Neuroprotective Effects and Mechanisms of Alpiniae oxyphyllae Fructus, a Medicinal and Edible Homologous Herb: Research Advances
Abstract
1. Introduction
2. Materials and Methods
3. Chemical Composition and Pharmacological Basis of AOF
4. Neuroprotective Effects and Mechanisms of AOF
4.1. The Neuroprotective Effect of AOF
4.1.1. Anti-Inflammatory Effect
4.1.2. Antioxidant and Antiapoptotic Effect
4.1.3. Promoting Cell Migration and Proliferation
4.1.4. Regulation of Metabolism
4.2. The Neuroprotective Mechanism of AOF: Signal Pathway
4.2.1. TREM2/PI3K/AKT Signaling Pathway
4.2.2. IGF-1R/PI3K/AKT Signaling Pathway
4.2.3. PI3K/AKT/Nrf2 Signaling Pathway
4.2.4. MAPK Signaling Pathway
5. Therapeutic Potential of AOF and Its Biologically Active Compounds in Animal Models of Neurological Disorders
5.1. Therapeutic Applications in AD
5.2. Therapeutic Applications in Depression
5.3. Therapeutic Applications in PD
5.4. Therapeutic Effects in Cerebral Ischemic Injury
6. Summary and Expectations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
5-HMF | 5-Hydroxymethylfurfural |
5-HT | 5-hydroxytryptamine |
AD | Alzheimer’s disease |
AKT | Serine/threonine-protein kinase B |
AOF | Alpiniae oxyphyllae Fructus |
AOVO | Alpinia oxyphylla Miq. volatile oil |
APP | Amyloid precursor protein |
Aβ | Amyloid-β |
BACE1 | β-site amyloid precursor protein cleaving enzyme 1 |
Bad | Bcl2-associated death promoter |
Bak | BCL2 antagonist/killer 1 |
Bax | Bcl-2-associated X protein |
BCL-2 | B-cell lymphoma-2 |
BCL-XL | B-cell lymphoma-extra large |
BDNF | Brain-derived neurotrophic factor |
CAT | Catalase |
CD | Cluster of differentiation |
CUMS | Chronic unpredictable mild stress |
CNS | Central nervous system |
DAG | Diacylglycerol |
DAP | DNAX activation protein |
ECM | Extracellular matrix |
ErK | Extracellular signal-regulated kinase |
GPx | Glutathione peroxidase |
GSH-Px | Glutathione peroxidase |
GSK3β | Glycogen synthase kinase 3β |
H2O2 | Hydrogen peroxide |
HPA | Hypothalamic–pituitary–adrenal |
IGF-1 | Insulin-like growth factor 1 |
IGF-1R | Insulin-like growth factor 1 receptor |
IKKα/β | IκB kinase alpha/beta |
IL | Interleukin |
iNOS | Inducible nitric oxide synthase |
IP3 | Inositol 1,4,5-trisphosphate |
IRAK4 | Interleukin-1 receptor-associated kinase 4 |
IκB | Inhibitor of NF-κB |
JNK | c-Jun N-terminal kinase |
Keap1 | Kelch-like ECH-associated protein 1 |
LPS | Lipopolysaccharide |
MAPK | Mitogen-activated protein kinase |
MDA | Malondialdehyde |
MDM2 | Mouse double minute 2 homolog |
MEK | Mitogen-activated protein kinase |
MMP | Mitochondrial membrane potential |
mPTP | Mitochondrial permeability transition pore |
mTOR | Mechanistic target of rapamycin |
MyD88 | Myeloid differentiation primary response gene 88 |
NF-κB | Nuclear factor kappa-B |
NKT | Nootkatone |
NLRP3 | NOD-like receptor thermal protein domain-associated protein 3 |
NO | Nitrogen dioxide |
Nrf2 | Nuclear factor erythroid 2-related factor 2 |
P38 | p38 mitogen-activated protein kinase |
P53 | Tumor protein 53 |
P65/Rel A | RELA proto-oncogene, NF-κB subunit |
p-Akt | Phosphorylated Akt |
PCA | Protocatechuic acid |
PCNA | Proliferating cell nuclear antigen |
p-CREB | Phosphorylated cAMP response element-binding protein |
PD | Parkinson’s disease |
PI3K | Phosphatidylinositol-3-kinase |
PIP3 | Phosphatidylinositol 3-phosphate |
PKC | Protein kinase C |
PLCγ | Phospholipase C-gamma |
PNS | Peripheral nervous system |
Raf | Rapidly accelerated fibrosarcoma |
Ras | Rat sarcoma virus oncogene |
RNS | Reactive nitrogen species |
ROS | Reactive oxygen species |
SHC | Src homology 2 domain-containing protein |
SOD | Superoxide dismutase |
Sos | Son of sevenless |
src | Proto-oncogene tyrosine-protein kinase Src |
syk | Spleen tyrosine kinase |
TAB1/2 | TAK1-binding protein 1 |
TAK1 | Transforming growth factor β-activated kinase 1 |
TCM | Traditional Chinese medicine |
TLR | Toll-like receptors |
TLR4 | Toll-like receptor 4 |
TNF-α | Tumor necrosis factor-α |
tPA | Tissue-type plasminogen activator |
TRAF6 | TNF receptor-associated factor 6 |
TREM2 | Triggering receptor expressed on myeloid cells 2 |
TrkB | Tropomyosin receptor kinase B |
TSC2 | Tuberous sclerosis complex 2 |
uPA | Urokinase-type plasminogen activator |
α-syn | α-synuclein |
References
- Wang, Y.; Wang, M.; Fan, K.; Li, T.; Yan, T.; Wu, B.; Bi, K.; Jia, Y. Protective effects of Alpinae Oxyphyllae Fructus extracts on lipopolysaccharide-induced animal model of Alzheimer’s disease. J. Ethnopharmacol. 2018, 217, 98–106. [Google Scholar] [CrossRef]
- Zhang, Q.; Zheng, Y.; Hu, X.; Hu, X.; Lv, W.; Lv, D.; Chen, J.; Wu, M.; Song, Q.; Shentu, J. Ethnopharmacological uses, phytochemistry, biological activities, and therapeutic applications of Alpinia oxyphylla Miquel: A review. J. Ethnopharmacol. 2018, 224, 149–168. [Google Scholar] [CrossRef]
