Table 2.
Biological and pharmacological activities of limonin—in vitro and in vivo studies summary.
| Pharmacological Effects | Detail | Cell Lines/Model | Dosage of Administration | Application | Ref. |
|---|---|---|---|---|---|
| Anticancer activity | Activation of endogenous apoptosis pathway | SW480 cells | IC50 = 54.74 μM | In vitro | [15] |
| Expression of apoptosis-related proteins promotes apoptosis of tumor cells | HCT-15 and SNU449 cells | 4.25, 42.5, and 425 nmol/mL | In vitro | [16] | |
| Inducing apoptosis | AOM-injected rats | 200 mg/kg | In vivo | [19] | |
| Decreased expression of c-Myc and MCP-1mRNA | Apc-mutant Min mice | 250 and 500 ppm | In vivo | [20] | |
| Inhibiting the growth of tumor cells | SMMC-7721 cells | IC50 = 24.42 µg/mL | In vitro | [21] | |
| Inducing apoptosis | HepG2 cells | IC50 = 60 μM | In vitro | [22] | |
| Inhibiting the activity of hexokinase-2 | Hepatocellular carcinoma cells | 25, 50, and 100 μM | In vitro | [23] | |
| Through the induction of xenobiotic enzymes | Aflatoxin B1 induced liver cancer rat | 50 mg/kg | In vivo | [24] | |
| Inducing apoptosis | MCF-7 and MDA-MB-231 cells | 1, 5, and 10 μM | In vitro | [28] | |
| Inhibiting the expression of p53 and p21 and activating the endogenous pathway | Panc-28 cells | IC50 = 42.4 μM | In vitro | [30] | |
| Inhibition of Wnt5/β-catenin pathway | IOMM-Lee and CH157MN cells | 25 μM | In vitro | [31] | |
| Inhibiting tumor proliferation | Lung cancer A549 cells | IC50 = 82.5 μM | In vitro | [32] | |
| Inhibiting the growth of tumor cells and promoting apoptosis | HeLa cells | 50 μM | In vitro | [33] | |
| Inhibiting the efflux of P-GP substrate rhodamine 123 | Caco-2 and CEM/ADR5000 cells | 20 μM | In vitro | [35] | |
| Increasing the expression of miR-216a-3p | MCF-7 and MDA-MB-231 cells | 5, 10, and 20 µM | In vitro | [36] | |
| Promoting the nuclear-cytoplasmic translocation of YAP | HeLa and Cervical carcinoma cell lines (C33A) cells | 5, 10, and 20 µM | In vitro | [37] | |
| Anti-inflammatory and analgesic activity | Inhibiting the proliferation of CD4+ T-cells | Transgenic mice | 200 mg/kg | In vivo | [38] |
| Inhibiting the activity of p38 MAP kinase in cells | Human aortic smooth muscle cells | 12.5, 25, and 50 µM | In vitro | [39] | |
| Decreasing serum AGEs, TNF- α, and MDA levels | Male albino rats | 50 mg/kg | In vivo | [40] | |
| Inhibition of NO production | RAW264.7 macrophages | IC50 = 231.4 µM | In vitro | [41] | |
| Decreasing the expression of iNOS gene | Wistar rats hepatocytes | IC50 = 16 µM | In vitro | [42] | |
| Inhibiting activation of NF-κB p65 | C57BL/6 mice | 50 mg/kg | In vivo | [44] | |
| Regulation of TLR4/NF-κB pathway | ALI mice | 10 mg/kg (ip) | In vivo | [45] | |
| Decreasing the mRNA expression level of IL-1 β, neutrophil chemoattractant 1 (CINC-1) and mucin gene (MUC5B, MUC5AC) | Airway inflammation Wistar rat | 20 µM (6mL) | In vivo | [46] | |
| Decreasing the mRNA expression of IL-2, IL-17a, TNF- α, and IFN- γ, and inhibiting the growth of T lymphocytes | BALB/c mice and CD3+ T cells | 5, 10, and 20 mg/kg, and 0.1, 1, 10, and 100 uM, respectively | In vivo and In vitro | [47] | |
| Regulating metabolic pathways | NBP male Wistar rats | 3.402 g/kg | In vivo | [48] | |
