Protective effects of osthole against inflammation induced by lipopolysaccharide in BV2 cells

Abstract

Inflammation and oxidative stress are implicated in the development of neurodegenerative diseases. Osthole is a compound that is extracted from She Chuang Zi, which is a type of traditional Chinese medicine. Osthole has previously been demonstrated to exhibit anticancer activities and has a low toxicity. However, to the best of our knowledge, the anti‑inflammatory effects of osthole in microglial cells have not been investigated extensively. The aim of the present study was to investigate the potential protective effects of osthole against inflammation induced by lipopolysaccharide (LPS) in microglial cells. The present study employed LPS‑stimulated BV2 mouse microglia to establish an inflammatory cell model and to investigate the anti‑inflammatory effects of osthole. Cells were pretreated with osthole for 1 h prior to LPS (10 µg/ml) stimulation. At 6 h after the addition of LPS, alterations in the levels of inflammatory factors, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑1β, were determined by ELISA. Furthermore, at 24 h after the addition of LPS, western blot analysis was performed to analyze the alterations in the protein expression of nuclear factor‑κB (NF‑κB) p65, phosphorylated‑NF‑κB p65, nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase (HO)‑1. The results demonstrated that the secretion of the inflammatory cytokines TNF‑α, IL‑6 and IL‑1β by LPS‑stimulated BV2 cells was significantly reduced by osthole treatment. Simultaneously, osthole treatment inhibited the LPS‑induced activation of the NF‑κB signaling pathway. In addition, osthole upregulated the expression of Nrf2 and HO‑1 in a dose‑dependent manner. Based on these results, osthole may exhibit anti‑inflammatory effects via the NF‑κB and Nrf2 pathways, indicating that osthole has the potential to be developed into an effective anti-inflammatory drug.

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

“…Osthole protected against Ang II-induced apoptosis of rat aortic endothelial cells through suppression of NF-κB and activation of Nrf2 and its downstream antioxidant genes and effectively inhibited Keap1, denoting its potential therapeutic effect against vascular injury [244]. In another study, osthole protected against LPS-induced inflammation in BV2 cells via NF-κB suppression and upregulation of the Nrf2/HO-1 pathway dose dependently [245]. Additionally, osthole exerted neuroprotective effects against global cerebral I/R injury by reducing oxidative stress via the upregulation of the Nrf2/HO-1 signaling pathway [246].…”

Phytochemistry, Ethnopharmacology, Pharmacokinetics and Toxicology of Cnidium monnieri (L.) Cusson

“…Osthole (100 and 200 mg/kg) demonstrated protective effects for sepsis-induced acute lung lesions via suppressing the inflammatory reaction, oxidative stress, and cell apoptosis [126]. From in vitro studies, osthole (4, 7 and 10 µg/mL) could shield inflammatory BV2 cells from inflammation-induced by lipopolysaccharide stimulation in the mechanism of inhibition of NF-κB and Nrf2 signaling pathways [127]. Osthole (12.5-100 µmol/L) could dramatically suppress the production of NO, IL-6 and TNF-α and other inflammatory cytokines.…”

“…Anti-fatty liver effect Osthole 10, 20, and 40 mg/kg for 6 weeks via gavage In vivo [117] Anti-fatty liver effect Osthole 10, 20, and 40 mg/kg for 6 weeks via gavage In vivo [118] Anti-fatty liver effect Osthole 0.1 mL/10 g body weight per day for 4 weeks via gavage In vivo [119] Anti-fatty liver effect Osthole 12.5, 25, 50, and 100 µmol/L In vitro [120] Anti-fatty liver effect Osthole 10, 20, and 40 mg/kg for 4 weeks via oral administration In vivo [121] Anti-inflammatory effect Osthole 50 mg/kg via oral administration for 7 days In vivo [122] Anti-inflammatory effect Osthole 10 and 30 mg/kg In vivo [123] Anti-inflammatory effect Osthole 10, 20, and 30 mg/kg via abdominal injection In vivo [124] Anti-inflammatory effect Cnidium Lactone Micro 2, 4, and 8 mg/mL In vivo [125] Anti-inflammatory effect Peroxyauraptenol, auraptenol Peroxyauraptenol:10 µM Auraptenol:100 µM In vitro [126] Anti-inflammatory effect Osthole 40 mg/kg for 4 days via gavage In vivo [127] Anti-inflammatory effect Osthole 100, 200 mg/kg twice a day with 12 h interval via abdominal injection In vivo [128] Anti-inflammatory effect Osthole 4, 7, and 10 µg/mL In vitro [129] Anti-inflammatory effect Osthole 12.5-100 µmol/L In vitro [130] Anti-inflammatory effect Osthole 10 µg/mL In vitro [131] Anti-inflammatory effect 17 Chemical compounds isolated from CMC with voucher number (CM-201010) IC 50 ≤ 7.31 µg/mL for 3 -O-methylmurraol, murraol, xanthotoxin, imperatorin, cnidimol A, IC 50 ≤ 7.83 µg/mL for osthenol, peroxyauraptenol, demethylauraptenol, bergapten, cnidimol A…”

The Chemical Compositions of Angelica pubescens Oil and Its Prevention of UV‐B Radiation‐Induced Cutaneous Photoaging

“…Both in vivo and in vitro studies have also shown that Angelica pubescens has effective analgesic and bactericidal effects . Among the components of the herb, ‘osthole’ has been reported as an active component of the anti‐inflammatory action . In addition, Angelica pubescens contains substantial amounts of antioxidants that protect cell components from free radical‐induced damage .…”

“…[10] Among the components of the herb, 'osthole' has been reported as an active component of the anti-inflammatory action. [11] In addition, Angelica pubescens contains substantial amounts of antioxidants that protect cell components from free radical-induced damage. [12] However, to the best of our knowledge, the essential oil extracted from the dry rhizomes of Angelica pubescens by hydrodistillation (AO) has not been investigated for its pharmacological activity, particularly with respect to anti-photoaging effects for development of skin care products.…”