Isolona hexaloba Engl. & Diels: Phytochemistry, Pharmacology and Future Directions: A Mini-Review

The aim of this review was to provide an updated knowledge on the Phytochemistry and Pharmacognosy of Isolona hexaloba Engl. & Diels. A literature search was conducted to obtain information about the phytochemistry and pharmacognosy of Isolona hexaloba from various electronic databases (PubMed Central, PubMed, Science Direct and Google scholar). The scientific name of this plant species was used as a keyword for the search, along with the terms phytochemistry and pharmacognosy. The chemical structures of the Isolona hexaloba and Isolona genus naturally occurring compounds were drawn using ChemBioDraw Ultra 12.0 software package. The findings revealed that this plant is traditionally used as a purgative and in treating sores, smoke from the bark as a strained muscle relaxant, infectious and parasitic pathologies, loss of appetite, rheumatism, intestinal cramps, headache, back pains, sexual weakness. This plant is reported to possess various biological properties like antioxidant, antimicrobial, antihyperglycemic, antileishmanial and antimalarial. These properties are due to the presence of numerous naturally occurring phytochemicals like flavonoids, alkaloids, tannins, saponins, reducting sugars, coumarins, terpenes and steroids. The present mini-review revealed that Isolona hexaloba Engl. & Diels is a good candidate for Tropical Plants Screening Research program for the development of lead compounds against genetic and parasitic diseases such as the evaluation of the anthelminthic activity.


Background
The World Health Organization (WHO) recognizes that traditional and complementary medicines (TCM) are a vital part of the global health care system [1]. In Africa, it is estimated that over 80% of the population continues to rely on medicinal plant for their primary health care needs [2]. In the Democratic Republic of the Congo (DRC), medicinal plants represent the key product for both urban and rural populations for their health care needs because the costs of conventional drugs are often unaffordable. These medicinal plants have found to have therapeutic value which fights against major health problems [3]. Isolona hexaloba (I. hexaloba) Engl. & Diels is a tree of the Isolona genus Engl. which belongs to Annonaceae family, Monodoroideae sub-family and is used in DRC and Republic of the Congo as a purgative and in treating sores, and the smoke from the bark as a strained muscle relaxant. However, it was reported to contain various secondary metabolites such as the alkaloids in the root bark [10] and terpenes [4]. Some different species of the Isolona genus (Annonaceae) have been extensively studied from both chemical and pharmacological points of view as I. cauliflora [8], I. ghesquiereina [9], I. zenkiri, I. pilosa [10] and some compounds identified in several Isolona species displayed the antimalarial and antitrypanosomial properties [11]. The present review aimed to provide updated information on the phytochemistry and pharmacognosy of this useful medicinal plant species and its integration in a future program of Tropical Plants Screening Research for anthelminthic properties mainly on animals.

Botany and Geographical Distribution
I. hexaloba Engl. & Diels (figure 1) is a tree of 10 -40 m high, with a trunk of 60 cm diameter. It grows in dense and humid forests of tropical Africa and has a soft bark of 1 cm of thickness. I. hexaloba is characterized by the horizontal positions of its flower, and its ovoidal to sub globular fruits with bumps and longitudinal ribs. Leaves are 6 -30 cm long, 3 -10 cm large and sub coriaceous [12]. Isolona genus belongs to the Annonaceae family, in Monodoroideae sub-family. This genus has 20 species which are originated from tropical Africa and Madagascar. Among the 20 species of this genus, most of species possess medicinal virtues. I. hexaloba Engl. & Diels is found in tropical and sub-tropical regions namely in DRC, Gabon, Cameroon, Ghana, Tanzania and Republic of the Congo.

