Ethnomedical Uses of Corymbia Species: Comparison
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Plants have been vital to human survival for aeons, especially for their unique medicinal properties. Trees of the Eucalyptus genus are well known for their medicinal properties. The Corymbia genus comprises bloodwood, spotted and ghost gum trees, which were previously classified as subspecies of the Eucalyptus genus. In 1995, however, DNA and morphological research concluded that bloodwood, spotted and ghost gum trees were genetically distinct from other Eucalyptus species, and they were, therefore, reclassified as members of the Corymbia genus of the Myrtaceae family

  • Corymbia
  • Ethnopharmacology
  • Biological Activities
  • Myrtaceae
  • Essential Oils
  • Ethnomedicine

1. Introduction

Over the past century, pharmaceutical interventions have become increasingly important in the treatment of ailments around the world, particularly in more developed nations. This is reflected in the ever-increasing investment of the pharmaceutical industry into drug research and development, which is reported to have increased from $2.3 billion USD in 1981 to $83 billion USD in 2019 [1]. This trajectory is unlikely to change anytime soon given the increasing prevalence of resistance to anti-microbials [2], and the need for more treatments to deal with the continual rise of conditions such as metabolic disorders and autoimmune diseases [3][4]. In less developed nations, however, access to pharmaceutical treatments is still limited, and as such, they continue to rely heavily upon medicinal plants for the treatment of many ailments [5].
For millennia, plants have been utilised by native cultures across the world for food, shelter, livelihood and medicine [6]. Even today, it is estimated that 65–80% of the world′s population continues to rely upon natural remedies due to a lack of access to modern medicine [7]. Ironically, it is to the native populations of the world who lack access to modern medicine that many researchers have been turning for inspiration and direction. Ethnopharmacology is becoming increasingly prevalent as a means of discovering new drug leads, as indigenous populations′ knowledge of plant medicinal properties can be utilised to direct the search for bioactive compounds [8]. The popularity of ethnopharmacological drug discovery is unsurprising given that approximately 40% of all small molecule therapeutics are natural products or derived from natural product pharmacophores [9] and that many of the over 50,000 medicinal plants known worldwide have not been screened for bioactive compounds to this day [7][10]. This is especially true of the many medicinal plants endemic to Australia.
Indigenous (aboriginal) Australians have lived from the land for thousands of years and have an intimate connection to and knowledge of endemic flora and their medicinal properties. Trees of the Eucalyptus genus (Myrtaceae) represent perhaps one of the most renowned Australian aboriginal bush medicines. These species are well-known for their volatile essential oils (EOs) which are extracted from the leaves and used to treat respiratory infections and inflammatory conditions around the world [11]. Further, Eucalyptus trees, while endemic to Australia, have been cultivated around the world and have become essential medicinal plants for other native populations around the world [12][13].
Despite the extensive knowledge and fame of the Eucalyptus genus for its medicinal properties, comparatively little is known about species of the Corymbia genus, which have similar phytochemical and medicinal properties [14]. The Corymbia genus comprises bloodwood, spotted and ghost gum trees, which were previously classified as subspecies of the Eucalyptus genus. In 1995, however, DNA and morphological research concluded that bloodwood, spotted and ghost gum trees were genetically distinct from other Eucalyptus species, and they were, therefore, reclassified as members of the Corymbia genus of the Myrtaceae family [15][16]. One key morphological characteristic of many Corymbia spp. is their production of kino, a resinous exudate which is used to treat many ailments by the aboriginal peoples of Australia [17]. Along with the known ethnomedical uses of various Corymbia species, a broad range of biological activities are observed in the EOs, crude extracts and compounds isolated from this genus [18][19][20][21], highlighting the potential of the Corymbia genus to provide new drug leads and treatments for many common diseases. 

