Gardenia ternifolia Schum. & Thonn. (Rubiaceae): Review of medicinal uses, phytochemistry and biological activities

Gardenia ternifolia Schum. & Thonn. is a shrub or small tree widely used as a traditional medicine throughout its distributional range in tropical Africa. Gardenia ternifolia is widespread in tropical Africa, extending from Senegal eastwards to Ethiopia and Kenya, through the Democratic Republic of Congo (DRC) southwards to Namibia, South Africa and Mozambique. This study was aimed at providing a critical review of the medicinal uses, phytochemistry and biological activities of G. ternifolia. Documented information on the medicinal uses, phytochemistry and biological activities of G. ternifolia was collected from several online sources which included Scopus, Google Scholar, PubMed and Science Direct. Additional information was gathered from pre-electronic sources such as book chapters, books, journal articles and scienti ic publications obtained from the university library. This study showed that the species is widely used as an aphrodisiac and protective charm, and traditional medicine for headache, migraine, respiratory infections, sore eyes, hypertension, diabetes, gastro-intestinal problems, erectile dysfunction, malaria, convulsions and epilepsy. Phytochemical compounds identi ied from the species include alkaloids, anthocyanins, coumarins, lavonoids, phenols, quinones, saponins, steroids, stereoisomeric neolignans, tannins and terpenoids. Pharmacological research revealed that G. ternifolia extracts and compounds isolated from the species have antibacterial, antiviral, anti-in lammatory, antileishmanial, antioxidant, antiplasmodial, antisickling, antitheilerial, hepatotoxicity, larvicidal and cytotoxicity activities. Future research on G. ternifolia should focus on detailed phytochemical evaluations, including toxicological, in vivo and clinical studies to corroborate the traditional medical applications of the species.


INTRODUCTION
Gardenia ternifolia Schum. & Thonn. is a shrub or small tree belonging to the Rubiaceae family. The genus Gardenia J. Ellis comprises of about 140 species recorded in Africa, Madagascar, East and Southeast Asia, western Paci ic and Hawaiian islands (Wong and Low, 2011). The genus name is in honor of Alexander Garden (1730-1791), a Scottish physician, botanist and zoologist who lived in Charleston, South Carolina and was a correspondent of Carl Linnaeus. The species name "ternifolia" is derived from the Latin word "ternifolius" which means leaves in threes. Three infra speci ic taxa of G. ternifolia are recognized, and these include G. terni-folia subsp. jovis-tonantis (Welw.) Verdc., G. ternifolia subsp. jovis-tonantis var. jovis-tonantis (Welw.) Aubrév., G. ternifolia subsp. jovis-tonantis var. goetzei (Stapf & Hutch.) Verdc., and G. ternifolia subsp. ternifolia (Verdcourt, 1979). In ethnobotanical literature, the infra speci ic taxa of G. ternifolia are rarely mentioned (Gelfand et al., 1985) therefore, in this study, G. ternifolia sensu lato is used throughout the manuscript. The bark of G. ternifolia is grey to yellowish-brown in color, smooth or slightly rough and peeling off in round pieces in thicker and older trees. The leaves are usually in whorls of three, clustered near the ends of short rigid branchlets.
The lowers are white to yellow while the fruits are oval, inely velvety and yellowish-brown in color. Gardenia ternifolia is widespread in tropical Africa, extending from Senegal eastwards to Ethiopia and Kenya, through the Democratic Republic of Congo (DRC) southwards to Namibia, South Africa and Mozambique (Hutchings et al., 1996). Gardenia ternifolia has been recorded in poor, rocky, compacted sandy and laterite soils, in wooded grassland, on kopjes, termite mounds, along streams and seasonally inundated vleis at sea level to 2100 m above sea level. The branches of G. ternifolia are used as toothbrushes while the young leaves are cooked as leafy vegetables in west Africa. The fruits of G. ternifolia are sold as traditional medicines in informal herbal medicine markets in South Africa. It is, therefore, within this context that the current study was undertaken aimed at documenting the pharmacological properties, phytochemistry and medicinal uses of G. ternifolia.

