The Ethnopharmacology, Phytochemistry and Bioactivities of the Corymbia Genus (Myrtaceae)

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; however, little is known of the ethnopharmacology and bioactivities of their close relatives in the Corymbia genus. Given the current lack of widespread knowledge of the Corymbia genus, this review aims to provide the first summary of the ethnopharmacology, phytochemistry and bioactivities of this genus. The Scopus, Web of Science, PubMed and Google Scholar databases were searched to identify research articles on the biological activities, phytochemistry and ethnomedical uses of Corymbia species. Of the 115 Corymbia species known, 14 species were found to have ethnomedical uses for the leaves, kino and/or bark. Analysis of the references obtained for these 14 Corymbia spp. revealed that the essential oils, crude extracts and compounds isolated from these species possess an array of biological activities including anti-bacterial, anti-fungal, anti-protozoal, anti-viral, larvicidal, insecticidal, acaricidal, anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic activities, highlighting the potential for this under-studied genus to provide lead compounds and treatments for a host of medical conditions.


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 Plants 2023, 12, 3686 2 of 29 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.To date, the ethnopharmacology, phytochemistry and biological activities of the Corymbia genus have not been reviewed, and it is therefore the aim of this study to provide the first ethnopharmacological summary for this genus and outline the biological activities of Corymbia spp.EOs, extracts and isolated compounds.

Literature Review Methods
Literature searches were initially performed using "Corymbia" as the keyword in the Scopus, PubMed and Web of Science databases.These references were filtered to include only journal articles, and the topics were limited to medicine, chemistry and pharmacology/pharmaceuticals in each database.Since Corymbia as a distinct genus classification has only existed since 1995 [15], all journal articles referring to these species were previously reported as Eucalyptus spp.Therefore, the names of the 115 known Corymbia species were identified using the World Flora Online database (https://www.worldfloraonline.org/,accessed on 4 May 2023) and each species was searched in Scopus as the equivalent "Eucalyptus spp." to find journal articles related to these species prior to 1995.Combination of the references from each database search and removal of any duplicates provided 323 references.An additional four references related to the ethnomedical uses of Corymbia spp.were found through Google Scholar searches using the search terms "Australian aboriginal medicinal plants ethnopharmacology".Of these 327 references, 105 references were determined to be relevant to the ethnopharmacology and biological testing of Corymbia spp.
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. 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].
-- 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].
- † [109] - 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 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-7enoate [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].
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].

The Phytochemistry of Corymbia Species 4.1. Essential Oils
The EOs of Corymbia species have been of significant interest for many years, with their chemical composition typically quantified through metabolomic studies using GC-MS.Like Eucalyptus EOs, the EOs of Corymbia species are complex mixtures composed primarily of monoterpenoids and sesquiterpenoids, which exhibit a broad spectrum of biological activities.The exact chemical composition varies significantly between different species and within species according to the local climatic conditions, soil and the part of the plant [85,105,106,119].
In addition to leaf EOs, the EOs of flowers, twigs and fruits have also previously been studied in C. citriodora and C. torelliana (Table 3).The major constituents of C. citriodora twig EO have been observed to be 1,8-cineole and p-cymene, while the fruit EO has been reported to mainly comprise α-pinene and γ-terpinene.The flower EO of C. citriodora has also been observed to contain α-pinene as the major terpenoid (54.1%), along with citronellol as a minor component (9.9%).In C. torelliana, α-pinene is observed to be the major constituent in both leaf and flower EOs, though differences are observed in the minor components of these EOs (β-caryophyllene and β-pinene, respectively).This variability in EO composition observed both between species and in different parts of the plant studied warrants further investigation and review as this presents an excellent opportunity for commercialisation as alternatives to traditional Eucalyptus oils, as these mixtures could be marketed according to the key bioactivities observed in the major components of these EOs.

Tes. [23]
Tor. [151] In addition to leaf EOs, the EOs of flowers, twigs and fruits have also previously been studied in C. citriodora and C. torelliana (Table 3).The major constituents of C. citriodora twig EO have been observed to be 1,8-cineole and p-cymene, while the fruit EO has been reported to mainly comprise α-pinene and γ-terpinene.The flower EO of C. citriodora has also been observed to contain α-pinene as the major terpenoid (54.1%), along with citronellol as a minor component (9.9%).In C. torelliana, α-pinene is observed to be the Plants 2023, 12, 3686 10 of 29 major constituent in both leaf and flower EOs, though differences are observed in the minor components of these EOs (β-caryophyllene and β-pinene, respectively).This variability in EO composition observed both between species and in different parts of the plant studied warrants further investigation and review as this presents an excellent opportunity for commercialisation as alternatives to traditional Eucalyptus oils, as these mixtures could be marketed according to the key bioactivities observed in the major components of these EOs.C. citriodora C. torelliana Leaf [106] Twig [60] Fruit [85] Flower [142] Leaf

Isolated Natural Products
Analysis of the compounds reported in Table 1 revealed that 147 distinct molecules have previously been isolated from Corymbia species, with the major classes of phytochemicals summarised in Table 4 below.Species of the Corymbia genus are rich in polyphenols, particularly flavonoids, which account for the potent anti-inflammatory properties observed in crude extracts (see Section 5.3).Terpenoids are also key metabolites isolated from Corymbia species, in particular, triterpenoids, in addition to the hundreds of monoterpenoids and sesquiterpenoids detected in the EOs of these species.Twenty polyketides have also been previously isolated, including 16 β-triketones from C. intermedia and C. torelliana which showed potent anti-protozoal activity (see Section 5.1.3).The chemical structures of key bioactive compounds previously isolated are presented throughout Section 5.