- Zuo, L.; Li, J.; Xue, L.; Jia, Q.; Li, Z.; Zhang, M.; Zhao, M.; Wang, M.; Kang, J.; Du, S.; et al. Integrated UPLC-MS/MS and UHPLC-Q-orbitrap HRMS Analysis to Reveal Pharmacokinetics and Metabolism of Five Terpenoids from Alpiniae oxyphyllae Fructus in Rats. Curr. Drug Metab. 2021, 22, 70–82. [Google Scholar] [PubMed]
- Li, J.; Du, Q.; Li, N.; Du, S.; Sun, Z. Alpiniae oxyphyllae Fructus and Alzheimer’s disease: An update and current perspective on this traditional Chinese medicine. Biomed. Pharmacother. 2021, 135, 111167. [Google Scholar] [CrossRef] [PubMed]
- Liao, J.; Zhao, X. Recent Research Progress on the Chemical Constituents, Pharmacology, and Pharmacokinetics of Alpinae oxyphyllae Fructus. Molecules 2024, 29, 3905. [Google Scholar] [CrossRef] [PubMed]
- Kirkland, A.E.; Sarlo, G.L.; Holton, K.F. The Role of Magnesium in Neurological Disorders. Nutrients 2018, 10, 730. [Google Scholar] [CrossRef]
- Nimgampalle, M.; Chakravarthy, H.; Sharma, S.; Shree, S.; Bhat, A.R.; Pradeepkiran, J.A.; Devanathan, V. Neurotransmitter systems in the etiology of major neurological disorders: Emerging insights and therapeutic implications. Ageing Res. Rev. 2023, 89, 101994. [Google Scholar] [CrossRef]
- Park, G.W.; Kim, H.; Won, S.H.; Kim, N.H.; Choi, S.R. Neurosteroids and neurological disorders. Korean J. Physiol. Pharmacol. 2025, 29, 157–164. [Google Scholar] [CrossRef]
- Dash, U.C.; Bhol, N.K.; Swain, S.K.; Samal, R.R.; Nayak, P.K.; Raina, V.; Panda, S.K.; Kerry, R.G.; Duttaroy, A.K.; Jena, A.B. Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications. Acta Pharm. Sin. B 2025, 15, 15–34. [Google Scholar] [CrossRef]
- Feigin, V.L.; Vos, T.; Nichols, E.; Owolabi, M.O.; Carroll, W.M.; Dichgans, M.; Deuschl, G.; Parmar, P.; Brainin, M.; Murray, C. The global burden of neurological disorders: Translating evidence into policy. Lancet Neurol. 2020, 19, 255–265. [Google Scholar] [CrossRef]
- Zhang, J.; Huang, Y.; Xu, J.; Zhao, R.; Xiong, C.; Habu, J.; Wang, Y.; Luo, X. Global publication trends and research hotspots of curcumin application in tumor: A 20-year bibliometric approach. Front. Oncol. 2022, 12, 1033683. [Google Scholar] [CrossRef] [PubMed]
- Jiang, S.; Liu, Y.; Zheng, H.; Zhang, L.; Zhao, H.; Sang, X.; Xu, Y.; Lu, X. Evolutionary patterns and research frontiers in neoadjuvant immunotherapy: A bibliometric analysis. Int. J. Surg. 2023, 109, 2774–2783. [Google Scholar] [CrossRef] [PubMed]
- Arruda, H.; Silva, E.R.; Lessa, M.; Proença, D., Jr.; Bartholo, R. VOSviewer and Bibliometrix. J. Med. Libr. Assoc. 2022, 110, 392–395. [Google Scholar] [CrossRef]
- Zhang, J.; Liu, H.; Che, T.; Zheng, Y.; Nan, X.; Wu, Z. Nanomaterials for diabetic wound healing: Visualization and bibliometric analysis from 2011 to 2021. Front. Endocrinol. 2023, 14, 1124027. [Google Scholar] [CrossRef]
- Zhang, Y.; Dong, L.; Zhang, Q.; Han, J.; Sui, W.; Wei, Z.; Zhang, Z.; Tong, Y.; Wang, S.; Han, F. Qualitative and quantitative analysis of Alpiniae oxyphyllae Fructus by high-performance liquid chromatography coupled to Fourier transform-ion cyclotron resonance mass spectrometry. J. Sep. Sci. 2022, 45, 1185–1194. [Google Scholar] [CrossRef]
- Xiao, T.; Pan, M.; Wang, Y.; Huang, Y.; Tsunoda, M.; Zhang, Y.; Wang, R.; Hu, W.; Yang, H.; Li, L.S.; et al. In vitro bloodbrain barrier permeability study of four main active ingredients from Alpiniae oxyphyllae fructus. J. Pharm. Biomed. Anal. 2023, 235, 115637. [Google Scholar] [CrossRef]
- Zhang, Y.; Huang, Z.; Zhou, Z.; Ma, N.; Wang, R.; Chen, M.; He, X.; Dong, L.; Xia, Z.; Liu, Q.; et al. Nootkatone, a Sesquiterpene Ketone From Alpiniae oxyphyllae Fructus, Ameliorates Metabolic-Associated Fatty Liver by Regulating AMPK and MAPK Signaling. Front. Pharmacol. 2022, 13, 909280. [Google Scholar] [CrossRef]
- Yang, X.; Yang, Y.; Chen, H.; Xu, T.; Li, C.; Zhou, R.; Gao, L.; Han, M.; He, X.; Chen, Y. Extraction, isolation, immunoregulatory activity, and characterization of Alpiniae oxyphyllae fructus polysaccharides. Int. J. Biol. Macromol. 2020, 155, 927–937. [Google Scholar] [CrossRef] [PubMed]
- Koo, B.S.; Lee, W.C.; Chang, Y.C.; Kim, C.H. Protective effects of alpinae oxyphyllae fructus (Alpinia oxyphylla MIQ) water-extracts on neurons from ischemic damage and neuronal cell toxicity. Phytother. Res. 2004, 18, 142–148. [Google Scholar] [CrossRef]
- Qiu, C.; Mu, L.; Wang, J.; Tang, R.; Hou, B.; Hu, W.; Zhang, R.; Chen, X. Sesquiterpenoids from the fruits of Alpinia oxyphylla Miq. and their neuroprotective effect. Phytochemistry 2023, 211, 113680. [Google Scholar] [CrossRef]
- Yu, X.; An, L.; Wang, Y.; Zhao, H.; Gao, C. Neuroprotective effect of Alpinia oxyphylla Miq. fruits against glutamate-induced apoptosis in cortical neurons. Toxicol. Lett. 2003, 144, 205–212. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.; Wang, F.; Guo, J.; Xu, C.; Cao, Y.; Fang, Z.; Wang, Q. Pharmacological Mechanisms Underlying the Neuroprotective Effects of Alpinia oxyphylla Miq. on Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 2701. [Google Scholar] [CrossRef] [PubMed]
