A review of the phytochemical and pharmacological properties of Amauroderma rugosum

Abstract

Amauroderma rugosum (AR) is a basidiomycete in the Ganodermataceae family that has been used traditionally to prevent epileptic attacks and constant crying in babies. However, AR has not been widely studied scientifically. In this review, we summarize the phytochemical components and pharmacological properties of AR that have been reported in the literature. Chemical analyses have revealed that the components of AR include sterols, flavonoids, fatty acids and esters, aromatic acids and esters, phenols, polysaccharides, and triterpenes. Pharmacological properties of AR include antioxidant, anti‐inflammatory, neuroprotective, anti‐cancer, anti‐hyperlipidemic, anti‐epileptic, and antibacterial effects. These findings suggest that AR and its bioactive ingredients have potential therapeutic applications, particularly for age‐related diseases.

1. INTRODUCTION

Amauroderma rugosum (AR), which is also called “jiazhi” or “wuzhi” in traditional Chinese medicine, is a basidiomycete in the Ganodermataceae family. It is mainly grown in tropical and subtropical zones, ¹ and its geographic distribution includes China, South Pacific, South Atlantic, Indonesia, Taiwan, Equatorial Guinea, and Australia. ² As shown in Figure 1, AR has a distinctive appearance. The cap of the fruiting body is round or subrotund, with a width of approximately 6–9 cm and a thickness of around 0.7–1.3 cm (sometimes up to 1.7 cm near the stipe). ³ The color of the cap is taupe to black. ³ Additionally, the cap is tomentose and irregularly wrinkled with thin or blunt edges. ³ The hymenium of AR has a white surface, which turns dark red when scratched. ³ , ⁴ Since it gives the appearance of bleeding when scratched, AR is sometimes called “Blood Lingzhi” in Chinese. The stipe of AR is 5–9 cm long, while the basidiospores are 9–12 μm long and 7–9 μm wide with a smooth exospore. ³

FIGURE 1.

The fruiting body of Amauroderma rugosum

There have been very few scientific studies on AR. The aim of this review is to summarize the phytochemical components and pharmacological effects of AR that have been reported and to discuss its possible applications and directions for future research.

2. CHEMICAL CONSTITUENTS OF AR

2.1. Sterols

Fourteen sterols have been identified in ethyl acetate and hexane fractions of AR (Table 1). Most of them, except ergosterol, ergosterol peroxide, and (22E,24R)‐ergosta‐7,22‐diene‐3β,5α,6α‐triol, were isolated from the Amauroderma genus for the first time. Many of the sterols found in AR are bioactive. ⁵ , ⁶ , ⁷ For instance, 3,3‐dimethoxy‐ergosta‐7,22‐diene, citreoanthrasteroid B, ergosta‐7,22‐dien‐3β‐yl linoleate, and 5α,8α‐epidioxyergosta‐6,22‐dien‐3β‐yl linoleate exhibit anti‐proliferative activity toward HepG2 and MDA‐MB‐231 cancer cells. Moreover, ergosterol, 1(10 → 6)abeo‐ergosta‐5,7,9,22‐tetraen‐3α‐ol, citreoanthrasteroid B, and ergosterol peroxide reduce nitric oxide production in RAW264.7 cells. ⁵ , ⁶ , ⁷ These findings suggest the potential anti‐inflammatory and anti‐cancer utility of AR.

TABLE 1.

