Protective effects of AKBA against hypoxia-induced cognitive dysfunction: potential involvement of SLC2A1, PTGS1, and BCL2L1
Abstract
IntroductionHypoxia-induced cognitive impairment (HICI) is associated with neuroinflammation, oxidative stress, and gut microbiota dysbiosis, highlighting the need for effective neuroprotective interventions. Acetyl-11-keto-β-boswellic acid (AKBA), a bioactive triterpenoid derived from frankincense, possesses anti-inflammatory and antioxidant properties, but its protective effects against hypoxia-associated cognitive dysfunction remain insufficiently understood.MethodsThis study investigated the neuroprotective potential of AKBA administered concurrently with hypoxic exposure and explored its associated molecular alterations. Network pharmacology, transcriptomic analysis, molecular similarity assessment, molecular docking, and molecular dynamics simulations were integrated to identify and prioritize candidate proteins. The protective effects of AKBA were subsequently evaluated in mice exposed to normobaric hypoxia (12.7% O2) for 10 days.ResultsAKBA administration attenuated hypoxia-associated cognitive deficits, accompanied by reduced inflammatory and oxidative stress markers, increased BDNF levels, decreased TUNEL-positive staining, and preservation of MBP immunoreactivity. These effects were associated with changes in cortical SLC2A1, PTGS1, and BCL2L1 expression, together with alterations in NF-κB- and Keap1/Nrf2-related protein levels. AKBA administration was also associated with changes in gut microbial composition, and exploratory correlation analyses suggested associations between selected bacterial taxa and cortical protein expression.ConclusionCollectively, these findings indicate that concurrent AKBA administration provides protection against hypoxia-associated cognitive dysfunction, potentially involving coordinated changes in inflammatory, antioxidant, and neurotrophic responses. However, the causal roles of the candidate proteins and gut microbiota alterations remain to be established through further functional investigations.
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BibTeX
@article{wang2026protective,
title = {{Protective effects of AKBA against hypoxia-induced cognitive dysfunction: potential involvement of SLC2A1, PTGS1, and BCL2L1}},
author = {Jiayi Wang and Liang Gao and Bowen Lv and Yajun Qiao and Guoqiang Li and Ruiying Cheng and Xiaohui Li and Xiaoli Shi and Hongtao Bi and Wen Jiang and Yi Ding and Xingfang Zhang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.2023356},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.2023356},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Protective effects of AKBA against hypoxia-induced cognitive dysfunction: potential involvement of SLC2A1, PTGS1, and BCL2L1
AU - Jiayi Wang
AU - Liang Gao
AU - Bowen Lv
AU - Yajun Qiao
AU - Guoqiang Li
AU - Ruiying Cheng
AU - Xiaohui Li
AU - Xiaoli Shi
AU - Hongtao Bi
AU - Wen Jiang
AU - Yi Ding
AU - Xingfang Zhang
PY - 2026
DA - 2026/11/06
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.2023356
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.2023356
AB - IntroductionHypoxia-induced cognitive impairment (HICI) is associated with neuroinflammation, oxidative stress, and gut microbiota dysbiosis, highlighting the need for effective neuroprotective interventions. Acetyl-11-keto-β-boswellic acid (AKBA), a bioactive triterpenoid derived from frankincense, possesses anti-inflammatory and antioxidant properties, but its protective effects against hypoxia-associated cognitive dysfunction remain insufficiently understood.MethodsThis study investigated the neuroprotective potential of AKBA administered concurrently with hypoxic exposure and explored its associated molecular alterations. Network pharmacology, transcriptomic analysis, molecular similarity assessment, molecular docking, and molecular dynamics simulations were integrated to identify and prioritize candidate proteins. The protective effects of AKBA were subsequently evaluated in mice exposed to normobaric hypoxia (12.7% O2) for 10 days.ResultsAKBA administration attenuated hypoxia-associated cognitive deficits, accompanied by reduced inflammatory and oxidative stress markers, increased BDNF levels, decreased TUNEL-positive staining, and preservation of MBP immunoreactivity. These effects were associated with changes in cortical SLC2A1, PTGS1, and BCL2L1 expression, together with alterations in NF-κB- and Keap1/Nrf2-related protein levels. AKBA administration was also associated with changes in gut microbial composition, and exploratory correlation analyses suggested associations between selected bacterial taxa and cortical protein expression.ConclusionCollectively, these findings indicate that concurrent AKBA administration provides protection against hypoxia-associated cognitive dysfunction, potentially involving coordinated changes in inflammatory, antioxidant, and neurotrophic responses. However, the causal roles of the candidate proteins and gut microbiota alterations remain to be established through further functional investigations.
SN - 1663-9812
ER -