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Antioxidants (Basel, Switzerland) Sep 2022Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural... (Review)
Review
Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural sources, including vegetable fats or oils from many plants. Currently, stigmasterol has been examined via in vitro and in vivo assays and molecular docking for its various biological activities on different metabolic disorders. The findings indicate potent pharmacological effects such as anticancer, anti-osteoarthritis, anti-inflammatory, anti-diabetic, immunomodulatory, antiparasitic, antifungal, antibacterial, antioxidant, and neuroprotective properties. Indeed, stigmasterol from plants and algae is a promising molecule in the development of drugs for cancer therapy by triggering intracellular signaling pathways in numerous cancers. It acts on the Akt/mTOR and JAK/STAT pathways in ovarian and gastric cancers. In addition, stigmasterol markedly disrupted angiogenesis in human cholangiocarcinoma by tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor receptor-2 (VEGFR-2) signaling down-regulation. The association of stigmasterol and sorafenib promoted caspase-3 activity and down-regulated levels of the anti-apoptotic protein Bcl-2 in breast cancer. Antioxidant activities ensuring lipid peroxidation and DNA damage lowering conferred to stigmasterol chemoprotective activities in skin cancer. Reactive oxygen species (ROS) regulation also contributes to the neuroprotective effects of stigmasterol, as well as dopamine depletion and acetylcholinesterase inhibition. The anti-inflammatory properties of phytosterols involve the production of anti-inflammatory cytokines, the decrease in inflammatory mediator release, and the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Stigmasterol exerts anti-diabetic effects by reducing fasting glucose, serum insulin levels, and oral glucose tolerance. Other findings showed the antiparasitic activities of this molecule against certain strains of parasites such as (in vivo) and on promastigotes and amastigotes of the (in vitro). Some stigmasterol-rich plants were able to inhibit , , and at low doses. Accordingly, this review outlines key insights into the pharmacological abilities of stigmasterol and the specific mechanisms of action underlying some of these effects. Additionally, further investigation regarding pharmacodynamics, pharmacokinetics, and toxicology is recommended.
PubMed: 36290632
DOI: 10.3390/antiox11101912 -
Biomedicine & Pharmacotherapy =... Sep 2022Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Although its pathogenesis remains unclear, studies have indicated microglia-mediated...
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Although its pathogenesis remains unclear, studies have indicated microglia-mediated neuroinflammation playing an important role. Phytosterols are a class of natural compounds presented in food, and have anti-inflammatory abilities. Recent studies suggested that phytosterols can traverse the blood-brain barrier and enter the brain, however, it remains largely unknown that whether phytosterols affect neuroinflammation in the AD pathogenesis. Here, we used APP/PS1 mice as the animal model of AD, and found that stigmasterol treatment attenuated cognitive deficits, and decreased Aβ concentration in cortex and hippocampus. Stigmasterol treatment also suppressed neuroinflammation, by reducing pro-inflammatory cytokine levels and microglia activation. Next, we simulated BV2 cells with Aβ oligomers, which induced inflammatory responses of microglia. Stigmasterol protected BV2 cells against Aβ oligomers induced inflammation, and mediated secretion of pro-inflammatory cytokines via NF-κB and NLRP3 signaling pathways by AMPK activation. Stigmasterol also alleviated the M1 polarization of BV2 cells. In general, our study demonstrates that stigmasterol ameliorated neuroinflammation in APP/PS1 mice, and suppressed inflammatory response of microglia to Aβ oligomers via AMPK/NF-κB and AMPK/NLRP3 signaling, which provides a mechanistic insight for stigmasterol in anti-inflammation and AD therapy.
Topics: AMP-Activated Protein Kinases; Alzheimer Disease; Animals; Anti-Inflammatory Agents; Cytokines; Mice; Microglia; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Stigmasterol
PubMed: 35772378
DOI: 10.1016/j.biopha.2022.113317 -
Frontiers in Immunology 2021Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance....
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance. Stigmasterol, a plant-derived sterol, has shown anti-inflammatory effects. Our study aimed to identify the effects of stigmasterol on experimental colitis and the related mechanisms. Stigmasterol treatment restored the Treg/Th17 balance and altered the gut microbiota in a dextran sodium sulfate (DSS)-induced colitis model. Transplantation of the faecal microbiota of stigmasterol-treated mice significantly alleviated inflammation. Additionally, stigmasterol treatment enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyrate. Next, human naïve CD4+ T cells sorted from IBD patients were cultured under Treg- or Th17-polarizing conditions; butyrate supplementation increased the differentiation of Tregs and decreased Th17 cell differentiation. Mechanistically, butyrate activated peroxisome proliferator-activated receptor gamma (PPARγ) and reprogrammed energy metabolism, thereby promoting Treg differentiation and inhibiting Th17 differentiation. Our results demonstrate that butyrate-mediated PPARγ activation restores the balance of Treg/Th17 cells, and this may be a possible mechanism, by which stigmasterol attenuates IBD.
