The Influence of Polysaccharide Fractions of the Lion's Mane Medicinal Mushroom Hericium erinaceus (Agaricomycetes) on the Immunomodulatory and Antioxidant Activity of Neutrophils Exposed to Stress of Different Durations.

Polysaccharide fractions from the mycelium of the lion's mane medicinal mushroom Hericium erinaceus BP 16, cultivated on sterile grain substrates (barley, oats, wheat, rice, rye), were isolated and characterized. One percent solutions were prepared from the resulting fractions, mixed with blood, which was then subjected to cold stress at a temperature of 6°C for 3, 5 and 7 d. It has been shown that the fraction of H. erinaceus grown on rye is characterized by a high content of the protein fraction and arabinose monosaccharide and contributes to the preservation of higher phagocytic, bactericidal and antioxidant activity cells throughout the entire period of stress. Polysaccharide fractions of the fungus H. erinaceus, grown on various grain substrates, can serve as an immunomodulatory and antioxidant food additive and provide significant benefits in the daily life of people with stress and reduced immunity.

Optimization of Mycelial Growth Parameters in Lion's Mane Edible Medicinal Mushroom Hericium erinaceus (Agaricomycetes) by Supplementation of Growth Hormones.

The present study was carried out to optimize the strain and evaluate the effect of amendment of growth media with different hormone concentrations for enhancing mycelium growth of lion's mane mushroom Hericium erinaceus under in vitro conditions. Among the five strains of H. erinaceus, He-04 strain showed maximum average GR (GRavr) of 4.78 mm d-1. Five different media, potato dextrose agar (PDA), malt extract agar, sawdust extract agar, wheat straw extract agar, and rice straw extract agar, amended with four concentrations (10, 20, 30, and 40 ppm) of gibberellic acid, kinetin, and indole acetic acid, were evaluated for promotion of mycelial growth of H. erinaceus. PDA was observed to be the best media promoting the mycelial growth of H. erinaceus. The highest mycelial GRavr 8.47 mm d-1 was observed in PDA amended with indole acetic acid (10 ppm) followed by gibberellic acid and kinetin (30 ppm) decreasing mycelial GRav to 8.15 and 7.75mm d-1, respectively. Temperature of 25°C and pH 7.0 was found to be the best for mycelium growth of H. erinaceus.

The chemical structures, biosynthesis, and biological activities of secondary metabolites from the culinary-medicinal mushrooms of the genus Hericium: a review.

Fungal phytochemicals derived from higher fungi, particularly those from the culinary-medicinal genus Hericium, have gained significant attention in drug discovery and healthcare. This review aims to provide a comprehensive analysis of the chemical structures, biosynthetic pathways, biological activities, and pharmacological properties of monomeric compounds isolated from Hericium species. Over the past 34 years, 253 metabolites have been identified from various Hericium species, including cyathane diterpenes, alkaloids, benzofurans, chromenes, phenols, pyrones, steroids, and other miscellaneous compounds. Detailed investigations into the biosynthesis of erinacines, a type of cyathane diterpene, have led to the discovery of novel cyathane diterpenes. Extensive research has highlighted the biological activities and pharmacological properties of Hericium-derived compounds, with particular emphasis on their neuroprotective and neurotrophic effects, immunomodulatory capabilities, anti-cancer activity, antioxidant properties, and antimicrobial actions. Erinacine A, in particular, has been extensively studied. Genomic, transcriptomic, and proteomic analyses of Hericium species have facilitated the discovery of new compounds and provided insights into enzymatic reactions through genome mining. The diverse chemical structures and biological activities of Hericium compounds underpin their potential applications in medicine and as dietary supplements. This review not only advances our understanding of Hericium compounds but also encourages further research into Hericium species within the realms of medicine, health, functional foods, and agricultural microbiology. The broad spectrum of compound types and their diverse biological activities present promising opportunities for the development of new pharmaceuticals and edible products.

Polysaccharides from Hericium erinaceus and its immunomodulatory effects on RAW 264.7 macrophages.

