Inflammopharmacology (2023) 31:1183–1198

https://doi.org/10.1007/s10787-023-01178-0 Inflammopharmacology
REVIEW

Review of natural compounds for potential psoriasis treatment

Omali Y. Elkhawaga1 · Mohamed M. Ellety1 · Sheref O. Mofty1 · Mohamed S. Ghanem1 · Abdallah O. Mohamed1

Received: 21 February 2023 / Accepted: 24 February 2023 / Published online: 30 March 2023
© The Author(s) 2023

Abstract
Psoriasis represents an immune-mediated disease with an unclear cause that’s marked by inflammation triggered by dysfunc-
tion in the immune system, which results in inflammation in various parts of the skin. There could be obvious symptoms, such
as elevated plaques; these plaques may appear differently depending on the type of skin. This disease can cause inflammation
in the elbows, lower back, scalp, knees, or other regions of the body. It can begin at any age, although it most commonly
affects individuals between the ages of 50 and 60. Specific cells (such as T cells) have been observed to play an obvious
role in the pathogenesis of psoriasis, in addition to specific immunological molecules such as TNF-, IL-12, IL-23, IL-17,
and other molecules that can aid in the pathogenesis of psoriasis. So, during the past two decades, biologists have created
chemical drugs that target these cells or molecules and therefore prevent the disease from occurring. Alefacept, efalizumab,
Adalimumab, Ustekinumab, and Secukinumab are a few examples of chemical drugs. It was discovered that these chemi-
cal drugs have long-term side effects that can cause defects in the patient's body, such as the development of the rare but
life-threatening disorder progressive multifocal leukoencephalopathy (PCL). Its rapidly progressive infection of the central
nervous system caused by the JC virus and other drugs may cause increased production of neutralising anti-drug antibodies
(ADA) and the risk of infusion reactions like pruritus, flushing, hypertension, headache, and rash. So, our context intends
to talk in our review about natural products or plants that may have therapeutic characteristics for this disease and may have
few or no side effects on the patient's body.

Keywords Psoriasis · Autoimmune · Plant · Natural · Dietary · Phytochemical

Introduction
Psoriasis represents an autoimmune, persistent inflammatory
disease that affects the skin and has a powerful hereditary
component. It is distinguished by persistent inflammation,
which results in uncontrolled keratinocyte growth and dif-
ferentiation (Pathogenesis 2019). In accordance with the
International Psoriasis Day Collaboration, psoriasis affects
125 million individuals globally, or around 2–3% of the
population. According to research, psoriatic arthritis affects
10–30% of psoriasis sufferers. Psoriasis has a detrimental
influence on sufferers' quality of life. Even though psoria-
sis` pathophysiology remains unknown, it is thought to be a
T-cell-triggered disorder because of the presence of T-helper
cells inside the psoriatic state (Pathogenesis 2019; Theses
* Omali Y. Elkhawaga
elkhawaga70s@mans.edu.eg
1
Biochemistry Division, Chemistry Department, Faculty
of Science, Mansoura University, Mansoura 35516, Egypt
and Devera 2020; Singhvi et al. 2020). Chronic plaque pso-
riasis (psoriasis vulgaris), inverse psoriasis, guttate psoria-
sis, Pustular psoriasis and erythrodermic psoriasis are the
two clinical classifications of psoriasis. Chronic psoriasis
vulgaris accounts for 80–90% of psoriasis patients. Psoriasis
vulgaris can be distinguished by erythematous, well-defined
plaques coated with silvery scales. Moreover, it can affect
limb extensor surfaces, scalp, and trunk. Inverted psoriasis
is characterised by somewhat erosive erythematous patches
and plaques in the folds and vaginal regions. This condition
is a mix of psoriasis and inflamed arthritis that affects the
joints and spine. This happens when there are no particular
antibodies in the blood or rheumatoid factor. Because of
societal shame and marginalisation, psoriasis patients suffer
poor mental and psychological health. Anxiety, sadness, and
suicide thoughts are more common in these people (Napoli-
tano, et al. 2016). The major signs of psoriasis appear as
itchiness and reddish, flaky skin areas coated in silver
scales. Other symptoms include tiny scale areas, cracked
skin, itching, pain, swollen or corroded nails, inflammatory

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1184
and genital sores, stiff joints, and extreme dandruff on the
scalp (Global report 2022). Psoriasis is a complex disease
influenced by genetic, environmental, and immunological
factors. Modifying variables include obesity, illness, trauma,
and a lack of active Vitamin D3.
Pathogenesis
Psoriasis represents a common inflammatory skin condition
with a complex pathophysiology that includes a hereditary
element, immune dysfunction, and environmental exposures.
It is linked to a variety of complications, including psoriatic
arthritis, cardiac disease, metabolic syndrome, and obesity.
Obesity appears to be a significant predictor for incident
psoriasis, aggravates established psoriasis, and may improve
the intensity of psoriasis in individuals. (Howell et al. 2019).
It is a genetic skin disease mediated by the immune
system. The pathomechanisms at work involve complex
communication between the immune system's innate and
adaptive systems. T cells communicate with dendritic cells,
keratinocytes, and macrophages via cytokines secreted by
these cells. Streptococcal infection, smoking, stress, obesity,
and alcohol consumption are all examples of environmental
triggers (Kamiya et al. 2019).
Psoriasis is linked to a number of complications, includ-
ing cardiovascular disease, cancer, and depression. For
mild to severe psoriasis, corticosteroids, vitamin D mim-
ics, and tazarotene were effective therapies. This illness can
indeed be caused by a variety of microorganisms, including
in psoriatic skin, where there was a rise in Corynebacte-
rium, Propionibacterium, Streptococcus, and Staphylococ-
cus (Thomas et al. 2021). Nevertheless, in another study,
Staphylococci were considerably lower in lesional skin in
comparison with healthy controls was a rise in Corynebac-
terium, Propionibacterium, Streptococcus, and Staphylococ-
cus (Thomas et al. 2021). Nevertheless, in another study,
Staphylococci were considerably lower in lesional skin in
comparison with healthy controls. Psoriasis has been linked
to fungi, including Malassezia as well as Candida albicans,
as well as viruses like the human papillomavirus. Malassezia
has been identified as the main prevalent fungus in both pso-
riatic and healthy skin. It has been discovered that disrup-
tions in the adaptive and innate cutaneous immunogenicity
are responsible for the formation and maintenance of pso-
riatic inflammation. Th1 cytokines, including c-interferon
(IFN-c), tumour necrosis factor-a (TNF-a), and interleukin
(IL)-12, were shown to be raised in psoriatic lesions, but
Th2 cytokines (IL-4, IL-5, and IL-10) were not (Blauvelt
and Chiricozzi 2018).
In psoriasis vulgaris areas, the bulk of epidermal T cells
may generate type 1 cytokines, including INF-c, IL-2, and
TNF-a, identifying cytotoxic T-lymphocytes (TC1) as well
13
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O. Y. Elkhawaga et al.
as TH1 effector populations. Psoriasis was identified as a
Th1-type illness based on these findings. However, neither
IFN-c nor TNF-a stimulate keratinocyte growth (Spa 2008).
