I.     Potential  Development of Ganoderma lucidum Polysaccharide Peptide (PsP) as Antioxidant and  Anti Inflammatory in an In Vivo Model of Atherosclerosis.

This is a joint study between  SLH-Labs and Faculty of Medicine, Brawijaya University, Malang-Indonesia, which was held from July to November 2013. The aim of this study is to reveal the effect of polysaccharide peptide (PsP) of Ganoderma lucidum mycelium extract on several chronic inflammatory and oxidative stress (oxidative damage) markers which occur during atherosclerosis process. The result of this pre-clinical trial demonstrates that PsP  has anti inflammatory and anti-oxidant activities. Thus, PsP could be used as complementary therapy for patients suffering from heart and cardiovascular diseases or those who are at high risk of cardiovascular disease.

I.1. Study Method

 

I.2. Study Result

I.2.1. Effect of PsP Administration on Chronic Inflammation Markers

a. Effect of PsP Administration on IL-6 (Interleukin-6)

             

IL-6 is a cytokine that is secreted by T-lymphocyte cells and macrophages to induce the immune system during tissue damage that causes inflammation. IL-6 is classified as pro-inflammatory cytokine. In atherosclerosis, endothelial damage followed by inflammation process will increase the level of IL-6 in blood. The administration of PsP with the dose of 50 – 300 mg/kg bw/day for 12 weeks has lowered the increasing IL-6 level in atherosclerotic condition.

b. Effect of PsP Administration on hs-CRP

hs-CRP (high sensitive C-reactive protein) is a protein that is mainly produced by the liver as a result of chromatic stimuli on acute endothelial vascular inflammation. hs-CRP has a relatively high sensitivity value. In atherosclerotic condition the administration of PsP with the dose 50 - 300 mg/kg bw/day for 12 weeks may lower the hs-CRP level in blood.

I.2.2. Effect of PsP Administration on Oxidative Stress Marker

a. Effect of PsP Administration on MDA

 

MDA (malondialdehyde) is an end product of lipid peroxidation. It is often used as a biomarker of oxidative stress. When vascular oxidative stress or damage occurs due to atherosclerosis, the MDA level in blood will increase. The administration of PsP as an anti-oxidant with the dose 50-300mg/kg/bw/day for 12 weeks is able to lower the MDA level in blood, therefore oxidative damage in atherosclerosis can be suppressed.  

b. Effect of PsP Administration on SOD

SOD (Superoxide Dismutase) is an anti-oxidant enzyme that catalyzes the conversion of superoxide radicals (O2-.)  into oxygen and hydrogen peroxide H2O2. Superoxide  is a secondary product of oxygen metabolism. Without any regulation, it will cause various oxidative damages in cells. PsP administration with the dose  150 mg/kg bw/day for 12 weeks proves to be an optimum dose in increasing the SOD level in blood and suppressing the oxidative damage and inflammation process in atherosclerosis.

I.2.3. Effect of PsP Administration on other Atherogenesis Factors

a. Effect of PsP Administration on Total Cholesterol

Cholesterol level is a parameter that describes lipid profiles in blood serum, besides LDL (Low-density Lipoprotein) and HDL (High-density Lipoprotein). Total cholesterol level, in general, will increase during the process of atherogenesis (vascular plaque formation process). This study shows that PsP administration with the dose 150mg/kg bw/day for 12 weeks in atherosclerotic condition is an effective dose to lower total cholesterol level. 

b. Effect of PsP Administration on LDL

High LDL level in serum indicates high risk potency of cardiovascular disease.  LDL is a lipoprotein which transports fats around the body through the blood into blood vessel walls. LDL can experience oxidation due to free radicals so that in the end the plaque will be deposited at the blood vessel walls. The administration of PsP with the dose 50-300mg/kg bw/day for 12 weeks could lower the LDL level and thus inhibit atherosclerosis progressive process.

c. Effect of PsP Administration on HDL

The higher HDL level in blood represents the lower risk of cardiovascular disease. HDL is a lipoprotein which relocates fats on the blood vessel walls in order to inhibit LDL in atherogenesis process. The administration of PsP with the dose of 300mg/kg bw /day for 12 weeks will significantly increase HDL level in atherosclerotic condition.

d. Effect of PsP Administration on foam cells

During the atherosclerosis process, 'foam' cells are formed as a result of a group of macrophages that engulfs oxidized LDL at the blood vessel walls. The increase in the number of foam cells will trigger inflammation reaction and aggravate atherogenesis process. PsP’s anti oxidant activity is able to suppress the oxidized LDL resulting in the reduction of the number of macrophages which forms foam cells at the blood vessel walls.  PsP administration with a dose 50-300mg/kg bw/day for 12 days proves to reduce the number of foam cells.

I.3.  Conclusion

This study demonstrates that PsP administration with the dose of 50-300 mg/kg bw/day for 12 weeks at Rattus norvegicus Winstar strain male rats could inhibit the atherosclerosis progress at rats through its anti inflammation activities by reducing IL-6 and hs-CRP levels in blood. As an antioxidant it lowers the  MDA level as well as increases the SOD level. On the other hand, PsP administration with the above dose proves that it is able to improve the lipid profiles in blood. Further investigation at clinical trial using human subjects will be carried out to support the use of PsP as complementary therapy against atherosclerosis.

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