Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Research article

Safety assessment of the ethanolic extract of Gongronema latifolium Benth. leaves: a 90-day oral toxicity study in Sprague Dawley rats

Authors: Bassel Al-Hindi, Nor Adlin Yusoff, Mariam Ahmad, Item Justin Atangwho, Mohd Zaini Asmawi, Majed Ahmed Al-Mansoub, Yasser Mahfooth Tabana, Idris Bello, Mun Fei Yam

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

Login to get access

Abstract

Background

The leaves of Gongronema latifolium Benth. have long been recognized traditionally as a remedy for a variety of ailments in Africa. This study was conducted to evaluate the safety profile of the ethanolic extract of G. latifolium (GLES) leaves through a repeated dose 90-day oral toxicity study in male and female of Sprague Dawley rats.

Methods

GLES was orally administered at doses of 250, 500 and 1000 mg/kg/day consecutively for 90 days.

Results

No behavioral or physiological changes and mortality were observed. GLES did not have a marked impact on general hematological parameters and did not precipitate nephrotoxicity. However, compared to the control, serum triglycerides, total cholesterol and low-density lipoprotein levels were lower and white adipose tissue paired retroperitoneal fat depots were depleted in male rats treated with GLES3 by the end of the experiment. The liver was significantly enlarged in GLES-treated rats of both sexes. Negative gender-specific alterations were observed with the highest dose. Adverse risk was evident in the female rats mainly due to marked body weight gain and cerebrum weight reduction.

