Bioactive compounds and benefits of by-products of Amazon babassu oil production: potential for dietary supplement, biomedical and food applications

Abstract

Babassu coconut (Attalea speciosa syn. Orbignya phalerata) contains an oil-rich nut and is primarily found in South America's Amazon region. Future market researchers predict an increase in the babassu oil market from USD 227.7 million in 2022 to USD 347.0 million by 2032, and the yield of babassu oil from babassu-processed waste could reach 90%. Of these, mesocarp flour is an underrated by-product used only for animal feed purposes by local producers. This comprehensive review focuses on advances in knowledge and understanding of phytochemicals from babassu oil by-products considering the mechanisms of action – covering antioxidant, antimicrobial, antiparasitic, anti-inflammatory, antithrombotic, immunomodulatory, and anticancer effects. Babassu coconut fruit contains free fatty acids, (poly)phenols, phytosterols, and triterpenes. Pytochemicals, antiparasitic and antibacterial activities of babassu mesocarp flour were shown, but fungi and viruses can get more attention. Beyond its antioxidant capacity, babassu mesocarp flour showed potential as a dietary food supplement. Aqueous suspensions of mesocarp flour with a higher preference for cancer cells than normal cells and an antithrombotic effect were also identified, probably related to the antioxidant capacity of its secondary metabolites. Mesocarp flour, a starch-rich fraction, is promising for application as biodegradable packaging to improve the oxidative stability of foods. Finally, low-added value fractions can be considered bio-waste/co-products, and their phytochemicals may attract interest for applications in medicine and nutrition. Toxicological concerns, trends, and gaps are discussed for the future of foods and related sciences.

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Introduction

The babassu palm tree belongs to the Arecaceae, Attalea genus,^1,2 and is mainly found in South America's Amazon region. Martius first described the babassu palm in 1826 as Attalea speciosa and Orbignya phalerata in Bolivia in 1844.³ Later, babaçu palms in Brazil were examined by May and colleagues in 1985, described as Orbignya spp.⁴ and more profound knowledge was provided by Anderson and colleagues in 1991.⁵ These are the prominent scientific names found in the literature for the babassu palm. A more recent publication analyzed nomenclature and strongly recommended that Attalea speciosa Mart ex. Spreng be adopted.⁶ However, as Attalea speciosa is the accepted name in plant nomenclature indexes, and Orbignya phalerata was widely adopted by the scientific community, and currently used, in this study, we adopted these two prominent names in the binomial nomenclature system synonymizing A. speciosa under O. phalerata.

Babassu (or “babaçu”) coconut contains an oil-rich nut yielding babassu oil,⁷ a light-yellow vegetable oil that is extracted from babassu palm seeds. Babassu oil is extracted from seed kernels and is often used in food, cosmetics, and skin products.^8–10 Future market insight researchers predicted an increase in the babassu oil market from USD 227.7 million in 2022 to USD 347.0 million by 2032.¹¹ The babassu fruit has four parts, from the outermost to the inner (Fig. 1A): epicarp, mesocarp, endocarp, and almond (seed);¹² among these, the seed nut is the high-added-value fraction, which is used to manufacture the oil, but represents just 7% of the total weight of the fruit.¹³ The epicarp, mesocarp, and endocarp represent 11%, 23%, and 59%, respectively.² All seedless parts are a by-product of oil production or agri-food waste. Thus, in the processing of babassu coconut to yield oil from the seed kernel, the residue volume can make up 90% of the processed babassu fruit and 35% of the residual seed material (bagasse, peel).

Fig. 1 (A) Babassu (A. speciosa syn. O. phalerata) palm tree and babassu coconut fruit parts: almond (seed), endocarp, mesocarp, and epicarp. (B) Its potential functions in health and nutrition: Anti-inflammatory and antioxidant properties found for almond (Seed) oil Antineoplastic activity found for epicarp and mesocarp. Antiprotozoal, antimicrobial, antioxidant, and immunomodulatory/anti-inflammatory properties; potentials in biodegradable films;vaccine adjuvant; and thrombosis and dyslipidemia treatment found for mesocarp.

Beyond its economic value, some previously published studies have shown that it is a product with several uses for local producers, including food, construction, cosmetic, ritual, and domestic,¹⁴ once babassu oil and nut residues have been used for feed, skincare, and fuel purposes. A synopsis previously published based on the local population's knowledge reported the medicinal effects of babassu consumption (as it ameliorates the effects of abdominal pain, constipation, rheumatism, inflammation of the uterus and ovaries, arthritis, and menstrual pains and it is gastroprotective).¹⁵ Since then, researchers’ attention has increasingly focused on new products and technologies based on babassu derivatives for food science and technology, biomedical and pharmaceutical applications, aiming at delivery systems for nutraceutical foods and novel therapy approaches.^16–18 In the last two decades, there have been reports in the literature on the significant health benefits and biological properties of babassu derivatives and nut residues for relevant applications in food additives and packaging and in the medical and pharmaceutical¹⁹ fields: antiinflammation,^17,20,21 immunomodulation,^18,21–24 antioxidant,^13,25–29 antimicrobial,^{2,16,21,25,30–32} anticancer,^23,33,34 antiprotozoal,²² and antithrombotic properties,³⁵ and potential food supplements against dyslipidemia have all been described.³⁶ Furthermore, babassu mesocarp showed potential to treat leishmaniasis²⁴ and other infectious diseases caused by intracellular pathogens.^18,24 Nut residues were proposed for use in materials, food science and technology, fuels, medicine, animal feed, cosmetics, etc. (Fig. 1B).³⁷ For example, babassu mesocarp is a starch-rich fraction that stands out as a bioactive and biodegradable material for active packaging applications to extend the shelf life of foods.^13,25–29 The mesocarp could be a nutritious alternative to wheat flour in baking,³⁸ and an alternative adjuvant for developing novel vaccines and platforms against infectious diseases.^18,24 In materials engineering, babassu oil by-products (endocarp, mesocarp, epicarp, and activated carbon) were predicted to be promising adsorptive materials with potential as adsorptive species for inorganic and organic molecules.³⁹ The epicarp and endocarp have the potential for applications in handicrafts and as organic manure.⁴⁰ Babassu nut shells were also highly feasible for producing bioenergy and charcoal.⁴¹

In the last few years, our research group has been dedicated to understanding the health benefits of nutrients and bioactive compounds found in native species of Brazilian flora, with a particular interest in edible parts, agro-industrial by-products, and food waste.⁴² We have discussed several opportunities, from plant extracts to dietary supplements and novel technologies in the clinical and preclinical investigation stage with high potential for human nutrition and in the prevention/treatment of chronic or infectious diseases.⁴³ Therefore, we recently showed a green protocol to obtain babassu mesocarp flour extract rich in phytochemicals (i.e., phenolic and flavonoids) with significant antioxidant/antimicrobial effects and high feasibility to extend shelf lives and inhibit the oxidation of foods.⁴⁴ Additional investigations were recently published to show the capacity of babassu mesocarp flour as a food additive, specifically as an innovative alternative to reduce sodium in cheese, once it showed an antimicrobial effect and extended the shelf life of a salt-reduced fresh cheese.⁴⁵ In addition, we combined nanobiotechnology concepts with babassu oil to produce photoprotective nanoemulsions containing babassu (O. phalerata Mart.) lipophilic extract as a promising formulation for developing photoprotective products in sunscreen.⁹

Despite the high potential of babassu seed oil (high value-added fraction) as an anti-inflammatory and antioxidant agent for pharmaceutical applications previously discussed, to the best of our knowledge, there has been little focus on its bioactive compounds and their effects on human health and diseases, considering the main mechanisms of action. Moreover, the literature has not focused on its co-products and waste (low value-added fractions) to use nanobiotechnology approaches to improve the therapeutic efficacy of its vegetable oil. This review often associates the mechanism with bioactive compounds such as phytochemicals or their primary metabolites such as essential fatty acids screened in the epicarp, endocarp, mesocarp, and nut oil. Specifically, for each technology, potential applications in medicine and food technology, the babassu derivative and its high-added value compounds, underlying mechanisms, and novel opportunities are further discussed in detail.