Compounds identified in AR

Class	Compounds	Fractions	Parts of AR	Ref
Sterols	Ergosterol	Hexane	Mycelia, fruiting bodies	[5, 6]
	(22E,24R)‐Ergosta‐7,22‐diene‐3β,5α,6α‐triol 1(10 → 6)Abeo‐(22E)‐24‐methyl‐cholesta‐5,7,9,22‐tetraene‐3α,11α‐diol 1(10 → 6)Abeo‐ergosta‐5,7,9,22‐tetraen‐3α‐ol 3,3‐Dimethoxy‐ergosta‐7,22‐diene 5,8‐Epidioxy‐5α,8α‐ergosta‐6,9,22E‐tien‐3β‐ol 5α,8α‐Epidioxyergosta‐6,22‐dien‐3β‐yl linoleate 5α,8α‐Epidioxyergosta‐6,22‐dien‐3β‐yl stearate Citreoanthrasteroid B Ergosta‐4,6,8(14),22‐tetraen‐3‐one Ergosta‐7,22‐dien‐3‐one Ergosta‐7,22‐dien‐3β‐yl linoleate Ergosterol peroxide Isocyathisterol	Ethyl acetate	Fruiting bodies	[7]
Flavonoids	Apigenin Luteolin Naringenin	Ethyl acetate	Fruiting bodies	[8]
Fatty acids and ester	Ethyl linoleate	Hexane	Mycelia	[5]
	(10E,12E)‐9,14‐Dioxo‐10,12‐octadecadienoic acid (8E,10E)‐12‐Hydroxy‐7‐oxo‐8,10‐octadecadienoic acid (E)‐8‐Oxo‐9‐octadecenoic acid (E,E)‐13‐Oxooctadeca‐9,11‐dienoic acid (E,E)‐9‐Oxooctadeca‐10,12‐dienoic acid	Ethyl acetate	Fruiting bodies	[7]
Phenols	Amauroderma Caffeic acid cis‐3‐[2‐[1‐(3,4‐Dihydroxyphenyl)‐1‐hydroxymethyl]‐1,3‐benzodioxol‐5‐yl]‐(E)‐2‐propenoic acid Ethyl 3,4‐dihydroxybenzoate Methyl‐3,4‐dihydroxybenzoate N‐trans‐Caffeoyltyramine p‐Hydroxybenzoic acid Protocatechuic acid Vanillic acid	Ethyl acetate	Fruiting bodies	[7, 8]
Polysaccharides	Arabinose Fucose Galactose Galacturonic acid Glucose Glucuronic acid Mannose Rhamnose Ribose Xylose	Aqueous	Fruiting bodies	[14, 24, 25]
Aromatic acids and esters	bis(2‐Ethylhexyl)benzene‐1,2‐dicarboxylate Cinnamic acid Dibutyl phthalate Diisobutyl phthalate	Ethyl acetate	Fruiting bodies	[7, 8]
Misc. compounds	(−)‐Delobanone (−)‐Hinokinin Aurantiamide acetate Jacareubin	Ethyl acetate	Fruiting bodies	[7, 8]

2.2. Flavonoids

Luteolin, apigenin, and naringenin are the flavonoids found in AR. ⁸ Luteolin can be found in many traditional Chinese medicines, and it has anti‐cancer, ⁹ anti‐neuroinflammatory, ¹⁰ antioxidant, and anti‐allergic properties. ¹¹ Apigenin exhibits anti‐inflammatory, anti‐toxicant, and anti‐cancer effects. ¹² Naringenin has anti‐diabetic, antiatherogenic, anti‐depressant, immunomodulatory, anti‐tumor, anti‐inflammatory, and DNA‐protective properties. ¹³ The presence of these compounds suggests potential applications of AR for the therapy of inflammatory and malignant diseases.

2.3. Fatty acids and esters

Six fatty acids and esters have been identified in AR (Table 1). (E,E)‐13‐Oxooctadeca‐9,11‐dienoic acid, (E,E)‐9‐oxooctadeca‐10,12‐dienoic acid, (10E,12E)‐9,14‐dioxo‐10,12‐octadecadienoic acid, and (E)‐8‐oxo‐9‐octadecenoic acid inhibit proliferation of HepG2 and MDA‐MB‐231 cancer cells. ⁷ Among them, the anti‐proliferative effect of (E,E)‐13‐oxooctadeca‐9,11‐dienoic acid was strongest, with IC₅₀ values of 24.6 ± 2.5 and 21.9 ± 2.2 μM on HepG2 and MDA‐MB‐231 cell lines, respectively. In addition, (8E,10E)‐12‐hydroxy‐7‐oxo‐8,10‐octadecadienoic acid exhibits anti‐inflammatory activity. ⁷

