Effect of hop mixture containing xanthohumol on sleep enhancement in a mouse model and ROS scavenging effect in oxidative stress-induced HT22 cells

MIN, Byungjick; PARK, Chun Woong; AHN, Yeljin; HONG, Ki-Bae; CHO, Hyeok-Jun; LEE, Jang Hyun; JO, Kyungae; SUH, Hyung Joo

doi:10.1590/fst.29922

Byungjick MIN ^##These authors contributed equally to this work

Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, Republic of Korea

Lotte R&D Center, Seoul, Korea

Chun Woong PARK ^##These authors contributed equally to this work

Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, Republic of Korea

BK21FOUR R&E Center for Learning Health Systems, Korea University, Seoul, Republic of Korea

Yeljin AHN

Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, Republic of Korea

Ki-Bae HONG

Department of Food Science and Nutrition, Jeju National University, Jeju, Republic of Korea

Hyeok-Jun CHO

Lotte R&D Center, Seoul, Korea

Jang Hyun LEE

Lotte R&D Center, Seoul, Korea

Kyungae JO ^**Corresponding author: kyungae11@korea.ac.kr; suh1960@korea.ac.kr

Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, Republic of Korea

http://orcid.org/0000-0003-4056-6706

Hyung Joo SUH ^**Corresponding author: kyungae11@korea.ac.kr; suh1960@korea.ac.kr

Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, Republic of Korea

BK21FOUR R&E Center for Learning Health Systems, Korea University, Seoul, Republic of Korea

*Corresponding author: kyungae11@korea.ac.kr; suh1960@korea.ac.kr

#These authors contributed equally to this work

Ethical approval

Animal procedures were approved by the Korean University Institutional Animal Care and Use Committee (KUIACUC-2021-0020).

Conflict of interest

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures (6)
Tables (1)

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Figure 1
Effect of Sim/Sap and Saz/Sap mixtures on (A, B) sleep latency time and (C, D) sleep duration time in mice administered a hypnotic dose of pentobarbital (42 mg/kg, intraperitoneally). NOR, 0.9% NaCl (physiological saline)-administered group (normal control); BDZ, benzodiazepine-administered group (positive control, 200 μg/kg). Hops (Simcoe, Saphir, and Saaz) and their mixtures (Simcoe/Saphir and Saaz/Saphir) were orally administered at 100 mg/kg. Data are presented as the mean ± standard error of the mean (SEM) for each group (n=7). *p < 0.05, **p < 0.01, and ***p < 0.001 vs. normal group by Tukey’s multiple comparison test. Sim, Simcoe; Sap, Saphir; Saz, Saaz; Sim/Sap, Simcoe/Saphir (50:50) mixture; Saz/Sap, Saaz/Saphir (75:25) mixture.

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Figure 2
Effect of Sim/Sap and Saz/Sap mixtures on (A) sleep latency time and (B) sleep duration time in mice administered a hypnotic dose of pentobarbital (42 mg/kg, intraperitoneally). NOR, 0.9% NaCl (physiological saline)-administered group (normal control); BDZ, benzodiazepine-administered group (positive control, 200 μg/kg); Sim/Sap, Simcoe/Saphir (50:50; 100 and 150 mg/kg) mixture; Saz/Sap, Saaz/Saphir (75:25; 100 and 150 mg/kg) mixture. Data are presented as the mean ± standard error of the mean (SEM) for each group (n=7). ^*p < 0.05 and ^***p < 0.001 vs. normal group.

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Figure 3
Effect of the Saz/Sap and Sim/Sap mixtures on (A) sleep latency time and (B) sleep duration time in the caffeine-induced insomnia mice model. NOR, 0.9% NaCl (physiological saline)-administered group (normal control); CON, 40 mg/kg caffeine-administered group; BDZ, 200 μg/kg benzodiazepine and 40 mg/kg caffeine-administered group (positive control); Saz/Sap, oral administration of the Saaz/Saphir (75:25; 150 mg/kg) mixture and 40 mg/kg caffeine; Sim/Sap, oral administration of the Simcoe/Saphir (50:50; 150 mg/kg) mixture and 40 mg/kg caffeine. Data are presented as the mean ± standard error of the mean (SEM) for each group (n = 7). ^#p < 0.05, ^##p < 0.01, and ^###p < 0.001 vs. control group.

