A synthesis and review of medicinal uses, phytochemistry and biological activities of Markhamia zanzibarica

Markhamia zanzibarica (Bojer ex DC.) K. Schum.has been used in herbal medicine in tropical Africa since ancient times. Markhamia zanzibarica is indigenous to central, eastern and southern Africa. This extensive literature review synthesizes the information currently available on the medicinal uses, phytochemistry and biological activities of M. zanzibarica. The University library and electronic search engines Google Scholar, Scopus, Web of Science, ScienceDirect and PubMed were searched for pertinent information on the medicinal uses, phytochemistry and biological activities of M. zanzibarica. Traditionally, the species has been used as anthelmintic, and traditional medicine for backache, female reproductive problems, sexually transmitted infections, respiratory infections and gastro-intestinal problems. In vitro studies have con irmed the biological activities of M. zanzibarica which include antibacterial, antimycobacterial, antioxidant and cytotoxicity. Various phytochemicals such as alkaloids, anthraquinones, fatty acids, lavonoids, glycosides, phenolics, saponins, sterols, tannins and triterpenes have been isolated from M. zanzibarica. Documentation of the medicinal uses, phytochemistry and pharmacological properties ofM. zanzibarica is essential as this information provides baseline data required for future research and development of health-promoting and pharmaceutical products. However, further pharmacological studies including phytochemical, toxicological, in vitro and in vivo experiments are needed to provide evidence for the clinical effectiveness of remedies prepared from the species.


INTRODUCTION
Markhamia zanzibarica (Bojer ex DC. K. Schum), is a shrub or small tree in the family Bignoniaceae. The family Bignoniaceae consists of 104 genera and 860 plant species which are usually trees, shrubs or lianas and rarely herbs (Fischer et al., 2004). The family Markhamia, Consists of ten species, eight of these have been recorded in tropical Africa while two species have been recorded in southeast Asia (Fischer et al., 2004). The genus name Markhamia is in honour of Sir Clements Robert Markham (1830Markham ( -1916, an English geographer, writer, traveller and explorer (Palmer and Pitman, 1972). The species name "zanzibarica" means from Zanzibar (Bruschi et al., 2011), an island regarded as a region of Tanzania (Chhabra et al., 1987;Kigen et al., 2016) Anthelmintic Roots decoction taken orally Kenya and Tanzania (Kokwaro, 2009;Louppe et al., 2012) Aphrodisiac Roots mixed with those of Uvaria acuminata Oliv.
Tanzania (Chhabra et al., 1991) Yellow fever Stem bark is mixed with that of Mangifera indica L., Maesopsis eminii Engl. and Erythrina abyssinica DC.
The fruit is a slender, pendulous capsule, hairless with pale dots or lenticels, splitting into two halves. Markhamia zanzibarica has been recorded in deep sand, rocky ridges, hill slopes and riverine fringes in dry evergreen coastal forest, dry lowland forest, woodland, bushveld, grassland, secondary bush at sea level to 1500 m above sea level (Diniz and Bignoniaceae, 1988;Bidgood et al., 2006) Markhamia zanzibarica is indigenous to Zimbabwe, Angola, Somalia, Botswana, Malawi, the Democratic Republic of Congo (DRC), Zambia, Kenya, Mozambique, Tanzania and Namibia (Diniz and Bignoniaceae, 1988;Bidgood et al., 2006). Markhamia zanzibarica is used as a non-alcoholic beverage or famine food in Namibia and South Africa (Fox and Young, 1982;Koenen, 2001). The leaves of M. zanzibarica are browsed by game and livestock (Komwihangilo et al., 1995;Mtengeti and Mhelela, 2006). The leaves of M. zanzibarica are sold as traditional medicines in informal herbal medicine markets in Tanzania (Hilonga et al., 2019). Therefore, this extensive review was undertaken to evaluate the medicinal uses, phytochemistry and biological activities of M. zanzibarica.

MATERIALS AND METHODS
The University library and electronic search engines Google Scholar, Scopus, Web of Science, ScienceDirect and PubMed were searched for pertinent information on on the medicinal uses, phytochemistry and biological activities of M. zanzibarica. The keywords such as Markhamia zanzibarica, its synonyms, biological activities, phytochemistry, ethnopharmacology, toxicity, botany and ethnobotany were used separately and in combination used within the electronic databases of ScienceDirect, Scopus, PubMed, Web of Science and Google Scholar.

