





































Berkeley
Pharma Tech
Journal of Medicine

Correspondence: 
holstoncalifornia@gmail.com 

Keywords:
Autism Spectrum Disorder, 
Neuroinflammation, Mesenchymal 
STEM Cell Therapy, Oxytocin, 
Resveratrol, Sulforaphane, 
Combination Therapy

Submitted August 11, 2023 
Accepted April 5, 2024

Published June 28, 2024

Full Open Access

Creative Commons Attribution 
License 4.0

Abstract
One of the defining factors of Autism Spectrum Disorder (ASD) is 
neuroinflammation, which may be targeted to find effective therapies in 
managing ASD symptoms. Some promising treatments include mesenchymal 
STEM cell (MSCs) therapy, cxytocin (OT), sulforaphane (SFN), and resveratrol 
(RSV). MSCs are located in many parts of the body that can reduce secondary 
neurodegeneration and neuroinflammation while promoting neurogenesis and 
angiogenesis. OT is a hormone that moderates social and emotional 
communication, bonding, and social learning, while also having profound anti-
inflammatory effects. SFN is a naturally occurring compound in cruciferous 
vegetables, such as broccoli and sprouts, and activates a transcription factor 
which regulates anti-inflammatory and antioxidant genes. RSV is found in 
plants, such as grapes and berries, and helps stabilize the central and peripheral 
immune response and oxidative stress markers, subsequently reducing 
neuroinflammation. All of these treatments have shown promising potential, but it is 
abundantly clear that further research is needed in addition to combined therapies. 
Since ASD is a spectrum, not every case can be treated the exact same way. By 
targeting neuroinflammation, we can address the root cause of ASD rather than 
the symptoms.

Anti-Inflammatory Interventions for 
Autism Spectrum Disorder
By: Haily Holston, Avani Karvat, Simran Lallian, PingJu Wu



1. Introduction

ASD a�ects 1 in 36 children as of 2020,1 but the cause of the disorder is still 
unknown. While there is no clear consensus in the scienti�c community on 
the speci�c mechanism that leads to the development of ASD, some 
theories include genetic predispositions or environmental factors.2 

However, neuroin�ammation has been consistently found in individuals 
diagnosed with ASD. Some of the key characteristics of ASD are poorly 
developed social skills, di�culty with expressive and receptive 
communication, and the presence of restrictive and repetitive behaviors.3 

There is no current cure for ASD which poses a signi�cant call for action 
and attention to novel treatment.

There are many pharmacological therapies prescribed for ASD such as 
antipsychotics, hormones, CNS stimulants, and antidepressants to name a 
few.4 However, these interventions only target the symptoms of ASD 
instead of neuroin�ammation, and out of the symptoms only one aspect of 
ASD such as aggression, repetitive behaviors, hyperactivity/inattention, or 
social behavior. It is very di�cult to �nd treatments that cater to all the 
symptoms, for they mainly focus on accommodating symptoms and 
limitations associated with ASD such as speech, language, and learning 
de�cits. 75% of individuals with ASD also su�er from other associated 
disorders such as attention-de�cit hyperactivity disorder (ADHD), anxiety, 
bipolar disorder, depression, and many others.5 Non-pharmacological 
therapies that mediate symptoms of ASD include behavioral management 
treatment, cognitive behavior therapy, social skills training, and speech and 
language therapy. However, the focus of this review will be on novel forms 
of anti-in�ammatory treatments such as mesenchymal STEM cell therapy, 
oxytocin, sulforaphane, and resveratrol, which have been successful in 
reducing neuroin�ammation in animals and humans, providing synaptic 
protection, and relieving symptoms of ASD.

2. Pathophysiology of ASD and Neuroin�ammation

A single cause of ASD is yet to be found, but there are a large range of 
possible factors that play a signi�cant role in its onset, like genetics, 
environmental in�uences.