Topics: Animals; Anti-Inflammatory Agents; Butyrates; Cell Differentiation; Colitis; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; PPAR gamma; Stigmasterol; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 34691046
DOI: 10.3389/fimmu.2021.741934 -
Frontiers in Plant Science 2019A direct role for cholesterol signaling in mammals is clearly established; yet, the direct role in signaling for a plant sterol or sterol precursor is unclear.... (Review)
Review
A direct role for cholesterol signaling in mammals is clearly established; yet, the direct role in signaling for a plant sterol or sterol precursor is unclear. Fluctuations in sitosterol and stigmasterol levels during development and stress conditions suggest their involvement in signaling activities essential for plant development and stress compensation. Stigmasterol may be involved in gravitropism and tolerance to abiotic stress. The isolation of stigmasterol biosynthesis mutants offers a promising tool to test the function of sterol end products in signaling responses to developmental and environmental cues.
PubMed: 30984220
DOI: 10.3389/fpls.2019.00354 -
Frontiers in Oncology 2022Stigmasterol is a phytosterol derived from multiple herbaceous plants such as herbs, soybean and tobacco, and it has received much attention for its various... (Review)
Review
Stigmasterol is a phytosterol derived from multiple herbaceous plants such as herbs, soybean and tobacco, and it has received much attention for its various pharmacological effects including anti-inflammation, anti-diabetes, anti-oxidization, and lowering blood cholesterol. Multiple studies have revealed that stigmasterol holds promise as a potentially beneficial therapeutic agent for malignant tumors because of its significant anti-tumor bioactivity. It is reported that stigmasterol has anti-tumor effect in a variety of malignancies (e.g., breast, lung, liver and ovarian cancers) by promoting apoptosis, inhibiting proliferation, metastasis and invasion, and inducing autophagy in tumor cells. Mechanistic study shows that stigmasterol triggers apoptosis in tumor cells by regulating the PI3K/Akt signaling pathway and the generation of mitochondrial reactive oxygen species, while its anti-proliferative activity is mainly dependent on its modulatory effect on cyclin proteins and cyclin-dependent kinase (CDK). There have been multiple mechanisms underlying the anti-tumor effect of stigmasterol, which make stigmasterol promising as a new anti-tumor agent and provide insights into research on its anti-tumor role. Presently, stigmasterol has been poorly understood, and there is a paucity of systemic review on the mechanism underlying its anti-tumor effect. The current study attempts to conduct a literature review on stigmasterol for its anti-tumor effect to provide reference for researchers and clinical workers.
PubMed: 36578938
DOI: 10.3389/fonc.2022.1101289 -
International Journal of Molecular... Nov 2021Phytosterols constitute a class of natural products that are an important component of diet and have vast applications in foods, cosmetics, and herbal medicines. With... (Review)
Review
Phytosterols constitute a class of natural products that are an important component of diet and have vast applications in foods, cosmetics, and herbal medicines. With many and diverse isolated structures in nature, they exhibit a broad range of biological and pharmacological activities. Among over 200 types of phytosterols, stigmasterol and β-sitosterol were ubiquitous in many plant species, exhibiting important aspects of activities related to neurodegenerative diseases. Hence, this mini-review presented an overview of the reported studies on selected phytosterols related to neurodegenerative diseases. It covered the major phytosterols based on biosynthetic considerations, including other phytosterols with significant in vitro and in vivo biological activities.
Topics: Brain; Humans; Molecular Structure; Neurodegenerative Diseases; Neuroprotective Agents; Phytosterols; Phytotherapy; Plants, Medicinal; Sitosterols; Stigmasterol
PubMed: 34830148
DOI: 10.3390/ijms222212255 -
Iranian Journal of Basic Medical... 2023which is known as "Neermulli'' in the vernacular is an herbaceous plant native to Sri Lanka. Ancient medicinal literature suggests the use of whole plant or its parts... (Review)
Review
which is known as "Neermulli'' in the vernacular is an herbaceous plant native to Sri Lanka. Ancient medicinal literature suggests the use of whole plant or its parts for the treatment of different communicable and non-communicable diseases including diabetes mellitus and tuberculosis. Active constituents and secondary metabolites including alkaloids, tannins, steroids, proteins, flavonoids, and glycosides are identified to possess antimicrobial, antitumor, antioxidant, hepatoprotective, anthelmintic, nephroprotective, antidiabetic, anticataract, anti-inflammatory, anti-nociceptive, hematopoietic, diuretic, antiurolithiatic, antipyretic, neuroprotection, and anti-endotoxin activities. In this review, we reviewed clinical studies, patents, and analytical studies from the earliest found examples from 1886 to the end of 2021. We critically analyzed and attempt to summarize the information based on bioactivities and chemical composition of plant extracts which will be of future use for researchers in this field.