Interleukin-6 (IL-6) and other pro-inflammatory
cytokines can activate the hypothalamus-pituitary axis,
which has been linked to hypertension, obesity, and insu-
lin resistance. IL-6 can also stimulate the production of
C-reactive protein in hepatocytes and, in conjunction with
TNF-, alter insulin sensitivity via the insulin signalling sys-
tem (Liang et al. 2018). The formation of plaque in psoriasis
is not isolated to inflammation at the epidermal layer; it is
influenced by the keratinocyte’s interaction with many other
types of cells (adaptive and innate immune cells, vascula-
ture) across the dermis layer of skin. In certain cases, natural
immune system activation caused by intrinsic danger signals
or cytokines intermixes with autoinflammatory persistence,
whereas in others, T cell-driven autoimmune responses
occur. Thus, psoriasis exhibits disease characteristics on
an auto-inflammatory basis, with both pathways overlap-
ping and even amplifying each other (Meglio et al. 2014).
The aetiology of psoriasis may be divided into two phases:
the initiation phase, which may be induced by trauma (the
Koebner phenomenon), infections, or medicines; and the
maintenance phase, which is defined by continuous clinical
development. Psoriasis pathogens originate once keratino-
cytes are exposed to an external stimulus (infection/stress/
obesity/genetically), and as a result, keratinocytes secrete
antimicrobial peptides (AMPs) that are overexpressed in
psoriatic skin (Lai and Gallo 2009) (Fig. 1).
AMP are made up of twelve to fifty amino acids that help
the host defend itself by destroying pathogens such as pro-
tozoa, bacteria, fungus, and certain viruses.It also has an
impact on inflammatory responses by acting as an angio-
genic factor, chemotactic mediator, and cell proliferation
regulator. Several AMP, including -defensins, S100 pro-
teins, and cathelicidin, are abundantly expressed in psoriatic
lesions (Kiel 2004).
The -defensins have been divided into six subtypes known
as human neutrophil peptides, or 1-6HNP, of which HNP
1–3 are found in the scales of psoriatic lesions.-Defensins
are divided into four subtypes known as 1–4 human
-defensins (HD).
HD 1–2 were found to be highly expressed in psoria-
sis scales and are activated in keratinocytes by TNF- and/
or IFN-c (Lande et al. 2014). Furthermore, IL-22 and IL-
17A both cause HD 2. LL37, also known as cathelicidin,
has been linked to the pathogenesis of psoriasis. Injured
keratinocytes secrete LL37, which is then combined with
self-genetic materials from those damaged cells to form
complexes. LL37 represents one of the two T-cell autoan-
tigens examined in psoriasis. Research revealed specific
CD8+ and CD4+ T lymphocytes in two-thirds of individuals
with mild to severe plaque psoriasis. LL37-specific T cells
Review of natural compounds for potential psoriasis treatment 1185
Fig. 1  Basic pathogenesis of
psoriasis
produce IFN-, while CD4+ T cells produce IL-22, IL-21,
and IL-17. Specific T lymphocytes (LL37) could be detected
in skin lesions and blood, and their presence correlates with
disease activity (Morizane et al. 2012).
CD8+ T-cells stimulated by LL37 participate in autoanti-
gen detection, epidermotropism, and Th17 cytokine release.
The HLA-C*06:02-restricted autoantigen ADAMTSL5 was
discovered to be recognised because of a CD8+ T-cell TCR
that is autoreactive. This discovery identifies melanocytes as
immune target cells. TLR9 in plasmacytoid DCs is activated
by LL37 coupled to DNA (pDCs) (Arakawa, et al. 2015).
The activation of pDC, characterised by the production of
type I IFNs such as IFN- and IFN-, is essential for the forma-
tion of the psoriatic plaque. Type I IFN signalling promotes
myeloid dendritic cell (mDC) phenotypic development and
has been linked to Th1 and Th17 development and role,
including the production of IFN- and IL-17, respectively
(Morizane and Gallo 2011). LL37–DNA induces pDCs
via LL37, and TLR9 bound to RNA induces pDCs through
TLR7. Moreover, LL37–RNA complexes work on mDCs
via TLR8.
Activated Th17 cells release an excess of IL-17 and TNF-
a, which stimulate keratinocytes, increase hyperplasia of the
epidermis, attract neutrophils, and cause the generation of
antimicrobial peptides (AMP). IL-17 mRNA levels were
shown to be elevated in psoriasis lesions but never in non-
lesional tissue (Lowes et al. 2008).
IL-17 increased the levels of IL-8 and IL-6 in keratino-
cytes, which are cytokines that promote inflammation and
aggravate psoriasis (Ye et al. 2001).
Furthermore, IL-17 is required for neutrophil preserva-
tion and recruitment. Th17 cells are also known to release
IL-22, a participant in the IL-10 cytokine family (Wolk et al.
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
2006). Its expression can be elevated in the area of psoriatic
lesions on the skin and decrease in connection with antip-
soriatic treatment remission. These data imply that IL-22
stimulates keratinocyte development and plays a significant
role in psoriasis pathogenesis.
TNF- (tumor necrosis factor) plays an important role
in the pathophysiology of psoriasis (Jacobs and Harrison
1998). TNF- activates the nuclear factor (NF)-jB signalling
pathway, which affects lymphocyte and keratinocyte sur-
vival, proliferation, and anti-apoptotic activities (Kagami
et al. 2010).
TNF- stimulates Th17 to produce proinflammatory
cytokines via the NF-jB pathway in psoriatic lesions, and
blocking the NF-jB pathway reduces IL-17A production
by CD4+ T cells. Both anti-TNF and CsA agents reduced
the levels of IFN-c, IL-17A, IL-23p19, and (C–C motif)
chemokine ligand 20 in psoriasis lesions, indicating that pro-
inflammatory cytokines, particularly IL-17A, are involved in
the development of psoriasis (Ghoreschi et al. 2010).
These data imply that the IL-17 family is involved in pso-
riasis. When IL-23 binds to the receptor complex of IL17,
it phosphorylates signal transduction and the promoter
of transcription (STAT)3 via Jak2, which is found inside
the cytoplasmic domain of the subunit IL-23R. Phospho-
STAT3 proteins create homodimers in the nucleus, where
they boost the Th17 response by stimulating the production
of cytokines such as IL-22, 17A, IL-17F, and IFN-c (Fig. 2).
The missing heritability research that has been linked
with psoriasis genetic markers has fueled the epigenetic
alterations search. Cytosine and guanine (CpG) methyla-
tion, silencing microRNA (miRNA), and long noncod-
ing RNA (lncRNA) represent examples of epigenetic
processes that affect gene expression without modifying
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1186
Fig. 2  Schematic representa-
tion of IL-12 and IL-23, and
their receptors and downstream
signaling pathways
the chromosomal sequence. More than 971 lncRNAs
were identified as being differently expressed in psoriatic
patches versus normal skin (Gupta et al. 2016).
Psoriasis‑related genes
IL36RN
By 2011, IL36RN deficiency was discovered in a reces-
sive variety of IL36RN, and familial GPP was identified
as a causal gene for GPP (Johnston et al. 2012). The gene
IL36RN encodes IL-36 receptor antagonists (IL36Ra),
which inhibit the action of IL-36 (including IL-36a, IL-
36b, and IL-36c) from the IL-1 family. Those subtypes
are extensively expressed in affected lesions and seem to
be important regulators for neutrophil chemokines such as
CXCL1 and CXCL8 (Blumberg et al. 2007). The mouse
homolog of IL36RN, Il1f5, has similarly been demon-
strated to cause a skin condition in comparison with GPP
in mice; stimulation of neutrophils in GPP may be caused
by elevated IL-36 activity caused by IL36Ra malfunction.
CARD14
Caspase recruiting member 14 (CARD14) or (CARMA2)
is a scaffold protein that regulates NF-jB signalling via
TNF receptor-associated factor 2 (TRAF2). Many muta-
tions accompanied by function gains in CARD14, includ-
ing p. Gly117Ser, were discovered in GPP (Setta-kaffetzi
et al. 2014).
