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Antidepressant-like effects of the hydroalcoholic extracts of Hemerocallis citrina and its potential active components.

Du B, Tang X, Liu F, Zhang C, Zhao G, Ren F, Leng X - BMC Complement Altern Med (2014)

Bottom Line: The antidepressant-like effects of hydroalcoholic H. citrina extracts were mainly related to flavonoids, especially rutin and hesperidin.The antidepressant-like effects of hydroalcoholic H. citrina extracts are mainly related to flavonoids, especially rutin and hesperidin.The active extract is toxicologically safe for oral administration.

View Article: PubMed Central - PubMed

Affiliation: CAU & ACC Joint-Laboratory of Space Food, College of Food Science & Nutritional Engineering, Key Laboratory of Functional Dairy Science of Beijing and Ministry of Education, Beijing Higher Institution Engineering Research Center of Animal Product, Beijing Dairy Industry Innovation Team, China Agricultural University, No,17 Qinghua East Road, Haidian, Beijing 100083, People's Republic of China. gzhao1000@163.com.

ABSTRACT

Background: Herbal therapies are potential alternatives and adjuncts for depression treatment. The present study aims to investigate the antidepressant-like effects of hydroalcoholic Hemerocallis citrina extracts and its potential neuropharmacological components.

Methods: Hydroalcoholic H. citrina extracts were phytochemically analyzed. Behavioral models, including tail suspension tests and open field tests, were performed to evaluate the antidepressant-like effects of the extracts. A possible mechanism was explored by analyzing brain monoamine neurotransmitters. Toxicity and histopathological analyses were performed to determine whether or not the extracts are safe for oral administration.

Results: The antidepressant-like effects of hydroalcoholic H. citrina extracts were mainly related to flavonoids, especially rutin and hesperidin. The extract prepared using 75% ethanol (i.e., HCE75) exhibited the highest active flavonoid content and activity. Orally administered 400 mg/kg of HCE75 significantly induced an antidepressant-like effect, whereas the combination of equivalent rutin and hesperidin dosages exhibited the same profiles. Isobologram analysis showed sub-additive antidepressant interactions between rutin and hesperidin. HCE75 (400 mg/kg, p.o.) increased the serotonin and dopamine levels in the central nervous system. Mortality and lesions were not observed upon oral administration of up to 5000 mg/kg HCE75.

Conclusions: The antidepressant-like effects of hydroalcoholic H. citrina extracts are mainly related to flavonoids, especially rutin and hesperidin. The serotonergic and dopaminergic systems may have major roles. The active extract is toxicologically safe for oral administration.

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Related in: MedlinePlus

Effects of HCE75, the standardized flavonoid mixture containing equivalent rutin, hesperidin, quercetin, and quercitrin doses and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w), on (A) immobility time in TST and (B to D) their respective line crossings in OFT. The mice were tested 1 h after administration (p.o.) of the vehicle (physiological saline with 10% Tween 80), fluoxetine (20 mg/kg), HCE75 (20, 200, 400, 800, and 1600 mg/kg), standardized flavonoid mixtures (0.4, 4, 8, 16, and 32 mg/kg), and the fixed-ratio rutin and hesperidin combination (0.4, 4, 8, 16, and 32 mg/kg). Data are expressed as mean ± S.E.M. (n = 10). Data were analyzed using one-way ANOVA for multiple comparisons, followed by post hoc Student–Newman–Keuls test. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the control group (vehicle); ##p < 0.01 and ###p < 0.001 compared with the positive reference group (fluoxetine).
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Fig5: Effects of HCE75, the standardized flavonoid mixture containing equivalent rutin, hesperidin, quercetin, and quercitrin doses and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w), on (A) immobility time in TST and (B to D) their respective line crossings in OFT. The mice were tested 1 h after administration (p.o.) of the vehicle (physiological saline with 10% Tween 80), fluoxetine (20 mg/kg), HCE75 (20, 200, 400, 800, and 1600 mg/kg), standardized flavonoid mixtures (0.4, 4, 8, 16, and 32 mg/kg), and the fixed-ratio rutin and hesperidin combination (0.4, 4, 8, 16, and 32 mg/kg). Data are expressed as mean ± S.E.M. (n = 10). Data were analyzed using one-way ANOVA for multiple comparisons, followed by post hoc Student–Newman–Keuls test. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the control group (vehicle); ##p < 0.01 and ###p < 0.001 compared with the positive reference group (fluoxetine).

Mentions: HCE75 (200–800 mg/kg) exhibited a significant anti-immobility effect (p < 0.01) in TST compared with the control groups (Figure 5A). Doses more than 800 mg/kg increased immobility time and formed a U-shaped dose–response profile in antidepressant-like action. Insignificant variations in the OFT line crossings (Figure 5B) ruled out the psychostimulant and sedative effects. The phenomenon was often observed during rodent model screening (i.p. or p.o.) on potential antidepressants, which was attributed to either the activation of different pathways at diverse doses [34] or the suppression of the maximum response in the presence of antagonists through non-competitive antagonism [4]. The dose-dependent diversity of the mechanisms of the neuropharmacological effects should be studied further because the highest HCE75 dosage (i.e., 1600 mg/kg) for oral treatment resulted in a hypnotic response (data not shown). The response might negate the antidepressant-like effects.The standardized flavonoid mixture containing equivalent rutin, hesperidin, quercetin, and quercitrin doses and the fixed-ratio combination of rutin and hesperidin induced the same characteristics and changes without significantly changing the OFT line crossings (Figure 5C and 5D). These results indicate that rutin and hesperidin cause the antidepressant effects of HCE75. The contributions of quercetin and quercitrin in the effects were insignificant.Figure 5


Antidepressant-like effects of the hydroalcoholic extracts of Hemerocallis citrina and its potential active components.

