Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects

Abstract

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural non-toxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun N-terminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Keywords: 5-FU, 5-fluorouracil; ADM, Adriamycin; ALT, alanine aminotransferase; AMO, Atractylodes macrocephala volatile oil; AMPK, AMP-activated protein kinase; ARE, antioxidant response element; AST, aspartate aminotransferase; BMNC, bone marrow nucleated cells; CIA, chemotherapy-induced hair loss; CK, compound K; CP, cisplatin; CY, cyclophosphamide; CYP2E1, Cytochrome P450 E1; Chemotherapy; DAC, doses of docetaxel, doxorubicin as well as cyclophosphamide; ERG, enzyme-treated eRG; ERK, extracellular signal-regulated kinases; FBG, fermented black ginseng; FRG, probiotic-fermented eRG; FRGE, fermented red ginseng extract; GM-CSF, granulocyte macrophage colony-stimulating factor; Ginsenosides; HEI-OC1, House Ear Institute-Organ of Corti 1; HO-1, heme oxygenase-1; HSPCS, haematopoietic stem and progenitor cells; IL, interleukin; JNK, c-jun N-terminal kinase; KG-KH, the mixture of ginsenosides Rk3 and Rh4; LLC-PK1, porcine renal proximal epithelial tubular; LSK, Lin−Sca-1+c-kit+; MAPK, mitogen-activated protein kinase; MDA, malonaldehyde; MEK, mitogen activated protein kinase; MKK4, mitogen activated protein kinase kinase 4; Mechanism; NF-κB, nuclear factor-kappa B p65; NQO, NAD (P) H quinone oxidoreductase; Nrf2, nuclear factor erythroid related factor 2; PG; PG, Panax ginseng; PGFR, PG flower; PGLF, PG leaf; PGRT, PG root; PGS, PG total saponins; PGSD, PG seeds; PGSM, PG stem; PI3K, phosphatidylinositol 3-kinase; PPD, protopanaxadiol; PPT, protopanaxatriol; Pharmacological effects; RG, red ginseng; RGE, red ginseng extract; ROS, reactive oxygen species; SREBP-1, sterol regulatory element binding protein 1; Side effects; TNF-α, tumor necrosis factor-α; eRG, 50% ethanol-extracted RG; mTOR, mammalian target of rapamycin; wRG, water-extracted RG.