1. Introduction

2. Review Methodology

3. Ganoderma lucidum: Botanical Overview, Characterization, Uses in Traditional Medicine and Chemical Studies

4. Pharmacological and Toxicological Properties

4.3. Dosage Forms and Posology

G. lucidum is available in various dosage forms and can be consumed by different routes.

The appropriate dosage, and posology of G. lucidum may depend on factors such as the specific formulation, the individual’s age, overall health, and the intended purpose of use. Some of common dosage forms, and posology options for G. lucidum already presents in the market are:

Capsules or Tablets: G. lucidum is commonly available in the form of capsules or tablets. The recommended dosage may vary depending on the concentration of G. lucidum extract or powder in each capsule/tablet. A common dosage range is 1-3 capsules/tablets per day, taken with water or as directed by a healthcare professional [2,26].

Powder: G. lucidum powder can be mixed with water, juice, smoothies, or other beverages. The dosage may vary depending on the specific product, and the desired effects. Generally, a typical dosage range is 1-3 grams of G. lucidum powder per day [2,26]. It is advisable to start with a lower dosage, and gradually increase if needed, based on individual tolerance, and response.

Extracts: G. lucidum extracts are available in liquid or concentrated forms [2,26]. These extracts are often standardized to contain specific amounts of bioactive compounds. The dosage and posology for G. lucidum extracts can vary depending on the concentration and potency of the extract.

Tea or Decoction: G. lucidum can be brewed as a tea or decoction. Dried G. lucidum slices or powder can be simmered in water for a certain period to extract the bioactive compounds. The dosage of G. lucidum tea or decoction can vary depending on the concentration, brewing time, and individual preferences [1,2]. It is recommended to start with a small amount, and adjust the dosage based on taste, and individual response.

Topical Formulations: G. lucidum extracts or creams are also available for topical use. These formulations are often used for skin health or cosmetic purposes [2,26]. The dosage and posology for topical products may depend on the specific formulation, and intended use.

Table 4. G. lucidum dosage forms, and posology available [2,26].

Table 4. G. lucidum dosage forms, and posology available [2,26].

Dosage Forms	Posology
Tablets or Capsules	1-3 capsules/tablets of G. lucidum per day.
Powder	1-3 grams of G. lucidum powder per day.
Extracts	Can vary depending on the concentration, and potency of the extract.
Tea or Decoction	Can vary depending on the concentration, brewing time, and individual preferences.
Topical formulations	Can may depend on the specific formulation, and intended use.

It’s important to note that the optimal dosage form, and posology of G. lucidum can vary depending on individual factors, and the specific health goals. Consulting with a healthcare professional or a qualified herbalist is recommended to determine the appropriate dosage, and posology for your specific needs, and to ensure safe, and effective use of G. lucidum.

5. Application of Ganoderma lucidum in Cancer Therapy

6. Application of Ganoderma lucidum in Nanotechnology

7. Regulatory Issues and Clinical Trials

7.1. Preclinical Studies

Preclinical studies that explore the application of G. lucidum in nanotechnology have shown promising results for various therapeutic purposes. These studies have been utilized nanotechnology-based approaches to enhance the delivery, efficacy, and selectivity of bioactive compounds derived from G. lucidum.

Enhanced Drug Delivery: Nanoparticles loaded with G. lucidum bioactive compounds have been investigated for improved drug delivery in cancer therapy. In one study, polymeric nanoparticles loaded with GLPs exhibited enhanced cellular uptake, and cytotoxicity against cancer cells, when compared with free polysaccharides [3,19]. The resulted NPs demonstrated sustained release of the bioactive compounds, resulting in prolonged anticancer effects.

Targeted Therapy: Targeted delivery of G. lucidum bioactive compounds to cancer cells has been achieved using functionalized nanoparticles. In a preclinical study, folate-conjugated NPs encapsulating GLTs selectively targeted folate receptor-expressing cancer cells.^[3,19] This targeted delivery approach improved the efficacy of the bioactive compounds, and reduced toxicity to healthy cells.