2.4. Phenolic compounds

The total phenolic compound content found in an aqueous extract of the fruiting body of AR was 5.53 ± 0.11 mg gallic acid equivalent per gram. ¹⁴ Interestingly, the total phenolic compound content in mycelia was 25‐fold higher than that of the fruiting body. ⁵ Using ethyl acetate as extractant increased the total phenolic compound content fivefold, whereas ethanol was slightly less effective than water for the extraction of phenolic compounds from AR. ⁵ The total phenolic compound content of wild and domesticated AR was found to be comparable. ¹⁵

Nine phenolic compounds have been found in ethyl acetate extracts of AR (Table 1). Vanillic acid exhibits antioxidant, ¹⁶ antibacterial, ¹⁷ and chemopreventive effects. ¹⁸ p‐hydroxybenzoic acid has antidiabetic and antioxidant properties. ¹⁹ , ²⁰ Cis‐3‐[2‐[1‐(3,4‐dihydroxyphenyl)‐1‐hydroxymethyl]‐1,3‐benzodioxol‐5‐yl]‐(E)‐2‐propenoic acid is a new natural compound isolated from AR, and its biological properties have not been elucidated yet. ⁷ Ethyl 3,4‐dihydroxybenzoate exhibits anti‐cancer activity on esophageal squamous cell carcinoma cells. ²¹ Caffeic acid has antioxidant, anti‐inflammatory, and anti‐cancer properties, ²² while N‐trans‐caffeoyltyramine induces insulin promoter activity. ²³

2.5. Polysaccharides

Polysaccharide contents of aqueous and ethanol extracts of AR are around 1.12 ± 0.23 mg glucose equivalent per gram (mg GE/g) ¹⁴ and 3.22% ± 0.26%, respectively. ²⁴ The chemical components of polysaccharides found in AR are mainly galactose, glucose, and mannose ²⁵ (Table 1). It has been reported that polysaccharide fractions of AR with molecular masses of 1498, 450, and 7 kDa exhibit 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS) and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical‐scavenging activities, ²⁶ which indicates the antioxidant potential of AR.

2.6. Triterpenes

The triterpene content in aqueous extracts of AR ranges from 1.00% ± 0.08% to 0.32% ± 0.14%. ¹⁴ , ²³ However, further chemical analysis is required to identify these triterpenes.

2.7. Aromatic acids and esters

Cinnamic acid, bis(2‐ethylhexyl) benzene‐1,2‐dicarboxylate, dibutyl phthalate, and diisobutyl phthalate are the aromatic acids and esters present in AR. ⁷ , ⁸ Cinnamic acid has anti‐cancer, anti‐microbial, and anti‐diabetic properties. Its effects on Zika virus infection and neurological disorders have also been reported. ²⁷ , ²⁸ Larvicidal activity against mosquitoes has been demonstrated for DEHP. ²⁹ Dibutyl phthalate may induce oxidative stress in the zebrafish brain ³⁰ and delayed neurodevelopment in mice. ³¹ It may also disrupt circadian rhythm in Drosophila and human cells. ³² Diisobutyl phthalate may affect fertility and cause liver toxicity. ³³

2.8. Miscellaneous compounds

In addition to the above classes of chemicals, AR contains a variety of other compounds, such as (−)‐delobanone, a sesquiterpene; aurantiamide acetate, an alkaloid; (−)‐hinokinin, a dibenzyl butyrolactone lignan; and jacareubin, a xanthone derivative. ⁷ , ⁸ Aurantiamide acetate has been shown to suppress malignant gliomas, ³⁴ inflammation, influenza A virus infection, ³⁵ and neuroinflammation. ³⁶ (−)‐Hinokinin enhances the anti‐cancer effect of doxorubicin on breast cancer cells. ³⁷ Jacareubin exhibits antibacterial, ³⁸ antioxidant, ³⁹ and anti‐cancer activities. ⁴⁰