- Dong, J.; Zhou, M.; Pan, D.B.; Qin, Q.Y.; Li, T.; Yao, X.S.; Li, H.B.; Yu, Y. Eremophilane and cadinane sesquiterpenoids from the fruits of Alpinia oxyphylla and their anti-inflammatory activities. Food Funct. 2023, 14, 9755–9766. [Google Scholar] [CrossRef]
- Xu, M.; Yang, Y.; Peng, J.; Zhang, Y.; Wu, B.; He, B.; Jia, Y.; Yan, T. Effects of Alpinae Oxyphyllae Fructus on microglial polarization in a LPS-induced BV2 cells model of neuroinflammation via TREM2. J. Ethnopharmacol. 2023, 302, 115914. [Google Scholar] [CrossRef] [PubMed]
- Li, R.; Wang, L.; Zhang, Q.; Duan, H.; Qian, D.; Yang, F.; Xia, J. Alpiniae oxyphyllae fructus possesses neuroprotective effects on H2O2 stimulated PC12 cells via regulation of the PI3K/Akt signaling Pathway. Front. Pharmacol. 2022, 13, 966348. [Google Scholar] [CrossRef]
- Bian, Y.; Chen, Y.; Wang, X.; Cui, G.; Ung, C.O.L.; Lu, J.-H.; Cong, W.; Tang, B.; Lee, S.M.-Y. Oxyphylla A ameliorates cognitive deficits and alleviates neuropathology via the Akt-GSK3β and Nrf2-Keap1-HO-1 pathways in vitro and in vivo murine models of Alzheimer’s disease. J. Adv. Res. 2021, 34, 1–12. [Google Scholar] [CrossRef]
- Qi, Y.; Cheng, X.; Gong, G.; Yan, T.; Du, Y.; Wu, B.; Bi, K.; Jia, Y. Synergistic neuroprotective effect of schisandrin and nootkatone on regulating inflammation, apoptosis and autophagy via the PI3K/AKT pathway. Food Funct. 2020, 11, 2427–2438. [Google Scholar] [CrossRef]
- Ju, D.-T.; Kuo, W.-W.; Ho, T.-J.; Paul, C.R.; Kuo, C.-H.; Viswanadha, V.P.; Lin, C.-C.; Chen, Y.-S.; Chang, Y.-M.; Huang, C.-Y. Protocatechuic Acid from Alpinia oxyphylla Induces Schwann Cell Migration via ERK1/2, JNK and p38 Activation. Am. J. Chin. Med. 2015, 43, 653–665. [Google Scholar] [CrossRef]
- Chang, Y.-M.; Chang, H.-H.; Tsai, C.-C.; Lin, H.-J.; Ho, T.-J.; Ye, C.-X.; Chiu, P.-L.; Chen, Y.-S.; Chen, R.-J.; Huang, C.-Y.; et al. Alpinia oxyphylla Miq. fruit extract activates IGFR-PI3K/Akt signaling to induce Schwann cell proliferation and sciatic nerve regeneration. BMC Complement. Altern. Med. 2017, 17, 184. [Google Scholar] [CrossRef]
- Zhou, S.; Liu, L.; Zhang, Y.; Zhang, Z.; Li, H.; Fan, F.; He, J.; Kang, J.; Zuo, L. Integrated untargeted and targeted metabolomics to reveal therapeutic effect and mechanism of Alpiniae oxyphyllae fructus on Alzheimer’s disease in APP/PS1 mice. Front. Pharmacol. 2023, 13, 1104954. [Google Scholar] [CrossRef]
- Duncan, R.E.; Sun, Z.; Zhang, Y.; Zhang, M.; Zhou, S.; Cheng, W.; Xue, L.; Zhou, P.; Li, X.; Zhang, Z. Integrated brain and plasma dual-channel metabolomics to explore the treatment effects of Alpinia oxyphyllaFructus on Alzheimer’s disease. PLoS ONE 2023, 18, e0285401. [Google Scholar]
- Singh, N.; Baby, D.; Rajguru, J.P.; Patil, P.B.; Thakkannavar, S.S.; Pujari, V.B. Inflammation and cancer. Ann. Afr. Med. 2019, 18, 121–126. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Zhang, Y.; Wang, J.; Li, S.; Wang, Y.; Zhang, Z.; Zhang, J.; Xin, C.; Wang, Y.; Rong, P. Anti-neuroinflammation effects of transcutaneous auricular vagus nerve stimulation against depression-like behaviors via hypothalamic α7nAchR/JAK2/STAT3/NF-κB pathway in rats exposed to chronic unpredictable mild stress. CNS Neurosci. Ther. 2023, 29, 2634–2644. [Google Scholar] [CrossRef]
- Hong, X.; Chen, T.; Liu, Y.; Li, J.; Huang, D.; Ye, K.; Liao, W.; Wang, Y.; Liu, M.; Luan, P. Design, current states, and challenges of nanomaterials in anti-neuroinflammation: A perspective on Alzheimer’s disease. Ageing Res. Rev. 2025, 105, 102669. [Google Scholar] [CrossRef] [PubMed]
- Kwon, H.S.; Koh, S.-H. Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes. Transl. Neurodegener. 2020, 9, 42. [Google Scholar] [CrossRef]
- Beltran-Velasco, A.I.; Clemente-Suárez, V.J. Impact of Peripheral Inflammation on Blood-Brain Barrier Dysfunction and Its Role in Neurodegenerative Diseases. Int. J. Mol. Sci. 2025, 26, 2440. [Google Scholar] [CrossRef]
- Zhang, X.W.; Feng, N.; Liu, Y.C.; Guo, Q.; Wang, J.K.; Bai, Y.Z.; Ye, X.M.; Yang, Z.; Yang, H.; Liu, Y.; et al. Neuroinflammation inhibition by small-molecule targeting USP7 noncatalytic domain for neurodegenerative disease therapy. Sci. Adv. 2022, 8, eabo0789. [Google Scholar] [CrossRef]
- Deczkowska, A.; Keren-Shaul, H.; Weiner, A.; Colonna, M.; Schwartz, M.; Amit, I. Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration. Cell 2018, 173, 1073–1081. [Google Scholar] [CrossRef]
- Yoshikawa, T.; You, F. Oxidative Stress and Bio-Regulation. Int. J. Mol. Sci. 2024, 25, 3360. [Google Scholar] [CrossRef]
- Chang, W.L.; Ko, C.H. The Role of Oxidative Stress in Vitiligo: An Update on Its Pathogenesis and Therapeutic Implications. Cells 2023, 12, 936. [Google Scholar] [CrossRef]