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Neuroin�ammation is found to be an underlying factor of ASD and other 
neurodevelopmental disorders. Although this correlation is apparent, it is 
still unclear whether neuroin�ammation is a symptom of ASD or if ASD is 
a result of neuroin�ammation.6 Neuroin�ammation refers to an 
in�ammatory response taking place in the central nervous system (CNS). At 
low levels, neuroin�ammatory signaling is critical for learning and memory 
functions, but at higher or chronic levels from CNS injuries, it can be a 
causing factor of neurodegenerative diseases and even aging.6

The neuroin�ammatory response involves microglia cells in the CNS and 
their polar nature. In ASD patients, neuroin�ammation has been observed 
in the cerebellum in early developmental stages and continues to the later 
stages of their lives.6 Neuroin�ammation can be detected through an 
increase in microglial cell density and somal volume in the white matter of 
the brain.6 Once microglia are activated, there are two in�ammatory 
pathway options:the pro-in�ammatory response in the M1 phenotype and 
the anti-in�ammatory response in the M2 phenotype.6 Pro-in�ammatory 
cytokines that commonly increase in patients with ASD are IL-6, TNF-ɑ, 
GMCSF, and IL-8, while those that decrease are TGF-β and IL-10.7 

Furthermore, chronic glial activation of the pro-in�ammatory pathway 
leads to the overall in�ammatory response being altered.8

Additionally, transforming growth factors (TFGβ 1, 2, 3) play vital roles as 
regulators in the immune system and general homeostasis including the 
regulation of in�ammation. For instance, ASD patients with decreasing 
behavioral measures have been found to have decreased TFGβ plasma.7

An environmental factor, maternal immune activation (MIA), is one of the 
most signi�cant factors linked to ASD in children. MIA triggers 
in�ammation of the placenta and neuroin�ammation in the mother.9 MIA 
can increase IL-17A expression, which leads to neuron cell death and thus 
hinders normal social behaviors as found in embryonic mouse brains.9 

Other ASD symptoms are found to be induced by MIA including 
anxiety-related repetitive behaviors.9 Neuroin�ammation caused by MIA 
has also been correlated to oxidative stress, another factor in causing ASD. 
Oxidative stress triggers negative feedback leading to unnatural and

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disrupted brain development, which is a key factor ASD and other
neurodevelopmental disorders.9

Figure 1: The in�ammatory response in the central nervous system and brain is mediated
by genes and cytokines.10 The increased TNF-alpha gene expression leads to the release of
pro-in�ammatory cytokines in the PNS.

3. Anti-In�ammatory Interventions

3.1 Mesenchymal STEM Cell Therapy

MSCs are stem cells that can be found in any postnatal tissue, including the
brain, it can perform a variety of functions, such as reducing secondary
neurodegeneration and neuroin�ammation, or promoting neurogenesis
and angiogenesis.11 The popularity of MSC therapy is due to its ability to be
harvested from various locations in the body, being easy to culture in lab,
having little ethical considerations, and being well-tolerated when
implanted into patients.6 In addition, there are no signi�cant safety
concerns during infusion or after.12

The way MSCs function is through bidirectional immunomodulatory
e�ects, caused by direct contact that increase in�ammation when the
immune system is under-active and decrease in�ammation when it is
over-active.6 Secondly, MSCs secrete extracellular vesicles (EVs), growth
factors, chemokines, and cytokines.6 EVs are known to be essential for

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regulating the in�ammatory response, mediating cell communication, and
transmitting mediators during in�ammation to ensure the
anti-in�ammatory response.13 Growth factors are hormone-like proteins
such as nerve growth factors (NGFs) in the brain, that can help suppress
in�ammation and switch the immune response to anti-in�ammatory.14

Cytokines and chemokines are proteins that help regulate the immune
response; when they are not in control it can lead to neuroin�ammation,
neurodegeneration, and demyelination of the CNS and PNS.15

Pre-clinical studies demonstrate the potential of MSC therapy. An in vitro
study demonstrated that MSCs modulate neuroin�ammation through
signi�cant reduction of mRNA expression of proin�ammatory cytokines in
microglia.16 MSCs were harvested from male mouse tibia and �bula, then
tested with BV2 and primary microglia isolated from mouse pup brains.16

Another study utilized in vitro culture exosomes from MSCs derived from
human umbilical cords (hUC), which proceeded to be administered
intranasally into mice. There was improved sociability and decreased
repetitive behaviors in mice treated with valproic acid, which closely mimics
ASD.12

A clinical study was conducted on 37 children with ASD from ages 3-14
years old, during which umbilical cord-derived mesenchymal stem cells
(UCMSC) in conjunction with human cord blood mononuclear cells
(CBMNCs) were tested. The subjects were divided into three groups in a
non-randomized, open-label, single center phase I/II trial, which are most
suitable for establishing medication dosages with the highest e�cacy.17 The
CBMNC group consisted of 14 participants, who all received a transfusion
of CBMNCs and rehabilitation therapy. The 9 participants in the
combination group received both CBMNC and UCMSC transfusions, as
well as rehabilitation therapy (9 subjects). The control group, which also
had fourteen participants, received only rehabilitation therapy. The
CBMNC group had signi�cant results in comparison to the control group,
however the combination group had the most signi�cant results based on
three scales: the Aberrant Behaviour Checklist (ABC), Clinical Global
Impression scale (CGI) and Childhood Autism Rating Scale (CARS), with
no signi�cant safety issues.17 This study demonstrated the e�ectiveness of
bothMSC therapy and the impact of dual therapy.

