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.

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.

Discovery of a New Compound, Erinacerin W, from the Mycelia of Hericium erinaceus, with Immunomodulatory and Neuroprotective Effects.

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

Hericium erinaceus Promotes Anti-Inflammatory Effects and Regulation of Metabolites in an Animal Model of Cerebellar Ataxia.

Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although previous study demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), the mechanisms of H.E. treatment on the neuroinflammatory response, neurotransmission, and related metabolites remain largely unknown. We demonstrated that 3-AP rats treated with 25 mg/kg H.E. extracts had improved motor coordination and balance in the accelerated rotarod and rod tests. We showed that the H.E. treatment upregulated the expression of Tgfb1, Tgfb2, and Smad3 genes to levels comparable to those in the non-3-AP control group. Interestingly, we also observed a significant correlation between Tgfb2 gene expression and rod test performance in the 3-AP saline group, but not in the non-3-AP control or H.E.+3-AP groups, indicating a relationship between Tgfb2 gene expression and motor balance in the 3-AP rat model. Additionally, we also found that the H.E. treatment increased mitochondrial COX-IV protein expression and normalized dopamine-serotonin neurotransmission and metabolite levels in the cerebellum of the H.E.+3-AP group compared to the 3-AP saline group. In conclusion, our findings suggest that the H.E. treatment improved motor function in the 3-AP rat model, which was potentially mediated through neuroprotective mechanisms involving TGFB2-Smad3 signaling via normalization of neurotransmission and metabolic pathways.

Smart pH-Sensitive Hydrogel Based on the Pineapple Peel-Oxidized Hydroxyethyl Cellulose and the Hericium erinaceus Residue Carboxymethyl Chitosan for Use in Drug Delivery.

Pineapple and hericium erinaceus (HE) produce a lot of residues in the process of food processing. These processed residues are good potential derivative precursors. In this investigation, a simple and non-toxic method was developed to prepare one new composite hydrogel by the Schiff base reaction between the aldehyde group of oxidized hydroxyethyl cellulose (OHEC) from processed pineapple peel residue and the amino group of carboxymethyl chitosan (CMCS) from processed HE residue. Subsequently, a series of experiments toward these new hydrogel polymers including structure characterization and performances were applied. The resultant hydrogel polymers were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy and confirmed with thermogravimetry. It was observed that the modification of cellulose and chitin was adequate, and the synthesis of OHEC/CMCS hydrogel polymers was successful. The gelation time experiments indicated that the shortest gel time was 33 s at a mass ratio of 4:6 (OHEC-70:CMCS). The hydrogel showed good swelling properties. The maximum swelling rate reached 11.58 g/g, and the swelling rate decreased with the increase of the oxidation degree of OHEC. The drug delivery applications of the prepared hydrogel were evaluated with bovine serum albumin (BSA) as a model drug releasing in vitro. It was discovered that the BSA release from the hydrogel was pH sensitive under simulated gastrointestinal conditions. All of these attributes indicate that the novel prepared hydrogel polymers have the potential as good carriers for oral delivery of protein-type drugs.

Ameliorating Effect of the Edible Mushroom Hericium erinaceus on Depressive-Like Behavior in Ovariectomized Rats.

Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17ß-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERß) is expressed in the brain, and activation of ERß ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.

Secondary Metabolites from Hericium erinaceus and Their Anti-Inflammatory Activities.

Hericium erinaceus, a culinary and medicinal mushroom, is widely consumed in Asian countries. Chemical investigation on the fruiting bodies of Hericium erinaceus led to the isolation of one new ergostane-type sterol fatty acid ester, erinarol K (1); and eleven known compounds: 5α,8α -epidioxyergosta-6,22-dien-3ß-yl linoleate (2); ethyl linoleate (3); linoleic acid (4); hericene A (5); hericene D (6); hericene E (7); ergosta-4,6,8(14),22-tetraen-3-one (8); hericenone F (9); ergosterol (10); ergosterol peroxide (11); 3ß,5α,6α,22E-ergosta-7,22-diene-3,5,6-triol 6-oleate (12). The chemical structures of the compounds were determined by 1D and 2D NMR (nuclear magnetic resonance) spectroscopy, mass spectra, etc. Anti-inflammatory effects of the isolated aromatic compounds (5-7, 9) were evaluated in terms of inhibition of pro-inflammatory mediator (TNF-α, IL-6 and NO) production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. The results showed that compounds 5 and 9 exhibited moderate activity against TNF-α (IC50: 78.50 µM and 62.46 µM), IL-6 (IC50: 56.33 µM and 48.50 µM) and NO (IC50: 87.31 µM and 76.16 µM) secretion. These results supply new information about the secondary metabolites of Hericium erinaceus and their anti-inflammatory effects.

