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Identification of Beta-Sitosterol and Stigmasterol as Possible Inhibitors of 5 Alpha-Reductase 1: An In-Silico Study



Background: Dihydrotestosterone (DHT), the most critical pathogenic androgen in hair loss, is identified as an etiologic factor of androgenetic alopecia (AGA). The AGA is a genetically common disorder among men and is characterized by the progressive conversion of hair follicles into small vellus hair. Steroid 5 alpha-reductase type 1 (5AR1) is a crucial target responsible for this gradual replacement. The 5AR1 function is determined by converting testosterone to DHT. The inhibitors of 5AR1 play their role by blocking the DHT production pathway. Objectives: This study focused on the potent inhibitors of the 5AR1 enzyme to suggest effective synthetic drugs for restoring hair loss with fewer side effects. Methods: The three-dimensional structure of 5AR1 was created using homology modeling methods. Then, the inhibitory effects of some significant compounds from natural sources were examined on the 5AR1 protein using molecular docking approaches. Results: The obtained results suggest that two natural compounds isolated from Serenoa repens, including beta-sitosterol and stigmasterol, could inhibit the regular activity of 5AR1 and can be recommended as safe and novel AGA medicines for hair restoration.
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Precis Med Clin OMICS. 2021 December; 1(1):e121545.
Published online 2022 January 22.
doi: 10.5812/pmco.121545.
Research Article
Identification of Beta-Sitosterol and Stigmasterol as Possible
Inhibitors of 5 Alpha-Reductase 1: An In-Silico Study
Pardis Zamani 1, Omid Mokhtari1and Fariba Dehghanian 1, *
1Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
*Corresponding author: Department of Celland Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. Email:
Received 2021 December 02; Revised 2022 January 04; Accepted 2022 January 05.
Background: Dihydrotestosterone (DHT), the most critical pathogenic androgen in hair loss, is identified as an etiologic factor of
androgenetic alopecia (AGA). The AGA is a genetically common disorder among men and is characterized by the progressive con-
version of hair follicles into small vellus hair. Steroid 5 alpha-reductase type 1 (5AR1) is a crucial target responsible for this gradual
replacement. The 5AR1 function is determined by converting testosterone to DHT. The inhibitors of 5AR1 play their role by blocking
the DHT production pathway.
Objectives: This study focused on the potent inhibitors of the 5AR1 enzyme to suggest effective synthetic drugs for restoring hair
loss with fewer side effects.
Methods: The three-dimensional structure of 5AR1 was created using homology modeling methods. Then, the inhibitory effects of
some significant compounds from natural sources were examined on the 5AR1 protein using molecular docking approaches.
Results: The obtained results suggest that two natural compounds isolated from Serenoa repens, including beta-sitosterol and stig-
masterol, could inhibit the regular activity of 5AR1 and can be recommended as safe and novel AGA medicines for hair restoration.
Keywords: DHT, 5AR1, Homology Modeling, Molecular Docking
1. Background
Androgenetic alopecia (AGA), or male-pattern hair loss
(MPHL), is the most common form of hair loss occurring
in 80% of men aged 80 years or older (1). The AGA is an
androgen-dependent disorder, and the miniaturization of
scalp hair follicles results in decreased hair density, thin
fibers, and severe forms that cause baldness (2,3). Dihy-
drotestosterone (DHT) is the primary specific androgen
hormone involved in AGA. In the DHT biosynthesis path-
way, an integral membrane enzyme, 5 alpha-reductase
(5AR), plays a regulatory role by reducing testosterone to
The 5AR family is related to androgen-dependent dis-
orders and consists of two isozymes, 5 alpha-reductase
type 1 (5AR1) and 5 alpha-reductase type 2 (5AR2) (4,5).
The 5AR1 and 5AR2 are nicotinamide adenine dinucleotide
phosphate-dependent enzymes and share a low sequence
identity of 47%. These two isozymes are encoded by SRD5A1
and SRD5A2 genes, located in different chromosomal loca-
tions. The 5AR1 is located on the 5p15.31 chromosome; how-
ever, 5AR2 is located on chromosome 2P23.1 in the human
genome (6).
Moreover, the tissue expression patterns of 5AR1 and
5AR2 are different. Type 1 is expressed in nongenital skin,
fetal scalp, and liver; nevertheless, type 2 is predominantly
expressed in male genital tissues, prostate, and seminal
vesicles. The 5AR2 is responsible for virilizing the external
male genitalia during puberty, benign prostatic hyperpla-
sia (BPH), and prostate adenocarcinoma tissues (7-9). Since
it has been reported that DHT-related disorders include
AGA, BPH, and prostate cancer,which can be treated by low-
ering DHT levels, 5AR is identified as an efficient drug tar-
get (10).
