- Email: [email protected]
The potential of saponin from Jamaica’s Blighia sapida (ackee) as a substitute for sodium lauryl sulphate in toothpaste
Journal Pre-proofs The Potential of Saponin from Jamaica’s Blighia Sapida (Ackee) as a Substitute for Sodium Lauryl Sulphate in Toothpaste Tomlin J. Paul, Tanielle A. Taylor, Arvind Babu Rajendra Santosh PII: DOI: Reference:
S0306-9877(19)31224-1 https://doi.org/10.1016/j.mehy.2020.109555 YMEHY 109555
To appear in:
Medical Hypotheses
Received Date: Revised Date: Accepted Date:
30 October 2019 19 December 2019 5 January 2020
Please cite this article as: T.J. Paul, T.A. Taylor, A.B. Rajendra Santosh, The Potential of Saponin from Jamaica’s Blighia Sapida (Ackee) as a Substitute for Sodium Lauryl Sulphate in Toothpaste, Medical Hypotheses (2020), doi: https://doi.org/10.1016/j.mehy.2020.109555
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© 2020 Published by Elsevier Ltd.
1
ARTICLE TYPE: REVIEW TITLE OF THE ARTICLE: THE POTENTIAL OF SAPONIN FROM JAMAICA’S BLIGHIA SAPIDA (ACKEE) AS A SUBSTITUTE FOR SODIUM LAURYL SULPHATE IN TOOTHPASTE RUNNING TITLE: SAPONIN AS A SUBSTITUTE FOR SLS
Paul, Tomlin J, MB BS, MPH, DFPHM, FAcadMEd1 Taylor, Tanielle A, BB Med Sci2 Rajendra Santosh, Arvind Babu, BDS, MDS3
1Faculty
of Medical Sciences, University of the West Indies, Mona
2Department
of Community Health and Psychiatry, Faculty of Medical Sciences, University
of the West Indies, Mona 3School
of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona
Correspondence: Arvind Babu Rajendra Santosh, School of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica. Email: [email protected]
Acknowledgements: All authors declare that no financial support exists regarding any of the work done within this study.
Author contributions: All authors have contributed significantly and are in agreement with the content of the manuscript.
Conflict of interest: There are no conflicts of interest to declare.
2 Abstract Discovering novel means of protection from harmful substances in toothpaste is essential due to its mass production, and frequent exposure to its ingredients by consumers. This method of safeguarding through discovery demonstrates toothpaste safety, which is at risk of being stifled by other commercial priorities. Among the ingredients in toothpaste that cause adverse effects is sodium lauryl sulphate (SLS). An understanding of this source and its effects therefore allows for investigating preventative strategies through the use of safer alternatives. Saponin, a naturally occurring chemical in several plant species was discovered to be an alternative compound that may parallel the effects of sodium lauryl sulphate, yet exude less ill effects. This article highlights the benefits of saponin and its presence in a heavily consumed and exported fruit in Jamaica (ackee, Blighia sapida). The possibility of extracting saponin from ackee, and its use in the toothpaste industry as an alternative to sodium lauryl sulphate are discussed. Through consideration of this alternative, the potential exists to improve the safety of toothpastes and consequently improve oral health.
Key words: saponin, sodium lauryl sulphate, Blighia sapida, aphthous ulcers
Introduction Proper oral hygiene involves the use of aptly formulated products that aim to promote and maintain good oral health. Toothpastes (dentifrices) are among those formulations designed to control and prevent periodontal disease and dental caries1. The safety of these products is vital as their recommended daily use provides the opportunity for denaturing effects, bioaccumulation of their components, and other undesirable outcomes. Extensive laboratory tests are conducted on dentifrices to determine their safety and efficacy2. Amidst the tested constituents in toothpastes is Sodium lauryl sulfate (SLS), which has a significant role in enticing consumers, due to its foaming effect - a visual indicator that, to some, suggests the product is effective. Popularly used for its detergent property, SLS however produces side effects that may steer consumers to opt for SLS-free dentifrices. This review proposes the possible substitution of SLS with the Blighia sapida’s (Ackee’s) saponin, which has similar detergent properties, but assumes less adverse effects. Sodium lauryl sulfate
Commented [Office1]: Change was made to address the comment “more an economical/chemistry appeal than medical”
3 Sodium lauryl sulphate (SLS) (C12H25NaO4S) is a synthetic and almost universal excipient in dentifrices, used for its foaming, wetting and dispersing properties. The molecule is ampiphilic with a hydrophilic sulphate head, and a 12-carbon long tail that is hydrophobic (Figure 1). It is anionic and plays a role as a surfactant (or detergent) in exerting a potent cleansing effect through a surface action. SLS lowers the surface tension of liquids by migrating to their surface and accumulating with other SLS molecules, allowing for easier spreading and mixing of the liquid.
