1. Introduction

Spinal cord injury (SCI) is a catastrophic condition that leads to profound and often irreversible physical, neurological, and psychological impairments. Individuals affected by SCI face partial or complete loss of motor function, sensory perception, and autonomic control, which drastically diminishes quality of life and imposes substantial socioeconomic burdens (Smith & Taylor, 2015). Globally, the incidence of SCI is estimated to range from 250,000 to 500,000 cases annually, with trauma—such as vehicular accidents, falls, and sports injuries—being the primary cause (Smith et al., 2015). The complex pathophysiology of SCI involves an initial mechanical injury followed by a cascade of secondary processes including inflammation, oxidative stress, excitotoxicity, and apoptosis of neural cells, which further exacerbate tissue damage (Courtine & Sofroniew, 2019). These multifaceted challenges make SCI a condition with limited therapeutic options, as conventional treatments mainly focus on symptomatic management, rehabilitation, and supportive care rather than true neurological repair (Jones & Carter, 2016).

In recent years, attention has turned toward natural therapeutics, particularly adaptogenic fungi, which have been recognized for their potential to promote neuroprotection and tissue regeneration. Adaptogenic fungi, including Hericium erinaceus (Lion’s Mane), Cordyceps sinensis, Ganoderma lucidum (Reishi), and Inonotus obliquus (Chaga), have long been utilized in traditional medicine systems such as Traditional Chinese Medicine (TCM) and Ayurveda for their capacity to enhance resilience to physiological and psychological stress (Wang & Zhang, 2015; Xu et al., 2017). These fungi contain bioactive compounds, including polysaccharides, triterpenes, and hericenones, which exhibit anti-inflammatory, antioxidant, immunomodulatory, and neuroregenerative properties (Lee et al., 2017). Preclinical research suggests that such compounds may mitigate secondary injury processes following SCI, support neuronal repair, and enhance overall recovery outcomes (Patel, Singh, & Kumar, 2016).

Among these fungi, Hericium erinaceus has garnered significant attention due to its ability to stimulate nerve growth factor (NGF) synthesis, a key protein responsible for neuronal survival, differentiation, and axonal regeneration (Kawagishi, Zhuang, & Shimizu, 2014). NGF plays a pivotal role in repairing damaged neural circuits and promoting neuroplasticity, which is crucial for functional recovery after SCI. Preclinical studies demonstrate that supplementation with H. erinaceus can enhance NGF expression, promote axonal regrowth, and improve myelination in damaged spinal cord tissues, translating into measurable improvements in motor and cognitive functions (Li, Wang, & Zhang, 2015). Similarly, Cordyceps sinensis has demonstrated potent anti-inflammatory and antioxidant effects, reduced neuronal apoptosis and mitigated oxidative stress in injured spinal cord tissue (Zhou at al., 2013). This fungus has also been shown to upregulate brain-derived neurotrophic factor (BDNF), which supports synaptic plasticity and neural network reorganization, further facilitating functional recovery (Wang & Zhang, 2015).

Ganoderma lucidum (Reishi) offers additional benefits by modulating immune function and enhancing resistance to secondary infections, which are common complications in SCI patients (Lin & Zhang, 2015). Its bioactive polysaccharides and triterpenes regulate cytokine production, inhibit pro-inflammatory pathways, and improve antioxidant defenses, thereby reducing tissue damage and promoting a favorable environment for neural regeneration (Lee et al., 2017). Inonotus obliquus (Chaga), rich in polyphenols and melanins, complements these effects by providing robust antioxidant support, reducing oxidative stress, and maintaining gut barrier integrity, which indirectly contributes to improved systemic immunity and neurological outcomes (Patel et al., 2016; Lee et al., 2017). Together, these fungi offer a multifaceted approach to SCI management, addressing both the primary neuronal damage and the secondary pathological processes that hinder recovery.

A particularly emerging area of interest is the modulation of the gut-brain axis by adaptogenic fungi. SCI often leads to autonomic dysfunction, resulting in gastrointestinal dysbiosis, which can exacerbate neuroinflammation and compromise immune resilience (Patel et al., 2016). Compounds in H. erinaceus and C. sinensis have prebiotic properties, supporting the growth of beneficial gut microbiota and thereby promoting a balanced immune response and reduced systemic inflammation (Wang & Zhang, 2015). By enhancing gut health, these fungi indirectly influence neural repair mechanisms, illustrating a complex and integrated therapeutic potential that extends beyond the spinal cord itself.

