Research Paper a Review on Ziziphus Mucronata

Research Paper

A review on Ziziphus mucronata Willd (Rhamnaceae) commonly used to treat infections and inflammation-related conditions in southern Africa

Accepted 24th June, 2019

ABSTRACT

In under-resourced areas of developing countries, a significant number of people are heavily reliant on medicinal plants for primary health care needs. Extracts of Ziziphus mucronata are among the widely used ethnomedicine to treat infections and relief pain. The focus of this review is to collect all available information on the ethnomedicinal uses, pharmacology and cytotoxicity of the extracts of Z. mucronata. Information was sourced from online search engines such as Google scholar, Science Direct, PubMed, Web of Science, academic books and published thesis etc. Extracts of the root, bark, leaves and fruits are used to treat microbial infections, type-2 diabetes, malaria, some types of cancer as well as analgesics. Absolutely, extracts of Z. mucronata possess additional medicinal benefits such as anti-inflammatory, anti-microbial, anti-plasmodial and anti-helminthic. The observed pharmacological activities are attributed to the constituent cyclopeptide alkaloids and other phytochemicals present in various parts of the plant. The isolated cyclopeptide alkaloids were found to possess potent anti-microbial Salmon A. Adebayo and P. Masoko* properties. The plant species is widely distributed across Africa, and there are no reports of a threat to its existence in the wild. This under-utilised plant species is Faculty of Science and Agriculture, widely distributed in Africa, and its extracts are used to treat various diseases. Department of Biochemistry, Microbiology and Biotechnology, Reports on the biological activities of the extracts may partly support its University of Limpopo, Private Bag ethnomedicinal uses but other potential biological activities are yet to be explored. X1106, Sovenga 0727, Limpopo, South Also, the mode of action of the isolated compounds is not fully known. Phyto- Africa. compounds with proven biological activities and relatively safe profile could be

*Corresponding author. E- used as templates for the development of potent drugs. mail:[email protected]. Tel: (+27) 015-268 2340. Fax: (+27)015 268 Key words: Ziziphus mucronata, ethnopharmacology, phytochemistry, 3012. ethnomedicinal use, taxonomical description.

INTRODUCTION

Medicinal plants continue to play a significant role in eighty-six species, of which Z. mucronata Willd is among the meeting the primary health care needs of people living in most common and best-known trees of southern Africa. The resource limited areas of developing countries, such as members of the taxon are drought tolerant and very those in Africa. One of the most important albeit scarcely resistant to heat, sometimes are found growing in very arid exploited medicinal plants endemic to Africa is Ziziphus areas (Paroda and Mal, 1989).The ancient Greeks refer to mucronata Willd (Rhamnaceae), but it was not listed among the tree as zizyphon, from the Arabic zizouf, a name for the the commercially important medicinal plants of South mythical lotus. This was taken into Latin as zizyphum, or Africa (Street and Prinsloo, 2013). The Rhamnaceae family zizypha for the fruits. The species name mucronata is Latin consists of forty-nine genera and nine hundred plant meaning pointed, probably referring to its thorns or the species (Simpson, 2006). The genus Ziziphus includes apex of its leaves. Z. mucronata Willd. subsp. mucronata Academia Journal of Medicinal Plants; Adebayo and Masoko. 136