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Another clinical trial observed the impact of intravenous (IV) infusions of
human cord tissue mesenchymal stromal cells (hCT-MSCs) in 12 children
with ASD from ages 4 to 9 through an open-label, phase I study.18 The
hCT-MSCs were provided by a third party manufacturer, and each child
underwent one, two, or three doses with 2 month intervals in between.
Clinical and laboratory assessments were conducted in person initially and
at the 6-month mark for a baseline, then remotely again at the 12-month
point following the last infusion. Upon the end of the study, 50% of all the
children across all groups showed signs of improvement in at least 2 ASD
measures. The tests used to gauge e�cacy were the Vineland Adaptive
Behavior Scale, Pervasive Developmental Disorder-Behavior Inventory, and
Clinical Global Impression Scale. It is uncertain whether this was only due
to the treatment, but it was concluded that hCT-MSCs improves
communication and socialization in ASD patients. Once the trial treatment
was also determined to be well-tolerated and safe for children, hCT-MSCs
were successfully manufactured.18 However, it is important to note further
trials are necessary to con�rm the long-term e�ects and safety of the
treatment for the general population.18

In summary, the bene�ts of MSC therapy is limited to improvement of
symptoms without reversing the condition itself, making it a promising
supplementary treatment for managing ASD.12 More research on a larger
scale is necessary to understand the full extent of the treatment’s e�cacy in
managing varying degrees of ASD symptoms and characteristics.

3.2 Oxytocin

Oxytocin (OT), or the “social hormone”, is a neuropeptide naturally
produced by the human body. It is most widely known for its ability to
moderate social and emotional communication, bonding, and learning in
the human brain. Oxytocin is produced in the brain’s hypothalamus and is
released into the bloodstream by di�erent regions of the brain, such as the
pituitary gland, and the spinal cord.

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Figure 2: Map of the key pathways by which oxytocin modulates social functioning in the
brain. Oxytocin in�uences the modulation of sensory input (olfactory system in rodents),
social learning through interactions with serotonin systems in the nucleus accumbens, and
amygdala and limbic circuit activity. It also directly a�ects the brainstem nuclei to promote
bonding, trust, and social interactions.19

Oxytocin has profound anti-in�ammatory e�ects in multiple organ systems,
including but not limited to the inhibition of the immune system’s
activation of in�ammatory cells, signi�cant reduction of NADPH oxidase
and ROS production, and the lowering of pro-in�ammatory cytokine
production and neurotoxicity in the nervous system.20 A 2008 study
researching the role of oxytocin’s anti-in�ammatory properties conducted
trials with OT and lipopolysaccharide (LPS) treatments through both
individual and combination therapies. The results found that in 10 healthy
men who received the treatments, through individual or combination
therapies, there was long-term reduction of endotoxin-induced macrophage
in�ammatory protein-1-alpha, macrophage in�ammatory protein-1-beta,
cortisol, and VEGF levels, among other proteins responsible for generating
in�ammatory responses in the body.21 Most notably, OT had a signi�cant
e�ect on decreasing neuroendocrine cell and cytokine expression; these are
two components that play a vital role in cell signaling between the nervous
system and other organs that coordinate the body’s in�ammatory immune
response. Oxytocin’s moderation of the release of these proteins has been

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shown to relieve in�ammation in the body. In conclusion, oxytocin
demonstrates noteworthy therapeutic potential for ASD not only because
of its anti-in�ammatory properties, but because of the vital role the
hormone plays in the development of complex social behaviors.22

