Saikosaponin D

Saikosaponin D at a Glance

Saikosaponin D is the most-studied oleanane saponin of Bupleurum, and it carries a genuinely paradoxical profile: antifibrotic in the liver, yet hepatotoxic — protective against scarring in some models while damaging hepatocytes in others, with dose the likely discriminator.

It also has estrogenic activity and induces CYP3A4, which is a real interaction mechanism rather than a theoretical one, since CYP3A4 metabolises a large share of prescription drugs.

That combination is the main reason Bupleurum preparations warrant more caution than their gentle reputation suggests.

The Antifibrotic–Hepatotoxic Paradox

Saikosaponin D is the reason Bupleurum has both a liver reputation and a liver warning, and the two come from the same molecule.

The protective side is old and reproducible in its own model. The first report dates to 1982, when saikosaponin D isolated from Bupleurum falcatum protected rat liver against carbon tetrachloride ^{17Reference 17Abe H et al. · 1982AnimalProtective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat — animal modelView study →}; a later study found 1–2 mg/kg reduced CCl₄-induced hepatic fibrogenesis in rats ^{1Reference 1Dang SS et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in ratsView study →}. That result, read alone, made saikosaponin D a candidate for chronic liver disease and underwrote a good deal of chai hu’s modern liver framing.

The damaging side is recent, mechanistic, and specific. Saikosaponin D activates the Fas death-receptor pathway and Bid in hepatocytes to cause apoptosis ^{4Reference 4Zhang F et al. · 2016Activation of the Fas death-receptor pathway and Bid in hepatocytes is involved in saikosaponin-D induction of hepatotoxicityView study →}; and rather than merely being toxic in parallel with an insult, it disables the liver’s defence against one — it exacerbates acetaminophen-induced injury by sabotaging GABARAP–SNARE complex assembly in protective autophagy ^{3Reference 3Fan G et al. · 2025Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP–SNARE complex assembly in protective autophagyView study →}. That is a different and worse kind of finding than a high-dose toxicity signal, because it means the molecule can be harmless on its own and harmful in company.

Three things reconcile them, and none of them makes the paradox go away:

• Dose is the likeliest discriminator. The antifibrotic result sits at 1–2 mg/kg in rats ^{1Reference 1Dang SS et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in ratsView study →}; the anticancer literature runs at micromolar concentrations that are frankly cytotoxic ^{2Reference 2Manoharan S et al. · 2022Chemotherapeutic potential of saikosaponin D: experimental evidenceView study →}, and it is the same cytotoxicity that damages hepatocytes. There is no safe-margin consensus separating the two.
• Target cell differs. Antifibrotic activity acts on hepatic stellate cells — suppressing the cells that lay down scar — while the toxicity acts on hepatocytes. A molecule that kills activated stellate cells and also kills hepatocytes is not straightforwardly protective.
• Context decides. In a fibrosis model there is scarring to suppress; alongside paracetamol there is an autophagic defence to disable ^{3Reference 3Fan G et al. · 2025Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP–SNARE complex assembly in protective autophagyView study →}.

The practical reading is that saikosaponin D should not be described as hepatoprotective without the counterweight, and that traditional vinegar or wine processing of Bupleurum root — which lowers saikosaponin a and d content — functions as a safety step ^{9Reference 9Wang S et al. · 2017AnimalContent decline of the SERCA inhibitors saikosaponin a and d attenuates the cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri — animal modelView study →}. It is also why the isolated molecule carries more risk than the processed herb.

The same caution covers its epimer. Saikosaponin A differs from saikosaponin D only in the orientation of one hydroxyl at C-16 ^{8Reference 8Lu CN et al. · 2012In vitroSaikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of the NF-κB signalling pathway — in vitroView study →}, the two occur together in the root, and vinegar-frying lowers them together — so preparations concentrated in one are generally concentrated in the other, and this section is the hepatotoxicity reference for both. What is specific to saikosaponin A rather than shared is its VEGFR2-mediated anti-angiogenic activity; what is specific to saikosaponin D is the hepatocyte apoptosis and the autophagy sabotage described here.