Willd., also known as buffalo thorn, is a small to medium- young with branches in ziz-zag arrangement. The bark is sized tree, with a spreading canopy. It is distributed reddish brown or roughly mottled grey, cracked into small throughout the rainfall areas of sub-Saharan Africa, rectangular blocks, revealing a red and stringy under the extending from western Africa across tropical sub-Saharan surface (Figure 1b). The thorns are paired along the stems, Africa to Ethiopia and Arabia, then southwards to southern one facing forward and the other facing backward. Leaves Africa. are simple, alternate, ovate or broadly ovate, varying There are several known ethnomedicinal uses of various enormously in size from tree to tree. The leaves are parts of the plant to treat ailments in both humans and for tapering or often with mucronate apex, strongly ethnoveterinary applications. Its bark and roots are used asymmetrical base, cordate to rounded on one side; margin medicinally for the treatment of gonorrhoea, rheumatism, finely serrated, often badly eaten by insects, glossy green gastrointestinal problems and snake bites (Adamu et al., above, slightly hairy and paler below; 3- to 5-veined from 2005; Tas et al., 1991). Decoctions made of boiled roots and the base; veins covered with fine hairs when young; petiole leaves are applied externally to boils, sores and glandular up to 20 mm long; stipules, when present, take the form of swellings for pain relief while warm bark infusions are used small thorns at the nodes, one straight and one hooked. for body pains, expectorants in cough, respiratory Leaves turn golden yellow in autumn (Figure 1d). Flowers infections and chest problems (Amusan et al., 2005; Venter are borne in dense clusters in leaf axils; green to yellow; ± 4 and Venter, 2002). In the northern region of Nigeria, a mm in diameter; inconspicuous (October-February). The decoction of the plant is used traditionally to treat type-2 fruit is a smooth, shiny, leathery, spherical drupe, 12-20 diabetes mellitus (Etuk et al., 2010; Onakpa and Owoleke, mm in diameter, reddish-brown or deep red when ripe, 2010). slightly sweet, the pulp is dry (Figure 1e). The fruit A recent review of this plant species provided sparse sometimes stays on the plant long after the leaves have records on ethnomedicinal uses and related fallen (March-August), roughly the size of a grape, and pharmacological activities of its extracts (Mokgolodi et al., ripen into a deep brown-red. The seeds are usually solitary, 2011). This updated review expanded on such report and elliptic and compressed. It can survive in a variety of soil summarizes recorded ethnomedicinal uses, types, occurring in many habitats, mostly open woodlands, phytochemistry, pharmacological activities and potential often on soils deposited by rivers, and grows frequently on cytotoxicity of extracts of Z. mucronata Willd sub-species termite mounds. mucronata. While several attempts have been made to demonstrate the efficacy of some of the anecdotal claims of its traditional uses using in vitro and in vivo studies, the Distribution and habitat mode of action of the constituent bioactive compounds is still poorly understood. Furthermore, it is hoped that this The buffalo thorn is distributed throughout the summer information would stimulate further investigations into the rainfall areas of sub-Saharan Africa, extending from South mechanisms and basis of action of some of the isolated Africa northwards to most parts of Africa and Arabia. compounds that could be used as templates for the Z. mucronata grows in areas dominated by thorny development of bioactive drugs. vegetation in both temperate and tropical climates (Maier et al., 2006). It is also found in a wide range of habitats such as woodlands, open scrubland, on rocky koppies, open Taxonomical description grasslands, on a variety of soils along streams, nutrient-rich valley bottoms and forest margins. It reaches its largest size Z. mucronata Willd. subsp. mucronata (Rhamnaceae) has on the margins of scrub forest and on deep, alluvial soils several common names including buffalo thorn (English), near water. Its presence is said to indicate the presence of blinkblaar-wag-'n-bietjie (Afrikaans), umphafa, underground water. This particular plant can survive a umlahlankosi, isilahla (isiZulu), umphafa wide variety of soil conditions, heat, cold frost and drought (isiXhosa),umlahlabantu (Swazi); mokgalo (Tswana), (Maier et al., 2006). mukhalu (Venda), mphasamhala (Tsonga), mokgalô, moonaona (Northern Sotho). In northern Nigeria, it is known as magaryankura (Adamu et al, 2005), Conservation status kanguaKankolonkole (Bemba), ngwelulu (Lola), sula (Hemba) by some tribes in the Democratic Republic of This plant species is not considered to be endangered in Congo (Mpiana et al, 2008) and omukekete in the South Africa as it was not listed among the red-listed plants Ohangwena and Oshikoto regions of Namibia of the South African National Biodiversity Institute’s (Cheikhyoussef and Embashu, 2013), respectively (Table threatened species programme (SANBI, 2017). There are no 1). This plant species is a spiny, small deciduous shrub to records of threats to its existence in South Africa medium-sized tree, 3-20 m in height, with a spreading (Mthethwa, 2009; Semenya et al., 2013) or elsewhere in canopy (Figure 1a). The main stem is green and hairy when Africa where the trees are well distributed. Factors that Academia Journal of Medicinal Plants; Adebayo and Masoko. 137

Table 1: The various local names, habitat and ethnomedicinal uses of different tribes in Africa.

