


































[3] Identification of anti-inflammatory compounds present in Nigella sativa and analyzing their effects on the inflammation pathway using in silico techniques 


ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 

 

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. 
 

IDENTIFICATION OF  
ANTI-INFLAMMATORY  

COMPOUNDS PRESENT IN 

NIGELLA SATIVA AND  
ANALYZING THEIR  
EFFECTS ON THE  
INFLAMMATION  
PATHWAY USING  

IN SILICO TECHNIQUES 
 

HABIBA ABDELHALIM 
SONIA ARORA, PHD (FACULTY ADVISOR) 
 

✵  ABSTRACT  
Nigella sativa, also known as black cumin, is 

an herb native to Asia, the Middle East, and the 
Mediterranean. The chemical constituents found in 
Nigella sativa seeds have been known to have a 
wide array of pharmacological actions. Previous 
studies have primarily focused on identifying the 
structures of these compounds and their medicinal 
properties based on physiochemical analysis. There 
have been few studies that explain how these com-
pounds interact with enzymes found in the human 
body. Hence, the objective of this study was to iden-
tify anti-inflammatory compounds present in Nigella 
sativa from previous literature and see if these com-
pounds can be used to target the cyclooxygenase-
2 inflammatory pathway. We compiled a list of 
twenty-three chemical compounds present in Ni-
gella sativa and then constructed a comprehensive 
molecular database of their three-dimensional 
structures using chemical modeling approaches. 
We then docked these compounds into two differ-
ent cyclooxygenase-2 molecules, using in silico 

techniques, to observe their conformation as well as 
binding affinity. Furthermore, we analyzed the inter-
action patterns of the five most stable compounds 
to understand their effects on the cyclooxygenase 
binding pocket. In conclusion, using structural bio-
informatics approaches, we have identified novel 
compounds derived from Nigella sativa that can be 
used as possible agents to target inflammation. 

 

1 INTRODUCTION  
Ethnobotany is the study of traditional cus-

toms observed by humans in relation to plants re-
garding their medicinal, nutritional, and religious 
values1. Historically, plants and the natural com-
pounds they produce have been used differently by 
different societies; thus ethnobotany has a wide ar-
ray of applications ranging from plant dyes to guid-
ing drug discovery and development. Previously, 
researchers have collected plant samples and per-
formed phytochemistry studies that would later be 
used in clinical studies. Although synthetic bio-
chemistry has greatly reduced the need to use nat-
ural compounds derived from plants, ethnobotani-
cal studies have been of extreme academic interest 
in recent years2. This interest stems from the fact that 
more plant-derived drug interactions have been ob-
served as traditional and herbal medicines become 
more popular. As of 2019, the World Health Organ-
ization reports that about 80% of the world popula-
tion relies on traditional medicine3. Consequently, it 
is important to have clear regulations on these types 
of conventional medicine. Studying the possible in-
teractions these natural compounds have on mole-
cules and enzymes in the human body is the first 
step in establishing these guidelines.  

Nigella sativa, also known as black cumin or 
black seed, is a plant native to Eastern Europe and 
Western Asia. It has also naturalized over to North 
Africa and parts of the Middle East4. The seeds of 
Nigella sativa have been used in traditional Islamic 
and Ayurvedic medicine for generations5. Tradition-
ally, it is used postpartum to aid with lactation and 
menstruation5. It is also thought to have a wide array 
of pharmacological actions including anti-microbial, 
antioxidant, anti-hyperlipidemic, and the focus of 
our research, anti-inflammatory action5. Several 



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

chemical compounds present in Nigella sativa, 
namely thymoquinone, can reduce asthma symp-
toms and treat rheumatoid arthritis by targeting the 
inflammatory pathway5.  