Key metabolism pathways and regulatory mechanisms of high polysaccharide yielding in Hericium erinaceus.

BACKGROUND: Hericium erinaceus, a rare edible and medicine fungus, is widely used in the food and medical field. Polysaccharides from H. erinaceus are the main bioactive compound that exert high bioactive value in the medical and healthcare industries. RESULTS: The genome of H. erinaceus original strain HEA was reported 38.16 Mb, encoding 9780 predicted genes by single-molecule, real-time sequencing technology. The phylogenomic analysis showed that H. erinaceus had the closest evolutionary affinity with Dentipellis sp. The polysaccharide content in the fermented mycelia of mutated strains HEB and HEC, which obtained by ARTP mutagenesis in our previous study, was improved by 23.25 and 47.45%, and a new ß-glucan fraction with molecular weight 1.056 × 106 Da was produced in HEC. Integrative analysis of transcriptome and proteomics showed the upregulation of the carbohydrate metabolism pathway modules in HEB and HEC might lead to the increased production of glucose-6P and promote the repeating units synthesis of polysaccharides. qPCR and PRM analysis confirmed that most of the co-enriched and differentially co-expressed genes involved in carbohydrate metabolism shared a similar expression trend with the transcriptome and proteome data in HEB and HEC. Heatmap analysis showed a noticeably decreased protein expression profile of the RAS-cAMP-PKA pathway in HEC with a highly increased 47.45% of polysaccharide content. The S phase progression blocking experiment further verified that the RAS-cAMP-PKA pathway's dysfunction might promote high polysaccharide and ß-glucan production in the mutant strain HEC. CONCLUSIONS: The study revealed the primary mechanism of the increased polysaccharide synthesis induced by ARTP mutagenesis and explored the essential genes and pathways of polysaccharide synthesis.

Total Synthesis, Structure Revision, and Neuroprotective Effect of Hericenones C-H and Their Derivatives.

The first total syntheses of hericenones C-H and "putative 3-hydroxyhericenone F" were achieved. Highlights of the synthesis include the straightforward construction of the resorcinol core and geranyl side chain, assembly of the natural product skeleton by sequential O-geranylation and a clay/zeolite-mediated O → C rearrangement reaction, and a biomimetic cyclization to form a variety of bicyclic natural hericenones and their congeners. The structure of the "putative 3-hydroxyhericenone F" was revised as the 5-exo cyclization product (named: hericenone Z) of epoxyhericenone C through in-depth analyses of the cyclization modes in addition to NMR spectroscopic studies. To gain insights into the biological functions of geranyl-resorcinols in Hericium erinaceus, potential neuroprotective effects against endoplasmic reticulum (ER) stress-dependent cell death were evaluated systematically to clarify a fundamental structure-activity relationship. Among the compounds assayed, the linoleate-containing hericenone analogue, i.e., the regioisomer of hericene D, was found to possess the most potent neuroprotective effect against tunicamycin and thapsigargin-induced ER stress-dependent cell death.

Neurotrophic isoindolinones from the fruiting bodies of Hericium erinaceus.

Four compounds, hericerin (1), isohericerinol A (2), N-de-phenylethyl isohericerin (3) and corallocin A (4) were isolated from the fruiting bodies of Hericium erinaceus, a lion's mane mushroom (Hericiaceae). Among them, isohericerinol A (2) was newly reported in nature. Further investigation of the neurotrophic effect of isolated compounds demonstrated that isohericerinol A (2) strongly increased the nerve growth factor (NGF) production in C6 glioma cells followed by corallocin A (4) and hericerin (1). Increased NGF production by these compounds promoted the neurite outgrowth in N2a neuronal cells. Western blot analysis also showed the increased protein expression of NGF, brain-derived neurotrophic factor (BDNF) and synaptophysin (SYP) in C6-N2a cells. Taken together, our present study characterized the neurotrophic constituents of H. erinaceus, which may support the potential use of memory improvement.

Whole genome sequence of an edible and medicinal mushroom, Hericium erinaceus (Basidiomycota, Fungi).

Hericium erinaceus is a well-known culinary and medicinal mushroom in China. The biological and genetic studies on this mushroom is rare, thereby hindering the breeding of elite cultivars. Herein, we performed de novo sequencing and assembly of H. erinaceus monokaryon CS-4 genome using the Illumina and PacBio platform. The generated genome was 41.2 Mb in size with a N50 scaffold size of 3.2 Mb, and encoded 10,620 putative predicted genes. A wide spectrum of carbohydrate-active enzymes, with the total number of 341 CAZymes, involved in lignocellulose degradation were identified in H. erinaceus. A total of 447 transcription factors were identified. This present study also characterized genome-wide microsatellites and developed markers in H. erinaceus. A comprehensive microsatellite markers database (HeSSRDb) containing the information of 904 markers was generated. These genomic resources and newly-designed molecular markers would enrich the toolbox for biological and genetic studies in H. erinaceus.

Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging.

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.

Effect of Water and Ethanol Extracts from Hericium erinaceus Solid-State Fermented Wheat Product on the Protection and Repair of Brain Cells in Zebrafish Embryos.

Extracts from Hericium erinaceus can cause neural cells to produce nerve growth factor (NGF) and protect against neuron death. The objective of this study was to evaluate the effects of ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product on the brain cells of zebrafish embryos in both pre-dosing protection mode and post-dosing repair mode. The results showed that 1% ethanol could effectively promote zebrafish embryo brain cell death. Both 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product protected brain cells and significantly reduced the death of brain cells caused by 1% ethanol treatment in zebrafish. Moreover, the zebrafish embryos were immersed in 1% ethanol for 4 h to cause brain cell damage and were then transferred and soaked in the 200 ppm of ethanol and water extracts from H. erinaceus solid-state fermented wheat product to restore the brain cells damaged by the 1% ethanol. However, the 200 ppm extracts from the unfermented wheat medium had no protective and repairing effects. Moreover, 200 ppm of ethanol and water extracts from H. erinaceus fruiting body had less significant protective and restorative effects on the brain cells of zebrafish embryos. Both the ethanol and hot water extracts from H. erinaceus solid-state fermented wheat product could protect and repair the brain cells of zebrafish embryos damaged by 1% ethanol. Therefore, it has great potential as a raw material for neuroprotective health product.

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.

Hericium Erinaceus Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells.

Hericium Erinaceus (HE) is a medicinal plant known to possess anticarcinogenic, antibiotic, and antioxidant activities. It has been shown to have a protective effect against ischemia-injury-induced neuronal cell death in rats. As an extending study, here we examined in pheochromocytoma 12 (PC12) cells, whether HE could exert a protective effect against oxidative stress and apoptosis induced by di(2-ethylhexyl)phthalate (DEHP), a plasticizer known to cause neurotoxicity. We demonstrated that pretreatment with HE significantly attenuated DEHP induced cell death. This protective effect may be attributed to its ability to reduce intracellular reactive oxygen species levels, preserving the activity of respiratory complexes and stabilizing the mitochondrial membrane potential. Additionally, HE pretreatment significantly modulated Nrf2 and Nrf2-dependent vitagenes expression, preventing the increase of pro-apoptotic and the decrease of anti-apoptotic markers. Collectively, our data provide evidence of new preventive nutritional strategy using HE against DEHP-induced apoptosis in PC12 cells.

Secretory Production of the Hericium erinaceus Laccase from Saccharomyces cerevisiae.

Mushroom laccases play a crucial role in lignin depolymerization, one of the most critical challenges in lignin utilization. Importantly, laccases can utilize a wide range of substrates, such as toxicants and antibiotics. This study isolated a novel laccase, named HeLac4c, from endophytic white-rot fungi Hericium erinaceus mushrooms. The cDNAs for this enzyme were 1569 bp in length and encoded a protein of 523 amino acids, including a 20 amino-acid signal peptide. Active extracellular production of glycosylated laccases from Saccharomyces cerevisiae was successfully achieved by selecting an optimal translational fusion partner. We observed that 5 and 10 mM Ca2+, Zn2+, and K+ increased laccase activity, whereas 5 mM Fe2+ and Al3+ inhibited laccase activity. The laccase activity was inhibited by the addition of low concentrations of sodium azide and L-cysteine. The optimal pH for the 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt was 4.4. Guaiacylglycerol-ß-guaiacyl ether, a lignin model compound, was polymerized by the HeLac4c enzyme. These results indicated that HeLac4c is a novel oxidase biocatalyst for the bioconversion of lignin into value-added products for environmental biotechnological applications.

The potential therapeutic role of Hericium erinaceus extract in pathologic conditions involving the urogenital-gut axis: insights into the involved mechanisms and mediators.

In this review we focused on the putative therapeutic effect of Hericium erinaceus extract in the treatment of pathologic conditions of the lower urinary tract in which intestinal inflammation may play a role. To this aim we reviewed the available evidence on pelvic cross-organ sensitization as a possible mechanism through which intestinal inflammation and dysbiosis may affect the lower urinary tract. Also, we reviewed the clinical and experimental evidence supporting the role of Hericium erinaceus extract as an anti-inflammatory agent highlighting the role of a number of putative mediators and mechanisms which might make this nutraceutical suitable for the management of 'difficult to treat' lower urinary tract disorders.

The ethnopharmacology, phytochemistry and pharmacology of the genus Hericium.

