Maroyi Tropical Journal of Pharmaceutical Research March 2019; 18 (3): 669-676 ISSN: 1596-5996 (print); 1596-9827 (electronic) © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. Available online at http://www.tjpr.org http://dx.doi.org/10.4314/tjpr.v18i3.30 Review Article Medicinal uses, phytochemistry, pharmacology and toxicological properties of Elaeodendron croceum Alfred Maroyi Medicinal Plants and Economic Development (MPED) Research Centre, Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa *For correspondence: Email: [email protected]; Tel: +27-719600326 Sent for review: 16 November 2018 Revised accepted: 24 February 2019 Abstract Elaeodendron croceum is a shrub or a small tree used as an emetic, purgative and herbal medicine for cough, sore throat, fever, tuberculosis, blood in sputum, chest congestion, human immunodeficiency virus (HIV) opportunistic infections and to clean the digestive tract. Phytochemical compounds identified from the species include alkaloids, cardiac glucoside, flavonoids, phenols, proanthocyanidins, saponins, sugars, tannins and triterpenoids. Pharmacological studies revealed that E. croceum extracts and compounds have antimycobacterial, anti-arthritic, antibacterial, anti-HIV, antioxidant, anti-inflammatory, antifungal and cytotoxicity activities. Future studies should focus on ethnopharmacological safety and efficacy of E. croceum extracts and compounds isolated from the species using in vivo preclinical studies and clinical trials. Keywords: Celastraceae, Elaeodendron croceum, Herbal medicine, Southern Africa, Traditional medicine This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus, International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, Directory of Open Access Journals (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts INTRODUCTION scarce in KwaZulu Natal province in South Africa based on the information provided by traditional Elaeodendron croceum (Thunb.) DC. is a shrub healers [3-5]. The could be as a result of over- or a small evergreen tree species which belongs collection as the species is widely sold in to the Celastraceae family. The species is informal herbal medicine markets in both rural commonly referred to as forest saffron, saffron or and urban areas of Gauteng [6] and KwaZulu wood saffron. E. croceum has in the past Natal provinces in South Africa [4]. Over- classified under several scientific names such as collection of wild populations of E. croceum as a Cassine crocea (Thunb.) Kuntze, C. papillosa source for medicinal plant trade and other (Hochst.) Kuntze, Crocoxylon croceum Thunb. N. anthropogenic activities such as habitat Robson, C. excelsum Eckl. & Zeyh., E. capense destruction and land clearing for agricultural Eckl. & Zeyh., Salacia zeyheri Planch. ex Harv., purposes have caused a severe reduction in the Ilex crocea Thunb., E. croceum Thunb. DC. and population size of the species [7]. E. croceum is E. papillosum Hochst. [1,2]. E. croceum is among regarded as Least Concern on the IUCN Red List the top 15 medicinal plants that are becoming of Threatened Species [8] but due to local ----------------------------------------------------------------------------------------------------Trop -------------------------J Pharm Res, March------------------------ 2019; 18(3):669 © 2019 The author. This work is licensed under the Creative Commons Attribution 4.0 International License Maroyi conservation concern in South Africa as the margins and along the escarpment, mainly on population of the species is declining, the seepage zones. The main stem is red-brown to species has been flagged as declining following grey in colour and may have some dark lenticels recommendations made by Williams et al [9], when young characterized by pale grey and thin Von Staden et al [10] and Victor and Keith [11]. It bark, peeling off to reveal bright orange and is against this background that the medicinal yellow under-bark [13]. The leaves are opposite uses, phytochemistry, pharmacology and to sub-opposite in arrangement and oblong to toxicological properties of E. croceum were elliptic in shape. The apex and base of the reviewed. leaves is broadly tapering, leaf margins are strongly serrated and sometimes spined. The METHODS leaves are glossy green above and little paler below with prominent venation on both sides. Data on medicinal uses, botany, phytochemistry, The flowers are small, whitish or pale