Inflammation is a biological immune re-
sponse that can be triggered by many external fac-
tors such as bacteria, viruses, and foreign bodies. 
Pain, swelling, redness and warmth are some of the 
symptoms associated with an inflammatory re-
sponse. On the cellular level, cytokines, small cell-
signaling proteins, are released to recruit other im-
mune cells to the site of infection. Vasodilation and 
increased permeability allow other signaling mole-
cules to diffuse across to address the inflammation. 
In normal circumstances, an acute defense mecha-
nism is employed to protect cells and eliminate en-
dogenous compounds. However, uncontrolled in-
flammatory responses may become chronic leading 
to extreme pain and, in extreme cases, tissue 
death6. There are typically two routes by which in-
flammation can proceed. One includes cytokine se-
cretion due to the recognition of pathogen-associ-
ated molecular patterns (PAMPS) by toll-like recep-
tors (TLRs); the other is bradykinin synthesis, which 
triggers prostaglandin formation and leads to vaso-
dilation7. We focus on the latter pathway here. Ara-
chidonic acid found in poultry and meat is con-
verted by cyclooxygenase-1 and 2 (COX-1 and 
COX-2) into prostaglandins. These two enzymes can 
be targeted by traditional non-steroidal anti-inflam-
matory drugs (NSAIDs). Since COX-1 is an important 
enzyme for gastric protection and platelet function, 
selective NSAIDs need to target only COX-2, which 
is responsible for pain and inflammation8. The ob-
jective of this research is to create a comprehensive 
database of chemical constituents present in Nigella 
sativa and analyze their interaction with COX-2 us-
ing in silico docking methods.  

 

2 METHODOLOGY 
CONSTRUCTION OF MOLECULAR DATABASE FOR  
NIGELLA SATIVA CONSTITUENTS  

PubChem and PubMed were used to com-
pile the database. PubChem is a database that pro-
vides information on chemicals and their activity. 

PubChem Compound, one of PubChem’s inter-
linked databases, shows a wide array of compounds 
and uses another database, PubChem Bioassay, to 
compile each chemical’s information9. PubMed 
houses an extensive number of biomedical journals 
and peer-reviewed literature. In addition, it provides 
access to related entries in other National Center for 
Biotechnology Information (NCBI) databases10. We 
used PubMed to retrieve the structure of the chem-
ical compounds from scientific literature and com-
pile them into an Excel spreadsheet. After recording 
twenty-three different chemical compounds, their 
chemical structures were downloaded as Standard 
Delay Format (SDF) files from PubChem. The Pro-
tein Data Bank (PDB), which is a database containing 
3D structures of biological molecules, was then 
used to obtain three different COX-2 files with inhib-
itors in their binding pockets. The three targets were 
5F1A, 5IKT, and 5KIR with salicylate acid, tolfenamic 
acid, and Vioxx as the inhibitors, respectively. The 
three files used differed only in the type of inhibitor 
that was bound to the COX-2 molecule.  Since the 
focus of the paper is on surrounding the anti-inflam-
matory properties of these novel compounds, the 
three files were specifically selected, as all three in-
hibitors are used in a variety of NSAIDs. Salicylate 
acid and tolfenamic acid are nonselective, while Vi-
oxx is selective to COX-2.  

 
MOLECULAR MODELING STUDIES WITH AUTODOCK VINA 

AND UCSF CHIMERA 
We then performed molecular docking us-

ing UCSF Chimera to study the ligand conformation 
and binding affinity of the different compounds in 
the COX-2 binding pocket11. The twenty-three lig-
ands (chemical constituents) were then docked into 
the three targets (COX-2) using Autodock Vina inte-
grated into UCSF Chimera. These two programs vis-
ualize interactions and molecular structures by 
providing high-quality images and docking trajecto-
ries11. After obtaining the delta G values from the 
docking, the five most stable ligands were further 
analyzed in Pymol to study the amino acid interac-
tions in the binding pocket. PyMOL is a cross-plat-



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

form tool that allows for 3D visualization of macro-
molecular analysis, protein-ligand docking, and mo-
lecular docking simulations among other features12.  

 

3 RESULTS 
TABLE 1 was compiled from all the different 

compounds found in the literature. Twenty-three 
compounds were recorded along with their loca-
tions within the plant, pharmacological activity, ex-
tract type, and percent yield present in the overall 
composition of the plant. TABLE 2 shows the x, y, and 
z calculations of where the original ligands for both 
targets can be found. These calculations were used 
to re-dock the original ligands, salicylate acid and 
Vioxx, in their respective targets by defining the size 
of the binding pocket. Tolfenamic acid (5KIT) was 
excluded from the findings of the paper as there 
were some issues with the docking of the chemical 
ligands into that file: appropriate x, y, and z calcula-
tions could not be obtained for that target. The delta 
G values and root mean squared deviation (RMSD) 
values were also recorded in this table. The RMSD 
values signify the deviation between the original 
and redocked ligands. The RMSD value is used as a 
control to highlight that the original ligand can be 
redocked into the same target. The best confor-
mation, denoted by the highest delta G value and 
RMSD < 2.5, was used to compare the remaining 25 
ligands and obtain the delta G values, measured in 
kcal/mol. The delta G values, along with the confor-
mation of each docking for targets, were recorded 
in TABLE 3. The average delta G value for both targets 
was also recorded in these tables. The interactions 
between the five most stable ligands and the bind-
ing pockets of both targets were analyzed and rec-
orded in TABLE 4. Visualization of these interactions 
was also recorded to observe the hydrophobicity 
and hydrophilicity of each interaction. Visualization 
of these interactions can be observed in FIGURE 2 and 
FIGURE 3.  