Ethnobotany
I. hexaloba Engl. & Diels is a multipurpose plant with high traditional and medicinal uses for the maintenance of free health life. Traditionally, this plant is used in DRC as a purgative and in treating sores, smoke from the bark is used as a strained muscle relaxant [8] and infectious and parasitic pathologies [15], loss of appetite, rheumatism, intestinal cramps, headache, back pains and sexual weakness [16]. However, in the Ivory Coast I campanulata Engl. & Diels is used as an aphrodisiac and for increasing fertility in sterile women [6][7]. In contribution to systematic chemical studies of African medicinal plants, an extensive survey of literature revealed the structure determination of the methyl 7-(5',5'-dimethyltetrahydrofuran-2'-yl)-3-methylocta-2,6-die neoate (cazolobine), a new sesquiterpene isolated from the root of I hexaloba Engl. & Diels while the major secondary metabolite group identified was the alkaloids as reported in several studies [10].

Antileishmanial Activity
The African family plant which has the best antileishmanial effect is the Annonaceae family. Plants belonging to this family seem to have some medicinal properties and contain chemical compounds that have leishmanicidal effects. Plants of this family include Pistacia atlantica, Anonidium mannii, Enantia chlorantha, Isolona hexaloba, Annona glauca, Annona senegalensis and Annickia kummeriae. [13]. The aqueous decoction of root bark of I. hexaloba from DRC revealed the antileishmanial activity with an IC 50 of 8.00 µg.mL -1 [14].

Antiplasmodial Activity
Relying on an ethnopharmacological survey conducted in the Bolongo area, Bandundu province, the antiplasmodial potential of 33 selected medicinal plants was evaluated [16]. To mimic the traditional methods of preparation, lyophilized aqueous extracts were used during this screening assay. Out of all the extracts tested, 9 aqueous decoctions were found to have pronounced activity against the chloroquine and pyrimethamine-resistant K1strain of P. falciparum. Among them, the aqueous extracts from Quassia africana root bark and stem bark were the most active ones (IC 50 ‹1.5 mg.mL -1 ). The 7 other extracts (5 mg.mL -1 ‹IC 50 ‹15 mg.mL -1 ) included A. cordifolia leaves, Enantia chlorantha stem bark, Harungana madagascariensis stem bark, Isolana hexaloba root bark, Ocimum gratissimum leaves, Piptadeniastrum africanum stem bark, Psidium guajava leaves and Triclisia dictyophilla leaves [17].

Antioxidant and Antihyperglycemic Activities
Ngombe et al. [24] reported that the antioxidant and antihyperglycemic activities of crude extracts of I. hexaloba using DPPH scavenging method and glucose overloaded hyperglycemic rat models at dose levels of 200 and 400 mg/kg of body weight. The results showed that the total ethanolic extract and its fractions have an antioxidant potential. These results are promising especially as the potential antioxidant of plant extracts help to maintain health and to protect against coronary heart disease and diabetes in particular has a strong interest among scientists [25]. The phytochemical analysis of total crude extract showed presence of flavonoids, alkaloids, tannins, saponins, reducting sugars, coumarins, terpenes and steroids. It is known that flavonoids are potent antioxidants and are known to modulate the activities of various enzymes due to their interaction with various biomolecules. The activity of this biologically active compound could be attributed to the presence of these substances.

Conclusion
The present mini-review was undertaken with the aim of providing highlight and updated information on the medically and scientific evidence supporting the multiple uses of I. hexaloba in Traditional Medicine. Medicinal plant species are rich in secondary metabolites of pharmaceutical relevance. The advantages of their therapeutic uses in various ailments are their safety besides being economical, effective and available.
I. hexaloba Engl. & Diels. is pharmacologically and chemically much studied plant species but limited to only some activities, although the diversity of secondary metabolites present in the plant species especially alkaloids, saponins tannins, flavonoids, terpenoids (cazolobine), phytostérols and fatty acids have already been isolated from it. This makes it a good candidate for the development of new lead compounds against genetic and parasitic diseases such as the evaluation of anthelminthic activity. Plant species from Annona genus are also good drug candidates for external use like wound healing medicines.