2. Ethnomedical Uses of Corymbia Species

The ethnopharmacological data for the Corymbia genus presented in Table 1 show that of the 115 species known, ethnomedical uses have only been reported for 14 of these species. Of those 14 species, the kino was used medicinally in 12 spp., followed by the leaves (7 spp.) and bark (3 spp., Figure 1).
Figure 1. The use of plant parts in ethnomedically utilised Corymbia species (N = 14).
Table 1. Ethnopharmacological data for Corymbia spp. plants and biological testing performed.
Species Origin of Plant Studied Part(s) of Plant Studied § Ethnomedical Uses Compounds Isolated Biological Testing Performed
C. bleeseri (Blakely) Australia K Kino is applied to cuts and wounds to promote healing [22] and is used to treat skin lesions, scabies, cramps, sore throats and coughs [17]. – † [23] –
C. calophylla

(Lindl.)		 Australia K, B Kino is used to treat chronic bowel conditions and dysentery [17]. Aromadendrin; kaempferol; ellagic acid [24]; oleanolic acid acetate [25]; (+)-afzelechin *; pyrogallol; (+)-catechin [26]; leucopelargonidin *; aromadendrin; sakuranetin [27]. –
C. citriodora (Hook.) Algeria; Australia; Bangladesh; Benin; Brazil; China; Colombia; Cote d′Ivoire; Democratic Republic of the Congo; Egypt; India; Türkiye; Kenya; Madagascar; Morocco; Nigeria; Pakistan; Portugal; Taiwan; Thailand; USA L, K, T, Fr, H Leaves and bark are used as antiseptics, expectorants, and treatments for influenza and colds, toothaches [28][29] and diarrhoea [29]; hot water extracts of the dried leaves are used to treat colds, influenzas, respiratory infections and sinus congestion [30][31][32][33][34][35]; water extracts are also used to treat, vomiting, nausea, indigestion, bloating, irritable bowel and abdominal pain [30]; leaves are used in India and Africa to treat obesity, ageing, cardiovascular illnesses, diabetes and respiratory problems [36][37]; in Nigeria, leaves are boiled and consumed for the treatment of typhoid fever, stomach aches and malaria [38]; Dharawal people use leaves to treat inflammation, wounds and fungal infections [39].

Kino is traditionally used to treat diarrhoea and bladder inflammation and is applied to cuts and abrasions [40][41].		 Shikimic acid; quinic acid; glutaric acid; succinic acid; malic acid; citric acid [42]; (±)-(trans)-p-menthane-3,8-diol; (±)-(cis)-p-menthane-3,8-diol [43]; 6-[1-(p-hydroxyphenyl) ethyl]-7-O-methyl aromadendrin [40]; citronellol acetate [44]; 3,5,4′,5″-tetrahydroxy-7-methoxy-6-[1-(p-hydroxy-phenyl)ethyl]flavanone; 3,5,7,4′,5″-pentahydroxy-6-[1-(p-hydroxy-phenyl)ethyl] flavanone [45]; 1-O,2-O-digaloil-6-O-trans-p-coumaroyl-β-D-glucoside; 1-O-trans-p-coumaroyl-6-O-cinamoil-β-D-glucoside; α- and β-6-O-trans-p-coumaroyl-D-glucoside; 7-methylaromadendrin-4′-O-6″-trans-p-coumaroyl-β-D-glucoside; aromadendrin; aromadendrin-7-methyl ether; naringenin; sakuranetin; kaempferol-7-methyl ether; gallic acid [46]; citriodora A *; 3β,7β,25-trihydroxycucurbita-5,23-(E)-dien-19-al; kuguacin A; kuguacin H; 3β,7β-dihydroxy-25-methoxycucurbita-5,23-(E)-dien-19-al; kuguacin S [47]; trans-calamenene; T-muurolol; α-cadinol; 2β-hydroxy-α-cadinol; 4-hydroxy-3,5-dimethoxybenzaldehyde; 4-hydroxy-3,5-dimethoxybenzoic acid; linoleic acid; squalene; α-tocopherol; erythrodiol; morolic acid; betulonic acid; cycloeucalenol; cycloeucalenol vernolitate *; β-sitosterol; β-sitosteryl-β-D-glucoside; sitostenone; yangambin; sesamin [48]; rhamnocitrin; 6-[1-(p-hydroxyphenyl)ethyl]-7-O-methyl aromadendrin *; 6-[1-(p-hydroxyphenyl)ethyl]-rhamnocitrin; kaempferol; 7-O-methyl aromadendrin [49]; citriodolic acids A–C *; rosmarinic acid; ferulic acid; gallic acid [50]; ellagic acid; gallic acid; quercetin; myricetin; 3-O-methylellagic acid-4′-O-α-L-rhamnoside; quercetin-3-O-β-D-galactoside; kaempferol-3-O-β-D-glucoside; quercetin-3-O-β-D-glucuronide; quercetin-3-O-rutinoside; 3,3′,4-tri-O-methylellagic acid-4′-O-β-D-glucopyranosyl [39]; rhodomyrtosone E *; betulinic acid; oleanolic acid; ursolic acid; corosolic acid; asiatic acid; madasiatic acid; euscaphic acid; 5,7,4′-trihydroxy dihydroflavanol; isoquercitrin; isomyricitrin; myricitrin; gallic acid [51]; citrioside A *; hesperidin; baicalin; puerarin; trifolirhizin 6′-monoacetate; trifolirhizin [52]; citrioside C *; kaempferol-3-O-β-D-glucopyranosyl (12)-α-L-rhamnoside; kaempferol-3-O-α-L-rhamnoside; quercetin-3-O-α-L-rhamnoside [53]; 7-O-methylaromadendrin; aromadendrin-dimethyl ether; 7-O-methylkempferol; ellagic acid [54]. Anti-Fungal Activity: potent fungicidal activity of leaf EO against C. albicans, C. krusei and C. tropicalis [55]; anti-fungal activity of leaf EO against M. canis, M. gypseum, T. mentagrophytes and T. rubrum [56]; anti-fungal activity of leaf EO against A. alternata, C. lunata and B. specifera [57]; leaf EO enhanced wound healing rate of C. albicans-infected wounds in rats [44]; anti-fungal activity of petroleum ether leaf extract [58]; anti-fungal activity observed in leaf/twig EO [33]; fungicidal activity of leaf EO against C. albicans [36]; anti-fungal activity against P. notatum, A. niger and F. oxysporium observed for 7-O-methylaromadendrin, 7-O-methylkaempferol and ellagic acid [54].

