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Daucosterol (DAU) was isolated from the methanol-chloroform crude extract of six Nepeta species (N. aristata , N. baytopii, N. italica, N. nuda albiflora, N. stenantha and N. trachonitica) using sephadex and silica-gel columns via bioactivity-guided isolation. Spectroscopic methods and comparisons with similar data in the literature determined its structure. DAU was evaluated for enzyme inhibitions, kinetics, DNA protection, and molecular interactions. The inhibition activities of AChE, tyrosinase, BChE, and urease were found to be 21.32±1.24, 3.17±0.45, 16.73±0.10 and 12.95±0.21 μM, respectively. The K i values of the inhibition kinetics of the same enzymes were observed as 0.11, 0.05, 0.12, and 0.12 mM, respectively. DAU exhibited effective protection activity against DNA damage induced by H 2 O 2 and ultraviolet radiation in DNA protection tests. DFT analysis showed low hardness and high softness values. The best binding affinity of DAU was achieved by the enzymes AChE and BChE (for both: −9.90 kcal/mol). As a result of the interaction of standards and DAU with enzymes, it was observed that DAU bound with a higher potential than the standards. Molecular dynamics simulations of these enzymes were examined for 100 ns, and the energy results of the simulation were determined by MM/PBSA calculation in the last 10 ns. Additionally, its pharmacokinetic properties were investigated with SwissADMET, and it was noted that it had low toxic effects and gastrointestinal absorption. Thus, in vitro and in silico analysis determined that the DAU molecule could protect against DNA oxidative damage and an active metabolic enzyme inhibitor. [Display omitted] • Daucosterol was isolated from six different Nepeta species by activity-guided isolation • Daucosterol had potent enzyme inhibition and DNA protection activities • Urease inhibition kinetics and molecular interactions of daucosterol were studied for the first time • Daucosterol exhibited favorable binding constants and affinities with BChE and tyrosinase. [ABSTRACT FROM AUTHOR]

Daucosterol, a natural saponin from Eleocharis dulcis peel, exhibited anti-hyperglycemic properties. This study investigated daucosterol's effects on glycemic control, insulin resistance, and gut microbiota in type 2 diabetic mice. The results demonstrated that daucosterol treatment reduced fasting glucose, improved glucose intolerance and pancreatic islet damage. It decreased HOMA-IR and increased ISI, indicating enhanced insulin sensitivity. Daucosterol supplementation enriched gut microbiota diversity, including reducing Firmicutes and Desulfobacterota while increasing Bacteroidia. This involved an increase in Enterococcus, Akkermansia, Alistipes, Clostridium_sensu_stricto_1, and Odoribacter, coupled with decreased Aerococcus, Desulfovibrio, and Blautia, improved gut health. Uncultured_bacterium_g_Clostridium_sensu_stricto_1 and Bifidobacterium_pseudolongum were identified as major biomarkers. PICRUSt analysis revealed daucosterol improved the pathways of glycan biosynthesis and metabolism, lipid metabolism, carbohydrate metabolism, and some organismal systems. Therefore, daucosterol act as a potential anti-hyperglycemic agent, improving insulin resistance and optimizing gut microbiota to alleviate type 2 diabetes.

Osteoporosis is a debilitating condition characterized by reduced bone mass and density, leading to compromised structural integrity of the bones. While conventional treatments, such as bisphosphonates and selective estrogen receptor modulators (SERMs), have been employed to mitigate bone loss, their effectiveness is often compromised by a spectrum of adverse side effects, ranging from gastrointestinal discomfort and musculoskeletal pain to more severe concerns like atypical fractures and hormonal imbalances. Daucosterol (DC), a natural compound derived from various plant sources, has recently garnered considerable attention in the field of pharmacology. In this study, we investigated the anti-osteoporosis potential of DC by characterizing its role in osteoclasts, osteoblasts, and lipopolysaccharide (LPS)-induced osteoporosis. The inhibitory effect of DC on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining, F-actin ring formation by fluorescent staining, and bone resorption by pit formation assay. In addition, the calcification nodule deposition effect of osteoblasts was determined by Alizarin red S staining. The effective mechanisms of both cells were verified by Western blot and reverse transcription polymerase chain reaction (RT-PCR). To confirm the effect of DC in vivo, DC was administered to a model of osteoporosis by intraperitoneal administration of LPS. The anti-osteoporosis effect was then characterized by micro-CT and serum analysis. The results showed that DC effectively inhibited osteoclast differentiation at an early stage, promoted osteoblast activity, and inhibited LPS-induced bone density loss. The results of this study suggest that DC can treat osteoporosis through osteoclast and osteoblast regulation, and therefore may be considered as a new therapeutic alternative for osteoporosis patients in the future. [ABSTRACT FROM AUTHOR]

Daucosterol is a phytosterol glycoside with hepatoprotective properties. The objective of the present study was to confirm the role of daucosterol in liver failure. Exosomes were isolated from primary mouse umbilical cord mesenchymal stem cells (UCMSCs). A liver failure mouse model was generated by injecting lipopolysaccharide/D-galactosamine. Mice were treated with exosomes alone or in combination with daucosterol (5, 10, or 20 mg/kg). Liver tissue damage was examined by hematoxylin-eosin, Masson’s trichrome, and TUNEL staining. The levels of genes, proteins, and inflammatory factors were determined using real-time qPCR, western blotting, and enzyme-linked immunosorbent assay, respectively. Compared with normal mice, we noted severe damage, fibrosis, and apoptosis in the liver tissues of liver failure-induced mice. UCMSC-derived exosomes effectively alleviated hepatic damage in the mouse model. Compared with exosome treatment alone, exosomes combined with daucosterol significantly and dose-dependently reduced pathological changes in model mice. Exosome treatment alone or combined with daucosterol also markedly decreased the liver index and reduced levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in model mice. Exosome treatment alone or combined with daucosterol suppressed mRNA expression levels of IL-6 and signal transducer and activator of transcription (STAT3) and STAT3 protein expression in model mice. Our findings revealed that treatment with daucosterol combined with UCMSC-derived exosomes was superior to exosomes alone for alleviating hepatic damage in mice with liver failure by regulating the IL-6/STAT3 signaling pathway. Accordingly, daucosterol combined with UCMSC-derived exosomes may be a prospective treatment strategy for liver failure.

