Bioactive components of Ganoderma lucidum and their efficacy and application in cosmetics
灵芝的生物活性成分及其功效与化妆品应用

Ganoderma lucidum is a fungus belonging to the genus Ganoderma and which are widely distributed in China. A large number of modern studies have proven that G. lucidum has antioxidant^[1], hypoglycemic^[2], antitumor^{[3, 4]}, and anti-inflammatory^[5] activities, and they have shown great application potential in improving bread quality^[6], lowering lipid levels^[7], and protecting liver function^{[8, 9]}. Utilizing the wealth of G. lucidum resources to the fullest and actively and successfully creating derivatives of G. lucidum can help the industry flourish in a variety of ways and the market for G. lucidum to keep growing. At present, G. lucidum has been successfully applied in some healthy foods or medicines, such as G. lucidum tea^[10], G. lucidum coffee^[11], G. lucidum wine^[12], and G. lucidum pressed tablet confectionery^[13]. However, the application of G. lucidum as a cosmetic ingredient is rarely reported. With the development of social and economic conditions, people’s requirements for quality cosmetics have gradually increased, and the cosmetics required to be used will not have an impact on the skin and body, but also possess certain skincare and beauty effects. However many of the cosmetics sold in the market are made of chemical raw materials. The emulsifiers, flavors, fragrances, colors, and preservatives added to cosmetics can increase the performance, quality, value, and service life of the cosmetics, but long-term use of cosmetics containing such additives may lead to adverse effects on the skin^[14]. Therefore, there is an urgent need to find some safe and effective cosmetic ingredients to meet people’s current demand for natural and green cosmetics.
灵芝是广泛分布于中国的一种灵芝属真菌。大量现代研究证明， 灵芝具有抗氧化 ^[1] 、降血糖 ^[2] 、抗肿瘤 ^{[3, 4]} 和抗炎 ^[5] 等活性，在改善面包品质 ^[6] 、降低血脂 ^[7] 、保护肝功能 ^{[8, 9]} 等方面展现出巨大的应用潜力。充分利用丰富的灵芝资源，积极开发灵芝衍生物，可以促进灵芝产业的多元化发展，并保持灵芝市场的持续增长。目前， 灵芝已成功应用于一些健康食品或药品中，如灵芝茶 ^[10] 、 灵芝咖啡 ^[11] 、 灵芝酒 ^[12] 、 灵芝压片糖果 ^[13] 等，但灵芝作为化妆品成分应用的报道较少。随着社会经济条件的发展，人们对化妆品品质的要求逐渐提高，要求使用的化妆品既不能对皮肤和身体造成影响，又要具备一定的护肤美容功效。然而市面上销售的化妆品很多都是由化学原料制成的，添加到化妆品中的乳化剂、香精、香料、色素、防腐剂等，可以提高化妆品的性能、质量、价值和使用寿命，但长期使用含有此类添加剂的化妆品可能会对皮肤产生不良影响 ^[14] 。 因此，迫切需要寻找一些安全、有效的化妆品成分来满足人们当前对天然、绿色化妆品的需求。

G. lucidum, as a popular traditional Chinese herb, has many effects in cosmetics, such as anti-aging, whitening, spot-reducing, anti-sensitivity, hydrating, and moisturizing^[15]. Factors such as oxidation, inflammation, radiation, etc., may cause certain problems in the skin, and adding reishi to cosmetics can improve these conditions^[14]. In addition, G. lucidum has low irritation, mild action, and remarkable effect when used. Some famous cosmetic brands have used products such as G. lucidum extract and G. lucidum spore oil in their cosmetics. G. lucidum is regarded as an ideal and beneficial ingredient for the human body in the fields of food, traditional Chinese medicine, and cosmetology. Therefore, in this study, the constituents of G. lucidum, such as polysaccharides and total triterpenes, and their main efficacies in cosmetic products were reviewed. G. lucidum-related cosmetic products were also outlined. We are looking forward to the future development of G. lucidum in light of the domestic and international research results.
灵芝作为一种常见的传统中药，在化妆品中具有抗衰老、美白、淡斑、抗敏感、补水保湿等功效 ^[15] 。氧化、炎症、放射等因素会导致皮肤出现某些问题，在化妆品中添加灵芝可以改善这些问题 ^[14] 。此外， 灵芝刺激性小，作用温和，使用效果显著，一些知名化妆品品牌在其化妆品中使用灵芝提取物、 灵芝孢子油等产品。 灵芝在食品、中药和美容领域被视为对人体有益的理想成分。因此，本研究综述了灵芝的多糖和总三萜等成分及其在化妆品中的主要功效，并概述了灵芝相关化妆品。结合国内外研究成果，我们对灵芝未来的发展充满期待。