Anti-Bacterial Activity: anti-bacterial activity of leaf extracts against M. aureus, E. coli and My. Pheli [54]; anti-bacterial activity of petroleum ether leaf extract [58]; anti-bacterial activity observed from leaf/twig EO [33]; anti-bacterial activity of leaf EO against S. sanguinis and S. salivarius with anti-biofilm activity [18]; bactericidal activity of leaf EO against E. coli and S. aureus [36]; bactericidal activity of leaf EO [37]; anti-bacterial activity of aqueous EtOH leaf extract [59]; anti-bacterial activity of fruit and twig EOs against several species [60]; anti-bacterial activity of leaf extract against S. aureus [61]; airborne TB inhibition by volatile leaf EO components [62]; leaf EO inhibits the growth of V. campbellii BB120 bacteria [63] and treatment of brine shrimp infected with V. campbellii with EO enabled their survival [64].

Acaricidal Activity: acaricidal activity of leaf EO against A. nitens larvae [65]; leaf EO and citronellal reduced R. microplus reproductive parameters and increased larval mortality [66].

Anti-Protozoal Activity: anti-trypanosomal activity of leaf EO against T. brucei [67], T. evansi [67] and T. cruzi [68]; anti-trypanosomal activity of EtOH extract against T. brucei [69]; anti-plasmodial activity observed against P. falciparum 3D7 and INDO strains [70].

Anti-Viral Activity: potent anti-viral activity against RSV observed in citriodolic acids A–C [50], citrioside A [52] and quercetin-3-O-α-L-rhamnoside [53].

Insecticidal Activity: fumigant activity against the R. speratus [71]; larvicidal activity against A. aegypti [72]; larvicidal activity of leaf hexane extract against An. Stephensi, Cx. Quinquefasciatus and Ae. Aegypti [73]; larvicidal activity of aqueous EtOH leaf extract [59]; larvicidal activity of leaf EOs against S. frugiperda larvae [74]; insecticidal activity of MeOH extract against T. castaneum [75].