Isolated Natural Products
Analysis of the compounds reported in Table 1 revealed that 147 distinct molecules have previously been isolated from Corymbia species, with the major classes of phytochemicals summarised in Table 4 below.Species of the Corymbia genus are rich in polyphenols, particularly flavonoids, which account for the potent anti-inflammatory properties observed in crude extracts (see Section 5.3).Terpenoids are also key metabolites isolated from Corymbia species, in particular, triterpenoids, in addition to the hundreds of monoterpenoids and sesquiterpenoids detected in the EOs of these species.Twenty polyketides have also been previously isolated, including 16 β-triketones from C. intermedia and C. torelliana which showed potent anti-protozoal activity (see Section 5.1.3).The chemical structures of key bioactive compounds previously isolated are presented throughout Section 5.

Overview of Biological Testing in Corymbia Species
Analysis of the 105 publications reported for Corymbia spp.(excluding purely ethnopharmacological studies) in Table 1 revealed that C. citriodora was the most-studied species (N = 63), followed by C. maculata (N = 11), C. torelliana (N = 9) and C. calophylla (N = 4), highlighting the dearth of study into most species of this genus (Figure 2).Further analysis of references reporting biological activities revealed that the leaf Eos and leaf extracts of Corymbia species were the most commonly studied (N = 68), followed by kino (N = 17) and bark (N = 6) extracts (Figure 3A).When analysed according to biological activity, antimicrobial and anti-viral activities were found to account for almost half of the references (N = 32), followed by anti-inflammatory/anti-oxidant (N = 17), anti-cancer (N = 8) and insecticidal (N = 7) activities (Figure 3B).These biological activities are discussed in the subsections below.[33,36,[55][56][57].The major constituent of C. citriodora EO, citronellal [33,56], has previously been shown to have potent anti-fungal activity against R. solani and H. oryzae [156].The fruit EO of C. citriodora and two key components of this mixture (τ-cadinol and α-cadinol) can also inhibit the growth of A. clavatus, A. niger, Cl.Cladosporioides, Ch.Globosum, M. verrucaria, P. citrinum and T. viride [60].Recently, C. citriodora leaf EO and citronellol acetate (a minor constituent of the EO) were shown to effectively treat and enhance the rate of healing of rats with C. albicans-infected wounds [44].The enhanced wound healing observed in rats treated with the EO was suggested to be the result of the presence of α-pinene, which promotes collagen formation, deposition and maturation [44,157].
cies (N = 63), followed by C. maculata (N = 11), C. torelliana (N = 9) and C. calophylla (N = 4), highlighting the dearth of study into most species of this genus (Figure 2).Further analysis of references reporting biological activities revealed that the leaf Eos and leaf extracts of Corymbia species were the most commonly studied (N = 68), followed by kino (N = 17) and bark (N = 6) extracts (Figure 3A).When analysed according to biological activity, antimicrobial and anti-viral activities were found to account for almost half of the references (N = 32), followed by anti-inflammatory/anti-oxidant (N = 17), anti-cancer (N = 8) and insecticidal (N = 7) activities (Figure 3B).These biological activities are discussed in the subsections below.[33,36,[55][56][57].The major constituent of C. citriodora EO, citronellal [33,56], has previously been shown to have potent anti-fungal activity against R. solani and H. oryzae [156].The fruit EO of C. citriodora and two key components of this mixture (τ-cadinol and α-cadinol) can also inhibit the growth of A. clavatus, A. niger, Cl.Cladosporioides, Ch.Globosum, M. verrucaria, P. citrinum and T. viride [60].Recently, C. citriodora leaf EO and citronellol acetate (a minor constituent of the EO) were shown to effectively treat and enhance the rate of healing of rats with C. albicans-infected wounds [44].The enhanced wound healing observed in rats treated with the EO was suggested to be the result of the presence of α-pinene, which promotes collagen formation, deposition and maturation [44,157].
Extracts of C. citriodora have been studied to a lesser degree than leaf EOs, but they have been shown to possess anti-fungal activity.The petroleum ether leaf extract of C. citriodora has been shown to possess moderate inhibitory and fungicidal activity against A. flavus and A. parasiticus [58].Compounds, including 7-O-methylaromadendrin 1, 7-Omethylkaempferol 2 and ellagic acid 3, isolated from the kino of C. citriodora (Figure 4) have also been shown to have varying anti-fungal activities against P. notatum, A. niger and F. oxysporium  Plants 2023, 12, 3686 13 of 29

Anti-Bacterial Activity
Given the anti-fungal activity observed in the EO of C. citriodora, it is unsurprising that it also exhibits broad spectrum anti-bacterial activity.Inhibitory and bactericidal activity have been reported against A. tumefaciens, B. cereus, D. solani, E. coli, P. atrosepticum, P. carotovorum and S. aureus [33,36].Thirty-two components of the C. citriodora leaf EO have been identified as being able to inhibit airborne M. tuberculosis [62], while anti-bacterial and possible anti-biofilm activity have been observed against various strains of S. sanguinis and S. salivarius [18].Twig and fruit EOs from C. citriodora have also been shown to inhibit B. cereus, S. aureus, E. aerogenes, K. pneumoniae, P. aeruginosa, V. parahaemolyticus, S. epidermidis and E. coli bacteria with MIC values ranging from 125 to 1000 µg/mL [60].The leaf EO of C. citriodora has also been shown to inhibit the growth of V. campbelli and was successfully used to treat gnotobiotic brine shrimp (Artemia franciscana) infected with V. campbellii and enable their survival [63,64].
Research over recent years has also shown the anti-bacterial potential of C. torelliana.Moderate anti-bacterial activities were observed for the leaf and fruit EOs of C. torelliana against B. cereus, S. aureus, E. coli, P. aeruginosa, C. albicans and A. niger [111].Leaf extracts of C. torelliana have been shown to have potent inhibitory activity against several strains of H. pylori [110], while crude propolis derived from the kino of C. torelliana and C-methyl flavones isolated therefrom exhibited bactericidal activity against S. aureus [116].Hydroxymyristic acid methyl ester 4 and methyl (E)-and (Z)-6-(8-oxooctadecahydrochrysen-1yl)non-7-enoate 5 isolated from the leaves of C. torelliana (Figure 4) also exhibited bactericidal activity against M. tuberculosis [115].

