Depression is a major psychiatric disease in the 21st century (Rehm and Shield, 2019). Depression is caused by a combination of factors, including heredity, psychology, and environment. The symptoms of depression affect a patient's family and friends, economic status, daily life, physical function, and emotional well-being (Han et al., 2018). Changes in the dendritic length and spine density in the cortex and hippocampus are contributed to the neurobiology of depression (Wohleb et al., 2016). Depression causes a depletion of monoamines in the brain, including serotonin (5-HT), norepinephrine, and dopamine (Hellweg et al., 2007). The treatments for depression are antidepressants (Cuijpers et al., 2019). The action of mechanisms of anti-depressants are mediated by blocking these changes (Schmidt et al., 2007). Selective serotonin reuptake inhibitors (Fluoxetine, citalopram) are the commonly used anti-depressants (Zhang et al., 2017). However, anti-depressants cause side effects, such as agitation, tremors, anxiety diarrhea, constipation, insomnia, and headaches (Khawam et al., 2006). Herbal medicines should be an alternative treatments to prevent depression.

Gouteng (Uncaria rhynchophylla) arrests convulsions, ameliorates symptoms of the liver, calms the liver wind, and disperses stagnated liver qi to relieve qi stagnation (Compendium of Materia Medica) which was used in anti-depression (Dai et al., 2022). Studies have demonstrated that gouteng has a neuroprotective effect which is used to treat epilepsy (Hsieh et al., 2009; Tang et al., 2010), Parkinson's disease (Fujiwara et al., 2006; Shim et al., 2009), Alzheimer's disease (Hsieh et al., 2010; Jung et al., 2006), anxiety (Kang et al., 2004), and inflammation (Yuan et al., 2009). The active pharmacological components of gouteng is rhynchophylline (RH). The pharmacological effects of RH are similar to those of gouteng (Zhou and Zhou, 2010). RH exerts a protective effect on inhibiting N-methyl-D-aspartate and 5-HT2 receptor–mediated neurotoxicity during ischemia. It also affects the levels of 5-HT in the cortex, striatum, hippocampus, and hypothalamus (Hsu et al., 2012). The anti-depressive-like effect of RH is worthy of study.

BDNF and CREB are associated with numerous psychiatric disorders, including treatment of mood disorders such as depression (Rasmusson et al., 2002). BDNF regulation is affected by increasing neuronal activation followed by CREB activation. Therefore, the two factors are considered to regulate neuronal components (Siuciak et al., 1997). Whether BDNF and CREB signaling plays a role in the anti-depressive effect of RH needs to be investigated.

CUMS has been widely used to induce depression in animals. It is considered an appropriate model of the causes of human depression and is widely used in depressive research (Maccari et al., 2001; Mo et al., 2014; Yu et al., 2014). The depressive symptoms of CUMS mice include loss of pleasure and lack of interest in activities (Willner et al., 1992). During experiments, stress is induced in mice by manipulating the environment, such as by tilting the cage, crowding, water deprivation, fasting, and day–night reversal (Willner et al., 1987). The OFT is used to assess mice's rearing and grooming because CUMS mice exhibit reduced frequencies of the two behaviors (Gould et al., 2009). The FST (Porsolt et al., 1977) and TST (Steru et al., 1985) are used to observe mice's immobility time.

Therefore, CUMS model was used to examine whether RH would exert anti-depressive effect by analyzing mouse behaviors in an OFT, FST, and TST. The level of 5-HT and the expressions of CREB and BDNF detected in the cortex and hippocampus were aimed to investigate the anti-depressive mechanism of RH.