**4. Anti-lipidemic effects of** *Cordyceps sinensis*

*Apolipoproteins, Triglycerides and Cholesterol*

thereby concluding its life cycle.

verified its potency, is listed in **Table 3**.

cancer cells

stellate cell activation

**3. Ethnopharmacological uses of** *Cordyceps sinensis*

death become a rigid structure due to the production of the fungal sclerotia, which could pause the germination for a while to produce spores. Right after the end of the winter season, the formation of the mushroom body continues, and along with that, the perithecial stroma grows upward in order to emerge above the ground soil,

*Cordyceps sinensis* is presently regarded as a highly priced fungus at present due to its precious medicinal value especially in the field of traditional Chinese medicine (TCM). This is primarily for the treatment of kidney disease, fatigue, sexual dysfunctions, diabetes, and cancers, which are highly prevalent nowadays. *Cordyceps sinensis* is also regarded as a Bhutanese indigenous medicine other than TCM [10]. It is said that the *Cordyceps* organism was discovered by yak herders in the Himalayas of ancient Tibet and Nepal who, recognizing the ardent behavior of their animals after grazing on *Cordyceps* at high altitudes in the spring, sought the causal agent for their own usage and medical applications [3]. The capless mushroom was then incorporated into TCM ever since starting with kidney, lung, and heart ailments, male and female sexual dysfunction, fatigue, cancer, hiccups, and serious injury, to relieve pain, and the symptoms of tuberculosis and hemorrhoids, to restore general health and appetite and to promote longevity [3]. A tabulated description of the health benefits of *Cordyceps sinensis* in their traditional applications against disease conditions and scientific studies, which have

In modern times, *Cordyceps sinensis* appears to be actively used by the elderly people and athletes as well to boost their energy [16]. Experiments show that although *Cordyceps sinensis* could be used as an energy booster, only a small portion of extra energy could be achieved due to the increase of cellular adenosine triphosphate (ATP) when it is taken as an herbal supplement. The energy output and its oxygen capacity help with treating cold intolerance and decreasing fatigue. It is also noteworthy that compared with other medicinal herbs, *Cordyceps sinensis* has

**Disease Description and effect References**

*sinensis* has an anti-inflammatory as well as an antifibrotic effect *Cordyceps sinensis* culture had helped in the inhibition of hepatocytes and hepatic

the lungs and the respiratory system such as phlegm, cough, and various

in increasing 17-ketosteroid and 17-hydroxycorticosteroids levels in the human body resulting in the prevention of kidney disease. In the meantime, the consumption of *Cordyceps sinensis* by patients with renal failure has helped them decrease their blood pressure by 15%

AIDS/HIV *Cordyceps sinensis* has been used to treat HIV infections in West Africa [15]

*Disease conditions which have ethnopharmacologically utilized* Cordyceps sinensis *and studies elucidating* 

[11]

[12]

[13]

[14]

Cancer *Cordyceps sinensis* has been able to demonstrate the inhibition of colorectal

Liver fibrosis Experiments have shown that ergosterol in cultured mycelium *Cordyceps* 

Respiratory *Cordyceps sinensis* is used to ease various kinds of diseases associated with

other diseases associated with the bronchial and asthma

Kidney Studies showed that consumption of *Cordyceps sinensis* stem helps

**174**

**Table 3.**

*their scientific verifications.*

Age-related diseases are rising as a common issue in the present era due to the evolutionary changes that take place in the dietary patterns and lifestyle changes of humans. Studies which are being carried out to mitigate these rising health issues show methodological approaches to prevent and mitigate them by utilizing the medicinal values of traditional medicines across the globe.

Complications related to lipid metabolism have been identified as an agerelated disease condition [17]. As a detrimental health effect related to lipid metabolism, the incidence of obesity has also been increasing steadily in the developed and developing countries worldwide. Analysis of the global burden of obesity revealed that there were 396 million adults with obesity in 2005 and that the expected number is projected to be 573 million individuals in 2030, without the application of an adjustment for secular trends [18]. Excessive fat accumulation that increases the risk of adverse health effects is one of the definitions of obesity [19]. It is a condition that is implicated as a risk factor for various diseases such as hypertension, coronary heart disease, and type II diabetes [20].

