Antioxidant Potential of Ethiopian Medicinal Plants and Their Phytochemicals: A Review of Pharmacological Evaluation

Background Free radicals are very reactive molecules produced during oxidation events that in turn initiate a chain reaction resulting in cellular damage. Many degenerative diseases in humans, including cancer and central nervous system damage, are caused by free radicals. Scientific evidence indicates that active compounds from natural products can protect cells from free radical damage. As a result, the aim of this review is to provide evidence of the use of diverse Ethiopian medicinal plants with antioxidant properties that have been scientifically validated in order to draw attention and foster further investigations in this area. Methods The keywords antioxidant, radical scavenging activities, reactive oxygen species, natural product, Ethiopian Medicinal plants, and 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH) were used to identify relevant data in the major electronic scientific databases, including Google Scholar, ScienceDirect, PubMed, Medline, and Science domain. All articles with descriptions that were accessed until November 2022 were included in the search strategy. Results A total of 54 plant species from 33 families were identified, along with 46 compounds isolated. More scientific studies have been conducted on plant species from the Brassicaceae (19%), Asphodelaceae (12%), and Asteraceae (12%) families. The most used solvent and extraction method for plant samples are methanol (68%) and maceration (88%). The most examined plant parts were the leaves (42%). Plant extracts (56%) as well as isolated compounds (61%) exhibited significant antioxidant potential. The most effective plant extracts from Ethiopian flora were Bersama abyssinica, Solanecio gigas, Echinops kebericho, Verbascum sinaiticum, Apium leptophyllum, and Crinum abyssinicum. The best oxidative phytochemicals were Rutin (7), Flavan-3-ol-7-O-glucoside (8), Myricitrin (13), Myricetin-3-O-arabinopyranoside (14), 7-O-Methylaloeresin A (15), 3-Hydroxyisoagatholactone (17), β-Sitosterol-3-O-β-D-glucoside (22), Microdontin A/B (24), and Caffeic acid (39). Conclusion Many crude extracts and compounds exhibited significant antioxidant activity, making them excellent candidates for the development of novel drugs. However, there is a paucity of research into the mechanisms of action as well as clinical evidence supporting some of these isolated compounds. To fully authenticate and then commercialize, further investigation and systematic analysis of these antioxidant-rich species are required.


Introduction
Te generation of reactive oxygen species (ROS) and other free radicals during metabolism is a natural activity that is adequately compensated for by an elaborate endogenous antioxidant defense mechanism [1].Oxidative stress results from the overproduction of free radicals and an imbalance in their elimination.In diseases including cancer, cardiovascular disease, infammatory disease, and cataract development, oxidative damage at the cellular or subcellular level is now considered a major event.Reactive oxygen radicals exert an adverse efect on cells due to their ability to promote lipid peroxidation in cellular membranes, which results in lipid peroxides that severely damage membranes and cause chromosomal damage through membrane contact [2,3].Hydrogen peroxide, superoxide anion, and hydroxyl radicals are examples of oxygen free radicals that have been linked to the development of several pathological disorders, including diabetes, atherosclerosis, ischemia, and infammatory diseases.In many cases, the frst stage of these disorders is endothelial cell damage.Tese oxidants can be immediately scavenged by the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), which are present intracellular or released into the extracellular milieu.Tey can also prevent these oxidants from becoming toxic species.It is well known that ROS and reactive metabolic intermediates produced by diferent chemical carcinogens play a signifcant role in cell damage as well as the beginning and development of carcinogenesis.In recent decades, there has been a growing understanding of the connection between nutrition and chronic diseases, particularly cancer and cardiovascular disorders.Many degenerative diseases, including cancer, cataract, type 2 diabetes, neurological diseases, cardiovascular diseases, and infammatory diseases, as well as the natural aging process, are now thought to be primarily caused by oxidative stress.Consequently, there is currently a lot of interest in the potential role of natural antioxidants in delaying or suppressing oxidative stress [4,5].Exogenous antioxidants need to be consumed or taken as supplements to maintain the body's endogenous antioxidant system.It has been appreciated that both nutrient and non-nutrient-rich diet components have antioxidant capabilities and consequent potential benefts.Tere has been a growing interest in natural antioxidants found abundantly in plants [6,7].Since the dawn of human civilization, medicinal plants have been identifed and customarily used throughout the world [8,9].
Medicinal plants are a rich source of novel drugs that form the ingredients in traditional systems of medicine [10,11].Most developing countries rely on traditional medicinal plants for their healthcare.Terefore, it should come as no surprise that some of these plants contain chemical compounds that have therapeutic potential and could be utilized to treat serious diseases like malaria, cancer, and pathogenic microbes [12].According to studies, more than 80% of Ethiopians use plant-based traditional medicine as their primary healthcare system.Tis high adoption rate can be largely ascribed to the fact that it draws on locally accessible wild plant resources [13,14].Tis is in part because the vast majority of rural residents cannot access modern medical services because of their high cost, lack of transportation, and scarcity of healthcare centers [15].However, the limited number of medicinal plants has been the focus of the available reviews on the antioxidant potential of Ethiopian natural products [16].In spite of this, there is a paucity of comprehensive ethnopharmacological research review on Ethiopian antioxidant medicinal herbs.Tis review examined the phytochemistry of the plants used in traditional Ethiopian medicine as well as numerous investigations that have been done to scientifcally validate their antioxidant potential.Tis evaluation may pave the way for additional complementary studies as well as the development of some readily available and afordable antioxidant phytomedicines, in line with the objectives of the WHO's "Traditional Medicine Strategy" [17].

