Dark Reishi

Metadata

Regulatory Status

China

• Chinese Pharmacopoeia: Not listed as an official drug.
• Traditional use: Used in Chinese folk medicine (TCM-adjacent) for treatment of indigestion, acute and chronic nephritis, and inflammation. Not a first-tier TCM herb but recognized in regional traditional practices, particularly in southern China and Southeast Asia.
• Classification: Known as “Blood Lingzhi” due to its dramatic blood-red bruising reaction, connecting it culturally to the Lingzhi/Reishi tradition of the Ganodermataceae family.

Southeast Asia

• Traditional use: A. rugosum grows in tropical and subtropical zones across China, Taiwan, Indonesia, Australia, the South Pacific, and Equatorial Guinea. Local ethnomedicinal traditions in several of these regions employ A. rugosum for various health conditions.

United States and Europe

• Not marketed: A. rugosum is not available as a commercial dietary supplement in Western markets. Research interest is primarily academic, led by Hong Kong university groups.
• No regulatory status in any Western jurisdiction.

Conditions & Indications

Primary Indications (Preclinical Evidence)

• Neuroprotection against oxidative stress-induced neurotoxicity — A. rugosum extract protects PC12 cells (rat pheochromocytoma neurons) against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity, a standard model for Parkinson’s disease-related oxidative neuronal death. The extract decreased cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis through antioxidant and antiapoptotic mechanisms (Seow et al. 2021). Subsequently, polysaccharides and gallic acid from A. rugosum were confirmed to protect SH-SY5Y human neuroblastoma cells against 6-OHDA toxicity (Choy et al. 2024). Additionally, A. rugosum extract protected hippocampal cells against glutamate-induced excitotoxicity (Chan et al. 2022).
• Age-related cognitive decline — In d-galactose-induced aging mouse models, A. rugosum aqueous extract alleviated impaired cognitive function, memory loss, anxiety, and reduced locomotor ability. Mechanisms involved mTOR pathway activation, upregulation of antioxidant enzymes, and modulation of gut microbiota (Rangsinth et al. 2025).

Secondary Indications (Preclinical Evidence)

• Cardioprotection against doxorubicin toxicity — A. rugosum extract protected against doxorubicin-induced cardiotoxicity in cardiac cell models by suppressing oxidative stress, mitochondrial dysfunction, and apoptosis through activation of Akt/mTOR and Nrf2/HO-1 signaling pathways. Notably, the cardioprotective activity of A. rugosum was greater than that of Ganoderma lucidum in direct comparison (Li et al. 2022).
• Anti-inflammatory activity — A. rugosum extract suppressed inflammatory responses in TNF-alpha/IFN-gamma-stimulated HaCaT keratinocytes by reducing NF-kB expression and inhibiting phosphorylation of MEK/ERK, Akt, and mTOR pathways (Choy et al. 2022). In LPS-stimulated RAW264.7 macrophages, the extract attenuated TNF-alpha and nitric oxide production while upregulating anti-inflammatory IL-10 (Chan et al. 2015).
• Ulcerative colitis — The ethanolic extract of domesticated A. rugosum alleviated DSS-induced ulcerative colitis in mice by repairing the intestinal barrier (Kim et al. 2024). A separate study confirmed protective effects through regulation of macrophage polarization and suppression of oxidative stress (Park et al. 2024).

Emerging/Preclinical Indications

• Proangiogenic activity — A polysaccharide fraction from A. rugosum demonstrated proangiogenic effects in vitro and in vivo, potentially relevant to wound healing and tissue repair (Wang et al. 2024).
• Antioxidant and free radical scavenging — Aqueous extract demonstrated significant radical-scavenging activities against DPPH, ABTS, and hydroxyl radicals.
• Anti-hyperlipidemic effects — Reported in preclinical models, though data are limited.
• Anti-epileptic activity — Reported in the Zheng et al. (2022) review, though primary data are limited.

Mechanism of Action

Primary Mechanisms

1. Neuroprotective antioxidant and antiapoptotic pathways A. rugosum extract protects neuronal cells against oxidative stress-induced death through multiple concurrent mechanisms:

• Reduction of intracellular reactive oxygen species (ROS) accumulation
• Preservation of mitochondrial membrane potential, preventing mitochondrial dysfunction
• Inhibition of caspase-3 and caspase-9 activation, blocking the intrinsic apoptosis cascade
• Upregulation of antioxidant enzymes via Nrf2/HO-1 pathway activation
• The active neuroprotective compounds include polysaccharides and gallic acid

2. mTOR pathway-mediated cognitive protection In aging models, A. rugosum activates the mTOR (mammalian target of rapamycin) signaling pathway, which regulates cell growth, protein synthesis, and autophagy. Western blot analysis showed upregulated phosphorylation of mTOR and increased expression of antioxidant enzymes in brain tissue of treated aging mice.