- Veluthakal, R.; Esparza, D.; Hoolachan, J.M.; Balakrishnan, R.; Ahn, M.; Oh, E.; Jayasena, C.S.; Thurmond, D.C. Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression. Int. J. Mol. Sci. 2024, 25, 1504. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Shen, X.; Yuan, X.; Huang, J.; Zhu, Y.; Zhu, T.; Zhang, T.; Wu, H.; Wu, Q.; Fan, Y.; et al. Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis. Nat. Commun. 2024, 15, 3213. [Google Scholar] [CrossRef] [PubMed]
- Han, Y.; Zhang, M.; Yu, S.; Jia, L. Oxidative Stress in Pediatric Asthma: Sources, Mechanisms, and Therapeutic Potential of Antioxidants. Front. Biosci. Landmark Ed. 2025, 30, 22688. [Google Scholar] [CrossRef]
- Choi, E.H.; Kim, M.H.; Park, S.J. Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment. Int. J. Mol. Sci. 2024, 25, 7952. [Google Scholar] [CrossRef] [PubMed]
- Gogna, T.; Housden, B.E.; Houldsworth, A. Exploring the Role of Reactive Oxygen Species in the Pathogenesis and Pathophysiology of Alzheimer’s and Parkinson’s Disease and the Efficacy of Antioxidant Treatment. Antioxidants 2024, 13, 1138. [Google Scholar] [CrossRef]
- Li, Y.; Zhang, W.; Zhang, Q.; Li, Y.; Xin, C.; Tu, R.; Yan, H. Oxidative stress of mitophagy in neurodegenerative diseases: Mechanism and potential therapeutic targets. Arch. Biochem. Biophys. 2025, 764, 110283. [Google Scholar] [CrossRef]
- Xiao, C.L.; Lai, H.T.; Zhou, J.J.; Liu, W.Y.; Zhao, M.; Zhao, K. Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury. Mol. Neurobiol. 2025, 62, 2230–2249. [Google Scholar] [CrossRef]
- Wen, P.; Sun, Z.; Gou, F.; Wang, J.; Fan, Q.; Zhao, D.; Yang, L. Oxidative stress and mitochondrial impairment: Key drivers in neurodegenerative disorders. Ageing Res. Rev. 2025, 104, 102667. [Google Scholar] [CrossRef]
- Üremiş, N.; Üremiş, M.M. Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases. J. Biochem. Mol. Toxicol. 2025, 39, e70133. [Google Scholar] [CrossRef]
- Tamagno, E.; Guglielmotto, M.; Vasciaveo, V.; Tabaton, M. Oxidative Stress and Beta Amyloid in Alzheimer’s Disease. Which Comes First: The Chicken or the Egg? Antioxidants 2021, 10, 1479. [Google Scholar] [CrossRef]
- Wang, J.; Liu, M.; Zhao, J.; Hu, P.; Gao, L.; Tian, S.; Zhang, J.; Liu, H.; Xu, X.; He, Z. Oxidative stress and dysregulated long noncoding RNAs in the pathogenesis of Parkinson’s disease. Biol. Res. 2025, 58, 7. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Shen, X.; Zhang, Y.; Zheng, X.; Cepeda, C.; Wang, Y.; Duan, S.; Tong, X. Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells. Glia 2023, 71, 1383–1401. [Google Scholar] [CrossRef]
- Bunge, R.P. Expanding roles for the Schwann cell: Ensheathment, myelination, trophism and regeneration. Curr. Opin. Neurobiol. 1993, 3, 805–809. [Google Scholar] [CrossRef] [PubMed]
- Kampanis, V.; Tolou-Dabbaghian, B.; Zhou, L.; Roth, W.; Puttagunta, R. Cyclic Stretch of Either PNS or CNS Located Nerves Can Stimulate Neurite Outgrowth. Cells 2020, 10, 32. [Google Scholar] [CrossRef]
- Cárdenas, A.; Kong, M.; Alvarez, A.; Maldonado, H.; Leyton, L. Signaling pathways involved in neuron-astrocyte adhesion and migration. Curr. Mol. Med. 2014, 14, 275–290. [Google Scholar] [CrossRef] [PubMed]
- Su, Y.; Wang, X.; Yang, Y.; Chen, L.; Xia, W.; Hoi, K.K.; Li, H.; Wang, Q.; Yu, G.; Chen, X.; et al. Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development. Neuron 2023, 111, 190–201.e198. [Google Scholar] [CrossRef]
- Oshima, K.; Yoshinaga, S.; Kitazawa, A.; Hirota, Y.; Nakajima, K.; Kubo, K.I. A Unique “Reversed” Migration of Neurons in the Developing Claustrum. J. Neurosci. 2023, 43, 693–708. [Google Scholar] [CrossRef]
- Matsumoto, M.; Matsushita, K.; Hane, M.; Wen, C.; Kurematsu, C.; Ota, H.; Bang Nguyen, H.; Quynh Thai, T.; Herranz-Pérez, V.; Sawada, M.; et al. Neuraminidase inhibition promotes the collective migration of neurons and recovery of brain function. EMBO Mol. Med. 2024, 16, 1228–1253. [Google Scholar] [CrossRef]
- Wang, Y.T.; Yuan, H. Research progress of endogenous neural stem cells in spinal cord injury. Ibrain 2022, 8, 199–209. [Google Scholar] [CrossRef]
- Rueger, M.A.; Androutsellis-Theotokis, A. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: Novel approaches. Curr. Pharm. Des. 2013, 19, 6499–6506. [Google Scholar] [CrossRef]
- Mubuchi, A.; Takechi, M.; Nishio, S.; Matsuda, T.; Itoh, Y.; Sato, C.; Kitajima, K.; Kitagawa, H.; Miyata, S. Assembly of neuron- and radial glial-cell-derived extracellular matrix molecules promotes radial migration of developing cortical neurons. Elife 2024, 12, RP92342. [Google Scholar] [CrossRef] [PubMed]
- Taylor, K.R.; Monje, M. Neuron-oligodendroglial interactions in health and malignant disease. Nat. Rev. Neurosci. 2023, 24, 733–746. [Google Scholar] [CrossRef]
- Ott, C.M.; Constable, S.; Nguyen, T.M.; White, K.; Lee, W.A.; Lippincott-Schwartz, J.; Mukhopadhyay, S. Permanent deconstruction of intracellular primary cilia in differentiating granule cell neurons. J. Cell Biol. 2024, 223, e202404038. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Duan, S.; Apostolou, P.E.; Wu, X.; Watanabe, J.; Gallitto, M.; Barron, T.; Taylor, K.R.; Woo, P.J.; Hua, X.; et al. CHD2 Regulates Neuron-Glioma Interactions in Pediatric Glioma. Cancer Discov. 2024, 14, 1732–1754. [Google Scholar] [CrossRef] [PubMed]