 

4 DISCUSSION 
Chronic inflammation occurs when an infec-

tion remains unresolved. This could lead to a wide 

array of problems including tissue death and in-
creased risk of cancer18. Non-steroidal anti-inflam-
matory drugs (NSAIDs) have proven to be effective 
against many types of inflammation. NSAIDs work 
by inhibiting cyclooxygenase (COX) enzymes and 
preventing the conversion of arachidonic acid to 
prostaglandins. Most of the NSAIDs currently on the 
market are not selective and work by inhibiting both 
COX-1 and COX-2 enzymes. This can lead to many 
adverse effects such as decreased platelet for-
mation, which can cause bleeding and gastrointes-
tinal complications19. Thus, it is crucial to find a more 
selective inhibitor for the COX-2 enzyme. Nigella sa-
tiva has been proven to reduce inflammation along 
with many other pharmacological actions, but 
mechanisms by which these natural constituents in-
teract with the inflammatory pathway remain un-
clear. Identification of the ligand interactions that 
mediate the anti-inflammatory effect of Nigella sa-
tiva will facilitate the development of more selective 
COX-2 inhibitors and help create more comprehen-
sive guidelines on traditional medicine usage.   

In this study, we researched the interactions 
between the chemical constituents and the binding 
pocket of COX-2 molecules to identify the best 
compounds for inhibition. Through a combination 
of in silico docking techniques, we identified five dif-
ferent ligands for each COX-2 molecule that have a 
more stable interaction than the original inhibitors.  

Salicylate acid, the inhibitor found in the 
5F1A target, is the active constituent present in as-
pirin. Although a low dosage of aspirin has been 
proven to help with age-related diseases, extensive 
usage has been shown to cause gastrointestinal 
damage and compromise kidney function20. This is 
due to salicylate acid inhibiting COX-1, which is im-
portant in the production of prostaglandin-1, a hor-
mone responsible for maintaining homeostasis and 
platelet function. Thus, it is important to find alterna-
tives that do not inhibit COX-1 and have stable bind-
ing with COX-2. The five compounds observed to 
have a better binding affinity are thymoquinone, ni-
gellicimine, 4-terpineol, thymol, and carvacrol (TABLE 

4). 
Vioxx, the inhibitor of the other COX-2 tar-

get, is the active constituent present in Rofecoxib. 



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

Rofecoxib was a drug marketed as a safer alterna-
tive to NSAIDs for treating rheumatoid arthritis and 
migraines. The drug was later withdrawn from the 

market due to studies showing increased probabil-
ity of cardiovascular disease in users21.  Although

 
TABLE 1: Chemical constituents present in Nigella sativa. The part of the plant, pharmacological activity, extract, and percent-
age yield for each compound are also noted. 
 

Chemical Constituent Part of 
Plant 

Activity Extract Percent yield 
(%) 

Thymoquinone14 seed  anti-inflammatory + anti-
fungal + anticancer  

methanol  48 

Carvacrol15 seed  antioxidant + anti-inflam-
matory 

ethanol 12 

t-anethole15 seed  antioxidant + anti-inflam-
matory 

ethanol 4 

4-terpineol15 seed  antioxidant + anti-inflam-
matory 

ethanol 7 

sesquiterpene longifo-
lene15 

seed  antibacterial + anti-inflam-
matory  

ethanol 8 

α-pinene16 seed  anti-inflammatory  ethanol trace amounts 
Thymol16 seed  anti-inflammatory  ethanol trace amounts 
Nigellicimine16 seed  antifungal methanol 2 
nigellicimine-N-oxide16 seed  antifungal methanol 2 
Nigellidine16 seed  anti-inflammatory  aqueous  trace amounts 
Nigellicine16 seed  anti-inflammatory  aqueous  trace amounts 
alpha-hederin16 seed  antidiabetic aqueous  trace amounts 
Longifolene16 leaves/seed antibacterial + anti-inflam-

matory  
aqueous  trace amounts 

Thujene16 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

Sabinene17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

beta-sitosterol17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

Phellandrene17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

α-hederin17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

Carvone17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

Limonene17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

β-pinene17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

d-citronellol17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

Saponin17 leaves/seed antibacterial + anti-inflam-
matory  

aqueous  trace amounts 

 
  