3. Gut-brain axis modulation A. rugosum polysaccharides altered gut microbiota composition in aging mice, increasing the relative abundance of beneficial bacteria (Lactobacillus reuteri) and decreasing harmful bacteria (Clostridium scindens). This gut microbiota modulation is hypothesized to contribute to neuroprotective effects through the microbiota-gut-brain axis.

4. NF-kB and MAPK anti-inflammatory signaling A. rugosum suppresses inflammatory cascades through:

• Reduction of total NF-kB protein expression
• Inhibition of MEK/ERK phosphorylation
• Inhibition of Akt and mTOR phosphorylation in inflammatory contexts (distinct from the mTOR activation seen in neuroprotective contexts)
• Attenuation of TNF-alpha and nitric oxide production in macrophages
• Upregulation of anti-inflammatory IL-10

Secondary Mechanisms

• Akt/mTOR cardioprotective signaling: Rescue of Akt/mTOR and Nrf2/HO-1 pathways in doxorubicin-challenged cardiac cells
• Intestinal barrier repair: Restoration of tight junction proteins and regulation of macrophage polarization in colitis models
• Proangiogenic activity: Polysaccharide-mediated stimulation of angiogenesis for tissue repair

Key Active Compounds

Clinical Evidence Summary

No clinical trials have been conducted on A. rugosum. All evidence is preclinical (in vitro and animal models).

Key Preclinical Studies

Genome Sequencing

• Costa et al. (2021) published the complete genome of A. rugosum, identifying 377 carbohydrate-active enzymes (CAZymes) and 15 secondary metabolite biosynthetic gene clusters, providing a genomic basis for understanding its diverse bioactive compound production.

Evidence Limitations

• No clinical trials of any kind. All evidence is preclinical.
• Most studies are from a single research group at the University of Hong Kong, limiting independent replication.
• The neuroprotective effects are demonstrated in cell culture models (PC12, SH-SY5Y) and aging mice, which do not fully recapitulate human neurodegenerative disease.
• The cardioprotection study comparing AR with G. lucidum was retracted (Li et al. 2022, Oxidative Medicine and Cellular Longevity), requiring caution in interpreting those specific findings.
• Dosage translation from preclinical models to human use is not established.
• The taxonomic revision to Sanguinoderma may create confusion in literature searches.
• Wild vs. domesticated specimens may differ in bioactive compound content.

Safety Profile

General Assessment

A. rugosum has been consumed in traditional Chinese folk medicine for indigestion and nephritis, suggesting a degree of historical safety. However, no formal safety studies, toxicology assessments, or controlled human consumption studies have been conducted. The species is edible and has been used as a food mushroom in some Southeast Asian communities.

Contraindications

• Pregnancy and lactation: No safety data. Avoid.
• Autoimmune disease: Immunomodulatory and anti-inflammatory activities suggest potential immune system effects; use with caution.
• Pre-surgical: Precautionary discontinuation due to potential effects on inflammatory pathways and unknown effects on hemostasis.

Drug Interactions

• No drug interactions documented. However, based on the pharmacological profile:
• Anti-inflammatory drugs: Potential additive effects with NSAIDs or corticosteroids. Severity: Theoretical.
• Immunosuppressants: Immunomodulatory potential may interfere. Severity: Theoretical.
• Doxorubicin and chemotherapeutics: The cardioprotective effects suggest potential interaction with chemotherapy; this could be beneficial but requires clinical supervision. Severity: Theoretical; potentially beneficial but unvalidated.

Side Effects

• No adverse event reports exist for A. rugosum in the literature.
• Traditional use reports do not document significant side effects.

Clinical Dosage

No established human dosage guidelines exist for A. rugosum. The following information is derived from preclinical studies and traditional use.

Traditional Use

• TCM folk medicine: Used as a decoction for indigestion and nephritis; specific dosing conventions are not well-documented in available literature.

Dried Fruiting Body

• Inferred dose: No standardized dose. Traditional decoction preparations are used in folk medicine.

Aqueous Extract

• Preclinical reference: Studies used various concentrations of aqueous extract; polysaccharide content is approximately 5% of dried fruiting body weight.
• Active neuroprotective compounds: Polysaccharides and gallic acid identified as key active components, suggesting that hot water extraction captures the primary neuroprotective fractions.

Special Consideration

• Wild A. rugosum should be carefully identified. The blood-red bruising reaction of the pore surface is a key diagnostic feature.
• Domesticated (cultivated) A. rugosum has been shown to retain anti-inflammatory activity comparable to wild specimens (Chan et al. 2015), suggesting cultivation feasibility.

