Bupleurum

Bupleurum root, Chái Hú, is one of the central herbs of Chinese medicine. It moves stuck liver Qi, and because the liver governs the smooth flow of Qi through the whole body, that one action reaches a long list of complaints: liver tension, digestive upset, muscle spasm, lumps and masses, bleeding from heat, and menstrual irregularity ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

Its other classical role is in the lesser-yang (shaoyang) stage of a fever, with alternating chills and heat in an illness that has moved past the surface but not yet gone deep. This is the indication behind Xiao Chai Hu Tang, the formula bupleurum leads.

It is rarely given alone. Chai hu is added to formulas as a director, both to move Qi and to point the other herbs at a particular organ, and the organ depends on what it is combined with ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}. It is paired with peony and dong quai for menstrual irregularity and painful periods. The essential oil is used separately, to release surface heat ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}.

It is also given for chest and rib-side pain, and for sinking of the clear Qi: the weakness and chronic diarrhoea of a body whose Qi has dropped ^{40,47Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic HerbsReference 47Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.)}. In Xiaoyaosan and Chaihu Shugan San it is used for low mood ^{25Reference 25Ran S et al. · 2024ReviewBupleurum in the treatment of depression disorder: a comprehensive review — reviewView study →}.

Two cautions travel with it. Chai hu can bring on headaches and irritability, and in severe toxicity skin sores ^{40Reference 40Teeguarden · 2000The Ancient Wisdom of the Chinese Tonic Herbs}. It is avoided where tinnitus, deafness, dizziness or headache come from yin-deficient fire or rising liver yang, because it lifts Qi upward ^{41,46Reference 41Wu · 2005An Illustrated Chinese Materia MedicaReference 46Bone · 2003A Clinical Guide to Blending Liquid Herbs}.

Western herbal practice uses bupleurum along the lines of its Chinese indications. It is given for hepatitis, microbial infection, cancer and malarial fever ^{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.)}.

In Western practice it is given as a 1:2 liquid extract.

In rats given carbon tetrachloride, saikosaponin-d injected at 1.0–2.0 mg/kg/day for six weeks reduced liver fibrosis and lowered NF-κB, TNF-α and IL-6 ^{6Reference 6Dang et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in rats — animal modelView study →}.

Saikosaponin-a, given in the diet at 0.004% for eight weeks, improved the liver’s antioxidant capacity, lowered ALT and AST, and eased fibrosis ^{7Reference 7Wu et al. · 2008AnimalCurcumin or saikosaponin a improves hepatic antioxidant capacity and protects against CCl₄-induced liver injury in rats — animal modelView study →}.

Saikosaponin B1, a hydrolysed form, reduced chemically induced liver fibrosis in mice by targeting lactate production in the fibrosis-driving stellate cells ^{8Reference 8Wang G et al. · 2026AnimalSaikosaponin B1 alleviates hepatic fibrosis by targeting the LDHA-MCT1/4 axis to inhibit lactate-driven profibrogenic signaling — mouse modelView study →}.

Reviews attribute the antifibrotic effect to hepatic stellate-cell apoptosis and to PPARα/SREBP-1c lipid signalling ^{9Reference 9Zhu S et al. · 2026ReviewThe dual role of saikosaponins in liver disease treatment: a comprehensive review of pharmacology and toxicity — reviewView study →}.

The only controlled human data are for the seven-herb formula Sho-saiko-to. In a randomized, non-blinded trial of 260 patients with cirrhosis, 7.5 g/day for five years lowered the cumulative rate of liver cancer, but not significantly overall (P = 0.071). The difference was significant in patients without hepatitis B surface antigen (P = 0.024) ^{1Reference 1Oka et al. · 1995RCTProspective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9) — randomized controlled trialView study →}.

The same saikosaponins are dose-dependently toxic to the liver. Saikosaponin-d worsened paracetamol liver injury in mice by blocking protective autophagy ^{10Reference 10Fan G et al. · 2025AnimalSaikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP-SNARE complex assembly in protective autophagy — mouse modelView study →}. Saikosaponins caused liver injury in mice that rose with dose and time, with 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 →}. Reviews describe a dual role in the liver, protective and toxic ^{9,14Reference 9Zhu S et al. · 2026ReviewThe 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: the dose window between liver protection and liver toxicity has never been defined. Every positive result is a rodent model or a multi-herb formula, so there is no human figure to anchor either end of it.