Synergistic Effects: Nanotechnology has been employed to combine G. lucidum bioactive compounds with other therapeutic agents, leading to synergistic effects. For example, in a preclinical study, co-encapsulation of GLTs, and some chemotherapeutic drugs (e.g., Paclitaxel, Doxorubicin, Cisplatin, 5-Fluorouracil, Gemcitabine, Etoposide, and Vinblastine) within nanoparticles resulted in enhanced cytotoxicity against cancer cells compared to the individual treatments alone [3,19]. The combination therapy demonstrated improved antitumor activity, and reduced drug resistance.

Immunomodulation: Nanotechnology-based formulations incorporating G. lucidum bioactive compounds have shown potential for immunomodulatory effects. In a preclinical study, nanocarriers loaded with GLPs effectively stimulated immune responses, and enhanced the activation of immune cells, leading to improved anticancer immune responses [3,19]. The nanotechnology-mediated delivery facilitated the targeted modulation of the immune system.

Theranostics: GL-based nanomaterials have been explored for theranostic applications, combining therapy, and diagnostics. In a preclinical study, multifunctional nanoparticles loaded with G. lucidum bioactive compounds were developed as theranostic agents for simultaneous cancer therapy, and imaging technology [3,19]. The NPs exhibited selective tumor accumulation, efficient tumor regression, and imaging capabilities for real-time monitoring of treatment response.

These preclinical studies highlight the potential of G. lucidum in combination with nanotechnology for enhanced therapeutic outcomes in cancer therapy [3,19]. While these studies show promising results, further research is necessary to evaluate the safety, long-term effects, and clinical translation of these nanotechnology-based approaches. Nevertheless, these preclinical studies lay the foundation for future investigations, and the development of novel therapeutic strategies utilizing G. lucidum in nanotechnology for treatment of chronic diseases like cancer.

A total of 210 articles were reviewed for preclinical studies, investigating the potential activities of G. lucidum in various areas such as anticancer, antiaging, antibacterial, antiobesity, antidepressant, antiosteoporotic, anxiolytic, antidiabetic, anti-dyslipidemia, antiepileptic, antihypertensive, antihypertensive, antihyperlipidaemic, anti-inflammatory, antimicrobial, antimutagenic, antioxydant, cardio-protective, hepatoprotective, immune-boosting, immunomodulatory, neuroprotective, sedative, nootropic, and radio-protective effects (Venturella et al., 2021; Xie et al., 2016; Ekiz et al., 2023). Among these studies, approximately 33% utilized G. lucidum extract in different forms, 21% focused on isolated polysaccharides, 5% examined triterpenes, and 3% explored the effects of G. lucidum spore powder. The remaining 38% of studies investigated other preparations of G. lucidum. Regarding the study models employed, approximately 40% of the studies utilized mice, 33% used rats, 17% employed various types of cell lines, while a smaller proportion of the studies involved pigs, chickens, bacterial strains, and clinical isolates. The in vitro studies employed a dose range of 1-1,000 μg/mL, while in vivo studies used doses ranging from 10-10,000 mg/kg [3,19].

Table 5. Preclinical studies and their therapeutic effects realized in G. lucidum.

Table 5. Preclinical studies and their therapeutic effects realized in G. lucidum.