Alcoholic liver disease (ALD) is caused by chronic excessive alcohol consumption, which leads to inflammation, oxidative stress, lipid accumulation, liver fibrosis/cirrhosis, and even liver cancer. However, there are currently no effective drugs for ALD. Herein, we report that a natural phytosterol Daucosterol (DAU) can effectively protect against liver injury caused by alcohol, which plays anti−inflammatory and antioxidative roles in many chronic inflammatory diseases. Our results demonstrate that DAU ameliorates liver inflammation induced by alcohol through p38/nuclear factor kappa B (NF−κB)/NOD−like receptor protein−3 (NLRP3) inflammasome pathway. Briefly, DAU decreases NF−κB nuclear translocation and inhibits NLRP3 activation by decreasing p38 phosphorylation. At the same time, DAU also protects against hepatic oxidative stress and lipid accumulation. In conclusion, our research provides a new clue about the protective effects of naturally active substances on ALD. [ABSTRACT FROM AUTHOR]

This study investigated the novel application of daucosterol, a natural saponin from eleocharis dulcis peel, in stabilizing emulsion gels with γ-oryzanol. While daucosterol has known health benefits, its ability to stabilize emulsion gels had not yet been explored. This research examined the emulsification properties, microstructure, rheological behavior, stability, and intermolecular interactions of the resulting emulsion gels. Results showed that daucosterol effectively stabilized the emulsion gels, forming structured networks at higher concentrations. FT-IR analysis revealed significant intermolecular hydrogen bonding between daucosterol and γ-oryzanol, and XRD profiles indicated a transition from crystalline to amorphous structures. SEM images displayed denser network formations with increased daucosterol levels. Contact angle measurements demonstrated enhanced hydrophobicity with rising daucosterol concentration, which favored stable water-in-oil emulsions. Rheological assessments confirmed strong thermal stability, robust mechanical properties, and partial thixotropic recovery at higher daucosterol levels. Additionally, daucosterol-stabilized emulsions showed remarkable stability through storage, freeze-thaw cycles, and heat treatments. This stability was attributed to dense, network-like structures that effectively inhibited phase separation and droplet coalescence. Molecular interaction simulations further supported the formation of stable complexes between daucosterol and γ-oryzanol, sustained by hydrogen bonds and van der Waals forces. This study highlights daucosterol's potential as an innovative stabilizer for oil-water emulsion gels. • This study first reveals that daucosterol effectively acts as an emulsifier and stabilizer for W/O emulsions. • Daucosterol promotes the formation of a stable emulsion gels with strong mechanical properties. • The self-assembly of daucosterol and γ-oryzanol provides the mechanism for forming stable emulsion gels. [ABSTRACT FROM AUTHOR]

Daucosterol is a saponin present in various natural sources, including medicinal plant families. This secondary metabolite is produced at different contents depending on species, extraction techniques, and plant parts used. Currently, daucosterol has been tested and explored for its various biological activities. The results reveal potential pharmacological properties such as antioxidant, antidiabetic, hypolipidemic, anti-inflammatory, immunomodulatory, neuroprotective, and anticancer. Indeed, daucosterol possesses important anticancer effects in many signaling pathways, such as an increase in pro-apoptotic proteins Bax and Bcl2, a decrease in the Bcl-2/Bax ratio, upregulation of the phosphatase and tensin homolog (PTEN) gene, inhibition of the PI3K/Akt pathway, and distortion of cell-cycle progression and tumor cell evolution. Its neuroprotective effect is via decreased caspase-3 activation in neurons and during simulated reperfusion (OGD/R), increased IGF1 protein expression (decreasing the downregulation of p-AKT3 and p-GSK-3b4), and activation of the AKT5 signaling pathway. At the same time, daucosterol inhibits key glucose metabolism enzymes to keep blood sugar levels within normal ranges. Therefore, this review describes the principal research on the pharmacological activities of daucosterol and the mechanisms of action underlying some of these effects. Moreover, further investigation of pharmacodynamics, pharmacokinetics, and toxicology are suggested. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) has been increasing in the population in recent years and is mainly characterized by preserved left ventricle ejection fraction (LVEF), diastolic dysfunction and systemic inflammation. Daucosterol (DAU), a glycoside of β -sitosterol, has good anti-inflammatory and antioxidative properties; however, its effects and mechanisms in HFpEF have not been investigated. To detect whether DAU could alleviate HFpEF, C57BL/6J male mice were fed with N-nitro-l-arginine methyl ester (L-NAME) in drinking water and high fat diet (HFD) and treated with DAU by gavage (i.g.) for 10 weeks. The results showed that DAU treatment significantly alleviated HFpEF in mice. Mechanistically, by controlling PPAR α and preventing NF- κ B phosphorylation, DAU reduced oxidative stress and the inflammatory response. In conclusion, our study provides a new clue for natural product DAU in alleviating HFpEF., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Shuang Zhang reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China. Shuang Zhang reports financial support was provided by 10.13039/501100003995Anhui Provincial Natural Science Foundation. Shuang Zhang reports financial support was provided by Fundamental Research Funds for the Central Universities (10.13039/501100013773Hefei University of Technology). Yajun DUAN has patent #CN116036107B licensed to The First Affiliated Hospital of USTC (Anhui Provincial Hospital). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

