PERAN ASTAXANTHIN DALAM

PENATALAKSANAAN
COVID-19
COVID-19

Sistem Imun

Inflamasi

Radikal bebas
 Sistem Imun

ADAPTIVE
INNATE [1][2][3]
[1][2][3]
Source : Journal of Pharmaceutical Analysis (2020)[2]
Source : https://www.immunitrack.com/free-coronavirus-report-for-download/[3]
 Inflamasi

Cytokine Storm

Organ Failure 🡪 ARDS

Chemokine

Cells & Tissue Damage

 Cytokines Storm

IL-18

IL-6
IL-1β
IL-12

IFN-α

TNF-α TGF-β IL-33

IFN-γ
 ARDS

One of the main mechanisms for

ARDS is the cytokine storm[2]

the deadly uncontrolled systemic

inflammatory response resulting from the
release of large amounts of pro-inflammatory
cytokines and chemokines[2]
 Reactive oxygen species (ROS) are key signaling molecules that play an
important role in the progression of inflammatory disorders [5]

An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of

inflammation causes endothelial dysfunction and tissue injury [5]

The intricate balance between cell death and cell survival is largely modulated by intracellular
ROS generation
Uncontrolled VS controlled

Cytokines Cells
storm Integrity
 Tantangan Kita???

Menemukan perlakuan dan menggunakannya secara

tepat
 Immunomodulator & Antioksidan

Menurunkan reaksi inflamasi (memblokade sitokin

Immunomodulator pro inflamasi)

Mempertahankan keseimbangan
prooksidan&antioksidan sehingga menjaga
integritas seluler
Antioksidan

Tidak membentuk dan meninggalkan

prooksidan baru
 Preclinical study 1[6]

ASX treatment alleviated oxidative/nitrative stress, inflammation levels and pulmonary apoptosis in

lung tissues.

ASX treatment markedly down-regulated the expression of inducible nitric oxide synthase (i-NOS), 
nitrotyrosine (NT) and nuclear factor-kappa B (NF-Κb) P65 in the lung tissues

Astaxanthin treatment had markedly protective effect against ALI in mice, and the potential
mechanism is associated with its ability to inhibit the inflammatory response, oxidative/nitrative stress,
and pulmonary apoptosis, as well as down-regulate NF-κB P65 expression.
 Preclinical study 2[7]

AST had a dose-dependent anti-inflammatory effect on EIU. In particular, the

ocular anti-inflammatory effect of 100 mg/kg of AST was as strong as that of 10
mg/kg prednisolone. A possible mechanism for the ocular anti-inflammatory
effect of AST is the suppression of production of NO, PGE2, and TNF-α by directly
blocking NOS enzyme activity
 Quenching Activities of Common Hydrophilic and Lipophilic Antioxidants
against Singlet Oxygen Using Chemiluminescence Detection System [8]

The singlet oxygen quenching activities among common hydrophilic and lipophilic antioxidants
such as polyphenols, tocopherols, carotenoids, ascorbic acid, coenzyme Q10 and α-lipoic acid
were recorded under the same test condition: the chemiluminescence detection system for
direct 1 O2 counting using the thermodissociable endoperoxides of 1,4-dimethylnaphthalene
as 1 O2 generator in DMF : CDCl3 (9 : 1).

Carotenoids exhibited larger total quenching rate constants than other antioxidants, with
astaxanthin showing the strongest activity. α-Tocopherol and α-lipoic acid showed considerable
activities, whereas the activities of ascorbic acid, CoQ10 and polyphenols were only slight;
these included capsaicin, probucol, edaravon, BHT and Trolox. This system has the potential of
being a powerful tool to evaluate the quenching activity against singlet oxygen for various
hydrophilic and lipophilic compounds.
 Astaxanthin decreased oxidative stress and inflammation and
enhanced immune response in humans[9]

Participants (averaged 21.5 yr) received 0, 2, or 8 mg astaxanthin (n = 14/diet) daily for 8 wk in a randomized
double-blind, placebo-controlled study. Immune response was assessed on wk 0, 4 and 8, and tuberculin test performed
on wk 8.