Methodology
Tis review was compiled from various databases, including Google Scholar, ScienceDirect, PubMed, Medline, and Science domain from September 2022 to November 2022, to identify natural products from Ethiopian fora and fauna with antioxidant potential.Each database search was done independently.Until November 2022, original studies about antioxidant plants that were published in peerreviewed journals were included in the study databases.Te keywords antioxidant, radical scavenging activities, antiaging principles, reactive oxygen species, free radicals, natural product, 2, 2-Diphenyl-1-picrylhydrazyl radical scavenging assay (DPPH), and reducing properties were used to identify relevant data.All valuable data previously published in English have been gathered.Te reviewers found relevant articles and gathered the following information from them: plant species, plant family, parts of the plant used, extraction methods, extraction solvent, IC 50 values, and isolated compounds.

Categorization of Antioxidant Activities.
For evaluating the in vitro antioxidant potencies of natural compounds and extracts, many techniques have been developed.Tese techniques are based on two important chemical processes: electron transfer reactions and hydrogen atom reactions.Electron transfer reactions are used to measure the following parameters to determine the antioxidant potencies of extracts and compounds using hydrogen atom transfer mechanisms: ferric reducing antioxidant power (FRAP), diphenyl-2-picryl-hydroxyl radical scavenging assay (DPPH), Trolox equivalent antioxidant capacity (TEAC), hydroxyl radical scavenging assay, superoxide anion radical scavenging assay, and nitric oxide radical scavenging [18].Despite the recent increase in interest in antioxidant studies, it has been difcult to evaluate research fndings from various research groups due to a lack of standardized assays [19].To increase the reliability of the antioxidant results, more than one protocol was used, and the antioxidant potencies of natural products reviewed in this study were classifed into three groups based on previous studies: high or signifcant antioxidant capacity with IC 50 < 50 μg/mL (extract) or IC 50 < 10 μg/mL (compounds), moderate antioxidant capacity with 50 < IC 50 < 100 μg/mL (extract) or 10 < IC 50 < 20 μg/mL (compounds), and low antioxidant capacity with IC 50 > 100 μg/mL (extract) or IC 50 > 20 μg/mL (compounds) [16,20].All activity data were converted to IC 50 values in μg/mL.

