Abstract
Fifteen unreported compounds in Anemarrhena asphodeloides, iriflophene (3), hostaplantagineoside C (7), tuberoside G (8), spicatoside B (9), platycodin D (14), platycoside A (15), platycodin D2 (16), polygalacin D2 (17), platycodin D3 (18), isovitexin (20), vitexin (21), 3,4-dihydroxyallylbenzene-3-O-α-l-rhamnopyranosyl(1→6)-β-d-glucopyranoside (22), iryptophan (24), adenosine (25), α-d-Glucose monoallyl ether (26), together with eleven known compounds (1, 2, 4–6, 10–13, 19 and 23), were isolated from the rhizomes of Anemarrhena asphodeloides. The chemical structures of these compounds were characterized using HRMS and NMR. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit LPS-induced NO production in N9 microglial cells. Timosaponin BIII (TBIII) and trans-hinokiresinol (t-HL) exhibited significant inhibitory effects on the NO production in a dose-dependent manner with IC50 values of 11.91 and 39.08 μM, respectively. Immunoblotting demonstrated that TBIII and t-HL suppressed NO production by inhibiting the expressions of iNOS in LPS-stimulated N9 microglial cells. Further results revealed that pretreatment of N9 microglial cells with TBIII and t-HL attenuated the LPS-induced expression tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) at mRNAs and protein levels. Moreover, the activation of nuclear factor-κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were inhibited by TBIII and t-HL, respectively. Our findings indicate that the therapeutic implication of TBIII and t-HL for neurogenerative disease associated with neuroinflammation.
Highlights
Microglia, the specialized macrophages, are the major cellular source and regulate cerebral inflammatory reactions in the central nervous system (CNS) [1]
Phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor-κB (NF-κB) are the upstream signaling pathways to regulate the expressions of inflammatory mediators in microglia [8,9]
All compounds were characterized by the determination of purity, HRMS and NMR data. By comparison of their spectroscopic data with those reported in the literature, the chemical structures of the isolated compounds were established as 2,6,40 -trihydroxy-4-methoxybenzophenone (1), Zimoside A (2), Iriflophene (3), Anemarrhenasaponin II (4), Anemarrhenasaponin I (5), Anemarnoside B (6), Hostaplantagineoside
Summary
The specialized macrophages, are the major cellular source and regulate cerebral inflammatory reactions in the central nervous system (CNS) [1]. They can be over-stimulated during neuropathological conditions and neurodegenerative disorders, including multiple sclerosis [2], Parkinson’s disease [3] and Alzheimer’s disease [4]. The inductions of pro-inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin-6 and nitric oxide (NO), are indicators of microglial activation. Phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor-κB (NF-κB) are the upstream signaling pathways to regulate the expressions of inflammatory mediators in microglia [8,9]
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