Bupleurum

What Is Bupleurum?

Bupleurum root (Chai Hu) is one of the most important herbs in traditional Chinese medicine, used chiefly for the liver and as the principal (“monarch”) herb in classic formulas such as Sho-saiko-to. Its best-characterised modern evidence is anti-inflammatory and hepatoprotective/antifibrotic, driven by its triterpenoid saikosaponins.

Its Western reputation as a broad-spectrum antiviral is overstated: those claims trace mostly to quercetin and rutin — flavonoids common to many plants — and to decades-old in-vitro assays. The one reasonably specific antiviral signal is against hepatitis B, and there the active compound is saikosaponin c, not the abundant a/d forms. Importantly, the same saikosaponins that drive its activity are dose-dependently hepatotoxic and cardiotoxic, and the bupleurum formula Sho-saiko-to is the leading cause of herb-induced interstitial pneumonitis in Japan — see Safety.

What Is Bupleurum Used For?

Bupleurum is used mainly as a liver herb and a bitter, and as a component of TCM formulas. Its Western reputation as an antiviral runs ahead of the single-herb evidence (see the research section below). Traditional Chinese medicine has a wide range of uses for bupleurum, mainly involving its interaction with the liver. It’s a common addition to many herbal formulas for a wide range of conditions.

Traditional Uses

Western Herbal Medicine

It has been used for colds and flu, and inflammation throughout Europe in the form of a herbal tea or decoction ^{34Reference 34Ashour et al. · 2014In vitroAnti-infective and cytotoxic properties of Bupleurum marginatum — in vitroView study →}. Some of its less common traditional uses include hepatitis, cancer, microbial infections, and fever associated with malaria ^{39,41,42Reference 39Zhou · 2011Encyclopedia of Traditional Chinese Medicines, VolReference 41Wu · 2005An Illustrated Chinese Materia MedicaReference 42Fundukian · 2009The Gale Encyclopedia of Alternative Medicine (3rd ed.)}.

Traditional Chinese Medicine

Bupleurum root is one of the most important herbs used in Chinese herbalism. It’s used to relieve liver tension and digestive disturbances. It’s detoxificating and antimicrobial as well. ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

Bupleurum is often combined with other herbs to clear stagnation anywhere in the body. It’s used to relieve muscle spasms, lumps, and bleeding due to heat, and menstrual irregularities. ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

The essential oil of Bupleurum root is used to relieve surface heat. ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

This herb is rarely used alone, but is very common in combinations. It’s usually added to improve the detoxification of a target organ, and regulate the flow of Qi through the body. ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

Bupleurum is commonly used in traditional Chinese medicine to detoxify various target organs (depending on the other herbs in combination), relieve liver tension, and regulate the flow of Qi throughout the body ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

Pinyin

Cháí Hú

Energy

Cold ^{46,47Reference 46Bone · 2003A Clinical Guide to Blending Liquid HerbsReference 47Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.)} (Some list as slightly warm ^{41Reference 41Wu · 2005An Illustrated Chinese Materia Medica}).

Taste

Bitter ^{46,47Reference 46Bone · 2003A Clinical Guide to Blending Liquid HerbsReference 47Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.)} (Some list this as sweet and pungent ^{41Reference 41Wu · 2005An Illustrated Chinese Materia Medica}).

Channels

Gallbladder, liver, pericardium, triple burner ^{41Reference 41Wu · 2005An Illustrated Chinese Materia Medica}.

Actions

Resolves lesser yang disorders to reduce fever, spreads liver Qi to relieve stagnation, raises center Qi, regulates gastrointestinal and liver functions ^{46,47Reference 46Bone · 2003A Clinical Guide to Blending Liquid HerbsReference 47Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.)}

Indications

Liver tension, digestive disturbances, stagnation, muscle spasms, bleeding due to heat, menstrual irregularities, common cold, alternating chills and fever, malaria, chest and rib-side descending pain, sinking of clear Qi (lack of strength, chronic diarrhea) ^{40,47Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic HerbsReference 47Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.)}.

Cautions & Safety

May cause rapid detoxification, with symptoms such as headaches and anger. In situations of severe toxicity skin sores may result ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}. Avoid using with tinnitus, deafness, dizziness, or headache caused by fire from yin deficiency and/or hyperactive liver yang ^{41,46Reference 41Wu · 2005An Illustrated Chinese Materia MedicaReference 46Bone · 2003A Clinical Guide to Blending Liquid Herbs}.