Du B, Tang X, Liu F, Zhang C, Zhao G, Ren F, Leng X - BMC Complement Altern Med (2014)

Effects of HCE75, the standardized flavonoid mixture containing equivalent rutin, hesperidin, quercetin, and quercitrin doses and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w), on (A) immobility time in TST and (B to D) their respective line crossings in OFT. The mice were tested 1 h after administration (p.o.) of the vehicle (physiological saline with 10% Tween 80), fluoxetine (20 mg/kg), HCE75 (20, 200, 400, 800, and 1600 mg/kg), standardized flavonoid mixtures (0.4, 4, 8, 16, and 32 mg/kg), and the fixed-ratio rutin and hesperidin combination (0.4, 4, 8, 16, and 32 mg/kg). Data are expressed as mean ± S.E.M. (n = 10). Data were analyzed using one-way ANOVA for multiple comparisons, followed by post hoc Student–Newman–Keuls test. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the control group (vehicle); ##p < 0.01 and ###p < 0.001 compared with the positive reference group (fluoxetine).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4289322&req=5

Fig5: Effects of HCE75, the standardized flavonoid mixture containing equivalent rutin, hesperidin, quercetin, and quercitrin doses and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w), on (A) immobility time in TST and (B to D) their respective line crossings in OFT. The mice were tested 1 h after administration (p.o.) of the vehicle (physiological saline with 10% Tween 80), fluoxetine (20 mg/kg), HCE75 (20, 200, 400, 800, and 1600 mg/kg), standardized flavonoid mixtures (0.4, 4, 8, 16, and 32 mg/kg), and the fixed-ratio rutin and hesperidin combination (0.4, 4, 8, 16, and 32 mg/kg). Data are expressed as mean ± S.E.M. (n = 10). Data were analyzed using one-way ANOVA for multiple comparisons, followed by post hoc Student–Newman–Keuls test. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the control group (vehicle); ##p < 0.01 and ###p < 0.001 compared with the positive reference group (fluoxetine).
Mentions: HCE75 (200–800 mg/kg) exhibited a significant anti-immobility effect (p < 0.01) in TST compared with the control groups (Figure 5A). Doses more than 800 mg/kg increased immobility time and formed a U-shaped dose–response profile in antidepressant-like action. Insignificant variations in the OFT line crossings (Figure 5B) ruled out the psychostimulant and sedative effects. The phenomenon was often observed during rodent model screening (i.p. or p.o.) on potential antidepressants, which was attributed to either the activation of different pathways at diverse doses [34] or the suppression of the maximum response in the presence of antagonists through non-competitive antagonism [4]. The dose-dependent diversity of the mechanisms of the neuropharmacological effects should be studied further because the highest HCE75 dosage (i.e., 1600 mg/kg) for oral treatment resulted in a hypnotic response (data not shown). The response might negate the antidepressant-like effects.The standardized flavonoid mixture containing equivalent rutin, hesperidin, quercetin, and quercitrin doses and the fixed-ratio combination of rutin and hesperidin induced the same characteristics and changes without significantly changing the OFT line crossings (Figure 5C and 5D). These results indicate that rutin and hesperidin cause the antidepressant effects of HCE75. The contributions of quercetin and quercitrin in the effects were insignificant.Figure 5

Bottom Line: The antidepressant-like effects of hydroalcoholic H. citrina extracts were mainly related to flavonoids, especially rutin and hesperidin.The antidepressant-like effects of hydroalcoholic H. citrina extracts are mainly related to flavonoids, especially rutin and hesperidin.The active extract is toxicologically safe for oral administration.

View Article: PubMed Central - PubMed

Affiliation: CAU & ACC Joint-Laboratory of Space Food, College of Food Science & Nutritional Engineering, Key Laboratory of Functional Dairy Science of Beijing and Ministry of Education, Beijing Higher Institution Engineering Research Center of Animal Product, Beijing Dairy Industry Innovation Team, China Agricultural University, No,17 Qinghua East Road, Haidian, Beijing 100083, People's Republic of China. gzhao1000@163.com.

ABSTRACT

Background: Herbal therapies are potential alternatives and adjuncts for depression treatment. The present study aims to investigate the antidepressant-like effects of hydroalcoholic Hemerocallis citrina extracts and its potential neuropharmacological components.

Methods: Hydroalcoholic H. citrina extracts were phytochemically analyzed. Behavioral models, including tail suspension tests and open field tests, were performed to evaluate the antidepressant-like effects of the extracts. A possible mechanism was explored by analyzing brain monoamine neurotransmitters. Toxicity and histopathological analyses were performed to determine whether or not the extracts are safe for oral administration.

Results: The antidepressant-like effects of hydroalcoholic H. citrina extracts were mainly related to flavonoids, especially rutin and hesperidin. The extract prepared using 75% ethanol (i.e., HCE75) exhibited the highest active flavonoid content and activity. Orally administered 400 mg/kg of HCE75 significantly induced an antidepressant-like effect, whereas the combination of equivalent rutin and hesperidin dosages exhibited the same profiles. Isobologram analysis showed sub-additive antidepressant interactions between rutin and hesperidin. HCE75 (400 mg/kg, p.o.) increased the serotonin and dopamine levels in the central nervous system. Mortality and lesions were not observed upon oral administration of up to 5000 mg/kg HCE75.

Conclusions: The antidepressant-like effects of hydroalcoholic H. citrina extracts are mainly related to flavonoids, especially rutin and hesperidin. The serotonergic and dopaminergic systems may have major roles. The active extract is toxicologically safe for oral administration.

Show MeSH
Related in: MedlinePlus