Review of Ethnopharmacology and phytochemistry of Acacia ataxacantha

Purpose: To provide ethnopharmacological and phytochemical properties of Acacia ataxacantha as initial steps of assessing medicinal value and importance of the species in tropical Africa. Methods: Information on the medicinal uses, phytochemistry and pharmacological activities of A. ataxacantha was collected from several sources including books, theses, scientific reports and journal articles obtained from internet sources such as SciFinder, Web of Science, Pubmed, BMC, Elsevier, Science Direct, Scielo and Scopus. Results: Acacia ataxacantha is an important herbal medicine in tropical Africa used against abscesses, backache, cough, dental caries and toothache, headache, malaria, pneumonia, sores and wounds, and stomach problems. The chemical constituents of A. ataxacantha include alkaloids, anthracene derivatives, carbohydrates, coumarins, flavonoids, lignan, naphtoquinone, polyphenols, reducing sugars, saponins, steroids, tannins, terpenoids and triterpenoids. The biological activities demonstrated include antibacterial, antifungal, anti-diabetic, anti-inflammatory, antioxidant, laxative and ulceroprotective. Conclusion: The phytochemical properties and pharmacological activities of A. ataxacantha lend some support for the traditional medicinal applications of the species against several diseases.


INTRODUCTION
Acacia ataxacantha DC. is a member of the family Fabaceae and belongs to the subfamily Mimosoideae. Following recommendations from phylogenetic analysis, A. ataxacantha was renamed Senegalia ataxacantha (DC.) Kyalangaliwa & Boatwr. [1]. But international centres of botanical and taxonomical research such as Missouri Botanical Garden, St. Louis, Missouri, USA and the Royal Botanic Gardens, Kew, UK regard S. ataxacantha as an unresolved name and recognize A. ataxacantha instead. The specific name "ataxacantha" is made up of two Greek words "taxis" and "akantha" which mean "arrangement" and "thorns", respectively in reference to the many scattered thorns on the stems and shoots of the METHODS Information on the medicinal uses, phytochemistry and pharmacological activities of A. ataxacantha was collected from several sources including books, book chapters, theses, scientific reports and journal articles obtained from internet sources such as SciFinder, Web of Science, Pubmed, BMC, Elsevier, Science Direct, Scielo and Scopus. The search for this information was carried out between February to December 2017. The keywords used in the search included "ethnobotany", "ethnomedicinal uses", "medicinal uses", "phytochemistry", "biological activities", "pharmacological properties", "Acacia ataxacantha", "Senegalia ataxacantha", the synonym of the species "Acacia eriadenia Benth." and "Acacia lugardiae N. E. Br", and the English common names "flame acacia" and "flame thorn". The internet search generated 674 articles in total. After duplicate articles and those with limited raw data were excluded, 33 articles were included in this study.
These articles included 27 journal articles, books (two), one book chapter, scientific report, thesis and website (one each).