ETHNOPHARMACOLOGICAL RELEVANCE: Mushrooms in the genus Hericium are used as functional food and traditional medicines for a long history in East Asian countries such as China, India, Japan, and Korea. Some species of Hericium are called as monkey head mushroom (Houtougu) in China and Yamabushitake in Japan, which are traditionally considered as rare and precious health promoting food and medicinal materials for the treatment of dyspepsia, insomnia, chronic gastritis, and digestive tract tumors. THE AIM OF THE REVIEW: This review aims to summarize the ethnopharmacology and structural diversity of secondary metabolites from Hericium species, as well as the pharmacological activities of the crude extracts and pure compounds from Hericium species in recent years. MATERIALS AND METHODS: All the information was gathered by searching Scifinder, PubMed, Web of Science, ScienceDirect, Springer, Wiley, ACS, CNKI, Baidu Scholar, Google Scholar databases and other published materials (books and Ph.D. and M. Sc. Dissertations) using the keywords "Hericium", "Traditional uses", "Chemical composition", "Quality control" and "Pharmacological activity" (1971-May 2023). The species name was checked with https://www.mycobank.org/. RESULTS: The traditional uses of Hericium species were summarized, and 230 secondary metabolites from Hericium species were summarized and classified into six classes, mainly focusing on their chemical diversity, biosynthesis, biological activities. The modern pharmacological experiments in vivo or in vitro on their crude and fractionated extracts showed that the chemical components from Hericium species have a broad range of bioactivities, including neuroprotective, antimicrobial, anticancer, α-glucosidase inhibitory, antioxidant, and anti-inflammatory activities. CONCLUSIONS: The secondary metabolites discovered from Hericium species are highly structurally diverse, and they have the potential to be rich resources of bioactive fungal natural products. Moreover, the unveiled bioactivities of their crude extracts and pure compounds are closely related to critical human health concerns, and in-depth studies on the potential lead compounds, mechanism of pharmacological effects and pharmaceutical properties are clearly warranted.

Effects of different extraction methods on the structural and biological properties of Hericium coralloides polysaccharides.

In current study, polysaccharides from Hericium coralloides were extracted by heat reflux, acid-assisted, alkali-assisted, enzyme-assisted, ultrasonic-assisted, cold water, pressurized hot water, hydrogen peroxide/ascorbic acid system and acid-chlorite delignification methods, which were named as HRE-P, ACE-P, AAE-P, EAE-P, UAE-P, CWE-P, PHE-P, HAE-P, and ACD-P, respectively. Their physicochemical properties, structural characteristics, and antioxidant activities were investigated and compared. Experimental outcomes indicated notable variations in the extraction yields, chemical compositions, monosaccharide constituents and molecular weights of the obtained nine polysaccharides. HRE-P demonstrated the highest activity against ABTS and OH radicals, CWE-P against ABTS, DPPH, and superoxide radicals, and UAE-P against DPPH radicals. In addition, UAE-P, CWE-P, and HAE-P exhibited better protective effects on L929 cells, when compared to the other obtained polysaccharides. Additionally, correlation analysis indicated that monosaccharide composition and total polyphenol content were two prominent variables influencing the bioactivity of H. coralloides polysaccharides.

Effects of Hericium erinaceus polysaccharide in porcine IPEC-J2 intestinal epithelial cells against apoptosis induced by oxidative stress.

This study was intended to investigate whether Hericium erinaceus polysaccharides (HEP) prevent oxidative stress and apoptosis of intestinal porcine epithelial cells from jejunum (IPEC-J2 cells) induced by hydrogen peroxide (H2O2). Crude HEP were extracted and purified by chromatography. The ultraviolet and infrared spectra and monosaccharide composition of HEP were analyzed. Reactive oxygen species (ROS) generation was quantified by flow cytometry method, and lactate dehydrogenase (LDH) and malondialdehyde (MDA) production were determined by TBARS. Also, apoptosis was analyzed by flow cytometry method and the apoptosis-related regulatory molecules were determined by microplate or western blotting method. Our results showed that pretreatment of IPEC-J2 cells with HEP significantly scavenged ROS and reduced LDH and MDA production. HEP also reduced apoptosis and kept polarity of the mitochondrial membrane potential. Moreover, HEP increased the content of caspase-3 and PARP, and protein expression of Bcl-2, while inhibited Bax and Bad and reduced the content of caspase-9 and release of CytC. Meanwhile, HEP inhibited the protein expression of TNFR1, FAS, and FASL, and decreased the content of caspase-8. The results indicated that HEP had a protective effect against oxidative stress in IPEC-J2 cells and the underlying mechanism was reducing apoptosis via mitochondrial and death receptor pathways.