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Figure 4
Scavenging effects of Sim/Sap (75:25) and Saz/Sap (50:50) mixtures on (A) ABTS and (B) DPPH radicals. Data are presented as the mean ± standard deviation (SD). ^*p < 0.05, ^**p < 0.01, and ^***p < 0.001 vs. Saz/Sap and ^#p < 0.05, ^###p < 0.001 vs. Sim/Sap. Saz, Saaz; Sap, Saphir; Sim, Simcoe; Saz/Sap, Saaz/Saphir (75:25) mixture; Sim/Sap, Simcoe/Saphir (50:50) mixture.

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Figure 5
Effect of (A) hops and hop mixtures and (B) xanthohumol on ROS production in H₂O₂-treated HT22 cells. HT22 cells were treated with 100 μg/mL of hops (Saaz, Saphir, and Simcoe), their mixtures (Saaz/Saphir and Simcoe/Saphir), and 0.6 (Xan-L) and 0.8 μg/mL (Xan-H) of xanthohumol. Data are presented as the mean ± standard deviation (SD) for each group. ^***p < 0.001 vs. control group. NOR, normal; CON, control; Saz, Saaz; Sap, Saphir; Sim, Simcoe; Saz/Sap, Saaz/Saphir (75:25) mixture; Sim/Sap, Simcoe/Saphir (50:50) mixture.

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Figure 6
Effect of hop mixtures on the expression of antioxidant enzymes in H2O2-treated HT22 cells. HT22 cells were treated with 100 μg/mL of hops (Saaz, Saphir, and Simcoe), hop mixtures (Saaz/Saphir and Simcoe/Saphir), and 0.6 (Xan-L) and 0.8 μg/mL (Xan-H) of xanthohumol. Data are presented as the mean ± standard deviation (SD) for each group. ^**p < 0.01 and ^***p < 0.001 vs. control group. NOR, normal; CON, control; Xan, xanthohumol; SOD-1, superoxide dismutase-1; CAT, catalase; GPx-1, glutathione peroxidase-1; Saz, Saaz; Sap, Saphir; Sim, Simcoe; Saz/Sap, Saaz/Saphir (75:25) mixture; Sim/Sap, Simcoe/Saphir (50:50) mixture.

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Table 1
α-acid, β-acid, xanthohumol, polyphenol, and flavonoid contents and yield of hops and hop mixtures.

Variety	α-acid (μg/mg)		β-acid (μg/mg)		Xanthohumol	Polyphenols	Flavonoids
Variety	Cohumulone	Adhumulone	Colupulone	Adlupulone	(μg/mg)	(μg/mg)	(μg/mg)
Saaz	5.41 ± 0.01	17.91 ± 0.05	20.68 ± 0.06	28.83 ± 0.53	2.51 ± 0.13	99.70 ± 2.78	13.08 ± 0.12
Saphir	3.14 ± 0.09	27.67 ± 0.24	27.13 ± 0.07	39.24 ± 0.10	4.23 ± 0.14	117.19 ± 4.39	15.88 ± 0.28
Simcoe	21.24 ± 0.23	96.96 ± 0.99	12.64 ± 0.08	19.13 ± 0.11	1.94 ± 0.06	83.09 ± 3.42	5.94 ± 0.04
Saz-Sap	4.82 ± 0.03	20.35 ± 0.098	22.30 ± 0.063	31.43 ± 0.42	2.94 ± 0.13	104.07 ± 3.18	13.78 ± 0.16
Sim-Sap	12.19 ± 0.16	62.19 ± 0.62	19.89 ± 0.075	29.19 ± 0.11	3.09 ± 0.10	100.14 ± 3.91	10.91 ± 0.163.92

[1] *Corresponding author: kyungae11@korea.ac.kr; suh1960@korea.ac.kr

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Effect of hop mixture containing xanthohumol on sleep enhancement in a mouse model and ROS scavenging effect in oxidative stress-induced HT22 cells

Abstract