With the in-depth study of G. lucidum, many domestic and foreign researchers have isolated many kinds of effective bioactive components from G. lucidum with certain theoretical basis. The main active components of G. lucidum are polysaccharides, triterpenoids, G. lucidum proteins, and other effective components.
随着对灵芝研究的深入，国内外许多研究者从灵芝中分离得到多种有效的生物活性成分，并有一定的理论基础， 灵芝的主要活性成分有灵芝多糖、三萜类化合物、 灵芝蛋白及其他有效成分。

G. lucidum polysaccharides (GLPs) are highly active natural polymers with a helical three-dimensional conformation similar to that of DNA and RNA with helical layers held together by hydrogen bonds and with molecular weights ranging from several thousand to hundreds of thousands^[16]. More than 200 types of GLP have been isolated to date. Natural Ganoderma polysaccharides, which can be isolated from substrates or spores obtained from wild or commercial cultivation, are formed by combining glucose, mannose, galactose, xylose, fucose, and arabinose in different ratios and glycosidic bonds^[17]. Based on modern separation analysis and detection methods, the traditional methods of extracting Ganoderma polysaccharides include hot-water extraction, microwave-assisted extraction, ultrasound-assisted extraction, enzymatic extraction, ultrasound-microwave synergistic extraction, and low-eutectic solvent extraction. The main principles and process of these methods are shown in Table 1. Modern pharmacological studies have shown that Ganoderma polysaccharides have unique antitumor, immunomodulatory, hypoglycemic, lipid-lowering, and antioxidant properties, regulating and improving intestinal barrier function, microbial community diversity, and many other nonbiological activities^[18-21]. Various types of polysaccharides are isolated and extracted from G. lucidum of different origins, parts, species, growth periods, and forms, and the variability in their chemical structures and compositions may affect their specific biological functions^[22-25].
灵芝多糖（GLP）是一种高活性天然高分子化合物，具有类似 DNA 和 RNA 的螺旋三维构象，螺旋层通过氢键连接，分子量从几千到几十万 ^[16] 。迄今为止，已分离出 200 多种 GLP。天然灵芝多糖可从野生或商业栽培的底物或孢子中分离得到，是由葡萄糖、甘露糖、半乳糖、木糖、岩藻糖和阿拉伯糖按不同比例和糖苷键结合而成 ^[17] 。基于现代分离分析和检测方法， 灵芝多糖的传统提取方法包括热水提取、微波辅助提取、超声波辅助提取、酶法提取、超声波-微波协同提取、低共晶溶剂提取等。这些方法的主要原理和流程如表 1 所示。现代药理研究表明， 灵芝多糖具有独特的抗肿瘤、免疫调节、降血糖、降脂、抗氧化、调节和改善肠道屏障功能、微生物群落多样性等多种非生物活性 ^[18-21] 。从不同来源、部位、种类、生长时期和形态的灵芝中分离提取出不同类型的多糖，其化学结构和组成的多样性可能影响其特定的生物学功能 ^[22-25] 。

