for the development of modern medicine. The present review provides useful information to researchers, students, health professionals, policymakers and, traditional medicine practitioners.

Acknowledgments

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Supplementary Information

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Titel: Efficacy, safety and phytochemistry of medicinal plants used for the management of diabetes mellitus in Ethiopia: a systematic review
verfasst von: Serawit Deyno
Kassahun Eneyew
Sisay Seyfe
Elias Wondim
Publikationsdatum: 01.12.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Phytoscience / Ausgabe 1/2021
Elektronische ISSN: 2199-1197
DOI: https://doi.org/10.1186/s40816-021-00251-x

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Efficacy, safety and phytochemistry of medicinal plants used for the management of diabetes mellitus in Ethiopia: a systematic review

Abstract

Background

Methods

Results

Conclusion

Supplementary Information

Publisher’s Note

Background

Methods 1

Study design

Search strategy

Study selection and data extraction

Definition of terms

Results

Characteristics of included studies

In vitro studies

In vivo studies

Clinical studies

Toxicology

Phytochemistry

Discussion

Strengths and limitation of the studies

Conclusion

Acknowledgments

Competing interests

Publisher’s Note

Supplementary Information

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

Supplementary Information

Publisher’s Note

Background

Methods 1

Study design

Search strategy

Study selection and data extraction

Definition of terms

Results

Characteristics of included studies

In vitro studies

In vivo studies

Clinical studies

Toxicology

Phytochemistry

Discussion

Strengths and limitation of the studies

Conclusion

Acknowledgments

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Supplementary Information

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