Anti-Oxidant/Anti-Inflammatory Activity: leaf EO showed significant inhibition and IC50 values of 4.8–344 µg/mL in DPPH assays [31][33][76][77][78][79][80]; floral EO showed moderate DPPH inhibition [31]; leaf EO showed potent peroxidation inhibition in a linoleic acid/β-carotene assay [33]; leaf and floral EOs showed micromolar protease inhibition [31]; anti-inflammatory properties via inhibition of LOX-1 [28]; kino EtOH extract [32] and flavanols isolated from kino exhibited 15-LOX inhibition [49]; potential anti-inflammatory and anti-viral activity of leaf EO via LOX and ACE2 inhibition [81]; potent anti-inflammatory and gastroprotective properties of ellagitannin fraction in rats [20]; potent inhibition of LPS-induced inflammation in RAW264.7 macrophages [82]; ellagic acid isolated from C. citriodora leaves showed anti-inflammatory and gastroprotective activity in an EtOH-induced acute gastric ulcer mouse model [39]; leaf EO showed significant anti-inflammatory and analgesic activity in rats and mice [35].

Anti-Diabetic Activity: betulinic acid and corosolic acid isolated from C. citriodora leaves enhanced GLUT-4 translocation activity [51]; aqueous leaf extract enhanced insulin secretion and glucose uptake in vitro and had anti-diabetic effects in high-fat-fed rats [80][83]; EtOH leaf extract had anti-diabetic and insulinotropic activity in high-fat-fed rats [21].

Anti-Cancer Activity: Anti-proliferative activity of aqueous extract against MIA, PaCa-2, BxPC-3, CFPAC-1 and HPDE cells [30]; leaf EO exhibited anti-proliferative activity against THP-1 cells [84]; EtOAc fraction of EtOH kino extract and isolated 6-[1-(p-hydroxyphenyl) ethyl]-7-O-methylaromadendrin exhibited potent anti-proliferative activity and apoptosis induction in B16F10 melanoma cells [40]; aqueous fraction of EtOH kino extract inhibited cell growth and induced apoptosis in HepG2 cells [41]; leaf EO showed potent anti-cancer activity against HCT-116, MCF-7 and hepG-2 cells [76]; moderate cytotoxicity of leaf EO against A-549, PC-3, T98G and T47D cells [57]; fruit EO was cytotoxic toward A549, HeLa and CHOK1 cells [85].

Other Bioactivity: aqueous extract of leaves and branches detoxified mycotoxins aflatoxins B1 and B2 [86]; leaf EO exhibited anti-spasmodic effects via inhibition of acetylcholine-induced contraction of a rat ileum [29]; mosquito repellence [43][87]; acetone leaf extract delayed loss of climbing ability and reduced oxidative stress in transgenic Drosophila expressing h-αS in the neurons [88].
C. dichromophlo-ia (F. Muell.) Australia – Kino infusions are used to treat respiratory complaints [17]; mixed with water as a general tonic and analgesic mouth rinse for toothaches [17][89]; mixed with water for sore eyes, lips, wounds, skin lesions, burns, scabies, cramps and sore throats [17]; kino sucked or decoction prepared as tonic for cardiac complaints [17][89].

Leaves are boiled in water and consumed for respiratory conditions [22].		 – –
C. eximia (Schauer) Australia L Dharawal people use leaves to treat colds, fever, chest and muscle pain, extreme diarrhoea and syphilitic sores and as a wash for joints [90]. – Ethanolic leaf extract showed anti-inflammatory properties in RAW 264.7 macrophages [90].
C. gummifera (Gaertn.) Australia K, L Leaves used for respiratory conditions and as a wash for joints [90].

Leaves and kino are used as haemostatics and to treat diarrhoea, ringworm, venereal sores and other STIs [17][91].		 Aromadendrin; ellagic acid [24]. Moderate anti-inflammatory activity observed in RAW 264.7 macrophages [90].
C. intermedia (R.T. Baker) Australia K, L, FL The Yaegl aboriginal community uses kino to treat warts and wounds and as a haemostatic [92][93]. Intermediones A–D *; (4S)-ficifolidione [19]. Intermediones A, B and D showed moderate anti-plasmodial activity against P. falciparum 3D7 [19]; intermedianone A also displayed anti-proliferative activity against HEK-293 cells [19].
C. maculata (Hook.) Australia, Egypt, India, Nigeria L, K, B Kino is applied directly to burns, and used to treat muscle aches, cramps, wounds, scabies, ringworm, venereal sores, muscle aches and cramps [94]; kino is also ingested to treat coughs, colds, influenza and other infections, dysentery and diarrhoea [94]; kino is also used to treat chronic bowel inflammation [17].