Botanical Information

Bupleurum is a member of the Apiaceae or “carrot family” of plants. This family contains roughly 3700 species and 434 genera. It is, in fact, the 16th largest family of plants and contains other medicinal species including Angelica, chervil, coriander, lovage, and the poisonous herb hemlock.

The Bupleurum genus contains about 190 different species. However, Bupleurum falcatum is by far the most common medicinal species in this group.

Harvesting, Collection & Preparation

Mainly cultivated in Hebei, Henan, Liaoning, Shananxi, and Gansu provinces of China, and collected in the spring or autumn ^{41Reference 41Wu · 2005An Illustrated Chinese Materia Medica}.

The root is generally sun-dried and sliced. It can be used raw this way, or fried in wine or vinegar. ^{41Reference 41Wu · 2005An Illustrated Chinese Materia Medica}.

Phytochemistry

The characteristic and most-studied constituents of bupleurum root are the saikosaponins — a family of oleanane-type triterpenoid saponins that are the principal anti-inflammatory, hepatoprotective, antiviral and cytotoxic agents ^{38,34,33Reference 38Hsu et al. · 2004The antiproliferative activity of saponin-enriched fraction from Bupleurum kaoi is through a Fas-dependent apoptotic pathway in human non-small-cell lung cancer A549 cellsReference 34Ashour et al. · 2014In vitroAnti-infective and cytotoxic properties of Bupleurum marginatum — in vitroView study →Reference 33Ashour et al. · 2011ReviewGenus Bupleurum: a review of its phytochemistry, pharmacology and modes of action — reviewView study →}. They are the largest class of secondary metabolites in the root, reported at roughly 2–8% of dry weight (around 7% in some analyses). Of the seven or so saikosaponins identified, saikosaponin a and saikosaponin d are the most abundant and the most pharmacologically active; saikosaponin c is also a major form ^{43,33Reference 43Huang et al. · 2008Characterization and identification of saikosaponins in crude extracts from three Bupleurum species using LC-ESI-MSReference 33Ashour et al. · 2011ReviewGenus Bupleurum: a review of its phytochemistry, pharmacology and modes of action — reviewView study →}.

A second, complementary group is the flavonoids, chiefly quercetin and its glycoside rutin, credited with hepatoprotective and antiviral effects — quercetin and rutin are active against HSV-1, HIV, poliovirus, parainfluenza and respiratory syncytial virus ^{34Reference 34Ashour et al. · 2014In vitroAnti-infective and cytotoxic properties of Bupleurum marginatum — in vitroView study →}. The root also contains aryltetralin lignans, which add antiviral (tubulin-, reverse-transcriptase- and topoisomerase-targeting) and cytotoxic activity, plus coumarins, polysaccharides, polyacetylenes and an essential oil ^{34,44,45Reference 34Ashour et al. · 2014In vitroAnti-infective and cytotoxic properties of Bupleurum marginatum — in vitroView study →Reference 44Ashour et al. · 2012A novel cytotoxic aryltetralin lactone from Bupleurum marginatum (Apiaceae)Reference 45Charlton · 1998Antiviral activity of lignans}.

Constituent Summary

Figures are share of dried root and vary with Bupleurum species, provenance and processing ^{43,33Reference 43Huang et al. · 2008Characterization and identification of saikosaponins in crude extracts from three Bupleurum species using LC-ESI-MSReference 33Ashour et al. · 2011ReviewGenus Bupleurum: a review of its phytochemistry, pharmacology and modes of action — reviewView study →}.

