Traditional Herbal Remedies in the Management of Metabolic Disorders in Ethiopia: A Systematic Review of Ethnobotanical Studies and Pharmacological Activities

Background MetS are common throughout the world, including Ethiopia. These have traditionally been treated using medicinal plants, particularly in rural areas where they are freely accessible. This systematic review tried to investigate the treatment of MetS with Ethiopian medicinal herbs and made recommendations for more validation research. A careful analysis of the literature was also conducted on the therapeutic effects of these and other Ethiopian medicinal plants with hepatoprotective and antihypertensive activities. Methods The relevant keywords “Ethnomedicinal + hypertension,” “Ethnopharmacological + hypertension,” “Ethnomedicinal + hepatitis, jaundices, and liver disease,” “Ethnopharmacological + hepatic disorder,” and “Ethnomedicinal + weight loss” were used to search for relevant articles in the major electronic scientific databases, including PubMed, Science Direct, Web of Science, and Google Scholar. The search strategy included all articles with descriptions that were accessible until April 30, 2022. The study's subjects, methods, or year of publication were no restrictions in the search. The outcomes were compiled using descriptive statistics. Results Fifty-four (54) studies were examined in the review that satisfied the inclusion and exclusion criteria for the treatment of MetS in Ethiopia. The most often used ethnobotanical plant species for the treatment of hypertension and hepatic disorders were Moringa stenopetala and Croton macrostachyus. Both hepatic and hypertensive disorders were treated more frequently with leaves (52% and 39%, respectively) than with roots (20% and 13%, respectively). Some intriguing studies came from an ethnobotanical investigation into medicinal herbs' hepatoprotective and antihypertensive properties. The most often investigated medicinal plant for its antihypertensive effects is Moringa stenopetala. Conclusion The study revealed that Ethiopians often use anti-MetS herbal remedies. We advocate the experimental validation of the commonly used medicinal plants with the identification of active compounds and the development of effective alternative drugs for the treatment of MetS.


Introduction
Metabolic syndrome (MetS), a cluster of interrelated metabolic disorders, is becoming more common around the world. According to the International Diabetes Federation, MetS afects around 25% of the world's adult population, and its prevalence is expected to rise in the next few decades [1]. MetS are on the rise and pose a serious threat to public health, especially in countries in sub-Saharan Africa with limited resources [2]. Governments in underdeveloped countries have already spent billions of dollars to tackle the widespread efects of MetS and related risk factors [3]. Te emergence of risk factors for MetS and an increase in its incidence worldwide have all been related to genetic, epigenetic, and environmental factors [4]. Te adoption of sedentary lifestyles, which are defned by low physical activity or exercise and the intake of high-energy foods, is also to blame for this epidemic [5]. Te risk factors for MetS are being addressed through dietary modifcations and the use of pharmaceutical drugs that primarily target specifc biochemical pathways involved in food metabolism [6]. Pharmaceutical medications usually cost a lot of money, have poor patient compliance, and have been associated with the emergence of a variety of undesirable side efects with prolonged usage. In addition, they are monotherapeutic, concentrating on just a few health outcomes associated with metabolic dysregulation. Alternative and complementary approaches to the management of metabolic diseases must be studied and developed urgently. Herbal remedies should be used in these alternate MetS risk factor management strategies. Medicinal plants are defned as any plant or plant preparation that has benefcial therapeutic and/or preventive properties or that provides health-promoting properties and temporary relief [7]. Medicinal plants are now accepted by healthcare providers as having a role to play in the management and prevention of metabolic disorders [8]. Te use of herbal medicine is no longer limited to developing countries; it has grown into a multibillion-dollar industry that spans all demographic and socioeconomic groups [9]. Medicinal plants include pharmacodynamic bioactive compounds that have a therapeutic impact that is additive and synergistic in the treatment of metabolic disorders [10]. Most pharmaceutical drugs are derived from medicinal plants using local knowledge and then isolating the main active compounds [11]. Plant material utilized in the preparation of medicinal remedies could be used as a template for the development of pharmaceutical drugs. Te identifcation of benefcial phytochemical compounds in medicinal plants and their application in the treatment of MetS have reduced the fnancial burden of relying on costly synthetic pharmaceutical drugs. According to the WHO, even in the presence of pharmaceutical drugs, most rural and urban-based communities in Africa still rely on traditional remedies for their primary healthcare [12]. When compared to some of the pharmaceutical drugs now being used in the management of metabolic disorders, another driving factor in the usage of medicinal plants is the impression that they are free of adverse side efects and acute toxicity [13]. Despite the fact that some people prefer to use medicinal plants due to their perceived safety, scientifc validation is required to ensure the safety and consistency of medicinal preparations. In fact, the WHO recommends demonstrating safety before determining the therapeutic beneft of medicinal plants used in primary care [14]. In this review, we looked at how medicinal plants are currently being used or studied in Ethiopia to treat and prevent MetS risk factors such as obesity, cardiovascular disease, and liver disease.

