Academic Journal
Προβολή σε EDS

Steroidal alkaloid H89712 ameliorates neuroinflammation and memory deficits: Enhancing cerebral oxidative phosphorylation in APP/PS1 mice.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Steroidal alkaloid H89712 ameliorates neuroinflammation and memory deficits: Enhancing cerebral oxidative phosphorylation in APP/PS1 mice.
Συγγραφείς: Jiang L; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China., Zhang Z; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China., Luo X; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China., Wu H; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China., Huang Z; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China., Wu W; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China., Xu S; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Phase I Clinical Trial Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China., Pan J; Clinical Research Laboratory, the Second Affiliated Hospital of University of South China, Hengyang, 421001, Hunan, China. Electronic address: 13787702128@139.com., Tan Z; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China. Electronic address: 803119@csu.edu.cn.
Πηγή: Life sciences [Life Sci] 2026 Oct 01; Vol. 402, pp. 124583. Date of Electronic Publication: 2026 Jul 08.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE
Imprint Name(s): Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
Ιατρικοί όροι (MeSH): Memory Disorders*/drug therapy , Memory Disorders*/metabolism , Oxidative Phosphorylation*/drug effects , Neuroinflammatory Diseases*/drug therapy , Neuroinflammatory Diseases*/metabolism , Alkaloids*/pharmacology , Alzheimer Disease*/drug therapy , Alzheimer Disease*/metabolism , Steroids*/pharmacology, Amyloid beta-Protein Precursor/genetics ; Hippocampus/drug effects ; Hippocampus/metabolism ; Neuroprotective Agents/pharmacology ; Maze Learning/drug effects ; Presenilin-1/genetics ; Apoptosis/drug effects ; Animals ; Mice ; Male ; Mice, Transgenic ; Disease Models, Animal
Περίληψη: Aims: Alzheimer's disease (AD) poses a major health challenge with limited therapeutic options. This study aimed to investigate the anti-AD potential and underlying mechanism of a novel steroidal alkaloid, H89.
Materials and Methods: In vitro, Aβ25-35-exposed HT-22 hippocampal neurons and LPS-stimulated BV2 microglia were used to assess H89 neuroprotection and anti-inflammatory activity. In vivo, 6-month-old APP/PS1 mice were orally administered H89 for 2 months. Spatial memory was assessed by Y-maze (YM) and Morris water maze (MWM). Hippocampal morphology, neuronal apoptosis (TUNEL/NeuN), Aβ deposition (IHC), microglial activation (Iba1), inflammatory cytokines (ELISA), and oxidative phosphorylation (RNA-seq, qRT-PCR, Western blot) were examined. Brain malondialdehyde (MDA), ATP, and cellular ROS were quantified.
Key Findings: H89 (10 and 50 nM) significantly protected HT-22 cells against Aβ25-35-induced injury and attenuated LPS-induced TNF-α, IL-1β, and IL-6 secretion while elevating IL-10 in BV2 cells. In APP/PS1 mice, H89 increased novel arm exploration in the YM and target quadrant residence in the MWM, indicating improved spatial learning and memory. H89 ameliorated hippocampal neuronal morphology, reduced apoptosis, attenuated Aβ plaques and microglial activation (Iba1), decreased TNF-α, IL-6 and MDA, and elevated IL-10 and cerebral ATP. Transcriptomic and molecular analyses confirmed that H89 upregulated oxidative phosphorylation-related genes and proteins (ATP5E, ATP5J2, NDUFA13, NDUFB3, COX7C, COX11). Cerebral ATP positively correlated with spatial memory but negatively correlated with neuroinflammation and oxidative stress.
Significance: H89 exerts neuroprotective effects by enhancing mitochondrial oxidative phosphorylation and brain energy supply, concurrently suppressing neuroinflammation, oxidative stress, and neuronal apoptosis, suggesting its potential as a therapeutic candidate for AD.