Pharmacology & Research

Bupleurum root has a large but lopsided evidence base: several hundred preclinical papers on its triterpenoid saponins (the saikosaponins), a smaller flavonoid and polysaccharide literature, and almost no human data on the single herb. The one tier of clinical evidence that exists comes from multi-herb Japanese/Chinese formulas in which bupleurum is the principal ingredient — above all Sho-saiko-to (Xiao Chai Hu Tang, TJ-9) — so it cannot be cleanly attributed to bupleurum alone ^{1,3Reference 1Oka et al. · 1995RCTProspective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9) — randomized controlled trialView study →Reference 3Zhang et al. · 2019Meta-analysisXiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B — systematic review and meta-analysisView study →}. The most consistent and mechanistically detailed signals are anti-inflammatory and hepatoprotective/antifibrotic, both driven by saikosaponin a and saikosaponin d acting on NF-κB ^{4,6Reference 4Lu et al. · 2012In vitroSaikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of the NF-κB signaling pathway — in vitroView study →Reference 6Chen et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in rats — animal modelView study →}. The page’s headline framing as a “researched antiviral” overstates a body of work that is almost entirely in-vitro and, for hepatitis B, points to saikosaponin c rather than the abundant a/d forms ^{17,18Reference 17Chiang et al. · 2003In vitroCytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species — in vitroView study →Reference 182019In vitroSaikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis — in vitroView study →}. Two cautions run through the whole literature and are absent from the current page: the same saikosaponins are dose-dependently hepatotoxic, and the bupleurum-containing formula Sho-saiko-to is the leading cause of herb-induced interstitial pneumonitis in Japan ^{11,28Reference 11Li et al. · 2017AnimalSaikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study — animal modelView study →Reference 28Enomoto et al. · 2017ReviewJapanese herbal medicine-induced pneumonitis: a review of 73 patients — reviewView study →}. Most studies use B. chinense, B. scorzonerifolium, B. kaoi or B. yinchowense rather than the B. falcatum named on this page — a species-transfer caveat that applies to nearly every claim below.

0. Evidence by indication

Support is an experimental score I’m building — a composite weighted by study type (human > animal > in vitro > review) and study volume. It’s a beta: a fast way to rank strength of evidence at a glance, not a validated metric, and I’ll keep honing the formula over time. Each indication name links down to its write-up.

Indication	Support	Rests on
Hepatoprotective & antifibrotic	███████░░░ 70%	Replicated rat/mouse CCl₄-fibrosis models (SSd, SSa, SB1) + one formula-level human RCT; but a dual hepatotoxic signal and multi-herb attribution cap it.
Anti-inflammatory	███████░░░ 66%	Consistent NF-κB / iNOS / COX-2 suppression by SSa & SSd across cell and rodent colitis/inflammation models; no single-herb human data.
Anticancer (antiproliferative)	██████░░░░ 56%	Large, coherent in-vitro apoptosis/autophagy literature for SSd across many lines; animal xenografts; no human single-agent data.
Antidepressant & neuroprotective	█████░░░░░ 54%	Growing, consistent rodent chronic-stress data (SSa, SSd, total saikosaponins); entirely preclinical, mostly non-falcatum species.
Antiviral (anti-HBV)	█████░░░░░ 52%	In-vitro anti-HBV for saikosaponin c; broader antiviral claims rest on flavonoids not unique to bupleurum; human data only formula-level and very-low-certainty.
Immunomodulatory	█████░░░░░ 50%	Root polysaccharides activate macrophages via TLR2/4 in vitro and restore immunity in immunosuppressed mice; preclinical only.

