Animal and Environmental Biology

Duration Dependent Impact of Sacoglottis Gabonensis on Aspartame Induced Hepatotoxicity


This study was aimed at evaluating the duration-dependent effect of Aspartame and the potential protective role of Sacoglottis gabonensis in Swiss male mice. Ninety animals were used for this study and all animals were fed standard rodent pellets and cool clean water ad libitum The ninety mice were. divided into 6 groups (A-G) each group containing 18 mice, with 30 days,60 days and 90 days treatment made of 6 animals each. A served as the negative control, and received water and feed only. Group B, served as positive control and was administered 50mg/kg/bw of aspartame only. Group C, was administered, 50mg/kg/bw of aspartame and 250mg/kg/bw/day of the bark of Sacoglottis. gabonensis. Tincture… Group D, was administered 50mg/kg/bw of aspartame and 250mg/kg/bw/day of the leaf tincture of Sacoglottis. gabonensis. Group E, was administered 50mg/kg/bw of aspartame and 250mg/kg/bw/day of combined tincture of bark and leaf of S. gabonensis. Group F, was administered, 50mg/kg/bw of aspartame and 750mg of the combined bark and leaf extract of S. gabonensis. experimental animals were euthanized At the end of each exposure period, for analysis 60days,60 days and 90 days.

Endogenous liver biomarkers showed a significant increase in GSH, CAT, and MDA with low SOD in the group that received aspartame in 30 days of exposure. 60 and 90 days of exposure showed a significant increase in GSH, SOD, and CAT with decreased MDA and GSH in the aspartame group as against the group that received an extract of S. gabonensis and the negative control group. Exogenous liver biomarkers showed elevated AST, ALT, ALP, GLU and TC in the group that received aspartame in all the exposure periods, AST was elevated in the group that received the bark extract of S. gabonensis in 30 and 60 exposure, TC and GLU, were also high in the group that received the leaf extract in 90 days exposure. There is a significant increase in electrolytes such as K, Na, HCO3, and Ca2+ decreased Cl in the group that received aspartame in 30 days of exposure. K, Na, were increased, Cl decreased HCO3 was stable Ca2+ stable in control groups and decreased in other groups in 60 days. K, Na was decreased, and Cl and HCO3 increased Ca2+ stability in control groups in 90 days. Hormones such as FSH, LH, TET, and E2 were increased in the group that received bark extract of S. gabonensis while PROG decreased in 30 days of exposure. All the hormones increased in the group that received aspartame alone except E2 in 60 and 90 days. Histological examination showed numerous spaces in the central vein, degenerated hepatocytes apoptotic cells and necrosis observed in the group that received only aspartame, the groups that received S. gabonensis showed regeneration of hepatocytes, several mitotic figures, binuclear cells, mitotic telophase few necrotic cells.



1.1 Background of the Study

The world’s population is on the increase and an ever-increasing number of people all over the world are constantly being afflicted with one form of neurodegenerative disease or the other. Contributory factors to the physical and general health status of the ever-increasing world population can be attributed to lifestyle. In modern affluent societies, the diseases exacting the greatest mortality and morbidity are degenerative diseases. They can be attributed to environmental factors such as occupational hazard exposure, smoking, alcohol intake, diet as well as genetic pre-disposition of individuals Some food additives in recent times have been linked to degenerative diseases such as cancer, diabetes, Alzheimer diseases, Parkinson’s disease, parkinsonian syndromes, multiple system atrophy, progressive supranuclear palsy, amyotrophic lateral sclerosis, cardiovascular diseases, overweight, spinal muscular atrophy and hypertension

Artificial sweeteners are one of the most used additives worldwide. They are used as sugar substitutes in dietary soda, chewing gum, ice cream, breakfast cereal and most sugar-free foods. The majority of people all over the world consume food that has one sweetener or the other despite the fact that the foods are termed sugar-free. In recent times, some degenerative diseases, especially diabetes, which was once believed to be adult-lifestyle-based diseases are now diagnosed in children. This may be a result of the high consumption of sweetened food, juices, cakes and chocolates that are highly demanded by children.

