TABLE 2.
Pharmacological effects of crude extracts and bioactive compounds of A. carambola.
| Pharmacological activity | Compounds/Extracts | Types | Testing subjects | Doses/Duration | Effects/Mechanisms | References |
|---|---|---|---|---|---|---|
| Antioxidant activity | ||||||
| MEACL | In vitro | DPPH and ABTS+ assays | 50–375 μg/ml | Showed moderate free radical scavenging activity against DPPH and ABTS+ free radical with the IC50 were 62.0 and 6.0 μg/ml, respectively | Siddika et al. (2020) | |
| PRAC | In vitro | DPPH and ABTS+ assays | 0.5–2.5 mg/ml | Showed significant free radical scavenging activity against DPPH and ABTS+ with the IC50 of 0.10 and 0.33 mg/ml, respectively | Liao et al. (2019b) | |
| EEBAC | In vitro | α-glucosidase, elastase, ABTS+, DPPH, and tyrosinase enzyme assays | 1.0, 3.0, 10, 30, and 100 μg/ml | Showed significant antioxidant activity, and the IC50 values were 7.15, 20.34, 26.29, 55.55 and 56.46 μg/ml, respectively | Islam et al. (2020) | |
| 40 | In vitro | DPPH and ABTS+ assays | 2.5, 5, and 10 μg/ml | Showed significant radical scavenging activity against the DPPH and ABTS+ with the IC50 values of 4.9 and 9.63 μg/ml, respectively | Islam et al. (2020) | |
| Anti-hyperglycemic activity | ||||||
| REAC | In vivo | STZ-induced diabetic mice | 150, 300, 600, and 1,200 mg/kg, daily for 21 days | Blood glucose, TC, TGs, and FFAs levels ↓; insulin level ↑; caspase-3, caspase-8, caspase-9, and Bax protein expressions ↓; Bcl-2 protein expression ↑ | Xu et al. (2014) | |
| REAC | In vivo | STZ-induced diabetic mice | 300, 600, and 1,200 mg/kg, i.g., daily for 14 days | FBG, IL-6 and TNF-α levels ↓; TLR4 and NF-κB mRNA and protein expression | Xu et al. (2015) | |
| REAC | In vivo | STZ-induced diabetic mice | 300, 600, and 1,200 mg/kg, i.g., daily for 42 days | FBG, Cr, BUN, and MDA levels ↓; SOD, GSH-Px, CAT activities ↑; Cyto-C, AIF, and caspase-3 protein expressions ↓ | Xu et al. (2017) | |
| FPAC | In vivo | Fluoride-induced hyperglycemia, hypercholesterolemia, and oxidative stress of rat’s model | 2.5, 5.0, and 10 g, i.g., for 30 days | Blood glucose, G-6-pase, SGOT, SGPT, ACP, and ALP levels ↓; hepatic glycogen and hexokinase, and FRAP activities ↑; plasma AIP, TL, TC, TG, LDL-C, VLDL-C, hepatic lipids-TL, TC and TG levels ↓; HDL-C level ↑; CAT, SOD, GPx, GSH, TAA activities ↑; MDA level ↓ | Vasant and Narasimhacharya (2014) | |
| JEAC | In vivo | STZ-induced diabetic mice | 25, 50, and 100 mg/kg, i.g., once a day for 21 days | FBG, FFA, TC, TG, Scr, BUN, and MDA levels ↓; SDH, cAMP, SOD, and insulin activities ↑; CTGF and TGF-β1 mRNA and protein expressions ↓ | Pham et al. (2017) | |
| JEAC | In vivo | STZ-induced diabetic mice | 5, 10, and 20 g/kg, orally, once a day for 14 days | FBG, blood glucose, area under curve, LDH, GC and pyruvate ↓; FINS level ↑ | Yang et al. (2019a) | |
| TFACL | In vivo | Alloxan-induced diabetic mice and STZ-induced diabetic rats | 0.2, 0.4, and 0.8 g/kg, i.g., daily for 7 days | FBG level ↓; glucose tolerance ↑ | Liu et al. (2013) | |
| EEACB | In vivo | STZ-induced diabetic mice | 50 and 100 mg/kg, i.g., for three successive days | Blood glucose level ↓ | Islam et al. (2020) | |
| 47 | In vivo | STZ-induced diabetic rats | 20 and 50 mg/kg, i.g., for 3 h | Serum blood glucose level ↓; insulin secretion ↑ | Cazarolli et al. (2012) | |