Anti-Bacterial Activity
Given the anti-fungal activity observed in the EO of C. citriodora, it is unsurprising that it also exhibits broad spectrum anti-bacterial activity.Inhibitory and bactericidal activity have been reported against A. tumefaciens, B. cereus, D. solani, E. coli, P. atrosepticum, P. carotovorum and S. aureus [33,36].Thirty-two components of the C. citriodora leaf EO have been identified as being able to inhibit airborne M. tuberculosis [62], while anti-bacterial and possible anti-biofilm activity have been observed against various strains of S. sanguinis and S. salivarius [18].Twig and fruit EOs from C. citriodora have also been shown to inhibit B. cereus, S. aureus, E. aerogenes, K. pneumoniae, P. aeruginosa, V. parahaemolyticus, S. epidermidis and E. coli bacteria with MIC values ranging from 125 to 1000 µg/mL [60].The leaf EO of C. citriodora has also been shown to inhibit the growth of V. campbelli and was successfully used to treat gnotobiotic brine shrimp (Artemia franciscana) infected with V. campbellii and enable their survival [63,64].
Research over recent years has also shown the anti-bacterial potential of C. torelliana.Moderate anti-bacterial activities were observed for the leaf and fruit EOs of C. torelliana against B. cereus, S. aureus, E. coli, P. aeruginosa, C. albicans and A. niger [111].Leaf extracts of C. torelliana have been shown to have potent inhibitory activity against several strains of H. pylori [110], while crude propolis derived from the kino of C. torelliana and C-methyl flavones isolated therefrom exhibited bactericidal activity against S. aureus [116].Hydroxymyristic acid methyl ester 4 and methyl (E)-and (Z)-6-(8-oxooctadecahydrochrysen-1-yl)non-7-enoate 5 isolated from the leaves of C. torelliana (Figure 5) also exhibited bactericidal activity against M. tuberculosis [115].

Anti-Protozoal Activity
The leaf EO of C. citriodora has been shown to have anti-trypanosomal activity against T. brucei, T. evansi and T. cruzi [67,68], while crude EtOH leaf extracts have shown potent inhibitory activity against T. brucei and P. falciparum 3D7 and INDO strains [69,70].
Crude extracts and one isolated compound from the leaves of C. maculata showed inhibitory activity against T. brucei [101].Eucalyptin 6, myciaphenone A 7 and flavonoid glycosides 8-12 (Figure 6) isolated from the leaves of C. torelliana have also shown potent anti-leishmanial activity against L. donovani [96].A comprehensive study of the biological activities of over 100 flavonoids and polyphenols against Leishmania donovani, Trypanosoma brucei rhodesiense and Trypanosoma cruzi has been previously reported; however, despite

Anti-Protozoal Activity
The leaf EO of C. citriodora has been shown to have anti-trypanosomal activity against T. brucei, T. evansi and T. cruzi [67,68], while crude EtOH leaf extracts have shown potent inhibitory activity against T. brucei and P. falciparum 3D7 and INDO strains [69,70].
Crude extracts and one isolated compound from the leaves of C. maculata showed inhibitory activity against T. brucei [101].Eucalyptin 6, myciaphenone A 7 and flavonoid glycosides 8-12 (Figure 6) isolated from the leaves of C. torelliana have also shown potent anti-leishmanial activity against L. donovani [96].A comprehensive study of the biological activities of over 100 flavonoids and polyphenols against Leishmania donovani, Trypanosoma brucei rhodesiense and Trypanosoma cruzi has been previously reported; however, despite these efforts, clear quantitative structure-activity relationships (SARs) could not be established [158].More recent work has shown that various flavonoid glycosides, including Plants 2023, 12, 3686 14 of 29 quercetin-3-O-β-D-galactoside 10, inhibit Leishmania amazonensis arginase [159], which may represent an important mode of action for the anti-protozoal activity observed in flavonoid glycosides and could be a target for further drug lead development and SAR optimisation.A new class of anti-plasmodial β-triketones has also been discovered in recent years, with micromolar inhibition of P. falciparum observed in torellianones C-F 13-16, ficifolidones 17-18, kunzeanone A 19 (Figure 7) and intermedianones A, B and F 20-22 (Figure 8) isolated from the flowers of C. torelliana and C. intermedia, respectively [19,112].Three additional anti-plasmodial β-triketones, watsonianones A-C, have also been previously A new class of anti-plasmodial β-triketones has also been discovered in recent years, with micromolar inhibition of P. falciparum observed in torellianones C-F 13-16, ficifolidones 17-18, kunzeanone A 19 (Figure 7) and intermedianones A, B and F 20-22 (Figure 8) isolated from the flowers of C. torelliana and C. intermedia, respectively [19,112].Three additional anti-plasmodial β-triketones, watsonianones A-C, have also been previously isolated from the flowers of C. watsoniana (F.Muell.)[160].Although no molecular tar-gets have been identified for these β-triketones at this stage, these results emphasise the pharmacological potential for Corymbia species to provide new lead compounds for the treatment of significant diseases.

