Journal of Pharmacognosy and Phytotherapy Volume 6 Number 5, June 2014 ISSN 2141-2502

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Prof. Dr. Adeolu Alex Adedapo Dr. Yuanxiong Deng Department of Veterinary Physiology, Dept of Pharmaceutical Science and Pharmacology School of Medicine University of Ibadan, Nigeria Hunan Normal University Tongzipo Road 371, Changsha 410013, Dr. Joana S. Amaral Hunan China Campus de Sta Apolónia, Ap. 1134, 5301-857 Bragança, Portugal Prof. Maha Aboul Ela

Beirut Arab University, Faculty of Pharmacy, Beirut Dr. Asad Ullah Khan Campus Interdisciplinary Biotechnology UNIT Aligarh Muslim University, Dr. S. RAJESWARA REDDY India Assistant Professor, Division of Animal Biotechnology Department of Biotechnology, School of Herbal Dr. Sunday Ene-ojo Atawodi Studies and Naturo Sciences, Biochemistry Department Dravidian University, Kuppam – 517 425, A.P. Ahmadu Bello University India Zaria, Nigeria

Dr. Mekhfi Hassane Prof. Fukai Bao University Mohammed the First, Faculty of Sciences, Department of and Immunology, Department of biology, Oujda, Morocco Kunming Medical College Morocco China

Dr. Ilkay Erdogan Orhan Dr. Bhaskar C Behera Faculty of Pharmacy, Gazi University, Agharkar Research Institute Ankara, Turkey Dept. of Secience &Technology, Turkey Plant Science Division India Dr. Arun Kumar Tripathi Central Insttute of Medicinal and Aromatic Plants Prof. R. Balakrishna Bhat P.O. CIMAP, LUCKNOW-226015, Walter Sisulu University India Department of Botany Mthatha, South Africa Dr. Wesley Lyeverton Correia Ribeiro Universidade Estadual do Ceará, Faculdade Dr. Mohammad Nazrul Islam Bhuiyan de Veterinária/Laboratório de Doenças BCSIR Laboratories; Parasitárias Av. Paranjana, 1700 Chittagong cantonment; Itaperi - Fortaleza Chittagong-4220; 60740-903, CE - Brazil Bangladesh

Dr. Baojun Bruce Xu Dr. Adibe Maxwell Ogochukwu Beijing Normal University-Hong Kong Baptist Clinical Pharmacy and Pharmacy Management, University United International College Zhuhai, Faculty of Pharmaceutical Sciences, Guangdong Province, University of Nigeria, Nsukka China Enugu state, Nigeria. Dr. Hamad H. Issa Department of Physical Sciences, Dr. Odukoya, Olukemi Abiodun School of natural Sciences, Department of Pharmacognosy, The University of Dodoma, Faculty of Pharmacy Tanzania University of Lagos. Nigeria. Dr. Gagan Deep Department of Pharmaceutical Sciences Dr. Qinxue Richard Ding School of Pharmacy, Medical Center at Stanford University, University of Colorado Denver, Palo Alto, Colorado, USA USA Dr. Sulejman Redžic Dr. Fengguo Xu Faculty of Science of the University of Sarajevo Dept of Epidemiology and Public Health, 33-35 Zmaja od Bosne St., Yong Loo Lin School of Medicine, Sarajevo, National University of Singapore, Bosnia and Herzegovina Singapore Dr. Michal Tomczyk Dr. Haitao Lv Medical University of Bialystok, Medicine and Endocrinology, Faculty of Pharmacy, Albert Einstein College of Meidicine, Department of Pharmacognosy, Yeshiva University, Poland USA Dr. Ugur Çakilcioglu Hassane MEKHFI Firat University, University Mohammed the First, Faculty of Science and Arts, Faculty of Sciences, Department of Biology, Department of biology, Elazig Laboratory of Physiology and Ethnopharmacology, Turkey Morocco

Dr. Subhash C. Mandal Prof. Samson Sibanda Division of Pharmacognosy National University of Science and Technology Pharmacognosy and Phytotherapy Research Cnr Gwanda Road/Cecil Avenue, Laboratory, Ascot, Bulawayo, Department of Pharmaceutical Technology, Zimbabwe Jadavpur University, India.

Journal of Pharmacognosy and Phytotherapy

Table of Contents: Volume 6 Number 5 June 2014

ARTICLES

Research Articles

Risk of liver damage, reduced serum T3 and TSH, reduced placental and litter birth weights are some of the outcomes of Hybanthus enneaspermus infusion to pregnant rats 54 Awobajo F. O., Iranloye B. O., Olatunji-Bello I. I. and Adegoke O. A.

African medicinal plant derived products as therapeutic arsenals against multidrug resistant microorganisms 59 Assob Jules Clement Nguedia and Nsagha Dickson Shey

Vol. 6(5), pp. 54-58, June 2014 DOI: 10.5897/JPP2014.0310 Article Number: 7E1D00945350 Journal of Pharmacognosy and ISSN 2141-2502 Copyright © 2014 Phytotherapy Author(s) retain the copyright of this article http://www.academicjournals.org/JPP

Full Length Research Paper

Risk of liver damage, reduced serum T3 and TSH, reduced placental and litter birth weights are some of the outcomes of Hybanthus enneaspermus infusion to pregnant rats

Awobajo F. O., Iranloye B. O., Olatunji-Bello I. I. and Adegoke O. A.

Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Nigeria.

Received 27 Jan, 2014: Accepted 30 May, 2014

Hybanthus enneaspermus is used by traditional birth attendants (TBAs) in southwest Nigeria in antenatal care. We examined the effects of oral administration of aqueous leaf extract of H. enneaspermus (HEaq) on liver weight and assay, maternal-thyroid hormones, foetal growth and litters birth weights in Sprague-Dawley (SD) rats. Twelve pregnant SD rats were used for this study. Control group received distilled water while the test group received 2 g/kg body weight of HEaq orally throughout the period of pregnancy. On day 19 of pregnancy, animals were sacrificed by CO2 asphyxiation and cervical dislocation. Blood samples were withdrawn into sterile tubes and centrifuged to obtain serum that was used for assay. Liver hormogenate was used for liver function test. The following were assayed; alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), thyroid hormone, thyrotrophin and TSH in both control and treated rats. Some rats were allowed to carry their pregnancy to term. All rules guiding animal care and humane handling methods of laboratory animals in animal experimentation were followed. The results of the study showed a significant increase in serum and liver homogenate level of biomarkers of liver injury (ALP, ALT and AST). The serum T3 and TSH were significantly lowered in all extract treated rats compared to control, while T4 and thyrotrophin were not significantly altered. A significant reduction in placenta and foetal birth weights were recorded in the extract treated group. Oral administration of HEaq during pregnancy adversely affected maternal thyroid hormones, placental and foetal development. HEaq administration to pregnant rats also precipitated increased biomarkers of liver damage.

