Albizia Adianthifolia: Botany, Medicinal Uses, Phytochemistry, and Pharmacological Properties

The bark, leaves, and roots of Albizia adianthifolia are highly sought after in tropical Africa as herbal medicines. Therefore, the aim of this study was to review the botany, medicinal uses, phytochemistry, and pharmacological properties of A. adianthifolia so as to provide baseline data required for evaluating the therapeutic potential of the species. Information on the botanical profile, medicinal uses, phytochemistry, and pharmacological properties of A. adianthifolia was undertaken using databases such as ScienceDirect, SciFinder, Pubmed, Google Scholar, Medline, SCOPUS, EThOS, ProQuest, OATD, and Open-thesis. Preelectronic literature search of conference papers, scientific articles, books, book chapters, dissertations, and theses was carried out at the University library. Literature search revealed that A. adianthifolia is used as purgative and herbal medicine for diabetes, eye problems, gastrointestinal problems, haemorrhoids, headache, neurodegenerative disorders, reproductive problems in women, respiratory problems, wounds and pain, skin diseases, sexually transmitted infections, and ethnoveterinary medicine. Phytochemical compounds identified from the species include apocarotenoids, chalcone, dipeptide, elliptosides, essential oils, fatty acids, flavonoids, histamine, imidazolyl carboxylic acid, prosapogenins, steroids, triterpene saponins, and triterpenoids. Pharmacological studies revealed that A. adianthifolia extracts and compounds have acetylcholinesterase enzyme inhibitory, anthelmintic, antiamoebic, antibacterial, antimycobacterial, anti-sexually transmitted infections, antifungal, anti-inflammatory, antioxidant, anxiolytic, and antidepressant, cognitive-enhancing, haemolytic, hypoglycemic and antihyperglycemic, immunomodulatory, and cytotoxicity activities. Detailed studies on the pharmacokinetics, in vivo, and clinical research involving compounds isolated from A. adianthifolia and extracts of the species are required.


Introduction
Albizia adianthifolia (Schumach.) W. Wight is a medium to large tree ( Figure 1) which belongs to the plant family Fabaceae and subfamily Mimosoideae. The species is a member of Albizia Durazz., a genus that is recognized worldwide for its high ecological, economical, and medicinal value [1]. Albizia species have been used in folk medicine for the treatment of cough, diarrhoea, insomnia, irritability, rheumatism, stomach ache, tuberculosis, and wounds [2]. Phytochemical studies done on different species of Albizia lead to the isolation of different classes of secondary metabolites, such as saponins, terpenes, alkaloids, and flavonoids [2,3]. The saponin compounds isolated from the genus Albizia have been reported to possess cancer related activities and other pharmacological properties which include analgesic, anthelmintic, antidysenteric, antihistaminic, anti-inflammatory, antimicrobial, antimutagenic, antiseptic, antispermatogenic, antitumour, anxiolytic, cytotoxic, immunomodulatory, nootropic, and apoptosis inducing properties [3]. According to Louppe et al. (2008) [1], A. adianthifolia is among 13 Albizia species regarded as socially and economically important in tropical Africa as sources of high quality timber, gum, fodder, and herbal medicines. It is, therefore, not surprising that A. adianthifolia is considered as one of the most important African medicinal plants by Iwu [4] and, recently, Van Wyk [5] listed the bark of the species as commercially relevant medicinal and aromatic component of herbal medicines in Kenya and South Africa. Albizia adianthifolia is also included in the book "medicinal when ripe. The seeds are flattened, swollen, globose in shape and brown in colour [21]. Albizia adianthifolia has been recorded in forests, woodlands, and areas that are transitional to woodland. The species occurs from South Africa through Madagascar, central and east Africa, to Senegal in the north ( Figure 2).
The bark of A. adianthifolia is one of the most commonly stocked herbal medicine products in the informal herbal medicine markets in South Africa [7][8][9][10][11][12][13] and Grace et al. (2003) [22] tried to authenticate dried bark of the species using thin layer chromatography (TLC). This study showed that dried bark of A. adianthifolia is often confused with dried bark of Acacia sieberiana DC., Acacia xanthophloea Benth. (family Fabaceae), and Croton sylvaticus Hochst. ex C. Krauss (family Euphorbiaceae), other three plant species sold as herbal medicines in the informal herbal medicine markets in South Africa. Grace et al. [22] argued that the notable similarities in the phytochemical fingerprints of Acacia sieberiana, Acacia xanthophloea, A. adianthifolia, and Croton sylvaticus may be an indicator of close usage relationships as similarities shown by TLC chromatograms may sometimes explain the phytochemical properties common to bark products that are purposefully substituted for one another, particularly in cases where taxonomically unrelated species are used [23].