In mouse models of ASD, oxytocin exhibits an increase in social recognition
and restoration of social behavior. Rodents, like most animals, rely on
e�cient extraction of sensory information using their olfactory system to
shape their behaviors and perceive the world around them. A study was
conducted to test whether OT would trigger the main olfactory system in
female adult Wistar rats to process social odor cues. The experiment found
that after invoking the release of endogenous OT in mice with an
olfaction-OT social recognition task, the mice that released endogenous OT
had longer anogenital investigation events in comparison to the control rats.
In rodents, anogenital investigation is vital for olfactory sampling and social
recognition; the rats with prompted endogenous OT release took more time
to investigate and draw social conclusions about their surroundings.23

Another study observing the restoration of social behavior in a Cntnap2
mouse model of ASD after exogeneous OT release concluded that the
treated mice with previously low sociability demonstrated stronger
preference to interact with other mice after OT treatment.24 Therefore,
studies tests on mouse models demonstrated how both endogenous and
exogenous OT release prompts heightened social engagement and learning.

Clinical trials testing the role of OT in relieving social de�cits in patients
with ASD have been vital to our understanding of OT's capacity as a
potential therapy. One of such studies was a randomized, double blinded,
and placebo controlled clinical trial observing probiotic and oxytocin
combination therapy in patients with ASD aged 3-20 years old. The patients
were separated into two groups: 1 placebo group and 1 probiotic group.
The groups were observed for 28 weeks and at week 16, OT was introduced
to both. The results indicated trends of improvement in scores based on the
study’s Aberrant Behavior Checklist, Social Responsiveness Scale, and
stereotypic behavior score in the probiotic and OT combination group, as
well as signi�cant CGI improvement.25

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Another clinical trial explored the e�ect of OT nasal spray on social
interaction de�cits observed in young children with autism. The study
administered the OT nasal spray in the morning and night over a 5-week
trial period, and concluded that it was both well-tolerated by children and
improved caregiver-rated social responsiveness in comparison to the
children in the placebo group.26 This study noted that children with ASD
found this method preferable and signi�cantly more tolerable, providing
valuable insight into the future testing of exogenous OT in younger
patients.

Though the success of oxytocin in both relieving in�ammation throughout
the body and promoting social processing and engagement is apparent, one
of the limitations of oxytocin as a therapy for ASD is the inconsistency of
studies on oxytocin treatment in humans. Not all clinical trials show
signi�cant behavior changes or relief from repetitive behaviors and social
de�cits in individuals with ASD.27

3.3 Sulforaphane

Sulforaphane (SFN) is a naturally occurring compound abundant in
cruciferous vegetables, such as broccoli and sprouts, and recent research has
demonstrated its e�cacy in alleviating symptoms associated with ASD.28

SFN's therapeutic e�ects stem from its ability to activate a master
transcription factor known as nuclear factor erythroid 2 related factor
(Nrf2). Nrf2 plays a pivotal role in regulating anti-in�ammatory and
antioxidant genes, making it crucial for the body's defense against oxidative
stress and in�ammation.29 While the exact underlying mechanism remains
uncertain, evidence from a rodent-model study suggests that sulforaphane's
activation of Nrf2 is likely to address elevated Th17 immune responses and
oxidative stress observed in individuals with ASD.30 As a result, this
correction of immune dysfunction and oxidative stress is expected to lead to
a reduction in ASD symptoms.

Several clinical trials have been conducted to explore the e�ects of SFN
treatment in ASD, yielding encouraging results. In one placebo-controlled,
double-blind, randomized trial done by Singh et al., 29 young men with
moderate to severe ASD received daily oral doses of SFN for 18 weeks.31 The
results demonstrated substantial and reversible improvements in behavior,

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as quanti�ed by widely accepted measures completed by parents/caregivers
and physicians. SFN's mechanism of action lies in its ability to upregulate
genes that protect cells against oxidative stress, in�ammation, and DNA
damage, all of which are prominent characteristics associated with ASD.
Even though two participants encountered unprovoked seizures following
treatment, it's essential to emphasize that SFN exhibited minimal toxicity,
making it a comparatively safe option for therapeutic use.

Another clinical trial investigated the e�ects of adjuvant treatment with
SFN and risperidone in alleviating irritability in 60 children with ASD.32

The combination of SFN and risperidone led to greater improvements in
irritability and hyperactivity/noncompliance symptoms compared to the
placebo group. These results support the safety and e�cacy of SFN as an
adjuvant treatment for behavioral improvements in children with ASD.