Inclusion and Exclusion Criteria.
Our inclusion criteria were as follows: (i) articles must be written in English; (ii) articles must be feld studies (surveys); (iii) studies must provide complete ethnobotanical information; and (iv) studies should include medicinal plants with antihypertensive and hepatoprotective activities. Exclusion criteria included (i) articles with no study areas or scientifc plant names, (ii) articles with only an abstract, (iii) articles written in a non-English language, (iv) newspapers, (v) reviews, and (vi) for species reported as "sp." without a species name, such as Euphorbia sp., which was not counted because other Euphorbia species were present.

Assessment of Methodological Quality.
Before being included in the review, all 54 papers were critically appraised using established procedures to ensure methodological validity [15]. Preferred Reporting of Systematic Reviews and Meta-Analysis (PRISMA) criteria were employed to ensure scientifc rigor (see selection process in Figure 1).

Data Abstraction and Review Process.
Using the inclusion/exclusion criteria, the articles underwent screening. Te following information was extracted from each study using abstraction forms: scientifc, family, plant parts used, methods of preparation and mode of action, extraction solvent utilized, models used, and efects of pharmacological medicinal plants. Te International Plant Name Index (https://www.ipni.org) and the Kew Botanical Garden plant name database (https://www.kew.org) were used to verify species names and synonyms. Data extraction was carried out twice independently, after which the datasheet was checked for methodological compliance and any errors were fxed. Te results were summarized by descriptive statistics.

Result and Discussion
3.1. Literature Search Results. Te scanning of databases yielded two hundred ffty-four (254) relevant articles, 95 of which were duplicates. After analyzing our inclusion and exclusion criteria, one hundred fve (105) articles were excluded, and the remaining ffty-four (54) articles were included ( Figure 1).

Medicinal Plants in the Management of Obesity.
According to the World Health Organization, risk factors related to being overweight or obese account for 2.8 million deaths annually, making obesity the seventh greatest cause of mortality [16]. In Africa, the overweight population of under-fves has risen by around 24% since 2000 [16]. According to a recent systematic review and meta-analysis obesity and overweight were found to be prevalent in Ethiopian cities at 22.4% and 6.2%, respectively [17]. Obesity occurs when eating a meal with a high calorifc value (carbohydrates) is combined with a decrease in physical activity to burn the calories absorbed [18]. Being overweight has been linked to a variety of comorbidities, including cardiovascular disorders (stroke and heart), type 2 diabetes mellitus, and the malignancies of breast, prostate, kidney, and colon cancer [19]. Leading a healthy lifestyle, engaging in regular physical activity, consuming less free sugars and salts, decreasing saturated fat consumption while increasing consumption of dietary vegetables and whole grains, as well as pharmacological therapies and surgical interventions, are all recommended for weight loss [20]. However, treating obesity is difcult because only 5-10% of people maintain their weight loss over time [21]. Tere is a reversal of weight loss when pharmacotherapy is stopped or a healthy lifestyle is abandoned [22]. Also, some of the synthetic drugs used have unfavorable side efects [23]. Herbal supplements are an alternative to pharmacological drugs for weight loss. Tey are efective, safe, and less expensive than pharmacological drugs. However, there is no serious attention given to obesity disease research in Ethiopia presently. In this review, we included some plants that are frequently consumed for weight loss in Ethiopia, along with their parts and preparation techniques (Table 1). Te mentioned herbal remedies have not been evaluated for their safety and efcacy in the management of obesity. Consequently, both in vitro and in vivo studies were necessary.

