# Plant polysaccharides in neuroprotection: mechanistic insights across central nervous system disorders

**Authors:** Qiyue Yu, Hui Chen, Zhuofeng Qu, Jialin Qu, Yan Wang, Lina Liang, Shouyu Hu

PMC · DOI: 10.3389/fphar.2025.1727705 · Frontiers in Pharmacology · 2026-02-11

## TL;DR

This review explores how plant polysaccharides protect the brain and spinal cord by reducing inflammation and stress in neurological disorders.

## Contribution

The paper provides a comprehensive overview of the neuroprotective mechanisms of plant polysaccharides across various CNS disorders.

## Key findings

- Plant polysaccharides suppress neuroinflammation and oxidative stress in preclinical models.
- They modulate autophagy and maintain gut microbiota balance to support neuronal health.
- Challenges like poor bioavailability and CNS penetration hinder clinical translation.

## Abstract

Central nervous system (CNS) disorders pose a major global health burden, and the limited efficacy and adverse effects of current pharmacotherapies underscore the need for more effective therapeutic strategies. Plant polysaccharides, as key bioactive metabolites of medicinal plants, have attracted increasing attention due to their broad biological activities and favorable safety profiles. In this review, we comprehensively summarize recent advances in understanding their neuroprotective effects, emphasizing mechanistic pathways that include the suppression of neuroinflammation, mitigation of oxidative stress, inhibition of neuronal apoptosis, modulation of autophagy, and maintenance of gut microbiota homeostasis. These mechanisms are examined across diverse preclinical models, with particular attention to model selection, dosing parameters, and experimental rigor to ensure reliable interpretation. Furthermore, we critically discuss major challenges hindering clinical translation, including structural heterogeneity, limited bioavailability, and restricted CNS penetration, while highlighting emerging solutions such as advanced delivery systems and targeted chemical modification. Overall, this review delineates the multi-pathway neuroprotective actions of plant polysaccharides and offers strategic direction for future mechanistic studies and translational development.