This study evaluates compounds isolated from Boehmeria nivea , identifies the chemical composition, and examines its toxicity to mosquito larvae. Liquid chromatography coupled to a mass spectrometer, as well as 1H and 13C nuclear magnetic resonance spectroscopy, were used to determine the chemical composition. The 3rd instar and early 4th instar larvae of Aedes aegypti, Aedes albopictus, Culex quinquefasciatus and Culex fuscocephala. were used as test subjects for the activity. There are 4 active ingredients extracted from B. nivea including 4-hydroxybenzoic acid, pomolic acid, ursolic acid, and daucosterol that have shown low toxicity to Moina macrocopa (48 h LC 50 of 16.34–22.32 µg/mL), against Aedes spp. larvae with 24 h LC 50 values between 28.10 and 55.04 µg/mL; against the larvae of Culex spp. with values of 24 h LC 50 between 8.0 and 17.66 µg/mL, and have shown synergistic or additive effects at binary combinations. This research opens up potential possibilities for developing environmentally friendly natural compounds that kill mosquito larvae and fight dangerous diseases caused by mosquitoes. [Display omitted] • Main larvicidal compounds against four mosquito species were isolated from Boehmeria nivea root. • Joint actions of larvicidal compounds were evaluated. • Larvicidal compounds were less toxic to plankton (Moina macrocopa). • Fraction containing larvicidal compounds was excellent against Aedes mosquitoes. [ABSTRACT FROM AUTHOR]

Daucosterol is a saponin present in various natural sources, including medicinal plant families. This secondary metabolite is produced at different contents depending on species, extraction techniques, and plant parts used. Currently, daucosterol has been tested and explored for its various biological activities. The results reveal potential pharmacological properties such as antioxidant, antidiabetic, hypolipidemic, anti-inflammatory, immunomodulatory, neuroprotective, and anticancer. Indeed, daucosterol possesses important anticancer effects in many signaling pathways, such as an increase in pro-apoptotic proteins Bax and Bcl2, a decrease in the Bcl-2/Bax ratio, upregulation of the phosphatase and tensin homolog (PTEN) gene, inhibition of the PI3K/Akt pathway, and distortion of cell-cycle progression and tumor cell evolution. Its neuroprotective effect is via decreased caspase-3 activation in neurons and during simulated reperfusion (OGD/R), increased IGF1 protein expression (decreasing the downregulation of p-AKT3 and p-GSK-3b4), and activation of the AKT5 signaling pathway. At the same time, daucosterol inhibits key glucose metabolism enzymes to keep blood sugar levels within normal ranges. Therefore, this review describes the principal research on the pharmacological activities of daucosterol and the mechanisms of action underlying some of these effects. Moreover, further investigation of pharmacodynamics, pharmacokinetics, and toxicology are suggested.

In the present study, Pimpinella affinis was collected from Dodangeh region in Sari (Mazandaran province in Iran). The ethyl acetate extract of leaves of the plant was fractionated byn column chromatography method. THEN,two phytosterols as β-sitosterol (1) and daucosterol (2) were identified using mass (EI-MS) and NMR (1H- NMR and 13C- NMR) spectrometry techniques. These natural sterols have specific biological properties such as anti-HIV, anti-cancer and anti-cholesterol. This study introduced P. affinis as a good source of useful phytosterols. Native people widely use this plant as a vegetable and so the results of this study can be useful for nutrition scientists.

This study aimed to evaluate the in vivo anticancer effects of daucosterol which was earlier reported to possess in vitro anticancer effects. Breast tumor was induced in 30 rats using the environmental carcinogen 7,12‐dimethylbenz(a)anthracene (DMBA) while 6 control rats received olive oil (NOR). Animals with palpable tumors were randomized into five groups (n = 6) each as follows: negative control group treated with the vehicle (DMBA); positive control group treated with 5 mg/kg BW doxorubicin (DOXO + DMBA); three groups treated with daucosterol at doses of 2.5, 5, and 10 mg/kg BW (DAU + DMBA). Treatment lasted 28 days afterward, tumor (mass, volume, cancer antigen [CA] 15‐3 level and histoarchitecture), hematological and toxicological parameters were examined. The tumor volume gradually increased in the DMBA group during the 28 days, with a tumor volume gain of ∼390 cm3. Daucosterol at all doses reduced tumor volume (∼133.7 cm3 at 10 mg/kg) as well as protein, malondialdehyde (MDA), and CA 15‐3 levels compared to DMBA rats. Tumor sections in daucosterol‐treated rats showed a lower proliferation of mammary ducts with mild (5 and 10 mg/kg) to moderate (2.5 mg/kg) inflammatory responses. Moreover, it exhibited an antioxidant effect, evidenced by a significant and dose‐dependent decreased in MDA levels, as well as an increase in catalase activity compared to the DMBA group. Daucosterol showed for the first time in vivo antitumor effects that corroborate its previous in vitro effects. [ABSTRACT FROM AUTHOR]

Purpose: To determine the involvement of NLRP3 signaling pathway in the preventive role of daucosterol in acute myocardial infarction (AMI). Methods: H9C2 cells were pretreated with daucosterol before hypoxia/reoxygenation (HR) injury. Myocardial ischemia reperfusion (IR) was established in male SD rats, followed by reperfusion. Myocardial infarct size was measured. The serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were determined using commercial kits. NLRP3 inflammasome activation was assessed by western blotting. Results: Myocardial infarct size was smaller after IR injury in rats pretreated with daucosterol (10 and 50 mg/kg) than that pretreated with daucosterol (0 and 1 mg/kg). The increase in LDH, CK, and MDA levels after IR injury was reduced following daucosterol pretreatment. Reactive oxygen species (ROS) production increased, whereas T-SOD activity decreased after IR injury. These changes were prevented by pretreatment of daucosterol (10 and 50 mg/kg). Protein expression of NLRP3 inflammasome increased after IR injury in H9C2 cells while pretreatment with daucosterol inhibited the upregulation of NLRP3 inflammasome. Conclusion: The cardioprotective effect of daucosterol pretreatment appears to be mediated via the inactivation of ROS-related NLRP3 inflammasome, suggesting that daucosteol might be a potential therapeutic drug for AMI. [ABSTRACT FROM AUTHOR]