Key words: Hybanthus enneaspermus, pregnancy outcome, thyroid hormone, litters birth weight, liver function test.

INTRODUCTION

The activities of the traditional birth attendants (TBAs) are enneaspermus is one of the most important medicinal still common in Nigeria society where they attend to > plants used in southwest Nigeria by the TBAs (Awobajo 50% of deliveries (Oruamabo, 2007). One of the tools et al., 2013). The TBAs claimed that administration of the used by the TBAs is medicinal plant. Hybanthus concoction of the leaf extract of the H. enneaspermus

Awobajo et al. 55

(HEaq) plant invigorate the pregnant woman, boost the following assays were carried out; alanine aminotransferase (ALT), haematological parameters and make delivery easy and aspartate aminotransferase (AST), alkaline phosphatase (ALP) and safe (Awobajo et al., 2013). However, these claims are thyroid hormones assay. AST, ALT, ALP was measured using commercially available kits ELISA kit and a UV-spectrophotometer not scientifically verified. Several other medicinal plants (Hitachi 736-60, Japan). Hormonal assay was carried out with have been shown to possess some advantages while Randox assay kit, (UK) according to manufacturer specification. many others have deleterious effects on body system The liver was dissected out over ice pack, homogenized in phos- (Dahanukar et al., 2000). phate buffer after which it was centrifuged at 1500 g for 15 min. The H. enneaspermus (Linn) F. Mull commonly called supernatant from liver hormogenate and serum from blood samples were stored frozen at -8°C until used for the assays. “Abiwere” in Yoruba land, south west Nigeria is a shrub that belongs to the Violaceae family. We have earlier reported on the identification, extraction, phytochemistry Pregnancy outcome and lethal dose (LD50) determination of the leaf extract of the plant (Awobajo et al., 2009a). Analysis of the The remaining rats from each group were allowed to carry the chemical constituent has been reported (Anand and pregnancy to term. Weights of litter were taken few minutes after delivery. Foetal and placenta recovered from rats sacrificed on 19th Gokulakrishnan, 2012). Other reported activities includes day of pregnancy were also recorded after laparotomy. antimicrobial activities against some urinary tract pathogens (Sahoo et al., 2006; Awobajo et al., 2009), anticonvulsant and free radical scavenging activity Statistical analysis (Hemalatha et al., 2003), antiplasmodial activity (Weniger et al., 2004), antidiabetic and antioxidant potentials (Patel Results were analysed using analysis of variance (ANOVA) and presented in Tables as Mean ± standard error of mean (SEM). et al., 2011). The oral infusion of the aqueous leaf extract Level of significance was placed at p ≤ 0.05. All experimental of HEaq to pregnant rats precipitated poor pregnancy protocols adopted in this study including animals handling were outcome (Awobajo et al., 2013). The aim of this present approved by the University and are in compliance with International study was to further investigate the effects of HEaq on guidelines on care and use of laboratory animals in biomedical thyroid hormone and liver toxicity when administered research. orally to pregnant rats.

RESULTS MATERIALS AND METHODS The results of the weight gain during pregnancy showed Animal grouping and treatment no significant (at p ≤ 0.05) difference in maternal weight gain over the duration of the pregnancy between control Two groups (control and HEaq) of mature female Sprague-Dawley rats weighing 170 to 180 g (12 rats per group) and four adult male and treated rats, neither was there any difference in the rats were used for this study. They were housed in standard cages pregnancy duration (Table 1). Foetal weight, placenta (4 rats/cage) at room temperature and provided clean water and rat weight and litter birth weights in HEaq treated group of chow ad libitum throughout the experiment. Pregnancy was rats were all significantly reduced (p ≤ 0.05) compared established by the presence of sperm cells in the vagina smear of with control group as recorded on day 19 of pregnancy normal cycling rats after 24 h cohabitation with adult male rat. The day sperm cells were discovered in the smear taken as day one of (Table 2). Maternal thyroid hormone level on day 19th of pregnancy. HEaq treated group were force-fed at a dose of 2 g/kg pregnancy showed a significant reduction in T3 and TSH. body weight (Awobajo et al., 2013) throughout the gestation The T4 level also was decreased but the decrease duration, while the control rats received equal volume of distilled recorded was not significant. The T4/T3 ratio was water; the vehicle. We have reported the method of identification, significantly increased in the extract treated group extraction and LD50 (LD50; 8.14 ± 0.30 or 8.24 ± 0.35 g/kg body compared to control (Table 4). There were no significant weight) determination of the HEaq in previous publication (Awobajo et al., 2009a). Weekly weights of all animals were monitored. change to the weight gained and duration of pregnancy in HEaq group and control rats (weight gained control; 40.00 ± 5.77, HEaq; 40.00 ± 5.52, gestational duration Blood collection and assay procedures control and HEaq; 21.00 ± 0.32). The results of the liver function test showed a sig- On pregnancy day 19, half the numbers of rats in each group were nificant increase and a significant decrease (p ≤ 0.05) in sacrificed by cervical dislocation after CO2 asphyxiation. Blood samples were collected via cardiac puncture and centrifuged at serum and liver homogenate level of AST, respectively in 1500 g for 15 min to obtain the serum used for various assays. The HEaq rats compared to control. ALT was also significantly

*Corresponding author. E-mail: [email protected]. Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4.0 International License

56 J. Pharmacognosy Phytother.

Table 1. Effects of oral administration of HEaq on Gestational length and weight gain during pregnancy.

Weight gain during Gestational Group gestational period (g) duration (days) Control 40.00 ± 5.77 21.00 ± 0.32 HEaq 40.00 ± 5.52 21.00 ± 0.32

*Significantly reduced (p ≤ 0.05) compared with control.

Table 2. Effects of oral administration of HEaq during pregnancy on fetal and placental weight on day 19 of pregnancy and litter weight at birth.

Group Fetal weight (g) Placenta weight (g) Litter weight (g) Control 2.23 ± 0.07 0.53 ± 0.04 4.51 ± 0.22 HEaq (2 g/kg) 1.72 ± 0.04* 0.41 ± 0.03* 3.68 ± 0.21*

*Significantly reduced (p ≤ 0.05) compared with control.