Conclusion

Further research is needed to reach more specific conclusions about to the safety of ingesting high doses of GLES for long periods of time.
Literature
1.
go back to reference Ugochukwu NH, Babady NE, Cobourne MK, Gasset SR. The effect of Gongronema latifolium extracts on serum lipid profile and oxidative stress in hepatocytes of diabetic rats. J Biosci. 2003;28:1–5.PubMedCrossRef Ugochukwu NH, Babady NE, Cobourne MK, Gasset SR. The effect of Gongronema latifolium extracts on serum lipid profile and oxidative stress in hepatocytes of diabetic rats. J Biosci. 2003;28:1–5.PubMedCrossRef
2.
go back to reference Johnkennedy N, Adamma E. The protective role of Gongronema latifolium in acetaminophen induced hepatic toxicity in Wistar rats. Asian Pac J Trop Biomed. 2011;1:S151–S4.CrossRef Johnkennedy N, Adamma E. The protective role of Gongronema latifolium in acetaminophen induced hepatic toxicity in Wistar rats. Asian Pac J Trop Biomed. 2011;1:S151–S4.CrossRef
3.
go back to reference Agbo CU, Baiyeri KP, Obi IU. Indigenous knowledge and utilization of Gongronema latifolia Benth.: A case study of women in University of Nigeria, Nsukka. Bio-Res. 2006;3:66–9.CrossRef Agbo CU, Baiyeri KP, Obi IU. Indigenous knowledge and utilization of Gongronema latifolia Benth.: A case study of women in University of Nigeria, Nsukka. Bio-Res. 2006;3:66–9.CrossRef
4.
go back to reference Ekong MB, Peter MD, Peter AI, Eluwa MA, Umoh IU, Igiri AO, et al. Cerebellar neurohistology and behavioural effects of Gongronema latifolium and Rauwolfia vomitoria in mice. Metab Brain Dis. 2014;29:521–7.PubMedCrossRef Ekong MB, Peter MD, Peter AI, Eluwa MA, Umoh IU, Igiri AO, et al. Cerebellar neurohistology and behavioural effects of Gongronema latifolium and Rauwolfia vomitoria in mice. Metab Brain Dis. 2014;29:521–7.PubMedCrossRef
5.
go back to reference Akpaso MI, Atangwho IJ, Akpantah A, Fischer VA, Igiri AO, Ebong PE. Effect of combined leaf extracts of Vernonia amygdalina (bitter leaf) and Gongronema latifolium (Utazi) on the pancreatic β-cells of streptozotocin-induced diabetic rats. Br J Med Med Res. 2011;1:24–34.CrossRef Akpaso MI, Atangwho IJ, Akpantah A, Fischer VA, Igiri AO, Ebong PE. Effect of combined leaf extracts of Vernonia amygdalina (bitter leaf) and Gongronema latifolium (Utazi) on the pancreatic β-cells of streptozotocin-induced diabetic rats. Br J Med Med Res. 2011;1:24–34.CrossRef
6.
go back to reference Morebise O, Fafunso MA, Makinde JM, Olajide OA, Awe E. Antiinflammatory property of the leaves of Gongronema latifolium. Phytother Res. 2002;16:75–7.CrossRef Morebise O, Fafunso MA, Makinde JM, Olajide OA, Awe E. Antiinflammatory property of the leaves of Gongronema latifolium. Phytother Res. 2002;16:75–7.CrossRef
7.
go back to reference Nwosu MO, Okafor JI. Preliminary studies of the antifungal activities of some medicinal plants against Basidiobolus and some other pathogenic fungi. Mycoses. 1995;38:191–5.PubMedCrossRef Nwosu MO, Okafor JI. Preliminary studies of the antifungal activities of some medicinal plants against Basidiobolus and some other pathogenic fungi. Mycoses. 1995;38:191–5.PubMedCrossRef
8.
go back to reference Gamaniel K, Akah P. Analysis of the gastrointestinal relaxing effect of the stem extract of Gongronema latifolium. Phytomedicine. 1996;2:293–6.PubMedCrossRef Gamaniel K, Akah P. Analysis of the gastrointestinal relaxing effect of the stem extract of Gongronema latifolium. Phytomedicine. 1996;2:293–6.PubMedCrossRef
9.
go back to reference Chime SA, Onyishi IV, Ugwoke PU, Attama AA. Evaluation of the properties of Gongronema latifolium in Phospholipon 90H based solid lipid microparticles (SLMs): an antidiabetic study. J Diet Suppl. 2014;11:7–18.PubMedCrossRef Chime SA, Onyishi IV, Ugwoke PU, Attama AA. Evaluation of the properties of Gongronema latifolium in Phospholipon 90H based solid lipid microparticles (SLMs): an antidiabetic study. J Diet Suppl. 2014;11:7–18.PubMedCrossRef
10.