What It's Used For

Saikosaponin D (SSd) is the most-studied triterpenoid saponin of Bupleurum (Chai Hu), and its entry is defined by a paradox. The historical flagship result is anti-fibrotic — SSd reduced carbon-tetrachloride-induced liver fibrosis in rats ^{1Reference 1Dang SS et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in ratsView study →} — yet the same molecule is a dose-dependent hepatotoxin that worsens drug-induced liver injury ^{3,4Reference 3Fan G et al. · 2025Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP–SNARE complex assembly in protective autophagyView study →Reference 4Zhang F et al. · 2016Activation of the Fas death-receptor pathway and Bid in hepatocytes is involved in saikosaponin-D induction of hepatotoxicityView study →}.

Both are real, and the antifibrotic framing must never stand without the hepatotoxic counterweight. Two further caveats matter as much: SSd is a large, glycosylated saponin with poor oral bioavailability, so nearly all its verified activity is from injected or in-vitro exposure; and it is estrogenic and a CYP3A4 inducer ^{5,6Reference 5Wang P et al. · 2010In vitroEstrogen-like activities of saikosaponin-d in vitro: a pilot studyView study →Reference 6Li H et al. · 2021Effects of saikosaponin-d on CYP3A4 in HepaRG cells and a protein-ligand docking studyView study →}.

There are no human trials of the isolated molecule — the well-known Sho-saiko-to safety episodes belong to the multi-herb formula, not to SSd.

Evidence by IndicationStrength of support · Beta

01Anti-fibrotic (paradoxical)Shaky34%One rat CCl₄ study — set against its own hepatotoxicity ^{1,3Reference 1Dang SS et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in ratsView study →Reference 3Fan G et al. · 2025Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP–SNARE complex assembly in protective autophagyView study →}

02Anti-inflammatory / antidepressantShaky30%Rodent NLRP3-inflammasome mechanism ^{7Reference 7Gao T et al. · 2024Saikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activationView study →}

03AnticancerShaky28%Broad in-vitro, cytotoxic concentrations ^{2Reference 2Manoharan S et al. · 2022Chemotherapeutic potential of saikosaponin D: experimental evidenceView study →}

04Estrogenic activityShaky18%One in-vitro pilot — a caution more than a benefit ^{5Reference 5Wang P et al. · 2010In vitroEstrogen-like activities of saikosaponin-d in vitro: a pilot studyView study →}

Mechanisms

Pharmacokinetics

SSd is a large oleanane triterpenoid saponin (bisdesmoside) — high molecular weight and glycosylated, so it is poorly membrane-permeable with poor oral bioavailability, the generic saponin liability. On top of that it is acid-labile in a specific and complete way: the strained 13,28-epoxy ether opens under mild acid to a heteroannular diene, converting saikosaponin d entirely into saikosaponin b2 — a conversion reliable enough that the standard HPLC assay of Radix Bupleuri performs it deliberately and measures the b-series product instead ^{10Reference 10Li XQ et al. · 2005High-performance liquid chromatographic assay of saikosaponins from Radix Bupleuri in ChinaView study →}. A swallowed dose therefore meets a stomach that rearranges it, on top of the extensive gut-microbial and hepatic biotransformation the saikosaponins undergo generally ^{15Reference 15Yang Y et al. · 2025ReviewResearch progress on the extraction, purification, biotransformation, pharmacological effects, toxicity, combined therapy and new dosage forms of saikosaponins — reviewView study →}. No dedicated human pharmacokinetics is available, and essentially all verified activity comes from injected or in-vitro exposure — so oral human relevance of isolated SSd is unestablished, and ingesting it should not be assumed to reproduce the preclinical concentrations. The rearrangement cuts both ways for safety: it means an oral dose delivers less intact saikosaponin D than the label suggests, and also that the species reaching the liver is only partly the one the hepatotoxicity studies used.

Clinical Trials

There are no human trials of isolated saikosaponin D. The well-known clinical safety episode — interstitial pneumonitis and hepatic injury associated with Sho-saiko-to (Xiao Chai Hu Tang) — concerns the multi-herb Bupleurum formula, not the isolated molecule, and belongs on the herb/formula pages.

Last checked: September 2026.