(Copyright © 2026 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Alzheimer's disease; H89712; Mitochondrial dysfunction; Neuroinflammation; Oxidative phosphorylation; Steroidal alkaloid
Substance Nomenclature: 0 (Alkaloids)
0 (Amyloid beta-Protein Precursor)
0 (Neuroprotective Agents)
0 (Steroids)
0 (Presenilin-1)
Entry Date(s): Date Created: 20260707 Date Completed: 20260811 Latest Revision: 20260811
Update Code: 20260812
DOI: 10.1016/j.lfs.2026.124583
PMID: 42413720
Βάση Δεδομένων: MEDLINE
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://www.doi.org/10.1016/j.lfs.2026.124583?
    Name: ScienceDirect (all content) (s7799221)
    Category: fullText
    Text: View record from ScienceDirect
    MouseOverText: View record from ScienceDirect
  – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=18790631&ISBN=&volume=402&issue=&date=20261001&spage=124583&pages=124583&title=Life sciences&atitle=Steroidal%20alkaloid%20H89712%20ameliorates%20neuroinflammation%20and%20memory%20deficits%3A%20Enhancing%20cerebral%20oxidative%20phosphorylation%20in%20APP%2FPS1%20mice.&aulast=Jiang%20L&id=DOI:10.1016/j.lfs.2026.124583
    Name: Full Text Finder (for New FTF UI) (ns324271)
    Category: fullText
    Text: Full Text Finder
    MouseOverText: Full Text Finder
Header DbId: cmedm
DbLabel: MEDLINE
An: 42413720
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Steroidal alkaloid H89712 ameliorates neuroinflammation and memory deficits: Enhancing cerebral oxidative phosphorylation in APP/PS1 mice.
– Name: Author
  Label: Authors
  Group: Au
  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Jiang+L%22&quot;&gt;Jiang L&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhang+Z%22&quot;&gt;Zhang Z&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Luo+X%22&quot;&gt;Luo X&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wu+H%22&quot;&gt;Wu H&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Huang+Z%22&quot;&gt;Huang Z&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Wu+W%22&quot;&gt;Wu W&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Xu+S%22&quot;&gt;Xu S&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Phase I Clinical Trial Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Pan+J%22&quot;&gt;Pan J&lt;/searchLink&gt;; Clinical Research Laboratory, the Second Affiliated Hospital of University of South China, Hengyang, 421001, Hunan, China. Electronic address: 13787702128@139.com.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Tan+Z%22&quot;&gt;Tan Z&lt;/searchLink&gt;; Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, 410008, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, 410008, Hunan, China. Electronic address: 803119@csu.edu.cn.
– Name: TitleSource
  Label: Source
  Group: Src
  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%220375521%22&quot;&gt;Life sciences&lt;/searchLink&gt; [Life Sci] 2026 Oct 01; Vol. 402, pp. 124583. &lt;i&gt;Date of Electronic Publication: &lt;/i&gt;2026 Jul 08.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: &lt;i&gt;Publisher: &lt;/i&gt;&lt;searchLink fieldCode=&quot;PB&quot; term=&quot;%22Elsevier%22&quot;&gt;Elsevier &lt;/searchLink&gt;&lt;i&gt;Country of Publication: &lt;/i&gt;Netherlands &lt;i&gt;NLM ID: &lt;/i&gt;0375521 &lt;i&gt;Publication Model: &lt;/i&gt;Print-Electronic &lt;i&gt;Cited Medium: &lt;/i&gt;Internet &lt;i&gt;ISSN: &lt;/i&gt;1879-0631 (Electronic) &lt;i&gt;Linking ISSN: &lt;/i&gt;&lt;searchLink fieldCode=&quot;IS&quot; term=&quot;%2200243205%22&quot;&gt;00243205 &lt;/searchLink&gt;&lt;i&gt;NLM ISO Abbreviation: &lt;/i&gt;Life Sci &lt;i&gt;Subsets: &lt;/i&gt;MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: &lt;i&gt;Publication&lt;/i&gt;: &lt;2008-&gt;: Amsterdam : Elsevier&lt;br /&gt;&lt;i&gt;Original Publication&lt;/i&gt;: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: &lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Memory+Disorders%22&quot;&gt;Memory Disorders*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Memory+Disorders+drug+therapy%22&quot;&gt;drug therapy&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Memory+Disorders%22&quot;&gt;Memory Disorders*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Memory+Disorders+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Oxidative+Phosphorylation%22&quot;&gt;Oxidative