1. Introduction
ecause of widespread prevalence of diabetes worldwide, especially in developing countries, its management is of particular importance. In addition to glucose-lowering medicines, special dietary regimes and the use of functional foods are recommended. One of the foods that has been long considered due to having beneficial compounds and low Glycemic Index value are mushrooms family [1]. Among them, ganoderma lucidum is well-known for its specific bioactive compounds and different nutritional compositions, and currently is used in food products. It contains essential fatty acids, essential amino acids and a wide range of polysaccharides; all of which seems to be effective in lowering blood sugar. 
This study aims to review the effective compounds of ganoderma lucidum and summarize the possible mechanisms of its powder and extracts in controlling hyperglycemia and diabetes. The anti-oxidation and anti-inflammatory properties of this mushroom are also investigated.
2. Materials and Methods
The search was conducted in SID, MagIran, Scopus, PubMed, Web of Science and Google Scholar databases on articles in Persian and English related to the anti-diabetic effects of ganoderma lucidum conducted from 2001 to 2020 using the keywords: Powder, active ingredients, ganoderma lucidum, diabetes mellitus, hyperglycemia, clinical trial, and metabolic syndrome (alone or combined). Both in vivo and in vitro studies were included in this review. 
3. Results
Ganoderma lucidum contains more than 400 biologically active compounds, including terpenoids, sterols, steroids, essential fatty acids, phenols, glycoproteins and polysaccharides. All essential amino acids are presented in this mushroom [2]. The three active compounds of this mushroom including polysaccharides, carbohydrate-binding proteins and triterpenoids had more effective role in controlling blood sugar [3, 4]. Supplementation with ganoderma lucidum mostly in animal models reduced fasting blood sugar, glycosylated hemoglobin and insulin resistance. The studies on the regulating effects of ganoderma lucidum in experimental models were mainly on polysaccharides, ganodran B, and extracted proteoglycans which could inhibit hepatic glucose synthesis [5], reduce apoptosis, and repair pancreatic β-cells [6]. These metabolites improved glucose metabolism and enhanced serum insulin level through various mechanisms and led to lowered blood glucose level. Moreover, it was shown that proteins of ganoderma played an important role in reducing blood sugar by stimulating the immune system via activation of Forkhead box P3 (FOXP3+) regulatory cells, CD-18 production, and down-regulating CD-45 [7]. Furthermore, the triterpenoids of ganoderma including different ganoderic acids could ameliorate diabetes complications through inhibition of sorbitol accumulation and reducing intestinal glucose uptake by inhibiting aldose reductase and α-glucosidase secretion [8, 9]. The effectiveness of ganoderma lucidum in controlling blood glucose and diabetes complications may be due to its anti-oxidation and anti-inflammatory properties. Ganoderma proteoglycan extract increased enzymatic and non-enzymatic antioxidants in diabetic rats [10, 11]. Similarly, ganoderma lucidum spores could amend B lymphocytes and reduce the CD4+/CD8+ T ratio in diabetic mice led to the regulation of the immune system and controlling the inflammation caused by hyperglycemia [12]. There were only a few studies on human models. Although ganoderma uptake could improve blood sugar in some studies [13, 14], but were not effective at all dosages in other studies [15, 16]. The possible mechanisms were not investigated in these clinical trials. In comparing the effect of ganoderma lucidum with hypoglycemic drugs, the results of some studies indicated that polysaccharides, proteoglycans, ganoderic acids [17, 18, 19], and extract of ganoderma [20] had effects similar to metformin and glibenclamide. The effects of the active ingredients of ganoderma lucidum on the blood glucose regulating enzymes are shown in Figure 1. 4. Discussion and Conclusion 
The beneficial effects of ganoderma lucidum on regulating blood glucose and glycosylated hemoglobin have been demonstrated according to the mechanisms described in animal studies. Since limited human studies have examined its effect on hyperglycemia and no mechanism for it has been suggested, more clinical trials are needed to claim that ganoderma has anti-diabetic effects in humans. Overall, it can be concluded that consumption of ganoderma lucidum in both diabetic patients and general population may have regulatory effect on blood glucose; although the effective dosage, side effects, and drug interactions are needed to be clarified. The practical use of this mushroom in food industry can be considered for the production of functional foods which may promote health status of general people and prevent diabetes.

Ethical Considerations
Compliance with ethical guidelines
No data have been fabricated or manipulated to support our conclusions in the current work. All available studies in this area are included for review.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.  

Authors' contributions
Conceptualization: Mansooreh Sadat Mojani Qomi; Methodology: Monireh Hatami; Data curation, writing- original draft preparation, writing- review & editing: Mansooreh Sadat Mojani Qomi; Visualization, supervision, administration, validation, investigation, and resources: All authors.  

Conflicts of interest
The authors declared no conflict of interest.

Acknowledgements
The authors would like to thank the Vice Chancellor for Research in Tehran Medical Sciences, Islamic Azad University for their support.


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