Isolate vs. Plant Studies

All of it is isolate, and none of it is human. The CCl₄ antifibrotic work ^{1,17Reference 1Dang SS et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in ratsView study →Reference 17Abe H et al. · 1982AnimalProtective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat — animal modelView study →}, the Fas/Bid hepatocyte apoptosis ^{4Reference 4Zhang F et al. · 2016Activation of the Fas death-receptor pathway and Bid in hepatocytes is involved in saikosaponin-D induction of hepatotoxicityView study →}, the acetaminophen-sensitisation study ^{3Reference 3Fan G et al. · 2025Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP–SNARE complex assembly in protective autophagyView study →}, the anticancer cell-line literature ^{2Reference 2Manoharan S et al. · 2022Chemotherapeutic potential of saikosaponin D: experimental evidenceView study →}, the oestrogen-receptor pilot ^{5Reference 5Wang P et al. · 2010In vitroEstrogen-like activities of saikosaponin-d in vitro: a pilot studyView study →}, the CYP3A4 induction ^{6Reference 6Li H et al. · 2021Effects of saikosaponin-d on CYP3A4 in HepaRG cells and a protein-ligand docking studyView study →} and the NLRP3 antidepressant model ^{7Reference 7Gao T et al. · 2024Saikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activationView study →} all use purified saikosaponin D in cells or rodents.

The clinical material is at the other end of a long chain. Bupleurum is used as a whole herb inside a multi-herb formula — Xiao Chai Hu Tang, or Sho-saiko-to in Japan — and the famous safety episode attached to that formula, interstitial pneumonitis with hepatic injury, belongs to the formula, not to this molecule. That distinction is easy to blur in the wrong direction: it would be as wrong to pin Sho-saiko-to’s adverse events on saikosaponin D as to credit chai hu’s traditional use to it.

Two features make the transfer weaker here than on most saponin pages:

• The molecule rearranges before it arrives. Acid converts saikosaponin d completely to saikosaponin b2 ^{10Reference 10Li XQ et al. · 2005High-performance liquid chromatographic assay of saikosaponins from Radix Bupleuri in ChinaView study →}, so an oral dose delivers a different compound to the gut than the one dosed into a culture dish.
• The preparation is designed to remove it. Vinegar- or wine-frying the root lowers saikosaponin a and d content, and demonstrably attenuates the associated cardio- and hepatotoxicity ^{9Reference 9Wang S et al. · 2017AnimalContent decline of the SERCA inhibitors saikosaponin a and d attenuates the cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri — animal modelView study →}. The processed herb is deliberately not the isolate.

So the honest summary is narrow: saikosaponin D is a real and well-characterised hepatotoxin as an isolated molecule at sufficient exposure, and a real antifibrotic in one rodent model at a low dose — and neither of those is a statement about drinking a chai hu decoction.

Its Role in Plants

Saikosaponins are Bupleurum’s dominant root metabolites, and laser-microdissection mapping shows they are concentrated in the outer tissues rather than spread through the root. Across Bupleurum scorzonerifolium, B. chinense and B. falcatum, the cork and cortex carry more saikosaponin types and higher contents of a, c and d than the phloem and xylem; within those outer layers the pattern is species-specific, with cork richer than cortex in B. scorzonerifolium and B. falcatum, and the reverse in B. chinense ^{11Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →}.

That is the placement of a defence compound — a membrane-active glycoside in the tissue that meets the soil, working against soil fungi and underground herbivores. Two practical consequences follow. Trimming or peeling the outer root removes the tissue the saikosaponins are in; and because the species differ in which outer layer is richest, morphologically similar roots from different species can differ chemically for reasons that are invisible in the finished herb ^{11Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →}.

Prevalence in Nature

Saikosaponin D is a Bupleurum molecule (Apiaceae) with no dietary occurrence. It is one of the three principal saikosaponins of chai hu root alongside saikosaponin A and saikosaponin C, and it occurs in all the medicinal species — B. chinense and B. scorzonerifolium, the two officially recognised Chinese sources, and B. falcatum, the Japanese saiko ^{11,14Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →Reference 14Ashour ML · 2011ReviewGenus Bupleurum: a review of its phytochemistry, pharmacology and modes of action — reviewView study →}.

Two variables move the content more than species does. Tissue — the cork and cortex hold most of it, the phloem and xylem much less ^{11Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →}. And processing — vinegar- or wine-frying deliberately lowers saikosaponin a and d, and the toxicity falls with them ^{9Reference 9Wang S et al. · 2017AnimalContent decline of the SERCA inhibitors saikosaponin a and d attenuates the cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri — animal modelView study →}. A page figure for “saikosaponin D content” is therefore a statement about a particular root, cut a particular way, prepared a particular way.