Anti-Viral Activity
Very few studies into the anti-viral activities of Corymbia species have been published.A molecular docking study suggested that several components of the EO of C. citriodora, particularly 1,8-cineol and α-pinene, could potentially inhibit the M Pro protein of SARS-CoV-2 [139].Further research revealed that citronellal (the major component of C. citriodora EO) and 1,8-cineol are inhibitors of ACE2 and LOX, suggesting the EO may have potential for use as an anti-viral and anti-inflammatory agent [81].
Significantly more work has been performed with an eye toward isolating anti-viral compounds against respiratory syncytial virus (RSV) in the laboratory of Zhong-liu Zhou.

Anti-Viral Activity
Very few studies into the anti-viral activities of Corymbia species have been published.A molecular docking study suggested that several components of the EO of C. citriodora, particularly 1,8-cineol and α-pinene, could potentially inhibit the M Pro protein of SARS-CoV-2 [139].Further research revealed that citronellal (the major component of C. citriodora EO) and 1,8-cineol are inhibitors of ACE2 and LOX, suggesting the EO may have potential for use as an anti-viral and anti-inflammatory agent [81].
Significantly more work has been performed with an eye toward isolating anti-viral compounds against respiratory syncytial virus (RSV) in the laboratory of Zhong-liu Zhou.

Anti-Viral Activity
Very few studies into the anti-viral activities of Corymbia species have been published.A molecular docking study suggested that several components of the EO of C. citriodora, particularly 1,8-cineol and α-pinene, could potentially inhibit the M Pro protein of SARS-CoV-2 [139].Further research revealed that citronellal (the major component of C. citriodora EO) and 1,8-cineol are inhibitors of ACE2 and LOX, suggesting the EO may have potential for use as an anti-viral and anti-inflammatory agent [81].
Significantly more work has been performed with an eye toward isolating anti-viral compounds against respiratory syncytial virus (RSV) in the laboratory of Zhong-liu Zhou.Citriodolic acids A-C 23-25 (Figure 9) were isolated from the EtOH extract of C. citriodora leaves and showed potent activity against RSV (IC 50 = 1.8-4.8µg/mL) comparable to that reported for ribacirivin, a drug already approved for the treatment of RSV infections [50].Further extractions and isolations of C. citriodora leaves also yielded citrioside A 26 and quercetin-3-O-α-L-rhamnoside 27, which also showed potent activity against RSV (Figure 10).Although further research is required to elucidate the modes of action for the anti-viral activity of these compounds, these results highlight the potential of Corymbia gum trees to provide new anti-viral lead compounds [52,53].
Plants 2023, 12, x FOR PEER REVIEW 18 of 31 Citriodolic acids A-C 23-25 (Figure 9) were isolated from the EtOH extract of C. citriodora leaves and showed potent activity against RSV (IC50 = 1.8-4.8µg/mL) comparable to that reported for ribacirivin, a drug already approved for the treatment of RSV infections [50].
Further extractions and isolations of C. citriodora leaves also yielded citrioside A 26 and quercetin-3-O-α-L-rhamnoside 27, which also showed potent activity against RSV (Figure 10).Although further research is required to elucidate the modes of action for the antiviral activity of these compounds, these results highlight the potential of Corymbia gum trees to provide new anti-viral lead compounds [52,53].

Insecticidal Activity
A variety of studies have been reported on the insecticidal activities of Corymbia species, mainly focussing upon the application of crude extracts and crude EOs.Larvicidal and acaricidal activity of the EO of C. citriodora has been reported in a variety of species, including A. aegypti mosquitoes [72], the brine shrimp Artemia salina [59], the fall armyworm Spodoptera frugiperda [74], the Asian blue tick Rhipicephalus microplus [66] and the tropical horse tick Anocentor nitens [65].Insecticidal and fumigant activities have also been reported for the leaf EO of C. citriodora against the cabbage moth Plutella xylostella [150] and Japanese termite Reticulitermes speratu [71], respectively.The leaf EOs of C. citriodora, C. maculata and C. torelliana also exhibit moderate fumigant and repellent activity against coffee berry borer Hypothenemus hampei females [151].Larvicidal activity has been reported for the hexane extract of C. citriodora leaves against Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti mosquitos [73], while the MeOH extract is lethal to the red flower beetle Tribolium castaneum [75].

Anti-Inflammatory and Anti-Oxidant Activity
The anti-inflammatory and anti-oxidant activities of the Corymbia species are well established in the literature.Many publications on the EOs of C. citriodora report very low IC50 and high percent inhibition values in DPPH assays [31,33,[76][77][78][79].The floral EO of C. citriodora is reported to have more moderate anti-oxidant activities [31], while the aqueous extract of C. citriodora leaves and MeOH extract of C. maculata resin exhibited potent activities in DPPH assays [80,102].
The potent anti-inflammatory properties of the EO of C. citriodora have also been demonstrated further in vitro through the low µg/mL IC50 values obtained in β-Carotenelinoleic acid and protease inhibitory assays [31,33].One study also found that the floral EO of C. citriodora exhibited potent protease inhibition with an IC50 = 2.59 µg/mL [31].
The leaf EO of C. citriodora and its constituents citronellal and 1,8-cineol have been observed to inhibit ACE2 and LOX enzymes in vitro, suggesting there are multiple antiinflammatory modes of action [81].Additional studies have also shown that the leaf EO and resin extracts of C. citriodora inhibit LOX-1 and 15-LOX, respectively [28,32].Extraction and purification of the EtOAc fraction of the EtOH extract of C. citriodora kino led to the isolation of 7-O-methylaromadendrin 1, 7-O-methylkaempferol 2 and flavonoids 28-30 (Figure 11), which were also shown to inhibit 15-LOX [49].