decreased in the serum while it was increased in the liver which has already placed high demand on the maternal homogenate in pregnant rats exposed to HEaq. ALP was liver function. The relative liver weight was also increased only significantly increased (p ≤ 0.05) in the serum of significantly in the extract treated group, a sign of HEaq rats while its level in the liver homogenate was not hypertrophy possibly as a result of increase detoxification different from the results recorded for the control group activities. (Table 3). Although, there were no significant effect on maternal weight gained during pregnancy; foetal weight and placenta weight at day 19 of pregnancy were significantly DISCUSSION reduced in HEaq treated rats. This also translated into a significant reduction in the weights of the litter delivered Several environmental contaminants and phytoestrogens at term by all HEaq treated rats. Foetal nutrition has a lot are known to affect the normal growth and development to do with functional placenta which serve not only as the of the foetus despite the fact that the genome regulates channels through which nutrient and gases are the various stages of the development. Medicinal plants exchanged between the maternal and foetal blood but contain several phytochemicals, some of which are also secretes some hormones for sustenance of preg- known to mimic some hormones in the body (Hughes, nancy (Sanin et al., 2001). Other authors have also linked 1998; Dweck, 2006). Through the interactions of these the incident of intrauterine growth restriction to reduced phytochemicals with various receptors found in the body, placenta size, volume and weight (Metzenbauer et al., they act as agonist or antagonist in the regulation of 2002). While increase in placenta weight during preg- various cellular activities. There are reports of potential nancy has been well established to initiate corresponding abortifacient activities of some of these medicinal plants fetal weight gain (Sanin et al., 2001), increased maternal (Nath et al., 1992), while others have been reported to thyroxine level has also been shown to stimulate placenta produce birth defects (Costa et al., 2012). growth (Spencer et al., 1993). Therefore, the decrease in The present study on toxic effects of HEaq in pregnant placenta weight recorded in HEaq group might have been rats revealed a significant increase in serum level of ALP precipitated by the decrease in T3 level. Thus, the and AST, and a significant increase in liver tissue level of decreased placenta growth may have resulted in reduced ALT on pregnancy day 19 compared to control. Serum or foetal growth and the significant reduction in birth weights liver homogenate level of ALT (gold standard biomarker), of litter born to all HEaq treated rats. ALP and AST are established biomarkers of liver injury, Going by the importance of thyroid hormone to normal routinely used in assessing liver functions (Schomaker et growth and development of the foetus and the reported al., 2013). This result showed that although HEaq may 8.8% hypothyroidism prevalence in Saharan Africa have wide oral toxic safety margin (Awobajo et al., (Sidibe, 2007), one may conclude that the prevalence 2009a), its administration to pregnant rats precipitated may be worsened by the use of such medicinal plants toxic effects. This will be detrimental to the pregnancy with antithyroid potentials during pregnancy. However,

Awobajo et al. 57

Table 3. Effects of oral administration of aqueous leaf extract of Hybanthus enneaspermus to pregnant rats on maternal Thyroid hormones, TRH and Thyrotropin on day 19 of pregnancy.

T T TSH TRH Group 3 4 T /T ratio (nmol/l) (nmol/l) 4 3 (µIu/ml) (Iu/ml) Control 2.76 ± 0.08 74.00 ± 1.17 26.85 ± 0.57 3.35 ± 0.64 26.55 ± 3.61 HEaq 1.77 ± 0.09* 70.14 ± 0.43 40.14 ± 2.54† 1.12 ± 0.26* 26.70 ± 7.35

*Significantly lowered compare to the control (p ≤ 0.05). †Significantly increased compared to control (p ≤ 0.05). #significantly lowered compared to T4 level.

Table 4. Maternal serum and liver homogenate level of AST, ALT and ALP on day 19 of pregnancy in rats treated with aqueous leaf extract of HEaq compared with control.

Serum Liver homogenate Group Control HEaq Control HEaq Aspartate aminotransferase „AST‟ (U/L) 177.50 ± 7.76 210. 21 ± 48.99† 39.60 ± 6.49 6.45 ± 3.31* Alanine aminotransferase „ALT‟ (U/L) 222.95 ± 37.21 36.30 ± 2.04 * 22.05 ± 7.23 217.15 ± 25.60† Alkaline phosphatase „ALP‟ (U/L) 80.43 ± 21.28 137.96 ± 1.71† 29.77 ± 6.16 21.16 ± 6.99

*Significantly lowered compare to the control (p ≤ 0.05). †Significantly increased compared to control (p ≤ 0.05).

further studies will be required to establish the safety. OA, Adeleke TL (2009). Acute oral toxicity test and mechanism via which HEaq produced alteration in photochemistry of some West African medicinal plants. Niger. Q. J. Hosp. Med. 19(1):53-58. placenta development and a possible link to the Costa KCS, Bezerra SB, Norte CM, Nunes LMN, Olinda TM reduced foetal growth. Conflict of Interests (2012). Medicinal plants with teratogenic potential: current considerations. Braz. J. Pharm. Sci. 48(3):427-433. The author(s) have not declared any conflict of Dahanukar SA, Kulkarni RA, Rege NN (2000). Pharmacology Conclusion of medicinal plants and natural products. Indian J. Pharm. interests. 32:S81-S118. Dweck AC (2006). Isoflavones, phytohormones and Oral administration of aqueous leaf extract of H. phytoesterols. J. App. Cosmetol. 24:17-33. enneaspermus at a dose of 2 g/kg body weight to REFERENCES Hughes CL (1998). Phytochemical mimicry of reproductive pregnant Sprague-Dawley rats increased risk of hormones and modulation of herbivore fertility by Anand T, Gokulakrishnan K (2012). GC–MS analysis and anti- phytoestrogens. Environ. Health perspect. 78:177-175. liver damage, precipitated reduction in placental microbial activity of bioactive components of Hybanthus Metzenbauer M, Hafner E, Schuchter K, Philipp K (2002). First growth and a reduction in maternal T3 and TSH enneaspermus. Int. J. Pharm. Pharm. Sci. 4(3):646-650 trimester placental volume as a marker for chromosomal with resultant reduction in litter birth weights. Awobajo FO, Olatunji-Bello II, Adegoke OA, Odugbemi TO anomalies: preliminary results from an unselected There is need to properly evaluate the merits and (2009). Phytochemical and antimicrobial screening of population .Ultras. Obstet. Gynecol. 19:240-242 Hybanthus enneaspermus and Parquetina nigrescens. Nath D, Sethi N, Singh RK, Jain AK (1992). Commonly used demerits of the various medicinal plants used by Recen. Res. Sci. Tech. 1(4):159-160 Indian abortifacient plants with special reference to their TBAs in care of pregnant women to ascertain their Awobajo FO, Omorodion-Osagie E, Olatunji-Bello II, Adegoke teratologic effects in rats. J. Ethnopharm. 36(2):147-154.

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Oruamabo RS (2007). Neonatal tetanus in Nigeria: does it still pose a Schomaker S, Warner R, Bock J, Johnson K, Potter D, VanWinkle J, major threat to neonatal survival? Arch. Dis. Child 92:9–10. Aubrech J (2013). Assessment of emerging biomarkers of liver injury Patel DK, Kumar R, Prasad SK, Sairam K, Hemalatha S (2011). in human subjects. Toxicol. Sci. 132(2):276-283. Antidiabetic and in vitro antioxidant potential of Hybanthus Spencer GS, Robinson GM (1993). Stimulation of placental, fetal and enneaspermus (Linn) F. Muell in streptozotocin-induced diabetic rats. neonatal growth by thyroxine administration to pregnant rats. J. Asian Pacif. J. Trop. Biomed. 316-322 Endocrinol. 139(2):275-279. Sahoo S, Kar DM, Mohapatra S, Rout SP, Dash SK (2006). Antibacterial activity of Hybanthus enneaspermus against selected urinary tract pathogens. Indian J. Pharmaceut. Sc. 68(5):653-655. Sanin LE, López SR, Olivares ET, Terrazas MC, Silva MAR, Carrillo ML (2001). Relationship between birth weight and placenta weight. Neonatology, 80(2):113-117.

