Herbal Medicines for the Management of Diabetic Mellitus in Ethiopia And

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ISSN: 2321-547X http://www.imedpub.com/advanced-drug-delivery/

Review Article Herbal Medicines for the Management of Diabetic Mellitus in Ethiopia and Eretria including their Phytochemical Constituents Asfaw Meresa*, Worku Gemechu, Hirut Basha, Netsanet Fekadu, Firehiwot Teka, Rekik Ashebir and Ashenif Tadele Directorate of Traditional and Modern Medicine Research, Ethiopian Public Health Institute, Addis Ababa, Ethiopia

Date of Receipt- 31/03/2017 ABSTRACT Date of Revision- 15/04/2017 Date of Acceptance- 23/04/2017 Background: Diabetes mellitus (DM) is a serious metabolic disorder which causes blood glucose to rise in blood streams abnormally emanating from the difficulty in insulin secretion, its action or the two. The absence of effective modern treatments, the lifelong treatment with modern medicine their associated health side effects and their expensive prices etc. are among the challenging existing realities which devastate/worsen the health and economic burdens of the disease, especially in developing nations. In light of these, the search for cheaper, safe and potential drugs from medicinal plants is very crucial. Objective: The aim of this review is to document existing information on Ethiopian and Eretrian medicinal plants used to treat DM from various sources. The following documents (published scientific papers, MSc thesis, books and research reports on ethno-botany as well as different on-line sources) using the search words, diabetics, medicinal plants and ethno botanical studies, are used in order to compile this review article. One hundred five plant species claiming to have anti-diabetic activity were reported in this study. Moringa stenoptela, Allium sativum, Caylusea abyssinica, Ajuga remota, Calpurnia aurea, and Psidium guajava are among them which are the most frequently mentioned medicinal plant species. Only few numbers of medicinal plants were scientifically evaluated for their anti-diabetic effects in animal models in the countries, whereas the majority of them are not yet evaluated. Next to leaf, root is the second most frequently employed part in the anti-diabetic herbal preparations. Conclusion: The prevalence of diabetes mellitus carries on escalating all over the World and no effective treatments that can manage diabetes have ever been discovered till present. Medication with commercial oral hypoglycemic drugs is getting very difficult due their expensive costs and associated adverse side effects on the health of the patient. Hence, the search for effective and safe drugs from the available medicinal plants should be consolidated in order to alleviate the above mentioned problems. Moreover, the indigenous knowledge of medicinal plants has to be documented in order to initiate or motivate interested researchers to find out anti-diabetic promising candidate drug from folk medicine that might cure or manage the cases and enable self-reliance in the future. Keywords: Diabetics, Prevalence, Medicinal plants, Ethnobotany, Phytoconstituents, Efficacy, Safety.

American Journal of Advanced Drug Delivery http://www.imedpub.com/advanced-drug-delivery/ Meresa A et al______ISSN 2321-547X

Abbreviations: CVD: Cardiovascular Disease; BP: Blood Pressure; NCD: Non-Communicable Disease; WHO: World Health Organization; GC: Gas Chromatography; GC-MS: Gas Address for Chromatography Mass Spectrometer; DM: Diabetes Mellitus; Correspondence IDDM: Insulin Dependent Diabetes Mellitus; NIDDM: Non- Directorate of Traditional and Insulin Dependent Diabetes Mellitus; ASCVD: Atherosclerotic Modern Medicine Research, cardiovascular Disease; MI: Myocardial Infarction; IGT: Ethiopian Public Health Institute, Impaired Glucose Tolerance, HIV-1: Human Immunodeficiency P.O Box 1242, Addis Ababa, Virus type 1; HIV-2: Human Immunodeficiency Virus type 2; Ethiopia NMR: Nuclear Magnetic Resonance, TC: Total Cholesterol; TG: E-mail: Triglyceride, DEMLWE : Department of Environment, Ministry [email protected] of Land, Water and Environment

INTRODUCTION risk of developing cardiovascular problems Diabetes mellitus (DM) is a common endocrine such as atherosclerotic cardiovascular disease disorder characterized by hyperglycemia (ASCVD) myocardial infarction (MI), stable manifesting often with symptoms and signs of or unstable angina, coronary or other arterial osmotic diuresis such as polyuria, polydypsia, revascularization, stroke, transient ischemic calorie loss, generalized weakness, polyphagia attack, or peripheral arterial disease presumed and weight loss resulting from either an absolute to be of atherosclerotic origin which is the deficiency (Type 1) or a relative deficiency (Type leading cause of morbidity and mortality among 2) of the hormone, Insulin1,2. Type 1 diabetes which individuals with diabetes and is the largest formerly known as insulin dependent DM which contributor to the direct and indirect costs of usually occurred in childhood or in early adult diabetes. The common conditions coexisting age is caused by β-cell destruction, with absolute with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk factors for ASCVD, deficiency in insulin which is multifactorial 6 causes such as genetic predisposition resulting and diabetes itself confers independent risk . from an autoimmune reaction to proteins of the According to the World Health Organization islets cells of the pancreas. The other type of DM (WHO) report, about 422 million adults were is Type 2 diabetes, also referred to as non- insulin diabetic patients in 2014 globally, which increased dependent DM usually occur in people >40 years by four times within three decade years who of age occurs with intact beta islet cell but there were only 108 million in 1980. This metabolic is peripheral tissue resistance to insulin1,2. These disorder is the cause of death for 1.5 million disorders associated with reversible and acute in 2012. Number of diabetic patients increased complication such as ketoacidosis become fatal twice from 4.7% to 8.5% in adult population if treatment is delayed3. since1980. This is the results of increase in obesity which is one of the predisposing factors Disabling chronic complication affecting vision, for the on-set of DM. Form the past ten years kidneys, the nerves, blood vessels and heart are on ward diabetes prevalence increased largely common in those who diagnosed very late or in undeveloped and under developed countries those who are in improper medical follow up or compared to developed counties7. care4. Even though the exact cause of this disorder is not clearly known yet there are common Diabetes and its associated health problems are the main global heath burdens that challenge factors that contribute to the on-set diabetes. mankind globally despite discovery and This factor is called predisposing or risk factors. utilization of hypoglycemic drugs to manage the Environmental factors such as diet, overweight case8. Besides affecting the quality of life, the or obesity and physical inactivity and genetic patients do not perform their daily usual business predisposition such as familial aggregation are as they visit heath facilities so many times. This among common mentioned risks particularly for 4-6 has decreased their income directly and created the rise of type 2 DM . high economic loss of the country indirectly as it Diabetes also puts people at a much higher impedes the development of nation at large9. It is