Additionally, a larger randomized clinical trial with 108 subjects in China
further substantiated the potential of SFN treatment.33 Clinician-rated
scales showed a signi�cant improvement in the SFN group, with one-third
of participants experiencing a signi�cant decrease in scores after 12 weeks of
treatment. SFN was well-tolerated across all age groups, including young
children, and its e�ects appeared to be greater in participants over 10 years
of age. However, inconsistencies between caregiver and clinician-rated scales
indicate the need for more clinical trials to con�rm and re�ne the �ndings.

While SFN treatment holds promising potential for addressing ASD
symptoms, it also has limitations. Not all clinical trials have yielded
statistically signi�cant improvements in behavior, and the e�ects may vary
depending on age groups and assessment methods. In some studies, SFN
treatment did not show signi�cant clinical improvement in the behavioral
outcome measures evaluated in children with ASD.34, 35 Moreover, the
sample sizes in some trials were limited, which may impact the
generalizability of the �ndings. Further research with larger cohorts is
necessary to better understand SFN's e�ects and determine the optimal
dosages and treatment duration for di�erent age groups and severity levels
of ASD.

The need to validate the responses to SFN treatment in ASD has led to
studies exploring potential biomarkers. These candidate molecular markers,

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associated with ASD in three physiological pathways, include cytoprotective
enzymes, heat shock proteins, and pro-in�ammatory markers.36 Ex vivo
experiments using peripheral blood mononuclear cells (PBMCs) from
healthy subjects showed that all markers exhibited quanti�ability, accuracy,
and reproducibility after SFN treatment. When administered orally to ASD
patients, SFN led to an increase in cytoprotective enzymes and heat shock
proteins, while pro-in�ammatory markers decreased. These encouraging
results indicate that these markers have the potential to be utilized as
guidance for the development of SFN interventions for ASD.

In a nutshell, the promising potential of SFN treatment in ASD o�ers hope
for the development of mechanism-based therapeutic approaches. SFN's
ability to modulate oxidative stress and in�ammation highlights its
relevance in addressing the underlying pathophysiology of ASD.
Nevertheless, additional clinical trials along with biomarker establishment
are required to address the limitations and validate the consistency and
robustness of SFN's e�ects on ASD symptoms.

3.4 Resveratrol

Resveratrol (RSV) is a polyphenolic stilbenoid acting as a phytoalexin that
has been found to reduce common symptoms of ASD in animal models due
to its anti-in�ammatory and anti-oxidative properties.37 RSV is naturally
made in plants, such as grapes and berries, as they respond to pathogen
attacks.37

RSV can decrease neuroin�ammation by inhibiting activation of the
pro-in�ammtory pathway and the proin�ammatory cytokine release.38, 39

TNF-ɑ and MMP-9 levels signi�cantly decrease in the presence of RSV,
therefore reducing neuroin�ammation39. MMP-9 stimulates
proin�ammatory cytokines as well as processes the NLGN3 (neuroligin)
and NRXN1 (neurexin) genes that are linked to ASD39. MicroRNA-155
(MiR-15) also increases microglia’s in�ammatory response, which is
decreased by RSV to reduce neuroin�ammation.29

RSV has shown its e�ectiveness in reducing neuroin�ammation in several
studies di�ering in models used, dosage amounts, and methods of
administration. RSV admitted orally (5, 10, 15 mg/kg) was found to

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decrease pro-in�ammatory cytokine concentrations such as IL-6 and
TNF-ɑ, which in turn counteracts neuroin�ammatory markers.37 In a study
performed with RSV being injected at 0 hours, 8 hours, and 18 hours, RSV
was found to increase the anti-in�ammatory M2 phenotype polarization
and reduce the M1 pro-in�ammatory response.29

The valproic acid model (VPA), a fatty acid used as an antiepileptic drug
and mood stabilizer, is often used to study ASD.37 VPA is also a potent
teratogen, leading to abnormalities in embryonic development which can
induce ASD.38 VPA exposure during pregnancy has been associated with
ASD in o�spring and can cause developmental neurotoxicity in the child’s
central nervous system.37

In a study with RSV administration of 3.6 mg/kg for 12-13 days, there was
a signi�cant prevention and reduction of social de�cits of ASD in the VPA
model37. In this model, RSV decreased negative e�ects of ASD to the
nest-seeking behavior of the rats; however, RSV didn’t have an e�ect on
latency to decision making37.

In a separate study with the VPA model with rats, RSV was found to
prevent impairments in reciprocal social interaction40. Nose-to-nose sni�ng
habits of rats were also signi�cantly di�erent when treated with RSV40.
Decreased decision accuracy caused in the VPA model was also prevented
with RSV41. However, RSV couldn’t prevent food preference changes or
the behavior of repetitive self-grooming as it was a�ected by VPA
exposure40.