Vol. 6(5), pp. 59-69, June 2014 DOI: 10.5897/ JPP2013.0322 ISSN 2141-2502 Journal of Pharmacognosy and Article Number: 8AFB4AA45353 Copyright © 2014 Phytotherapy Author(s) retain the copyright of this article http://www.academicjournals.org/JPP

Full Length Research Paper

African medicinal plant derived products as therapeutic arsenals against multidrug resistant microorganisms

Assob Jules Clement Nguedia1* and Nsagha Dickson Shey2

1Department of Biomedical Sciences, Faculty of Health Sciences, University of Buea, Cameroon. P. O. Box 63 Buea, Cameroon. 2Department of Public Health and Hygiene, Faculty of Health Sciences, University of Buea, Cameroon. P. O. Box 63 Buea Cameroon.

Received 16 November, 2013; Accepted 5 May, 2014

Infectious diseases due to resistant pathogenic strains are rampant and the burden is worsened by the emergence and spread of microorganisms resistant to cheap and effective first-choice drugs. Medicinal plants could be an alternative solution to this and the aim of the present review is to summarize available evidence and knowledge concerning African medicinal plants used to treat multidrug resistant (MDR) bacteria, fungi and protozoa infectious agents. A literature search using the keywords: Africa, medicinal plants and multi-resistant microorganisms on google scholar, African Index Medicus, PubMed, Medline and EMBASE was conducted. We also scanned reference lists for important citations. Key pharmaceutical journals, workshop and conference proceedings were reviewed. Common medicinal plants found are Brucea javanica, Prunus Africana, Mangifera indica, Picralima nitida, Aloe arborescence, Aloe striata, Vernonia adoensis, Markhamia tomentosa, Garcinia lucida, Garcinia kola, Phyllanthus muellerianus, Gladiolus gregasius, Sida alba, Trichila heudelotti, Piptadeniastrum africana and Dorstenia picta. Most researches on the use of medicinal plants to treat multidrug resistant agents were conducted in South Africa, Nigeria, Cameroon, Congo, Kenya, Zimbabwe, Burkina Faso and Uganda. African medicinal plants possess important therapeutic agents that can be used as new phyto- medicines against MDR microorganisms.

Key words: Africa, medicinal plants, therapeutic products and multidrug resistant microorganisms.

INTRODUCTION

The spread of microorganisms which are resistant to centers and consumption of drugs without medical cheap and effective first-choice drugs, although a natural supervision and during insufficient length of time. Other phenomenon, is becoming a public health concern. confounding factors include frequent movements of Favorable factors accounting for this include auto- population, overcrowding which provides opportunities for medication, treatment outside of recognized treatment the rapid spread of microorganisms including multidrug

*Corresponding author. E-mail: [email protected]. Tel: 00237 79239483. Author(s) agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4.0 International License 60 J. Pharmacognosy Phytother.

resistant strains (Njunda et al., 2012). Multidrug compounds have been proven to possess inhibitory resistance to as many as seven antibiotics has been properties on multidrug resistant microorganisms. How- observed in many epidemiological studies in Africa (Iruka ever, phytomedicines as antimicrobial agents have been and Sosa, 2008; Njunda et al., 2012). Antibiotics that evaluated scientifically in various countries in Africa. usually face resistance are ampicillin, amoxicillin, co- They present a low risk of resistance development to trimoxazole, gentamicin, ceftriaxone and augmentin their action, because they are complex mixtures, making (amoxicillin + clavulinic acid) because of their wide microbial adaptability very difficult (Daferera et al., 2003). indiscriminate use. Microorganisms that usually cause This review summarizes the currently available antibiotherapy failure include those that affect the knowledge on medicinal plants used to treat multidrug urogenital tract such as beta-lactamase producers resistant infections and the efficacy of plant-derived Neisseria gonorrhoeae, , Pseudomonas extracts and compounds across Africa. aeruginosa, Proteus mirabilis, methicilin resistant Staphyloccocus aureus (MRSA) and mycoplasmas (Njunda et al., 2011). Those responsible for pulmonary METHODOLOGY infections include Mycobacterium tuberculosis, Klebsiella pneumonia and Streptococcus pneumonia. Agents A literature search using the keywords: Africa, medicinal plants and multi-resistant microorganisms on Google scholar, African Index responsible for gastrointestinal infections include Medicus, PubMed, Medline and EMBASE was conducted. We also Escherichia coli, Entamoeba histolica, Salmonella typhi scanned reference lists for important citations. Key pharmaceutical and Shigella dysenteriae (Njunda et al., 2011). journals, workshop and conference proceedings were reviewed. Various mechanisms to acquire or develop intrinsic African researchers of medicinal plants were contacted. resistance to antibiotics which are developed by pathogens include active efflux of drugs, alteration of target sites, enzymatic degradations and propagation of RESULTS resistance genes (Sibanda and Okoh, 2007). Bacterial resistance to penicillin is expanding to cephalosporins Plant compounds with activity against multi-resistant leading to the development of plasmid-mediated bacteria pathogens in Africa extended spectrum β-lactamases (ESBLs) strains. As new antimicrobial compounds are discovered, there is a Some isolated pure compounds of plant origin have been need to assess their potentials in combination therapies reported to have resistance modifying activities in vitro. with old antibiotics that have been rendered ineffective by This has prompted the search for such compounds from the development of resistant strains (Sibanda and Okoh, a variety of medicinal plants. Some of the compounds 2007). which have been observed to have direct antimicrobial Management of infectious diseases caused by beta- activity were also able to potentiate the activity of antibio- lactam-resistant bacteria strains in developing countries tics when used at low minimum inhibitory concentration where efficient antibiotics are not affordable for the (MIC) levels. For instance the antimicrobial property of majority of the population is becoming urgent and tea (Camellia sinensis) is due to polyphenols (Kim et al., alternative agents can be obtained from medicinal plants. 2000). Bioassay directed fractionation of its extracts In Africa, medicinal plants are used in the fight against revealed its content in bioactive components such as many infectious ailments; they still play a great role as epicatechin gallate (ECG), epigallocatechin gallate therapeutic agents in many African countries (Kuete et (EGCG), epicatechin (EC) and caffeine (CN). Used in al., 2011). They may form a good source of antimicrobial combination in vitro, ECG and CG reduced MIC values medications or resistance modifying agents to be for oxacillin from 256 and 512 to 1 and 4 mg/L against discovered. Treatment of endemic infections using methicilin resistant Staphyloccocus aureus (MRSA) (Kim available natural resources would provide more efficient et al., 2000). Ethyl gallate is a congener of alkyl gallates, drugs to patients. Many medicinal plants and their purified from a dried pod of tara (Caesalpinia spinosa) derived products now form part of the therapeutic native to South America, intensified beta-lactam suscep- arsenals of Africa, faced with ever increasing infectious tibility in MRSA and MSSA strains (Kim et al., 2000). diseases, emerging and re-emerging infectious diseases Twenty six species of medicinal plants belonging to 19 due to multidrug resistant microorganisms and immune families were described in previous studies were shown deficient diseases such as HIV/AIDS. It is estimated that to possess antimicrobial properties on multidrug resistant more than 5,000 active principles have been identified in bacteria species in six different countries across Africa fruits, vegetables and grains, but a large percentage still (Table 1). These plants are used in traditional folk remain unknown and need to be studied to increase our medicine against all types of infectious ailments including understanding of their health benefits (Kuete and Efferth, gastrointestinal, pulmonary, genito-urinary tracts and skin 2010). and skin infections. Seeds, stem barks, leaves, bulbs, Studies on the antimicrobial properties of medicinal twigs and roots are the plants’ parts extracted using extracts on resistant strains of microorganisms are mostly methanol, water and acetone as major solvents. scanty and only few antimicrobial agents as isolated Although these studies indicated inhibitory activities on Assob and Nsagha 61

