Korean Red Ginseng Suppresses the Expression of Oxidative Stress Response and NLRP3 Inflammasome Genes in Aged C57BL/6 Mouse Ovaries

Abstract

Female infertility and subfertility have been increasing in prevalence worldwide. One contributing factor is ovarian function, which is highly age-dependent. Korean red ginseng is widely used as an herbal medicine and has many beneficial properties. We aimed to determine the effect of the Korean red ginseng saponin fraction (KRGSF) on ovarian function in female C57BL/6 mice. Ovaries were isolated from 6- and 12-month-old female mice and treated with KRGSF, and then RNA was extracted and microarray analysis was performed. The expression of key genes was subsequently verified using quantitative RT-PCR. Aging markedly increased the expression of genes encoding oxidative stress factors and NLRP3 inflammasome components, but the expression of these genes was significantly reduced by KRGSF treatment. Thus, the reduction in ovarian health with age is associated with greater oxidative stress response and inflammation, but KRGSF treatment may limit these age-related changes.

The role of oxidative stress in ovarian aging: a review

“…A previous study showed that the levels of the products of OS damage (carbonylated and nitrated proteins) and inflammatory markers (TNF-α, IL-1β) were significantly higher in the ovaries of aged mice than in younger mice [ 39 ]. Ovarian RNA transcriptome analysis further revealed that OS-related proteins (Nrf2, SOD2, CAT, GSH-px1) and genes encoding NLRP3 inflammatory vesicles could be used as key biomarkers to differentiate between young and aging mice [ 40 ]. A variety of models of functional ovarian damage were shown to exhibit high levels of inflammatory factors and OS markers [ 41 , 42 ].…”

Panax ginseng as a potential therapeutic for neurological disorders associated with COVID-19; Toward targeting inflammasome

“…Saponins from P. japonicus treatment have been shown to alleviate high-fat diet (HFD)-induced recognitive impairment and depression-like behaviors in HFD-fed Balb/c mice, which could partly be due to the ability of saponins from P. japonicus to mitigate neuroinflammation through inhibition of NLRP3 inflammasome (NLRP3, caspase-1, ASC, and IL-1β) and upregulation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors signaling pathway [ 71 ]. Saponin fraction of KRG reveals an anti-inflammatory effect by ameliorating the mRNA expression of genes encoding NLRP3 inflammasome components (Nlrp3, Asc, pro-IL-1β, IL-1β, pro-caspase-1, and caspase-1) in cultured ovaries from aged C57BL/6 mice [ 72 ] ( Table 1 ). Taken together, these findings indicate that saponin fraction may be used as a potential agent for the treatment of infection and inflammation-related neurological diseases.…”

Potential benefits of ginseng against COVID-19 by targeting inflammasomes

“…Rb1, Rg1, Rg2, Rg3, Rg5, Rd, Re, Rh1, 25-OCH 3 -PPD, and compound K (CK) in Panax ginseng inhibit NLRP3 inflammasome stimulation, leading to suppressed inflammatory responses and multiple disease conditions, such as obesity, gouty arthritis, atherosclerosis , non-alcoholic fatty liver disease, liver injury, hyperlipidemia, type I diabetes, myocardial hypertrophy and dysfunction, cerebral ischemia and reperfusion injury, colitis, hepatic fibrosis, sepsis, neuronal damage, kidney injury, and cognitive deficits [ [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] ]. Korean red ginseng (KRG) extract and KRG saponin fraction in Panax ginseng also inhibited inflammatory responses by inhibiting NLRP3 inflammasome activation in macrophages, monocytes, sepsis mice, and aging mice [ 65 , 74 ]. Chikusetsu saponin IVa, a major active triterpenoid saponin in Panax japonicus , inhibited NLRP3 inflammasome activation, hence ameliorating obesity and neuroinflammation in macrophages, adipocytes, primary neurons, and postoperative cognitive dysfunction rats [ 75 , 76 ].…”