Culture Country Ethnomedicinal uses Reference Umphafa, umlahlankosi, isilahla Zulu South Its bark and roots are used to treat rheumatism, gastrointestinal Tas et al., 1991. van Wyk et al., Umphafa Xhosa Africa complaints and snake bites. Warm bark infusions are used as 1997 Mokgalo Tswana expectorants in cough and chest problems while root infusions are popular as a remedy for diarrhoea and dysentery. Decoctions of Mphasamhala,ncecenyi Tsonga roots and leaves are applied externally to boils, sores and Mokgalô, moonaona Sepedi glandular swellings for pain relief Van der Merwe, 2000 Liengme, 1981 Mutshetshete Venda Decoctions of the leaves and roots are used to treat sores, wound and burns Semenya et al., 2013 The fruits are eaten by children Chauke et al., 2015 The roots are used to treat gonorrhoea and chlamydia Moteetee and van Wyk, 2006 The roots are used in Limpopo with other plants to treat different kinds of diseases Long, 2005 Mokhalo Sesotho Lesotho Umlahlabantu Swati Swaziland Leaf, roots and bark infusions used for chest complaints, boils, wounds, pain relief, skin infections and syphilis. Edible fruit eaten as porridge and meal. The fruits and seeds can be fermented for beer.

Mabyana-a-mala-a-tupa, moketekete, Batswana Botswana The leaves are used locally as food and a health drink; the leaf Setshogo and Venter, 2003, Kwape mokgalo paste can also be used in the treatment of boils. The root of the et al., 2013, Koeven, 2001 plant is usually used in the treatment of a wide range of painful conditions.The roots, bark and leaves are used in the treatment of arthritis, chest pains and boils. The sweet fruits of the plant are widely eaten or dried, ground to powder and cooked as porridge

Omukekete Ovambo Namibia Ethnoveterinary uses of the root extracts to treat diarrhoea in Cheikhyoussef and Embashu, 2013 cattle. Extracts of the fruits are used to make wine and medicine. Extracts of the leaves and roots are used to treat skin allergy, sore fingers and rash

Omukaru Herero Quattrocchi, 2016

Muchechete, Mwichechete Tonga/Tokaleya/ Zambia Root or leaf infusion is taken orally to treat gonorrhoea, syphilis, Chinsembu, 2016 Lozi boils, pneumonia and cough

muChecheni, chiNanga, muPakwe, Shona Zimbabwe The leaves, roots and fruit are used for wounds, abnominal pains Maroyi, 2011 muPasamala, muTsosomva and infertility in women

Umpafa Ndebele Academia Journal of Medicinal Plants; Adebayo and Masoko. 138

Table 1: Continued.

Muchechene ChiTewe and Mozambiqu The roots are macerated in water and used for stomach ache; Bruschi et al., 2011 ChiNdau e constipation and muscular pain

KanguaKankolonkole Bemba Democratic Decoctions of roots and bark is used to treat blennorrhagia, Mpiana et al., 2008 Gwelulu, Lola Republic of feminine sterility, dysmenorrhoea while powdered stem bark is Sula Hemba Congo used for treating wounds

Magaryankura, kurna Hausa Nigeria Decoction of the root/bark is used to treat gonorrhoea. Extracts of Adamu et al., 2005, Kudi and Myint, the leaves are used to treat enteric conditions. A decoction of the 1999, Etuk et al., 2010 plant is also used to treat type-2 diabetes mellitus