Ganoderma triterpenoids are the main constituents of G. lucidum and are highly oxidized lanosterane derivatives with molecular weights ranging from 400 Da to 600 Da^[37]. Some triterpenoids are bitter, and their content varies depending on the species, growth conditions, and reproduction stage, with bitter G. lucidum containing a higher content of triterpenoids. Triterpenoids are first isolated from the seed bodies of G. lucidum by Kubota et al.^[38] in 1982. Since then more than 300 triterpenoid species have been detected from G. lucidum based on the gradual improvement of isolation and detection methods^[39]. Ganoderic and ganoderenic acids are the unique triterpenoid species found in G. lucidum, particularly ganoderic acids A, B, C2, D, F, G, and H and ganoderic acids B, C, and D, which have evident anticancer effects^[40]. The methods currently used for extracting Ganoderma triterpenoids are shown in Table 2. Most Ganoderma triterpenoids are isolated and purified from Ganoderma mycelium, spore powder, substrates, and fermentation broth. Domestic and international studies have shown that Ganoderma triterpenoids have a slightly bitter taste and various activities, such as antioxidant properties^[41], prevention of ultraviolet damage^[42], antiviral^[43], hepatoprotection^[44], anti-inflammatory^[45], and regulation of intestinal flora, thereby lowering blood glucose and blood lipid levels^[46].
灵芝三萜是灵芝的主要成分，是高度氧化的羊毛甾烷衍生物，分子量为 400 至 600 Da ^[37] 。有些三萜类化合物具有苦味，其含量随品种、生长条件和繁殖阶段的不同而变化，味苦的灵芝含有更高的三萜类化合物。三萜类化合物最早由 Kubota 等 ^[38] 于 1982 年从灵芝种子体中分离得到。此后，随着分离和检测方法的逐步改进，已从灵芝中检测到 300 多种三萜类化合物 ^[39] 。灵芝和灵芝酸是灵芝中特有的三萜化合物，其中灵芝酸 A、B、C2、D、F、G、H 和灵芝酸 B、C、D 具有明显的抗癌作用 ^[40] 。目前用于提取灵芝三萜的方法如表 2 所示， 灵芝三萜大部分是从灵芝菌丝体、孢子粉、底物和发酵液中分离纯化的。国内外研究表明， 灵芝三萜味微苦，具有抗氧化 ^[41] 、防止紫外线损伤 ^[42] 、抗病毒 ^[43] 、保肝 ^[44] 、抗炎 ^[45] 、调节肠道菌群，从而降低血糖、血脂 ^[46] 等活性。

Apart from polysaccharides and triterpenes, G. lucidum contains a wide range of active ingredients such as proteins, sterols, nucleosides, and alkaloids. G. lucidum contains a variety of proteins and amino acids at high levels, which have immunomodulatory and antitumor effects because of their special immunogenicity. The basic steps of protein extraction are in the following order: washing tissues lysing cells centrifugation to remove membrane fractions obtaining protein extracts^[58]. The most researched G. lucidum protein is the immunomodulatory protein LZ-8. Cheng et al.^[59] verified that recombinant LZ-8 alleviated oxidative stress and inflammatory responses in Parkinson’s disease by establishing a Parkinson’s disease model in mice. Sterols are secondary metabolites of G. lucidum, among which ergosterol was found to be the most abundant. Researchers and scholars have shown that Ganoderma stanols have some anti-inflammatory and antibacterial properties, and they protect cells against oxidative damage^{[60, 61]}. G. lucidum contains a variety of nucleoside analogs such as uracil, adenine, and G. lucidum purine^[7]. Sheng et al.^[62] established micellar electrokinetic chromatography for the determination of 10 nucleosides and bases in different batches of G. lucidum and found that the different geographical origins primarily influence the nucleosides and bases in G. lucidum. Alkaloidal components are low in G. lucidum. Zhao et al.^[63] extracted four new alkaloids from G. lucidum substrates with some antibacterial and anti-inflammatory effects.
除多糖和三萜外， 灵芝还含有蛋白质、固醇、核苷和生物碱等多种活性成分。 灵芝富含多种蛋白质和氨基酸，由于其特殊的免疫原性，具有免疫调节和抗肿瘤作用。蛋白质提取的基本步骤如下：清洗组织→裂解细胞→离心去除膜组分→获得蛋白提取物 ^[58] 。研究最多的灵芝蛋白质是免疫调节蛋白 LZ-8。Cheng 等 ^[59] 通过建立小鼠帕金森病模型，证实重组 LZ-8 可减轻帕金森病中的氧化应激和炎症反应。固醇是灵芝的次级代谢产物，其中麦角固醇含量最丰富。研究者和学者已经证明灵芝甾烷醇具有一定的抗炎和抗菌特性，并且它们可以保护细胞免受氧化损伤 ^[60，61] 。 灵芝含有多种核苷类似物，例如尿嘧啶，腺嘌呤和灵芝嘌呤 ^[7] 。Sheng 等 ^[62] 建立了胶束电动色谱法，用于测定不同批次灵芝中的 10 种核苷和碱基，发现不同的地理来源主要影响灵芝中的核苷和碱基。 灵芝中的生物碱成分较低。Zhao 等 ^[63] 从灵芝底物中提取了 4 种新的生物碱，具有一定的抗菌和抗炎作用。

