Table 4 Baseline characteristics, intervention, methods, and main results of in vivo studies

Azevedo et al. [41]

Male (C57BL/6); 8–12 w.o.; 20–25 g; n = 20

Antithrombotic effect: carrageenan-induced thrombosis, evaluation of necrosis frequency and extension; Onco BCG injection for NO induction in peritoneal cells; platelets, PT, and aPTT analysis

Mesocarp aqueous solution; 500 mg/kg/day; 240 days

↓ induced thrombosis; ↑ PT, and aPTT, no changes in platelets number; ↑ NO production by peritoneal macrophages previously activated by Onco BCG

Barbosa et al. [26]

Male (Mesocricetus auratus); 7–10 w.o.; 122–146 g; n = 39

Macromolecular permeability and leukocyte adhesion in cheek pouch after ischemia induction. After reperfusion, histamine topical application. Less than 10 leaks/site accepted; IL-1, IL-6, and TNF-α analysis

Crude kernel oil; 0.02 ml, 0.06 ml, 0.18 ml twice/day; 14 days

↓ ischemia-induced leaks during reperfusion in higher doses; ↑ leaks in lowest dose; less pronounced microvascular permeability after histamine in higher doses; ↓ leukocyte adhesion in lowest dose; no significant changes in TNF-α, IL-1, and IL-6

Barroqueiro et al. [27]

Male/female (C3H/HePas); 8–12 w.o.; 25 g; n = 40

Acute toxicity: weight, macroscopic, and histological analysis of heart, liver, spleen, kidney, and brain; glucose, urea, creatinine, ALP, TC, TG analysis

MEE; 1000 mg, 3000 mg, 5000 mg/kg; single dose

No deaths after 14 days; no significant increase in body weight; no cutaneous, neurological or behavioral changes, glucose, TC, or creatinine; ↑ ALP in 3000 and 5000 mg/kg groups; ↑ urea in all groups; ↑ TG in 1000 mg/kg

Gaitan et al. [22]

Female (Sprague–Dawley); 7 w.o.; weight (NA); n = 25

Antithyroid effect: 14 mcg/day of iodine-rich diet; MAE and KPPS acute intake. After 1 h, i.p. Bq Na¹²⁵I; ¹²⁵I uptake and organification analysis by MIT + DIT coupling in thyroid tissue

MAE (16 g) and KPPS (2 g); single dose

Distinct antithyroid effects for MAE and KPPS; ↓ iodine uptake in 16 g MAE group; ↑ inorganic iodine % in MAE and KPPS; ↓ iodine % as MIT + DIT; ↑ ratio ¹²⁵I/MIT + DIT in MAE and KPPS

Maia and Rao [24]

Male/female (Wistar); age (NA); 180–220 g; n = 107. Male and female (Swiss); age (NA); 25–30 g; n = 88

Anti-inflammatory effect: carrageenan-induced inflammation in paw and edema analysis; subcutaneous cotton pellet implant-induced granuloma, pellet removal and weighing; formaldehyde-induced arthritis in paw and edema analysis; carrageenan-induced inflammatory exudate by leukocyte migration. Ulcerogenesis: gastric lesion assessment. Coagulation: bleeding time after opening the abdomen, micropuncture in a mesenteric vein, and time of hemostasis; Antipyretic: S. cerevisiae-induced pyrexia; Analgesia: hot-plate positive response; writhing induced by acetic acid; acute toxicity after 72 h

Mesocarp chloroformic extract; 125 mg/kg, 250 mg/kg (carrageenan, hot-plate, writhing) in a single dose; 250 mg/kg (granuloma) for 7 days; (arthritis) for 10 days; (ulcer) for 21 days; (pyrexia) in a single dose; up to 4 g/kg (toxicity); dose (NA) (exudate) 3 times/24 h; dose (NA) (bleeding) for 3 days

↓ dose-dependent acute inflammatory edema after carrageenan induction; ↓ granuloma; ↓ edema in arthritis on 7th and 8th days; absence of peptic ulcer; no influence on leukocyte migration, no effects on bleeding time and pyrexia control; no significant effect on hot-plate response; ↓ writhing; no overt acute toxicity

Pinheiro et al. [39]

Male (BALB/c, DBA/2, CBA, C3H/HePas, C57BL/6); 8–12 w.o.; 20–30 g; n = 10

Glycolipid profile: TC and urea analysis. Immunotoxicity: medullary and splenic cell analysis

MAE; 50 mg/kg/day; 30 days

↓ splenic cells in C3H/HePas and BALB/c; no changes in medullary cells; ↑ TC in CBA and ↓ in C3H/HePas; ↓ U in all strains, except in C57BL/6

Scheibe et al. [43]