Amuranju Yoruba Not stated Obanifa, 2016

Ghallandi, isanzu la kimbughu Tanzania Not stated Quattrocchi, 2016

Esilang/ mkunazi Turkana/Swahili Kenya A decoction of roots a remedy for snake bite, Poultice from roots Quattrocchi, 2016 and leaves applied to boils and skin infection. Fruits and leaves anti-pyretic, tonic for colds. Bark used as antihelmintic, vermifuge, cough and chest pains as well as to treat rheumatism

promote the disappearance of plant species from on traditional uses and distribution were sourced. concoction of the bark and the leaves is used for the wild includes unsustainable over-harvesting, The results obtained were systematically compiled respiratory ailments and other septic swellings of habitat degradation due to agricultural practices and presented in this report to provide an update the skin. Pastes of the root and leaves can be and urban development or mining. These practices on the importance of this plant species in the lives applied to treat boils, swollen glands, wounds and subsequently affect plants’ biodiversity and may of people living in under-resourced communities. sores. Steam baths from the bark are used to purify result in the extinction of certain plant species from and improve the complexion (Palmer and Pitman, the wild if conservation strategies are not timely 1972). In East Africa, roots are used for treating implemented. RESULTS AND DISCUSSION snake bites (Hutchings et al., 1996). Most of the ethnopharmacological uses may be attributed to the Ethnomedicinal and supplementary uses peptide alkaloids and antifungal principles isolated MATERIALS AND METHODS from the bark and the leaves. The leaves are also Extracts of the leaves, stem-bark and root of Z. edible and can be cooked into spinach. The seeds Online search engines such as Google Scholar, Web mucronata are used to treat chronic cough, boil, can be roasted and ground as a substitute for coffee of Science, PubMed, PubChem, Scopus, Science tooth ache, rheumatism and swellings in South (Heuzé and Tran, 2017). The leaves and fruits are direct and academic books, reports, journal and Africa (Iwalewa et al., 2007). A decoction of the also a valuable source of forage for livestock (Heuzé thesis were explored for information. Reports on glutinous roots is commonly administered as a and Tran, 2017). The berries are edible and are ethnobotanical uses, ethnopharmacology and painkiller for all sorts of pains, gastrointestinal used to make a porridge or as a coffee substitute phytochemistry of Z. mucronata, including surveys problems and dysentery (van Wyk et al., 1997). A (Long, 2005; Kwape et al., 2013a). The seeds are Academia Journal of Medicinal Plants; Adebayo and Masoko. 139

(a) (b)

(e)

Figure 1: (a) The “Buffalo thorn” Ziziphus mucrona tree (b) the stem bark (c) the leaf and thorn (d) the flowers and (e) the fruits.

also ground and used as a coffee substitute while the and culture believes in the application of this tree for Ovambo people in Namibia use the seeds to distill “ombike”, spiritual beliefs and superstitions (Hutchings, 2007). The a traditional beer. The fruit can also make a beer if Zulus and Swazis of southern African use the buffalo thorn fermented properly (Cheikhyoussef and Embashu, 2013). relating to burial rites. The part of the tree was also placed In addition to the ethnomedicinal uses, there are other at a Zulu chief’s burial site to signify his resting place supplementary uses of this plant species such as in (Hutchings, 2007). It is thought that a twig from the tree spirituality and construction (Hutchings, 2007; attracts, carries and accompanies the spirit of the deceased Cheikhyoussef and Embashu, 2013). The African tradition from the place of death to the new resting place. When a Academia Journal of Medicinal Plants; Adebayo and Masoko. 140

Figures 2a-e

a b c

d e

Figure 2: The chemical structures of some of the cyclopeptide alkaloids that have been isolated from the extracts of Z. mucronata. (a) mucronine A, (b) mucronine B, (c) mucronine E, (d) sanjoinine-A (Frangufoline A), (e) abyssenine B.