2
Evidence-Based Complementary and Alternative Medicine

Promising Antioxidant Medicinal
Plants from the Ethiopian Flora.Te in vitro antioxidant activities of extracts from 54 plant species from 33 plant families were identifed .Table 1 provides a summary of the plant species that were tested, their family, the portions of the plants that were utilized to generate the test samples, the solvent used during the extraction process, the assay methods, and their potencies based on the categorization/protocol used.Tis shows that Ethiopia has a diverse fora and that numerous people use several plant species for medicinal purposes [59].Asteraceae 6 (19%), Brassicaceae 4 (12%), and Asphodelaceae 4 (12%) are the three plant families with the greatest antioxidant activity studied in Ethiopia (Figure 1 and Table 1).
Te aforementioned family, which can be found in every foristic region of the country, may be the subject of this account [60].Leaves 24 (42%) and roots 15 (26%) are the most investigated parts (Figure 2).Tis study indicates that using leaves for studies is crucial for medicinal plant conservation since, unlike with roots or whole plant collections, leaf harvesting may not be harmful to plants [61,62].
Maceration (88%) is one of the most used plant sample extraction methods.Perhaps this is because solvent extraction, or more specifcally, maceration, is one of the most popular and straightforward techniques for isolating plant antioxidants [63,64].Methanol is the most popular extraction solvent, although more polar solvents such as water and ethanol are frequently recommended in traditional preparations [65].Surprisingly, in most studies, methanol (68%) plant extracts correlated with the antioxidant activity of the plant species studied.Tis is advantageous because it permits medicinal substances to absorb through the stomach lumen into the circulatory system, where they are required, following Lipinski's rules of 5 [66].Terefore, active substances function through cell surface receptors, with polar components ofering therapeutically signifcant potency in vivo.Te antioxidant potential of plant extracts from 30 plants was signifcant (56%) (IC 50 < 50 μg/mL).Te antioxidant activity of eight plant extracts was moderate (15%), with IC 50 values ranging from 50 to 100 μg/mL.With IC 50 values greater than 100 μg/mL, 14 plant extracts showed low (26%) antioxidant activities, whereas two plant extracts exhibited both signifcant and moderate (2%) antioxidant activities.Tis implies that Ethiopian medicinal herbs were found to have strong antioxidant properties, indicating that, if thoroughly examined, they might produce valuable pharmaceutical drugs for the treatment of oxidative stress disease.

Promising Antioxidant Phytochemicals Derived from the
Ethiopian Flora.More than 40 compounds from diferent chemical classes have so far been found in Ethiopian medicinal plants.Flavonoids 15 (32%), terpenoids 7 (15%), and organic acids 7 (15%) are the main components isolated from diverse plant species (Figure 3 and Table 2).Serial extraction, bioassayguided extraction, successive fractionation using various polarity solvents, and column chromatography are the techniques used to isolate novel compounds for the plants of the species.Te rising interest in using traditional medicine as an alternative and complementary therapy is encouraging activity-guided bioactive compound isolation to gain attention at the moment [70].
3.2.5.Alkaloids.Alkaloids are secondary metabolites that were frst described as pharmacologically active molecules largely made of nitrogen [89].Evidence-Based Complementary and Alternative Medicine  Evidence-Based Complementary and Alternative Medicine Evidence-Based Complementary and Alternative Medicine [89].Te mechanism of action of alkaloids' antioxidant properties is demonstrated in Figure 5     Evidence-Based Complementary and Alternative Medicine agent for treating a variety of diseases [92][93][94].Te antioxidant compound mangiferin (42), which was isolated from the leaves of Bersama abyssinica, had a signifcant antioxidant activity with an IC 50 value of 6.72 μg/mL [38].

Conclusion and Future Prospects
Oxidative stress results from an excessive free radical formation that is out of balance with the elimination of those radicals.Oxidative stress has been linked to the etiology of cancer, infammatory diseases, cardiovascular disease, and other serious diseases.Antioxidants are substances that impede oxidative processes, prolonging or suppressing oxidative stress in the process.Natural antioxidants that are present in plants are gaining popularity.From a safety perspective, herbs and spices are the most crucial objectives when looking for natural antioxidants.Strong antioxidant, anti-infammatory, antimutagenic, and cancer-preventive properties are shared by a wide range of phenolic compounds found in spices that are frequently employed as food additives.Te current review provides a summary of  (39).It is hoped that competent researchers and interested individuals will investigate some of these plants and compounds further to provide a thorough verifcation and subsequently facilitate commercialization.Te detailed isolation, characterization, mechanisms of action, safety investigations, quality control, and clinical trials on some of these herbs and their isolated compounds are far from satisfactory, although the majority of the studies examined are preliminary.Terefore, further in vivo studies on these species are needed, as well as a systematic analysis of these antioxidant-rich species.

Data Availability
Te data used in this study are included within the article.Evidence-Based Complementary and Alternative Medicine

Table 1 :
Antioxidant potential of plant extracts from Ethiopian fora.

Table 2 :
Antioxidant compounds isolated from Ethiopian fora.