| 48 | ||||||
| 48 | In vitro | 14C-glucose uptake in rat soleus muscle | 50 and 100 μM for 1 h | Glucose uptake and glucose transport ↑ | Cazarolli et al. (2009) | |
| 105 | In vivo | STZ-induced diabetic mice | 20, 40, and 80 mg/kg, i.g., daily for 14 days | FBG, FINS, and ISI levels ↓; NF-κB, caspase-3, caspase-8, caspase-9, and Bax protein expressions ↓ | Wen et al. (2013) | |
| 106 | ||||||
| 121 | In vivo | STZ-induced diabetic mice | 30, 60, and 120 mg/kg, i.g., once daily, for 21 days | FBG, TC, TG, FFA, GHb, FINS, MCP-1, TNF-α, IL-6 and MDA levels ↓; SOD, GSH activities ↑ | Qin et al. (2019) | |
| 121 | In vivo | STZ-induced diabetic mice | 30, 60, and 120 mg/kg, i.g., once daily, for 21 days | TLR4, MyD88, p-NF-κB, TNF-α, and IL-6 mRNA and protein expression levels ↓ | Qin et al. (2020) | |
| 122 | In vivo | Type 2 diabetic KKAy mice | 12.5, 25, and 50 mg/kg, i.g., daily, for 56 days | FBG, AGEs glycosylated protein and TC levels ↓; albumin level ↑ | Zheng et al. (2013) | |
| 122 | In vivo | Type 2 diabetic KKAy mice | 12.5, 25, and 50 mg/kg, i.g., daily, for 56 days | FBG level ↓; RAGE, NF-B, TGF-β1 and CML protein expression levels ↓ | Zheng et al. (2021) | |
| 122 | In vivo | DN model established by STZ in TLR4 knockout mice and wild-type mice | 12.5, 25, and 50 mg/kg, i.g., daily for 28 days | TC, TG, HDL, LDL, Scr, BUN, and blood glucose ↓; IL-6 and TNF-α level ↓; TLR4, MyD88 and NF-κB mRNA and protein expressions ↓ | Lu et al. (2019) | |
| 122 | In vitro | HG-induced HK-2 cells | 30 μM for 48 h | Blood glucose ↓; Vimentin mRNA and protein level ↑; TLR4 and E-cadherin mRNA and protein levels ↓; BAMBI ↑; Smad2/3 ↓ | Zhang et al. (2019) | |
| 122 | In vivo | Diabetic kidney disease mice model induced by Wild type and TLR4 knockout | 12.5, 25, and 50 mg/kg, i.g., once daily, for 28 days | TC, TG, LDL-C, FBG, CysC, and urinary albumin levels ↓; TLR4, TGF-β1 and Smad2/3 mRNA and protein levels ↓ | Zhang et al. (2020) | |
| Antihyperlipidemic activity | ||||||
| IFRF | In vivo | Murine model | Diets formulations, i.g., for 30 days | TG, TC, HDL, and LDL levels ↓ | Herman-Lara et al. (2014) | |
| FF | ||||||
| MEACL | In vivo | Poloxamer-407-induced hyperlipidemic rat model | NM | TC, TG, LDL-C, VLDL-C and AI levels ↓ | Saghir et al. (2016) | |
| MEACL | In vivo | HFD-induced hyperlipidemic rats | 250, 500, and 1,000 mg/kg, i.g., daily, for 35 days | TC, TG, LDL-C, VLDL-C, and AI ↓; HDL-C ↑; GSH, GPx, SOD, CAT activities ↑; MDA level ↓ | Aladaileh et al. (2019) | |
| Anti-obesity activity | ||||||
| CEPAC | In vitro | 3T3-L1 preadipocytes | 10, 100, 500, and 1,000 mg/ml | TG accumulation ↓; PPAR-γ and C/EBPα mRNA expressions ↓; PPAR-α mRNA expression ↑ | Rashid et al. (2016) | |
| 122 | In vivo | high-fat diet (HFD) in mice | 12.5, 25, and 50 mg/kg, i.g., daily for 28 days | BW and adipose tissue weights, blood glucose, insulin, TC, TG, FFA, IL-6, TNF-α levels ↓; TLR4 and MyD88 expressions ↓; insulin secretion ↑ | Li et al. (2016) | |
| Antitumor activity | ||||||
| ACE | In vivo | DENA-induced and CCl4-promoted liver cancer in mice | 25 mg/kg, i.g., for five consecutive days | Tumor incidence, tumor yield, tumor burden ↓; LPO level ↓; GSH, SOD, CAT, total proteins content activities ↑ | Singh et al. (2014) | |
