Meshima

Metadata

Regulatory Status

South Korea

• Pharmaceutical approval: Mesima, a polysaccharide extract from P. linteus mycelial culture produced by submerged liquid fermentation, is an approved pharmaceutical in South Korea for cancer adjunctive immunotherapy. This makes Meshima one of only a few medicinal mushrooms worldwide to achieve formal pharmaceutical status, alongside Turkey Tail PSK (Japan) and Shiitake lentinan (Japan).
• Traditional medicine: Sanghwang is one of the most revered medicinal mushrooms in Korean traditional medicine (Hanbang). Wild Sanghwang fruiting bodies are extremely rare and highly prized, historically commanding prices comparable to precious materials.
• Market significance: Korea represents the primary market for P. linteus pharmaceutical and supplement products.

Japan

• Recognition: Meshimakobu is recognized in Japanese traditional medicine. The common Japanese name refers to Meshima Island (Women’s Island) in Nagasaki Prefecture, where the mushroom was historically collected.
• Research significance: The landmark Ikekawa et al. (1968) study that initiated modern medicinal mushroom research screened P. linteus alongside other species, finding it achieved a 96.7% tumor inhibition rate against sarcoma 180 in mice — one of the highest rates among all species tested.
• Pharmaceutical status: No specific pharmaceutical approval, though it is available as a health food supplement.

China

• Traditional use: Known as Song Gen in traditional Chinese medicine. Used for treating bleeding, amenorrhea, and as a tonic. Not listed in the Chinese Pharmacopoeia as an official monograph entry.

European Union

• Novel Food: Meshima extracts have not received formal Novel Food authorization under Regulation (EU) 2015/2283.
• No EMA/HMPC monograph or assessment report.

United States

• Dietary supplement: Available as a dietary supplement under DSHEA. Products include fruiting body extracts, mycelium powders, and standardized polysaccharide preparations.
• FDA GRAS: No specific GRAS determination for Phellinus linteus extracts.

Conditions & Indications

Primary Indications (Moderate Evidence)

• Immune modulation and cancer adjunctive therapy — Meshima polysaccharides activate innate immune cells (macrophages, NK cells, dendritic cells) through pattern recognition receptors, enhancing antitumor immune surveillance. The Korean pharmaceutical Mesima is approved specifically for this indication. Cho et al. (2010) reported that Phellinus linteus mycelial extract enhanced immune parameters in gastric cancer patients receiving chemotherapy, including improved NK cell activity and T-cell subset ratios. Multiple Korean clinical studies have demonstrated immune enhancement in oncology patients receiving Meshima alongside conventional treatment.
• Immunostimulation in immunocompromised states — Beta-glucan polysaccharides from Phellinus linteus enhance innate immune function through Dectin-1 and TLR-2 receptor activation. Kim et al. (1996) demonstrated that polysaccharide from P. linteus stimulated both humoral and cell-mediated immunity in mice, enhancing splenocyte proliferation, NK cell cytotoxicity, and macrophage phagocytic activity.

Secondary Indications (Preliminary Evidence)

• Anti-allergic and anti-inflammatory activity — Hispolon and polysaccharide fractions have demonstrated anti-allergic effects through inhibition of IgE-mediated mast cell degranulation and suppression of Th2 cytokine production (IL-4, IL-5, IL-13). Choi et al. (2006) showed that Phellinus linteus water extract inhibited anaphylaxis-like reactions and mast cell activation.
• Hepatoprotection — Phellinus linteus extracts demonstrate liver-protective effects in animal models. Shon et al. (2003) showed that hot-water extract exhibited significant antioxidant and free radical scavenging activity, providing a mechanistic basis for hepatoprotective effects.

Emerging/Preclinical Indications

• Direct antitumor activity (preclinical) — Hispolon has demonstrated direct cytotoxicity against multiple cancer cell lines in vitro, including breast, prostate, gastric, and hepatocellular carcinoma. Mechanisms include apoptosis induction through caspase activation, cell cycle arrest at G2/M phase, and NF-kB inhibition. Chen et al. (2008) and Lu et al. (2009) characterized hispolon’s proapoptotic mechanisms. Clinical translation remains unestablished.
• Anti-angiogenic effects — Polysaccharide fractions inhibit VEGF-induced angiogenesis in preclinical models. Lee et al. (2010) demonstrated suppression of angiogenesis through downregulation of VEGF and MMP-9 expression. Song et al. (2011) showed protein-bound polysaccharide from P. linteus inhibited tumor growth and angiogenesis in mice.
• Chemosensitization — Collins et al. (2006) demonstrated that P. linteus extract sensitized prostate cancer cells to doxorubicin-induced apoptosis, and Tsuji et al. (2010) confirmed these chemosensitizing effects in an athymic nude mouse model.
• Antidiabetic activity — Preclinical evidence suggests P. linteus extracts may improve insulin sensitivity and reduce blood glucose through enhanced GLUT-4 translocation and improved beta-cell function.

