Wood Ear Mushroom Polysaccharide Shows Bone-Building Power Against Osteoporosis

A humble ingredient long prized in Asian kitchens may hold a surprising answer to one of aging’s most stubborn health problems. Scientists in China have extracted and characterized polysaccharides from the wood ear mushroom, Auricularia auricula, and demonstrated that the compound can protect bone in a rat model of postmenopausal osteoporosis while promoting osteoblast maturation in cell culture. The work, published in the Journal of Agriculture and Food Research, points to the insulin-like growth factor 1 receptor pathway as a central mediator of the mushroom’s bone-building effects, and suggests that a safe, food-derived alternative to conventional osteoporosis drugs may be within reach.

Postmenopausal osteoporosis arises when declining estrogen levels tip the balance of bone remodeling toward resorption, producing reduced bone mass, deteriorated trabecular microstructure, and elevated fracture risk. As populations age worldwide, the disease imposes a growing public health burden on elderly women. Current first-line treatments, including bisphosphonates and hormone replacement therapy, effectively slow bone loss, but long-term use carries well-documented concerns ranging from gastrointestinal damage to cardiovascular risks and potential carcinogenic hazards. That trade-off has driven researchers to search for natural compounds with genuine anti-osteoporotic activity and favorable safety profiles.

The research team, led by Zhaoguo Wang of Southern Medical University, turned to Auricularia auricula, an edible medicinal fungus whose polysaccharides have previously shown antioxidant, anti-inflammatory, and gut-regulating properties. To maximize yield, the group developed an ultrasound-assisted enzymatic extraction method, first screening cellulase, pectinase, and a combination of the two. The enzyme cocktail proved decisively superior, lifting the extraction yield to 27.72 percent compared with 24.02 percent for cellulase alone and 15.23 percent for pectinase alone, a synergy attributed to the enzymes attacking different structural components of the fungal cell wall simultaneously.

With the enzyme system selected, the researchers systematically optimized each extraction variable. Single-factor experiments identified a cellulase-to-pectinase ratio of 1.5:1, an enzyme concentration of 3000 units per 100 milliliters, a four-hour enzymolysis, a 1:40 solid-to-liquid ratio, twenty minutes of sonication, and an ultrasonic power of 2 watts per milliliter as favorable conditions. A Box-Behnken response surface design then refined four key parameters into a predictive model with strong explanatory power, achieving a coefficient of determination of 0.9156 and a non-significant lack-of-fit test. Validation runs under practical near-optimal conditions delivered an experimental yield of 30.15 percent, within 2.87 percent of the model prediction and inside the 95 percent prediction interval, confirming the reliability of the optimized process.

Characterization revealed that the resulting Auricularia auricula polysaccharide, or AAP, is an acidic heteropolysaccharide rich in glucose, mannose, and glucuronic acid, with smaller contributions from fucose and xylose. Total sugar content reached 74.07 percent, uronic acid 10.37 percent, and protein only 2.63 percent, while endotoxin levels remained low across the tested concentration range. Infrared spectroscopy identified hallmark polysaccharide absorptions, including hydroxyl stretching near 3000 to 3500 inverse centimeters, a carbonyl band consistent with glucuronic acid carboxyl groups, and a signal at 848 inverse centimeters indicating beta-configured sugar units. Molecular weight analysis showed a heterogeneous mixture spanning roughly one thousand to one and a half million Daltons, and thermal analysis demonstrated stability up to approximately 270 degrees Celsius, well above physiological temperatures.

The structural profile matters because polysaccharide bioactivity is thought to depend heavily on molecular weight and monosaccharide composition. Acidic, uronic-acid-rich polysaccharides cannot cross cell membranes, but their negatively charged carboxyl groups can engage positively charged receptor domains through electrostatic attraction. Notably, the extracellular domain of the insulin-like growth factor 1 receptor is enriched in arginine and lysine residues, making it a plausible anchoring target for anionic polysaccharides. This structural logic shaped the team’s central hypothesis: that AAP might stimulate osteoblasts not through the canonical BMP/Smad or Wnt/beta-catenin routes used by neutral fungal glucans, but through the IGF-1/IGF-1R signaling axis.