MATERIALS AND METHODS
Results of the current study are based on a literature search on phytochemistry, pharmacological properties and medicinal uses of G. ternifolia using information derived from several internet databases. The databases included Scopus, Google Scholar, PubMed and Science Direct. Other sources of information such as pre-electronic sources which included journal articles, theses, books, book chapters and other scienti ic articles were gathered from the university library.

Medicinal uses of Gardenia ternifolia
The aerial parts, bark, fruit and roots of G. ternifolia are mainly used as an aphrodisiac and protective charm, and traditional medicine for headache, migraine, respiratory infections, sore eyes, hypertension, diabetes, gastro-intestinal problems, erec-tile dysfunction, malaria, convulsions and epilepsy (Table 1, Figure 1). Other medicinal applications of G. ternifolia that have been recorded in two countries and supported by at least two literature records include the use of the species as ethnoveterinary medicine in Cameroon and Ethiopia, and traditional medicine for earache in South Africa and Zimbabwe, infertility (Benin and Zimbabwe), insanity (Malawi and Uganda), sexually transmitted infections (Ghana and Guinea), skin infections (Ghana and Guinea) and snake bites (Kenya and Uganda) ( Table 1).

Nutritional and phytochemical composition of Gardenia ternifolia
Several researchers investigated the nutritional and phytochemical properties of G. ternifolia (Table 2 ). A wide variety of nutrients associated with different plant parts of G. ternifolia (Table 2) imply that the species could be a source of health-promoting nutrients such as calcium, carbohydrates, copper, crude ibre, fat, iron, magnesium, phosphorus, potassium, proteins, sodium and zinc. Phytochemical compounds identi ied from the aerial parts, fruits, leaves, roots and stem bark of G. ternifolia include alkaloids, anthocyanins, coumarins, lavonoids, phenols, quinones, saponins, steroids, stereoisomeric neolignans, tannins and terpenoids. Some of these chemical compounds may be responsible for the biological activities of the species.

Biological activities of Gardenia ternifolia
Pharmacological research revealed that different extracts of G. ternifolia and compounds isolated from the species have various biological activities such as antibacterial, antiviral, anti-in lammatory, antileishmanial, antioxidant, antiplasmodial, antisickling, antitheilerial, hepatotoxicity, larvicidal and cytotoxicity activities.  (Ngbolua et al., 2014) Aphrodisiac and erectile dysfunction