This study aimed to optimize the extraction of Hericium erinaceus polysaccharides (HEP) using ultrasound-assisted enzymatic extraction combined with Plackett-Burman design (PBD) and response surface methodology (RSM). The optimal extraction conditions were identified as: 33 min extraction time, 30:1 liquid to material ratio, 38 °C extraction temperature, 9 g/kg cellulase amount, pH 4, and 20 % ethanol concentration. Under these conditions, the extraction yield of HEP was 5.87 ± 0.16 %, consistent with the predicted results. Additionally, the potential immunomodulatory activity of HEP on RAW 264.7 macrophage was evaluated. The results revealed that HEP improved the immunostimulatory activity of RAW264.7 cells, evident from increased production of IL-6 and TNF-α. These findings suggest that HEP is capable of enhancing the immune activity of RAW 264.7 macrophage.

Structural characterization of Hericium coralloides polysaccharide and its neuroprotective function in Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder. Polysaccharides have been scientifically demonstrated to possess neuroprotective properties. In this study, a polysaccharide was isolated from the fruiting bodies of Hericium coralloides using hot water extraction and purified using column chromatography. This H. coralloides polysaccharide (HCP) is a galactan with a main chain of →6)-α-d-Galp-(1 â†’ and a molecular weight of 16.06 kDa. The partial α-l-Fucp-(1 â†’ substitution takes place at its O-2 position. The neuroprotective effects of HCP were investigated in an APP/PS1 mouse model of Alzheimer's disease. The step-down and Morris water maze tests demonstrated that HCP effectively ameliorated cognitive impairment. After 8-week treatment, HCP reduced amyloid-ß plaques and phosphorylated tau protein deposition. In combination with the gut microbiota and metabolites, proteomic analysis suggested that the neuroprotective effects of HCP are associated with neuroinflammation and autophagy. Immunofluorescence and western blotting analyses confirmed that HCP facilitated the polarization of M2 microglia by augmenting autophagy flux, thereby effectively reducing levels of amyloid-ß plaques and neuroinflammation. These data demonstrate that HCP effectively mitigates neuroinflammation by enhancing autophagic flux, demonstrating its potential for the treatment of AD.

Unveiling the Chemical Composition and Biofunctionality of Hericium spp. Fungi: A Comprehensive Overview.

In recent years, research on mushrooms belonging to the Hericium genus has attracted considerable attention due to their unique appearance and well-known medicinal properties. These mushrooms are abundant in bioactive chemicals like polysaccharides, hericenones, erinacines, hericerins, resorcinols, steroids, mono- and diterpenes, and corallocins, alongside essential nutrients. These compounds demonstrate beneficial bioactivities which are related to various physiological systems of the body, including the digestive, immune, and nervous systems. Extensive research has been conducted on the isolation and identification of numerous bioactive chemicals, and both in vitro and in vivo studies have confirmed their antimicrobial, antioxidant, immunomodulatory, antidiabetic, anticholesterolemic, anticancer, and neuroprotective properties. Therefore, this review aims to provide a comprehensive summary of the latest scientific literature on the chemical composition and secondary metabolites profile of Hericium spp. through an introduction to their chemical characteristics, speculated biosynthesis pathways for key chemical families, potential toxicological aspects, and a detailed description of the recent updates regarding the bioactivity of these metabolites.

Hericium VN, an undescribed compound isolated from Hericium erinaceus and its cytotoxic activity on human brain astrocytoma.

Hericium erinaceus is a species of mushroom with high nutritional value that is used mainly as food in tropical countries. Phytochemical study of H. erinaceus led to the isolation of an undescribed compound, named as hericium VN (1), together with nine known compounds, 1-(2-formyl-1-pyrrolyl)butanoic acid (2), herierin III (3), 5'-(methylthio)adenosine (4), adenosine (5), nicotinic acid (6), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3ß-ol (7), 5α,8α-peroxycerevisterol (8), (22E,24R)-5α,8α-epidioxy-egosta-6,22-diene 3-O-ß-D-glucopyranoside (9), and cerevisterol (10) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configuration of compound 1 was determined by experimental combined with calculated electronic circular dichroism spectra. Compound 7 exhibited cytotoxic effects against brain tumor cell line CCF-STTG1 with the IC50 value of 15.50 µM, compared to that of the positive control compound, doxorubicin, which showed IC50 value of 15.84 µM.

