Abstract

INTRODUCTION

The plant kingdom is an inexhaustible resource, exploited since antiquity for therapeutic remedies. This is possible through the utilization of qualitative ethnobotanical data, which provide ethnopharmacological leads.[1] Most chemical entities from combinatorial and computational chemistry have their origin in molecules from the plant kingdom. Herbal formulations are ubiquitous as health care products and are the most patronized resource in developing countries due to their proven safety, inexpensiveness, efficacy, and availability. Globally, many medicinal plants with PDE-5 inhibitors or aphrodisiac activity have been reported.[2,3] Many plants with aphrodisiac potential have been reviewed in West and Southern Africa.[4,5] One such plant, named in many reports, is Carpolobia of the Polygalaceae family, more particularly the two species Carpolobia alba (CA) and Carpolobia lutea (CL).[6,7,8]

Polygalaceae, the “milkwort” family, belongs to the order Fabales and has over 800 species distributed in 12-20 genera.[9] Extensive phylogenetic analysis of Fabales has revealed interfamilial relationships and patterns of floral evolution;[10] the roles of biotic and abiotic factors in the evolution of ant dispersal in the milkwort family has been reported.[11] The Polygalaceae family is divided into three tribes: Xanthophylleae, Moutabeae, and Polygalae; Polygalae is the most important because it is a well-researched genus and represents about half of the members of this family. The genus Polygala has a cosmopolitan geographical distribution except in New Zealand, Polynesia, and the Antarctic zone; Polygalaceae from West and Southern Africa belong to the genera Atroxima, Polygala, Carpolobia, Muraltia, and Securidaca.[9] A review of the chemistry and the biological activities of Polygalaceae saponins have been reported.[9]

CARPOLOBIA

The genus Carpolobia is well-known across West and Southern Africa; it has over 14 species. They are Carpolobia afzeliana, CA, Carpolobia caudate, Carpolobia conradsiana, Carpolobia delvauxii, Carpolobia dubia, Carpolobia glabrescens, Carpolobia goetzei, Carpolobia leandriana, CL, Carpolobia macrostachya, Carpolobia suaveolens, Carpolobia versicolor, and Carpolobia zenkeri.[12] Ten of these species are native to tropical West Africa.[12] Of all these species, only two species, CA and CL, have been pharmacologically and phytochemically investigated and reported. CA from natural forest habitat is shown in Figure 1a and the flower is shown in Figure 1b.

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Figure 1

(a) Carpolobia lutea. from forest natural habitat. (b) Flower of Carpolobia lutea G. Don(Abstracted from “Aphrodisiacs from Around the World” (juanwhite.com). Original illustration from flower wholesaler trade association

Carpolobia is a popular aphrodisiac herbal medicine, and various studies reporting on the plant have described the following activities: curing male sterility; increasing libido; induction of penile erection; enhancement of aphrodisiac prowess; enhancement of virility and male fertility; and augmentation of male sexual functions.[6,8,13,14,15,16] Terpenoids from the leaf essential oil of CL,[17] polyphenols from the leaf,[17] and triterpenoid saponins from the root[18] have been isolated.

Biodiversity surveys indicate that CA and CL shrubs are native to West and Central Africa.[14,15,19,20,21,22,23] Among the Pygmies of Cameroon, Ipassa of Garbon; and the Yoruba, Ibo, Efik, and Ijaw peoples of Nigeria, Carpolobia is patronized for its effect of boosting libido.[14,15,17] The chewing sticks prepared from the stem and root of CA and CL are expensive because men use them to boost their sexual performance. In addition, the stem bark is used to cure headaches and general pain, and to stave off sleepiness due to fatigue. To release its aphrodisiac power, the root is soaked in water for a week and ingested. Though Carpolobia is a popular aphrodisiac, there are no scientific data reviewing reports of its biopharmacological and phytochemical properties.[9]

To execute this review, books, postgraduate theses, graduate dissertations, and peer-reviewed journals were consulted. Besides, systematic database searches of SCOPUS, ScienceDirect, PubMed, Web of Knowledge, Science Citation Index, Google Scholar, and MEDLINE were conducted using keywords such as “aphrodisiacs,” “erectile dysfunction,” “infertility,” “fertility,” and “sterility” in relation to “Carpolobia,” “CA", and “CL” for the last 15 years, and they formed the basis of the current analysis. The aim of this work is to collate all available published scientific reports in the literature on Carpolobia in a review paper.