The new flavone glycosides tanoside I and II in addition to three known flavonoids and daucosterol were isolated from the Georgian endemic species Astragalus tanae Sosn. Their structures were elucidated as chrysoeriol-7-O-β-D-glucopyranosyl-4′ -O-α-L-rhamnopyranoside, chrysoeriol-4′ -O-α-Lrhamnopyranoside, kaempferol-3-O-β-D-glucopyranosyl(2→1)-O-α-L-rhamnopyranoside (kaempferol-3-O-β-D-neohesperidoside), tamarixin, apigenin, and β-sitosterol-3-O-β-D-glucopyranoside (daucosterol). [ABSTRACT FROM AUTHOR]

[Display omitted] • Daucosterol from Eleocharis dulcis peel has potential anti-hyperglycemic effects in type 2 diabetic mice. • Daucosterol treatment improves glucose metabolism and pancreatic islet health. • Daucosterol supplementation enhances gut microbiota richness and diversity. • Key biomarkers, including uncultured_bacterium_g_Clostridium_sensu_stricto_1 and Bifidobacterium_pseudolongum, were identified. Daucosterol, a natural saponin from Eleocharis dulcis peel, exhibited anti-hyperglycemic properties. This study investigated daucosterol's effects on glycemic control, insulin resistance, and gut microbiota in type 2 diabetic mice. The results demonstrated that daucosterol treatment reduced fasting glucose, improved glucose intolerance and pancreatic islet damage. It decreased HOMA-IR and increased ISI, indicating enhanced insulin sensitivity. Daucosterol supplementation enriched gut microbiota diversity, including reducing Firmicutes and Desulfobacterota while increasing Bacteroidia. This involved an increase in Enterococcus, Akkermansia, Alistipes, Clostridium_sensu_stricto_1, and Odoribacter, coupled with decreased Aerococcus, Desulfovibrio, and Blautia, improved gut health. Uncultured_bacterium_g_Clostridium_sensu_stricto_1 and Bifidobacterium_pseudolongum were identified as major biomarkers. PICRUSt analysis revealed daucosterol improved the pathways of glycan biosynthesis and metabolism, lipid metabolism, carbohydrate metabolism, and some organismal systems. Therefore, daucosterol act as a potential anti-hyperglycemic agent, improving insulin resistance and optimizing gut microbiota to alleviate type 2 diabetes. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance Lagotis Brachystachya: Maxim is a traditional ethnic medicine commonly used in Tibet. In Tibetan medicine theory, Lagotis brachystachya is mainly used for the treatment of inflammatory related diseases. However, the active components and mechanism of the anti-inflammatory activity of Lagotis brachystachya are not clear., Aim of the Study: The putative anti-inflammatory active compounds from Lagotis brachystachya Maxim and its anti-inflammation related mechanism involving in the TLR4/MyD88/NF-κB and NLRP3 signaling pathways were investigated., Materials and Methods: In this study, we investigated the anti-inflammatory activity and mechanism of 32 compounds extracted from Lagotis brachystachya in HepG2 and THP-1 cells using the alcohol-induced HepG2 cell injury model and the monosodium urate (MSU) combined with lipopolysaccharide (LPS)-induced THP-1 cell inflammation model., Results: The results found that six compounds, including Echinacoside, Quercetin, Homoplantaginin, Tricin-7-O-glucoside, Apigenin and Luteolin-7-O-beta-d-glucopyranoside, were shown to exhibit significant anti-inflammatory effects in both cell models. Furthermore, these compounds were shown to inhibit the TLR4/MyD88/NF-κB and NLRP3 signaling pathways and reduce the release of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in both cell models., Conclusion: These findings suggest that Echinacoside, Quercetin, Homoplantaginin, Tricin-7-O-glucoside, Apigenin and Luteolin-7-O-beta-d-glucopyranoside from Lagotis brachystachya have promising potential as natural anti-inflammatory agents for the treatment of inflammatory-related diseases. The discovery of bioactive compounds from this plant opens up possibilities for the development of novel treatments for inflammatory-related diseases, potentially providing alternative or adjunctive options to conventional therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper titled “Anti-inflammatory activity and mechanism of six active compounds from Lagotis brachystachya Maxim in HepG2 and THP-1 cells via TLR4/MyD88/NF-κB and NLRP3 pathways”., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Daucosterol (DS) is a plant phytosterol which is shown to induce oxidative stress mediated apoptosis in various cancer cell lines. However, the molecular mechanism underlying its cellular action has not been documented against Non- Small Cell Lung Cancer (NSCLC). Therefore, we attempted to decipher the mechanisms responsible for DS-induced anti-proliferation on human NSCLC cells. The present study showed, DS strongly inhibits the growth of A549 cells after 72 h time point with an IC 50 value of ∼20.9 μM. Further DS elicits increased reactive oxygen species level and promote intrinsic apoptotic cell death on A549 cells as evidenced by increased expression of caspase-3, caspase-9, Bax, PARP inactivation, cytochrome-c release, and diminished expression of bcl-2 protein. DS failed to display its apoptotic actions upon pretreatment with the reactive oxygen species inhibitor NAC (N-acetyl cysteine). Indeed, apoptotic signal which was enhanced through p53/p21 activation and knockdown of p53 expression also moderately affected the DS induced apoptosis. In addition, DS preferentially inhibited the cell growth of p53 wild-type NSCLC cell lines than the mutant p53 models. Further, we show that inhibition of Thioredoxin (TrxR) redox system is principally associated with DS induced oxidative stress mediated apoptotic cell death on A549 cells. Moreover, we also demonstrated that DS stably interacted with serine residues in TrxR active sites. The obtained results confirmed that the anti-proliferative mechanism and increased reactive oxygen species level of DS was associated with down-regulation of TrxR1 pathway which triggers the p53 mediated intrinsic apoptotic mode of cell death in NSCLC cells. Image 1 [ABSTRACT FROM AUTHOR]