Dharawal people use leaves to treat respiratory infections, fever, chest and muscle pain, and as a wash for joints [90]; juice extracted from the leaves is used to treat paralysis and rheumatism in India [30].

In Australian bush medicine, gum derived from the bark is used to treat bladder infections [30].		 β-Germacrenol [95]; 8-demethyl eucalyptin; 8-demethyleucalyptin; myrciaphenone A–B; quercetin-3-O-β-D-xyloside; myricetin-3-O-α-L-rhamnoside; quercetin-3-O-β-D-galactoside; quercetin-3-O-β-D-glucoside; quercetin-3-O-α-L-rhamnoside; syringic acid; gallic acid-3-methyl ether; gallic acid-4-methyl ether; gallic acid [96]; ellagic acid; p-coumaric acid; naringenin; 7-O-methylaromadendrin [97]; leucopeargoniidin-3-O-α-L-rhamno-β-D-glucoside *; 5,7-dihydroxy 4′-methoxy flavanone [98]; cinnamic acid; 7-O-methyl aromadendrin; sakuranetin; 1,6-dicinnamoyl-O-α-D-glucoside* [99]; p-coumaric acid; 1-O-cinnamoyl 6-O-coumaroyl-β-D-glucoside *; 7-methylaromadendrin-4′-O-(6′′-trans-p-coumaroyl)-β-D-glucoside * [100]; 3β,13β-dihydroxy-urs-11-en-28-oic acid [101]; 6-[1-(p-hydroxyphenyl)ethyl]-7-O-methylaromadendrin [40]. Potent anti-leishmanial activity against L. donovani observed in eucalyptin, Myciaphenone A and five flavonoid glycosides [96]; potent anti-trypanosomal activity against T. brucei [101]; leaf aqueous extract inhibited PaCa-2 cell proliferation [30]; MeOH extract showed anti-inflammatory properties in vitro [102]; EtOH leaf extract exhibited anti-inflammatory properties in RAW 264.7 macrophages [90]; MeOH kino extract showed significant anti-inflammatory properties in rats [102]; 7-O-methylaromadendrin, sakuranetin and 1,6-dicinnamoyl-O-α-D-glucoside isolated from the kino [99] exhibited anti-oxidant and hepatoprotective properties in rats [103].
C. opaca (D.J. Carr & S.G.M. Carr) Australia – Kino is applied directly to scabies, cuts and sores, and the gum is boiled in water and applied to sore eyes [22]. – –
C. papuana (F. Muell.) Australia B Kino is used as a decoction for sores, cramps, burns, pains and cuts, skin lesions, scabies, sore throat and cough; infusions are used for colds and sore eyes [17]. Morolic acid [104]. –
C. polycarpa (F. Muell.) Iran L Kino is used to treat sores, burns, cuts, burns, yaws, ulcers, dysentery and toothaches [17][91]. – † [105][106] Anti-bacterial activity of leaf EO against S. aureus [107].
C. terminalis (F. Muell.) Australia – Kino is applied to wounds, cuts, sores, toothaches, scabies, skin lesions scabies and cramps [17][22]; it is also taken in water for diarrhoea, headaches, coughs, heart disease and blood conditions [17][22][89].

