Bupleurum — Benefits Deep Dive
Bupleurum root, chai hu, is one of the pillars of Chinese and Japanese herbal medicine. It anchors several of the most-prescribed classical formulas, its saikosaponins have generated hundreds of laboratory papers, and its traditional role as a herb that "soothes the liver" has made it a favourite subject of research on liver disease and on mood. It also carries one of the clearest safety signals of any herbal formula: the Japanese formula sho-saiko-to is the herbal medicine most often reported as a cause of drug-induced interstitial pneumonia.
These four pages separate those strands. In short: the human trials all tested multi-herb formulas, never bupleurum alone; the reviewers who pooled those trials rated them low quality with a high risk of bias; the "liver-protecting" evidence is mostly from mice and cell culture, and the same compounds are toxic to the liver at high doses; and the lung reports are real, sometimes fatal, and attached to a formula that contains skullcap and licorice as well as bupleurum. Each page reports what the abstracts say, with the study type named every time.
Deep-Dive Articles
Sho-Saiko-To and Interstitial Pneumonia
The safety record that defines this herb in Japan: 73 published pneumonitis cases led by sho-saiko-to, a national database signal on the scale of some cancer drugs, a regulator's warning against combining it with interferon, and the open question of which of its seven herbs is responsible.
Read the deep dive →Saikosaponins and the Liver
The "liver herb" examined in both directions: fatty-liver and fibrosis results in mice, hepatitis B formula trials that beat nothing against placebo, and reviews that list the same saikosaponins among the herb's liver toxins at high or accumulated doses.
Read the deep dive →Xiao Yao San and Mood Research
Fifty-five randomized trials of bupleurum formulas for depression, pooled: what the numbers showed, why the reviewers still called the evidence low quality, and what the mouse work on saikosaponins and brain inflammation does and does not add.
Read the deep dive →Chai Hu in Traditional Chinese Medicine
Two thousand years of use explained in plain language: the formulas built around chai hu, what "soothing the liver" and "harmonizing" mean, which species count as the real herb, why species confusion matters for safety, and how a Han-dynasty decoction became a Japanese prescription drug.
Read the deep dive →Table of Contents
- Deep-Dive Articles
- The Evidence, in One Page
- Evidence Ledger at a Glance
- Who the Research Raises Concerns For
- What Nobody Knows Yet
- How to Read These Pages
- One Herb, Many Names
- Key Research: Sho-Saiko-To and the Lungs
- Key Research: The Liver, Protection and Injury
- Key Research: Mood and the Brain
- Key Research: Chemistry, Tradition and Other Lab Work
- External Resources
- Connections
The Evidence, in One Page
If you read nothing else in this section, read this.
Bupleurum is studied mostly as part of formulas. Xiao chai hu tang (sho-saiko-to in Japan) contains seven herbs; xiao yao san contains eight. When a trial reports that "a bupleurum formula" helped, it cannot say whether bupleurum did anything at all. The 2020 depression meta-analysis is explicit that it studied "Bupleurum chinense herbal formula," not the root.
The trials are many but weak. The depression review pooled 55 comparisons and found the formulas did better on the Hamilton depression scale, but rated the evidence "low quality and at risk of bias," with very high heterogeneity (the trials disagreed with each other far more than chance would explain). The hepatitis B review found one good-quality trial among 16, and against placebo the formula made no difference to viral clearance or liver tests.
The laboratory work is broad. Saikosaponins reduce inflammation, protect the liver, slow cancer-cell growth and change depression-like behaviour in mice and cell culture. A 2018 review also describes "contradictory roles" in cell death, oxidative stress and liver fibrosis, and reports overdose and accumulation liver toxicity.
The safety record is specific. Sho-saiko-to tops the list of Japanese herbal medicines reported as causing pneumonitis, a minority of cases were fatal, and Japan's regulator carried a warning against combining it with interferon. Liver injury has been reported with the formula and with chai hu. A 2000 Lancet review lists reduced prednisolone blood levels with the formula.
Evidence Ledger at a Glance
- Depression (formulas, human RCTs): positive pooled result; low-quality, high-bias trials, mostly from China.
- Chronic hepatitis B (xiao chai hu tang, human RCTs): better with antivirals than antivirals alone in poor-quality trials; no different from placebo.
- Fatty liver (saikosaponin d): mice and cultured liver cells only.
- Liver fibrosis (sho-saiko-to): animal studies only, per a 2002 review.
- Colitis (saikosaponin a): mice only.
- Cancer (saikosaponin d): cell culture and animals only.
- Interstitial pneumonia (sho-saiko-to): human case series and national pharmacovigilance data; regulatory warning with interferon.
- Liver injury (chai hu, xiao chai hu tang): human case reports with causality assessed in a 2015 compilation; dose-related toxicity in research.
Who the Research Raises Concerns For
Based on the reports summarized in these four pages, the research raises concerns mainly for:
- People receiving interferon, the combination named in Japan's regulatory warning about interstitial pneumonia.
- Older adults; the Japanese adverse-event analysis found the lung signal rose with age, and the case-series patients averaged 63.
