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This TCM formula alters brain pathways to alleviate anxiety-like behavior

According to the American Psychological Association (APA), anxiety is “an emotion characterized by feelings of tension, worried thoughts and physical changes like increased blood pressure.” Experiencing anxiety occasionally is a normal part of life and may even be useful in certain situations, but some people deal with feelings of anxiety frequently. Those with anxiety disorders suffer from intense and persistent worry and fear that could disrupt their day-to-day activities.

There are many signs and symptoms of anxiety. The most notable of which include feeling nervous and restless, hyperventilating, sweating, having trouble concentrating or thinking and having a sense of impending danger or doom. Although experts still don’t fully understand what causes anxiety disorders, traumatic events often trigger symptoms, especially in people who are prone to anxiety.

But in a recent study, researchers at Beijing University of Chinese Medicine found that a traditional Chinese medicine (TCM) formula known as xiao yao san (XYS) can alleviate anxiety-like behaviors in rats. They reported that XYS exerts its effects by altering the expression of genes involved in the c-Jun N-terminal kinase (JNK) signaling pathway. This pathway plays a role in the induction of chronic stress.

The researchers reported their findings in an article published in the journal Biological and Pharmaceutical Bulletin.

XYS is an effective treatment for anxiety

Xiao yao san means happy, carefree powder in TCM. Its most well-known use is as a treatment for menopausal anxiety and depression. Some reports also suggest that when combined with acupuncture and moxibustion, XYS relieves anxiety and depression following procedures such as placenta transplantation and test tube fertilization.


According to TCM records, XYS is composed of eight different medicinal herbs, namely, Bupleurum chinense (Chinese thorow wax, chai hu), Angelica sinensis (female ginseng, dang gui), Paeonia lactiflora (white peony, bai shao), Atractylodes macrocephala (white atractylodes, bai zhu), Poria cocos (poria mushroom, fu ling), Zingiber officinale (ginger, sheng jiang), Mentha piperita (Chinese peppermint, bo he) and Glycyrrhiza uralensis (licorice, gan cao). Several clinical trials have found that the combination of these TCM herbs is more powerful than modern antidepressants.

In their previous study, the researchers reported that XYS exerts anxiolytic effects in rats subjected to two weeks of chronic immobilization stress (CIS). They hypothesized that these effects may be attributed to the influence of XYS on JNK, a stress-activated enzyme. Different types of stressors are known to activate the JNK signaling pathway, which can ultimately lead to cell damage and apoptosis.

To test their hypothesis, the researchers employed 40 rats and divided them into five groups: the control group, which received deionized water; the model group, which also received deionized water; the SP600125 group, which underwent surgery; the per se group, which also underwent surgery; and the XYS group, which received 3.9 g/kg XYS daily.

The researchers injected 1 percent dimethyl sulfoxide (DMSO) citrate buffer solution and SP600125 separately and bilaterally into the rats (via the brain’s ventricular system) in the two surgery groups. They then subjected all the groups except for the control to 14 days of CIS. (Related: Relieve anxiety with essential oils.)

On Day 15, the researchers measured the bodyweight of the rats and subjected the animals to the elevated plus maze (EPM) and novelty suppressed feeding (NSF) tests. They then examined JNK signaling pathway indices, including phosphorylated JNK (P-JNK), JNK, phosphorylated c-Jun (P-c-Jun) and cytochrome C (cyt-C). The release of cyt-C into the cytosol of cells is said to trigger programmed cell death, or apoptosis.

Based on body weight and behavioral analyses of the model rats, the researchers confirmed the successful induction of anxiety-like behaviors in the animals. They reported that CIS altered the expression of P-JNK, JNK and P-c-Jun in the hippocampus of the model rats. However, treatment with XYS and SP600125, a known JNK inhibitor, for 14 days changed rat body weight and behaviors, along with P-JNK, JNK and P-c-Jun expression levels, for the better. Both XYS and SP600125 had no effect on cyt-C.

These results suggest that XYS reduces anxiety-like behaviors induced by CIS by inhibiting JNK signaling in the hippocampus.

Sources include:

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