AJADD[5][01][2017]040-058 Meresa A et al______ISSN 2321-547X also expected to happen to be one of the major benefits and can have a negative financial burden disablers and killers worldwide within the next on both individual patients and the society 25 years5. Managing DM has become a global at large18,19. Strictly follow-up the prescription problem in recent times due to the absence of of medical treatment by the patient becomes a successful treatments10. The currently existing challenge for the health care deliverer and scientific therapies for diabetes which include insulin and community. Hence a number of patients do not the various oral hypoglycemic agents caused benefited from medical treatment resulting. This brings a profound negative effect on their quality unnecessary side effects like hepatocellular 20-23 injury; exacerbate renal diseases, lactic acidosis of life and social impacts in many aspects . In and diarrhea11. Ethiopia, the anti-diabetic medication adherence found to be 68.8 to 85 due to poor economic status, Epidemiology of Diabetics low education level and inadequate knowledge about the disease and its medication24-28. The prevalence and incidence of diabetes has been reported to vary among populations and Herbal Medicines for the Management of DM among age groups of the same population. in Ethiopia According to the IDF 2015 estimate, the world Diabetic mellitus prevalence rise globally and will wide prevalence is 1 in 11 adults; more than expected to reach 642 million by 2040. Lifestyle 415 million of people have diabetes which will change, consume carbohydrate rich dish and rise to 642 million in 2040. Among these Africa overweight are the main factors contribute for the account a 14.2 million people with diabetes growth number of diabetic patient. From time to which is likely to increase 34.2 million in time the use of traditional medicine throughout 2035and death of 5.0 million from diabetes in world increases due to the locally availability, 20156. In Ethiopia, the number of people aged easily accessible, simple to use and assumed to 25-29 20-79 years living with diabetes was estimated be safe . As in the other cases people from different parts of the world use herbal medicines to be 1.3 million adults with diabetes, and the 30 prevalence was 2.9%6. This figure is projected to to treat diabetes mellitus and its complications . reach 1.8 million by 203012. World health organization gives recognition for the treatment of herbal medicine for variable According to the recent community based study, communicable and non-communicable chronic the prevalence of diabetics in Ethiopia was disease like DM31. The paradigm shift of diabetic 6%13. Several risk contributing factors to type 2 treatments from conventional drugs to herbal diabetes include: family history of diabetes, the medicine might be due to the belief that herbal demographic and behavioral factors (age group, medicines have low or no side effects and the area of residence, alcohol consumption, adding fact that users feel that they able to control their 32 salt to food, not engaged in vigorous physical choice of medication . This review article aims activity, chewing chat) and biological risk factors to document the medicinal plants that have been used for the management of diabetic mellitus (raised BP or currently on medication or impaired 33 glucose tolerance (IGT)) were significantly from the Ethiopian and Eritrean flora . It also associated (p<0.001) with raised blood glucose, covers the traditional uses, efficacy, safety and phyto-constituents of the anti-diabetic medicinal being overweight, history of gestational diabetes plants which have been evaluated scientifically. and poor nutrition during pregnancy to name a few5,13,14. TRADITIONAL USES, EFFICACY, SAFETY AND PHYTO CONSTITUTENTS Adherence Challenge for the Management of STUDIES FOR MOST COMMONLY USED Diabetics PLANTS Different studies in the world have shown that Plant name: Stevia rebaudiana adherence to diabetes treatment has been highly varied and may range from 1.4 to 88.0%15-17. Low Family: Asteraceae adherence to prescribed diabetes medications Local name: (not stated) accounts for 30% to 50% of treatment failures, leading to worse treatment outcomes and which Part used: Leaf cause damages to vital organs. Treatment failure Traditional uses: The product has been added is in turn associated with reduced treatment to tea and coffee, cooked or baked goods,

AJADD[5][01][2017]040-058 Meresa A et al______ISSN 2321-547X processed foods, beverages34 and used safely leaves of O. integrifolia41 (Figure 2). in herbal medicines, tonics, for diabetes and in Plant name: Ajuga remota Benth the daily usage products like mouthwashes and toothpastes35. It can be used in chocolates and Family: Lamiaceae 35,36 candies for diabetes and tooth decay . Local name: Akorarach (A) Efficacy data: A study showed that both the Part used: Leaf aqueous and 70% ethanolic leaf extracts of Stevia rebaudiana resulted in a fall in blood Traditional uses: In the Ethiopian traditional glucose level in alloxan-induced diabetic mice medicine, the fresh or dried leaves of A. remota as a function of concentration. However, the was infused with water and sometimes with aqueous extract showed a better reduction Alcohol, locally called “Arekie” and the infusions towards blood glucose level as compared with were used as remedy to heal diseases such as the ethanol extract37. diabetes, malaria, pain and fevers, toothache, hypertension, stomachache, pneumonia etc42-44. Safety and toxicity profile: Acute toxicity Sometimes honey is added in to the preparation conducted on overnight fasted Swiss albino mice to make it palatable, since it has a bitter taste, of both sexes for three consecutive days clearly and to store for longer periods for later use37. showed that no significant changes in behaviors such as alertness, motor activity, breathing, Pharmacological activities: The plant was found to have most of the traditionally claimed restlessness, diarrhea, convulsions, coma and activities including antiviral activity against appearance of the animals as well as mortality Human Immunodeficiency Virus type 1, (HIV- were seen up to the maximum of 5000 mg/kg 1) and Type 2 (HIV-2), antipyretic, antifeedant, doses of both solvents’ leaf extracts, indicating antihypertensive, insecticidal, antifungal, the non-toxic effect of plant extracts37. antimalarial activities37. Phytochemical constituents: The leaves Phytochemical constituents: Five different contain diterpene glycosides (Figure 1) namely, neo-clerodane diterpenes namely (Figure 3): stevioside, steviolbioside, rebaudioside A-F and Ajugarin Ι, ΙΙ, ΙΙΙ, ΙV and V and clerodin were ducloside A, which are responsible for the typical 38 isolated and characterized from the leaves sweet taste . Labdanediterpene (e.g. sterebins of A. remota. Bioactive compounds namely I-N), triterpenes, sterols and flavonoids are some ajugalactone, ergosterol-5, 8-endoperoxide and of the non-sweet secondary metabolites that 39 8-O- acetylharpagide were also reported from have also been identified from the leaves . An this plant44-46 (Figure 3). experiment demonstrated that steviol glycosides possesses activities like antioxidant, mutagenic Efficacy profile: A study showed that both the and bactericidal, antiviral, gastro protective, aqueous and 70% ethanolic leaf extracts of the and their effectiveness on renal function, blood plant resulted in a fall in blood glucose level in pressure and blood glucose40 (Figure 1). alloxan-induced diabetic mice as a function of concentration. However, the aqueous extract 41 Tesso and Konig have also reported the showed a better reduction towards blood glucose phytochemical contents of O. integrifolia level as compared with the ethanol extract37. (Figure 2). From the dried leaves of the plant 40 constituents have been isolated by Safety and toxicity profile: Acute toxicity hydro-distillation. A class of terpenes such as conducted on overnight fasted Swiss albino mice monoterpenes, sesquiterpenes, diterpenes and of both sexes foe three consecutive days clearly their derivatives were reported to be present in showed that no significant changes in behaviors the distillate. Trans-Sabinol [A], β-cyclocitral such as alertness, motor activity, breathing, [B], dihydroedulan [C], theaspirane [D] and restlessness, diarrhea, convulsions, coma and (+)-axinyssene [E] (prenylbisabolane diterpenes) appearance of the animals as well as mortality were seen up to the maximum of 5000 mg/kg were identified as the marker compounds. The doses of both solvents’ leaf extracts, indicating prefuranic and furanic labdane diterpenoids, the non-toxic effect of plant extracts47. otostegindiol [F] and preotostegindiol [G] along with pentatriacontane and stigmasterol were also Plant name: Otostegia integrifolia Benth reported in the chloroform extract of the dried Family: Lamiaceae