Medicinal Uses of Albizia adianthifolia
The bark, leaf sap, leaves, roots, and stem bark of A. adianthifolia are used as remedies for human and animal diseases (Table 1). Ethnomedicinal uses of the species have been recorded in Burundi, Cameroon, the Democratic Republic of Congo (DRC), Guinea, Madagascar, Guinea-Bissau, Mozambique, Nigeria, Sierra Leone, Rwanda, Swaziland, South Africa, Tanzania, Uganda, Zimbabwe, and Togo, representing 51.6% of the countries where the species is indigenous (Figure 3). Major diseases and ailments recorded in at least two countries include diabetes, eye problems, gastrointestinal problems, haemorrhoids, headache, neurodegenerative disorders, purgative, reproductive problems in women, respiratory problems, wounds and pain, skin diseases, sexually transmitted infections, and ethnoveterinary medicine (Figure 3). Albizia adianthifolia is used to manage and treat top three ailments and diseases regarded by the World Health Organization [24] as the leading causes of death in low-income countries, and these are lower respiratory infections, diarrhoeal diseases, and ischaemic heart disease. The bark, leaves, and stem bark of A. adianthifolia are used as herbal remedies against bronchitis, cough, respiratory problems, and sinusitis in Cameroon, Mozambique, Nigeria, and South Africa [25][26][27][28][29], which can be categorized as the lower respiratory infections. The bark, leaves, and roots of A. adianthifolia are used as herbal remedies against diarrhoea, dysentery, and stomach ache in the DRC, Madagascar, Mozambique, South Africa, and Tanzania [26,[30][31][32][33][34][35][36]. The leaves of A. adianthifolia are used as herbal remedies against hypertension in Togo [37], which is one of the most common chronic diseases in modern societies. There is, therefore, a need for further research aimed at correlating some of the ethnomedicinal uses of A. adianthifolia to the phytochemical and biological activities of both the crude extracts and chemical compounds isolated from the species. Moreover, the World Health Organization has recognized the important role played by traditional medicines in the provision of primary healthcare in the resource-poor regions like tropical and subtropical Africa [38]. In addition to this, several studies have demonstrated the efficacy and importance of medicinal plants in the development of new pharmaceutical drugs and health products [39,40].
Sexually transmitted infections are treated with multitherapeutic applications involving A. adianthifolia herbal concoctions. For example, in Sierra Leone, stem bark of A. adianthifolia is mixed with fruits of Citrus aurantiifolia (Christm.) Swingle and taken orally as herbal medicine for gonorrhoea [41]. In South Africa, the leaves of A. adianthifolia are mixed with the bark of Trichilia dregeana Sond. and taken orally as herbal medicine for syphilis [42]. In the Democratic Republic of Congo, leaves of A. adianthifolia are mixed with those of Gynura scandens O. Hoffm. and fruits of Musa paradisiaca L. and applied topically as herbal medicine for visible blisters on livestock [43].

