Noble 3,4-Seco-triterpenoid Glycosides from the Fruits of Acanthopanax sessiliflorus and Their Anti-Neuroinflammatory Effects

Abstract

Acanthopanax sessiliflorus (Araliaceae) have been reported to exhibit many pharmacological activities. Our preliminary study suggested that A. sessiliflorus fruits include many bioactive 3,4-seco-triterpenoids. A. sessiliflorus fruits were extracted in aqueous EtOH and fractionated into EtOAc, n-BuOH, and H2O fractions. Repeated column chromatographies for the organic fractions led to the isolation of 3,4-seco-triterpenoid glycosides, including new compounds. Ultra-high-performance liquid chromatography (UPLC) mass spectrometry (MS) systems were used for quantitation and quantification. BV2 and RAW264.7 cells were induced by LPS, and the levels of pro-inflammatory cytokines and mediators and their underlying mechanisms were measured by ELISA and Western blotting. NMR, IR, and HR-MS analyses revealed the chemical structures of the nine noble 3,4-seco-triterpenoid glycosides, acanthosessilioside G–O, and two known ones. The amounts of the compounds were 0.01–2.806 mg/g, respectively. Acanthosessilioside K, L, and M were the most effective in inhibiting NO, PGE2, TNF-α, IL-1β, and IL-6 production and reducing iNOS and COX-2 expression. In addition, it had inhibitory effects on the LPS-induced p38 and ERK MAPK phosphorylation in both BV2 and RAW264.7 cells. Nine noble 3,4-seco-triterpenoid glycosides were isolated from A. sessiliflorus fruits, and acanthosessilioside K, L, and M showed high anti-inflammatory and anti-neuroinflammatory effects.

Kuwanon T and Sanggenon a Isolated from Morus alba Exert Anti-Inflammatory Effects by Regulating NF-κB and HO-1/Nrf2 Signaling Pathways in BV2 and RAW264.7 Cells

“…In our previous study, moracin M had anti-inflammatory effect on alveolar macrophages, but our results showed a different pattern. However, since each cell has different characteristics, different activities may appear even with the same mechanism [38]. Therefore, as in the results of this paper, it was confirmed that moracin M had no anti-inflammatory activity in BV2 and RAW264.7 cells up to the treatment concentration.…”

Triterpenoids as Reactive Oxygen Species Modulators of Cell Fate

“…The acanthosessilioside triterpenoids are large molecules highly decorated with sugars, which improves their solubility properties, rendering them as promising preclinical candidates for further development against inflammatory and neuro-inflammatory disorders. 32 Other related steroidal glycosides with potential therapeutic value are the natural products isolated from the starfish Ogmaster capella (capelloside A, coscinasteroside B), which have been shown to reduce intracellular ROS levels in the LPS-activated murine macrophage RAW264.7 cell line, while showing little to no cytotoxicity toward normal cells at concentrations up to 100 μM, indicating the therapeutic index. 33 …”

“…The natural products 3,4-seco-triterpenoid glycosides, including acanthosessilioside K (a representative of their large family, compound 38 , Figure ) from Acanthopanax sessiliflorus ( Araliaceae ) fruits, have been reported to deactivate or reduce the expression of inflammation markers (NO, PGE2, TNF-α, IL-1β, IL-6, iNOS, and COX-2) in lipopolysaccharide (LPS)-activated BV2 and RAW264.7 murine cells. The acanthosessilioside triterpenoids are large molecules highly decorated with sugars, which improves their solubility properties, rendering them as promising preclinical candidates for further development against inflammatory and neuro-inflammatory disorders . Other related steroidal glycosides with potential therapeutic value are the natural products isolated from the starfish Ogmaster capella (capelloside A, coscinasteroside B), which have been shown to reduce intracellular ROS levels in the LPS-activated murine macrophage RAW264.7 cell line, while showing little to no cytotoxicity toward normal cells at concentrations up to 100 μM, indicating the therapeutic index …”

Phytochemistry and Pharmacology of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S.Y.Hu: A Review

“…Triterpenoids and polyphenols in E. sessiliflorus have inhibited BV2 and RAW264.7 cells induced by lipopolysaccharides. These compounds effectively reduce the production of inflammatory mediators such as NO, PGE2, TNF- α , IL-1 β , and IL-6, thereby exerting potent anti-inflammatory effects [ 9 , 16 , 83 ]. Additionally, the root barks of E. sessiliflorus have been found to inhibit osteoclast differentiation activated by RANKL in bone marrow macrophages and prevent bone loss induced by ovariectomy [ 119 ].…”

“…These include monoterpenoids, sesquiterpenoids, and triterpenoids, as well as simple phenylpropanoids, lignans, coumarins, flavonoids, volatile oils, organic acids and their esters, nitrogenous compounds, quinones, phenolics, and carbohydrates. Notably, triterpenoids and lignans have gained significant attention in chemical composition research due to their remarkable potential for further research and development [ 6 , 7 , 8 , 9 ]. Since its approval as a new food resource by the Ministry of Health of the People’s Republic of China in 2008, E. sessiliflorus has become the foundation for a series of health products, such as tea, concentrated solutions, and wines, continuously entering the market.…”