Phosphorylation*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Oxidative+Phosphorylation+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Neuroinflammatory+Diseases%22&quot;&gt;Neuroinflammatory Diseases*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Neuroinflammatory+Diseases+drug+therapy%22&quot;&gt;drug therapy&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Neuroinflammatory+Diseases%22&quot;&gt;Neuroinflammatory Diseases*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Neuroinflammatory+Diseases+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Alkaloids%22&quot;&gt;Alkaloids*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Alkaloids+pharmacology%22&quot;&gt;pharmacology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Alzheimer+Disease%22&quot;&gt;Alzheimer Disease*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Alzheimer+Disease+drug+therapy%22&quot;&gt;drug therapy&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Alzheimer+Disease%22&quot;&gt;Alzheimer Disease*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Alzheimer+Disease+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Steroids%22&quot;&gt;Steroids*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Steroids+pharmacology%22&quot;&gt;pharmacology&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Amyloid+beta-Protein+Precursor%22&quot;&gt;Amyloid beta-Protein Precursor&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Amyloid+beta-Protein+Precursor+genetics%22&quot;&gt;genetics&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus%22&quot;&gt;Hippocampus&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus%22&quot;&gt;Hippocampus&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Hippocampus+metabolism%22&quot;&gt;metabolism&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Neuroprotective+Agents%22&quot;&gt;Neuroprotective Agents&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Neuroprotective+Agents+pharmacology%22&quot;&gt;pharmacology&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Maze+Learning%22&quot;&gt;Maze Learning&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Maze+Learning+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Presenilin-1%22&quot;&gt;Presenilin-1&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Presenilin-1+genetics%22&quot;&gt;genetics&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Apoptosis%22&quot;&gt;Apoptosis&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Apoptosis+drug+effects%22&quot;&gt;drug effects&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Animals%22&quot;&gt;Animals&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Mice%22&quot;&gt;Mice&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Male%22&quot;&gt;Male&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Mice%2C+Transgenic%22&quot;&gt;Mice, Transgenic&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Disease+Models%2C+Animal%22&quot;&gt;Disease Models, Animal&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Aims: Alzheimer&#39;s disease (AD) poses a major health challenge with limited therapeutic options. This study aimed to investigate the anti-AD potential and underlying mechanism of a novel steroidal alkaloid, H89.&lt;br /&gt;Materials and Methods: In vitro, Aβ&lt;subscript&gt;25-35&lt;/subscript&gt;-exposed HT-22 hippocampal neurons and LPS-stimulated BV2 microglia were used to assess H89 neuroprotection and anti-inflammatory activity. In vivo, 6-month-old APP/PS1 mice were orally administered H89 for 2&#160;months. Spatial memory was assessed by Y-maze (YM) and Morris water maze (MWM). Hippocampal morphology, neuronal apoptosis (TUNEL/NeuN), Aβ deposition (IHC), microglial activation (Iba1), inflammatory cytokines (ELISA), and oxidative phosphorylation (RNA-seq, qRT-PCR, Western blot) were examined. Brain malondialdehyde (MDA), ATP, and cellular ROS were quantified.