Medicinal Plants in the Management of Cardiovascular
Diseases. According to the World Health Organization (WHO), high blood pressure is responsible for an estimated 62% of cardiovascular diseases (CVDs) and 49 percent of ischemic heart disorders worldwide [27].
Hypertension (HTN) is a chronic medical disorder in which the blood pressure (BP) in the arteries is too high. It makes it more difcult for the heart to pump blood via the blood vessels. Hypertension afects an estimated 1.28 billion adults worldwide aged 30 to 79, with the majority (two-thirds) living in low-and middle-income nations [29]. HTN accounts for at least 45 percent of all heart disease deaths and 51 percent of all stroke deaths [30]. According to a meta-analysis of the prevalence of HTN in Ethiopia, it is on the increase, with an estimated prevalence of 19.6% [31]. In this section of the review, we looked at how medicinal plants are used in Ethiopian traditional and complementary medicine to treat liver disease. Twentytwo (22) medicinal plants from fourteen (14) families were found in this ethnobotanical review, and the traditional healer used them to treat hypertension. Te plant families with the most species are Lamiaceae (n = 4), Fabaceae (n = 2), and Polygonaceae (n = 2) ( Table 1). Analysis of the eligible ethnobotanical fndings revealed that diferent parts of the medicinal plants were utilized in the preparation of MetS remedies. Te antihypertensive medicinal 'plants' leaves (39%) and roots (13%) are the parts that are most frequently harvested ( Figure 2). Te most often cited ethnobotanical plant species for the treatment of hypertension was Moringa stenopetala (Table 2 and Figure 3). Moringa stenopetala, often known as the African Moringa or cabbage tree, is a deciduous tree native to Kenya and Ethiopia in the Moringa genus of fowering plants [54]. M. stenopetala contains alkaloids, amino acids, essential oils, fatty acids, favonoids, phenolic compounds, and sterols [55]. Some pharmacological activities of M. stenopetala have been reported in the literature including antimicrobial [56][57][58], antidiabetic [59][60][61], antitrypanosomal [62], antimalarial [63], anti-Leishmania  Evidence-Based Complementary and Alternative Medicine  Evidence-Based Complementary and Alternative Medicine [64], anti-infammatory and analgesic [65,66], antihypertensive [67], antioxidant [61,68,69], anticancer [70], and thyroid function [71]. It could be more efective than other antihypertensive medicinal plants in terms of treatment.

Antihypertensive Activity of Potential Ethiopian Medicinal Plants. Te antihypertensive properties of six (6)
Ethiopian medicinal plants from fve (10) families were investigated in Ethiopia. Male Wistar rats, guinea pigs, and Sprague-Dawley rats have all been utilized as a variety of animal models to test these herbs' potential antihypertensive efects. Blood pressure (SBP, MABP, and DBP), diuretic, natriuretic, kaliuretic, and aortic relaxation were among the parameters used to assess these plants. In all models, it was discovered that the medicinal plants had a signifcant antihypertensive efect. Four of the plant species included in (Table 2) have antihypertensive activity (Table 3), which supports their traditional uses. Tymus schimperi, Moringa stenopetala, Otostegia integrifolia, and Satureja punctata are a few examples. Te most studied plant parts were leaves, and the most extractive solvents were aqueous.