The effects of daucosterol have been identified in cancer therapy and neuronal diseases. However, the regulatory function of daucosterol in DSS-induced colitis has not yet been investigated. In this study, we evaluated the immunological and therapeutic effects of daucosterol in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Unlike vehicle mice, mice pre- or post-treated with daucosterol showed inhibition of body weight loss and the decrease in the disease activity index (DAI). In addition, daucosterol treatment rescued the DSS-induced decrease in colon length and disruption of the epithelial lining. Furthermore, it reduced DSS-induced production of reactive oxygen species (ROS), infiltration of macrophages, and expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Mice with colitis showed a decreased population of Foxp3+ cells, which was upregulated by daucosterol treatment. Furthermore, daucosterol increased natural killer (NK) cell activity and inhibited excessive IgA levels in mice with DSS-induced colitis. Collectively, our findings demonstrated that daucosterol significantly alleviated DSS-induced colitis, indicating the possibility of daucosterol as a therapeutic option for colitis. • Daucosterol prevented clinical symptoms of DSS-induced colitis. • Daucosterol alleviated inflammation in DSS-induced colitis. • Daucosterol recovered the number of Treg cells reduced by DSS-induced colitis. • Daucosterol is good candidate therapeutic for colonic diseases including DSS-induced colitis. [ABSTRACT FROM AUTHOR]

Plant sterols (phytosterols) have been widely accepted as a natural anti-cancer agent in multiple malignant tumors. This study was designed to investigate the functions of daucosterol in prostate cancer progression and its possible molecular mechanisms. Our results showed that daucosterol inhibited cell proliferation and induced cell cycle arrest. Moreover, daucosterol treatment obviously promoted apoptosis and autophagy. An autophagy inhibitor, 3-methyladenine (3-MA) was proved to counteract daucosterol-triggered autophagy, growth inhibition, and apoptosis, indicating that daucosterol-induced apoptotic response was dependent on autophagy. Additionally, treatment with daucosterol resulted in increased phosphorylation of c-Jun N-terminal kinase (JNK). Furthermore, pre-treatment with a JNKspecific inhibitor SP600125 abated daucosterol-elicited autophagy and apoptotic cell death. Taken together, our findings demonstrated that daucosterol blocked prostate cancer growth at least partly through inducing autophagic-dependent apoptosis via activating JNK signaling, providing a promising candidate for the development of antitumor drugs in prostate cancer treatment. [ABSTRACT FROM AUTHOR]

• The 15 DPA groups showed the highest metabolic variation compared to other developmental stages. • Primary and secondary metabolites are related to amino acids and derivatives, alkaloids and glycoalkaloids, fatty acids, organic acids, sugars, sugar alcohol, and terpenoids. • Pigments, alkaloids, terpenoids, flavonoids, and glycoalkaloids was noted as secondary metabolites. • Biostimulatory role of the He-Ne laser was revealed in the present study with significant alterations in the abundance of bioactive molecules and their associated pathways. • Potential interactions between plants and laser rays and the possible use of the He-Ne laser to modulate and enhance fruit metabolites. Seed germination, seedling growth and healthy, virtue-based, uniform crop establishment are essential for considerable agricultural productivity. Physical and chemical techniques are widely utilized to promote and speed up seed germination. Due to their low cost, lack of side effects, environmental friendliness, non-destructive and low-power irradiation techniques such as laser, magnetic energy, and ultrasound are utilized successfully in various crops. The most well-known and well-studied laser in the agriculture sector is the Helium-Neon laser. The current study aimed to examine potential interactions between plants and laser rays and the possible use of the He-Ne laser to alter and enhance fruit metabolites. Fruits from field-grown brinjal (Solanum melongena L.) plants were collected at various developmental stages, such as 15, 30, 45, and 60 days post-anthesis (DPA), from the un-irradiated control and laser-irradiated plants for fruit metabolite profiling. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) indicated that the 15 DPA groups showed the highest variation compared to the other developmental stages. The observed metabolites were primarily divided into primary and secondary metabolites and are related to amino acids and derivatives, alkaloids and glycoalkaloids, fatty acids, organic acids, sugars, sugar alcohol, and terpenoids. Furthermore, the secondary metabolites were identified and classified into pigments, alkaloids, terpenoids, flavonoids, and glycoalkaloids. In the fruit tissues of the laser-irradiated groups, it was observed that the shikimate-derived phenolic pathway was not altered. On the other hand, the mevalonate route (MVP) and methylerythritol 4-phosphate (MEP) pathways were changed in the fruit tissues from the laser irradiation groups, according to the characterization of sterols, terpenoids, and alkaloids. Based on our previous reports and the current analysis, the biostimulatory role of the He-Ne laser was revealed with significant alterations in the abundance of bioactive molecules and their associated pathways in the developmental stages of brinjal fruits. [Display omitted] [ABSTRACT FROM AUTHOR]