Literature search methods

This review article contains results of searches for all biological activities already found for different fractions of babassu coconut (epicarp, mesocarp, endocarp, and nut) evaluated as drug delivery systems and dietary supplements. We searched for articles in the Science Direct, Scopus, PubMed, Web of Science, and Embase databases with keywords and synonyms for babassu (babassu OR babaçu OR “Attalea speciosa” OR “Orbignya phalerata”) AND biological/health benefits (antioxidant OR antimicrobial OR anti-inflammatory). However, we also accepted and included in our review research papers evaluating other biological activities/health benefits associated with different fractions of babassu coconut, considered co-products or waste after babassu oil extraction.

Primary and secondary metabolites in babassu (A. speciosa syn. O. phalerata) coconut

Several authors studied the babassu palm tree's leaves and different fruit parts (i.e., mesocarp, epicarp, nut/seeds). They presented antioxidant, antimicrobial (antibacterial, antifungal, and antiseptic), immunomodulatory, anti-inflammatory, antinociceptive, and wound healing capacity in the preclinical stage of an investigation. The main phytochemicals are often chemically characterized and discussed in the papers overviewed, considering oil seeds and mesocarp flour extracts as sources (Fig. 2). Oil seed covers significant quantities of polyunsaturated fatty acids (PUFA)^46,47 but also minor amounts of (poly)phenols, tri-, diglycerides, terpenes, and phytosterols.⁴⁸Table 1 shows some babassu derivatives rich in phytochemicals reviewed in this work based on the preparation method and there is an overview of the primary class of phytochemicals screened in studies. This table is quite revealing in several ways. First, babassu derivative products studied are rich in PUFA (omega 3, 6, and 9) that are of nutritional value to the human body and growth. An exciting mixture of ω3 and ω6 was identified in palm tree leaf extracts (ω3/ω6 ratio of 1 : 5)³² recommended by regulatory agencies as being crucial for health promotion and to reduce the risk of cardiovascular and other chronic diseases.^49,50 Moreover, researchers identified apigenin as the main flavonoid in the dichloromethane fraction (DF) of babassu leaf ethanolic extract by nuclear magnetic resonance (NMR) and this was confirmed by other chromatographic analysis. This result is interesting because once the authors investigated the babassu leaf DF and apigenin using nociception models (acetic acid-induced abdominal writhing, formalin, and hot plate) they observed strong evidence of the antinociceptive activity of O. speciosa Mart. (babassu) leaves. Moreover, the authors also studied the possible mechanisms involved. They concluded that the in vivo antinociceptive effect of babassu leaves due to apigenin might be associated, in part, with opioid and cholinergic systems.

Fig. 2 Primary metabolites and phytochemicals found in babassu fruit and by-products generated during babassu oil extraction from seed oil.

Table 1 Primary metabolites and phytochemicals found in babassu (A. speciosa syn. O. phalerata) coconut oil and its by-products

Babassu by-product	Extraction method (solvent)	Primary metabolites/phytochemicals			Potential health benefits	Ref.
		Identification/quantification method	Chemical compounds	Results
AlCl3: aluminium chloride; —: not reported; ^1H and ^13C NMR: proton (^1H) and carbon-13 (^13C) nuclear magnetic resonance; GC/MS: gas chromatography/mass spectrometry; HPLC: high-performance liquid chromatography; TLC: thin-layer chromatography; GAE: gallic acid equivalent; CE: catechin equivalent; QE: quercetin equivalent; MW: molecular weight; UAE: ultrasound-assisted extraction.
Leaves	Solvent extraction (ethanol), dichloromethane fraction	TLC	Complex mixtures of terpenes, steroids, and possibly other flavonoids	Isolation and identification of apigenin	Antinociceptive effects	Pinheiro et al. 2012^51
		HPLC	Apigenin	Retention time 11.51 min, 98% purity
		^1H and ^13C NMR	5,7,4-Trihydroxyflavone (apigenin)
Leaves	Soxhlet (ethanol)	GC-MS	Linolenic acid (ω3)	A = 20.65	Antimicrobial potential	Oliveira et al., 2016^32
			Linoleic acid (ω6)	A = 4.62
			Palmitic acid	A = 3.27
			Capric acid	A = 2.26
			Stearic acid	A = 1.93
			Citronellol	A = 7.65
Mesocarp	Solvent extraction (ethanol)	Spectrophotometry (Folin–Ciocalteu)	(Poly)phenols	56% (55% phenolic acids and 1% flavonoids)	Antimicrobial, antiseptic, immunomodulation	Barroqueiro et al., 2016^21
Mesocarp	Maceration (hydro alcoholic), ethyl acetate fraction	Spectrophotometry (Folin–Ciocalteu)	Total (poly)phenols	646.50 mg GAE/g	Antioxidant activity	Romero Hernández et al. 2017^52
		Spectrophotometry (vanillin-HCl)	Proanthocyanidins	453.70 mg CE/g
		HPLC, GS/MS	(−)-Epicatechin oligomers	MW: 290 to 1154 g mol^−1
Mesocarp	Successive maceration (methanol); chromatographic fractionation	GC/MS, ^1H and ^13C NMR	Arachidic acids	38.67%	—	de Farias et al. 2019^48
			11-Octadecenoic acids	21.73%
		GC/MS	Phytosterols	32.0%
			Sesquiterpene (nerolidol)	24.9%
			Diterpene (17-acetoxy-19-kauranal;)	15.2%
	Maceration (methanol); liquid–liquid partition	^1H and ^13C NMR	Phytosterol–ergostane-type steroids
Residual almond material after oil extraction	Soxhlet (methanol)	Qualitative tests–phytochemical screening	Phenols, leucoanthocyanidins, flavones, flavonols, flavononols, flavonones, xanthones, chalcones, aurones, catechins		Antioxidant	Nobre et al., 2018^53
Mesocarp	UAE (ethanol) (varying mesocarp : ethanol ratio w/v from 1 : 4 to 1 : 25)	Spectrophotometry (Folin–Ciocalteu)	Total (poly)phenols	Up to 5124.86 mg GAE per 100 g	Antioxidant and antimicrobial	Lima et al., 2023^44
		Spectrophotometry (AlCl3 complexation)	Total flavonoids	Up to 493.53 mg QE per 100 g

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Babassu mesocarp as a dietary antioxidant for health promotion

‘Oxidative stress’ is a term associated with an imbalance between oxidative products and antioxidant agents,⁵⁴ and this results in a loss of homeostasis, contributing to health emergencies, such as chronic kidney diseases,⁵⁵ atherosclerosis,⁵⁶ and neurodegenerative disorders (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis).⁵⁷ Moreover, food (i.e., meat, fish, milk, cheese) is also susceptible to oxidation due to components such as lipids and proteins. So, oxidation of these compounds could increase the consumption of malefic compounds known as “cholesterol oxidation products” (COPs), which are associated with the emergence of diseases such as those mentioned in the previous sentence. Internal and external factors can induce oxidation, and reactive species from oxygen and nitrogen molecules can cause biochemical reactions. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can interact with macromolecules and produce oxidized molecules. Thus, ingesting antioxidants from food, for example, could reduce oxidative molecules in food and the body.^13,58 Perhaps other fields of antioxidant applications can take advantage of phenolic compounds inside different babassu fruit waste fractions (mesocarp, epicarp, and endocarp) to improve the oxidative stability of foods.¹³ A hydroalcoholic extract of babassu (HEB) showed a total phenolic compound (TPC) content of 414.40 mg GAE per g. However, that extract when subjected to liquid–liquid fractionation using ethyl acetate (EAF) and a hydroalcoholic fraction (HAF) showed higher TPC amounts of 646.50 and 508.90 mg GAE per g, respectively. Nevertheless, the results observed in the antioxidant analyses (FRAP, DPPH, and ABTS) did not change for the different samples. In FRAP, the authors obtained values for the HEB, EAF, and HAF of 11.46, 15.41, and 4.89 (mmol Fe²⁺/g), respectively. For the DPPH assay, HEB, EAF, and HAF showed IC₅₀ values of 4.00, 3.38, and 3.82 (μg mL⁻¹), respectively. And for ABTS analyses, the results were reported as IC₅₀ activity, with values of 2.74, 2.04, and 2.98 (μg mL⁻¹) for HEB, EAF, and HAF, respectively.⁵⁹ Very recently, ultrasound-assisted ethanolic extraction of mesocarp flour by applying different mesocarp : ethanol ratios (1 : 4, 1 : 10, and 1 : 25 w/v) showed high antioxidant capacity with 3327.43, 3167.82, and 4037.56 FRAP (μmol TEAC/100 g), respectively. Moreover, in the DPPH assay, mesocarp : ethanol ratios of 1 : 4 and 1 : 25 w/v showed similar EC₅₀ values (37.23 and 36.78, respectively). This antioxidant capacity is probably associated with high phenolic contents and flavonoids recovered by the greener ultrasound-assisted extraction protocol, as observed by phytochemical screening.⁴⁴