Polysaccharides from an edible mushroom, Hericium erinaceus, alleviate ulcerative colitis in mice by inhibiting the NLRP3 inflammasomes and reestablish intestinal homeostasis.

This study aimed to assess the effects of polysaccharides extracted from Hericium erinaceus fruiting bodies (HEFPs) on the inflammatory response to oxidative stress in a mouse model of ulcerative colitis (UC) induced by ingestion of dextran sodium sulfate. The results indicated reduced oxidative damage in the HEFPs groups, as evidenced by significantly decreased malondialdehyde levels and significantly increased levels of the antioxidant enzymes superoxide dismutase and catalase in colon homogenates, compared with those in the Model Control (MC) group. Additionally, compared with the levels in the MC group, the levels of the pro-inflammatory factors IL-6, IL-1ß, and TNF-α in the positive-control (PC) and HEFPs groups were significantly lower, and that of the anti-inflammatory factor IL-10 was significantly higher. qRT-PCR analyses revealed that the colon expression patterns of IL-6, IL-1ß, TNF-α, and IL-18 were consistent with the serum levels. Western-blotting results indicated significantly lower levels of NLRP3, ASC, and caspase 1 P20 in the HEFPs and PC groups than in the MC group. These findings suggest that HEFPs alleviate UC by suppressing the NLRP3 inflammasome/Caspase-1 pathway. Lachnospiraceae, Clostridiales, Parabacteroides, Oscillibacter, and Clostridium XlVa genera were more abundant in the gut microbiota of the HEFPs group than that of the MC group.

The Monkey Head Mushroom and Memory Enhancement in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder, and no effective treatments are available to treat this disorder. Therefore, researchers have been investigating Hericium erinaceus, or the monkey head mushroom, an edible medicinal mushroom, as a possible treatment for AD. In this narrative review, we evaluated six preclinical and three clinical studies of the therapeutic effects of Hericium erinaceus on AD. Preclinical trials have successfully demonstrated that extracts and bioactive compounds of Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD. A limited number of clinical studies have been conducted and several clinical trials are ongoing, which have thus far shown analogous outcomes to the preclinical studies. Nonetheless, future research on Hericium erinaceus needs to focus on elucidating the specific neuroprotective mechanisms and the target sites in AD. Additionally, standardized treatment parameters and universal regulatory systems need to be established to further ensure treatment safety and efficacy. In conclusion, Hericium erinaceus has therapeutic potential and may facilitate memory enhancement in patients with AD.

A Mixture of Ginkgo biloba L. Leaf and Hericium erinaceus (Bull.) Pers. Fruit Extract Attenuates Scopolamine-Induced Memory Impairments in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by loss of memory and cognitive impairment via dysfunction of the cholinergic nervous system. In cholinergic dysfunction, it is well known that impaired cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) signaling are major pathological markers and are some of the strategies for the development of AD therapy. Therefore, this study is aimed at evaluating whether a mixture comprising Ginkgo biloba L. leaf (GL) and Hericium erinaceus (Bull.) Pers. (HE) fruit extract (GH mixture) alleviated cognitive impairment induced in a scopolamine-induced model. It was discovered that GH reduced neuronal apoptosis and promoted neuronal survival by activating BDNF signaling in an in vitro assay. In addition, the GH (p.o. 240 mg/kg) oral administration group significantly restored the cognitive deficits of the scopolamine-induced mouse group (i.p. 1.2 mg/kg) in the behavior tests such as Y-maze and novel object recognition task (NORT) tests. This mixture also considerably enhanced cholinergic system function in the mouse brain. Furthermore, GH markedly upregulated the expressed levels of extracellular signal-regulated kinase (ERK), CREB, and BDNF protein levels. These results demonstrated that GH strongly exerted a neuroprotective effect on the scopolamine-induced mouse model, suggesting that an optimized mixture of GL and HE could be used as a good material for developing functional foods to aid in the prevention of neurodegenerative diseases, including AD.

Aflatoxin B1 Toxicity in Zebrafish Larva (Danio rerio): Protective Role of Hericium erinaceus.

