European Journal of Molecular & Clinical Medicine

ISSN 2515-8260 Volume 08, Issue 03, 2021

THE EFFECTIVENESS OF POLY-HERBAL AS

ADJUVANTS FOR THE STANDARD TREATMENT OF
COVID 19 IN PATIENTS WITH MODERATE DEGREE
OF SARS COV2 BASED ON CLINICAL AND
LABORATORY SYMPTOMS
Lusi Nursilawati Syamsi, Chaidir Amin, Nurita Andayani, Syamsudin Abdillah
Postgraduate Programme, Faculty of Pharmacy, Universitas Pancasila, Jakarta, Indonesia
Corresponding author: syamsudin.abdillah@univpancasila.ac.id

Abstract
This study aims to examine the effectiveness of polyherbal (ONOIWA MX) capsules
containing 5100mg Channa striata extract, Curcuma xanthorriza 240mg and Moringa
oleifera 240mg as adjuvants for standard treatment of Covid 19 in the management of
moderate pneumonia.
Method
This is a clinical randomized controlled single blind parallel study conducted during the
COVID-19 pandemic on patients having symptoms as well as positive cases, meanwhile,
patients were follow-up for 7 days after the last dose of Onoiwa MX. A total of 48 patients
were COVID-19 positive and divided into 2 groups namely group I (n = 24) given standard
therapy 2x200mg hydrochloroquine, 1x 500mg azithromycin injection, 2x75mg oseltamivir as
well as 750mg Levofloxacin injection and Onoiwa MX 3x1 sachet for 7 days. Meanwhile,
patients in the second group were given 2x200mg hydrochloroquin, 1x500mg azithromycin,
2x75mg oseltamivir as well as 750mg Levofloxacin injection + C.striata sachet 3 times a day
for 7 days. Furthermore, a clinical and vital signs examinations were carried out on the
patient daily.
CONCLUSION
The administration of ONOIWA MX sachet as an adjuvant therapy for standard COVID-19
treatment reduce parameters such as D-dimer, CRP and clinical symptoms.
Keywords: ONOIWA MX sachet, COVID-19

Introduction
Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is a new type of Coronavirus that has
never been previously identified in humans. At least two types are known to cause diseases
resulting in severe symptoms such as Middle East Respiratory Syndrome (MERS) and Severe
Acute Respiratory Syndrome (SARS). The common signs and symptoms of COVID-19 infection

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include acute respiratory problems such as fever, cough and shortness of breath. Furthermore, the
mean incubation period was 5-6 days with the longest incubation period being 14 days 1,2.
Severe cases of COVID-19 cause pneumonia, acute respiratory syndrome, kidney failure, and
even death 2,4.
Based on data from countries affected by the initial pandemic, 40% of cases experience mild and
moderate diseases such pneumonia respectively, 15% experience serious illness, while 5%
experience critical condition. Patients with mild symptoms recovered after 1 week, meanwhile,
there were no signs of viral pneumonia or hypoxemia in mild cases based on the criteria for
severe cases in adults, while in moderate cases, clinical manifestations of pneumonia were found
with symptoms of fever, cough, shortness of breath and rapid breathing with oxygen saturation
above 90 mmHg, but no symptoms of severe pneumonia were found. Moreover, in severe cases,
saturation decreased below 90 mmHg with symptoms of pneumonia, namely fever, cough,
shortness of breath and rapid breathing2,6,7. In critical cases, Acute Respiratory Distress
Syndrome (ARDS), sepsis and septic shock, multi-organ failure, including kidney or acute heart
failure are found which ultimately result to death. Meanwhile, COVID-19 severely attacks
patients with comorbid factors such as metabolic syndrome, kidney and heart failure, as well as
other secondary infections such as Human Immunodeficiency Virus (HIV), tuberculosis and non-
COVID-19 pneumonia3,5. The WHO has highlighted the appropriate use of natural products as a
prime candidate to explore bioactive Moringa oliefera in anti-viral research. This is because there
is no effective vaccine and the supply of expensive drugs is insufficient for socio-economic
demands 9,10. Therefore, the problem examined in this study is the role of natural medicines
with various properties as adjuvant therapy in the management of COVID19. Patient recovery is
very important while treatment is very dependent on the body's immune response and the speed
of health workers in handling acute cases or emergencies 8. This study aims to examine the
combination of Channa striata, Curcuma xanthoria and Moringa oliefera, each with properties
expected to provide better improvement in the standard treatment of COVID 19 patients. The
combination has several properties including immunostimulants, anti-inflammatory, anti-
microbial, anti-viral, anti-oxidant and also function as a hepatoprotector, preventing
hypoalbunemia and dyslipidemia in metabolic syndrome 9.