A variety of biological components of G. lucidum, such as polysaccharides, triterpenes, proteins, and sterols, each with different activities, have been used in medicines, health foods, and cosmetics. At present, G. lucidum has become an important medicinal and food material in China, according to the Notice on the Pilot Management of nine Substances such as Codonopsis pilosula that are Traditionally Used as Both Food and Chinese Herbal Medicinal Materials, which was jointly issued by the National Health and Health Commission and the State General Administration of Market Supervision.
灵芝中含有多种生物活性成分，例如多糖、三萜、蛋白质和甾醇等，已被广泛应用于医药、保健食品和化妆品等领域。根据国家卫生健康委员会、国家市场监督管理总局联合发布的《关于开展党参等 9 种传统食品药材两用管理试点的通知》， 灵芝目前已成为我国重要的药食同源原料。

As shown in Fig. 1, domestic and international studies have indicated that G. lucidum possesses a variety of cosmetic and skin care benefits such as antioxidant, anti-aging, anti-inflammatory, anti-allergy, anti-radiation, whitening, and light spotting, thereby increasing the overall value of G. lucidum in cosmetics. In recent years, the pursuit of green and harmless cosmetic products has directly increased the demand for G. lucidum. Consumers often purchase Lingzhi products for its biological activity, but its complex structure and chemical composition result in more cosmetic benefits of Lingzhi that are still being explored.
如图 1 所示，国内外研究表明， 灵芝具有抗氧化、抗衰老、抗炎、抗过敏、抗辐射、美白、淡斑等多种美容护肤功效，从而提升了灵芝在化妆品中的总体价值。近年来，人们对化妆品绿色无害化的追求直接增加了灵芝的需求。消费者购买灵芝产品往往是因为其生物活性，但灵芝复杂的结构和化学成分使其更多的美容功效尚待探索。

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Figure 1  图 1Main effects of G. lucidum in cosmetology.
灵芝在美容方面的主要功效。