Dietary astaxanthin dramatically decreased one DNA damage biomarker (plasma 8-OHdG), and this
protective effect was observed by wk 4 of feeding. 
 Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute
Diseases [10]

Astaxanthin, a dietary carotenoid, is present in algae, shrimp, lobster, crab, salmon,

and some other organisms

Its antioxidant activity is far exceeding the existing antioxidants.

The ROS-scavenging capacity is 6000 times that of VC,
800 times that of coenzyme Q10,
550 times that of VE,
200 times that of polyphenols,
150 times that of anthocyanins,
and 75 times that of α-Lipoic acid

Most importantly, no apparent side effects or negative results have been reported for
astaxanthin. In leukocyte cells, half of the total astaxanthin is distributed in the mitochondria.
Astaxanthin is also distributed in microsomes and nuclei [66].
Therefore, it is a mitochondrion-permeable antioxidant
 Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated
Acute Diseases [10]

for ROS-burst-mediated acute diseases, mitochondrion-permeable antioxidants

should be used in the early stage.

Hypothesis of Astaxanthin Injection

 White Paper : Astaxanthin (ASTX): A safe, natural, and multi-faceted
anti-inflammatory for maintaining lung health and possibly minimizing
SARS-CoV-2 effects

Importantly to lung inflammation and SARS-CoV2 infection, ASTX has been shown to
significantly decrease NF-kB pathway signaling both in vitro and in vivo

ASTX has also been shown to reduce inflammatory cell infiltration (neutrophils, eosinophils,
macrophages) in a lung model of inflammation

ASTX has been shown to reduce the numbers of M1 macrophages displaying M1 phenotype
in favor of M2 phenotype

In addition to inhibition of NF-kB pathway activation, reduction in the M1/M2 macrophage

phenotype ratio is important in decreasing levels of inflammatory cytokines
 Referensi

1. Shi, Y., Wang, Y., Shao, C. et al. COVID-19 infection: the perspectives on immune
responses. Cell Death Differ (2020). https://doi.org/10.1038/s41418-020-0530-3
2. Li, X., Geng, M., Peng, Y. et al. Molecular immune pathogenesis and diagnosis of
COVID-19. Journal of Pharmaceutical Analysis (2020).
https://doi.org/10.1016/j.jpha.2020.03.001
3. Coronavirus Data Release: Identification of Novel CD4 and CD8-Stimulating Epitopes
From COVID-19.
https://www.immunitrack.com/free-coronavirus-report-for-download/
4. Guan, W., Ni, Z., Hu, Y., et al. Clinical Characteristics of Coronavirus Disease 2019 in
China. New England Journal of Medicine (2020).
https://www.nejm.org/doi/10.1056/NEJMoa2002032
5. M, Manish., R S, Mohammad., T, Khiem., et al. Reactive Oxygen Species in
Inflammation and Tissue Injury. Antioxid Redox Signal (2014).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929010/
6. B,Jianbin., C, Ruixia., L, Zeyu., et al. Astaxanthin alleviated acute lung injury by
inhibiting oxidative/nitrative stress and the inflammatory response in mice.
Biomedicine & Pharmacotherapy (2017).
https://www.sciencedirect.com/science/article/abs/pii/S0753332217339896
7. K, Ohgami., K, Shiratori., S,Kotake., et al. Effects of astaxanthin on
lipopolysaccharide-induced inflammation in vitro and in vivo. Physiology and
Pharmacology (2003)
8. Yasuhiro Nishida*, Eiji Yamashita and Wataru Miki . Quenching Activities of Common
Hydrophilic and Lipophilic Antioxidants against Singlet Oxygen Using Chemiluminescence
Detection System. Carotenoid Science (2007)
9. Jean Soon Park,1 Jong Hee Chyun,2 Yoo Kyung Kim., et al. Astaxanthin decreased oxidative
stress and inflammation and enhanced immune response in humans. Nutr Metab (Lond)  (2010).
10. Zhong-Wei Zhang,1 Xiao-Chao Xu,2 Ting Liu,3  Shu Yuan. Mitochondrion-Permeable
Antioxidants to Treat ROS-Burst-Mediated Acute Diseases. Oxidative Medicine and Cellular
Longevity (2016). https://doi.org/10.1155/2016/6859523
11.
QS 2: 31-32
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