## Full-text entities

- **Genes:** Prkcb (protein kinase C, beta) [NCBI Gene 18751] {aka PKC-B, PKC-Beta, Pkcb, Prkcb1, Prkcb2}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, P2rx7 (purinergic receptor P2X, ligand-gated ion channel, 7) [NCBI Gene 18439] {aka P2X(7), P2X7R}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Casp9 (caspase 9) [NCBI Gene 58918] {aka Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], Ntrk2 (neurotrophic tyrosine kinase, receptor, type 2) [NCBI Gene 18212] {aka GP145-TrkB/GP95-TrkB, Tkrb, trk-B, trkB}, Pcna (proliferating cell nuclear antigen) [NCBI Gene 18538], Tet2 (tet methylcytosine dioxygenase 2) [NCBI Gene 214133] {aka Ayu17-449, E130014J05Rik, mKIAA1546}, Hspa5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 14828] {aka Bip, D2Wsu141e, D2Wsu17e, Grp78, Hsce70, SEZ-7}, Shh (sonic hedgehog) [NCBI Gene 20423] {aka 9530036O11Rik, Dsh, HHG-1, Hhg1, Hx, Hxl3}, Nfkbia (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) [NCBI Gene 18035] {aka Nfkbi}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Eif2a (eukaryotic translation initiation factor 2A) [NCBI Gene 229317] {aka D030048D22, D3Ertd194e}, Map1lc3a (microtubule-associated protein 1 light chain 3 alpha) [NCBI Gene 66734] {aka 1010001H21Rik, 4922501H04Rik, LC3, LC3a}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, Grin2a (glutamate receptor, ionotropic, NMDA2A (epsilon 1)) [NCBI Gene 14811] {aka GluN2A, GluRepsilon1, NMDAR2A, NR2A}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], mucin [NCBI Gene 100508689], Xbp1 (X-box binding protein 1) [NCBI Gene 22433] {aka D11Ertd39e, TREB-5, TREB5, XBP-1}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Eif2ak3 (eukaryotic translation initiation factor 2 alpha kinase 3) [NCBI Gene 13666] {aka Pek, Perk}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], Sirt3 (sirtuin 3) [NCBI Gene 64384] {aka 2310003L23Rik, Sir2l3}, Apaf1 (apoptotic peptidase activating factor 1) [NCBI Gene 11783] {aka 6230400I06Rik, Apaf-1, Apaf1l, fog, mKIAA0413}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Tph1 (tryptophan hydroxylase 1) [NCBI Gene 21990] {aka Tph}, Map3k7 (mitogen-activated protein kinase kinase kinase 7) [NCBI Gene 26409] {aka B430101B05, Tak1}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}, Grin2b (glutamate receptor, ionotropic, NMDA2B (epsilon 2)) [NCBI Gene 14812] {aka GluN2B, GluRepsilon2, NR2B, Nmdar2b}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Iba1 (induction of brown adipocytes 1) [NCBI Gene 114737], Ern1 (endoplasmic reticulum to nucleus signalling 1) [NCBI Gene 78943] {aka 9030414B18Rik, Ire1a, Ire1alpha, Ire1p}, Atf6 (activating transcription factor 6) [NCBI Gene 226641] {aka 9130025P16Rik, 9630036G24, Atf6alpha, ESTM49}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Hsf1 (heat shock factor 1) [NCBI Gene 15499] {aka HSTF, HSTF 1, Hsf1alpha, Hsf1beta}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Ocln (occludin) [NCBI Gene 18260] {aka Ocl}, Bnip3 (BCL2/adenovirus E1B interacting protein 3) [NCBI Gene 12176] {aka Nip3}, Casp8 (caspase 8) [NCBI Gene 12370] {aka CASP-8, FLICE, MACH, Mch5}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Mapk7 (mitogen-activated protein kinase 7) [NCBI Gene 23939] {aka BMK-1, BMK1, ERK-5, ERK5, Erk5-T, PRKM7}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Atg5 (autophagy related 5) [NCBI Gene 11793] {aka 2010107M05Rik, 3110067M24Rik, Apg5l, Atg5l, Paddy}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Eno2 (enolase 2, gamma neuronal) [NCBI Gene 13807] {aka D6Ertd375e, Eno-2, NSE}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Skn1 (skin antigen 1) [NCBI Gene 103985] {aka Sk-1, Skn-1}
- **Diseases:** infarct (MESH:D007238), hypoxic (MESH:D002534), depressive (MESH:D003866), neurological diseases (MESH:D020271), neuronal (MESH:D009410), cerebral edema (MESH:D001929), C6 glioma (MESH:C567307), cerebral thrombosis (MESH:D020767), acute stroke (MESH:D020521), neurological pathologies (MESH:D005598), acute neurological diseases (MESH:D000208), spinal cord injury (MESH:D013119), hypoxic/ischemic injury (MESH:D020925), necrosis (MESH:D009336), post-traumatic stress disorder (MESH:D013313), amnesia (MESH:D000647), ischemia (MESH:D007511), neurological deficits (MESH:D009461), Brain tumors (MESH:D001932), synaptic damage (MESH:D012183), hypoxia (MESH:D000860), memory impairment (MESH:D008569), Neurological injuries and disorders (MESH:D009422), microglial damage (MESH:D020263), cognitive deficits (MESH:D003072), apoptosis (MESH:D065703), disability (MESH:D009069), epilepsy (MESH:D004827), reperfusion injury (MESH:D015427), neural injury (MESH:D014947), disease (MESH:D004194), neurodegeneration (MESH:D019636), optic nerve injury (MESH:D020221), inflammation (MESH:D007249), PD (MESH:D010300), mitochondrial damage (MESH:D028361), middle cerebral artery occlusion (MESH:D020244), brain injury (MESH:D001930), brain impairment (MESH:D001927), demyelination (MESH:D003711), nervous system injuries (MESH:D020196), vascular dementia (MESH:D015140), diabetes (MESH:D003920), retinal ischemia (MESH:D012173), Huntington's disease (MESH:D006816), Gut dysbiosis (MESH:D064806), cerebral ischemic injury (MESH:D017202), cerebral ischemia (MESH:D002545), cerebral infarction (MESH:D002544), cancer (MESH:D009369), AD (MESH:D000544), behavioral dysfunction (MESH:D001523), OGD (MESH:C536050), cardiovascular disorders (MESH:D002318), coagulation (MESH:D001778), neurotoxic (MESH:D020258), CNS disorders (MESH:D002493), mucosal edema (MESH:D004487), Neuroinflammation (MESH:D000090862), disorder of pyruvate and glucose metabolism (MESH:D044882)
