Dataset Information

Prevention of Fine Dust-Induced Vascular Senescence by Humulus lupulus Extract and Its Major Bioactive Compounds.

ABSTRACT: Both short- and long-term exposure to fine dust (FD) from air pollution has been linked to various cardiovascular diseases (CVDs). Endothelial cell (EC) senescence is an important risk factor for CVDs, and recent evidence suggests that FD-induced premature EC senescence increases oxidative stress levels. Hop plant (Humulus lupulus) is a very rich source of polyphenols known to have nutritional and therapeutic properties, including antioxidant behavior. The aims of this study were to evaluate whether Humulus lupulus extract prevents FD-induced vascular senescence and dysfunction and, if so, to characterize the underlying mechanisms and active components. Porcine coronary arteries and endothelial cells were treated with FD in the presence or absence of hop extract (HOP), and the senescence-associated-beta galactosidase (SA-?-gal) activity, cell-cycle progression, expression of senescence markers, oxidative stress level, and vascular function were evaluated. Results indicated that HOP inhibited FD-induced SA-?-gal activity, cell-cycle arrest, and oxidative stress, suggesting that HOP prevents premature induction of senescence by FD. HOP also ameliorated FD-induced vascular dysfunction. Additionally, xanthohumol (XN) and isoxanthohumol (IX) were found to produce the protective effects of HOP. Treatment with HOP and its primary active components XN and IX downregulated the expression of p22^ph^o^x, p53, and angiotensin type 1 receptor, which all are known FD-induced redox-sensitive EC senescence inducers. Taken together, HOP and its active components protect against FD-induced endothelial senescence most likely via antioxidant activity and may be a potential therapeutic agent for preventing and/or treating air-pollution-associated CVDs.

SUBMITTER: Shiwakoti S

PROVIDER: S-EPMC7762380 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Prevention of Fine Dust-Induced Vascular Senescence by <i>Humulus lupulus</i> Extract and Its Major Bioactive Compounds.

Shiwakoti Saugat S Adhikari Deepak D Lee Jeong Pyo JP Kang Ki-Woon KW Lee Ik-Soo IS Kim Hyun Jung HJ Oak Min-Ho MH

Antioxidants (Basel, Switzerland) 20201207 12

Both short- and long-term exposure to fine dust (FD) from air pollution has been linked to various cardiovascular diseases (CVDs). Endothelial cell (EC) senescence is an important risk factor for CVDs, and recent evidence suggests that FD-induced premature EC senescence increases oxidative stress levels. Hop plant (<i>Humulus lupulus</i>) is a very rich source of polyphenols known to have nutritional and therapeutic properties, including antioxidant behavior. The aims of this study were to evalu ...[more]

PMID: 33297587

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Project description:Humulus lupulus L. (hops) is a popular botanical dietary supplement used by women as a sleep aid and for postmenopausal symptom relief. In addition to its efficacy for menopausal symptoms, hops can also modulate the chemical estrogen carcinogenesis pathway and potentially protect women from breast cancer. In the present study, an enriched hop extract and the key bioactive compounds [6-prenylnarigenin (6-PN), 8-prenylnarigenin (8-PN), isoxanthohumol (IX), and xanthohumol (XH)] were tested for their effects on estrogen metabolism in breast cells (MCF-10A and MCF-7). The methoxyestrones (2-/4-MeOE1) were analyzed as biomarkers for the nontoxic P450 1A1 catalyzed 2-hydroxylation and the genotoxic P450 1B1 catalyzed 4-hydroxylation pathways, respectively. The results indicated that the hop extract and 6-PN preferentially induced the 2-hydroxylation pathway in both cell lines. 8-PN only showed slight up-regulation of metabolism in MCF-7 cells, whereas IX and XH did not have significant effects in either cell line. To further explore the influence of hops and its bioactive marker compounds on P450 1A1/1B1, mRNA expression and ethoxyresorufin O-dealkylase (EROD) activity were measured. The results correlated with the metabolism data and showed that hop extract and 6-PN preferentially enhanced P450 1A1 mRNA expression and increased P450 1A1/1B1 activity. The aryl hydrocarbon receptor (AhR) activation by the isolated compounds was tested using xenobiotic response element (XRE) luciferase construct transfected cells. 6-PN was found to be an AhR agonist that significantly induced XRE activation and inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced XRE activity. 6-PN mediated induction of EROD activity was also inhibited by the AhR antagonist CH223191. These data show that the hop extract and 6-PN preferentially enhance the nontoxic estrogen 2-hydroxylation pathway through AhR mediated up-regulation of P450 1A1, which further emphasizes the importance of standardization of botanical extracts to multiple chemical markers for both safety and desired bioactivity.

Project description:Transcriptional profiling of hop samples throughout in vitro culture on medium with sucrose and hormones IAA and BAP Study of gene expression involved in stress response during in vitro culture and in organogenic nodule formation Hop (Humulus lupulus L.) is an economically important plant forming organogenic nodules which can be used for genetic transformation and micropropagation. We are interested in the mechanisms underlying reprogramming of cells through stress and hormone treatments. To investigate the spatio-temporal sequence of events that underlies competence acquisition for organogenesis three main stages were selected: (i) internodes at the time of excision from the parent plant (T0); (ii) internodes grown for 15 days on culture medium in which several prenodular structures are formed inside the calli (T15d); and (iii) nodule forming tissue after 28 days of culture (T28d). Additionally a control was included corresponding to 28 days of culture without hormones, lacking nodule formation and plantlet regeneration abilities, in order to identify genes specifically involved in morphogenesis (T28dWH). Organogenic nodule formation is a morphogenic process that shares features with somatic embryogenesis though in the former no shoot/root pole is established and plantlet regeneration can occur from different peripheral regions of nodules. Previous studies have shown that the organogenesis-determining period (when cells are determined to form nodules) occurs in between 15 and 25 days of culture corresponding to prenodular and first nodular stages. When nodules are fully developed they are surrounded by layers of elongated, highly vacuolated cells that may degenerate when nodules start differentiating plantlets. Plantlet regeneration from organogenic nodules can be observed after 45 days of culture. However, organogenic nodules after 28 days of culture are already determined to undergo plantlet regeneration, since they no longer require exogenous supply of hormones. Explants cultured in medium without hormones can develop incipient prenodular structures with vascular tissue but not nodules, thus lacking morphogenic potential. Keywords: Plant development, Time course

Dataset Information

Prevention of Fine Dust-Induced Vascular Senescence by Humulus lupulus Extract and Its Major Bioactive Compounds.

Publications

Prevention of Fine Dust-Induced Vascular Senescence by <i>Humulus lupulus</i> Extract and Its Major Bioactive Compounds.

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