stock owner is dead and buried according to customary abyssenine A and mucronine D from the root bark. This was beliefs within the cattle or goat kraal, some branches would followed by the isolation of mucronine A-J and frangufoline be placed on the grave so that the animals nibbled on leaves from the stem and root barks (Figure 2a-g). Cyclopeptide and twigs, and so understood that their master had died alkaloids are widely distributed in the Rhamnaceae family (Palmer and Pitman, 1972). In other parts, locals drag a but they have also been isolated in other plant families such branch around the village to protect them from evil spirits, as Asteraceae and Rubiaceae amongst others consisting of as it is believed to keep evil spirits away (Hutchings et al., 0.01-1% of dried plant materials (Gournelis et al, 1998). 1996). In Botswana as well as most parts of South Africa, the residents believe that the plant species may provide protection against lightning, such that anyone standing Phytochemistry under the tree in a storm would be safe. It is also believed that if it is felled in summer, a drought, hail or lightning will In a screening for the phytochemical constituents of the certainly follow. Wood from this tree is used for timber, extracts of Z. mucronata, the analysis indicated the wagon making and fence posts as it yields a yellow, fine- presence of polyphenols, flavonoids, tannins, alkaloids and grained, heavy wood which contains 12.2-15.7% tanning saponins. Polyphenols and flavonoids are thought to be matter (Watt and Brandwijk, 1962). The elasticity of the responsible for some of the biological activity of the shoots makes it suitable for bows and whip sticks. Some extracts such as antioxidant, anti-inflammatory and anti- farmers use the thorny branches to make kraals or hedges microbial activities (Kwape et al., 2013b; Iwalewa et al., to protect their livestock from predators. 2007;Adewusi and Steenkamp, 2011; McGaw et al., 2007). Olajuyigbe and Afolayan (2011) reported the presence of significant amounts of polyphenols in the ethanol fruit Phytochemistry and pharmacological activities extracts, followed by the acetone and aqueous extracts, respectively. Phenolic compounds either act by inactivating The scientific validation of various parts of Z. Mucronata lipid free radicals or by preventing the decomposition of ethnomedical applications have been undertaken, to hydroperoxides into free radicals (Maisuthisakul et al., decipher its ability to treat infections; inflammation-related 2007). As such, this prevents oxidation and damage to conditions and pain relief have yielded several cyclopeptide delicate nuclear molecules such as the DNA. alkaloids. Subsequent to the isolation of some cyclopeptide Flavonoids are a group of natural phenolics with several alkaloids from the bark, Auvin et al. (1997) further isolated biological activities such as anti-inflammatory, anti-allergic, Academia Journal of Medicinal Plants; Adebayo and Masoko. 141

anti-microbial and anti-cancer activities. Olajuyigbe and protection against foreign invaders and injury. However, Afolayan (2007) detected the presence of impaired inflammatory process is implicated in the proanthocyanidins in the bark extracts of Z. mucronata. progression of several chronic diseases such as rheumatoid Although found in minute quantities, proanthocyanidins arthritis, obesity, type-2 diabetes mellitus and Alzheimer’s are most likely implicated in the anti-sickling activity seen disease. Painful symptom is one of the classical signs of an in the extracts (Mpiana et al, 2008). Other complex inflammatory process and it contributes significantly to the polyphenolic compounds such as tannins have also been severity of a chronic disease. Acetylcholine esterase is a key studied in the phytochemical profile of extracts of Z. enzyme involved in the hydrolysis of neurotransmitter, mucronata. The broad spectrum anthelmintic activity of acetylcholine. A deficiency or low levels of this extracts of this plant species is suspected to be due to the neurotransmitter in the brain is responsible for Alzheimer’s presence tannins (Watermann et al., 2010). Alkaloids are disease. Some traditionally used plants have shown natural anti-inflammatory and analgesic compounds potentials in the inhibition of acetylcholine esterase as a synthesized by some plants. The isolated alkaloids, therapy for the disease. Adewunmi and Steenkamp (2011) particularly cyclopeptide alkaloids from its extracts are demonstrated the ability of ethyl acetate root extracts of Z. believed to be responsible for the analgesic, anti- mucronata to significantly inhibit the activities of inflammatory and anti-plasmodial activities. acetylcholine esterase.