Table 1. Plants used in Africa against multi-resistant bacteria species with evidence of their antimicrobial properties.

Traditional Solvent used/screened Antibiogram resistance Family Species Country Plant parts used Bioactive compounds Microbial strains References treatment activity profile Ethanolic extract, efflux tannins, phenols, K. pneumonia ; S. Chitemerere and Anacardiaceae Mangifera indica Zimbabwe cough and diarrhea twigs and leaves inhibitory activity of extract aureus ; P. aeroginosa ; - Mukanganyama comparable to reserpine alkaloids, glycosides Bacillus cereus 2011

E. coli 25922 , E. aerogenes E. cloacae, K. AMX, Pip, CE, AMX, Pip, Picralima nitida Hypertension, fever, pneumoniae K. CE, AMX, Pip, CE, ESBL, Gangoué- (Stapf.) T. & malaria, anti- Methanolic:1.25

ESBL positive Amx, Amp, TLC fingerprint Treatment of aztreonam, Aloe Leaves revealed the presence Bisi-Johnson South Africa diarrhoea and Acetone. C=0.078mg/ml S. typhimurium Pip/tazobactam, COT arborescence of flavonoids and et al., 2012 stomach ailments Oxazole and Tet with triterpenoids reduced susceptibility to CI Ashodelaceae

ESBL positive TLC fingerprint Treatment of Leaves revealed the presence Amx, Amp, aztreonam, Bisi-Johnson Aloe striata; South Africa diarrhoea and Acetone. C=0.078 mg/ml S. typhimurium of flavonoids and Pip/tazobactam, COT et al., 2012 stomach ailments triterpenoids Oxazole and Tet with reduced susceptibility to CI

Chitemerere Ethanolic extract. Efflux K. pneumonia, S. boiled decoction and Asteraceae V. adoensis Zimbabwe Leaves inhibitory activity of extract - aureus, P. aeroginosa, - active against TB Mukanganyam with reserpine as reference B. cereus a 2011

Anti snake S. aureus; NCTC6571 Markhamia venom/bite, sore B. subtilis ; NCIB 3610 PV CE EM ; Aug Tet PV Aladesanmi et Bignoniaceae tomentosa Nigeria Leaves methanolic extract - eyes, heart pain, CE EM ; Nal PV CE EM al., 2007 (Benth) K. Schum P. aeruginosa. ATCC scrotal elephantiasis 10145

Gastric ulcer, E. coli 25922 ,E. fermentation of palm aerogenes E. cloacae, AMX, Pip, CE ; AMX, Pip, wine, gynecological K. pneumoniae, K. Gangoué- Methanolic: 1.25

62 J. Pharmacognosy Phytother.

Table 1. Contd.

Gastric ulcer, E. coli 25922 ,E. fermentation of palm aerogenes E. cloacae, AMX, Pip, CE, AMX, Pip, wine, gynecological Gangoué- Methanolic:1.25

E. coli, K. pneumonia, Phyllanthus Use for infectious All resistant against, Amp Assob et al., Cameroon Stem barks Methanolic Ant, Fla, Pol P. aeruginosa,P. muellerianus ailments mirabilis, S. flexneri, S. Augmentin 2011 typhi

Euphorbiaceae E. coli 25922 ,E. Cough, aerogenes, E. cloacae, AMX, Pip, CE, AMX, Pip, antimicrobial,diarrho Gangoué- Bridelia micantha Methanolic:1.25

Diarrhoea, infected E. coli 25922 , E. wounds, anti- aerogenes E. cloacae, AMX, Pip, CE, AMX, Pip, Gangoué- inflammatory, Methanolic: 1.25 36 µg/ml hydroxylonchocarpin (4- 2010 LCP), stipulin (SPL), amentoflavone (AMF)

ESBL positive TLC fingerprint Use in the treatment Acetone: C=0.312-0.625 revealed the presence Amx, Amp, aztreonam, Bisi-Johnson Psidium guajava South Africa of diarrhoea and Leaves S. Typhimurium mg/ml of flavonoids and Pip/tazobactam, COT et al., 2012 stomach ailments triterpenoids. Oxazole and Tet with Myrtaceae reduced susceptibility to CI

Chitemerere Antibacterial, Ethanolic extract, efflux K. pneumonia, S. Calistermon and Zimbabwe hemorrhoid Leaves inhibitory activity of extract - aureus, P. aeroginosa - citrinus Skeels Mukanganya treatment comparable to reserpine Bacillus cereus ma 2011 Assob and Nsagha 63

Table 1. Contd.

E. coli, K. pneumonia, Gladiolus Use for infectious P. aeruginosa, P. All resistant against Amp Assob et al., Iridaceae Cameroon Bulbs Methanolic Sap Tan Gly CG RS gregasius Baker ailments mirabilis, S. flexneri, S. Augmentin 2011 typhi

Use in treating infectious diseases in children, malaria, Aqueous/acetone (80%, Shigella dysenteriae fever, pain, variola, v/v). Synergistic effect Shigella boydii Kiessoun et Malvaceae Sida alba L. Burkina Faso antibacterial, anti- Leaf stems when polyphenol rich Polyphenols All resistant to COT al., 2012 inflammatory, fractions are combined to Enterococcus faecalis analgesic activities COT Proteus mirabilis and hepatoprotective

E. coli NCTC 10418 ,S. aureus , NCTC6571 Nal Aug Tet Amx CL PV Sores, heart Methanolic extract ID CE EM , PV CE EM , Aug Kuete et al., Meliaceae Trichila heudelotti Nigeria Leaves - B. subtilis , NCIB 3610 troubles, pile obtained at 250 mg/ml Tet PV CE EM , Nal PV 2010 P. aeruginosa. ATCC CE EM 10145

E. coli, K. pneumonia, Piptadeniastrum Use for infectious P. aeruginosa,P. All resistant against Amp Assob et al., Mimosaceae Cameroon Leaves Methanolic Fla Pol Cou Gly CG RS africana ailments mirabilis, S. flexneri, Augmentin 2011 S. typhi

Diabetes, anti Aug Tet Kuete et al., Nyctaginaceae Boerhavia diffusa Nigeria inflammatory, Leaves methanolic - B. subtilis NCIB 3610 2010 Abscess, boils PV CE EM

E. coli 25922 , E. Campylobacter aerogenes E. cloacae, AMX, Pip, CE, AMX, Pip, Gangoué- densiflorum Chest and gastric Methanolic: 1.25

64 J. Pharmacognosy Phytother.

Table 1. Contd.

