Pocahemiketone A, a Sesquiterpenoid Possessing a Spirocyclic Skeleton with a Hemiketal Endoperoxide Unit, Alleviates Aβ_25–35-Induced Pyroptosis and Oxidative Stress in SH-SY5Y Cells

Abstract

Pocahemiketone A, a novel sesquiterpenoid possessing a unique spirocyclic skeleton with a hemiketal endoperoxide unit, was isolated from the essential oil of Pogostemon cablin. Its structure was determined by spectroscopic methods and single-crystal X-ray diffraction analyses. Pocahemiketone A exhibits a significant neuroprotective effect against Aβ 25−35 -induced damage in SH-SY5Y cells by inhibiting NLRP3 inflammasome-mediated pyroptosis and oxidative stress. These results indicate that pocahemiketone A has great potential for use in the treatment of Alzheimer′s disease.

Pogocablanols A--G, a new class of sesquiterpenoids from Pogostemon cablin and their activities

“…1,10 bond of bulnesene is oxidatively cleaved to form intermediatei , which contains two characterized carbonyl units. [19] The Prins reaction is an acid-catalyzed condensation of alkenes with ketones, which is widely used in the fragrance industry. Due to the non-stereoselectivity, intermediatei is likely to undergo an intramolecular Prins reaction to construct two epimers (intermediates ii andiii ).…”

“…Successive oxidation, nucleophilic substitution, and etherification of 5 would afford pogocablanols A and C (1 and 3 ) due to the stereoselectivity in the epoxidation and nucleophilic substitution processes. [19] Pogocablanol B (2 ) could be yielded from intermediate iii through the same reaction processes used for the generation of pogocablanols A and C (1and 3 ).…”

“…[8] Our previous studies of patchouli oil led to the isolation of several sesquiterpenoids. [16][17][18][19] In this study, seven bicyclic sesquiterpenoids (pogocablanols A-G, 1 -7 ) featuring a nonisoprenoid system with a C5-C1-C6 carbon skeleton were obtained (Figure 1), and this new type of sesquiterpenoids was named pogocablane-type sesquiterpenoids. Pogocablanols A-C (1 -3 ) are isomers possessing an interesting 1-oxaspiro [4,4]nonane moiety; pogocablanol D (4 ) has a 1-O-8 linkage to form a pyran ring fused with the five-and six-membered carbocycles; and pogocablanols F and G (6 and 7 ) are epimers.…”

Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection

“…A novel sesquiterpenoid, Pocahemiketone A from Pogostemon cablin , was shown to alleviate NLR -family pyrin domain-containing 3 (NLRP3) inflammasome-dependent pyroptosis and oxidative stress, suggesting neuroprotective effects against Aβ 25–35 -mediated damage in SH-SY5Y cells [ 89 ]. Myricetin and dihydromyricetin, flavonoids present in many fruits and vegetables, have been shown to have an array of biological effects, such as antioxidant, anti-neuroinflammation, and inhibitory efficacy against Aβ oligomers in AD.…”

Rapid screening of unprecedented sesquiterpenes with distinctive ring skeletons from Daphne aurantiaca employing an integrated strategy

“…[1][2][3] Rearrangement, oxidative cleavage, and aldol condensation occurring spontaneously at multiple sites of the structure typically, operated by the energy derived from the enzymatic catalysis of spontaneous reactions, immensely increase the structural diversity of natural guaiane-type sesquiterpenoids. [4][5][6][7][8] The unusual rearranged and highly oxygenated structural features make us take a fresh look at efficient strategies for precision mining of novel skeletal structures with promising pharmacological activities.…”