Antimicrobial potential of babassu coconut mesocarp

According to the World Health Organization (WHO), antimicrobial resistance has emerged as a global challenge in health promotion and therapy for infectious diseases.⁶⁰ Thus, several nanobiotechnology scientists are researching novel antimicrobial alternatives. Mesocarp and seed oil from babassu are potential candidates for novel tools to manage infectious diseases caused by Gram-positive pathogens due to their antimicrobial activity. The starch-rich mesocarp fraction has attracted attention from researchers (Table 2) due to polysaccharide chains (linear amylose formed by D-glucose α-1–4 bonds, branched amylopectin formed by α-1–4 bonds, and α-1–6 D-glucose bonds)⁶¹ due to interesting properties like biocompatibility, biodegradability, and non-toxicity.² A pioneering study showed that the aqueous extract of babassu mesocarp from the lyophilized hydroalcoholic (1 : 1) extract showed antimicrobial activity against 7 strains of S. aureus, including 2 strains considered MRSA (methicillin-resistant S. aureus) isolated hospital strain: wound discharge and nasal exudate.⁶² Barroqueiro et al. (2016) demonstrated that the mesocarp ethanol extract showed antimicrobial activity only against Gram-positive bacteria (Enterococcus faecalis, Staphylococcus aureus, and MRSA). The authors chemically screened mesocarp with 56% total (poly)phenols (including 55% phenolic acid and 1% flavonoids).²¹ These compounds were described to have antimicrobial activity through the mechanism of cell wall damage by inhibiting the enzymatic system essential to synthesizing the cell wall.⁶³ Moreover, the authors also reported in vivo effects against lethal sepsis.²¹ Later, a drug delivery system based on babassu mesocarp/carboxymethylcellulose films loaded with tannic acid showed an antimicrobial effect against S. aureus. Thus, the authors suggest that the babassu delivery system helps carry antibiotics to treat MRSA.²⁵ According to Dong et al. (2018), tannic acid acts against the S. aureus peptidoglycan of the cell wall, promoting cell membrane construction.⁶⁴ In contrast, the green synthesis of spherically shaped silver nanoparticles (AgNPs) used babassu starch as a reduction/stabilizer agent to provide anatomizing antimicrobial effects against both S. aureus (Gram-positive) and Escherichia coli (Gram-negative). A greater antimicrobial effect was observed against E. coli.² Recently, Lima et al. (2023) first identified the antimicrobial activity of babassu mesocarp ethanolic extract against other Gram-negative bacteria (Salmonella enteritidis) beyond E. coli using different solid–liquid ratios in the extraction protocol.⁴⁴ The authors reported concentrations of 40, 100, and 250 mg mL⁻¹ and an inhibition halo range from 9.70 to 11.83 mm for E. coli and 10.45 to 12.48 mm for S. enteritidis. This result is probably because of a thinner cell wall, which favors the interaction between AgNPs and the lipopolysaccharides of the bacterial wall.² This interaction promotes cell death by membrane damage, affecting bacterial respiration, leading to pores in the membrane and nutrient release.⁶⁵

Table 2 Babassu fractions and technologies based on babassu derivatives with antimicrobial properties

Babassu part	Babassu derived product	Method	Pathogen	Dosage	Outcome	Ref.
Microbiocidal effect
Almond (seed)	Pure oil	Acridine orange method	Diarrheagenic E. coli (EPEC) (serotype 0111: H- AL-, eae+, eaf+, bfp+)	100 ng mL^−1	Cell viability: 94.3 ± 3.1%	Honório-França et al., 2014^18
					Phagocytosis index: 63.5 ± 9.4%
					Bactericidal index: 45.9 ± 5.4%
Almond (seed)	O/W microemulsion (babassu oil dispersed in aqueous phase)			100 ng mL^−1	Cell viability: 98.0 ± 0.8%
					Phagocytosis index: 69.1 ± 12.3%
					Bactericidal index: 31.8 ± 5.2%

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Babassu part	Babassu product/technology	Method	Pathogen	Dosage	Outcome	Ref.
Antifungal effect
Leaves	Ethanolic extract	Disk diffusion (Kirby–Bauer)	C. albicans;	25, 50, and 100 mg mL^−1	No effect	Oliveira et al., 2016^32
			C. parapsilosis