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

TABLE 2: XYZ calculations of the original binding site for the two COX-2 targets. These calculations were used to dock the 
chemical ligands obtained. Redocking of the original ligands and RMSD associated with the ligands were noted.  
 

Target PDB file X Y Z Delta G (kcal/mol) RMSD 
5KIR 23.38 x 1.34 x 34.57 -7.9 1.7 
5F1A 1.60 x 24.07 x 240.24 -6.3 2.114 

 

 

 

 

 

 

                   FIGURE 1A.                                      FIGURE 1B. 

FIGURE 1. A)  Crystal structure of 5F1A (COX-2) with redocked salicylate acid ligand. B) Crystal structure of 5KIR (COX-2) with 
redocked Vioxx ligand.  
 
 
TABLE 3: Delta G values and of the conformation obtained from the docking of chemical ligands obtained. Average of all 
dockings was also recorded. 
 

Ligand Delta G value for 5F1A(kcal/mol) Delta G value for 5KIR(kcal/mol) 
Thymoquinone  -7 -6.6 
carvacrol -6.3 -6.8 
t-anethole -6.3 -6.4 
4-terpineol -6.6 -6.4 
sesquiterpene longifolene -2.8 -6 
α-pinene -6.2 -6.1 
thymol -6.4 -6.3 
nigellicimine  -6.8 -7 
nigellicimine-N-oxide -5 -6 
nigellidine -4 -8.8 
nigellicine -5.2 -8.3 
alpha-hederin -6 -7 
Longifolene  -6.3 -6 
thujene  -6 -6.1 
sabinene -6.5 -6.1 
beta-sitosterol -2.1 -5.5 
α-hederin -5.7 -6.9 
Phellandrene  -6.3 -6.3 
carvone  -6.3 -6.8 
limonene  -6 -6.3 
β-pinene -5.4 -5 
d-citronellol -5.5 -6 
saponin -5 -5 
Average -5.6 -6.4 



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

    
FIGURE 2: Visualization of the amino acid interactions for the five ligands and the original ligand associated with the 5F1A 
target. Red refers to interactions that are extremely hydrophobic while blue refers to interactions that are extremely hydro-
philic. The range of colors determines the level of hydrophobicity or hydrophilicity. a-f) Amino acid interactions for salicylate 
acid, thymoquinone, nigellicimine, 4-terpineol, thymol and carvacrol respectively.  

            

  

 
 
FIGURE 3: Visualization of the amino acid interactions for the five ligands and the original ligand associated with the 5KIR target. 
Red refers to interactions that are extremely hydrophobic while blue refers to interactions that are extremely hydrophilic. The 
range of colors determines the level of hydrophobicity or hydrophilicity. A-F) Amino acid interactions for Vioxx, nigellidine, 
nigellicine, nigellicimine, alpha hederin, and carvacrol respectively. 

FIGURE 2A 

FIGURE 2D 

FIGURE 2B FIGURE 2C 

FIGURE 2E FIGURE 2F 

FIGURE 3A FIGURE 3B FIGURE 3C 

FIGURE 3D FIGURE 3E FIGURE 3F 



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

TABLE 4: Amino acid interactions of the five most stable chemical ligands as well as the original ligands docked into the two 
COX-2 targets. These interactions include hydrophobic, hydrophilic, ionic, and hydrogen bonds.  
 

Ligand Interaction pattern in 
5F1A 

Ligand Interaction pattern in 5KIR 

Original ligand 
(salicylate acid) 

PHE487 TRP356  TYR354. 
TYR317. LEU321. VAL318. 
VAL492. PHE 350 SER499   

Original ligand 
(Vioxx) 

PHE529.  TRP360. TYR466.  
LEU508. VAL434. PHE463 

Thymoquinone PRO335 PHE487.  CYS340.  
PRO320. LYS470. VAL318.  
PHE350.  SER499 

Nigellidine  TYR460. ARG456. GLU380. 
ARG150. TYR466. LEU503. 
GLU502  

Nigellicimine  TYR348. PHE198. LEU390. 
TRP387. PHE518. LEU352. 
PHE529. SER530 

Nigellicine  LEU508  PRO389. ALA435. 
VAL434. LYS436. LEU507.  