The 5AR inhibitors are applied in restoring hair loss
and regenerating miniaturized hair. Hair restoration is
defined by the change in terminal hair count and width.
Nonsurgical hair restoration options ranging from drug
therapy to laser treatments are cheaper and do not carry
risks associated with surgical hairline restoration, includ-
ing hair transplantation (11). In this regard, two potent syn-
thetic drugs, including finasteride and dutasteride, have
been established to inhibit 5AR1 and 5AR2. Finasteride, a
synthetic azo-steroid, is a more potent 5AR2 inhibitor than
5AR1, and dutasteride, widely used as AGA or BPH drug, in-
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Zamani P et al.
hibits both 5AR1 and 5AR2 (12).
According to the research conducted on the above-
mentioned two drugs, it has been detected that finasteride
can reduce the DHT level in serum by 70%, and the dutas-
teride inhibition effect showed a reducing amount of DHT
level up to 90% in serum (13). Although finasteride and du-
tasteride performed well as efficient 5AR1 inhibitors and
have been approved by the United States Food and Drug Ad-
ministration (FDA), there have been more concerns about
these two drugs’ long-lasting side effects occurring in ther-
apy within the last few years. Recent research has shown
that finasteride and dutasteride have several sexual ad-
verse effects, including libido reduction, dysfunction of
erectile, ejaculation disorders, and gynecomastia (14,15).
Due to the safety concerns of these drugs, the detection of
new, safe, and more effective 5AR inhibitors has become a
new medication approach in the drug industry. As it is ev-
idenced that 5AR1 is primarily expressed in the scalp, the
inhibition of 5AR1 is the primary approach for AGA medi-
cation (16).
2. Objectives
Multiple traditional herbals are suggested as potent
drugs to prevent this enzyme from working normally. The
current study provided a library of herbal components as
natural inhibitors and evaluated 5AR1 through homology
modeling and molecular docking techniques. The current
study library includes Cedrus and the henna tree (Lawso-
nia inermis), widely used in home remedy medications as
topical therapy on the scalp. In various studies, other com-
pounds mentioned as effective 5AR1 inhibitors that sug-
gested stimulating hair regrowth and strengthening hair
follicles are saw palmetto (Serenoa repens) and green tea
(Camellia sinensis). Another highly recommended com-
pound is vitamin B2, also known as riboflavin. Moreover,
two approved drugs, finasteride, and dutasteride, were
chosen as positive controls to be compared with the afore-
mentioned natural compounds (17-21).
3. Materials and Methods
3.1. Molecular Modeling
Since no three-dimensional (3D) structure of 5AR1 is
currently available in the Protein Data Bank, homology
modeling was utilized to generate the structure of SRD5A.
Modeling approaches are the most reliable methods of
predicting the 3D structure of an unknown protein based
on known homologous reference protein with high iden-
tity to the novel protein as a template. The FASTA format
of the 5AR1 enzyme protein sequence was retrieved from
the UniProt database (UniProtKB) with the accession num-
ber P18405. Based on best sequence alignment, the 3D
structure of the protein was modeled using I-TASSER on-
line server. The model was validated using various tools,
such as ERRAT (22) and PROCHECK (23), to generate the Ra-
machandran plot.
3.2. Dataset Collection
The data of this study contained several medicinal
plants widely used in home remedy medications. The
present study identified the main components of these
selected herbs. Cedrol, Cedrene, and Thujopsene are de-
tected in Cedar (Cedrus). Cedarwood essential oil is used
as a skincare agent and hair growth medication (24). 1,4-
naphthoquinone and Lawsone are active compounds iso-
lated from Lawsonia inermis, also known as the henna tree.
Studies evaluated that Lawsonia inermis compounds can
slow hair loss and help nourish the scalp (25). Epicatechin
gallate (ECG) and Epigallactocatechin gallate (EGCG) are
extracted from Camellia sinensis leaves (26-28). Other com-
pounds are β-sitosterol and stigmasterol isolated from
Serenoa repens. It is a popular herbal remedy that boosts
hair growth and helps maintain scalp health (29,30). Ri-
boflavin (vitamin B2) is a known antioxidant present in var-
ious plants. Research showed that riboflavin deficiency is
associated with hair loss (31). Finasteride and dutasteride,
used orally as 5AR1 inhibitors, were selected as positive con-
trols. Figure 1 depicts the two-dimensional (2D) structure
of all compounds.