Therapeutic effect	Action mechanisms	Model	Reference
Anticancer
In vitro In vivo	↑ CD47/CD8+ ratio ↑ Immune system activity ↑ Apoptosis ↑ Expression of Bax and caspase-3 ↑ mRNA expression ↑ Protein production ↑ Population of Tc-cells ↓ Activation of Akt and its downstream regulator	Cell lines related to melanoma, lung cancer, prostate cancer, colorectal cancer, breast cancer, osteosarcoma, and human prostate cancer.	[3,19,27,28,41,47,56,92,93]
	↓ Cellular levels; Activation of Akt and its downstream regulators; Inhibition of STAT3 signaling; cell viability, autophagy flux, Rac activity and downstream signaling pathway, osteosarcoma cell activity, and expression of anti-apoptotic proteins; ↑ Autophagy through Akt/TOR signaling, apoptosis with cell cycle arrest via NAG-1 induction, and autophagosome accumulation; ↓ Tumor volume; ↓ Growth; ↓ Metastasis; Progression and release of matrix metalloproteinases; ↑ Cytotoxicity; ↑ Apoptosis; ↑Immunomodulatory activity.	Breast cancer, mammary adenocarcinoma, ascitic tumor, cervical carcinoma, hepatoma, lung tumor, and glioma
Antibacterial
In vitro In vivo	↑ Cell permeability and leakage; ↑ Polysaccharides binding to leukocyte surfaces; Activation of Th/NK/macrophages,; Upregulation of IgA/RD-5, 6/TLR4 mRNA levels; Improved attachment and permeability, lncreased oxidative stress and killing of pathogens.		[3,19,94]
	↓ Firmicutes-to-Bacteroidetes ratio; ↓ Proteobacteria abundance; ↓ Levels of Aerococcus, Ruminococcus, and Corynebacterium.	Mice with dysbiosis and rats with type-2 diabetes
Anti-obesity
In vitro In vivo	↓ mRNA expression of SREBP-1c, C/EBPa and PPARy; Inhibition of MAPK pathway increases energy expenditure with the inhibition of 3T3-L1 pre-adipocytes proliferation and differentiation.	Murine pre-adipocyte cells; M. miehei lipase.	[3,19,95]
	↓ Body and liver weight; ↓ Subcutaneous fat; ↑ Microbiome-gut-liver and gut-brain axes; Regulate metabolism by modulating gut microbiota composition; ↑ Levels of Clostridiales, Lachnospiraceae, Oscillospira, and Ruminococcaceae; ↓ Levels of Lactobacillus, Bifidobacterium, and Roseburia.	High-fat diet-fed; MK-fat mice.
Hepatoprotective
In vivo	↑ Antioxidant activity; ↓ Oxidative stress; Regulating key molecular pathways: FOXO4/mTOR/SIRT1; ↓ Expression of hepatic glucose regulatory enzymes, p-AMPK/AMPK, lipid peroxidation, protein oxidation, MDA, and heat shock proteins; ↓ Expression of inflammatory markers: iNOS, COX2, TNF-α, NF-KB, and IL-6; ↑ Superoxide dismutase activity, lipid peroxidation, and apoptosis; Inhibits fatty acid synthesis; ↓ Serum ALT levels indicating its potential in protecting liver health.		[3,19,96]
Anti-dyslipidaemia
In vitro In-vivo	↓ 3T-L1 pre-adipocytes proliferation/differentiation; ↓ Key lipid-metabolizing enzymes.		[3,19,97]
	↓ Haemorrhage/thrombosis; ↓ Stroke, cardiac necrosis; ↓ Atherosclerotic plaque; ↑ HDL-c; ↑ Total BAs.
Cardioprotective
In vitro In vivo:	↓ Cardiomyocyte necrosis; Reperfusion contracture; Antioxidant effects; Activation of PI3K/AKT signaling pathway; Modulation of specific molecular targets.		[3,19,97]
	↓ Haemorrhage/thrombosis; ↓ Stroke; ↓ Cardiac necrosis; ↓ Atherosclerotic plaque; ↑ Anti-angiogenic; ↑ Antioxidant properties.
Antidiabetic
In vitro In vivo	↓ Hepatic PECK gene expression; ↓ Glucose level; ↓ SREBP1; ↓ FAS-mRNA expression; ↓ mRNA level for gluconeogenesis enzymes and H2O;	Human breast adenocarcinoma cell line (MCF-7/ADR) and HepG2 cells	[3,19,97]
	↑ Glucose uptake ↑ Insulin level ↑ Hepatic glycogen level ↑ Insulin sensitivity ↑ Glycogen synthesis ↑ Glucose transport via the PI3K/Akt pathway.	Mice and rat models