Sources

• Zheng G, Ren H, Li H, et al. A review of the phytochemical and pharmacological properties of Amauroderma rugosum. Kaohsiung J Med Sci. 2022;38(8):727-739
• Seow SLS, Eik LF, Naidu M, David P, Wong KH, Sabaratnam V. Amauroderma rugosum protects PC12 cells against 6-OHDA-induced neurotoxicity through antioxidant and antiapoptotic effects. Oxid Med Cell Longev. 2021;2021:6653753
• Choy CT, Wang C, Lim HY, et al. Neuroprotective effects of polysaccharides and gallic acid from Amauroderma rugosum against 6-OHDA-induced toxicity in SH-SY5Y cells. Molecules. 2024;29(5):953
• Chan PM, Kanagasabapathy G, Tan YS, Sabaratnam V, Kuppusamy UR. Amauroderma rugosum (Blume & T. Nees) Torrend: nutritional composition and antioxidant and potential anti-inflammatory properties. Food Funct. 2013;4(12):1830-1837
• Chan PM, Tan YS, Chua KH, Sabaratnam V, Kuppusamy UR. Attenuation of inflammatory mediators (TNF-alpha and nitric oxide) and up-regulation of IL-10 by wild and domesticated basidiocarps of Amauroderma rugosum in LPS-stimulated RAW264.7 cells. Evid Based Complement Alternat Med. 2015;2015:309891
• Choy CT, Leung GPH, Sabaratnam V, et al. Amauroderma rugosum extract suppresses inflammatory responses in TNF-alpha/IFN-gamma-induced HaCaT keratinocytes. Molecules. 2022;27(19):6533
• Li Y, Choy CT, Leung GPH, et al. Protective effects of Amauroderma rugosum on doxorubicin-induced cardiotoxicity through suppressing oxidative stress, mitochondrial dysfunction, apoptosis, and activating Akt/mTOR and Nrf2/HO-1 signaling pathways. Oxid Med Cell Longev. 2022;2022:9266178
• Rangsinth P, Choy CT, Leung GPH, et al. Amauroderma rugosum extract improves brain function in d-galactose-induced aging mouse models via the regulatory effects of its polysaccharides on oxidation, the mTOR-dependent pathway, and gut microbiota. Food Front. 2025;6:e543
• Chan PM, Ng SJ, Sabaratnam V. Neuroprotective properties of wild medicinal mushroom, Sanguinoderma rugosum (Agaricomycetes), extracts against glutamate-induced hippocampal cells. Int J Med Mushrooms. 2022;24(4):59-67
• Wang J, Zheng G, Li H, et al. Characterization of a polysaccharide from Amauroderma rugosum and its proangiogenic activities in vitro and in vivo. Int J Biol Macromol. 2024;283:137384
• Kim M, Park S, et al. The ethanolic extract of domesticated Amauroderma rugosum alleviated DSS-induced ulcerative colitis via repairing the intestinal barrier. Food Sci Biotechnol. 2024;33(11):2561-2573
• Costa IPMW, Nerde CC, et al. Genome sequencing and annotation and phylogenomic analysis of the medicinal mushroom Amauroderma rugosum. IMA Fungus. 2021;12:3
• Cui BK, Li YC, He SH, et al. Taxonomy and phylogeny of Sanguinoderma rugosum complex with descriptions of a new species and a new combination. Front Microbiol. 2022;13:1087212

Connections

• Compare with Lion’s Mane (Hericium erinaceus) for neuroprotective applications: Lion’s Mane acts primarily through NGF/BDNF neurotrophic factor stimulation, while A. rugosum acts through antioxidant/antiapoptotic neuroprotection and mTOR pathway activation — complementary rather than overlapping mechanisms
• Reishi (G. lucidum sensu lato) shares family-level taxonomy (Ganodermataceae) and some bioactive compound classes (ganoderic acid G, ergosterol, polysaccharides); the Li et al. (2022) comparison showed A. rugosum with greater cardioprotective activity than G. lucidum in the doxorubicin model
• Ganoderma sinense (Purple Lingzhi) is the other “dark-colored” Ganodermataceae species in Chinese medicine, providing a cultural parallel to the “Blood Lingzhi” tradition
• The gut-brain axis modulation by A. rugosum polysaccharides (Rangsinth et al. 2025) connects to the emerging field of microbiome-mediated neuroprotection, paralleling similar findings with Reishi polysaccharides (Chang et al. 2015, Nature Communications)
• The anti-inflammatory mechanisms (NF-kB inhibition, MEK/ERK pathway modulation) are shared across the Ganodermataceae family, including Turkey Tail and Reishi, suggesting a conserved family-level pharmacological feature