- Araragi, N.; Petermann, M.; Suzuki, M.; Larkum, M.; Mosienko, V.; Bader, M.; Alenina, N.; Klempin, F. Acute Optogenetic Stimulation of Serotonin Neurons Reduces Cell Proliferation in the Dentate Gyrus of Mice. ACS Chem. Neurosci. 2025, 16, 781–789. [Google Scholar] [CrossRef]
- Cai, R.; Wang, Y.; Huang, Z.; Zou, Q.; Pu, Y.; Yu, C.; Cai, Z. Role of RhoA/ROCK signaling in Alzheimer’s disease. Behav. Brain Res. 2021, 414, 113481. [Google Scholar] [CrossRef]
- Medd, M.M.; Yon, J.E.; Dong, H. RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer’s Disease. Curr. Issues Mol. Biol. 2025, 47, 124. [Google Scholar] [CrossRef]
- Ramakrishan, P.; Rajangam, J.; Mahinoor, S.S.; Bisht, S.; Mekala, S.; Upadhyay, D.K.; Solomon, V.R.; Sabarees, G.; Pelluri, R. Unveiling the mTOR pathway modulation by SGLT2 inhibitors: A novel approach to Alzheimer’s disease in type 2 diabetes. Metab. Brain Dis. 2025, 40, 132. [Google Scholar] [CrossRef]
- Salzer, J.; Feltri, M.L.; Jacob, C. Schwann Cell Development and Myelination. Cold Spring Harb. Perspect. Biol. 2024, 16, a041360. [Google Scholar] [CrossRef]
- Anton, E.S.; Sandrock, A.W., Jr.; Matthew, W.D. Merosin promotes neurite growth and Schwann cell migration in vitro and nerve regeneration in vivo: Evidence using an antibody to merosin, ARM-1. Dev. Biol. 1994, 164, 133–146. [Google Scholar] [CrossRef]
- Torigoe, K.; Tanaka, H.F.; Takahashi, A.; Awaya, A.; Hashimoto, K. Basic behavior of migratory Schwann cells in peripheral nerve regeneration. Exp. Neurol. 1996, 137, 301–308. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, A.L.; West, J.M.; Saffari, T.M.; Nguyen, M.; Moore, A.M. Promoting Nerve Regeneration: Electrical Stimulation, Gene Therapy, and Beyond. Physiology 2022, 37, 302–310. [Google Scholar] [CrossRef]
- Nocera, G.; Jacob, C. Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury. Cell Mol. Life Sci. 2020, 77, 3977–3989. [Google Scholar] [CrossRef]
- Tagliatti, E.; Desiato, G.; Mancinelli, S.; Bizzotto, M.; Gagliani, M.C.; Faggiani, E.; Hernández-Soto, R.; Cugurra, A.; Poliseno, P.; Miotto, M.; et al. Trem2 expression in microglia is required to maintain normal neuronal bioenergetics during development. Immunity 2024, 57, 86–105.e9. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.; Zhang, S.; Cheng, R.; Jiang, A.; Qin, X. Knockdown of RGMA improves ischemic stroke via Reprogramming of Neuronal Metabolism. Free Radic. Biol. Med. 2024, 218, 41–56. [Google Scholar] [CrossRef] [PubMed]
- Qiu, S.; Wu, Q.; Wang, H.; Liu, D.; Chen, C.; Zhu, Z.; Zheng, H.; Yang, G.; Li, L.; Yang, M. AZGP1 in POMC neurons modulates energy homeostasis and metabolism through leptin-mediated STAT3 phosphorylation. Nat. Commun. 2024, 15, 3377. [Google Scholar] [CrossRef]
- Nixon, R.A. Autophagy-lysosomal-associated neuronal death in neurodegenerative disease. Acta Neuropathol. 2024, 148, 42. [Google Scholar] [CrossRef]
- He, K.; Zhao, Z.; Zhang, J.; Li, D.; Wang, S.; Liu, Q. Cholesterol Metabolism in Neurodegenerative Diseases. Antioxid. Redox Signal. 2024, 41, 1051–1072. [Google Scholar] [CrossRef]
- Ma, X.; Di, Q.; Li, X.; Zhao, X.; Zhang, R.; Xiao, Y.; Li, X.; Wu, H.; Tang, H.; Quan, J.; et al. Munronoid I Ameliorates DSS-Induced Mouse Colitis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Via Modulation of NLRP3. Front. Immunol. 2022, 13, 853194. [Google Scholar] [CrossRef]
- Jiang, S.; Li, H.; Zhang, L.; Mu, W.; Zhang, Y.; Chen, T.; Wu, J.; Tang, H.; Zheng, S.; Liu, Y.; et al. Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics. Nucleic Acids Research 2024, 53, D1670–D1676. [Google Scholar] [CrossRef]
- Peng, X.; Guo, H.; Zhang, X.; Yang, Z.; Ruganzu, J.B.; Yang, Z.; Wu, X.; Bi, W.; Ji, S.; Yang, W. TREM2 Inhibits Tau Hyperphosphorylation and Neuronal Apoptosis via the PI3K/Akt/GSK-3β Signaling Pathway In vivo and In vitro. Mol. Neurobiol. 2023, 60, 2470–2485. [Google Scholar] [CrossRef] [PubMed]
- Qin, Q.; Teng, Z.; Liu, C.; Li, Q.; Yin, Y.; Tang, Y. TREM2, microglia, and Alzheimer’s disease. Mech. Ageing Dev. 2021, 195, 111438. [Google Scholar] [CrossRef] [PubMed]
- Nugent, A.A.; Lin, K.; van Lengerich, B.; Lianoglou, S.; Przybyla, L.; Davis, S.S.; Llapashtica, C.; Wang, J.; Kim, D.J.; Xia, D.; et al. TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge. Neuron 2020, 105, 837–854.e839. [Google Scholar] [CrossRef] [PubMed]
- Rachmian, N.; Medina, S.; Cherqui, U.; Akiva, H.; Deitch, D.; Edilbi, D.; Croese, T.; Salame, T.M.; Ramos, J.M.P.; Cahalon, L.; et al. Identification of senescent, TREM2-expressing microglia in aging and Alzheimer’s disease model mouse brain. Nat. Neurosci. 2024, 27, 1116–1124. [Google Scholar] [CrossRef]