3.3. Protein and Herbal Compounds Preparation
AutoDock Vina tools 1.5.6 were used to prepare 5AR1
and all compounds. The modeled structure of 5AR1 was
obtained from I-TASSER online server and imported to the
AutoDock Vina tools program. All water molecules were
merged, polar hydrogens were added, and Kollman charge
(32) and AD4 atom type were assigned. All the above-
mentioned 3D structures of compounds were retrieved
from PubChem data bank. Then, nonpolar hydrogens were
eliminated; finally, Gasteiger charge was assigned to calcu-
late the partial charge of all inhibitors.
3.4. Docking Studies
A molecular docking experiment was employed to de-
termine the binding modes of selected components with
5AR1 active site residues. This study used AutoDock Vina to
perform docking procedures to predict all inhibitors’ best
configuration within 5AR1 protein. The grid box parame-
ter values were adjusted with the size of 25*25*25 in spe-
cific coordinates of x, y, and z-axis (x = 64.899, y = 62.246,
and z = 66.772) and the space value of 1 Å to confirm the
2 Precis Med Clin OMICS. 2021; 1(1):e121545.
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Zamani P et al.
Figure 1. Chemical structure of 5 alpha-reductase type 1 inhibitors from natural sources
best binding affinity of the inhibitor-protein complex. The
Lamarckian genetic algorithms (33) were selected to per-
form docking. The best confirmation with the lowest bind-
ing energy estimated by Autodock Vina was visualized with
PyMOL (34) and LigPlot plus (35) to provide a 2D diagram of
the compound’s interaction against 5AR1.
4. Results
4.1. Constructed Model of 5AR1 and Validation
Figure 2A illustrates the constructed homology model
of 5AR obtained from I-TASSER. PROCHECK and ERRAT
were used to evaluate the model structure. ERRAT results
showed an overall quality factor of 92.0319. The Ramachan-
dran plot of the model in Figure 2B shows that 86.97% of
residues are in the most favored regions (red), 9.8% in addi-
tional allowed regions, 1.8% in generously allowed regions,
and 1.8% in disallowed regions. These statistics indicated
that the modeled structure was suitable for docking simu-
4.2. Docking Studies and Visualization
AutoDock Vina results revealed the orientation and in-
teraction of all natural compounds against 5AR1. The most
active compounds of the present study data collection are
listed in Table 1. In addition, the binding energy, H bonds,
and hydrophobic interactions are also shown. The docking
results demonstrated that two compounds, β-sitosterol,
and stigmasterol from Serenoa repens, had the strongest
docking affinity of -10.7 and -10.1 kcal/mol, respectively,
compared to the rest of the collection. In the second place,
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Zamani P et al.
Figure 2. (A) Three-dimensional modeled structure of 5 alpha-reductase type 1 (5AR1) enzyme using I-TASSER online server; (B) Ramachandran plot of 5AR1 model built via
ECG and EGCG isolated from Camellia sinensis leaves had
the binding energy values of -9.9 and -9.6. kcal/mol, respec-
tively. Riboflavin also showed high affinity (-9.1 kcal/mol)
but weaker than the last two groups and equal to or greater
than finasteride and dutasteride. Cedrus’s three main com-
pounds (ie, Cedrol, Cedrene, and Thujopsene) displayed
well but were weaker than the positive controls with the
binding energy of -8.2, -8.3, and -7.9 kcal/mol, respectively.
Lawsone and 1,4-naphthoquinone isolated from Lawsonia
inermis exhibited the weakest affinity among other com-
pounds with the active site residues of 5AR1. Screening the
interaction details of the 5AR1-inhibitor complex from Lig-
Plot+ showed that almost every compound interacts with
Ser36, Tyr38, Trp56, Glu60, Tyr95, Ala116, Met119, Ala120,
Phe123, Phe224, and Phe228. It could be inferred that these
residues are critical in the binding site and can be consid-
ered important residues for inhibitors to bind within the
active pocket of 5AR1. The most vital interaction regions
of 5AR1 are shown in brown parts in Figure 3A. The 5AR1
residues involved in the interaction with stigmasterol and
β-sitosterol are represented in 3D and 2D structures in Fig-
ures 3B-3C and 4A-4B, respectively.