Leaves and roots
Cameroon and Ethiopia (Yineger and Yewhalaw, 2007;Tsobou et al., 2013) Antibacterial activities (Silva et al., 1996) evaluated the antibacterial activities of ethanol extract of G. ternifolia roots against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Shigella dysenteriae, Salmonella typhimurium, Streptococcus faecalis, Vibrio cholera, Campylobacter jejuni, Campylobacter coli and Staphylococcus aureus using agar diffusion method. The extract exhibited activities against Campylobacter jejuni, Campylobacter coli and Staphylococcus aureus with zones of inhibition ranging from 9.0 mm to 14.0 mm (Silva et al., 1996). (Magassouba et al., 2007) evaluated the antibacterial activities of methanol extract of G. ternifolia root bark mixed with those of Swartzia madagascariensis Desv., Isoberlinia Doka Craib & Stapf, Annona senegalensis Pers., Terminalia glaucescens Planch. Ex Benth., and leaves of Erythrina senegalensis DC. against Staphylococcus aureus using broth dilution method with rifampicin as a positive control. The extract exhibited activities against tested pathogens with minimum inhibitory concentration (MIC) value of 62.5 µl/ml (Magassouba et al., 2007). (Pesewu et al., 2008) evaluated the antibacterial activities of ethanol, water, chloroform and blender extracts of G. ternifolia leaves against Escherichia coli, Staphylococcus aureus, Proteus Vulgaris, Pseudomonas aeruginosa and Streptococcus pyogenes using agar-well diffusion and microdilution methods. The ethanol, water and blender extracts exhibited activities against Staphylococcus aureus and Streptococcus pyogenes with inhibition zones ranging from 8.0 mm to 18.0 mm, and MIC and minimum bactericidal concentration (MBC) values ranging from 12.5 mg/ml to >50.0 mg/ml (Pesewu et al., 2008). (Ngbolua et al., 2014) evaluated the antibacterial activities of anthocyanins and organic acids isolated from G. ternifolia leaves against Lactobacillus fermentum, Staphylococcus aureus, Enterococcus faecalis, Salmonella typhimurium and Escherichia coli using agar disc diffusion and broth micro-dilution methods. The anthocyanin and organic acid extracts exhibited activities with MIC and MBC values ranging from 62.5 µg/mL to >500.0 µg/mL (Ngbolua et al., 2014). (Roger et al., 2015) evaluated the antibacterial activities of ethanol extract of G. ternifolia bark against Salmonella typhi and Salmonella paratyphi using agar well diffusion and microdilution methods with cipro loxacin (10.0 µl/ml) as a positive control. The extract exhibited weak activities against Salmonella typhi with inhibition zone ranging from 9.5 mm to 11.0 mm, MIC value of 512.0 µl/ml and MBC value of 2048.0 µl/ml (Roger et al., 2015). (Silva et al., 1997) evaluated the antiviral activities of ethanol extract of G. ternifolia roots against Herpes simplex virus type 1 (HSV-1) and African swine fever virus (ASFV). The extract exhibited activities with HSV-1 and ASFV exhibiting inhibition effect of 60.0% and 80.0%, respectively. (Larsen et al., 2015) evaluated the antiin lammatory activities of ethanol extract of G. ternifolia leaves using the cyclooxygenase-1 assay.

Antioxidant activities
Antiplasmodial activities (Ochieng et al., 2010) evaluated the anti-plasmodial activities of acetone and methanol extracts of G. ternifolia aerial parts and the compounds naringenin-7- 4, isolated from the aerial parts of the species against chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum using an automated microdilution technique with crude extract of Artemisia annua and chloroquine as positive controls. The extracts and the compounds β-sitosterol, quercetin-4,7-O-dimethyl ether, kaempferol-7-O-methyl ether and naringenin-7-Omethyl ether exhibited activities with IC 50 values ranging from 0.9 µg/mL to 17.0 µg/mL (Ochieng et al., 2010). Nureye et al. (2018) evaluated the antiplasmodial activities of methanol crude extract, aqueous, butanol and chloroform fractions of G. ternifolia root bark using a 4-day suppressive test against Plasmodium berghei (ANKA strain) in Swiss albino mice. The chemo suppressive effect exerted by the crude extract and fractions ranged from 14.0% to 59.0% (Nureye et al., 2018). (Mpiana et al., 2015) evaluated the antisickling activities of methanol and ethyl acetate fractions, and anthocyanin crude extracts of G. ternifolia leaves on sickle erythrocytes by the Emmel's test. The extracts exhibited antisickling activities (Mpiana et al., 2015). (Ngbolua et al., 2014) evaluated the antisickling activities of anthocyanins, and organic acids isolated from G. ternifolia leaves using Emmel. The anthocyanin and organic acid extracts exhibited activities with normalization rates ranging from 68.0% to 72.0% at a concentration of 6.25 µg/mL (Ngbolua et al., 2014). (Hayat et al., 2012) evaluated the antitheilerial activities of aqueous extracts of G. ternifolia fruits against Theileria lestoquardi using the lymphocyte cells infected with the parasite. The extract exhibited activities against Theileria lestoquardi macroschizonts.

CONCLUSIONS
Some reports in the literature indicate that the roots of G. ternifolia could be poisonous. Therefore, there is a need for detailed clinical and toxicological evaluations of crude extracts and compounds isolated from the species. Therefore, the use of G. ternifolia as traditional medicine for the treatment of human diseases and ailments should be treated with caution and rigorous toxicological and clinical studies are recommended.

ACKNOWLEDGEMENT
I am grateful to the reviewers who kindly commented on my manuscript.