Figure 1: SLS molecule showing hydrophobic tail and hydrophilic head It is inexpensive and Generally Regarded as Safe (GRAS), with varying concentration between 1 to 2% w/w in commercial toothpastes3. Its foaming action allows it to be suspended, and its detergency properties enable it to reach otherwise inaccessible areas and cavities in the mouth. Studies have also shown it to have antibacterial and antiplaque effects.3,9 Aphthous ulcerations are the most common oral mucosal pathology across the world. Recently conducted systematic reviews had reported that SLS based dentifrice is likely to influence recurrent aphthous stomatitis. Their results also stated that SLS-free dentifrices showed significant reduction on number, duration, episodes and pain among recurrent aphthous ulceration (Sutton’s disease) patients (Babatunde et al. 2019). In addition, effectiveness of sodium lauryl sulfate in toothpaste on oral epithelial cells was also studied investigating for integrity of those cells and aphthous ulcer formation (Table 1). Despite its widespread use, SLS has been found to have a number of potential side effects that pose a threat to oral health. By eliminating the mucin protective coating and reducing the resistance of the oral mucosa SLS has been shown to have irritant qualities, inducing oral mucosal desquamation4. SLS may also have a negative influence on patients with recurrent aphthous ulcers5. Shim et al6 noted that the duration of ulcers and mean pain scores were significantly decreased when SLS-free dentifrices were used compared to two SLS-containing dentifrices (1.5%). Synthetic detergents like SLS can pass through permeable mucous membranes and bioaccumulate in the body, leading to toxic overload and disease7. Table 1 shows evidence of adverse reactions related to the presence of SLS in toothpaste. Despite its adverse effects, SLS continues to be used widely in dentifrices given its desired foaming ability, acceptable taste and low cost compared to other surfactants. There are very few types of toothpaste on the market that contain surfactant other than SLS8. There
4 is therefore a need for researchers to investigate natural and innovative substances that can fill the role provided by SLS in toothpastes, without the potential for harm. Plants and their extracts were once explored for personal hygiene products but were seen as insufficient means of sustainability. This has however come full circle given consumers’ desire for more natural products that substitute synthetic ones. The plant-derived saponin may prove beneficial in replacing SLS in dentifrices, thus improving their safety.
Table 1: Findings of the effectiveness of SLS/SLS-free toothpaste
Saponin Saponins are naturally occurring surfactants present in several plant species, with a molecular structure that consists of a hydrophilic sugar attached to an aglycone (sapogenin). The aglycone is usually one of two main groups: steroids and triterpenoids. The only major differences between these two groups is triterpenoids tend to be acidic in pH and occur more commonly in dicots, and steroidal saponins tend to be neutral in pH and occur more commonly in monocots16. They however have most properties in common. Hoffman16 further classifies saponins based on the number of sugar chains in their structure: Monodesmosidic (single chain linkage at C-3), Bidesmosidic (two chain linkages at C-3 and either C-26 or C28) and Tridesmosidic (rare type having three sugar chain linkages). Though bidesmosides show less activity than monodesmosides, their surface tension properties remain unchanged. The hydrophilic-hydrophobic arrangement of the molecule makes the compound able to lower surface tension. In fact, the name saponin is derived from the Latin word ’sapo’, which defines a plant that consists of a frothing agent when diluted in aqueous solution17. These agents also cause hemolysis of red blood cells and thus they are highly toxic when injected directly into the blood stream18. However, saponins are relatively harmless when taken orally19. Toxicity is minimised during ingestion by low absorption and by hydrolysis18. Saponins have thus displayed diverse physicochemical and biological properties that have spawned commercial applications in several industries including cosmetics and pharmaceuticals. As natural non-ionic surfactants, they appear as emulsifying, foaming agents and detergents in shower gels, shampoos, lotions, liquid soaps, mouthwashes, and toothpastes19. A unique organic toothpaste characterised by the use of Quillaya and Yucca
Commented [Office2]: change was made to address the comment “more an economical/chemistry appeal than medical”
5 saponins as the cleansing and foaming agent has been developed. The content of saponins may form up to 10% by weight of the toothpaste13. There have been limitations, however, to the commercial use of this ingredient. Firstly, these compounds are not as potent surfactants as synthetic options, and second, the supply from plant sources has been quite limited, which makes these products less available and relatively expensive. To offset these issues, one might suggest that though the foaming properties of saponin might be inferior to a synthetic agent such as SLS, it may still produce substantial effect that is visible and favorable to consumers. Limitations on plant sources may also be adjusted by seeking yield from frequently discarded plant material, and a potential reserve of such material is the Jamaican Ackee.
Physical properties, and uses of Jamaican Ackee Blighia is a genus comprising four species of flowering plants belonging to the soapberry family, Sapindaceae, which is native to tropical Africa particularly in the zone from Guinea east to Kenya. Ackee (Blighia sapida) is the national fruit of Jamaica. In order to be safely consumed, the seeds and internal median pink tissue (Fig. 2) must be removed a process called “yawning”. Neglecting this step is likely to cause acute toxicity labeled as Jamaican vomiting sickness, first noted in 187521. The toxicity associated with the Jamaican ackee and vomiting sickness is however unrelated to saponins, but Hypoglycin A – a toxic material found in the pods and seeds of the fruit.
Figure 2: Photograph showing parts of the ackee fruit: A – seed; B – seed pod; C – aril After yawning, arils are parboiled in water, and then lightly fried in butter or oil. Codfish, onions and tomatoes are often seen accompanying the fruit in Jamaican dishes. The parboiled ackee arils may also be added to salt pork or stew beef with a range of herbs and spices. Furthermore, they are sometimes curried and eaten with rice. Beside its culinary applications, the ackee fruit is also used for making soap, perfumes and medicines. Folk medicinal uses involve as many as 22 diseases having been reportedly healed with ackee22. Repeated small doses of an aqueous seed extract have been used to expel parasites. Ackee pod poultice has been used for skin infections, ringworm and liver spots. The ripe arils, with sugar and cinnamon, have been given as a febrifuge and as a treatment for dysentery23. With
6 regard to its supply, scores of plant material such as the seeds and pods of the Blighia sapida are discarded, accounting for 70% (w/w) of the ackee fruit24. Blighia unijugata another of the four species means ‘with one pair of leaflets’ which is in actual fact. The plant and its fruit though not endemic to Jamaica, has similar properties and uses as Blighia sapida. Blighia welwitschii is found in Sierra Leone to DR Congo and Uganda.