1. Hepatoprotective & antifibrotic

This is bupleurum’s strongest efficacy signal, and also its most double-edged. In rats given carbon tetrachloride, saikosaponin-d (1.0–2.0 mg/kg/day) reduced hepatic fibrogenesis and downregulated NF-κB, TNF-α and IL-6 ^{6Reference 6Chen et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in rats — animal modelView study →}; saikosaponin-a (dietary ~0.004%) improved hepatic antioxidant capacity and lowered ALT/AST over eight weeks ^{7Reference 7Wu et al. · 2008AnimalCurcumin or saikosaponin a improves hepatic antioxidant capacity and protects against CCl₄-induced liver injury in rats — animal modelView study →}; and the hydrolysed congener saikosaponin B1 attenuated CCl₄-induced fibrosis via lactate/LDHA-axis signalling in mice ^{8Reference 82026AnimalSaikosaponin B1 alleviates hepatic fibrosis by targeting the LDHA-MCT1/4 axis to inhibit lactate-driven profibrogenic signaling — mouse modelView study →}. Mechanistically the antifibrotic effect is attributed to induction of hepatic stellate-cell apoptosis and modulation of PPARα/SREBP-1c lipid signalling ^{9Reference 92026ReviewThe dual role of saikosaponins in liver disease treatment: a comprehensive review of pharmacology and toxicity — reviewView study →}. At the human level, the only controlled data are for the seven-herb formula Sho-saiko-to, not isolated bupleurum: a 260-patient randomised trial in cirrhosis found a lower five-year cumulative incidence of hepatocellular carcinoma with 7.5 g/day, reaching significance in the HBsAg-negative subgroup ^{1Reference 1Oka et al. · 1995RCTProspective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9) — randomized controlled trialView study →}. The critical counterweight — omitted from the current page — is that these same saikosaponins are dose-dependently hepatotoxic: SSd worsened acetaminophen-induced liver injury in mice by disrupting protective autophagy ^{10Reference 102025AnimalSaikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP-SNARE complex assembly in protective autophagy — mouse modelView study →}, triterpene saponins caused overt liver injury via CYP2E1 induction and oxidative stress ^{11Reference 11Li et al. · 2017AnimalSaikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study — animal modelView study →}, and reviews now frame saikosaponins as having a genuinely dual hepatic role ^{9,14Reference 92026ReviewThe dual role of saikosaponins in liver disease treatment: a comprehensive review of pharmacology and toxicity — reviewView study →Reference 14Li et al. · 2018ReviewA comprehensive review and perspectives on pharmacology and toxicology of saikosaponins — reviewView study →}.

Gap: every positive result is either a rodent model or a multi-herb formula; there is no human trial of standardised bupleurum extract, and the therapeutic-versus-toxic dose window is undefined.

2. Anti-inflammatory

The anti-inflammatory action is the best-characterised mechanism in the herb. In LPS-stimulated macrophages, saikosaponin-a and its epimer saikosaponin-d suppress iNOS and COX-2 — lowering nitric oxide, PGE₂, TNF-α and IL-6 — by blocking activation of the NF-κB pathway ^{4Reference 4Lu et al. · 2012In vitroSaikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of the NF-κB signaling pathway — in vitroView study →}. The same axis carries through to disease models: SSd (8 mg/kg) eased dextran-sulfate-sodium colitis in mice while modulating the gut microbiota ^{5Reference 5Chen et al. · 2020AnimalSaikosaponin-d ameliorates dextran sulfate sodium-induced colitis by suppressing NF-κB activation and modulating the gut microbiota — mouse modelView study →}, SSa ameliorated ulcerative colitis via the CH25H/25-OHC axis and NLRP3 inhibition ^{37Reference 372025AnimalSaikosaponin A ameliorates ulcerative colitis by targeting the CH25H/25-OHC axis to inhibit NLRP3 inflammasome — mouse modelView study →}, and SSd blunts T-cell activation through PKCθ/JNK/NF-κB signalling ^{36Reference 36Sun et al. · 2005In vitroSaikosaponin-d inhibits T-cell activation through modulation of PKCθ, JNK, and NF-κB — in vitroView study →}. Beyond the gut, SSd has anti-inflammatory activity in osteoarthritis and metabolic-inflammation models ^{15Reference 152022ReviewChemotherapeutic potential of saikosaponin D: experimental evidence — reviewView study →}. Almost all of this is cell-line or rodent work; there is no controlled human anti-inflammatory trial of the isolated herb, and effects are consistently reported for purified saikosaponins rather than whole-root preparations.

Gap: no human data, and the doses used in rodents (mg/kg purified saponin) do not map cleanly onto a root decoction or 1:2 tincture.

3. Anticancer (antiproliferative)

Bupleurum’s cytotoxic reputation rests on a large and internally consistent in-vitro literature for saikosaponin-d, which induces apoptosis, autophagy, pyroptosis and ferroptosis across lung, gastric, pancreatic, colorectal, endometrial and breast cancer lines, typically through STAT3, COX-2, MKK4/JNK and PI3K/Akt/mTOR modulation ^{15,16Reference 152022ReviewChemotherapeutic potential of saikosaponin D: experimental evidence — reviewView study →Reference 162020In vitroSaikosaponin D inhibits proliferation and induces apoptosis of non-small cell lung cancer cells — in vitroView study →}. Older work on saponin-enriched fractions showed Fas-dependent apoptosis in non-small-cell lung cancer cells, and the whole formula Sho-saiko-to is cytotoxic to hepatoma and lung lines in vitro. The strongest translational hint is again formula-level: the same 7.5 g/day Sho-saiko-to that lowered HCC incidence in cirrhotic patients ^{1Reference 1Oka et al. · 1995RCTProspective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9) — randomized controlled trialView study →}. But no isolated bupleurum or saikosaponin has been tested as a single anticancer agent in humans, and the concentrations that kill cells in vitro overlap the range that is hepatotoxic and cardiotoxic ^{13,14Reference 132017In vitroContent decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity during vinegar processing of Bupleurum — in vitroView study →Reference 14Li et al. · 2018ReviewA comprehensive review and perspectives on pharmacology and toxicology of saikosaponins — reviewView study →}.