5. Discussion
This study investigated the possible interactions be-
tween herbal inhibitors and 5AR1 protein using bioinfor-
matics tools for AGA medication. Previously, Lin et al.
worked on 5AR1 inhibitors to treat BPH; however, contrary
to the present work, they used AutoDock for the docking
procedure (36). In comparison to AutoDock 4, AutoDock
Vina significantly increases the average accuracy of the
binding mode predictions and is incredibly faster. It has
always been among the six first choices for docking analy-
sis globally. In the present study, this software could define
the interactions properly.
The current study findings revealed that all inhibitors
have possible interactions with 5AR1. Moreover, among
the selected inhibitors, the highest binding (-10.7 kcal/mol)
belongs to stigmasterol. The present analyses indicated
that stigmasterol binds to 5AR1 through only hydropho-
bic forces, and 13 amino acid residues were detected in
the interaction site (Figure 3B). Therefore, it can be con-
cluded that stigmasterol might be the best inhibitor. This
inhibitor is suggested as the new choice for further inves-
tigations in this field. In the second rank, β-sitosterol was
placed, with -10.1 kcal/mol. In the interaction site of β-
sitosterol, 13 amino acid residues weredetected (Figure 3C).
The highenergy value of thisinhibitor showed thepossible
potential of this component to inhibit 5AR1.
Similar to the present study results, previous stud-
ies confirmed the possible ability of stigmasterol and β-
sitosterol to inhibit 5AR. Prager et al. established the
effectiveness of β-sitosterol to control AGA. For the first
time, Prager et al. used a placebo-controlled double-blind
method to examine the benefit of this botanical substance
(37). In addition, Cabeza et al. reported the effect of β-
sitosterol to inhibit 5AR1 in the hamster prostate (38). They
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Table1. List of Most Active Compounds
Compounds Binding Energy
H-bond Hydrophobic Interaction
Stigmasterol -10.7 - Ser36, Val37, Tyr38,Trp56, GLN59, Glu60, Tyr95, Ala116, Met119, Ala120, Glu202,
Phe224, and Phe228
Beta-sitosterol -10.1 Tyr95 and Glu202 Arg30, Ser36, Tyr38, His46, Glu60, Leu115, Ala116, Met119, Ala120, Phe224, and
-9.9 Tyr56, Arg176, Tyr183,
Arg232, and Tyr240
Tyr38, Gly39, Ala52, Tyr102, Met106, Gly108, Gly109, Met112, Leu172, Tyr199, and
Epicatechin gallate -9.4 Arg98, Asn165, Asp169,
and Asn198
Tyr38, Trp56, Glu60, Met119, Ala120, Phe123, Glu202, Phe221, Phe224, Phe228,
and Leu229
Riboflavin -9.1 Arg98 and Glu202 Tyr38, Trp56,Gln59, Glu60, Tyr95, Ala116, Met119, Ala120, Phe123, Phe224,
Phe228, and Leu229
Dutasteride -9.1 Arg30, Asn31, and Glu60 Ser36, Val37, Tyr38,His46, Gln59, Trp56, Leo115, Ala116, Met119, Ala120, Phe224,
and Phe228
Finasteride -8.5 Tyr95 and Arg98 Arg30, Ser36, Val37, Glu60, Ala116, Met119, Ala120, Phe123, Phe224, and Phe228
Cedrene -8.3 - Trp56, GLN59, Glu60, TYR95, Ala120, Phe123, Glu202, Phe221, Phe224, Thr225,
and Phe228
Cedrol -8.2 Glu60 Gln59, Tyr95, Ala120, Phe123, Phe221, Phe224, and Phe228
Thujopsene -7.9 - Glu60, Tyr95, Met119, Ala120, Phe123, Phe221, Phe224, THR225, and Phe228
Lawsone -7.4 Arg30 and Ser36 Val27, Tyr38, Ala116, Met119, Ala120, Phe224, and Phe228
1,4-naphthoquinone -7.1 Arg30 and Ser36 Tyr38, Ala116, Met119, Ala120, Phe224, and Phe228
Figure 3. Most Critical interaction sites (brown regions) of 5 alpha-reductase type 1 (5AR1) protein (A); Active site residues of 5AR1 binding within stigmasterol (B) and beta-
sitosterol (C)
showed β-sitosterol could decrease the prostate weight,
and this effect was not related to the binding of β-sitosterol
to the androgen receptor but the inhibition of 5AR. How-
ever, both targets were present in the prostate.
Furthermore, Upadhyay et al. investigated the effect
of β-sitosterol phyto-vesicles to treat AGA. The aforemen-
tioned study confirmed the ability of β-sitosterol in the
control of alopecia, and phyto-vesicles could increase this
compound’s water and lipid solubility (39). Finally, Chen et
al. showed the potential of stigmasterol and β-sitosterol to
target 5AR and inflammatory pathways, which confirmed
the efficacy of these components to treat AGA and BPH.
In Chen et al.’s study, in vitro assays were used. The re-
sults of the aforementioned study determined the down-
regulation of messenger ribonucleic acid expression pro-
file characteristics of both disease processes in AGA (hair
follicle dermal papilla cells) and BPH (LNCaP prostate
cells) cell lines treated with stigmasterol or β-sitosterol.
The aforementioned study proved that stigmasterol and
β-sitosterol targeting 5AR and inflammatory mediators
might represent a rational approach in treating AGA and
BPH (40). Currently, available drugs for AGA are finasteride
Precis Med Clin OMICS. 2021; 1(1):e121545. 5
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Zamani P et al.
Figure 4. Two-dimensional diagram of most potent inhibitors, namely stigmasterol (A) and beta-sitosterol (B), interactions within 5 alpha-reductase type 1
and dutasteride, which are synthetic. However, these two
FDA-approved drugs have good inhibitory activity. Recent
studies have shown that they can lead to severe adverse
effects, including ejaculation disfunction, reduction of li-
bido, gynecomastia, and erectile disorder (41).
Docking analysis showed that dutasteride had a
stronger binding affinity (-9.1 kcal/mol) than finasteride.
In both inhibitors’ interaction sites, H-bonds and hy-
drophobic forces get involved. In line with the present
study results, some previous studies showed the in-
hibitory activity of these inhibitors. Rabasseda et al. and
Olsen et al. indicated that dutasteride increased scalp
hair growth in men with MPHL and suggested that type 1
and type 2 5AR might be important in the pathogenesis
and treatment of MPHL (42,43). In addition, Gubelin
Harcha et al. determined that dutasteride increased hair
growth and restoration in men with AGA. Gubelin Harcha
et al. showed that dutasteride 0.5 mg could remarkably
increase hair width and hair terminal count more than
finasteride 1 mg, suggesting that dutasteride is more effec-
tive than finasteride in hair loss restoration (44). Eun et al.
cited in Dhurat and Shanshanwal showed the potential of
dutasteride to inhibit 5AR (type 1 and type 2), converting
testosterone to DHT (45). Moreover, Inadomi et al., Shapiro
et al., and Yanagisawa et al. conducted different pilot stud-
ies, and their results showed that finasteride is effective
in the treatment of AGA patients (46-48). Finally, Arif et al.
and Jung et al. introduced dutasteride as a treatment of
choice for AGA (49,50).
Liao et al. showed that EGCG and ECG extracted from
green tea could inhibit 5AR in the sex gland in the rat. Fur-
thermore, Hiipakka et al. determined that EGCG can affect
5AR in cell-free but not whole-cell assays. They suggested
that EGCG with long-chain fatty acids is active in both cell-
free and whole-cell assay systems (26,51). Koseki et al. sug-
gested the potential of ECG to inhibit 5AR, which results
in inhibiting the androgen-related pathogenesis of acne,
testosterone conversion, and sebum synthesis. Therefore,
it was proposed that it can be a helpful agent in the thera-
peutic strategy of acne (52). The present study confirmed
the possible interactions between EGCG and ECG with 5AR
by computational methods, similar to the aforementioned
studies. Both inhibitors’ energy values were about -9
The docking results of the present study estimated the
strong interaction with -9 kcal/mol binding energy. More-
over, Nakayama et al. introduced riboflavin as a 5AR in-
hibitor. It was confirmed by Cho et al. that riboflavin has
stronger potent inhibitory activity than other compounds,
such as emodin and alizarin (53,54). Although the bind-
ing energy of Cedrol (-8 kcal/mol) is not close to the high-
est ones, it was predicted to be a strong inhibitor. Zhang
et al. showed the beneficial effect of Cedrol on hair loss
and confirmed that it has a strong hair growth promo-
tion effect (55). In addition, Deng et al. suggested that
Cedrol nanoemulsion significantly improved pharmacoki-
netic properties and hair growth (56).