Pharmacology Anti-diabetic activities

The reported biological activities of extracts of Z. Type-2 diabetes mellitus is a chronic disease resulting from mucronata are due to the pharmacological attributes of the insulin resistance and pancreatic β-cell malfunctioning, constituent compounds. Some of these activities may be which is characterised by sustained hyperglycaemia (Salas- linked to the ethnomedicinal uses of extracts of the plant to Salvado et al., 2011). Because most of the anti-diabetic treat infection, painful symptoms and chronic diseases such drugs in current use are associated with adverse effects as type-2 diabetes mellitus (Table 2). The results in Table 2 such as liver problems, diarrhoea and nausea (Fujisawa, suggest that bioactive compounds are extracted more with 2005), attention has shifted to alternative strategies such as polar solvents with an exception of the dichloromethane the use of natural products. Decoctions made from the plant extracts for anti-helmintic activity. This may partly support is used traditionally in Northern Nigeria to treat type-2 the anecdotal claims of its efficacy by local users because diabetes mellitus (Etuk et al., 2010). This ethnomedicinal decoction and infusions made of water are the common uses for type-2 diabetes mellitus was the basis of scientific mode of preparation and use. evaluation in recent studies (Mpiana et al., 2008; Waterman et al., 2010; Adewusi and Steenkamp, 2011). A bioassay guided study resulted in the isolation of a butanol fraction Antibacterial activities with potent α-glucosidase and α-amylase inhibitory activity (Ibrahim and Islam, 2007). The butanol fraction had Pathogens are constantly evolving and the development of significant anti-hyperglyceamic activity at a dose of 300 resistance to available medication continues unabated. mg/kg body weight in rats but could not alleviate Therefore, there is always a need for alternative complications associated with type-2 diabetes (Ibrahim and therapeutic strategies to combat this trend. Aqueous Islam, 2007). The anti-hyperglyceamic of the extracts of Z. extracts of the bark/root of Z. mucronata significantly mucronata was further demonstrated by Mousinho (2013) inhibited the growth of Proteus mirabilis, Pseudomonas using methanol extracts with the best bioactivity observed aeruginosa, Staphylococcus aureus and Escherichia coli in a at 62.5 µg/mL. However, the mechanism of action of study by Adamu et al. (2005). Comparable results were also extracts of this plant species was believed to be obtained by McGaw et al (2007) using aqueous extracts of independent of insulin. The mechanism of hypoglycaemic the leaf on same bacteria species, as well as Enterococcus action was via the inhibition of both α-glucosidase and α- faecalis. These results suggest that the extracts contained amylase possibly involving the activation of certain useful phyto-compounds that could be helpful in treating receptors without insulin. This could present an alternative diseases associated with these organisms. These therapeutic strategy for treating this type of disease in the compounds could be exerting their biological activity either future. in isolation or in synergy with other compounds present in the extracts. Antioxidant activities

Anti-inflammatory and analgesic activities The fruit extracts of Z. mucronata had a dose-dependent antioxidant activity and in direct correlation with the Inflammation is a complex biological process designed as a polarity of the extractant (Kwape et al., 2013b). Significant Academia Journal of Medicinal Plants; Adebayo and Masoko. 142

Table 2: Some recorded biological activities based on ethnomedicinal uses of extracts of Z. mucronata.

Plant part Ethnomedicinal uses Solvent used Biological assay References Fruits Extracts of the fruits are used to make wine and medicine. Extracts of the Water, ethanol, acetone Free radical scavenging activity Kwape et al., 2013b; leaves and roots are used to treat skin allergy, sore fingers and rash 11 Olajuyigbe and Afolayan, (Cheikhyoussef and Embashu, 2013) 2011

Bark/root Decoctions of the leaves and roots are used to treat sores, wound and Water/ Ethanol Anti-bacterial activity against Proteus Adamu et al., 2005; burns (van der Merwe, 2000) mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli, Klebsiella pneumoniae

Root Decoction of root is used as a remedy for snake bite; Poultice from roots Methanol Anti-fungal activity against Adamu et al., 2006 and leaves are applied to boils and skin infection (Quattrocchi, 2016) Trichophytum rubrum, Trichophytum mentagraphytes, Aspergillus fumigatus and Microsporum gratis

Leaf Extracts of the leaf used to treat enteric conditions (Kudi and Myint, Methanol Anti-viral activity against poliovirus Kudi and Myint, 1999 1999) and astrovirus