In addition to RSV’s success in the VPA model, in the BTBR model RSV
reduced persistent self-grooming, a repetitive habit in rats with ASD, with
doses of 20-40 mg/kg37. In human patients with ASD, these repetitive
behaviors include �dgeting or sni�ng. In the BTBR mice, CCR and
CXCR, chemokine receptors related to in�ammation, were signi�cantly
higher, but decreased with RSV treatment37.

In the propanoic acid (PPA) model, studies found the association of MMP
activation to in�ammatory cytokines and mitochondrial dysfunction39.
With this PPA model, RSV has proven to improve modi�cations of rats

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with ASD because of its properties, speci�cally being anti-TNF-ɑ and
anti-MMP-939.

Further studies and clinical trials can help to further investigate RSV’s
e�ectiveness against neuroin�ammation and in turn, symptoms of ASD.
Additional research will also be able to �nd how to utilize RSV while
minimizing side e�ects such as fetal abnormalities37.

4. Practical Applications

4.1 Mesenchymal STEM Cell Therapy

There is a large potential for MSC Therapy because it is very easy to obtain
through bone marrow, adipose tissue, placenta, skin, umbilical cord blood,
umbilical cord perivascular cells, umbilical cord Wharton’s jelly, amniotic
�uid, breast milk, and more42. MSCs are easy to isolate and expand, and are
unique due to their self-renewal and di�erentiation properties42. These cells
are also able to cross the blood-brain-barrier which helps it migrate to sites
of tissue injury and in�ammation.

Although there are numerous proof of concept studies, there is a signi�cant
shortage of clinical trials and other therapies researching practical use of
MSCs. Further investigation of the MSCs as a potential therapy for ASD is
necessary to determine the e�ectiveness on patients with varying severities.
Since most clinical trials have studied young children, study participants
within a wider range of age groups would signi�cantly increase our
understanding of MSCs and adult patients with ASD.

Furthermore, the e�cacy of this therapy based on MSCs di�erent tissue
types and varying administration methods has yet to be explored42.
Researchers are unsure whether systematic delivery (ex: intravenous) is
enough to reach the brain, compared to direct implantation, or intranasal
administration which is non-invasive42. Additionally, it is unclear whether
MSCs obtained from di�erent sources in the body will have di�ering or
similar therapeutic e�ectiveness42.

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ASD is also associated with a myriad of other autoimmune conditions such
as autoimmune thyroiditis, rheumatoid arthritis, ulcerative colitis, celiac
disease, and type 1 diabetes42. There is potential to investigate the use of
MSCs in helping manage these conditions alongside symptoms of ASD,
however many of these are either in the pre-clinical or early clinical trial
phases.

Although ASD still remains without a cure, MSC therapy emerges as an
intervention with great potential as MSCs can bene�t synaptic health and
have the potential to target tissue damage, regeneration/repair,
in�ammation, and ultimately aid in addressing the underlying pathology of
neuroin�ammation42. MSCs can be transplanted directly with no genetic
modi�cation, or pretreatment, can di�erentiate itself, and don’t have any
signi�cant side e�ects such as tumors42.

4.2 Oxytocin

OT has tremendous therapeutic potential for ASD speci�cally because of its
role in promoting social learning and bonding, as well as its
anti-in�ammatory properties in various systems in the body22. The
neuropeptide has been highly studied throughout the past few decades to
investigate how it may relieve one of ASD’s most notable characteristics:
social de�cit. Studies have shown that in both animals and humans, OT has
the capacity to heighten social problem solving skills and increase social
engagement in both patients with ASD and rodent models of autism.

Although there are a plethora of successful clinical trials exploring OT and
the social changes it creates in ASD patients, further research of OT in
humans is necessary in order to develop useful therapies. While OT shows
great promise for increasing sociability in patients with ASD, many clinical
trials in humans show inconsistent results in treatments using OT alone27.
Most notably, there are many unsuccessful clinical trials investigating OT
where there have been no signi�cant increases in social engagement or a
decrease in repetitive behaviors in patients with ASD27.

The strength of OT lies in combination therapy. When used with
probiotics simultaneously, OT treatment has shown drastic increases in the
patients’ caregiver rated sociability and decreases in repetitive behavior

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patterns25. Further research, especially exploring successful combinations of
OT and other potential therapies, is necessary to better understand how to
target and relieve speci�c symptoms of ASD.