1,4-naphthoquinone was extracted from a natural
source for the first time by Ishiguro et al. that showed
the significant testosterone 5AR inhibitory activity (57). Al-
6 Precis Med Clin OMICS. 2021; 1(1):e121545.
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Zamani P et al.
though Ishiguro et al. examined the inhibitory activity
of 1,4-naphthoquinone, the current study findings showed
that it has the lowest binding energy (-7.1 kcal/mol), com-
pared to other inhibitors. Therefore, it can be concluded
that this inhibitor has the weakest interaction with 5AR1.
Although Lawsone, Thujopsene, and Cedrene were listed as
5AR1 inhibitors in some reviews, any experimental studies
related to these components were detected. By consider-
ing the docking results of the present study, it can be con-
cluded that among these inhibitors, Cedrene is more capa-
ble of inhibiting 5AR1 due to the highest binding affinity
(-8.3 kcal/mol), compared to Thujopsene and Lawsone with
binding energy values of -7.9 and -7.4 kcal/mol, respectively.
Docking analysis showed that some regions were criti-
cal in the interaction between selected inhibitors and 5AR1,
shown in Figure 3A as brown regions. Among amino acid
residues involved in all interactions, 11 amino acids (ie,
Ser36, Tyr38, Trp56, Glu60, Tyr95, Ala116, Met119, Ala120,
Phe123, Phe224, and Phe228) were detected in the majority
of inhibitors and 5AR1 interaction sites. Therefore, it can be
suggested that the aforementioned residues are essential
to inhibit this protein and might be helpful in designing
new targets for the next generation of 5AR1 inhibitors.
5.1. Conclusions
The present study aimed to examine the potential ac-
tivity of herbal components as 5AR1 inhibitors using in-
silico analysis, which can be helpful for AGA treatments
and restoration of hair follicles. In conclusion, the present
predictions determined two inhibitors (ie, β-sitosterol and
stigmasterol) with the most robust interactions as the sug-
gested compounds to be used in further investigations as
the next generation of drugs to control AGA.
Authors’ Contribution: Pardis Zamani and Omid
Mokhtari performed in-silico analyses and wrote the
manuscript. Fariba Dehghanian helped in editing the
Conflict of Interests: The authors declare that they have
no conflict of interest.
Funding/Support: This study was performed at the Uni-
versity of Isfahan, Iran, and supported by the Graduate
Studies Office at this university.
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... IC50 data indicated that β-sitosterol is a less effective 5αR inhibitor than finasteride [26]. Zamani et al. (2021) suggest β-sitosterol and stigmasterol, two naturally occurring substances derived from Serenoa repens, are suggested to be safe and new AGA medications for hair regrowth since they may impede the normal function of 5αR type 1 [27]. According to Roy et al. (2008), E. alba has a large amount of β-sitosterol, which has been proven to be a potent 5αR inhibitor. ...
Full-text available
Objective: The present study was aimed to develop topical gel containing β-sitosterol using carbopol 940 as a gelling agent and to investigate 5 alpha reductase (5α-reductase) inhibitory activity of suitable gel formulation and compare it with a commercial product used topically for alopecia. Methods: Three different batches of β-sitosterol hair gel formulation were manufactured and evaluated. Additionally, the 5α-reductase inhibitory activity of the prepared formulation, finasteride as a positive control, was evaluated and compared to the commercial herbal formulation used. Results: According to the analytical findings of three different batches, the gel formulation is good in appearance, homogeneous, and easily spreadable. Based on findings from HPLC and HPTLC, the amount of β-sitosterol in those formulations complies with the label claim. By checking different critical parameters of those batches, we established the manufacturing process method validation and the process reproducibility. In vitro results showed the good 5α-reductase inhibitory potential of prepared gel formulation and then commercial product. The IC50 value of the prepared formulation was 118.960±0.634 (µg/ml) and standard beta-sitosterol 88.854±0.70 (µg/ml), whereas Finasteride (positive control) 224.372±3.103 (ng/ml). Conclusion: Thus, β-sitosterol formulation utilises a straightforward, low-cost production, less time-consuming process with minimal facility and equipment requirements. The formulation may be a promising candidate for future investigation into their antiandrogenic activities.
... Testosterone-induced alopecia involves the progressive hair loss, in response to circulating androgens [57]. Till date, only two FDA-approved "hair loss drugs" finasteride (5-αreductase inhibitor) and minoxidil (antihypertensive potassium channel opener) are supremely used in the current clinical practice [58], but adverse reactions, like itching and dermatitis, have been reported. ...