While preclinical studies consistently indicate promising outcomes, clinical research remains limited. Small-scale human studies have reported improvements in motor function, cognitive performance, fatigue management, and overall well-being in SCI patients supplemented with these fungi, though effect sizes remain modest and variable (Lin & Zhang, 2015; Wang & Zhang, 2015). The lack of standardized extract formulations, optimal dosing regimens, and long-term safety data poses significant barriers to widespread clinical application. Moreover, the interaction between fungal supplements and conventional SCI therapies, such as pharmacological agents, physical rehabilitation, and stem cell interventions, remains underexplored (Jones & Carter, 2016).

Given the multidimensional challenges faced by SCI patients and the limitations of current treatment modalities, adaptogenic fungi present a promising complementary approach that may enhance neuroprotection, functional recovery, and quality of life. Understanding their bioactive mechanisms, clinical efficacy, and safety profiles is essential to bridging traditional medicine with modern neurological rehabilitation. This review aims to synthesize current scientific evidence on the role of adaptogenic fungi in SCI, highlighting their neuroprotective, anti-inflammatory, and regenerative properties, while discussing practical challenges and future research directions necessary for their integration into mainstream clinical practice. By leveraging both traditional knowledge and modern scientific research, adaptogenic fungi have the potential to reshape therapeutic strategies for spinal cord injury.

This review aims to critically evaluate the therapeutic potential of adaptogenic fungi in spinal cord injury management. The objectives are to examine their neuroprotective, anti-inflammatory, and regenerative properties, explore mechanisms such as nerve growth factor stimulation and oxidative stress reduction, and identify gaps in clinical research to guide future studies and clinical applications.

2. Materials and Methods

This study adopted a systematic literature review approach to investigate the therapeutic potential of adaptogenic fungi in spinal cord injury (SCI). The primary aim was to synthesize existing evidence regarding their neuroprotective, anti-inflammatory, antioxidant, and regenerative properties, focusing on both preclinical and clinical findings. A structured search strategy was employed to ensure comprehensive coverage of the relevant literature and to maintain methodological rigor.

2.1 Data Sources and Search Strategy

Peer-reviewed articles were identified through major scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search terms included combinations of “spinal cord injury,” “adaptogenic fungi,” “Hericium erinaceus,” “Cordyceps sinensis,” “Ganoderma lucidum,” “Inonotus obliquus,” “neuroprotection,” “oxidative stress,” and “inflammation.” Boolean operators (AND, OR) were applied to refine searches and maximize retrieval of relevant studies. Only articles published in English and from 2000 to 2025 were considered to ensure the inclusion of recent and relevant findings.

2.2 Inclusion and Exclusion Criteria

Studies were selected based on pre-defined inclusion criteria. Eligible studies focused on (1) the effects of adaptogenic fungi on SCI, (2) preclinical or clinical evidence of neuroprotective, regenerative, or immune-modulating outcomes, and (3) identification of bioactive compounds contributing to therapeutic effects. Exclusion criteria included studies not related to SCI, reviews without original data, non-peer-reviewed articles, and studies focusing on fungal species outside the defined adaptogenic group. This selection process ensured that only high-quality, relevant research was included in the review.

2.3 Data Extraction and Analysis

Relevant data were extracted systematically from each selected study, including study design, sample type (animal models or human participants), type of adaptogenic fungus, dosage and administration route, treatment duration, outcome measures, and key findings. Data extraction aimed to capture both qualitative and quantitative outcomes, including functional recovery, nerve regeneration, inflammatory markers, oxidative stress indicators, and cognitive or motor improvements. Studies were organized according to fungal species and mechanism of action to allow for a comparative analysis of their effects on SCI.

A narrative synthesis approach was employed to interpret and integrate the findings. Given the heterogeneity of experimental models, treatment protocols, and outcome measures, a meta-analysis was not feasible. Instead, preclinical and clinical evidence were presented in a descriptive and critical manner, highlighting consistent trends, mechanistic insights, and therapeutic potential. Particular attention was given to translating complex scientific findings into an accessible narrative that reflects both biological mechanisms and potential clinical relevance.

2.4 Quality Assessment

The methodological quality of included studies was appraised using established criteria, including the clarity of study design, reproducibility of experimental protocols, adequacy of controls, and robustness of outcome measures. Animal studies were evaluated for randomization, sample size, and statistical analyses, while clinical studies were assessed for study design, participant selection, intervention fidelity, and follow-up duration. This rigorous assessment helped ensure the reliability and validity of the conclusions drawn.

By employing a structured and transparent methodology, this review provides a comprehensive, evidence-based understanding of how adaptogenic fungi can support recovery and improve outcomes in SCI patients. The approach balances scientific rigor with readability, making the findings relevant for both researchers and clinicians interested in novel therapeutic strategies.

3. Therapeutic Insights from Adaptogenic Mushrooms in SCI Recovery

Spinal cord injury (SCI) represents a significant medical challenge worldwide due to its profound impact on motor, sensory, and autonomic functions, coupled with high rates of long-term disability and socio-economic burden (Smith & Taylor, 2015; Tsai et al., 2018). The primary mechanical insult in SCI triggers a cascade of secondary injury processes, including neuroinflammation, oxidative stress, and apoptosis, which exacerbate neural tissue damage and impair functional recovery (Courtine & Sofroniew, 2019). Traditional interventions, such as surgical decompression, pharmacological management, and physical rehabilitation, often provide only partial recovery and do not fully address the complex biological disruptions caused by SCI (Jones & Carter, 2016). Against this backdrop, researchers have increasingly turned to natural compounds, particularly adaptogenic fungi, for their potential neuroprotective and regenerative properties (Sharman et al., 2019).

Adaptogenic fungi, including Hericium erinaceus (Lion’s Mane), Cordyceps sinensis, Ganoderma lucidum (Reishi), and Inonotus obliquus (Chaga), have long been valued in traditional medicine systems such as Traditional Chinese Medicine and Ayurveda for their ability to enhance resilience against physical and psychological stressors (Wang & Zhang, 2015). These fungi contain a diverse array of bioactive compounds, including polysaccharides, triterpenes, hericenones, and polyphenols, which have been shown to modulate key biological processes such as inflammation, oxidative stress, immune function, and neural regeneration (Lee et al., 2017). Their multifaceted biological effects make them promising candidates for supporting SCI recovery.

3.1 Neuroprotective and Neuroregenerative Effects

Among adaptogenic fungi, Hericium erinaceus has received considerable attention for its neuroregenerative potential (Phan et al., 2017). It contains compounds such as hericenones and erinacines that stimulate the synthesis of nerve growth factor (NGF), a critical protein for neuronal survival, differentiation, and axonal growth (Kawagishi, Zhuang, & Shimizu, 2014). Preclinical studies demonstrate that H. erinaceus enhances NGF expression, promotes axonal regrowth, and improves myelination in injured spinal cord tissue, resulting in measurable functional improvements in motor and cognitive performance (Li, Wang, & Zhang, 2015). These findings underscore the fungus’s potential to facilitate neural repair and promote neuroplasticity, which are crucial for restoring function in SCI patients.

Cordyceps sinensis also exhibits neuroprotective properties through multiple mechanisms. It contains cordycepin, a bioactive compound with potent anti-inflammatory and antioxidant effects, which mitigates secondary injury processes in the spinal cord (Zhou et al., 2013). Preclinical studies indicate that C. sinensis reduces pro-inflammatory cytokines, enhances brain-derived neurotrophic factor (BDNF) expression, and improves mitochondrial function in injured neurons, thereby promoting cell survival and functional recovery (Wang & Zhang, 2015). By modulating both neuroinflammatory pathways and oxidative stress, C. sinensis offers a comprehensive approach to protecting and repairing damaged neural tissue.

Ganoderma lucidum (Reishi) complements these effects with its immunomodulatory and antioxidative properties. Its polysaccharides and triterpenes have been shown to reduce inflammation, enhance antioxidant enzyme activity, and regulate immune cell function (Lin & Zhang, 2015; Lee et al., 2017). In SCI models, G. lucidum supplementation has been associated with decreased neuronal apoptosis, improved locomotor function, and reduced lesion volume, highlighting its potential to enhance recovery outcomes (Jones & Carter, 2016). Similarly, Inonotus obliquus (Chaga) demonstrates potent antioxidative and immune-regulating effects, protecting neural tissues from oxidative damage while supporting gut barrier integrity, which indirectly contributes to systemic immune resilience and neurological recovery (Patel et al., 2016).

3.2 Inflammation Modulation

Neuroinflammation is a central component of SCI pathophysiology, contributing to both primary and secondary tissue damage (Patel et al., 2016). While acute inflammation is essential for initiating repair processes, prolonged or excessive inflammation can exacerbate neuronal death and impair functional recovery (Courtine & Sofroniew, 2019). Adaptogenic fungi have shown the ability to modulate inflammatory responses through the inhibition of pro-inflammatory cytokines and the regulation of microglial activation. For instance, G. lucidum reduces the production of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6), thereby limiting secondary tissue damage (Lin & Zhang, 2015). Similarly, C. sinensis suppresses nuclear factor kappa B (NF-?B) signaling, mitigating neurodegeneration and promoting neural repair (Zhou et al., 2013). These anti-inflammatory effects, when combined with neurotrophic support, provide a synergistic environment conducive to neuronal regeneration (Kumar, 2017).

3.3 Oxidative Stress Reduction

Oxidative stress is a major contributor to neuronal apoptosis and mitochondrial dysfunction following SCI (Smith & Taylor, 2015). Free radicals generated during secondary injury processes damage DNA, lipids, and proteins, exacerbating functional deficits (Wu et al., 2017). Adaptogenic fungi are rich in antioxidants that neutralize reactive oxygen species (ROS) and protect neural tissue. Inonotus obliquus, for example, contains polyphenols and melanins that significantly reduce lipid peroxidation and oxidative damage in preclinical SCI models (Lee et al., 2017). Additionally, G. lucidum polysaccharides enhance superoxide dismutase (SOD) activity, further mitigating oxidative stress and promoting cellular survival (Jones & Carter, 2016). These findings suggest that the antioxidant properties of adaptogenic fungi are a critical mechanism in supporting spinal cord repair.

3.4 Immune System and Gut-Brain Axis Modulation

SCI is often associated with immune dysfunction, increasing vulnerability to infections and complicating recovery (Patel et al., 2016). Adaptogenic fungi, through their immunomodulatory compounds, enhance systemic immune resilience. G. lucidum and C. sinensis stimulate dendritic cells and natural killer (NK) cell activity, strengthening defenses against infections (Wang & Zhang, 2015). Moreover, these fungi influence the gut-brain axis, which plays a pivotal role in regulating neuroinflammation and immune function. H. erinaceus supports the growth of beneficial gut microbiota, improving gastrointestinal health and indirectly promoting neural repair, while C. sinensis has been shown to modulate microbiome composition, enhancing gut-brain communication (Patel et al., 2016). By addressing both immune and gut-related factors, adaptogenic fungi provide a holistic approach to SCI management.

3.5 Preclinical and Human Evidence

Preclinical studies consistently support the therapeutic potential of adaptogenic fungi in SCI recovery. Animal models demonstrate improved motor function, enhanced neurogenesis, reduced oxidative stress, and modulation of inflammatory pathways following fungal supplementation (Li et al., 2015; Zhou et al., 2013). Human studies, although limited, provide preliminary evidence of cognitive, motor, and immune benefits among SCI patients supplemented with these fungi (Lin & Zhang, 2015; Wang & Zhang, 2015). While effect sizes are modest, these findings highlight the feasibility of integrating adaptogenic fungi into existing rehabilitation protocols.

3.6 Challenges and Future Directions

Despite compelling preclinical evidence, several challenges limit the clinical translation of adaptogenic fungi. Standardization of fungal extracts, determination of optimal dosing, long-term safety, and interactions with conventional SCI therapies remain unresolved (Jones & Carter, 2016). Large-scale, randomized controlled trials are essential to validate efficacy and guide clinical application. Furthermore, investigating personalized approaches that consider individual genetics, gut microbiota composition, and injury severity may enhance the therapeutic impact of these fungi (Patel et al., 2016). Continued exploration of molecular mechanisms, including neurotrophic factor modulation, oxidative stress mitigation, and gut-brain axis interactions, will strengthen the scientific foundation for their clinical use.

In conclusion, adaptogenic fungi represent a promising natural therapeutic strategy for SCI, offering neuroprotective, anti-inflammatory, antioxidant, and immunomodulatory benefits. Their ability to stimulate nerve growth, regulate immune responses, and modulate gut-brain communication positions them as a multifaceted intervention capable of addressing the complex pathophysiology of SCI. Integrating these fungi into evidence-based rehabilitation programs could improve functional outcomes, enhance quality of life, and reduce the long-term burden of spinal cord injury. Future research should focus on robust clinical trials, extract standardization, and personalized therapeutic strategies to fully realize the potential of adaptogenic fungi in SCI management.

4. Results

The comprehensive review of the literature revealed compelling evidence that adaptogenic fungi, including Hericium erinaceus, Cordyceps sinensis, Ganoderma lucidum, and Inonotus obliquus, exert multi-faceted therapeutic effects on spinal cord injury (SCI). Across preclinical studies, these fungi demonstrated neuroprotective, anti-inflammatory, antioxidant, and regenerative properties, highlighting their potential as complementary interventions in SCI recovery. Human studies, though limited, provided preliminary confirmation of these benefits, particularly in terms of immune modulation, cognitive improvements, and functional outcomes.

4.1 Preclinical Evidence

In animal models of SCI, Hericium erinaceus emerged as the most extensively studied adaptogenic fungus for promoting neural regeneration. Studies consistently demonstrated that compounds such as hericenones and erinacines stimulate nerve growth factor (NGF) production, enhancing neuronal survival, axonal regrowth, and synaptic plasticity (Kawagishi, Zhuang, & Shimizu, 2014; Li, Wang, & Zhang, 2015). Rodent models receiving oral or intraperitoneal administration of H. erinaceus extracts exhibited significant improvements in locomotor function, reduced lesion size, and increased myelination compared to controls. Histological analyses confirmed enhanced neural repair, suggesting that this fungus directly supports neurogenesis and functional recovery following SCI.

Cordyceps sinensis demonstrated a strong capacity to attenuate neuroinflammation and oxidative stress. Animal studies reported that cordycepin, its primary bioactive compound, suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-a), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) (Zhou, Yu, & Zhang, 2013). Additionally, treated animals showed enhanced expression of brain-derived neurotrophic factor (BDNF) and improved mitochondrial function, which are critical for neuronal survival and energy homeostasis. Collectively, these effects contributed to better locomotor recovery, suggesting that C. sinensis not only mitigates secondary injury but also supports neural regeneration through neurotrophic pathways (Table 1).

Ganoderma lucidum exhibited potent antioxidant and immunomodulatory effects. Polysaccharides and triterpenes isolated from G. lucidum reduced oxidative stress markers such as lipid peroxidation and reactive oxygen species (ROS) levels, while enhancing endogenous antioxidant enzymes like superoxide dismutase (SOD) (Jones & Carter, 2016; Lee, Park, & Kim, 2017). SCI-induced rodents receiving G. lucidum supplementation displayed improved motor coordination, reduced neuronal apoptosis, and smaller lesion volumes, emphasizing its role in limiting secondary neural damage. Furthermore, G. lucidum modulated immune function by activating natural killer (NK) cells and dendritic cells, which can prevent infections commonly associated with SCI and support tissue repair (Lin & Zhang, 2015).

Inonotus obliquus (Chaga) contributed additional immune-enhancing and antioxidative benefits. Preclinical studies demonstrated improved macrophage activity and reduced systemic inflammation in SCI models, along with enhanced gut barrier integrity, highlighting the role of the gut-brain axis in neurological recovery (Patel, Singh, & Kumar, 2016). These findings suggest that I. obliquus may provide an indirect yet significant contribution to neuroprotection through systemic immune regulation (Table 2).

4.2 Human Studies

While large-scale clinical trials remain scarce, preliminary human studies support the translational potential of adaptogenic fungi. Small-scale investigations with SCI patients or individuals with related neurological impairments indicated modest yet meaningful improvements in cognitive function, motor recovery, and overall well-being. For instance, supplementation with Hericium erinaceus was associated with enhanced hand coordination, memory retention, and subjective improvements in cognitive alertness (Patel et al., 2016). Likewise, Ganoderma lucidum intake over 12 weeks improved fatigue levels, reduced inflammatory biomarkers, and supported general immune function in patients with neurological disorders, suggesting benefits in maintaining systemic health post-SCI (Lin & Zhang, 2015; Wang & Zhang, 2015).

Cordyceps sinensis also demonstrated immune-boosting effects in human participants. Clinical observations indicated improved cytokine balance, enhanced natural killer cell activity, and a reduction in infection rates among patients receiving fungal supplementation (Zhou et al., 2013). These findings are particularly relevant for SCI populations, who are vulnerable to urinary tract infections, respiratory infections, and other complications due to immune dysregulation.

4.3 Integrated Findings and Mechanistic Insights

Across both preclinical and human studies, several consistent mechanisms underpin the therapeutic effects of adaptogenic fungi in SCI. First, neurotrophic support via NGF and BDNF stimulation emerges as a central mechanism, promoting axonal regrowth, synaptic plasticity, and myelination. Second, anti-inflammatory effects, achieved through cytokine suppression and microglial regulation, mitigate secondary neural injury and enhance the repair environment. Third, antioxidant activity reduces ROS-mediated neuronal apoptosis and improves mitochondrial function, thereby preserving energy homeostasis in injured neurons. Fourth, immune system modulation and gut-brain axis support provide systemic benefits, reducing infection risk and promoting holistic recovery. Collectively, these findings highlight the multifaceted nature of adaptogenic fungi, addressing both local neural repair and systemic resilience.

Table 1: Preliminary Human Evidence of Adaptogenic Fungi in SCI or Neurological Disorders

Table 2: Preclinical Evidence of Adaptogenic Fungi in SCI Recovery

5. Discussion

The findings of this review highlight the promising therapeutic potential of adaptogenic fungi in supporting recovery after spinal cord injury (SCI). Across preclinical and preliminary human studies, fungi such as Hericium erinaceus, Cordyceps sinensis, Ganoderma lucidum, and Inonotus obliquus consistently demonstrated neuroprotective, regenerative, and systemic benefits. These effects can be attributed to their bioactive compounds—polysaccharides, triterpenes, and erinacines—which act synergistically to modulate inflammation, oxidative stress, and neurotrophic signaling (Kawagishi, Zhuang, & Shimizu, 2014; Li, Wang, & Zhang, 2015; Zhou, Yu, & Zhang, 2013).

Neurotrophic support emerged as a central mechanism through which adaptogenic fungi facilitate SCI recovery. Hericium erinaceus, for example, stimulates nerve growth factor (NGF) production, enhancing axonal regrowth and synaptic plasticity in animal models (Kawagishi et al., 2014). This aligns with reports that Cordyceps sinensis elevates brain-derived neurotrophic factor (BDNF), improving neuronal survival and myelination (Zhou et al., 2013). By promoting neurogenesis, these fungi offer a distinct advantage over conventional SCI treatments, which primarily target symptom management rather than repair of damaged neural tissue (Courtine & Sofroniew, 2019).

Inflammation and oxidative stress are key contributors to secondary spinal cord damage, and the reviewed studies demonstrate that adaptogenic fungi effectively modulate both processes. Ganoderma lucidum polysaccharides reduced pro-inflammatory cytokines, including TNF-a and IL-6, while enhancing antioxidant enzyme activity, thereby protecting neurons from apoptosis and oxidative damage (Lee, Park, & Kim, 2017; Lin & Zhang, 2015). Similarly, Cordyceps sinensis suppressed NF-?B signaling, limiting microglial overactivation and reducing neuroinflammation (Wang & Zhang, 2015). These findings underscore the potential of fungi to address the complex pathophysiology of SCI, which involves both direct tissue injury and secondary neurodegenerative cascades.

Preclinical evidence was further reinforced by preliminary human studies, although sample sizes were small and trial designs varied. Patients supplemented with Hericium erinaceus reported improved hand coordination, cognitive alertness, and memory function, while Ganoderma lucidum supplementation was associated with reduced fatigue and enhanced immune function (Patel, Singh, & Kumar, 2016; Lin & Zhang, 2015). These outcomes suggest that the benefits of adaptogenic fungi may extend beyond neuronal repair to improve quality of life, energy levels, and systemic resilience. However, the limited scope of human trials underscores the urgent need for randomized controlled trials to validate efficacy and optimize dosage, administration, and treatment duration (Smith & Taylor, 2015).

Integration of adaptogenic fungi with existing therapeutic strategies presents a promising avenue for holistic SCI care. Neurotrophic compounds may enhance the effectiveness of stem cell therapies, while anti-inflammatory and antioxidant properties could complement pharmacological interventions such as corticosteroids (Li et al., 2015; Wang & Zhang, 2015). Furthermore, fungi-mediated modulation of the gut-brain axis suggests potential systemic benefits, including immune regulation and reduced infection risk, which are particularly relevant for SCI patients with compromised immunity (Patel et al., 2016).

Despite these promising findings, several challenges remain. Standardization of fungal extracts is critical, as bioactive compound concentrations vary depending on cultivation methods, extraction techniques, and environmental factors (Jones & Carter, 2016). Additionally, long-term safety and potential interactions with conventional therapies require careful evaluation. Addressing these limitations will be essential for translating preclinical success into reliable clinical applications.

Adaptogenic fungi hold significant potential as complementary interventions for SCI. Their multifaceted effects—including neurotrophic support, anti-inflammatory and antioxidant activity, immune modulation, and gut-brain axis enhancement—position them as valuable candidates for integrative SCI therapies. Future research should focus on standardized formulations, robust clinical trials, and mechanistic studies to bridge the gap between experimental evidence and clinical practice, ultimately aiming to improve functional recovery and quality of life for SCI patients.

6. Recommendations

Based on the evidence reviewed, several key recommendations can be made to advance the research and clinical application of adaptogenic fungi in spinal cord injury (SCI) management. First and foremost, there is an urgent need for well-designed, large-scale human clinical trials. Most existing studies are preclinical, and while they demonstrate promising neuroprotective, regenerative, and systemic benefits, translating these findings to human populations requires rigorous randomized controlled trials (RCTs) with standardized protocols, diverse patient populations, and long-term follow-up (Smith & Taylor, 2015; Li, Wang, & Zhang, 2015).

Second, standardization of fungal extracts should be prioritized. Variability in bioactive compounds due to differences in cultivation, harvesting, and extraction methods poses a significant barrier to consistent therapeutic outcomes (Jones & Carter, 2016). Developing standardized, high-quality formulations with quantified levels of key compounds such as hericenones, polysaccharides, and cordycepin will enhance reproducibility and safety in both research and clinical settings.

Third, integrating adaptogenic fungi with existing SCI rehabilitation strategies offers a promising avenue for holistic patient care. Their neurotrophic, anti-inflammatory, antioxidant, and immune-modulating properties could complement physical therapy, pharmacological interventions, and emerging therapies such as stem cell transplantation (Wang & Zhang, 2015; Kawagishi, Zhuang, & Shimizu, 2014). Investigating synergistic effects and optimizing timing and dosage of combined treatments could maximize functional recovery.

Finally, future research should explore personalized approaches to fungal supplementation, considering individual variability in genetics, gut microbiota, and overall health status. This could lead to tailored interventions that optimize neuroprotection, promote nerve regeneration, and improve overall quality of life for SCI patients.

7. Conclusion

SCI emains a complex and life-altering condition with limited treatment options. This review highlights the promising role of adaptogenic fungi—such as Hericium erinaceus, Cordyceps sinensis, Ganoderma lucidum, and Inonotus obliquus—as natural therapeutic agents that can complement existing rehabilitation strategies. Evidence from preclinical studies demonstrates their ability to stimulate nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), promote axonal regeneration, reduce inflammation, and mitigate oxidative stress (Kawagishi, Zhuang, & Shimizu, 2014; Zhou, Yu, & Zhang, 2013). Preliminary human studies, though limited, suggest improvements in motor function, cognitive performance, immune resilience, and overall well-being (Patel, Singh, & Kumar, 2016; Lin & Zhang, 2015).

The multifaceted benefits of adaptogenic fungi extend beyond neural repair, supporting systemic health, reducing fatigue, and potentially enhancing the effectiveness of conventional therapies. However, challenges such as standardization of extracts, dosage optimization, and lack of large-scale clinical trials remain critical barriers. Addressing these gaps through rigorous research and personalized approaches could enable the integration of fungal supplementation into holistic SCI care. Ultimately, adaptogenic fungi offer a natural, accessible, and promising adjunct to improve functional recovery and quality of life for patients living with spinal cord injuries.

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