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Babassu part	Babassu product/technology	Method	Pathogen	Dosage	Outcome (MIC/MBC/IZ)	Ref.
O/W: oil-in-water; MIC: minimum inhibitory concentration; MBC: minimum bactericidal concentration; IZ: inhibition zone; MRSA: methicillin-resistant S. aureus; PLA: polylactic acid polymer AgNP: silver nanoparticles; CMC: carboxymethylcellulose; BHI: brain heart infusion; MCFA: medium-chain fatty acid; ES + SC: prepared using electrospinning (ES) and solvent casting technique (SC).a Antibacterial activity of pristine tannic acid (5 mg mL^−1) was 10.0 ± 1.00 mm and 10.7 ± 1.53 mm against S. aureus and E. coli, respectively.b S. aureus was resistant to standard antibiotics (5 μg ciprofloxacin IZ: ≤32 mm for E. coli and IZ: ≥28 mm for P. aeruginosa; 10 μg gentamicin IZ: ≤18 mm for E. coli and IZ: ≥21 mm for P. aeruginosa).
Antibacterial effect
Mesocarp	Aqueous extract from lyophilized hydroalcoholic extract (1 : 1)	Disk diffusion	S. aureus ATCC 6538 – AM 103	30 mg mL^−1	IZ: 18 mm	Caetano et al. 2002^62
			S. aureus ATCC 9144 – AM 108		IZ: 18 mm
			S. aureus AM 189		IZ: 17 mm
			S. aureus AM 211		IZ: 16 mm
			S. aureus AM 221		IZ: 14 mm
			S. aureus AM 349		IZ: 16 mm
			S. aureus AM 355		IZ: 16 mm
Leaves	Ethanolic extract	Disk diffusion	S. aureus, E. coli, E. faecalis, P. aeruginosa	25, 50, and 100 mg mL^−1	No effect	Oliveira et al., 2016^32
Mesocarp flour	Mesocarp extract powder	Disk diffusion	E. coli	250 mg mL^−1	IZ: 0 mm	Barroqueiro et al., 2016^21
				500 mg mL^−1	IZ: 0 mm
			P. aeruginosa	250 mg mL^−1	IZ: 0 mm
				500 mg mL^−1	IZ: 0 mm
			E. faecalis	250 mg mL^−1	IZ: 12.4 ± 0.2 mm
				500 mg mL^−1	IZ: 14.4 ± 0.4 mm
			S. aureus	250 mg mL^−1	IZ: 15.0 ± 0.3 mm
				500 mg mL^−1	IZ: 18.5 ± 0.9 mm
			MRSA	250 mg mL^−1	IZ: 15.3 ± 0.3 mm
				500 mg mL^−1	IZ: 17.4 ± 0.3 mm
Almond (seeds)	Oil	Microdilution method	S. aureus ATCC 12692	8–512 μg mL^−1	MIC: 512 μg mL^−1	Nobre et al., 2018^53
			S. aureus Sa 358		MIC: 256 μg mL^−1
			P. aeruginosa ATCC 15442		MIC: 512 μg mL^−1
			E. coli ATCC 25922		MIC: 64 μg mL^−1
			E. coli Ec 27		MIC: 32 μg mL^−1
Mesocarp	(+glycerol 5 wt%) films loaded with tannic acid	Disk diffusion	S. aureus	5 mg mL^−1 of tannic acid^a	IZ: 7.0 ± 1.00 mm	de Sousa Leal et al., 2018^25
			E. coli		IZ: 6.0 mm
Mesocarp	(+glycerol 2 wt% + CMC) films loaded with tannic acid		S. aureus	5 mg mL^−1 of tannic acid^a	IZ: 6.0 mm	de Sousa Leal et al., 2018^25
			E. coli		IZ: 6.0 mm
Mesocarp flour	Mesocarp extract powder	Broth dilution (BHI)	E. facealis ATCC 29212	0.9 to 500 mg mL^−1	MIC: 7.8 mg mL^−1	Barroqueiro et al., 2016^21
			S. aureus ATCC 25922		MIC: 31.2 mg mL^−1
			MRSA		MIC: 31.2 mg mL^−1
			E. coli ATCC 25922		No effect
			P. aeruginosa ATCC 27853		No effect
Babassu oil	MCFA hydrolyzed oil (purchased from Sweet Natural Botanicas-USA)	Broth microdilution	C. perfringens UGent 56	0.14–4.5 mg ml^−1	MIC: 0.56 mg ml^−1	Hovorková et al., 2018^30
			C. perfringens CIP 105178		MIC: 0.56 mg ml^−1
			E. cecorum CCM 3659		MIC: 4.5 mg ml^−1
			E. cecorum CCM 4285		MIC: 2.25 mg ml^−1
			L. monocytogenes		MIC: >4.5 mg ml^−1
			S. aureus		MIC: 1.13 mg ml^−1
			S. aureus (MRSA)		MIC: 31.2 mg mL^−1
Almond (seeds)	Oil	Broth dilution (BHI)	S. aureus SA–ATCC 6538	1024 to 1.0 μg mL^−1	MIC: 812.75 μg mL^−1	Machado et al., 2019^31
			K. pneumoniae KP-ATCC 10031		MIC: 406.37 μg mL^−1
			S. aureus SA–10		MIC: ≥1024 μg mL^−1
			B. cereus BC-ATCC 33018		MIC: ≥1024 μg mL^−1
			E. coli EC-ATCC 10536		MIC: ≥1024 μg mL^−1
			P. aeruginosa PA-ATCC 9027		MIC: ≥1024 μg mL^−1
			S. flexneri EC-ATCC 12022		MIC: ≥1024 μg mL^−1
			P. vulgaris PV-ATCC 13315		MIC: ≥1024 μg mL^−1
Mesocarp starch	+AgNP	Microdilution	E. coli ATCC 25922	3.37 to 27 μg Ag mL^−1	MIC: 6.75 μg mL^−1	Araruna et al., 2020^2
					MBC: 6.75 μg mL^−1
			S. aureus ATCC 29213		MIC: 13.5 μg mL^−1
					MBC: >27 μg mL^−1
Commercial Babassu oil	PLA–babassu oil membranes (by ES + SC)	Disk diffusion	E. coli ATCC 23784	1% (v/v) of babassu oil was added to PLA membranes	No effect	Fernandes et al., 2021^16
			S. aureus ATCC 11632^b		No effect
			P. aeruginosa ATCC 9027^b		IZ: 0.40 mm
Mesocarp	Ethanolic extract	Disk diffusion	E. coli ATCC 25922	250 mg mL^−1	IZ: 9.70 ± 1.00 mm	Lima et al., 2023^44
				100 mg mL^−1	IZ: 9.59 ± 0.60 mm
				40 mg mL^−1	IZ: 11.83 ± 1.42 mm
Mesocarp	Ethanolic extract	Disk diffusion	S. enteritidis ATCC 13076	250 mg mL^−1	IZ: 12.48 ± 0.43 mm	Lima et al., 2023^44
				100 mg mL^−1	IZ: 10.45 ± 0.54 mm
				40 mg mL^−1	IZ: 11.56 ± 0.76 mm

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Antimicrobial and wound healing potential of babassu coconut oil

Nut oil is the high-added-value fraction of babassu widely studied in terms of antimicrobial activity (Table 2). Due to its antimicrobial and anti-inflammatory activities, researchers applied it in a wound healing-drug delivery system based on polylactide (PLA) membranes (produced by electrospinning and solvent casting techniques).¹⁶ PLA/babassu oil membranes inhibited Pseudomonas aeruginosa growth¹⁶ but did not inhibit E. coli and S. aureus growth. Babassu nut oil is rich in medium-chain saturated fatty acids, mainly lauric acid.²⁰ Reports in the literature generally recognize that free fatty acids can pass across the cell membrane,⁶⁶ promoting intracellular acidification and growth inhibition.⁶⁷ However, the fatty acid could change the plasma membrane, changing membrane permeability and disrupting the electron transport chain.³⁰ Other associated mechanisms involve the influence of enzyme activity, nutrient take up, and the generation of toxic peroxidation and autoxidation products.⁶⁸

Babassu added as an oily phase O/W microemulsion increased the bactericidal index, phagocyte activity, and consequently, phagocytosis of enteropathogenic (diarrheagenic) E. coli (EPEC). Phagocytes produce free radicals and promote the antimicrobial effect, so the authors highlighted the potential of babassu nut oil as a potential candidate for vaccine adjuvants in immunotherapy in future investigations.¹⁸ Later, Machado et al. (2019) reported that fixed oil extracted from babassu nuts presented antimicrobial activity against both Gram-positive (S. aureus) and Gram-negative (Klebsiella pneumoniae) bacteria; this was mainly attributed to the free fatty acid profile.³¹ Likewise, the hydrolyzed oil containing medium-chain fatty acids also inhibited the activity of several Gram-positive bacteria (i.e., S. aureus, Enterococcus decorum, and Listeria monocytogenes), mainly Clostridium perfringens with an outstanding MIC value of 0.56 mg mL⁻¹.³⁰ The oil comprised fatty acids, primarily lauric acid,³⁰ previously associated with antimicrobial activity.^31,68–70 The detergent property of fatty acids acts against the amphipathic structure of the cell membrane, solubilizing its components (i.e., lipids and proteins), altering the membrane structure and hence, affecting processes that are essential to bacteria like metabolic process, the electron transport chain, and oxidative phosphorylation.³¹ It also damages the membrane through complex nutrient absorption enzyme inactivation, causes toxic peroxidation generation,^68,69 and affects bacterial efflux pumps due to the hydrophobic compounds. On the other hand, the ethanolic extract from leaves of the A. speciosa palm tree prepared by a Soxhlet protocol³² did not present antimicrobial activity against S. aureus, E. faecalis, E. coli, and P. aeruginosa by disk diffusion (Table 2).³² However, gas chromatography (GC/MS) analysis revealed high levels of citronellol – a widely known antimicrobial metabolite – and higher contents of essential fatty acids (omega 3, omega 6, palmitic, and capric acid) of importance in human nutrition, indicating the biotechnology potential of A. speciosa palm trees. The extracts did not show antifungal activity.³² Nobre et al. (2018) observed the antimicrobial activity of the fixed oil of babassu by MIC analysis. The authors reported a MIC range from 32 to 512 μg mL⁻¹ against bacteria such as S. aureus, P. aeruginosa, and E. coli. and the same study observed the association of this fixed oil with an antibiotic from the aminoglycoside class, which showed a significant reduction in MIC values, conferring a synergistic action with the antibiotic.⁵³

Anti-inflammatory and immunomodulatory capacity

Beyond the potential of babassu coconut fractions as food ingredients, as previously discussed in this review, their immunomodulatory capacity makes them a novel substance for the pharmaceutical and chemical industries.