go back to reference Al-Hindi B, Yusoff NA, Atangwho IJ, Ahmad M, Asmawi MZ, Yam MF. A soxhlet extract of Gongronema latifolium retains moderate blood glucose lowering effect and produces structural recovery in the pancreas of STZ-induced diabetic rats. Medical Sciences. 2016;4:9.PubMedCentralCrossRef Al-Hindi B, Yusoff NA, Atangwho IJ, Ahmad M, Asmawi MZ, Yam MF. A soxhlet extract of Gongronema latifolium retains moderate blood glucose lowering effect and produces structural recovery in the pancreas of STZ-induced diabetic rats. Medical Sciences. 2016;4:9.PubMedCentralCrossRef
11.
go back to reference Ogundipe O, Moody J, Akinyemi T, Raman A. Hypoglycemic potentials of methanolic extracts of selected plant foods in alloxanized mice. Plant Foods Hum Nutr. 2003;58:1–7.CrossRef Ogundipe O, Moody J, Akinyemi T, Raman A. Hypoglycemic potentials of methanolic extracts of selected plant foods in alloxanized mice. Plant Foods Hum Nutr. 2003;58:1–7.CrossRef
12.
go back to reference Edet E, Akpanabiatu M, Eno A, Umoh I, Itam E. Effect of Gongronema latifolium crude leaf extract on some cardiac enzymes of alloxan-induced diabetic rats. Afr J Biochem Res. 2009;3:366–9. Edet E, Akpanabiatu M, Eno A, Umoh I, Itam E. Effect of Gongronema latifolium crude leaf extract on some cardiac enzymes of alloxan-induced diabetic rats. Afr J Biochem Res. 2009;3:366–9.
13.
go back to reference Sylvester EG, Israel EU, Olajumoke AD. The effect of Gongronema latifolium leaf extract on blood biochemical assay in diabetic rats. Journal of Scientific Research and Reports. 2015;6(7):514–22.CrossRef Sylvester EG, Israel EU, Olajumoke AD. The effect of Gongronema latifolium leaf extract on blood biochemical assay in diabetic rats. Journal of Scientific Research and Reports. 2015;6(7):514–22.CrossRef
14.
go back to reference Effiong GS, Udoh IE, Mbagwu HOC, Ekpe IP, Asuquo EN, Atangwho IJ, et al. Acute and chronic toxicity studies of the ethanol leaf extract of Gongronema latifolium. Int Res J Biochem Bioinform. 2012;2(7):155–61. Effiong GS, Udoh IE, Mbagwu HOC, Ekpe IP, Asuquo EN, Atangwho IJ, et al. Acute and chronic toxicity studies of the ethanol leaf extract of Gongronema latifolium. Int Res J Biochem Bioinform. 2012;2(7):155–61.
15.
go back to reference Iannaccone PM, Jacob HJ. Rats! Disease Models and Mechanism. 2009;2:206–10.CrossRef Iannaccone PM, Jacob HJ. Rats! Disease Models and Mechanism. 2009;2:206–10.CrossRef
16.
go back to reference Shin S-H, Koo K-H, Bae J-S, Cha S-B, Kang I-S, Kang M-S, et al. Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague–Dawley rats. Food Chem Toxicol. 2013;55:617–26.PubMedCrossRef Shin S-H, Koo K-H, Bae J-S, Cha S-B, Kang I-S, Kang M-S, et al. Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague–Dawley rats. Food Chem Toxicol. 2013;55:617–26.PubMedCrossRef
17.
go back to reference Arsad SS, Esa NM, Hamzah H, Othman F. Evaluation of acute, subacute and subchronic oral toxicity of Rhaphidophora decursiva (Roxb.) Schott extract in male Sprague Dawley rats. Journal of Medicinal Plants Research. 2013;7(41):3030–40. Arsad SS, Esa NM, Hamzah H, Othman F. Evaluation of acute, subacute and subchronic oral toxicity of Rhaphidophora decursiva (Roxb.) Schott extract in male Sprague Dawley rats. Journal of Medicinal Plants Research. 2013;7(41):3030–40.
18.
go back to reference United States Food and Drug Administration. Redbook 2000. Toxicological principles for the safety assessment of food ingredients. IV.C.4.a. Subchronic toxicity studies with rodents: FDA; 2003. United States Food and Drug Administration. Redbook 2000. Toxicological principles for the safety assessment of food ingredients. IV.C.4.a. Subchronic toxicity studies with rodents: FDA; 2003.
19.
go back to reference Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.PubMed Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.PubMed
20.
go back to reference Martirosyan DM, Miroshnichenko LA, Kulakova SN, Pogojeva AV, Zoloedov VI. Amaranth oil application for coronary heart disease and hypertension. Lipids Health Dis. 2007;6:1–12.PubMedPubMedCentralCrossRef Martirosyan DM, Miroshnichenko LA, Kulakova SN, Pogojeva AV, Zoloedov VI. Amaranth oil application for coronary heart disease and hypertension. Lipids Health Dis. 2007;6:1–12.PubMedPubMedCentralCrossRef
21.