Saponin levels in Jamaican ackee The presence of saponin is a common feature of the Blighia species (Table 2). Saponin is distributed throughout all of the Blighia sapida (ackee) fruit, but special emphasis is placed on the seeds and pods since these are discarded byproducts of the canning industry in Jamaica. Instead of being rejected their potential use for saponin production can be of great importance in improving toothpaste safety. The shiny black seed has been shown to contain saponin, described by Parkinson24 as a physiologically active polyphenolic compound that forms a soapy lather with water. Characterisation of the moderate presence in both ripe and unripe ackee seeds18 supports the further exploration of ackee as a source of surfactant for toothpastes and other industry products. The plant Blighia species was investigated on saponin action (see table 2) however further research is required investigation on the potential use in dentifrices and improving the safety. In addition to the seeds, triterpenoid and steroidal saponins were also obtained from the ackee pods24. Beside the more commonly discarded components, saponin may also be derived from the arils of the ackee fruit – many of which are also discarded after not being able to ripen for canning. Relatively high saponification values were achieved after investigating the foaming ability from oil extracts of the fruit’s arils26.
Table 2: Study findings of saponin in Blighia species
Future contributions of Jamaican ackee towards saponin-based toothpaste safety
7 Toothpastes with saponin derivatives are not yet in any widespread use. US Patent US 6485711 B120 shows the use of saponin derived from the bark of the Quillaja and/or Yucca tree in an organic toothpaste formulation. The safety of saponin in relation to its opponent SLS, is one to consider. Being a natural source, it is biodegradable and less likely to bioaccumulate and cause toxicity and disease. Although limited, there are also no studies that show the occurrence of recurrent aphthous ulcers from the use of these formulations.
Hypothesis on Saponin Formulation in Tooth paste and its relevance to oral hygiene care:
The ampiphilic property of saponins lend for a range of biological activity. Based on the chemical structure of Saponin, the properties include membranolytic effects and antimicrobial effects.31 Jyothi & Sehagiri (2012) explored the molecule’s antimicrobial response to dental plaque-forming microorganisms. They found antibacterial and fungicidal activity displayed by plant extracts of Bauhinia Purpurea, Madhuca Longifolia, Celastrus Paniculatus and Semecarpus Anacardium. Inhibition was seen in Bauhinia Purpurea, and Madhuca Longifolia to a lesser extent, against Streptococcus mutans, Streptococcus mitis, Staphylococcus aureus and Lactobacillus acidophilus, thus proving the saponin components in these plants may effectively control formation of plaque and caries32. The study concluded that saponins “may reduce the incidence of caries, periodontal problems and may help sustain a healthy oral environment”. Conclusion Further research is necessary to determine the fruit’s therapeutic applications, and its potential contribution to the commercialization of SLS-free products such as toothpaste. Confirmation of the benefits of ackee-derived toothpaste can boost its production and contribute to a better valorization of the enormous quantity of seeds and pods that are often discarded annually in Jamaica. There is a clear need to engage in further work to develop the industry to extract and conduct research on the use of these substances in the toothpaste industry. Given the popularity and acceptance of ackee in Jamaica, toothpaste derived with ingredients from the ackee plant is likely to find high acceptability. This innovation will expand the impact of ackee farming for the country and countries with similar sources and capacities.
Commented [Office3]: Change was made to address “more an economical/chemistry appeal than medical”
8
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Park, Sang-Rye ; Kim, Young-Min ; Choi, Byul-Bora ; Kim, Ji-Young. The effect of the cytotoxicity of sodium lauryl sulfate containing toothpaste on HaCaT and NIH3T3 cells. Journal of Korean Society of Dental Hygiene 2015; 15(4): 719-25
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Inalegwu B, Sodipo OA. Antimicrobial and foam forming activities of extracts and purified saponins of leaves of Tephrosia vogelii. Eur J Exp Biol 2015; 5(5): 49-53.
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Anderson-Foster EN, Adebayo AS, Justiz-Smith N. Physico-chemical properties of Blighia sapida (ackee) oil extract and its potential application as emulsion base. Afr. J. Pharm. Pharmacol. 2012 Jan; 6(3): 200-210.
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Garg HS, Mitra CR. Blighia sapida. I. Constituents of the fresh fruit. Planta Medica. 1967 Feb; 15(1): 74-80.
31. Price KR, Johnson IT, Fenwick GR. The chemistry and biological significance of saponins in foods and feedingstuffs. Crit Rev Food Sci Nutr 1987;26(1):27-135.
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Jyothi, KS, Seshagiri, M. In-Vitro Activity of Saponins of Bauhinia Purpurea, Madhuca Longifolia, Celastrus Paniculatus and Semecarpus Anacardium on Selected Oral Pathogens. J Dent (Tehran). 2012. 9(4): 216–223
13 ARTICLE TYPE: REVIEW TITLE OF THE ARTICLE: THE POTENTIAL OF SAPONIN FROM JAMAICA’S BLIGHIA SAPIDA (ACKEE) AS A SUBSTITUTE FOR SODIUM LAURYL SULPHATE IN TOOTHPASTE RUNNING TITLE: SAPONIN AS A SUBSTITUTE FOR SLS Abstract Discovering novel means of protection from harmful substances in toothpaste is essential due to its mass production, and frequent exposure to its ingredients by consumers. This method of safeguarding through discovery demonstrates toothpaste safety, which is at risk of being stifled by other commercial priorities. Among the ingredients in toothpaste that cause adverse effects is sodium lauryl sulphate (SLS). An understanding of this source and its effects therefore allows for investigating preventative strategies through the use of safer alternatives. Saponin, a naturally occurring chemical in several plant species was discovered to be an alternative compound that may parallel the effects of sodium lauryl sulphate, yet exude less ill effects. This article highlights the benefits of saponin and its presence in a heavily consumed and exported Jamaican fruit in Jamaica (ackee, Blighia sapida). The possibility of extracting saponin from ackee, and its use in the toothpaste industry as an alternative to sodium lauryl sulphate are discussed. Through consideration of this alternative, the potential exists to improve the safety of toothpastes and provide further economic growth for Jamaica.