Table 3 shows a brief overview of the anti-inflammatory activity from babassu derivatives (mainly nut oil) reported in the literature, showing their potential in folk medicine to treat skin wounds.²⁰ The bioactive polysaccharide glucan in babassu aqueous extract showed a significant capacity to inhibit the increased vascular permeability induced by acetic acid.⁷¹ An ethanolic extract made with babassu almond was evaluated for benign prostatic hyperplasia (BPH) treatment. However, the chemical composition (rich in oil) was not soluble in culture media (aqueous). So, a B8 viscogel was used to intercalate the extract of Orbignya speciosa kernels, resulting in the development of a nanoparticulate system (NanoOSE), which was a stock solution containing 30 mg mL⁻¹, and this was diluted to obtain a 300 μg mL⁻¹ solution. The cell culture was treated with NanoOSE, which effectively induced morphological changes in the cell structure, diminished cell proliferation, and triggered necrosis/apoptosis in both BPH cells and tissues.⁷² A significant reepithelization effect of babassu mesocarp aqueous extract (BMAE) on the healing process of skin surgical wounds of rats was recognized in the experimental group compared with the control group by microscopic analysis.⁷³ Later, the same research group found a pleurodesis action, revealing BMAE as a potential therapeutic agent for patients with spontaneous pneumothorax or malignant pleural effusion. In vivo, interventions with BMAE were highly irritating to the rats’ pleura and lung parenchyma. Numerous adhesions and inflammation were observed macroscopically without significant changes evidenced microscopically.⁷³ When any injury or stress occurs to the membrane cell, there is a stimulus to repair the problem; hence, inflammation occurs.⁷⁴ The mechanism includes activation via the toll-like receptor (TLR) with inflammatory gene activation⁷⁵ and increased synthesis and secretion of mediators like cytokines, tumor necrosis factor-α (TNF-α), and interleukin.⁷⁶ The fatty acid-rich babassu oil contains natural phenols like phytosterols and tocopherols (Table 1). Natural (poly)phenols have been found to interfere with protein kinase C (PKC) signaling pathways, which are essential mediators of immune cells.⁷⁷ Therefore, in an in vivo model of induced inflammatory reaction, Barbosa et al. (2012) reported higher anti-inflammatory activity after oral administration of unrefined babassu oil (0.18 mL per dose) compared to mineral oil in the control group.⁷⁸

Table 3 In vivo anti-inflammatory effects of technologies based on babassu mesocarp or nut oil

Babassu derivative	Product/technology used	In vivo model	Inflammation model	Administration mode	Dosage	Outcome	Ref.
TNF-α: tumor necrosis factor alpha; IL-6: interleukin 6; IL-8: interleukin 8; O/W: oil-in-water; PMA: phorbol 12-myristate 13-acetate; AA: arachidonic acid; —: not reported/not identified.
Mesocarp	Aqueous extract	Male BALB/c mice	Acetic acid-induced vascular permeability	Orally	100 mg kg^−1	Inhibited the increase in vascular permeability	Silva and Parente 2001^71
Mesocarp flour	Aqueous extract	Adult Wistar rats	Skin surgical wounds – punch	Topical anesthetics	25 mg mL^−1	Reepithelization effect on the healing process	Amorim et al. 2006^73
Mesocarp flour	Aqueous extract	Male Wistar rats	Pleurodesis model	Intrapleural injection	25 mg mL^−1 for 50 mg kg^−1	Irritation to the pleura and pulmonary parenchyma without microscopic pleura adhesion	Amorim et al. 2006^73
Mesocarp flour	Mesocarp extract	Swiss mice	Sepsis induction	Subcutaneous	125 mg kg^−1	Inhibition: TNF-α, IL-6, and IL-8 production	Barroqueiro et al., 2016^21
					250 mg kg^−1	Inhibition: peritoneal cell migration; TNF-α and IL-6 production
Seed oil	100% (pure oil)	Male Swiss and BALB/c mice	PMA-induced ear edema	Topical	10 μL per ear	58% (p < 0.001) edema inhibition	Reis et al., 2017^17
Seed oil	100% (pure oil)		AA-induced ear edema	Topical	10 μL per ear	78.5% (p < 0.001) edema inhibition
Seed oil	100% (pure oil)	Male Swiss and BALB/c mice	PMA-induced ear edema	Oral	100 mg kg^−1	23.5% (p < 0.001) edema inhibition	Reis et al., 2017^17
					300 mg kg^−1	39.7% (p < 0.001) edema inhibition
					1000 mg kg^−1	51.9% (p < 0.001) edema inhibition
Seed oil	12.2% oil diluted in acetone	Male Swiss and BALB/c mice	PMA-induced ear edema	Topical	—	17.5% (not significant) edema inhibition	Reis et al., 2017^17
Seed oil	12.2% oil in O/W microemulsion		PMA-induced ear edema	Topical	—	66.2% (p < 0.001) edema inhibition
Seed oil	Unrefined oil	Male golden hamsters	Ischemia/reperfusion-induced (hamster cheek pouch)	Oral	0.02, 0.06, and 0.08 mL per dose	Lower: ischemia-induced micro-vascular leaks during reperfusion, histamine-induced microvascular permeability, leucocyte adhesion, and cytokine levels.	Barbosa et al., 2012^78
Seed oil	Fixed oil	Male Swiss mice	Ear edema induced by multiple applications of croton oil	Topical	10 μL per ear	Reduced ear thickness, epidermal hyperplasia, and myeloperoxidase activity	Santos et al., 2020^20

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Likewise, in vivo interventions with babassu mesocarp extract (125 and 250 mg kg⁻¹) showed anti-inflammatory activity in mice with induced sepsis (the inflammatory process was triggered due to puncture injuries on the cecum of mice) due to no pro-inflammatory cytokine production (e.g. TNF-α, interleukin 1 (IL-1) and 6 (IL-6)).²¹ Subcutaneous administration of 125 mg kg⁻¹ mesocarp extract provided 40% survival after 24 hours, maintaining the survival rate on the 10th day. In contrast, 250 mg kg⁻¹ administration showed 60% survival after 24 hours, decreasing to 40% after 36 hours, and maintaining the survival rate on the 10th day.²¹ We provided a schematic representation of the in vivo immunomodulatory effect after subcutaneous administration of babassu mesocarp extract, providing a new way to inhibit the inflammatory chain (Fig. 3). TNF-α is the first pro-inflammatory cytokine, promoting increased leukocyte recruitment to the inflammatory regions. Monocytes produce IL-6 and endothelial cells, fibroblasts, and other cells like TNF-α are also responsible for inducing inflammatory activity. Phorbol 12-myristate 13-acetate (PMA) can induce the activation of an inflammatory mechanism through PKC, activation of nuclear factor kappa B (NF-κβ), and the production of TNF-α, cyclooxygenase-2 (COX2), and prostaglandin E2 (PGE2). Furthermore, mast cell infiltration with mediator liberation increases permeability and neutrophil influx.^79,80 Topical administration of pure lauric acid (10 μL per ear) inhibited PMA-induced ear edema by 90.3% (p < 0.001), while dexamethasone inhibited ear edema by 79.7% (p < 0.001).¹⁷ Interestingly, pure babassu oil (10 μL per ear) inhibited ear edema by 54.1% (p < 0.001) and demonstrated an anti-inflammatory ability,¹⁷ probably associated with the presence of lauric acid as its main component (data from Table 3 can be compared with data in Table 1, which shows the chemical profiles). Such a compound can interfere with arachidonic acid metabolism, inhibiting phospholipase A2 (PLA2), COX2, and lipoxygenase (LOX), and hence, PMA-induced inflammation. Interestingly, the authors also argued that babassu oil could have a possible barrier effect on ear surfaces. Thus, babassu oil was also systematically (100–1000 mg kg⁻¹ oral dosages) tested against PMA-induced ear edema and showed up to 51.9% (p < 0.001) edema inhibition at a dose of 1000 mg kg⁻¹; the nonsteroidal anti-inflammatory drug indomethacin (10 mg kg⁻¹) inhibited ear edema by 62.0% (p < 0.001). Furthermore, the topical anti-inflammatory potential was also confirmed against another inflammation model: babassu oil (10 μL per ear) reduced arachidonic acid-induced ear edema by 78.5% (p < 0.001). In contrast, the non-selective COX-1/2 inhibitor indomethacin (0.5 mg per ear) reduced ear edema by 61.5% (p < 0.001).¹⁷

Fig. 3 Immunomodulatory, anti-inflammatory mechanism of babassu mesocarp ethanolic extract on a treated group and inflammatory process in an untreated group through an in vivo assay.

