Alfred Maroyi /J. Pharm. Sci. & Res. Vol. 11(10), 2019, 3491-3496 A review of botany, medicinal uses, phytochemistry and biological activities of Cotyledon orbiculata Alfred Maroyi Department of Biodiversity, University of Limpopo, Private Bag X1106, Sovenga 0727, South Africa. Abstract Cotyledon orbiculata is a succulent shrub widely used as herbal medicine throughout its distributional range in southern Africa. This study is aimed at providing a critical review of the botany, biological activities, phytochemistry and medicinal uses of C. orbiculata. Documented information on the botany, biological activities, medicinal uses and phytochemistry of C. orbiculata was collected from several online sources which included BMC, Scopus, SciFinder, Google Scholar, Science Direct, Elsevier, Pubmed and Web of Science. Additional information on the botany, biological activities, phytochemistry and medicinal uses of C. orbiculata was obtained from pre-electronic sources such as book chapters, books, journal articles and scientific publications sourced from the University library. This study showed that the leaves, leaf sap and roots of C. orbiculata are mainly used as herbal medicines for earache, epilepsy, infertility, respiratory problems, sexually transmitted infections, skin problems, sores and wounds, toothache, ulcers and worms. Phytochemical compounds identified from C. orbiculata include cardiac glycosides, flavonoids, gallotannin, phenols, reducing sugar, saponins, tannins and triterpene steroids. Pharmacological research revealed that C. orbiculata extracts have anthelmintic, antibacterial, antifungal, anticancer, anticonvulsant, antinociceptive, anti-inflammatory, Aβ42 protein reduction, GABAA benzodiazepine receptor- binding, antioxidant and cytotoxicity activities. Future research should focus on evaluating the phytochemical, pharmacological and toxicological properties of C. orbiculata crude extracts as well as compounds isolated from the species. Keywords: Cotyledon orbiculata, Crassulaceae, ethnopharmacology, herbal medicine, indigenous pharmacopeia INTRODUCTION Botanical profile of Cotyledon orbiculata Cotyledon orbiculata L. is a succulent shrub belonging to The genus name “Cotyledon” is derived from the Greek the Crassulaceae or stonecrop or orphine family. word “kotyledon” which means “cup-shaped hollow” in Cotyledon orbiculata is an important ornamental plant reference to the leaves of some species of the genus.16 The throughout the world.1-6 Cotyledon orbiculata is listed as a species name “orbiculata” is derived from the Latin word weed in the global collection of weeds by Randall7 and the meaning “round” or “circular” in reference to the shape of species is naturalized and categorized as an invasive the segments. The English common names of the species species in Australia, California, New Zealand, Portugal include “cotyledon”, “pig’s ear” and “round-leafed navel- and Spain.4-8 In Portugal and Spain, C. orbiculata has wort”. Cotyledon orbiculata is a complex species, divided escaped from gardens and occurs on slopes where it into five varieties, namely, C. orbiculata var. dactylopsis reproduces both sexually and vegetatively.4.5,8 In Tölken, C. orbiculata var. flanaganii (Schönland & Baker Australia, California and New Zealand, C. orbiculata f.) Tölken, C. orbiculata var. oblonga (Haw.) DC., C. is well-established on rocks in coastal areas and spreading orbiculata var. orbiculata and C. orbiculata var. spuria in coastal sage scrub and bushland, and invading natural (L.) Tölken.17 These varieties are separated based on and semi-natural habitats as well as managed afforested differences in leaf and flower shape, shape and size of the areas and maritime protected areas.6 In South Africa, C. corolla tube and their geographical distribution patterns.17 orbiculata is managed in home gardens in the Limpopo Cotyledon orbiculata var. flanaganii is categorized as and North-West provinces as an ornamental plant and Near Threatened in South Africa,18 this is a poorly known source of traditional medicines.9-13 The leaves of C. taxon likely to occur in less than 10 locations in the orbiculata are sold as herbal medicines in the informal country and potentially threatened by overgrazing and herbal medicine markets in the Eastern, Gauteng and trampling by livestock.19 Cotyledon orbiculata is a Western Cape provinces of South Africa.14,15 Moreover, C. succulent shrub with woody branches, thick and fleshy orbiculata is one of the valuable medicinal plant species in leaves which may vary from green to grey in colour, often South Africa, and the species is included in the book with a red line around the leaf margins and covered with a “medicinal plants of South Africa,” a photographic guide waxy layer on the surface.2,16 The leaves are obovate to to the most commonly used traditional medicines in the narrowly ovoid in shape. The flowers are yellow to country, including its botany, major medicinal applications orange-red in colour, usually hanging, tubular and bell- and active phytochemical compounds.2 It is within