Insecticidal Activity
A variety of studies have been reported on the insecticidal activities of Corymbia species, mainly focussing upon the application of crude extracts and crude EOs.Larvicidal and acaricidal activity of the EO of C. citriodora has been reported in a variety of species, including A. aegypti mosquitoes [72], the brine shrimp Artemia salina [59], the fall armyworm Spodoptera frugiperda [74], the Asian blue tick Rhipicephalus microplus [66] and the tropical horse tick Anocentor nitens [65].Insecticidal and fumigant activities have also been reported for the leaf EO of C. citriodora against the cabbage moth Plutella xylostella [150] and Japanese termite Reticulitermes speratu [71], respectively.The leaf EOs of C. citriodora, C. maculata and C. torelliana also exhibit moderate fumigant and repellent activity against coffee berry borer Hypothenemus hampei females [151].Larvicidal activity has been reported for the hexane extract of C. citriodora leaves against Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti mosquitos [73], while the MeOH extract is lethal to the red flower beetle Tribolium castaneum [75].

Anti-Inflammatory and Anti-Oxidant Activity
The anti-inflammatory and anti-oxidant activities of the Corymbia species are well established in the literature.Many publications on the EOs of C. citriodora report very low IC 50 and high percent inhibition values in DPPH assays [31,33,[76][77][78][79].The floral EO of C. citriodora is reported to have more moderate anti-oxidant activities [31], while the aqueous extract of C. citriodora leaves and MeOH extract of C. maculata resin exhibited potent activities in DPPH assays [80,102].
The potent anti-inflammatory properties of the EO of C. citriodora have also been demonstrated further in vitro through the low µg/mL IC 50 values obtained in β-Carotenelinoleic acid and protease inhibitory assays [31,33].One study also found that the floral EO of C. citriodora exhibited potent protease inhibition with an IC 50 = 2.59 µg/mL [31].
The leaf EO of C. citriodora and its constituents citronellal and 1,8-cineol have been observed to inhibit ACE2 and LOX enzymes in vitro, suggesting there are multiple antiinflammatory modes of action [81].Additional studies have also shown that the leaf EO and resin extracts of C. citriodora inhibit LOX-1 and 15-LOX, respectively [28,32].Extraction and purification of the EtOAc fraction of the EtOH extract of C. citriodora kino led to the isolation of 7-O-methylaromadendrin 1, 7-O-methylkaempferol 2 and flavonoids 28-30 (Figure 11), which were also shown to inhibit 15-LOX [49].
In a cell-based in vitro assay of LPS-induced RAW264.7 macrophages, the leaf EO of C. citriodora showed anti-inflammatory effects (reduced levels of NO, IL-6, TNF-α, COX-2 and iNOS expression) through the inhibition of MAPK and NF-κB pathways [82].A similar study of LPS-induced RAW264.In a cell-based in vitro assay of LPS-induced RAW264.7 macrophages, the leaf EO of C. citriodora showed anti-inflammatory effects (reduced levels of NO, IL-6, TNF-α, COX-2 and iNOS expression) through the inhibition of MAPK and NF-κB pathways [82].A similar study of LPS-induced RAW264.7 macrophages was performed on crude extracts of gummifera, C. maculata and C. eximia, which were shown to exert anti-inflammatory properties through the inhibition of NO and TNF- production [90].
An in vivo investigation of the anti-inflammatory and analgesic activities of the leaf EO of C. citriodora was performed in rats and showed that the EO inhibits central and peripheral nociception, as well as neutrophil-independent and neutrophil-dependent inflammation [35].Another in vivo investigation showed the ellagitannin-rich fraction extracted from the leaves of C. citriodora had anti-inflammatory and gastroprotective effects in EtOH-induced rats [20].This research was expanded upon, wherein the ellagitannin ellagic acid 3 (Figure 12) was isolated from the leaves of C. citriodora and shown to have significant anti-inflammatory (increased IL-10 and PGE2 levels and decreased IL-6, TNFα and COX-2 levels) and anti-gastric ulcer effects in EtOH-induced mice [39].Analysis of the aspartate aminotransferase and creatine levels also showed li le change between the control and ellagic acid 3 treatment groups, suggesting that ellagic acid has no adverse effect on liver and kidney function, highlighting the potential therapeutic value of this natural product [39].In a cell-based in vitro assay of LPS-induced RAW264.7 macrophages, the leaf EO of C. citriodora showed anti-inflammatory effects (reduced levels of NO, IL-6, TNF-α, COX-2 and iNOS expression) through the inhibition of MAPK and NF-κB pathways [82].A similar study of LPS-induced RAW264.7 macrophages was performed on crude extracts of C. gummifera, C. maculata and C. eximia, which were shown to exert anti-inflammatory properties through the inhibition of NO and TNF-α production [90].
An in vivo investigation of the anti-inflammatory and analgesic activities of the leaf EO of C. citriodora was performed in rats and showed that the EO inhibits central and peripheral nociception, as well as neutrophil-independent and neutrophil-dependent inflammation [35].Another in vivo investigation showed the ellagitannin-rich fraction extracted from the leaves of C. citriodora had anti-inflammatory and gastroprotective effects in EtOH-induced rats [20].This research was expanded upon, wherein the ellagitannin ellagic acid 3 (Figure 12) was isolated from the leaves of C. citriodora and shown to have significant anti-inflammatory (increased IL-10 and PGE2 levels and decreased IL-6, TNF-α and COX-2 levels) and anti-gastric ulcer effects in EtOH-induced mice [39].Analysis of the aspartate aminotransferase and creatine levels also showed little change between the control and ellagic acid 3 treatment groups, suggesting that ellagic acid has no adverse effect on liver and kidney function, highlighting the potential therapeutic value of this natural product [39].
α and COX-2 levels) and anti-gastric ulcer effects in EtOH-induced mice [39].Analy the aspartate aminotransferase and creatine levels also showed li le change betwe control and ellagic acid 3 treatment groups, suggesting that ellagic acid has no ad effect on liver and kidney function, highlighting the potential therapeutic value o natural product [39].The kino of C. maculata has also garnered some attention for its anti-inflammatory and anti-oxidant activities.The chloroform extract of the kino of C. maculata and isolated compounds 7-O-methylaromadendrin 1, sakuranetin 31 and 1,6-dicinnamoyl-O-α-Dglucoside 32 (Figure 13) were shown to protect against acetaminophen lethality in rats and significantly reduced the rise in aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase levels induced by acetaminophen [99,103].More recently, the MeOH extract of C. maculata kino was shown to reduce levels of NF-κB, TNF-α, COX-2 and NO inflammatory biomarkers and significantly reduced paw thickness in carrageenan-induced paw oedema in rats [102].The kino of C. maculata has also garnered some a ention for its anti-inflammatory and anti-oxidant activities.The chloroform extract of the kino of C. maculata and isolated compounds 7-O-methylaromadendrin 1, sakuranetin 31 and 1,6-dicinnamoyl-O-α-D-glucoside 32 (Figure 13) were shown to protect against acetaminophen lethality in rats and significantly reduced the rise in aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase levels induced by acetaminophen [99,103].More recently, the MeOH extract of C. maculata kino was shown to reduce levels of NF-κB, TNF-α, COX-2 and NO inflammatory biomarkers and significantly reduced paw thickness in carrageenan-induced paw oedema in rats [102].