Consumers and food manufacturers have long been interested in enhancing flavour while reducing calorie intake. Artificial sweeteners have been classified as nutritive and non-nutritive depending on whether they are a source of calories. The nutritive sweeteners include monosaccharide polyols (e.g., sorbitol, mannitol, and xylitol) and disaccharide polyols (e.g., maltitol and lactitol) Artificial sweeteners are many times sweeter than table sugar. Smaller amounts are needed to create the same level of sweetness, which is either not metabolized in the human body or does not significantly contribute to the energy content of foods and beverages. They provide the sweetness of sugar without calories and produce a low glycaemic response.

Aspartame is an artificial (non-nutritive) sweetener used to replace sugar in food and drinks. Nutritive sweeteners are naturally occurring sweeteners such as sucrose and fructose. On the other hand, non-nutritive sweeteners synthesized in the laboratory such as aspartame, stevia and sucralose. Non-nutritive sweeteners, also referred to as high-intensity sweeteners, are typically used in small amounts to reduce the caloric intake while sustaining the desired taste in many food products The non-nutritive sweeteners, better known as artificial sweeteners, include substances from several different chemical classes that interact with taste receptors and typically exceed the sweetness of sucrose by a factor of 30 to 13,000 times Aspartame is most stable between pH values of 3 and 5 even with increasing temperature. However, it breaks down and loses its sweetness in normal cooking or baking. Thus its use is limited to tabletop sweeteners in dry foods, soft drinks, and frozen foods like ice cream because of its low caloric contribution in producing the same level of sweetness as sucrose (approximately 160-200 times sweeter than sucrose), it is used extensively in ‘diet’ products Since the discovery of Aspartame in 1965, studies carried out on both humans and animals have shown a considerable controversy regarding its safety for human consumption including possible neurologic and behavioural side effects. Concerns relating to the possible adverse effects have been raised due to aspartame’s metabolic components produced during its breakdown, namely phenylalanine (Phe), aspartic acid (aspartate), diketopiperazine (DKP) and methanol. Aspartame is produced commercially from the methyl ester of two amino acids: L-aspartic and L-phenylalanine methyl-ester which builds the chemical structure of the aspartame. Aspartame in 1981 received approval for safe consumer use from the Food and Drug Administration (FDA). The American Dietetic Association have numerous studies, in which they challenged the safety of aspartame The accepted daily recommended amount by the FDA is 50mg/Kg body weight/day while the accepted or/and approved daily dose by the World Health Organization (WHO) is 40 mg/kg/day.

Aspartame is an artificial sweetener that has been trademarked by many companies including Equal, NutraTaste and NutraSweet. Aspartame represents 62% value of the intense sweetener marketed and consumed worldwide in over 100 countries  It was first approved by Food and Drug Administration (FDA) for its use in dry foods in 1981 and in carbonated soft drinks in 1983. Since then, consumption of aspartame has increased as a sweetener in a variety of soft drinks and processed foods as well as a low-calorie alternative to table sugar ( Sweeteners have a primary importance in nutritional guidance for dieticians and diabetic patients, a disease with increasing incidence in developing and developed countries. Aspartame is used in day-to-day life and is consumed in many ways. It is used as a sweetener in food products including dry beverage mixes, chewable multi-vitamins, breakfast cereals, chewing gum, puddings and fillings, carbonated beverages, refrigerated and non-refrigerated ready-to-drink beverages, yoghurt-type products and pharmaceuticals. This sweetener is added to many soft beverages, cakes etc., and its usage is increasing in health-conscious societies as used in the weight reduction regime.

Aspartame (APM; L aspartyl-L-phenylalanine methyl ester), is found in many products in the market worldwide, especially in unsweetened or sugar-free products. It is mostly consumed on purpose by people trying to lose weight or patients with diabetes, including children. A recent observation indicated that aspartame is slowly making its way into ordinary products used every day, which is not indicated for people on diets or diabetics. Although there is concern suggesting possible adverse neurological and behavioural effects due to aspartame’s metabolic components (phenylalanine, aspartic acid (aspartate), diketopiperazine and methanol), which are produced during its breakdown Aspartame is incorporated into several products including 600 pharmaceutical products, it is consumed by millions of humans internationally and this may result in oxidative stress by affecting a variety of cells and tissues and inflicting deregulation of cellular function.

