Stigmasterol Research Articles

Anti-Inflammatory Activity and Acute Toxicity Of Pereskia aculeata, In Zophobas morio Larvae.

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (β-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as β-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 μg/mL; STIG and β-SIT showed toxicity up to 25 μg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and β-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for β-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.

Effect of stigmasterol and polyglycerol polyricinoleate concentrations on the preparation and properties of rapeseed oil-based gel emulsions

Emulsion gels mimic the rheological properties of solid and semi-solid fats, offering a viable solution to replace conventional fats in low-fat food formulations. In this study, gel emulsions stabilized with stigmasterol (ST) and polyglycerol polyricinoleate (PGPR) complexes were prepared. Initially, we examined the effect of the ST/PGPR complex on the mechanism of gel emulsion stabilization. Our findings revealed that the gel emulsion formulated with 3% PGPR and ST exhibited a robust structure, effectively stabilizing the entire system and ensuring uniform distribution, and increasing ST concentration led to greater stability of the gel emulsion system. Stability assessments demonstrated that gel emulsions containing 3% PGPR and varying ST concentrations exhibited remarkable thermal stability and effectively delayed oil oxidation. These results underscore the high stability of gel emulsions stabilized with the ST/PGPR complex, highlighting their potential as a margarine substitute.

Stigmasterol Activates the mTOR Signaling Pathway by Inhibiting ORP5 Ubiquitination to Promote Milk Synthesis in Bovine Mammary Epithelial Cells.

Stigmasterol (ST), a phytosterol found in food, has various biological activities. However, the effect of ST on milk synthesis in dairy cows remains unclear. Therefore, bovine primary mammary epithelial cells (BMECs) were isolated, cultured, and treated with ST to determine the effect of ST on milk synthesis. The study revealed that 10 μM ST significantly increased milk synthesis in BMECs by activating the mammalian target of rapamycin (mTOR) signaling pathway. Further investigation revealed that this activation depends on the regulatory role of oxysterol binding protein 5 (ORP5). ST induces the translocation of ORP5 from the cytoplasm to the lysosome, interacts with the mTOR, recruits mTOR to target the lysosomal surface, and promotes the activation of the mTOR signaling pathway. Moreover, ST was found to increase ORP5 protein levels by inhibiting its degradation via the ubiquitin-proteasome pathway. Specifically, the E3 ubiquitin ligase membrane-associated cycle-CH-type finger 4 (MARCH4) promotes the ubiquitination and subsequent degradation of ORP5. ST mitigates the interaction between MARCH4 and ORP5, thereby enhancing the structural stability of ORP5 and reducing its ubiquitination. In summary, ST stabilizes ORP5 by inhibiting the interaction between MARCH4 and ORP5, thereby activating mTOR signaling pathway and enhancing milk synthesis.

Enhancing the effectiveness of paclitaxel with stigmasterol bioactive compounds for cancer treatment

This study examines the anticancer activity of stigmasterol bioactive compounds combined with paclitaxel. Drug resistance and high toxicity in chemotherapy present a challenge in treating cancer. However, no study has reported the combination therapy of SS with PTX up to now. We evaluated the potential effects of stigmasterol (SS) combined with Paclitaxel (PTX) on cell viability and apoptosis in liver cancer (HepG2) and normal liver (AML 12) cells. The SS showed the highest cytotoxic effects on HepG2 cells (IC50= 117.75 µg/ml) compared to PTX (IC50= 294.59 µg/ml); however, SS and PTX did not affect normal cells, and SS caused higher apoptotic activity in the sub-G1 phase in HepG2 cells after being treated with SS alone compared to other treatments. In combination therapy for both cells, PTX: SS significantly increased cell viability (IC50 of 464.44 and 1056.44 µg/ml for HepG2 and AML 12, respectively) that differed from the drug alone and the compound, confirming that the PTX combined with SS did not enhance cytotoxic performance against HepG2 cell lines. However, this study found that PTX: SS could reduce the side effects arising from the treatment with PTX. This research indicates that SS is a potential anticancer agent for liver cancer. Furthermore, the current study introduces a novel synergistic therapy that can target various cell lines or enhance the concentration of both SS and PTX to investigate the delivery technologies of both compounds.