this shaped, carried in clusters on the ends of an elongated context that this review was undertaken aimed at flower stalk. Cotyledon orbiculata has been recorded in reviewing the botany, medicinal uses, phytochemistry and Angola, Lesotho, Mozambique, Namibia, South Africa biological activities of C. orbiculata so as to provide and Swaziland in sandy or in rocky soils or rocky outcrops baseline data required in evaluating the therapeutic in depressions, river banks, grassland, scrub, fynbos and potential of the species. karoo biomes at an altitude ranging from 50 m to 3000 m above sea level.16,17,20-26 3491 Alfred Maroyi /J. Pharm. Sci. & Res. Vol. 11(10), 2019, 3491-3496 Medicinal uses of Cotyledon orbiculata with those of Commelina africana L. as traditional Leaves, leaf sap and roots of C. orbiculata are mainly used medicine for female infertility in Lesotho.27,28 In Lesotho, as traditional medicines for earache, epilepsy, infertility, the leaves of C. orbiculata are mixed with those of respiratory problems, sexually transmitted infections, skin Senecio asperulus DC. as traditional medicines for sore problems, sores and wounds, toothache, ulcers and worms throat and ulcers.27 (Table 1, Figure 1). The roots of C. orbiculata are mixed Table 1: Medicinal uses of Cotyledon orbiculata Medicinal use Parts used Country References Aching feet Roots South Africa Mogale et al.15 Diarrhoea Leaves and roots South Africa Masafu et al.29; Van Wyk et al.2; Duarte et al.3; Harris16; Moteetee and Van Wyk27; Lum30; James31; Jacot Guillarmod32; Schmitz33; Bhat and Jacobs34; Hutchings et al.35; Thring and Weitz36; Amabeoku et Leostho and 37 38 39 40 Earache Leaf sap al. ; Van Wyk and Gericke ; Van Wyk ; Aremu et al. ; South Africa Moffett41; De Beer and Van Wyk42; Amabeoku and Kabatende43; Ndhlala et al.44; Wintola and Afolayan45; Kumari et al.46; Terblanche et al.47; Hulley and Van Wyk48; Moteetee et al.49; Ondua et al.50 Van Wyk et al.2; Duarte et al.3; Harris16; Lum30; Hutchings et al.35; Thring and Weitz36; Amabeoku et al.37; Van Wyk and Epilepsy Leaf sap South Africa Gericke38; Van Wyk39; Amabeoku and Kabatende43; Ndhlala et al.44; Kumari et al.46; Terblanche et al.47; Watt51; Sobiecki52; Stafford et al.53; Philander54; Masondo et al.55; Thakur et al.56 Eye problems Leaves Lesotho Dyubeni and Buwa57 Fractures and sprains Leaf sap South Africa Thring and Weitz36 Haemorrhoids Leaves South Africa Hulley and Van Wyk48 Roots mixed with Infertility those of Commelina Lesotho Moteetee and Van Wyk27; Moteetee and Kose28 africana L. Insect bite Leaf sap Lesotho Moteetee and Van Wyk27 Respiratory problems South Africa 15 38 39 58 Leaf sap and roots Mogale et al. ; Van Wyk and Gericke ; Van Wyk ; Long (flu and sore throat) and Swaziland Leaves mixed with Sore throat those of Senecio Lesotho Moteetee and Van Wyk27; asperulus DC. Sexually transmitted Mogale et al.15; Masafu et al.29; Lum30; Hutchings et al.35; Thring infections (gonorrhoea, Leaves, leaf sap and and Weitz36; Kumari et al.46; Terblanche et al.47; Watt and South Africa syphilis and venereal roots Breyer-Brandwijk59; Erasmus et al.60; Semenya et al.61; Semenya diseases) et al.62 Van Wyk et al.2; Duarte et al.3; Maroyi and Mosina11; Harris16; Moteetee and Van Wyk27; Lum30; James31; Bhat and Jacobs34; Hutchings et al.35; Thring and Weitz36; Amabeoku et al.37; Van Skin problems Wyk and Gericke38; Van Wyk39; Aremu et al.40; De Beer and Van Lesotho, South (abscesses, boils, burns, Wyk42; Amabeoku and Kabatende43; Ndhlala et al.44; Wintola and Leaves and leaf sap Africa and 45 46 47 corns, inflammation, Afolayan ; Kumari et al. ; Terblanche et al. ; Hulley and Van Swaziland rash and warts) Wyk48; Philander54; Long58; Watt and Breyer-Brandwijk59; Felhaber63; Mabona and Van Vuuren64; Mabona et al.65; Nortje and Van Wyk66; Xaba and Buwa67; Moteetee and Kose68; Adebayo and Amoo69; Sagbo and Mbeng70 Thring and Weitz36; De Beer and Van Wyk42; Hulley and Van Sores and wounds Leaves and leaf sap South Africa 48 66 Wyk ; Nortje and Van Wyk Van Wyk et al.2; Duarte et al.3; Harris16; Moteetee and Van Wyk27; Lum30; James31; Hutchings et al.35; Thring and Weitz36; Amabeoku et al.37; Van Wyk and Gericke38; De Beer and Van Toothache Leaf sap South Africa 42 43 44 Wyk ; Amabeoku and Kabatende ; Ndhlala et al. ; Wintola and Afolayan45; Kumari et al.46; Terblanche et al.47; Hulley and Van Wyk48; Ondua et al.50; Philander54; Akhalwaya et al.71 Lesotho and Moteetee and Van Wyk27; Nortje and Van Wyk66; Moteetee and Ulcers and mouth ulcers Leaves 68 South Africa Kose Leaves mixed with Ulcers Lesotho Moteetee and Van Wyk27 those of S. asperulus Van Wyk et al.2; Duarte et al.3; Harris16; Van Wyk and Gericke38; South Africa 40 44 45 Worms Leaves and leaf sap Aremu et al. ; Ndhlala et al. ; Wintola and Afolayan ; Terblanche and Swaziland et al.47; Long58; Cock et al.72 3492 Alfred Maroyi /J. Pharm. Sci. & Res. Vol. 11(10), 2019, 3491-3496 35 30 25 20 15 10 5 0 Infertility Sores and Sexually Epilepsy Toothache Ulcers Respiratory Worms Earache Skin wounds transmitted problems problems infections No.