Compound Monograph
Saikosaponin C
Saikosaponin C is a minor oleanane triterpenoid saponin of Bupleurum (Chai Hu) root — distinct from its better-known siblings for a molecule-specific anti-HBV signal (HNF1α/HNF4α suppression, telbivudine synergy) and a pro-angiogenic endothelial effect. Preclinical only, no human trials of the isolate, and notably less cytotoxic than saikosaponin D — though the saikosaponin class carries a real hepatotoxicity caveat.
Sources · 2
Where Does It Come From?
Saikosaponin C is a naturally occurring triterpenoid saponin (oleanane, bisdesmoside), found in Bupleurum / Chai Hu and 1 other source. It is well tolerated orally (low toxicity).
Concentration
Content by Source
Concentrations not reported. No percent-dry-weight or mg/g figures have been published for this compound in its source plants.
Saikosaponin C at a Glance
Saikosaponin C is a minor oleanane saponin of Bupleurum root, and it is distinguished from its better-known siblings by two molecule-specific effects.
It carries an anti-hepatitis-B signal — suppressing HNF1-alpha and HNF4-alpha, with reported synergy alongside the antiviral drug telbivudine — and it is pro-angiogenic, which is the opposite direction from saikosaponin A’s VEGFR2 blockade.
Members of the same saponin family in the same root doing opposite things is worth noting when reading whole-extract claims.
What It's Used For
Saikosaponin C is a minor oleanane triterpenoid saponin of Bupleurum (Chai Hu) root, and one of the three principal saikosaponins (a, c, d). Its honest distinction is that it has two genuinely molecule-specific signals that differ from its siblings: an anti-HBV effect (with low cytotoxicity, unlike other saikosaponins) and a pro-angiogenic endothelial effect (whereas saikosaponin a suppresses angiogenesis). By contrast, Chai Hu’s anti-inflammatory/hepatoprotective/anticancer reputation is class- or whole-herb-level (saikosaponin a/d and the formula), not demonstrated for saikosaponin C. There are no human trials of the isolate, and clinical use of Bupleurum is the whole herb/formula (e.g. Xiao Chai Hu Tang / Sho-saiko-to).
Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. No human isolate data, so scores stay low by design.
Saikosaponin C’s flagship and most molecule-specific result. It was first isolated as an anti-HBV saikosaponin without the cytotoxicity of its siblings 1Reference 1Cytotoxicity and anti-hepatitis-B-virus activities of saikosaponins from Bupleurum speciesView study →; later work localized the mechanism to downregulation of the hepatic transcription factors HNF1α/HNF4α, suppressing HBV pregenomic-RNA synthesis (↓ HBeAg, ↓ HBV-DNA) 2Reference 2Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesisView study →, with additive/synergistic effect alongside the nucleoside analogue telbivudine 3Reference 3Combination of saikosaponin C and telbivudine synergistically enhances anti-HBV activityView study →.
Gap: entirely in-vitro (HepG2.2.15 cell model), with no animal efficacy and no human data — a laboratory signal, not a therapy, and the effective concentrations are unlikely to be reached from oral herb intake 1,
In a single HUVEC study, saikosaponin C induced endothelial proliferation, migration and capillary-tube formation via MMP-2, VEGF and p42/p44 MAPK (ERK) 4Reference 4Saikosaponin C induces endothelial-cell growth, migration and capillary-tube formationView study → — genuinely SSc-specific and mechanistically distinct from saikosaponin a, which blocks VEGFR2-driven angiogenesis.
Gap: a single in-vitro study in one cell type, with no in-vivo confirmation, and the direction of benefit is context-dependent — potentially relevant to wound healing/tissue repair but a caution in oncology, since tumors depend on angiogenesis 4Reference 4Saikosaponin C induces endothelial-cell growth, migration and capillary-tube formationView study →.
Chai Hu’s traditional “harmonizing/liver” use and its anti-inflammatory (NF-κB/iNOS/COX-2) and hepatoprotective (CCl₄) data belong to saikosaponin a/d and the whole herb/formula, not to saikosaponin C 5Reference 5ReviewGenus Bupleurum: a review of its phytochemistry, pharmacology and modes of actionView study →.
Gap: no saikosaponin-C-specific anti-inflammatory or hepatoprotective study exists — this is guilt-by-class, and Bupleurum’s clinical use is the whole herb/formula, never the isolate 5Reference 5ReviewGenus Bupleurum: a review of its phytochemistry, pharmacology and modes of actionView study →.