| MEACL | In vivo | EAC cell bearing mice | 25 and 50 mg/kg, i.g., for 5 days | viable cells and body weight ↓; survival time ↑; Hgb, WBC, RBC numbers ↑; p53 and Bax protein expression ↑ | Siddika et al. (2020) | |
| 122 | In vitro | Human breast cancer MCF-7 and BT20 cells | 10, 32, 100 μM for 24 h | Caspase-3/7, -8, and -9 activities ↑; TRAIL-R1, TRAIL-R2, Bad, and BID protein expressions ↑; cIAP, XIAP, and Survivin protein expressions ↓; G1 phase cell cycle arrest, ROS ↑; NF-κB ↓ | Gao et al. (2015) | |
| 122 | In vivo | Transplanted 4T1 breast cancer cells bearing mouse | 25, 50 and 100 mg/kg, i.g., for 14 days | Survival time ↑; tumor growth ↓; TNF-α, IL-6, IL-12, TGF-β, VEGF ↓; Bax, cleaved caspases-3 and -9 ↑; Bcl-2, MMP-2 and -9, NF-κB and IκBα ↓ | Chen et al. (2017b) | |
| 122 | In vitro | Radio-sensitivity of 4T1 breast carcinoma cell lines | 100 μM for 2 or 24 h | TIE, TRD ↓; radio-sensitivity of the 4T1 cells ↑ | Muhammed et al. (2019) | |
| 122 | In vitro | Lung cancer H1299 cells | 4.0, 6.0, and 8.0 μg/ml for 24 h | Cell apoptosis ↑; ERK/MAPK ↓; inhibition rates were 22.50, 30.13, and 58.87%, respectively | Zhou et al. (2019) | |
| 122 | In vivo | Hepatocarcinoma in nude mice | 25, 50, and 100 mg/kg, i.g., daily for 12 days | Tumor weight ↓; liver and spleen indexes ↓; IL-2 and IL-10 levels ↓; inhibition rates were 66.39, 63.11, and 47.33%, respectively; WBC, HGB, and PLT numbers ↑; TLR4, MyD88, and NF-κB expressions ↓ | Wu et al. (2020a) | |
| Anti-inflammatory activity | ||||||
| EEACL | In vivo | Croton oil-induced mouse ear edema | 0.03–1.0 mg/ear | Edema (IC50: 0.05) ↓; MPO activity (IC50: 0.22) ↓ | Cabrini et al. (2011) | |
| PFSCW | In vivo | Adult female Swiss mice | 100 and 300 mg/kg | Paw edema ↓ | Leivas et al. (2016a) | |
| 122 | In vivo | Pancreatic β-cell line Min6 cells | 10, 15, and 20 μmol/L | TNF-α, IL-6 and MCP-1 level ↓; cleaved-caspase-3, -8 and -9, TLR4, MyD88, and NF-KB expressions ↓; Bcl-2/Bax ratio ↑ | Xie et al. (2016) | |
| Hepatoprotective activity | ||||||
| FPEAC | In vivo | Leptin receptor- deficient (db/db) mice | 10, 20, and 30 g/kg, i.g., daily, for 8 weeks | TG, TC, LDL-C, and NEFA level ↓; AST and ALT activities ↓; HDL-C level ↑; p-AMPK protein expression ↑; SREBP-1c, FAS and SCD1 mRNA and protein expression levels ↓; mircoRNA-34a and mircoRNA-33 expression levels ↓ | Pang et al. (2017) | |
| FJAC | In vivo | STZ-induced diabetic mice | 5, 10, and 20 g/kg, i.g., daily for 14 days | MAD and cAMP levels ↓; SDH, MDA, and SOD activities ↑ | Yang et al. (2018) | |
| EACR | In vivo | CCl4-induced acute liver injury in mice | 0.3, 0.6, and 1.2 g/kg, i.g., dialy, for 7 days | f AST, ALT, IL-1, IL-6, MDA levels ↓; SOD, GSH, GSH-Px activities ↑; TNF-α, NF-κB, caspase-3 protein expression levels ↑ | Huang et al. (2019) | |
| EACR | In vivo | Liver fibrosis (HF) rats induced by CCl4 | 0.25, 0.5, and 1.0 g/kg, i.g., dialy, for 28 days | Albumin/globulin (A/G) ratio ↑; TBIL and TC levels ↓; NF-κB and Bax expression levels ↓; Bcl-2 expression level ↑ | Liang et al. (2020b) | |