Ethnoveterinary medicine
Coccidiosis and wounds Roots Zimbabwe [61,62] Ethnoveterinary medicine Blisters treated with leaves mixed with those of Gynura scandens O. Hoffm. and fruits of Musa paradisiaca L.
DRC [43] 6 The Scientific World Journal    The Scientific World Journal -d-glucopyranosyl} ester 82 which have been shown to be cytotoxic against a large panel of cancer cells [3,66]. Further comprehensive studies focusing on chemical constituents of A. adianthifolia and their pharmacological activities are required. Chemical structures of aurantiamide acetate 9, docosanoic acid 65, n-hexadecanoic acid 66, octadecanoic acid 67, oleic acid 68, 16 -

Acetylcholinesterase Enzyme
Inhibitory Activities Risa

Antiamoebic Activities
McGaw et al. (2000) [74] evaluated antiamoebic activities of ethanol and water leaf extracts of A. adianthifolia using microdilution technique against the enteropathogenic Entamoeba histolytica with metronidazole as the positive control. The extracts showed weak activities with IC 50 value of >5.0 mg/ml which was higher than 0.20 g/ml exhibited by metronidazole [74]. and Salmonella typhi using the broth microdilution method with gentamicin as the positive control. The ethyl acetate extract and aurantiamide acetate 9 were active against all the tested pathogens with MIC values ranging from 0.09 mg/ml to 0.78 mg/ml and 0.05 mg/ml to 0.1 mg/ml, respectively [27]. The compound lupeol 86, a mixture of n-hexadecanoic acid and oleic acid 68, and a mixture of compounds docosanoic acid 65, n-hexadecanoic acid 66, and octadecanoic acid 67 were active against Enterococcus faecalis, Staphylococcus aureus, Proteus mirabilis, and Shigella flexneri with MIC values ranging from 0.1 mg/ml to 0.4 mg/ml, 0.05 mg/ml to 0.4 mg/ml, and 0.1 mg/ml to 0.8 mg/ml, respectively. The exhibited minimum bactericidal concentrations (MBC) were 0.39 mg/ml to 1.56 mg/ml for ethyl acetate extract, 0.1 mg/ml to 0.4 mg/ml (n-hexadecanoic acid 66 and oleic acid 68), 0.2 mg/ml to 0.8 mg/ml (docosanoic acid 65, nhexadecanoic acid 66 and octadecanoic acid 67), 0.2 mg/ml to 0.4 mg/ml (compound lupeol 86), and 0.05 mg/ml to 0.1 mg/ml (aurantiamide acetate 9) [27]. The documented antibacterial activities exhibited by different extracts and compounds isolated from A. adianthifolia corroborate the traditional application of the species as herbal medicine against bacterial infections causing diarrhoea, dysentery, and stomachache in DRC, Madagascar, Mozambique, South Africa, and Tanzania [26,[30][31][32][33][34][35][36].

Antimycobacterial Activities
Eldeen and Van Staden [76] evaluated the antimycobacterial activities of dichloromethane, ethyl acetate, and ethanol bark and leaf extracts of A. adianthifolia against Mycobacterium aurum A+ using the broth microdilution method. Only the ethanol root extract exhibited moderate activity with MIC value of 6.3 mg/ml [76]. These findings show potential of A. adianthifolia in the treatment and management of respiratory problems such as bronchitis, cough, and sinusitis in Cameroon, Mozambique, Nigeria, and South Africa [25][26][27][28][29].

