β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice

Panayotis, Nicolás; Freund, Philip A.; Marvaldi, Letizia; Shalit, Tali; Brandis, Alexander; Mehlman, Tevie; Tsoory, Michael; Fainzilber, Mike

doi:10.1016/j.xcrm.2021.100281

Cited by 24 publications

(20 citation statements)

References 64 publications

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“…Meanwhile, β-sitosterol exhibits antidepressant and anxiolytic effects (179) (273), possibly mediated through serotonergic, GABAergic and dopaminergic mechanisms. Furthermore, phytosterols modulate the activity of endogenous steroid receptors.…”

Section: Phytosterol Impact On the Microbiota-gut-brain Axismentioning

confidence: 99%

Gut feelings: the microbiota-gut-brain axis on steroids

Savidge

2022

American Journal of Physiology-Gastrointestinal and Liver Physi

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The intricate connection between central and enteric nervous systems is well established with emerging evidence linking gut microbiota function as a significant new contributor to gut-brain axis signaling. Several microbial signals contribute to altered gut-brain communications, with steroids representing an important biological class that impacts central and enteric nervous system function. Neuroactive steroids contribute pathologically to neurological disorders, including dementia and depression, by modulating the activity of neuroreceptors. However, limited information is available on the influence of neuroactive steroids on the enteric nervous system and gastrointestinal function. In this review, we outline how steroids can modulate enteric nervous system function by focusing on their influence on different receptors that are present in the intestine in health and disease. We also highlight the potential role of the gut microbiota in modulating neuroactive steroid signaling along the gut-brain axis.

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Section: Phytosterol Impact On the Microbiota-gut-brain Axismentioning

confidence: 99%

Gut feelings: the microbiota-gut-brain axis on steroids

Savidge

2022

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Previous studies have shown that increased time spent in the central area in the OFT, light compartment in the LDT and open arms of the EPMT, and less time of latency to eat is one indicator of the effectiveness of anti-anxiety drugs. 39,40 Our study found that compared with NS, administration of OD-CDs for 7 days resulted in significant anti-anxiety effects, close in potency to diazepam, a typical benzodiazepine drug that is often used in the animal model of anxiety as a positive control drug and has a clinically stable antianxiety effect. 41,42 DZP did not have sedative effects at 2 mg/kg.…”

Section: Discussionmentioning

confidence: 80%

Carbon Dots Derived from Os Draconis and Their Anxiolytic Effect

Chen¹,

Xiong²,

Zhang³

et al. 2022

IJN

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Background At present, people are susceptible to developing depression and anxiety disorders in response to stress. However, there is no specific medicine for anxiety. Os Draconis (OD, named “Long gu” in Chinese) are fossilized bones that have been used in traditional Chinese medicine to treat neurological diseases for thousands of years. Thus, we conducted this study to determine the biological basis for the anxiolytic effect of OD. Methods In this study, novel carbon dots (OD-CDs) from OD decoctions were discovered and separated. OD-CDs were anatomized using nanomaterials characterization methods to characterize the morphological structure, optical properties, and functional group properties. Four behavioural tests were conducted to observe the behavioural activities of mice, including the open field test (OFT), light/dark box test (LDT), elevated plus maze test (EPMT), and novelty-suppressed feeding test (NSFT), to determine its anxiolytic effects. Moreover, we assessed the possible mechanisms of the OD-CDs by detecting hormones associated with the hypothalamic-pituitary-adrenal (HPA) axis. Results OD-CDs were spherical and monodispersed with a narrow size distribution between 1 and 5 nm and had a yield of 3.67%. OD-CDs increased the activity time of mice in the central zone in the OFT. The mice in the experimental group showed more frequent activity in the light compartment and the open arms, in LDT and EPMT, respectively. In addition, OD-CDs shortened the feeding latency in the NSFT. Furthermore, the results after OD-CDs intervention showed a significant increase in serum serotonin (5-HT) and norepinephrine (NE). In addition, the concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ATCH), and corticosterone (CORT) were decreased. Conclusion These results demonstrate a definite anxiolytic effect of OD-CDs and reveal the possible mechanism of action of OD-CDs’ anxiolytic effect, which supports the research of OD for neurological disorders and a promising new trend of therapeutic approach and drug development.

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“…LC-MS found that all these molecules were present in the aqueous extract of WDD we prepared. After a systematic literature search, naringenin, 56 quercetin, 57 , 58 glabridin, 59 beta-sitosterol, 60 luteolin 61 , 62 of them was the candidate molecule for anxiety. Among them, the anxiolytic effects of quercetin, luteolin and narigenin are closely related to the inhibition of inflammatory response, suggesting that inhibition of inflammatory response may be the potential mechanism of Wendan Decoction in treating GAD.…”

Section: Discussionmentioning

confidence: 99%

Network and Experimental Pharmacology to Decode the Action of Wendan Decoction Against Generalized Anxiety Disorder

Jin¹,

Li²,

Chen³

et al. 2022

DDDT

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The mechanism of Wendan Decoction (WDD) against Generalized Anxiety Disorder (GAD) was predicted by network pharmacology and validated by in vivo and in vitro experiments. Methods: The targets of WDD for the treatment of GAD were obtained by a search of online databases. Further, PPI network and KEGG enrichment were used to identify the key targets and pathways. Ultimately, these key targets and pathways were validated by in vivo experiments on GAD mice modeled by repeated restraint stress (RRS) and in vitro experiments on inflammatory factor stimulated BV-2 cells. Results: Through searching the databases, the 137 ingredients of WDD that correspond to 938 targets and 4794 targets related to GAD were identified. Among them, 569 overlapping targets were considered as the therapeutic targets of WDD for GAD. PPI analysis showed that the inflammation-related proteins IL-6, TNF, SRC and AKT1 were the key targets, and KEGG enrichment suggested that PI3K/AKT and MAPK signaling pathways were key pathways of WDD in the treatment of GAD. In vivo experiments, RRS mice exhibited abnormality in behavioristics in open field test (OFT) and elevated plus maze (EPM) and increases in serum corticosterone and the percentage of lymphocytes positive for IL-6 in peripheral blood. These abnormal changes can be reversed by WDD and the positive control drug paroxetine. In vitro experiments, WDD can inhibit IL-6 induced activation of PI3K/AKT and MAPK signaling pathways in BV2 cells, and suppress the ensuing release of inflammatory factors TNF-α, IL-1β and PGE 2 , and showed a dosedependent effect. Conclusion: WDD is able to resist GAD by relieving inflammatory response in peripheral and central system.

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β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice

Cited by 24 publications

References 64 publications

Gut feelings: the microbiota-gut-brain axis on steroids

Gut feelings: the microbiota-gut-brain axis on steroids

Carbon Dots Derived from Os Draconis and Their Anxiolytic Effect

Network and Experimental Pharmacology to Decode the Action of Wendan Decoction Against Generalized Anxiety Disorder

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