Key words: saponin, sodium lauryl sulphate, Blighia sapida, aphthous ulcers 33. TITLE OF THE ARTICLE: THE POTENTIAL OF SAPONIN FROM JAMAICA’S BLIGHIA SAPIDA (ACKEE) AS A SUBSTITUTE FOR SODIUM LAURYL SULPHATE IN TOOTHPASTE RUNNING TITLE: SAPONIN AS A SUBSTITUTE FOR SLS
Paul, Tomlin J, MB BS, MPH, DFPHM, FAcadMEd1 Taylor, Tanielle A, BB Med Sci2
14 Rajendra Santosh, Arvind Babu, BDS, MDS3
1Faculty
of Medical Sciences, University of the West Indies, Mona
2Department
of Community Health and Psychiatry, Faculty of Medical Sciences, University
of the West Indies, Mona 3School
of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona
Correspondence: Arvind Babu Rajendra Santosh, School of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica. Email: [email protected]
Acknowledgements: All authors declare that no financial support exists regarding any of the work done within this study. Author contributions: All authors have contributed significantly and are in agreement with the content of the manuscript. Conflict of interest: There are no conflicts of interest to declare. 34.
Published study
Study hypothesis
Study findings
Babatunde et al.
Conducted systematic review to
The study suggested that
20199
evaluate the effects of SLS and
RAS individuals may
SLS-free toothpastes on
benefit from using SLS
individuals with Recurrent
free toothpastes for their
Aphthous stomatitis (RAS).
routine oral hygiene practices. The study identified that SLS-free
15 toothpastes showed significantly reduced number, duration, episodes and pain among individuals with aphthous ulcerations. Tadin A et al.
In vivo evaluation of fluoride and
SLS based dentifrice
201910
sodium lauryl sulphate in
increase the number of
toothpaste on buccal epithelial
nuclear morphological
cells toxicity.
changes in buccal epithelial cells
Salzar et al.
Effectiveness of dentifrices
The results of the study
201611
without and with sodium lauryl
stated equal
sulfate on plaque, gingivitis, and
effectiveness of a
gingival abrasion.
dentifrice, however absence of SLS had a beneficial effect on recurrent aphthous ulcer patients.
Bart et al. 201512
The Evaluation of Sodium Lauryl
Morphological analysis of
Sulphate in Toothpaste on
the oral mucosa
Toxicity on Human Gingiva and
demonstrated severe
Mucosa:
necrosis after exposure to toothpastes consisting
16 of sodium laurly sulphate. The presence of SLS in toothpaste formulation may be responsible for the toxicity observed in in vitro findings. They had concluded that patients with history of aphthous ulcerations should be informed not to use toothpaste containing SLS. Park et al. 201513
Identify the toxic effects of SLS
The study concluded that
over human keratinocyte and
SLS had toxic effects on
fibroblast cells.
human keratinocyte cell and mouse fibroblast cells. The findings also stated SLS induced cytotoxicity is time and dose dependent. The findings of the study provided the data on appropriate SLS concentration in
17 dentifrices to prevent cytotoxic effects. Groeger et al.
Evaluated the toothpaste for
Toothpaste with SLS
201614
barrier function of gingival
dose-dependently
keratinocytes in an established
modulated barrier
invitro model. In addition, they
function of human
measured the permeability of
gingival keratinocyte
tight junctions in vitro, the
invitro without increased
Transepithelial Electrical
cytotoxicity. In addition,
Resistance (TER).
high dilutions showed TER enhancing properties whilst lower dilutions decreased the TER.
Gimba et al.
Investigated the levels of Sodium
The concentrations of
201415
Lauryl Sulphate and Saccharin
SLS among tested
concentrations among locally
toothpastes were in
manufactured and international
range between 1.56×104
brands of toothpastes in Nigeria.
± 10.11 mg/Kg to 2.13×104 ±10.22 mg/Kg. Guideline indicate that SLS in drinking water is 0.5mg/L and relatable to 1.0 mg/L for other
18 purposes. Hence, they recommended that individuals must be cautioned not to swallow much of toothpaste containing SLS.
TABLE 1 Findings of the effectiveness of SLS/SLS-free toothpaste 35. Study
Species
Study findings
Petit B et al.
Blighia
A phytochemical investigation of
201927
unjugata
Blighia unijugata led to the
published period
isolation of eleven hederagenin glycosides. Among these compounds, six are previously undescribed, two are described in their native forms for the first time and three are known whereas firstly isolated from Blighia unijugata. Mazzola EP et al, 201128
Blighia sapida
The structures of three complex saponins from the fruit pods of Blighia sapida have been
19 elucidated and their (1)H and (13)C NMR spectra assigned employing a variety of one- and two-dimensional NMR techniques without degradative chemistry. Penders and
Blighia
A new glycosylated triterpene
Delaude, 199429
welwitschii
has been isolated from the fruit of Blighia welwitschii.
Garg and Mitra, 196730
Blighia sapida
Systematic chemical examination of the fresh fruit of Blighia sapida yielded from its pericarp, a complex 1,4–naphthaquinone, provisionally named, blighinone (I) and stigmasterol–fructoside. Oleanolic acid, in addition to hederagenin, has been found to be a genin constituent of the husk saponin. Glucose, rhamnose, arabinose and xylose have been identified in the sugar moiety of the husk saponin. The genin of the seed kernel saponin has been different from those of the husk saponin.
20
Table 2 Study findings of saponin in Blighia species 36.
Figure 1: SLS molecule showing hydrophobic tail and hydrophilic head.
37.
Figure 2: Photograph showing parts of the ackee fruit: A – seed; B – seed pod; C – aril
38.
S0306-9877(19)31224-1 https://doi.org/10.1016/j.mehy.2020.109555 YMEHY 109555
To appear in:
Medical Hypotheses
Received Date: Revised Date: Accepted Date:
30 October 2019 19 December 2019 5 January 2020
Please cite this article as: T.J. Paul, T.A. Taylor, A.B. Rajendra Santosh, The Potential of Saponin from Jamaica’s Blighia Sapida (Ackee) as a Substitute for Sodium Lauryl Sulphate in Toothpaste, Medical Hypotheses (2020), doi: https://doi.org/10.1016/j.mehy.2020.109555
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2020 Published by Elsevier Ltd.