Anti-Sexually Transmitted
Infections Activities Naidoo

Antifungal Activities
Abubakar and Majinda [68] evaluated antifungal activities of chloroform and n-hexane extracts of heartwood of A. adianthifolia against Candida albicans using the modified agar overlay method with miconazole as the positive control. The extracts exhibited weak activities with MIQ value of >100 g which was much higher than MIQ value of 0.25 g exhibited by miconazole [68]. Similarly, Tamokou  14. Anti-Inflammatory Activities Jäger et al. (1996) [78] evaluated anti-inflammatory activities of aqueous and ethanolic bark extracts of A. adianthifolia in an in vitro assay for cyclooxygenase inhibitors with indomethacin (0.5 g) as the control. The ethanolic extract of A. adianthifolia showed an inhibition of 69% which was higher than 66.5% inhibition exhibited by the indomethacin control. Based on these results, there might be a rationale for the ethnopharmacological claim that A. adianthifolia possess anti-inflammatory properties [78]. Similarly, Eldeen et al. (2005) [73] evaluated anti-inflammatory activities of aqueous, ethanol, and ethyl acetate bark and root extracts of A. adianthifolia using the cyclooxygenase (COX-1 and COX-2) assays. Aqueous, ethanol, and ethyl acetate bark and root extracts were active against COX-1 with inhibition percentage ranging from 61% to 90% while bark and root ethyl acetate, ethanol, and aqueous bark extracts were active against COX-2 with inhibition percentage ranging from 58% to 87% [73]. These finding support the traditional use of A. adianthifolia as herbal medicine for abdominal pains, back pain (lumbago), and anal wounds in Cameroon, Guinea-Bissau, and Mozambique [27,36,50,60].  [79] evaluated the antioxidant activity of aqueous leaf extracts of A. adianthifolia using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl, and malondialdehyde levels. The increased activities of superoxide dismutase, glutathione peroxidase, catalase, and glutathione level and the decreased levels of protein carbonyl and malondialdehyde induced by administration of the aqueous extract of A. adianthifolia leaves implied that this plant extract possesses strong antioxidant property [79]. Sulaiman et al. (2017) [80] evaluated the antioxidant activities of magnetic iron oxide nanoparticles synthesized using A. adianthifolia leaf extracts by using the DPPH free radical scavenging assay. The free radical scavenging potential of the magnetic iron oxide nanoparticles was confirmed based on its stable antioxidant effects [80].  Beppe et al. (2014) [28] evaluated the cognitive-enhancing activities of aqueous leaf extracts of A. adianthifolia in the 6-hydroxydopamine-lesion rodent model of Parkinson's disease. The extract was administered orally to male Wistar rats at 150 mg/kg and 300 mg/kg daily for 21 days and spatial memory performance was assessed using y-maze and radial arm-maze tasks. The 6-hydroxydopamine-treated rats exhibited a decrease of spontaneous alternations percentage within y-maze task and an increase of working memory errors and reference memory errors within radial armmaze task. Administration of the aqueous extract of A. adianthifolia leaves significantly improved these parameters, suggesting positive effects on spatial memory formation [28].