T-2 toxin is a common environmental pollutant and contaminant in food and animal feed that represents a great challenge to human and animal' health throughout the world. Using natural compounds to prevent the detrimental effects of T-2 toxin represents an attractive strategy. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a critical regulator in various cellular processes. Recently, PGC-1α activation has been reported to confer protection against neurological injuries. We aimed to identify a potent PGC-1α activator from plants as a chemopreventive compound and to demonstrate the efficacy of the compound in attenuating T-2 toxin-induced blood-brain barrier (BBB) toxicity. We identified daucosterol, which binds directly to the 71–74 (−1100 to −1000 bp) position of the second promoter of human PGC-1α by hydrogen bonding. An in vitro and in vivo T-2 toxin induced BBB injury model revealed that this compound can protect against this injury by increasing transepithelial/transendothelial electrical resistance, reducing sodium fluorescein (NaF) infiltration and increasing the expression of tight junction–related proteins (zonula occludens-1 (ZO-1), occludin (OCLN), claudin-5 (CLDN5)) expression. In conclusion, we identified daucosterol as representing a novel of PGC-1α activators and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated the feasibility of using natural compounds targeting PGC-1α as a therapeutic approach to protect humans from environmental insults that may occur daily such as lipopolysaccharide. [Display omitted] • Daucosterol directly activates the transcription of PGC-1α. • Daucosterol binds to −1100 to −1000 bp position of PGC-1α promoter by hydrogen bond. • PGC-1 increases BBB tightness in an injured state induced by T-2 toxin and LPS. [ABSTRACT FROM AUTHOR]

α-Amylase inhibitors play a critical role in the control of diabetes and many of medicinal plants have been found to act as α-amylase inhibitors. Swertia genus, belonging to the family Gentianaceae, comprises different species most of which have been used in traditional medicine of several cultures as antidiabetic, anti-pyretic, analgesic, liver and gastrointestinal tonic. Swertia longifolia Boiss. is the only species of Swertia growing in Iran. In the present investigation, phytochemical study of S. longifolia was performed and α-amylase inhibitory effects of the plant fractions and purified compounds were determined. Aerial parts of the plant were extracted with hexane, chloroform, methanol and water, respectively. The components of the hexane and chloroform fractions were isolated by different chromatographic methods and their structures were determined by 1 H NMR and 13 C NMR data. α-Amylase inhibitory activity was determined by a colorimetric assay using 3,5-dinitro salysilic acid. During phytochemical examination, α-amyrin, β-amyrin and β-sitosterol were purified from the hexane fraction,while ursolic acid, daucosterol and swertiamarin were isolated from chloroform fraction. The results of the biochemical assay revealed α-amylase inhibitory activity of hexane, chloroform, methanol and water fractions, of which the chloroform and methanol fractions were more potent (IC 50 16.8 and 18.1 mg/ml, respectively). Among examined compounds, daucosterol was found to be the most potent α-amylase inhibitor (57.5% in concentration 10 mg/ml). With regard to α-amylase inhibitory effects of the plant extracts, purified constituents, and antidiabetic application of the species of Swertia genus in traditional medicine of different countries, S. longifolia seems more appropriate species for further mechanistic antidiabetic evaluations.

Daucosterol is a phytosterol glycoside with hepatoprotective properties. The objective of the present study was to confirm the role of daucosterol in liver failure. Exosomes were isolated from primary mouse umbilical cord mesenchymal stem cells (UCMSCs). A liver failure mouse model was generated by injecting lipopolysaccharide/D-galactosamine. Mice were treated with exosomes alone or in combination with daucosterol (5, 10, or 20 mg/kg). Liver tissue damage was examined by hematoxylin-eosin, Masson's trichrome, and TUNEL staining. The levels of genes, proteins, and inflammatory factors were determined using real-time qPCR, western blotting, and enzyme-linked immunosorbent assay, respectively. Compared with normal mice, we noted severe damage, fibrosis, and apoptosis in the liver tissues of liver failure-induced mice. UCMSC-derived exosomes effectively alleviated hepatic damage in the mouse model. Compared with exosome treatment alone, exosomes combined with daucosterol significantly and dose-dependently reduced pathological changes in model mice. Exosome treatment alone or combined with daucosterol also markedly decreased the liver index and reduced levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in model mice. Exosome treatment alone or combined with daucosterol suppressed mRNA expression levels of IL-6 and signal transducer and activator of transcription ( STAT3 ) and STAT3 protein expression in model mice. Our findings revealed that treatment with daucosterol combined with UCMSC-derived exosomes was superior to exosomes alone for alleviating hepatic damage in mice with liver failure by regulating the IL-6/STAT3 signaling pathway. Accordingly, daucosterol combined with UCMSC-derived exosomes may be a prospective treatment strategy for liver failure.