go back to reference Castelli WP, Abbott RD, Mcnamara PM. Summary estimates of cholesterol used to predict coronary heart disease. Circulation. 1983;67:730–4.PubMedCrossRef Castelli WP, Abbott RD, Mcnamara PM. Summary estimates of cholesterol used to predict coronary heart disease. Circulation. 1983;67:730–4.PubMedCrossRef
22.
go back to reference Brehm A, Pfeiler G, Pacini G, Vierhapper H, Roden M. Relationship between serum lipoprotein ratios and insulin resistance in obesity. Clin Chem. 2004;50:2316–22.PubMedCrossRef Brehm A, Pfeiler G, Pacini G, Vierhapper H, Roden M. Relationship between serum lipoprotein ratios and insulin resistance in obesity. Clin Chem. 2004;50:2316–22.PubMedCrossRef
23.
go back to reference Dobiášová M. Atherogenic index of plasma [log (triglycerides/HDL-cholesterol)]: theoretical and practical implications. Clin Chem. 2004;50:1113–5.PubMedCrossRef Dobiášová M. Atherogenic index of plasma [log (triglycerides/HDL-cholesterol)]: theoretical and practical implications. Clin Chem. 2004;50:1113–5.PubMedCrossRef
24.
go back to reference Yam MF, Ang LF, Salman IM, Ameer OZ, Lim V, Ong LM, et al. Orthosiphon stamineus leaf extract protects against ethanol-induced gastropathy in rats. J Med Food. 2009;12:1089–97.PubMedCrossRef Yam MF, Ang LF, Salman IM, Ameer OZ, Lim V, Ong LM, et al. Orthosiphon stamineus leaf extract protects against ethanol-induced gastropathy in rats. J Med Food. 2009;12:1089–97.PubMedCrossRef
25.
go back to reference Zhang X. General guidelines for methodologies on research and evaluation of traditional medicine: World Health Organization; 2000. Zhang X. General guidelines for methodologies on research and evaluation of traditional medicine: World Health Organization; 2000.
26.
go back to reference Nwanjo H, Okafor M, Oze G. Anti-lipid peroxidative activity of Gongronema latifoluim in streptozotocin-induced diadetic rat. Niger J Physiol Sci. 2006;21:61–5.PubMed Nwanjo H, Okafor M, Oze G. Anti-lipid peroxidative activity of Gongronema latifoluim in streptozotocin-induced diadetic rat. Niger J Physiol Sci. 2006;21:61–5.PubMed
27.
go back to reference Ejike CE, Awazie SO, Nwangozi PA, Godwin CD. Synergistic postprandial blood glucose modulatory properties of Vernonia amygdalina (Del.), Gongronema latifolium (Benth.) and Occimum gratissimum (Linn.) aqueous decoctions. J Ethnopharmacol. 2013;149:111–6.PubMedCrossRef Ejike CE, Awazie SO, Nwangozi PA, Godwin CD. Synergistic postprandial blood glucose modulatory properties of Vernonia amygdalina (Del.), Gongronema latifolium (Benth.) and Occimum gratissimum (Linn.) aqueous decoctions. J Ethnopharmacol. 2013;149:111–6.PubMedCrossRef
28.
go back to reference Ugochukwu NH, Babady NE. Antihyperglycemic effect of aqueous and ethanolic extracts of Gongronema latifolium leaves on glucose and glycogen metabolism in livers of normal and streptozotocin-induced diabetic rats. Life Sci. 2003;73:1925–38.PubMedCrossRef Ugochukwu NH, Babady NE. Antihyperglycemic effect of aqueous and ethanolic extracts of Gongronema latifolium leaves on glucose and glycogen metabolism in livers of normal and streptozotocin-induced diabetic rats. Life Sci. 2003;73:1925–38.PubMedCrossRef
29.
go back to reference Atsafack SS, Kuiate J-R, Mouokeu RS, Mogtomo MLK, Tchinda AT, De Dieu TJ, et al. Toxicological studies of stem bark extract from Schefflera barteri harms (Araliaceae). BMC Complement Altern Med. 2015;15:44.PubMedPubMedCentralCrossRef Atsafack SS, Kuiate J-R, Mouokeu RS, Mogtomo MLK, Tchinda AT, De Dieu TJ, et al. Toxicological studies of stem bark extract from Schefflera barteri harms (Araliaceae). BMC Complement Altern Med. 2015;15:44.PubMedPubMedCentralCrossRef
30.
go back to reference Michael B, Yano B, Sellers RS, Perry R, Morton D, Roome N, et al. Evaluation of organ weights for rodent and non-rodent toxicity studies: a review of regulatory guidelines and a survey of current practices. Toxicol Pathol. 2007;35(5):742–50.PubMedCrossRef Michael B, Yano B, Sellers RS, Perry R, Morton D, Roome N, et al. Evaluation of organ weights for rodent and non-rodent toxicity studies: a review of regulatory guidelines and a survey of current practices. Toxicol Pathol. 2007;35(5):742–50.PubMedCrossRef
31.