Hypoglycemic and
Antihyperglycemic Activities Amuri et al. (2017) [45] evaluated the hypoglycemic and antihyperglycemic activities of leaf extracts of A. adianthifolia by administering 500 mg/kg to guinea pigs (Cavia porcellus), both in glucose baseline conditions and in oral glucose tolerance test with follow-up over 210 minutes. In hypoglycemic tests, the extract induced activities, lowering the normal glycemia by 33% which was comparable to the activities of the positive control, and glibenclamide (6 mg/kg) which induced a blood glucose lowering effect of 55%. In oral glucose tolerance test, the extract was active, causing inhibition of glycemia increase of 57% which was comparable to the hyperglycemic inhibition rate of glibenclamide of 50% [45]. These findings support the traditional use of A. adianthifolia leaf and stem bark decoction as herbal medicine for diabetes in the DRC [45] and Nigeria [29].  Naidoo et al. (2013) [77] evaluated cytotoxicity activities of aqueous and dichloromethane and methanol (1:1) bark 14 The Scientific World Journal extracts of A. adianthifolia using the 3-[4,5-dimethyl-2thiazol-yl]-2,5-diphenyl2H-tetrazolium bromide (MTT) cellular viability assay on the human embryonic kidney epithelial (Graham, HEK-293) cell line. The cell viability assay indicated that the extracts were nontoxic at 100 mg/ml against the human kidney epithelial cell line, but 110% and 112% cell growth exhibited by aqueous and organic extracts, respectively, appeared to increase cellular activity, which would be effective in wound healing [77]. Kuete et al. (2016) [84] evaluated the cytotoxicity activities of methanol bark and root extracts of A. adianthifolia against the sensitive leukemia CCRF-CEM cells. The extracts were further tested on a panel of eight human cancer cell lines, including MDR phenotypes. In the preliminary assay using CCRF-CEM cells, the bark and root extracts exhibited activities with IC 50 values of 0.98 g/mL and 1.5 g/mL, respectively. Both bark and root extracts were active against other cell lines and normal AML12 hepatocytes with IC 50 values ranging from 2.7 g/mL to 10.8 g/mL towards glioblastoma U87MG.ΔEGFR cells, breast adenocarcinoma MDA-MB-231-BCRP cells, and colon carcinoma HCT116(p53 −/− ) cells. The root extracts induced apoptosis in CCRF-CEM cells through caspases activation and loss of mitochondrial membrane potential [84]. Sulaiman et al. (2017) [80] evaluated the cytotoxic activities of magnetic iron oxide nanoparticles synthesized using A. adianthifolia leaf extracts on human breast (AMJ-13) and (MCF-7) cancer cells. The observed antiproliferative effects towards AMJ-13 and MCF-7 are due to cell death and inducing apoptosis. Mitochondrial membrane potential and acridine orange-propidium iodide staining assays as well as single cell and DNA gel electrophoresis analyses indicated that magnetic iron oxide nanoparticles induce cell death only by apoptosis [80].   [82] evaluated cytotoxic activities of silver nanoparticles (AgNP) synthesized from aqueous leaf extracts of A. adianthifolia on the A549 human lung cancer cell line and normal healthy human peripheral lymphocytes using MTT, ATP, and lactate dehydrogenase assays. Viability data for A549 cells showed a 21% (10 g/ml) and 73% (50 g/ml) cell viability after 6 hours exposure to AgNPs compared to 117% (10 g/ml) and 109% (50 g/ml) cell viability of normal peripheral lymphocytes [82]. Govender et al. (2013) [83] evaluated the cytotoxicity activities of silver nanoparticles (AgNP) synthesized from aqueous leaf extracts of A. adianthifolia on A549 lung cells. Cell viability was determined by the MTT assay by determining cellular oxidative status, lipid peroxidation and glutathione levels, ATP concentration, caspase-3/-7, caspase-8, and caspase-9 activities, apoptosis, mitochondrial membrane depolarization (flow cytometry) and DNA fragmentation, and CD95 receptors, p53, bax, PARP-1, and smac/DIABLO [83]. The silver nanoparticles of A. adianthifolia caused a dose-dependent decrease in cell viability with a significant increase in lipid peroxidation, decreased intracellular lipid peroxidation and glutathione, decrease in cellular ATP, elevation in mitochondria depolarization, higher apoptosis, decline in expression of CD95 receptors, reduction in caspase-8 activity, and increases in

Conclusion
Albizia adianthifolia has been used as herbal medicine in tropical Africa for several centuries and significant breakthrough has been made in the last 40 years elucidating the phytochemical and pharmacological properties of the species. However, there are still some research gaps regarding correlating the ethnomedicinal applications of the species with the chemical compounds and pharmacological properties of the compounds and extracts of the species. Detailed studies on the pharmacokinetics, in vivo, and clinical research involving compounds isolated from A. adianthifolia and extracts of the species are required. The bark of A. adianthifolia is known to be toxic [25] and roots of the species are used as fish poison in Mozambique [85]. Similarly, in southern Cameroon, the gum from the bark of A. adianthifolia is used as a hunting poison and in the Central African Republic, the bark and leaves of the species are used as fish poison [86]. These reports highlight the need for detailed toxicological evaluations of both the extracts of the species as well as the compounds isolated from A. adianthifolia to establish the toxicity and/or any side effects that can arise when the species and its products are used as herbal medicines.

Conflicts of Interest
The author declares that there are no conflicts of interest regarding the publication of this paper.