Immunomodulatory
In vitro In vivo	Upregulation of immunomodulators IL-12, IF-4, IL-2, IL-6, IL-4, IL-17, TNF-a, IFN-%, granulysin, perforin, and NKG2D/NCR cell surface receptors; ↑ Production of nitric oxide (NO); Activates ERK, JNK, and p38 signaling pathways.	Mice, rats, and pigs	[3,19,27,28,41,47,56,92–97]
	Activates humoral and cellular immune responses; Promotes antigen-specific IgG production; Enhances haematopoiesis, macrophage phagocytosis, and proliferation of spleen lymphocytes and undifferentiated spleen cells; Stimulates the activity of T/B-cells, LAK cells, CD3+, CD4+, and CD8+ T-cells; Activation of NF-KB/MAPK, NK cells, NF cells, TNF activity, and cytokine secretion.
Anti-inflammatory
In vitro In vivo	↓ Expression of NF-κB, MAPK, and AP-1; ↓ Activity of G-CSF, IL-1α, MCP-5, and MIP3α; ↓ mRNA expression of CHUK and NFκB1/p150; ↓ NO, MDA, TNF-α, IL-1β, and IL-6 levels; ↓ iNOS and COX-2 expression; ↑level of SOD.		[3,19]
	Suppression of inflammatory mediators TNF-α, IFN-γ, IL-1β, IL-6, MCP1, and hydroxyproline; ↑ Expression of keratinocyte differentiation markers; ↓ Serum Ig-E level; ↑ SOD/TOAC level.
Neuroprotective
In vivo	Downregulating caspases-3, -8, and -9; Modulation of Bcl-2/Bax ratio; Protects DNA and cell membranes from the harmful effects of radiation; ↑ Cerebral blood flow; ↓ Neuronal damage and apoptosis; Promotes mitochondrial movement; Enhances the production of anti-inflammatory cytokines; Improves spatial learning and memory-related behavior; ↓ Production of pro-inflammatory cytokines induced by Aβ and oxidative stress induced by spinal cord injury; Inhibits apoptosis caused by hydrogen peroxide, lipid peroxidation, and GSH.		[3,19]
Anti-epileptic
In vivo	↓ Hippocampal neurons; ↓ Number of excitatory neurons and delays the onset of epilepsy; Prevents CA3 degeneration; ↓ Astrocytic reactivity; ↓ Levels of pro-inflammatory; ↑ Cytokines IL-1B and TNF-α; threshold for psychomotor seizures; ↑ Content of GABA; ↓ Seizures and convulsions.		[3,19]
Sedative
In vivo	Inducing a hypnotic effect in rat and mice models; Promote relaxation and sleep; Modulation of cytokines, specifically TNF-a; Sedative effects; Regulate sleep-related processe; ↓ Sleep latency; ↑ Sleep duration.		[3,19]
Nootropic
In vivo	Improving cerebral blood flow, brain energy supply, memory-related neurotransmitters, and cognition; ↓ Brain cell apoptosis and ameliorates spatial memory deficits; Inhibits acetylcholinesterase activity; Antioxidant properties; Improves anterograde amnesia.		[3,19]
Antidepressant
In vivo	Blocking 5-HT2A receptors; Inhibiting MAO; Antagonizing preganglionic 5-HT receptors; ↓Depression-related activities.		[3,19]
Anti-osteoporotic
In vivo	Promoting bone healing; Regeneration; ↑ Trabecular bone volume; Inhibits osteoclastogenesis and reverses bone loss; ↑ OPG/RANKL ratio; ↓ Bone differentiation; Formation of RANKL-induced osteoclast; Facilitates cross-talk between the Wnt/B-catenin and BMP/SMAD signaling pathways; Protective effects on bone.		[3,19]
Anxiolytic
In vivo	↓ Anxiety levels at ranging doses between 20 to 400 mg/kg.	Swiss Albino mice	[3,19]
Radioprotective
In vivo	Antioxidant and free radical scavenging properties; ↑ Levels of GSH; Protection against radiation-induced damage; ↓ Reactive oxygen species ROS; Restoration of TNF-d production; Repair of damaged T-cells; Protection against gamma rays; Reducing DNA strand breaks and micronuclei formation; ↓ MDA levels; Promoting the recovery of SOD activity.		[3,19]