Methods
Study design
This is a clinical randomized controlled single blind parallel study conducted during the COVID-
19 pandemic on patients having symptoms and as well as positive cases. Patients were follow-up
for 7 days after last dose of Onoiwa MX. A total of 48 patients were COVID-19 positive13,15.

Study population
The inclusion criteria for the sample include patients confirmed to have Covid-19 through
positive PCR, aged 18–60 years, no comorbid factors, not pregnant/breastfeeding, patients with
compos mentis awareness / no loss of consciousness, willing to take part in the study after

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signing the informed consent, not hypersensitive, and do not have a history of allergies to certain
drugs, ingredients or food. In contrast, the exclusion criteria include patients with other
pulmonary infections such as tuberculosis, bacterial pneumonia, as well as pregnant/lactating
women, hypersensitivity to certain drugs, substances, or food, patients with decreased
consciousness or mental disorders, and under 18 or over 60 years. Based on the inclusion and
exclusion criteria, a total of 48 patients were recruited and divided into 2 groups:
Group I (Intervention) : 24 patients were given 2x200mg of hydroxychloroquine, 1x500mg
injection of azithromycin, 2x75mg of oseltamivir, and 750 mg of Levofloxacin + Onoiwa MX 3
times a day, 1 sachet for 7 days.
Group II (control) : 24 patients were given 2x200mg hydroxychloroquine, 1x500mg
azithromycin, 2x75mg oseltamivir, and 750mg Levofloxacin injection + control for 7 days. The
patients were subjected to clinical and vital signs examinations daily.

Consent and ethical approval

This study was approved by the Institutional Ethics Committee and registered prospectively at
Sentra Medika Hospital (001/Suket/KEPK/III/2021). The patients were recruited based on the
inclusion and exclusion criteria after the eligible patients submitted a written informed consent.

Intervention
This study used the standard therapy for COVID-19 patients as follow:
Onoiwa MX produced by PT Nuswantara Nirmala Nusantara, Bintaro, Indonesia. Each capsule
contains Channa striata extract 5100mg, Curcuma xanthorriza 240mg, and Moringa oleifera
240mg as an adjuvant to standard treatment given for the management of Covid-19 patients
confirmed with moderate pneumonia with a dose of 3x1 sachet per day orally for 7 days. The
treatment results were assessed for improvement in clinical and laboratory symptoms every 5
days of patient care.
Table 1. Criteria for Clinical Symptoms and Manifestations 1,2

Symptom Clinical Definition

criteria manifestations
No The mildest The SARS-CoV-2 test results were
Symptoms conditions positive without any clinical signs and
symptoms
Mild ill Mild pain Symptomatic patients without evidence
without of viral pneumonia or hypoxia.
complications Symptoms include fever, cough,
fatigue, anorexia, shortness of breath,
myalgia. In addition, other non-specific
symptoms such as sore throat, nasal
congestion, headache, diarrhea, nausea
and vomiting, loss of smell (anosmia),

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or loss of taste (ageusia) that appear

before the onset of respiratory
symptoms are also frequently reported.
Aged patients had
immunocompromised atypical
symptoms such as fatigue, decreased
consciousness, and mobility