3. TOXICITY OF AR

The usual dose of AR in traditional Chinese medicine is 10–15 g per decoction. ⁴¹ From long‐term medicinal and dietary history, no adverse effects or toxicity of AR have been reported. Neither aqueous nor ethanolic extracts of AR exhibit toxic effects on RAW264.7 cells at concentrations below 10 μg/ml. ¹⁵ Similarly, an aqueous extract of AR did not decrease PC‐12 cell viability at a concentration of 2 mg/ml. ¹⁴ An in vivo study found that there was no change in body weight and no pathological changes in different organs in Sprague–Dawley rats receiving a single dose of AR mycelial powder as high as 2 g/kg. ⁴²

4. POTENTIAL PHARMACOLOGICAL ACTIVITIES OF AR

In traditional Chinese medicine, AR is used for the treatment of indigestion as well as acute or chronic nephritis. ⁴¹ Although there have been few pharmacological studies on AR, its antioxidant, anti‐inflammatory, neuroprotective, anti‐cancer, anti‐hyperlipidemic, anti‐epileptic, and anti‐microbial effects have been reported (Table 2). Most of these effects were determined from in vitro studies, while in vivo data are rare.

TABLE 2.

Potential pharmacological effects of Amauroderma rugosum (AR)

Potential pharmacological effect	Parts of AR	Extraction method	Findings	Ref
Antioxidant	Mycelia	Ethyl acetate	Strong antioxidant activity based on DPPH and ABTS assays	[5]
	Fruiting bodies	Aqueous	DPPH‐scavenging activity and Cu2+‐reducing antioxidant capacity Decreased 6‐hydroxydopamine (OHDA)‐induced reactive oxygen species (ROS) production Reduced mitochondrial functions	[14, 26]
		Ethanol	DPPH‐scavenging activity and ABTS cation‐scavenging activity	[15, 43]
		Ethyl acetate	Antioxidant effect via total phenolic content DPPH‐scavenging activity and Cu2+‐reducing antioxidant capacity Reduced lipid peroxidation Chelation of ferrous ion	[8, 44]
Anti‐inflammatory	Mycelia	Hexane	Dose‐dependent inhibition of NO production in lipopolysaccharide (LPS)‐stimulated RAW264.7 cells NO radical‐scavenging activity	[5, 6]
	Fruiting bodies	Aqueous	Inhibition of NO production in LPS‐stimulated in RAW264.7 cells	[7]
		Ethyl acetate	Inhibition of NO production in LPS‐stimulated in RAW264.7 cells	[7]
		Ethanol	Scavenging of NO radicals and suppression of NO production in LPS‐stimulated RAW264.7 cells Downregulation of pro‐inflammatory cytokines IL‐6 and TNF‐α Upregulation of anti‐inflammatory cytokine, IL‐10	[15]
Neuroprotective	Fruiting bodies	Aqueous	Protection against 6‐OHDA‐induced toxicity in PC‐12 cells Anti‐apoptotic effect against 6‐OHDA‐induced apoptosis in PC‐12 cells by downregulating pro‐apoptotic protein expressions and upregulating the Akt/mTOR and MEK/ERK‐dependent signaling pathways	[14]
Anti‐cancer	Fruiting bodies	Aqueous	Inhibition of MCF7 breast carcinoma growth Increased production of pro‐inflammatory cytokines TNF‐α and IL‐6 Anti‐proliferative effect of polysaccharides on A549 and HT‐29 cancer cells	[7, 26, 45]
		Methanol	Inhibition of A549 cancer cell and human lung adenocarcinoma NCI‐H1975 cell growth	[46]
		Ethanol and ethyl acetate	Inhibition of HepG2 and MDA‐MB‐231 cancer cell growth	[7]
Anti‐hyperlipidemic	Fruiting bodies	Ethyl acetate	Inhibition of Cu2+‐induced low‐density lipoprotein (LDL) oxidation Inhibition of HMG‐CoA reductase activity Downregulation of sterol‐regulatory element binding factors in oleate‐induced HepG2 cells Raising high‐density lipoprotein (HDL) and suppressing LDL and very‐low‐density lipoprotein (VLDL) production through the reverse cholesterol transport‐mediated pathway Decreasing intracellular and secreted total triglyceride and total cholesterol in oleate‐induced HepG2 cells by downregulation of ApoB‐100 and ApoE and upregulation of ApoA1	[8, 44, 47]
Anti‐epileptic	Mycelia, fruiting bodies	Hexane	Decreasing kainic acid‐induced epileptic seizure symptoms in rats	[6]
Anti‐microbial	Fruiting bodies	Ethanol	Strong inhibition of Clostridium difficile, Streptococcus pyogenes, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli	[43]