Later, the potential of using pure babassu oil in folk medicine for skin wound healing was suggested by the in vivo anti-inflammatory effect of nut oil in a chronic ear edema model, as proved by reduced ear thickness, epidermal hyperplasia, and myeloperoxidase activity after the topical administration of 10 μL babassu oil per ear.²⁰

Healing potential of babassu mesocarp

The healing process is a multifaceted biological event encompassing inflammation, chemotaxis, cellular proliferation, differentiation, and remodeling.⁸¹ An aqueous extract made with 25 mg mL⁻¹ babassu mesocarp was evaluated. The authors observed that mice with colon anastomosis treated with 50 mg per kg per weight doses could be healed.⁸² In another study, an aqueous extract of mesocarp at the same concentration (25 mg mL⁻¹) applied intra-peritoneally via a single dose of 50 mg kg⁻¹ was observed to target stomach healing by aiding the bringing together of the edges of the gastrorrhaphy in animals that had been sacrificed on the 7^th day of the postoperative period.⁸³ At the same concentration (25 mg mL⁻¹), the aqueous extract of babassu mesocarp was applied inside the peritoneal cavity of the rats in a single dose of 50 mg kg⁻¹ to observe the healing process of linea alba. The authors observed a potential healing effect based on the animals treated with the extract, which had better results for the tensiometric parameter and more excellent resistance.⁸⁴ Under the same conditions, an aqueous extract of babassu mesocarp induced better healing of surgical injuries of the bladder.⁸⁵ An apparent circular incision of 2 cm in diameter with a metallic puncture was made in mice. It was possible to observe the healing effect of the aqueous extract (similar concentration and dose to those previously described), and it was possible to observe that the aqueous extract had an essential effect on healing at the microscopic level, on mononuclear variables and collagen fibers.⁸⁶ The healing of colonic anastomosis in rats was evaluated by administration aqueous mesocarp extract at 50 mg per kg per body weight. The results showed superior healing of the cecum when compared to the control group.⁸⁷ With the same objective, an aqueous extract made with babassu powder at a concentration of 25 mg mL⁻¹in vivo was administered orally by daily gavage at a dose of 50 mg kg⁻¹. This study agrees with other works already observed in the literature, reporting the effectiveness of babassu extract in the surgical healing process, with excellent parameters observed in the healing process for cecorrhaphy in rats.⁸¹ An effect was observed in peptic ulcer treatment: rats were treated orally with an aqueous extract made with 2 g kg⁻¹ babassu mesocarp, and results demonstrated the potential therapeutic effect in the treatment of gastric ulcer, with behavior like that of the control group treated with omeprazole.⁸⁸

Babassu almond oil in emulsions

Nanobiotechnology concepts using babassu oil in a microemulsion system for topical delivery were related to striking results of topical and systemic anti-inflammatory effects against ear edema induced by PMA. Babassu oil showed short-term stability in oil-in-water (O/W) nanoemulsions by emulsification phase inversion and was considered a promising dispersive system for pharmaceutical and cosmetic applications.⁸⁹ Later, Reis et al. (2017) evaluated the in vivo anti-inflammatory activity of a babassu nanocarrier based on an oil-in-water (O/W) microemulsion using babassu as an oily phase. A classical microemulsion system formulation (9% water as the aqueous phase, 12.2% babassu as the oil phase, and 48.8% surfactant system) inhibited ear edema by 66.2% (p < 0.001), showing an enhanced activity promoted by the microemulsification of babassu oil, since babassu oil at 12.2% (final concentration in the O/W microemulsion) did not have a significant effect (please see Table 3). Microemulsification of babassu oil seems to enhance the skin permeation of active anti-inflammatory compounds (e.g., lauric acid) found in the oil, reaching the same percentage of edema inhibition as pure babassu oil with a lower oil concentration, producing a remarkable outcome.

Babassu mesocarp in drug delivery systems towards parasitic and infectious diseases

Drug-releasing systems have attracted significant attention from the pharmaceutical industry for drug administration due to several therapeutic benefits such as efficiency, principal selectivity, long-term efficacy, and minimized side effects.⁹⁰ Thus, drug release from natural products and biocompatible biopolymers has been studied, targeting novel alternatives to treat neglected infectious diseases of high mortality, such as leishmaniasis.^22,25 Leishmaniasis is an endemic disease with a substantial impact on human health and high prevalence in 90 countries and tropical areas.⁹¹ What is quite interesting is that standard anti-leishmanial drugs present limitations such as severe toxicity and drug resistance.⁹² As a drug alternative treatment against leishmaniasis, da Silva et al. (2018) showed that an aqueous extract of mesocarp (BMAE) encapsulated by poly(lactic-co-glycolic acid) (PLGA) was effective against promastigote forms of Leishmania amazonensis.²² At the same time, other research groups reported the starch-rich mesocarp of babassu (Orbignya sp.) and carboxymethylcellulose (CMC) films as a tannic acid releasing matrix with in vitro cytotoxicity on sarcoma-180 (91.86 ± 9.97%) and promastigote forms of Leishmania major (100%).²⁵ Moreover, the babassu mesocarp–CMC films showed controlled drug release (release of 71.01% of TA from the matrix after 24 h) and good antioxidant activity by DPPH (∼79–82%) and ABTS (82–89%) assays.²²

Other potential health benefits of babassu low-added-value fractions

Table 4 displays other potential health benefits of babassu derivatives due to their antiprotozoal, anticancer, antithrombotic, and anti-dyslipidemia effects reported in the literature in the preclinical stage of an investigation.

Table 4 Preclinical studies reporting biological, pharmaceutical, and health effects of babassu (A. speciosa syn. O. phalerata) fractions as extracts and drug delivery systems – antithrombotic, anticancer, and antiprotozoal effects

Babassu fraction	Drug delivery system	Organism	Dosage	Outcome	Ref.
Antiprotozoal effects
Mesocarp	MMP-loaded PLGA microparticles	Promastigote forms of Leishmania amazonensis	300 μL, 10 mg mL^−1	IC50 = 12 pg mL^−1 (P < 0.05)	Silva et al., 2018^22
Mesocarp	Babassu mesocarp–CMC films loaded with TA	Promastigote forms of Leishmania major	6.25 to 800 800 μg mL^−1; SI: 0.94	Release of 71.01% of TA of the matrix after 24 h; Antioxidant activity; IC50 = 100%	de Sousa Leal et al., 2018^25

