Review of phytochemistry, biological activities and therapeutic potential of Brachylaena discolor

Brachylaena discolor DC. is a shrub or tree widely used as herbal medicine in southern Africa. Brachylaena discolor is indigenous to Botswana, Eswatini, Mozambique, South Africa, Zambia and Zimbabwe. This study was aimed at reviewing the phytochemistry, biological activities and therapeutic potential of B. discolor. Information on phytochemistry, biological activities and therapeutic potential of B. discolor was collected from online sources such as Google Scholar, PubMed and Science Direct, and pre-electronic sources such as books, book chapters, theses and journal articles obtained from the University library. This investigation revealed that the bark, leaf, root, stem and twig infusion or decoction of B. discolor are mainly used for magical purposes and as anthelmintic and tonic, and traditional medicine for female infertility, skin infections, renal problems, diabetes, gastro-intestinal problems and respiratory infections. Chemical compounds identi ied from B. discolor include alkaloids, lavonoids, phenolics, phlobatannins, saponins, sesquiterpene lactones, steroids, tannins and terpenoids. Ethnopharmacological review showed that B. discolor and phytochemical compounds identi ied from the species have anticancer, anthelmintic, anti-hyperglycaemic, antibacterial, cytotoxicity, antifungal, antidiabetic, antioxidant and leishmanicidal activities. Advanced ethnopharmacological research on B. discolor should focus on the possible biochemical mechanisms of both the crude extracts and identi ied phytochemical compounds including toxicological, in vivo and clinical studies to corroborate the traditionalmedicinal applications of the species.


INTRODUCTION
Brachylaena discolor DC. is a shrub or tree belonging to Compositae or Asteraceae family which is commonly referred to as sun lower, aster or daisy family.
The genus name Brachylaena R. Br. is a contraction of two Greek words "brachus" meaning "short" and "klaina" meaning "cloak", in reference to the lorests which are longer than the bracts surrounding the lower head (Venter and Venter, 2015). The speci ic name "discolor" which translates to "two-coloured" refers to the leaves, the upper surface of which is darker than the lower (Palmer and Pitman, 1972). The common name of the species "coastal silveroak", mostly refer to the silver-grey under-surface of the leaves which often gives the tree a silvery appearance (Palmer and Pitman, 1972). Brachylaena discolor is distinguished into three infraspeci ic taxa, namely var. discolor, var. rotundata (S. Moore) Beentje and var. transvaalensis (E. Phillips & Beentje) Beentje. Brachylaena discolor is an evergreen or deciduous shrub or tree growing up to 30 m in height (Beentje, 2000); (Germishuizen and Meyer, 2003). The bark of B. discolor is rough, light black to reddish-brown in colour with lenticellate branches. The leaves of B. discolor are lanceolate to ovate in shape, dull green above and light green to whitish below. The leaf margins of B. discolor are entire or are slightly serrated. The lower heads of B. discolor are grouped into axillate panicles with creamy-white coloured lowers. The fruits of B. discolor are small achenes characterized by apical tuft of creamy brown bristles (Palgrave and Keith, 2002); (Wyk and Wyk, 2013). Brachylaena discolor is indigenous to Zimbabwe, Botswana, Eswatini, Zambia, South Africa and Mozambique (Beentje, 2000). The species is found on termite mounds, sandy soils, secondary bushland, evergreen, dune, kloof, gully forests, forest margins, deciduous woodland, rocky outcrops and hillsides at sea level up to 1900 m above sea level (Germishuizen and Meyer, 2003); (Schmidt et al., 2017). Brachylaena discolor is a valuable medicinal plant species in tropical Africa as the roots and leaves of the species are traded in informal herbal medicine markets in KwaZulu-Natal and Gauteng provinces of South Africa (Cunningham, 1993); (Williams et al., 2001). Thus, the aim of this review is to summarize the phytochemistry, biological activities and therapeutic potential of B. discolor.

Medicinal uses of Brachylaena discolor
The twig, stem, bark, root and leaf infusion or decoction of B. discolor are mainly used for magical purposes and as anthelmintic and tonic, and traditional medicine for female infertility, skin infections, renal problems, diabetes, gastro-intestinal problems and respiratory infections (  (Bryant, 1966); (Hutchings et al., 1996) (Wet et al., 2013).

Phytochemistry of Brachylaena discolor
Several researchers investigated the phytochemical properties of B. discolor aerial parts and leaves (Table 2). Phytochemical compounds such as alkaloids, lavonoids, phenolics, phlobatannins, saponins, sesquiterpene lactones, steroids, tannins and terpenoids have been identi ied from B. discolor. Some of the documented chemical compounds could be responsible for the pharmacological properties associated with the species.