Cytotoxic Activity of Cambodian Leaves Extract (Plumeria acuminate) on Breast Cancer Cells and COX-2 Targeted Prediction of Its Chemical Contents

Cambodian leaves are suspected to contain stigma sterol which may target Cyclo-Oxygenase-2 (COX-2) or Estrogen Receptor (ER) to contribute to its cytotoxic activity on breast cancer cells. This study aimed to determine the potential of Cambodian leaf compounds and extracts as chemopreventive agents for luminal breast cancer with a molecular target of COX-2. Ethanol was used to extract the active compound of Cambodian leaves. The study on chemical activity against COX-2 employed molecular docking with Molecular Operating Environment (MOE) and the cytotoxic property of Cambodian leaf extract (CLE) on T47D was determined using the trypan blue exclusion method. The extraction yielded as 4.87% w/w CLE. Thin layer chromatography showed that Cambodian leaves contain sterol. Molecular docking confirmed that several sterol compounds have greater affinity to COX-2 than native ligands indicating that they are potent as COX-2 inhibitors. They are Stigmast-7-en-3-ol, Lupeol Acetate, and Lupeol carboxylic acid with docking scores of -14.3874, -13.8098, and -14.1045 kcal/mol respectively. The CLE exhibited cytotoxic activity on T47D cells with an IC50 value of 18 μg/mL. Therefore, CLE has a potential effect as a chemopreventive agent for breast cancer and potentially as a COX-2 inhibitor.Keywords: Cambodian leaf extract, breast cancer, COX-2 inhibitor, chemopreventive.

Stigmasterol Exerts an Anti-Melanoma Property through Down-Regulation of Reactive Oxygen Species and Programmed Cell Death Ligand 1 in Melanoma Cells.

Cancer immunotherapy as a promising anti-cancer strategy has been widely studied in recent years. Stigmasterol (STIG), a phytosterol, is known to have various pharmacological effects, including anti-inflammatory effects. However, the pharmacological role of STIG on melanoma immunotherapy has not been investigated. The present study demonstrates the anti-melanoma potency of STIG through the regulation of PD-L1 levels. The results reveal that STIG reduces reactive oxygen species (ROS) levels induced by hydrogen peroxide and increases glutathione levels decreased by α-MSH in B16F10 cells. Moreover, STIG significantly decreases melanin content and tyrosinase activities elevated by α-MSH. It also suppresses nitric oxide production induced by α-MSH. Additionally, STIG induces apoptosis with the up-regulation of PARP activation. STIG inhibits IFN-γ-induced PD-L1 expression and STAT1 phosphorylation levels. STIG also reverses the up-regulation of PD-L1 and phosphorylated STAT1 levels augmented by cisplatin, and STIG enhances CD8(+) T-cell-mediated cell death against B16F10 cells. These findings represent the first evidence of pro-apoptotic activity of STIG on melanoma cells through the down-regulation of ROS and PD-L1 pathways. Therefore, STIG may be an effective candidate for melanoma immunotherapy.

In Silico Analysis of Selected Mikania Constituents As Human HMG-CoA Reductase, Human Inducible Nitric Oxide Synthase, and Human Squalene Synthase Inhibitory Agents.

Background Numerous pharmacological activities have been reportedin Mikania species. In the present investigation, we aimed to evaluate 26 selected constituents of Mikania as potent inhibitory agents of human HMG-CoA reductase (hHMGR), human inducible nitric oxide synthase (hiNOS), and human squalene synthase (hSQS) using the in silico method. Methodology Twenty-six selected constituents of Mikania were investigated based on the docking behavior of three target enzymes, namely hHMGR, hiNOS, and hSQS, using the Cdocker method (Discovery Studio® 3.1, Accelrys, Inc., San Diego, CA). Results Docking analysis showed that methyl-3,5-di-O-caffeoyl quinate (MCQ) has the maximum binding energy (BE) (-39.63, -50.65, and -58.56 kcal/mol) with hHMGR, hiNOS, and hSQS enzymes. On the other hand, six ligands (kaurenoic acid (KAA), stigmasterol (SS), grandifloric acid (GA), kaurenol (KA), spathlenol (SP), and taraxerol (TA)) of Mikania failed to dock with either of the targetenzymes (hHMGR, hiNOS, or hSQS). Conclusions The findings of the current study provide new insight regarding 26 selected ligands of Mikania as potent inhibitory agents of hHMGR, hiNOS, and hSQS.

