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

Alfred Maroyi

doi:https://doi.org/10.26452/ijrps.v11i4.3201

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

1 Department of Biodiversity, University of Limpopo, Private Bag X1106, Sovenga 0727, South Africa, 0027719600326

Abstract

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 identified from B. discolor include alkaloids, flavonoids, phenolics, phlobatannins, saponins, sesquiterpene lactones, steroids, tannins and terpenoids. Ethnopharmacological review showed that B. discolor and phytochemical compounds identified 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 identified phytochemical compounds including toxicological, in vivo and clinical studies to corroborate the traditional medicinal applications of the species.

Keywords

Asteraceae, Brachylaena discolor, Compositae, Indigenous knowledge, Traditional medicine

Introduction

Brachylaena discolor DC. is a shrub or tree belonging to Compositae or Asteraceae family which is commonly referred to as sunflower, 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 florests which are longer than the bracts surrounding the flower head (Venter & Venter, 2015). The specific name “discolor” which translates to “two-coloured” refers to the leaves, the upper surface of which is darker than the lower (Palmer & Pitman, 1972). The common name of the species “coastal silver-oak”, mostly refer to the silver-grey under-surface of the leaves which often gives the tree a silvery appearance (Palmer et al., 1972). Brachylaena discolor is distinguished into three infraspecific 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 & 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 flower heads of B. discolor are grouped into axillate panicles with creamy-white coloured flowers. The fruits of B. discolor are small achenes characterized by apical tuft of creamy brown bristles (Palgrave & Keith, 2002); (Wyk & 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 et al., 2003); (Schmidt, Lotter, & Mccleland, 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, Balkwill, & Witkowski, 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 (Table 1, Figure 1). The leaves of B. discolor are mixed with those of Ekebergia capensis Sparrm., Clausena anisata (Willd.) Hook. f. ex Benth., Volkameria glabra (E. Mey.) Mabb. & Y.W. Yuan, Zanthoxylum capense (Thunb.) Harv. and roots of Cymbopogon marginatus (Steud.) Stapf. ex Burtt-Davy, Erythrophleum lasianthum Corbishley, Margaritaria discoidea (Baill.) Webster and Hypoxis spp. and used as anthelmintic (Bryant, 1966); (Hutchings, Scott, Lewis, & Cunningham, 1996). The twigs of B. discolor are mixed with stems of Euphorbia tirucalli L., Hypoxis hemerocallidea Fisch., C.A. Mey. & Avé-Lall. (corm), Ozoroa engleri R. Fern. & A. Fern. (bark) and Senecio serratuloides DC. (leaves) and applied topically on sores (Wet, Nciki, & Vuuren, 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, flavonoids, phenolics, phlobatannins, saponins, sesquiterpene lactones, steroids, tannins and terpenoids have been identified 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.

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/80f6d18a-b738-4112-b1d4-67c3586c4332/image/225f6517-63d7-4c49-a9e5-207c32798ba2-upicture1.png — **Figure 1: Medicinal uses of Brachylaena discolor derived from literature records**

Anthelmintic activities

(Mcgaw, Jäger, & Staden, 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, Naidoo, & Eloff, 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 (EC₅₀) 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).

