**4. Preclinical, In Vivo, and Clinical Studies on Ethiopian Anticancer Plants**

Preclinical studies generate data on the efficacy, safety, and pharmacokinetic properties of lead compounds, which will later be used to select better molecules for clinical trials. Assessment of the findings of preclinical in vivo animal studies supports the traditional use of plants to manage cancer in Ethiopia (Table 6). Despite the preclinical efficacy data, there are no clinically significant anticancer agents isolated from traditionally used Ethiopian plants. Moreover, there are also no clinical trials conducted on anticancer plants that are collected from Ethiopia. Among reviewed phytochemicals only ursolic acid, secoisolariciresinol (**52**), and colchicines (**41**), isolated from plants collected elsewhere, were considered further for clinical trial.


**6.**Animalefficacystudies,clinicaltrials,and/orclinicallyapprovedagentsEthiopiananticancer


**Table 6.** *Cont.*

#### **5. Conclusions**

Despite the traditional use of various Ethiopian plants for the treatment of cancer by herbal medicine practitioners for many decades, only a few active anticancer crude extracts, herbal preparations, and pure compounds were tested and so far no clinical trial was conducted on them. In this review, an attempt has been made to document antiproliferative, antitumor, and cytotoxic natural products small molecules isolated from medicinal plants that are traditionally used to treat cancer in Ethiopia. However, among the reported active compounds, only few have been isolated from plants that are originated and collected from Ethiopian geographic location, despite their wider presence and traditional claim at home. The majority of compounds reported in this review are isolated from plants (corresponding to Ethiopian species) that were collected from different regions of the world. However, the comprehensive list of active compounds (IC50 and ED50 values) provided in this review will help to identify the most potent source(s) of these compounds, as bioactive marker(s), of local flora. Based on the higher frequency of citation *Croton macrostachyus*, *Jatropha curcas*, *Plumbago zeylanica*, and *Vernonia hymenolepsis* are potential candidates for follow-up bioassay guided investigations. Furthermore, plants with reported antiproliferative compounds such as *Podocarpus falcatus*, *Linum usitatissimum*, and *Zehneria scabra* should also be examined for additional cytotoxic compounds and evaluated against a battery of cancer cell lines.

Generally, the ecological variation has a huge impact on the biosynthesis, yield of active constituent and biological potency of secondary metabolites produced by plants of similar species from different geographical regions. Thus, Ethiopian anticancer plants might have novel active constituents to fight cancer, based on traditional medical use, than those collected from other regions due to their unique geographical location and inherent climatic condition of the diverse landscape. Unfortunately, these valuable plant resources are disappearing rapidly due to climate change, rapid urbanization, agricultural land expansion, and artificial deforestation; therefore, Ethiopian flora is facing a great challenge, and thus it is high time to examine the anticancer plants systematically with the aim to carry out chemical and biological invesigations, as well as clinical trials on promising anticancer plant extracts based on ethnopharmacological knowledge.

**Author Contributions:** I.M., K.A., S.T. and E.L.; developed the concept, analyzed the data, and wrote the manuscript. Y.A., M.K. and E.T.; performed the literature searches, and contributed to draft the manuscript. All authors have read and agreed to the published version of this manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** M.K. and I.M. would like to thanks NCNPR, University of Mississippi, for technical support in preparing the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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