Lastly, OT demonstrates therapeutic capability for ASD due to its method
of administration. OT is produced in the brain’s hypothalamus, it is one of
the body’s naturally occurring neuropeptides. Exogenous OT treatments
are commonly distributed intranasally, and this method has been reported
to be tolerable by children and show low levels of uncomfortability in
patients.

The human body’s OT can also be evoked to collaborate in treatment
methods26.

Some limitations of the trials using OT are that only healthy men were
included as participants, and no women were involved.21 Additionally, the
proposed half-life of OT was only around 20 minutes in the mammalian
brain25, the small sample size limited the ability to e�ectively analyze
subgroups, population heterogeneity led to subjects with varying treatment
responses, and cultural and language barriers potentially in�uenced
behavioral assessments26.

Overall, OT shows great potential in helping patients with ASD boost
social awareness, increase social engagement and social behaviors and
decrease repetitive behaviors patterns. The neuropeptide’s capability to
collaborate with other treatment methods such as probiotics in
combination therapy must be further researched to determine the most
useful amalgamation to relieve the most notable characteristics revolving
around the social de�cits of ASD.

4.3 Sulforaphane

Further research is essential to determine the most suitable dosage of SFN
tailored to individuals with varying body weights. The emerging evidence
regarding SFN's favorable e�ects on alleviating symptoms associated with
ASD is undeniably promising, underscoring the need for additional
exploration to unveil the most e�ective dosing regimen that maximizes its
therapeutic bene�ts while minimizing potential adverse e�ects.

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Studies conducted thus far have reported encouraging outcomes in
individuals with ASD who have consistently integrated SFN into their
dietary routine31, 32, 33. This naturally occurring compound, abundantly
found in various food sources such as broccoli, brussels sprouts, and
cabbage, provides a convenient and readily accessible method of
supplementation28. Given its ubiquitous presence in everyday foods, SFN
represents a safe option for oral consumption, enhancing its appeal as a
potential treatment for ASD.

SFN possesses multifaceted attributes that position it as an exceptionally
promising candidate in the search for e�ective therapies for ASD. Beyond
its easy availability, SFN boasts various pharmacological properties that
contribute to its therapeutic potential. As a potent antioxidant, SFN
combats oxidative stress, a common feature associated with ASD43, 44.
Additionally, it exhibits anti-in�ammatory e�ects that can alleviate
neuroin�ammation, frequently observed in individuals with autism8, 45, 46.

Furthermore, SFN's impact on the body's detoxi�cation mechanisms is
noteworthy. By enhancing phase II detoxi�cation enzymes, it facilitates the
elimination of harmful substances and toxins, further promoting the overall
health and well-being of individuals with ASD47, 48.

SFN's versatility reaches beyond its capacity as a standalone therapy.
Considering that individuals with ASD can derive bene�ts from
personalized combinations of treatments and services, there is a signi�cant
opportunity to synergize SFN with other compounds or medications33, 34.
Such integration has the potential to enhance SFN's therapeutic impact on
ASD symptoms, presenting a promising pathway for future therapeutic
interventions and optimizing its overall e�cacy.

While these developments are encouraging, it is crucial to acknowledge that
research in the �eld of autism is continuously evolving. Delving deeper into
the complexities of ASD and exploring the precise mechanisms through
which SFN exerts its e�ects will enable us to re�ne treatment protocols
better, catering to individual needs more e�ectively.

Overall, SFN's potential as a therapeutic agent for ASD shines brightly. Its
accessibility, presumed safety, and bene�cial e�ects on alleviating symptoms

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have garnered signi�cant attention from the scienti�c community. As
further investigations are conducted to establish ideal dosages and explore
potential synergistic e�ects with other treatments, the path towards
harnessing the full potential of SFN in enhancing the lives of individuals
with ASD becomes closer. This dedicated pursuit represents a crucial step
towards o�ering comprehensive and e�ective solutions to those living with
this neurodevelopmental condition.

4.4 Resveratrol

Because RSV can cross the brain-blood barrier, studying its e�ects is helpful
in investigating neurodevelopmental disorders37. Due to this characteristic,
RSV has low concentrations in the brain and high concentrations in the
blood, meaning RSV isn’t very e�ective when administered orally with only
a 1% bioavailability due to how easily it is absorbed and excreted49. This low
bioavailability makes RSV more bene�cial while being used in combination
with other therapies49.