Anti-Cancer Activity
The EOs and extracts of several Corymbia species have been shown to have cytotoxic and anti-proliferative effects in a range of different cancers.The EO of C. citriodora has been shown to exhibit anti-proliferative effects against leukaemia THP-1 cells [84] and cytotoxicity against lung cancer A-549, prostate cancer PC-3, glioblastoma T98G, breast cancers T47D and MCF-7, colon cancer HCT-116 and liver cancer Hep G-2 cells [57,76].The fruit EO of C. citriodora also showed cytotoxic activity in A549, HeLa and CHOK1 cells [85].In a like manner, the leaf and fruit EOs of C. torelliana were also observed to have cytotoxicity toward PC-3, Hep G2, Hs 578T and MDA-MB-231 cell lines [111].
Anti-proliferative effects have been observed in the aqueous extracts of C. citriodora and C. maculata leaves against PaCa-2 cells [30].The aqueous fraction obtained from the EtOH extract of C. citriodora kino was observed to inhibit cell growth and induce apoptosis in Hep G2 cells [41].The EtOAc kino extract of C. citriodora and its major constituent, flavonoid 30 (Figure 14

Anti-Cancer Activity
The EOs and extracts of several Corymbia species have been shown to have cytotoxic and anti-proliferative effects in a range of different cancers.The EO of C. citriodora has been shown to exhibit anti-proliferative effects against leukaemia THP-1 cells [84] and cytotoxicity against lung cancer A-549, prostate cancer PC-3, glioblastoma T98G, breast cancers T47D and MCF-7, colon cancer HCT-116 and liver cancer Hep G-2 cells [57,76].The fruit EO of C. citriodora also showed cytotoxic activity in A549, HeLa and CHOK1 cells [85].In a like manner, the leaf and fruit EOs of C. torelliana were also observed to have cytotoxicity toward PC-3, Hep G2, Hs 578T and MDA-MB-231 cell lines [111].
Anti-proliferative effects have been observed in the aqueous extracts of C. citriodora and C. maculata leaves against PaCa-2 cells [30].The aqueous fraction obtained from the EtOH extract of C. citriodora kino was observed to inhibit cell growth and induce apoptosis in Hep G2 cells [41].The EtOAc kino extract of C. citriodora and its major constituent, flavonoid 30 (Figure 14

Anti-Diabetic Activity
Very few studies have investigated the anti-diabetic properties of Corymbia species; however, recent studies have shown the leaves of C. citriodora may have potential for utility in this area.Betulinic acid 33 and corosolic acid 34 (Figure 15) isolated from the aqueous extract of C. citriodora were shown to enhance GLUT-4 translocation activity by 2.38and 1.78-fold, respectively, in vitro [51].Further research on the aqueous extracts of C. citriodora leaves has shown their ability to stimulate insulin production and glucose uptake in BRIN-BD11 clonal pancreatic β-cell cells, islets of Langerhans and in high-fat-fed rats [83].Another study performed in alloxan-induced diabetic mice revealed that treatment with C. citriodora aqueous extracts significantly lowered blood glucose levels, comparable to the levels observed in the glibenclamide control [80].Most recently, the EtOH extract of C. citriodora leaves was shown to have significant anti-diabetic and insulinotropic activity in BRIN-BD11 cells, islets of Langerhans and in a high-fat-fed rat model [21], underscoring the need for further research into the anti-diabetic potential of other Corymbia spp.and the molecular targets through which the C. citriodora aqueous extracts exert activity.

