The Antidepressant And Cognitive Improvement Activities Of The Traditional Chinese Herb Cistanche Ⅲ
Jun 23, 2022
4. Discussion
In this study, the antidepressant activities and improvement of memory and learning of herb Cistanche were defined, which might shed a new light on herb Cistanche function and give clues to expanding the therapeutic application range. Previous studies show that herb Cistanche is a multifunctional Chinese drug with biological activities of antiaging, antioxidant, estrogenic, antiosteoporotic, aphrodisiac, and anti-inflammation effects.
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Herb Cistanche has been recognized as a treatment of kidney deficiency, infertility, and chronic constipation (Pharmacopoeia Committee of China, 2010). Herb Cistanche decoction is composed of volatile oils, nonvolatile phenylethanoid glycosides (PeGs), iridoids, lignans, alditols, oligosaccharides, and polysaccharides. Echinacoside and verbascoside are generally viewed as the main bioactive ingredients. There are four main Cistanche species including C. deserticola Y.C.Ma, C. tubulosa, Cistanche sinensis G. Beck, and Cistanche salsa var. albiflorashi et al. [35]; we chose C. deserticola Y.C.Ma and C. tubulosa as our model to determine the PeGs content, and C. deserticola Y.C.Ma possessed a higher content of PeGs (Figure 1), which may explain the higher efficacy of C. deserticola Y.C.Ma. The results indicate that the content of the main bioactive ingredients determines the efficacy of herb Cistanche.
Previous studies indicate that herb Cistanche products are beneficial for treating neurodegenerative disorders by upregulating nerve growth factor (NGF) in the hippocampus of mice [36, 37], but no research has been reported on the antidepressant and cognitive learning activities of herb Cistanche in the mammal models. In this study, herb Cistanche decoction was proven to be effective to alleviate the stress level and substantially increase the survival behavior in tail suspension test (Figure 2) and improve the spatial learning and memory capacity in the water maze model (Figure 3). Lin et al. proved that herb Cistanche improved the olfactory-associated memory in the fruit-fly model [23]; we focused our research on the antidepressant effect and adopted a different animal model; the outcome proved that herb Cistanche improved a variant type of cognitive function, namely, the spatial learning ability in mice. According to the monoamine theory, the stress experience and depression are closely linked to the brain level of monoamine neurotransmitters, such as DA, NE, 5-HT, and epinephrine [38]. And we found that the herb Cistanche decoction could undermine the MAO activity (Figure 4) and augment the central DA concentration (Figure 5(a)). Surprisingly, the central 5-HT concentration was downregulated by herb Cistanche decoction treatment (data not shown), because previous research showed that the reduced central 5-HT activity is associated with depression [39]. Dysregulation of the hypothalamic-pituitary-adrenal axis is frequently associated with depression [40], intervention with the glucocorticoid receptor (GR) system successfully reversed the depressant phenotype in mice [41], and we found that herb Cistanche significantly alleviated the serum concentration of CORT (Figure 6(b)). Modulation of the monoamine system and HPA axis both contributes to the antidepressant effect of herb Cistanche. The echinacoside could cross the blood-brain barrier freely and act upon the central nervous system [42], which may explain why herb Cistanche decoction possessed an antidepressant function. For the first time, we characterized the antidepressant property and its relationship to cognitive improvement activities in the mouse model, and the preliminary mechanism was explored. Still, the mechanism of antidepressant property of Cistanche has not been clarified on the molecular level, and further research is needed to elucidate the comprehensive antidepressant mechanism of herb Cistanche.
Considering that herb Cistanche decoction is mixture of compounds, there might be multiple ways of herb Cistanche decoction exerting the antidepressant effect and boosting learning ability. Oxidative stress affects many cellular functions of neurons, and overproduction of reactive oxygen species (ROS) causes cell damage, apoptosis, and death [43]. Echinacoside extracted from the stems of C. salsa exhibits a neuroprotective effect by reducing production of ROS and mitochondria-mediated apoptosis [44]; acteoside, an extremely strong antioxidative compound, might be partly responsible for the neuroprotective effect [45]. Besides the traditional method of decoction, application of modern pharmaceutic methods such as controlled release glycoside capsules might boost the effect of herb decoction, because the bioactive ingredients could be digested and degraded by the gastrointestinal tract [37].
5. Conclusions
In this study, we found that decoctions of C. deserticola Y.C.Ma and C. tubulosa exhibited an antidepressant effect and improved the spatial learning and memory ability in the mouse model, and decoctions of C. deserticola Y.C.Ma and C. tubulosa had a significant impact on the HPA axis; C. deserticola Y.C.Ma showed a stronger pharmacological function. C. deserticola and C. tubulosa might hold the potential of being developed as alternative therapy drug for depression.