- People with existing liver disease, who were the main users of sho-saiko-to in Japan and in whom liver-injury reports are hardest to interpret.
- People on prescription drugs, given the reported prednisolone interaction and saikosaponin d's effects on drug-metabolizing enzymes in research.
- Anyone in the first three months of taking sho-saiko-to or related formulas, the window in which 89% of the published pneumonitis cases began.
Decisions about herbal formulas and medicines belong with a clinician who knows a person's full medication list.
What Nobody Knows Yet
- Whether bupleurum root on its own does anything measurable in people for any condition.
- Which of sho-saiko-to's seven herbs triggers the lung reaction; the 2017 case review points to skullcap and licorice as common ingredients of the implicated formulas, and a 2022 case report names bupleurum and skullcap as the suspects (Internal Medicine, 2022).
- How much saikosaponin reaches the body by mouth; a 2021 review calls the oral bioavailability of saikosaponin d "still controversial."
- The dose at which liver protection seen in animals turns into liver toxicity.
- Whether the depression results would survive well-blinded, independent, placebo-controlled trials.
- How much of the market is mixed or substituted species; a 2026 review describes confusion between B. marginatum and B. chinense.
How to Read These Pages
Every claim on the four deep dives is labelled by the kind of study behind it, because the kind of study decides how much it can tell you:
- Cell culture (in vitro): a compound added to cells in a dish. Useful for finding mechanisms; doses and conditions often differ from anything a person would experience.
- Animal studies: usually mice or rats, often with a disease induced by diet, chemicals or surgery. Closer to life than a dish, still not people.
- Randomized controlled trials: people assigned by chance to a treatment or a comparison. The strongest single design, but only if well run, blinded and large enough.
- Systematic reviews and meta-analyses: all the trials on a question gathered and, where possible, pooled. Their value depends on the quality of the trials inside them, which is why the reviewers' own quality ratings are quoted.
- Case reports, case series and pharmacovigilance databases: records of harms in real patients. They cannot give a rate, but they are how rare and serious reactions are first recognized.
For bupleurum, the benefit evidence sits mostly in the first two categories and in low-quality formula trials, while the harm evidence sits mostly in the last. That asymmetry is common in herbal medicine and is part of what these pages try to make visible.
One Herb, Many Names
Searching for bupleurum research means searching under several names. Chai hu is the Chinese name; saiko is the Japanese reading used in Kampo; Radix Bupleuri or Bupleuri Radix is the pharmacopoeial Latin. The formula xiao chai hu tang is spelled Xiaochaihu Tang in some papers and appears in Japanese as sho-saiko-to, shosaikoto or syo-saiko-to. Xiao yao san appears as Xiaoyaosan, and chai hu shu gan san as Chaihu Shugan San. The compounds appear as saikosaponin a, b2, c and d, sometimes abbreviated SSa, SSb2, SSc and SSd. The PubMed searches linked further down this page use several of these spellings.
Key Research: Sho-Saiko-To and the Lungs
- Enomoto Y Md, Nakamura Y Md PhD, Enomoto N Md PhD, et al. Japanese herbal medicine-induced pneumonitis: A review of 73 patients. Respiratory investigation. 2017;55(2):138-144. PubMed PMID: 28274529
- Matsumoto K, Nakao S, Hasegawa S, et al. Analysis of drug-induced interstitial lung disease using the Japanese Adverse Drug Event Report database. SAGE open medicine. 2020;8:2050312120918264. PubMed PMID: 32528682
- Nakayama M, Bando M, Hosono T, et al. [Evaluation of the drug lymphocyte stimulation test (DLST) with shosaikoto]. Arerugi = [Allergy]. 2007;56(11):1384-9. PubMed PMID: 18059152
Key Research: The Liver, Protection and Injury
- Qin XK, Li P, Han M, et al. [Xiaochaihu Tang for treatment of chronic hepatitis B: a systematic review of randomized trials]. Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine. 2010;8(4):312-20. PubMed PMID: 20388470
- Qi FH, Wang ZX, Cai PP, et al. Traditional Chinese medicine and related active compounds: a review of their role on hepatitis B virus infection. Drug discoveries & therapeutics. 2013;7(6):212-24. PubMed PMID: 24423652
- Stickel F, Brinkhaus B, Krähmer N, et al. Antifibrotic properties of botanicals in chronic liver disease. Hepato-gastroenterology. 2002;49(46):1102-8. PubMed PMID: 12143213
- Takahashi Y, Soejima Y, Kumagai A, et al. Japanese herbal medicines shosaikoto, inchinkoto, and juzentaihoto inhibit high-fat diet-induced nonalcoholic steatohepatitis in db/db mice. Pathology international. 2014;64(10):490-8. PubMed PMID: 25229199