Root The roots are macerated in water and used for stomach ache; constipation Methanol Good inhibitory action on Adewusi and Steenkamp, and muscular pain (Bruschi et al., 2011) acetylcholine esterase activity 2011; Kwape et al., 2013a

Root Root infusions are popular as a remedy for diarrhoea and dysentery (van Ethanol Anti-bacterial activity against. Olajuyigbe and Afolayan, Wyk et al., 1997) Escherichia coli, Staphylococcus aureus 2011 and E. faecalis

Stem bark Used to treat fever (Adamu et al., 2006) Ethyl acetate Anti-malarial activity against Zininga et al., 2017 Plasmodium falciparum

Root bark Used to treat sickle cell anaemia 10 (Mpiana et al., 2007) Water Anti-sickling activity on erythrocytes Mpiana et al., 2008

Twig/wood/r Extract of the bark is used as anti-helmintic (Quattrocchi, 2016) Dichloromethane/meth Anti-helmintic activity against Waremann et al., 2010; ootbark ano (1:1) and water Caenorhabditis elegans, Moolgard et al., 2001 Hymenolepisdiminuta, Schistosoma mansoni

Leaf Extracts of the leaf are used locally as health drink (Kwape et al., 2013a) Methanol Protective effect on liver function Kwape et al, 2013a

Bark A decoction of the plant is also used to treat type-2 diabetes mellitus Water/Butanol/methan Anti-diabetic Ibrahim and Islam, 2007; (Etuk, 2010) ol Mousinho, 2013 Academia Journal of Medicinal Plants; Adebayo and Masoko. 143

free radical scavenging activity was observed with the the mode of action of the extracts was via the deactivation methanol extracts but less activity with the hexane extracts of oxidative radicals which could be harmful to hepatic using the 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic cells. acid (ABTS) method. Similar results were previously reported by Olajuyigbe and Afolayan (2011) using the ABTS and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical Other pharmacological activities scavenging activity methods. The ethanol extract had the highest antioxidant activity, followed by the acetone extract Methanol extracts of the root of Z. mucronata inhibited the while the aqueous extract was the least active. The growth of Trichophytum rubrum, Trichophytum respective IC50 values of 0.0306 ± 0.04, 0.0317 ± 0.04 and mentagraphytes, Aspergillus fumigates and Microsporum 0.0429 ± 0.04 mg/mL were obtained using the ABTS gratis (Adamu et al., 2006). These organisms have been methods, while IC50 values of 0.0422 ± 0.03, 0.0482 ± 0.02 implicated in superficial skin infections such as cutaneous and 0.0646 ± 0.02 mg/mL were obtained using the DPPH mycoses, thus extracts of Z. mucronata may be helpful in methods for the ethanol, acetone and water extracts of the the treatment of such disease. Aqueous extracts of the root bark (Olajuyigbe and Afolayan, 2011). These reports bark also had good activity against cestodes of indicated the presence of antioxidant compounds in parts Hymenolepsis diminuta (Mølgaard et al., 2001), a causative of Z. mucronata that could be beneficial in the management organism of schistosomiasis. In another study to of oxidative stress. Oxidative stress has been implicated in demonstrate anti-sickling activity, aqueous extracts of Z. the pathogenesis of many chronic diseases, therefore mucronata actively prevented sickling of erythrocytes extracts having potential as antioxidants could be useful in (Mpiana et al., 2008). The anthocyanin and tannin contents the management of such disease. of the extracts were presumed to be responsible for this bioactivity (Mpiana et al., 2008). The anti-plasmodial activity of ethyl acetate fraction of the stem bark of Z. Potential anti-viral activity mucronata was active against Plamosdium falciparum (Zininga et al., 2017). An ethnobotanical survey conducted in Zambia listed Z. mucronata among the plant species used to treat HIV/AIDS related diseases (Chisembu, 2016). A previous study on the Cytotoxicity methanol leaf extracts indicated significant activity on poliovirus and astrovirus (Kudi and Myint, 1999). Although Medicinal plants are usually extracted and administered by recent breakthroughs in the development of anti-retroviral traditional healers using water or ethanol as solvents. drugs have been recorded, HIV/AIDS remains a lethal There are no reports of adverse health effects resulting disease, especially in resource limited areas of developing directly from the consumption of herbal products made of countries. There are no scientific records on the inhibition extracts of Z. mucronata. The dichloromethane extracts of of HIV virus by Z. mucronata extracts, but the the root of Z. Mucronata was reported to have mutagenic ethnomedicinal uses of its plant extracts for related effects on strain TA98 in the presence or absence of diseases and the inhibition of the growth of other viruses metabolic activation (Elgorashi et al., 2003). Also, the (Kudi and Myint, 1999) could serve as a motivation for such methanol extracts of the leaf were found to be relatively evaluation. cytotoxic to HT-29 human colonic cancer cells (Kudi and Myint, 1999). However, administration of 300 mg/kg body weight of methanolic extracts of the leaf (Kwape et al., Hepato-protective activities 2013), root and twig (Taylor et al., 2003) did not show any sign of toxicity in rats. It is plausible that organic solvents Oxidative stress is implicated in the pathogenesis and such as dichloromethane can transform the bio-activity of progression of many chronic ailments including liver the constituent of phyto-compounds. diseases. Induction of lipid peroxidation by dimethaote can cause oxidative stress, and this hypothesis was tested to determine the capacity of Z. mucronata extracts to protect Conclusions the liver in a mice model. Treatment with methanol extracts of the leaf of Z. mucronata was found to prevent lipid Extracts of Z. mucronata are widely used as food, beverages peroxidation in rats (Kwape et al., 2013a). In addition, the and medicines to treat infections and relieve painful methanol fruit extracts also protected the liver in a similar conditions. The observation on these ethnomedicinal uses manner (Kwape et al, 2013b), suggesting that the bio- has led to the isolation of potent compounds with protective compounds are present in both the leaves and demonstrable biological activities. However, some of the fruits. The methanol fruit extracts further demonstrated ethnomedicinal uses of extracts of the plant, such as anti- good free radical scavenging activity, which suggests that diarrhoea, anti-viral and anti-cancer activities are yet to Academia Journal of Medicinal Plants; Adebayo and Masoko. 144