Medicinal uses of A. ataxacantha
A total of 33 medicinal reports of A. ataxacantha have been reported in literature with a high degree of consensus for abscesses, backache, cough, dental caries and toothache, headache, malaria, pneumonia, sores and wounds, and stomach problems (Table 1). Acacia ataxacantha is reported to be herbal medicine for these diseases in at least two countries (Table 1). In Benin and Swaziland, leaves and bark of A. ataxacantha is used against abscesses [6,7] while roots and young leaves are used for backache in Kenya and Nigeria [2,8]. In Chad, Kenya and Nigeria, bark, leaves and roots of A. ataxacantha are used as cough remedies [9][10][11] while bark, flowers, leaves and roots are used for dental caries, dentition and tooth decay in Chad, Benin and Nigeria [1][2][3][4][5][6][7][8][9][10][11][12].
In Namibia and Nigeria, bark, leaves and roots of A. ataxacantha are used as headache remedies [10,13] while flowers, leaves and roots are used against malaria in Benin and Burkina Faso [12,14]. Bark, leaves and roots of A. ataxacantha are used as remedies for pneumonia in Kenya and Namibia [2,5,9,13] while flowers, leaves, roots, pods and seeds are used against stomach problems in Benin and Nigeria [3,12]. Bark, leaves and roots of A. ataxacantha are used for burns, sores and wounds in Chad and Nigeria [10,11]. Information on other ethnomedicinal applications of A. ataxacantha is provided in Table 1.   The extracts showed no activity against Corynebacterium ulcerans, Proteus mirabilis and Streptococcus faecalis but extracts and compound 5 showed some activity against the other pathogens with the zone of inhibition ranging from 17 mm to 30 mm for crude extracts, 25 mm to 31 mm for α-amyrenol (3β)-Urs-12-en-3-ol 5, which compared favourably with 35 to 42 mm exhibited by sparfloxacin, the positive control. The MIC values ranged from 2.5 to 10 mg/mL, minimum bactericidal concentration (MBC) values ranged from 2 to 20 mg/mL, while MIC and MBC values of α-amyrenol (3β)-Urs-12en-3-ol 5 were 12.5 to 25 mg/mL and 25 to 50 mg/mL, respectively [ The MBC values ranged from 25 to 50 µg/mL compared to 0.8 to 1.6 µg/mL exhibited against the control [30]. These results support the traditional medicinal uses of the species against infectious diseases such as dental caries, dentition and tooth decay in Benin, Chad and Nigeria [10][11][12], dysentery in Nigeria [3,8], gonorrhoea in Kenya [2], stomach ache and stomach problems in Benin and Nigeria [3,12], burns, sores and wounds in Chad and Nigeria [10,11].

Antifungal activities
Aba et al [26] evaluated antifungal activities of chloroform, methanol, ethyl acetate and petroleum ether root bark extracts of A. ataxacantha and α-amyrenol (3β)-Urs-12-en-3-ol 5 isolated from the species against Candida albicans, Candida tropicalis and Candida krusei using well diffusion method with cefuroxime as the positive control. The extracts showed no activity against Candida tropicalis but exhibited activities against other pathogens with the zone of inhibition ranging from 18 mm to 23 mm for crude extracts, 24 mm to 31 mm for α-amyrenol . These findings corroborate the traditional medicinal uses of the species against fungal infections such as dental caries, dentition and tooth decay in Benin, Chad and Nigeria [11,12,22], stomachache and stomach problems in Benin and Nigeria [3,12], burns, sores and wounds in Chad and Nigeria [10,11]. ataxacantha roots in streptozotocin-induced diabetic rats. Blood glucose was significantly reduced after 7 days of oral administration of the plant extract at 125 mg/kg body weight with a value of 110.0 ± 9.6 mg/dl which was comparable to that of the control with value of 106.3 ± 4.13 mg/dl. There was an increase in the alanine aminotransferase and aspartate aminotransferase activities of the liver and serum of rats, triglyceride and the serum total cholesterol were decreased upon administration of the plant extract and metformin. These results revealed that the ethanolic extract of A. ataxacantha root reduced blood glucose in streptozotocin-induced hyperglycemic rats to levels comparable to the reference clinical drug metformin after 7 days [28]. Therefore, these findings imply that A. ataxacantha may be considered as an alternative source in the search for new leads of anti-diabetic agents.

Anti-inflammatory activities
Abbas et al [27] evaluated the anti-inflammatory activities of methanol leaf extracts of A. ataxacantha in rats using the carragenaan and albumin induced paw edema. The extract showed significant anti-inflammatory activity which was demonstrated by swelling of the hindpaw oedema which occurred progressively from time 0 -2 h after carragenaan injection, but at the 3rd hour oedema reduction occurred in a dose dependent manner and was significant only in rats pre-treated with extract at doses 200 and 400 mg/kg body weight. However, at the 4 th hour there was significant difference in the swelling of oedema at 100, 200 and 400 mg/kg when compared with the normal saline, the negative control [27]. Similarly, there was significant inhibition of inflammation at the 20 th , 40 th , 60 th and 120 th min post extract administration in albumin induced hind-paw inflammation [27].