Aflatoxin B1 (AFB1), a secondary metabolite produced by fungi of the genus Aspergillus, has been found among various foods as well as in fish feed. However, the effects of AFB1 on fish development and its associated toxic mechanism are still unclear. In the present study, we confirmed the morphological alterations in zebrafish embryos and larvae after exposure to different AFB1 doses as well as the oxidative stress pathway that is involved. Furthermore, we evaluated the potentially protective effect of Hericium erinaceus extract, one of the most characterized fungal extracts, with a focus on the nervous system. Treating the embryos 6 h post fertilization (hpf) with AFB1 at 50 and 100 ng/mL significantly increased oxidative stress and induced malformations in six-day post-fertilization (dpf) zebrafish larvae. The evaluation of lethal and developmental endpoints such as hatching, edema, malformations, abnormal heart rate, and survival rate were evaluated after 96 h of exposure. Hericium inhibited the morphological alterations of the larvae as well as the increase in oxidative stress and lipid peroxidation. In conclusion: our study suggests that a natural extract such as Hericium may play a partial role in promoting antioxidant defense systems and may contrast lipid peroxidation in fish development by counteracting the AFB1 toxicity mechanism.

Erinacine A-Enriched Hericium erinaceus Mycelium Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice.

There have been many reports on the neuroprotective effects of Hericium erinaceus mycelium, in which the most well-known active compounds found are diterpenoids, such as erinacine A. Previously, erinacine A-enriched Hericeum erinaceus mycelium (EAHEM) was shown to decrease amyloid plaque aggregation and improve cognitive disability in Alzheimer's disease model APP/PS1 mice. However, its effects on brain aging have not yet been touched upon. Here, we used senescence accelerated mouse prone 8 (SAMP8) mice as a model to elucidate the mechanism by which EAHEM delays the aging of the brain. Three-month-old SAMP8 mice were divided into three EAHEM dosage groups, administered at 108, 215 and 431 mg/kg/BW/day, respectively. During the 12th week of EAHEM feeding, learning and memory of the mice were evaluated by single-trial passive avoidance and active avoidance test. After sacrifice, the amyloid plaques, induced nitric oxidase synthase (iNOS) activity, thiobarbituric acid-reactive substances (TBARS) and 8-OHdG levels were analyzed. We found that the lowest dose of 108 mg/kg/BW EAHEM was sufficient to significantly improve learning and memory in the passive and active avoidance tests. In all three EAHEM dose groups, iNOS, TBARS and 8-OHdG levels all decreased significantly and showed a dose-dependent response. The results indicate that EAHEM improved learning and memory and delayed degenerative aging in mice brains.

Preclinical Bioavailability, Tissue Distribution, and Protein Binding Studies of Erinacine A, a Bioactive Compound from Hericium erinaceus Mycelia Using Validated LC-MS/MS Method.

Erinacine A, derived from the mycelia of Hericium erinaceus, has attracted much attention due to its neuroprotective properties. However, very few studies have been conducted on the bioavailability, tissue distribution, and protein binding of erinacine A. This study aimed to investigate the bioavailability, tissue distribution, and protein binding of erinacine A in Sprague-Dawley rats. After oral administration (po) and intravenous administration (iv) of 2.381 g/kg BW of the H. erinaceus mycelia extract (equivalent to 50 mg/kg BW of erinacine A) and 5 mg/kg BW of erinacine A, respectively, the absolute bioavailability of erinacine A was estimated as 24.39%. Erinacine A was detected in brain at 1 h after oral dosing and reached the peak at 8 h. Protein binding assay showed unbound erinacine A fractions in brain to blood ratio is close to unity, supporting passive diffusion as the dominating transport. Feces was the major route for the elimination of erinacine A. This study is the first to show that erinacine A can penetrate the blood-brain barrier of rats by the means of passive diffusion and thus support the development of H. erinaceus mycelia for the improvement of neurohealth.

Effect of Cytokinin-Containing Extracts from Some Medicinal Mushroom Mycelia on HepG2 Cells In Vitro.