In LPS-stimulated macrophages, saikosaponin-a and its epimer saikosaponin-d suppressed iNOS and COX-2, lowering nitric oxide, PGE₂, TNF-α and IL-6, by blocking activation of NF-κB. Both also reduced paw swelling in rats and vascular leakage in mice ^{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 pathway carries through to disease models. Saikosaponin d at 8 mg/kg eased chemically induced colitis in mice and shifted the gut microbiota ^{5Reference 5Li et al. · 2020AnimalSaikosaponin-d ameliorates dextran sulfate sodium-induced colitis by suppressing NF-κB activation and modulating the gut microbiota — mouse modelView study →}. Saikosaponin a eased ulcerative colitis in mice through the CH25H/25-OHC axis and NLRP3 inhibition ^{37Reference 37Yang X et al. · 2025AnimalSaikosaponin A ameliorates ulcerative colitis by targeting the CH25H/25-OHC axis to inhibit NLRP3 inflammasome — mouse modelView study →}, and saikosaponin d blunted T-cell activation through PKCθ/JNK/NF-κB signalling ^{36Reference 36Leung et al. · 2005In vitroSaikosaponin-d inhibits T-cell activation through modulation of PKCθ, JNK, and NF-κB — in vitroView study →}.

Saikosaponin d also has anti-inflammatory activity in models of osteoarthritis and metabolic inflammation ^{15Reference 15Manoharan S et al. · 2022ReviewChemotherapeutic potential of saikosaponin D: experimental evidence — reviewView study →}.

Almost all of this is cell or rodent work with purified saikosaponins rather than whole-root preparations, and the mg/kg rodent doses do not map onto a decoction or a 1:2 tincture.

Saikosaponin-d induces apoptosis, autophagy and other forms of cell death in lung, gastric, pancreatic, colorectal, endometrial and breast cancer cell lines, through STAT3, COX-2, JNK and PI3K/Akt/mTOR signalling ^{15,16Reference 15Manoharan S et al. · 2022ReviewChemotherapeutic potential of saikosaponin D: experimental evidence — reviewView study →Reference 16Wu S et al. · 2020In vitroSaikosaponin D inhibits proliferation and induces apoptosis of non-small cell lung cancer cells — in vitroView study →}. In lung cancer cells it inhibited growth at concentrations of 3.6–8.5 µM ^{16Reference 16Wu S et al. · 2020In vitroSaikosaponin D inhibits proliferation and induces apoptosis of non-small cell lung cancer cells — in vitroView study →}.

A saponin-enriched fraction of B. kaoi triggered Fas-dependent apoptosis in lung cancer cells ^{38Reference 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 cells}. Sho-saiko-to inhibits chemically induced liver cancer in animals and suppresses the growth of hepatoma cells ^{2Reference 2Shimizu · 2000ReviewSho-saiko-to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma — reviewView study →}. In people, the one anticancer signal is the formula-level cirrhosis trial ^{1Reference 1Oka et al. · 1995RCTProspective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9) — randomized controlled trialView study →}.

No isolated bupleurum or saikosaponin has been tested as a single anticancer agent in people. Saikosaponin d is also toxic to liver cells and heart cells in vitro ^{13,14Reference 13Wang S et al. · 2017In 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 →}.

Saikosaponin-a at 20 mg/kg a day reduced depressive-like behaviour in mice exposed to chronic mild stress, acting on the TLR4/NF-κB/BDNF pathway and lowering oxidative stress ^{22Reference 22Tan L et al. · 2025AnimalTLR4 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 →}. In mice exposed to social-defeat stress, it promoted the growth of new neurons in the hippocampus through Tet1/Dll3/Notch1 signalling ^{23Reference 23Tong Y et al. · 2024AnimalSaikosaponin a activates Tet1/Dll3/Notch1 signalling and promotes hippocampal neurogenesis to improve depression — mouse modelView study →}.

Saikosaponin-d eased depression in stressed mice by promoting the breakdown of NLRP3 and blocking inflammasome activation ^{21Reference 21Gao T et al. · 2024AnimalSaikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activation — mouse modelView study →}.

Total saikosaponins of B. yinchowense reduced depressive and anxiety-like behaviour in mice treated with corticosterone, and raised synaptic-protein expression through AMPA-receptor/mTOR signalling ^{24Reference 24Sun 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 →}.

A 2024 review describes actions on serotonin and dopamine, the NMDA system and BDNF ^{25Reference 25Ran S et al. · 2024ReviewBupleurum in the treatment of depression disorder: a comprehensive review — reviewView study →}.

Every study is an animal model, mostly with B. chinense, B. scorzonerifolium or B. yinchowense rather than B. falcatum. The traditional use is inside formulas such as Xiaoyaosan and Chaihu Shugan San, not as a single herb ^{23,25Reference 23Tong Y et al. · 2024AnimalSaikosaponin a activates Tet1/Dll3/Notch1 signalling and promotes hippocampal neurogenesis to improve depression — mouse modelView study →Reference 25Ran S et al. · 2024ReviewBupleurum in the treatment of depression disorder: a comprehensive review — reviewView study →}.