7.3. Critical Assessments of the Pharmacological Activities

7.3.1. Preclinical Studies

Preclinical studies play a vital role in advancing our understanding of human diseases. These studies involve investigating the biochemical events, physiological processes, and behavioral implications associated with diseases. They also allow for the testing of novel pharmacotherapeutic interventions. In this context, in vitro studies are commonly conducted as they are relatively easy to perform, requiring lower costs, and do not necessitate high technical skills. However, it’s important to note that the controlled laboratory environment in in vitro studies may not accurately replicate the complexities of the natural environment, resulting in limited chances of identifying lead compounds with therapeutic potential. On the other hand, in vivo models provide valuable tools for studying the mechanisms, and etiology of human diseases. By using living organisms, such as animal models, researchers can better understand the interactions between various physiological systems, and assess the effects of potential interventions. In vivo studies allow for a more holistic evaluation of the disease process and its response to treatments. However, despite their advantages, it is worth noting that the number of new leads identified through in vivo studies that ultimately reach clinical trials is relatively limited. While in vitro studies offer advantages like cost-effective, and accessible methods for preliminary screening, they may have limitations in terms of replicating the complex natural human environment. In vivo models provide a more comprehensive understanding of diseases but may face challenges in translating findings to successful clinical trials. Both approaches are important and complement each other in preclinical research to enhance our understanding, and development of potential therapies for human diseases. The translation of preclinical studies to clinical studies faces limitations, and hindrances, which can contribute to the lack of reproducibility in many preclinical trials. The findings and data from preclinical studies often do not withstand the test of time. To address these issues, it is recommended that preclinical investigators be blinded to the treatment, and control arms, and use rigorously validated reagents.^[19] Experiments should include appropriate positive, and negative controls. Critical investigations should be repeated, preferably by different investigators within the same laboratory, and only after obtaining consistent results should the final data set be published.

Several reasons can be inferred for the limited number of preclinical studies transitioning to clinical studies. These include the lack of proper preclinical models, inadequate blinding of investigators to treatment protocols, and the use of reagents, chemicals, and tools without rigorous validation [3]. Additionally, many studies focused on known species, and diseases without delving into the underlying mechanisms or understanding them in-depth.

Improper standards, and strains used in preclinical studies also contribute to limitations. The standards (positive and negative controls), and their doses used in these reports may not be comparable to the test doses, hampering the development of novel conclusions, and drug advancements [3,19]. Moreover, the microbial strains utilized often represent common, and easily manageable species, lacking resistance traits. However, in recent years, there has been a significant increase in antibiotic resistance, highlighting the need for studies focusing on life-threatening species such as methicillin/vancomycin-resistant Staphylococcus aureus (MRSA/VRSA) [101]. The literature on G. lucidum has been observed to suffer from these deficiencies, and limitations in preclinical studies. Addressing these issues, and conducting studies with more robust methodologies, and relevant strains is crucial to obtain significant outcomes and develop novel interventions. One of the challenges in herbal extracts research, particularly with herbs like G. lucidum, is the unreliability of extracts, and geographical variation in the herb. The quality and quantity of mycochemicals can vary significantly when herbs are collected from different geographic origins. Different authors have reported the same pharmacological activity using G. lucidum collected from different locations. However, the statistical significance of the results can vary widely due to the non-uniform distribution of active compounds in the samples used for similar pharmacological activity [3,19]. Another factor that contributes to the complexity, and reproducibility of the data is the application of different statistical models in each study, even when G. lucidum is collected, and extracted from similar origins. This variation in statistical models can make it challenging to compare, and reproduce experimental data across studies. The dose range used in many studies may not be applicable in clinical settings, and needs to be reconsidered.^[19] Additionally, while some studies mention proposed mechanisms of action, these mechanisms are often cited from previous literature, and may not be unanimously investigated or informative for further studies. The presence of multiple mycochemicals in a plant can contribute to its pharmacological effects, making it difficult to hypothesize a single mechanism of action [3,19].