Free radicals are generated in the normal metabolic process of organisms and are produced in large quantities after being subjected to various stimuli (temperature, machinery, pathogens, etc.)^[64]. Large quantities of free radicals primarily cause oxidative stress, sub-health, and a decline in productive function in people. Studies have shown that G. lucidum water-soluble polysaccharides, fermentation broth polysaccharides, and alkali-extracted polysaccharides can prevent lipid peroxidation and reduce the production of hydroxyl, ABTS, and DPPH free radicals to varying degrees^[65-68]. The mechanism of the antioxidant effects on organisms is shown in Fig. 2^[69]. These polysaccharides have three main pathways. First, in the Kelch-like epichlorohydrin-associated protein 1-nuclear factor E2-related factor 2/antioxidant response element (Keap1-Nrf2/ARE) pathway, GLP upregulates the expression level of the Nrf2 gene and downregulates the expression level of the Keap1 gene, which improves the content and vitality of antioxidant enzymes and scavenging of free radicals. Second, GLP scavenges excess free radicals and alleviates the oxidative damage by increasing the content and vitality of endogenous enzymes. Third, GLP reduces the oxidative effect of reactive oxygen species (ROS) on the body and blocks lipid peroxidation^[69]. Zhao et al.^[70] found that GLP fermented with Lactobacillus plantarum was structurally the same, but the antioxidant activity increased, with a stronger ability to regulate the Nrf2-ARE pathway in cells. Milovanovic et al.^[71] extracted wild and cultivated G. lucidum with supercritical carbon oxides and compared the antioxidant capacity and enzyme inhibition potential between the two samples. The results revealed that the cultivated sample contained higher total phenolic content than wild Ganoderma and possessed higher antioxidant capacity and relatively weak lipase activity, indicating that cultivated Ganoderma may be an important source of natural bioactive agents for the preparation of health products.
自由基是在生物体正常代谢过程中产生的，在受到各种刺激(温度、机械、病原体等)后会大量产生 ^[64] 。大量的自由基主要导致人体氧化应激、亚健康状态、生产力下降等。研究表明， 灵芝水溶性多糖、发酵液多糖和碱提多糖都能不同程度地防止脂质过氧化，减少羟基、ABTS 和 DPPH 自由基的产生 ^[65-68] 。其对生物体的抗氧化作用机制如图 2 所示 ^[69] 。这些多糖主要有 3 条途径。首先，在 Keap1-Nrf2/ARE 通路中，GLP 通过上调 Nrf2 基因表达水平、下调 Keap1 基因表达水平，提高抗氧化酶的含量和活力，清除自由基。其次，GLP 通过增加内源酶的含量和活力，清除过量的自由基，减轻氧化损伤。第三，GLP 能降低活性氧（ROS）对机体的氧化作用，阻断脂质过氧化 ^[69] 。Zhao 等 ^[70] 研究发现，用植物乳杆菌发酵得到的 GLP 结构相同，但抗氧化活性提高，对细胞内 Nrf2-ARE 通路的调控能力更强。Milovanovic 等[ 71]研究发现，用植物乳杆菌发酵得到的 GLP 结构相同，但抗氧化活性提高，对细胞内 Nrf2-ARE 通路的调控能力更强。 ^[71] 提取野生和栽培的 G. 采用超临界 CO2 对灵芝进行处理，比较了两种样品的抗氧化能力和酶抑制潜力。结果表明，栽培灵芝样品的总酚含量高于野生灵芝 ，且具有较高的抗氧化能力和相对较弱的脂肪酶活性，表明栽培灵芝可能是制备保健产品的重要天然活性剂来源。

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Figure 2Mechanism of modulation of antioxidant effects of G. lucidum on the organism^[69].

In general, multiple indicators are used to evaluate the antioxidant capacity of substances. At present, the evaluation of the antioxidant capacity of substances has not established a unified evaluation system, although there is a theoretical guidance. In the future, a complete system of the antioxidant effect of G. lucidum should be established, and the system must be improved in accordance with the development of science and technology, so as to form the use of practice.