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O. Y. Elkhawaga et al.
AP1S3
AP1S3 generates a component of AP-1, a transcription ele-
ment that affects the expression of keratin in keratinocytes.
GPP patients were found to have AP1S3 mutations and may
stimulate CXCL8, IL-36, and IL-1b expression via NF-jB
signalling malfunctions. It was discovered that the differ-
entiation of specific keratins 1 and 10, which are mostly
expressed inside the spinous layers, is reduced in the affected
epidermis, whereas keratins 6 and 16 are enhanced. 55 Fur-
thermore, in psoriatic skin, transglutaminase 1, keratin 17,
and involucrin are raised, although profilagrin is reduced
(Wright 1991).
Natural sources of psoriasis treatment
Omega‑3 sources
A number of studies have explored the efficacy of dietary
supplementation using fish oils (Article 2018), partly
because fish oil contains high levels of LC-3 PUFAs and
partly because of the theory that increased production of
pro-inflammatory eicosanoids via ARA is important to the
pathophysiology of psoriasis. In humans, -3 PUFAs per-
form a variety of activities, including restricting and heal-
ing inflammatory processes. They have been extensively
researched for their capacity to reduce mortality and mor-
bidity in people with cardiovascular disease (Hamilton et al.
1990). PUFAs have been used as a safe adjunct therapy in
various skin diseases due to their anti-inflammatory and
anti-chemotactic properties. Inhibition of inflammation
by ALA and its derivatives is based on barrier function
Review of natural compounds for potential psoriasis treatment 1187
maintenance, stratum corneum maturation and differentia-
tion, proinflammatory eicosanoid inhibition, lamellar body
formation, cytokine suppression, and lipoxygenase inhibi-
tion (Ricketts et al. 2010).
Resolvens control neutrophil migration in both animals
and humans, which may be one of the key anti-inflamma-
tory effects of -3 FAs on psoriasis (Mccusker and Grant-
kels 2010). Nevertheless, animal research has indicated
the -3 PUFAs' therapeutic benefit for lesions resembling
psoriasis, but human studies have yielded conflicting find-
ings (Maurice et al. 1987). According to in vitro studies,
adding fish oil to the diets of psoriasis patients results in
an increase in plasma EPA-to-ARA ratio and platelets, as
well as a significant decrease in LTB4 production by neu-
trophils (Soyland et al. 1993). Additional advantages of -3
PUFA administration in psoriasis patients include possible
hypolipidemic consequences and the avoidance of insulin
resistance and obesity. Because psoriasis sufferers are more
likely to be overweight than the overall population (Watson
2013), reducing the inflammatory load associated with an
elevation in the quantity of fatty tissue might undoubtedly
help to treat psoriasis. This is due to increased levels of sys-
temic circulating inflammatory cytokines like IL-6, TNF-,
and adiponectin produced by visceral fat activating rapamy-
cin complex 1 (mTORC1) signaling, which is important for
controlling T-cell homeostasis as well as proinflammatory
signalling of keratinocytes via the NF-B pathway (Timoszuk
and Bielawska 2018).
A study was done to explore the effectiveness of petro-
leum ether that has been extracted from Annona squamosa
seed (ASO) for use as an antipsoriatic drug (Bhoir et al.
2018). In mice, the extract, which is mostly composed of
PUFAs (LA and OA), inhibits keratinocyte proliferation
Fig. 3  Chemical structures
of Vitamin D synthesis and
activation
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more effectively than the corticosteroid clobetasol propi-
onate (CP). There was a reduction in inflammatory lesion
cytokines (INF-, TNF-, IL6, IL17, and GM-CSF) after ASO
administration, and no side effects were seen, indicating
that further research into this new antipsoriatic cream for
treatment in humans is warranted. PUFA supplementation
might help with psoriasis therapy and comorbidity preven-
tion. Even a slight improvement in psoriasis severity caused
by PUFA may reduce the use of currently available medica-
tions, lowering the risk of adverse effects.
Vitamin D
The vitamin D system is important for intracellular calcium
and bone metabolism, although studies throughout the last
20 years have shown a wide variety of biological activities,
including cell differentiation, suppression of cellular devel-
opment, immunomodulation, and regulation of many other
hormonal systems.
This vitamin seems to be a prohormone that is physi-
ologically metabolised to 1,25-dihydroxyvitamin D
[1,25(OH)2D] that activates its cellular receptor (VDR or
receptor of vitamin D), causing changes in the transcrip-
tion levels of target genes involved in biological responses
(Fig. 3).
Vitamin D may be derived from animal products like cod
liver oil, salmon, tuna, beef, eggs, and chicken breast, as well
as milk, yoghurt, and cheese (especially cheddar). Certain
mushrooms contain vitamin D2; moreover, some commer-
cially marketed mushrooms contain increased levels of D2
as a result of being purposefully exposed to high levels of
UV radiation.
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The epidermal keratinocytes are unique in that they not
only synthesise vitamin D but also have the enzymatic
mechanism to convert vitamin D into its active form, cal-
citriol (1,25(OH) (Zahoor et al. 2021). The level of epider-
mal pigment and the exposure intensity both correspond
with the passage of time necessary to obtain this optimum
previtamin D3 concentration, but they have no effect on
the highest level attained. Melanin inside the epidermis
can diminish the efficiency of sunlight in creating vita-
min D3 within the skin by absorbing UV rays (Maurice
et al. 1987; Zahoor et al. 2021) Once generated inside the
skin, previtamin D3 undergoes thermal isomerization to
vitamin D3. After attaching to specific binding proteins,
vitamin D3 is delivered towards the liver organ, where it
can be hydroxylated and then transformed into 25-OHD.
Vitamin D-binding proteins transport 25-OH D to the
kidney, where it is converted to 1,25(OH)2D, the hormo-
nally active form. (Niino et al. 2015). Sunlight destroys
any extra vitamin D3 or previtamin D3, therefore exces-
sive sun exposure does not result in vitamin D3 overdose
(Niino et al. 2015).
TLRs are activated by bacterial stimuli, which enhance
VDR synthesis and 25-hydroxyvitamin D-1-hydroxylase
activity. Cathelicidins seem to be proteins that bind to and
kill bacteria. Several studies, on the other hand, found that
vitamin D and VDR had an effect on both B and T cells,
as well as the adaptive immune response (El-domyati et al.
2007). However, vitamin D might alter B-cell activity by
limiting differentiation and proliferation, inducing apoptosis,
and, lastly, lowering immunoglobulin synthesis, including
autoantibodies. Vitamin D may potentially alter T-cell activ-
ity by lowering T helper (Th) cell proliferation as well as
differentiation and supporting a transition from a pro-inflam-
matory into a more tolerogenic immunological condition.
Vitamin D has been discovered in research to inhibit the
cytokine production required for Th17 and Th1 differentia-
tion, encourage T cells to release IL-10, which is an anti-
inflammatory Th2 cytokine, and thus decrease the expres-
sion of cytokines such as TNF- and IL-8, IL-2 interferon-y,
and decrease the intensity of class II molecules of the
main histocompatibility complex that affect dendritic cells
(Islands 2005). Such substantial impacts on T-cell growth
and cytokine expression contribute to the processes behind
vitamin D's therapeutic activity on psoriatic skin. The char-
acteristic clinical signs of erythematous scaling plaques
in psoriatic skin are, as previously stated, the outcome of
keratinocyte hyperproliferation and aberrant differentiation.