Laxative activities
Akapa et al [32] evaluated the laxative activities of aqueous extract of A. ataxacantha leaves against loperamide induced constipated rats. Constipated control rats received normal saline while the treatment constipated rats were given 100, 200 and 400 mg/kg body weight per day of the extract for ten days with senokot used as a standard reference drug. The feacal properties, water intake, feeding characteristics, laxative activity and gastrointestinal transit ratio were assessed. The extract produced significant laxative activities and reduced loperamide induced constipation in dose dependent manner as seen in the elevated feacal properties compared to the normal control rats. The 400 mg/kg body weight of the extract showed the best efficacy and the effect of the extract compared favourably with senokot, a standard laxative drug [32]. These findings corroborate the traditional use of A. ataxacantha leaves as traditional medicine for constipation in Zimbabwe [15].

Ulcero-protective activities
Akapa et al [20] evaluated the ulcero-protective activities of methanolic leaf extract of A. ataxacantha against indomethacin and stress induced gastric ulcer in experimental rats. The leaf extracts at the dose of 100 and 200 mg/kg body weights were administered to male albino rats 30 minutes before the administration of indomethacin and subjected to stress. Ranitidine was used as a standard antiulcer drug and rats were then sacrificed and various gastric parameters such as gastric pH levels, gastric ulcer indices and gastric ulcer percentage inhibition were assessed.
Animals pretreated with A. ataxacantha extracts (100 and 200 mg/kg body weight) showed significant reduction in ulcer index to indomethacin and stress induced ulcer models in a dose dependent manner when compared to the negative control group. Authors recorded significant decrease in the gastric pH levels of both ulcer models which were normalized by A. ataxacantha extracts and various percentages of gastric ulcers inhibition were statistically significant in groups pretreated with A. ataxacantha extracts and the overall effect of the extract was comparable to that of the standard drug, ranitidine used in this study [20]. Therefore, these findings corroborate the traditional uses of leaves of A. ataxacantha as herbal medicine against gastric ulcers in Senegal [20].

Safety
Preliminary safety evaluation of A. ataxacantha extracts seem to suggest the plant extracts to be atoxic. Amoussa et al [33] evaluated the oral acute toxicity of the crude hydroethanolic bark extract of A. ataxacantha on rats using a single dose of 2000 mg/kg given to three female rats with distilled water (10 ml/kg body weight) given to three female rats as a control. All tested animals were physically active and no deaths were reported. No significant changes were observed in haematological parameters, biochemical parameters and body weight of treated animals compared with the controls. The histopatological analysis of kidney and liver showed normal architecture suggesting no morphological disturbances [33]. Therefore, these results suggest that the hydroalcoholic bark extract of A. ataxacantha is non-toxic up to 2000 mg/kg body weight.
Abbas et al [27] evaluated acute toxicity of methanol leaf extract of A. ataxacantha in rats with extracts at doses of 10, 100, 1000, 1600, 2900 and 5000 mg/kg body weight and the rats were monitored for 24 h for signs of toxicity and mortality. The oral median lethal dose (LD 50 ) of the extract was found to be greater than 5000 mg/kg body weight [27], therefore, the extract is practically non-toxic when administered orally.

CONCLUSION
A. ataxacantha is used as herbal medicine in at least two countries against abscesses, backache, cough, dental caries and toothache, headache, malaria, pneumonia, sores and wounds, and stomach problems. The observed high degree of consensus for these diseases calls for detailed in vitro and in vivo studies to corroborate traditional medicinal applications of A. ataxacantha against these diseases. Some of the ethnomedical uses of A. ataxacantha have been confirmed by the species' pharmacological properties and these include antibacterial, antifungal, anti-diabetic, anti-inflammatory, antioxidant, laxative and ulcero-protective. Therefore, the pharmacological and phytochemical activities of A. ataxacantha provide credence to the traditional medicinal applications of the species against various diseases, and hence the need for detailed in vitro and in vivo studies.