Against hepatitis B, activity tracks to saikosaponin-c, not to the abundant a and d forms. In HBV-producing HepG2.2.15 cells, saikosaponin c lowered HBeAg and HBV DNA, while saikosaponin d killed the cells but did not 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 that saikosaponin c suppresses HBV by lowering HNF1α and HNF4α expression, and that it is active against drug-resistant HBV mutants ^{18Reference 18Pan Y et al. · 2019In vitroSaikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis — in vitroView study →}. In cells it added to the effect of nucleoside drugs, most strongly telbivudine ^{19Reference 19Li X et al. · 2020In vitroCombination of saikosaponin c and telbivudine synergistically enhances anti-HBV activity — in vitroView study →}.

Sho-saiko-to and crude saikosaponins of B. chinense also inhibit HBV in the same cell model, with a selectivity index of 6.7 for the formula. Sho-saiko-to contains so little saikosaponin that its effect may come from other ingredients ^{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 wider claim that bupleurum inhibits HSV, HIV, poliovirus, parainfluenza and RSV traces to quercetin and rutin, flavonoids found across the plant kingdom, and to older 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. It found the clinical effects unclear, on very-low-certainty evidence from small, poor-quality trials ^{3Reference 3Kong et al. · 2019Meta-analysisXiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B — systematic review and meta-analysisView study →}.

Gap: the anti-HBV activity belongs to saikosaponin c, a minor form, while the marker compounds a and d were inactive or cytotoxic in the same assay ^{17Reference 17Chiang et al. · 2003In vitroCytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species — in vitroView study →}. An extract standardized to a and d says nothing about its antiviral potential.

Bupleurum root polysaccharides have immune activity distinct from the saponins. Radix Bupleuri polysaccharides activated RAW264.7 macrophages through TLR2/TLR4 and MAPK/NF-κB signalling, and in immunosuppressed mice they restored immune function, partly by reshaping the gut microbiota ^{26Reference 26Wu X et al. · 2025In vitroImmunomodulatory mechanism of Radix Bupleuri polysaccharide on RAW264.7 cells and cyclophosphamide-induced immunosuppressed mice — in vitro and animal modelView study →}.

Polysaccharides from a related species, Bupleurum smithii var. parvifolium, blocked LPS-driven inflammation through the TLR4 pathway and eased acute lung injury in rats ^{27Reference 27Wu et al. · 2013In vitroBupleurum polysaccharides attenuate lipopolysaccharide-induced inflammation via modulating Toll-like receptor 4 signaling — in vitroView study →}.

Gap: these polysaccharides are water-soluble and are largely absent from an alcohol tincture, the form in which bupleurum is most often dispensed in the West. A decoction extracts them.

Liver. Saikosaponins caused liver injury in mice that rose with dose and duration, with 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 →}. Saikosaponin d worsened paracetamol liver injury in mice by blocking protective autophagy ^{10Reference 10Fan G et al. · 2025AnimalSaikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP-SNARE complex assembly in protective autophagy — mouse modelView study →}.

Heart. Saikosaponins a and d bind the SERCA calcium pump and are more toxic to heart and liver cells in vitro than the other saikosaponins. Baking the root with vinegar, a traditional processing step, lowers their content ^{13Reference 13Wang S et al. · 2017In vitroContent decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity during vinegar processing of Bupleurum — in vitroView study →}.

Lung. A review of 73 published Japanese cases of herbal-medicine pneumonitis (1996–2015) found Sho-saiko-to the most often involved formula, in 26% of cases. The formulas most often involved share skullcap and liquorice. Most cases began within three months of starting treatment, and three patients (4%) died ^{28Reference 28Enomoto et al. · 2017ReviewJapanese herbal medicine-induced pneumonitis: a review of 73 patients — reviewView study →}.

Drug interactions. In human liver cells, saikosaponin d inhibited CYP3A4 expression and activity ^{29Reference 29Li H et al. · 2021In vitroEffects of saikosaponin-d on CYP3A4 in HepaRG cells and protein-ligand docking study — in vitroView study →}, and total saikosaponins reduced CYP3A4 expression ^{30Reference 30Tang Y et al. · 2024In vitroEffects of total saikosaponins on CYP3A4 and CYP1A2 in HepaRG cells — in vitroView study →}. This could raise blood levels of the many drugs that CYP3A4 clears, so care is needed alongside prescription medicines.