Gap: entirely preclinical for the single herb; selectivity between tumour cytotoxicity and normal-tissue toxicity has not been established in vivo at translatable doses.

4. Antidepressant & neuroprotective

A rapidly growing rodent literature — most of it published since this page was last updated — reports antidepressant and anxiolytic effects for bupleurum saikosaponins. Saikosaponin-a reduced depressive-like behaviour in chronic-unpredictable-mild-stress mice by acting on the TLR4/NF-κB/BDNF axis and lowering oxidative stress ^{22Reference 222025AnimalTLR4 as a therapeutic target: antidepressant mechanism of saikosaponin A in regulating the NF-κB/BDNF axis and mitigating oxidative stress and inflammation — mouse modelView study →}, and promoted hippocampal neurogenesis via Tet1/Dll3/Notch1 signalling ^{23Reference 232024AnimalSaikosaponin a activates Tet1/Dll3/Notch1 signalling and promotes hippocampal neurogenesis to improve depression — mouse modelView study →}; saikosaponin-d eased depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activation ^{21Reference 212024AnimalSaikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activation — mouse modelView study →}; and total saikosaponins of B. yinchowense reduced depressive/anxiety behaviour and raised synaptic-protein expression through AMPA-receptor/mTOR signalling ^{24Reference 24Chen et al. · 2018AnimalTotal saikosaponins of Bupleurum yinchowense reduce depressive, anxiety-like behavior and increase synaptic protein expression in chronic corticosterone-treated mice — animal modelView study →}. Reviews now treat bupleurum’s mood effects as a coherent theme, noting actions on 5-HT/dopamine, the NMDA system and BDNF ^{25Reference 252024ReviewBupleurum in the treatment of depression disorder: a comprehensive review — reviewView study →}. Every study is an animal model, frequently in B. scorzonerifolium or B. yinchowense rather than B. falcatum, with no human trial of the single herb.

Gap: no clinical data; the traditional use is as part of formulas (Xiaoyaosan, Chaihu-Shugan-San), so single-herb antidepressant efficacy in people is unproven.

5. Antiviral (anti-HBV)

The evidence does not support bupleurum as a broad, potent antiviral, and the specifics matter. Against hepatitis B, activity tracks to saikosaponin-c, not the abundant a/d forms: in HBV-producing HepG2.2.15 cells, saikosaponin c lowered HBeAg and HBV-DNA whereas saikosaponin d was cytotoxic but failed to inhibit the virus ^{17Reference 17Chiang et al. · 2003In vitroCytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species — in vitroView study →}. Later work showed SSc suppresses HBV by attenuating HNF1α/HNF4α expression ^{18Reference 182019In vitroSaikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis — in vitroView study →} and synergises with the nucleoside analogue telbivudine ^{19Reference 192020In vitroCombination of saikosaponin c and telbivudine synergistically enhances anti-HBV activity — in vitroView study →}; the whole Sho-saiko-to formula and crude saikosaponins also inhibit HBV in the same cell model, with a modest selectivity index ^{20Reference 20Chang et al. · 2007In vitroSho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins inhibit hepatitis B virus in a stable HBV-producing cell line — in vitroView study →}. The broader “inhibits HSV, HIV, poliovirus, parainfluenza, RSV” claim on the page derives largely from quercetin and rutin — flavonoids widespread in plants and not specific to bupleurum — plus decades-old saikosaponin assays ^{34Reference 34Ashour et al. · 2014In vitroAnti-infective and cytotoxic properties of Bupleurum marginatum — in vitroView study →}. The only human antiviral evidence is a Cochrane review of Xiao Chai Hu Tang for chronic hepatitis B, which found the clinical effects “unclear” on very-low-certainty evidence from small, low-quality trials ^{3Reference 3Zhang et al. · 2019Meta-analysisXiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B — systematic review and meta-analysisView study →}.