- **Chemicals:** citrate (MESH:D019343), GSH (MESH:D005978), alpha-linolenic acid (MESH:D017962), free radicals (MESH:D005609), butyric acid (MESH:D020148), aluminum trichloride (MESH:D000077410), taurine (MESH:D013654), polyglutamine (MESH:C097188), water (MESH:D014867), ATP (MESH:D000255), Gal (MESH:C101993), Astragaloside IV (MESH:C052064), propionic acid (MESH:C029658), arabinose (MESH:D001089), nonesterified fatty acid (MESH:D005230), LPS (MESH:D008070), lipid (MESH:D008055), arachidonic acid (MESH:D016718), minocycline (MESH:D008911), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (MESH:C002502), edaravone (MESH:D000077553), iron (MESH:D007501), acetic acid (MESH:D019342), tryptophan (MESH:D014364), cadmium (MESH:D002104), glutamate (MESH:D018698), gamma-aminobutyric acid (MESH:D005680), norepinephrine (MESH:D009638), dopamine (MESH:D004298), NAD+ (MESH:D009243), hydroxyl (MESH:D017665), SCFA (MESH:D005232), calcium (MESH:D002118), D-galactose (MESH:D005690), saponins (MESH:D012503), ROS (MESH:D017382), paraquat (MESH:D010269), Glucose (MESH:D005947), 5-hydroxytryptamine (MESH:D012701), cadmium chloride (MESH:D019256), nitric oxide (MESH:D009569), curcumin (MESH:D003474), hypotaurine (MESH:C003949), linoleic acid (MESH:D019787), ethyl ferulate (MESH:C099085), levodopa (MESH:D007980), mannose (MESH:D008358), NO (MESH:D009614), superoxide (MESH:D013481), C. yanhusuo polysaccharides (-), H2O2 (MESH:D006861), fat (MESH:D005223), succinic acid (MESH:D019802), oxygen (MESH:D010100), pentylenetetrazole (MESH:D010433), sugars (MESH:D000073893), polyunsaturated fatty acids (MESH:D005231), Ginsenoside Rg1 (MESH:C035054), salidroside (MESH:C009172), temozolomide (MESH:D000077204)
- **Species:** Lepidium meyenii (species) [taxon 153348], Gynochthodes officinalis (ba ji, species) [taxon 266091], Basella alba (Ceylon-spinach, species) [taxon 3589], Argentina anserina (silverweed cinquefoil, species) [taxon 57926], PX clade (clade) [taxon 569578], Fagopyrum esculentum (common buckwheat, species) [taxon 3617], Platycodon grandiflorus (balloon flower, species) [taxon 94286], Cyclocarya paliurus (qing qian liu, species) [taxon 117167], C. elegans [taxon 328850], Codonopsis pilosula (species) [taxon 86864], Eubacterium xylanophilum (species) [taxon 39497], Clostridia (class) [taxon 186801], Schisandra chinensis (Chinese magnolia-vine, species) [taxon 50507], Acorus tatarinowii (species) [taxon 123564], Glochidion eriocarpum (species) [taxon 648869], Akkermansia muciniphila (species) [taxon 239935], Faecalibacterium (genus) [taxon 216851], Alterileibacterium (genus) [taxon 1980680], Corydalis yanhusuo (species) [taxon 458692], Scrophularia ningpoensis (xuan shen, species) [taxon 291326], Agaricus bisporus (common mushroom, species) [taxon 5341], HC [taxon 11103], Aronia melanocarpa (black chokeberry, species) [taxon 661339], Glycyrrhiza uralensis (Chinese licorice, species) [taxon 74613], Bacteroides (genus) [taxon 816], Hippophae rhamnoides (sallowthorn, species) [taxon 193516], Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239], Alistipes (genus) [taxon 239759], Rattus norvegicus (brown rat, species) [taxon 10116], Prevotella (genus) [taxon 838], Dendrobium officinale (species) [taxon 142615], Rehmannia glutinosa (Chinese foxglove, species) [taxon 99300], Gastrodia elata (species) [taxon 91201], Lactobacillus (genus) [taxon 1578], Momordica charantia (balsam pear, species) [taxon 3673], Epimedium brevicornu (species) [taxon 253618], Lycium barbarum (Duke of Argyll's teatree, species) [taxon 112863], Homo sapiens (human, species) [taxon 9606], Olsenella (genus) [taxon 133925], Aster tataricus (species) [taxon 588669], Polygonatum sibiricum (species) [taxon 261423], Helicobacter (genus) [taxon 209], Dubosiella (genus) [taxon 1937008]
- **Cell lines:** SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), BV2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182), RP01-1 — Mus musculus (Mouse), Hybridoma (CVCL_G342), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), N2a — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470), HT-22 — Mus musculus (Mouse), Transformed cell line (CVCL_0321)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932451/full.md

## References

197 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932451/full.md

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Source: https://tomesphere.com/paper/PMC12932451