1
ARTICLE TYPE: REVIEW TITLE OF THE ARTICLE: THE POTENTIAL OF SAPONIN FROM JAMAICA’S BLIGHIA SAPIDA (ACKEE) AS A SUBSTITUTE FOR SODIUM LAURYL SULPHATE IN TOOTHPASTE RUNNING TITLE: SAPONIN AS A SUBSTITUTE FOR SLS
Paul, Tomlin J, MB BS, MPH, DFPHM, FAcadMEd1 Taylor, Tanielle A, BB Med Sci2 Rajendra Santosh, Arvind Babu, BDS, MDS3
1Faculty
of Medical Sciences, University of the West Indies, Mona
2Department
of Community Health and Psychiatry, Faculty of Medical Sciences, University
of the West Indies, Mona 3School
of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona
Correspondence: Arvind Babu Rajendra Santosh, School of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica. Email: [email protected]
Acknowledgements: All authors declare that no financial support exists regarding any of the work done within this study.
Author contributions: All authors have contributed significantly and are in agreement with the content of the manuscript.
Conflict of interest: There are no conflicts of interest to declare.
2 Abstract Discovering novel means of protection from harmful substances in toothpaste is essential due to its mass production, and frequent exposure to its ingredients by consumers. This method of safeguarding through discovery demonstrates toothpaste safety, which is at risk of being stifled by other commercial priorities. Among the ingredients in toothpaste that cause adverse effects is sodium lauryl sulphate (SLS). An understanding of this source and its effects therefore allows for investigating preventative strategies through the use of safer alternatives. Saponin, a naturally occurring chemical in several plant species was discovered to be an alternative compound that may parallel the effects of sodium lauryl sulphate, yet exude less ill effects. This article highlights the benefits of saponin and its presence in a heavily consumed and exported fruit in Jamaica (ackee, Blighia sapida). The possibility of extracting saponin from ackee, and its use in the toothpaste industry as an alternative to sodium lauryl sulphate are discussed. Through consideration of this alternative, the potential exists to improve the safety of toothpastes and consequently improve oral health.
Key words: saponin, sodium lauryl sulphate, Blighia sapida, aphthous ulcers
Introduction Proper oral hygiene involves the use of aptly formulated products that aim to promote and maintain good oral health. Toothpastes (dentifrices) are among those formulations designed to control and prevent periodontal disease and dental caries1. The safety of these products is vital as their recommended daily use provides the opportunity for denaturing effects, bioaccumulation of their components, and other undesirable outcomes. Extensive laboratory tests are conducted on dentifrices to determine their safety and efficacy2. Amidst the tested constituents in toothpastes is Sodium lauryl sulfate (SLS), which has a significant role in enticing consumers, due to its foaming effect - a visual indicator that, to some, suggests the product is effective. Popularly used for its detergent property, SLS however produces side effects that may steer consumers to opt for SLS-free dentifrices. This review proposes the possible substitution of SLS with the Blighia sapida’s (Ackee’s) saponin, which has similar detergent properties, but assumes less adverse effects. Sodium lauryl sulfate
Commented [Office1]: Change was made to address the comment “more an economical/chemistry appeal than medical”
3 Sodium lauryl sulphate (SLS) (C12H25NaO4S) is a synthetic and almost universal excipient in dentifrices, used for its foaming, wetting and dispersing properties. The molecule is ampiphilic with a hydrophilic sulphate head, and a 12-carbon long tail that is hydrophobic (Figure 1). It is anionic and plays a role as a surfactant (or detergent) in exerting a potent cleansing effect through a surface action. SLS lowers the surface tension of liquids by migrating to their surface and accumulating with other SLS molecules, allowing for easier spreading and mixing of the liquid.
Figure 1: SLS molecule showing hydrophobic tail and hydrophilic head It is inexpensive and Generally Regarded as Safe (GRAS), with varying concentration between 1 to 2% w/w in commercial toothpastes3. Its foaming action allows it to be suspended, and its detergency properties enable it to reach otherwise inaccessible areas and cavities in the mouth. Studies have also shown it to have antibacterial and antiplaque effects.3,9 Aphthous ulcerations are the most common oral mucosal pathology across the world. Recently conducted systematic reviews had reported that SLS based dentifrice is likely to influence recurrent aphthous stomatitis. Their results also stated that SLS-free dentifrices showed significant reduction on number, duration, episodes and pain among recurrent aphthous ulceration (Sutton’s disease) patients (Babatunde et al. 2019). In addition, effectiveness of sodium lauryl sulfate in toothpaste on oral epithelial cells was also studied investigating for integrity of those cells and aphthous ulcer formation (Table 1). Despite its widespread use, SLS has been found to have a number of potential side effects that pose a threat to oral health. By eliminating the mucin protective coating and reducing the resistance of the oral mucosa SLS has been shown to have irritant qualities, inducing oral mucosal desquamation4. SLS may also have a negative influence on patients with recurrent aphthous ulcers5. Shim et al6 noted that the duration of ulcers and mean pain scores were significantly decreased when SLS-free dentifrices were used compared to two SLS-containing dentifrices (1.5%). Synthetic detergents like SLS can pass through permeable mucous membranes and bioaccumulate in the body, leading to toxic overload and disease7. Table 1 shows evidence of adverse reactions related to the presence of SLS in toothpaste. Despite its adverse effects, SLS continues to be used widely in dentifrices given its desired foaming ability, acceptable taste and low cost compared to other surfactants. There are very few types of toothpaste on the market that contain surfactant other than SLS8. There
4 is therefore a need for researchers to investigate natural and innovative substances that can fill the role provided by SLS in toothpastes, without the potential for harm. Plants and their extracts were once explored for personal hygiene products but were seen as insufficient means of sustainability. This has however come full circle given consumers’ desire for more natural products that substitute synthetic ones. The plant-derived saponin may prove beneficial in replacing SLS in dentifrices, thus improving their safety.
