Notoginsenoside R1 Suppresses Inflammatory Signaling and Rescue Renal Ischemia-reperfusion Injury in Experimental Rats

Abstract

Departmental sources Background:Notoginsenoside R1 (NR) is a major dynamic constituent of Panax notoginseng found to possess anti-inflammatory activity against various inflammatory diseases. However, its protective effects against renal ischemiareperfusion (I/R) injury have not been elucidated. In male Wistar rats, we induced I/R under general anesthesia by occluding the renal artery for 60 min, followed by reperfusion and right nephrectomy. Material/Methods:Rats were randomized to 4 groups: a sham group, an I/R group, an NR-pretreated (50 mg/kg) before I/R induction group, and an NR control group. All animals were killed at 72 h after I/R induction. Blood and renal tissues were collected, and histological and basic renal function parameters were assessed. In addition, levels of various kidney markers and proinflammatory cytokines were measured using RT-PCR, ELISA, and immunohistochemistry analysis. Results:After I/R induction, the onset of renal dysfunction was shown by the elevated levels of serum urea, creatinine levels, and histological evaluation, showing a 2-fold increase in the renal failure markers kim-1 and NGAL compared to control rats. Rats pretreated with NR before I/R induction had significantly better renal functions, with attenuated levels of oxidative markers, restored levels of inflammatory cytokines such as tumor necrosis factor-a (TNF-a), tumor growth factor-b1 (TGF-b1), INF-g, and IL-6, and increased anti-inflammatory cytokine levels (IL-10) compared to I/R-induced rats. Conclusions:NR suppressed I/R-induced inflammatory cytokines production by suppressing oxidative stress and kidney markers, suggesting that NR is a promising drug candidate for prevention, progression, and treatment of renal dysfunction.

COVID-19, cytokines, inflammation, and spices: How are they related?

“…PNS imparted protective roles against human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) and DSS-induced colitis via regulating the levels of caspase-3, 8, 9, and PI3K/AKT signaling pathway respectively [ [284] , [285] ]. Further, Notoginsenoside R1 (NR), isolated from Panax notoginseng , imparted protective effects against the rat model of renal ischemia-reperfusion (I/R) injury via downregulation of certain oxidative and inflammatory factors such as TNF-α, TGF-ß1, IFN-γ, and IL-6 [ 286 ]. Ginsenoside Rg3 (GRg3) induces anti-inflammatory effects and ameliorates RA in vivo via the CD4 + CD25 + Foxp3 + Treg cells [ 287 ].…”

Notoginsenoside R1 attenuates oxidative stress‐induced osteoblast dysfunction through JNK signalling pathway

“…In animal studies, NGR1 has been proven to have various effective therapeutic functions, such as neuroprotection, anti‐diabetes, certain organ protection, bone metabolism regulation, anti‐cancer and osteoporosis, which can be largely attributed to its potent antiapoptotic, anti‐inflammatory and anti‐oxidative properties 13,51 . NGR1 has been shown to effectively protect various types of cells from oxidative damages triggered by other pathological factors, such as AGEs (advanced glycation end products), 16 ischaemia‐reperfusion injury 52 and oxidized low‐density lipoprotein 53 . NGR1 can decrease ROS production and prevent protein and lipid peroxidation by improving the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione 15,52,54 .…”

“…NGR1 has been shown to effectively protect various types of cells from oxidative damages triggered by other pathological factors, such as AGEs (advanced glycation end products), 16 ischaemia‐reperfusion injury 52 and oxidized low‐density lipoprotein 53 . NGR1 can decrease ROS production and prevent protein and lipid peroxidation by improving the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione 15,52,54 . As expected, our current study also showed that NGR1 antagonized the H 2 O 2 ‐induced OS, restored cell viability and decreased apoptosis rate of osteoblast (Figure 1A–C).…”

Mechanisms and Efficacy of Chinese Herbal Medicines in Chronic Kidney Disease

“…Panax notoginseng (Burkill) F.H.Chen and panax notoginseng saponins could protect kidney from diabetes via the mechanism of upregulating SIRT1, therefore activating antioxidant proteins and inhibiting inflammation by decreasing the inflammatory cytokines ( Du et al, 2016 ). Notoginsenoside R1 is a promising drug for the prevention and treatment of renal insufficiency through inhibition of the production of inflammatory cytokines induced by ischemic reperfusion and inhibition of oxidative stress ( Fan et al, 2020 ). In vitro , notoginsenoside R1 protects human renal proximal tubular epithelial cells from lipopolysaccharide (LPS)-induced inflammatory injury by upregulating miR-26a and inactivating the NF-κB pathway ( Liu et al, 2019b ).…”