Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Mol Cell Biochem. 2024 Nov 6. doi: 10.1007/s11010-024-05153-3. Online ahead of
 print.

Novel hypothesis and therapeutic interventions for irritable bowel syndrome: 
interplay between metal dyshomeostasis, gastrointestinal dysfunction, and 
neuropsychiatric symptoms.

Nakagawa Y(1), Yamada S(2).

Author information:
(1)Center for Pharma-Food Research (CPFR), Division of Pharmaceutical Sciences, 
Graduate School of Integrative Pharmaceutical and Nutritional Sciences, 
University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka, 422-8526, Japan. 
gp1958@u-shizuoka-ken.ac.jp.
(2)Center for Pharma-Food Research (CPFR), Division of Pharmaceutical Sciences, 
Graduate School of Integrative Pharmaceutical and Nutritional Sciences, 
University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka, 422-8526, Japan.

Irritable bowel syndrome is a gastrointestinal disorder due to multiple 
pathologies. While patients with this condition experience anxiety and depressed 
mood more frequently than healthy individuals, it is unclear how 
gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data 
suggest that irritable bowel syndrome patients predominantly display a lower 
zinc intake, which presumably impairs enterochromaffin cells producing 
5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and 
barrier system in the intestine, with the accompanying constipation, diarrhea, 
low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and 
zinc concentrations as well as elevated pro-inflammatory cytokine levels in the 
blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus 
coeruleus neuroinflammation and hyperactivation with resultant amygdalar 
overactivation and dorsolateral prefrontal cortex hypoactivation as found in 
neuropsychiatric disorders. The dysregulation between the dorsolateral 
prefrontal cortex and amygdala is likely responsible for visceral pain-related 
anxiety, depressed mood caused by anticipatory anxiety, and visceral pain 
catastrophizing due to catastrophic thinking or cognitive distortion. 
Collectively, these events can result in a spiral of gastrointestinal symptoms 
and neuropsychiatric signs, prompting the progression of irritable bowel 
syndrome. Given that the negative feedback mechanism in regulation of the 
hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric 
cases, dorsolateral prefrontal cortex abnormality accompanied by 
neuropsychiatric symptoms may be a more significant contributing factor in 
brain-gut axis malfunction than activation of the hypothalamic 
corticotropin-releasing hormone system. The proposed mechanistic model could 
predict novel therapeutic interventions for comorbid irritable bowel syndrome 
and neuropsychiatric disorders.

© 2024. The Author(s), under exclusive licence to Springer Science+Business 
Media, LLC, part of Springer Nature.

DOI: 10.1007/s11010-024-05153-3
PMID: 39503802


2. Aging Dis. 2024 Oct 7. doi: 10.14336/AD.2024.0834. Online ahead of print.

Systemic Modulators: Potential Mechanism for the 5-HT System to Mediate Exercise 
Amelioration in Alzheimer's Disease.

Wu Q(1), He Q(1), Zhang X(1), Chen S(2), Xue X(1).

Author information:
(1)School of Physical Education, Shandong University, Jinan, Shandong, China.
(2)School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong 
University, Jinan, Shandong, China.

As a neurodegenerative disease closely related to age-related changes, 
Alzheimer's disease (AD) is rapidly becoming one of the most resource-intensive 
and deadly diseases of this century. As a systemic neurotransmitter system with 
widespread distribution throughout the central and peripheral nervous systems, 
the 5-hydroxytryptamine (5-HT) system not only plays an important role in 
antidepressant therapy but also shows potential value in improving AD symptoms. 
The 5-HT system may facilitate the prevention and treatment of AD by impacting 
its pathological processes through various pathways, such as the regulation of 
Aβ deposition, hyperphosphorylation of Tau, central and peripheral 
neuroinflammation, and the interactions with the cholinergic and BDNF systems. 
In addition, regular exercise, as a non-pharmacological intervention, provides 
systemic and multi-level physical health benefits. Given the high sensitivity of 
the 5-HT system to exercise, this paper reviews its crucial role and potential 
mechanisms in alleviating AD through exercise. From perspective of the 
integrative biology of exercise, we propose several crosstalk mechanisms between 
the peripheral and central systems mediated by the 5-HT system. These mechanisms 
serve as a bridge for the treatment of AD and offer novel ideas and strategies 
for future therapeutic approaches.

DOI: 10.14336/AD.2024.0834
PMID: 39500357


3. Medicine (Baltimore). 2024 Nov 1;103(44):e40160. doi: 
10.1097/MD.0000000000040160.

Efficacy and mechanism of Tiaoshu Anshen Decoction in treating insomnia with 
spleen and stomach Qi dysfunction: A retrospective study.

Zhou F(1), Du L(1), Yu L(1), Zhang D(1), Jin H(2), Li Z(2).