Hyperlipidemia is another age-related disease condition. This occurs due to the presence of too much low-density lipoprotein (LDL) in the blood, while it threatens the health of the circulatory system, risking the blockage of arteries with the deposition of fats and lipids. In addition, hyperlipidemia acts as the root cause of diabetes and functional depression in organs such as the liver, heart, and kidney [3, 4].

*Cordyceps sinensis* has been used in modern times for the treatment of lipidrelated disorders. A summary of the anti-lipidemic effects of *Cordyceps sinensis* is shown in **Figure 2**. The fruiting body part of *Cordyceps sinensis* contains a composition of nucleosides, exopolysaccharides (EPS), proteins, and sterols. These bioactive components which play a significant role in treating diseases are also

**Figure 2.**

*Schematic depicting the anti-lipidemic effects of* Cordyceps sinensis*.*

used in treating diseases like hyperlipidemia due to their anti-lipidemic and anticholesterolemic ability which have demonstrated to lower cholesterol. Treatment of mice with the extract of *Cordyceps sinensis* mycelia has demonstrated to significantly reduce cholesterol and triglyceride concentrations and the synthesis of very-lowdensity lipoprotein (VLDL, an LDL precursor). Therefore, given these functions, a useful mechanism of action present in *Cordyceps sinensis* for obesity prevention could be considered as the inhibition of preadipocyte differentiation.

In human as well as animal studies, administration of *Cordyceps sinensis* has been associated with a reduction in cholesterol and triglyceride and an increase in the ratio of high-density lipoprotein (HDL) to LDL cholesterol [17]. Whether the causative mechanism for this lipid-balancing effect is through blood sugar stabilization, enhancing liver function, or any other as hitherto unknown cause remains to be seen.

Interestingly, in addition to their mycelium effects obtained from solid-state fermentation, *Cordyceps sinensis* biomass obtained from submerged fermentation has been recognized as an effective agent in lipid metabolism [21]. This hypothesis was supported by some evidence which surfaced about glucan isolated from the *Cordyceps sinensis*. Current interest in the effect of glucans on lipid metabolism mainly is centered on the possibility that the glucans could entrap bile acids in the intestine and thus increase bile acid exclusion in the feces. The results by Freire Dos Santos et al. [22] suggest that *Cordyceps sinensis* biomass supplementation in high-fat diet (HFD)-fed rats for 4 months normalizes the blood lipid and the low testosterone levels induced by HFD. Despite the outcomes of the study, it has to be borne in mind nevertheless that *Cordyceps sinensis* biomass supplementation cannot replace the use of currently available drug regiments for lipid reduction but can easily complement them. It may also enable the use of lower doses of therapeutic drugs, thereby decreasing the risk of dose-related side effects. Furthermore, Freire Dos Santos et al. demonstrated that a long-term intake of HFD caused a significant liver damage which has been reverted by *Cordyceps sinensis* biomass supplementation and, this in turn, normalized decreasing testosterone levels observed in HFD-fed rats.

Leptin, a newly discovered hormonal product of the obesity (ob) gene, is expressed by white adipose tissue. It has been implicated in the regulation of body weight, glucose metabolism, and fertility. Leptin deficiency produces severe obesity, insulin resistance, and impaired glucose tolerance in ob/ob mice, and also, congenital leptin deficiency in humans leads to hyperphagia and marked obesity. Choi suggested that *Cordyceps sinensis* originated EPS are excellent candidates to develop as functional food additives or therapeutic agents for anti-obesity and antidiabetic purposes through improvement in glucose homeostasis and preservation of insulin reserves [23].

Tiamyom et al. [17] investigated the effects of *Cordyceps sinensis* extract and *Gymnema inodorum* extract, used alone and combined, on antiadipogenesis in 3T3-L1 cells. Results from this study indicated that both herbs and their combination had inhibitory effects on lipid accumulation in the adipocytes. The pancreatic lipase assay results indicated that *Cordyceps sinensis* extract inhibited the pancreatic lipase activity in a dose-dependent manner. These results suggested that the use of *Cordyceps sinensis* extract alone and in combination with *Gymnema inodorum* extract may be efficacious as a complementary therapy for hyperlipidemia and obesity management.

