Table 5 Baseline characteristics, intervention, methods, and main results of studies

Barroqueiro et al. [46]

E. coli (ATCC 25922), P. aeruginosa (ATCC 27853), E. faecalis (ATCC 29212), S. aureus (ATCC 25923), S. aureus (MRSA)

AMA: disk diffusion method by analyzing zones of inhibition; MIC: growth absence or presence after inoculation in tubes

MEE; 500 and 250 mg/mL (disk diffusion); 500 to 0.9 mg/mL (MIC)

Disk diffusion: inhibition > 7 mm on S. aureus, MRSA, and E. faecalis; no inhibition on E. coli and P. aeruginosa. Complete inhibition on S. aureus, MRSA, and E. faecalis by the highest concentration. MIC: 7.8 mg/mL (E. faecalis)

Bezerra et al. [38]

Promastigote forms of L. amazonensis

Leishmanicidal activity: promastigotes incubated during 24 h with extract. Count of living protozoa after 24 h by flagellar motility. CL₅₀

MAE; serial concentrations 500 to 31.25 μg/mL

CL₅₀ > 500 μg/mL. Deaths about 20% in all concentrations

Caetano et al. [37]

S. aureus (ATCC6538, ATCC9144), S. aureus MRSA (2 nosocomial strains), S. aureus MSSA (3 nosocomial strains)

AMA: disk diffusion method by analyzing zones of inhibition

Mesocarp hydroalcoholic extract; 30 mg/mL

Growth inhibition on all strains (14 to 18 mm zones)

Ferreira et al. [45]

AMA: S. epidermidis (ATCC12228), S. aureus (ATCC25923), E. coli (ATTC11229), P. aeruginosa (ATTC27853); DPPH^•; A. salina

AMA disk diffusion method by analyzing zones of inhibition; AA: DPPH^• scavenging. EC₅₀; Lethality: A. salina assay for 24 h. CL₅₀

Kernel oil; 10 mg/mL (AMA); 300, 250, 200, 150, and 100 mg/mL (DPPH^•); 50 to 0.05 mg/mL (lethality)

AMA: no inhibition; DPPH^•: EC₅₀ 70.57 mg/mL; CL₅₀ > 1000 μg/mL

Gaitan et al. [22]

Porcine thyroid slices; TPO

Antithyroid effect: thyroid hormone synthesis assessed by measuring total accumulated iodine and iodine organification in MIT + DIT, and T₃ + T₄; TPO: spectrophotometry by oxidation of I⁻ to I³⁻. Inhibition of TPO-catalyzed iodination, compared to PTU concentration. I₅₀

MAE, MME, kernel skin, KPPS, kernel oil; cellular assays: 1 × 10⁵ μg/5 mL (MAE, skin); 5 × 10⁴ μg/5 mL (KPPS, oil); TPO: 100 to 200 μg/mL

Cellular: antithyroid effect in all extracts by ↑ ¹²⁵I/MIT + DIT ratio, ↓ % ¹²⁵I demonstrated as T₃ + T₄ (NA). Kernel oil 1/5 from KPPS I/MIT + DIT ratio (I/MIT + DIT = 15). Higher ratio for mesocarp; TPO: ↑ inhibition % by MME and kernel skin

Hovorková et al. [8]

E. cecorum (CCM3659, CCM4285), C. perfringens (CIP105178, CNCTC5454, UGent 56), Listeria monocytogenes (ATCC7644), S. aureus (ATCC25923), Bifidobacterium animalis (CCM4988, MA5), Bifidobacterium longum (TP1, CCM4990), Lactobacillus fermentum (CCM91), Lactobacillus acidophilus (CCM4833)

AMA: previous kernel oil hydrolysis with porcine pancreatic lipase. Inoculation of each strain with emulsion. Growth assessment by the culture turbidity read at 405 nm. MIC₈₀

Kernel hydrolyzed lipid emulsion; 4.5 mg/mL

MIC₈₀: 0.56 mg/mL on C. perfringens, 1.13 mg/mL on S. aureus, and 2.25 mg/mL on E. cecorum. No effect on pathogenic strains before hydrolysis or on commensal strains

Nobre et al. [30]