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Local name: Tinjute [A] 500mg/kg, resulted in no mortality or any adverse 48 Part used: Leaf side effects up on the experimental animals . Traditional uses: In Ethiopian folk medicine, Plant name: Croton macrostachys the leaves of the stated medicinal plant have Family: Euphorbiaceae been utilized to diabetes mellitus by the Local name: Bisana [A] community. As cited by a study, several studies also confirmed the uses of the various species Part used: Root of the genus Otostegia as having an ophthalmic, Traditional uses: Several ethno botanical mosquito repellent, antimicrobial, anti-diabetic studies done on different parts of Ethiopia have as well as antioxidant activities both in nature as reported the medicinal uses of the plant for the 48 well as scientifically . management of malaria, skin diseases, urinary Phytochemical constituents: Results of the retention, intestinal parasites, hepatitis, amoebas general phytochemical investigations reported and bronchitis49-51. the presence of phenolic compounds, saponins, Phytochemical constituents: The general reducing sugars and flavonoids but the lack of chemical screening tests on the hydro-ethanolic alkaloids, tannins and steroidal compounds in root extract Croton macrostachyus confirm the 48 the 80% methanol leaf extract of this plant . An presence of alkaloids, phenolic compounds, investigation on the essential oil and chloroform tannins, terpenoids, saponins, phlobatannins and extract of air-dried leaves gas chromatography Flavonoids52. A compound (Figure 5), named as (GC), GC-mass spectrometry (MS) and NMR crotepoxide was isolated and characterized from techniques confirm the identification of many the CH3Cl extract of the berries of this plant using constituents belonging to the class of terpenes various chromatographic and spectroscopic and their derivatives. The major component techniques53. isolated includes (+)-1-methyl-4-(5, 9-dimethyl- 1-methylene-deca-4, 8-dienyl)-cyclohexene41. Efficacy profile: According to a study, the hydro alcoholic root extract of C. macrostachys Two labdane type diterpenoids, (15, 16-epoxy- had shown a significant blood glucose lowering 3a, 9a-dihydroxy-labda-13(16) & 14-diene effect and improved glucose tolerance after and 9(13), 15(16) - diepoxy-3a-hydroxy-16- administration of oral glucose solution. It is dihydrolabda-14-ene] as well as saturated reported that the crude extract has maximum hydrocarbon called as pentatriacontane and pharmacological effect at the dose of 300 mg/ stigmasterol were also isolated from the kg and it is comparable with the standard drug chloroform extract of the leaves (Tesso&König, 52 2004). Isolation and structural elucidation of a glibenclamide . prenylbisabolane type diterpene, (+)-axinyssene Safety and toxicity profile: Results of toxicity and two labdanediterpenes, otostegindiol, study on experimental mice for the first 24 hrs preotostegindiol and pentatriacontane from as well as 14 consecutive days indicated that the air-dried leaves of the medicinal plant O. the root extract of Croton macrostachys did 41 integrifolia Benth are reported (Figure 4) . not result in mortality as well as Physical and Efficacy profile: An experiment has reported behavioral signs on the test subjects at 2000 mg that 80% O.integrifolia leaf methanol crude and 5000 mg doses of the extract per kg of B.W. extract reduces blood glucose level in normal This shows the plant extract is safe up to the and diabetic mice as well as in glucose induced maximum dose being administered52. hyperglycemic rats. As their study 200 mg/kg has Plant name: Justicia schimperiana shown maximum anti-diabetic, hypoglycemic and oral glucose tolerance activities in treated Family: Acanthaceae mice. Thus 200 mg/kg is the dose that lowered Local name: Sensel [A] the high glucose level in streptozotocine-induced diabetic mice which is close to the normal range Part used: Leaf 48 like the standard drug glibenclamide . Traditional uses: In Ethiopia, Justicia Safety and toxicity profile:The methanolic leaf Schimperiana, belonging to the family extract of the plant, up to the maximum dose of acanthaceae, is locally utilized to heal ailments

AJADD[5][01][2017]040-058 Meresa A et al______ISSN 2321-547X such as stomachache, burning, constipation, skin (P<0.05), improved serum lipid profiles, liver lesion, tooth ache and Scabies. The leaf macerate enzymes and kidney functions in diabetic rats Justicia Schimperiana is claimed to have anti- after 14 days63. 54 diabetic activity around Wolayta Sodo . The effect of n-butanol fraction of ethanol leaf Phytochemical constituents: Phytochemical extract Moringa stenopetala, at 500 mg oral dose analysis results confirmed the detection of administration per kg body weight, on blood secondary metabolites such as alkaloids, glucose levels of alloxan induced diabetic mice polyphenols, flavonoids, glycosides, were evaluated over a period of one month. phytosterols, saponins, triterpenes, and quinines The findings of this study revealed that a large as a major class of compounds55. Phytochemical decrease in BGL was recorded all rats treated analysis indicated the presence of saponins and with the fraction at third week treatment period alkaloids in chloroform, methanol and aqueous and later. On the last day of the month, the butanol fractions of the leaf extract of J. schimperiana, fraction treated groups showed a net reduction while terpenoids were detected only in the in BGL of 5.14% over those which received the chloroform fraction and flavonoids in methanol standard drug, Glibenclamide. At the same time, and aqueous fractions56. the administration of butanol fraction caused Efficacy data: An investigation on the effect of Serum total cholesterol (TC) and triglyceride the aqueous leaf extract of Justicia Schimperiana (TG) levels to decline a large extent. on normal and diabetic mice uncovered that the A study also added that the ethanol and aqueous plant extract at two doses of [200 mg/kg and 400 extracts as well as the various solvents’ fractions mg/kg] post oral administration has shown a fall of ethanol crude extracts and aqueous residue, in blood glucose in all experimental models for each at 300 mg/kg single and repeated doses 54 the treatment periods . administration showed a huge fall in blood Toxicity profile: The median lethal concentration glucose level in both hypoglycemic and anti- of the water leaf extract of the plant was hyperglycemic mice. All the above studies concluded to be greater than 2000 mg/kg as no confirm the blood glucose lowering effect mortality or physical and behavioral signs up on of moringa stenopetala leaves as well as the the experimental rats were seen during the test traditional claims. 54 periods . Phytochemical constituents: Phytochemical Plant name: Moringa stenopetala screening tests on the crude aqueous leaf extracts and butanol fraction of Moringa stenopetala Family: Moringaceae detect the presence of alkaloids, saponins, Local name: Shiferaw [A] polyphenols, flavonoids, coumarins, terpenoids, Part used: Leaf anthraquinones, tannins, phytosterols and cardiac glycosides and the presence of all the Traditional uses: The different parts of this secondary metabolites except saponins in 70% medicinal plant have locally been utilized by the alcohol fractions58,64. Ethiopian communities to manage diseases like malaria, hypertension, asthma, diabetes, stomach Rutin (Figure 6), which is the marker component, pain57,58. was isolated from the leaves of M. stenopetala leaves65. Pharmacological properties: Various literatures reported the uses of Moringastenopetala The other four compounds (Figure 7) are isolat- as anti-malarial, antileishmenial and anti- ed from acetone extract of root wood of Moringa fertility59, hypotensive60, anti-hypertensive61, stenopetala by subjecting the extract to column vasodilatory61, hypoglycemic62, and anti-diabetic chromatographic separation. Based on the physi- effects58,63. cal properties and spectroscopic (IR and NMR) data as well as literature reports, the chemical Efficacy data: An efficacy study illustrated that structures of the compounds were found to be oral administration of the aqueous ethanol and cholest-5-en-3-ol, palmitic acid, n-octaco- n-butanol extracts of Moringastenopetala leaves sane and oleic acid, respectively. Three of (500 mg/kg body weight) and metformin (150 the isolated compounds, namely cholest-5- mg/kg) significantly reduced blood glucose level en-3-ol, palmitic acid and oleic acid pro-