Moderate Mild In adolescent or adult patients: Those

ill pneumonia with clinical signs of pneumonia (fever,
cough, shortness of breath, rapid
breathing), but no signs of severe
pneumonia including SpO2> 93% with
room air.
Severe ill Severe In adolescent or adult patients: Those
pneumonia / with clinical signs of pneumonia (fever,
severe ARI cough, shortness of breath, rapid
breathing) and one of respiratory rate>
30 x/second, severe respiratory distress,
or SpO2 <93% in room air.
Critical Acute Patients experience rapidly progression
Respiratory to acute respiratory distress syndrome
Distress (ARDS) or respiratory failure, develop
Syndrome shock, encephalopathy, myocardial
(ARDS) damage or heart failure, coagulopathy,
acute renal impairment, and multiple
organ dysfunction or other
manifestations of sepsis.

Clinical examination was conducted from November 2020 to January 2021 after passing the
Ethics review. The study commenced by initially filling in the informed consent, signing it, and
thereafter proceeded to the selection, treatment, and post-treatment phase respectively. During
the study, clinical symptoms, complete blood count, C reactive protein, D dimer were assessed
before and after COVID 19 treatment.

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Study treatments
The study framework is presented as follows:

CRP repair
The period of
hospitalization
D-dimer
Improvement of clinical
symptoms

Patients were divided into 2 groups namely:

Group I; given 2x200mg hydroxychloroquine, 1x500mg injection of azithromycin, 2x75mg
oseltamivir, and 750mg Levofloxacin injection + ONOIWA Mx 3x1 sachet for 7 days.
Group II: given 2x200mg Hydrocloroquin, 1x500mg azithromycin, 2x75 mg oseltamivir, and
750 mg Levofloxacin injection + control 3x1 sachet for 7 days. The patients were subjected to
clinical and vital signs examination daily.

RESULTS

A total of 315 patients were excluded because the data were incomplete while 48 patients were
included based on the inclusion requirements. The patients' demographic data and clinical
characteristics are presented in Table 1.
Table 1. Demographic and clinical characteristics of the participans at baseline

Variables Grou I Group II

Age
< 40 year 4 6
40-60 year 16 15
61-79 year 4 3
Respiratory Symptoms
Cough 87,5% 95,8%
Dyspnea 75% 75%
Fever 75% 79,2%
Anosma 12,5% 4,2%

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Based on the table above, majority of the respondents had cough symptoms (87.5% in the
intervention and 95.8% in the placebo group), fever (75.0% in the intervention, and 79.2% in the
placebo group), and Dyspnea (75,% in the intervention and 75.0% in the placebo group), while
8.3% of respondents had anosmia symptoms (12.5% in the intervention and 4.2% in the placebo
group). Therefore, it was concluded that the majority of respondents have symptoms of cough,
shortness of breath (Dyspnea), and fever.

60
54,2

50
Co-morbid conditions of patients

41,7
40 37,5

30

20,8
20 16,7 16,7
12,5
10 8,3 8,3 8,3 8,38,3
4,2
0
0
Diabetes CKD HF CVD Asma COPD Hypertension
Comorbidity status

Group I Group II

Figure 1. Co-morbid conditions of patients

Based on Figure 1, the most common comorbid suffered by therespondents include hypertension
(41.7% in the intervention and 54.2% of the placebo group) and Diabetes Mellitus (DM) (20.8%
of the intervention and 37.5% the placebo group). Meanwhile, the least suffered comorbid
include CKD (4.2% of the intervention and 8.3% of the placebo group) and Asthma (8.3% of the
placebo group).