Male (Wistar); age (NA); 271.3 g (average); n = 54

Wound healing: laparotomy with cecum exteriorization. Monitoring and euthanasia on 7th, 14th, and 21st day; macroscopic wound evaluation (infection, dehiscence, haematoma,and fistulae); abdominal cavity evaluation (collection, infection, fistulae, and adherence); terminal ileum air insufflation test; vascular congestion analysis, edema, presence of mono and polymorphonuclear leukocytes, angiogenesis, fibrosis, and collagen deposition

MAE; 50 mg/kg/day; 7, 14, 21 days

Adequate healing in all animals; no evidence of infection, dehiscence, haematoma, abscess; widespread adhesion, without adhering to the abdominal wall (grade III) in 1 rat on 7th day, grade II adherence on the 21st day in 100% of the animals; ↓ burst pressure over time after insufflation test; ↓ polymorphonuclear leukocytes, congestion, angiogenesis, fibroblast proliferation, and collagen deposition on the 14th day

Silva et al. [23]

Male (Swiss); 8 w.o.; 25–30 g; n = 28

Locomotor activity: total crossings in activity cage. Motor coordination: remaining time on rotarod test (180 s at 9 RPM)

MAE; 1, 2, 3 g/kg; single dose

No significant changes in the number of crossings or in remaining time on the rotarod test

Silva et al. [44]

Male (Wistar); 7–8.5 w.o.; 275.6 g (average); n = 54

Colonic healing: cecorrhaphy by laparotomy an exteriorization of the colon. Euthanasia on 7th, 14th, and 21st days. Animal weighing, wound analysis (infection, dehiscence, haematoma, and fistulae); abdominal cavity analysis (collection, infection, fistulae, and adhesion); terminal ileum air insufflation test; analysis of congestion, edema, presence of mono and polymorphonuclear leukocytes, angiogenesis, and fibrosis

MAE; 50 mg/kg; single dose

No dehiscence, fistulae or other complications; ↑ grade II adherence on 21st day; moderate/severe mononuclear leukocytes, congestion, and angiogenesis on the 7th day; ↓ congestion and angiogenesis on 14th day

Silva et al. [25]

Non-obese diabetic male mice (strain NA); 12 w.o.; 29–33 g; n = 25

Onset of diabetes: individual average of extract, water, and food intake for 6 days; weighing, blood glucose analysis on 0, 30th, 90th, and 120th day; anti-insulin IgM antibodies, and total antibodies (IgG, IgM) with anti-immunoglobulin antibodies

MAE; average 66 mg/day; 120 days

Daily average intake of MAE 3.3 ± 0.9 ml; ↑ weight from 20 to 50th day and ↓ after 50th; ↓ glucose on 30th day; ↓ IgM; no significant changes in anti-insulin IgM and IgG

Silva and Parente [40]

Male (BALB/c); age (NA); 15–20 g; n = 15

AIE and IME: Evans blue and i.p. acetic acid-induced vascular permeability. Leak analysis in the peritoneal cavity; phagocytic activity by colloidal carbon injection. Blood sample dissolved in Na₂CO₃ and absorbance determination at 660 nm

Mesocarp isolated α-glucan; 100 mg/Kg (AIE) single dose; 50 mg/kg/day (IME) for 5 days

↓ vascular permeability; ↑ phagocytic activity

Soares et al. [6]

Male (Swiss); 8.5 w.o.; 35–40 g; n = 32

Lipid profile and IME: pre and post-euthanasia weighing; macroscopic and histological analysis of heart, liver, kidneys, spleen, gastrocnemius muscle, and retroperitoneal fat. AST, ALT, TC, LDL, HDL, TG, glucose, urea, creatinine, IL-6, and TNF-α analysis; immunophenotyping of splenic cells; RT: stair climbing with load adjustment in daily sessions, 5 days a week for 8 weeks

MAE; 5 mg/kg/day; 5 days/week for 8 weeks

MAE: ↓ total weight; ↓ fat tissue; ↓ TG; ↓ TC; ↑ AST; ↑ medullary cells; ↑ B lymphocytes; ↓ activated macrophages; ↓ IL-6; ↑ TNF-α

MAE/RT: ↓ total weight; ↑ kidneys weight but no histological changes; ↓ fat tissue; ↓ TG; ↓ TC; ↑ AST/ALT; ↓ splenic or medullary cells; ↓ activated Th; ↑ activated B lymphocytes; ↑ macrophages; ↓ activated macrophages; ↓ IL-6; ↑ TNF-α

Torres et al. [42]

Male (Wistar); 6 w.o.; 180–240 g; n = 40

Prevention and treatment of peptic ulcer: macroscopic analysis (ulceration, mucosal hyperemia, loss of fold, and/or bleeding; histopathological analysis (inflammation, necrosis, fibroblasts, fibrosis, reepithelialization, neocapillar generation)

MAE; 2 g/kg/day; 3 days

Prophylaxis: ↓ peptic ulcer, mucosal hyperemia, loss of fold, and bleeding; treatment: ↓ necrosis, fibrosis, reepithelialization, and neocapillar generation; marked inflammation and mucosal ulceration