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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

Temporal evolutions of the antidepressant-like effects caused by HCE75, the standardized flavonoid mixture containing equivalent doses of rutin, hesperidin, quercetin, and quercitrin and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w) on mice in TST. The mice were tested 0, 0.5, 1, 2, 3, 4, and 8 h after administering (p.o.) with the vehicle (physiological saline with 10% Tween 80), HCE75 (400 mg/kg), standardized flavonoid mixture (8 mg/kg), and rutin/hesperidin fixed-ratio combination (8 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 (tested 1 h after vehicle treatment).
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Fig4: Temporal evolutions of the antidepressant-like effects caused by HCE75, the standardized flavonoid mixture containing equivalent doses of rutin, hesperidin, quercetin, and quercitrin and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w) on mice in TST. The mice were tested 0, 0.5, 1, 2, 3, 4, and 8 h after administering (p.o.) with the vehicle (physiological saline with 10% Tween 80), HCE75 (400 mg/kg), standardized flavonoid mixture (8 mg/kg), and rutin/hesperidin fixed-ratio combination (8 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 (tested 1 h after vehicle treatment).

Mentions: The previous analysis reveals that HCE75 is the most active H. citrina extract. The temporal behavior of the antidepressant-like effects and the dose-dependent properties (100 mg/kg to 1600 mg/kg) of the extract was estimated. The standardized flavonoid mixture prepared using four types of pure flavonoids and the combination with pure rutin and hesperidin at a fixed ratio (75:21.5, w/w) with respect to the real flavonoid composition of HCE75 (75% rutin, 21.5% hesperidin, 2% quercetin, and 1.5% quercitrin, w/w) were compared. Figure 4 shows the comparison of the three samples. The antidepressant-like effects of HCE75, standardized flavonoid mixture, and rutin/hesperidin fixed-ratio combination reached their maxima (p < 0.001) at 1, 0.5, and 0.5 h, respectively. The anti-depressant effects remained significant (p < 0.01) up to 4 h after p.o. administration. The temporal evolution curves were consistent. Psychostimulant effects were not observed in OFT (data not shown). Therefore, the functionality of the major antidepressants in HCE75 is mediated by rutin and hesperidin, whereas the contributions of quercetin and quercitrin are insignificant.Figure 4


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)

Temporal evolutions of the antidepressant-like effects caused by HCE75, the standardized flavonoid mixture containing equivalent doses of rutin, hesperidin, quercetin, and quercitrin and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w) on mice in TST. The mice were tested 0, 0.5, 1, 2, 3, 4, and 8 h after administering (p.o.) with the vehicle (physiological saline with 10% Tween 80), HCE75 (400 mg/kg), standardized flavonoid mixture (8 mg/kg), and rutin/hesperidin fixed-ratio combination (8 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 (tested 1 h after vehicle treatment).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Temporal evolutions of the antidepressant-like effects caused by HCE75, the standardized flavonoid mixture containing equivalent doses of rutin, hesperidin, quercetin, and quercitrin and the fixed-ratio combination of rutin and hesperidin (75:21.5, w/w) on mice in TST. The mice were tested 0, 0.5, 1, 2, 3, 4, and 8 h after administering (p.o.) with the vehicle (physiological saline with 10% Tween 80), HCE75 (400 mg/kg), standardized flavonoid mixture (8 mg/kg), and rutin/hesperidin fixed-ratio combination (8 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 (tested 1 h after vehicle treatment).
Mentions: The previous analysis reveals that HCE75 is the most active H. citrina extract. The temporal behavior of the antidepressant-like effects and the dose-dependent properties (100 mg/kg to 1600 mg/kg) of the extract was estimated. The standardized flavonoid mixture prepared using four types of pure flavonoids and the combination with pure rutin and hesperidin at a fixed ratio (75:21.5, w/w) with respect to the real flavonoid composition of HCE75 (75% rutin, 21.5% hesperidin, 2% quercetin, and 1.5% quercitrin, w/w) were compared. Figure 4 shows the comparison of the three samples. The antidepressant-like effects of HCE75, standardized flavonoid mixture, and rutin/hesperidin fixed-ratio combination reached their maxima (p < 0.001) at 1, 0.5, and 0.5 h, respectively. The anti-depressant effects remained significant (p < 0.01) up to 4 h after p.o. administration. The temporal evolution curves were consistent. Psychostimulant effects were not observed in OFT (data not shown). Therefore, the functionality of the major antidepressants in HCE75 is mediated by rutin and hesperidin, whereas the contributions of quercetin and quercitrin are insignificant.Figure 4

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