Zhi-Zi-Chi Decoction Reverses Depressive Behaviors in CUMS Rats by Reducing Oxidative Stress Injury Via Regulating GSH/GSSG Pathway

Abstract

Depression is one of the main diseases that lead to disability and loss of ability to work. As a traditional Chinese medicine, Zhi-zi-chi decoction is utilized to regulate and improve depression. However, the research on the antidepressant mechanism and efficacy material basis of Zhi-zi-chi decoction has not been reported yet. Our previous research has found that Zhi-Zi-chi decoction can reduce glutamate-induced oxidative stress damage to PC 12 cells, which can exert a neuroprotective effect, and the antidepressant effect of Zhi-Zi-chi decoction was verified in CUMS rat models. In this study, the animal model of depression was established by chronic unpredictable mild stimulation combined with feeding alone. The brain metabolic profile of depressed rats was analyzed by the method of metabolomics based on ultra-performance liquid chromatography-quadrupole/time-of-flight mass. 26 differential metabolites and six metabolic pathways related to the antidepressant of Zhi-zi-chi decoction were screened and analyzed. The targeted metabolism of the glutathione metabolic pathway was analyzed. At the same time, the levels of reactive oxygen species, superoxide dismutase, glutathione reductase, glutathione peroxidase in the brain of depressed rats were measured. Combined with our previous study, the antioxidant effect of the glutathione pathway in the antidepressant effect of Zhi-zi-chi decoction was verified from the cellular and animal levels respectively. These results indicated that Zhi-zi-chi decoction exerted a potential antidepressive effect associated with reversing the imbalance of glutathione and oxidative stress in the brain of depressed rats.

Unleashing lactoferrin's antidepressant potential through the PI3K/Akt/mTOR pathway in chronic restraint stress rats

“…The CRS has been used in the current research as a model of generating depressive-like symptoms because it induces behavioral, neurological, and hormonal changes that are similar in some extent to how humans can experience depression. [33][34][35] The current experiment showed that CRS increased depressive-like behavior as evidenced by reduced sucrose grooming time in the splash test and swimming time in the FST as well as increased immobility time in the TST. Consistent with our results, in previous studies, CRS led to decreased sucrose consumption and grooming frequency in splash tests, and extended immobility time in the FST 36 and TST.…”

“…The CRS has been used in the current research as a model of generating depressive-like symptoms because it induces behavioral, neurological, and hormonal changes that are similar in some extent to how humans can experience depression. 33–35…”

“…[51][52][53] In accordance with this approach, the current data showed that rats exposed to CRS developed higher levels of reactive oxygen species (ROS) (TBARS) and lower levels of antioxidants in the brain (GSH). 34 The increased oxidative stress is likely related to the elevated glucocorticoid levels and increased glucose metabolism and oxygen consumption in response to stress, as well as the decreased antioxidant defense mechanisms in the brain that cause different generation of ROS. 54 Moreover, neuroinflammation, a significant factor in the development of neural injury, may be induced by oxidative stress in the central nervous system.…”

Multi-omics analysis reveals the molecular basis of flavonoid accumulation in fructus of Gardenia (Gardenia jasminoides Ellis)

“…Geniposides is another important constituent in gardenia, and its medicinal value in gardenia fruit also has nonnegligible role. The abundant presence of flavonoids and geniposides is thought to account for the advantageous properties associated with gardenia fruits [ 31 ]. Therefore, analyzing the metabolites of gardenia fruits at different developmental stages is not only beneficial to understand the coloring process of gardenia fruits, but also beneficial to the development of gardenia fruits health products.…”

Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota–gut–brain axis in corticosterone combined with chronic restraint stress‐induced mice

“… 13 Modern research has shown that the anti‐depression effect of ZZCD might be associated with PKA/CREB/BDNF/TrkB/PSD‐95 pathway influenced by metabolic changes. 14 In addition, another study also indicated that ZZCD exerts potential antidepressant effects by reversing the imbalance of glutathione and oxidative stress 15 and increasing short‐chain fatty acid production and anti‐inflammatory bacteria, as well as reducing inflammatory and tryptophan‐metabolizing bacteria. 16 GF is a Chinese medicinal with a variety of pharmacological functions, such as anti‐inflammatory and antidepressant effect, as well as improving cognition and ischemic brain damage.…”