E. coli 25922 , E. aerogenes E. cloacae, AMX, Pip, CE, AMX, Pip, Gangoué- Barteria fistulosa Infected wounds, Methanolic, 1.25

E. coli, K. pneumonia, Hileria latifolia Use for infectious P. aeruginosa,P. All resistant against Amp Assob et al., Phytolacaceae Cameroon leaves Methanolic Tri St Cou Gly CG RS (Lam.) H.Walt ailments mirabilis,S. flexneri, Aug 2011 S. typhi

Antibiotics: Nal: Nalidixic acid; Ofl: Ofloxacin; Aug: Augmentin; Amp: Ampicillin; Tet: Tetracycline; Amx: Amoxycillin; Cot: Cotrimoxazole (Trimethoprim/sulpha methoxazole); Nit: Nitrofurantoin; Gen: Gentamycin; CL: Chloramphenicol; CI: Ciprofloxacin; PV: Penicillin V; CE: Cephalothin; EM: Erythromycin. Pip: piperacillin ; ESBL: Extended spectrum beta lactamases; L+: betalactactamase producer; Alk: Alkaloids; Tri: Triterpens; St: Sterols; Ant: Anthraquinons; Fla: Flavonoids; Pol: Polyphenols; Sap: Saponins; Tan: Tannins; Cou: Coumarins; Gly: Glycosides; CG: Cardiac glycosides; RS: Reducing sugars; TLC: Thin Layer Chromatography.

activities on many gram+ and gram- multidrug its efficacy. approach in searching for new arsenals against resistant bacteria strains, only few presented the In Cameroon, the studies focused on beta- multi-resistant bacteria was seen in the study phytochemical composition of these plants. lactam-resistant bacteria (K. pneumoniae, K. carried out in Zimbabwe by Chitemerere and Alkaloids, flavonoids, phenols and triterpens oxytoca, Enterobacter cloacae, Serratia Mukanganyama (2011), who found that the appear to be the main compounds identified. marcescens, Acinetobacter baumannii, S. aureus ethanolic leaves extract of Calistermon citrinus Microbial strains that dominated in the studies and Enterococcus sp.) and reference strains of Skeels rich in tannins, phenols, alkaloids and were Escherichia coli, K. pneumonia, S. bacteria (E. coli ATCC 35218, Enterobacter glycosides showed an efflux inhibitory activity dysenteriae, E. faecalis, Salmonella typhi, P. aerogenes ATCC 29751, E. aerogenes ATCC against S. aureus, K. pneumonia, P. aeruginosa aeruginosa, S. aureus methicillin resistant and 13048, P. aeruginosa ATCC 27853 and and B. subtilus comparable to that of reserpine. Bacillus subtilus, Neisseria gonorrhea Enterococcus hirae ATCC 9790) by using disc-dif- Reserpine is an alkaloid and is a reference efflux betalactamase+. They were found to be resistant fusion and agar-dilution assays (Gangoué-Piéboji inhibitor with a useful counteracting mechanism to a wide range of antibiotics including amoxicillin, et al., 2009). The minimal inhibitory con-centration against microorganisms’ resistance. Antimicrobial ampicillin, augmentin, cephalotin, ciprofloxacin, (MIC) values of different plant extracts against the activity of Temnocalyx obovatus (Rubiaceae) root ofloxacin, cotrimoxazol, methicillin. Particularly of tested bacteria were found to range from ≤ 0.3 to extracts used in folk medicine in Zimbabwe interest, the study done in Burkina Faso on the ≥ 10 mg/ml. This study revealed that the most deployed significant activity against bacterial (S. aqueous acetone (80%) of Sida alba L., a syner- active plant extracts were Dorstenia picta and aureus, E. coli, Clostridium perfringens) and gistic effect was observed when polyphenol rich Bridelia micrantha on beta-lactam-resistant gram- fungal (Aspergillus niger and Candida albicans) fractions of this plant were combined to negative bacilli and the extracts from Bridelia. species with MIC values ranging from 10 to 60 cotrimoxazole against Shigella dysenteriae, micrantha, Mallotus oppositifolius, Garcinia lucida, μg/ml(Muna and Fauzia, 2012). Enterococcus faecalis and Proteus mirabilis Garcinia kola, Campylospermum densiflorum Other efflux inhibitory mechanisms were ob- (Konaté et al., 2012). This is an indication that (leaves) and Campylospermum zenkeri (root) on served by Aiyegoro et al. (2009) who showed that polyphenols could act in combination to co- beta-lactam-resistant gram-positive cocci the activity of presumed plant antimicrobials against trimoxazole for potentialization in order to increase (Gangoué-Piéboji et al., 2009). Another innovative gram+ and gram- organisms was significantly Assob and Nsagha 65