- Wang, S.; Sudan, R.; Peng, V.; Zhou, Y.; Du, S.; Yuede, C.M.; Lei, T.; Hou, J.; Cai, Z.; Cella, M.; et al. TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell 2022, 185, 4153–4169.e4119. [Google Scholar] [CrossRef]
- Miao, J.; Zhang, Y.; Su, C.; Zheng, Q.; Guo, J. Insulin-Like Growth Factor Signaling in Alzheimer’s Disease: Pathophysiology and Therapeutic Strategies. Mol. Neurobiol. 2025, 62, 3195–3225. [Google Scholar] [CrossRef]
- Wang, Y.; Wang, M.; Xu, M.; Li, T.; Fan, K.; Yan, T.; Xiao, F.; Bi, K.; Jia, Y. Nootkatone, a neuroprotective agent from Alpiniae oxyphyllae Fructus, improves cognitive impairment in lipopolysaccharide-induced mouse model of Alzheimer’s disease. Int. Immunopharmacol. 2018, 62, 77–85. [Google Scholar] [CrossRef]
- Liu, A.; Zhao, X.; Li, H.; Liu, Z.; Liu, B.; Mao, X.; Guo, L.; Bi, K.; Jia, Y. 5-Hydroxymethylfurfural, an antioxidant agent from Alpinia oxyphylla Miq. improves cognitive impairment in Aβ 1-42 mouse model of Alzheimer’s disease. Int. Immunopharmacol. 2014, 23, 719–725. [Google Scholar] [CrossRef]
- Zhang, Z.; Li, R.; Zhou, Y.; Huang, S.; Hou, Y.; Pei, G. Dietary Flavonoid Chrysin Functions as a Dual Modulator to Attenuate Amyloid-β and Tau Pathology in the Models of Alzheimer’s Disease. Mol. Neurobiol. 2025, 62, 4274–4291. [Google Scholar] [CrossRef]
- Chi, F.; Zhang, G.; Ren, N.; Zhang, J.; Du, F.; Zheng, X.; Zhang, C.; Lin, Z.; Li, R.; Shi, X.; et al. The anti-alcoholism drug disulfiram effectively ameliorates ulcerative colitis through suppressing oxidative stresses-associated pyroptotic cell death and cellular inflammation in colonic cells. Int. Immunopharmacol. 2022, 111, 109117. [Google Scholar] [CrossRef]
- Wu, B.; Gan, A.; Wang, R.; Lin, F.; Yan, T.; Jia, Y. Alpinia oxyphylla Miq. volatile oil ameliorates depressive behaviors and inhibits neuroinflammation in CUMS-exposed mice by inhibiting the TLR4-medicated MyD88/NF-κB signaling pathway. J. Chem. Neuroanat. 2023, 130, 102270. [Google Scholar] [CrossRef] [PubMed]
- Yan, T.; Wu, B.; Liao, Z.Z.; Liu, B.; Zhao, X.; Bi, K.S.; Jia, Y. Brain-derived Neurotrophic Factor Signaling Mediates the Antidepressant-like Effect of the Total Flavonoids of Alpiniae oxyphyllae Fructus in Chronic Unpredictable Mild Stress Mice. Phytother. Res. 2016, 30, 1493–1502. [Google Scholar] [CrossRef]
- Cui, L.J.; Yuan, W.; Chen, F.Y.; Wang, Y.X.; Li, Q.M.; Lin, C.; Miao, X.P. Pectic polysaccharides ameliorate the pathology of ulcerative colitis in mice by reducing pyroptosis. Ann. Transl. Med. 2022, 10, 347. [Google Scholar] [CrossRef]
- Yan, T.; Li, F.; Xiong, W.; Wu, B.; Xiao, F.; He, B.; Jia, Y. Nootkatone improves anxiety- and depression-like behavior by targeting hyperammonemia-induced oxidative stress in D-galactosamine model of liver injury. Environ. Toxicol. 2021, 36, 694–706. [Google Scholar] [CrossRef]
- Li, G.; Zhang, Z.; Quan, Q.; Jiang, R.; Szeto, S.S.; Yuan, S.; Wong, W.T.; Lam, H.H.; Lee, S.M.; Chu, I.K. Discovery, Synthesis, and Functional Characterization of a Novel Neuroprotective Natural Product from the Fruit of Alpinia oxyphylla for use in Parkinson’s Disease Through LC/MS-Based Multivariate Data Analysis-Guided Fractionation. J. Proteome Res. 2016, 15, 2595–2606. [Google Scholar] [CrossRef] [PubMed]
- Guo, C.; Zhu, J.; Wang, J.; Duan, J.; Ma, S.; Yin, Y.; Quan, W.; Zhang, W.; Guan, Y.; Ding, Y.; et al. Neuroprotective effects of protocatechuic aldehyde through PLK2/p-GSK3β/Nrf2 signaling pathway in both in vivo and in vitro models of Parkinson’s disease. Aging 2019, 11, 9424–9441. [Google Scholar] [CrossRef]
- Yao, Z.; Li, J.; Bian, L.; Li, Q.; Wang, X.; Yang, X.; Wei, X.; Wan, G.; Wang, Y.; Shi, J.; et al. Nootkatone alleviates rotenone-induced Parkinson’s disease symptoms through activation of the PI3K/Akt signaling pathway. Phytother. Res. 2022, 36, 4183–4200. [Google Scholar] [CrossRef] [PubMed]
- Graff-Radford, J.; Yong, K.X.X.; Apostolova, L.G.; Bouwman, F.H.; Carrillo, M.; Dickerson, B.C.; Rabinovici, G.D.; Schott, J.M.; Jones, D.T.; Murray, M.E. New insights into atypical Alzheimer’s disease in the era of biomarkers. Lancet Neurol. 2021, 20, 222–234. [Google Scholar] [CrossRef]
- Twarowski, B.; Herbet, M. Inflammatory Processes in Alzheimer’s Disease-Pathomechanism, Diagnosis and Treatment: A Review. Int. J. Mol. Sci. 2023, 24, 6518. [Google Scholar] [CrossRef]
- Liu, E.; Zhang, Y.; Wang, J.Z. Updates in Alzheimer’s disease: From basic research to diagnosis and therapies. Transl. Neurodegener. 2024, 13, 45. [Google Scholar] [CrossRef]
- Rostagno, A.A. Pathogenesis of Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 24, 107. [Google Scholar] [CrossRef] [PubMed]
- Athar, T.; Al Balushi, K.; Khan, S.A. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Mol. Biol. Rep. 2021, 48, 5629–5645. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.; Lv, M.; Hu, H.; Huai, L.; Zhu, B.; Fan, S.; Wang, Q.; Zhang, J. 5-Hydroxymethylfurfural and its Downstream Chemicals: A Review of Catalytic Routes. Adv. Mater. 2024, 36, e2311464. [Google Scholar] [CrossRef]