4-terpineol PHE335  TRP345  PRO335. 
CYS340. LEU321. TRP387. 
LYS470. PHE350 

Nigellicimine  TYR466  PHE529  ASN382.  
LEU508. TYR466. ARG150 

Thymol TYR385. TRP387. PHE198. 
TYR348. PHE 381. PHE529. 
LEU390. GLY526 

Alpha hederin ARG150. TYR460. TYR466. 
LEU503. LEU507. VAL525. 
PHE529. ASN382 

Carvacrol PHE357  ASN110. ALA111. 
TRP340. PRO335. LEU321. 
TRP387. PHE350 

Carvacrol PHE463. TYR466. LEU384. 
TYR504. LEU507. GLU510. 
TYR475 

Rofecoxib was successful in selectively inhibiting 
COX-2, its risks outweighed its benefits. The five 
compounds observed to have a better binding af-
finity are nigellidine, nigellicine, nigellicimine, alpha 
hederin, and carvacrol (TABLE 4). 
 
THYMOQUINONE 

Thymoquinone, the most abundant com-
pound in the Nigella seed (TABLE 1), has been proven 
to decrease nitric oxide synthesis as well as inhibit 
prostaglandin formation. Therefore, it could treat 
asthma and rheumatoid arthritis22. Thymoquinone 
had a higher delta G value than salicylate acid, prov-
ing it has the stability to potentially be used as an 
inhibitor to target the COX-2 enzyme (TABLE 3). The 
delta G value denotes the stability of the interaction 
between the ligand and the target. A higher delta G 
value indicates that the ligand binds strongly to the 
target, thus acting as an effective inhibitor. In addi-
tion, the interaction of serine and cysteine in the 
binding pocket shows strong hydrogen bonding 
between thymoquinone and COX-2 (TABLE 4). The 
presence of these hydrophilic amino acids stabilizes 
thymoquinone in the binding pocket. However, the 

presence of proline in the set of interactions shows 
a possibility that thymoquinone might not be stable 
enough for prolonged interactions, as the cyclic ring 
in proline can distort the structure. Overall, thymo-
quinone appears to have numerous hydrophilic in-
teractions that are required for sufficient protein-lig-
and interactions.  

 
NIGELLICIMINE 

Nigellicimine, a novel compound found 
mainly in the Nigella seed, also appears to have a 
higher delta G value compared to the original lig-
and of one of the COX-2 targets (5F1A) but not the 
other (5KIR). Serine, cysteine, and tyrosine appear to 
be the main amino acids in the interactions between 
nigellicimine and the 5F1A binding pocket (TABLE 4). 
Like thymoquinone, nigellicimine has a stable inter-
action in the binding pocket. Although there are hy-
drophilic interactions between nigellicimine and 
5KIR, the presence of multiple amino acids (phenyl-
alanine) with aromatic rings may destabilize the 
structure. Nigellicimine appears to have a higher 
delta G value compared to some of the other natural 
compounds present in Nigella sativa. The difference 



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

in interactions between the two targets could be at-
tributed to the original ligands (salicylate acid and 
Vioxx) not sharing the exact same binding pocket. 
This can be observed through the XYZ calculations 
denoting that there could be different amino acid 
interactions involved in each docking (TABLE 2).  

  
4-TERPINEOL AND THYMOL 

4-terpineol and thymol are compounds that 
are present in low or trace amounts in the Nigella 
seed (TABLE 1). It was quite unexpected to observe 
that they have a higher delta G value compared to 
salicylate acid (TABLE 3). The presence of tyrosine and 
cysteine supports the delta G value regarding the 
stability of the interaction. Yet, the presence of mul-
tiple phenylalanine and tryptophan amino acids in 
these interactions suggests a temporary binding 
that cannot be used for extended inhibition of COX-
2.   