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Babassu fraction	Extract	Model	Intervention/dose	Outcome	Ref.
In vivo anticancer potential
Epicarp/mesocarp	Crude ethanol extract (by maceration)	Against leukaemic cell lines (HL-60, K562, K562-Leucena 1);	Dose-dependent	Antineoplastic potential: higher cytotoxicity against tumoral than non-tumoral cells; stimulation of PFK activity observed on HL-60 cells	Rennó et al., 2008^34
		MCF-7 tumor cells, mouse fibroblast cell line 3T3-L1, and fresh human lymphocytes
Mesocarp flour	Aqueous extract	In vitro and in vivo assay: C3H/HePas mice peritoneal cellular	10 and 20 mg kg^−1	Macrophage activation (in vitro and in vivo), cytotoxic activity, and induction of inflammatory mediators	Nascimento et al., 2006^33
Mesocarp flour	Aqueous extract	In vivo: male Swiss mice with inoculation of MCF-7 tumor cells	100 μL of aqueous extract at 20 mg mL^−1	Induction of antitumor immune response; increased marker expression for granulocytes (Ly6G-LY6C), increased antigen presenting cells	Almeida et al. 2014^23

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Babassu fraction	Extract	Model	Intervention	Outcome	Ref.
MMP: aqueous extract of babassu mesocarp; PLGA: poly(lactic-co-glycolic acid); IC50: in vitro – 50% inhibitory concentration; PFK: 6-phosphofructokinase; TA: tannic acid as a standard drug; CMC: carboxymethylcellulose; SI: selectivity index; TNF-α: tumor necrosis factor-α; MFC-7: human breast cancer cell line.
Antithrombotic effect
Mesocarp flour	Aqueous extract	In vivo assay – C57Bl/6 mice	500 mg per kg per day	Slowed coagulation process; NO production; thrombosis inhibition	Azevedo et al., 2007^35
Babassu as a food supplement – treatment strategy for dyslipidemia
Mesocarp flour	Aqueous extract	In vivo – Swiss mice	Oral supplementation/5 mg kg−1	Reduction in cholesterol levels	Soares et al., 2021^93
Mesocarp flour	Aqueous extract	In vivo – Swiss mice	Oral supplementation + resistance training/5 mg kg^−1	Reduction in TNF-α	Soares et al., 2021^93
				Body weight
				Retroperitoneal and interstitial fat deposits
				Triglyceride levels
				Total number of lymphocytes
Antinociceptive effects
Palm tree leaves	Ethanolic extract	In vivo – Swiss mice (hot plate test)	Oral/10 mg kg^−1	48.7% writhing inhibition	Pinheiro et al. 2012^94
	Dichloromethane fraction			66.8% writhing inhibition

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Babassu mesocarp as a dietary supplement against dyslipidemia

After the COVID-19 pandemic affected the whole world, authorities have warned of other problems that have arisen, like obesity.⁹⁵ The WHO highlights that the “obesity epidemic” is increasing in Europe, with more than 60% overweight or obese adults and 7.9% overweight or obese children under five.⁹⁶ High body fat levels are an essential risk factor for cardiovascular, endocrine, and metabolic disorders like type 2 diabetes.⁹⁷ Recently, babassu mesocarp was proposed as a food supplement during training resistance and as a medicine to treat dyslipidemia.⁹³ An in vivo assay showed that babassu mesocarp aqueous extract had an immunomodulatory effect (increasing helper T lymphocyte count TCD4+ and CD69+) on lymphocyte, macrophage, and cytokine production; in addition, it had the capacity to control cholesterol and triglyceride levels, reducing TNF-α, body weight, retroperitoneal, and interstitial fat deposits.⁹³

Anticancer potential of babassu by-products and waste

Developing novel chemotherapy strategies with minor side effects for cancer treatment is one of the significant global challenges concerning health. In this review, we also identified preclinical interventions with extracts of babassu by-products (mesocarp) and wastes (epicarp) with antitumor effects showing a higher propensity for tumoral cells than normal cells.³⁴ The aqueous extract from the babassu mesocarp showed anti-tumoral activity due to increased macrophage activity. This can be caused by the ability to induce the production of inflammatory metabolites that promote increased cellular influx to the peritoneal cavity, MHC class II expression, and the spreading ability, and result in the production of NO, TNF, and H₂O₂.³³ The ethanolic extract of babassu epicarp and mesocarp showed a dose-dependent antineoplastic action against leukemic cell lines (HL-60, K562, K562-Leucena 1), human breast cancer cell line MCF-7, mouse fibroblast cell line 3T3-L1 and fresh human lymphocytes.³⁴ Cytotoxicity activity occurs through inhibiting a key glycolytic enzyme, 6-phosphofructo1-kinase (PFK). At the same time, the modification of cells, like a reduction in the size of cells, formation of rounded cells, and nuclear condensation are morphological singns of apoptosis.^98,99

The potential of BAE as an immunological adjuvant was also confirmed by reports of its antitumor immunity. Animals stimulated with MCF-7 tumor cells pretreated with BAE (97% cell viability) showed increased helper and cytotoxic T cells. It also showed an increase in phagocytic cells with PAMPs (pathogen-associated molecular patterns) on the cell surface, and some PAMPs can recognize carbohydrates such as mannose. This result may explain why animals treated with babassu extract showed better granulocytic cell activity, as the composition of the extract, rich in carbohydrates, induced this response, suggesting a pro-inflammatory effect.²³

Babassu mesocarp to avoid thrombosis events

Thrombosis, a venous disease that occurs when blood clots block blood vessels, is a serious but preventable disease that can cause disability and death.¹⁰⁰ An in vivo antithrombotic effect of babassu (O. phalerata) mesocarp flour suspended in 1 L of distilled water was reported by Azevedo et al. (2007); this suggests it is a prophylactic agent to avoid thrombosis events. An antithrombotic effect with a slow coagulation process was observed as a positive effect on coagulation factor levels, nitric oxide (NO) production by macrophages, and 88.9% reduction in the necrosis of the tail of carrageenin-induced thrombosis in mice orally treated (500 mg per kg per day) with babassu mesocarp.³⁵ NO was reported to be an essential agent against the thrombotic effect,^33,101 associated with its action on blood vessel relaxation, platelet adhesion, endothelial regeneration, and inhibition of leukocyte chemotaxis.³⁵ The antithrombotic effect of babassu mesocarp might be related to the antioxidant capacity of its bioactive compounds and nutrients. Some studies reported the antithrombosis role of food nutrition and dietary supplements¹⁰²via inhibition of platelet activation mechanisms¹⁰³ or by its relationship between oxidative stress and thrombosis, once several nutrients and foods bioactive compounds are antioxidants.^103,104

Babassu mesocarp as potential active food packaging material

It is important to comment on the viable usability of raw mesocarp flour instead of starch isolated from the mesocarp to make bioactive films. Although higher antioxidant and total phenolic compound (TPC) contents were observed using the raw babassu mesocarp flour¹⁰⁵ and its isolated starch to produce films, the packaging's mechanical and functional properties (resistance, WVP, transparency, water resistance, and hydrophobicity) were compromised due to the higher protein and fiber contents.¹³ However, suppose the application interest is for use as a food ingredient. In that case, direct use of the agro-industrial residue, babassu mesocarp flour, offers the best nutritional value and bioactive properties.

Antioxidant biodegradable films

Due to their prominent flexibility, softness, strength, transparency, water and moisture resistance, and barrier properties, conventional synthetic plastic films are widely used in everyday life, supermarkets, mulch films, and the packaging industries.¹⁰⁶ Currently, the use of synthetic plastics has triggered a worldwide alert, as accelerated use and incorrect disposal promote negative impacts on the environment and animal and human life.^106–108 Thus, the scientific community is looking for greener alternatives, such as biodegradable plastics.^109–111 Babassu mesocarp is a by-product of babassu oil extraction, mainly composed of cellulose and polysaccharides, and thus, a potential green and natural raw material alternative for the production of food-derived biopolymers and biodegradable plastics. The babassu mesocarp is a starch-rich fraction (∼71%) that can be combined with a plasticizer agent to overcome the brittle nature of starch to produce biodegradable films.¹¹² Furthermore, babassu mesocarp's phenolic compounds and antioxidant properties²⁹ make it an exciting alternative to synthetic plastics for active plastic coating/packaging applications that come into direct contact with food and attractive for food packaging and biomedical applications (Fig. 4).