4.1. Antioxidant effect

The antioxidant effect is the most reported bioactivity of AR. Both fruiting bodies and mycelia of AR exhibit strong antioxidant activity. Ethanolic, ethyl acetate, and aqueous extracts of AR all exhibit DPPH‐ and ABTS‐scavenging activity. ⁵ , ⁸ , ¹⁴ , ¹⁵ , ²⁶ , ⁴³ , ⁴⁴ Among these extracts, the antioxidant capacity of the ethyl acetate extract from AR fruiting bodies is strongest. ⁴⁴ A possible reason for this is that the ethyl acetate extract contains the highest concentration of phenolic compounds, which are known to have good antioxidant capacity. The aqueous extract of AR, which is rich in polysaccharides, also showed significant radical‐scavenging activities against DPPH, ABTS, and hydroxyl radicals. ²⁶

4.2. Anti‐inflammatory effect

It has been reported that the hexane extract of AR mycelia and aqueous, ethyl acetate, and ethanolic extracts of AR fruiting bodies decreases nitric oxide production in LPS‐stimulated RAW264.7 and BC‐2 microglial cells. ⁵ , ⁶ , ⁷ , ¹⁵ Moreover, AR downregulates gene expression of pro‐inflammatory cytokines such as tissue necrosis factor‐α, while upregulating gene expression of anti‐inflammatory cytokines such as IL‐10, in LPS‐stimulated RAW264.7 cells. ¹⁵ Interestingly, AR may increase concentrations of pro‐inflammatory cytokines TNF‐α and IL‐6 in RAW264.7 cells without pretreatment with lipopolysaccharide. ⁴⁵ This result suggests an immunomodulatory effect of AR, stimulating immune cells under basal conditions but suppressing the immune cell response under inflammatory conditions.

4.3. Neuroprotective effect

A recent study has demonstrated that AR can protect PC12 cells, a classical neuronal cell model, from 6‐OHDA‐induced toxicity. ¹⁴ The results of DPPH and total antioxidant capacity assays revealed that an aqueous extract of AR can scavenge reactive oxygen species. Moreover, an aqueous extract of AR decreased cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis of PC12 cells induced by 6‐OHDA. The neuroprotective effect of AR may be mediated by the downregulation of apoptotic proteins such as cleaved caspase 9, cleaved caspase 3, and cleaved PARP, with a concurrent upregulation of the Akt/mTOR and MEK/ERK‐dependent signaling pathways. ⁹

4.4. Anti‐cancer effect

Extracts of AR have been shown to significantly inhibit the proliferation of several cancer cell lines, including HepG2, ⁷ MDA‐MB‐231, ⁷ MCF‐7, ²⁶ HT‐29, ⁴⁵ A549, ⁴⁵ , ⁴⁶ and tyrosine kinase inhibitor (TKI)‐resistant NCI‐H1975. ⁴⁶ In a study comparing different crude extracts of Ganoderma and Amauroderma species, the methanol extract of AR exhibited the strongest anti‐proliferative activity toward A549 and TKI‐resistant NCI‐H1975 lung cancer cells. ⁴⁶