Pharmacological properties of Brachylaena discolor
The following pharmacological activities have been documented from the aerial parts and leaf extracts of B. discolor and compounds isolated from the species: anthelmintic, antibacterial, antifungal, anticancer, antidiabetic, antioxidant, anti-hyperglycaemic, leishmanicidal and cytotoxicity activities.  (Mcgaw et al., 2000) evaluated the anthelmintic activities of hexane, ethanol and water extracts of B. discolor leaves on the mortality and reproductive ability of the free-living nematode Caenorhabditis elegans in two different assays. All extracts exhibited activities at a concentration of 1.0 mg/ml and 2.0 mg/ml after the two and seven days incubation period (Mcgaw et al., 2000). (Adamu et al., 2013) evaluated the anthelmintic activities of the acetone extract of B. discolor leaves using the egg hatch assay and the larval development tests using Haemonchus contortus with albendazole as positive control. The extract exhibited activities with half maximal effective concentration (EC 50 ) values of 3.6 mg/ml and 17.2 mg/ml for the egg hatch and the larval development assays, respectively (Adamu et al., 2013). (Adamu et al., 2014) evaluated the antibacterial activities of acetone extract of B. discolor leaves against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis using a serial microdilution method with gentamicin as positive control. The extract exhibited activities  (Bryant, 1966); (Hutchings et al., 1996) Diabetes

Antidiabetic activities
The extracts exhibited activities on a-amylase and a-glucosidase with half maximal inhibitory concentration (IC 50 ) values ranging from 1.8 mg/ml to 11.0 mg/ml in comparison to IC 50 values of 0.03 mg/ml to 1.2 mg/ml exhibited by the positive control (Mellem et al., 2015). (Adamu et al., 2014) evaluated the antioxidant activities of acetone extract of B. discolor leaves using 2,2 ′ -azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 1,1-diphenyl-2picrylhydrazyl (DPPH) free radical scavenging assays. The extracts exhibited activities with a trolox equivalent antioxidant capacity (TEAC) value of 0.2 and an EC 50 value of 2.6, using ABTS and DPPH, respectively (Adamu et al., 2014). (Mellem et al., 2015) evaluated the antioxidant activities of the crude extracts of B. discolor leaves by using the DPPH free radical scavenging assay with rutin as positive control. The methanol and aqueous extracts exhibited activities with IC 50 values of 92.3 µg/ml and 82.8 µg/ml, respectively (Mellem et al., 2015). (Dikhoba et al., 2019) evaluated the antioxidant activities of acetone extract of B. discolor leaves using the ABTS and DPPH free radical scavenging assays with ascorbic acid (0.5 mg/ml) as positive control. The extract exhibited activities with IC 50 values of 0.03 mg/ml and 0.2 mg/ml against ABTS and DPPH, respectively (Dikhoba et al., 2019). (Mellem, 2013) evaluated the anti-hyperglycaemic activities of the methanol extract of B. discolor leaves using a streptozotocin-induced diabetic rat model. The doses of 50.0 mg/ml and 150.0 mg/ml) were administered daily to both streptozotocininduced and control rats and the biochemical pro ile of the rats assessed over 28 days. The extract at both doses caused a signi icant reduction in the blood glucose levels, and other observed changes included total bilirubin, creatinine, alkaline phosphatase and body weight (Mellem, 2013). (Monjane et al., 2018) evaluated the leishmanicidal activities of the compounds onopordopicrin and germacronolide epoxide isolated from the leaves of B. discolor against Leishmania amazonensis and Leishmania braziliensis using the colorimetric method-XXT with miltefone as positive control. The compound onopordopicrin exhibited activities with IC 50 values of 39.6 µM and 27.9 µM against Leishmania amazonensis and Leishmania braziliensis, respectively compared to IC 50 values of 12.5 µM and 12.0 µM exhibited by the positive control (Mon-jane et al., 2018). (Adamu et al., 2012) evaluated the cytotoxicity activities of acetone extracts of B. discolor leaves against Vero monkey kidney cells using the tetrazolium-based colorimetric 3-5-dimethyl thiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay. The extract exhibited activities with half maximal lethal dose (LD 50 ) value of 0.004 mg/mL (Adamu et al., 2012). (Adamu et al., 2013) evaluated the cytotoxicity activities of acetone extract of B. discolor against African Green Monkey kidney (Vero) cells using the tetrazolium-based colorimetric MTT assay. The extract exhibited activities with half maximal lethal concentration (LC 50 ) value of 0.008 mg/ml (Adamu et al., 2013). (Mellem et al., 2015) evaluated the cytotoxicity activities of the crude extracts of B. discolor leaves against the HeLa cell line using the colorimetric MTT assay. Both extracts stimulated the growth of the HeLa cell line with an increase in cell viability in a concentration dependent manner implying that the extracts are safe for use (Mellem et al., 2015) (Mellem et al., 2015). (Mellem et al., 2015) Mellem et al. (2015 evaluated the mutagenicity activities of aqueous and methanol extract of B. discolor leaves using the Salmonella typhimurium TA 100 and TA 98 strains mutagenicity assay. Both extracts exhibited no mutagenic activities up to the highest concentration tested which was 1000.0 µg/ml (Mellem et al., 2015). (Mellem et al., 2015) evaluated the toxicity activities of aqueous and methanol extracts of B. discolor leaves using the brine shrimp assay with organophosphate as positive control. Both extracts showed 100% shrimp survival at the highest concentration tested which was 1000.0 µg/ml while the positive control showed 100 % mortality (Mellem et al., 2015).

CONCLUSIONS
The present review summarizes the phytochemistry, biological activities and therapeutic potential of B. discolor. Brachylaena discolor is a variable species, distinguished into three varieties, var. discolor, var. rotundata and var. transvaalensis which are deemed as highly potent traditional medicines for various human diseases and ailments. These three varieties have overlapping distributional range in southern Africa and are quite similar in appearance and often confused when growing together. There are similarities and overlaps in terms of ethnomedicinal uses, phytochemistry and biological activities. From a phytochemical and pharmacological point of view, no chemical varia-tion studies have been conducted on these three varieties. Future studies should try to establish whether there are phytochemical compounds and pharmacological properties that could be used to distinguish these three varieties as this information will complement the taxonomical characters used to distinguish the three varieties.

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