Discussion

This study aims to prove whether extract Ganoderma lucidum that given can
decrease inflammation process in patient with STEMI and NSTEMI history. Atherosclerosis is
chronic blood vessel disease in medium or large size which happened because of
immunology and inflammation reaction. Inflammation process is the core of atherosclerosis
process. Formation of fatty streak occurs when activated endothel and chemokine
expression along with molecul adhesion which cause the monocyte recruitment,
lymphocyte which infiltrate into subendothelial. This process also occurs on another blood
vessel when the plaque and thrombus occurs.

Understanding the inflammation role in atherosclerosis pathogenesis make

inflammation as target therapy within this disease, even as prevention or therapeutic stage.
Potential target in prevention of atherosclerosis is to prevent central signalling or
inflammation through inhibiton of NF-κB activation. Transcription route target of NF-κB for
chronic disease such as atherosclerosis are promising strategy to prevent inflammation
within atherosclerosis (Libby, 2002; Hansson, 2009). One of the mechanism is prevention of
NF-κB activation is using the antioxidant (Curtiss, 2009).

Natural antioxidant is abundant at nature, one of them is on Ganoderma lucidum.

Ganoderma lucidum contains active chemical compound of 1,3 β-d-Glukan which has
natural anti-inflammation and antioxidant (Pedraza-Chaverri et al., 2008; Huang et al.,
2001). Contents of the highest 1,3 β-d-Glukan is at Ganoderma lucidum (Bumrungpert,
2009). 1,3 β-d-Glukan is active substrate that has natural antioxidant property in the nature.
Fruit of Ganoderma lucidum from study is known to have 50.... 1,3 β-d-Glukan from 200....
1,3 β-d-Glukan in nature, which occur at isolation of Ganoderma lucidum which cintain anti
oxidant and anti inflammation (Pedraza-Chaverri et al., 2008; Huang et al., 2001).

1,3 β-d-Glukan inside Ganoderma lucidum in some study reported has

antiinflammation, antioxidant and cardioprotection effect. Effect of anti inflammation inside
Ganoderma lucidum fruit, expected strongly from protein which induce pro inflammation
gene which is nuclear factor kappa B (NF-κB). NF-κB is factor which induce transcription of
gen and sensitive within the response of oxidative stress. Nakatani et al. (2004) shows that
1,3 β-d-Glukan can prevent degradation of ikB and activation of NF- κB, has potential effect
which is absorbed into circulation and can prevent the inflammation process. Ganoderma
lucidum also proven to decrease the activity of intracellular reactive oxygen species (ROS)
(Pedraza-Chaverri, 2008). In oxidative process, especially ROS can cause kinase activation
which activates NF-κB as one of the process that play roles in inflammation process and
make atherosclerosis, where NF-κB stimulate transcription process one of the
proinflammation cytokines, those are TNF-α and IL-1 (Pasceri et al., 2000; Kleemann et al.,
2008). IL-1 induce some of protein synthesis, which are proinflammatory cytokines (IL-
6,TNF), mediators (cyclooxigenase, inducible NOS), active phase protein (C-reacttve protein,
complement factor), or growth factor (FGF). Proatherogenic effect IL-1 bind to its role to
modulate some important event happen in the inflammation process, leucocyte
chemotaxis, and plaque rupture. Increase of metalloproteinase matrix which induced by IL-1
that can make destabilization of atherosclerosis which cause.... Significant role of IL-1 as
important agent of atherogenesis is strengthened by study which prove that deficency of
antagonis receptor IL-1 has proatherogenic effect.

By the mecahnisms explained above, it is expected that 1,3 β-d-Glukan in

Ganoderma lucidum extract can inhibit the activation of NF-κB, so that there is not
ubiquitination and degradation of NF-κB and IkB complex at cytoplasm. As consequences,
there will be no translocation NF-κB into the nucleus and there won’t be any pro-
inflammatory protein transcription and translation. One of the mechaism is to decrease the
level of TNF-α and IL-1.

In this study, shows that Ganoderma lucidum extract can decrease the content of
MDA significantly and increase the level of SOD significantly. MDA is aldehid compound and
last product from lipid peroxidation inside the body (Cook et al., 2006).lipid peroxidation is a
process which lipid has double chain carbon that can react with oxidant (Ottaviani et al.,
2010; Briganti et al., 2003). Hydroperoxide lipid is the main product of lipid peroxide process.
The high content of MDA can describe the oxidation process of membrane cell that can
harm the membran cell (Cook et al., 2006). This is because the structure of hydroperoxide
lipid is not so stable and can easily change into malondialdehide (MDA), 4-hydroxy-2-
nonenal (4-HNE), and some other form of aldehide, where MDA is the main secondary
product because it is more mutagenic compared to another aldehide (Ayala et al., 2014).

Moreover, MDA characteristic which is stable chemically make the compound more
often used as marker of oxidative stress rather than 4-HNE. (Palmieri et al., 2007; Grotto et
al., 2009). MDA increase the occurance of unstable atherosclerotic plaque by increase the
level of Ox-LDL and formation of foam cell by increase the receptor affinity of free radical
where foam cell is Ox-LDL particle which is uptaken by macrophage (Griendlinget al., 2003;
Grotto et al., 2009). So that antioxidant mechanism as defense mechanism against free
radical. One of the main antioxidant is SOD (superoxide dismutase). SOD is an antioxidant
enzyme that can neutralize superoxide (Griendlinget al., 2003).

But, inside the body there is EPC (endothelial progenitor cell) cel that arises from
stem cell inside the bone marrow and monocyte cell which differentiated and migrated to
perivascular space to secrete proangiogenesis cytokines so it can repair the ischemic tissue
due to release of CEC (circulating endothelial cell), vascular endothelial cell which circulate
into the peripher blood (Lin et al., 2000; Lee et al., 2014).

In this study, shows that Ganoderma lucidum extract can increase the amount of EPC
significantly and decreace CEC although not significant. Dysfunction of endothel can be
caused by imbalance of vasodilatation and vasoconstriction (also abundant oxidant that also
trigger endothelial dysfunction. Endothelial dysfunction will be worsening the
atherosclerosis lession by increase the endotel permeability, aggregation of platelet,
monocyte attachment, and release of cytokines.
 In this study, shows that Ganoderma lucidum extract can decrease the amount of NO
significantly. NO is free radical which widely produce inside the body of macrophage,
endothelial cell, neutrophil, hepatocyte, neuron cell and another cell and also uniquely NO
can act as double promising agent as oxidant or antioxidant. NO function which is no less
important are relaxation of smooth muscle (vasodilatation), neurotransmitter, inhibitor of
adhesion, activation and aggregation of platelet, cytoprotection, signal transduction and
antioxidant. NO can recieve or donor the electron depends to other environment, so it can
make NO and peroxynitrite which also a strong oxidator and related to pathogenesis of DM.
Normally, NO is produced by endothelial cell from L-arginine and oxygen molecule from
three type of NOS; neuronalnitric oxide synthase (n-NOS), inducible nitric oxide synthase
(iNOS) and endothelial nitric oxide synthase (eNOS). P13K signal from Akt has role on
prosurvival and proangiogenic mechanism, the signal excite phosphorilation and activation of
eNOS which produce NO for physiological activity.