| Antibacterial, antiviral and anti-insect activities | Inhibiting proliferation | Xanthomonas sp.SK12; X. campestris pv. Compestris KC94-17-XCC; X. oryzae pv. oryzae KX019-XCO; X. campestris pv. Vesicatoria YK93-4-XCV; |
MIC = 15.62, 31.25, 31.25, and 62.5 µg/mL | In vitro | [57] |
| Combination with DapF and MurA | Acinetobacter baumannii | 25, 50, 75, and 100 µL | In vitro | [58] | |
| Inhibition of biofilm formation and TTSS | E. Coli O157:H7 | 6.25, 12.5, 25, 50, and 100 µg/mL | In vitro | [60] | |
| Inhibiting cell–cell signaling and biofilm formation | Escherichia coli, Vibrio harveyi | 6.25, 12.5, 50, and 100 mg/mL | In vitro | [61] | |
| Inhibition of HIV-1 protease activity | HIV-1 | EC50 = 60.0 µM | In vitro | [62] | |
| Anti-HSV activities | HSV-1 and HSV-2 | 100 µg/mL | In vitro | [64] | |
| Inhibiting the expression of HTLV-1 Tax/rex and HIV-1 gag | HTLV-1 infected cells; HIV-1 infected cells | IC50 = 1.07 and 0.92 µg/mL, respectively | In vitro | [65] | |
| Inhibition of growth and development | New ring-stage P. falciparum parasites | IC50 = 2.7 µM | In vitro | [66] | |
| Nematocidal toxicity | Meloidogyne incognita | LC50 = 197.37 µg/mL | In vitro | [67] | |
| Antiparasitic activity | Mice harboring Schistosoma mansoni | 50 and 100 mg/kg | in vivo | [68] | |
| Antioxidant activity | Reducing the accumulation of fatty acid oxidation products | Syrian Golden Hamsters plasma | 10 µM | In vitro | [73] |
| Increasing plasma antioxidant status | Orchidectomized male rats | 200 mg/kg | In vivo | [85] | |
| Reducing MDA and GSH-Px levels, increasing SOD, GSH-Px activity and T-AOC capability | Natural aging SD rats | 50 and 150 mg/kg | In vivo | [74] | |
| Liver protection activity | Down-regulation of TLR signaling pathway | (I/R) liver injury rat | 100 mg/kg | In vivo | [79] |
| Reducing inflammation and oxidative stress | D-GalN- induced liver injury rat | 50 and 100 mg/kg | In vivo | [80] | |
| Other pharmacological activity | Enhancing the expression of neuroprotective proteins | Rat cortical cells | 0.05 and 0.1 µM | In vitro | [84] |
| Protecting nerve cells | Natural apolexis SD rats | 50 and 150 mg/kg | In vivo | [74] | |
| Preserving bone calcium concentration and increasing antioxidant status | Orchidectomized male rats | 200 mg/kg | In vivo | [85] | |
| Increasing bone mineral density and osteoblast differentiation | Ovariectomised rats and MC3T3-E1 cells | 250 mg/kg, and 5, 10, 20, and 40 µM, respectively | In vivo and in vitro | [87] | |
| Inhibiting the differentiation of adipocytes and increase the level of lipid metabolism genes | Mouse Preadipocyte (3T3-L1) cells and Diet-induced obese mice | 30, 50, and 100 mg/mL, and 100 mg/kg, respectively | In vitro and in vivo | [90] | |
| Inhibition of adeno-kinase activity | Balb/c inbred mice | 5, 10, and 20 mg/kg | In vivo | [91] | |
| Mediated IgE suppression | Human B-cell line (U266) cells | 1.25, 2.15, 5, 10, and 20 µM | In vitro | [92] | |
| Inhibition of arginase activity | Rat aortic smooth muscle cells | 25 and 50 µM | In vitro | [93] | |
| Reducing inflammation and oxidative stress | Pulmonary fibrosis mice and MLE-12 cells | 25 and 50 mg/kg, and 3, 10, and 30 µM, respectively | In vivo and in vitro | [94] | |
| Inhibiting OST pathway | T lymphocytic line (3T3-L1) cells | 200, 400, 600, and 800 µM | In vitro | [96] |