go back to reference Amacher DE, Schomaker SJ, Boldt SE, Mirsky M. The relationship among microsomal enzyme induction, liver weight, and histological change in cynomolgus monkey toxicology studies. Food Chem Toxicol. 2006;44(4):528–37.PubMedCrossRef Amacher DE, Schomaker SJ, Boldt SE, Mirsky M. The relationship among microsomal enzyme induction, liver weight, and histological change in cynomolgus monkey toxicology studies. Food Chem Toxicol. 2006;44(4):528–37.PubMedCrossRef
32.
go back to reference Greaves P. Histopathology of preclinical toxicity studies: interpretation and relevance in drug safety evaluation. Canada: Academic Press; 2011. Greaves P. Histopathology of preclinical toxicity studies: interpretation and relevance in drug safety evaluation. Canada: Academic Press; 2011.
33.
go back to reference Sellers RS, Mortan D, Michael B, Roome N, Johnson JK, Yano BL, et al. Society of Toxicologic Pathology position paper: organ weight recommendations for toxicology studies. Toxicol Pathol. 2007;35(5):751–5.PubMedCrossRef Sellers RS, Mortan D, Michael B, Roome N, Johnson JK, Yano BL, et al. Society of Toxicologic Pathology position paper: organ weight recommendations for toxicology studies. Toxicol Pathol. 2007;35(5):751–5.PubMedCrossRef
34.
go back to reference Ekong MB, Peter AI, Davies K, Bassey EI, Aquaisua AN, Akpanabiatu MI, et al. Gongronema latifolium ameliorates Rauwolfia vomitoria-induced behavior, biochemicals, and histomorphology of the cerebral cortex. J Neurochem. 2013;125:269. Ekong MB, Peter AI, Davies K, Bassey EI, Aquaisua AN, Akpanabiatu MI, et al. Gongronema latifolium ameliorates Rauwolfia vomitoria-induced behavior, biochemicals, and histomorphology of the cerebral cortex. J Neurochem. 2013;125:269.
35.
go back to reference Ekong MB, Peter AI. Co-treatment of Rauwolfia vomitoria and Gongronema latifolium affects cerebellar cell population in mice. J Anim Husb Dairy Sci. 2017;1(1):1–7. Ekong MB, Peter AI. Co-treatment of Rauwolfia vomitoria and Gongronema latifolium affects cerebellar cell population in mice. J Anim Husb Dairy Sci. 2017;1(1):1–7.
36.
go back to reference Adenuga D, Carrillo J-C, Mckee RH. The sub-chronic oral toxicity of 1, 3, 5-trimethylbenzene in Sprague–Dawley rats. Regul Toxicol Pharmacol. 2014;69:143–53.PubMedCrossRef Adenuga D, Carrillo J-C, Mckee RH. The sub-chronic oral toxicity of 1, 3, 5-trimethylbenzene in Sprague–Dawley rats. Regul Toxicol Pharmacol. 2014;69:143–53.PubMedCrossRef
37.
go back to reference Greaves P. Liver and pancreas: histopathology of preclinical toxicity studies. Third ed. London, UK: Elsevier; 2007.CrossRef Greaves P. Liver and pancreas: histopathology of preclinical toxicity studies. Third ed. London, UK: Elsevier; 2007.CrossRef
38.
go back to reference Hall AP, Elcombe CR, Foster JR, Harada T, Kaufmann W, Knippel A, et al. Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes—conclusions from the 3rd international ESTP expert workshop. Toxicol Pathol. 2012;40:971–94.PubMedCrossRef Hall AP, Elcombe CR, Foster JR, Harada T, Kaufmann W, Knippel A, et al. Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes—conclusions from the 3rd international ESTP expert workshop. Toxicol Pathol. 2012;40:971–94.PubMedCrossRef
39.
go back to reference Lewis RW, Billington R, Debryune E, Gamer A, Lang B, Carpanini F. Recognition of adverse and nonadverse effects in toxicity studies. Toxicol Pathol. 2002;30:66–74.PubMedCrossRef Lewis RW, Billington R, Debryune E, Gamer A, Lang B, Carpanini F. Recognition of adverse and nonadverse effects in toxicity studies. Toxicol Pathol. 2002;30:66–74.PubMedCrossRef
40.
go back to reference Carrillo J-C, Adenuga MD, Mckee RH. The sub-chronic toxicity of regular white spirit in rats. Regul Toxicol Pharmacol. 2014;70:222–30.PubMedCrossRef Carrillo J-C, Adenuga MD, Mckee RH. The sub-chronic toxicity of regular white spirit in rats. Regul Toxicol Pharmacol. 2014;70:222–30.PubMedCrossRef
41.
go back to reference Gaidos JKJ, Hillner BE, Sanyal AJ. A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis. Liver Int. 2008;28(5):650–8.PubMedCrossRef Gaidos JKJ, Hillner BE, Sanyal AJ. A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis. Liver Int. 2008;28(5):650–8.PubMedCrossRef