&lt;br /&gt;Key Findings: H89 (10 and 50&#160;nM) significantly protected HT-22 cells against Aβ&lt;subscript&gt;25-35&lt;/subscript&gt;-induced injury and attenuated LPS-induced TNF-α, IL-1β, and IL-6 secretion while elevating IL-10 in BV2 cells. In APP/PS1 mice, H89 increased novel arm exploration in the YM and target quadrant residence in the MWM, indicating improved spatial learning and memory. H89 ameliorated hippocampal neuronal morphology, reduced apoptosis, attenuated Aβ plaques and microglial activation (Iba1), decreased TNF-α, IL-6 and MDA, and elevated IL-10 and cerebral ATP. Transcriptomic and molecular analyses confirmed that H89 upregulated oxidative phosphorylation-related genes and proteins (ATP5E, ATP5J2, NDUFA13, NDUFB3, COX7C, COX11). Cerebral ATP positively correlated with spatial memory but negatively correlated with neuroinflammation and oxidative stress.&lt;br /&gt;Significance: H89 exerts neuroprotective effects by enhancing mitochondrial oxidative phosphorylation and brain energy supply, concurrently suppressing neuroinflammation, oxidative stress, and neuronal apoptosis, suggesting its potential as a therapeutic candidate for AD.&lt;br /&gt; (Copyright &#169; 2026 Elsevier Inc. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: &lt;i&gt;Keywords: &lt;/i&gt;Alzheimer&#39;s disease; H89712; Mitochondrial dysfunction; Neuroinflammation; Oxidative phosphorylation; Steroidal alkaloid
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Alkaloids)&lt;br /&gt;0 (Amyloid beta-Protein Precursor)&lt;br /&gt;0 (Neuroprotective Agents)&lt;br /&gt;0 (Steroids)&lt;br /&gt;0 (Presenilin-1)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: &lt;i&gt;Date Created: &lt;/i&gt;20260707 &lt;i&gt;Date Completed: &lt;/i&gt;20260811 &lt;i&gt;Latest Revision: &lt;/i&gt;20260811
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260812
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1016/j.lfs.2026.124583
– Name: AN
  Label: PMID
  Group: ID
  Data: 42413720
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42413720
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.lfs.2026.124583
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 124583
    Subjects:
      – SubjectFull: Amyloid beta-Protein Precursor genetics
        Type: general
      – SubjectFull: Hippocampus drug effects
        Type: general
      – SubjectFull: Hippocampus metabolism
        Type: general
      – SubjectFull: Neuroprotective Agents pharmacology
        Type: general
      – SubjectFull: Maze Learning drug effects
        Type: general
      – SubjectFull: Presenilin-1 genetics
        Type: general
      – SubjectFull: Apoptosis drug effects
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Mice, Transgenic
        Type: general
      – SubjectFull: Disease Models, Animal
        Type: general
      – SubjectFull: Memory Disorders drug therapy
        Type: general
      – SubjectFull: Memory Disorders metabolism
        Type: general
      – SubjectFull: Oxidative Phosphorylation drug effects
        Type: general
      – SubjectFull: Neuroinflammatory Diseases drug therapy
        Type: general
      – SubjectFull: Neuroinflammatory Diseases metabolism
        Type: general
      – SubjectFull: Alkaloids pharmacology
        Type: general
      – SubjectFull: Alzheimer Disease drug therapy
        Type: general
      – SubjectFull: Alzheimer Disease metabolism
        Type: general
      – SubjectFull: Steroids pharmacology
        Type: general
    Titles:
      – TitleFull: Steroidal alkaloid H89712 ameliorates neuroinflammation and memory deficits: Enhancing cerebral oxidative phosphorylation in APP/PS1 mice.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Jiang L
      – PersonEntity:
          Name:
            NameFull: Zhang Z
      – PersonEntity:
          Name:
            NameFull: Luo X
      – PersonEntity:
          Name:
            NameFull: Wu H
      – PersonEntity:
          Name:
            NameFull: Huang Z
      – PersonEntity:
          Name:
            NameFull: Wu W
      – PersonEntity:
          Name:
            NameFull: Xu S
      – PersonEntity:
          Name:
            NameFull: Pan J
      – PersonEntity:
          Name:
            NameFull: Tan Z
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 10
              Text: 2026 Oct 01
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1879-0631
          Numbering:
            – Type: volume
              Value: 402
          Titles:
            – TitleFull: Life sciences
              Type: main
ResultId 1