Comparative antimalarial and toxicological effects of artemisinin with methanolic extract of Carica papaya leaves and bark of Alstonia broonai in animal models.
Malaria is one of the most prevalent, devastating parasitic infectious diseases in the world. Each year, 300-500 million clinical cases and 1.5-2.7 million deaths associated with malaria are reported globally (WHO, 2005). According to the World Health Organization (2005), malaria is endemic in 91 countries, predominantly in Africa, Asia and Latin America with about 40% of the world's population at risk (Palaniswamy et al., 2008). Around 800,000 children under the age of five die from malaria each year, making this disease one of the major causes of infant and juvenile mortality (WHO, 2005). The disease has been associated with substantial number of miscarriages and low birth weight of babies. Given the fact that about 46% of an average household income is expended on the treatment of malaria. The disease has remained a major cause of poverty in Nigeria (Coker et al., 2001).
Four species of Plasmodium, namely P. malariae, P. ovale, P. vivax and P. flaciparum may infest man of which P. flaciparum is responsible for the often fatal cerebral malaria (Philipson and Wright, 1991). Although malaria presents these impressive figures, there is a broad therapeutic arsenal against it. Unfortunately, these arsenals present numerous draw back including several side effects and problems of drug resistance and cross resistance (Coker et al., 2001). These problems are further compounded with the fact that only 10% of global research and development resources are directed at diseases including malaria, that account for 90% of global diseases burden (WHO, 2005). All these factors have therefore created urgent needs to search for new drugs and alternative medicine for malaria that are cheaper, safe and highly potent. Plants have been considered as sources of medicinal agents for the treatment of various diseases. Alstonia broonai and Carica papaya are among the local medicinal plants used by the middle-belt and south-western people of Nigeria to treat malaria. The efficacy of Alstonia broonai has been established (Gill and Siakpered, 1990) as well as that of Carica papaya (Leaman et al., 1995). However, there is paucity of information on their comparative efficacy and safety. This work is therefore aimed at investigating the comparative efficacy and safety profiles of these two herbal remedies with artemisinin--a drug of proven efficacy and safety.
Materials And Methods
Chemicals and Assay Kits:
Absolute ethanol was a product of Sigma Aldrich, Steinhem, Switzerland. Dihydroartemisinin was obtained from Biotech Co., Beijing Factory II, China. Assay kits for alkaline phosphatase, alanine amino transferase and aspartate amino transferase were obtained from Randox Laboratories Limited, UK. All other reagents used for this study were of analytical grade and were prepared in all glass-distilled water.
Sources of Experimental Animals and Parasites:
Twenty five adult Swiss albino mice with an average weight of 20g were obtained from the Animal Breeding Unit of the Department of Biochemistry, University of Ibadan, Oyo state, Nigeria. Fourty albino rats (Rattus novergicus) with an average weight of 148.35g were obtained from the small Animal Holding Unit of the Department of Biochemistry, University of Ilorin, Ilorin, Nigeria. The animals were housed in plastic cages and maintained under standard laboratory conditions with free access to rat pellets and tap water ad-libitum. The study adhered to the Principles of Laboratory Animal Care (NIH, publication number 85-23, revised in 1985). A drug-sensitive strain of Plasmodium berghei (K173) was obtained from the Institute for Advanced Medical Research and Training (IAMRAT), College of Medicine, University of Ibadan, Oyo state, Nigeria.
Preparation of Plant Extract:
Fresh leaves of C. papaya and bark of Alstonia broonai were harvested in Ilorin, Kwara state, Nigeria, in July 2006. The plants were botanically authenticated at the Department of Plant Biology, University of Ilorin, Ilorin, Nigeria. C. papaya leaves were sun-dried for two weeks while A. broonia bark was obtained in dried form. They were separately milled to powdered forms using a milling machine. 200g of each of the crude powder were extracted using 70% methanol and thereafter filtered using whatman filter paper. Each of the filtrate was then evaporated to dryness by heating on a water bath at 65[degrees]C.
Anti-malarial study was investigated in mice. Twenty five mice were grouped into five. Group A consisted of uninfected mice and received 0.2ml distilled water. The mice in group B consisted of infected mice and also received 0.2ml distilled water. Group C, D and E were infected with P. berghei and treated with 200mg/kg body weight of C. papaya, 200mg/kg body weight A. broonai and 0.1mg/kg body weight artemisinin, respectively. Treatment was commenced 72 hours after inoculation of the parasite.
Toxicological evaluation of the extract was carried out in rats. The design consisted of ten rats per group. Each group was further divided into two for seven (7) and fourteen (14) days administration of the extracts and artesunate respectively. Five of the rats in each group were treated for seven days while the remaining five for 14 days. Group A and B served as controls, with group A receiving 1 ml of distilled water daily and B were administered 4mg/kg body weight of artesunate on day 1 while they received 2 mg/kg body weight for the remaining days. Group C and D were administered 200 mg/kg body weight methanolic extract of Carica papaya and Alstonia broonai respectively.
Inoculation and Confirmation of Malaria Parasite:
The mice were screened for malaria parasites in their blood and only those that were free from malarial parasites were selected for this study. The mice were acclimatized for two weeks in the laboratory after which each mouse was induced with standard inocula of 1 x [10.sup.7] Plasmodium berghei via intra-peritoneal route. The parasite was then allowed to incubate in the mice for 72 hours after which thin blood film was prepared from tail snip, and stained using Giemsa stain and the parasitaemia confirmed by viewing using x100 objective of the light microscope. This method was also used for parasitaemia count throughout the period of study and percentage parasitaemia determined.
At the end of the experimental period, venous blood was collected from the experimental animals according to the method of Narayanan et al. (1984). The serum was prepared by centrifuging the blood samples at 3000 rpm for 5 min (Ogbu and Okechukwu, 2001) and collected by pipetting. The animals were thereafter quickly dissected and the liver and kidney removed. The organs were separately suspended in ice-cold 0.25 M sucrose solution and homogenized. The resulting homogenates were diluted appropriately with 0.25 M ice-cold sucrose solution to give a final volume of five folds the initial tissue weight. The homogenates were kept frozen overnight to ensure maximum release of the enzymes (Ngaha et al., 1989). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed using the method of Reitman and Frankel (1957). The procedure described by Roy (1970) was used to assay alkaline phosphatase (ALP) activity. Serum creatinine level was determined by the method of Eknoyan et al., 2003, urea by Veniamin and Vakirtzi-Lemonias (1970), potassium and sodium by the method of Tietz et al. (1996) and serum bicarbonate level by the method of Roth and Chan (2001).
Packed cell volume (PCV), hemoglobin level (Hb), white blood cells count (WBC), mean corpuscular hemoglobin concentration (MCHC) and platelets count were determined using the methods of Adewuyi and Olatunji (1995).
All data were analyzed using a one-way ANOVA. In all cases, probability level of 95% was taken as significant (Mahajan, 1997).
Figure 1 shows the activity of the extract and artemisinin on the level of parasitemia. Artemisinin reduced the level of parasite than either of the two extract. Carica papaya however, reduced the level of parasitemia than Alstonia broonai. Their antimalarial effects is in the order of artemisinin > C. papaya > A. broonai.
Table 1 presents the chemosuppressive property of the extract and sodium artesunate. Sodium artesunate demonstrated the highest activity, while the chemosuppresive activity of Alstonia broonai is the lowest of the three. Carica papaya demonstrated higher potency when compared to Alstonia broonai as depicted by the percentage chemosuppression produced by Carica papaya, 82.22% against 53.73% by Alstonia broonai on day 5 of the treatment.
The effect of the extracts on alkaline phosphatase, alanine aminotransferase and aspartate aminotransfrase activity of liver, kidney and serum is representend in Tables 2, 3 and 4 respectively. There was a significant reduction (p<0.05) in liver and kidney ALP activity following 7 days administration of the extract while the activity of the enzyme was found to have increased significantly (p<0.05) following the 14 days administration for Alstonia broonai when compared with the control. However, there was no significant difference (p<0.05) in the serum activity of the enzyme following both period of administration. There was significant duration dependent decrease (p<0.05) in AST activity of the liver and kidney following administration of both extract for 7 and 14 days. The serum activity of AST showed a significant (p<0.05) drop following the 14 days administration of both extract but there was no significant difference in activity (p>0.05) following the 7 days administration when compared with the controls. Liver ALT activity was significantly raised (p<0.05) following 7 days administration of both extract but prolonged administration revealed a significant drop (p<0.05) in activity when compared with the controls. The activity was significantly raised (p<0.05) following 7 and 14 days administration of Alstonia broonia but the activity was significantly reduced (p<0.05) in C. papaya administered rats when compared with the controls. The serum ALT however increased significantly (p<0.05) following administration of both extract for both durations of administration.
[FIGURE 1 OMITTED]
Table 5 presents the effect of the extract and artesunate on the levels of rat serum electrolytes, creatinine and urea. Administration of the extract of Alstonia broonai bark for 14 days and Carica papaya leaf for 7 and 14 days caused a significant reduction (p<0.05) in the level of serum bicarbonate, chloride and sodium while there existed no significant difference (p>0.05) in serum potassium, urea and creatinine concentrations of all the treatment groups as well as in the serum bicarbonate concentration of the group administered Alstonia broonai for 7 days.
Table 6 shows the effect of the extract and artesunate on some haematological parameters. There was no significant difference (p>0.05) in the level of circulating haemoglobin in all the treatment goups when compared to the controls. However, the 7 days administration of both extract led to a significant reduction (p<0.05) in the level of WBC while their 14 days administration resulted to a significant elevation (p<0.05) of WBC. Also, both extract caused a significant increase (P<0.05) in platelet counts when compared to the controls.
The methanolic extracts of Carica papaya leaf and Alstonia broonai bark showed considerable antimalarial activity against Plasmodium berghei infection in mice. The pattern of result on the effect of the extract on percentage parasitemia and their chemosuppresive property ranks the antimalarial activity of Carica papaya next to artemisinin which was used as control in this experiment. The antimalarial activities demonstrated by these extract could be attributed to tannins, phenolics, saponins and flavonoids components. The two extract compared fairly with artemisinin which is known to be rapidly absorbed from the gastrointestinal tract and are primarily metabolized in the liver (Dhingra et al., 2000). This activity of Carica papaya may be due to its antimicrobial property (Anibijuwon and Udeze, 2009) and its antiplasmodial effect reported by Egwin et al. (2002). The search of effective malarial chemotherapeutic agents aims at identifying drugs of low toxicity, fast action and broad activity against various forms in the life cycle of malaria parasite (WHO, 1991; TRD, 2000). The present study revealed that the two extract have fast action and broad activity since they were able to reduce parasite counts within 4 days of treatment.
Hematological parameters were studied to assess the toxic effect of the extracts on blood components. White blood cells play active role in the immune system. The significant reduction observed in white blood cells following 7 days administration of the extract might suggest immunosuppressive potential of the extract. However, the significant increase in the WBC count following the 14 days administration is suggestive that WBC depression would revert to normal upon withdrawal of both extract after treatment of infection. The significant increase in platelet counts by both extract may be a compensatory attempt to boost or modulate the immune suppression due to WBC depression since antigen A and B are known to be present on thrombocytes (Reid and Lomas-Francis, 2004). Platelets are characterized by expert functions in assisting and modulating inflammatory reactions and immune responses. This is achieved by the regulated expression of adhesive and immune receptors on the platelet surface and by the release of a multitude of secretory products including inflammatory mediators and cytokines, which can mediate the interaction with leukocytes and enhance their recruitment. In addition, platelets are characterized by an enormous surface area and open canalicular system, which in concert with specialized recognition receptors may contribute to the engulfment of serum components, antigens, and pathogens. Platelet-dependent increases in leukocyte adhesion may not only account for an exacerbation of diseased state, but also for lymphocyte trafficking during adaptive immunity and host defense (von Hundelshausen, 2007).
The functional capacity of the kidney can be measured by tests such as concentration and dilution tests, clearance test and examining blood concentrations of excretory and electrolyte constituents. The relevance of renal function tests is to asses the presence or absence of active lesions in the kidney, or to assess the normal functioning capacity of different parts of the nephron. Inorganic electrolytes occur in large quantities in both extracellular and intracellular fluids of the body. The significant decrease in sodium and potassium ions caused by the extract may be an indication that the functional capacity of the nephron has been compromised. The sodium pump maintains the intracellular [K.sup.+] of 140mM against the extracellular [K.sup.+] concentration of 5mM (Gadsby et al., 1993). The decrease in serum sodium and potassium concentrations observed could suggest a possible adverse effect of these extract on the normal functioning of the sodium pump. A glance on the anionic profile of the serum following 7 and 14 days administration of these extract showed a significant decline in serum chloride ion concentration similar to those observed for sodium. This observation may be adduced to the fact that cations in solution do not exist in isolation but co-exist with anions. Thus, the decrease observed in [Na.sup.+] is justified by the decrease in Cl-. Bicarbonate ion is of relevance in maintenance of acid base balance of the body. The observed decrease in bicarbonate ion could be an indication of low pH of the body and possibly indicating systemic acidosis. The kidney plays an important role in homeostasis, secreting an excess of hydrogen ions which may result in increase in sodium bicarbonate into the extracellular fluid (Guyton and Hall, 2000). The significant reduction in serum bicarbonate concentration following 14 days administration suggests that chronic administration of A. broonai may cause acidosis. The administration of C. papaya for 7 days also signals acidotic conditions, however prolonged administration increased the serum bicarbonate, a reflection that the kidney is beginning to counteract the acidotic condition. It is possible that this condition that resulted from administration of A. broonai will return to normal since administration for 7 days did not cause an initial acidosis as seen with C. papaya. The drop in urea and creatinine observed in this study could be traced to increase in functionality of the kidney. Kidney plays an active role cleaning urea and creatinine off the blood, thereby reducing their concentration.
The measurement of the activities of various enzymes in tissues and body fluids play a significant and well-known aid in disease investigation and diagnosis and tissues cellular damage (Malomo, 2000). It is also a means of assessing drug or herbal safety as well as toxicity risk. ALP is a marker enzyme for the plasma membrane and endoplasmic reticulum (Wright and Plummer, 1974). It is often employed to assess the integrity of the plasma membrane (Akanji et al., 1993). The administration of C. papaya and A. broonai resulted into drop in ALP activity in the liver and serum. This was also similar to the pattern observed in the kidney except for the 14 days administration. The reduction in activity of ALP in these organs may be attributed to inhibition of the enzyme molecule in situ (Akanji et al., 1993)). This is further justified by lack of concurrent increase in serum ALP. Such reduction in ALP activity following administration of the extract will limit or hinder adequate transportation of required ions or molecules across the plasma membrane. It may also lead to less availability of phosphate groups needed for the synthesis of some phospholipids. AST and ALT are useful marker enzymes in assessing damage to the liver (Shahjahan et al., 2004). Their presence in the serum may give information on tissue injury and organ dysfunction (Wells et al., 1986). The elevation in liver AST following 7 and 14 days administration of C. papaya and A. broonai extracts may be attributed to increase in functional capacity of the liver. The increase observed in AST without a corresponding increase in serum activity of the enzyme indicated that the increase is unlikely due to de novo synthesis. Increased liver ALT activity following 7 days administration of both extract was followed by decreased activity. This could be an indication that prolonged administration of the extract may be toxic to the liver. This is further justified by elevation in serum ALT after 14 days administration of both extract.
Methanolic extract of both Alstonia broonai and Carica papaya displayed low toxicity during acute exposure. However prolonged administration may be deleterious to cellular functions and structures. Both extract could thus be used as an alternative to standard drugs in the short term management of malaria. However, C. papaya leaf extract showed more efficacy against malarial parasites.
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R.O. Arise, S.O. Malomo and M.M. Lawal
(1) Department of Biochemistry, University of Ilorin, Kwara State, Nigeria.
Correspondence Author: Arise R.O., Department of Biochemistry, University of Ilorin, Kwara State, Nigeria.
