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Infectious Agents and Cancer Apr 2023Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) does not respond well to current treatment options like sorafenib, and there is an urgent need for...
BACKGROUND
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) does not respond well to current treatment options like sorafenib, and there is an urgent need for developing therapeutical strategies for HBV + HCC. Brassicasterol has previously shown anti-cancer and anti-viral activities, however, its value against HBV + HCC remains to be explored.
METHODS
The inhibitory effect of brassicasterol and sorafenib was evaluated on HBV + HCC cell lines and xenograft mouse model. The cytotoxicity of brassicasterol on normal liver cells were measured by LDH assay. AKT agonist was used to identify the targeted signaling pathway by brassicasterol.
RESULTS
Brassicasterol induced HBV + HCC cell death in a both dose-dependent and time-dependent manner, and such inhibition was more potent than sorafenib. Brassicasterol did not show apparent cytotoxicity to normal liver cells. Xenograft mouse model further confirmed the inhibitory effect of brassicasterol on the growth of HBV + HCC. Furthermore, signaling pathway analysis showed that brassicasterol-treated HBV + HCC cells had decreased level of phosphor-AKT expression while the addition of AKT agonist could counteract the inhibitory effect of brassicasterol on HCC, indicating that brassicasterol suppressed AKT pathway to exhibit anti-cancer activity in HBV + HCC cells. In addition, brassicasterol showed similar levels of inhibition on HBV- and HBV + HCC cells.
CONCLUSION
Brassicasterol possesses anti-cancer activity against HCC through the downregulation of AKT pathway and such activity is independent of HBV infection.
PubMed: 37081537
DOI: 10.1186/s13027-023-00502-1 -
Biomedicines Sep 2020In the Compendium of Materia Medica, seahorse () is considered effective for the reinforcement of kidney and men's health. However, the role of seahorse on human health...
In the Compendium of Materia Medica, seahorse () is considered effective for the reinforcement of kidney and men's health. However, the role of seahorse on human health lacks scientific evidence. Therefore, we evaluated the effect of seahorse on human prostate cancer using various in vitro methods and identified bioactive compound. Seahorse lipid extract (SHL) decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in dihydrotestosterone (DHT)-induced LNCaP cells of prostate cancer. Gas Chromatography (GC)-mass spectrometry data showed that brassicasterol was present in . Brassicasterol downregulated the expression of AR and PSA in DHT-induced LNCaP cells. Brassicasterol induced apoptosis accompanied by sub-G1 phase arrest and inhibited migration in LNCaP cells. We confirmed that AKT and AR mediated the anti-cancer effect of brassicasterol using siRNA transfection. Brassicasterol exerts an anti-cancer effect in AR-independent cancer as well as in AR-dependent cells by AKT inhibiting. Our findings suggest that SHL has the anticancer potential via inhibition of AR and demonstrated that brassicasterol from exerted an anti-cancer effect by dual-targeting AKT and AR signaling in prostate cancer.
PubMed: 32972001
DOI: 10.3390/biomedicines8090370 -
Biomedicines May 2020While few studies have revealed the biological properties of brassicasterol, a phytosterol, against some biological and molecular targets, it is believed that there are...
While few studies have revealed the biological properties of brassicasterol, a phytosterol, against some biological and molecular targets, it is believed that there are still many activities yet to be studied. In this work, brassicasterol exerts a therapeutic utility in an in vitro setting against herpes simplex virus type 1 (HSV-1) and (Mtb) as well as a considerable inhibitory property against human angiotensin-converting enzyme (ACE) that plays a dynamic role in regulating blood pressure. The antireplicative effect of brassicasterol against HSV-1 is remarkably detected (50% inhibitory concentration (IC): 1.2 µM; selectivity index (SI): 41.7), while the potency of its effect is ameliorated through the combination with standard acyclovir with proper SI (IC: 0.7 µM; SI: 71.4). Moreover, the capacity of this compound to induce an adequate level of antituberculosis activity against all Mtb strains examined (minimum inhibitory concentration values ranging from 1.9 to 2.4 µM) is revealed. The anti-ACE effect (12.3 µg/mL; 91.2% inhibition) is also ascertained. Molecular docking analyses propose that the mechanisms by which brassicasterol induces anti-HSV-1 and anti-Mtb might be related to inhibiting vital enzymes involved in HSV-1 replication and Mtb cell wall biosynthesis. In summary, the obtained results suggest that brassicasterol might be promising for future anti-HSV-1, antituberculosis, and anti-ACE drug design.
PubMed: 32456343
DOI: 10.3390/biomedicines8050132 -
Analytical Methods : Advancing Methods... Dec 2022A previous study has shown that brassicasterol- was detected in the serum of stroke-prone spontaneously hypertensive rats after oral administration of ergosterol-. To...
Simultaneous determination of deuterium-labeled ergosterol and brassicasterol in stroke-prone spontaneously hypertensive rats by ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry.