Fig. 4 Starch isolated from babassu mesocarp with antioxidant properties for use as biodegradable films in active packaging production: a potential alternative to improve the oxidative stability of foods.

When an aqueous extract of O. phalerata mesocarp was made by suspending mesocarp powder in demineralized water (at a concentration of 20%), the authors did not observe a strong in vitro antioxidant effect by thiobarbituric acid-reactive substances (TBARS), nitric oxide (NO), and hydroxyl radical scavenging assays.²⁷ The authors observed a positive reaction for (poly)phenols in phytochemical screening, suggesting that the compounds extracted may interact with OH radicals, reactive oxygen species (ROS), instead of with NO, a reactive nitrogen species.²⁷

On the other hand, starch was successfully isolated from babassu mesocarp with swelling power and antioxidant activity using steeping in water (WS), in alkaline (KS),²⁹ and an acid (AS) medium.¹³ However, although alkaline steeping provided purer starch (99%) in a higher yield (85%), a more significant loss of total phenolic compounds (TPC) (8.2 mg of GAE per 100 g) was caused compared to water steeping (63.7 mg of GAE per 100 g).^13,29 This behavior can be understood by the possibility of an alkaline medium generating phenoxides from phenolic compounds related to chromophores that can be oxidized by air, producing a darker material, as confirmed by the authors during color evaluation.²⁹ Thus, the authors verified that the acid medium isolated starch with higher antioxidant activity (70%) due to the considerable content of TPC.¹³ Nonetheless, films prepared with babassu mesocarp starch by steeping in water showed high potential as packaging materials for oxidation-sensitive foods. The WS method yielded purer starch films with a significant content of amylose and, hence, higher mechanical and functional properties when the authors plasticized it with glycerol (i.e., stronger, more rigid, less water-vapor permeable (WVP), more crystalline, with a denser and ordered homogeneous structure).¹³ Later, this same group evaluated the effect of varied plasticizer types to obtain films based on babassu starch isolated by WS, AS, and KS methods with lower hydrophilicity and good mechanical properties. Each extraction method produces starch with a particular chemical structure and composition and hence affects the plasticizer–starch interaction in the film.²⁸ The authors showed that sorbitol was the most suitable for AS and KS starch films. In contrast, glycerol was the most suitable plasticizer for WS starch, producing films with mechanical resistance.²⁸

Safety and toxicological concerns

This review has discussed how researchers focus on the bioactive compounds of babassu and its by-products due to their valuable applications in the health care, cosmetics for skin care, and food sectors. Considering the increasing attention being paid to research on babassu waste using nanotechnology concepts (i.e., nanoemulsions, nanocomposites, and hybrids with organic and inorganic materials), the analysis of chemical migration (i.e., nanoparticles, plasticizers, phytochemicals) from food packaging is needed.

Moreover, tannins, saponins, and flavonoids are the most common phytochemicals in babassu mesocarp, and this review shows their valuable therapeutic activities and potential for food packaging applications. Although other plant extracts of these compounds have been reported to have low toxicity, evaluating acute toxicity by oral administration of single/multiple doses of babassu by-product extracts is fundamental to advancing toxicological research and risk assessment. It is crucial to mention other materials science strategies that could also contribute to advancing the safety of babassu mesocarp and its phytochemicals in drug delivery or novel chemotherapy approaches to treat cancer. Recently, films based on babassu mesocarp were reported as strong candidates for drug release once they served as a release matrix for tannic acid with in vitro toxicity against leishmania parasites and tumor cell strains without high toxicity on normal cells.³⁴ The in vivo low toxicity of babassu mesocarp extract was proved by oral administration of a single high dose (up to 5000 mg kg⁻¹) of babassu mesocarp extract to mice once no alterations were identified at the tissue level or body and organ weight (i.e., glucose, triacyl glyceride, cholesterol, and creatinine).¹¹³ However, some changes in biochemistry levels (i.e., increase in alkaline phosphatase and reduction in urea) with a long-lasting effect were observed, which the authors considered to be an accidental finding and unrelated to treatment.¹¹³ In 2017, researchers revisiting Amazonian plants commented that babassu seed oil for dermatologic and cosmetic applications was increasing rapidly in applications such as skin rehydration and soothing; anti-inflammatory, antiaging, and antiparasitic effects; hair care; burn and wound healing; and the amelioration of rosacea and psoriasis. However, such usage did not consider possible harmful effects and is limited in empirical knowledge.⁸

Conclusions and outlook

The nut of babassu coconut (the high added-value product of babassu coconut) presents benefits attributed to its bioactive compounds, which may be influenced by how the raw material is obtained, extraction methods, and processing. As it is a natural product, the processes for obtaining beneficial metabolites must be detailed and standardized for reproducible results. Considering babassu by-products, their low-added fractions are rich in bioactive compounds, such as primary (essential fatty acids, polysaccharides) and secondary metabolites (i.e., (poly)phenols) with antioxidant capacity, antiparasitic properties, and microbiocidal and antimicrobial activity. Thus, recent preclinical investigations showed the potential of using babassu by-products and waste in cancer therapy, for their immunomodulation and anti-inflammatory properties, as drug delivery agents to avoid thrombotic events, to treat hypercholesterolemia, dyslipidemia, and infectious and parasitic diseases, as biodegradable materials in food packaging, and as food additive substituents (i.e., salt replacer in cheese) with antimicrobial effects.

Babassu mesocarp starch could be an alternative for active and biodegradable plastic packaging materials. Thus, bioplastic made with babassu appears to be an alternative to protect foods while improving their oxidation stability.

Other studies showed the potential of babassu mesocarp flour as a dietary supplement for dyslipidemia and trends in other metabolic disorders. Likewise, the high capacity of babassu oil to inhibit pro-inflammatory cytokines was improved using concepts of nanobiotechnology (i.e., micro/nano-emulsification), looking to boost the anti-inflammatory behavior.

Technology based on babassu derivatives (i.e., mesocarp and seed oil) also appears in this review as a potential tool to improve the human immune system through its application as a vaccine adjuvant. Moreover, the macrophage production ability of babassu mesocarp was also discussed and related to its in vivo anti-tumoral activity. We identified gaps and future opportunities for mesocarp and other low-added fractions of babassu coconut (i.e., endocarp and epicarp) that can be conveniently studied, proposing their application as novel substances for the pharmaceutical and chemical industry. For example, the epicarp and endocarp were discussed as (i) fiber-reinforcement filler for composite materials, (ii), valuable raw materials for lignocellulosic-feedstock biorefinery, and (iii) an immunomodulatory biomaterial for immunomodulation strategies in tissue repair. On the other hand, nanoemulsification of babassu components can be conveniently evaluated in delivery systems for food science and technology, like food additives and functional foods.

Finally, as demonstrated by in vivo investigations, babassu showed an antithrombotic effect, which might be related to the antioxidant capacity of its bioactive compounds and nutrients. However, the possible consumption of babassu oil or its by-products within a balanced diet may be considered before hypothesizing possible health effects. Until now, advances have been shown only in the preclinical stage of investigations since papers considered in this review related to health effects obtained results from in vitro or animal models, and no human studies have been reported so far.

Author contributions

Rayssa Cruz Lima: formal analysis, investigation, writing – original manuscript preparation. Anna Paula Azevedo de Carvalho: conceptualization, methodology, supervision, project administration, writing – original manuscript preparation, funding acquisition. Antonio Eugenio Castro Cardoso de Almeida: supervision, writing – reviewing and editing. Carlos Adam Conte-Junior: supervision, writing – reviewing and editing. All authors read and approved the final version of the manuscript.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The authors thank the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) [grant numbers E-26/201.402/2023, E-26/210.385/2022, E-26/200.621/2022, E-26/200.891/2021]; the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant numbers 313119/2020-1, 152936/2022-0]; and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [grant number 88887.696241/2022-00] for financial support.

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