# Therapeutic potential of combination medicinal mushrooms (NevG) in ischemic stroke: correlating motor function, cognitive recovery, and hippocampal integrity in MCAO rats

**Authors:** Nur Athirah Azlan, Misya Afiqah Noor Tuah, Nik Nasihah Nik Ramli, Hussin Muhammad, Zolkapli Eshak, Liao Peng, Chen Bo, Yatinesh Kumari, Imran Jazuli, Che Mohd Nasril Che Mohd Nasir, Syntyche Seow Ling Sing, Cheng Poh Guat, Hafizah Abdul Hamid, Zaw Myo Hein, Muhammad Danial Che Ramli

PMC · DOI: 10.3389/fphar.2025.1698883 · Frontiers in Pharmacology · 2026-02-06

## TL;DR

A combination of medicinal mushrooms called NevG shows promise in improving recovery after ischemic stroke in rats by reducing brain damage and inflammation.

## Contribution

The study introduces a novel combination of medicinal mushrooms (NevG) and evaluates its therapeutic effects in ischemic stroke.

## Key findings

- NevG reduced infarct volume by 32%–58% in MCAO rats.
- NevG improved cognitive and sensorimotor functions and lowered inflammatory cytokine levels.
- NevG preserved hippocampal neurons and axonal integrity in ischemic stroke models.

## Abstract

Ischemic stroke is a major neurological disorder that is characterized by cognitive decline and sensorimotor impairment. Despite the potential of therapeutic effects and anti-inflammatory properties of medicinal mushrooms, most current research focuses on single-species effects rather than combined formulations. This gap highlights the need to investigate the potential of a combination of medicinal mushrooms named NevG, containing Lignosus rhinocerus, Hericium erinaceus, and Ganoderma lucidum, focusing on their therapeutic effects in the context of ischemic stroke.

Forty adult male Sprague–Dawley rats were randomly assigned to five groups (n = 8): normal, MCAO-induced, and NevG in oral doses of 250 mg/kg, 500 mg/kg, and 1,000 mg/kg for 28 days. Ischemia was induced using the Koizumi method and confirmed through triphenyltetrazolium chloride (TTC) staining and mNSS scoring. Cognitive abilities were assessed using the Morris water maze and T-maze tests, and sensorimotor function was evaluated using the open-field, rotarod, and pole tests. Mechanistic analyses involved measuring anti-inflammatory serum cytokine pathways (TNF-α, IL-1β, IL-6, and NF-κβ).

NevG significantly reduced infarct volume by 32%–58% compared with the middle cerebral artery occlusion (MCAO) group (p < 0.05). Cognitive performance improved, with a 25%–46% reduction in the Morris water maze (MWM) escape latency (p < 0.01) and an increase in T-maze spontaneous alternation. Sensorimotor functions were enhanced, as evidenced by increases in the open-field test (OFT), rotarod retention time (p < 0.01), and decreased descent time in the pole test. The cresyl violet staining of the neurons in the hippocampus shows improvement in pyramidal cell counts, and the ultrastructural transmission electron microscope (TEM) analysis shows better preservation of the nucleus and mitochondria, intact myelin sheath, and improved axonal integrity. NevG significantly lowered the inflammatory serum cytokine level (p < 0.05) and promoted neuronal survival.

NevG demonstrates significant neuroprotective effects in ischemic stroke, achieved through reduced neuroinflammation and improved neuronal survival, indicating its potential as a natural therapeutic agent.

## Linked entities

- **Diseases:** ischemic stroke (MONDO:1060198)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Ca3 (carbonic anhydrase 3) [NCBI Gene 54232] {aka Car3}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Ngf (nerve growth factor) [NCBI Gene 310738] {aka Ngfb, beta-NGF}
- **Diseases:** metabolic syndrome (MESH:D024821), inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), Ischemic (MESH:D002545), brain infarction (MESH:D020520), reduced attention (MESH:D001523), aneurysm (MESH:D000783), edema (MESH:D004487), neuroinflammation (MESH:D000090862), hemorrhagic (MESH:D006470), brain edema (MESH:D001929), impairments in sensorimotor function (MESH:D020233), white matter degeneration (MESH:D056784), language disturbance (MESH:D007806), Stroke (MESH:D020521), deficits in memory, learning, and motor function (MESH:D007859), Neurological deficits (MESH:D009461), Ischemia (MESH:D007511), term disability (MESH:D000088562), bradykinesia (MESH:D018476), brain damage (MESH:D001925), MCAO (MESH:D020244), neurological damage (MESH:D020196), demyelination (MESH:D003711), impaired motor coordination (MESH:D001259), hippocampal dysfunction (MESH:D001927), ischemic brain injury (MESH:D001930), death (MESH:D003643), ischemic damage (MESH:D017202), post (MESH:D000094025), fatalities (MESH:C565541), Ischemic stroke (MESH:D002544), , and psychological impairments (MESH:D000067073), toxicity (MESH:D064420), infarct (MESH:D007238), neuronal cell degeneration (MESH:D009410), executive dysfunction (MESH:D006331), necrosis (MESH:D009336), deficits in both spatial and non-spatial memory (MESH:D008569), motor impairment (MESH:D000068079), neuronal apoptosis (MESH:D065703), neurological impairments (MESH:D009422), Cognitive and motor impairments (MESH:D003072), axonal damage (MESH:D001480), tissue damage (MESH:D017695)
- **Chemicals:** ginsenosides (MESH:D036145), paraffin (MESH:D010232), oxygen (MESH:D010100), ganoderic acids (MESH:C572163), osmium tetroxide (MESH:D009993), 2,3,5-triphenyltetrazolium chloride (MESH:C009591), phosphate (MESH:D010710), DPX (MESH:C027512), xylene (MESH:D014992), polysaccharides (MESH:D011134), erinacines (MESH:C000608927), water (MESH:D014867), terpenoid (MESH:D013729), alkaloids (MESH:D000470), CV (MESH:C028911), silicone (MESH:D012828), ethanol (MESH:D000431), TTC (-), isoflavones (MESH:D007529), amino acids (MESH:D000596), uranyl acetate (MESH:C005460), triterpenes (MESH:D014315), lignin (MESH:D008031), propylene oxide (MESH:C009068), paraformaldehyde (MESH:C003043), alcohol (MESH:D000438), glutaraldehyde (MESH:D005976), beta-glucans (MESH:D047071), formalin (MESH:D005557), glucose (MESH:D005947), flavonoids (MESH:D005419)
- **Species:** Hericium erinaceus (bearded tooth mushroom, species) [taxon 91752], Agaricus bisporus (common mushroom, species) [taxon 5341], Theronia sp. MM s.n. (species) [taxon 495684], Ganoderma steyaertianum (species) [taxon 496552], Ganoderma lucidum (species) [taxon 5315], Lignosus rhinocerus (species) [taxon 483020], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Ganoderma multipileum (species) [taxon 1173714]

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## References

76 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920536/full.md

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Source: https://tomesphere.com/paper/PMC12920536