AJADD[5][01][2017]040-058 Meresa A et al______ISSN 2321-547X duced the highest activity against E.coli66 quiterpene lactone), Vernoniosides (Steroid Glu- (Figure 7). cosides) and flavonoids such as luteolin, luteolin 7-O-glucosides, luteolin 7-O-glucuronide etc are Three glycoside compounds were also among the compounds being isolated70. detected in ethanol leaf extract and identified as rutin, 4-(4’-O-acetyl-rhamnosyloxy)- Another study also confirmed that two benzyl isothiocyanate and 4-(4’-O-acetyl- compounds, named as epivernodalol and rhamnosyloxy)-benzaldehyde. Two glycerides elemanolide, were isolated and characterized in the dichloromethane fraction of this medicinal named as 1, 3”dilinoleoyl-2”olein and 1, 71 3”dioleoyl-2-linoleic were characterized from plant . In an experiment, a compound called root extract of Moringastenopetala that showed 3-amino-5-methylhex-5-enyl 3-amino-6- methylhept-6-enyl terephthalate was isolated good activity on aethiopica intracellular 68 amastigotes67. from the leaf of given medicinal plant . Toxicity: For this study, the test animals were Efficacy data: The ethanolic extracts from both orally given ascending concentrations (300, the old and young leaves of the given medicinal plant resulted a significant ( <0.05) anti- 2000, 5000 mg/kg) of the fraction and the result 69 indicated that no detectable changes in behaviors hyperglycemic activity . 푝 such as alertness, motor activity, breathing, Plant name: Aloe camperi restlessness, diarrhea, convulsions, coma and Family: Asphodelaceae appearance of the animals were observed. Similarly, no mortality was recorded at the above Local name: Ere [T] higher limit dose. Part used: Leaf Plant name: Vernonia amygdalina Traditional uses: The latex or leaf extract of Family: Asteraceae Aloe camperi is traditionally utilized for the management skin burns, dandruff, stomach pain, Local name: Grawa [A] hypertension, hair fall as well as diabetes by Part used: Leaf communities living in the Central and Southern 72,73 Traditional uses: As compiled by a study, Zones of Eritrea . Vernonia Amygdalina, belonging to the Phytochemical constituents: A study reported Asteraceae family, is generally utilized for the that alkaloids, phenols, terpenoids, phenols, management of various ailments including tannis saponins, flavonoids, glycosides, malaria schistomiasis, amoebic dysentery, carbohydrate and proteins were contained in the headache, fever, venereal diseases, wounds, methanol extract of the plant where as saponins hepatitis, high blood pressure, hyperglycemia, steroids, terpenoids and coumarines were present and gastrointestinal problems. Furthermore, its in the hexane extract73. leaf is eaten as vegetables to facilitate digestion Efficacy data: Studies have evaluated the anti- besides washing vessels employed for the aim of diabetic activities of methanol leaf extracts of fermentation68. this medicinal plant by administering 200 and Phytochemical constituents: Preliminary 400 mg/kg doses of the extract orally in diabetic screening of ethanolic extracts of both young induced experimental rats. The methanolic and old V. amygdalina leaves revealed the pres- extract resulted in a dose-dependent lowering ence of alkaloids, tannins, saponins, cardiac of FBG levels and the result exhibited very glycosides, terpenes, and steroids despite the ab- significant (P<0.001) decreases in FBG level sence and presence of flavonoids in the young by the end of the experimental day as compared and old leaves of the plant extract respectively69. to the diabetic control. The extract at 400 mg/ A study showed that a large number of isolated kg concentration produced significant anti- bioactive compounds belonging to the various hyperglycemic effect which is comparable to secondary metabolites have been obtained from standard drug. An Oral glucose tolerance test the leaf part this plant by many investigators. (OGTT) on normal rats also indicated that the Vernodalin (Sesquiterpene lactone), Epivernod- hyperglycemia with glucose challenge was alol (Sesquiterpene lactone), Vernomygdin (Ses- significantly brought down (P<0.001) by the