The hyperproliferative condition is distinguished by a rising
prevalence of proliferating basal cells, a shorter keratinocyte
cell cycle (36 h against 311 h in normal skin), and a reduced
epidermal turnover period (4 days from the basal cell layer
to the stratum corneum, versus 28 days in normal tissue)
(Trémezaygues and Reichrath 2011).
13
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O. Y. Elkhawaga et al.
The abnormal differentiation of the psoriatic area is more
severe, as indicated by a postponement in the production
of K10 and K1, which are found in healthy skin, as well as
K16 and K6 overexpression, which is seen in repairing skin.
Vitamin D promotes keratinocyte development and growth
and guards them against premature death at physiological
concentrations; however, at a pharmaceutical (106 m) dose,
vitamin D suppresses the proliferation of keratinocytes and
has a specific proapoptotic impact (Bernengo 1998).
These impacts on keratinocyte development and prolif-
eration are critical to vitamin D's function in the treatment
of psoriasis. Additionally, as previously stated, vitamin D
regulates the production of K10 and K10 inside the spino-
sum stratum, those essential keratins whose expression is
postponed in psoriatic skin (Zahoor et al. 2021).
Moreover, vitamin D has already been demonstrated
to restore the dispersion of integrins, including ICAM-1,
HLA-DR, and CD26, along the dermal-epidermal interface,
which is disrupted in lesional skin (Garbicz et al. 2022). It
is theorised that the different location of integrins causes
keratinocyte overproliferation and loss of adhesive ability
in psoriasis (Garbicz et al. 2022). The impact of vitamin
D topical therapies on integrin structures in non-lesional,
lesional psoriatic, as well as regular-skinned patients was
investigated. The staining patterns of the integrin subunit
were normalised in lesional psoriatic skin after treatment,
but not in non-lesional psoriatic skin before and after treat-
ment. (Meydani et al. 2018).
Vitamin E
Vitamin E, which is lipid-soluble, is a powerful antioxidant
found in all cell membranes. Vitamin E exists in eight forms
in nature (-, -, -, -tocopherols, and also -, -, -tocotrienols),
although -tocopherol is the most physiologically active (Ji
and Liu 2019). An investigation found a statistically sig-
nificant drop in vitamin E plasma levels in twenty psoriatic
patients when compared to normal individuals. Patients with
the most severe illnesses had the lowest vitamin E plasma
levels (“48.pdf”. 2022). Vitamin E levels in the blood of
seven individuals with psoriatic acral pustulosis or eryth-
rodermic psoriasis, whether or not linked with persistent
drinking, were also tested throughout and after the acute
stage. Only in individuals with a history of alcohol addic-
tion (n = 5) was vitamin E lowered to levels below the range
of normal during the severe psoriatic phase, indicating that
vitamin E insufficiency should be explored when pustular
psoriasis or erythrodermic is coupled with chronic drinking
(Paper 2013a). A new randomised case–control study of 60
patients with autoimmune skin disorders looked at vitamin
E levels in tissue and sera. Psoriasis, alopecia areata, and
vitiligo patients showed lower tissue and blood vitamin E
concentrations than healthy controls (n = 15 in each group,
Review of natural compounds for potential psoriasis treatment 1189
p 0.001). There exists a relationship between the pathophysi-
ology of several autoimmune illnesses and oxidative stress,
suggesting that antioxidant medicines may play a role in
their therapy (Fairris et al. 1989).
Many investigators reported that the antioxidant combina-
tion of vitamin E, selenium, and coenzyme Q (10) was intro-
duced to the diets of individuals having severe psoriasis to
evaluate its influence on disease progression (Miroddi et al.
2015). In this randomised, double-blind clinical research,
twenty-eight cases of severe psoriatic arthritis (PsA) and
thirty individuals with erythrodermic psoriasis (EP) were
included. EP and PsA patients were assigned at random to
either a treatment (antioxidant supplements plus conven-
tional therapy) or control subjects (placebo plus conventional
therapy). Throughout the trial period, clinical advancement
in the supplemented groups was substantially faster than in
the control groups. The patient group treated with conven-
tional medication plus antioxidant supplements had consid-
erably decreased illness severity at 30 days, as measured
by subjective grading. The antioxidant mix included 50 mg/
day of Coenzyme Q(10) (ubiquinone acetate), 50 mg/day of
natural vitamin E (-tocopherol), and 48 mg/day of selenium
(aspartate salt).
Aloe vera
Aloe barbadensis Miller (also called Aloe vera Linnaeus)
seems to be a succulent tropical plant of the Liliaceae
family. Aloe leaf pulp contains 98.5% water, while gel or
mucilage contains 99.5% water. Carbohydrates, proteins,
mucopolysaccharides, enzymes, anthraquinones, salicylic
acid, chromones, vitamins, and minerals also make up the
remaining 0.5–1%. (Aghmiuni 2017). Acemannan and Aloe-
emodin are antibacterial active ingredients that can help with
psoriasis. Furthermore, owing to its keratolytic activity,
salicylic acid eliminates psoriatic plaques. Aloe vera gel is
employed to treat psoriasis by reducing redness and scaling.
It is employed to make topical creams and lotions. (Choon-
hakarn et al. 2010). Aloe vera also has immunomodulatory,
antioxidant, anti-inflammatory, anti-fungal, and anti-tumor
properties. It also promotes skin hydration and wound heal-
ing by increasing collagen activity. This aids in the healing
of the psoriatic skin's negative consequences (Choonhakarn
et al. 2010).
In a randomised study of 80 individuals with mild and
moderate psoriasis vulgaris, Aloe vera and triamcinolone
acetonide (TA, 0.1%) were compared. The average Sever-
ity Index of Psoriasis Area (PASI) value decreased by 7.7
in the group using aloe vera and 6.6 in the group using
TA after eight weeks of therapy. The TA group's average
DLQI (Index of Dermatology Life Quality) declined by
5.8 points, while the Aloe Vera group's decreased by 6.1
points. It was discovered that aloe vera cream was much
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more effective (Dhanabal et al. 2011). Extracted Aloe
vera had 81.95% anti-psoriatic action in micetail models,
compared to 87.94% for tazarotene (Divya et al. 2016).
Divya et al. created a local nanogel with aloe-emodin (an
anthraquinone found in Aloe vera) and acitretin using chi-
tin. Their blood compatibility was demonstrated in vitro.
Investigations in Perry's mouse tail as well as skin safety
trials showed the formulation's potential effectiveness in
psoriasis therapy (Rajiv et al. 2019).
Angelica sinensis
Angelica sinensis (Dong Qquai, female ginseng) seems to
be a biennial or perennial plant in the family Apiaceae. It
is also known as Dong Quy. Something has long been uti-
lised in traditional Chinese medicine (TCM). TCM claims
that it stimulates and replenishes blood while also cor-
recting insufficiency. Psoralen, a powerful furocoumarin,
is found in Angelica sinensis extract. Psoralens are used
in the treatment of psoriasis as they behave as photosen-
sitizers when exposed to UV-A. Patients self-administer
PUVA therapy by eating Angelica sinens and then expos-
ing themselves to natural sunlight or UV. After consuming
Angelica sinens, UV exposure promotes DNA cross-link-
ing in the epidermis, slowing the frequency of epidermal
DNA synthesis (Richard 2020). Furthermore, they produce
mitochondrial malfunction, Langerhans cell toxicity, reac-
tive oxygen species formation, and keratinocyte and lym-
phocyte death (Sivanesan et al. 2009). In a randomised,
double-blind study, the PASI score was used to assess the
efficacy of psoralen orally plus UV-A in the treatment of
plaque psoriasis. After twelve weeks of therapy, two-thirds
of patients improved their PASI score by at least 75%,
compared to 0% in the placebo plus UV-A group (Kerkhof
et al. 2006).
Araroba tree (Vataireopsis araroba (Aguiar) Ducke)
Dithranol (synonym: anthralin), an anthracene deriva-
tive, is an effective topical therapy for psoriasis. It was
derived from chrysarobin, which was taken from the ara-
roba tree's bark, which thrives in the Amazon rain forests.
Dithranol suppresses the production of pro-inflammatory
cytokines as well as keratinocyte growth. A randomised
study on 106 patients with severe psoriasis lesions found
that 15:45 min of dithranol quick contact treatment with
stepwise increases in dithranol concentration up to 5%
once every day for twelve weeks were significantly more
effective than the standard care with 50 g/g of calcipotriol
ointment twice every day. (Moy et al. 2018).
13
1190
Barberry bark (Mahonia aquifolium (Pursh) Nutt.)
Mahonia aquifolium, sometimes called Oregon grape, is
just an evergreen shrub in the Berberidaceae family. It is
indigenous to the United States and is employed to treat a
variety of inflammatory cutaneous conditions. It has long
been used in TCM. The healing effect of Mahonia aquifo-
lium versus psoriasis is due to berberine, an alkaloid found
in the plant's extract. Berberine has been demonstrated to
have anti-inflammatory effects through a variety of mecha-
nisms, such as the downregulation of lipoxygenase as well
as lipid peroxidation, a decrease in the infiltration of T cells
in exposure lesions, a decrease in cyclooxygenase activ-
ity, resulting in a reduction in the suppression of IL-8, and
prostaglandin E2. Berberine suppresses cell development
by intercalating into DNA, preventing replication of DNA
and cell proliferation. Other alkaloids that inhibit lipoxy-
genase, such as oxyberberine, jatrorrhizine, corytuberine,
and columbamine, contribute to anti-inflammatory action.
(Wiesenauer and Lootke 1996). An individual study was car-
ried out to assess the performance of an ointment comprising
10% Mahonia aquifolium bark extract. It was thought to be
beneficial in treating moderately severe psoriasis vulgaris
(Kost et al. 2001). The Mahonia aquifolium crude extract
suppressed IL-8 production, which is significant in the treat-
ment of psoriasis. The crude extract's main components were
bisbenzylisoquinoline alkaloids and protoberberine. The first
group inhibited the production of IL-1, T cells, TNF-, and
TNF- (Ghazisaeedi et al. 2022).
Basil
The activated version of NF-B has been linked to osteopo-
rosis, psoriasis, septic shock, AIDS, and other inflammatory
illnesses (Cyclin 2003). It has previously been reported that
"holy basil" possesses chemopreventive properties. Urso-
lic acid, a tri-terpenoid produced from basil and rosemary,
has been demonstrated to limit NF-B activation by inhibit-
ing IKK, which in turn suppresses cyclin D1, COX-2, and
matrix metalloproteinase-9 (Woolf 2018).
Capsicum annum
Capsicum annuum is considered a plant species endemic
to southern North America, northern South America, and
the Caribbean. Cultivars derived from the native American
bird peppers can still be found in the Americas' warmer
areas. Some woody types of this species were previously
referred to as C. frutescens; however, the characteris-
tics used to differentiate those types are seen in numer-
ous species like C. annuum, but they are not consistently
13
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O. Y. Elkhawaga et al.
recognised in C. frutescens types. Numerous chemicals,
including neuropeptide Y, protein gene product 9.5 (PGP-
9.5), nerve growth factor (NGF), CGRP, and SP, have been
linked to itchy skin in psoriasis. NGF, PGP 9.5-reactive
nerve fibers, and the number of NGF-immunoreactive
keratinocytes have been found to be elevated in itch skin
and related to itch intensity. TrkA, an NGF high-affinity
receptor, is abundantly expressed in the epidermal and der-
mal nerve fibres, and this corresponds with itch intensity
(Henrich et al. 2015). Keratinocytes and nerve fibres in
itchy psoriatic skin have higher levels of SP and its recep-
tor expression. Furthermore, capsaicin was demonstrated
to considerably decrease itch in psoriasis patients, indicat-
ing a potential role for this neuropeptide in the aetiology
of psoriasis itching (Znajdek-awi 1124).
Centella asiatica L.
Guto Kola, Hydrocotyle asiatica L, or Centella asiatica is
commonly used in dermatology to treat skin problems.It
is a member of the Apiaceae family. The primary ingredi-
ents of Centella asiatica are centelloids, as these represent
pentacyclic triterpenoids that include madecassoside, asia-
ticoside, madecassic acid, and asiatic acid. It also includes
saponins of the oleanane and isothankunic acid types, such
as terminolic acid and centellasaponin D. It has saponins
(1–8%) and essential oils (1%) (Sampson et al. 2001).
Centella asiatica has long been used in Ayurvedic medi-
cine to treat a variety of diseases. It was discovered to
have tremendous promise as a natural antioxidant and a
DNA damage preventer. A research study compared the
madecassoside and asiaticoside anti-psoriatic actions on
the development of keratinocytes (SVK-14) with dithranol
and psoralen. The madecassoside and Asiaticoside IC50
values were discovered to be 8.6 0.1 M and 8.4 0.6, respec-
tively. In addition, the aqueous product of the herb Cen-
tella asiatica was shown to be less effective than Psoralea
corylifolia seeds. However, the findings were equivalent to
dithranol's IC50 value of 5.2 0.4 M (Ouyang et al. 2016).
Madecassoside ointment has been employed in research
to examine the impact of madecassoside against imiqui-
mod-induced psoriasis-like dermatitis using BALB/c mice.
Il-17 and IL-23 are important in the development of pso-
riasis. According to real-time PCR results, madecassoside
significantly reduced mRNA levels of IL-23 and IL-17.
Furthermore, keratinocyte proliferation was reduced using
haematoxylin, 5-bromo-2'-deoxyuridine (BrdU), and eosin
staining incorporation experiments. The number of Th17
cells was shown to be lower using flow cytometry. Con-
sequently, madecassoside ointment was discovered to be
beneficial in the treatment of psoriasis via the IL-17 and
IL-23 axes (Genoux and Duffy 2019).
Review of natural compounds for potential psoriasis treatment 1191
Cestrum diurnum
Cestrum diurnum, sometimes termed "wild jasmine," is a
member of the family Solanaceae and represents a West
Indian plant widely grown as a decorative plant. The plant's
leaves contain a strong steroid glycoside that mimics vita-
min D action. It includes 1,25-dihydroxycholecalciferol
glycosides. Vitamin D3 is normally generated at the skin
via UV light-dependent processes or obtained through food.
To produce the most activated vitamin D3, 1,25-dihydroxy-
cholecalciferol, vitamin D3 is hydroxylated twice, in the
liver and by the kidney (calcitriol) (Prema and Raghura-
mulu 1994). Topical vitamin D has a therapeutic impact via
two mechanisms: the vitamin D receptor-mediated method,
which inhibits keratinocyte growth, and the non-genomic
mechanism, which stimulates keratinocyte differentiation
due to elevated intracellular calcium. As a result, it has now
become a localised agent in the treatment of psoriasis.
Research was done to explore the effect of its supple-
mentation on psoriasis. For six months, patients were given
vitamin D2 only once every 2 weeks. Both the psoriasis area
and the PASI improved after 3 and 6 months. The average
PASI improvement was 34.21% versus 1.85% for the pla-
cebo. Vitamin D supplementation increased the results of
psoriasis therapy (Das et al. 2022). Aurochem Laboratories
Pvt. Ltd. markets Cestrum diurnum extract (3 g/g) as an
ointment and gel under the brand name PsoriaBan Natural.
It has shown up to 89% effectiveness. It has been proven to
be helpful in the healing of psoriasis in the face and scalp.
Cloves
Cloves' anti-inflammatory and antioxidant properties are
well documented. The active ingredients in cloves are euge-
nol and isoeugenol. Several studies have demonstrated that
these chemicals can inhibit NF-B activation by inhibiting IB
breakdown (Murakami et al. 2003). Murakami et al. (Barrea
et al. 2018). found that bis-eugenol, but not eugenol, inhibits
IB degradation and suppresses inflammatory cytokine pro-
duction at both the gene and protein levels.
Coffee
Coffee is considered one of the most commonly drunk
drinks, regardless of location. According to data (Manu-
script 2017), only tea and water are more commonly con-
sumed liquids. Coffee, furthermore, is a pharmacologically
active fluid. Its composition contains several physiologically
active chemicals (Gokcen and Sanlİer 2017). This would
include lipids, carbohydrates, nitrogenous chemicals, vita-
mins, minerals, antioxidants, phenolics, lactones, alkaloid
compounds, diterpenes, and caffeine, which accounts for
around 1% of all coffee composition. This compound has
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
a variety of medicinal properties and has been shown to
inhibit monocyte and neutrophil migration, lower levels of
glucose in the blood, have immunosuppressive and anti-
inflammatory properties and safeguard from neurodegen-
eration (Sharif et al. 2017).
Caffeine is the most researched component in coffee. It
inhibits Th1/Th2 cell proliferation, as well as the produc-
tion of pro-inflammatory cytokines like TNF-, IL-1, IL-6,
and IL-11, while simultaneously releasing anti-inflammatory
markers like adiponectin, IL-4, and IL-10 (Hall et al. 2015).
Furthermore, it inhibits cyclin Adenosine Monophosphate
(cAMP), which acts as an immunomodulator, increases the
production of anti-inflammatory cytokines, and acts as an
antagonist of the adenosine receptor. Moreover, the presence
of polyphenols in coffee's composition contributes to its
anti-inflammatory properties. A subset of these chemicals,
particularly chlorogenic acid and its metabolites block pro-
inflammatory cytokines, whereas caffeic acid lowers levels
of nitrite and eliminates inflammatory symptoms (Zampelas
et al. 2018).
According to Zampelas et al. (Fernandez et al. 2012), cof-
fee drinking boosts the body's inflammatory process, which
could have a negative correlation with psoriasis severity.
According to this study, drinking coffee on a daily basis
increased TNF-, CRP, and IL-6 levels, which resulted in
severe pathological manifestations of psoriasis. It is crucial
to note, however, that this study linked heavy coffee intake
(more than 200 mg per day) to psoriasis severity. The haz-
ard of psoriasis was shown to be modestly linked with an
elevation in coffee intake, albeit this was not significant sta-
tistically among cigarette consumers. It is worth noting that
this study may have had a significant limitation: a variety of
caffeine sources, such as sweetened beverages and overly
processed meals, were tested, which may have influenced
the outcomes reached. According to Sharif et al. (Hall et al.
2015), regular coffee consumption increases the level of
anti-inflammatory elements while decreasing the synthe-
sis of pro-inflammatory factors (particularly TNF-), which
is important in reducing the severity of psoriasis. Several
studies have found that the effect of coffee varies depending
on the dose. Moderate-intensity coffee consumption up to
three cups per day reduces psoriasis manifestations and has
an anti-inflammatory impact, whereas greater coffee con-
sumption, particularly more than four cups per day, worsens
clinical psoriasis symptoms and is related to a rise in pro-
inflammatory chemicals (Ammon and Wahi 1990).
Curcumin
Curcumin is indeed a polyphenol produced from the yellow
spice turmeric, a member of the Zingiberaceae family, with
several characteristics. It contains anti-tumor, anti-oxidant,
anti-inflammatory, and many other biological properties
13
1192
and is chemically identified as [1,7-bis(4-hydroxy-3-meth-
oxyphenyl)-1, 6-heptadiene-3, 5-dione] (Editor 2017). It's
apparent that curcumin's widespread usage in medicine is
due to its various qualities, which include anti-inflammatory,
antioxidant, anti-proliferative, anti-microbial, and anti-car-
cinogenic capabilities (Gupta et al. 2011). Curcumin is used
to treat a variety of ailments, including rheumatoid arthritis,
eye problems (such as uveitis anterior chronica and con-
junctivitis), menstrual irregularities, infections in the uri-
nary tract, and gastrointestinal and liver issues (e.g., irrita-
ble bowel disease, abdominal pain). It's also utilised as an
adjuvant treatment for cancer of the skin, wound repair, and
chicken pox (Anand et al. 2007). Dendritic cells have been
linked to the early stages of psoriasis. Myeloid dendritic
cells secrete IL-23 and IL-12, which stimulate IL-17-pro-
ducing Th22, Th1, and T cells, resulting in the production
of inflammatory cytokines such as IFN-, IL-17, IL-22, and
TNF, which trigger the cascade associated with psoriasis
inflammation (Skyvalidas 2020).
Curcumin contains anti-oxidative, anti-inflammatory,
and immunomodulatory properties and can decrease pro-
inflammatory factors, activation of T cells, and proliferation
via working on the AP-1, NF-B, and MAPK pathways. It
can keep DC immature, which affects cytokine generation,
stimulation of responsive T cells, and antigen presentation.
Curcumin inhibits the production of IL-17 by CD4+ T cells
(Campbell, et al. 2018). Curcumin inhibits the develop-
ment of imiquimod-induced differentiated HaCaT cells by
downregulating pro-inflammatory cytokines TNF-, IL-17,
and IFN- (Kang et al. 2016). IFN- and TNF-, as well as
IL-23, IL-22, IL-12, and IL-2, returned to normal levels in
mice after curcumin administration. This might be because
curcumin reduces Kv1.3 channel currents, inhibiting T cell
proliferation, or because curcumin influences AP-1, NF-B,
and MAPK signalling pathways inside psoriasis mice (He
et al. 2015). In an imiquimod-stimulated psoriatic model,
curcumin nanohydrogel restored the normally distributed
TJs proteins ZO1 and occludin while decreasing iNOS and
TNF- production (Zhang, et al. 2019). Following topical
application to mice, curcumin reduced inflammatory symp-
toms, mRNA levels of IL-1, IL-22, IL-17F, IL-17A, and
TNF-, and protein expression of CC Chemokine receptor 6
(CCR6) (Kurd et al. 2008).
Fennel and anise
As estrogenic agents, fennel (Foeniculum vulgare) and
anise (Pimpinella anisum) have been used. They are said to
enhance milk supply, induce menstruation, assist delivery,
decrease male climacteric symptoms, and boost libido. The
major ingredient of anise essential oils and fennel, anethol,
was thought to be a powerful estrogenic agent, but subse-
quent research reveals that the true pharmacologically active
13
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O. Y. Elkhawaga et al.
molecules are anethol polymers, including dianethol and
photoanethol (Sen et al. 1996). Anethole has been demon-
strated to inhibit inflammation as well as carcinogenesis. It
has been demonstrated to have antioxidant properties. We
demonstrated that anethole can limit NF-B activation by
inhibiting IB breakdown (Yilmaz et al. 2010).
Garlic
Garlic (Allium sativum) is a well-researched, great herbal
remedy that has been utilised for millennia to cure a variety
of health issues (Pazyar and Feily 2011). Its contents include
sulfur-containing molecules such as alliin, enzymes such
as alliinase, and chemicals enzymatically synthesised from
alliin as allicin. Garlic also contains other elements such as
oligosaccharides, flavonoids, arginine, and selenium (Alli-
son et al. 2006). One complicated combination is aged gar-
lic extract (AGE). Allin, cyclophilin, S-methyl-l-cysteine,
S-allyl- l -cysteine, S-acetylcysteine, S-allylmercapto-
l-cysteine, S-1 propionyl-l-cysteine, fructose-arginine, and
beta-chlorogenic are among its constituents. l-Arginine,
l-methionine, and l-cysteine are also present. Psoriasis is
now associated with the activity of the nuclear transcrip-
tion factor kappaB. Extensive investigation has revealed
this path. Garlic (S-allyl mercapto cysteine, diallyl sulfide,
ajoene) can inhibit this transcription factor (Singh and Tri-
pathy 2014).
Gaultheria procumbens L.
Gaultheria procumbens (eastern teaberry, boxberry, check-
erberry) seems to be an herbaceous plant that yields essen-
tial oils and belongs to the Ericaceae family. These oils
include the anti-inflammatory compound methyl salicylate
(Jurek and Olszewska 2019). The salicylate, as well as the
procyanidin-rich stem extract from Gaultheria procumbens,
suppresses pro-inflammatory proteins such as hyaluronidase,
COX-2, and lipoxygenase. Models created in vitro showed
antioxidant effects. Ex vivo experiments in human neutro-
phils stimulated with N-formyl-l-methionyl-l-leucyl-l-phe-
nylalanine and lipopolysaccharides reduced the production
of cytokines and proteinases, as well as reactive oxygen spe-
cies (Saha et al. 2014).
Ginger
Ginger (Zingiber officinale) would be a blooming medici-
nal plant with a spicy root or rhizome (plant stem) (Salaf-
zoon 2017). Furthermore, it is extensively utilised in
folk medicine due to its numerous health advantages in a
variety of conditions, covering chronic conditions such as
diabetes (Wang et al. 2011), cancer (Papers 2013b), ulcers
(Kukula-koch et al. 2018), Alzheimer's disease (Masuda
Review of natural compounds for potential psoriasis treatment 1193
et al. 2004), cardiovascular disease (Al et al. 1449), and
depression (Rabelo et al. 2014). Ginger's positive effect
on these disorders is mostly due to its antioxidant (Pkur-
maceutical 1933) and anti-inflammatory characteristics
(Tjendraputra et al. 2001).
The sharp scent and flavour of new ginger root are
caused by active volatile oils (e.g., shogaols, gingerols,
and zingerone), which account for around 1–3% of its
weight (Article 2001). Ginger also includes antioxidants
like vitamin C, vitamin E, lutein, beta-carotene, lycopene,
quercetin, genistein, and tannin (Wagesho and Chandra-
vanshi 2015). In addition, ginger includes important
nutrients such as manganese, selenium, copper, and zinc
(Wagesho and Chandravanshi 2015).
Gingerol, the active component, has already been dem-
onstrated to have chemopreventive properties (Tjendrapu-
tra et al. 2001). Gingerol also suppresses the nitric oxide
synthase enzyme and cyclooxygenase (COX-2), both of
which are recognised to be NF-B regulated (Article 2001).
Because gingerol may reduce platelet aggregation, synthe-
sised gingerol analogues with increased potency as platelet
aggregation inhibitors, similar to aspirin, may be useful in
cardiovascular disease (Getaneh et al. 2021). Since ginger
contains anti-inflammatory effects, it is a potential herbal
medicine for the treatment of psoriasis.
Indigo (Baphicacanthus cusia, Brem.)
TCM considers "Indigo naturalis" to be an important
medication. It's a blue powder obtained by grinding the
Baphicacanthus cusia plants, fermenting them, and add-
ing lime to them. Forty-two people with chronic plaque
psoriasis were given ointment containing 10% indigo once
a day for 12 weeks in a randomised placebo-controlled
experiment. The used indigo naturalis includes 1.4%
indigo and 0.16% indirubin. The indigo therapy allevi-
ated symptoms by 81%, whereas the placebo therapy
only reduced symptoms by 26% (Lin et al. 2014). Several
investigations using the indigo extract for psoriasis have
been conducted. A new randomized, controlled study of
100 psoriasis patients revealed dose-dependent efficacy
of indigo extract given twice daily for 8 weeks. The PASI
was lowered by 50% with indigo extraction (50 g/g) and
70% with indigo extract (200 g/g). Nasopharyngitis, infec-
tions of the upper respiratory tract, and local erythema
were reported in certain individuals. There were no severe
negative effects noted (Markham et al. 2003). Before and
after therapy, punch biopsies revealed normalisation of
epidermal appearance as well as a decrease in the main
pro-inflammatory cytokine in psoriasis (Markham et al.
2003).
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Lace flower (Ammi visnaga (L.) and Ammi majus (L.))
5-Methoxypsoralen (5-MOP) and furanocoumarins 8-meth-
oxypsoralen (8-MOP) is secluded for therapeutic applica-
tion from Ammi visnaga (L.) Lam. and Ammi majus (L.)
Psoralens are phototoxic chemicals that are photoactivated
via ultraviolet A (UVA) light and can induce extremely pho-
totoxic skin responses.
They limit keratinocyte growth and exhibit immuno-
suppressive effects in the healing environment of PUVA
treatment (psoralen and UVA), which is utilized to treat
strong inflammatory skin disorders such as psoriasis. Sev-
eral clinical investigations have demonstrated the effective-
ness of systemic PUVA (Vongthongsri et al. 2006), bath
PUVA (Amornpinyokeit and Asawanonda 2006), and cream
PUVA (0.1% 8-MO) (Bensouilah and Bensouilah 2003) in
psoriasis.
Matricaria recutita L.
Matricaria chamomile, or Matricaria recutita, is a part of
the Asteraceae family. It has traditionally been employed to
alleviate digestive issues. Chamazulene seems to be the pri-
mary phytochemical accountable for antipsoriatic action. It's
a derivative of the oil extraction matrix derived from flowers
(Rauf 2021). Chamazulene exerts anti-inflammatory action
by suppressing lipoxygenase, which inhibits leukotriene B4
synthesis (LTB4). LTB4 production then increases, result-
ing in psoriatic plaque. Therefore, Chamazulene's positive
impact will be demonstrated by inhibiting LTB4. The flavo-
noids and apigenin The flower contains quercetin (Bonesi
et al. 2018).
Quercetin is an anti-inflammatory, anti-tumor, antivi-
ral, and antibacterial flavonol. It inhibits both IFN-induced
STAT-1 stimulation and NF– activation. It reduces the gen-
eration of histamine and IgE. It inhibits the enzymes nitric
oxide synthase (iNOS), TNF-, and IL. Quercetin works
through many processes and might be used to treat psoria-
sis. Apigenin is indeed a flavone with anti-inflammatory
and antioxidant properties. It inhibits NF-B activation and
decreases TNF-induced luciferase reporter gene transac-
tivation (Jamalian et al. 2012). It also lowers TNF-, sup-
presses COX-2, IL-6, and IL-8 expression, and inhibits
TNF–induced luciferase reporter gene transactivation (Jama-
lian et al. 2012). It also protects against fungal infections
(Silva et al. 2019). Chamomile essential oil inhibits NF-,
TNF-, IL-1, IL-6, iNOS, and COX-2 (Gad et al. 2019).