Medicinal Plants in the Management of Hepatic Diseases.
Te liver is one of the body's largest and most infuential organs. It plays an important role in a variety of physiological processes, including macronutrient metabolism, blood volume regulation, immune system support, endocrine control of growth signaling pathways, lipid homeostasis, and xenobiotic detoxifcation, including drug detoxifcation [80]. Diferent illness conditions, on the other hand, afect its structure and function. Changes in lifestyle and dietary habits, contamination of food or drink, chemical and drug addiction, and hepatic infections have all contributed to an increase in the incidence of hepatic illnesses around the world. Hepatitis, cirrhosis, fatty liver, bile duct obstruction, and jaundice are the most common hepatic diseases. Globally, they constitute the leading cause of morbidity and mortality [81]. An earlier clinical investigation in Ethiopia found that liver disease was responsible for 12% of hospital admissions and 31% of hospital mortality [82]. Since a large portion of Ethiopia's population lives in poverty and has limited access to modern healthcare, traditional medicine is used to treat liver disease. Traditional medicines used to treat liver disease are thus an important topic to address in future discussions about how to treat this problem. A variety of plant species that are utilized by traditional healers and herbalists in the treatment of liver diseases have been identifed through ethnobotanical studies. In this section of the review, we'll look at how medicinal plants are used in Ethiopian traditional and complementary medicine to treat liver disease. In this ethnobotanical review, twenty-six (26) medicinal plants from twenty-one (21) families were identifed, and the traditional healer used them to treat liver disease. Fabaceae (n � 3) and Cucurbitaceae (n � 3) are the plant families with the most species (Table 4). Tis could be since these are among Ethiopia's Flora Regions' most widely spread families [90]. Te eligible ethnobotanical data analysis revealed that diferent parts of the medicinal plants were employed to make MetS remedies. Te leaves (52%) and roots (22%) of plants used as hepatic remedies are the parts that are harvested most frequently ( Figure 4). Croton macrostachyus was the most commonly employed ethnobotanical plant species for the treatment of hepatic disorders (Table 4, Figure 5). Croton macrostachyus is a medium-sized monoecious or deciduous tree that grows up to 30 meters tall in tropical Africa [96]. C. macrostachyus fruits, leaves, stem bark, and twigs contain alkaloids, amino acids, anthraquinones, carbohydrates, cardiac glycosides, coumarins, essential oil, fatty acids, favonoids, phenolic compounds, phlorotannins, polyphenols, phytosterols, saponins, sterols, tannins, terpenoids, and unsaturated sterols [97,98]. Some pharmacological activities of C. macrostachyus have been reported in the literature including anthelmintic [99], antibacterial [100], anticonvulsant and sedative [101], antidiabetic [102], antidiarrheal [97], anti-infammatory [103], anti-Leishmania  Evidence-Based Complementary and Alternative Medicine   [50]. (b) Tymus Schimperi [51]. (c) Rumex abyssinicus [52]. (d) Foeniculum vulgare [53]. In pre-contracted isolated entire, spirally cut thoracic aortic strips of Guinea pigs, both extracts had a relaxing (vasodilatory) efect in a dose-dependent manner [75] Evidence-Based Complementary and Alternative Medicine 7  Leaves Te fresh leaf of being squeezed and one glass of juice with milk or tella is drunk for three days [88] Roots Te root bark is dried and pounded into powder and two to three spoons of powder are added to a cup containing water. Treatment is taken for 21 days [43] Barks Dry bark is powdered and mixed with latex from its young twinges and applied to the wound [89] Leaves Leaf powder mixed with water is taken orally for seven days [27] 8 Evidence-Based Complementary and Alternative Medicine Leaf with roots of Asparagus sp. pounded and homogenized in water and given to the patient orally for three consecutive days. Half a glass is the limit for a day [90] Cofee Arabica Rubiaceae Buna Barks Te bark of C. africana is powdered together with the stem bark of Croton macrostachyus, the paste is then boiled with milk and given orally [91] Dodonaea angustifolia Sapindaceae Kitkita Leaves A fst of the leaf is grounded to get half a cup of juice, which is given orally in the morning and evening until the cure [91] Verbascum sinaiticum Scrophulariaceae Kutitina Roots Te fresh root is crushed, mixed with water, fltered, and drunk [88] Vitis vinifera Vitaceae Weyne Leaves Grinding the leave with Ficus carica leave separately; mix them with honey then drink 3 times a day by tea glass [92] Zehneria scabra Cucurbitaceae Hareg Resa Leaves Te fresh leaf is pounded and squeezed and then drunk in half a cup of tea [34] Leaves 52%

