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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 the pure rutin (A), hesperidin (B), quercetin (C), and quercitrin (D) on immobility time in TST. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), 20 mg/kg fluoxetine, 0.1, 1, 2, 4, and 8 mg/kg rutin, 0.03, 0.3, 1, 2, and 4 mg/kg hesperidin, 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercetin, and 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercitrin. 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 < 0.05, ##p < 0.01, and ###p < 0.001 compared with the positive reference group (fluoxetine).
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Fig3: Effects of the pure rutin (A), hesperidin (B), quercetin (C), and quercitrin (D) on immobility time in TST. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), 20 mg/kg fluoxetine, 0.1, 1, 2, 4, and 8 mg/kg rutin, 0.03, 0.3, 1, 2, and 4 mg/kg hesperidin, 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercetin, and 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercitrin. 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 < 0.05, ##p < 0.01, and ###p < 0.001 compared with the positive reference group (fluoxetine).

Mentions: Pure flavonoids were tested to confirm the hypothesis. Figure 3A and 3B show that pure rutin (2–8 mg/kg) and hesperidin (1–4 mg/kg) elicits significant antidepressant-like actions on mice in TST, similar to that evoked by the equivalent HCE50 (2.1 and 0.7 mg/kg rutin and hesperidin, respectively), HCE75 (6.7 and 2.3 mg/kg rutin and hesperidin, respectively), and HCE100 (5.9 and 1.9 mg/kg rutin and hesperidin, respectively). The orally administered quercetin and quercitrin doses did not exhibit antidepressant-like effects in the present conditions (Figure 3C and 3D). Traces of contributions from carbohydrates, proteins, and crude fat were not observed. Psychostimulant effects were likewise not observed in the OFT of the flavonoids (data not shown). Dimpfel [33] found that 5 to 80 mg/kg rutin doses produced electro-pharmacograms similar to those of clinical antidepressants in rats. A single i.p. hesperidin administration yielded antidepressant-like effects [9].Figure 3


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 the pure rutin (A), hesperidin (B), quercetin (C), and quercitrin (D) on immobility time in TST. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), 20 mg/kg fluoxetine, 0.1, 1, 2, 4, and 8 mg/kg rutin, 0.03, 0.3, 1, 2, and 4 mg/kg hesperidin, 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercetin, and 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercitrin. 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 < 0.05, ##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

Fig3: Effects of the pure rutin (A), hesperidin (B), quercetin (C), and quercitrin (D) on immobility time in TST. The mice were tested 60 min after they were administered (p.o.) with the vehicle (physiological saline with 2% Tween 80), 20 mg/kg fluoxetine, 0.1, 1, 2, 4, and 8 mg/kg rutin, 0.03, 0.3, 1, 2, and 4 mg/kg hesperidin, 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercetin, and 0.01, 0.1, 0.2, 0.4, and 0.8 mg/kg quercitrin. 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 < 0.05, ##p < 0.01, and ###p < 0.001 compared with the positive reference group (fluoxetine).
Mentions: Pure flavonoids were tested to confirm the hypothesis. Figure 3A and 3B show that pure rutin (2–8 mg/kg) and hesperidin (1–4 mg/kg) elicits significant antidepressant-like actions on mice in TST, similar to that evoked by the equivalent HCE50 (2.1 and 0.7 mg/kg rutin and hesperidin, respectively), HCE75 (6.7 and 2.3 mg/kg rutin and hesperidin, respectively), and HCE100 (5.9 and 1.9 mg/kg rutin and hesperidin, respectively). The orally administered quercetin and quercitrin doses did not exhibit antidepressant-like effects in the present conditions (Figure 3C and 3D). Traces of contributions from carbohydrates, proteins, and crude fat were not observed. Psychostimulant effects were likewise not observed in the OFT of the flavonoids (data not shown). Dimpfel [33] found that 5 to 80 mg/kg rutin doses produced electro-pharmacograms similar to those of clinical antidepressants in rats. A single i.p. hesperidin administration yielded antidepressant-like effects [9].Figure 3

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