evaluated scientifically. Although, the biological activities of Africa. the extracts have been attributed to the isolated Iwalewa EO, McGaw LJ, Naidoo V, Eloff JN (2007). Inflammation: the foundation of diseases and disorders. A review of phytomedicines of cyclopeptides alkaloids, proanthocyanidins, tannins and South African origin used to treat pain and inflammatory conditions. other polyphenols, but the mechanisms of action of these Afr. J. Biotechnol. 6(25): 2868-2885. compounds remain unclear. Kudi AC, Myint SH (1999). Antiviral activity of some Nigerian medicinal This plant species is widely available in Africa, and if the plant extracts. J. ethnopharmacol. 68(1-3): 289-294. Kwape TE, Chaturvedi P, Kamau JM, George S (2013a). Hepato-protective ethnomedicinal uses could be proven with scientific data, it potential of methanol extract of Leaf of Ziziphus mucronata (Zmlm) may serve as a cheaper alternative source for disease against dimethoate toxicity: biochemical and histological approach. treatment. Also, exploitation and possible exportation of Ghana Med. J. 47(3): 112-120. this natural resource to other parts of the World could Kwape TE, Chaturvedi P, Kamau M, Majinda R. (2013b) Anti-oxidant and hepatoprotective activities of Ziziphus mucronata fruit extract against provide extra income for communities in Africa. Apart from dimethoate-induced toxicity. J. Pharmacopuncture. 16(1): 21-29. a few in vivo studies on extracts of Z. mucronata (Ibrahim Long C (2005). Swaziland’s flora- siSwati names and uses. www.sntc.org.sz and Islam, 2007; Kwape et al, 2013a; Kwape et al, 2013b), . Accessed online on the 28th August 2017. most reports were based on in vitro evaluations. 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