Usnic acid enantiomers restore cognitive deficits and neurochemical alterations induced by Aβ1–42 in mice

Cazarin, Camila André; Dalmagro, Ana Paula; Gonçalves, Ana Elisa; Boeing, Thaise; Silva, Luísa Mota da; Corrêa, Rogério; Klein‐Júnior, Luiz Carlos; Pinto, Bernardo Carlesso; Lorenzett, Thaís Savoldi; Sobrinho, Thales Uchôa da Costa; Fátima, Ângelo de; Lage, Tiago Coelho de Assis; Fernandes, Sérgio Antônio; Souza, Márcia María de

doi:10.1016/j.bbr.2020.112945

Cited by 16 publications

(6 citation statements)

References 79 publications

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“…Our results speculated that 2′-FL and HMO reduced the expression of the Aβ protein, then affected the hyperphosphorylation Tau by blocking the formation or aggregation of Aβ, and might also protect the neuron or synaptic structure from damage, ultimately improving the occurrence of AD effectively, which is consistent with previous research . The previous study has shown that the aggregation of Aβ1–42 in the central nervous system structures initiates neuroinflammation, and the release of proinflammatory mediators such as IL-4, IL-6, and IL-1β occurs in AD, which is consistent with the results of cytokine levels obtained from ELISA (Figure ).…”

Section: Discussionsupporting

confidence: 92%

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

Gao,

Fang,

Sun

et al. 2023

J. Agric. Food Chem.

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Alzheimer's disease (AD) is distinguished by cognitive dysfunction and neuroinflammation in the brain. 2′-Fucosyllactose (2′-FL) is a major human milk oligosaccharide (HMO) that is abundantly present in breast milk and has been demonstrated to exhibit immunomodulatory effects. However, the role of 2′-FL and HMO in gut microbiota modulation in relation to AD remains insufficiently investigated. This study aimed to elucidate the preventive effect of the 2′-FL and HMO impact of AD and the relevant mechanism involved. Here, the behavioral results showed that 2′-FL and HMO intervention decreased the expression of Tau phosphorylation and amyloid-β (Aβ), inhibited neuroinflammation, and restored cognitive impairment in AD mice. The metagenomic analysis proved that 2′-FL and HMO intervention restored the dysbiosis of the gut microbiota in AD. Notably, 2′-FL and HMO intervention significantly enhanced the relative abundance of Clostridium and Akkermansia. The metabolomics results showed that 2′-FL and HMO enhanced the oleoyl-L-carnitine metabolism as potential drivers. More importantly, the levels of oleoyl-L-carnitine were positively correlated with the abundances of Clostridium and Akkermansia. These results indicated that 2′-FL and HMO had therapeutic potential to prevent AD-induced cognitive impairment, which is of great significance for the treatment of AD.

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Section: Discussionsupporting

confidence: 92%

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

Gao,

Fang,

Sun

et al. 2023

J. Agric. Food Chem.

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“…Usnic acid (2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2 H ,9b H )-dibenzo-furandione); C 18 H 16 O 7 , MW of 344.32 is a molecule metabolized by several species of lichens (symbiotic organisms composed of a fungus (mycobiont) in association with one or more photosynthetic partners (photobiont) which may be green algae, cyanobacteria or both), of the genera Cladonia , Usnea , Lecanora , Ramalina , Parmelia , and Evernia , widely distributed, present in the arctic, tropical and subtropical countries and the Antarctic [ 1 , 2 , 3 , 4 , 5 ]. Usnic acid is found naturally in two enantiomeric forms, such as (−) levogyrous and (+) dextrogyrous, due to the angular projection of the methyl group located in position 9b [ 6 , 7 ] being still characterized as a yellow pigmented substance; its forms can be varied, that is, depending directly on the solvent used in its recrystallization [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Natural Compound Hydrophobic Usnic Acid and Hydrophilic Potassium Usnate Derivative: Applications and Comparisons

et al. 2021

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Usnic acid is the best-studied lichen metabolite, presenting several biological activities, such as antibacterial, immunostimulating, antiviral, antifungal, anti-inflammatory, and antiparasitic agents; despite these relevant properties, it is a hydrophobic and toxic molecule. In this context, scientific research has driven the development of innovative alternatives, considering usnic acid as a source of raw material in obtaining new molecules, allowing structural modifications (syntheses) from it. The purpose is to optimize biological activities and toxicity, with less concentration and/or response time. This work presents a literature review with an analogy of the hydrophobic molecule of usnic acid with its hydrophilic derivative of potassium usnate, emphasizing the elucidation and structural characteristics, biological activities, and toxicological aspects of both molecules, and the advantages of using the promising derivative hydrophilic in different in vitro and in vivo assays when compared to usnic acid.

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“…Myeloperoxidase activity was slightly higher in both the hippocampus ( p = 0.18, F 2,28 = 2.08) and cortex ( p = 0.66, F 2,28 = 0.55) in AβO-injected mice treated with vehicle than in the control group. Other studies using the same animal model showed increased myeloperoxidase levels at 21 days after AβO administration . Conversely, in our study, differences were nonsignificant (Figure a,b, Table ).…”

Section: Results and Discussionmentioning

confidence: 52%

“…Other studies using the same animal model showed increased myeloperoxidase levels at 21 days after AβO administration. 57 Conversely, in our study, differences were nonsignificant (Figure 4a,b, Table 1). A possible explanation for this result is the difference in the assessment period.…”

Section: Effects Of Tga Onmentioning

confidence: 79%

Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment

Andrade,

M. Rodrigues,

Dias

et al. 2023

ACS Chem. Neurosci.

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Usnic acid enantiomers restore cognitive deficits and neurochemical alterations induced by Aβ1–42 in mice

Cited by 16 publications

References 79 publications

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

Effect of Human Milk Oligosaccharides on Learning and Memory in Mice with Alzheimer’s Disease

The Natural Compound Hydrophobic Usnic Acid and Hydrophilic Potassium Usnate Derivative: Applications and Comparisons

Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment

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