TBARS, deoxyribose degradation, DPPH^•, iron chelation, FRAP

AA: TBARS: phospholipids diluted in the extract with or without iron to induce peroxidation and absorbance with MDA; Deoxyribose degradation: induction of sugar decomposition by Fe/ H₂O₂ added to the extract to produce MDA; DPPH^•: scavenging, read at 518 nm; Iron chelation: chelation potential by extract (plus Fe²⁺, Tris–HCl, and phenanthroline), absorbance read at 510 nm; FRAP: ability to reduce the equivalent of 1 mM FeSO₄·7H₂O. IC₅₀, EC₅₀, EC

Kernel methanolic extract; 1000 to 100 μg/mL (TBARS, deoxyribose, DPPH^•, iron chelation); 50 to 5 μg/mL (FRAP)

No TBARS inhibition; deoxyribose IC₅₀ > 1000 μg/mL; DPPH^• EC₅₀ 3517.01 ± 77.07 μg/mL; iron chelation: < 20%, IC₅₀ > 1000 μg/mL; FRAP EC: 1560.2 ± 18.30 μmol.L⁻¹/g

Nobre et al. [10]

S. aureus (ATCC12692), P. aeruginosa (ATCC15442), E. coli (ATCC25922), E. coli (Ec27), S. aureus (Sa358)

Antibacterial activity: growth evidence after inoculating extract with resazurin solution into tubes. MIC

Fixed kernel oil: 512 to 8 μg/mL

Higher inhibition on E. coli 27 (MIC 23 μg/mL); ↓ MIC in the association between oil and amicacin on S. aureus 358 and P. aeruginosa, as well as neomycin on S. aureus 358, P. aeruginosa, and E. coli 27 (NA)

Pessoa et al. [31]

Enteropathogenic E. coli, mononuclear phagocytes

Cellular viability: slides fixed by acridine orange method; viability index by counting dead and alive cells in a total of 100. Functional activity by phagocytic index: number of cells that ingested at least 3 bacteria in a pool of 100 cells. Bactericidal index: dead/alive bacteria ratio by acridine orange

Kernel microemulsion and oil; 20 μL

↑ viability index and ↑ phagocytic index by microemulsion; ↑ bactericidal index by oil

Rennó et al. [28]

Leukaemic cell lines (HL-60, K562), K562-Lucena 1 MDR counterpart, lymphocytes, mouse fibroblast cell line (3T3-L1), human breast cancer cell line (MCF-7)

Cellular viability: erythroleukemic cells evaluated by permeability to trypan blue up to 24 h. Inhibition of cell proliferation calculated by comparing treated/untreated cells. Morphology: non-viable stained cells were separated in retained shape and lysed; lymphocytes evaluated with trypan blue after 24 h; MCF-7 and 3T3-L1 trypsinized and evaluated with trypan blue. Metabolism: 6-phosphofructo-1-kinase activity to convert into fructose-1,6-bisphosphate in HL-60. ID₅₀

Mesocarp with epicarp ethanolic extract; 2000, 1500, 1200, 600, 300, and 150 μg/mL

ID₅₀ more effective on HL-60; moderate sensitivity on K562, K562-Lucena 1, and MCF-7; Resistance on 3T3-L1 and lymphocytes; morphological changes by 1200 μg/mL on HL-60; ↑ 6-phosphofructo-1-kinase on HL-60

Santos et al. [33]

Mouse fibroblasts (L929) and peritoneal macrophages

Cellular viability: MTT assay up to 72 h; absorbance read at 560 nm; macrophages stimulated by LPS from E. coli for 1 h and treated with kernel oil. NO and cytokines measured after 24 h;

Scratch assay: fibroblasts migration in monolayers, production of 1.2001.500 μm width wounded area. Cellular migration measured each 6 h

Kernel oil; 100 to 1.56 μg/mL

No toxicity up to 100 μg/mL; cell proliferation with MTT metabolism ↑ above 25 μg/mL on L929; dose-related ↓ NO; ↑ IFN-γ, IL-6, and ↑TNF-α by 3.12 μg/mL; ↑ fibroblasts migration in scratch assay by 6.25 and 12.5 μg/mL

Santos et al. [32]

DPPH^•, mouse fibroblasts (NIH/3T3, ATCCR, CRL-1658)

AA: DPPH^• scavenging, read by electron spin resonance; EC₅₀; Cellular viability: MTT assay with nanoemulsion up to 72 h, IC₅₀

Kernel oil, lipidic nanoemulsion; 4.0; 24.9; 49.9; 74.8, and 99.8 mM (DPPH^•); 2500 to 39.06 μg.mL⁻¹ of nanoemulsion (MTT)