Antibacterial activities

(Adamu, Naidoo, & Eloff, 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

Table 1: Medicinal uses of Brachylaena discolor

Medicinal use	Part used	Reference
Abdominal pains	Root decoction taken orally	(Gelfand, Mavi, Drummond, & Ndemera, 1985)
Anthelmintic	Leaf and root infusion or decoction taken orally	(Thomas & Grant, 2013); (Constant & Tshisikhawe, 2018)
Anthelmintic	Leaves mixed with those of Ekebergia capensis Sparrm., Clausena anisata (Willd.) Hook. f. ex Benth., Volkameria glabra (E. Mey.) Mabb. & Y.W. Yuan, Zanthoxylum capense (Thunb.) Harv. and roots of Cymbopogon marginatus (Steud.) Stapf. ex Burtt-Davy, Erythrophleum lasianthum Corbishley, Margaritaria discoidea (Baill.) Webster and Hypoxis spp.	(Bryant, 1966); (Hutchings et al., 1996)
Diabetes	Leaf and root infusion and decoction taken orally	(Watt & Breyer-Brandwijk, 1962); (Erasto, Adebola, Grierson, & Afolayan, 2005)
Dysmenorrhoea	Root decoction taken orally	(Gelfand et al., 1985)
Female infertility and prevent miscarriage	Bark and root decoction taken orally	(Semenya, Maroyi, Potgieter, & Erasmus, 2013); (Mhlongo & Wyk, 2019)
Fever	Leaf infusion taken orally	(Pujol & Naturafrica, 1990)
Gastro-intestinal problems (diarrhoea and stomach ache)	Leaf and bark infusion taken orally or anally	(Wet, Nkwanyana, & Vuuren, 2010); (Monjane, Capusiri, Giménez, & Sterner, 2018)
Haemorrhoids	Root infusion applied topically	(Palmer et al., 1972)
Magical purposes	Leaves, roots and stems	(Cunningham, 1988); (Cunningham & Zondi, 1991)
Nervous system	Leaf infusion taken orally	(Hutchings, 1989)
Renal problems	Leaf infusion or decoction taken orally	(Mellem, 2013), (Mellem, Baijnath, & Odhav, 2015)
Respiratory infections (chest pains, cough, sore throat and tuberculosis)	Leaf and root decoction or infusion taken orally	(York, Wet, & Vuuren, 2011); (Semenya & Maroyi, 2018)
Skin infections (burns, cleaning facial skin and sores)	Leaf and twig infusion applied topically	(Afolayan, Grierson, & Mbeng, 2014); (Nciki, Vuuren, & Eyk, 2016)
Sores	Twigs mixed with Euphorbia tirucalli L. (stems), Hypoxis hemerocallidea Fisch., C.A. Mey. & Avé-Lall. (corm), Ozoroa engelri R. Fern. & A. Fern. (bark) and Senecio serratuloides DC. (leaves)	(Wet et al., 2013)
Syphilis	Root decoction taken orally	(Gelfand et al., 1985)
Tonic	Leaf decoction taken orally	(Palmer et al., 1972); (Hutchings, 1989)
Ulcers	Leaf infusion taken orally	(Chigora, Masocha, & Mutenheri, 2007)
Wounds	Leaf infusion applied topically	(Afolayan et al., 2014)
Ethnoveterinary medicine (anthelmintic)	Leaf infusion	(Hutchings et al., 1996)

Table 2: Phytochemical composition of Brachylaena discolor

Phytochemical compound	Plant part	Reference
3’-hydroxygenkwanin	Leaves	(Monjane et al., 2018)
3 -acetoxy-12-lupene	Aerial parts and leaves	(Bohlmann & Zdero, 1982); (Adam, 2017)
4β,15-Dihydrodehydrozaluzanin C	Aerial parts	(Bohlmann et al., 1982)
6’’-O-acetyl homoplantaginin	Leaves	(Monjane et al., 2018)
11β,13-Dihydrotubiferin	Aerial parts	(Bohlmann et al., 1982)
11β,13-Dihydrozaluzanin C	Aerial parts	(Bohlmann et al., 1982)
Brachylaenolide	Aerial parts	(Bohlmann et al., 1982)
Costunolide	Aerial parts	(Bohlmann et al., 1982)
α-D-Glucopyranose	Leaves	(Adam, 2017)
β-D-Glucopyranose	Leaves	(Adam, 2017)
Dehydrobrachylaenolide	Aerial parts	(Bohlmann et al., 1982)
Dehydrocostuslactone	Aerial parts	(Bohlmann et al., 1982)
Dehydrozaluzanin C	Aerial parts	(Bohlmann et al., 1982)
Dihydroxysinapic acid	Leaves	(Monjane et al., 2018)
Dihydrodehydrocostuslactone	Aerial parts	(Bohlmann et al., 1982)
Eupafolin	Leaves	(Monjane et al., 2018)
Furanoheliangolide	Aerial parts	(Bohlmann et al., 1982)
Germacranolide	Aerial parts	(Bohlmann et al., 1982)
Germacrene D	Aerial parts	(Bohlmann et al., 1982)
Genkwanin5-O-β-Dglucopyranoside	Leaves	(Adam, 2017)
Germacronolide epoxide	Leaves	(Monjane et al., 2018)
Hydroxytyrosol	Leaves	(Monjane et al., 2018)
Linoleic acid	Aerial parts	(Bohlmann et al., 1982)
Linolenic acid	Aerial parts	(Bohlmann et al., 1982)
Lupeol acetate	Aerial parts and leaves	(Bohlmann et al., 1982); (Zdero & Bohlmann, 1987)
Luteolin	Leaves	(Monjane et al., 2018)
Onopordopicrin	Aerial parts and leaves	(Bohlmann et al., 1982); (Zdero et al., 1987)
Onoporidin	Leaves	(Monjane et al., 2018)
9-oxo-nerolidol	Aerial parts	(Bohlmann et al., 1982)
Quercetin3-Oglucoside-7,3’,4’-trimethyl ether	Leaves	(Monjane et al., 2018)
Quercetin-3-O-β-D-galactopyranoside	Leaves	(Monjane et al., 2018)
Quercetin-7-galactopyranoside	Leaves	(Monjane et al., 2018)
Salonitenolide	Aerial parts	(Bohlmann et al., 1982)
Salonitenolide-8-O-2,3-epoxy isobutyrate	Aerial parts	(Bohlmann et al., 1982)
β-sitosteryl linelonate	Leaves	(Adam, 2017)
Tetrahydrodehydrozaluzanin C	Aerial parts	(Bohlmann et al., 1982)
α-tocopherol	Leaves	(Adam, 2017)
Tubiferin	Aerial parts	(Bohlmann et al., 1982)
Zaluzanin C	Aerial parts	(Bohlmann et al., 1982)

