A review on the protective effects of naringenin against natural and chemical toxic agents

Abstract

Naringenin (NRG), as a flavanone from flavonoids family, is widely found in grapefruit, lemon tomato, and Citrus fruits. NRG has shown strong anti‐inflammatory and antioxidant activities in body organs via mechanisms such as enhancement of glutathione S‐transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and catalase (CAT) activity, but reduction of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA). Furthermore, NRG anti‐apoptotic potential was indicated to be mediated by regulating B‐cell lymphoma (Bcl‐2), Bcl‐2‐associated X protein (Bax) and caspase3/9. Overall, these properties make NRG a highly fascinating compound with beneficial pharmacological effects. Based on the literature, NRG‐induced protective effects against toxicities produced by natural toxins, pharmaceuticals, heavy metals, and environmental chemicals, were mainly mediated via suppression of lipid peroxidation, oxidative stress (through boosting the antioxidant arsenal), and inflammatory factors (e.g., TNF‐α, interleukin [IL]‐6, IL‐10, and IL‐12), and activation of PI3K/Akt and MAPK survival signaling pathways. Despite considerable body of evidence on protective properties of NRG against a variety of toxic compounds, more well‐designed experimental studies and particularly, clinical trials are required before reaching a concrete conclusion. The present review discusses how NRG protects against the above‐noted toxic compounds.

Multiple Myeloma Inhibitory Activity of Plant Natural Products

“…However, in the case of naringenin racemization occurs in aqueous solutions [ 107 ]. Same as apigenin, naringenin showed anticancer activity via different mechanisms of action and additionally exhibited protective effects against natural and chemical toxic agents [ 108 ]. Additionally, for naringenin bioavailability is a major issue, which has been evaluated in several clinical trials [ 109 ].…”

Naringenin protects swine testis cells from bisphenol A‐induced apoptosis via Keap1/Nrf2 signaling pathway

“…NRG has shown a strong protection against apoptosis induced by several toxic chemicals via activation of Nrf2 signaling pathway and suppression of oxidative stress, 32,[50][51][52] for example, NRG inhibits hydrogen peroxide-induced SH-SY5Y cells injury and apoptosis through Nrf2/HO-1 signaling pathway, 51 and attenuates methylglyoxal-induced neurite damage and apoptotic death by Nrf2 signaling pathway, 52 and antagonizes HOinduced mitochondrial apoptosis through the Nrf2-dependent mechanism in SH-SY5Y cells. 53 Similar to these reports, here, we monitored oxidative stress by the levels of ROS, MDA, GPx, SOD, and CAT in BPA treated cells, and assessed apoptosis via flow analysis and expression of apoptosis-associated genes (Cytc, Caspase 9, Caspase 3, Bax and Bcl-2) (Figures 2-4), and additionally determining levels of Nrf2 signaling pathway-related genes (Figure 5), we observed that NRG not only inhibited BPA-induced oxidative stress and mitochondrial pathway apoptosis, but also activated Nrf2 signaling pathway, indicating that NRG alleviated BPA-induced mitochondrial pathway apoptosis in ST cells through activation of Nrf2 signaling pathway and suppression of oxidative stress.…”

“…Naringenin (NRG) is a dihydroflavonoid that is mainly found in fruits of Ruta graveolens L ., for example, grapefruit, tomatoes, grapes, and citrus. Studies have shown that NRG has a variety of functions, including antioxidant, free radical scavenging, anti‐inflammatory, antibacterial and anticancer, 29,30 and antioxidant has been reported to be a mechanism by which NRG antagonizes multiple diseases, for example, reproductive, cardiovascular and neurodegenerative diseases, 31,32 especially pathologies induced by chemical poison, including natural toxins, 33 heavy metals 34 and pesticide 35 …”

“…28 Naringenin (NRG) is a dihydroflavonoid that is mainly found in fruits of Ruta graveolens L., for example, grapefruit, tomatoes, grapes, and citrus. Studies have shown that NRG has a variety of functions, including antioxidant, free radical scavenging, anti-inflammatory, antibacterial and anticancer, 29,30 and antioxidant has been reported to be a mechanism by which NRG antagonizes multiple diseases, for example, reproductive, cardiovascular and neurodegenerative diseases, 31,32 especially pathologies induced by chemical poison, including natural toxins, 33 heavy metals 34 and pesticide. 35 Herein, to elucidate the toxic mechanism of BPA in male porcine reproductive organ and the antagonistic effect of NRG, we performed a molecular docking between NRG and Keap1, and determined oxidative damage and mitochondrial apoptosis, as well as the key genes in mitochondrial apoptosis and Keap1/Nrf2 signaling pathways.…”

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

“…Mitochondrial quality control can be acted in many forms including molecular, organellar and cellular levels. It’s worth noting that CAT, SOD and GSH-PX, as molecular-level oxidative stress defense mechanisms, can effectively decelerate the pace of oxidative damage to mitochondria ( Naraki et al, 2021 ). However, the ROS-scavenging system cannot completely prevent excessive ROS-mediated damage to mitochondria.…”