A previous study has shown that brassicasterol- was detected in the serum of stroke-prone spontaneously hypertensive rats after oral administration of ergosterol-. To quantitatively evaluate the serum concentration of brassicasterol-, an ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the simultaneous determination of picolinyl ester-derivatized ergosterol- and brassicasterol-. The separation was performed on an ODS column (Waters Acquity UPLC BEH C18) with a mobile phase consisting of methanol and water containing 0.1% acetic acid (95/5, v/v). Linear calibration curves in the presence of the serum were obtained in a concentration range of 0.04-8 μg mL. Recovery rates of 95.6-119% were obtained with an RSD ( = 6) of less than 7.5%. The method was applied to the determination of time-concentration curves of ergosterol- and brassicasterol- in stroke-prone spontaneously hypertensive rats, showing a pharmacokinetic profile of ergosterol- where the peak serum concentration of brassicasterol- was 3-fold higher than that of ergosterol-.
Topics: Animals; Rats; Ergosterol; Chromatography, High Pressure Liquid; Rats, Inbred SHR; Deuterium; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Stroke
PubMed: 36416170
DOI: 10.1039/d2ay01705a -
Acta Psychiatrica Scandinavica Sep 2011
The search of new biomarkers to identify Alzheimer's disease: an editorial comment to T. Vanmierlo et al. 'The plant sterol brassicasterol and additional CFS biomarker in Alzheimer's Disease' (1).
Topics: Alzheimer Disease; Apolipoprotein E4; Cholesterol; Female; Humans; Male; Phytosterols; tau Proteins
PubMed: 21564039
DOI: 10.1111/j.1600-0447.2011.01714.x -
Acta Psychiatrica Scandinavica Sep 2011Plant sterols (sitosterol, campesterol, stigmasterol and brassicasterol) are solely dietary-derivable sterols that are structurally very similar to cholesterol. In...
OBJECTIVE
Plant sterols (sitosterol, campesterol, stigmasterol and brassicasterol) are solely dietary-derivable sterols that are structurally very similar to cholesterol. In contrast to peripheral cholesterol, plant sterols can cross the blood-brain barrier and accumulate within mammalian brain. As an impaired function of the cerebrospinal fluid (CSF)-blood barrier is linked to neurodegenerative disorders, i.e. Alzheimer's disease (AD), we investigated whether this results in altered plant sterol concentrations in CSF.
METHOD
Applying gas chromatography/mass spectrometry analysis, plant sterol concentrations were measured in plasma and CSF of patients with AD (n = 67) and controls (n = 29). Age, gender, plasma-to-CSF albumin ratio, CSF Aβ(42) , CSF pTau, APOE4 genotype, and serum creatinine were applied as covariates in the statistical analysis for individual plant sterols in order to compare plasma and CSF plant sterol concentrations between patients with AD and controls.
RESULTS
Albumin quotient was a consistent predictor in CSF for cholesterol and methyl plant sterols campesterol and brassicasterol. Comparison of lipid parameters per diagnosis based on relevant predictors revealed significantly lower concentrations of brassicasterol (P < 0.001) in CSF of patients with AD. Binary logistic regression analysis revealed that brassicasterol improved the predictive value when added to pTau and Aβ42 in a biomarker model.
CONCLUSION
Brassicasterol might be a relevant additional biomarker in AD.
Topics: Age Factors; Aged; Alzheimer Disease; Apolipoprotein E4; Biomarkers; Blood-Brain Barrier; Brain; Cerebrospinal Fluid; Cholesterol; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Phytosterols; Predictive Value of Tests; Risk Factors; Sex Factors; tau Proteins
PubMed: 21585343
DOI: 10.1111/j.1600-0447.2011.01713.x -
Journal of Natural Medicines Sep 2020We previously revealed that Choreito, a traditional Kampo medicine, strongly inhibits bladder carcinogenesis promotion. We have also shown that Polyporus sclerotium,...
We previously revealed that Choreito, a traditional Kampo medicine, strongly inhibits bladder carcinogenesis promotion. We have also shown that Polyporus sclerotium, which is one of the crude drugs in Choreito, has the strongest bladder carcinogenesis inhibitory effect and that the ergosterol contained in Polyporus sclerotium is the main active component. In this study, we analyzed the mechanism by which ergosterol inhibits bladder carcinogenesis. Rats were given an N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) solution ad libitum, and then a promoter [saccharin sodium (SS), DL-tryptophan, or BHBN] was administered together with ergosterol or its metabolite, brassicasterol. The bladders were removed from rats, and the inhibitory effect on carcinogenesis promotion was evaluated by an agglutination assay with concanavalin A (Con A). Although the oral administration of ergosterol inhibited the promotion of bladder carcinogenesis with SS, the intraperitoneal administration of brassicasterol showed a stronger effect. The effect of brassicasterol on carcinogenesis promotion was observed regardless of the type of promoter. Administration of testosterone to castrated rats increased the number of cell aggregates caused by Con A. In contrast, intraperitoneal administration of brassicasterol to castrated rats treated with testosterone significantly decreased the number of cell aggregates, confirming the inhibition of bladder carcinogenesis promotion. The inhibitory effect of ergosterol on bladder carcinogenesis is due to brassicasterol, a metabolite of ergosterol. The action of brassicasterol via androgen signaling may play a role in the inhibitory effect on bladder carcinogenesis promotion.