#### **5. Bioactive compounds of interest**

*Cordyceps sinensis* appears to contain all of the essential amino acids, vitamins E and K, as well as the water-soluble vitamins B1, B2, and B12. In addition, it contains

**177**

**Figure 4.**

**Figure 3.**

*Therapeutic Properties and Anti-Lipidemic Activity of* Cordyceps sinensis

(D-mannitol), have been also identified in *Cordyceps sinensis* [17].

*Chemical structure of cordycepin, which has been isolated from* Cordyceps sinensis*.*

*Chemical structure of CPS-2, which was isolated by Wang et al. [27]. The structure was found to be mostly of α-(1 → 4)-d-glucose and α-(1 → 3)-D-mannose, branched with α-(1 → 4,6)-d-glucose every 12 residues on average.*

many sugars, including mono-, di-, and oligosaccharides, and many complex polysaccharides, proteins, sterols, nucleosides, and trace elements. Characterization of cordycepin (**Figure 2**) and 2′-deoxyadenosine was reported by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy in an extract of *Cordyceps sinensis* [24, 25]. Cordycepin has been identified as one of the compounds involved in the anti-lipidemic effects of *Cordyceps sinensis*, and thus, within the context of this chapter needs to be highlighted as the primary bioactive compound involved in lipid metabolism and regulation. Cordycepin inhibits adipocyte differentiation and accumulation of lipid in mature adipocytes [26]. As cordycepin blocks both adipocyte differentiation and lipid accumulation, it has the potential to be an effective therapeutic agent for obesity and obesity-related disorders [26].

Nucleosides have been found in all species of *Cordyceps*, including uridine. A number of polysaccharides and other sugar derivatives, such as cordycepic acid

In recent years, much interest has been focused on EPS produced by *Cordyceps sinensis* and its other varieties due to their various biological and pharmacological

*DOI: http://dx.doi.org/10.5772/intechopen.92616*

#### *Therapeutic Properties and Anti-Lipidemic Activity of* Cordyceps sinensis *DOI: http://dx.doi.org/10.5772/intechopen.92616*

*Apolipoproteins, Triglycerides and Cholesterol*

remains to be seen.

used in treating diseases like hyperlipidemia due to their anti-lipidemic and anticholesterolemic ability which have demonstrated to lower cholesterol. Treatment of mice with the extract of *Cordyceps sinensis* mycelia has demonstrated to significantly reduce cholesterol and triglyceride concentrations and the synthesis of very-lowdensity lipoprotein (VLDL, an LDL precursor). Therefore, given these functions, a useful mechanism of action present in *Cordyceps sinensis* for obesity prevention

In human as well as animal studies, administration of *Cordyceps sinensis* has been associated with a reduction in cholesterol and triglyceride and an increase in the ratio of high-density lipoprotein (HDL) to LDL cholesterol [17]. Whether the causative mechanism for this lipid-balancing effect is through blood sugar stabilization, enhancing liver function, or any other as hitherto unknown cause

Interestingly, in addition to their mycelium effects obtained from solid-state fermentation, *Cordyceps sinensis* biomass obtained from submerged fermentation has been recognized as an effective agent in lipid metabolism [21]. This hypothesis was supported by some evidence which surfaced about glucan isolated from the *Cordyceps sinensis*. Current interest in the effect of glucans on lipid metabolism mainly is centered on the possibility that the glucans could entrap bile acids in the intestine and thus increase bile acid exclusion in the feces. The results by Freire Dos Santos et al. [22] suggest that *Cordyceps sinensis* biomass supplementation in high-fat diet (HFD)-fed rats for 4 months normalizes the blood lipid and the low testosterone levels induced by HFD. Despite the outcomes of the study, it has to be borne in mind nevertheless that *Cordyceps sinensis* biomass supplementation cannot replace the use of currently available drug regiments for lipid reduction but can easily complement them. It may also enable the use of lower doses of therapeutic drugs, thereby

decreasing the risk of dose-related side effects. Furthermore, Freire Dos Santos et al. demonstrated that a long-term intake of HFD caused a significant liver damage which has been reverted by *Cordyceps sinensis* biomass supplementation and, this in

Tiamyom et al. [17] investigated the effects of *Cordyceps sinensis* extract and *Gymnema inodorum* extract, used alone and combined, on antiadipogenesis in 3T3-L1 cells. Results from this study indicated that both herbs and their combination had inhibitory effects on lipid accumulation in the adipocytes. The pancreatic lipase assay results indicated that *Cordyceps sinensis* extract inhibited the pancreatic lipase activity in a dose-dependent manner. These results suggested that the use of *Cordyceps sinensis* extract alone and in combination with *Gymnema inodorum* extract may be efficacious as a complementary therapy for hyperlipidemia and obesity management.