Aging is a complex natural physiological process, and skin aging is primarily affected by endogenous and exogenous factors. Endogenous factors include gene doctrine, free radical doctrine, non-enzymatic glycosylation aging doctrine, etc., whereas exogenous factors include photoaging, smoke, pollution, etc. The anti-aging efficacy of G. lucidum has been well established in a large number of studies, and its pharmacological mechanism is shown in Fig. 3^[72]. The anti-aging effect is achieved by inhibiting the production of β-galacturonic acid and ROS and enhancing the expression level of 14-3-3ɛ protein, thereby promoting Nrf2 nuclear translocation and Heme Oxygenase-1/NAD(P)H:quinone oxidoreductase 1 (HO-1/NQO1) protein expression. Xu et al.^[73] found that β-1, 3 glucan synthase (GLS) and glucose pyrophosphorylase (ugp) were simultaneously overexpressed in G. lucidum for the first time during their study, and the simultaneous expression of both genes can increase the production of polysaccharides, while demonstrating a stronger anti-aging activity. In investigating the anti-oxidative stress and anti-aging effects of the aqueous extracts of G. lucidum, Cuong et al.^[74] used the nematode Cryptobacterium hidradenii as a model to elucidate its specific pharmacological mechanisms. The results showed that the aqueous extract of G. lucidum could effectively increase nematode resistance to paraquat and heavy metal–induced oxidative stress and prolonged the lifespan of wild-type nematodes; however, this effect was dependent on glucagon-like peptide-1 (GLP-1) but not entirely on DAF-16 (the only forkhead box transcription factors class O (FoxO) homolog in Caenorhabditis elegans). Thus, further studies are necessary.

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Figure 3Regulatory mechanism of the anti-aging effect of G. lucidum on the organism.

In future studies, a more in-depth analysis of the interactions of the active substances within G. lucidum must be conducted to find better ratios and to optimize the anti-aging effects of G. lucidum, as well as to explore the effects of different signaling pathways on the subjects.

The color of the human skin, eyes, and hair depends on the production of melanin, which, depending on its quantity, quality, and distribution, plays an important role in protecting the skin from the harmful effects of UV radiation and oxidative stress from various environmental pollutants^[75]. Most organisms naturally synthesize melanin, where tyrosinase, catecholase, and phenol oxidase catalyze the formation of melanin from a substrate called DOPA (dihydroxyphenylalanine)^[76]. However, excessive melanin in the body can cause pigmentation, resulting in dark skin or freckles, which affects beauty, and tyrosinase inhibition is a common whitening method. Li et al.^[77] found that the inhibition rate of the fermentation broth on complexinase reached 95.1% by optimizing the composition of the G. lucidum fermentation medium and fermentation conditions, and metabolomic analysis of the fermentation broth was performed using mass spectrometry. Liu^[78] investigated the anti-aging and skin-whitening effects of recombinant the G. lucidum immunomodulatory protein (rLZ-8) on D-galactose-induced senescent mice and found that the recombinant protein inhibited the proliferation of melanoma cells, reduced the activity of the rate-limiting enzyme TYR during melanin synthesis, and destroyed melanoma cells, thereby achieving skin-whitening effects.

Inflammation is the body’s defense response to stimuli, and it manifests as redness, swelling, heat, pain, and dysfunction. In general, inflammation is beneficial and is the body’s automatic defense response, but local damage caused by inflammation cannot be ignored. Skin allergy can eventually cause an inflammatory reaction when allergens enter the body, prompting the body to produce the corresponding antibodies, thereby triggering an antigen–antibody reaction^[79]. Some studies have proven that G. lucidum plays an important role in the treatment of inflammation and allergic reactions. Fan et al.^[80] investigated whether GLPs had a protective effect against inflammatory damage and determined its mechanism. The results showed that GLP can effectively reduce lipopolysaccharides (LPS)-induced α-tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) production as well as prevent inflammatory cell injury. Liu et al.^[81] investigated the therapeutic effects of different molecular weights of G. lucidum β-D-glucans on ulcerative colitis and their corresponding mechanisms. The results of the study showed that lowering the molecular weight of G. lucidum by degradation could effectively improve its anti-inflammatory activity. After certain studies, G. lucidum extract has been proven to play an important role in the treatment of histamine-mediated allergic reactions and block histamine release^[22].

