Isoastragaloside I inhibits NF-κB activation and inflammatory responses in BV-2 microglial cells stimulated with lipopolysaccharide

Abstract

The excessive activation of microglia in many neurodegenerative diseases is detrimental to neuronal survival. Isoastragaloside I (ISO I) is a natural saponin molecule found within the roots of Astragalus membranaceus, a famous traditional Chinese medicine. In the present study, the anti‑inflammatory effects and the mechanisms of action of ISO I on activated BV-2 cells stimulated with lipopolysaccharide (LPS) were investigated. ISO I dose‑dependently inhibited the excessive release of nitric oxide (NO) and tumor necrosis factor (TNF)-α in the LPS-stimulated BV-2 cells. Moreover, it decreased the production of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), and mitigated the gene expression of interleukin (IL)-1β, TNF-α and iNOS induced by LPS. Further experiments revealed that ISO I decreased the phosphorylation levels of nuclear factor-κB (NF-κB), and suppressed its nuclear translocation and transactivation activity. In addition, it inhibited the activation of signaling pathway molecules, such as PI3K, Akt and mitogen-activated protein kinases (MAPKs). Taken together, our findings suggest that ISO I prevents LPS-induced microglial activation probably by inhibiting the activation of the NF-κB via PI3K/Akt and MAPK signaling pathways, indicating its therapeutic potential for neurological diseases relevant to neuroinflammation.

Metabolomic Determination of Specialized Metabolites Using Liquid Chromatography-Tandem Mass Spectrometry in the Traditional Chinese Medicines Astragali Radix and Hedysari Radix

“…33 Moreover, formononetin, 34 calycosin, 35 and soyasaponin I 36 have been reported to significantly inhibit the NO production; therefore, the active ingredients of both AR and HR were considered. Ononin, 37 astragaloside IV, 38 and isoastragaloside I 39 in AR and indolelactic acid 40 and afromosin 41 in HR have also reported the function in the NO production inhibition, which may be related to the anti-inflammatory activity of AR and HR.…”

Screening of immune cell activators from Astragali Radix using a comprehensive two-dimensional NK-92MI cell membrane chromatography/C18 column/time-of-flight mass spectrometry system

“…They are typical cycloartane triterpene glycoside structures with the same parent nucleus as cycloastragalus alcohol (tetracyclic triterpenoids) and several glycoside groups [ 25 ]. It has been reported that tetracyclic triterpenoids have pharmacological activity by enhancing nonspecific immune responses and reversing the immunosuppressive effect of chemotherapeutic drugs to achieve antitumor effects [ 26 ]. Astragaloside IV, a representative component of cycloastragalus alcohol saponins in AR, has dual activities as astragalus polysaccharides and terpenes [ 27 , 28 ].…”

Anti-Aging of the Nervous System and Related Neurodegenerative Diseases With Chinese Herbal Medicine

“…In addition, Astragaloside IV promotes mitochondrial autophagy, thus reducing the accumulation of damaged mitochondria and the production of mitochondrial reactive oxygen species. 14,[96][97][98][99][100][101][102][103] To conclude, the mechanism of Astragali Radix against aging-related neurodegenerative diseases mainly involves anti-neurotoxicity, anti-neuroinflammation and antioxidation. Astragali Radix is a dietary herb, applied with many potential signal regulations, including neurotransmitters and receptors, anti-inflammatory activity, inhibiting amyloid aggregation, inducing myelin repair and neurogenesis, and activating signal pathways related to neurological diseases.…”