GEOGRAPHICAL DISTRIBUTION

Carpolobia biodiversity is found in the Republic of Sierra Leone, Liberia, Republic of Côte d’Ivoire, the Republic of Ghana (formerly the Gold Coast), Togo, Southern Nigeria, the Republic of Benin (Dahomey), and Cameroon (British Cameroons). CL is a small tree distributed in West and Central tropical Africa. It grows in rainforests and the Guinea Savannah area from Sierra Leone to Cameroon between April and September. CL is called “cattle stick” (English), “Ikpafum” (Ibibio), “Agba” or “Angalagala” (Igbo), and “Egbo Oshunshun” (Yoruba) in Nigeria.[24]

Phytochemistry, phytochemical screenings, and isolated compounds

The chemical screening of the stem revealed the presence of tannins, saponins, flavonoids, cardiac glycosides, and anthraquinones.[21] Alkaloids in detectable quantity, saponins, and cardenolides were detected in the plant extract.[29] Phytochemical screenings confirmed the presence of tannins, saponins, and flavonoids.[30] The phytochemical screening of the methanolic root of CL revealed the presence of saponins, anthraquinones, flavonoids, cardiac glycosides, simple sugars, and terpenes; it was found to be devoid of alkaloids and tannins.[31,32] The preliminary phytochemical screening of CL ethanolic leaf extract revealed alkaloids, saponins, tannins, anthraquinone, cardiac glycosides, and flavonoids.[33] Phytochemical screening of the root methanolic extract revealed the presence of tannins, saponins, flavonoids, cardiac glycosides, anthraquinones, and terpenes; alkaloids were absent.[34]

The hydrodistillation of the leaf using a Clevenger-type apparatus afforded a yield of essential oil (0.06-0.10%), which contained terpenoids, hexahydro farnesyl acetone, (E)-geranyl acetone, (E)-2-decenal, farnesyl acetone, germacrene B, and α-calacorene.[7] Chromatographic fractionation of the ethyl acetate fraction (EAF) afforded two new cinnamonyl 1-deoxy-glucopyranosides (1 and 2) and two new p-coumaroyl 1-deoxy-glucopyranosides (4 and 5), besides cinnamic acid (3) [Figure 2].[17] Three new acetylated triterpene saponins were isolated from the roots of CA and CL.[19]

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Figure 2

Structures of isolated compounds from C. lutea ethyl acetate leaf fraction

Antioxidants, ionic, and amino acid profile

Nwidu et al.,[42] observed minimal radical-scavenging activity in a spectrophotometric assay using 2, 2-diphenyl-1- picrylhydrazyl (DPPH) of all the leaf and stem fractions investigated. The elemental profile was established by the inductively coupled argon-plasma emission spectrometer and the ionic analyses by potentiometric titration, which revealed the most abundant cations in the aqueous leaf extract to be potassium and phosphorus, while the most abundant anion was phosphate. But higher values of potassium, phosphorus, sulfate in the leaf and a lower amount of sulfate ions were observed in the stem extract.[37] Amino acid analysis by cation-exchange chromatography with automated amino acid analyzer revealed proline, alanine, serine, valine, glycine, glutamate, and lysine in the ethanol fraction, and lysine, phenyl alanine, glycine, and serine in the ethyl acetate fraction, but not in the nonpolar fractions n-hexane and chloroform. The ethyl acetate fraction indicated an abundant amount of lysine, phenyl alanine, glycine, and serine compared to the other leaf fractions. The pH of the aqueous leaf extract is 3.17 ± 0.08 and that of the stem extract is 4.06 ± 0.05.[42]

Neuropharmacological evaluations

The ethyl acetate fraction of the leaf extract revealed a dose-dependent, significant prolongation of sleeping time duration but no effect on sleeping time latency; a decrease in locomotor activity and 60% and 40% protection in instances of PTZ- and strychnine-induced convulsions in mice, respectively, were observed. The effects of the chloroform, n-hexane, and ethanol fractions were not as significant compared to the ethyl acetate fraction.[43]

Antidiabetic and hypolipidemic effects

The antidiabetic activity of CL ethanolic leaf extract was observed to be comparable to that of glibenclamide. Besides, a considerable decrease in serum total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol, and an increase in high-density lipoprotein (HDL) cholesterol were reported; the results suggest that the leaf extract of CL has antidiabetic and hypolipidemic effects.[44]

