II. Potential Development of Ganoderma lucidum Polysaccharide Peptide (PsP) as Antioxidant  and Anti Inflammation  in In Vivo Diabetes Mellitus type II Model

PsP’s pre-clinical trial of Ganoderma lucidum mushroom mycelium extract in in vivo Diabetes Mellitus type II model is a continuum to pre-clinical trial at atherosclerosis in vivo model. The high prevalence of DM patients with atherosclerosis becomes the base of conducting this trial. The aim of this trial is to prove that PsP has anti inflammation and anti-oxidant activities during atherosclerosis process which occurs at DM patients.

II.1. Study Method

II.2. Study Result

 II.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 IL-6 level in blood. The administration of PsP with the dose of 50 – 300 mg/kg bw/day for 3 weeks has lowered the increasing IL-6 level in atherosclerotic condition.

b. Effect of PsP Administration on IL-10

IL – 10 is an anti inflammatory cytokine and an immunosuppressive substance that is produced by mast cell.
IL – 10 inhibits pro inflammatory cytokine synthesis. The administration of PsP with the dose of 50 – 300 mg/kg bw/day for 3 weeks is able to increase IL-10 level in blood. This proves that PsP is able to suppress inflammation process which occurs in atherosclerosis and the progress of atherosclerosis can be inhibited.

c. 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, PsP administration with a dose 50 – 300 mg/kg bw/day for 3 weeks may lower the hs-CRP level in blood.

d. Effect of PsP Administration on TNF-a

TNF-a is a pro inflammatory cytokine which is secreted by monocytes, macrophages, neutrophils, lymphocyte T cells and NK cells (Natural Killer Cells). It regulates the immune cells and is involved in systemic inflammation. During atherogenesis process, there is an increase of TNF-a level in the blood due to inflammation at the blood vessel walls. The administration of PsP with the dose 50-300mg /kg  bw/day for 3 weeks proves that it can lower TNF-a  level in blood.

II.2.2. Effect of PsP Administration on Oxidative Stress

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 a dose 50 – 300 mg/kg bw/day for 12 weeks is able to lower the MDA level in blood; therefore, oxidative damage at 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 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. The administration of PsP 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.

II.3. Study Conclusion

The administration of PsP with a dose 50-300mg /kg bw/day for 3 weeks to Rattus norvegicus Winstar strain male rats which are inducted with diabetes by STZ 30 mg/bw injection and high-fat diet has proved that  PsP  is able to inhibit atherosclerosis progressivity through its as anti inflammatory and anti oxidant activities. Anti inflammatory activity is exposed by the decrease of IL -6, hs-CRP, TNF-α levels and by the increase of IL-10 level. Antioxidant activity is confirmed by the decrease of MDA level and the increase of SOD level. Further clinical study using human subjects will be carried out to support the use of PsP as complementary therapy for DM with the purpose of inhibiting cardiovascular complication due to DM.

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