Radiation refers to the phenomenon in which a portion of the electromagnetic energy emitted by an emitting source propagates away from the field source and does not return to the field source, and the energy spreads outward in the form of electromagnetic waves or particles. It is widely present in the daily life environment. Radiation pollution has become a major invisible factor endangering human health, which can lead to diseases of the immune system or metabolism, and in serious cases, cause cancer. Domestic and international studies have shown that Ganoderma components such as polysaccharides, glycoproteins, and total triterpenoids play an important role in protecting against radiation and in combating photoaging. Smina et al.^[82] evaluated the application potential of Ganoderma total triterpenoids in preventing γ-radiation-induced damage to hepatic mitochondrial and microsomal membranes as well as to DNA strand breaks in rats and found that Ganoderma triterpenoids exhibited a protective effect against DNA and membrane damage caused by the deleterious effects of radiation. Yu et al.^[83] investigated the preventive effect of GLP and its serum metabolomic mechanism on radiation-damaged mice. The results of the study indicated that platelets in the GLP group were higher than those in the control group, and low-taurine metabolism and glycerophospholipid metabolism were identified as potential biomarkers in GLP-treated mice. Zhou^[84] investigated the mechanism of G. lucidum glycoproteins (Gl-Gp) on photoaging repair by studying the viability of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of malondialdehyde (MDA) and hydroxyproline (HYP), and the expression level of related factors in the homogenates of rat back skin tissues. The results indicated that Gl-Gp repaired the erythematous ulceration of rat back skin after UV irradiation, restored the orderly arrangement of tissue structure and elastic fibers, repaired collagen and elastin, and inhibited the expression level of tumor necrosis and inflammatory factors. The above studies show that the effective biological activity in G. lucidum has a certain effect on radiation protection and the treatment of photoaging, and has a certain prospect for the development of sunscreen and other related cosmetics.

Studies have shown that G. lucidum contains ingredients that can treat frostbite, but the effect is not good because of its poor solubility and drug penetration, so improving its penetration to the skin is necessary. Shen^[85] constructed a G. lucidum triterpene nanogel transdermal drug delivery system by combining nanosuspension and gel to improve the solubility of the drug. This system was validated to have remarkably improved in vitro permeation, retention, and anti-frostbite effect, which is an effective method to improve the transdermal absorption of insoluble active sites, thereby enhancing the efficacy of the drug. Shen et al.^[86] prepared a topical gel of G. lucidum triterpenoids and evaluated its effect on frostbite. The result showed that the penetration rate of the gel was higher than that of the emulsion, whereas the gel was more effective than the emulsion for the treatment of frostbite. Thus, this gel could be used as a novel carrier for the topical treatment of skin diseases.

When the temperature decreases, the skin stratum corneum cannot regulate enough moisturizing factors in time. Consequently, the sebaceous gland activity decreases; the face oils up; the moisture decreases; the skin becomes tight, and fine lines appear under the eyes and beside the nose. Thus, skincare and skin nourishing products with similar effects are used to moisturize the skin, prevent water evaporation, improve microcirculation, and improve the moisturizing properties of the skin. Most of the G. lucidum with moisturizing function are GLPs. Liu et al.^[87] have proven that polysaccharides have a good moisturizing effect because of the hydroxyl group inside the polysaccharides. Liu et al.^[88] made a nanofiber film containing G. lucidum fermentation broth, which was confirmed to be moisturizing, antioxidant, and safe for the skin. Liu et al.^[89] compounded G. lucidum deep culture fluid with various natural additives to prepare skin care products with moisturizing and synergistic functions. The experimental results showed that G. lucidum deep culture fluid can improve the water-locking function of the skin barrier structures and increase the water content of the skin stratum corneum. G. lucidum deep culture fluid also has a moisturizing and synergistic effect, which indicates its great application potential in the development of skincare products.