Topics: Animals; Cholestadienols; Ergosterol; Humans; Male; Medicine, Kampo; Phytosterols; Rats; Rats, Wistar; Urinary Bladder Neoplasms
PubMed: 32488609
DOI: 10.1007/s11418-020-01419-4 -
Lipids Dec 1982The major 4α-monomethyl sterol of the dinoflagellateGymnodinium simplex was identified as (24S)-4α,24- dimethylcholestan-3β-ol. The major 4-demethyl sterols were...
The major 4α-monomethyl sterol of the dinoflagellateGymnodinium simplex was identified as (24S)-4α,24- dimethylcholestan-3β-ol. The major 4-demethyl sterols were characterized as (24R)-24-methylcholesta-5,22-dien-3β-ol (brassicasterol) and 27-nor-(24R)-24-methylcholesta-5,22-dien-3β-ol. The latter sterol has the opposite configuration at C-24 to that assigned to occelasterol, which has the same basic structure and has previously been reported as a constituent of the sterols of a marine worm. 24-Nor-cholesta-5,22-dien-3β-ol was also identified along with several other trace sterols. The co-occurrence of 27-nor-(24R)-cholesta-5,22-dien-3β-ol together with 24-nor-cholesta-5,22-dien-3β-ol and brassicasterol provides new evidence for the biosynthetic origins of the two former nor-sterols. It is suggested that they may be produced de novo by a route involving nor-isoprenoid pyrophosphates and nor-squalene as intermediates, rather than as bacterial degradation products of brassicasterol (or related sterols) as previously suggested in the literature.
PubMed: 27519432
DOI: 10.1007/BF02534578 -
Journal of Food Science and Technology Jul 2020Plants consist of triterpenoids such as phytosterols (PT) (CHO) with steroidal nuclei, including sitosterol, stigmasterol, brassicasterol and campesterol. They are... (Review)
Review
Plants consist of triterpenoids such as phytosterols (PT) (CHO) with steroidal nuclei, including sitosterol, stigmasterol, brassicasterol and campesterol. They are hydrophobic but soluble in alcohol and other organic solvents and are isolated from industrial waste deodorizer distillates of various edible oil industries. They exist as free PT or their ester derivatives in soybean, rice, wheat, oat, cottonseed and corn fiber, and other cereals and grains. Conventional isolation techniques such as solvent extraction, distillation, evaporative fractionation, saponification and chemical esterification are employed for isolation and purification of PT. The present article reviews the various advanced separation techniques like solvent crystallization, supercritical fluid extraction, high speed counter-current chromatography and enzymatic process as strategic methods to isolate and purify sterols.
PubMed: 32549589
DOI: 10.1007/s13197-019-04209-3 -
Lipids Jul 2018Several feeding trials with Atlantic salmon fed naturally high phytosterol concentrations due to dietary rapeseed oil inclusion have shown changes in lipid metabolism...
Several feeding trials with Atlantic salmon fed naturally high phytosterol concentrations due to dietary rapeseed oil inclusion have shown changes in lipid metabolism and increased hepatic lipid storage in the fish. An in vitro trial with Atlantic salmon hepatocytes was, therefore, performed to study the possible direct effects of phytosterols on lipid storage and metabolism. The isolated hepatocytes were exposed to seven different sterol treatments and gene expression, as well as lipid accumulation by Oil Red O dyeing, was assessed. Fucosterol, a sterol found in many algae species, had an effect on the size of individual lipid droplets, leading to smaller lipid droplets than in the control without added sterols. A sterol extract from soybean/rapeseed led to an increase in the percentage of hepatocytes with visible lipid droplets at 20× magnification, while hepatocytes of both the sterol extract-treated groups and fucosterol-treated groups had a larger proportion of their area covered with lipids compared to control cells. Brassicasterol, a sterol characteristic of rapeseed oil, was the only sterol treatment leading to a change in gene expression, affecting the expression of the nuclear receptors, peroxisome proliferator-activated receptor gamma (pparg) and retinoid X receptor (rxr). The current study thus shows that phytosterols can have direct, although subtle, effects on both hepatic lipid storage and gene expression of Atlantic salmon in vitro.
Topics: Animals; Cholestadienols; Hepatocytes; Lipid Metabolism; Lipids; Phytosterols; Salmon; Stigmasterol
PubMed: 30259993
DOI: 10.1002/lipd.12083