Endogenous cytokinins in mycelia of medicinal mushrooms Hericium coralloides and Fomitopsis officinalis grown in vitro were identified using high-performance liquid chromatography coupled with mass spectrometry. High amounts of zeatin-type cytokinins and isopentenyladenine were found. The qualitative composition and quantitative content of cytokinins were species-specific traits of mushrooms. Optical microscopy was used to perform a comparison analysis of the influence of crude extracts and purified cytokinin fractions from both species' mycelial biomass on HepG2 tumor cell growth in vitro and morphology. The results showed that purified cytokinin fractions from H. coralloides and F. officinalis mycelia demonstrated a cytotoxic effect on HepG2 cells, unlike crude extracts. Under the influence of all mushroom extracts, similar patterns of changes in HepG2 cell morphology were observed, but they were more pronounced for H. coralloides compared with F. officinalis. Purified fractions of both mushroom species caused an increased level of apoptosis compared to crude extracts. Some increase in glucose uptake by cultured cells was found in all investigated samples wherein the influence of H. coralloides extracts was approximately twice the effect of the corresponding F. officinalis extracts. The data obtained confirm the assumption that cytokinins are involved in the expression of therapeutic effects of medicinal mushrooms and indicate the need to take into consideration the methods of cytokinin extraction when preparing pharmacologically active drugs based on fungal raw materials. Thus, extracts from H. coralloides and F. officinalis mycelial biomass are promising in the search for anticancer agents.

Evaluation of In Vitro Antioxidant and Antihyperglycemic Activities of Extracts from the Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes).

To obtain activated fractions, the ethanol extract (EE) of Hericium erinaceus was fractionated to get petroleum ether fraction (PEF), chloroform fraction (CF), ethyl acetate fraction (EAF) and n-butanol fraction (NF). Total phenol content (TPC) and total flavonoid content (TFC) in the fractions were determined, and the phenolic compounds were characterized and quantitated using liquid chromatography-electrospray ionization-mass spectrometry. Meanwhile, in vitro antioxidant and antihyperglycemic activities of extracts were evaluated respectively based on their 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging abilities as well as α-amylase and α-glucosidase inhibitory abilities. Finally, the inhibition modes of extracts on α-amylase and α-glucosidase were detected by kinetic assay. The results showed that TPC, TFC, and the content of phenolic compounds in the extracts were different. EAF contained the highest contents of both TPC and TFC and exhibited strongest inhibitory effects on α-amylase and α-glucosidase, with half maximal inhibitory concentration (IC50) values of 0.47 ± 0.02 and 0.63 ± 0.01 mg/mL, respectively. However, CF showed the highest scavenging abilities on DPPH and ABTS radicals, with IC50 values of 2.30 ± 0.12 and 1.72 ± 0.06 mg/mL, respectively. Correlation analysis showed that the high antihyperglycemic ability of EAF may be related to ferulic acid, whereas cinnamic acid may be responsible for the high antioxidant ability of CF. Furthermore, all fractions were found to exert inhibition on α-amylase and α-glucosidase in mixed-type and competitive manners, respectively. Overall, these results suggest that H. erinaceus has a potential effect on antihyperglycemic and antioxidant activity.

Multi-walled carbon nanotube polysaccharide modified Hericium erinaceus polysaccharide as an adjuvant to extend immune responses.

In recent years, the utilization of CS-MWCNT as targeted drug carriers has attracted considerable attention. Hericium erinaceus polysaccharide (HEP) has been reported as an immunostimulant to improve immune responses. This study was focussed on developing CS-MWCNT encapsulating HEP (CS-MWCNT-HEP). Using in mice peritoneal macrophages, we found the immune response could be effectively regulated by CS-MWCNT-HEP, promoted the expression of the MHCII, CD86, F4/80 and gp38. Moreover, the mice immunized with CS-MWCNT-HEP nanoparticles significantly extended PCV2-specific IgG immune response and the levels of cytokines. The results demonstrated that CS-MWCNT-HEP may be a promising drug delivery system for immuno-enhancement.

Construction of hydrogels based on the homogeneous carboxymethylated chitin from Hericium erinaceus residue: Role of carboxymethylation degree.