Gap: no single-herb human antiviral data; the specific anti-HBV activity tracks to saikosaponin c rather than the more abundant a/d forms, and much of the broader antiviral reputation rests on non-specific flavonoids.

6. Immunomodulatory

Distinct from the saponins, bupleurum root polysaccharides show reproducible immunomodulatory activity. Radix Bupleuri polysaccharides activate RAW264.7 macrophages through TLR2/TLR4 and MAPK/NF-κB signalling, and in cyclophosphamide-immunosuppressed mice they restored immune function partly by remodelling the gut microbiota ^{26Reference 262025In vitroImmunomodulatory mechanism of Radix Bupleuri polysaccharide on RAW264.7 cells and cyclophosphamide-induced immunosuppressed mice — in vitro and animal modelView study →}. A separate polysaccharide fraction inhibited LPS-driven inflammation by modulating the TLR4 pathway ^{27Reference 27Wu et al. · 2013In vitroBupleurum polysaccharides attenuate lipopolysaccharide-induced inflammation via modulating Toll-like receptor 4 signaling — in vitroView study →}, and an arabinogalactan and pectic polysaccharides show related anti-inflammatory and mucosal effects. This is a mechanistically plausible, preclinical-only story; the polysaccharides are also a different preparation problem, being water-extractable and largely absent from an ethanolic tincture.

Gap: cell and mouse data only; the immunoactive polysaccharides are not captured by the alcohol-based liquid extract this herb is usually dosed as.

Mechanisms

Mechanism	Drives	Key compounds
NF-κB ↓, iNOS/COX-2 ↓, TNF-α/IL-6 ↓	anti-inflammatory, hepatoprotective	saikosaponin-a, saikosaponin-d
Hepatic stellate-cell apoptosis; PPARα/SREBP-1c lipid modulation	antifibrotic	saikosaponin-d, saikosaponin B1
Mitochondrial + Fas/Bid apoptosis, autophagy, STAT3/JNK/mTOR	anticancer (and hepatotoxicity at higher dose)	saikosaponin-d
TLR4/NF-κB/BDNF, NLRP3 inflammasome ↓, AMPA/mTOR synaptic	antidepressant, neuroprotective	saikosaponin-a, saikosaponin-d
HNF1α/HNF4α ↓ → HBV pgRNA ↓; viral-polymerase/capsid binding	antiviral (anti-HBV)	saikosaponin-c, quercetin, rutin
TLR2/TLR4 → MAPK/NF-κB macrophage activation	immunomodulatory	polysaccharides
SERCA (Ca²⁺-ATPase) inhibition; CYP2E1 induction, oxidative stress	cardiotoxicity, hepatotoxicity	saikosaponin-a, saikosaponin-d

Clinical trials

No registered trials test bupleurum or isolated saikosaponins as single agents; all human evidence comes from the multi-herb formula Sho-saiko-to / Xiao Chai Hu Tang (chronic hepatitis C, HCC after embolization, chemotherapy gut-toxicity), and the strongest single result — a cirrhosis/HCC-prevention RCT — was only borderline significant overall ^{1,3Reference 1Oka et al. · 1995RCTProspective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9) — randomized controlled trialView study →Reference 3Zhang et al. · 2019Meta-analysisXiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B — systematic review and meta-analysisView study →}.

Completed	Planned	Terminated	Preclinical
3 (formula)	3 (formula)	1 (withdrawn)	~several hundred

Last checked: February 2025.

Dosage

Human dosing exists only for the multi-herb formula, not for standardised single-herb bupleurum; the rest of the doses below are purified saikosaponins in rodents, which do not back-convert to a root decoction or tincture.