AJADD[5][01][2017]040-058 Meresa A et al______ISSN 2321-547X plant extract at 60 and 120 min relative to the Meriandra dianthera also showed a fall in blood negative control74. The methanol leaf extract glucose after oral administration of the extract of Aloe camperi also showed a fall in blood in normal rats74. This might be attributed to the glucose after oral administration of the extract presence of hypoglycemic bioactive molecules in normal rats74. This might be attributed to the like flavonoids, terpenoids, alkaloids or saponins presence of hypoglycemic bioactive molecules contained within the leaf plant73. like flavonoids, terpenoids, alkaloids or saponins 73 Toxicity data: Acute toxicity test confirmed non- contained within the leaf plant . toxic nature of the methanolic leaf exact of this Toxicity data: Acute toxicity test confirmed non- medicinal plant the median lethal concentration toxic nature of the methanolic leaf exact of this of exact is shown to be beyond 2000 mg/kg per medicinal plant the median lethal concentration body weight74. of exact is shown to be beyond 2000 mg/kg per 74 Plant name: Pentas schimperiana (A. Rich) body weight . Vatke Plant name: Meriandra dianthera Family: Rubiaceae Family: Lamiaceae Local name: Woinagrefet Local name: Nehiba/Mezeguf (T) Part used: Leaf Part used: Leaf Traditional uses: In Ethiopia, its fresh dry root Traditional uses: M. dianthera has wider bark powder mixed with water is taken orally applications in the treatment of diabetes and for epilepsy51 and the of leaf decoction for other ailments in the traditional medical practices management of diabetes mellitus76. of the communities in the Central and Southern 72 Phytochemical constituents: The results of Zones of Eritrea . An ethnobotanical study in general phytochemical analysis confirmed Saharti samire, Southern part of Tigray, Ethiopia the detection of saponins, flavonoids, tannins, showed the uses of this plant for management of 75 steroidal and phenolic compounds in the 80% hypertension and diarrhea . methanolic leaf extract of the medicinal plant. Phytochemical constituents: A study by Efficacy profile: Both the hydro-methanolic reported that phenols, terpenoids, phenols, fresh leaf extract as well as the hydro-methanolic tannins, saponins, glycosides, carbohydrate and aqueous dried leaf extracts of P. schimperiana and proteins were contained in the methanol resulted in the reduction of blood glucose as a extract of the plant where as saponins steroids, function of time and concentration in alloxan- terpenoids and coumarines were present in the 73 induced diabetic mice. Similarly, the effect of hexane extract . oral administration of various solvent fractions Efficacy data: A study has evaluated the anti- of the plant on alloxan-induced diabetic mice diabetic activities of methanol leaf extracts of each at a dose of 500 mg/kg also revealed that this medicinal plant by administering 200 and only the methanol and aqueous fractions caused 400 mg/kg doses of the extract orally in diabetic a significant reduction blood glucose level where induced experimental rats. The methanolic as the chloroform and acetone fractions did not76. extract resulted in a dose-dependent lowering Acute toxicity test: The study results of FBG levels and the result exhibited very demonstrated that the total aqueous and hydro significant (P<0.001) decreases in FBG level alcoholic extracts of P. schimperiana resulted by the end of the experimental day as compared in no physical and behavioral signs such as to the diabetic control. The extract at 400 mg/ restlessness, breathing, diarrhea etc. as well kg concentration produced significant antihyperglycemic effect which is comparable to as caused no mortality up to 5000 mg/kg administered which also showed a median LD50 standard drug. An Oral glucose tolerance test 76 (OGTT) on normal rats also indicated that the is above the tested dose . hyperglycemia with glucose challenge was We used the following documents: published significantly brought down (P<0.001) by the papers, MSc theses, books and research reports on plant extract at 60 and 120 min relative to the ethno botany as well as different on-line sources negative control74. The methanol leaf extract of in order to compile this review article77-108.

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RESULTS compounds contained within the plants have Diabetes is a metabolic problem that contributes shown beneficial effects that can delay the onset to major economic decline, there by hampering of diabetic problems and adjust the metabolic the growth of nations. Besides, unmanaged disorders. Nevertheless, the pharmacological diabetes results in several chronic complications actions and chemistry of many of the medicinal such as blindness, heart failure, and renal plants have not been well studied scientifically. failure. In order to prevent this increasing health Therefore, further characterization of the burdens, the development of research into new active compounds, efficacy, evaluation of the hypoglycemic and potentially anti-diabetic mechanism of action and toxicity of the medicinal agents from plant origin is of great interest in plants should be carried out. A research that can recent times. Thus, this review article lists a strengthen the documentation of the indigenous total of one hundred five medicinal plants which knowledge which contributes for the drug are utilized for the management of diabetics in development and for self-reliance in the future is Ethiopia (Supplementary table 1). also recommended. [A]=Amharic, [O]=Affan Oromo, [T]=Tigrigna, COMPETING INTERESTS [Sm]=Somaligna, [Sd]=Sidamigna All authors declare that they have no competing (Figure 8) shows the common plant part used interests. were leaf followed by root. ACKNOWLEDGMENTS Also, (Supplementary table 2) shows that We greatly thank all authors who contribute a lot Allium sativum, Cayluseaabyssinica, Calpurnia to the completion of this review. aurea, Moringastenoptela, Psidiumguajava and Thymus schimperiwere are the most commonly REFERENCES used medicinal plants for the management of 1. Ozougwu JC, Obimba KC, Belonwu CD, et diabetics in Ethiopia. al. The pathogenesis and pathophysiology of CONCLUSION Type 1 and Type 2 diabetes mellitus. J Physiol Pathophysiol. 2013;4(4):46-57. The prevalence of diabetes mellitus carries on escalating all over the World and no effective 2. Huang THW, Peng G, Kota BP, et al. treatments that can manage diabetes have ever Anti-diabetic action of Punica granatum been discovered till the present. Medication flower extract: Activation of PPAR-c and with commercial oral hypoglycemic drugs is identification of an active component. Toxicol getting very difficult due their expensive costs App Pharmacol. 2005;207:160-9. and associated side effects on the health of the 3. Kumar P, Clark M. Diabetes mellitus and other patient. Herbal medicines have recently been disorders of metabolism. In: Clinical Medicine gaining increasing popularity by both developing (2nd edn). Elsevier, London. 2002;1069-71. and developed nations for the management of 4. Kaku K. Pathophysiology of Type 2 diseases, including diabetes. In this review, a diabetes and its treatment policy. JMAJ. total of one hundred five medicinal plants have 2010;53(1):41-6. been identified and documented for their use in management of diabetics. This article also presents 5. Deepashree BN, Prakash JA. Study on the traditional medicinal uses, efficacy, toxicity nutritional status of diabetics and associated as well as the bioactive compounds of some anti- risk factors. J Human Ecol. 2007;21:269-74. diabetic plants found in Ethiopia and Eretria. 6. http://www.idf.org/about-diabetes/risk-factors Most of these medicinal plants are widely 7. http://apps.who.int/iris/bitstream/10665/2048 utilized in different parts of the country; only the safety and efficacy of Moringa stenopetala, 204871/1/9789241565257_eng.pdf Stevia rebaudiana, Pentas schimperiana, 8. Burke JP, Williams K, Narayan KMV, et al. A Meriandra dianthera, Vernonia Amygdalina, population perspective on diabetes prevention: Justicia Schimperiana and Otostegia integrifolia Whom should we target for preventing weight were scientifically tested in animal models. As gain. Diabetes Care. 2003;26:1999-2004. demonstrated by many scholars, the bioactive 9. Mahabir D, Gulliford MC. Use of medicinal

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Table 1. List of medicinal plants used to manage diabetes mellitus

