Sansoninto (Suan Zao Ren Tang) for behavioral abnormalities due to social isolation stress

A study entitled “Sansoninto, a traditional herbal medicine, ameliorates behavioral abnormalities and down-regulation of early growth response-1 expression in mice exposed to social isolation stress” by researchers from the University of Toyoma and Setsunan University in Japan was published in the Journal of Traditional and Complementary Medicine in 2017.

The study aimed to study the effects of Sansoninto on psychiatric symptoms related to attention-deficit/hyperactivity disorder (ADHD) on mice exposed to social isolation.

Sansoninto (SST) or Suan Zao Ren Tang

This formula is commonly used for insomnia, anxiety, irritability, poor memory, and fatigue.

  • Suan Zao Ren zizyphi spinosae
  • Fu Ling poria
  • Zhi Mu anemarrhenae radix
  • Chuan Xiong ligustici radix
  • Gan Cao glycyrrhizae radix

How was this study performed?

Four-week old mice were housed in groups or socially isolated. The socially isolated mice were then assigned to 3 different groups: 1. Vehicle control group, 2. Lower-dosage (800mg/kg) of SST, and 3. Higher-dosage (2400mg/kg) of SST.

Two weeks in, the socially isolated mice in the lower- and higher-dosage groups were administered SST once daily, while the socially isolated vehicle control group and the grouped mice were given water.

What were the results?

SST increased sociability.

Five weeks in, the Sociability Test was performed. It measured the amount of interaction the mice made with a stranger mouse’s cage compared to an empty cage.

In the training trial, the authors state the socially isolated mice showed a dysfunction in social-interaction behavior because there was “no difference in the exploratory time for stranger and empty cages.”

The test trial showed that for the “low- and high-dose SST treated mice, exploratory time of the stranger cage was significantly greater than that of the empty.”

SST increased attention-related behavior.

Six weeks in, the Water-Finding Test was performed, measuring how long it took the mice to find and drink water after being deprived for 24 hours. This measured attention-related behavior.

The socially-isolated mice had higher drinking latency, meaning it took longer for them to reach the water. Results showed socially-isolated mice given high-dose SST had reduced drinking latency, while the low-dose SST had no effect.

SST slightly decreased fear memory deficits.

Seven weeks in, the Fear-Conditioning Test was performed. Fear condition is a form of learning in which a neutral/conditional stimulus is associated with an aversive stimulus. This eventually results in a fearful expression to the neutral/conditional stimulus.

In this study, the neutral stimuli were contextual (a chamber for the mice to explore) and auditory (an acoustic tone). The aversive stimulus was electrical foot shocks. The fearful expression analyzed was freezing.

The results showed that the socially isolated mice had deficits in fear-memory, determined by shorter freezing times when exposed to the neutral stimuli. SST administration only slightly increased the freezing time.

“SST reversed the stress-induced down-regulation of Egr-1 expression in the brain.”

The authors then studied the levels of Egr-1 in the hippocampus and frontal cortex. Egr-1 (early growth response 1) plays a role in synaptic plasticity, which makes it closely related to learning and memory.

The socially-isolated mice had decreased levels of Egr-1 in the hippocampus and frontal cortex. Those given high-dose SST showed restored brain levels of Egr-1.

Are there possible flaws in this study?

A couple of points to note about this study is 1. The number of mice used doesn’t appear to be indicated, and 2. the dosages of SST administered in the mice were 3 and 10 times stronger than used in typical human subjects.


Overall, the authors conclude that SST may be used to treat “some symptoms of patients with developmental disorders such as ADHD.”

Study Referenced: Fujiwara, H., Tsushima, R., Okada, R., Awale, S., Araki, R., Yabe, T., & Matsumoto, K. (2017). Sansoninto, a traditional herbal medicine, ameliorates behavioral abnormalities and down-regulation of early growth response-1 expression in mice exposed to social isolation stress. Journal of Traditional and Complementary Medicine,8(1), 81-88. doi:10.1016/j.jtcme.2017.03.004

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