PubMed: 37605731
DOI: 10.22038/IJBMS.2023.67965.14877 -
Journal of Food Science and Technology Jul 2020Plants consist of triterpenoids such as phytosterols (PT) (CHO) with steroidal nuclei, including sitosterol, stigmasterol, brassicasterol and campesterol. They are... (Review)
Review
Plants consist of triterpenoids such as phytosterols (PT) (CHO) with steroidal nuclei, including sitosterol, stigmasterol, brassicasterol and campesterol. They are hydrophobic but soluble in alcohol and other organic solvents and are isolated from industrial waste deodorizer distillates of various edible oil industries. They exist as free PT or their ester derivatives in soybean, rice, wheat, oat, cottonseed and corn fiber, and other cereals and grains. Conventional isolation techniques such as solvent extraction, distillation, evaporative fractionation, saponification and chemical esterification are employed for isolation and purification of PT. The present article reviews the various advanced separation techniques like solvent crystallization, supercritical fluid extraction, high speed counter-current chromatography and enzymatic process as strategic methods to isolate and purify sterols.
PubMed: 32549589
DOI: 10.1007/s13197-019-04209-3 -
Mediators of Inflammation 2022Airway inflammation in asthma is managed with anti-inflammatory steroids such as dexamethasone (DEX). However, about 20% of asthmatics do not respond to this therapy and...
Airway inflammation in asthma is managed with anti-inflammatory steroids such as dexamethasone (DEX). However, about 20% of asthmatics do not respond to this therapy and are classified as steroid-resistant. Currently, no effective therapy is available for steroid-resistant asthma. This work therefore evaluated the effect of a plant sterol, stigmasterol (STIG), and stigmasterol-dexamethasone combination (STIG+DEX) in LPS-ovalbumin-induced steroid-resistant asthma in Guinea pigs. To do this, the effect of drugs on inflammatory features such as airway hyperreactivity and histopathology of lung tissue was evaluated. Additionally, the possible pathway of drug action was assessed by measuring events such neutrophil levels, oxidative and nitrative stress, and histone deacetylase 2 (HDAC2) and interleukin 17 (IL-17) levels. STIG alone did not affect inflammatory features, although it caused some changes in the molecular events associated with steroid-resistant asthma. However, STIG+DEX caused significant modulation of inflammatory features by protecting against destruction of lung tissue. The modulation of inflammatory features was associated with significant inhibition of neutrophilia and oxidative and nitrative stress, decrease in HDAC2, and increase in IL-17 levels that are usually associated with steroid-resistant asthma. Our findings show that although STIG and DEX individually do not protect against steroid-resistant asthma, their coadministration results in significant modulation of inflammatory features and the associated molecular events that lead to steroid-resistant asthma.
Topics: Animals; Asthma; Dexamethasone; Drug Resistance; Guinea Pigs; Interleukin-17; Steroids; Stigmasterol
PubMed: 36060927
DOI: 10.1155/2022/2222270 -
Pharmaceutical Biology Dec 2023Stigmasterol has significant anti-arthritis and anti-inflammatory effects, but its role in immune and inflammatory diseases is still unclear.
CONTEXT
Stigmasterol has significant anti-arthritis and anti-inflammatory effects, but its role in immune and inflammatory diseases is still unclear.
OBJECTIVE
The potential advantages of stigmasterol in asthma were explored in IL-13-induced BEAS-2B cells and asthmatic mice.
MATERIALS AND METHODS
The optimal target of stigmasterol was confirmed in asthma. After detecting the cytotoxicity of stigmasterol in BEAS-2B cells, 10 μg/mL and 20 μg/mL stigmasterol were incubated with the BEAS-2B cell model for 48 h, and anti-inflammation and antioxidative stress were verified. Asthmatic mice were induced by OVA and received 100 mg/kg stigmasterol for 7 consecutive days. After 28 days, lung tissues and BAL fluid were collected for the following study. To further verify the role of NK1-R, 0.1 μM WIN62577 (NK1-R specific antagonist), and 1 μM recombinant human NK1-R protein were applied.
RESULTS
NK1-R was the potential target of stigmasterol. When the concentration of stigmasterol is 20 μg/mL, the survival rate of BEAS-2B cells is about 98.4%, which is non-toxic. Stigmasterol exerted anti-inflammation and antioxidant stress in a dose-dependent manner and decreased NK1-R expression in IL-13-induced BEAS-2B. Meanwhile, assay also indicated the anti-inflammation and antioxidant stress of stigmasterol after OVA challenge. Stigmasterol inhibited inflammation infiltration and mucus hypersecretion, and NK1-R expression.
DISCUSSION AND CONCLUSIONS
The protective effect of stigmaterol on asthma and its underlying mechanism have been discussed in depth, providing a theoretical basis and more possibilities for its treatment of asthma.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Antioxidants; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Inflammation; Interleukin-13; Lung; Mice, Inbred BALB C; Ovalbumin; Receptors, Neurokinin-1; Respiratory Hypersensitivity; Stigmasterol
PubMed: 36788676
DOI: 10.1080/13880209.2023.2173252