To test the hypothesis in living animals, the researchers used an ovariectomized rat model, the standard experimental surrogate for postmenopausal bone loss. Female rats underwent bilateral ovariectomy and, after a week of recovery, received daily oral AAP at 100, 300, or 500 milligrams per kilogram for twelve weeks, alongside sham, ovariectomy-only, and estradiol-treated control groups. Micro-computed tomography of the proximal tibia showed that only the high dose significantly increased bone mineral density and improved trabecular microarchitecture relative to untreated ovariectomized animals. Histological staining corroborated the imaging: high-dose AAP increased the bone area fraction and reduced the osteoclast-covered bone surface, mirroring the effects of estradiol without stimulating uterine tissue, a key safety distinction for any non-hormonal therapy.

Serum biomarkers told a consistent story. Ovariectomized rats displayed elevated CTX-1 and RANKL, markers of rampant bone resorption, alongside depressed P1NP, OPG, and the protective OPG-to-RANKL ratio. High-dose AAP reversed all of these shifts and restored serum IGF-1, which had fallen sharply after ovariectomy. Because IGF-1 is the most abundant growth factor stored in bone matrix and a well-established driver of osteoblast differentiation, proliferation, and survival, its recovery pointed directly toward the signaling axis the team suspected. Importantly, no abnormalities appeared in major organ indices or histology across the treatment groups, and AAP did not raise the uterine index at any dose tested.

In vitro experiments then dissected the mechanism at cellular resolution. AAP did not alter the proliferation of bone marrow stromal cells or MC3T3-E1 pre-osteoblasts, but the high concentration markedly enhanced osteogenic differentiation, boosting alkaline phosphatase activity at day seven and matrix mineralization at day twenty-one. Western blotting revealed increased IGF-1 and IGF-1R protein levels, elevated phosphorylation of IGF-1R, IRS-1, AKT, and ERK, and upregulation of core osteogenic genes including RUNX2, ALP, COL-1, OSX, and OPG. Total protein levels of Smad2, Smad3, Wnt4, and beta-catenin were unchanged, though the authors caution that this alone cannot exclude activation of those pathways. The decisive experiment came with CRISPR/Cas9-generated IGF-1R knockout cells: in these, the AAP-driven gains in alkaline phosphatase activity, mineralization, and osteogenic gene expression were largely abolished, providing functional proof that the receptor is required for the full effect.

The team also addressed a question critical to any functional food: does the compound survive digestion? Simulated oral, gastric, and intestinal digestion phases left AAP’s osteogenic activity essentially intact, with all digested fractions sustaining elevated alkaline phosphatase activity in human osteoblasts indistinguishable from the undigested compound. The authors acknowledge limitations, including the imperfect fidelity of the ovariectomy model to human disease and the absence of formal pharmacokinetic and long-term toxicity studies, though pharmacokinetic data from a structurally analogous Auricularia polysaccharide suggest efficient oral absorption. Further work to purify individual molecular weight fractions, map upstream receptor interactions, and complete safety profiling will determine whether this kitchen-staple fungus can move from the wok to the clinic as a bone-protective functional food.

Subject of Research: Osteoprotective effects and IGF-1/IGF-1R mechanism of Auricularia auricula polysaccharides in postmenopausal osteoporosis

Article Title: Preparation and physicochemical characterization of polysaccharides from Auricularia auricula and their osteogenic potential in vitro and in vivo

Article References: Wang, Z., Liu, G., Lai, F., Xiao, X., & Xu, S. (2026). Preparation and physicochemical characterization of polysaccharides from Auricularia auricula and their osteogenic potential in vitro and in vivo. Journal of Agriculture and Food Research, 31, Article 103263. https://doi.org/10.1016/j.jafr.2026.103263

Image Credits: AI Generated

DOI: 10.1016/j.jafr.2026.103263

Keywords: Auricularia auricula, wood ear mushroom, polysaccharides, postmenopausal osteoporosis, osteogenic differentiation, IGF-1/IGF-1R signaling, bone mineral density, ovariectomized rats, ultrasound-assisted enzymatic extraction, functional food, bone metabolism, natural products