In vitro antioxidant activity, antidiabetic activity and in silico docking studies of 3,3′,4′,5,7-pentahydroxyflavone and stigmasta-5,22-dien-3β-ol isolated from aerial parts of Euphorbia milii. Des moul

This research focused on evaluating the in vitro antioxidant, antidiabetic activities and Insilco docking properties of two phytocompounds 3,3′,4′,5,7-Pentahydroxyflavone (Quercetin) and Stigmasta-5,22-dien-3β-ol (Stigma sterol). These compounds were isolated from the methanol extract of stem and ethanol extract of flower of the E. milii plant. The antioxidant properties of these phytocompounds were studied using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A comparison was made between the antioxidant activity of quercetin, stigma sterol, and the standard drug ascorbic acid. The results indicated that quercetin showed significant antioxidant activity, suggesting its potential as an effective antioxidant. Additionally, in vitro antidiabetic activity was investigated through α-amylase and α-glucosidase inhibition assays. Screened compounds exhibited significant % of inhibition values against two carbohydrate hydrolysing enzymes, α-amylase and α-glucosidase compared to reference drug (acarbose). Furthermore, molecular docking studies were conducted to analyse the interaction of the compounds with α-d-glucose (PDB ID: 3A4A) and PTP1B I (PDB ID: 1T49) as target molecules. These docking studies provided further insights to support the biological findings of the compounds isolated from E. milii aerial parts.

GC/MS Analysis and Isolation of Stigmasterol from Viola Odorata Cultivated in Iraq

Viola odorata is a viola family flowering plant native to Europe and Asia. This is a small, hardy, herbaceous, perennial plant. It is also known as sweet violet and English violet. Numerous pharmacological properties of this flowering plant include anticancer, antibacterial, anti-inflammatory, antioxidant and antipyretic properties. Previous literature review of different parts of Viola odorata resulted in detection of different chemical constituents such as flavonoids (Quercetin, kaempferol), glycosides (Rutin) and terpenoids (stigma sterol). Stigmasterol was detected using TLC and GC-MS in this study. It was isolated from Viola odorata using preparative layer chromatography. HPLC and FTIR analysis confirmed the isolated Stigmasterol

Network Pharmacology Followed by Experimental Validation to Explore the Mechanism of Stigmasterol in Sangbaipi Decoction Regulating PI3K/Akt Signaling to Alleviate Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Sangbaipi decoction (SBPD), a traditional Chinese medicine (TCM) prescription, has been widely used to treat acute exacerbation of chronic obstructive pulmonary disease (AECOPD), while the underlying pharmacological mechanism remains unclear due to the complexity of composition. A TCM-active ingredient-drug target network of SBPD was constructed utilizing the TCM-Systems-Pharmacology database. AECOPD-relevant proteins were gathered from Gene Cards and the Online-Mendelian-Inheritance-in-Man database. Protein-protein interaction, GO and KEGG enrichment analyses of the targets from the intersection of SBPD and AECOPD targets were performed to identify the core signaling pathway, followed by molecular docking verification of its interaction with active ingredients. The network pharmacology results were checked using in-vivo experiments. To induce AECOPD, rats were exposure to combined tobacco smoke and lipopolysaccharide (LPS). Then rats underwent gavage with stigmasterol (SM) after successful modeling. The involvement of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling was investigated using its inhibitor, LY294002. Lung function and histopathology were examined. The levels of inflammatory cytokines in the lung and serum were assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and/or Enzyme-linked immunosorbent assay (ELISA). SM was recognized as an active ingredient of SBPD and stably bound to Akt1. SM improved lung function and histological abnormalities, concomitant with suppressed PI3K/Akt signaling, downregulated lung and serum Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) levels and serum transforming growth factor-β (TGF-β) levels and upregulated lung and serum Interleukin 10 (IL-10) levels in AECOPD rats. In AECOPD rats, LY294002 restored lung function, and it also improved lung histological abnormalities and inflammation, which was found to be potentiated by SM. SM targets PI3K/Akt signaling to reduce lung injury and inflammation in AECOPD rats.

Stigmasterol and gastrodin, two major components of banxia-baizhu-tianma decoction, alleviated the excessive phlegm-dampness hypertension by reducing lipid accumulation