S. Scientific name Family Local name Parts used Method of preparation Other Medicinal Uses Reference No water and sugar boiled 1. Aloe pulcherrima G Xanthorrhoeaceae Set-eret (A) Latex together and given Asthma, diabetes dandruff [79] orally Dried stem and leaf Thymus schimperi Stem, leaf, 2. Lamiaceae, Tosign (A) powder boiled with tea Diabetes [80, 79] Ronniger, Whole plant is given orally Anti diabetic activity, 3. Croton macrostachys Euphorbiaceae Bisana (A) Root malaria, purgative and anti- [52, 81] inflammatory effects, 4. Aloe vera Asphodelaceae Eret (A) Fresh leaf Not specified Diabetes [82] The plant is cut and squeezed until enough Diabetes, Homorroids, 5. Euphorbia sp. Gmel Euphorbiaceae Kulkual (A) Latex is collected, a cup and [83] ascaries half is drunk three times a day before food Give the dikus with Diabetes, nekersa, urine Asparagus africanus Sereti (A)Sarritt/ food and drinks retention, chest pain, 6. Asparagaceae Root, Leaf [79,84] Lam qastanticha Powdered and taken sleeping, Snake bite, orally poisoning, diabetes Discopodium Eat the boiled leaf as a 7. Solanceae Ameraro (A) Leaf Diabetes [84] penninervum Hoschst cabbage stomachache , skin Caylusea absyssinica [43, 8. Resedaceae Rench (A) Leaves Not specified diseases, diabetes mellitus (fresen) 85-87] and amoeba Aqueous and sometimes Malaria, toothache, skin Ajuga integrifolia Ham- Harmagusa[O] “Arekie” (alcohol) disease whooping cough, [37,43, 9. lamiaceae Leaves, Root Buch. Labiatae Akorarach (A) infusion of the fresh or pneumonia,hypertension, 84,87] dried leaves diabetes etc… Seeds taken out Solanum marginatum Zerch embuay, ,washed, dried and Cough, lung problem, 10. Solanaceae seeds [84] L.f (A) drunk with goats kebe diabetes or milk after boiling Gum and Betazma mar lewuso Cough, lung problem, 11. Podocarpus gracilis Podocarpaceae Zigba (A) [43,84] shoot meblat(1/2 spoon) diabetes, Crinum Yejib shinkutrt Shoot tip- Squeezed, mixed with 12. abyssinicum(Hochst) ex (Amaryllidaceae) Hypertension, diabetes [88] (A) fresh water, drink A. Rich Wounds, ulcers, Boil with the leaves bronchitis,hypoglycemic , [73,88, 13. Psidium guajava Myrtaceae Zeytun (A) Leaves of camellia sinesis and anti hyperglycemic, anti- 89] drink inflammatory effect etc.. FoeniculumVulgare Hypertension, diabetes, 14. Apiaceae Ensilsl (A) Fresh leaves Boil and drink [88] Miller. gonorrhea Dry or fresh leaves crushed, pounded, and 15. Argemone thiopia .L papaveraceae Wajo uta (Sd) leaves filtered then infusion Diabetes [90] drunk in the middle of night Dry or fresh leaves crushed, pounded, and Delonix regia (Boj.ex 16. Fabaceae Mimi (Sd) leaves filtered then infusion Diabetes [90] Hook) drunk in the middle of night Fresh leaves cooked as Hyperglycemia, kidney [58,87,88, 17. Moringa- stenoptela Moringaceae Shiferaw (A) Fresh leaves food and eaten or Boil infection, cold, malaria 90-92] and drink its soup Malaria, diarrhea, diabetes, [49,93, 18. Calpurnia aurea Fabaceae Digita (A) Leaf Not specified rabies, hypertension 111] amoebiasis , giardiasis etc 19. Lens culinaris Medik Fabaceae Misir [A] seed Not specified Diabetes [49] Decoction of the seed or bark is used or Malaria, cough, dysentery, Acacia nilotica (L.) seed, stem 20. Fabaceae Ghered (T) Regularly fruits are insect repellent Diabetes, [73,94] seed, stem bark bark given in spoonful before diarrhea, hemorrhage, tooth break fast

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Reheumatic pains, asthma, 21. Ambrosia maritma L Asteraceae Whole plant Not specified biliharziasis, diabetes and [94] to expel renal stones Bitter tonic, ameliorate the condition of diabetic 22. Bryonia cretica L. Cucurbitaceae Not specified Not specified [94] persons, whooping cough, bronchitis and tonsillitis Gastric and abdominal Centaurium pulchelum Infusion of the herb is pain, diabetes, 23. Gentiaceae [94] (Swartz) druce used for diabetes hypertension, renal colic, rheumatic pains etc… 5 gm of paste powder Cleome droserifolia Hyperglycemia (diabetes), 24. Cleomaceae is topically used before [94] (Forssk)Delile wounds and for dermatitis meal for treatment 25. Glinus lotoides Molluginaceae Fruit Not specified Anti-diabetic [95] diabetes, hypertension, Stevia rebaudiana 26. Asteraceae Leaf Aqueous leaf extract antimicrobial, anti obesity [37] Bertoni and antioxidant activities Skin burns, dandruff, Aloe camperi fresh leaves, Extract of the latex or 27. Aloaceae Sandai-ere (T) stomach pain, hypertension, [73,74] Schweinfurth latex leaf is used regularly hair fall Hypertension, diarrhea, Meriandra dianthera Nehiba/Mezeguf Extract of the leaf is 28. Lamiaceae fresh leaves diabetic gastritis, bronchial [73,75] (Roth) Briq. (T) taken 1 cup daily asthma, purgative, diarrhea, Gynecological problems, Otostegia integrifolia Extract of the leaves inflammation, insecticidal, 29. Lamiaceae Ch’endog (T) Leaf [48,73] Benth. taken in the evening antioxidant, anti diabetic activity, etc… Pentas schimperiana 30. Woina grefet Leaves decoctions of leaves diabetes, epilepsy [ 76] Subsp. Fresh bulb is eaten raw or added in sauce Asthma, antiseptic, Shiguerti-tsada [73,87, 31. Allium sativum Lilliceae bulb The powdered bulb is diuretic, hypertension, (T) 93,96,97] dispersed in decocted expectorant root. Anti-diabetic, antioxidant Seeds and effect, antimicrobial 32. Sesbania sesban (L) Papilionoideae, girangire (A) Not specified [98] leaves activity, anti fertility agent, ethno veterinary use treatment of liver diseases, Satureja punctata leaves are cooked and 33. Lamiaceae) Lomishet (A) leaves hypertension, diabetes and [99] Benth. Briq the extract drank other disorders The root is decocted Toothache, asthma, 34. Datura stramonium L. Solonaceae Asangra (O) Root overnight and mixed hypertension, diabetes [97] with rancid butter mellitus Lagenaria abyssinica The powdered flower is 35. Cucurbitaceae Buqe setena (O) Flower Diabetic Mellitus, rabies [97] (hook.f.) C.Jeffrey dispersed in water It is crushed with whole part of Cucumis ficifolius, boiled in the 36. Guizotia Schimperi Asteraceae Adey Abeba (A) Whole part Diabetes [100] water and one glass is taken orally until recovery. Leaves powdered and Indigofera spicata 37. Fabaceae Reencii (O) leaves mixed in water and Diabetes [101] Forssk. taken when need arises The aqueous decoction cancer, liver and kidney Leaves,aerial 38. Cineraria abyssinica Asteraceae) ‘Esemefirh’(G) of the leaves and aerial diseases, hypertension, [102] parts parts diabetes 39. Myrts commuis Myrtaceae Ades (A) Leaves Fruit Not specified Anti-hyperglycemic [103] Hypoglycemic, anti- Freshly cut bulb is often hyperglycemic activity in 40. Allium Cepa Alliaceae Qey-shnkurt (A) bulb [73, 87] used normal and STZ induced diabetic rats etc… Antihyperglycemic effect 41. Curcuma longa Zingeberaceae Ird (A) Not specified in STZ induced diabetic [87] rats Hypoglycemic effect in 42. Coriandrum- sativum Apiaceae Dimbelal (A) Not specified [87] normal rats