The anti‐proliferative effects of ethanol and ethyl acetate extracts of AR have been compared in A549, HepG2, and MDA‐MB‐231 cancer cells, with the ethyl acetate extract exhibiting the most potent activity. ⁷ Furthermore, several anti‐proliferative compounds have been identified in ethyl acetate extracts of AR, such as (E,E)‐13‐oxooctadeca‐9,11‐dienoic acid, which inhibits the proliferation of HepG2 and MDA‐MB‐231 cells with IC₅₀ values of 24.6 ± 2.5 and 21.9 ± 2.2 μM, respectively. As mentioned earlier, AR increases the production of pro‐inflammatory cytokines, such as TNF‐α and IL‐6, in murine macrophage cells. ⁴⁵ It is of interest to note that such an immunostimulatory effect of AR could play a vital role in the prevention and treatment of cancer. ⁴⁵

4.5. Anti‐hyperlipidemic effect

The ethyl acetate extract of the AR fruiting body has been shown to reduce total cholesterol and total triglyceride levels in oleate‐stimulated HepG2 cells. ⁴⁴ , ⁴⁷ This effect is mediated via downregulation of ApoB‐100 and ApoE, combined with upregulation of ApoA1. Extracts of AR also inhibit the oxidation of LDL and reduce HMG‐CoA reductase activity. ⁸ , ⁴⁴ In addition, AR increases the production of HDL but suppresses the production of LDL and VLDL. ⁴⁴ , ⁴⁷ These findings suggest that AR may be beneficial for the management of atherosclerosis.

4.6. Anti‐epileptic effects

Interestingly, necklaces made of AR have traditionally been worn in Malaysia for the prevention of epileptic episodes and baby crying at night. ⁴⁸ Although there are limited data on the anti‐epileptic effects of AR, it has been shown to decrease symptoms induced by kainic acid in a rat model of epileptic seizure. ⁶

4.7. Anti‐microbial effects

Ethanolic extracts of AR have been shown to inhibit the growth of C. difficile, S. pyogenes, P. aeruginosa, S. aureus, and E. coli. ⁴³ Among these bacteria, AR exhibited the strongest anti‐microbial effects against S. pyogenes and P. aeruginosa. S. pyogenes is a leading cause of life‐threatening infectious disease, ⁴⁹ while P. aeruginosa can lead to conditions such as pneumonia, urinary tract infection, and septic shock. ⁵⁰ The potential development of AR as an anti‐microbial product for the prevention of infectious diseases requires further study.

5. DISCUSSION AND FUTURE PROSPECTS

This review summarizes studies on the phytochemistry and potential pharmacological properties of AR. More than 50 compounds have been identified in AR. Biological activities such as antioxidant, anti‐inflammatory, anti‐cancer, neuroprotective, anti‐hyperlipidemic, and anti‐epileptic effects of AR have also been reported.

AR is not as commonly used as Ganoderma lucidum (GL) in traditional Chinese medicine. However, some of the biological properties of AR may be comparable to or even stronger than those of GL. A recent study has shown that total polysaccharides and triterpenes were similar in aqueous extracts of AR and GL. Interestingly, the AR extract contained more phenolic compounds than the GL extract, ⁵¹ which suggests that AR may have better antioxidant properties than GL. Consistent with this, a study comparing the radical‐scavenging activities of AR, GL, and Ganoderma sinense (GS) found that the scavenging effect of AR extract was two‐ to threefold higher than those of GL and GS extracts. This finding supports the superior antioxidant effect of AR. ¹⁰ In another study on the inhibition of nitric oxide production in LPS‐treated RAW264.7 cells, the effect of a crude polysaccharide fraction of AR was similar to that of GL. ⁵² , ⁵³