- Hao, Y.; Ge, H.; Sun, M.; Gao, Y. Selecting an Appropriate Animal Model of Depression. Int. J. Mol. Sci. 2019, 20, 4827. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Long, Y.; Yu, S.; Li, D.; Yang, M.; Guan, Y.; Zhang, D.; Wan, J.; Liu, S.; Shi, A.; et al. Natural volatile oils derived from herbal medicines: A promising therapy way for treating depressive disorder. Pharmacol. Res. 2021, 164, 105376. [Google Scholar] [CrossRef]
- Martins, J.; Brijesh, S. Phytochemistry and pharmacology of anti-depressant medicinal plants: A review. Biomed. Pharmacother. 2018, 104, 343–365. [Google Scholar] [CrossRef]
- Yan, T.; Nian, T.; Liao, Z.; Xiao, F.; Wu, B.; Bi, K.; He, B.; Jia, Y. Antidepressant effects of a polysaccharide from okra (Abelmoschus esculentus (L) Moench) by anti-inflammation and rebalancing the gut microbiota. Int. J. Biol. Macromol. 2020, 144, 427–440. [Google Scholar] [CrossRef]
- Chen, B.; Li, J.; Xie, Y.; Ming, X.; Li, G.; Wang, J.; Li, M.; Li, X.; Xiong, L. Cang-ai volatile oil improves depressive-like behaviors and regulates DA and 5-HT metabolism in the brains of CUMS-induced rats. J. Ethnopharmacol. 2019, 244, 112088. [Google Scholar] [CrossRef]
- Yan, T.; Sun, Y.; Xiao, F.; Wu, B.; Bi, K.; He, B.; Jia, Y. Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain-derived neurotrophic factor. Phytother. Res. 2019, 33, 3177–3190. [Google Scholar] [CrossRef]
- Yan, T.; He, B.; Wan, S.; Xu, M.; Yang, H.; Xiao, F.; Bi, K.; Jia, Y. Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism. Sci. Rep. 2017, 7, 6903. [Google Scholar] [CrossRef]
- Figueroa-Hall, L.K.; Paulus, M.P.; Savitz, J. Toll-Like Receptor Signaling in Depression. Psychoneuroendocrinology 2020, 121, 104843. [Google Scholar] [CrossRef] [PubMed]
- Zhao, J.; Bi, W.; Zhang, J.; Xiao, S.; Zhou, R.; Tsang, C.K.; Lu, D.; Zhu, L. USP8 protects against lipopolysaccharide-induced cognitive and motor deficits by modulating microglia phenotypes through TLR4/MyD88/NF-κB signaling pathway in mice. Brain Behav. Immun. 2020, 88, 582–596. [Google Scholar] [CrossRef]
- Hayes, M.T. Parkinson’s Disease and Parkinsonism. Am. J. Med. 2019, 132, 802–807. [Google Scholar] [CrossRef]
- Bloem, B.R.; Okun, M.S.; Klein, C. Parkinson’s disease. Lancet 2021, 397, 2284–2303. [Google Scholar] [CrossRef] [PubMed]
- Zhou, H.; Li, S.; Li, C.; Yang, X.; Li, H.; Zhong, H.; Lu, J.H.; Lee, S.M. Oxyphylla A Promotes Degradation of α-Synuclein for Neuroprotection via Activation of Immunoproteasome. Aging Dis. 2020, 11, 559–574. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Li, G.; Law, H.C.H.; Chen, H.; Lee, S.M. Determination of Oxyphylla A Enantiomers in the Fruits of Alpinia oxyphylla by a Chiral High-Performance Liquid Chromatography-Multiple Reaction Monitoring-Mass Spectrometry Method and Comparison of Their In Vivo Biological Activities. J. Agric. Food Chem. 2020, 68, 11170–11181. [Google Scholar] [CrossRef]
- He, Y.; Chen, S.; Tsoi, B.; Qi, S.; Gu, B.; Wang, Z.; Peng, C.; Shen, J. Alpinia oxyphylla Miq. and Its Active Compound P-Coumaric Acid Promote Brain-Derived Neurotrophic Factor Signaling for Inducing Hippocampal Neurogenesis and Improving Post-cerebral Ischemic Spatial Cognitive Functions. Front. Cell Dev. Biol. 2020, 8, 577790. [Google Scholar] [CrossRef]
Subject | Test Model | Research Results | Effect | Ref. |
---|---|---|---|---|
Sesquiterpenoids in AOF | LPS-stimulated BV-2 microglia | It can significantly inhibit the secretion of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), down-regulate the expression of inflammation-related genes and proteins, and suppress the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase (p38) in the mitogen-activated protein kinase (MAPK) signaling pathway. | anti-inflammatory | [23] |
Chrysin, etc. | LPS-stimulated BV-2 microglia | It can promote the transformation of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, reduce the secretion of pro-inflammatory factors (NO, TNF-α, etc.), and increase the expression of anti-inflammatory factors such as interleukin-10 (IL-10), etc. | anti-inflammatory | [24] |
AOF extract, PCA, NKT, etc. | Hydrogen peroxide (H2O2) stimulated PC12 cells | It activates the phosphatidylinositol-3-kinase (PI3K)/serine/threonine-protein kinase B (Akt) signaling pathway, up-regulates the expression of B-cell lymphoma-2 (Bcl-2), inhibits the activation of Bcl-2-associated X protein (BAX) and caspase-3, and simultaneously reduces the reactive oxygen species (ROS) level and enhances the activity of superoxide dismutase (SOD)/catalase (CAT)/glutathione peroxidase (GSH-Px) antioxidant enzymes. | Antioxidant, antiapoptotic | [25] |
Oxyphylla A | N2a/APP cells, SAMP8 mice | It can reduce amyloid-β (Aβ) production and improve cognitive deficits in AD models by inhibiting oxidative stress (dependent on the Akt/GSK3β and Nrf2/Keap1/HO-1 pathway). | Antioxidant | [26] |