Carboxymethyl chitin hydrogels with different degree of substitution (DS) were prepared by the homogeneous carboxymethylation of chitin extracted from Hericium erinaceus residue. The effect of DS on gel structure and property were studied. Results showed that the DS of carboxymethyl chitin hydrogels can be increased by increasing the amount of sodium chloroacetate. The equilibrium swelling degree and pH swelling sensitivity of the hydrogels were enhanced as the increase of DS. Zeta potential, low-field nuclear magnetic resonance, contact angle and molecular dynamics simulation results suggested that the introduction of carboxymethyl functional group enhanced the negative charge, water mobility, surface hydrophilicity and the ability to form hydrogen bonds with water of the hydrogels, resulting in an increased swelling degree of the hydrogels. Moreover, the prepared hydrogels showed different adsorption capability to various dyes, and the adsorption performance of the prepared hydrogels for cationic dyes could be enhanced as the increase of DS.

Value added immunoregulatory polysaccharides of Hericium erinaceus and their effect on the gut microbiota.

Hericium erinaceus polysaccharides (HEPs) were isolated from the fruiting bodies of H. erinaceus with 53.36 % total carbohydrates and 32.56 % uronic acid. To examine whether HEPs can alter the diversity and the abundance of gut microbiota, adult mice and middle-aged and old mice were fed with HEPs for 28 days. Based on the result of 16S sequencing of gut microbiota it was found that the relative abundances of Lachnospiraceae and Akkermansiaceae significantly increased, while the relative abundance of Rikenellaceae and Bacteroidaceae appeared to decrease. Bacterial solutions from different murine intestinal segments and feces were collected to ferment HEPs in vitro. It was found that HEPs remarkably promoted the production of NO, IL-6, IL-10, INF-γ and TNF-α. Moreover, HEPs significantly increased phosphorylation of signaling molecules, indicating that the immunomodulatory activity was completed via NF-кB, MAPK and PI3K/Akt pathways. Collectively, HEPs have potential to be developed as functional ingredients or foods to promote health.

Isolation, purification and identification of immunologically active peptides from Hericium erinaceus.

Biologically active peptides released by proteins are important in regulating immunity. The purpose of this study was to isolate and purify an immunologically active peptide from Hericium erinaceus (H. erinaceus) and to explore its effect on cytokine secretion and differentiation of macrophages. An active peptide with an amino acid sequence, Lys-Ser-Pro-Leu-Tyr (KSPLY) was obtained from H. erinaceus protein by ultrafiltration combined with multistage chromatography separation and identification technology. Subsequently, it was confirmed that the synthetic peptide KSPLY had a good immunomodulatory activity at a concentration of 100 µmol/L and could promote the secretion of NO, IL-1ß, IL-6 and TNF-α by macrophages. The effects of KSPLY on M1 macrophages and M2 macrophages were also studied. Results showed that KSPLY inhibited the secretion of NO and IL-6 by M1 macrophages and promoted the tendency of M2 macrophages to transform to M1 macrophages. Therefore, it can be concluded that KSPLY is an effective immunomodulatory peptide that may be beneficial in cancer treatment and human health improvement.

Effects of Hericium erinaceus polysaccharide on immunity and apoptosis of the main immune organs in Muscovy duck reovirus-infected ducklings.

To investigate the effects of Hericium erinaceus polysaccharide (HEP) on immunity in Muscovy duck reovirus (MDRV)-infected ducklings and explore its mechanism of action, an MDRV contact-infection model was established. Then, we investigated the influence of HEP on morphology of main immune organs in MDRV-infected ducklings by HE staining, while antioxidant capacity (T-AOC, MDA), serum protein levels (TP, ALB, GLO), complement levels (C3, C4) and antibody levels (IgA, IgM, IgG) were detected. Apoptotic indexes (apoptosisi rate and FAS-L) were also quantified by TUNEL method and immunohistochemical staining. Meanwhile, FADD and CytC (apoptosis-related genes), were tested by quantitative RT-PCR. Results showed that HEP could reduce the injuries of immune organs caused by MDRV. Additionally, HEP markedly diminished MDA (p < 0.01), while significantly increased T-AOC, TP, ALB, GLO, C3, C4, IgA, IgM and IgG (p < 0.01 or p < 0.05). Then, HEP shifted apoptosis time to an early MDRV-infected stage and reduced apoptosis at later MDRV-infected stage. This was associated with changes of FADD and CytC. Collectively, our data suggested that HEP could reduce the immunesuppression by many ways, such as decreasing organs' injuries, improving antioxidant capacity, serum proteins levels, antibody levels and complement levels, while diminish the apoptosis by lowering the FADD and CytC.