green in pharmacological and toxicological properties of colour, occurring axillary clusters. The fruits are E. croceum were collected from multiple internet fleshy, ovoid in shape and creamy to yellowish in sources including Science Direct, SciFinder, colour [14]. The species has been recorded in Pubmed, BMC, Elsevier, Google Scholar, Mozambique, South Africa, Swaziland, Scopus and Web of Science. Complementary Zimbabwe and naturalized in St Helena [1,14]. information was gathered from pre-electronic sources such as books, book chapters, theses, scientific reports and journal articles obtained from the University library. The search for this information was carried out between May 2017 to August 2018. The keywords used in the search included “ethnobotany”, “ethnomedicinal uses”, “medicinal uses”, “phytochemistry”, “biological activities”, “pharmacological properties”, “toxicological properties”, “Elaeodendron croceum”, the synonym of the species and the English common names “forest saffron”, “saffron” or “wood saffron”. The internet search generated Figure 1: E. croceum branch showing a fruit and 562 articles in total. After duplicate articles and leaves (photo: D Becking) those with limited raw data were excluded, 36 articles were included in this study. These E. croceum bark is used as an emetic and articles included 21 journal articles, books (nine), purgative [15,16] as herbal medicine against scientific report (three), websites (two) and a human immunodeficiency virus (HIV) single book chapter. opportunistic infections [17]. The bark is also traditionally used to treat and manage FINDINGS AND DISCUSSION tuberculosis [18] and other related diseases such as blood in sputum [18], chest congestion Botanical profile and medicinal uses of E. [12,16,19-21], cough [18] and sore throat [16]. croceum The bark is used to manage and treat fever [18] and bark, roots and leaves of the species as E. croceum (Figure 1) grows up to a height of 15 herbal medicine to clean the digestive tract metres with a trunk diameter of 250 mm [12]. The [12,16,19-21]. species has been recorded in montane forest Table 1: Medicinal uses of E. croceum Medicinal use P[ant part(s) used Country Reference(s) Blood in sputum Bark infusion taken orally South Africa [18] Chest congestion Bark infusion taken orally South Africa [12,16,19-21] Clean digestive tract Bark, leaf and root infusion taken orally South Africa [12,16,19-21] Cough Bark decoction taken orally South Africa [18] Emetic Bark infusion taken orally Swaziland [15] Fever Bark decoction taken orally South Africa [18] HIV Bark decoction taken orally South Africa [17] Purgative Bark infusion taken orally South Africa [16] Sore throat Bark decoction taken orally South Africa [16] Tuberculosis Bark infusion taken orally South Africa [18] Trop J Pharm Res, March 2019; 18(3):670 Maroyi Phytochemistry and pharmacological epitingenone and tingenone against three human properties of E. croceum cancer cell lines, HeLa, MCF-7, and SNO showed IC50 values ranging between 2.5 µM to Reports on the phytochemical screening of E. 0.4 µM [21]. croceum leaf, root and stem bark extracts revealed the presence of alkaloids, flavonoids, phenols, proanthocyanidins, saponins and tannins [22,23]. Drewes and Mashimbye [24] isolated flavonoids, sugar and triterpenoids and these compounds included (+)-6R,13R-11,11- (+)-6R,13R-11,11-dimethyl- (-)-4’-0-methoxyepiga- dimethyl-1,3,8,10-tetrahydroxy-9-methoxy- 1,3,8,10-tetrahydroxy-9- llocatechin peltogynan, (-)-4’-0-methoxyepigallocatechin, methoxy-peltogynan ouratea proanthocyanidin A, galactitol, tingenone, tingenin B, canophyllol, 3- hydroxyIupeol and 30-hydroxylup 20(29)-en-3- one from the stem bark of E. croceum (Figure 2). Prinsloo et al [20] isolated a cardiac glucoside, digitoxigenin-glucoside from E. croceum bark extracts (Figure 2). Yelani et al [21] isolated triterpenoids such as 20-hydroxy-20- epitingenone, tingenone, tingenine B, 11α- Ouratea proanthocyanidin A Galactitol hydroxy-β-amyrin and naringenin from the leaves of E. croceum (Figure 2). Prinsloo et al [20] evaluated anti-HIV activities of the compound digitoxigenin-glucoside isolated from E. croceum extracts by assessing the inhibition of recombinant HIV strain in an MT-2 VSV-pseudotyped recombinant virus assay. The Tingenone Tingenin B compound showed significant inhibition of 90% at 0.2 µM [20]. Prinsloo et al [20,25] evaluated the cytotoxicity