| EACR | In vivo | CCl4-induced acute liver injury in rats | 0.25, 0.5, and 1.0 g/kg, i.g., dialy, for 8 weeks | AST, ALT, AKP, Hyp, HA, LN, Col III, Col IV, MDA levels ↓; SOD and GSH-Px activities ↑; COL-1a1, α-SMA, TIMP2, TGF-β1, Smad-2 and Smad-4 mRNA expression levels ↓; α-SMA, TIMP2, TGF-β1, Smad-2, Smad-3 and Smad-4, Bax and cleaved caspase-3 proteins expression levels ↓; Smad-7 mRNA expression and Smad-7 and Bcl-2 protein expression ↑ | Huang et al. (2020) | |
| Cardioprotective activity | ||||||
| AEAC | In vivo | Rats with ventricular remodelling induced by isoprenaline | 50, 100, and 200 mg/kg, i.g., daily, for 14 days | TGF-β, Ang II, iNOS, ECE, ET-1 levels and expressions ↓; VR index, CVF ↓; tNOS, eNOS protein expression levels ↑ | Liang et al. (2020a) | |
| Antihypertensive activity | ||||||
| AELAC | In vivo | Normotensive rats | 12.5–50.0 mg/kg, i.v. | MAP ↓; Ca2+-free medium ↓ | Soncini et al. (2011) | |
| EEACR | In vivo | Normal rats | 150, 300, and 600 mg/kg, i.g. | Blood pressure ↓ | Tang et al. (2017) | |
| FACF | In vivo | Normal rats and rats with hypertension induced by L-NAME | 300, 600, and 1,200 mg/kg, i.g., daily, for 5 weeks | SBP, DBP, MBP, blood pressure ↓ | Huang et al. (2017) | |
| Neuroprotective activity | ||||||
| 122 | In vivo | APP/PS1 transgenic AD mice | 12.5, 25, and 50 mg/kg, i.g., once a day for 21 days | Spatial learning and memory deficit, fear memory deficit apoptosis and loss of neuron ↑; Bcl-2/Bax ratio ↑ | Wei et al. (2018) | |
| 122 | In vitro | PC-12 cells | 5, 10, and 20 μmol/L | Bcl-2 mRNA and protein expressions ↑; Bax mRNA and protein expressions ↓; caspase-3 and caspase-9 expressions ↑; Bcl-2/Bax ratio ↑ | Wei et al. (2018) | |
| 122 | In vitro | SH-SY5Y cells induced by Aβ1-42 | 5, 10, and 20 μmol/L | cell viability loss and apoptosis ↓; Bax, caspase-3, caspase-8 and caspase-9 protein expression levels ↓; Bcl-2 protein expression ↑ | Lu et al. (2020) | |
| Reducing UVB-induced skin damage | ||||||
| EFAC | In vitro | Human HaCaT keratinocytes induced by UVB | 50, 100, and 250 µg/ml | Apoptotic cells number ↓; caspase 3 expression ↓; CPD ↓ | Ronpirin et al. (2016) | |
| AFAC | ||||||
NM, not mentioned; ACL, A. carambola leaves; MEACL, methanol extract of A. carambola leaves; EEBAC, ethanol extracts of bark from A. carambola; REAC, root extracts of A. carambola; FPAC, fruit powder of A. carambola; JEAC, juice extracts of A. carambola; TFACL, total flavones from A. carambola leaf; EEACB, ethanol extracts of A. carambola bark; MEACL, methanolic extract of A. carambola leaves; CEPAC, crude extract from peel of A. carambola; PEFAC, a homogenous polysaccharide extracted from the fruit of A. carambola; ACE, A. carambola extracts; EEACL, ethanol extract of A. carambola leaves; FPEAC, free phenolic extract from A. carambola; FJAC, fruit juice of A. carambola; EACR, extract of A. carambola root; AEAC, aqueous extract of A. carambola; AELAC, aqueous extract of leaves of A. carambola; EEACR, ethanol extracts of A. carambola root; FACF, flavonoids in A. carambola fruit; EFAC, ethanol fractions of A. carambola; AFAC, aqueous fractions of A. carambola; 40, Norathyriol; 47, Carambolaflavone A; 48, Carambolaflavone B; 105, (+)-lyoniresinol 3α-O-β-D-glucopyranoside; 106, (−)-lyoniresinol 3α-O-β-D-glucopyranoside; 121, 2-methoxy-6-nonyl-cyclohexa-2,5-diene-1,4-dione; 122, 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione.