Bioactive constituents of Hericium erinaceus: extraction strategies, health benefits and food applications

Abstract

Hericium erinaceus (H. erinaceus), better known as Lion’s Mane mushroom, is an edible and medicinal fungus that has been an integral part of traditional Asian medicine practices. Even today, it is recognized for its benefits in mental health, digestion, and overall vitality. This review discusses the nutritional value, bioactive substances (primarily erinacines and hericenones), their extraction and numerous pharmacological activities. H. erinaceus is mainly composed of polysaccharides (chiefly β-glucans), terpenoids, phenolic compounds, and sterols, which exhibit a wide range of activities such as neuroprotective, antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory effects. According to preclinical research, the fungus protects against amyloid beta toxicity, reduces oxidative stress, modulates the gut-brain axis, promotes neurogenesis, and slows down mechanisms linked to neurodegenerative diseases. It also plays a role in the synthesis of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). A limited number of human trials have been conducted, with promising results in cognitive function, mood, and mild cognitive impairment in the elderly, particularly with erinacine A-rich mycelia. Additional benefits are attributed to improved gut health, decreased inflammation, and potential anti-cancer activity. However, there are still significant gaps in the scientific literature, such as the need for larger, standardized, multicenter clinical trials, better dose response data, and improved extraction standardization so extraction is consistent for bioavailability. The majority of the evidence comes from in vitro and animal work. Additionally, extraction techniques vary greatly in terms of general uniformity, efficiency, and reproducibility. Then, even with a promising bioactive potential, there are several obstacles to overcome before it can be developed into a food product that is both safe and effective and that customers will really accept. The objective of this review is to critically compile the available data regarding the bioactive components, novel extraction techniques, health advantages, and current and potential food uses of H. erinaceus.

1 Introduction

Surrounded by natural helpers, remedies and functional foods, many fungi like Lion’s Mane Mushroom (Hericium erinaceus) have gained significant attention for their neuroprotective, antioxidant, and therapeutic potential in promoting human health and wellbeing (Kunca et al., 2018). It is a remarkable mushroom with its unique appearance resembling a lion’s flowing mane and outstanding bioactivities. It has been utilized for centuries in traditional medicine, especially in Asian cultures like those of China and Japan (Thongbai et al., 2015). Hericium erinaceus belongs to the fungal family Hericiaceae and the fresh specimens have a rubbery texture that becomes tough and yellow when they are aged or dried (Kunca et al., 2018). Hericium erinaceus has a broad temperate distribution across the Northern Hemisphere, native to North America (Canada to southern U.S., on beech, maple, oak) (Koga et al., 2025), Europe (UK and Scandinavia to Central/Eastern regions) and rare introduced populations appear in New Zealand (Van Der Merwe et al., 2023). Cultivation has increased its global availability, though wild populations face potential threats from climate change and habitat loss (Gonkhom et al., 2022). Its look with, icicle-like spines distinguishes it from other edible mushrooms, making it not only a favorite in the kitchen but also an intriguing subject for modern scientific research in fields like pharmacology and nutrition (Friedman, 2015; Thongbai et al., 2015). With its rich history and promising health benefits, Lion’s Mane continues to capture the attention of both chefs and scientists alike.

The historical journey of H. erinaceus, frequently referred to as the monkey head mushroom or Pom mushroom, ‘houtou’ is the name of this mushroom in China, while ‘Yamabushitake’ is the name in Japan (Wang et al., 2014). These names denote the esteemed position of the mushroom as the giver of vitality and longevity, which was even claimed by the mushroom hundreds of years ago (Mori et al., 2009). Traditional Chinese medicine has always considered its health advantages, applying it in the management of gastrointestinal problems like gastritis and ulcers, as well as in enhancing mental power and battling mental tiredness among others (Nagano et al., 2010; Vigna et al., 2019). These ancient practices provide a hint at the wide range of bioactive compounds that modern scientists are just beginning to factor into their studies (Gravina et al., 2023). The remarkable H. erinaceus has captured such a large market today because of the natural health product sector, which is becoming more and more popular with the elderly population and the rise of neurodegenerative diseases (Brandalise et al., 2023). In biological terms, this very interesting fungus is placed in the category of white-rot fungi, which turn out to be the most significant decomposers in the ecosystems, as they dismantle the lignin present in the wood of the cut or dying trees (Das et al., 2011). Hence, the nutrient cycling back into the forest is made through this process, thus showing the fungi’s ecological role as being far more important than just its culinary and medicinal uses.

The mushrooms are either found in natural environments or cultivated in artificial settings to achieve their maximum health benefits. The cultivation of these mushrooms has advanced through new methods, which show that wheat grain substrates provide optimal growth conditions at 25 °C–30 °C temperatures and 4–5.5 pH levels (Gonkhom et al., 2022). The ideal conditions for H. erinaceus growth have resulted in higher production levels of vital substances such as erinacines, which now enable H. erinaceus to reach more locations than ever before, extending beyond its native environments. The taxonomy of this species now follows a clearer structure because recent studies utilized multiple genetic markers for their research, which included ITS, LSU, TEF-1α, and RPB2. The markers have enabled researchers to distinguish H. erinaceus from other fungal species, which include Hericium coralloides H. alpestre and Hericium americanum while the markers have discovered new species which include Hericium oregonense and Hericium ophelieae from different geographical areas (Koga et al., 2025; Van Der Merwe et al., 2023). Hericium erinaceus offers therapeutic benefits due to its multiple bioactive compounds. Research emphasizes its health benefits for neurodegenerative disorders, as certain secondary metabolites have neurotrophic effects that support brain health. The mushroom contains polysaccharides, terpenoids, phenolic acids, sterols and proteins (Li et al., 2018; Yang et al., 2022). The polysaccharides β-glucans demonstrate both immunomodulatory effects and antioxidant capabilities. The fruiting bodies of the plant contain hericenones A through H, while the mycelia contain erinacines A through I, which both show strong neurotrophic effects (Kawagishi et al., 1991; Lee et al., 2000). Mycelial extracts contain high concentrations of erinacine A, stimulate nerve growth factor and brain-derived neurotrophic factor production (Li et al., 2019; Shimbo et al., 2005). The research identified bioactive compounds, antioxidants, phenolic compounds and fatty acids through GC-MS and HPTLC techniques, and these bioactive compounds together provide antioxidant and antimicrobial effects (Martínez-Mármol et al., 2020; Suleiman et al., 2022).

The neurological advantages of H. erinaceus show extremely interesting properties and the increasing occurrence of neurodegenerative diseases, which include Alzheimer’s disease (AD) and Parkinson’s disease (PD). It has created a greater demand for natural substances that help protect brain cells. Research has proven that this mushroom extract can promote neurite development while it protects neurons from neurotoxic effects caused by amyloid-beta, which acts as a major contributor to Alzheimer’s disease (Huang et al., 2021). This medicinal fungus H. erinaceus, provides multiple health benefits that extend beyond its effects on cognitive abilities. The substance possesses antioxidant abilities, which enable it to effectively remove free radicals from the body and it has anti-inflammatory properties, which decrease the levels of IL-6 and TNF-α and it can kill specific bacteria and viruses. Hericium erinaceus extracts display potential use in cancer therapy because it causes tumor cells to undergo programmed cell death and they also show potential as an effective brain health solution for people seeking to improve their mental abilities and general health (Blagodatski et al., 2018; Suleiman et al., 2022; Thi My Ngan et al., 2021).

2 Methodology

This narrative review was carried out through a comprehensive literature search of PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and CNKI databases, supplemented with relevant regulatory documents. Studies published primarily between 2000 and 2025 were taken into account, but because of their fundamental importance, older, groundbreaking studies on hericenones and erinacines were also included. The key terms, such as “H. erinaceus,” “Lion’s Mane mushroom,” “erinacines,” “hericenones,” “polysaccharides,” “β-glucans,” “NGF,” “BDNF,” “neuroprotection,” “cognitive function,” “nutraceutical,” and “functional food,” were used to search the literature. Original or synthesized data on H. erinaceus’s bioactive compounds, extraction techniques, pharmacological activity, safety, and food uses were included as eligible investigations. Editorials, duplicate records, and non-peer-reviewed articles were excluded.

3 Scope and relevance in functional foods

Functional foods are now recognized as a vital element because people understand how diets affect their health and their ability to avoid diseases. Functional foods are defined as foods that, beyond providing basic nutrition, deliver additional physiological benefits or reduce the risk of chronic diseases. Edible and medicinal mushrooms function as essential active components because their extensive safe usage history, together with their high active compound content provide them as functional elements. Hericium erinaceus stands out because it possesses unique neurotrophic characteristics together with its antioxidant and immunomodulatory properties and its ability to enhance gut health (Wang et al., 2014).

The bioactive components of H. erinaceus include polysaccharides, β-glucans, diterpenoids, bioactive proteins and phenolic compounds (Figure 1) which are essential for the development of functional foods. Hericium erinaceus attracts special interest in the food science field because of its mild taste, its sound nutritional properties and its ability to work with different food products. It can be used in traditional foods like soups and bakery items, dairy substitutes and drinks, and it can also be used in contemporary products like fortified snacks, instant powders and fermented items (Łysakowska et al., 2024). The progress in extraction methods, stabilization techniques and encapsulation processes has made it possible to use standardized bioactive-rich extracts without any negative effects on flavor or product shelf life (Cheung, 2013; Heleno et al., 2015).

FIGURE 1

4 Bioactive components

Lion’s Mane Mushroom is a distinctive fungus that is very beneficial to health due to its incredible bioactive compounds (Figure 2). The mushrooms are very rich in polysaccharides which may make up as 53% of their dry weight. The primary components are (1→3)- and (1→6)-β-D-glucans, which are acclaimed for their roles in immune support, antioxidant provision, and nerve cell protection (Yang et al., 2022). Another group of compounds present in Lion’s Mane is phenolic compounds, which strengthen the mushroom’s antioxidant properties, in addition to sterols like ergosterol, which are anti-inflammatory (Suleiman et al., 2022). There are also other exceptional bioactive compounds, such as isoindolinones, pyrones, and linoleic acid, which belong to the fatty acid family. One can also consider proteins/peptides like hericerin derivatives and the antioxidant ergothioneine (Friedman, 2015; Martínez-Mármol et al., 2020) to be a factor in the tremendous array of biological activities of the Lion’s Mane mushroom. The mushroom with its broad compounds presents a good prospect for therapy that includes triggering neuronal differentiation, bringing about cancer cell death, and working on inflammation through BDNF-related pathways.

FIGURE 2

4.1 Polysaccharides (β-glucans)

The primary bioactive macromolecular group of H. erinaceus polysaccharides (HEPs) consists of heteropolysaccharides that have molecular weights that extend between 2.1 kDa and 75,000 kDa (Sun et al., 2025; Yu et al., 2025). The β-glycosidic linkages that connect the structural elements of H. erinaceus polysaccharides generate branched chains with triple-helical or random-coil conformations. High-performance size-exclusion chromatography (HPSEC), gas chromatography (GC), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR) are frequently used to assess these structural properties (Ge et al., 2025; Yang et al., 2022). The conventional method of extraction employs hot water techniques together with alcohol precipitation methods, while modern techniques, including ultrasonic extraction, enzymatic hydrolysis and steam explosion pretreatment, end up improving extraction efficiency. For instance, steam explosion pretreatment can increase total polysaccharide yield by 245% and β-glucan content by 34.60%–49%, and at the same time, it lowers molecular weight to support better solubility and bioaccessibility (Chen et al., 2024; Yu et al., 2025). The process of purification uses ion-exchange or gel-filtration chromatography to separate xylans, glucoxylans, heteroxyloglucans, and galactoxyloglucans (Ge et al., 2025; Niu et al., 2025). The polysaccharides exhibit diverse biological functions, including immunomodulatory activity through macrophage activation and cytokine production of TNF-α, IL-6 and NF-κB pathway modulation. They also display antitumor properties that induce cell death, stop tumor development, and antioxidant abilities that exceed 90% ROS elimination at 1 mg/mL concentration or above. They possess anti-aging properties together with liver protection, hypoglycemic activity by inhibiting α-amylase and regulating glucose metabolism. They protect the gastrointestinal tract through their effects on the PI3K/Akt pathway and gut health improvement by promoting beneficial bacteria such as Firmicutes, increasing short-chain fatty acid (SCFA) production, while they eliminate pathogens such as Escherichia-Shigella (Liu et al., 2022; Yang et al., 2022; Yu et al., 2025). HEPs find their practical uses as functional food components that support immune function and provide antioxidants, while they serve as biomaterials for tissue regeneration through hydrogels and as drug carriers through β-glucan-chitosan nanoparticles, which deliver resveratrol to improve its anti-inflammatory effects and bioavailability (Ge et al., 2025; Niu et al., 2025).

The essential polysaccharide subclass of β-Glucans exists as the main polysaccharide component of H. erinaceus because it contains a glucose backbone that connects through β-(1→3) links and has β-(1→6) branches that create helical structures with high viscosity and their molecular weight ranges from 2.158 × 10^6 g/mol to 6.944 × 10^6 g/mol (Chen et al., 2024; Sun et al., 2025). The organisms exist in both fruiting bodies and mycelium, which exhibit different content levels depending on the strain and processing method used. The extraction process uses alkaline solutions or β-1,3-glucanase and β-1,6-glucanase enzymes to separate different glucan fractions while steam explosion pretreatment increases yield and total sugar content by 51.22% and β-glucan content by 34.60% while it decreases molecular weight to enhance functional performance (Chen et al., 2024). The branching ratios determine the total SCFA production and it raises the gut microbiota abundance of Lactococcus when the branching ratio increases to 1:3 while the 2:7 branching ratio leads to greater acetic and propionic acid production through Prevotellaceae and Lachnospira enrichment (Chen et al., 2025). β-Glucans, particularly with β-1,3 linkages, function as immunomodulators by increasing the production of cytokines, having antitumor effects, scavenging reactive oxygen species (ROS), and stimulating the gut microbiota through prebiotic mechanisms that increase the production of SCFA. β-glucans are also linked with better blood sugar control, because they inhibit starch digestion. Studies suggest that β-1,3-glucan is more effective than β-1,6-glucan when it comes to disrupting α-amylase activity, because of its structural details. The molecule is arrangement gives it an advantage, even if it is not totally simple. These properties also back the idea of developing products aimed at immune support, plus low-glycemic index foods, and even approaches used for dementia prevention, or at least risk reduction. Overall, the β-glucans from H. erinaceus really show promising ability for gut health, immune balance and metabolic regulation, although more investigations are still needed to enhance bioavailability (Contato and Conte-Junior, 2025; Ge et al., 2025; Yu et al., 2025).

4.2 Terpenoids

Hericium erinaceus contains terpenoids as its primary bioactive secondary metabolites which produce medicinal effects (Contato and Conte-Junior, 2025). The compounds show structural variety because they originate from isoprene units and contain diterpenoids and meroterpenoids as their subclasses (Qi et al., 2024; Szućko-Kociuba et al., 2023). Hericium erinaceus shows terpenoid distribution through its fruiting bodies and mycelia which contain more than 200 identified secondary metabolites that include sterols, phenolics, hericenones, erinacines and other terpenoid compounds (Chen et al., 2017; Kostanda et al., 2024; Qi et al., 2024). The genomics research demonstrates that terpenoid biosynthesis pathways have different expression patterns because gene clusters in mycelia and fruiting bodies lead to cyathane diterpenoid and polyketide production (Chen et al., 2017; Doar et al., 2025; Ma et al., 2021). The terpenoids show neuroprotective properties through their ability to activate nerve growth factor and brain-derived neurotrophic factor production, while they decrease oxidative stress and control inflammation and support neuronal protection and repair processes (Brandalise et al., 2023; Contato and Conte-Junior, 2025; Spangenberg et al., 2025). The compounds function as treatments for neurodegenerative disorders because they pass through the blood-brain barrier through passive diffusion to affect the MAPK/ERK and PI3K/Akt signaling pathways (Spangenberg et al., 2025; Szućko-Kociuba et al., 2023). The terpenoids demonstrate multiple health benefits through their ability to fight inflammation and oxidative stress and microbial infections and cancer cells while their low toxicity makes them safe for medical use (Contato and Conte-Junior, 2025; Mahadevan et al., 2025).

4.2.1 Hericenones

Hericenones are meroterpenoids that exist primarily in H. erinaceus fruiting bodies, and they have several sub-types, such as hericenones a, b, c, d, e, f, g, h, i, j, k, and l that show characteristics of aromatic benzyl alcohol derivatives that possess geranyl side chains (Table 1). The biosynthetic process creates various variants which contain oxidized geranyl moieties, and polyketide synthase (PKS) pathways together with HerA (PKS) and HerB (carboxylic acid reductase) enzymes use orsellinic acid (ORA) as their starting material (Iacovelli et al., 2024; Othman et al., 2026; Qi et al., 2024). The structural analysis, which combines NMR and MS techniques, reveals fused ring systems together with functional groups that activate NGF stimulation. Hericenone C contains an aromatic structure that enhances its bioactivity through its unique design (Kawagishi et al., 1991; Phan et al., 2014). The extraction process uses either methanol or ethanol, and the extraction yields depend on the growth stage which reaches its maximum during the 14–21 day period (Sevindik et al., 2024; Valu et al., 2020). Hericenones show strong neurotrophic effects because they stimulate NGF production in glial cells (e.g., astrocytes) which leads to neurite growth and neuronal development and synaptic strength changes. Neurotransmitter release occurs when the markers βIII-tubulin and synaptotagmin increase, although proliferation decreases because PCNA/CD133 levels drop and neuronal excitability increases through voltage-gated sodium current activation (Phan et al., 2014; Szućko-Kociuba et al., 2023). Neuroprotective mechanisms function through three processes which include 3-hydroxyhericenone F, which protects against ER stress-induced neuronal death, and 3-hydroxyhericenone F and EB-plaque reduction and gliosis and neuroinflammation in AD research models and 3-hydroxyhericenone F which protects against apoptosis while protecting pro-survival pathways (Roda et al., 2021; Szućko-Kociuba et al., 2023). The compound exhibits various biological activities, which include antioxidant action through ROS scavenging and anti-inflammatory activity by blocking NF-κB and cytokine production and antimicrobial effects through bacterial membrane disruption and potential anti-coagulant properties through hericenone B, which reduces blood clotting (Contato and Conte-Junior, 2025; Qi et al., 2024).

4.2.2 Erinacines

The mycelia of H. erinaceus produce erinacines, which are cyathane diterpenoids that contain a distinct fused 5-6-7 ring system constructed from isoprene units. Based on their structures and molecular weights, they have several variants, including A-K and P-S (Table 2), whereas erinacine A demonstrates the highest effectiveness together with best absorption properties (Li et al., 2018; Spangenberg et al., 2025). Biosynthesis depends on gene clusters such as eriE and eriG and eriI which interact with different environmental conditions and substrate types to determine erinacine Q and P and A and C production (Doar et al., 2025; Ma et al., 2021). The rendering of structures through NMR and MS analysis revealed the presence of isomers which include A and B and E and F that possess C25H36O6 formula and contain stereocenters which permit them to enter the bloodstream barrier (Kawagishi et al., 1994; Kostanda et al., 2024). The process of mycelia extraction uses ethanol or water as solvents while HPLC serves as the method for measuring substance levels. Erinacines induce strong increases of NGF and BDNF production within glial cells which activate neurotrophin release through Trk receptors to support neuronal life and growth and rehabilitation processes. Their treatment elevates insulin-degrading enzyme (IDE) levels while they affect p53 pathways to decrease Aβ plaques and gliosis and neurotoxic effects in Alzheimer disease models through their promotion of neurogenesis in the hippocampus and their support of oligodendrocyte development through their enhancement of MBP/PLP levels (Huang et al., 2021; Li et al., 2018; Spangenberg et al., 2025). The anti-inflammatory actions include blocking iNOS and NO and cytokines, which include TNF-α and IL-6, while the antioxidant actions decrease both ROS and ER stress and the anti-apoptotic actions create an equilibrium between pro-survival (PI3K/Akt) and pro-death pathways (Contato and Conte-Junior, 2025; Wang et al., 2019). The preclinical research shows that erinacines improve both motor functions and cognitive abilities and symptoms of depression in rodent models, which have Parkinson’s disease, stroke and neuropathy with benefits that depend on the dosage level from 1 to 30 mg/kg. They also reduce neuropathic pain while improving gut microbiota and displaying anti-cancer activity through their ability to cause apoptosis in leukemia cells (Li et al., 2018; Spangenberg et al., 2025).

4.3 Phenolic compounds

The phenolic components of H. erinaceus contain phenolic acids which include protocatechuic acid and p-coumaric acid plus flavonoids and hericerins and hericenes and related aromatic compounds, which become concentrated in ethanolic or methanolic extracts to provide significant benefits for antioxidant and anti-inflammatory and antimicrobial activities (Darmasiwi et al., 2022; Qiu et al., 2024; Sevindik et al., 2024). The total phenolic content of a sample can reach maximum values of 1,652 μg/mL which shows strong relationships with antioxidant capabilities because total flavonoid content shows an r value of 0.979 that connects with DPPH inhibition performance (Darmasiwi et al., 2022). The analysis of these compounds utilizes high-performance liquid chromatography-mass spectrometry (HPLC-MS), which shows that protocatechuic acid and p-coumaric acid are the main acids, together with the detection of sterols (Darmasiwi et al., 2022; Li et al., 2017) and cerebrosides and other aromatic compounds that researchers extracted from fruiting bodies, which total 51 compounds that include 35 ergostane-type sterols. The phenolic compounds show their mechanistic functions through their ability to scavenge ROS which activates endogenous antioxidants while they block NF-κB activity to decrease cytokine levels and they disrupt bacterial cell membranes plus enzymes which creates their antimicrobial and antibiofilm effects against Pseudomonas mirabilis while they protect neurons from oxidative stress and inflammation (Contato and Conte-Junior, 2025; Darmasiwi et al., 2022; Kushairi et al., 2019). The low toxicity of the product which includes multiple components has been established through various tests which assess its potential as a natural preservative and nutraceutical and supplement that provides antitumor and immunomodulatory and hypolipidemic and hepatoprotective advantages (Chen et al., 2022; Mahadevan et al., 2025). The current research aims to enhance yield factors while improving bioavailability because this will increase commercial uses of the product (Qiu et al., 2024; Valu et al., 2020).

4.4 Proteins, peptides, and other minor bioactives

Proteins constitute a significant portion of the nutritional profile of H. erinaceus, which contains 20.8 to 42.9 percent of its dry weight as proteins in both its fruiting bodies and mycelial structures (Contato and Conte-Junior, 2025; Friedman, 2015). The protein material exhibits essential amino acids in a ratio of 44.59 percent while leucine valine and phenylalanine function as amino acid components. The protein material shows an in vitro digestibility value of 71.33 percent (Silva et al., 2025). These proteins include bioactive lectins (carbohydrate-binding proteins) that exhibit immunomodulatory, antimicrobial, and hemagglutinating activities by interacting with cell-surface sugars, thereby influencing immune cell responses and inhibiting pathogens (Contato and Conte-Junior, 2025; Kim, 2018). Other proteins encompass enzymes that include laccase and proteases which produce antioxidant and anti-inflammatory effects according to scientific evidence. The H. erinaceus proteins protect against high-fat diet-induced liver damage by reducing liver triglycerides and cholesterol and malondialdehyde levels while boosting superoxide dismutase and glutathione peroxidase activities (Lu et al., 2025). The proteins enable oligodendrocyte maturation through their function of increasing myelin basic protein and proteolipid protein expression, which assists in neuroregeneration (Huang et al., 2021). The proteomics analyses detected proteins with different expression patterns that participate in anti-inflammatory processes, which include p53 modulation for gastric injury protection (Gravina et al., 2023). The proteins support functional food applications, which promote metabolic health and immune defense and brain protection, while subchronic research has confirmed their low toxicity (Chen et al., 2022; Contato and Conte-Junior, 2025; Mahadevan et al., 2025).

The primary method for obtaining peptides from H. erinaceus involves using enzymes to break down protein structures, which results in bioactive peptides that have molecular weights below 0.65–10 kDa. The main components of this study include KSPLY which functions as a pentapeptide to protect HepG2 cells from H₂O₂-induced oxidative damage through its ability to activate the Keap1/Nrf2 pathway, which decreases ROS and MDA levels while increasing antioxidant enzyme production (Xu et al., 2023). The experiments conducted with hydrophobic peptides from pulsed electric field-assisted or microbial protease hydrolysis which contained 50 to 100 percent hydrophobic amino acids demonstrated their ability to reduce inflammation through 36.2 percent NO inhibition and 31.8 percent IL-6 reduction results (Sangtitanu et al., 2020). Most peptides show bioactivities such as anti-inflammatory effects through NF-κB inhibition and antioxidant radical scavenging and gastroprotection against Helicobacter pylori damage and immunomodulation and apoptosis induction in lung cancer cells through caspase activation. The therapeutic potential of these peptides extends to treating inflammation and cancer and improving nutrient absorption, while their extraction process achieves a 42.44 percent yield increase through pulsed electric field extraction methods.

Hericium erinaceus includes bioactive compounds which exist in minor amounts because it has two main macromolecular components. They include sterols which include ergosterol as the primary sterol because it exhibits anti-inflammatory and anticancer and vitamin D₂ precursor functions when exposed to ultraviolet radiation (Friedman, 2015; Kostanda et al., 2024). The fatty acids present in H. erinaceus include linoleic acid [C18:2], oleic acid [C18:1] and palmitic acid [C16:0] because these acids provide anti-obesity and lipid-lowering benefits, it also include vitamins B1 and B2 and B3 and D and E and C and minerals which include potassium at 254 mg per 100 g of dry weight and phosphorus and magnesium and zinc and manganese and trace elements (Contato and Conte-Junior, 2025). The bioactive compound ergothioneine acts as a sulfur-containing “longevity vitamin” that protects mitochondria against oxidative stress and neurodegenerative damage (Contato and Conte-Junior, 2025; Harasym et al., 2025). The compounds cerebrosides and isoindolinones show immunomodulatory effects together with their ability to prevent cell growth, while ergothioneine stores itself in mitochondria to address age-related cellular decline. These minor components improve overall antioxidative capacity through their ability to scavenge ROS, while they also enhance anti-tumor activities and regulate metabolic processes and support neuroprotective aging processes and their safety studies showed no harmful outcomes during clinical tests and subchronic assessments.

5 Extraction and characterization techniques

Various techniques are utilized to extract bioactive compounds from H. erinaceus. However, it has been observed that green (innovative techniques) have several advantages, such as being less time-consuming, eco-friendly, highly efficient, yielding higher yields, and producing minimal residues compared with conventional methods (Table 3).

5.1 Conventional extraction methods

The choice of extraction methodology establishes three vital outcomes that determine the yield of bioactive compounds, their chemical composition and biological activity from H. erinaceus. The primary method for using traditional extraction techniques enables researchers to extract key bioactive components, including low-molecular-weight polysaccharides and secondary metabolites. The washing, drying, milling, and sieving of fruiting bodies or mycelial biomass occur before extraction to create more accessible surface areas, which enhance solvent–matrix interactions for better extraction results (Yu et al., 2025; Zhang et al., 2007). The traditional method that most researchers use to extract H. erinaceus polysaccharides (HEPs) involves hot water extraction to obtain these compounds specifically from β-glucans. The process begins with extracting powdered materials through distilled water at temperatures between 80 °C and 100 °C for multiple hours before researchers proceed to the steps of filtration, concentration, ethanol precipitation and deproteinization. The extraction parameters, which include temperature, extraction time and solid-to-liquid ratio, have a strong impact on polysaccharide yield, molecular weight distribution, branching degree and conformational features, which determine biological activity (Ge et al., 2025; Yang et al., 2022; Yu et al., 2025).

The recovery process of low-molecular-weight and moderately polar compounds, such as hericenones, phenolic acids, and sterol derivatives, relies primarily on organic solvent extraction. Ethanol and aqueous ethanol systems are gaining popularity because they deliver effective results while users can modify their polarity to match food and nutraceutical needs. The process of selective solubilization for these secondary metabolites depends on three factors, i.e., solvent polarity, extraction duration and solvent-to-material ratio (Kawagishi et al., 1991; Kostanda et al., 2024). The process of acid and alkali extraction methods supports better polysaccharide release because these methods break through the chitin and glucan-based barriers of fungal cell walls. The chemical treatments successfully improve extraction results, but the use of strong acid or base conditions will cause depolymerization, change molecular structure, and create new functional groups, which makes it essential to optimize procedures for protecting structural integrity and biological activity (Qiao et al., 2024; Zhang et al., 2007). Most conventional approaches, like hot water and organic solvent extraction, tend to be more cost-effective and easier to scale up for big batches, mainly because the equipment is cheaper and the infrastructure setup is simpler. They usually end up needing more solvent and more energy as time goes on (Ge et al., 2025).

5.2 Green and advanced extraction technologies

Hericium erinaceus research now uses advanced green extraction technologies to extract bioactive compounds with better efficiency while using less solvent and protecting bioactive compounds from thermal destruction. The process of ultrasound-assisted extraction (UAE) uses high-frequency acoustic waves to create cavitation effects that break down fungal cell walls while allowing better solvent absorption and improved mass transfer. The response surface methodology optimization studies demonstrated that the Ultrasound-assisted extraction (UAE) method enhanced phenolic compounds and diterpenoids, such as erinacine A extraction, with less time, resulting in extracts with improved antioxidant properties under optimized conditions (Valu et al., 2020; Yu et al., 2024). The microwave-assisted extraction method (MAE) uses microwave energy to create molecular rotation and localized heating in materials, which produces pressure gradients. This process causes cell rupture and accelerates the diffusion process of internal cell contents into the solvent. MAE has been used in two ways: first, as a complete method and second, within a series of extraction processes that include supercritical CO₂ extraction. The combined MAE-supercritical CO₂ method helps in isolating a bunch of different kinds of bioactive compounds, so there are chances of getting a higher recovery of polysaccharides and phenolic compounds, like up to 15%–20% better total extract yield than when using one method alone. It also pulls out more lipophilic terpenoids, including things such as hericenones and ergosterol (Cheung, 2013; Ge et al., 2025). Supercritical fluid extraction (SFE) employs supercritical carbon dioxide as its primary solvent while using ethanol for a food-grade co-solvent to achieve selective extraction of lipophilic bioactive compounds, which include hericenones, sterols and terpenoid-like metabolites. Supercritical CO₂ extraction enables effective solvent-free extraction through its adjustable solvating capabilities, which operators manage by manipulating both pressure and temperature (Cao et al., 2023; Joradon et al., 2024). Subcritical water extraction (SWE) utilizes water under conditions of high temperature and pressure to achieve a decreased dielectric constant, which allows the extraction of polar and moderately polar compounds that include polysaccharides and phenolic compounds. The process of SWE has received more attention in research about other edible and medicinal fungi. However, it shows great potential as a sustainable extraction method for H. erinaceus because it avoids traditional solvent-based methods. The application of SWE to H. erinaceus shows potential as an eco-friendly extraction technique (Parada et al., 2015; Rodríguez-Seoane et al., 2021).

Currently, “green” technologies, such as ultrasound-assisted extraction, enzyme-assisted extraction, and supercritical fluid extraction, often show better efficiency, less solvent usage, and improved retention of the bioactives, so in the longer run, they can be more sustainable Zhu et al. (2014), (Qiu et al., 2024). Even though the starting capital for advanced equipment (SFE systems) is higher, they can still end up being price-competitive at industrial scale, especially when yields are higher, processing takes less time, and the downstream purification steps are reduced. For food related use, food-grade solvents are preferred, and cleaner options (UAE and EAE) are favoured because of regulatory expectations, consumers’ expectations, and clean-label products (Joradon et al., 2024; Yu et al., 2025).

5.3 Analytical tools for bioactive characterization

After extraction, scientists need to conduct complete tests because these tests will determine the exact elements, the purity, and the fabric features of H. erinaceus bioactive compounds. The structural analysis of polysaccharide fractions demands deproteinization followed by ethanol fractionation and then two separate chromatographic purification steps, which use DEAE-Sepharose and size-exclusion media (Niu et al., 2025; Zhang et al., 2007). HPLC with UV or MS detection stands as the standard method for separating and measuring small-molecule secondary metabolites, which include erinacines and phenolic derivatives and gas chromatography (GC) serves as the ideal method for analyzing volatile and lipid components after derivatization (Kawagishi et al., 1994). FT-IR spectroscopic tools enable functional group profiling, whereas NMR spectroscopy provides complete structural details, which include glycosidic linkages and monosaccharide configurations and mass spectrometry like LC–MS/MS gives precise molecular mass measurements and fragmentation analysis, which helps identify compounds (Li et al., 2018; Zhang et al., 2007). The new analytical methods, which use hyphenated techniques to combine chromatographic separation with advanced MS processing and spectroscopic detection, have improved researchers’ ability to distinguish between two different classes of polysaccharide fractions and minor secondary metabolites that exist in H. erinaceus extracts (Cheung, 2013; Qiu et al., 2024; Yang et al., 2021).

6 Health benefits and biological activities

6.1 Antioxidant and anti-inflammatory effects

Antioxidants protect cells from oxidative stress, lipid peroxidation, and cellular damage, which occurs during aging, chronic diseases and neurodegenerative disorders by neutralizing reactive oxygen species and free radicals. Hericium erinaceus demonstrates strong antioxidant properties through its bioactive compounds (Table 4), which include polysaccharides, phenolic compounds and terpenoids that contain hericenones and erinacines and other metabolites that fight free radicals, increase internal antioxidant enzymes and decrease malondialdehyde (Cornford and Charnley, 2025). Ethanol and hot water extracts display strong reducing power and DPPH radical scavenging and ferrous ion chelation according to in vitro research, which shows that ethanol extracts typically show higher performance (Jiang et al., 2016). Research on extraction methods based on polarity demonstrates that different extraction techniques result in different antioxidant activity levels because ethanol extracts produce better DPPH and superoxide anion scavenging than other methods. The Drosophila melanogaster model demonstrates that fruiting body ethanol extracts provide strong DNA protection and antioxidant activity, which protects against oxidative stress while reducing genotoxicity at safe dosage levels (Cvetković et al., 2025). Various other characteristics originate from ROS scavenging and enzyme induction, which produce health advantages that include neuroprotection (Friedman, 2015; Spelman et al., 2017).

The anti-inflammatory effects of this treatment system use cytokine modulation and pro-inflammatory pathway suppression together with anti-inflammatory mediator activation to decrease excessive immune responses that cause chronic inflammation in neurodegenerative diseases, obesity and gastrointestinal disorders. Hericium erinaceus exerts these effects through its bioactive compounds, which block pro-inflammatory cytokine production and nitric oxide synthesis while increasing anti-inflammatory pathway functions. Research demonstrates that ethyl acetate extracts block TNF-α and IL-6 production by inhibiting TLR4-JNK pathway activity in adipocyte-macrophage coculture systems. The animal research demonstrates that H. erinaceus extracts increase multiple anti-inflammatory genes in 3-acetylpyridine-induced cerebellar ataxia rats while the animal research shows that these extracts boost motor abilities through their effects on neuroinflammation. The extracts reduce ulcerative colitis symptoms through their ability to decrease MPO and NO and MDA and pro-inflammatory cytokines while they boost SOD levels (Diling et al., 2017). The characteristics of H. erinaceus make it a natural treatment option for inflammation-related diseases, which produces fewer adverse effects when compared to standard medical approaches.

6.2 Neuroprotective and cognitive enhancement

The neuroprotective effects safeguard neurons through their ability to shield neurons from all types of damage which includes both neurodegeneration and their final death. The main active compounds in this study come from mycelia as erinacines and from fruiting bodies as hericenones because both of these compounds can cross the blood-brain barrier to activate NGF production and neurotrophin levels while stimulating both ERK1/2 and BDNF pathways (Martínez-Mármol et al., 2020; Szućko-Kociuba et al., 2023). Researchers used preclinical models of ischemia, Parkinson’s disease, Alzheimer’s disease, and stroke to show that erinacine-enriched mycelia can decrease amyloid-beta plaques and neuroinflammation while restoring behavioral functions, mitochondrial performance and neuronal firing abilities (Brandalise et al., 2023; Chiu et al., 2018). The extracts show protection against H₂O₂-induced oxidative damage and LPS-induced inflammation in HT22 hippocampal neurons and BV2 microglia because they preserve mitochondrial membrane potential while decreasing Bax expression (Kushairi et al., 2019). Erinacines increase antioxidant defense systems while boosting pro-survival mechanisms, neurogenesis and improving behavioral results (Martínez-Mármol et al., 2020).

H.erinacines known for its capability to produce nerve growth factor (NGF) through hericenones and erinacines, which can penetrate the blood-brain barrier, enables neurogenesis while it protects neurons. H. erinacines extracts acts like a brain protector, mainly because it boosts NGF and BDNF signaling. The process creates new neurons while decreasing two major factors that lead to cognitive decline and Alzheimer’s disease pathogenesis. The mushroom contains hericerin compounds, which activate BDNF-like pathways in hippocampal neurons to produce superior neuron development and recognition memory advancement in animal models and cell culture (Kawagishi et al., 1994; 1996a; Szućko-Kociuba et al., 2023). Its extracts have shown they can stimulate NGF and BDNF synthesis and then cross the blood-brain barrier to support neurogenesis and cognitive development (Martínez-Mármol et al., 2020). The H. erinaceus compounds in laboratory experiments have demonstrated their ability to enhance NGF production, which may lead to Alzheimer’s disease prevention through protection against amyloid-beta harmful effects. The studies show that erinacine A-rich extracts lead to increased BDNF levels and improved cognitive performance among participants in supplementation research (Brandalise et al., 2023; Chiu et al., 2018; Tsai-Teng et al., 2016). The research findings demonstrate widespread neurotrophic effects through TrkB signaling activation, which results in enhanced memory and brain cell growth (Kawagishi et al., 1991; 1994; Szućko-Kociuba et al., 2023).

6.3 Immunomodulatory and anticancer properties

The term immunomodulatory properties describes how substances can control immune system activity to boost or reduce immune reactions for maintaining body balance while fighting off illnesses. The bioactive compounds of H. erinaceus produce these effects through their primary constituents, which are polysaccharides that interact with immune cells to induce their maturation, activation and cytokine production. Dendritic cells, macrophages and T-cells respond to the polysaccharides by producing anti-inflammatory cytokines such as IL-10 while they simultaneously decrease the production of pro-inflammatory cytokines like TNF-α which results in immune system stabilization that may benefit people with autoimmune disorders or infectious diseases (Diling et al., 2017; Yang et al., 2022).

The polysaccharides found in mushrooms help to change the gut microbiota, which leads to better immune health because they promote the growth of helpful bacteria and short-chain fatty acids (SCFAs) that support whole-body immunity (Song et al., 2025; Wu et al., 2024). The mechanisms that stop cancer cell growth, activate programmed cell death, block cancer spread and boost tumor immune detection compose the anticancer effects of these properties. The extracts of H. erinaceus exhibit these effects by treating different cancer types, which include gastrointestinal cancers, through their ability to stop tumor development and tumor spread while maintaining safety for users Xie et al. (2021). The ethanol extracts demonstrated strong anticancer activity against gastric, liver, colon and breast cancer cell lines because they produced IC50 values that matched 5-fluorouracil while triggering apoptosis through caspase activation and blocking matrix metalloproteinase (MMP) activity (Li et al., 2014). The hot water and ethanol extracts blocked lung metastasis by 66%–69% because they assisted with apoptosis while creating fewer tumor nodes and did not harm the host (Kim et al., 2013). The high molecular weight polysaccharides protect against amyloid beta-induced neurotoxicity which shows importance for cancers that cause neurological problems because they decrease oxidative stress and cell death (Cheng et al., 2016).

6.4 Metabolic and gut health benefits

The metabolic advantages include better glucose and lipid metabolic processes, together with improved insulin sensitivity and energy balance control, which help people avoid or treat diabetes, obesity and metabolic syndrome. The antidiabetic, antihyperlipidemic and anti-obesity effects of H. erinaceus stem from its bioactive compounds, which include polysaccharides and hericenones that control oxidative stress and inflammation together with their metabolic effects. These substances reduce blood glucose levels and enhance lipid profiles while increasing metabolic rates because it contains high levels of antioxidants and polysaccharides (Friedman, 2015).

The low-calorie and high-fiber properties of this product enable weight control and metabolic regulation through its use in functional foods that help prevent obesity (Venturella et al., 2021). Hericium erinaceus provides multiple health benefits which include cardioprotective and hepatoprotective effects, thus making it an effective supplement to treat metabolic disorders. The advantages of gut health maintenance include extended intestinal barrier protection, changes in microbiome composition, inflammatory control, and improved digestive performance that helps to prevent IBD, ulcer, and dysbiosis disorders. The polysaccharides from H. erinaceus (HEPs) function as prebiotics, which support the growth of beneficial bacteria while increasing microbiota biodiversity and producing short-chain fatty acids (SCFAs) which maintain gut epithelial integrity and control immune responses. The systematic reviews demonstrate that HEPs provide relief from colitis symptoms while protecting mucosal tissues and controlling intestinal microbiota, together with their anti-inflammatory properties, which decrease MPO activity and cytokine production (Diling et al., 2017; Ren et al., 2023). The properties of H. erinaceus create a natural substance that supports gut health because it contains prebiotics and anti-inflammatory properties that can be used in functional food products to treat gastrointestinal disorders (Venturella et al., 2021).

7 Applications in food and functional products

7.1 Functional foods and beverages

Hericium erinaceus functions as a desirable functional food because of its mild taste, its compatibility with different food products, and its ability to withstand various processing methods. Hericium erinaceus enables higher product levels because its taste and texture remain intact, while most medicinal mushrooms become less appealing to consumers through their bitter taste and strong smells. The characteristic enables its use in various food production methods, which extend to beverages, solid foods, fermented products, and nutraceuticals (Mori et al., 2009; Łysakowska et al., 2024). The recognition of diet-based approaches for preserving brain function, digestive health, and immune system defense has increased the importance of H. erinaceus for developing new functional food products (Mori et al., 2009). People can consume H. erinaceus through functional foods and beverages, which offer continuous bioactive compound release at low dosages. Adding up to 12% Lion’s Mane powder to wheat bread maintained acceptable sensory results, with overall ratings remaining above 3.5 on a 5-point hedonic scale. Taste, texture, and appearance did not significantly change at the 3%–6% range, but as the level increased, a deeper tone with subtle earthy undertones was observed (Łysakowska et al., 2024). In oat-based desserts designed for dysphagia patients, Lion’s Mane at up to 5% helped keep a good texture, and mouthfeel stayed agreeable while still meeting IDDSI requirements (Gunathilake et al., 2025). Fresh mushrooms may have a mild seafood-like flavor, but when it becomes powder, it may have an earthy flavor that may require flavor masking. (Raja-Razali et al., 2026). Whole mushroom powder and aqueous or hydroalcoholic extracts are used in soups and broths, bakery products, noodles, cereal-based foods, snack bars, dairy substitutes, and ready-to-drink beverages. Liquid and semi-solid foods benefit from polysaccharide-rich extracts because of their solubility and water-holding capacity and their ability to enhance viscosity and mouthfeel. Hericium erinaceus polysaccharides use their physicochemical properties to serve as bioactive compounds and functional elements, which provide health benefits and enhance product quality (Mau et al., 2001; Wang et al., 2014). Hericium erinaceus extracts have been tested in beverage systems, such as herbal teas, functional coffees, smoothies, and fermented drinks that enhance cognitive abilities and gut health. The prebiotic-like effects of polysaccharides, which modulate gut microbiota composition and metabolic activity, are supplemented by the antioxidant and anti-inflammatory effects of phenolic compounds and terpenoids. The dual mechanism operates through the gut–brain axis, which allows dietary components to impact neurological function by microbial metabolites, immune signaling and neural pathways (Cheung, 2013; Mori et al., 2009). The need for product stability and consumer acceptability requires companies to optimize particle size, extract concentration, and processing conditions because turbidity, sedimentation, and flavor stability present challenges.

7.2 Nutraceuticals and dietary supplements

The use of H. erinaceus in creating food and health products demonstrates how food science now prioritizes ingredients that provide research-backed health advantages that work with standard eating habits (Raja-Razali et al., 2026). Hericium erinaceus functions as an edible mushroom that provides bioactive substances that protect brain cells, modulate immune functions, fight oxidation and support digestive health (Gravina et al., 2023). The combination of bioactive substances, which include high-molecular-weight polysaccharides and β-glucans, diterpenoid compounds, phenolic antioxidants, and bioactive peptides provides multiple biological effects that enable the ingredient to function as a multifunctional substance instead of a single-use component (Ge et al., 2025; Thongbai et al., 2015).

The most successful commercial use of H. erinaceus exists in nutraceuticals and dietary supplements because manufacturers can produce standardized bioactive compounds in high concentration through their products. Manufacturers create products in the form of capsules, tablets, powders and liquid extracts from fruiting bodies and mycelium and submerged fermentation systems (Raja-Razali et al., 2026). Mycelium-based preparations, which contain erinacines, have become very popular because they can produce nerve growth factor synthesis which results in neuroprotective and cognitive-enhancing effects of H. erinaceus (Li et al., 2018). The development of fermentation technology has made it possible to produce erinacine-rich mycelial biomass through a process that maintains production control while decreasing output variability that occurs with wild or cultivated fruiting bodies (Krzyczkowski et al., 2010). Standardization strategies typically depend on measuring total polysaccharides or specific marker compounds like erinacine A. However, H. erinaceus supplements show biological activity because of interactions between multiple compounds, which work together instead of depending on one active ingredient. The limited number and small size of human clinical studies show that H. erinaceus supplementation improves cognitive function and mild cognitive impairment, which demonstrates its potential as a nutraceutical yet needs larger controlled studies to confirm long-term efficacy and dosage guidelines (Cornford and Charnley, 2025; Menon et al., 2025; Mori et al., 2009).

Hericium erinaceus has been introduced in a wide range of functional food products, like baked items (for instance bread), snacks, drinks, oat based desserts, and even plant substitutes. Commercial interest seems to be accelerating, the global functional mushroom market (including Lion’s Mane) is expected to grow a lot more, driven by consumers looking for cognition related and immune-supportive foods (Raja-Razali et al., 2026). Things like Lion’s Mane coffee, protein bars, gummies, and ready to drink beverages are getting more shelf space in big retailers, and this is backed by solid market momentum (CAGR numbers roughly 10%–19% in some recent summaries). Even though the commercial payoff is kind of moderate when compared with older, more famous functional ingredients. Several items stay niche; they are usually premium priced, and they’re promoted more through health stores and online platforms, not really through mainstream supermarkets. The hurdles, such as higher production costs, problems with steady supply, and ongoing rivalry from synthetic nootropics, are also challenging (Friedman, 2015).

7.3 Food fortification and novel product development

Hericium erinaceus food fortification provides a practical method to improve the nutritional value and functional benefits of common foods because it does not require people to change their eating habits (Gunathilake et al., 2025; Raja-Razali et al., 2026). The fortification methods used for this purpose combine three different techniques, which involve direct mushroom powder use, purified polysaccharide fraction addition, and protected bioactive extraction through encapsulation (Łysakowska et al., 2024). Hericium erinaceus dietary fiber and high-quality protein have been added to different confectionery items, such as bread, pasta, noodles, breakfast cereals, and plant-based meat alternatives (Gunathilake et al., 2025; Łysakowska et al., 2024; Raja-Razali et al., 2026).

The process of developing new products now focuses on creating combined formulas that use H. erinaceus together with probiotics and prebiotics, omega-3 fatty acids and plant-based polyphenols to deliver multiple health advantages. Studies show microencapsulation, nanoemulsion and biopolymer-based delivery systems to achieve three objectives, which include improving bioactive stability, masking off-flavors and enabling controlled release during digestion (Kamble et al., 2025; Ge et al., 2025; Sagar et al., 2022). The alternative protein industry shows interest in H. erinaceus because its fibrous texture and umami flavor enhance sensory quality and nutritional value of plant-based and hybrid meat products (Raja-Razali et al., 2026).

The putting together of plant based meats, hybrid products, and functional drinks with micro/nano encapsulated extracts shows promise, for better stability and more ready bioavailability (Kamble et al., 2025; Ge et al., 2025). Synergistic formulations with probiotics or polyphenols could target the gut-brain axis. Still, there are roadblocks like how to do sensory masking, keeping good shelf life, getting regulatory standardization right, and having solid clinical proof that holds up (Gunathilake et al., 2025; Menon et al., 2025). For future researchers should prioritize sensory profiling, ask consumers directly about acceptance, and run long term efficacy trials, so that the earlier, preclinical promise can become something closer to validated, market-ready commercial products.

7.4 Stability and shelf-life considerations

The commercial success and health benefits of H. erinaceus-based functional foods and nutraceuticals depend on their stability and shelf-life performance. High-molecular-weight polysaccharides demonstrate stable behavior under moderate heat and pH conditions but low-molecular-weight compounds, including phenolic, diterpenoids, and erinacines, show higher vulnerability to degradation during processing and storage and under oxygen and light exposure (Gąsecka et al., 2020). The retention of bioactivity depends on three factors, which are drying techniques, extraction solvents, and formulation matrices, while freeze-drying and low-temperature drying methods become the preferred choices for protecting sensitive compounds (Gąsecka et al., 2020; Silva et al., 2025). In complex food matrices, interactions between mushroom bioactives and other ingredients, such as proteins, lipids and carbohydrates, make changes that affect solubility and bioavailability and functional performance (Ge et al., 2025). The storage temperature, together with packaging materials, moisture content and oxygen permeability, determines how long products will remain usable while maintaining their original quality (Silva et al., 2025). The product development process now focuses more on three areas, which include shelf-life modeling, oxidative stability testing and the creation of standardized storage protocols. The product uses encapsulation methods together with protective packaging techniques to decrease product degradation while maintaining constant delivery of bioactive compounds until the end of the product’s designated shelf-life.

8 Safety, regulatory aspects, and challenges

8.1 Safety and toxicological considerations

The preclinical toxicological tests of H. erinaceus preparations which include whole mushroom powders and erinacine A-enriched mycelia and β-glucan extracts, have been performed according to OECD guidelines which were applied in most cases under Good Laboratory Practice (GLP) standards (Chen et al., 2022; Mahadevan et al., 2025). The research includes testing methods for acute toxicity, subchronic toxicity, developmental toxicity and genotoxicity. The research used a commercial organic Lion’s Mane powder which contained mycelial biomass grown on organic oats and fruiting body material, and followed Good Laboratory Practice (GLP) standards. The study found that acute oral toxicity testing with Wistar rats and Swiss albino mice at doses up to 2000 mg/kg body weight showed no mortality or clinical signs or body weight changes or macroscopic abnormalities, which resulted in an LD₅₀ value above 2000 mg/kg that indicated practical non-toxic status (Mahadevan et al., 2025). The research showed that subchronic (90-day) oral administration in rats at 0, 500, 1,000, and 2000 mg/kg/day revealed no treatment-related mortality, clinical observations, ophthalmological changes, urinalysis alterations, or histopathological lesions. The study determined a NOAEL of 2000 mg/kg/day because the study found minor non-dose-dependent variations in hematology, clinical chemistry, and organ weights which were within normal ranges and lacked histopathological correlates but were considered non-adverse (Mahadevan et al., 2025). The research found results that are similar to those found in earlier studies. The research found that Sprague-Dawley rats showed no adverse effects when they received 28-day repeated oral doses of erinacine A-enriched mycelium which contained 5 mg/g erinacine A at up to 3,000 mg/kg/day (Li et al., 2014) because these doses did not affect their clinical signs or body weight or hematology or serum biochemistry or organ weights or histopathology, which resulted in a NOAEL value above 3,000 mg/kg/day. The subchronic toxicity investigation of H. erinaceus β-glucan extract at the maximum dose of 2000 mg/kg/day for 90 days showed no significant toxic effects, which included clinical observations, body weights, feed consumption, clinical pathology, and necropsy findings, thus establishing a NOAEL of 2000 mg/kg/day (Chen et al., 2022). The genotoxicity tests, which involved bacterial reverse mutation through Ames test and in vitro chromosome aberration testing and in vivo micronucleus tests in mice showed negative results for all multiple test samples which proved that they lacked mutagenic and clastogenic properties (Chen et al., 2022; Mahadevan et al., 2025). Human consumption of H. erinaceus as food receives recognition in the United States as Generally Recognized as Safe (GRAS) while there have been no documented cases of hepatotoxicity or serious adverse effects (Menon et al., 2025). Less than 10% of participants in studies lasting four to 16 weeks report moderate, temporary gastrointestinal symptoms, such as nausea, diarrhea, and discomfort in the abdomen, although the majority of these symptoms go away on their own. According to the study, people with mushroom allergies occasionally developed skin rashes or allergic responses (Menon et al., 2025). The evidence base for human safety at 1 year or longer remains inadequate while the evidence base for human safety with pregnancy, lactation or medications remains inadequate. The preclinical research findings demonstrate that the safety margin for the study shows a significant safety margin because the NOAEL values exceed the typical daily human supplement intake, which ranges from 1 to 3 g (Li et al., 2014; Menon et al., 2025).

8.2 Regulatory status and quality standards

The regulatory classification of H. erinaceus changes depending on the specific jurisdiction and the type of preparation, which includes fruiting body and mycelium or extract, and the purpose of the product. In the United States, the fruiting body and several other preparations receive dietary supplement status according to the Dietary Supplement Health and Education Act DSHEA which permits their sale without premarket approval but demands safety proof and accurate product descriptions that do not include unapproved health claims (U.S. Food and Drug Administration, 2024). Specific β-glucans from certain strains (BCRC 35669) have received GRAS affirmation for food use at levels up to 150 mg/serving, FDA GRAS Notice 1,124 (U.S. Food and Drug Administration, 2023). Some mycelial products have undergone New Dietary Ingredient NDI notifications.

The European Union considers the fruiting body and its aqueous and ethanol extract powders as non-novel items that can be sold in food products and dietary supplements because they have been consumed extensively before 1997, according to Regulation EU 2015/2,283 on novel foods (European Commission, 2025; Finnish Food Authority, 2025). Recent consultations of Finland 2025 proved that the extract powder from the fruiting body is non-novel (Finnish Food Authority, 2025). The absence of historical proof for dehydrated mycelium powder results in its classification as a novel food, which mandates premarket authorization and prevents its sale until it receives approval.

Hericium erinaceus exists as a traditional medicine in China, Japan and Korea, where it appears in pharmacopoeias and receives official recognition for use in traditional medicine systems (Gravina et al., 2023; Tan et al., 2024). International quality standards establish requirements for product identity verification through macroscopic and microscopic and DNA testing methods, and for product purity assessment through testing of heavy metals, microbial contaminants, and pesticides and for product assessment according to standard food and supplement limits. The absence of standardized pharmacopoeial monographs for bioactive quantification of erinacines and hericenones and β-glucans leads to commercial product batch-to-batch variability (Li et al., 2018; Thongbai et al., 2015).

9 Current challenges and future prospects

Hericium erinaceus cannot reach its therapeutic potential because of multiple existing obstacles despite showing positive results in both preclinical tests and initial clinical studies. The bioactive content of fungi exists between different strains and their growing conditions because mycelium contains erinacines and fruiting bodies have hericenones and both parts contain polysaccharides (Li et al., 2018). Clinical trials are often constrained by small sample sizes, short durations, heterogeneous formulations, and limited focus on long-term outcomes in neurodegenerative or mood disorders (Cha et al., 2024; Cornford and Charnley, 2025; Menon et al., 2025). The bioavailability and pharmacokinetics of essential lipophilic compounds remain unclear because human research has not provided sufficient data about absorption, blood-brain barrier penetration, and tissue distribution (Chen et al., 2024). Due to different regulations that identify mycelium as an innovative substance in the EU, the marketing of products and international supply-chain activities are challenged.

The future directions show significant potential for success. Biotechnological optimizations, which involve strain selection and controlled submerged fermentation and genetic engineering, will produce better bioactive yields (Li et al., 2018). The combination of advanced extraction techniques, which include ultrasound-assisted extraction and supercritical fluid extraction with innovative delivery systems that use nanoparticles and liposomes, will enhance both solubility and bioavailability and targeted efficacy (Yu et al., 2025). The study requires large-scale multicenter randomized controlled trials that test standardized preparations to confirm cognitive benefits and neuroprotective effects, mood enhancements and to define dose-response relationships and long-term safety (Cornford and Charnley, 2025; Menon et al., 2025). Harmonized international quality standards, interdisciplinary collaboration, and evidence-based regulatory alignment could enable H. erinaceus to evolve from a popular supplement into a validated functional food or adjunct therapy for neurological and inflammatory conditions.

10 Conclusion

Hericium erinaceus is one of the most promising edible medicinal fungi, distinguished by its unique neurotrophic compounds (erinacines and hericenones) that can cross the blood–brain barrier and stimulate NGF and BDNF production, thereby supporting neurogenesis, neuronal survival, and synaptic plasticity. The mushroom demonstrates brain health benefits through its antioxidant, anti-inflammatory, immunomodulatory and prebiotic polysaccharides, which include β-glucans. The mushroom demonstrates excellent safety through its low acute and subchronic toxicity and absence of genotoxicity, and occurrence of mild gastrointestinal side effects in humans. The research framework must focus on conducting extensive multicenter studies that use random assignment to identify treatment effects through double-blind procedures that test standardized drug preparations. The research will show how biotechnology advances through strain selection and submerged fermentation together with green extraction technologies and delivery systems through encapsulation and nanoformulations to enhance product consistency, bioavailability and commercial viability. Hericium erinaceus shows strong potential to become an evidence-based dietary supplement for brain health and general health because the global population ages and more people search for natural treatments that target multiple health conditions. The research needs clinical testing to follow established methods which will evaluate the supplement’s effectiveness in treating cognitive decline, mood disorders, and inflammation-related diseases.

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