- Gu Y, Duan S, Ding M, et al. Saikosaponin D attenuates metabolic associated fatty liver disease by coordinately tuning PPARα and INSIG/SREBP1c pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2022;103:154219. PubMed PMID: 35691075
- Stickel F, Egerer G, Seitz HK. Hepatotoxicity of botanicals. Public health nutrition. 2000;3(2):113-24. PubMed PMID: 10948380
- Teschke R. Traditional Chinese Medicine Induced Liver Injury. Journal of clinical and translational hepatology. 2014;2(2):80-94. PubMed PMID: 26357619
- Teschke R, Zhang L, Long H, et al. Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases. Annals of hepatology. 2015;14(1):7-19. PubMed PMID: 25536637
- Li X, Li X, Huang N, et al. A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;50:73-87. PubMed PMID: 30466994
- Zhou P, Shi W, He XY, et al. Saikosaponin D: review on the antitumour effects, toxicity and pharmacokinetics. Pharmaceutical biology. 2021;59(1):1480-1489. PubMed PMID: 34714209
- Fugh-Berman A. Herb-drug interactions. Lancet (London, England). 2000;355(9198):134-8. PubMed PMID: 10675182
Key Research: Mood and the Brain
- Yang L, Shergis JL, Di YM, et al. Managing Depression with Bupleurum chinense Herbal Formula: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of alternative and complementary medicine (New York, N.Y.). 2020;26(1):8-24. PubMed PMID: 31328996
- Ran S, Peng R, Guo Q, et al. Bupleurum in Treatment of Depression Disorder: A Comprehensive Review. Pharmaceuticals (Basel, Switzerland). 2024;17(4). PubMed PMID: 38675471
- Wang X, Li S, Yu J, et al. Saikosaponin B2 ameliorates depression-induced microglia activation by inhibiting ferroptosis-mediated neuroinflammation and ER stress. Journal of ethnopharmacology. 2023;316:116729. PubMed PMID: 37277081
Key Research: Chemistry, Tradition and Other Lab Work
- Ashour ML, Wink M. Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action. The Journal of pharmacy and pharmacology. 2011;63(3):305-21. PubMed PMID: 21749378
- Teng L, Guo X, Ma Y, et al. A comprehensive review on traditional and modern research of the genus Bupleurum (Bupleurum L., Apiaceae) in recent 10 years. Journal of ethnopharmacology. 2023;306:116129. PubMed PMID: 36638855
- Sun P, Li Y, Wei S, et al. Pharmacological Effects and Chemical Constituents of Bupleurum. Mini reviews in medicinal chemistry. 2019;19(1):34-55. PubMed PMID: 29956627
- Tian Y, Guo J, Jiang X, et al. Exploring the Therapeutic Potential of Bupleurum in Medical Treatment: A Comprehensive Overview. Pharmaceuticals (Basel, Switzerland). 2025;18(9). PubMed PMID: 41011202
- Yang X, Yu Z, Yang M, et al. Bupleurum marginatum Wall.: A comprehensive review of the traditional uses, phytochemistry, pharmacology, and quality control. Journal of ethnopharmacology. 2026;365:121575. PubMed PMID: 41881320
- Zheng Q, Wang T, Wang S, et al. The anti-inflammatory effects of saponins from natural herbs. Pharmacology & therapeutics. 2025;269:108827. PubMed PMID: 40015518
- Yang X, Yang J, Wang A, et al. Saikosaponin A ameliorates ulcerative colitis by targeting the CH25H/25-OHC axis to inhibit NLRP3 inflammasome in macrophages. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2025;143:156844. PubMed PMID: 40414048
- Huang M, Yan Y, Deng Z, et al. Saikosaponin A and D attenuate skeletal muscle atrophy in chronic kidney disease by reducing oxidative stress through activation of PI3K/AKT/Nrf2 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2023;114:154766. PubMed PMID: 37002971
- Inoue M. Shosaikoto as a potential antiatherosclerotic agent. Drug news & perspectives. 2000;13(7):407-12. PubMed PMID: 12937613
PubMed Topic Searches
External Resources
- PMDA Pharmaceuticals and Medical Devices Safety Information No. 250 (2008) — Japan's regulator on interstitial pneumonia with interferon, including the sho-saiko-to label wording.
- Acute hepatitis induced by xiao-chai-hu-tang (Journal of the Chinese Medical Association, 2006) — a case report that also lists the formula's seven herbs.
- Research progress on xiaoyaosan in depression (Frontiers in Pharmacology, 2022) — source for the formula's history and eight ingredients.
Connections
- Heart, Liver and Metabolic Herbs — the parent category
- Bupleurum (Chai Hu) — the main topic page
- Sho-Saiko-To and Interstitial Pneumonia
- Saikosaponins and the Liver
- Xiao Yao San and Mood Research
- Chai Hu in Traditional Chinese Medicine
- Milk Thistle — the Western liver herb
- Schisandra — another Chinese herb studied for the liver
- Baicalin and Chinese Skullcap Research — a sho-saiko-to ingredient
- Licorice — in nearly every bupleurum formula
- He Shou Wu: Liver Hepatotoxicity Warning — another Chinese herb with liver-injury reports
- St John's Wort — the best-trialled herb for depression
- Interstitial Lung Disease
- Hepatitis C — the interferon era of the lung warnings