Melaleuca alternifolia
The Melaleuca plant is endemic to Oceania and is utilised
in traditional medicine in Australia. -terpinene, -terpineol,
terpinen-4-ol, 1,8-cineol, -pinene, terpinolene, sabinene,
13
1194
and limonene are all found in tea plant oil. Sesquiterpenes
and aromatic chemicals make up the remainder of the oil.
In vivo, tea tree oil also has substantial antibacterial and
antifungal properties. Methyl eugenol, terpinen-4-ol, and
1,8-cineol all play important roles in antibacterial action
(Pazyar and Yaghoobi 2012). Terpinen-4-ol has been shown
to reduce TNF-, IL-1, IL-8, and PGE2 production. It can
also influence vasodilation and plasma extravasation (Koh
et al. 2002). In a trial of 27 patients to assess the impact of
tea oil on weeping or flare induced by histamine, the vol-
ume of mean weeping decreased significantly after 10 min
of treatment (Khalil et al. 2004). Human and rodent inves-
tigations had similar findings. Tea plant oil reduced the
susceptibility to flared and wheal histamines. Tea tree oil,
on the other hand, has been linked to contact allergies in a
small number of people. Freshly extracted oil is a mild to
the moderate sensitizer, while oxidation elevates the oil's
allergenic action. The oil contains sensitizers such as -ter-
pinene, ascaridole, -phellandrene, -phellandrene, limonene,
and trihydroxymenthane. The majority of the responses are
caused by direct tea tree oil application (Ali and Blunden
2002), Tea tree oil taken orally can ultimately cause systemic
contact dermatitis, cognitive confusion, and coma (Jurek and
Olszewska 2019).
Nigella sativa
Nigella sativa is a popular therapeutic plant that has a long
religious and cultural background in Unani, Ayurvedic, Ara-
bic, and Chinese medicine. Many bioactive natural agents,
including alpha-hederin, alkaloids, thymoquinone, and sapo-
nins, are found in N. sativa and contribute to its wide spec-
trum of effects as a bronchodilator, diuretic, antidiabetic,
analgesic, antihypertensive, antibacterial, antineoplastic,
and anti-inflammatory agent, making it a promising thera-
peutic for dermatological diseases. Thymoquinone (TQ) is
the major bioactive ingredient, accounting for 30–40% of
essential oils (Arjumand et al. 2019). TQ's high antioxidant
and anti-inflammatory actions have prompted much inves-
tigation into its wide spectrum of health benefits. The N.
sativa treatment has been proven to dramatically decrease
inflammation via TQ-mediated secretion of proinflam-
matory cytokines as well as eosinophils (Arjumand et al.
2019). Several researchers investigated the impact of TQ on
attenuating inflammation of the airways in a rat model of
allergic asthma (El-mahdy et al. 2005). TQ intraperitoneal
administration prior to airway challenge showed a signifi-
cant reduction in eosinophilia in the lung, serum IgG and
IgE levels, and IL-13, IL-4, and IL-5 proinflammatory Th2
cytokines. N. sativa functions as an antioxidant by enhancing
free radical defence by inhibiting elastase, lipid peroxida-
tion, and myeloperoxidase (Sethi et al. 2008). Despite down-
regulating transcription factors such as NF-B and STAT3
13
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O. Y. Elkhawaga et al.
and antiapoptotic BCL2, N. sativa increases cellular death
by up-regulating proapoptotic caspases 8, 9, and 3 and the
B-cell lymphoma 2 associate X protein (BAX) (Forouzanfar
et al. 2016). Because of its antibacterial, anticancer, anti-
inflammatory, and other qualities, as well as its capacity to
cure hypopigmentation through enhanced melanin distribu-
tion, N. sativa has high promise for treating a variety of
dermatological diseases. N. sativa is a potential treatment for
plaque psoriasis since it has few side effects and is widely
available.
Olibanum (Boswellia serrata, Triana & Planch.)
Frankincense, also known as olibanum, is a yellowish-
brown oleo-gum resin extracted from Boswellia species
such as Boswellia serrata (Woolley et al. 2012). The genus
Boswellia has around 25 species (Balamurugan et al. 2022).
Several previous studies reported that 200 patients with mild
to moderate psoriasis were given an olibanum ointment con-
taining 5% 3-O-Acetyl-11-keto-boswellic acid three times
per day for twelve weeks. The PASI, as well as other blood
indicators including leukotriene B4, TNF, VEGF, and PGE2,
were dramatically decreased. Contact dermatitis occurred in
13 individuals (6.5%) (Balamurugan et al. 2022).
Pomegrante
Dried pomegranate, or Punica granatum, seeds are a popular
culinary spice. Pomegranate extract flavonoids have been
shown in atherosclerotic humans and mice to reduce the oxi-
dation of low-density lipoprotein and cardiovascular disease
(Aviram and Dornfeld 2001). Pomegranate juice is known to
suppress serum angiotensin-converting enzyme activity and
lower systolic blood pressure (Schubert et al. 2002). Pome-
granate can reduce NF-B activation in vascular endothelium
via a unique method, according to new research (Asogwa
and Okoye 2019).
Conclusion
From this review, it has become clear that naturally derived
compounds could very likely become key players in future
psoriasis treatments. This article has summarised some of
the compounds and plants that have been studied to date for
their possible anti-psoriasis properties. Many more untapped
resources, however, remain in nature. Phytochemicals have
been reported to possess numerous health benefits, and
ongoing research is being conducted to determine their phys-
iological effects. The traditional use of natural compounds in
psoriasis treatment is relatively cheap due to the availability
of plants and the simple methods used in product prepara-
tion. However, the commercialization of natural compounds
Review of natural compounds for potential psoriasis treatment 1195
for psoriasis treatment may result in the dwindling of natural
resources and problems with producing a consistent quality
of adulteration. However, the use of synthetic medications
has led to a variety of adverse effects, one of which is pso-
riasis. In recent years, a study in this sector has provided a
variety of treatment options for treating psoriasis. The use
of herbal medicine is one such expanding strategy. Several
herbs have been demonstrated to have anti-psoriatic capa-
bilities, as discussed within this review. Herbal treatment, on
the other hand, is currently limited to a restricted subset of
psoriasis patients. Herbal extracts may be used in conjunc-
tion with synthetic medications to treat psoriasis. The dual
use may lead to a lower synthetic drug dosage as well as a
recurrence of the negative effects. To guarantee the safety
and effectiveness of psoriasis treatment, the standardisation
of herbal medicines necessitates regulatory requirements
and quality control processes. To assess the therapeutic effi-
ciency of these natural chemicals, more studies with a larger
sample size are necessary. Fresh plant resources should also
be examined in this region.
Acknowledgements The authors would like to sincerely thank the
Biochemistry division, chemistry Department, Faculty of Sciences,
Mansoura University. We wish to express our scientific appreciation
to all the staff members for their help in performing fieldwork. Thanks
to all of the study participants.
Author contributions All the named authors played an active role in
the planning and writing of this publication. ME, SM. MG and AM are
students working on this project. OE is the supervisor of the study. All
the named authors contributed to the final review as it was submitted
to the journal be it by analysis of information, organizing of data and
construction of text.
Funding Open access funding provided by The Science, Technology &
Innovation Funding Authority (STDF) in cooperation with The Egyp-
tian Knowledge Bank (EKB).
Data availability A standardized approach of herbal medicine, is
needed to design larger trials which can ensure the effectiveness of the
treatment of psoriasis.Moreover, Further studies using newer herpal
plant are essential to establish the efficacy of these natural sources.
Declarations
Conflict of interest The authors declare no conflict of interest.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
were made. The images or other third party material in this article are
included in the article's Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
the article's Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will
need to obtain permission directly from the copyright holder. To view a
copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/.
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
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