In vitro Anti-Inflammatory and Anti-Oxidative Stress Activities of Kushenol C Isolated from the Roots of Sophora flavescens

Abstract

Kushenol C (KC) is a prenylated flavonoid isolated from the roots of Sophora flavescens aiton. Little is known about its anti-inflammatory and anti-oxidative stress activities. Here, we investigated the anti-inflammatory and anti-oxidative stress effects of KC in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The results demonstrated that KC dose-dependently suppressed the production of inflammatory mediators, including NO, PGE2, IL-6, IL1β, MCP-1, and IFN-β in LPS-stimulated RAW264.7 macrophages. The study demonstrated that the inhibition of STAT1, STAT6, and NF-κB activations by KC might have been responsible for the inhibition of NO, PGE2, IL-6, IL1β, MCP-1, and IFN-β in the LPS-stimulated RAW264.7 macrophages. KC also upregulated the expression of HO-1 and its activities in the LPS-stimulated RAW264.7 macrophages. The upregulation of Nrf2 transcription activities by KC in the LPS-stimulated RAW264.7 macrophages was demonstrated to be responsible for the upregulation of HO-1 expression and its activity in LPS-stimulated RAW264.7 macrophages. In HaCaT cells, KC prevented DNA damage and cell death by upregulating the endogenous antioxidant defense system involving glutathione, superoxide dismutase, and catalase, which prevented reactive oxygen species production from tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The upregulated activation of Nrf2 and Akt in the PI3K-Akt signaling pathway by KC was demonstrated to be responsible for the anti-oxidative stress activity of KC in HaCaT cells. Collectively, the study suggests that KC can be further investigated as a potential anti-inflammatory candidate for the treatment of inflammatory diseases.

Comparation of Anti‐Inflammatory and Antioxidantactivities of Curcumin, Tetrahydrocurcuminand Octahydrocurcuminin LPS‐Stimulated RAW264.7 Macrophages

“…LPS serving as an important component is present in the cell wall of Gram-negative bacteria, which can be widely used to stimulate macrophages to induce inflammation through binding to receptors on the membrane of macrophages [36]. LPS promotes macrophages to release numerous proinflammatory mediators and cytokines [37]. In addition, oxidative stress is also an important factor of boosting inflammation.…”

Kushenol C Prevents Tert-Butyl Hydroperoxide and Acetaminophen-Induced Liver Injury

“…Sophora flavescens is also used in the traditional Chinese medicine for the treatment of gastrointestinal hemorrhage, skin diseases and pyretic stranguria, and has been confirmed in many studies to have antitumor, antiviral and anti-inflammatory properties [ 1 , 2 , 3 , 4 ]. Phytochemical studies have also confirmed the presence of quinolizidine alkaloids and prenylated flavonoids, which, interestingly, have demonstrated pharmacological activities as antitumor, antiviral and anti-inflammatory agents, thus confirming the pharmacological benefits of Kushen as depicted in traditional Chinese medicine [ 5 , 6 , 7 ]. One of the prenylated flavonoids isolated from Kushen is Kushenol C (KC).…”

“…One study reported that KC possesses greater antioxidant activities, by preventing the generation of reactive oxygen species in a liver cell line, compared to other prenylated flavonoids such as kushenol A, 8-prenylkaempferol, formononetin and 8-prenylnaringenin isolated from the roots of S. flavescens [ 8 ]. We previously reported that KC inhibited the activation of signal transducer and activator of transcription 1 (STAT1), STAT6, and nuclear factor kappa B (NF-κB) in a stimulated macrophage cell line and upregulated the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Akt in the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway in a skin cell line, thereby conferring anti-inflammatory and antioxidative stress properties to KC [ 7 ]. KC was shown to inhibit the activities of cytochrome P450, the drug-metabolizing enzyme and drug transporter that plays a central role in the metabolism and elimination of drugs in the liver [ 9 ].…”

α‑rhamnrtin‑3‑α‑rhamnoside exerts anti‑inflammatory effects on lipopolysaccharide‑stimulated RAW264.7 cells by abrogating NF‑κB and activating the Nrf2 signaling pathway

“…Immunohistochemistry analysis was performed as previously described ( 22 ). The primary antibodies used were as follows: Anti-NLRC3 (1:500), anti-TRAF6 (1:500) and anti-NF-κB p65 (1:500), and an HRP-conjugated anti-rabbit antibody was used as the secondary antibody (Abcam; cat.…”