with minimum inhibitory concentration (MIC) values ranging from 0.2 mg/ml to 1.3 mg/ml in comparison to MIC value of <0.02 mg/ml exhibited by the positive control, and total activity ranging from 52.8 ml/g to 412.5 ml/g (Adamu et al., 2014). (Vuuren, Nkwanyana, & Wet, 2015) evaluated the antibacterial activities of dichloromethane : methanol (1:1) and aqueous extracts of B. discolor var. transvaalensis leaves against Staphylococcus aureus, Enterococcus faecalis, Proteus vulgaris, Bacillus cereus, Shigella flexneri, Salmonella typhimurium and Escherichia coli with ciprofloxacin as positive control. The aqueous extract exhibited activities against all tested pathogens with MIC values ranging from 0.3 mg/mL to 2.0 mg/mL while the organic extract exhibited weak activities against Shigella flexneri with MIC value of 4.0 mg/mL. The antibacterial interaction of B. discolor var. transvaalensis used in combination with Psidium guajava L. and Sclerocarya birrea (A. Rich.) Hochst. subsp. caffra (Sond.) Kokwaro was evaluated by calculating the sum of the fractional inhibitory concentrations (∑FIC) against Staphylococcus aureus, Enterococcus faecalis, Proteus vulgaris, Bacillus cereus, Shigella flexneri, Salmonella typhimurium and Escherichia coli with ciprofloxacin as positive control. The extracts exhibited activities against tested pathogens with MIC values ranging from 0.02 mg/mL to 12.0 mg/mL while the combination of B. discolor var. transvaalensis with other species resulted in synergistic to additive effects (Vuuren et al., 2015). (Nciki et al., 2016) evaluated the antibacterial activities of aqueous and dichloromethane : methanol (1:1) extracts of B. discolor twigs against Escherichia coli, Staphylococcus epidermidis, Brevibacterium agri, Pseudomonas aeruginosa, Brevibacterium linens, Propionibacterium acnes and Staphylococcus aureus using the micro-titer plate dilution assay with ciprofloxacin as positive control. The antibacterial interaction of B. discolor used in combination with Euphorbia tirucalli, Hypoxis hemerocallidea, Ozoroa engleri and Senecio serratuloides was evaluated by calculating ∑FIC against Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus aureus. The extracts showed activities with MIC values ranging from 190.0 µg/mL to > 8000.0 µg/mL which was much higher than MIC values of 0.1 µg/mL to 1.25 µg/mL showed by ciprofloxacin, the positive the control. The combination of B. discolor with other species resulted in synergistic to additive effects (Nciki et al., 2016).

