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. 2024 Mar 25;11:1389329. doi: 10.3389/fmed.2024.1389329

Table 3.

Summary of chemical compounds targeting the PI3K/AKT pathway for liver fibrosis alleviation.

Compounds In vitro activity In vivo activity Activity in human References
Adiponectin-based agonist called JT003 Y - HEK293 cells, HepG2 cells, and LX2 cells Yes - NASH mice Not assessed (105)
Aspirin, ticlopidine, and cilostazol Not assessed Yes - fisher 344 male rats Not assessed (106)
FTY720 Not assessed Yes - male Sprague–Dawley rats Not assessed (107)
Hesperetin Yes - HepG2 cells Yes - rats Not assessed (33)
Maltol Not assessed Yes - mice Not assessed (108)
A6 Not assessed Yes - mice Not assessed (109)
Ruangan granules (RGGs) Not assessed Yes - rat Not assessed (110)
Salvianolic acid A (SA-A) Not assessed Yes - rat Not assessed (111)
Salvianolic acid B (SAB) Not assessed Yes - male C57 mice Not assessed (66)
Simvastatin Not assessed Yes - male Wistar rats Not assessed (112)
Doxazosin Yes - HCS-LX-2 Yes - mouse Not assessed (73)
Artesunate (ART) HSC- LX-2 Not assessed Not assessed (113)
5-BDBD Not assessed Yes - C57BL/6 J mice Not assessed (114)
Nilotinib Yes - human HCS Yes - rat Yes (89)
Idazoxan Yes - LX-2 Yes - rat Not assessed (67)
Celecoxib Yes - human HSCs Yes - rat Not assessed (115)
Tenofovir disoproxil fumarate (TDF) Not assessed Not assessed Chronic hepatitis B (116)
Octreotide Yes - HSCs Yes - rat Not assessed (117)
JD5037 Not assessed Yes - rat Yes - liver fibrosis patients (118)
Imatinib mesylate (STI-571) Not assessed Yes - rat Assessed (119)
Pyrazinamide (PZA) Not assessed Yes - Sprague–Dawley (SD) rats Not assessed (120)
Metformin Not assessed Yes - rats Not assessed (121)
Metformin Yes - Cell lines (PLCPRF5 cells) Yes - NOG mice Yes - hepatocellular carcinoma (HCC) patients after liver transplantation (122)
Propranolol Yes - LX-2 Yes - mouse Not assessed (123)
Rapamycin Not assessed Yes - rats Not assessed (124)
Sorafenib Not assessed Yes - rats Not assessed (125)
Rimonabant Not assessed Yes - rats Not assessed (126)
1,8-cineole Not assessed Yes - knockout mice Not assessed (127)
Actein Not assessed Yes - mice Not assessed (128)
S-adenosylmethionine (SAM) Yes - human colon cancer cells Yes - MAT1A-KO mice Not assessed (129)
Sirolimus Not assessed Yes - PCK rats Not assessed (56)
Vevorisertib Yes - Hep3B, HepG2, HuH7, and PLC/PRF cell lines Yes - rats Not assessed (130)
Quercetin Not assessed Yes - mice Not assessed (131)
Resveratrol (RSV) Yes - HSC-T6 cells Yes - rat Not assessed (132)
Dihydromyricetin (DHM) Not assessed Yes - mice Not assessed (133)
Hemistepsin A (HsA) Yes - HSCs Yes - male ICR mice Not assessed (134)
Asiatic acid (AA) isolated from Centella asiatica Not assessed Yes - Rat Not assessed (135)
Cytisine derivatives, including compound 5f Human LX-Cell Not assessed Not assessed (136)
Atractylenolide III (ATL III) Not assessed Yes - mice Not assessed (137)
Tormentic Acid (TA) Not assessed Yes - Rat Not assessed (138)
Taxifolin Not assessed Yes - mouse Not assessed (139)
Honokiol Yes - AML-12 hepatocytes Yes - mouse Not assessed (140)
Hovenianin A Yes - HSCs Not assessed Not assessed (141)
Epigallocatechin-3-gallate (EGCG) Yes - human HSC-XL-2 Yes - bile duct-ligated (BDL) rats. Not assessed (142)
Isovitexin Not assessed Yes - mice Not assessed (143)
Alpha mangostin Yes - HSC Not assessed Not assessed (144)
Hesperitin derivative-11 (HD-11) Yes - HSC-T6 cells Yes - rats Not assessed (145)
Matrine derivative WM130 Yes - HSC-IL-2 Yes - rats Not assessed (146, 147)