Most diet beverages and food products currently in the market contain aspartame as an artificial sweetener. However, controversy surrounds the effects of this non-nutritive artificial sweetener, as it is made up of components such as (phenylalanine, aspartic acid (aspartate), diketopiperazine and methanol), that may have adverse effects on neural functioning, particularly on neurotransmitters, neurons and astrocytes Following oral administration to humans and experimental animals, ASP is completely and rapidly metabolized by intestinal esterases and dipeptidases to aspartic acid, phenylalanine and methanol, substances normally found in the diet and body Low caloric sweeteners are widely used to prevent the increasing rates of obesity and diabetes mellitus in the growing population.

The bitter bark cherry tree (Sacoglottis gabonensis) is a tropical rainforest tree found in the tropical rainforest region of Africa and America. It belongs to the family Humiriaceae. In certain rural communities of Nigeria especially Abia, Akwa- Ibom, Rivers, Delta, Edo and Imo State, the stem bark of this tree is commonly used as an additive to palm wine, a local alcoholic brew which is an exudate from the phloem of Raphia species especially Raphia vinifera and palm trees (Elaeis guinensis). Palm wine is a generic name for a group of alcoholic beverages obtained by fermentation from the saps of palm trees and Raphia trees. Freshly harvested unfermented sap is a clear colourless liquid or suspension with a sweet sugary taste and low alcohol content. Following fermentation from its yeast content, it becomes milkier and increasingly less sugary with increased alcohol content which results in intoxication depending on the volume consumed. Upon fermentation by the endogenous microflora of the palm wine, the sugar is converted into ethanol and organic acids resulting in the rapid deterioration of the organoleptic quality of the juice. The stem bark extract of S. gabonensis is normally added when the palm wine is fresh as it is believed to prolong the shelf life and reduce foaming and effervescence. It impacts a bitter taste to the sugary palm wine thereby making the beverage more tasty and acceptable with the amber colour. It also delays the souring of palm wine).

1.2 Justification

Aspartame is an artificial sweetener that has been trademarked by many companies including Equal, NutraTaste and NutraSweet. Aspartame represents 62% value of the intense sweetener marketed and consumed worldwide in over 100 countries. Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioural and cognitive problems Possible neurophysiological symptoms include learning problems, headache, seizure), migraines, irritable moods, anxiety, depression and insomnia. To the best of my knowledge, there are over 200 million Nigerians that made up 2.64% of the world’s population ( People of all ages including infants are exposed to sweeteners including aspartame. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brain’s vulnerability to oxidative stress which may have adverse effects on neurobehavioral health.

Traditionally in central African countries, Cameroon and Congo in particular, the stem bark of Sacoglottis gabonensis are commonly taken to treat fever, diarrhoea, gonorrhoea and abdominal pain, and they are used to treat hypertension and diabetes sometimes The Kola pygmies and Mvae people of Cameroon use a decoction of the crushed bark mixed with leaves of Dioscorea minutiflora as a rectal enema to treat acute abdominal pain, it is used to cure difficult cases of dermatitis in Congo treat stomach-ache and used as a spice in food to induce heat in nursing and pregnant mothers in Sierra Diluted stem sap is used in hipbaths to promote muscle tone in women after childbirth in coastal Côte d’Ivoire In Gabon, an extract of the stem bark is drunk as an emetic Stem bark decoction is mixed with other plants and added to bath water to treat ovarian troubles, vaginal infections and children with fever in Senegal and Congo In southern part of Nigeria the stem bark is used to prolong the shelf life of palm wine, add potency, reduce foaming, impart a bitter taste and treat arthritis in old people. It is also believed to have aphrodisiac properties There is a growing concern about the attributed effects of artificial sweeteners such as aspartame, its long-time accumulation and the fate of the general population since they are found in ready-to-use consumables and the potential of S. gabonensis an indigenous plant as a remedy.

1.3 Aim

The aim of this study was to evaluate the potential adverse effects of aspartame and the protective role of Sacoglottis gabonensis on Swiss mice.