enhanced by synthetic multidrug-resistance (MDR) dichloromethane extract of Tulbaghia violacea Harv. inhibitors of MDR efflux proteins. Combinations of against M. aurum; Marrubium vulgare L., Pistacia antibiotics are progressively being used in the treatment lentiscus L, Quercus coccifera L, Thymus capitatus (L.) of drug resistant infections; this is advantageous because Hoffm. & Link are active against M. tuberculosis they deploy various mechanisms of action. The (Aiyegoro et al., 2009; Korir et al., 2012). production of intrinsic antimicrobial compounds by plants can have a MDR inhibitory property that improves the inhibitory effect of antibiotics (Aiyegoro et al., 2009). The Plant compounds with efficacy against multi- use of Catha edulis extracts for instance at sub-inhibitory resistant fungi pathogens in Africa levels was reported to reduce the MIC values of tetracycline and penicillin G against resistant oral A good number of studies have been done on the pathogens, Streptococcus oralis, Streptococcus sanguis efficacy of medicinal plants against fungi. In Nigeria, and Fusobacterium nucleate. Polyphenols (epicatechin Sphenoceutrum jollyanum Pierre (Menispermaceae) gallate and catechin gallate) were also found to be able used in traditional medicine as chewing sticks and for to reverse beta-lactam resis-tance in methicillin resistant stomach pains was shown to possess significant S. aureus (MRSA). Whereas diterpenes, triterpenes, antifungal activity against Candida albicans, Candida alkyl gallates, flavones and pyri-dines showed resistance pseudotropicalis and Trichophyton rubrum. In South modulating abilities on various antibiotics against Africa (Aladesanmi et al., 2007), extract of the rhizomes resistant strains of S. aureus (Aiyegoro et al., 2009). The Gunnera perpensa was proven effective against methanolic and ethylacetate extracts of Phyllanthus Penicillium notatum, Aspergillus flavus and A. niger (LC50 muellerianus and Piptadeniastum africanus were found to values ranging from 0.07 to 3.81). This is important as be highly active against gram+ and gram- infectious these fungi have been implicated in cases of immune- resistant microorganisms with MIC varying from 2.5 to compromised patients that frequently develop oppor- 0.31 mg/L. The in vivo acute toxicity study carried out on tunistic and superficial mycosis (Nkomo and Kambizi, the methanolic extracts of these two plants indicated that 2009). they were not toxic (Assob et al., 2011). This is important An important antifungal activity was obtained with the because selective inhibition is crucial to conclude on the acetone bark extract of Erythrina caffra Thunb. The bark efficacy of antimicrobial compounds. of E. caffra is used in South Africa to treat sores, Other studies from Cameroon on plant extracts showed tuberculosis, respiratory infections, wounds, abscesses, interesting results due to their exceptional inhibitory arthritis and toothache. Dose dependent inhibitory activity power on both bacteria and fungi. Among these are was observed against a wide range of fungi strains Bersama engleriana, Dorstenia angusticornis, Dorstenia (Candida krusei, C. albicans, Candida neoformans, barteri, Diospyros canaliculata, Diospyros crassiflora, Candida rugosa, P. notatum, A. niger, Aspergillus Newbouldia laevis, and Ficus cordata (Kuete et al., terreus, Aspergillus flavus, Absidia corymbifera, Candida 2010). Compounds like isobavachalcone, kanzanol C glabrata, Trichophyton mucoides, Trichophyton and 4-hydroxylonchocarpin isolated from Dorstenia spp., tonsurans and Fusarium Sporotrichioides) (Nkomo and plumbagin, crassiflorone and diospyrone isolated from Kambizi, 2009) with MIC and minimum fungicidal Diospyros spp., and also new boudiaquinone and concentrations (MFC) values ranging between 0.625 and lapachol isolated from Newbouldia laevis (16) displayed 20 mg/ml and indicating fungicidal activity (Olajuyigbe important inhibitory activity against resistance and Afolayan, 2012). In Cameroon, another study microorganisms. Thecacoris annobonae Pax & K. Hoffm presented the efficacy of Ficus polita (Moraceae) against (Euphorbiaceae) has a significant antimicrobial (MIC < 10 C. albicans (Kuete et al., 2011). The bark and roots μg/ml) activity against Mycobacterium tuberculosis infusions are used in the treatment of infectious diseases, H37Rv, B. cereus and P. aeruginosa (Kuete et al., 2011). abdominal pains and diarrhea. Phytochemical analysis of The effect of combinations of the methanolic extract of the plant indicated the presence of compounds with Helycrisum pendunculatum leaves and selected antibio- enough evidence of their antimicrobial microbial activities tics evaluated using the time-kill assay method showed a such as lupeol, betulinic acid, ursolic acid, b-sitosterol, synergy rate of 59.1% (Extract + Tetracycline; Extract + sitosterol-3-O-b-D-glucopyranoside (Kuete et al., 2011). Amoxycillin), 54.6% (Extract + Penicillin G; Extract + Cryptolepis sanguinolenta Lindl. Schltr. (Periplocaceae) Chloramphenicol), 63.6% (Extract + Ciprofloxacin; is a shrub that grows in the rainforest and the deciduous Extract + Oxytetracycline), 68.2% (Extract+ belt forest, found in the west coast of Africa. In vitro study Erythromycin) and 27.3% (Extract + Ampicillin) on all iso- showed inhibitory activity against bacteria species lates at both ½ MIC and MIC values. Overall, synergistic (specifically, enteric pathogens, most notably E. coli and response could attain 60% of all combinations of extract vibrio) as well as against Candida spp. (Iwu et al., 1999). and antibiotics against all tested organisms (Aiyegoro et Aframomum melegueta (Zingiberaceae) is a perennial al., 2009). herb used as an aphrodisiac and against measles and In Libya, antituberculosis activity was obtained with leprosy, taken for excessive lactation and post partum 66 J. Pharmacognosy Phytother.

Figure 1. Akuamine. Source: Titanji et al. (2008).

hemorrhage, purgative, galactogogue and anthelmintic as quinine from cinchona bark and artemisinin from and hemostatic agent contains gingerol, shagaol, paradol Artemisia annua (Saxena et al., 2003). One of such in its essential oil; its antifungal antishistosomal activities plants with anti-malarial and anti-protozoa potentials on have also been demonstrated (Iwu et al., 1999; Kuete et the African continent is Brucea sumatrana Roxb., a shrub al., 2011). Xylopic acid, one of the constituents of Xylopia belonging to the family Simaroubaceae (Ehata et al., aethiopica, Ethiopian Pepper (Abbibacceae) is active 2012). An important inhibitory activity was obtained in against C. albicans (Kuete et al., 2011; Korir et al., 2012). vitro with the seeds’ crude extracts of B. sumatrana Some extracts from Cameroonian medicinal plants inclu- against Trypanosoma cruzi, T. brucei brucei, ding those from Bersama engleriana, Dorstenia Leishamania infantum and chloroquine and angusticornis, Dorstenia barteri, Diospyros canaliculata, pyrimethamine-resistant K1 strain of P. falciparum in the Diospyros crassiflora, Newbouldia laevis and Ficus Democratic Republic of Congo (Ehata et al., 2012). cordata exhibited a wide range of inhibitory activity on Plants from Western Cameroon were screened in vitro both bacteria and fungi (Kuete et al., 2011). In Kenya, for their antiplasmodial activity and cytotoxicity. hexane extracts of Senna didymobotrya used in folk Dacryodes edulis exhibited the highest antiplasmodial medicine showed notably inhibitory activities activity, followed by Vernonia amygdalina, Coula edulis on Microsporum gypseum, Trichophyton and Eucalyptus globulus. Dacryodes edulis is a multi-pur- mentagrophyte and Microsporum gypseum (Omoregie pose plant in African folk medicine, as its various parts and Sisodia, 2012). are used as a remedy for parasitic skin diseases, jigger, mouthwash, tonsillitis, sickle cell and malaria (Zofou et al., 2011). Its phytochemistry revealed the presence of Plants with anti-malarial and other anti-protozoa phenolic compounds which have previously been shown multi-resistant efficacy as having antiplasmodial activity (Zofou et al., 2011). An alkaloid, akuamine (Figure 1) from the seeds of Picralima Malaria is a serious health concern in Sub-Saharan nitida possesses activity against Plasmodium (Titanji et Africa where it kills a child below five years every thirty al., 2008). V. amygdalina and Eucalyptus globulus seconds and more than 90% of deaths occur due to this extracts exhibited high activity (1 < IC50 ≤10 μg/ml) on pathology (Nsagha et al., 2011). Anti-malarial multidrug both chloroquine sensitive and multiresistant strains of P. resistance is a major public health problem in the world falciparum (10 < IC50 ≤ 25 μg/ml) (Titanji et al., 2008). especially in Africa where the health systems are weak Antiprotozoal activities of Albizia zygia (Fabaceae) resulting in many prescriptions by unqualified health stem bark and methanolic seeds’ extract of Harungana personnel (Nsagha et al., 2012) and home-based madagascarensis was obtained against P. falciparum K1 treatment (Htut, 2009) which affects its control. Over the chloroquine-resistant strain, Leishmania donovani, years, anti-malaria drug resistance has become one of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, the most important problems impeding malaria control protozoa responsible for malaria, visceral leishmaniasis, efforts (Sendagire et al., 2005). This led to the discovery Chagas disease and African trypanosomiasis by Lenta et of other antimalarial agents from medicinal plants such al. (2007). In Congo, it was found that the extracts from Assob and Nsagha 67