Dandruff and hair loss are primarily due to seborrheic dermatitis, neurodermatitis, and fungal infections. Malassezia spp. are lipophilic fungi that are part of the normal flora of the human skin and are pathogens of dandruff and seborrheic dermatitis^[90]. G. lucidum has remarkable antibacterial effects^[91], and it can promote blood circulation and damaged cell repair in the head skin to promote hair growth. Chen^[92] treated 40 cases of patchy baldness with compound G. lucidum hair growth tincture, with a cure rate of 70%, confirming the efficacy of G. lucidum topical hair growth solution.

In recent years, G. lucidum in cosmetic products still has several unknown effects and mechanisms other than the abovementioned effects. In the future, increasing the breadth and depth of G. lucidum in cosmetic skin care is necessary, and experimental research and product manufacturing must be combined, so that it is no longer used solely for scientific research and can be combined with industry, academia, and research in the future to adapt to the trend of the general public^[93].

In the pursuit of green and safe cosmetics and with the development of traditional Chinese skincare concepts, G. lucidum has gradually become a popular product in the cosmetic industry because of its unique efficacy^{[94, 95]}. A summary of G. lucidum-related cosmetics and their claimed efficacy in the market is shown in Table 3. The table illustrates that the majority of cosmetic goods containing G. lucidum are made in China due to the fact that the herb is a commonly used traditional Chinese medicine in that country. Traditionally, people have been highly evaluating G. lucidum; therefore, it is easier to accept G. lucidum cosmetic products. Given their geographic location and cultural development, foreign countries have little understanding of G. lucidum, and most of the cosmetic products they develop cater to the Chinese market; thus, they do not truly reflect its efficacy and add less G. lucidum. The development of G. lucidum focuses on G. lucidum, Ganoderma purpureum, and Ganoderma nigrum^[96], and only G. lucidum and G. purpureum are recorded in the Chinese Pharmacopoeia at present, which states that G. lucidum or G. purpureum can tonify qi, tranquilize the mind, and relieve cough and asthma. In addition, G. lucidum or G. purpureum is often used in cases of restlessness of mind and spirit, insomnia and palpitation, shortness of breath, and loss of appetite. At present, the development of G. lucidum focuses on the substrate, and fewer studies have been conducted on the addition of spore powder and mycelium. G. lucidum is used in cosmetics mostly in essence water, lotion, and mask and less in color cosmetics. Therefore, actively developing products with combined efficacy based on the existing G. lucidum series of cosmetics on the market is necessary.

The active ingredients and functional properties of G. lucidum have been extensively studied in food and medicine. His antioxidant, anti-aging and other functions have a great future in cosmetics, and other effects are also promising. The cosmetic industry is a sunrise industry. People are now more aware of green safety, and G. lucidum has a variety of effective activities, which can carry out multi-angle and multi-dimensional skin care^[97-100]. As a kind of cosmetic with developmental potential and efficacy, G. lucidum cosmetics must be continuously and deeply researched, developed, and applied. Some cosmetic products containing G. lucidum are already available in the market, but some aspects still need to be improved. Thus, in-depth research must be conducted as follows: 1) the efficacy of G. lucidum can be targeted to expand the scope of the research and develop more G. lucidum cosmetics with effects other than antioxidant and anti-aging; 2) further research should be carried out on GLPs, total triterpenoids, as well as proteins, nucleosides, and alkaloids to better apply their bioactive ingredients to cosmetics; 3) the additive mode of G. lucidum cosmetics is mostly in the form of extracts, which can be processed by biotransformation, which is a green and safe method; 4) cosmetic products and other disciplines can be combined, such as bioengineering and pharmaceutical engineering, to create safer and more effective G. lucidum cosmetics. Overall, the research of G. lucidum in cosmetics remains to be further studied, but cosmetics with multi-functionality is still worthy of attention, and its market and potential are still considerable.

This research was funded by the National Natural Science Foundation of China, (No. 32202044) and Zhejiang Provincial Natural Science Foundation (No. LY17C200017).