Table 1: Findings of the effectiveness of SLS/SLS-free toothpaste
Saponin Saponins are naturally occurring surfactants present in several plant species, with a molecular structure that consists of a hydrophilic sugar attached to an aglycone (sapogenin). The aglycone is usually one of two main groups: steroids and triterpenoids. The only major differences between these two groups is triterpenoids tend to be acidic in pH and occur more commonly in dicots, and steroidal saponins tend to be neutral in pH and occur more commonly in monocots16. They however have most properties in common. Hoffman16 further classifies saponins based on the number of sugar chains in their structure: Monodesmosidic (single chain linkage at C-3), Bidesmosidic (two chain linkages at C-3 and either C-26 or C28) and Tridesmosidic (rare type having three sugar chain linkages). Though bidesmosides show less activity than monodesmosides, their surface tension properties remain unchanged. The hydrophilic-hydrophobic arrangement of the molecule makes the compound able to lower surface tension. In fact, the name saponin is derived from the Latin word ’sapo’, which defines a plant that consists of a frothing agent when diluted in aqueous solution17. These agents also cause hemolysis of red blood cells and thus they are highly toxic when injected directly into the blood stream18. However, saponins are relatively harmless when taken orally19. Toxicity is minimised during ingestion by low absorption and by hydrolysis18. Saponins have thus displayed diverse physicochemical and biological properties that have spawned commercial applications in several industries including cosmetics and pharmaceuticals. As natural non-ionic surfactants, they appear as emulsifying, foaming agents and detergents in shower gels, shampoos, lotions, liquid soaps, mouthwashes, and toothpastes19. A unique organic toothpaste characterised by the use of Quillaya and Yucca
Commented [Office2]: change was made to address the comment “more an economical/chemistry appeal than medical”
5 saponins as the cleansing and foaming agent has been developed. The content of saponins may form up to 10% by weight of the toothpaste13. There have been limitations, however, to the commercial use of this ingredient. Firstly, these compounds are not as potent surfactants as synthetic options, and second, the supply from plant sources has been quite limited, which makes these products less available and relatively expensive. To offset these issues, one might suggest that though the foaming properties of saponin might be inferior to a synthetic agent such as SLS, it may still produce substantial effect that is visible and favorable to consumers. Limitations on plant sources may also be adjusted by seeking yield from frequently discarded plant material, and a potential reserve of such material is the Jamaican Ackee.
Physical properties, and uses of Jamaican Ackee Blighia is a genus comprising four species of flowering plants belonging to the soapberry family, Sapindaceae, which is native to tropical Africa particularly in the zone from Guinea east to Kenya. Ackee (Blighia sapida) is the national fruit of Jamaica. In order to be safely consumed, the seeds and internal median pink tissue (Fig. 2) must be removed a process called “yawning”. Neglecting this step is likely to cause acute toxicity labeled as Jamaican vomiting sickness, first noted in 187521. The toxicity associated with the Jamaican ackee and vomiting sickness is however unrelated to saponins, but Hypoglycin A – a toxic material found in the pods and seeds of the fruit.
Figure 2: Photograph showing parts of the ackee fruit: A – seed; B – seed pod; C – aril After yawning, arils are parboiled in water, and then lightly fried in butter or oil. Codfish, onions and tomatoes are often seen accompanying the fruit in Jamaican dishes. The parboiled ackee arils may also be added to salt pork or stew beef with a range of herbs and spices. Furthermore, they are sometimes curried and eaten with rice. Beside its culinary applications, the ackee fruit is also used for making soap, perfumes and medicines. Folk medicinal uses involve as many as 22 diseases having been reportedly healed with ackee22. Repeated small doses of an aqueous seed extract have been used to expel parasites. Ackee pod poultice has been used for skin infections, ringworm and liver spots. The ripe arils, with sugar and cinnamon, have been given as a febrifuge and as a treatment for dysentery23. With
6 regard to its supply, scores of plant material such as the seeds and pods of the Blighia sapida are discarded, accounting for 70% (w/w) of the ackee fruit24. Blighia unijugata another of the four species means ‘with one pair of leaflets’ which is in actual fact. The plant and its fruit though not endemic to Jamaica, has similar properties and uses as Blighia sapida. Blighia welwitschii is found in Sierra Leone to DR Congo and Uganda.
Saponin levels in Jamaican ackee The presence of saponin is a common feature of the Blighia species (Table 2). Saponin is distributed throughout all of the Blighia sapida (ackee) fruit, but special emphasis is placed on the seeds and pods since these are discarded byproducts of the canning industry in Jamaica. Instead of being rejected their potential use for saponin production can be of great importance in improving toothpaste safety. The shiny black seed has been shown to contain saponin, described by Parkinson24 as a physiologically active polyphenolic compound that forms a soapy lather with water. Characterisation of the moderate presence in both ripe and unripe ackee seeds18 supports the further exploration of ackee as a source of surfactant for toothpastes and other industry products. The plant Blighia species was investigated on saponin action (see table 2) however further research is required investigation on the potential use in dentifrices and improving the safety. In addition to the seeds, triterpenoid and steroidal saponins were also obtained from the ackee pods24. Beside the more commonly discarded components, saponin may also be derived from the arils of the ackee fruit – many of which are also discarded after not being able to ripen for canning. Relatively high saponification values were achieved after investigating the foaming ability from oil extracts of the fruit’s arils26.