Ethnopharmacological relevanceBanxia baizhu tianma decoction (BBTD) originated from the Qing Dynasty Chinese medicine book “Medical Xinwu”, which has a clinical application history of more than 300 years. It's a classic prescription for expelling phlegm, extinguishing wind, strengthening the spleen (traditional Chinese medicine, ie, TCM, refers to the spleen channel) and dissipating excessive fluid based on TCM theory. BBTD is particularly effective in the treatment of excessive phlegm-dampness hypertension. However, the precise pharmacological effect of each herb of BBTD on hypertension treatment is not yet fully understood. Aim of the studyTo investigate the pharmacological effects of each herb in BBTD on hypertension treatment and to explore the mechanisms behind them. Materials and methodsA high-fat-diet fed animal model was developed to evaluate the efficacy of different groups of drugs in BBTD for the treatment of hypertension. Untargeted metabolism was used to detect the metabolic changes after modeling and drug intervention. Then, Stigmasterol (STI) and gastrodin (GAS), major components of Pinellia Ternate Makino and Gastrodia elata Blume, were selected for treatment on HepG2 cell steatosis model. Real-time quantitative polymerase chain reaction and Western blotting were used to detect changes of corresponding gene and protein after drug intervention to explore the exam anti-hyperlipidemia mechanism of STI and GAS combination. ResultsThe weight gain, elevated blood pressure and increased blood lipids induced by high-fat-diet were significantly decreased (p < 0.05) after each prescription medicine intervention in a dose-dependent manner. In addition, 28 differential metabolites (DMs) were detected after modeling and were regulated to normal at varying degrees after each drug group treatment. In addition, eight of the 28 DMs were significantly different from the model group after the full prescription drug intervention, primarily related to four metabolic pathways, while only two metabolites were significantly different from the model group after the unprincipled drug intervention, related to one metabolic pathway. In HepG2 hyperlipidemia cell model, STI, GAS and their combination significantly decreased TC, TG levels and lipid accumulation (p < 0.05), and decreased sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1) and their protein expressions (p < 0.05), increased adenosine monophosphate-activated protein kinase (AMPK) and it's protein expression (p < 0.05). The two drugs work better in combination than alone. ConclusionBBTD has been shown to be effective in reducing lipid accumulation in a high-fat rat model, as well as in restoring the model-induced abnormal metabolites to normal levels in a dose-dependent manner. Pinellia ternata Makino and Gastrodia elata Blume, the main components of BBTD, may regulate lipid metabolism through fatty acid biosynthesis, arginine and proline metabolism. Their main active agents, STI and GAS, effectively reduce lipid accumulation and lipid content in cells and regulate the expression levels of genes and proteins associated with lipid metabolism. These results suggest that BBTD may regulate lipid metabolism via AMPK/SREBP-1c pathway.

Detection of Coumarin Derivatives of Viola odorata Cultivated in Iraq.

Like other members of the viola family, Viola odorata may be found naturally occurring in Europe and Asia. This little plant is tough and perennially herbaceous. It's also known as sweet violet and English violet. There are several medicinal uses for this flowering plant, including its ability to fight cancer, bacteria, and inflammation., antioxidant activity, and antipyretic activity. The phytochemical studies of different parts of Viola odorata resulted in the isolation of different chemical constituents such as Coumarins, caffeic acid, methyl salicylate, flavonoids (Quercetin, kaempferol), glycosides (Rutin), and terpenoids (stigma sterol). Coumarins are important natural phenolic compounds of the family of benzopyrone. Coumarin's basic structure consists of a pyrone ring fused with a benzene ring. Umbelliferone and esculetin are the most common simple coumarins in nature. Coumarins become an attractive backbone drug with innovative impacts on illnesses and reduced side effects on healthy cells. Anti-inflammatory, anti-carcinogenic, and other biological properties are among those attributed to coumarins derivatives. In this study, Umbelliferone and esculetin of Viola odorata were identified by TLC, and HPTLC.

Stigmasterol Protects Against Steatohepatitis Induced by High-Fat and High-Cholesterol Diet in Mice by Enhancing the Alternative Bile Acid Synthesis Pathway

BackgroundHepatic cholesterol accumulation is a significant risk factor in the progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis. However, the precise mechanism by which stigmasterol (STG) mitigates this process remains unclear. ObjectivesThis study aimed to investigate the potential mechanism underlying the protective effect of STG in mice with NAFLD progressing to steatohepatitis while being fed a high-fat and high-cholesterol (HFHC) diet. MethodsMale C57BL/6 mice were fed an HFHC diet for 16 wk to establish the NAFLD model. Subsequently, the mice received STG or a vehicle via oral gavage while continuing the HFHC diet for an additional 10 wk. The study evaluated hepatic lipid deposition and inflammation as well as the expression of key rate-limiting enzymes involved in the bile acid (BA) synthesis pathways. BAs in the colonic contents were quantified using ultra-performance liquid chromatography-tandem mass spectrometry. ResultsCompared with the vehicle control group, STG significantly reduced hepatic cholesterol accumulation (P < 0.01) and suppressed the gene expression of NLRP3 inflammasome and interleukin-18 (P < 0.05) in the livers of HFHC diet-fed mice. The total fecal BA content in the STG group was nearly double that of the vehicle control group. Additionally, the administration of STG increased the concentrations of representative hydrophilic BAs in the colonic contents (P < 0.05) along with the upregulation of gene and protein expression of CYP7B1 (P < 0.01). Furthermore, STG enhanced the α-diversity of the gut microbiota and partially reversed the alterations in the relative abundance of the gut microbiota induced by the HFHC diet. ConclusionsSTG mitigates steatohepatitis by enhancing the alternative pathway for BA synthesis.