Table 2. Initial laboratory data of the patients

Group I Group II
Variable Before treatment After treatment Before treatment After treatment
Hgb (g/dL) 13,43 gm/dL 13,35 gm/dL 13,676 gm/dL 13,518gm/dL
Lymphocyte (%) 16,95% 21,20% 18,375% 18,916%
CRP (mg/dL) 55,46 mg/dL 20,33 mg/dL 66,75 mg/dL 18,83 mg/dL

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D-Dimer 1380,58 412,60 799,11 379,56

NLR 6,875 7,0345 5,445 5,496
ALC 1,3535 1,6038 1,516 1,451

Table 2 shows the laboratory results data of group I administered with polyherbal
supplementation (ONIWA MX) compared to group II indicating the values of Hgb, lymphocytes,
CRP, D-dimer, NLR, and ALC before and after treatments. The lymphocyte yield in group I
before treatment was 16.95%, but after polyherbal supplementation for 7 days, it increased by
21.20%. This result was better than the comparison group II which yielded 18.375% and
18.916% before and after treatment respectively. The CRP value of group I before and after
treatment was 55.46 mg / dL and 20.33 mg/kg BW respectively, while in the comparison group,
the value was 66.75 mg/dl, and was 18.83 mg/dl. Moreover, the D-dimer value in group I was
1380.58 and 412, 60 before and after treatment while in group II, the value was 799.11 and
379.56.

In this study, the use of ONOIWA MX containing Channa striata extract, Curcuma xanthorriza,
andMoringa oleifera as an adjuvant for the treatment of COVID-19 was measured for its
effectiveness in reducing the length of stay (LOS), C-Reactive Protein (CRP), and D-dimer. By
measuring LOS reduction, it was found that the intervention group had a mean LOS of 10.25±
5.06 days), while the placebo group had a mean LOS of 9.00±3.96 days). The statistical tests
showed that there was no significant difference between LOS in the intervention (Group I) and
the placebo group (group II) (p = 0.6480). Although, the intervention and the placebo group had
no significant difference and even the placebo group's LOS was shorter, other factors played a
role. An example is a non-pharmacological intervention, such as the availability of a
ventilator18. Measurement of CRP before and after treatment in the intervention (group I) and
placebo (group II) showed that there was no significant difference in the mean CRP of the two
groups (α> 0.05) using the Mann-Whitney test. Although there was no statistically significant
difference, the difference in mean CRP before and after treatment in the intervention and placebo
group was 35.12 and 47.92 respectively. Therefore, It was concluded that there was a decrease in
the mean CRP in both groups. Inflammation that occurs in COVID-19 is indicated by several
signs, including Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-C-reactive protein
ratio (LCR) which shows the systemic inflammatory response in the body. Based on Tan et al.
(2020)17, correlation analysis showed that CRP (R = .62; P <.01) was positively associated with
CT severity values. In contrast, the lymphocyte count (R = −.37; P <.01) was negatively
associated with the CT severity value. Therefore, a high NLR value and a low LCR reflect an
inflammatory process that is indicative of a poor prognosis16.

DISCUSSION
There is currently no treatment for COVID-19, the therapy used including antivirals and
antibiotics, only relieves the symptoms. Apart from drugs, preventive measures such as
government's efforts to vaccinate the public are underway. Although, the vaccine is being

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distributed, other efforts to alleviate the impact of COVID-19 are still needed. This study used
clinical observations with the treatment group whichreceived the adjuvant (group I) and the
control group whichreceived the placebo (group II). The use of placebo in drugs clinical trials is
carried out to test the effectiveness. It is used not as a substitute for standard treatment, but in
addition to existing standard treatments. In this study, the use of adjuvants was not a substitute
for COVID-19 treatment, but as a treatment supplement15. Furthermore,in situations like
COVID-19 where there is no effective drug as cure, a placebo is used to improve the patient's
condition. Meanwhile, efforts to avoid adverse effects in patients are to be actively carried out.
ONOIWA MX containing extracts of Channa Striata, Curcuma Xanthorriza, and Moringa
oleifera with information on bioactive compounds and mechanisms of action are shown in Table
2.