Table 2: Study findings of saponin in Blighia species
Future contributions of Jamaican ackee towards saponin-based toothpaste safety
7 Toothpastes with saponin derivatives are not yet in any widespread use. US Patent US 6485711 B120 shows the use of saponin derived from the bark of the Quillaja and/or Yucca tree in an organic toothpaste formulation. The safety of saponin in relation to its opponent SLS, is one to consider. Being a natural source, it is biodegradable and less likely to bioaccumulate and cause toxicity and disease. Although limited, there are also no studies that show the occurrence of recurrent aphthous ulcers from the use of these formulations.
Hypothesis on Saponin Formulation in Tooth paste and its relevance to oral hygiene care:
The ampiphilic property of saponins lend for a range of biological activity. Based on the chemical structure of Saponin, the properties include membranolytic effects and antimicrobial effects.31 Jyothi & Sehagiri (2012) explored the molecule’s antimicrobial response to dental plaque-forming microorganisms. They found antibacterial and fungicidal activity displayed by plant extracts of Bauhinia Purpurea, Madhuca Longifolia, Celastrus Paniculatus and Semecarpus Anacardium. Inhibition was seen in Bauhinia Purpurea, and Madhuca Longifolia to a lesser extent, against Streptococcus mutans, Streptococcus mitis, Staphylococcus aureus and Lactobacillus acidophilus, thus proving the saponin components in these plants may effectively control formation of plaque and caries32. The study concluded that saponins “may reduce the incidence of caries, periodontal problems and may help sustain a healthy oral environment”. Conclusion Further research is necessary to determine the fruit’s therapeutic applications, and its potential contribution to the commercialization of SLS-free products such as toothpaste. Confirmation of the benefits of ackee-derived toothpaste can boost its production and contribute to a better valorization of the enormous quantity of seeds and pods that are often discarded annually in Jamaica. There is a clear need to engage in further work to develop the industry to extract and conduct research on the use of these substances in the toothpaste industry. Given the popularity and acceptance of ackee in Jamaica, toothpaste derived with ingredients from the ackee plant is likely to find high acceptability. This innovation will expand the impact of ackee farming for the country and countries with similar sources and capacities.
Commented [Office3]: Change was made to address “more an economical/chemistry appeal than medical”
8
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Shim YJ, Choi JH, Ahn HJ, Kwon JS. Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: a randomized controlled clinical trial. Oral Dis 2012 Oct; 18(7): 655-60.
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Sälzer S, Rosema NA, Martin EC, et al. The effectiveness of dentifrices without and with sodium lauryl sulfate on plaque, gingivitis and gingival abrasion--a randomized clinical trial. Clin Oral Investig. 2016;20(3):443–450. doi:10.1007/s00784-015-1535z
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Bart VV, Bard De W, Els Adriaens, Frans R, Peter Bottenberg. The Evaluation of Sodium Lauryl Sulphate in Toothpaste on Toxicity on Human Gingiva and Mucosa: A 3D in vitro Model. Dentistry 2015;5(9):325. doi:10.4172/2161-1122.1000325
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Park, Sang-Rye ; Kim, Young-Min ; Choi, Byul-Bora ; Kim, Ji-Young. The effect of the cytotoxicity of sodium lauryl sulfate containing toothpaste on HaCaT and NIH3T3 cells. Journal of Korean Society of Dental Hygiene 2015; 15(4): 719-25
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Hoffmann D. Medical Herbalism. Rochester, VA: Healing Arts Press; 2003.
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Inalegwu B, Sodipo OA. Antimicrobial and foam forming activities of extracts and purified saponins of leaves of Tephrosia vogelii. Eur J Exp Biol 2015; 5(5): 49-53.
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Dewick P. Medicinal Natural products: A Biosynthetic Approach. 2nd ed. West Sussex, England: John Wiley & Sons; 2002.
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Deore SL, Khadabadi SS, KP Chittam et al. Properties and Pharmacological Applications of Saponins. Pharmacologyonline 2009;2:61-84. http://pharmacologyonline.silae.it/files/newsletter/2009/vol2/8.Deore.pdf. Accessed August 11, 2016.
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Olmstead MJ. Organic toothpaste containing saponin. US Patent 6485711: 2002.
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Parkinson AA. Phytochemical analysis of ackee (Blighia sapida) pods. PhD thesis. New York, NY: The City University of New York; 2008.
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31. Price KR, Johnson IT, Fenwick GR. The chemistry and biological significance of saponins in foods and feedingstuffs. Crit Rev Food Sci Nutr 1987;26(1):27-135.
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Jyothi, KS, Seshagiri, M. In-Vitro Activity of Saponins of Bauhinia Purpurea, Madhuca Longifolia, Celastrus Paniculatus and Semecarpus Anacardium on Selected Oral Pathogens. J Dent (Tehran). 2012. 9(4): 216–223
13 ARTICLE TYPE: REVIEW TITLE OF THE ARTICLE: THE POTENTIAL OF SAPONIN FROM JAMAICA’S BLIGHIA SAPIDA (ACKEE) AS A SUBSTITUTE FOR SODIUM LAURYL SULPHATE IN TOOTHPASTE RUNNING TITLE: SAPONIN AS A SUBSTITUTE FOR SLS Abstract Discovering novel means of protection from harmful substances in toothpaste is essential due to its mass production, and frequent exposure to its ingredients by consumers. This method of safeguarding through discovery demonstrates toothpaste safety, which is at risk of being stifled by other commercial priorities. Among the ingredients in toothpaste that cause adverse effects is sodium lauryl sulphate (SLS). An understanding of this source and its effects therefore allows for investigating preventative strategies through the use of safer alternatives. Saponin, a naturally occurring chemical in several plant species was discovered to be an alternative compound that may parallel the effects of sodium lauryl sulphate, yet exude less ill effects. This article highlights the benefits of saponin and its presence in a heavily consumed and exported Jamaican fruit in Jamaica (ackee, Blighia sapida). The possibility of extracting saponin from ackee, and its use in the toothpaste industry as an alternative to sodium lauryl sulphate are discussed. Through consideration of this alternative, the potential exists to improve the safety of toothpastes and provide further economic growth for Jamaica.
