1,10-Seco-Eudesmane sesquiterpenoids as a new type of anti-neuroinflammatory agents by suppressing TLR4/NF-κB/MAPK pathways

Tang, Jiang‐Jiang; Wang, Min-Ran; Dong, Shuai; Huang, Lan-Fang; He, Qiu-Rui; Gao, Jin‐Ming

doi:10.1016/j.ejmech.2021.113713

Cited by 29 publications

(17 citation statements)

References 42 publications

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“…However, the adduct OABL-GSH at the 5–20 μM had no influence on the H 2 O 2 -induced PC12 cells damage ( Fig. S2D ), which was similar to that derivatives with reduction or adduction of α-methylene motifs of OABL losing the effective activity of anti-neuroinflammation [ 35 ].…”

Section: Resultssupporting

confidence: 61%

“…1 A and Fig. S1B ) and low reduction in cell survival (less than 5%) at 20 μM [ 35 ]. Notably, ABL and OABL both showed sound blood-brain barrier (BBB) penetration capacity ( P e = 7.5 × 10 −6 cm/s for ABL and 12.3 × 10 −6 cm/s for OABL), which is essential for the effectiveness of CNS drugs ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The existence of the characteristic α-methylene-γ-lactone motif is believed to be an essential pharmacophore, which could increase the Nrf2 levels because of molecules bearing a Michael system [ 69 , 70 ]. Our previous study showed that OABL and its derivatives could induce the antioxidant enzyme HO-1 [ 35 ]. Thus, OABL protects from oxidative stress-induced death via an indirect anti-oxidant mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…The ability to penetrate the blood−brain barrier (BBB) was evaluated by the parallel artificial membrane permeation assay (PAMPA) refer to the previous method [ 34 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

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Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone in 5xFAD Alzheimer's disease mice model

et al. 2022

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Alzheimer's disease (AD) is a neurodegenerative disease in which oxidative stress and neuroinflammation were demonstrated to be associated with neuronal loss and cognitive deficits. However, there are still no specific treatments that can prevent the progression of AD. In this study, a screening of anti-inflammatory hits from 4207 natural compounds of two different molecular libraries indicated 1,6- O,O -diacetylbritannilactone (OABL), a 1,10- seco -eudesmane sesquiterpene lactone isolated from the herb Inula britannica L., exhibited strong anti-inflammatory activity in vitro as well as favorable BBB penetration property. OABL reduced LPS-induced neuroinflammation in BV-2 microglial cells as assessed by effects on the levels of inflammatory mediators including NO, PGE 2 , TNF-α, iNOS, and COX-2, as well as the translocation of NF-κB. Besides, OABL also exhibited pronounced neuroprotective effects against oxytosis and ferroptosis in the rat pheochromocytoma PC12 cell line. For in vivo research, OABL (20 mg/kg B.W., i.p. ) for 21 d attenuated the impairments in cognitive function observed in 6-month-old 5xFAD mice, as assessed with the Morris water maze test. OABL restored neuronal damage and postsynaptic density protein 95 (PSD95) expression in the hippocampus. OABL also significantly reduced the accumulation of amyloid plaques, the Aβ expression, the phosphorylation of Tau protein, and the expression of BACE1 in AD mice brain. In addition, OABL attenuated the overactivation of microglia and astrocytes by suppressing the expressions of inflammatory cytokines, and increased glutathione (GSH) and reduced malondialdehyde (MDA) and super oxide dismutase (SOD) levels in the 5xFAD mice brain. In conclusion, these results highlight the beneficial effects of the natural product OABL as a novel treatment with potential application for drug discovery in AD due to its pharmacological profile.

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Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The ability to penetrate the blood−brain barrier (BBB) was evaluated by the parallel artificial membrane permeation assay (PAMPA) refer to the previous method [ 34 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

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Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone in 5xFAD Alzheimer's disease mice model

et al. 2022

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“…As shown in Figure 5, the inhibition effect of 1 and 3 on the production of TNF‐α and IL‐6, two anti‐inflammatory cytokines, [22] manifested their potential anti‐inflammatory activity in LPS‐induced RAW264.7 cells. Meanwhile, the production of reactive oxygen species (ROS) is also increased in the progression of inflammatory response by LPS stimulation of macrophages, which could lead to a certain oxidative stress in these cells [23] . The results of fluorescence microscope using the DCFDA probe indicated that the ROS was dramatically increased in LPS‐induced RAW264.7 macrophages which have subsequently been reduced by the addition of 1 and 3 ( Figure 6).…”

Section: Resultsmentioning

confidence: 99%

Carpelipines C and D, Two Anti‐Inflammatory Germacranolides from the Flowers of Carpesium lipskyi Winkl. (Asteraceae)

Zhong

Han

et al. 2022

Chemistry & Biodiversity

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Two new germacranolides, carpelipine C (1) and carpelipine D (2), together with four known ones (3–6), were isolated from Carpesium lipskyi Winkl. flowers, a folk Tibetan herbal medicine with antipyretic‐analgesic and anti‐inflammatory effects. The chemical structures of new structure were illuminated by diversified spectroscopic and X‐ray crystallographic analyses. Compounds 1 and 3 dramatically suppressed the synthesis of NO and decreased pre‐inflammatory protein expression of iNOS and COX‐2 in LPS‐induced RAW264.7 cells. Furthermore, it was revealed that NF‐κB/MAPK signaling pathway were involved in the anti‐inflammatory process of 1 and 3, and their effects on reducing oxidative stress by activating Nrf2/HO‐1 pathway were also measured. This article indicated that the traditional use of C. lipskyi to treat inflammatory diseases has a certain rationality.

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Synthesis of the dibenzylbutane lignan LCA derivatives and evaluation of their anti-inflammatory activities

Zhang,

Gai,

Wang

et al. 2024

Med Chem Res

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1,10-Seco-Eudesmane sesquiterpenoids as a new type of anti-neuroinflammatory agents by suppressing TLR4/NF-κB/MAPK pathways

Cited by 29 publications

References 42 publications

Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone in 5xFAD Alzheimer's disease mice model

Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone in 5xFAD Alzheimer's disease mice model

Carpelipines C and D, Two Anti‐Inflammatory Germacranolides from the Flowers of Carpesium lipskyi Winkl. (Asteraceae)

Synthesis of the dibenzylbutane lignan LCA derivatives and evaluation of their anti-inflammatory activities

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