Other Biological Activity
The extracts of Corymbia species have been observed to have a broad spectrum of bioactivities and effects.The EO of C. citriodora leaves is well known for its mosquito repellence activity, particularly through its major constituent, citronellal [87,161,162].More recently, isomers of p-menthane-3,8-diol isolated from the leaves of C. citriodora have also been shown to have repellent activity against A. gambiae mosquitoes [43].Various field trials investigating C. citriodora mosquito repellence have been performed using live plants

Anti-Diabetic Activity
Very few studies have investigated the anti-diabetic properties of Corymbia species; however, recent studies have shown the leaves of C. citriodora may have potential for utility in this area.Betulinic acid 33 and corosolic acid 34 (Figure 15) isolated from the aqueous extract of C. citriodora were shown to enhance GLUT-4 translocation activity by 2.38-and 1.78-fold, respectively, in vitro [51].Further research on the aqueous extracts of C. citriodora leaves has shown their ability to stimulate insulin production and glucose uptake in BRIN-BD11 clonal pancreatic β-cell cells, islets of Langerhans and in high-fatfed rats [83].Another study performed in alloxan-induced diabetic mice revealed that treatment with C. citriodora aqueous extracts significantly lowered blood glucose levels, comparable to the levels observed in the glibenclamide control [80].Most recently, the EtOH extract of C. citriodora leaves was shown to have significant anti-diabetic and insulinotropic activity in BRIN-BD11 cells, islets of Langerhans and in a high-fat-fed rat model [21], underscoring the need for further research into the anti-diabetic potential of other Corymbia spp.and the molecular targets through which the C. citriodora aqueous extracts exert anti-diabetic activity.

Anti-Diabetic Activity
Very few studies have investigated the anti-diabetic properties of Corymbia species; however, recent studies have shown the leaves of C. citriodora may have potential for utility in this area.Betulinic acid 33 and corosolic acid 34 (Figure 15) isolated from the aqueous extract of C. citriodora were shown to enhance GLUT-4 translocation activity by 2.38and 1.78-fold, respectively, in vitro [51].Further research on the aqueous extracts of C. citriodora leaves has shown their ability to stimulate insulin production and glucose uptake in BRIN-BD11 clonal pancreatic β-cell cells, islets of Langerhans and in high-fat-fed rats [83].Another study performed in alloxan-induced diabetic mice revealed that treatment with C. citriodora aqueous extracts significantly lowered blood glucose levels, comparable to the levels observed in the glibenclamide control [80].Most recently, the EtOH extract of C. citriodora leaves was shown to have significant anti-diabetic and insulinotropic activity in BRIN-BD11 cells, islets of Langerhans and in a high-fat-fed rat model [21], underscoring the need for further research into the anti-diabetic potential of other Corymbia spp.and the molecular targets through which the C. citriodora aqueous extracts exert anti-diabetic activity.

Other Biological Activity
The extracts of Corymbia species have been observed to have a broad spectrum of bioactivities and effects.The EO of C. citriodora leaves is well known for its mosquito repellence activity, particularly through its major constituent, citronellal [87,161,162].More recently, isomers of p-menthane-3,8-diol isolated from the leaves of C. citriodora have also been shown to have repellent activity against A. gambiae mosquitoes [43].Various field trials investigating C. citriodora mosquito repellence have been performed using live plants [163], burning leaves [164,165], leaf EOs [166] and a mosquito repellent product

Other Biological Activity
The extracts of Corymbia species have been observed to have a broad spectrum of bioactivities and effects.The EO of C. citriodora leaves is well known for its mosquito repellence activity, particularly through its major constituent, citronellal [87,161,162].More recently, isomers of p-menthane-3,8-diol isolated from the leaves of C. citriodora have also been shown to have repellent activity against A. gambiae mosquitoes [43].Various field trials investigating C. citriodora mosquito repellence have been performed using live plants [163], burning leaves [164,165], leaf EOs [166] and a mosquito repellent product (Quwenling) [167]; however, only moderate effectiveness has been observed.This lack of effectiveness is due to the volatility of citronellal and other mosquito-repellent components of the leaf EOs, which only protect individuals for the first hour of use [168].Additionally, one field trial indicated that biting midges (Culicoides imicola) were attracted to test sites using a mosquito repellent based on C. citriodora [166].
A recent study into the aqueous extracts of C. citriodora leaves and branches showed they had the capacity to detoxify mycotoxins aflatoxins B 1 and B 2 , both in vitro and in vivo in brine shrimp (Artemia salina) larvae [86].The acetone leaf extract of C. citriodora has also been observed to significantly delay the loss of climbing ability and reduce oxidative stress in transgenic Drosophila expressing h-αS in the neurons, suggesting that Corymbia spp.could have potential applications in the treatment of neurological diseases, such as Parkinson s disease [88].
Given the ethnomedical use of C. citriodora leaves as a remedy for diarrhoea, the leaf EO of C. citriodora was tested and found to have significant anti-spasmodic effects in rats experiencing acetylcholine-induced contraction of the ileum [29].Leaf and stem bark extracts of C. torelliana have also been shown to have gastroprotective and anti-secretory activities in rats induced with EtOH/HCl, illustrating the diversity of biological activities observed in Corymbia species and their potential for the discovery of new treatments for common ailments [118].