42.
go back to reference Rhiouani H, El-Hilaly J, Israili ZH, Lyoussi B. Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents. J Ethnopharmacol. 2008;118(3):378–86.PubMedCrossRef Rhiouani H, El-Hilaly J, Israili ZH, Lyoussi B. Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents. J Ethnopharmacol. 2008;118(3):378–86.PubMedCrossRef
43.
go back to reference Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol. 2000;32:56–67.PubMedCrossRef Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, et al. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol. 2000;32:56–67.PubMedCrossRef
44.
go back to reference Seiva FR, Chuffa LGA, Braga CP, Amorim JPA, Fernandes AAH. Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations. Food Chem Toxicol. 2012;50(10):3556–61.PubMedCrossRef Seiva FR, Chuffa LGA, Braga CP, Amorim JPA, Fernandes AAH. Quercetin ameliorates glucose and lipid metabolism and improves antioxidant status in postnatally monosodium glutamate-induced metabolic alterations. Food Chem Toxicol. 2012;50(10):3556–61.PubMedCrossRef
45.
go back to reference Himms-Hagen J. Brown adipose tissue thermogenesis: interdisciplinary studies. FASEB J. 1990;4:2890–8.PubMedCrossRef Himms-Hagen J. Brown adipose tissue thermogenesis: interdisciplinary studies. FASEB J. 1990;4:2890–8.PubMedCrossRef
46.
go back to reference Virtanen KA, Iozzo P, Hällsten K, Huupponen R, Parkkola R, Janatuinen T, et al. Increased fat mass compensates for insulin resistance in abdominal obesity and type 2 diabetes: a positron-emitting tomography study. Diabetes. 2005;54:2720–6.PubMedCrossRef Virtanen KA, Iozzo P, Hällsten K, Huupponen R, Parkkola R, Janatuinen T, et al. Increased fat mass compensates for insulin resistance in abdominal obesity and type 2 diabetes: a positron-emitting tomography study. Diabetes. 2005;54:2720–6.PubMedCrossRef
47.
go back to reference Bikman BT, Zheng D, Kane DA, Anderson EJ, Woodlief TL, Price JW, et al. Metformin improves insulin signaling in obese rats via reduced IKK. J Obes. 2010;2010:1–8.CrossRef Bikman BT, Zheng D, Kane DA, Anderson EJ, Woodlief TL, Price JW, et al. Metformin improves insulin signaling in obese rats via reduced IKK. J Obes. 2010;2010:1–8.CrossRef
48.
go back to reference Huffman DM, Barzilai N. Role of visceral adipose tissue in aging. BBA - Gen Subj. 2009;1790:1117–23.CrossRef Huffman DM, Barzilai N. Role of visceral adipose tissue in aging. BBA - Gen Subj. 2009;1790:1117–23.CrossRef
49.
go back to reference Rothstein HR, Sutton AJ, Borenstein M, editors. Publication bias in meta-analysis: prevention, assessment and adjustments. West Sussex, England: John Wiley & Sons Ltd; 2006. Rothstein HR, Sutton AJ, Borenstein M, editors. Publication bias in meta-analysis: prevention, assessment and adjustments. West Sussex, England: John Wiley & Sons Ltd; 2006.
50.
go back to reference Buli GA, Duga AG, Dessalegn E. Antimicrobial activity of Lippia adoensis var. koseret against human pathogenic bacteria and fungi. Am J Clin Exp Med. 2015;3(3):118–23.CrossRef Buli GA, Duga AG, Dessalegn E. Antimicrobial activity of Lippia adoensis var. koseret against human pathogenic bacteria and fungi. Am J Clin Exp Med. 2015;3(3):118–23.CrossRef
51.
go back to reference Turkmen N, Velioglu YS, Sari F, Polat G. Effect of extraction conditions on measured total polyphenol contents and antioxidant and antibacterial activities of black tea. Molecules. 2007;12(3):484–96.PubMedPubMedCentralCrossRef Turkmen N, Velioglu YS, Sari F, Polat G. Effect of extraction conditions on measured total polyphenol contents and antioxidant and antibacterial activities of black tea. Molecules. 2007;12(3):484–96.PubMedPubMedCentralCrossRef
52.
Metadata
Title
Safety assessment of the ethanolic extract of Gongronema latifolium Benth. leaves: a 90-day oral toxicity study in Sprague Dawley rats
Authors
Bassel Al-Hindi
Nor Adlin Yusoff
Mariam Ahmad
Item Justin Atangwho
Mohd Zaini Asmawi
Majed Ahmed Al-Mansoub
Yasser Mahfooth Tabana
Idris Bello
Mun Fei Yam
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2573-x

Other articles of this Issue 1/2019

BMC Complementary Medicine and Therapies 1/2019 Go to the issue