Journal name: Neuropsychiatric Disease and Treatment Article Designation: Review Year: 2016 Volume: 12 Neuropsychiatric Disease and Treatment Dovepress Running head verso: Feng et al Running head recto: Chinese herbal formulas as antidepressants open access to scientific and medical research DOI: http://dx.doi.org/10.2147/NDT.S114560 Open Access Full Text Article REVIEW Nine traditional Chinese herbal formulas for the treatment of depression: an ethnopharmacology, phytochemistry, and pharmacology review Dan-dan Feng Abstract: Depression is a major mental disorder, and is currently recognized as the Tao Tang second-leading cause of disability worldwide. However, the therapeutic effect of antidepressants Xiang-ping Lin remains unsatisfactory. For centuries, Chinese herbal formulas (CHFs) have been widely used in Zhao-yu Yang the treatment of depression, achieving better therapeutic effects than placebo and having fewer Shu Yang side effects than conventional antidepressants. Here, we review the ethnopharmacology, phy- Zi-an Xia tochemistry, and pharmacology studies of nine common CHFs: “banxia houpo” decoction, “chaihu shugansan”, “ganmaidazao” decoction, “kaixinsan”, “shuganjieyu” capsules, “sinisan”, Yun Wang “wuling” capsules, “xiaoyaosan”, and “yueju”. Eight clinical trials and seven meta-analyses have Piao Zheng supported the theory that CHFs are effective treatments for depression, decreasing Hamilton Yang Wang Depression Scale scores and showing few adverse effects. Evidence from 75 preclinical studies Chun-hu Zhang has also elucidated the multitarget and multipathway mechanisms underlying the antidepres- Laboratory of Ethnopharmacology, sant effect of the nine CHFs. Decoctions, capsules, and pills all showed antidepressant effects, Institute of Integrated Traditional ranked in descending order of efficacy. According to traditional Chinese medicine theory, these Chinese and Western Medicine, Xiangya Hospital, Central South CHFs have flexible compatibility and mainly act by soothing the liver and relieving depression. University, Changsha, People’s This review highlights the effective treatment choices and candidate compounds for patients, Republic of China practitioners, and researchers in the field of traditional Chinese medicine. In summary, the current evidence supports the efficacy of CHFs in the treatment of depression, but additional large-scale randomized controlled clinical trials and sophisticated pharmacology studies should be performed. Keywords: traditional Chinese medicine, Chinese herbal formula, antidepressant, phytochemistry, pharmacological bioactivity Introduction Depression is a common chronic mental health problem,1–3 with a global prevalence of 4.4%–5%.4 It is characterized by a loss of interest in daily activities and feelings of low self-worth, disappointment, sadness, and hopelessness. According to the Global Burden of Disease Study 2013, major depressive disorder (MDD) is the second-leading Correspondence: Yang Wang; 5 Chun-hu Zhang global cause of years lived with disability. The population-attributable risk for depres- Laboratory of Ethnopharmacology, sion and all-cause death is 12.7%, and for depression and suicide it is 11.2%.6 The Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, economic burden of individuals with MDD in the US increased by 21.5% between Central South University, 87 Xiangya 2005 and 2010 (from $173.2 billion to $210.5 billion, inflation-adjusted).7 A recent Road, Changsha, Hunan 410008, meta-analysis of the prevalence of depressive symptoms in older Chinese adults from People’s Republic of China Tel +86 731 8432 7122 1987 to 2012 reported an overall prevalence of 23.6%.8–10 Fax +86 731 8432 8386 Conventional antidepressants, such as selective reuptake inhibitors of serotonin Email [email protected]; [email protected] (5-HT) or norepinephrine (NE), monoamine oxidase inhibitors, tricyclic antidepressants, submit your manuscript | www.dovepress.com Neuropsychiatric Disease and Treatment 2016:12 2387–2402 2387 Dovepress © 2016 Feng et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/NDT.S114560 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Feng et al Dovepress or N-methyl-D-aspartate receptor (NMDAR) antagonists, fail effective and classical CHFs available to date, which is a to help at least 40% of depressed patients.11 Existing treat- major impediment to the use of CHFs in modern medical ments for MDD usually take several weeks or months to practice. Here, we