Table 1: Percentage chemo suppression of the extract in P. berghei infected mice Day 4 Day 5 Groups Chemosupression Artesunate 3.43[+ or -]0.21 (a) 52.84[+ or -]1.66 (a) Carica papaya 0.78[+ or -]0.04 (b) 29.40[+ or -]1.12 (b) Alstonia broonai 1.25[+ or -]0.09 (c) 9.02[+ or -]0.72 (c) Day 6 Day 7 Groups (%) Artesunate 71.55[+ or -]2.11 (a) 85.67[+ or -]2.36 (a) Carica papaya 47.70[+ or -]1.98 (b) 67.32[+ or -]2.05 (b) Alstonia broonai 21.26[+ or -]1.06 (c) 31.57[+ or -]2.00 (c) Day 8 Groups Artesunate 96.60[+ or -]2.77 (a) Carica papaya 82.22[+ or -]2.51 (b) Alstonia broonai 53.73[+ or -]2.13 (c) Values are mean (n = 5) [+ or -] SEM. Values with different superscripts (a,b,c)... in each column are significantly different Table 2: Effects of methanolic extract of Astonia broonia bark and Carica papaya leaf on specific activity of alkaline phosphatase in the liver, kidney and serum of rat Specific enzyme activity (nM/min./mg protein) Groups Liver Kidney Control A 173.29[+ or -]2.03 (a) 871.59[+ or -]40.03 (a) Control B 172.30[+ or -]2.02 (a) 862.50[+ or -]50.02 (a) ABA 93.06[+ or -]0.73 * (b) 404.06[+ or -]31.43 * (b) ABB 113.25[+ or -]0.55 * (c) 511.15[+ or -]42.05 * (c) CPA 106.67[+ or -]0.71 * (d) 502.17[+ or -]44.91 * (d) CPB 163.52[+ or -]1.04 * (e) 561.74[+ or -]42.04 * (e) Groups Liver Control A 7.87[+ or -]0.01 (a) Control B 7.91[+ or -]0.02 (a) ABA 7.56[+ or -]0.04 (a) ABB 7.54[+ or -]0.04 (a) CPA 6.96[+ or -]0.01 (a) CPB 6.57[+ or -]0.01 (a) Values are mean (n = 5) [+ or -] SD. Values with different superscripts (a,b,c)... in each column are significantly different ABA: Alstonia broonai following 7 days administration; ABB: Alstonia broonai following 14 days administration; CPA: Carica papaya following 7 days administraton; CPB: Carica papaya following 14 days administration. Table 3: Effects of methanolic extract of Alstonia broonai bark and Carica papaya leaf on the specific activity of aspartate aminotransferase in the liver, kidney and serum of rat Specific enzyme activity (nM/min./mg/protein) Group Liver Kidney Control A 39.82[+ or -]1.01 (a) 2.31[+ or -]0.07 (a) Control B 38.87[+ or -]1.10 (a) 2.28[+ or -]0.09 (a) ABA 43.89[+ or -]2.02 (a) 2.06[+ or -]0.02 * (b) ABB 31.38[+ or -]2.07 * (c) 1.56[+ or -]0.07 * (c) CPA 87.22[+ or -]3.01 * (d) 2.34[+ or -]0.01 * (d) CPB 70.58[+ or -]3.02 * (e) 2.16[+ or -]0.08 * (e) Group Serum Control A 0.13[+ or -]0.007 (a) Control B 0.14[+ or -]0.006 (a) ABA 0.01[+ or -]0.024 * ABB 0.14[+ or -]0.001 (a) CPA 0.01[+ or -]0.030 CPB 0.10[+ or -]0.001 Values are mean (n = 5) [+ or -] SD. Values with different uperscripts (a,b,c)... in each column are significantly different ABA: Alstonia broonai following 7 days administration; ABB: Alstonia broonai following 14 days administration; CPA: Carica papaya following 7 days administration; CPB: Carica papaya following 14 days administration Table 4: Effects of administration of methanolic extract of Alstonia broonai bark and Carica papaya leaf on specific activity of alanine aminotransaminase in liver, kidney and serum Specific enzyme activity (nM/min./mg/protein) Group Liver Kidney Control a 299.00[+ or -]1.14 (a) 2.31[+ or -]0.007 Control b 298.01[+ or -]1.43 (a) 2.28[+ or -]0.01 (a) ABA 313.0[+ or -]1.00 * (b) 2.42[+ or -]0.02 * (b) ABB 199.00[+ or -]1.58 * (c) 2.35[+ or -]0.010 (a) CPA 321.20[+ or -]1.79 * (d) 0.63[+ or -]0.030 (c) 06CPB 187.00[+ or -]1.58 * (e) 1.65[+ or -]0.040 * (d) Group Serum Control a 0.01[+ or -]0.001 (a) Control b 0.02[+ or -]0.001 (a) ABA 0.06[+ or -]0.001 * (b) ABB 0.05[+ or -]0.001 * (c) CPA 0.06[+ or -]0.002 * (b) 06CPB 0.08[+ or -]0.001 * (d) Values are mean (n=5) [+ or -] SD. Values with different superscripts (a,b,c)... in each column are significantly different ABA: Alstonia broonai following 7 days administration, ABB: Alstonia broonai following 14 days administration CPA: Carica papaya following 7 days administraton, CPB: Carica papaya following 14 days administration Table 5: Effects of administration of methanolic extract of Carica papaya leaf and Alstonia broonai bark on selected electrolytes, creatinine and urea in rat serum Group Bicarbonate Chloride (mmole/L) (mmole/L) Control A 3.60[+ or -]0.55 (a) 21.00[+ or -]1.58 (a) Control B 3.59[+ or -]0.94 (a) 21.01[+ or -]1.50 (a) ABA 3.00[+ or -]1.58 (a) 19.40[+ or -]0.55 (a) ABB 1.40[+ or -]0.55 (b) 10.80[+ or -]1.30 (b) CPA 1.20[+ or -]0.45 (b) 15.00[+ or -]0.71 (c) CPB 1.80[+ or -]0.45 (b) 14.60[+ or -]0.55 (c) Group Sodium Potassium (mmole/L) (mmole/L) Control A 27.60[+ or -]0.55 (a) 1.94[+ or -]0.21 (a) Control B 27.63[+ or -]0.50 (a) 1.94[+ or -]0.21 (a) ABA 13.80[+ or -]1.80 (b) 1.12[+ or -]0.19 (a) ABB 22.60[+ or -]2.30 (c) 1.64[+ or -]0.15 (a) CPA 17.00[+ or -]1.00 (d) 1.50[+ or -]0.26 (a) CPB 17.60[+ or -]4.56 (d) 1.66[+ or -]0.74 (a) Group Urea Creatinine (mmole/L) (mg/dl) Control A 2.24[+ or -]0.72 (a) 14.44[+ or -]3.25 (a) Control B 2.23[+ or -]0.94 (a) 14.39[+ or -]3.50 (a) ABA 1.72[+ or -]0.40 (a) 15.12[+ or -]3.53 (a) ABB 2.44[+ or -]0.46 (a) 11.22[+ or -]4.65 (b) CPA 1.60[+ or -]0.34 (a) 12.68[+ or -]1.45 (b) CPB 2.18[+ or -]0.13 (a) 14.44[+ or -]3.25 (a) Values are mean (n = 5) [+ or -] SD. Values with different superscripts (a,b,c)... in each column are significantly different ABA: Alstonia broonai following 7 days administration, ABB: Alstonia broonai following 14 days administration CPA: Carica papaya following 7 days administraton, CPB: Carica papaya following 14 days dministration Table 6: Effects of administration of methanolic extract of Carica papaya leaf and Alstonia broonai bark on selected haematological parameters in rats Group Hb (g/dL) PCV (%) Control A 12.52[+ or -]0.47 (a) 42.80[+ or -]2.08 (a) Control B 12.53[+ or -]0.94 (a) 42.81[+ or -]1.90 (a) ABA 13.28[+ or -]1.78 (a) 41.40[+ or -]2.05 (a) ABB 13.50[+ or -]1.05 (a) 45.20[+ or -]2.30 (b) CPA 12.96[+ or -]1.15 (a) 40.80[+ or -]2.71 (a) CPB 13.10[+ or -]1.05 (a) 46.20[+ or -]1.48 (c) Group WBC MCHC (g/dL) Control A 21.24[+ or -]1.55 (a) 28.80[+ or -]1.61 (a) Control B 21.23[+ or -]1.50 (a) 28.80[+ or -]1.60 (a) ABA 12.74[+ or -]1.08 (a) 31.80[+ or -]1.30 (b) ABB 33.24[+ or -]1.67 (c) 29.40[+ or -]0.140 (b) CPA 16.52[+ or -]1.00 (d) 31.14[+ or -]0.74 (b) CPB 26.32[+ or -]1.56 (d) 31.40[+ or -]1.14 (b) Group PLATELETS Control A 1.94[+ or -]0.21 (a) Control B 1.89[+ or -]0.21 (a) ABA 4.12[+ or -]0.19 (b) ABB 4.64[+ or -]0.15 (b) CPA 5.50[+ or -]0.26 (b) CPB 4.66[+ or -]0.74 (b) Values are mean (n=5) [+ or -] SD. Values with different superscripts (a,b,c)... in each column are significantly different ABA: Alstonia broonai following 7 days administration, ABB: Alstonia broonai following 14 days administration, CPA: Carica papaya following 7 days administraton, CPB: Carica papaya following 14 days administration.
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|Title Annotation:||Original Article|
|Author:||Arise, R.O.; Malomo, S.O.; Lawal, M.M.|
|Publication:||Advances in Natural and Applied Sciences|
|Date:||Mar 1, 2012|
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