Enanatia chlorantha stem bark, Napoleona vogelii stem are in consonance with findings from the Asian species bark and Quassia africana root bark are active with IC50 that were investigated for their various biological activities values ranging between 1.87 and 5 μg/ml, against such as antimalarial, antiprotozoal against amoeba Trypanosoma cruzi, Leishmania infantum and P. (Camacho et al., 2003; Sawangjaroen and falciparum K1 (Musum), 7α- obacunyl acetate and a Sawangjaroen, 2005), Toxoplama gondii and Giardia cycloartane derivative which are isolated compounds intestinal (Camacho et al., 2003), Trypanosoma brucei from the dichloromethane - methanol (1:1) extract of the brucei and Leishmania donovani (Sawangjaroen and stem bark of Entandrophragma angolense (Meliaceae) Sawangjaroen, 2005), Blastocystis hominis (Bawm et al., with good activity, IC50 of 2 and 5.4 µg/ml, respectively 2008), Trypanosoma evansi (Subeki et al., 2007) and test against chloroquine resistant strain W2 of P. Babesia gibsoni (Elkhateeb et al., 2008; Okokon and falciparum malaria parasite in Cameroon (Bickii et al., Nwafor, 2009). Other studies on medicinal plants have 2007; Sha’a, et al., 2011). In Benin, two sesquiterpenic been reported from Cameroon (Lenta et al., 2007; lactones isolated (1(15-acetoxy-8β-[(2- Djeussi et al., 2013), Nigeria (Runyoro et al., 2006; methylbutyryloxy)]-14-oxo-4,5-cis-acanthospermolide) Balagon et al., 2010), South Africa (Wright et al., 1993), and 2 (9α-acetoxy-15-hydroxy-8β-(2-methylbutyryloxy)- Tanzania (Owuor and Kisangau, 2006), Uganda 14-oxo-4,5-trans-acanthospermolide)) from the aerial (Sendagire et al., 2005), Kenya (Mehjabeen et al., 2011) parts of Acanthospermum hispidum D.C showed in vitro and Congo (Wright et al., 1988). antiplasmodial activity against the chloroquine-sensitive strain (3D7) (IC50 of 2.9 ± 0.5 and 2.23 ± 0.09 μM, respectively), Trypanosoma brucei brucei (IC of 2.45 ± CONCLUSION AND FUTURE PROSPECTS 50 0.49 and 6.36 ± 1.42 μM, respectively) and Leishmania Several in vitro and in vivo antimicrobial activities have mexicana mexicana (IC50 of 0.94 ± 0.05 and 2.54 ± 0.19 been carried out on traditional medicinal plants and found μM, respectively) (Ganfon et al., 2012). to be good sources of numerous therapeutic agents, In Nigeria, the ethanolic extract of Jatropha tanjorensis however only few studies on the efficacy of medicinal leaves showed moderate sensitivity against P. plants and their derived compounds have been done so falciparum. Alkaloids, saponins, anthraquinones, tannins far on resistant strains of microorganisms. Many comple- and flavonoids are probably responsible for this activity mentary and alternative medicines are being given more (Ouattara et al., 2006; Omoregie and Sisodia, 2012). consideration because a large number of antimicrobial Ethanol extract of V. amygdalina induced an important agents derived from traditional medicinal plants are avail- inhibitory activity against P. falciparum with an IC50 of able for treating various infectious diseases. In most of 11.2 μg/ml (Ouattara et al., 2006; Sha’a et al., 2011). the studies, interesting antimicrobial properties of Whereas in Burkina Faso, methanolic extracts of extracts against MDR strains were obtained, suggesting Swartzia madagascariensis and Combretum glutinosum their potency, but only few studies have actually as well as alkaloidal extracts of Tinospora bakis were addressed the issue of selective toxicity. proven to be active against P. falciparum chloroquine- Emphasis should be oriented towards the discovery of resistant strain W2 in vitro (5 μg/ml < IC50 < 50 μg/ml) antibiotic resistance modifying compounds from plants (Ouattara et al., 2006; Dzomba and Muchanyereyi, sources which offer greater chances of reversing the 2012). resistance pattern of many antimicrobials which otherwise will be abandoned. Combined therapies of plants extracts and their derived products have to be DISCUSSION assessed in vivo as well as to determine their clinical relevance. This will surely lead to the production of In Africa, attitudes towards traditional, herbal medicines phytomedicines or medicinal plant-derived therapeutic vary strongly because of the confusion between herbal agents. In order to attain this goal, research institutions in medicine and witchcraft (Wright et al., 1988). The use of Africa should move further and put in place strong medicinal plants is often associated with superstition and protocols geared towards the evaluation and comparison therefore rejected by some people. However, there are of the cost-effectiveness and safety-tolerance levels of many Africans who prefer traditional methods of the medicinal plants and their derived products against treatment (Wright et al., 1993). The Chinese plant, multidrug resistant microbial agents. African states Artemisia annua is cultivated in East African countries to should reinforce these efforts by putting in place a supply pharmaceutical manufacturers in Europe (Wright common policy that fosters the integration of traditional et al., 1993). The bark of Prunus africana is used in and modern medicines. making treatments for prostate cancer (Wright et al., 1993). Brucea sumatrana have been proven to possess antiprotozoal activity against Trypanosoma cruzi, T. Competing interests brucei brucei, Leishmania infantum and chloroquine and pyrimethamine-resistant K1 strain of P. falciparum. These The authors declare that they have no competing interest 68 J. Pharmacognosy Phytother.

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