DPPH^• EC₅₀: nanoemulsion: 0.4329 mg mL⁻¹; oil: 0.5488  mg mL⁻¹; cytotoxicity by nanoemulsion ≥ 78.12 μg.mL⁻¹

Silva et al. [34]

DPPH^•, S. cerevisiae (BY4741)

AA: DPPH^• scavenging, read at 518 nm; IC_50. S. cerevisiae: incubation of 0.1 mg mL⁻¹ cells with 3 mM TBH and 5 mg ml⁻¹ extracts; microorganism viability assessed after 72 h

Endocarp, flowers, and leaves ethanolic extract; 1.0 mg ml⁻¹

DPPH^• IC₅₀: 4104.3 ± 6.7 μg.ml⁻¹ (endocarp); 427.4 ± 1.8 μg.ml⁻¹ (flowers), and 895.9 ± 2.3 μg.ml⁻¹ (leaves); no yeast survival

Silva et al. [23]

NO, TBARS, deoxyribose degradation

AA: nitrite measured by Griess reaction after NO generated in sodium nitroprusside decomposition. Absorbance read at 540 nm. TBARS: phospholipids diluted in the extract with AAPH as peroxidation inducing agent, absorbance read at 532 nm; OH^• production by MDA synthesis, a product of deoxyribose degradation induced by Fe/H₂O₂ added to the extract, absorbance read at 532 nm

MAE; 1000, 100, 10, and 1 μg/mL

No effect on NO and OH^• removal or over lipid peroxidation

Silva et al. [35]

DPPH^•, ABTS^•+, FRAP, tyrosinase

AA: DPPH^• scavenging, absorbance read at 517 nm; ABTS^•+ scavenging absorbance read at 734 nm; FRAP: analysis of ability to reduce Fe³⁺ into Fe²⁺ with, read at 593 nm; Tyrosinase inhibition: L-tyrosine for monophenolase reaction and 3,4-dihydroxyphenylalanine for diphenolase reaction. Absorbance read at 492 nm

Mesocarp hydroalcoholic extract and fractions (hexane, chloroform, ethyl acetate, hydroalcoholic); 100 to 5 μg/mL (DPPH^•), 6 to 1 μg/mL (ABTS^•+), 100 to 1 μg/mL (FRAP), 200 to 50 μg/mL (tyrosinase)

↑ AA by ethyl acetate fraction in DPPH^• IC₅₀: 3.38 ± 0.05 μg/mL, ABTS^•+ IC₅₀: 2.04 ± 0.03 μg/mL and FRAP: 15.41 ± 0.18 mmol Fe²⁺/g; IC₅₀ for tyrosinase: 48.43 ± 29.51 μg/mL (monophenolase) and 132.63 ± 5.71 (diphenolase)

Silva et al. [29]

Promastigote forms of L. amazonensis (IFLA/BR/67/PH8)

Leishmanicidal activity: promastigotes incubated with the isolated extract and mesocarp-loaded microparticles. Protozoa counting after 48 h by flagellar motility. CL₅₀

MAE; 500 to 62.5 μg/mL and mesocarp-loaded microparticles; 100 to 3.125 μg/mL

Lethality: pentamidine > microparticles > extract in solution. CL₅₀ microparticles: 12 pg/mL

Souza et al. [36]

Benign prostate hyperplasic cells

Cellular viability: MTT assay, absorbance read at 570 nm up to 72 h; cytotoxicity by LDH release: damage estimated after from 4 up to 48 h, absorbance read at 490 nm; Immunohistochemistry: cultures treated for 24 h, PCNA immunostained; Apoptosis: TUNEL test by blocking endogenous peroxidase. DNA fragmentation assessment; Histomorphometry: nuclei counting with PCNA or TUNEL stained, distribution and intensity of staining assessment inside the glandular epithelium or stroma; Morphology: indirect assessment using phalloidin after 4, 6 and 12 h

Kernel crude oil, oily extract, nanocomposite with lipophilic extract; 300 to 100 μg/mL (MTT), 300 μg/mL (LDH, Immunohistochemistry, histomorphometry, apoptosis)

Viability: ↑ dose-related inhibition by nanocomposite; time-dependent disorganization of the actin cytoskeleton; ↑ time-dependent LDH release; immunohistochemistry: preserved glandular architecture; ↓ cell proliferation in 24 h; diffuse apoptosis and ↑ in apoptotic index after 24 h