Key words: saponin, sodium lauryl sulphate, Blighia sapida, aphthous ulcers 33. TITLE OF THE ARTICLE: THE POTENTIAL OF SAPONIN FROM JAMAICA’S BLIGHIA SAPIDA (ACKEE) AS A SUBSTITUTE FOR SODIUM LAURYL SULPHATE IN TOOTHPASTE RUNNING TITLE: SAPONIN AS A SUBSTITUTE FOR SLS
Paul, Tomlin J, MB BS, MPH, DFPHM, FAcadMEd1 Taylor, Tanielle A, BB Med Sci2
14 Rajendra Santosh, Arvind Babu, BDS, MDS3
1Faculty
of Medical Sciences, University of the West Indies, Mona
2Department
of Community Health and Psychiatry, Faculty of Medical Sciences, University
of the West Indies, Mona 3School
of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona
Correspondence: Arvind Babu Rajendra Santosh, School of Dentistry, Faculty of Medical Sciences, University of the West Indies, Mona, Kingston, Jamaica. Email: [email protected]
Acknowledgements: All authors declare that no financial support exists regarding any of the work done within this study. Author contributions: All authors have contributed significantly and are in agreement with the content of the manuscript. Conflict of interest: There are no conflicts of interest to declare. 34.
Published study
Study hypothesis
Study findings
Babatunde et al.
Conducted systematic review to
The study suggested that
20199
evaluate the effects of SLS and
RAS individuals may
SLS-free toothpastes on
benefit from using SLS
individuals with Recurrent
free toothpastes for their
Aphthous stomatitis (RAS).
routine oral hygiene practices. The study identified that SLS-free
15 toothpastes showed significantly reduced number, duration, episodes and pain among individuals with aphthous ulcerations. Tadin A et al.
In vivo evaluation of fluoride and
SLS based dentifrice
201910
sodium lauryl sulphate in
increase the number of
toothpaste on buccal epithelial
nuclear morphological
cells toxicity.
changes in buccal epithelial cells
Salzar et al.
Effectiveness of dentifrices
The results of the study
201611
without and with sodium lauryl
stated equal
sulfate on plaque, gingivitis, and
effectiveness of a
gingival abrasion.
dentifrice, however absence of SLS had a beneficial effect on recurrent aphthous ulcer patients.
Bart et al. 201512
The Evaluation of Sodium Lauryl
Morphological analysis of
Sulphate in Toothpaste on
the oral mucosa
Toxicity on Human Gingiva and
demonstrated severe
Mucosa:
necrosis after exposure to toothpastes consisting
16 of sodium laurly sulphate. The presence of SLS in toothpaste formulation may be responsible for the toxicity observed in in vitro findings. They had concluded that patients with history of aphthous ulcerations should be informed not to use toothpaste containing SLS. Park et al. 201513
Identify the toxic effects of SLS
The study concluded that
over human keratinocyte and
SLS had toxic effects on
fibroblast cells.
human keratinocyte cell and mouse fibroblast cells. The findings also stated SLS induced cytotoxicity is time and dose dependent. The findings of the study provided the data on appropriate SLS concentration in
17 dentifrices to prevent cytotoxic effects. Groeger et al.
Evaluated the toothpaste for
Toothpaste with SLS
201614
barrier function of gingival
dose-dependently
keratinocytes in an established
modulated barrier
invitro model. In addition, they
function of human
measured the permeability of
gingival keratinocyte
tight junctions in vitro, the
invitro without increased
Transepithelial Electrical
cytotoxicity. In addition,
Resistance (TER).
high dilutions showed TER enhancing properties whilst lower dilutions decreased the TER.
Gimba et al.
Investigated the levels of Sodium
The concentrations of
201415
Lauryl Sulphate and Saccharin
SLS among tested
concentrations among locally
toothpastes were in
manufactured and international
range between 1.56×104
brands of toothpastes in Nigeria.
± 10.11 mg/Kg to 2.13×104 ±10.22 mg/Kg. Guideline indicate that SLS in drinking water is 0.5mg/L and relatable to 1.0 mg/L for other
18 purposes. Hence, they recommended that individuals must be cautioned not to swallow much of toothpaste containing SLS.
TABLE 1 Findings of the effectiveness of SLS/SLS-free toothpaste 35. Study
Species
Study findings
Petit B et al.
Blighia
A phytochemical investigation of
201927
unjugata
Blighia unijugata led to the
published period
isolation of eleven hederagenin glycosides. Among these compounds, six are previously undescribed, two are described in their native forms for the first time and three are known whereas firstly isolated from Blighia unijugata. Mazzola EP et al, 201128
Blighia sapida
The structures of three complex saponins from the fruit pods of Blighia sapida have been
19 elucidated and their (1)H and (13)C NMR spectra assigned employing a variety of one- and two-dimensional NMR techniques without degradative chemistry. Penders and
Blighia
A new glycosylated triterpene
Delaude, 199429
welwitschii
has been isolated from the fruit of Blighia welwitschii.
Garg and Mitra, 196730
Blighia sapida
Systematic chemical examination of the fresh fruit of Blighia sapida yielded from its pericarp, a complex 1,4–naphthaquinone, provisionally named, blighinone (I) and stigmasterol–fructoside. Oleanolic acid, in addition to hederagenin, has been found to be a genin constituent of the husk saponin. Glucose, rhamnose, arabinose and xylose have been identified in the sugar moiety of the husk saponin. The genin of the seed kernel saponin has been different from those of the husk saponin.
20
Table 2 Study findings of saponin in Blighia species 36.
Figure 1: SLS molecule showing hydrophobic tail and hydrophilic head.
37.
Figure 2: Photograph showing parts of the ackee fruit: A – seed; B – seed pod; C – aril
38.