Conclusions and Future Directions
This review has provided the first summary of the ethnopharmacology, phytochemistry and biological activities of the Corymbia genus.Of the 115 species of the Corymbia genus, 14 species were found to have ethnomedical uses for the leaves, kino and bark.Corymbia citriodora was the most studied species, followed by C. maculata and C. torelliana.Outside of these three species, no more than four references on bioactivities were found for any of the other 112 species of the Corymbia genus, revealing the current dearth of study into these species and their potential medicinal uses.
The leaf EOs of Corymbia spp.were found to differ greatly in chemical compositions and exerted a broad spectrum of biological activities.The leaf EO of C. citriodora in particular was shown to have excellent antiseptic, anti-microbial, insecticidal, anti-inflammatory, anti-oxidant and anti-cancer properties, making this an ideal product for further development and commercialisation as a lemon-scented alternative to Eucalyptus oil.Due to the variability observed in leaf EO composition, further studies would be required to standardise these mixtures to ensure consistent chemical compositions are obtained.Additional research analysing the EOs from other unstudied Corymbia spp.and EOs from other parts of the plant could also be fruitful in the development of commercial products with more specific uses (e.g., insecticidal EOs, anti-septic EOs or anti-inflammatory EOs) based upon the major constituents of the EOs and their key bioactivities.
The crude extracts of Corymbia spp.were also reported to exhibit even more broad bioactivities than the EOs, providing another area for further investigation.Of particular note are the potent anti-diabetic effects observed in the aqueous extracts of C. citriodora, supporting the ethnomedicinal use of these extracts in treating diabetes.These promising preliminary results observed in multiple in vivo models warrant investigations in phase I clinical trials as a crude mixture and further isolation to identify additional anti-diabetic lead compounds.
The low micromolar anti-plasmodial activities observed for eucalyptin 6, myciaphenone A 7 and flavonoid glycosides 8-12 against L. donovani and for torellianones C-F 13-16, ficifolidones 17-18, kunzeanone A 19 and intermedianones A, B and F 20-22 against P. falciparum emphasise the potential of Corymbia spp. as a source of anti-plasmodial lead compounds.Additional investigations are required to better define molecular targets and produce SARs for these anti-plasmodial lead compounds prior to preclinical trials.
The potent anti-viral activity of the novel compounds citriodolic acids A-C 23-25, citrioside A 26 and quercetin-3-O-α-L-rhamnoside 27 (isolated from the leaves of C. citriodora) against RSV merit additional investigations to elucidate modes of action and determine treatment efficacy in vivo.Additional research for further lead compound discovery and screening for anti-viral activity in other common viral pathogens could also be invaluable avenues for further exploration.
Overall, this review has provided a preliminary summary of the ethnopharmacology, phytochemistry and bioactivities of the Corymbia genus, highlighting the potential for these species to provide lead compounds to treat a host of common medical conditions.Since the extraordinary bioactivities of less than one fifth of the 115 Corymbia spp.have been studied previously, the question is this: what else is waiting to be discovered?
key monoterpenoids in the leaf EOs of many Corymbia species, including C. eximia, C. intermedia, C. maculata, C. polycarpa and C. torelliana.Both C. bleeseri and C. gummifera produce bicyclogermacrene and β-caryophyllene as the key components of their leaf EOs.Distinct major constituents are also observed in the leaf EOs of C. calophylla (γterpinene and (E,E)-farnesol) and C. tessellaris (aromadendrene and globulol), highlighting the extreme variability observed in leaf EO compositions.

Figure 2 .
Figure 2. A comparison of the number of research articles reported on Corymbia species.Other species* refers to C. blesseri, C. eximia, C. intermedia, C. papuana, C. terminalis and C. tessellaris which had

Figure 2 .
Figure 2. A comparison of the number of research articles reported on Corymbia species.Other species* refers to C. blesseri, C. eximia, C. intermedia, C. papuana, C. terminalis and C. tessellaris which had one reference each.No publications were reported for C. dichromophloia and C. opaca (excluding ethnomedical uses).

Figure 3 .
Figure 3.The number of references reported for ethnomedically significant Corymbia species, analysed according to (A) plant part studied and (B) biological activities investigated.Extracts of C. citriodora have been studied to a lesser degree than leaf EOs, but they have been shown to possess anti-fungal activity.The petroleum ether leaf extract of C. citriodora has been shown to possess moderate inhibitory and fungicidal activity against A. flavus and A. parasiticus[58].Compounds, including 7-O-methylaromadendrin 1, 7-Omethylkaempferol 2 and ellagic acid 3, isolated from the kino of C. citriodora (Figure4) have also been shown to have varying anti-fungal activities against P. notatum, A. niger and F. oxysporium[54].

Figure 3 .
Figure 3.The number of references reported for ethnomedically significant Corymbia species, analysed according to (A) plant part studied and (B) biological activities investigated.

Figure 4 .
Figure 4. Three flavonoids isolated from the kino of C. citriodora which exhibited anti-fungal activity [54].

Plants 2023 ,Figure 6 .
Figure 6.Flavonoids and flavonoid glycosides isolated from the leaves of C. maculata and their antileishmanial activity against L. donovani [96].

Figure 6 .
Figure 6.Flavonoids and flavonoid glycosides isolated from the leaves of C. maculata and their anti-leishmanial activity against L. donovani [96].

Figure 8 .
Figure 8. Intermedianones A, B and D 20-22 isolated from the flowers of C. intermedia and their antiplasmodial activities against P. falciparum 3D7 [19].

Figure 8 .
Figure 8. Intermedianones A, B and D 20-22 isolated from the flowers of C. intermedia and their antiplasmodial activities against P. falciparum 3D7 [19].

Figure 8 .
Figure 8. Intermedianones A, B and D 20-22 isolated from the flowers of C. intermedia and their anti-plasmodial activities against P. falciparum 3D7 [19].

Figure 9 .
Figure 9. Citriodolic acids A-C 23-25 isolated from the leaves of C. citriodora and their anti-viral activities against RSV [50].

Figure 11 .
Figure 11.Flavanols isolated from the kino of C. citriodora and their in vitro inhibitory activities against 15-LOX [49].

Figure 12 .
Figure 12.Ellagic acid 3, isolated from the leaves of C. citriodora, exhibited potent anti-inflammatory and gastroprotective properties in an EtOH-induced gastric ulcer mouse model [39].

Table 3 .
Major constituents of the EOs isolated from the leaf, twig, fruit and/or flowers in C. citriodora and C. torelliana.Values are expressed as percentages of total EO content.

Table 3 .
Major constituents of the EOs isolated from the leaf, twig, fruit and/or flowers in C. citriodora and C. torelliana.Values are expressed as percentages of total EO content.