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Antidiabetic influence in 43. Cuminum- cyminum Apaiaceae Ensilal (A) Not specified [87] STZ induced Diabetic rats Cymbopogon- thiopia Hypoglycemic effect in 44. Poaceae Lomi sar (A) Not specified [87] Stapf normal rats Antihyperglycemic effect 45. Linum- usitatissimum Linaceae Telba (A) Not specified in alloxan induced diabetic [87] rats Decoction of leaf Diuretic, diarrhea, leaf, stem [73,87, 46. Mangifera indica L. Anacardiaceae Mangus (T) or stem bark is used dysentery, anemia, bark 104], regularly bronchitis, hypertension Anti-hyperglycemic Seeds added in bread activity in diabetic rats, Abosoda (T) or a spoon of powdered 47. Nigella sativa L. Ranunculaceae Seed asthma, dysentery, [73,87] Tikur-Azmud (A) seeds taken orally hypertension, before meal gastrointestinal problems Diuretic, antipyretic, Extract of the dried and Trigonella foenum- Abe’ake (T) stomachic, anemia, 48. Fabaceae Seed powered seed is used [73,87] graecum L. Abish (A) hypertension, diabetes regularly gastrointestinal pains Digestive disorders, Zingiber officinale Tea of the rhizome 49. Zingiberaceae Zingible (T) Root stimulant, bronchitis, throat [73,87] Roscoe frequently used infections, hypoglycemia Fruits boiled in hot Expectorant, diabetes Fruit water or mixed with 50. Solanum incanum L. Solanaceae Uengule (T) stomach ache, fever, snake [73,105] Root yogurt or root is chewed bite, bronchitis. and swallowed. 51. Salvia lavandulifolia Lamiaceae Not specified Hypoglycemic activity [106] 52. Salvia officinalis Lamiaceae Not specified Hypoglycemic activity [106] 53. Salvia fruticosa Mill Lamiaceae Not specified Hypoglycemic activity [106] 54. Salvia splenden Lamiaceae Not specified Hypoglycemic activity [106] Hypoglycemic activity, Methanolic extract of headache, stomach trouble 55. Salvia tillifolia Lamiaceae Aerial part [106] aerial part and as memory enhancing herb 56. Ricinus communis Euphorbiaceae Gulo (A) Roots Not specified anti-diabetic [81] Malaria, rheumatism, diabetes, inflammation, Securidaca gonorrhea, palpitations, insanity and epilepsy, 57. longepedunculata Polygalaceae) root bark [107,108] pneumonia, syphilis, wounds, cough, venereal Fresen asthma diseases, snake bite etc Soaking crushed fresh 58. Balanites rotundifolia Balanitaceae Alayto (Sm) Leaves leaves in water and the Laxative, fevers , diabetes [109] water is taken orally Soaking crushed fresh Buxus hildebrandtii Diabetes, infections, 59. Buxaceae Gaydarto Leaves leaves in water and the [109] Baill. parasites water is taken orally Soaking crushed plants Plant parts Diabetes, sun burns, Lavandula without the leaves in 60. Lamiaceae Dananwada (Sm) without Kidney problems ,side ache [109] coronopifolia L. water and the water is leaves problems taken orally Soaking crushed whole 61. Melia azedarach L. Meliaceae Dat caxa (Sm) Whole plant plant in water and the Diabetes, Wound infections [109] water is taken orally Soaking crushed leaves Nepeta azurea R.Br. Ex Diabetes ,kidney diseases, 62. Lamiaceae Simitri (Sm) Leaves in boiled water and the [109] Benth. asthma water is taken orally Soaking crushed leaves Tarchonanthus thiopias Diabetes, Bladder 63. Asteraceae Galqaddo (Sm) in water for 1 h and the [109] L. inflammations water is taken orally 64. Cinnamomumverum Lauraceae Not specified Diabetes [110] Insect repellent, malaria, Azadirachta indica A. leaf, stem Leaf or bark decoction 65. Meliaceae Neem (T) skin diseases, anthelmintic, [73,110] Juss. bark used for drinking diuretic 66. Aloe megalacantha Asphodeloideae Not specified Diabetes [110] 67. Justicia Schimperiana Acantanceae Leaves Not specified Diabetes [54] Lysimachia ruhmeriana 68. primulaceae Not specified Diabetes, haemorrhoids [43] vatke Diabetes, hypertension, Thymus serrulatus 69. Labiatae Not specified rheumatism, menorrhagia, [43] Hochst ex Benth, amenorrhoea