Mechanism of Action

Primary Mechanisms

1. Beta-glucan polysaccharide activation of innate immunity Phellinus linteus produces a distinctive profile of acidic polysaccharides, including beta-1,3/1,6-D-glucans with unique branching patterns and heteropolysaccharides containing glucose, galactose, mannose, and xylose. These polysaccharides are recognized by pattern recognition receptors on innate immune cells, principally Dectin-1 (CLEC7A) on macrophages and dendritic cells, TLR-2 on monocytes, and complement receptor 3 (CR3) on NK cells and neutrophils. Receptor engagement triggers NF-kB and MAPK downstream signaling cascades, resulting in enhanced phagocytic activity, pro-inflammatory cytokine production (TNF-alpha, IL-1beta, IL-6, IL-12), augmented NK cell cytotoxicity, and dendritic cell maturation. The acidic polysaccharide fraction (PL-fraction) from mycelial culture broth forms the basis of the Korean pharmaceutical Mesima. Kim et al. (2003) demonstrated that this fraction activates macrophages through a signaling pathway involving nitric oxide and pro-inflammatory cytokine production.

2. Hispolon-mediated antitumor and anti-inflammatory activity Hispolon (6-(3,4-dihydroxyphenyl)-4-hydroxy-2H-pyran-2-one) is a polyphenolic compound relatively unique to Phellinus species and represents a pharmacological differentiator from other medicinal mushrooms. Hispolon exerts multiple mechanisms:

• Apoptosis induction: Activation of intrinsic (mitochondrial) apoptosis pathway through caspase-3, -8, and -9 activation, cytochrome c release, and modulation of Bcl-2 family proteins.
• NF-kB inhibition: Suppression of NF-kB activation and nuclear translocation, reducing expression of anti-apoptotic proteins and pro-inflammatory mediators (COX-2, iNOS).
• Cell cycle arrest: Induction of G2/M cell cycle arrest through modulation of cyclin-dependent kinases.
• ERK1/2 signaling: Lu et al. (2009) demonstrated hispolon induces apoptosis in breast and bladder cancer cells via MDM2-recruited ERK1/2 activity.

3. Immunomodulatory proteoglycans Phellinus linteus produces immunomodulatory proteoglycans, including interfungins A, that activate immune cells through mechanisms complementary to beta-glucan signaling. These proteoglycans enhance T-cell proliferation, promote Th1-type cytokine responses (IFN-gamma, IL-2, IL-12), and modulate the Th1/Th2 balance toward enhanced cell-mediated immunity.

4. Selective Th1/Th2 immunomodulation In contrast to its immunostimulatory effects on innate immunity and Th1 responses, Phellinus linteus selectively suppresses Th2-mediated allergic responses. Polysaccharide and polyphenolic fractions inhibit IgE-mediated mast cell degranulation, suppress eosinophil infiltration, and reduce Th2 cytokine production (IL-4, IL-5, IL-13). This selective immunomodulation — stimulating Th1 while suppressing Th2 — makes Phellinus linteus pharmacologically distinct among medicinal mushrooms.

Key Active Compounds

Pharmacological Note

Phellinus linteus is pharmacologically distinguished from other major medicinal mushrooms by two key features: (1) the presence of hispolon and related styrylpyrone compounds, providing direct cytotoxic and anti-inflammatory activity that complements immunomodulatory polysaccharides, and (2) the selective Th1-enhancing/Th2-suppressing immunomodulatory profile, making it useful in conditions involving both immune deficiency and immune dysregulation. Like reishi, dual extraction (hot water + ethanol) captures a more complete bioactive profile than either method alone. The PL-fraction from mycelial culture broth, which forms the basis of Mesima, is produced by submerged liquid fermentation, a distinct production method from traditional fruiting body cultivation.

Clinical Evidence Summary

Clinical evidence for Meshima is moderate in quality, concentrated primarily in Korean and Japanese oncology settings.