Toxicological evaluations

CA subchronic administration for 60 days indicated no toxicological effects on all parameters evaluated, including reproductive toxicity.[8] The median lethal dose (LD₅₀) of the crude ethanolic leaf extract of CL, as determined by Nwafor and Bassey,[30] is 2449.49 mg/kg body weight. Ettebong et al.[32] reported the LD₅₀ of the methanolic root extract, using Lorke's method, as 70.7 mg/kg body weight, with signs of toxicity such as excitation, gasping for breath, paw-licking, reduced movement, high respiratory rate, tonic-clonic convulsion, and death. Nwidu et al.,[45] reported the acute toxicity (LD₅₀) as 3850.0 mg/kg, 3240.4 mg/kg, and 1414.2 mg/kg for the ethanol fraction, crude ethyl acetate extract, and ethyl acetate leaf fractions, respectively. Nwidu et al.[46] estimated the LD₅₀ of the ethanolic stem extract as 866.025 mg/kg (i.p.). Taken together, the data from acute toxicity studies indicate the median lethal doses of the root > stem > leaves.[31,33,37] This moderate toxicity may have encouraged the local users in the age-long use of the plant for family planning and for its parasitic effects.[38,40] The subacute and subchronic toxicity reports showed an impingement on biochemical but not hematopoietic parameters.[45,46] These studies on Carpolobia are summarized in Tables ​Tables11 and ​and22.

Table 1

Species of Carpolobia, morphology, parts used, and reports of ethnomedicinal uses

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Table 2

Species of Carpolobia, phytochemical and pharmacology reports

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DISCUSSION AND CONCLUSION

Carpolobia enjoys extensive patronage as a herbal resource because of its aphrodisiac potential. The floral part is rich in saponins; a recent study indicated that the root extract has a high amount of saponins (21.02 mg/L) compared to other bioactive phytochemicals such as anthraquinones (5.11 mg/L), alkaloids (2.93 mg/L), flavonoids (1.82 mg/L), tannins (0.91 mg/L), and cardiac glycosides (0.09 mg/L).[6] This report corroborates the isolation and structural elucidation of triterpenoid saponins from both CL and CA by Mitaine-Offer et al.[19] However, triterpenoid saponins have been isolated from other members of the Polygalaceae family by Wang et al.[47] and reviewed by Lacaille-Dubois and Mittaine-Offer.[9] Though there is no report on the bioactivity-guided isolation of saponin-mediating aphrodisiac activity in Carpolobia, for other members of the Polygalaceae family such as Securidaca longipedunculata, bioactivity-guided study led to the isolation of xanthones, which mediates the relaxation of the corpus cavernosum, justifying ethnomedicinal usage in the treatment of erectile dysfunction in South Africa.[48]

The reported bioactivities of the saponins were extensively reviewed and the following were found: permeabilization of the cell membrane, stimulation of luteinizing hormone release leading to abortifacient properties, immunomodulatory potential;[49,50] antibacterial properties;[51,52] antioxidant properties,[53,54] antidiabetic properties, and anti-obesity properties;[55] protection against gastroenteritic disease;[56] moderate antibacterial activity against the Gram-positive organism Enterococcus faecalis;[57] molluscicidal, antifungal, and antiparasitic activities.[58,59] Other therapeutic properties of saponins reported in the literature include: cardioprotective effects against P. japonicus,[60] antithrombotic activity against Dioscorea zingiberensis[61] and anti-inflammatory and antiulcerogenic properties against the bulbs of A. ampeloprasum.[62] Reviews of saponin-mediated effects are observed in some pharmacological reports on Carpolobia, but bioactivity-guided studies will be required to fill this gap.

In sum, the pharmacological studies of Carpolobia reveal antitrypanosomal and antileishmanial properties[37] antiplasmodial and antimalarial properties,[38,39] contraceptive, estrogenic, and antiestrogenic properties,[13,32] antiulcerogenic and antidiarrheal properties,[30,36,37] gastroprotective effect,[33] antinociceptive properties,[17] anti-inflammatory and antipyretic effects,[41] antidiabetic and hypolipidemic effects,[44] antimicrobial properties,[31,35] antioxidants and amino acid profile,[42] and analgesic activity,[44] which reflects reviews of saponin biological activities. But no aphrodisiac activities,[6,8,13,14] antihemorrhoidal properties,[63] or neuropharmacological effects[43] were seen among the reviewed effects of the saponins.

Polyphenols have been isolated from the leaf extract.[17] However, aphrodisiac activity was revealed with polyphenols isolated from Mimosa pudica and Cydonia oblonga.[64,65,66] Recently, several terpenoids have been hydrodistilled from the leaf of CL[7] The reviewed bioactivity of terpenoids encompasses: cancer chemopreventive, antimicrobial, antifungal, antiparasitic, antiviral, anti-allergenic, antileishmanial, antispasmodic, antihyperglycemic, anti-inflammatory, immunomodulatory, insecticidal, and cytotoxic properties.[67,68,69]

Further studies are needed to ascertain which phytochemicals among the saponins, polyphenols, and terpenoids are responsible for the aphrodisiac and other biological effects of Carpolobia. These would lend firm credence to the ethnomedicinal uses of the leaf, stem, and root among the Ibo, Efiks, Ijaw, and Yoruba of Nigeria and the Pygmies of Cameroon.

ACKNOWLEDGMENTS

Footnotes

REFERENCES