Rheum turkestanicum has been used in Iranian folk medicine to treat diabetes mellitus. The present study was designed to isolate bioactive phytochemicals from the roots of R. turkestanicum using “bioassay-guided fractionation and purification” method. The α-amylase, α-glucosidase and DPPH inhibitory activities of various extracts ( n -hexane, dichloromethane, ethyl acetate, methanol and water) were evaluated. Also, the total phenolic contents of the extracts were evaluated and compared to their activities. Among all the extracts, ethyl acetate extract, as the most effective agent, was selected for isolation and identification of its active phytochemicals. The ethyl acetate extract was fractionated by column chromatography and all the fractions were assessed by α-amylase, α-glucosidase, DPPH, and total phenolic assays. As a result, chrysophanol, physcion, emodin, daucosterol and rhododendrin (betuloside) were isolated and identified from the most bioactive fractions by 1 H-, 13 C-, 2D-NMR, EI-MS and single-crystal X-ray diffraction. Also, the highest inhibitory activities were exerted by daucosterol with IC 50 values of 46.4 and 17.0 μM (similar to that of acarbose with IC 50 values of 47.4 and 16.4 μM) against α-amylase and α-glucosidase, respectively. Moreover, emodin and rhododendrin showed significant inhibitory activities against α-glucosidase with IC 50 values of 42.5 μM and 77.9 μM, respectively. Also, rhododendrin exhibited high antioxidant activity against DPPH radicals (IC 50  = 80.4 μM), more potent than that of BHT (IC 50  = 95.7 μM), as a commercial antioxidant. The overall results suggested that R. turkestanicum roots can be considered as a source of bioactive phytochemicals for developing novel lead compounds in drug design. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of daucosterol on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells, and then to discuss its mechanism. Methods HepG2 cells were cultured in vitro，and then were divided into the daucosterol group and control group. In the daucosterol group， HepG2 cells were inoculated on 96-well plates by 5 X 105/mL, and different concentrations (25 μg/mL, 50 μg/mL, 100 μg/mL, 150 μg/mL and 200 μg/mL) of daucosterol were added, and we did not add any drugs to the control group. At 48 h after culture, CCK-8 was used to meas­ure cell proliferation inhibition. HepG2 cells were inoculated on 6-well plates by 5 X 105/mL, and 50 and 100 μg/mL daucosterol were added to the daucosterol group, and the control group was not added. At 48 h, flow cytometer was used to detected the apoptosis rate of HepG2 cells. Western blotting was performed to analyze the expression of apoptosis relative protein (Bax, Bcl-2) , and Wnt/p-catenin pathway relative protein (WNT3A, β-catenin) in the HepG2 cells. Results The inhibition rate of cell proliferation in each daucosterol subgroup was higher than that in the control group，and the inhibition rate of cell proliferation increased along with the concentrations (25，50，100，150 and 200 μg/mL) of daucosterol ( all P <0.05). The apoptosis rates of HepG2 cells in the 50 and 100 μg/mL daucosterol subgroups was higher than that of the control group，and the apoptosis rate of the 100 μg/mL daucosterol subgroup were higher than that of the 50 μg/mL dau­costerol subgroup (all P <0.05). The relative expression of Bax protein in the control group and the 50 and 100 μg/mL daucosterol subgroups increased successively， and the relative expression of Bcl-2，WNT3A， and β-catenin protein de­creased (all P <0.05). Conclusion Daucosterol inhibits the proliferation and promotes the apoptosis of HepG2 cells by inhibiting the Wnt/ p-catenin signaling pathway and regulating the expression of apoptosis-related proteins. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The purpose of this study was to determine the effects of daucosterol on HCC by investigating Wnt/β-catenin signaling. In this study, HepG2 and SMMC-7721 cells were treated with varying concentrations of daucosterol, and the corresponding inhibitory effects on HCC cells were examined via CCK-8 assays. Cell migration and invasion abilities were detected via transwell assays.β-Catenin and phospho (p)-β-catenin levels were analyzed via western blotting. Our results showed that daucosterol reduced the proliferation, migration, and invasion capacities of HCC cells in a concentration-dependent manner. In addition, daucosterol reduced the levels of β-catenin and p-β-catenin in HepG2 and SMMC-7721 cells. Furthermore, the Wnt signaling pathway inhibitor SB-216763 was used to treat HepG2 and SMMC-7721 cells with daucosterol. Our results showed that co-treatment with daucosterol and SB-216763 abolished the effects of daucosterol on cell inhibition ratios, cell migration, and cell invasion. These findings indicated that daucosterol inhibited cell migration and invasion in HCC cells via the Wnt/β-catenin signaling pathway. Therefore, our study highlights the use of daucosterol as a promising therapeutic strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

The aim of the present investigation was to examine and demonstrate in detail the anti-cancer and apoptotic effects of daucosterol in human colon cancer cell line HCT-116. The effects of this compound on cell migration, cell invasion, cell cycle analysis and caspase signalling pathway were also studied. Cell viability was evaluated by MTT assay using different doses of the drug. In vitro wound healing assay was used to study cell migration. Flow cytometry was involved to examine cell apoptosis as well as cell cycle phase distribution. Daucosterol induced significant, dose-dependent as well as time-dependent cytotoxic effects with IC50 values of 26.6 and 47.3 µM at 24 and 48 hours time intervals respectively. The percent of cells that migrated decreased from 99% in case of untreated control to 84.2, 45.2, 39.5 and 14.4% in groups treated with 0, 5, 50, 75 and 100 µM of daucosterol respectively. Percentage of apoptotic cells increased from 2.5% in untreated control cells to 23.6, 46.9 and 74.2% in cells treated with 5, 50 and 100 µM dose of daucosterol respectively. Daucosterol at different doses induced cell cycle arrest at sub-G1 phase of the cell cycle. Video Clip of Methodology: Cell Migration Assay: 1 min Full Screen Alternate

Background: Salvia limbata is an aromatic herbaceous plant and grows widely in Iran Turkey and Afghanistan. In the previous study, six flavones together with rosmarinic acid were isolated from the ethyl acetate and methanol extracts of S. limbata. In this report, we focused on the isolation and identification of the glycosylated sterols and the main accumulated amino acid of the species S. limbata, which has not been previously reported. Methods: Aerial parts of the plant were dried, cut into small pieces and extracted with ethyl acetate and methanol by percolation at room temperature. The separation process was carried out using several chromatographic methods. Structural elucidation was based on NMR data, in comparison with those reported in the literature. Results: The isolated compounds (Figure 1) from the ethyl acetate and MeOH extracts of S. limbata were identified as beta-sitosterol (1), stigmasterol (2), daucosterol (3), stigmasterol 3- O-glucoside (4) and tryptophan (5) by comparison of their NMR spectral data with those reported in the literature Conclusions: S. limbata can accumulate the tryptophan as a major free amino acid together with sterols and their glucosides. Therefore, consumption of S. limbata (as a herbal tea or other preparations), which contains the essential amino acid tryptophan, might be useful for dietary deficiency of tryptophan.