Bark is used to treat dysentery [91].		 – ‡ [108] –
C. tessellaris (F. Muell.) Australia – Kino is consumed for dysentery [17]; gum is used for constipation [91]. –† [109] –
C. torelliana (F. Muell.) Australia, Papua New Guinea, Nigeria K, L, B FR, FL Leaves are used to treat gastrointestinal disorders, sore throats, bacterial respiratory and urinary tract infections [110]; leaf poultice is applied to ulcers and wounds [110]; hot water extracts of leaves are used in Nigerian traditional medicine as an analgesic, anti-inflammatory, cancer treatment and to alleviate intestinal disorders [111]. Torellianones A–F *; torellianol A *; ficifolidione; (4R)-ficifolidione; kunzeanone A–B [112]; (+)-pinene; (±)-α-pinene; (-)-β-pinene; ocimene; (+)-aromadendrene; benzaldehyde [113]; 5-hydroxy-7,4′-dimethoxy-6-methylflavone [114]; hydroxymyristic acid methyl ester; methyl (E)- and (Z)-6-(8-oxooctadecahydrochrysen-1-yl)non-7-enoate [115];

(2S)-cryptostrobin; (2S)-stroboponin; (2S)- cryptostrobin 7-methyl ether; (2S)- desmethoxymatteucinol; (2S)-pinostrobin; (2S)-pinocembrin [116]; 3,4′,5,7-tetrahydroxyflavanone; 3′,4′,5,7-tetrahydroxyflavanone; 4′,5,7-trihydroxyflavanone; 3,4′,5-trihydroxy-7-methoxyflavanone; (+)-(2S)-4′,5,7-trihydroxy-6-methylflavanone; 4′,5,7-trihydroxy-6,8-dimethylflavanone; 4′,5-dihydroxy-7-methoxyflavanone [117].		 Torellianones C–F, (4R)- and (4S)-ficifolidones and kunzeanone A exhibited anti-plasmodial activity against P. falciparum [112]; potent in vitro anti-H. pylori activity of leaf and stem extracts across various strains [110]; leaf and stem bark extracts and isolated compounds showed anti-TB activity [115]; anti-bacterial activity of stingless bee propolis, fruit resin and isolated flavonoids against S. aureus [116]; moderate anti-bacterial activities and potent cytotoxicity to PC-3, Hep G2, Hs 578T and MDA-MB-231 exhibited by leaf and fruit EOs [111]; anti-tuberculosis activity observed in hydroxymyristic acid methyl ester and methyl (E)- and (Z)-6-(8-oxooctadecahydrochrysen-1-yl)non-7-enoate [115]; MeOH extract of leaves and bark showed anti-secretory and gastroprotective properties in rats with EtOH/HCl-induced ulceration [118].
§ Code for part of plant studied: L = leaves; K = kino/resin/exudate; B = bark; FR = fruit; FL = flowers; T = twigs; H = heartwood. * Novel compound(s) that were isolated. † No compounds were isolated; however, a chemical profile of the leaf EO was reported. ‡ Raman spectrum of kino previously obtained.
The kino of Corymbia genus plants is commonly applied directly to cuts (haemostatic), burns and wounds by aboriginal people and is added to water to make antiseptic washes [17][22][92][93][94]. Kino is applied locally to treat infections such as ringworm, venereal sores and other STIs [17][91] and is also ingested to treat pulmonary and heart complaints, gastrointestinal and bladder infections, diarrhoea and dysentery [17][40][41][89]. The kino of C. terminalis is also used as a tonic to treat blood conditions and to relieve headaches [22].
Hot water extracts of Corymbia spp. leaves are frequently used by aboriginal people as antiseptics for wounds and infections, analgesic baths for rheumatism and are ingested to treat respiratory and urinary tract infections and severe diarrhoea [28][29][30][31][32][33][34][35][90]. The leaves of C. citriodora, C. maculata and C. torelliana have also been adopted by the native populations of Cote d′Ivoire, Nigeria, India and Brazil for the treatment of toothaches, obesity and diabetes, respiratory and intestinal complaints, skin conditions, cancer, typhoid fever and malaria [28][30][34][35][36][37][38][111].
The less commonly used barks of the Corymbia spp. also possess medicinal properties. Gum derived from the bark of C. maculata is used in Australian bush medicine to treat bladder infections [30], while the bark of C. terminalis is used by aboriginal communities in Queensland to treat dysentery [91]. The bark of C. citriodora is also reported to be used in Nigeria as an antiseptic and expectorant and as a treatment for toothaches, diarrhoea and snake bites [29].

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