Nutritional and phytochemical composition of
Markhamia zanzibarica (Dierenfeld et al., 1995). investigated the nutritional properties of the leaves and twigs of M. zanzibarica (Table 2). Some health-promoting nutrients such as calcium, copper, crude ibre, iron, magnesium, manganese, phosphorus, potassium, proteins, sodium and zinc have been identi ied from the species, and these reports corroborate the utilization of M. zanzibarica as fodder for both game and livestock in tropical Africa (Komwihangilo et al., 1995;Mtengeti and Mhelela, 2006). Phytochemical compounds identi ied from the aerial parts, leaves, roots and root wood of M. zanzibarica include alkaloids, anthraquinones, fatty acids, lavonoids, glycosides, phenolics, saponins, sterols, tannins and triterpenes. (Mayekiso et al., 2009) evaluated the antibacterial activities of acetone leaf extracts of M. zanzibarica against Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis and Enterococcus coli using the following microdilution method. The extract exhibited activities against the tested pathogens with minimum inhibitory concentration (MIC) values as low as 0.02 mg/ml. (Mayekiso et al., 2009) also evaluated the antimycobacterial activities of acetone leaf extracts of M. zanzibarica against Mycobacterium fortuitum and Mycobacterium smegmatis using the serial microdilution method. The extract exhibited activities against the tested pathogens with MIC values as low as 0.02 mg/ml (Mayekiso et al., 2009).  (El-Kersh et al., 2016) evaluated the antioxidant activities of n-hexane, ethyl acetate, butanol, chloroform and ethanol extracts of the aerial parts of M. zanzibarica using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay with ascorbic acid as standard.

Pharmacological properties of Markhamia zanzibarica
The ethyl acetate extract exhibited the highest activities with halfmaximal inhibitory concentration (IC 50 ) value of 154.6 µg/ml (El-Kersh et al., 2016). (Khan and Mlungwana, 1999) evaluated the cytotoxicity activities of the compounds γ-sitosterol, campesterol and tritriacontane isolated from M. zanzibarica using the brine shrimp (Artemia salina) assay with lapachol as reference drug. The compound γ-sitosterol exhibited activities with the median lethal concentration (LC 50 ) value of 4.0 ppm, which was lower than the LC 50 value of 5.0 ppm (Khan and Mlungwana, 1999). (McGaw et al., 2010) evaluated the cytotoxicity activities of acetone extracts of M. zanzibarica leaves against Vero kidney cells and bovine dermis cells. The extract exhibited activities with LC 50 values of less than 50.0 ug/ml against both cell types (McGaw et al., 2010;El-Kersh et al., 2016) evaluated the cytotoxicity activities of n-hexane, ethyl acetate, butanol, chloroform and ethanol extracts of the aerial parts of M. zanzibarica against the human cervical adenocarcinoma cell line (HeLa) using the sulforhodamine B colourimetric assay with doxorubicin as a posi-tive control. The extracts exhibited activities with IC 50 values ranging from 9.2 µg/ml to 49.6 µg/ml in comparison to IC 50 value of 7.3 µg/ml exhibited by the positive control (El-Kersh et al., 2016). Similarly, (El-Kersh et al., 2016) evaluated the cytotoxicity activities of n-hexane, ethyl acetate, butanol, chloroform and ethanol extracts of the aerial parts of M. zanzibarica against the HeLa, MCF-7, HEPG2, PC3 and A549 using the sulforhodamine B colourimetric assay with doxorubicin as a positive control. The extracts exhibited activities with the best activities against the cancer cells exhibiting IC 50 values ranging from 8.5 µg/ml to 18.4 µg/ml (El-Kersh et al., 2016).

CONCLUSIONS
This study reviewed the medicinal uses, phytochemistry and biological activities of M. zanzibarica. The current pharmacological studies indicate the potential biological activities of the phytoconstituents and crude extracts of M. zanzibarica, indicating the merit for more attention in future studies. More pharmacological studies including phytochemical, toxicological, in vitro and in vivo experiments are needed to provide evidence for the clinical effectiveness of remedies prepared from the species.

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