Overall, the unreliability of extracts, and the geographical variation of herbs, along with the use of different statistical models, and the complexities of dose range, and underlying mechanisms, pose challenges in herbal extract research, including studies on G. lucidum. Addressing these issues, and ensuring standardized protocols, and methodologies can improve the reliability, and comparability of research findings. In addition to efficacy and potency, it is crucial to monitor the toxicity, adverse effects, and chronic use of test drugs or products. Adverse effects, toxicities, allergies, and other potential risks should be assessed, particularly in chronic use or at high doses [102–104]. It is important to consider the potential of drugs or extracts to mask drawbacks or suppress certain physiological processes, as seen with some cancer drugs. Dependency and withdrawal effects should also be addressed. The impact of drugs or extracts on liver enzymes is significant, and a comprehensive understanding of enzyme saturation, interactions, agonistic/antagonistic effects, and the overall effect on liver function is necessary [3]. In the case of G. lucidum, which has been tested for diseases requiring long-term drug use such as epilepsy, and Alzheimer’s disease, establishing relevant preclinical models that accurately reflect the possible toxicities associated with its chronic use is very relevant. These suggested loopholes highlight the need to thoroughly investigate, and address the potential adverse effects, toxicities, and long-term usage implications of test drugs or extracts. Understanding and mitigating these factors are essential for improving the transition rate of preclinical studies into clinical studies, and trials.

7.3.2. Clinical Studies

Clinical studies are crucial for evaluating the effectiveness, and safety of medicinal products like G. lucidum. However, there is a limited number of clinical studies on G. lucidum mushroom compared to preclinical studies, which might be due to the challenges in translating preclinical findings into clinical settings. Most of the clinical studies on G. lucidum have small sample sizes, which can limit the interpretation of results, and increase the risk of false positive or negative outcomes. These preliminary studies provide valuable data that can be used to design larger confirmatory studies. To establish the efficacy and safety of G. lucidum for marketing purposes, advanced clinical studies covering different phases (Phase I to Phase V) are necessary. It is important to have a consistent dose range, and standardized preparation methods for G. lucidum in clinical studies. However, there is variation in the dose range used, and the reporting of mechanisms in some studies. A more systematic, and reproducible approach, including sequential Phase I to Phase III studies, is needed to generate reliable data [3,19]. The source of G. lucidum used in clinical studies also varies in terms of geographical origin, extraction methods, and final product concentration. This variability can lead to differences in the concentration of bioactive compounds, and subsequently affect the therapeutic, and toxic outcomes observed. Challenges such as heterogeneity, small sample sizes, inappropriate research methodologies, lack of multicenter involvement, and inadequate statistical models have hindered the progress of G. lucidum as a potential conventional drug for treatment [3,19].

In summary, there is a need for well-designed clinical studies with larger sample sizes, standardized dosing, reproducible data, appropriate research methodologies, and multicenter collaboration to fully explore the potential of G. lucidum as a conventional drug.

G. lucidum has attracted significant interest in cancer therapy, and other chronic diseases due to its bioactive compounds, and potential health benefits. As mentioned throughout this review, in recent years nanotechnology has emerged as a promising approach to enhance the delivery, and effectiveness of therapeutic agents, including G. lucidum bioactive compounds in cancer treatment [64]. The combination of G. lucidum with nanotechnology offers exciting prospects for improving cancer therapy, and patient outcomes. G. lucidum bioactive compounds, such as GLPs and GLTs, and other secondary metabolites, have shown promising anti-tumor properties in preclinical studies.^[21–25] Their ability to modulate immune responses, induce apoptosis, and inhibit tumor growth makes them attractive candidates for cancer therapy. Nanotechnology-based formulations can overcome the limitations for the delivery of G. lucidum bioactive compounds to specific target sites, including improved delivery, increased bioavailability and stability, targeted drug delivery, and synergistic effects with other therapeutic agents [24]. Nano-sized carriers, such as nanoparticles and liposomes, offer controlled, and sustained drug release, enhancing therapeutic efficacy [61–67,74–76,81–85]. Functionalized nanoparticles, and liposomes offer controlled and sustained drug release, can enhance targeted delivery to cancer cells, minimizing off-target effects, and maximizing therapeutic efficacy. Furthermore, the immunomodulatory effects of G. lucidum can be amplified through nanotechnology, leading to enhanced activation of the immune system against cancer cells [3,19]. Nanotechnology-based approaches also offer opportunities for cancer diagnostics, and imaging, facilitating early detection, and personalized treatment strategies. However, further research and clinical studies are needed to fully explore the potential of G. lucidum in nanotechnology-based cancer therapy. The safety, long-term effects, and clinical translation of these approaches require thorough investigation. Additionally, the scalability, standardization, and optimization of nanotechnology-based formulations incorporating G. lucidum need to be addressed to ensure their practical application in clinical settings. The combination of G. lucidum bioactive compounds with chemotherapeutic drugs within nanoparticles has demonstrated synergistic effects in preclinical studies [27–60]. This approach has the potential to enhance cytotoxicity against cancer cells, reduce drug resistance, and minimize systemic toxicity. Furthermore, nanoparticles can be engineered with specific surface modifications or ligands to enable targeted drug delivery to tumor cells, enhancing precision medicine approaches, and minimizing damage to healthy tissues. Although clinical studies specifically focusing on G. lucidum in nanotechnology-based approaches are currently limited.

