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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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Effects of HCE on immobility time in TST (A) and line crossings in OFT (B). The apparent correlations between (C) chemical and (D) flavonoid constituent dosages and the immobility time in HCE in the TST. The results are expressed as% immobility time relative to the control group (vehicle) for the antidepressant-like effects. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), fluoxetine (20 mg/kg), and HCE (400 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); and #p < 0.05, ##p < 0.01, and ###p < 0.001 compared with the positive reference group (fluoxetine). Linear regression was performed along with the ordinary least squares estimation.
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Fig2: Effects of HCE on immobility time in TST (A) and line crossings in OFT (B). The apparent correlations between (C) chemical and (D) flavonoid constituent dosages and the immobility time in HCE in the TST. The results are expressed as% immobility time relative to the control group (vehicle) for the antidepressant-like effects. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), fluoxetine (20 mg/kg), and HCE (400 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); and #p < 0.05, ##p < 0.01, and ###p < 0.001 compared with the positive reference group (fluoxetine). Linear regression was performed along with the ordinary least squares estimation.

Mentions: The effects of HCE treatment (400 mg/kg, p.o.) on immobility time in TST are presented in Figure 2A. HCE50 (p < 0.05), HCE75 (p < 0.001), and HCE100 (p < 0.01) significantly decrease immobility time compared with the control group, indicating good antidepressant-like performances. The reducing abilities of HCE75 were closest among the three to that of fluoxetine, which is the most common clinical therapy drug used as positive reference. Significant variations in OFT line crossings were not found in Figure 2B, indicating that HCE did not stimulate locomotor activity, thus the antidepressant-like effects of HCE in the TST were specific. The poor anti-immobility correlations with the carbohydrates (R2 = 0.16), proteins (R2 = 0.13), and crude fat (R2 = 0.03), unlike flavonoids (R2 = 0.92), derived from their dose–response regression analyses shown in Figure 2C indicate a possible disconnect with any antidepressant-like effect [32]. Quercetin (R2 = 0.05) and quercitrin (R2 = 0.08) were also ruled out in the regression analyses because of the apparent noncorrelation between the flavonoids and antidepressant-like performance (Figure 2D). By contrast, the high degree of correlation between immobility time and dose indicates that the antidepressant-like effects are closely associated with rutin (R2 = 0.96) and hesperidin (R2 = 0.97).Figure 2


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 HCE on immobility time in TST (A) and line crossings in OFT (B). The apparent correlations between (C) chemical and (D) flavonoid constituent dosages and the immobility time in HCE in the TST. The results are expressed as% immobility time relative to the control group (vehicle) for the antidepressant-like effects. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), fluoxetine (20 mg/kg), and HCE (400 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); and #p < 0.05, ##p < 0.01, and ###p < 0.001 compared with the positive reference group (fluoxetine). Linear regression was performed along with the ordinary least squares estimation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Effects of HCE on immobility time in TST (A) and line crossings in OFT (B). The apparent correlations between (C) chemical and (D) flavonoid constituent dosages and the immobility time in HCE in the TST. The results are expressed as% immobility time relative to the control group (vehicle) for the antidepressant-like effects. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), fluoxetine (20 mg/kg), and HCE (400 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); and #p < 0.05, ##p < 0.01, and ###p < 0.001 compared with the positive reference group (fluoxetine). Linear regression was performed along with the ordinary least squares estimation.
Mentions: The effects of HCE treatment (400 mg/kg, p.o.) on immobility time in TST are presented in Figure 2A. HCE50 (p < 0.05), HCE75 (p < 0.001), and HCE100 (p < 0.01) significantly decrease immobility time compared with the control group, indicating good antidepressant-like performances. The reducing abilities of HCE75 were closest among the three to that of fluoxetine, which is the most common clinical therapy drug used as positive reference. Significant variations in OFT line crossings were not found in Figure 2B, indicating that HCE did not stimulate locomotor activity, thus the antidepressant-like effects of HCE in the TST were specific. The poor anti-immobility correlations with the carbohydrates (R2 = 0.16), proteins (R2 = 0.13), and crude fat (R2 = 0.03), unlike flavonoids (R2 = 0.92), derived from their dose–response regression analyses shown in Figure 2C indicate a possible disconnect with any antidepressant-like effect [32]. Quercetin (R2 = 0.05) and quercitrin (R2 = 0.08) were also ruled out in the regression analyses because of the apparent noncorrelation between the flavonoids and antidepressant-like performance (Figure 2D). By contrast, the high degree of correlation between immobility time and dose indicates that the antidepressant-like effects are closely associated with rutin (R2 = 0.96) and hesperidin (R2 = 0.97).Figure 2

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