Indication	Preparation	Dose	Est. dried-herb equivalent	Source
HCC prevention / hepatoprotective (formula)	Sho-saiko-to (TJ-9) granule extract, 7-herb	7.5 g/day granules × 60 months	~7 g/day raw Bupleurum root (bupleurum’s share of the ~24 g raw-crude formula; stated assumption)	1Reference 1Oka et al. · 1995RCTProspective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9) — randomized controlled trialView study →
Anti-HBV (formula)	Xiao Chai Hu Tang decoction	varies by trial (low-quality)	— (proprietary/variable; no marker %)	3Reference 3Zhang et al. · 2019Meta-analysisXiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B — systematic review and meta-analysisView study →
Antifibrotic (preclinical)	Saikosaponin-d, i.p.	1.0–2.0 mg/kg/day, rat	— (purified saponin; not back-convertible to whole root)	6Reference 6Chen et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in rats — animal modelView study →
Anti-inflammatory / colitis (preclinical)	Saikosaponin-d, gavage	4–8 mg/kg/day, mouse	— (purified saponin)	5Reference 5Chen et al. · 2020AnimalSaikosaponin-d ameliorates dextran sulfate sodium-induced colitis by suppressing NF-κB activation and modulating the gut microbiota — mouse modelView study →
Antidepressant (preclinical)	Saikosaponin-a, oral	20 mg/kg/day, mouse	— (purified saponin)	22Reference 222025AnimalTLR4 as a therapeutic target: antidepressant mechanism of saikosaponin A in regulating the NF-κB/BDNF axis and mitigating oxidative stress and inflammation — mouse modelView study →

The Sho-saiko-to figure is an extract, not raw herb; the ~7 g whole-root equivalent is an order-of-magnitude guide, not a conversion factor or a recommendation. Purified-saponin mg/kg rodent doses cannot be back-converted to a human whole-herb weight and are left ”—”. These are research doses, not recommendations.

Traditional Dosage

System	Preparation	Dose
Traditional Chinese Medicine	Dried root, decoction (Chai Hu)	3–10 g/day
Western herbal medicine	1:2 liquid extract	25–60 mL/week (note: a weekly, not daily, range)
Western herbal medicine	Dried root, infusion/decoction	as part of a formula; rarely used alone

Safety

Bupleurum’s principal actives, the saikosaponins, are dose-dependently hepatotoxic and cardiotoxic: rodent studies show liver injury via CYP2E1 induction and oxidative stress at higher exposures, and saikosaponin d can worsen acetaminophen-induced liver damage by impairing protective autophagy ^{11,10Reference 11Li et al. · 2017AnimalSaikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study — animal modelView study →Reference 102025AnimalSaikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP-SNARE complex assembly in protective autophagy — mouse modelView study →}. Saikosaponins a and d inhibit the SERCA calcium pump, the basis of their cardiotoxic potential, which is one reason vinegar-processing (which lowers their content) is traditional ^{13Reference 132017In vitroContent decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity during vinegar processing of Bupleurum — in vitroView study →}. In-vitro data show saikosaponin d and total saikosaponins induce CYP3A4, creating a plausible interaction risk with the many drugs that enzyme metabolises, so caution is warranted with concurrent prescription medication ^{29,30Reference 292021In vitroEffects of saikosaponin-d on CYP3A4 in HepaRG cells and protein-ligand docking study — in vitroView study →Reference 302024In vitroEffects of total saikosaponins on CYP3A4 and CYP1A2 in HepaRG cells — in vitroView study →}. Most importantly, the bupleurum-containing formula Sho-saiko-to is the single most frequently implicated cause of Japanese herbal-medicine-induced interstitial pneumonitis, a potentially fatal reaction especially reported when combined with interferon ^{28Reference 28Enomoto et al. · 2017ReviewJapanese herbal medicine-induced pneumonitis: a review of 73 patients — reviewView study →}.

Pregnancy & lactation

Avoid. Saikosaponin d shows estrogen-like activity — it has a structure similar to estradiol and stimulates estrogen-receptor-positive (MCF-7) cell proliferation in vitro, an effect blocked by an estrogen-receptor antagonist ^{31Reference 31Wang et al. · 2010In vitroEstrogen-like activities of saikosaponin-d in vitro: a pilot study — in vitroView study →}. This phytoestrogenic behaviour, combined with the herb’s traditional use to move blood and regulate menstruation and the absence of any human pregnancy safety data, makes avoidance during pregnancy and lactation the prudent position. Reproductive and developmental toxicity have not been formally studied.

Synergy

Traditionally combined with Paeonia and Angelica sinensis for menstrual irregularities, PMS, dysmenorrhea in traditional Chinese medicine.

References

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