The excellent antioxidant and anti‐inflammatory effects of AR may make it useful for the treatment and prevention of age‐related problems. Aging is an unavoidable, universal biological phenomenon, in which tissue and organ functions progressively decline over time. Although different hypotheses have been put forward to explain the cellular and molecular mechanisms of aging, many studies have suggested that age‐associated functional loss is basically due to the accumulation of oxidative stress‐induced molecular damage. Exposure to ROS can induce mitochondrial damage. The resulting defective electron transfer and oxidative phosphorylation are associated with further increases in ROS production, thus establishing a vicious circle. Furthermore, increased oxidative stress leads to increased production of pro‐inflammatory cytokines, which causes chronic low‐grade inflammation that contributes to further generation of ROS. Therefore, another vicious circle is established in which chronic oxidative stress and inflammation feed each other. The benefits of antioxidant and anti‐inflammatory natural products have long been proposed for healthy aging. A typical example is the case of polyphenols, which are largely found in fruits, vegetables, cereals, and beverages. An epidemiological study found that French people had low incidence of cardiovascular diseases despite high consumption of saturated fat. ⁵⁴ This paradox might be attributed to their high wine consumption, which provides high levels of antioxidant polyphenols. ⁵⁵ Wine and/or polyphenols can also reduce the incidence of other age‐related pathologies, such as neurodegeneration, cancer, and osteoporosis. ⁵⁶ AR not only has promising antioxidant and anti‐inflammatory properties, but also exhibits potential anti‐cancer, anti‐hyperlipidemic, and neuroprotective effects. All of these biological activities of AR are beneficial to healthy aging, since cancer, hyperlipidemia, and neurodegenerative diseases are common problems in the elderly.

There is still a long way to go to confirm the beneficial effects of AR, and more studies are definitely required. For instance, the methodology of extraction should be optimized because it can affect the yield and types of bioactive compounds isolated from AR. The method of cultivation is also important because different conditions, such as temperature, light, humidity, and substrates, can affect the biosynthesis of compounds in AR. Indeed, it has been reported that while both wild and domesticated AR show anti‐inflammatory effects in LPS‐stimulated RAW264.7 cells, wild AR exhibits better radical‐scavenging activity than domesticated AR. ¹⁵

Almost all AR bioactivity studies reported have been conducted in in vitro models. It is necessary to confirm the pharmacological effects of AR in in vivo models of inflammatory diseases, neurological disorders, cancer, and other conditions. In addition, the mechanisms of action of AR and the active ingredients involved require thorough investigation. Similarly, because of limited toxicity data, more studies are needed to evaluate the acute and chronic toxicity of AR extract and its components in different animal models. The toxicity of AR should not be neglected because it contains dibutyl phthalate and diisobutyl phthalate, which may have detrimental effects as discussed earlier. Although the amounts of dibutyl phthalate and diisobutyl phthalate are supposedly very low, caution should still be taken when AR is used as a food supplement or medication. All of these aspects are crucial for future drug development and quality control. Clinical studies will also be required to validate its therapeutic applications. It has been reported that extracts from the mycelia of AR exhibit low toxicity toward MCF‐7 cancer cells, ⁴² but those from AR fruiting bodies significantly inhibited their growth. ⁵³ It is, therefore, important to compare different parts of AR (e.g., cap, stem, mycelium, and spores) because they may contain different levels and types of bioactive compounds, hence affecting their potential pharmacological effects and potency. It would be particularly worthwhile to compare the mycelium and fruiting bodies of AR. The reason for this is that the mycelium can be cultured in liquid media and growth is fast, potentially saving time and production cost. Furthermore, the chemical content of mycelium can be easily controlled and manipulated by modification of the liquid culture medium.

In conclusion, with its promising antioxidant, anti‐inflammatory, and anti‐cancer activities, among others, it is hoped that AR and/or its active ingredients can be developed as novel drugs or supplements that may be beneficial to human health and applicable in a wide variety of age‐related diseases.

CONFLICT OF INTEREST

All authors declare no conflict of interest.

Zheng C‐W, Cheung TM‐Y, Leung GP‐H. A review of the phytochemical and pharmacological properties of Amauroderma rugosum . Kaohsiung J Med Sci. 2022;38(6):509–516. 10.1002/kjm2.12554