Key Clinical Studies

Evidence from the Korean Mesima Program

• Preclinical package: Extensive in vitro and in vivo studies demonstrating activation of macrophages, NK cells, and dendritic cells; inhibition of tumor growth in multiple murine tumor models; enhancement of chemotherapy efficacy.
• Clinical studies: Korean clinical investigations supporting pharmaceutical approval demonstrated immune enhancement in cancer patients, including improved NK cell activity, enhanced T-cell function, and better tolerance of chemotherapy.
• Post-marketing experience: Mesima has accumulated clinical experience in Korean oncology practice since its approval, primarily as adjunctive immunotherapy.

Evidence Limitations

• No large-scale, multicenter, double-blind, placebo-controlled Phase III RCTs published in English-language journals.
• Most clinical data from Korean and Japanese studies, some published only in those languages.
• Clinical studies supporting the Mesima approval have not been fully reproduced by independent research groups outside Korea.
• Standardization varies significantly — Mesima uses a specific mycelial culture extract that may not be comparable to commercially available supplements.
• Sample sizes in published clinical studies are small to moderate (n=30-68).
• Taxonomic confusion within the Phellinus genus complicates interpretation; some authorities have reclassified P. linteus as Tropicoporus linteus.
• Much of the strongest evidence is preclinical; clinical translation of hispolon-mediated antitumor effects remains unestablished.

Safety Profile

General Assessment

Phellinus linteus has been consumed in Korean, Japanese, and Chinese traditional medicine for centuries and is generally well-tolerated at standard doses. Clinical studies and the Mesima pharmaceutical program have reported no serious adverse events attributable to P. linteus supplementation.

Contraindications

• Autoimmune disease: Due to immune-stimulating properties, use with caution in patients with autoimmune conditions. Immunostimulation could theoretically exacerbate autoimmune activity.
• Organ transplant recipients: Immunostimulatory effects may counteract immunosuppressive therapy. Contraindicated unless under direct specialist supervision.
• Pre-surgical: Discontinue at least 2 weeks before scheduled surgery.
• Pregnancy and lactation: Insufficient human safety data. Avoid until safety is established.

Drug Interactions

• Immunosuppressants (cyclosporine, tacrolimus, mycophenolate, corticosteroids): Immune-stimulating beta-glucan activity may counteract immunosuppressive therapy. Severity: High. Avoid without specialist supervision.
• Chemotherapy agents: Designed to be used alongside chemotherapy in its approved indication; Korean studies show safety and potential synergy. Severity: Low when supervised by oncologist.
• Checkpoint inhibitor immunotherapy: Theoretical concern for additive immune stimulation. No clinical interaction data exists. Severity: Unknown. Consult oncologist.
• Anticoagulants and antiplatelets: Limited preclinical evidence of mild antiplatelet effects. Severity: Low. Monitor if combining.
• Antidiabetic agents: Preclinical data suggests possible blood glucose lowering. Severity: Low. Monitor blood glucose.

Side Effects

• Common: Generally very well-tolerated. Mild GI symptoms (nausea, bloating, loose stools) reported occasionally.
• Uncommon: Allergic reactions in individuals sensitive to mushrooms.
• Rare: No serious adverse events reported in published studies or Mesima post-marketing surveillance.

Pregnancy and Lactation

• Category: Avoid. No controlled human studies exist.

Clinical Dosage

Mesima (Korean Pharmaceutical Extract)

• Standard dose: 1.5-3 g/day of Mesima (dried mycelial culture extract) in divided doses
• This is the approved pharmaceutical preparation, produced from submerged liquid fermentation of P. linteus mycelium
• Note: Mesima is a specific pharmaceutical product; supplement-grade products may not be equivalent

Hot-Water Extract (Fruiting Body)

• Standard dose: 1-3 g/day of hot-water extracted fruiting body, standardized to polysaccharide content
• Preparation: Traditional decoction involves simmering 5-10 g of dried fruiting body in water for 2-3 hours

Dried Fruiting Body Powder

• Standard dose: 1-3 g/day in capsule form
• Note: Wild-harvested fruiting bodies are extremely rare and expensive; most commercial products use cultivated material

Dual-Extract Tincture

• Standard dose: 2-4 mL of 1:5 dual-extract tincture (hot water + ethanol), two to three times daily
• Captures both water-soluble polysaccharides and alcohol-soluble hispolon/phenolic compounds