Full-text available
The objective of the present study was to develop a novel nanogel containing Beta vulgaris L. hydroalcoholic extract and assess its efficacy for treating testosterone-induced alopecia. Beta vulgaris L. leaf hydroalcoholic extract nanogel (BVEN) was prepared by ionic gelation method, incorporated in carbopol 934 gel. Optimization of particle size and entrapment efficiency as the responses was carried out by central composite design response surface methodology. Prepared nanoparticles were evaluated for entrapment efficiency, particle size, zeta potential, polydispersity index, Fourier transform infrared spectroscopy, transmission electron microscopy, and differential scanning calorimetry. Nanogel was evaluated for pH, colour, appearance and homogeneity, viscosity, spreadability, in vitro release study, and stability studies. Further, 2.5% and 5% BVEN were also evaluated for antialopecic activity in Swiss albino mice by using parameters as hair growth initiation, testosterone content, total protein, prostate weight measurement, hair follicular density, anagen/telogen ratio, and histopathological studies. The resulting nanoparticles had better entrapment efficiency with particle size of 274 nm, polydispersity index of 0.259, and zeta potential of +28.8. BVEN pH 6.5, drug content, i.e., quercetin 99.84 ± 1.30 % and stigmasterol 99.89 ± 1.52 % , spreadability 20.3 ± 0.5925 g cm / sec , and viscosity 110 × 10 5 cps were observed. Stability studies showed that nanogel was stable at 4 ° C ± 2 ° C / 60 % ± 5 % RH. It was found that 5% BVEN showed better antialopecic activity as compared to 2.5% BVEN.
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Androgenetic alopecia (AGA) is a multi‐factorial disease that carries a significant psychological burden with it. Dihydrotestosterone, the main pathogenic androgen in AGA, is produced by conversion of testosterone, which is catalyzed by the 5‐alpha reductase (5‐AR) isoenzyme family. Finasteride and dutasteride are inhibitors of these enzymes. Finasteride, which is a single receptor 5‐alpha reductase inhibitor (5‐ARI), acts by blocking dihydrotestosterone (DHT). Dutasteride, a dual receptor DHT blocker, has a higher potency than its predecessor, finasteride. This review corroborates the evidence of superiority of dutasteride over finasteride, and its comparable safety profile concerning fertility, teratogenicity, neurotoxicity, and hepatotoxicity. This article is protected by copyright. All rights reserved.
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Though hair does not serve any crucial physiological function in modern humans, it plays an important role in our self-esteem. Androgenic baldness (androgenic alopecia) and circular/spot baldness (alopecia areata) are the most common forms of hair loss. Many active ingredients of synthetic origin are available for treatment; however, they have a number of limitations. Their effectiveness and safety are questionable and the amount of time needed to achieve the effect is both long and unclear. This has increased interest in finding an alternative approach against hair loss using preparations containing plants and/or their isolated active ingredients. A number of studies (mostly randomized, placebo-controlled) of plants and preparations made of plants have been performed to confirm their effectiveness in treating hair loss. The plants with the most evidence-based effect against alopecia are Curcuma aeruginosa (pink and blue ginger), Serenoa repens (palmetto), Cucurbita pepo (pumpkin), Trifolium pratense (red clover), and Panax ginseng (Chinese red ginseng). The assumed mechanism of action is predominately inhibition of 5α-reductase, with enhanced nutritional support and scalp blood circulation playing a role as well.
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The second most common alopecia—Androgenetic alopecia (AGA)—occurs due to hormonal imbalance. Dihydrotestosterone (DHT) an androgenic hormone is a sex steroid, produced in the gonads. The target sites of DHT are similar to that of testosterone, and it attaches easily remaining bound for 53 minutes as compared to 35 minutes of testosterone. Excess of DHT causes miniaturization of hair reducing the anagen phase and increasing the telogen phase leading to hair loss. Normally up to ten percent of testosterone in the body irreversibly gets converted into DHT by the action of enzyme 5‐alpha‐reductase. Inadequate blood flow to the scalp can also be another reason for hair loss encountered due to lower oxygen and nutrients reaching it. AGA affects both sexes; however in males, it leads to major hair loss. Conventional drugs such as minoxidil and finasteride are widely used for the treatment. However, several drawbacks such as allergic contact dermatitis, burning, ejaculation disorder, and decreased libido are reported. Available literature suggests the role of herbal drugs to have the action against 5‐alpha‐reductase enzyme inhibiting it and reducing the hair loss. This can be further potentiated since they exhibit lesser side effects. Recent advancements observed in the medicinal, cosmetic, and engineering fields can prove to be an asset. This article focuses on herbs which can be used in AGA. A review of Saw palmetto (Serenoa repens), Green tea (Camellia sinensis), Pumpkin seed (Curcurbita pepo), Rosemary (Rosmarinus officinalis), Grape seed (Vitis vinifera), and Licorice (Glycyrrhiza glabra) is attempted.