Table 2. Information of the key ingredients of Onoiwa MX

Ingredients Main active compounds Known effects and possible

mechanisms of actions
Channa striata Albumin In COVID-19 patients, the level
of serum albumin is decreased and
the body requires more serum
albumin

SARS-CoV-2 virions bind to

Moringa oleifera
albumin and reduce the
concentration of glycocalyx,
therefore, deplete the endothelial
glycocalyx layer11.
Quercetin In a bioinformatics study,
Flavonoid researchers have investigated the
quercetin-3-glycoside, potential of compounds derived
rutin, from Moringa oleifera in
kaempferol glycosides inhibiting SARS-CoV-2 proteases
and chlorogenic acids and made a comparison with
known antiviral drugs.

Quercetin-3-O-β-galactoside
binds to SARS-Cov 3 Cl protease
and inhibits its proteolytic activity
with an IC50 of 42.79 ± 4.95 µM

Que was also identified as being

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able to block SARS-coronavirus

entry into Vero E6 cells with a
half-effective concentration
(EC50) of 83.4 µM and low
cytotoxicity (CC50 3.32
5,6,10,12
mM) .

Curcuma xanthorrhizae Curcumin Curcumin as (1) potential

Flavonoids inhibitory agent blocking the host
viral interaction (viral spike
protein—ACE2 receptor) at an
entry site in humans and (2) as an
attenuator via modulating the
proinflammatory effects of
Angiotensin II-AT1 receptor-
signalling pathways and reducing
respiratory distress in the
14
treatment of COVID19 .

The hypothesis for the SARS-CoV-2 treatment strategy is through the simultaneous targeting of
extracellular and intracellular viral particles. Meanwhile, the viral action strategy is through the
potential to internalize the effect of drugs on the activity of viral protease enzymes, polymerase,
and RNA8,9,11. Serum albumin is used as an excellent vehicle for drug action and it is a
multifunctional protein i.e both intracellular and extracellular(11). The highest serum albumin
concentration is extracellular, namely in the skin, muscles, intestines, cerebrospinal fluid, pleural
fluid, and secretions such as sweat, tears, saliva, and milk. There is a relationship between the
level of inflammation and extracellular albumin levels. It is known that infected cells under
stress conditions increase the need for albumin, both physiologically and pathologically.
Therefore, a combination capsule of Channa striata5100mg, Curcuma xanthorriza 240mg and
Moringa oleifera 240mg (ONOIWA MX) is very useful in the treatment of SARS-Cov2. This
combination inhibits the fusion and entry of the virus into the cell while the other drug
internalizes the target of several viral components and signals the cell to stop the spread of the
virus. Recent searches for the treatment of SARS-Cov2 infection on PubMed revealed that the
use of traditional medicines in treating COVID-19 showed the high potential of curcumin in
neutralizing viral activity. According to recent studies, albumin therapy supports COVID-19
patients due to the complex relationship between albumin concentration and ACE2 receptor
expression in cells, and the ACE2 receptor is essential in mediating viral infection 11.
Furthermore, albumin is used to stabilize and transport curcumin to intracellular viral targets

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with a drug combination component that blocks viral fusion and/or entry into cells, this strategy
is an effective way of treating SARS CoV-2 virus infection. Curcumin is very effective in
treating variety of pathological conditions by increasing the main cellular signal. The inhibition
of this main cellular pathway also helps in inhibiting the multiplication of viruses within cells as
reported in the case of SARS-CoV14. Apart from its antiviral results, curcumin also has anti-
inflammatory, antioxidant, and immunomodulatory effects.

Conclusion

Based on the results, the administration of ONOIWA MX sachet containing a combination of

Channa striata5100mg, Curcuma xanthorriza 240mg, and Moringa oleifera 240mg is an
effective adjuvant therapy for the treatment of COVID-19.

Acknowledgements

The authors acknowledged all the participants for their time.

Authors’ contributions

LNS conceptualized and designed the study. LNS, C, SA, NA enrolled the participants and
collected the data. LNS and NA analyzed the data. SA wrote the first draft of the manuscript.
LNS, C, SA and NA made significant inputs into the final version of the manuscript. SA
provided important advice at all stages of the study. All authors read the final version of the
manuscript and confirmed it for publication.

Conflict of interests

The authors declare no conflict of interests

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