Anti-proliferative potential and oxidative reactivity of thermo-oxidative degradation products of stigmasterol and stigmasteryl esters for human intestinal cells

Stigmasterol in free and esterified form is incorporated in LDL cholesterol-lowering food products, intended for direct consumption and cooking, baking, and frying. Under thermal treatment, stigmasterol compounds may constitute a source of thermo-oxidative degradation products and oxyderivatives with potentially adverse health effects. This study aimed to analyze the anti-proliferative potential and genotoxicity of thermo-oxidatively treated stigmasterol (ST), stigmasteryl linoleate (ST-LA), and oleate (ST-OA). The effects on cell viability and proliferation, cell cycle progression, intracellular reactive oxygen species (ROS) generation, and DNA damage were analyzed in normal human intestinal cells. The mutagenic potential was assessed in a bacterial reverse mutation test using Salmonella enterica serovar Typhimurium strains involving metabolic activation. Stigmasteryl esters showed a significantly lower potential to affect intestinal cell viability and proliferation than non-esterified ST, regardless of heating. Thermo-oxidatively treated ST suppressed intestinal cell proliferation by arresting the cell cycle in the G2/M phase and DNA synthesis inhibition. The enhanced intracellular ROS generation and caspase 3/7 activity suggest targeting intestinal cells to the apoptosis pathway. Also, heated ST-LA intensified ROS production and elicited pro-apoptotic effects. Thermo-oxidative derivatives of ST and ST-LA may evoke harmful gastrointestinal effects due to their high oxidative reactivity towards intestinal cells.

Characterization of Non-Cholesterol Sterols in Microglia Cell Membranes Using Targeted Mass Spectrometry.

Non-cholesterol sterols, as well as plant sterols, cross the blood-brain barrier and, thus, can be incorporated into cell membranes, affecting the cell's inflammatory response. The aim of our work was to develop an analytical protocol for a quantitative assessment of the sterol composition within the membrane microdomains of microglia. A protocol for cell membrane isolation using OptiPrepTM gradient ultracentrifugation, in combination with a targeted mass spectrometry (LC-MS/MS)-based assay, was developed and validated for the quantitative analysis of free sterols in microglia cell membranes. Utilizing an established LC-MS/MS assay, cholesterol and seven non-cholesterol sterols were analyzed with a limit of detection from 0.001 to 0.05 mg/L. Applying the detergent-free isolation of SIM-A9 microglia cell membranes, cholesterol (CH), desmosterol (DE), lanosterol (LA) stigmasterol (ST), beta-sitosterol (SI) and campesterol (CA) were quantified with coefficients of variations between 6 and 29% (fractions 4-6, n = 5). The highest concentrations of non-CH sterols within the microglia plasma membranes were found in the microdomain region (DE>LA>SI>ST>CA), with ratios to CH ranging from 2.3 to 435 lower abundancies. By applying our newly developed and validated analytical protocol, we show that the non-CH sterol concentration is about 38% of the total sterol content in microglia membrane microdomains. Further investigations must clarify how changes in the non-sterol composition influence membrane fluidity and cell signaling.

The effects of the nature of the sterol on the properties and stability of niosome bilayer vesicles

Niosome vesicles as potential nanocarriers for drug delivery systems have been in development since the mid-1980s. These vesicles form by self-assembly of cholesterol and nonionic surfactants in an aqueous phase. The aim of the present molecular dynamics (MD) simulation study is to determine how changes in the sterol side chain and ring affect the structure and stability of sorbitan monostearate (Span60) niosome bilayers. Five sterols are examined: cholesterol (CHL), β-sitosterol (BST), ergosterol (ERG), stigmasterol (STS), and lanosterol (LST). Different sets of simulations were performed by varying the number of molecules (30, 40, and 50 % sterol concentration). The interactions between Span60 and the different sterols are found to be strongly dependent on the sterol’s side chain and head group. BST is found to markedly reduce the effectiveness of the sterol on the ordering of the bilayers, a result that persists over the whole range of concentrations examined in this work.