Roots 22%
Stems 3% Barks 10% Fruits 3% Seeds 10%  [93]. (b) Cucumis fcifolius [94]. (c) Acokanthera schimperi [95]. structural integrity was only marginally protected; however, at 500 mg/kg, there was no ballooning and a signifcant level of protection Te levels of ALP, ALT, and AST were lower than those in mice that had been CCl4-induced. Especially in terms of preserving ALT and AST levels, the percentage of hepatoprotective activity at 500 mg/kg was comparable to the standard drug silymarin at 100 mg/kg 5000 [118] 10 Evidence-Based Complementary and Alternative Medicine [104], antioxidant [105], and antimalarial [106]. It could be more efective than other antihepatic medicinal plants in terms of treatment.

Hepatoprotective Activity of Potential Ethiopian Medicinal Plants.
Te hepatoprotective activity of sixteen (16) Ethiopian medicinal plants from ten (10) families was investigated in Ethiopia. Tese plants have been scientifcally tested for hepatotoxicity using a variety of experimental models, including CCl 4 and paracetamol. Several parameters, including liver markers (AST, ALT, ALP, total protein, albumin, and bilirubin) and histopathological examination, were used to evaluate these plants. In animal models, all of the medicinal herbs were revealed to have a signifcant hepatoprotective efect. Some of the plant species listed in Table 5 have hepatoprotective activity, which supports the traditional uses listed in Table 4. Tese include Verbascum sinaiticum, Croton macrostachyus, Cucumis fcifolius, Justicia shimperans, Phytolacca dodecandra, Treminalia brownie, and Rumex abyssinicus. Although more polar solvents such as water, methanol, and ethanol are frequently recommended for use only in traditional preparations [119]. Signifcantly, the majority of the plant species studied had hepatoprotective efcacy that matched high-polarity (methanol) plant extracts in most studies. Tis is advantageous because it permits therapeutic components to absorb through the gut lumen into the circulatory system, where they are needed, according to Lipinski's rules of 5 [120]. As a result, active compounds interact with cell surface receptors, and polar components ofer in vivo potency that is therapeutically meaningful. In oral acute toxicity tests, the majority of the test extracts exhibited LD 50 values greater than or equivalent to 2000 mg/kg, which would account for the plant's safe folkloric use.

Conclusion
Noncommunicable diseases, as well as MetS risk factors, add signifcantly to Ethiopia's healthcare burden. Ethiopia has a diverse plant biodiversity with ethnobotanically and scientifcally confrmed therapeutic characteristics that can and should be used to reduce the cost of providing health care. Te gut microbiota's function in metabolic disorders has gotten a lot of attention recently. A large variety of plants used by indigenous people to treat various disorders, including MetS (obesity, hypertension, and hepatic problems), have been described as a result of numerous ethnobotanical investigations conducted in Ethiopia. Moringa stenopetala and Croton macrostachyus were the most commonly employed ethnobotanical plant species for the treatment of hypertension and liver diseases. Leaves were utilized as a therapeutic preparation more frequently than other parts. Te antihypertensive and hepatoprotective properties of the species studied are discussed. Some ethnobotanical studies of medicinal plants investigated their antihypertensive and hepatoprotective properties, and they found some good results. Moringa stenopetala is the most commonly studied medicinal plant for its antihypertensive properties. Tis indicates that plants have traditionally been used to treat hypertension and liver disorders. However, there was no evidence of further study into the efcacy of some plant species that have been identifed as having antihypertensive and hepatoprotective properties. More studies are needed to identify active compounds and develop successful novel drugs for the treatment of MetS.

Data Availability
All data generated or analyzed during this study are included in this published article.

Conflicts of Interest
Te authors declare that they have no conficts of interest.