Sources

• Ikekawa T, Nakanishi M, Uehara N, Chihara G, Fukuoka F. Antitumor action of some basidiomycetes, especially Phellinus linteus. Gann. 1968;59(2):155-157
• Kim GY, Oh YH, Park YM. Acidic polysaccharide isolated from Phellinus linteus induces nitric oxide and proinflammatory cytokine production in murine macrophages. J Ethnopharmacol. 2003;88(1):109-116
• Kim GY, Kim SH, Hwang SY, et al. Oral administration of proteoglycan isolated from Phellinus linteus in the prevention and treatment of collagen-induced arthritis in mice. Biol Pharm Bull. 2003;26(6):823-831
• Kim SH, Song YS, Kim SK, Kim BC, Lim CJ, Park EH. Anti-inflammatory and related pharmacological activities of the n-BuOH subfraction of mushroom Phellinus linteus. J Ethnopharmacol. 2004;93(1):141-146
• Kim HM, Han SB, Oh GT, et al. Stimulation of humoral and cell mediated immunity by polysaccharide from mushroom Phellinus linteus. Int J Immunopharmacol. 1996;18(5):295-303
• Cho JH, Cho SD, Hu H, et al. The roles of ERK1/2 and p38 MAP kinases in the preventive mechanisms of mushroom Phellinus linteus against the inhibition of gap junctional intercellular communication by hydrogen peroxide. Carcinogenesis. 2002;23(7):1163-1169
• Chen W, Zhao Z, Li L, et al. Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway. Free Radic Biol Med. 2008;45(1):60-72
• Lu TL, Huang GJ, Lu TJ, et al. Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells. Food Chem Toxicol. 2009;47(8):2013-2021
• Choi YH, Yan GH, Chai OH, et al. Inhibition of anaphylaxis-like reaction and mast cell activation by water extract from the fruiting body of Phellinus linteus. Biol Pharm Bull. 2006;29(7):1360-1365
• Lee YS, Kim YH, Shin EK, et al. Anti-angiogenic activity of methanol extract of Phellinus linteus and its fractions. J Ethnopharmacol. 2010;131(1):56-62
• Song KS, Li G, Kim JS, et al. Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, angiogenesis, and tumor-associated macrophage in mice. BMC Cancer. 2011;11:109
• Shon MY, Kim TH, Sung NJ. Antioxidants and free radical scavenging activity of Phellinus linteus (Berry & Curtis) Teng (Hymenochaetaceae) extracts. Food Chem. 2003;82(4):593-597
• Zhu T, Kim SH, Chen CY. A medicinal mushroom: Phellinus linteus. Curr Med Chem. 2008;15(13):1330-1335
• Sliva D, Jedinak A, Kawasaki J, Harvey K, Slivova V. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling. Br J Cancer. 2008;98(8):1348-1356
• Lee IK, Yun BS. Styrylpyrone-class compounds from medicinal fungi Phellinus and Inonotus spp., and their medicinal importance. J Antibiot (Tokyo). 2011;64(5):349-359
• Collins L, Zhu T, Guo J, Bhatt AP, Slivova V, Sliva D. Phellinus linteus sensitizes apoptosis induced by doxorubicin in prostate cancer. Br J Cancer. 2006;95(2):282-288
• Tsuji T, Du W, Bhatt AP, et al. Phellinus linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude mice. PLoS One. 2010;5(3):e9885

Connections

• Compare with other medicinal mushroom immunomodulators: Turkey Tail (Trametes versicolor — PSK/PSP polysaccharides, strongest clinical evidence base with Japanese pharmaceutical approval), Reishi (Ganoderma lucidum — dual polysaccharide + triterpenoid pharmacology, Cochrane review), Maitake (Grifola frondosa — D-fraction beta-glucans, Phase I/II data)
• Meshima is pharmacologically distinguished from other medicinal mushrooms by its hispolon and styrylpyrone content, providing direct antitumor mechanisms (NF-kB inhibition, apoptosis induction) that complement the immunomodulatory beta-glucan pathway shared across mushroom species
• The selective Th1-enhancing/Th2-suppressing immunomodulatory profile is noteworthy; while most medicinal mushroom beta-glucans are broadly immunostimulatory, Meshima’s ability to suppress allergic (Th2) responses while enhancing antitumor (Th1) immunity may offer advantages in patients with concurrent atopic conditions
• Compare with Chaga (Inonotus obliquus), another member of the Hymenochaetaceae family; both produce melanin pigments and share some styrylpyrone compounds, though their primary pharmacological profiles differ (Chaga emphasizes betulinic acid and antioxidant activity)
• Like Turkey Tail PSK and Shiitake lentinan, Meshima’s Korean pharmaceutical approval (Mesima) demonstrates the viability of mushroom-derived biological response modifiers as approved therapeutic agents in East Asian regulatory systems
• Meshima’s prominence in Korean traditional medicine (Hanbang) parallels the importance of Reishi in Chinese medicine (TCM) and Turkey Tail in Japanese medicine (Kampo), illustrating how different East Asian medical traditions have championed distinct medicinal mushroom species