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People commonly inquire about vitamin and mineral supplementation and diet as a means to prevent or manage dermatological diseases and, in particular, hair loss. Answering these queries is frequently challenging, given the enormous and conflicting evidence that exists on this subject. There are several reasons to suspect a role for micronutrients in non-scarring alopecia. Micronutrients are major elements in the normal hair follicle cycle, playing a role in cellular turnover, a frequent occurrence in the matrix cells in the follicle bulb that are rapidly dividing. Management of alopecia is an essential aspect of clinical dermatology given the prevalence of hair loss and its significant impact on patients’ quality of life. The role of nutrition and diet in treating hair loss represents a dynamic and growing area of inquiry. In this review we summarize the role of vitamins and minerals, such as vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, iron, selenium, and zinc, in non-scarring alopecia. A broad literature search of PubMed and Google Scholar was performed in July 2018 to compile published articles that study the relationship between vitamins and minerals, and hair loss. Micronutrients such as vitamins and minerals play an important, but not entirely clear role in normal hair follicle development and immune cell function. Deficiency of such micronutrients may represent a modifiable risk factor associated with the development, prevention, and treatment of alopecia. Given the role of vitamins and minerals in the hair cycle and immune defense mechanism, large double-blind placebo-controlled trials are required to determine the effect of specific micronutrient supplementation on hair growth in those with both micronutrient deficiency and non-scarring alopecia to establish any association between hair loss and such micronutrient deficiency. Plain Language Summary: Plain language summary available for this article.
Purpose: To carry out in silico design of 5α-reductase inhibitors and study their potential for use in the treatment of benign prostate hyperplasia (BPH). Methods: In silico molecular docking simulation-based virtual screening of NCI Diversity Set-II containing 1880 diverse ligands was performed against human 5α-reductase for identification of potential lead molecules. The pharmacological properties and toxicity of the lead compounds were determined using software, Marvin Sketch and OSIRIS online programs, respectively. Results: Three compounds: ZINC13099050, ZINC01569237 and ZINC17995347_2 showed potent inhibition of 5α-reductase enzyme protein and good pharmacokinetic properties without any serious toxic effects. Conclusion: The selected lead molecules are promising inhibitors of 5α-reductase. They are recommended for further structure-based development of drugs for the treatment of BPH.
5-α-Reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, a potent androgen responsible for male sexual development during the fetal period and later during puberty. Its deficiency causes an autosomal recessive disorder of sex development characterized by a wide range of under-virilization of external genitalia in patients with a 46,XY karyotype. Mutations in the SRD5A2 gene cause 5-α-Reductase deficiency; although it is an infrequent disorder, it has been reported worldwide, with mutational heterogeneity. Furthermore, it has been proposed that there is no genotype-phenotype correlation, even in patients carrying the same mutation. The aim of this review was to perform an extensive search in various databases and to select those articles with a comprehensive genotype and phenotype description of the patients, classifying their phenotypes using the external masculinization score (EMS). Thus, it was possible to objectively compare the eventual genotype-phenotype correlation between them. The analysis showed that for most of the studied mutations no correlation can be established, although the specific location of the mutation in the protein has an effect on the severity of the phenotype. Nevertheless, even in patients carrying the same homozygous mutation, a variable phenotype was observed, suggesting that additional genetic factors might be influencing it. Due to the clinical variability of the disorder, an accurate diagnosis and adequate medical management might be difficult to carry out, as is highlighted in the review.
The 5-α-reductase inhibitors finasteride and dutasteride are frequently used in the treatment of androgenetic alopecia and benign prostatichyperplasia. These drugs are effective at reducing levels of dihydrotestosterone, the primary androgen responsible for the pathogenesis of both these conditions. However, finasteride and dutasteride have also been shown to produce an increase in the incidence of sexual dysfunction, namely, impotence, decreased libido, and ejaculation disorder. The purpose of this study is to review the existing medical literature with regard to the sexual side effects of 5-α-reductase inhibitor therapy. This review is an extensive look at the sexual effects of 5-α-reductase inhibitors and compares outcomes for finasteride versus dutasteride in addition to comparing sexualside effects for each of the different dosages prescribed of finasteride and dutasteride.