 
CARVACROL 

Carvacrol, the second most abundant com-
pound in the Nigella seed (TABLE 1), is known to re-
duce inflammation but the mechanism by which it 
does so remains unclear. Some researchers have hy-
pothesized that its anti-inflammatory activity could 
be caused by induction of interleukin-10 which in 
turn reduces other inflammatory cytokines23. Car-
vacrol appears to have a stable interaction with both 
COX-2 targets, but it does not have a higher delta G 
value than salicylate acid and Vioxx (TABLE 3). This 
could be due to the presence of phenylalanine and 
tryptophan which cause distortions in the binding 
structure due to their large side chains that give 
them a bulky nature. Interactions with 5F1A appear 
to be more polar compared to interactions with 5KIR 
(TABLE 4). Further analysis would be required to know 
the effects of prolonged interactions of carvacrol on 
the COX-2 targets in question as the data regarding 
this compound appear to be inconclusive.   

 
NIGELLIDINE AND NIGELLICINE 

Nigellidine and nigellicine were observed 
to have a higher delta G value compared to Vioxx. 
Both compounds have been found to reduce in-
flammation related to viral infections. Most notably, 

nigellidine and nigellicimine have been found to 
help reduce COVID-19-related inflammation and in-
hibit interleukins involved in “cytokine storm”24. The 
presence of asparagine and leucine in the binding 
pocket interactions suggests that ionic bonds are 
present which stabilize the structure (TABLE 4). Similar 
to other compounds, serine, cystine, and tyrosine 
are involved as polar contacts for nigellidine and ni-
gellicine (TABLE 4). The presence of these residues 
stabilizes the ligand in the pocket of the COX-2 pro-
tein. In addition, nigellidine appears to be more sta-
ble compared to nigellicine. This could be at-
tributed to the extra aromatic ring present in nigel-
lidine, which is known to increase ligand-receptor 
binding and lead to increased effectiveness of the 
compound25.  

 
ALPHA-HEDERIN 

Alpha-hederin is found in trace amounts in 
the Nigella seed. Additionally, it has anti-cancer and 
anti-diabetic pharmacological action (TABLE 1). Sur-
prisingly, it was one of the five constituents that had 
a stable interaction with 5KIR. Alpha-hederin ap-
peared to have a high delta G value compared to 
other constituents but did not exceed that of Vioxx 
(TABLE 3). This decrease in delta G could be at-
tributed to the presence of multiple phenylalanine 
residues as well as basic residues (like lysine) that 
can cause distortions in the structure. The presence 
of multiple tyrosine residues in this interaction de-
notes that there are polar contacts that can stabilize 
the structure.  

In conclusion, thymoquinone and nigelli-
dine were found to have the most stable interaction 
with COX-2 targets. This research indicates that tra-
ditional medicine has the potential to aid in the first 
step of the drug discovery process: identifying 
chemical compounds. Using naturally occurring 
compounds can greatly reduce adverse effects that 
result from using drugs like NSAIDs. However, fur-
ther analysis and studies are needed to understand 
if these compounds can interact unfavorably with 
other drugs or molecules in the human body∎ 

 
 
 



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

5  REFERENCES  
[1] Jain, S. K. (1986). Ethnobotany. Interdisciplinary Sci-

ence Reviews, 11(3), 285-292. 
[2] Süntar, I. (2020). Importance of ethnopharmacologi-

cal studies in drug discovery: role of medicinal 
plants. Phytochemistry Reviews, 19(5), 1199-1209. 

[3] World Health Organization. (2019). WHO global re-
port on traditional and complementary medicine 
2019. World Health Organization 

[4] Ali, B. H., & Blunden, G. (2003). Pharmacological and 
toxicological properties of Nigella sativa. Phytother-
apy Research: An international journal devoted to 
pharmacological and toxicological evaluation of nat-
ural product derivatives, 17(4), 299-305. 

[5] Ahmad, Aftab, et al. "A review on therapeutic poten-
tial of Nigella sativa: A miracle herb." Asian Pacific 
journal of tropical biomedicine 3.5 (2013): 337-352. 

[6] Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., 
... & Zhao, L. (2018). Inflammatory responses and in-
flammation-associated diseases in organs. Oncotar-
get, 9(6), 7204. 

[7] Jeon, Jin-Woo, Un-Hwan Ha, and Se-Hwan Paek. "In 
vitro inflammation inhibition model based on semi-
continuous toll-like receptor biosensing." PloS 
one 9.8 (2014): e105212. 

[8] Van der Heide, Huub JL, et al. "Rofecoxib inhibits het-
erotopic ossification after total hip arthroplasty." Ar-
chives of orthopaedic and trauma surgery 127.7 
(2007): 557-561. 

