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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]

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]

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. [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]

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]

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]

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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]

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]

Achillea tenuifolia Lam (Asteraceae) afforded a methanolic extract from which after fractionation in solvents with different polarities two known flavones 3', 5- dihydroxy- 4', 6, 7- trimethoxy flavone (eupatorine, compound 3), 5- hydroxy- 3', 4', 6, 7- tetramethoxyflavone (compound 4), besides stearic acid (compound 1 ), lupeol (compound 2), daucosterol (β- sitosterol 3-O- β- D- glucopyranoside, compound 5), 2, 4- dihydroxy methyl benzoate (compound 6) were isolated for the first time. The structure of isolated compounds was elucidated by means of different spectroscopic methods such as UV, IR, Mass and ¹H- NMR (1D and 2D) and 13C-NMR. For further confirming of structures of isolated compounds, comparison of the spectral data of them with those reported in the litratures have been done. [ABSTRACT FROM AUTHOR]

The methanolic extract of the seeds of Arctium lappa was found to show inhibitory activity against prostate cancer cell lines. Bioactivity-guided fractionation of a 95% ethanol extract from the seeds of A. lappa led to the isolation of seven compounds: β-sitosterol ( 1 ), daucosterol ( 2 ), lappaol C ( 3 ), lappaol A ( 4 ), and arctignan E ( 5 ), lappaol F ( 6 ), and arctiin ( 7 ). Their structures were elucidated by UV, IR, MS, and NMR data, as well as by comparison with those of the literature. Compounds 3 - 7 were studied for their cytotoxicity using a prostate cancer cell line. Compounds 3 , 4 , and 6 showed activity against the LNCaP prostate cancer cell line with IC 50 values of 8, 16, and 40 µg/mL, respectively. [ABSTRACT FROM AUTHOR]

Four compounds of a coumarin, a steroid and two flavonoids were isolated from the herba of Artemisia apiacea by open column chromatography. Their structures were elucidated as artemicapin C, apigenin, daucosterol and cacticin by chemical and spectroscopic analysis. This is the first report of the isolation of these compounds from this plant. [ABSTRACT FROM AUTHOR]