Simultaneous Estimation of Stigmasterol and Lupeol in Adenanthera pavonina using HPTLC Method

Adenanthera pavonina , a well-known medicinal plant has been used traditionally to treat diarrhea and inflammation. Its medicinal properties result from its active phyto-constituents, including non-protein amino acids, sterols, dulcitol, and fixed oil. Stigmasterol (STIGMA) and lupeol (LPL) are significant phytosterols in the plant’s bark as they possess anti-inflammatory activities that may be used in multiple therapies. To design an accurate HPTLC method for the simultaneous estimation of lupeol and stigmasterol from the bark of Adenanthera pavonina. The STIGMA and LPL were isolated using silica gel (60–120 #) column chromatography and estimated using HPTLC. The TLC aluminium plates were pre-coated with silica gel 60F254; the mobile phase comprised toluene and methanol in the ratio of 92:8v/v, and the compounds were detected using the vanillin-phosphoric acid reagent by densitometric scanning at 550 nm. The R f value for STIGMA and LPL was 0.430.02and0.550.02 with linearity in the range of 100– 500 ng/spot and 400-2000 ng/spot, respectively. The mean % recovery was in the range of 93.8–97.2 % for STIGMA and 94.9 –95.6 % for LPL with LOD and LOQ values of 11.74 and 35.58 ng/spot for STIGMA and 90.44 and 274.06 ng/spot for LPL, respectively. Our HPTLC method was accurate and precise for simultaneous estimation of STIGMA and LPL from the bark of Adenanthera pavonina, thereby making it effective in quality control investigations of the herbal formulations. Keywords: Adenantherapavonina; HPTLC; Stigmasterol; Lupeol

Stigmasterol attenuates hepatic steatosis in rats by strengthening the intestinal barrier and improving bile acid metabolism

Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively alleviates lipid metabolism disorder induced by a high-fat diet (HFD). Moreover, we also show that fecal microbiota transplantation from ST-treated rats displays similar protective effects in rats fed on an HFD. Our data confirm that the gut microbiota plays a key role in attenuating HFD-induced fat deposition and metabolic disorders. In particular, ST reverses HFD-induced gut microbiota dysbiosis in rats by reducing the relative abundance of Erysipelotrichaceae and Allobaculum bacteria in the gut. In addition, ST treatment also modifies the serum and fecal BA metabolome profiles in rats, especially in CYP7A1 mediated BA metabolic pathways. Furthermore, chenodeoxycholic acid combined with ST improves the therapeutic effects in HFD-induced dyslipidemia and hepatic steatosis. In addition, this treatment strategy also alters BA metabolism profiles via the CYP7A1 pathway and gut microbiota. Taken together, ST exerts beneficial effects against HFD-induced hyperlipidemia and obesity with the underlying mechanism being partially related to both the reprogramming of the intestinal microbiota and metabolism of BAs in enterohepatic circulation. This study provides a theoretical basis for further study of the anti-obesity effects of ST and consideration of the gut microbiota as a potential target for the treatment of HFD-induced dyslipidemia.

Coadministration of Stigmasterol and Dexamethasone (STIG+DEX) Modulates Steroid-Resistant Asthma

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.

Antioxidant activity of edible sprouts and phytosterol contents by HPLC/UV analysis

This study evaluated the in vitro radical scavenging activities of edible tree sprouts, particularly those of the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), hydroxyl radical, and singlet oxide radical, to assess their antioxidant activities. Additionally, stigmasterol (ST) and β-sitosterol (BS) were analyzed using HPLC/UV. The edible sprouts of Eleutherococcus senticosus (ESC) and Morus alba (MAB) exhibited the highest DPPH scavenging activity among other edible sprouts. A reverse-phase column was used in an isocratic elution system, after which UV detection was performed at 210 nm. ST and BS analyses indicated that ESC sprouts contained the highest amounts of ST (9.99 mg·g− 1 extract), whereas MAB sprouts contained the highest concentrations of BS (14.69 mg·g− 1 extract). In conclusion, the highest antioxidant activity was observed in the edible sprouts with the highest phytosterol content. Therefore, our findings provide a theoretical basis for the development of plant-based functional foods or supplements with antioxidant properties.