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Diabetes, scabies, colic, Verbascum sinaiticum anti-emetic, amoebiasis, 70. Scrophulariaceae Not specified [43] Benth. diarrhoea, epilepsy, aphrodisiac, infertility Anti-emetic, malaria, 71. Verbena officinalis L Verbenaceae Not specified diabetes, burns, respiratory [43] diseases Liver disorders , diabetes, 72. Rubus steudneri Rubiaceae Enjori (A) Leaf Not specified cough, gum pain, anti- [43] oxidant In prepared foodstuffs 73. Arachis hypogeal l. Leguminaseae flower such as biscuits and Diabetes [43] sweetmeats Blood glucose level decreased in mice after 74. Coffea Arabica L. Rubiaceae Buna [A] Green seed Not specified [43] oral administration of the substance Cucurma domestic Reduces or helps to control 75. zingibraceae Rhizome Not specified [43] valeton blood sugar Shows anti-hyperglycemic 76. morus spp Moraceae Not specified [43] activity in vivo. Diabetes ,diuretic, Leaf extract is used in 77. Ammi visnaga (L.) Lam. Apiacea E’bna (T) leaf hypotensive, hair-care, [73] the morning antispasmodic, asthma Diabetes, diarrhea, eye Anethum graveolens Tea of the leaves is 78. Apiacea Shilan-maedo (T) leaf problems, indigestion, [73] Linn taken twice daily stomachache Balanites aegyptica Leaf extract or ripe fruit Purgative, insecticidal, 79. Balanitaceae Mekie (T) leaf, fruit [73] (L.) Del. is taken laxative, stomach aches Gastrointestinal disorder, Seed decoction is used 80. Brassica nigra Koch. Brassicaceae Adri (T) Seed stimulant, diuretic, [73] regularly bronchitis Skin diseases, anthelmintic, Calotropis procera stem bark, Crushed bark or latex 81. Asclepiadaceae Ghinde’a (T) expectorant, wounds, [73] (Ait.) latex are mixed with butter diarrhea Tooth ache, cough, Capparis thiopia stem bark, Infusion of stem bark or 82. Caparidiacea Sorob[T] arthritis, anthelmintic, [73] (Forssk.) leaf leaf is used malaria, inflammation Amoebicide, hypertension, Decoction of seed or constipation, expel worms, 83. Carica papaya L. Caricaceae Papaya (T) leaf, seed leaf is drunk 1 beaker in laxative, Hypoglycemic [73,87] the morning and Antihyperglycemic effects Anthelmintic, Extract of stem bark is 84. Carissa edulis (Forssk) Apocynaceae Agam (T) stem bark inflammation, hypotensive, [73] drunk regularly diuretics, headache Cooked properly and Appetizer, febrifuge, anti- 85. Cichorium endivia L. Asteraceae Shikoria (T) Leaf [73] eaten with enjera allergic Leaf or stem bark Abdominal pains, snake Clerodendrum Sur-betri / stem bark, 86. Lamiaceae extract is drunk bites, hemorrhoids, eye [73] myricoides (Hochst) Ugandense (T) leaf regularly disease Clutia lanceolata Leaf extract is taken Malaria, diarrhea, colds, 87. Euphorbiaceae Tish-belalito (T) / Leaf [73] (Forssk) twice a day gynecological problems Tuber is eaten in raw or Diuretic, inflammation, 88. Daucus carota L. Apiacea Caroti (T) tuber [73] with salad leprosy, worms troubles Entada abyssinica stem bark, Decoction of the stem Gastrointestinal problems, 89. Fabaceae Halke (T) [73] Steud. Ex A. leaf bark or leaf cold, candidiasis Insect repellent, Eucalptus thiopia Tsaeda- Leaf extract is taken 1 90. Myrtaceae Leaf tuberculosis, bronchitis, [73] (Labill.) kelamintos(T) cup per day malaria, skin diseases Decoction of fresh leaf Antispasmodic, diarrhea, 91. Ferula communis L. Apiacea Diog (T) seed, leaf [73] or dried seed expectorant ,dermatitis daily Cough, Gymnema sylvestre inflammations, 92. Asclepiadaceae Shankuk (T) Leaf Leaf extract is taken [73] Roxb. constipation, haemorrhoids, bronchitis Constipation, tapeworm, Kigelia thiopia (Lam.) Mederba/Zelzale 93. Bignoniaceae Fruit Fruits are eaten dysentery, gynecological [73] Benth. (T) disorders

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Diuretic, cough, laxative, The seed extract is 94. Lepidium sativum L. Brassicaceae Shinfae (T) Seed asthma, diarrhea, malaria, [43,73] taken before bed hypoglycemic effects Fresh leaf juice taken Asthma, constipation, skin 95. Moringa oleifera Lam. Moringaceae Moringa (T) / Leaf every morning in empty diseases, diarrhea, stomach [73] stomach pain, hypertension Stimulant, abortifacient, Decoction of stem or 96. Plumbago zeylanica L. Plumbaginaceae Aftooh (T) root, stem inflammation, bronchitis, [73] roots used trice a day itching Psiada panctulata Decoction of the leaves Cough, anti-abortion, 97. Asteraceae Tsehaiferhet (T) leaf, root [73] (DC.) Vatke - or roots is used asthma Stomach pains, Rosmarius officianilis A spoon of leaf or stem 98. Lamiaceae Azmarino (T) y Leaf, stem gynecological problems, [73] L. is added in daily food bad breath, migraine Decoction of either leaf Sore-throat, ulcer, diuretic, Steganotaenia Mewets denagl 99. Apiaceae leaf, seed or seed mixed with milk stomachache, dysentery, [73] araliacea Hochst. (T) is taken in the morning hypotensive Extract of the fruit is Malaria, fever, stomach 100. Tamarindus indica L. t Fabaceae Humer (T) fruit [73] taken twice a day ache, wounds, purgative Terminalia thiopi stem bark, Decoction of the stem Wounds, malaria, 101. Combretaceae weiba (T) [73] Fresen leaf bark or leaf dermatitis, tuberculosis Hypertension, diarrhea, Trachyspermum ammi Kamun/Tsakida Seed powder is soaked 102. Apiaceae Seed asthma, anti-helminthic, [73] (L.) (T) in water or milk diuretic Stomach ache, skin Vernonia amygdalina leaf, stem The extract of fresh 103. Asteraceae Grawa (T) infections, tooth ache, [73] Del. bark leaves in water is used cough, malaria, Roots are immersed in Diabetes, constipation, skin 104. Withania somnifera (L.) Solanaceae Agol (T) root, leaf hot water and the juice [73] infection, rheumatism of the leaves Diarrhea, dandruff, skin Zizyphus spina-christi Infusion of the leaves 105. Rhamnaceae Gaba (T) Leaf infections, bronchitis, [73] (L.) used regularly malaria [A]= Amharic, [O] = Affan Oromo, [T]= Tigrigna, [Sm]= Somaligna, [Sd]= Sidamigna

Table 2. List of medcinal plants in terms of citation Plant name N % Moringastenopetaa 6 5.7 Allium sativum 5 4.8 Caylusea- abyssinica 4 4.8 Ajugaintegrifolia. 4 4.8 Psidiumguajava 3 2.8 Calpurnia aurea 3 2.8 Thymus schimperi 2 1.9 Acacia nilotica L. 2 1.9 Allium Cepa 2 1.9 Asparagus africanus 2 1.9 Azadirachtaindica 2 1.9 Carica papaya 2 1.9 Croton macrostachys 2 1.9 Glinuslotoides 2 1.9 LepidiumsativumL. 2 1.9 Mangiferaindica 2 1.9 Meriandradianthera 2 1.9 Nigella sativa 2 1.9 OtostegiaintegrifoliaBenth 2 1.9 Podocarpusgeacilior 2 1.9 Securidacalongepedunculata 2 1.9 Solanumincanum 2 1.9 Trigonella-foenumgraceum 2 1.9 Zingiber-officinale 2 1.9 Aloe camperi 2 1.9 Rest 1 0.9 Total 105

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tevioside teviolbioside

ebaudioside ebaudioside

ebaudioside ebaudioside D ebaudioside E

ebaudioside Ducloside Figure 1. Structures of diterpene glycosides

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Trans-abinol β-cyclocitral Dihydroedulan heaspirane

()-axinyssene otostegindiol reotostegindiol Figure 2. Compounds isolated from Otostegia integrifolia

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Ajugarin Ι Ajugarin ΙΙ

ugarin clerodin

ugalactone Ergosterol- -endoperoxide Figure 3. Compounds isolated from Ajuga remota Benth

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entatriacontane tigmasterol

Otostegindiol ()-axinyssene Figure 4. Some isolated compounds of Otostegia integrifolia Benth

rotepoxide Figure 5. Some isolated compounds of Croton macrostachys

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Figure 6. Chemical structure of Rutin

cholest--en-3-ol almitic acid

n-octacosane Oleic acid Figure 7. Some of the isolated compounds of Moringa stenopetala

Figure 8. Medicinal plant parts used for the management of diabetics in Ethiopia

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