Antifungal activities

(Adamu, Naidoo, & Eloff, 2012) evaluated the antifungal activities of acetone extract of B. discolor leaves against Aspergillus fumigatus, Cryptococcus neoformans and Candida albicans using serial microdilution method. The extract exhibited activities with MIC values ranging from 0.08 mg/mL to 0.6 mg/mL and total activity values ranging from 108.0 mL/g to 825.0 mL/g (Adamu et al., 2012). (Nciki et al., 2016) evaluated the antifungal activities of aqueous and dichloromethane : methanol (1:1) extracts of B. discolor twigs against Microsporum canis, Candida albicans and Trichophyton mentagrophytes using the micro-titer plate dilution assay with amphotericin B as positive control. The extracts exhibited weak activities with MIC values ranging from 250.0 µg/mL to > 8000.0 µg/mL which was much higher than MIC values of 0.01 µg/mL to 0.1 µg/mL showed by the positive control (Nciki et al., 2016). (Dikhoba, Mongalo, Elgorashi, & Makhafola, 2019) evaluated the antifungal activities of acetone extract of B. discolor leaves against Fusarium verticillioides, Aspergillus flavus and Aspergillus ochraceous using the microplate dilution method with amphotericin B as positive control. The extract exhibited weak activities against tested pathogens exhibiting MIC values ranging from 0.2 mg/ml to 2.5 mg/ml and total activity of 17.0 ml/g to 271.0 ml/g at both 24 hour and 48 hour incubation periods (Dikhoba et al., 2019).

Anticancer activities

(Fouche et al., 2008) evaluated the anticancer activities of dichloromethane extracts of B. discolor var. rotundata leaves against melanoma UACC62, renal TK10 and breast MCF7. The extracts exhibited activities against melanoma UACC62, renal TK10 and breast MCF7 with total growth inhibition (TGI) values of 13.1 µg/ml, 15.0 µg/ml and 26.0 µg/ml, respectively. The authors also evaluated the anticancer activities of dichloromethane extracts of B. discolor var. rotundata leaves against leukaemia SR, ovarian OVCAR-5 and colon HT 29. The extracts exhibited activities against leukaemia SR, ovarian OVCAR-5 and colon HT 29 with TGI values of 12.3 µg/ml, 20.0 µg/ml and 24.6 µg/ml, respectively (Fouche et al., 2008).

Antidiabetic activities

(De et al., 2008) evaluated the antidiabetic activities of organic and aqueous extracts of B. discolor leaves, roots and stems against 3T3-L1 adipose, C2C12 muscle and Chang liver cells using a glucose utilisation assay with 1.0 µM metformin for Chang liver cells, 1.0 µM insulin for C2C12 and 3T3-L1 cells as positive controls. The extracts demonstrated activities (De et al., 2008). (Mellem et al., 2015) evaluated the antidiabetic activities of the aqueous and methanol extracts of B. discolor leaves by using the α-amylase inhibition and a-glucosidase inhibition assays with acarbose as positive control. The extracts exhibited activities on a-amylase and a-glucosidase with half maximal inhibitory concentration (IC₅₀) values ranging from 1.8 mg/ml to 11.0 mg/ml in comparison to IC₅₀ values of 0.03 mg/ml to 1.2 mg/ml exhibited by the positive control (Mellem et al., 2015).

Antioxidant activities

(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-2-picrylhydrazyl (DPPH) free radical scavenging assays. The extracts exhibited activities with a trolox equivalent antioxidant capacity (TEAC) value of 0.2 and an EC₅₀ 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 IC₅₀ 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 IC₅₀ values of 0.03 mg/ml and 0.2 mg/ml against ABTS and DPPH, respectively (Dikhoba et al., 2019).

Anti-hyperglycaemic activities

(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 streptozotocin-induced and control rats and the biochemical profile of the rats assessed over 28 days. The extract at both doses caused a significant reduction in the blood glucose levels, and other observed changes included total bilirubin, creatinine, alkaline phosphatase and body weight (Mellem, 2013).

Leishmanicidal activities

(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 IC₅₀ values of 39.6 μM and 27.9 μM against Leishmania amazonensis and Leishmania braziliensis, respectively compared to IC₅₀ values of 12.5 μM and 12.0 μM exhibited by the positive control (Monjane et al., 2018).

Cytotoxicity, toxicity and mutagenicity activities

(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 (LD₅₀) 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 (LC₅₀) 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 variation 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.

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