Polyphenols, including RSV, aren’t naturally synthesized in animals, and
thus plant-rich diets are a more e�ective way to achieve its e�ects49. Foods
with high amounts of RSV include grapes, peanuts, and plums in addition
to several other recommended options31.

Even with RSV’s high potential to be used as an additional therapeutic
agent to reduce and improve the symptoms of ASD on a biochemical,
molecular, and behavioral scale, more research must be done to e�ectively
utilize its abilities39. More trials and research can help to better understand
RSV’s mechanisms of action in various conditions50.

It is important to note the participants of most RSV studies are
predominantly male animals, leaving room for questions regarding how
females may experience di�erent interactions with

RSV for ASD symptoms37. There have been studies with evidence of
di�erences in levels of estrogen receptors in ASD patients and with limited
knowledge of how sex hormones play a role in RSV, this is a future area if
study necessary to further prove RSV’s e�ectiveness37.

Berkeley Pharma Tech Journal of Medicine | 76



A notable negative e�ect of RSV’s use is particularly on pregnant women
because of fetal birth defects as shown in a study with Japanese macaques37.
The risk to pregnant women may also be accompanied with symptoms of
diarrhea and nausea31. Further study of these e�ects is bene�cial to provide
better care with less risk.

RSV shows promising results to patients with ASD particularly because of
its ability to reduce neuroin�ammation. With the goal of alleviating the
symptoms of ASD these patients face, further research of RSV in
combination with other therapeutic options would be extremely bene�cial.
Even with this further research, it is crucial to acknowledge the diversity of
ASD patients and their symptoms, leading to evolving information about
this treatment.

5. Future Directions

MSC, OT, SFN, and RSV are all anti-in�ammatory treatments that have
demonstrated their individual capacities to relieve in�ammation in the
body, namely neuroin�ammation, one of the hallmark underlying factors of
ASD. Each of these treatments have their own strengths and weaknesses, for
example OT shows signi�cant promise in increasing social engagement and
social problem solving in patients but has inconsistent results in humans
when not used in combination therapy. One discrepancy to note is that OT
has shown consistent measurable increases in sociability when administered
intranasally in mice, yet when administered intranasally in children, there is
great variation in results. In future, more research with other methods of
distribution of OT may lead to more consistent results and higher levels of
sociability in human patients with ASD. Further research to investigate the
capacity of each of these therapies in combination must be explored in
order to gauge their combined therapeutic potential. Combination
therapies that utilize the strong points of MSC, OT, SFN, and RSVmust be
studied in order to eventually create individualized therapies for ASD
patients that are speci�cally designed for that patient’s symptoms and
de�cits. Since ASD is a spectrum, individualized combination treatment
therapy holds immense promise in alleviating each patients’ most notable

Berkeley Pharma Tech Journal of Medicine | 77



symptoms. Currently, there is no literature speci�cally exploring MSCs,
OT, RSV, and SFN in combination to alleviate symptoms of ASD.
Exploring these therapies in combination with current treatments,
especially probiotic treatments, is necessary to create e�ective and tolerable
treatments to reduce neuro-in�ammation in patients with ASD.

6. Conclusions

Research of potential therapies for Autism Spectrum Disorder has
signi�cantly advanced in recent years as scientists explore new remedies for
the symptoms and underlying causes of ASD. However, current treatments
focus on alleviating common symptoms of ASD rather than targeting the
foundational causes of ASD such as neuroin�ammation. Although there is
no cure for ASD, treatments targeting both neuroin�ammation and critical
symptoms of ASD such as

Mesenchymal STEM Cell Therapy (MSC), Oxytocin (OT), Sulforaphane
(SFN), and Resveratrol (RSV) show immense therapeutic potential. Most
notably, ASD is a spectrum. No individual therapy studied thus far has the
capacity to be e�ective in all individuals with ASD. Potential interventions
serve to resolve some of the overarching consequences of ASD, particularly
neuroin�ammation, and social de�cits such as repetitive behavior patterns,
poorly developed social skills, and di�culty with expressive and receptive
communication. It is imperative that further research studying the
e�ciency of individualized combination therapy of MSC, OT, SFN, and
RSV be explored to create the most e�ective medicinal combinations for
individuals with ASD.

Berkeley Pharma Tech Journal of Medicine | 78



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