introduce nine common and important achieve their therapeutic effects.12,13 During this lag period, antidepressant CHFs with regard to their source, composition, patients continue to have depressive symptoms and risk self- chemical constituents, indications, TCM and antidepressant harm.12 Despite this, there has been little notable progress effects, mechanisms, and side effects from a review of ethno- in the development of drugs to treat depression over the last pharmacology, phytochemistry, and pharmacology studies. few decades.14 Scientists are seeking new, improved thera- peutic approaches to deal with depression, and the drive to Materials and methods develop next-generation drugs with improved safety profiles Available references that recorded the use of the nine CHFs has intensified.15,16 in depression were analyzed via PubMed and Web of Science Traditional Chinese medicine (TCM) is attracting increas- (from inception to June 2, 2016). Further comprehensive ing attention as a method for meeting the demands for higher resources were searched for each CHF in PubMed, Web remission rate, faster onset, persistent antidepressant action, of Science, Science Direct, China National Knowledge and fewer adverse effects.17,18 TCM is one of the oldest Infrastructure, Wanfang Data, Chinese Scientific Journals medical systems in the world, and includes Chinese herbal Full-Text Database, and Google Scholar. Relevant TCM medicine, acupuncture, and massage. Herbal medicine has information was from http://www.tcmwiki.com/w/TCM_ been used for the treatment of depression in People’s Repub- Wiki and the Pharmacopoeia of the People’s Republic of lic of China for centuries, and is becoming more frequently China (2015). used in Western countries. “Yuzheng”, meaning “depression Database searches included the following keywords: syndrome”, first appeared in the Ming Dynasty Tuan Yu’s (“depression” or “depressive disorder” or “antidepres- Yi Xue Zheng Zhuan, although discussions about depression sant”) and (“Chinese prescription” or “Chinese formula” or can be traced back to Huangdi Neijing (The Inner Canon of “Chinese decoction” or “Chinese herbal formula” or each Huangdi).19 Then, in the Eastern Han Dynasty, Jingui Yaolue CHF by name). The keywords were modified for use with (Synopsis of Prescriptions of the Golden Chamber) first different databases. Full-text articles in English or Chinese described the symptoms of lily disease, globus hystericus, and were included. “zangzao” syndrome, which are thought to belong to depres- sion syndrome; this document also recorded “banxia houpo” Results decoction (BHD) and “ganmaidazao” decoction (GMDZD), The source, TCM effects, and syndromes of the nine most both used very frequently for depression.20 commonly prescribed CHFs for treating depression are pro- Interestingly, modern TCM for the treatment of depres- vided in Table 1. Photographs of each formula are presented sion has started to be integrated into evidence-based medi- in Figure 1. All correspond to the typical principles of TCM cine. A PubMed search revealed that the first randomized treatment of yuzheng according to their effects and Chinese- controlled trial (RCT) of Chinese herbal formulas (CHFs) syndrome patterns, including soothing the liver, relieving in depression investigated “gengnianle”, a defined formula depression, promoting the circulation of chi, and resolving of Chinese medicinal herbs for the relief of perimenopausal phlegm. Importantly, we found a considerable amount of depression.21 The earliest herbal pharmacology study evidence-based research for most of the CHFs we examined, investigated BHD.22 A systematic review of the treatment meaning the results can be used to guide clinical practice and of menopausal symptoms started with the study of “erxian” research in related fields. decoction,23 and the first meta-analysis was conducted on the clinical effects of “chaihu shugansan” (CSS).24 Further Banxia houpo decoction studies showed that liver depression and chi stagnation were Composition the main syndromes,25 and that the main treatment principle is Banxia (Pinellia rhizome) 12 g, “fuling” (Poria) 12 g, houpo the regulation of chi, relief of depression, and empathy.26 (Magnolia officinalis cortex) 9 g, “shengjiang” (Zingiber Following Synopsis of Prescriptions of the Golden officinale rhizome) 9 g, “suye” (Perilla folium) 6 g. Chamber, numerous antidepressant CHFs were recorded in ancient books. Although some systematic reviews