Despite the promising preclinical findings, more research is needed to further elucidate the mechanisms of action, and optimize the formulations of GL-based nanomedicines. Rigorous preclinical studies, and clinical trials are essential to evaluate the safety and efficacy of these novel therapies. Future perspectives in this field involve the development of robust clinical trials specifically focused on G. lucidum in nanotechnology-based approaches for cancer therapy. These trials should evaluate the safety, efficacy, and long-term outcomes of these formulations. Furthermore, efforts should be made to establish standardized manufacturing processes, quality control measures, and regulatory frameworks for these nanotechnology-based formulations.

In this way, the future perspectives in this field could involve:

• Continued research on the bioactive compounds of G. lucidum, and their interactions with nanocarriers will provide valuable insights for designing optimized nano-formulations.
• Large-scale preclinical studies, and well-designed clinical trials are necessary to validate the effectiveness, and safety of G. lucidum-based nanomedicines in humans.
• The development of personalized nanotherapies using G. lucidum bioactive compounds tailored to individual patient profiles could pave the way for personalized cancer treatment strategies.
• Further exploration of the combination of G. lucidum with other advanced therapies, such as immunotherapy, and targeted therapies, may open new avenues for synergistic cancer treatment approaches.
• Collaboration between researchers, clinicians, and pharmaceutical industries is crucial to accelerate the translation of G. lucidum-based nanotherapies from the laboratory to clinical applications.

G. lucidum, in nanotechnology for cancer therapy holds great promise as a complementary approach to conventional treatments. Harnessing the potential of G. lucidum, bioactive compounds in nanoparticles, and other nanocarriers presents an exciting opportunity to advance cancer treatment strategies, and improve patient outcomes.

Table 6. Clinical studies and their therapeutic effects realized in G. lucidum.

Table 6. Clinical studies and their therapeutic effects realized in G. lucidum.

Activity	Effect
Anticancer	↑Mitogenic reactivity to concanavalin-A and phytohemagglutinin; Lymphocyte; CD3/CD4 and natural killer cells activity; CD3/CD4/CD8/CD56, IL-2 IL-6, IFN-Y, and NK activity.
Antioxidant and hepatoprotective	↑Antioxidant activity ↓Thiobarbituric acid, 8-OH-dG. GOT and GPT levels; ↓Triglycerides; ↑HDL-c.
Cardioprotective	↓Blood pressure and atherosclerosis; Improve chest pain/ palpitation/angina pectoris; ↓Diastolic/systolic pressure, TAG, MDA, CEC, EPC levels; ↑ capillary loop diameter, density, RBC velocity, and HDL-cholesterol.
Antidiabetic	↓Cell resistance to insulin and HbA1c, FPG, and PPG values; The antiplatelet effect GL though contains a high level of adenosine; Lack of effect on platelets aggregation.
Anti-histaminic	Most symptoms were relleved in hay fever patients due to restored normal balance between Th1 and Th2.
Anti-viral	Inhibition of virus replication in hepatitis-B and HIV patients; ↓HBeAg. HBV, DNA, and liver enzymes.
Immunomodulatory	↑CD3+, CD4+, CD8+ T cells.
Anti-fibromyalgia	Aerobic endurance was improved along with lower body flexibility and velocity via the antioxidant effect of GL.
Anti-Alzheimer	↓Ab, 3, 4-methylenedioxyamphetamine, Fasl, caspase-3, and tau hyperphosphorylation.
Anti-macular degeneration	Improvement of pre-ganglionic retinal elements in age-related macular degeneration patients with an increase in mfERG R1 and R2, and RADs.

8. Conclusions

9. Patents

Abbreviations

References

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