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| HNF1α / HNF4α (hepatic transcription factors) | downregulated → ↓ HBV pregenomic-RNA synthesis | anti-HBV (SSc-specific) |
| HBV replication (HepG2.2.15) | ↓ HBeAg, ↓ HBV-DNA; synergy with telbivudine | anti-HBV (SSc-specific) |
| MMP-2, VEGF, p42/p44 MAPK (ERK) | induced → endothelial growth, migration, tube formation | pro-angiogenesis (SSc-specific) |
| NF-κB / iNOS / COX-2 (class) | suppressed (saikosaponin a; not shown for SSc) | anti-inflammatory — class only |
Pharmacokinetics
Saikosaponin C is a large oleanane bisdesmoside saponin, with the expected class liabilities: poor passive membrane permeability, extensive gut/acid hydrolysis and low oral bioavailability. It is measurable in rat plasma by LC-MS/MS after dosing of Bupleurum preparations, confirming that some intact SSc is absorbed but at low levels 6Reference 6AnimalA reliable LC-MS/MS method for the quantification of five bioactive saponins of crude and processed Bupleurum scorzonerifolium in rat plasmaView study →; no dedicated single-compound oral-bioavailability or human pharmacokinetic study exists, so parameters are inferred from the class. The practical implication is that the in-vitro anti-HBV concentrations are unlikely to be reached from oral herb intake.
Clinical trials
There are no human trials of isolated saikosaponin C. All Bupleurum clinical experience is with the whole herb or multi-herb formula (e.g. Xiao Chai Hu Tang / Sho-saiko-to), which cannot be attributed to this saponin.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| —(none, isolate) | — | — | Modest(anti-HBV-led) |
Last checked: July 2026.
Toxicity & Safety
Saikosaponin C is the mild sibling of the saikosaponins — isolated precisely because it was anti-HBV without the cytotoxicity of its relatives. The real cautions here belong to the class and the whole herb rather than to the molecule, but it travels in toxic company.
- The least cytotoxic saikosaponin. No cardiotoxicity or hepatotoxicity signal is attributed specifically to saikosaponin C.
- Avoid in pregnancy. No reproductive-safety data.
- Class hepatotoxicity. Saikosaponin d is a documented dose-dependent hepatotoxin; the class carries a real liver caveat.
- Formula-level reports. Bupleurum-containing formulas such as Sho-saiko-to carry interstitial-pneumonia and hepatotoxicity reports — the formula, not this saponin.
- Pro-angiogenic activity. A theoretical caution in cancer and proliferative-retinopathy settings.
- Saponins are hemolytic at high concentration. A generic class property.
Full Safety & Interactions Detail
Saikosaponin C carries a low flag for the specific molecule — the foundational isolation study separated it as anti-HBV with low cytotoxicity, in contrast to more cytotoxic saikosaponins 1Reference 1Cytotoxicity and anti-hepatitis-B-virus activities of saikosaponins from Bupleurum speciesView study →, and no SERCA-inhibition/cardiotoxicity or hepatotoxicity signal is attributed specifically to SSc (those belong to saikosaponin a and d) 7Reference 7Content decline of the SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix BupleuriView study →.
But the class/whole-herb caveat must not be buried: saikosaponins as a class can be hepatotoxic (saikosaponin d is a documented dose-dependent hepatotoxin), Bupleurum-containing formulas (Sho-saiko-to) carry well-known interstitial-pneumonia and hepatotoxicity reports in the formula context, and saponins are inherently hemolytic at high concentration — saikosaponin C is the mild sibling, but it travels in toxic company. Its pro-angiogenic activity 4Reference 4Saikosaponin C induces endothelial-cell growth, migration and capillary-tube formationView study → is a further theoretical caution in cancer/proliferative-retinopathy settings.
Dosage
There is no established or safe human dose — saikosaponin C has never been dosed as an isolate in humans, and all figures in the literature are in-vitro (µM) or animal-plasma research concentrations, not recommendations. Any real-world exposure is as a minor fraction of whole Chai Hu root/formula.
References
- Chiang LC, et al. (2003). Cytotoxicity and anti-hepatitis-B-virus activities of saikosaponins from Bupleurum species. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/14531019/
- Pan Y, Ke Z, Ye H, et al. (2019). Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis. Inflammation Research. https://pubmed.ncbi.nlm.nih.gov/31531682/
- Li X, Ke Z, Lian D, et al. (2020). Combination of saikosaponin C and telbivudine synergistically enhances anti-HBV activity. Inflammation Research. https://pubmed.ncbi.nlm.nih.gov/32313973/
- Shyu KG, et al. (2004). Saikosaponin C induces endothelial-cell growth, migration and capillary-tube formation. Life Sciences. https://pubmed.ncbi.nlm.nih.gov/15581913/
- Ashour ML, Wink M (2011). Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/21749378/
- Tao Y, Huang S, Yan J, et al. (2019). A reliable LC-MS/MS method for the quantification of five bioactive saponins of crude and processed Bupleurum scorzonerifolium in rat plasma. Biomedical Chromatography. https://pubmed.ncbi.nlm.nih.gov/31049981/
- Wang S, Zhang Y, Zhang Q, et al. (2017). Content decline of the SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri. Environmental Toxicology and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/28412648/