Background: Some studies have shown that daucosterol has potential anti-tumor activity, but its therapeutic effect on multiple myeloma (MM) has not been reported. This study aimed to evaluate the therapeutic effect daucosterol against MM and explore its possible mechanism through network pharmacology., Methods: We collected daucosterol and approved drugs for MM, and their potential target profiles were obtained. We used 2 major methods to collect the gene sets related to the physiological process of MM. Based on the protein-protein interaction (PPI) network in the STRING database, the correlation between the therapeutic targets of daucosterol and MM-related genes was calculated by using the random walk with restart (RWR) algorithm to systematically evaluate the therapeutic potential of daucosterol for MM. On this basis, through intersection analysis, the potential targets of daucosterol in treating MM were identified, and the signaling pathways were mined. Furthermore, the key targets were identified. Finally, the regulatory relationship between the predicted daucosterol and potential targets was verified by molecular docking method, and the interaction mode between daucosterol and key targets was analyzed., Results: A total of 13 approved drugs reported to treat MM were retrieved from the DrugBank database. A total of 35 potential targets of daucosterol were obtained, including 8 known targets and 27 newly predicted targets. In the PPI network, the target of daucosterol was significantly correlated with MM-related genes, indicating that it has therapeutic potential for MM. A total of 18 therapeutic targets for MM were obtained, which were significantly enriched in the FoxO signaling pathway, prostate cancer, the PI3K-Akt signaling pathway, insulin resistance, the AMPK signaling pathway, and pathways related to the regulation of TP53 . The core targets were HSP90AA1 , MDM2 , GSK3B , AKT3 , PRKAA1 , and PRKAB1 . Molecular docking suggested that daucosterol had potential direct regulatory effects on 13 of the 18 predicted targets., Conclusions: This study highlights the use of daucosterol as a promising therapeutic drug for MM treatment. These data provide new insights into the potential mechanism of daucosterol in the treatment of MM, which may provide references for subsequent research and even the clinical treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-456/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Several Salvia species have been used to enhance memory in European traditional medicine. Accordingly, we aimed to evaluate the acetone extract of the roots of Salvia syriaca for anti-Alzheimer constituents. Structures of purified compounds were determined as ursolic acid, corosolic acid, β -sitosterol, urs-12-en-2 α ,3 β -diol and daucosterol (1–5). β -sitosterol and daucosterol exhibited high acetylcholinesterase inhibitory activities (24.1 and 34.3 μg/mL, respectively). The experimental results were also confirmed by docking analysis. [ABSTRACT FROM AUTHOR]

Aims We investigated the neuroprotective effects and action mechanism of three major compounds [daucosterol (Dau), pectolinarin (Pec), and astragalin (Ast)] isolated from edible plants against H 2 O 2 -induced cell death of human brain neuroblastoma SK-N-SH cells. Main methods Cytotoxicity was determined by MTT and lactate dehydrogenase (LDH) assays. Apoptotic cell death was monitored by annexin V-FITC/PI double staining and by TUNEL assay. The formation of reactive oxygen species (ROS), expression of antioxidant enzymes and phosphorylation of mitogen-activated protein kinase (MAPK) were determined by 2,7-dichlorofluorescein diacetate (DCF-DA) assay, RT-PCR, and western blotting, respectively. Key findings The ethyl acetate fractions from Cirsium setidens (CSEA) and Aster scaber (ASEA) showed neuroprotective effects in SK-N-SH cells. The phytochemicals were isolated from CSEA and ASEA and identified by spectral analyses, as β-sitosterol, Dau, Pec, Ast, or isoquercitrin. Pretreatment with Dau, Pec, or Ast showed protective effects against H 2 O 2 -induced cell death and inhibited ROS generation by oxidative stress. HO-1 mRNA and protein levels were increased by the presence of H 2 O 2 and were further elevated by pretreatment with Dau and Ast. Dau pretreatment resulted in further increases of H 2 O 2 -induced enhancement in levels of CAT and SOD2. Pretreatment with Dau, Pec, and Ast inhibited phosphorylation of MAPK, such as extracellular protein regulated protein kinase, p38, and c-Jun N-terminal kinase by H 2 O 2 . Significance Dau exerts its neuroprotective effects by down regulation of MAPK pathways and upregulation of the HO-1, CAT and SOD2 antioxidant genes and is associated with reduced oxidative stress in SK-N-SH cells. [ABSTRACT FROM AUTHOR]

α-Amylase inhibitors play a critical role in the control of diabetes and many of medicinal plants have been found to act as α-amylase inhibitors. Swertia genus, belonging to the family Gentianaceae, comprises different species most of which have been used in traditional medicine of several cultures as antidiabetic, anti-pyretic, analgesic, liver and gastrointestinal tonic. Swertia longifolia Boiss. is the only species of Swertia growing in Iran. In the present investigation, phytochemical study of S. longifolia was performed and α-amylase inhibitory effects of the plant fractions and purified compounds were determined. Aerial parts of the plant were extracted with hexane, chloroform, methanol and water, respectively. The components of the hexane and chloroform fractions were isolated by different chromatographic methods and their structures were determined by ¹H NMR and 13C NMR data. α-Amylase inhibitory activity was determined by a colorimetric assay using 3,5-dinitro salysilic acid. During phytochemical examination, α-amyrin, β-amyrin and β-sitosterol were purified from the hexane fraction, while ursolic acid, daucosterol and swertiamarin were isolated from chloroform fraction. The results of the biochemical assay revealed α-amylase inhibitory activity of hexane, chloroform, methanol and water fractions, of which the chloroform and methanol fractions were more potent (IC50 16.8 and 18.1 mg/ml, respectively). Among examined compounds, daucosterol was found to be the most potent α-amylase inhibitor (57.5% in concentration 10 mg/ml). With regard to α-amylase inhibitory effects of the plant extracts, purified constituents, and antidiabetic application of the species of Swertia genus in traditional medicine of different countries, S. longifolia seems more appropriate species for further mechanistic antidiabetic evaluations. [ABSTRACT FROM AUTHOR]