Author information:
(1)Department of Emergency, Wuhan Traditional Chinese Medicine Hospital, Wuhan, 
Hubei, China.
(2)Department of Encephalopathy, Wuhan Traditional Chinese Medicine Hospital, 
Wuhan, Hubei, China.

This study investigates the clinical efficacy of Tiaoshu Anshen Decoction in 
treating insomnia characterized by spleen and stomach Qi dysfunction. According 
to the differences of previous treatment, 94 patients were divided into 
treatment group and control group. The treatment group was treated with Tiaoshu 
Anshen Decoction, and the control group was treated with oral esazolam for 2 
weeks. We compared serum levels of 5-hydroxyindoleacetic acid (5-HIAA), 
5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), DASS-21, and 
HAMD scores before and after treatment. We also evaluated gastrointestinal 
function, traditional Chinese medicine syndrome scores, quality of life, and 
adverse reactions, with statistical analysis conducted using SPSS 25.0. The 
overall efficacy and clinical outcomes were comparable between the 2 groups. 
Both groups showed increased serum factor levels and decreased Pittsburgh Sleep 
Quality Index (PSQI), HAMD, and DASS-21 scores post-treatment. Notably, the 
treatment group exhibited significant improvement in stool consistency, 
digestive symptoms, DOB < 4 and DOB ≥ 4 distribution, and TCM syndrome scores, 
outperforming the control group. No adverse reactions were reported in either 
group. This study suggests that spleen and stomach Qi dysfunction significantly 
contribute to insomnia, affecting its occurrence, type, and severity. Tiaoshu 
Anshen Decoction effectively enhances 5-HIAA, 5-HT, NE, and DA levels, reduces 
inflammatory factors, and improves sleep quality, gastrointestinal function, and 
overall quality of life. The decoction may exert its effects by regulating Qi 
dynamics and gastrointestinal function, indicating the gastrointestinal system 
as a potential key target in treating sleep disorders.

Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.

DOI: 10.1097/MD.0000000000040160
PMCID: PMC11537584
PMID: 39495997 [Indexed for MEDLINE]

Conflict of interest statement: The authors have no conflicts of interest to 
disclose.


4. Front Pharmacol. 2024 Oct 18;15:1461873. doi: 10.3389/fphar.2024.1461873. 
eCollection 2024.

Asiaticoside improves depressive-like behavior in mice with chronic 
unpredictable mild stress through modulation of the gut microbiota.

Ren Q(#)(1), He C(#)(1), Sun Y(#)(2), Gao X(2), Zhou Y(1)(2), Qin T(1)(2), Zhang 
Z(2), Wang X(3), Wang J(1)(2), Wei S(1)(2)(4), Wang F(1)(2).

Author information:
(1)Pharmaceutical Technology Key Laboratory of Luzhou, Central Nervous System 
Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical 
University, Luzhou, China.
(2)Department of Pharmacology, School of Pharmacy, Southwest Medical University, 
Luzhou, China.
(3)Department of Hepatobiliary Disease, The Affiliated Traditional Chinese 
Medicine Hospital, Southwest Medical University, Luzhou, China.
(4)Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources 
(Guangxi Normal University), Guilin, China.
(#)Contributed equally

BACKGROUND: Asiaticoside, the main active ingredient of Centella asiatica, is a 
pentacyclic triterpenoid compound. Previous studies have suggested that 
asiaticoside possesses neuroprotective and anti-depressive properties, however, 
the mechanism of its anti-depressant action not fully understood. In recent 
years, a growing body of research on anti-depressants has focused on the 
microbiota-gut-brain axis, we noted that disruption of the gut microbial 
community structure and diversity can induce or exacerbate depression, which 
plays a key role in the regulation of depression.
METHODS: Behavioral experiments were conducted to detect depression-like 
behavior in mice through sucrose preference, forced swimming, and open field 
tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) 
levels in mouse feces were analyzed 16S rRNA sequencing and gas 
chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic 
factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice 
was assessed by western blotting. Changes in serum levels of inflammatory 
factors, neurotransmitters, and hormones were measured in mice using ELISA.
RESULTS: This study revealed that oral administration of asiaticoside 
significantly improved depression-like behavior in chronic unpredictable mild 
stress (CUMS) mice. It partially restored the gut microbial community structure 
in CUMS mice, altered SCFA metabolism, regulated the 
hypothalamic-pituitary-adrenal axis (HPA axis) and inflammatory factor levels, 
upregulated BDNF and 5-HT1A receptor protein expression, and increased serum 
serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that 
asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis.
CONCLUSIONS: These results suggested that asiaticoside exerts antidepressant 
effects through the microbiota-gut-brain axis in a CUMS mouse model.

Copyright © 2024 Ren, He, Sun, Gao, Zhou, Qin, Zhang, Wang, Wang, Wei and Wang.

DOI: 10.3389/fphar.2024.1461873
PMCID: PMC11527651
PMID: 39494347

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest.