NKT | PC12 cells induced by Aβ1–42 | The combination of NKT and schisandrin (SCH) can synergistically inhibit Aβ generation and tau phosphorylation through the PI3K/AKT pathway while alleviating oxidative stress and apoptosis. | Antioxidant, antiapoptotic | [27] |
PCA | RSC96 Schwann cells | It can significantly promote the migration of Schwann cells by activating the ERK1/2, JNK, and p38 MAPK signaling pathways, promoting the expression and activity of urokinase-type plasminogen activator (uPA), tissue plasminogen activator (tPA), and metalloproteinase 2/9 (MMP2/9). | Promote cell migration | [28] |
AOF extract (spray-dried powder) | Sciatic nerve defect model in rats, RSC96 Schwann cells | It can activate the IGF1R-PI3K/Akt signaling pathway and promote the proliferation of Schwann cells, the cell cycle process (transition from G1 phase to S phase), and the expression of cyclins (Cyclin D1, E, and A), thereby promoting sciatic nerve regeneration. | Promote cell proliferation | [29] |
AOF extract | APP/PS1 transgenic mice, RSC96 Schwann cells | It can regulate the metabolism of bile acids and sphingolipids in the plasma of mice, improve cognitive function, and reduce the deposition of Aβ in the brain. | Regulate metabolism | [30] |
AOF extract | Aβ1–42 -induced AD rat model | It can regulate biomarkers related to amino acids, lipids, and energy metabolism (such as arginine, lysophospholipids, and acylcarnitine), improve cognitive function, and reduce Aβ deposition in the brain. | Regulate metabolism | [31] |
Diseases | Components | Mechanism of Action | Ref. |
---|---|---|---|
AD | NKT | It significantly reduced the expression levels of inflammatory factors (IL-1β, IL-6, TNF-α, NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), and NF-κB p65) in the hippocampal region, indicating that its protective effects are mediated through the suppression of neuroinflammation. | [87] |
5-hydroxymethylfurfural | It inhibited β-secretase activity, thereby reducing the levels of Aβ1–42 and malondialdehyde (MDA), while enhancing the activity of antioxidant enzymes (SOD, GPx). | [88] | |
Chrysin | It reduced the levels of Aβ and phosphorylated tau and exhibited dual inhibitory activity against BACE1 and GSK3β. | [89] | |
PCA | It alleviated the inhibitory effect of Aβ25–35 on the autophagy–lysosome pathway in primary neurons. | [90] | |
Depression | Alpinia oxyphylla Miq. volatile oil (AOVO) | It inhibited the TLR4-mediated myeloid differentiation primary response gene 88 (MyD88)/NF-κB signaling pathway, significantly reducing the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the hippocampal region while simultaneously up-regulating serotonin (5-hydroxytryptamine and 5-HT) levels. | [91] |
Flavonoids | It up-regulated the expression of BDNF and its receptor TrkB in the hippocampal region, activating downstream signaling molecules (phosphorylated cAMP response element-binding protein (p-CREB) and p-Akt). | [92] | |
Chrysin | It inhibits microglial activation, reducing NLRP3 and IL-1β expression, and blocks Fyn phosphorylation, thereby suppressing the expression of the NLRP3 inflammasome and the NF-κB pathway. | [93] | |
NKT | It activated the Keap1/Nrf2/HO-1 antioxidant signaling pathway, enhancing cellular defense mechanisms against oxidative stress. | [94] | |
PD | Oxyphylla A | It activates the NRF2 pathway, alleviating chemically induced primary neuron damage in vitro, and mitigating chemically induced dopaminergic neuron loss and behavioral deficits in vivo. | [95] |
PCA | It reduces oxidative damage by means of the Polo-like kinase 2/p-GSK3 signaling pathway and alleviates mitochondrial dysfunction via the β/Nrf2 pathway. | [96] | |
NKT | It activates the PI3K/Akt signaling pathway to inhibit the expression of MAPK3. | [97] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wei, Y.; Gao, K.; Sun, Y.; Sheng, Q.; Guo, J. Neuroprotective Effects and Mechanisms of Alpiniae oxyphyllae Fructus, a Medicinal and Edible Homologous Herb: Research Advances. Int. J. Mol. Sci. 2025, 26, 6230. https://doi.org/10.3390/ijms26136230
Wei Y, Gao K, Sun Y, Sheng Q, Guo J. Neuroprotective Effects and Mechanisms of Alpiniae oxyphyllae Fructus, a Medicinal and Edible Homologous Herb: Research Advances. International Journal of Molecular Sciences. 2025; 26(13):6230. https://doi.org/10.3390/ijms26136230
Chicago/Turabian StyleWei, Yongyi, Ke Gao, Yidong Sun, Qing Sheng, and Jianjun Guo. 2025. "Neuroprotective Effects and Mechanisms of Alpiniae oxyphyllae Fructus, a Medicinal and Edible Homologous Herb: Research Advances" International Journal of Molecular Sciences 26, no. 13: 6230. https://doi.org/10.3390/ijms26136230
APA StyleWei, Y., Gao, K., Sun, Y., Sheng, Q., & Guo, J. (2025). Neuroprotective Effects and Mechanisms of Alpiniae oxyphyllae Fructus, a Medicinal and Edible Homologous Herb: Research Advances. International Journal of Molecular Sciences, 26(13), 6230. https://doi.org/10.3390/ijms26136230