*Cordyceps sinensis* appears to contain all of the essential amino acids, vitamins E and K, as well as the water-soluble vitamins B1, B2, and B12. In addition, it contains

turn, normalized decreasing testosterone levels observed in HFD-fed rats. Leptin, a newly discovered hormonal product of the obesity (ob) gene, is expressed by white adipose tissue. It has been implicated in the regulation of body weight, glucose metabolism, and fertility. Leptin deficiency produces severe obesity, insulin resistance, and impaired glucose tolerance in ob/ob mice, and also, congenital leptin deficiency in humans leads to hyperphagia and marked obesity. Choi suggested that *Cordyceps sinensis* originated EPS are excellent candidates to develop as functional food additives or therapeutic agents for anti-obesity and antidiabetic purposes through improvement in glucose homeostasis and

preservation of insulin reserves [23].

**5. Bioactive compounds of interest**

could be considered as the inhibition of preadipocyte differentiation.

**176**

many sugars, including mono-, di-, and oligosaccharides, and many complex polysaccharides, proteins, sterols, nucleosides, and trace elements. Characterization of cordycepin (**Figure 2**) and 2′-deoxyadenosine was reported by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy in an extract of *Cordyceps sinensis* [24, 25]. Cordycepin has been identified as one of the compounds involved in the anti-lipidemic effects of *Cordyceps sinensis*, and thus, within the context of this chapter needs to be highlighted as the primary bioactive compound involved in lipid metabolism and regulation. Cordycepin inhibits adipocyte differentiation and accumulation of lipid in mature adipocytes [26]. As cordycepin blocks both adipocyte differentiation and lipid accumulation, it has the potential to be an effective therapeutic agent for obesity and obesity-related disorders [26].

Nucleosides have been found in all species of *Cordyceps*, including uridine. A number of polysaccharides and other sugar derivatives, such as cordycepic acid (D-mannitol), have been also identified in *Cordyceps sinensis* [17].

In recent years, much interest has been focused on EPS produced by *Cordyceps sinensis* and its other varieties due to their various biological and pharmacological

#### **Figure 4.**

*Chemical structure of CPS-2, which was isolated by Wang et al. [27]. The structure was found to be mostly of α-(1 → 4)-d-glucose and α-(1 → 3)-D-mannose, branched with α-(1 → 4,6)-d-glucose every 12 residues on average.*

activities. These polysaccharides are effective in regulating blood sugar and appear to have antimetastatic and antitumor effects [27]. *Cordyceps sinensis* contains proteins, peptides, polyamines, and all essential amino acids as well [28]. Steroltype compounds have also been found in *Cordyceps sinensis*, including ergosterol, delta-3 ergosterol, ergosterol peroxide, 3-sitosterol, daucosterol, and campesterol [27, 28]. Twenty-eight saturated and unsaturated fatty acids and their derivatives have been isolated from *Cordyceps sinensis* [14]. Polar compounds of *Cordyceps sinensis* extracts include many compounds of alcohols and aldehydes; polycyclic aromatic hydrocarbons produced by *Cordyceps sinensis* as secondary metabolites were also reported. A water-soluble polysaccharide (CPS-2), isolated from the cultured *Cordyceps sinensis*, was obtained by hot water extraction, anion exchange, and gel permeation chromatography by Wang et al. [14]. The changes in blood urea nitrogen and serum creatinine in this particular study revealed that CPS-2 could significantly relieve renal failure caused by fulgerizing kidney. An image of this polysaccharide is shown in **Figure 3**. It is believed that there are several other polysaccharides as such with therapeutic potential in terms of lipid regulation in *Cordyceps sinensis* (**Figure 4**).