1.3.2 Objectives

The objectives of this study were;

  1. To determine the phytochemical properties of Sacoglottis gabonensis
  2. To evaluate potential systemic toxicity induced by aspartame using body weight
  3. To evaluate the potential nephrotoxicity of aspartame by analysing kidney biomarkers
  4. To evaluate the potential hepatotoxicity of aspartame by analysing liver biomarkers and histopathological sections of the liver
  5. To determine the effect of aspartame on the hormonal Profile of test animals
  6. To evaluate the effect of aspartame on cell electrolytes
  7. To evaluate the effect of aspartame on germ cells
  8. To evaluate the effect of aspartame on male reproduction by the mating of exposed male to unexposed female
  9. To determine the effect of aspartame on sex ratio, litter size, birth weight, potential abnormality and infertility
  10. To evaluate the potential role of Sacoglottis gabonensis as an antioxidant.


Bazzaz, A. A.  & Al-Johani, N. S. (2018). Acute Impact of Artificial Sweetener, Aspartame on Blood Parameter in Mice. Advances in Bioscience and Biotechnology. 9, 549-560.

Beastall, G.H. Ferguson, K. M. O’Really, D. S. Seth, J. & Sheridan, B. (1987). Assays for follicle-stimulating hormone and luteinising hormone: guidelines for the provision of a clinical biochemistry service. Annals of Clinical Biochemistry. Doi: 10.1177/000456328702400303.

Bohm, B. A. & Koupai-Abyazani, M. R. (1994). Flavonoids and Condensed Tannins from Leaves of Hawaiian Vaccinium reticulatum and V. calycinum (Ericaceae). Pacific Science. 48, (4), 458-463.

Brigitte, K. K. Euserbe, A. A. Mama, K.  Duni, S. & Paul, Y. A. (2018). Influence of an aqueous extract of Sacoglottis gabonensis (Baille) urban (Humiriaceae) stems bark, a plant used in the traditional treatment of Buruli ulcer, on anthropometric and haematological parameters in Wistar rat. The Pharma Innovation Journal. 7, (3), 104-110.

Brown, R.C. Lockwood, A.H. & Sonawane, B.R. (2005). Neurodegenerative diseases: an overview of environmental risk factors. Environmental health perspective. 113, (9) 1250-1256.

Carl, A. B. Edward R. A & David, E. B. (201O). Tietz fundamentals of Clinical Chemistry. 6th edition. ISBN: 978-81-312-1374-2.

Choudhary A. K.  & Lee, Y. Y. (2017). Neurophysiological symptoms and aspartame: What is the connection? Nutritional Neuroscience, DOI: 10.1080/1028415X.2017.1288340.

Choudhary A. K. Sundareswaran, L. & Sheela Devi, R. (2016). Effects of aspartame on the evaluation of electrophysiological response in Wistar albino rats. Journal of Taibah University for Science, 10, 505–512.

Choudhary, A. K. & Lee, Y. Y. (2018). The debate over neurotransmitter interaction in aspartame usage. Journal of Clinical Neuroscience. https://

Choudhary, A. K. & Sheela Devi, R. (2014). Serum biochemical responses under oxidative stress of aspartame in wistar albino rats. Asian Pacific Journal of Tropical Disease. 4, (Suppl1), S403-S410.

Choudhary, A. K. & Sheeladevi, R. (2014). Effect of aspartame on lipid peroxidation and membrane bound enzymes in immune organs of rats. Oxidative and Antioxidant Medical Science. 3, (2):129-134.

Choudhary, A. K. Sundareswaran, L. & Sheela Devi, R. (2016). Aspartame induced cardiac oxidative stress in Wistar albino rats. Nutritional and Clinical Metabolism.

Clairborne, A. (1985). Catalase activity. In: Greenwald, R. A. ED. CRC Handbook of Methods for Oxygen Radical Research, CRC Press, Boca Raton, 283-284.

Marinovich M, Galli CL, Bosetti C, Gallus S, La Vecchia C. Aspartame, low-calorie sweetener and disease: regulatory safe

Walsh R. 2011 Lifestyle and mental health. American Psychology 66(7),579-92.

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