5. Therap Adv Gastroenterol. 2024 Oct 24;18:17562848241278125. doi: 
10.1177/17562848241278125. eCollection 2024.

Mirtazapine for gastrointestinal and neuropsychological symptoms in older adults 
with irritable bowel syndrome.

Khan A(1), Menon R(2), Corning B(3), Cohn S(3), Kumfa C(4), Raji M(4).

Author information:
(1)Department of Internal Medicine, University of Texas at Medical Branch, 301 
University Blvd, 5.138 RS, Galveston, TX 77555-5302, USA.
(2)Department of Internal Medicine, University of Texas at Medical Branch, 
Galveston, TX, USA.
(3)Department of Gastroenterology and Hepatology, University of Texas at Medical 
Branch, Galveston, TX, USA.
(4)Division of Geriatrics and Palliative Medicine, University of Texas at 
Medical Branch, Galveston, TX, USA.

Irritable bowel syndrome (IBS) is a common and potentially modifiable 
contributor to excess disability, morbidity, and poor quality of life. Clinical 
trials of medications for IBS have largely been in younger adults. Yet, a 
growing number of adults aged 65 and older are living with IBS. No data exist to 
guide clinicians in the safe and effective use of medications (e.g., 
anticholinergics, anti-spasmodics, and tricyclic antidepressants (TCA)) for IBS 
in the geriatric population. These medications-especially anticholinergics and 
TCAs-carry a high risk of adverse effects (ADE) in older adults because of 
age-associated decline in drug metabolism and the high prevalence of multiple 
chronic conditions. Five or more medications (polypharmacy) are frequently used 
to treat common psychiatric and medical comorbidities of IBS: anxiety, 
depression, insomnia, migraine headache, diarrhea, nausea, poor appetite, 
pruritus/skin atopy, and fibromyalgia. These neurological and psychiatric 
comorbidities reflect shared pathogenic mechanisms and bidirectional crosstalk 
of high inflammation, alteration of gut microbiota, and dysregulation of 
multiple gastrointestinal and central nervous system-active neurotransmitters 
(e.g., serotonin, neuropeptides). Currently, these IBS-associated conditions are 
treated with multiple medications-which increase the risk of adverse drug-drug 
interactions. One way to reduce the number of medications used for 
IBS-associated conditions is the use of one medication that treats many or all 
of these conditions-Mirtazapine. In this perspective article, we present 
evidence from basic science, case series, observational and epidemiological 
studies, clinical studies, and clinical trials supporting mirtazapine, a 
noradrenergic and specific serotonergic receptor antagonist-with 
5-hydroxytryptamine-2 and 3 antagonism, as a potential pharmacotherapeutic 
intervention for the myriad symptoms and conditions associated with IBS. 
Specifically, we found evidence of mirtazapine's role in treating diarrhea, 
insomnia, migraine headache, nausea, and poor appetite. We propose a large 
randomized controlled trial to study mirtazapine as a potential one-stop 
treatment for multiple IBS symptoms, with the potential to reduce polypharmacy 
and ADEs, especially in the geriatric population.

Plain Language Summary: Mirtazapine for gastrointestinal and neuropsychological 
symptoms in older adults with irritable bowel syndrome A growing number of 
adults aged 65 and older are living with irritable bowel syndrome (IBS). 
Clinical trials of medications for IBS have largely focused on younger adults, 
leaving a gap in data to guide clinicians in the safe and effective use of these 
medications for the geriatric population. Many of these medications—especially 
anticholinergics and tricyclic antidepressants (TCAs)—carry a high risk of 
adverse effects (ADEs) in older adults. Additionally, polypharmacy, defined as 
the use of five or more medications, is frequently employed to treat common 
IBS-associated conditions, including anxiety, depression, insomnia, migraine 
headaches, diarrhea, nausea, poor appetite, pruritus/skin atopy, and 
fibromyalgia. One strategy to reduce the number of medications used for 
IBS-associated conditions is to manage these conditions with a single agent: 
mirtazapine, a noradrenergic and specific serotonergic receptor antagonist. In 
this perspective article, we present evidence from basic and clinical studies 
supporting mirtazapine as a potential therapy for the myriad gastrointestinal 
and neuropsychological symptoms associated with IBS. Specifically, we found 
strong evidence for mirtazapine’s role in treating diarrhea, insomnia, anxiety, 
migraine headaches, and nausea, as well as modest evidence for its effectiveness 
in treating pruritus/skin atopy and fibromyalgia. We propose a large-scale study 
on mirtazapine as a potential one-stop treatment for multiple IBS symptoms, with 
the potential to reduce polypharmacy and ADEs, especially in the geriatric 
population.

© The Author(s), 2024.

DOI: 10.1177/17562848241278125
PMCID: PMC11526313
PMID: 39493642

Conflict of interest statement: The authors declare that there is no conflict of 
interest.