[9] Kim, Sunghwan, et al. "PubChem substance and com-
pound databases." Nucleic acids research 44.D1 
(2016): D1202-D1213. 

[10] Canese, K., & Weis, S. (2013). PubMed: the biblio-
graphic database. In The NCBI Handbook [Internet]. 
2nd edition. National Center for Biotechnology Infor-
mation (US). 

[11] Pettersen, Eric F., et al. "UCSF Chimera—a visualiza-
tion system for exploratory research and analy-
sis." Journal of computational chemistry 25.13 (2004): 
1605-1612. 

[12] DeLano, Warren L. "Pymol: An open-source molecu-
lar graphics tool." CCP4 Newsletter on protein crystal-
lography40.1 (2002): 82-92. 

[13] Ali, B. H., & Blunden, G. (2003). Pharmacological and 
toxicological properties of Nigella sativa. Phytother-
apy Research: An international journal devoted to 

pharmacological and toxicological evaluation of nat-
ural product derivatives, 17(4), 299-305. 

[14] Burits, M., & Bucar, F. (2000). Antioxidant activity of 
Nigella sativa essential oil. Phytotherapy re-
search, 14(5), 323-328. 

[15] Ahmad, A., Husain, A., Mujeeb, M., Khan, S. A., Najmi, 
A. K., Siddique, N. A., ... & Anwar, F. (2013). A review 
on therapeutic potential of Nigella sativa: A miracle 
herb. Asian Pacific journal of tropical biomedi-
cine, 3(5), 337-352. 

[16] Forouzanfar, F., Bazzaz, B. S. F., & Hosseinzadeh, H. 
(2014). Black cumin (Nigella sativa) and its constituent 
(thymoquinone): a review on antimicrobial ef-
fects. Iranian journal of basic medical sci-
ences, 17(12), 929. 

[17] Nergiz, C., & Ötleş, S. (1993). Chemical composition 
of Nigella sativa L. seeds. Food chemistry, 48(3), 259-
261. 

[18] Shacter, Emily, and Sigmund A. Weitzman. "Chronic 
inflammation and cancer." Oncology (Williston Park, 
NY) 16.2 (2002): 217-26. 

[19] Thakur, Sourav, et al. "Novel drug delivery systems 
for NSAIDs in management of rheumatoid arthritis: 
An overview." Biomedicine & Pharmacotherapy 106 
(2018): 1011-1023. 

[19] Vane, J. R., and R. M. Botting. "The mechanism of ac-
tion of aspirin." Thrombosis research 110.5-6 (2003): 
255-258. 

[20] Ross, Joseph S., and Harlan M. Krumholz. "Bringing 
Vioxx back to market." (2018). 

[21] Darakhshan, Sara, et al. "Thymoquinone and its ther-
apeutic potentials." Pharmacological research 95 
(2015): 138-158. 

[22] Da Silva Lima, Milena, et al. "Anti-inflammatory effects 
of carvacrol: evidence for a key role of interleukin-
10." European journal of pharmacology 699.1-3 
(2013): 112-117. 

[23] Maiti, Smarajit, et al. "Active-site Molecular docking 
of Nigellidine with nucleocapsid-NSP2-MPro of 
COVID-19 and to human IL1R-IL6R and strong antiox-
idant role of Nigella-sativa in experimental 
rats." Journal of Drug Targeting just accepted (2020): 
1-23. 

[24] Ritchie, Timothy J., and Simon JF Macdonald. "The 
impact of aromatic ring count on compound devel-
opability–are too many aromatic rings a liability in 
drug design?" Drug discovery today 14.21-22 (2009): 
1011-1020.

 
 

 
 



ARESTY RUTGERS UNDERGRADUATE RESEARCH JOURNAL, VOLUME I, ISSUE IV 
 

 
 
 
Habiba Abdelhalim is a senior at Rutgers University majoring in biotechnology 
and minoring in Biochemistry. Habiba’s research focused on the anti-inflamma-
tory effects of Nigella sativa, a herb that is commonly used in her culture. Working 
under Dr. Sonia Arora, Habiba was able to learn about various in silico techniques 
used in the drug discovery process.  Currently, Habiba is part of the Ahmed Lab 
at Rutgers University working on implementing Artificial Intelligence and Ma-
chine Learning in the field of Precision Medicine.  

 
Habiba can be reached at: ha375@scarletmail.rutgers.edu. 


