Anxiolytic and antidepressants’ effect of Crataegus pinnatifida (Shan Zha): biochemical mechanisms

Keren Nitzan, Dekel David, Motty Franko, Roni Toledano, Sharon Fidelman, Yaarit Simchon Tenenbaum, Maya Blonder, Shir Armoza-Eilat, Alon Shamir, Moshe Rehavi, Yair Ben-chaim, Ravid Doron

Research output: Contribution to journalArticlepeer-review


Depression and anxiety disorders are highly prevalent. Selective serotonin reuptake inhibitors (SSRIs) are the current first-line treatment for depression, but they have pronounced limitations. Traditional Chinese medicine can serve as a safe and effective alternative to conventional drugs, particularly since many herbal remedies have already been approved for human use as food additives, making the transition from bench to bedside more efficient. We previously demonstrated that a novel herbal treatment (NHT) induces anxiolytic- and antidepressant-like effects. NHT consists of four herbs: Crataegus pinnatifida (Shan Zha), Triticum aestivum (Fu Xiao Mai), Lilium brownii (Baihe), and the fruit of Ziziphus jujuba (Da Zao). In the current study, we examined the antidepressant-like and anxiolytic-like activities of each individual herb on stressed mice and compared those to the effects of NHT and escitalopram. We show here that Shan Zha is sufficient to produce an anxiolytic and antidepressant-like effect similar to NHT or the escitalopram through activation of 5-HT1A receptor and an elevation in BDNF levels in the hippocampus and Pre-frontal cortex (PFC). Chronic treatment with Shan Zha did not alter serotonin transporter levels in the PFC, as opposed to escitalopram treatment. These results were confirmed in vitro, as none of the herbs blocked SERT activity in Xenopus oocytes. Notably, Shan Zha is sold as a nutritional supplement; thus, its transition to clinical trials can be easier. Once its efficacy and safety are substantiated, Shan Zha may serve as an alternative to conventional antidepressants.

Original languageEnglish
Article number208
JournalTranslational Psychiatry
Issue number1
StatePublished - 19 May 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).


  • Animals
  • Anti-Anxiety Agents/pharmacology
  • Antidepressive Agents/pharmacology
  • Crataegus
  • Mice
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors/pharmacology


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