Major Natural Sources

Source	Part	Saikosaponin D
Bupleurum chinense (chai hu)	Root — cortex and cork	Present; cortex richer than cork 11Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →
Bupleurum scorzonerifolium (nan chai hu)	Root — cork and cortex	Present; cork richer than cortex 11Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →
Bupleurum falcatum (Japanese saiko)	Root — cork and cortex	Present; cork richer than cortex 11Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →
Bupleurum root, phloem and xylem	Root — inner tissues	Lower, and fewer saikosaponin types 11Reference 11Liang Z et al. · 2014Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometryView study →
Vinegar- or wine-fried root	Processed root	Deliberately reduced, and toxicity falls with it 9Reference 9Wang S et al. · 2017AnimalContent decline of the SERCA inhibitors saikosaponin a and d attenuates the cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri — animal modelView study →

Discovery & Synthesis

The saikosaponins are named for the herb, not the chemistry: saiko (柴胡) is the Japanese name for Bupleurum root, and the aglycones were correspondingly called saikogenins. The chemistry was settled in Japan in the 1960s — the structure of saikogenin A was established in 1966 by Shoji Shibata, Isao Kitagawa and Haruhiro Fujimoto in part XV of the Chemical Studies on Oriental Plant Drugs series ^{12Reference 12Shibata S et al. · 1966The chemical studies on oriental plant drugsView study →}, the same Tokyo programme that produced the ginsenoside and astragaloside structures. Shimaoka, Seo and Minato characterised the b-series saponins in 1975 ^{13Reference 13Shimaoka A et al. · 1975Saponins isolated from Bupleurum falcatum L.; components of saikosaponin bView study →}; those are the acid-rearrangement products, and identifying them is what made a workable assay for saikosaponins a and d possible ^{10Reference 10Li XQ et al. · 2005High-performance liquid chromatographic assay of saikosaponins from Radix Bupleuri in ChinaView study →}.

Pharmacology arrived soon after, and it arrived on the protective side first: Abe, Sakaguchi, Odashima and Arichi reported in 1982 that saikosaponin D isolated from Bupleurum falcatum protected rat liver against carbon tetrachloride ^{17Reference 17Abe H et al. · 1982AnimalProtective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat — animal modelView study →}. The hepatotoxicity literature is decades younger, which is a large part of why the protective framing travelled further than the cautionary one.

There is no total synthesis of saikosaponin D in use. It is an oleanane triterpene with a disaccharide and a 13,28-epoxy ether labile enough that acid alone rearranges it — awkward to make and easy to get from the plant. Commercial material is isolated from Bupleurum root by solvent extraction and chromatography, and the same lability is used analytically, converting it to saikosaponin b2 before measurement ^{10Reference 10Li XQ et al. · 2005High-performance liquid chromatographic assay of saikosaponins from Radix Bupleuri in ChinaView study →}. A related route runs downstream rather than upstream: enzymatic hydrolysis of saikosaponin b2 is an established way to prepare the rarer prosaikogenin D ^{16Reference 16Wu M et al. · 2020In vitroEfficient and clean preparation of rare prosaikogenin D by enzymatic hydrolysis of saikosaponin B2 and response surface methodology optimization — in vitroView study →}.

Patents: not yet researched (future patent-loop pass).

Toxicity & Safety

Saikosaponin D is a dose-dependent hepatotoxin — the same cytotoxicity that produces its anticancer results — and it also sensitizes the liver to other insults. Traditional vinegar or wine processing of Bupleurum root lowers saikosaponin content precisely because of this, so the isolated molecule carries more risk than the processed herb.

Safety at a Glance

⚠️ Moderate toxicityLiver riskDrug interactions

• Dose-dependent hepatotoxin. Triggers hepatocyte apoptosis via the Fas death-receptor pathway and Bid, with no safe-margin consensus.
• Sensitizes the liver to other drugs. Worsens acetaminophen-induced injury by disabling protective autophagy.
• Avoid in pregnancy. Estrogenic activity plus hepatotoxicity.
• Estrogenic (ER agonist). Proliferative in a hormone-sensitive cell line — an endocrine caution, not a benefit.
• Induces CYP3A4. Can lower plasma levels of CYP3A4-substrate medications.
• No human data, no established dose. All activity is preclinical and mostly from injected or in-vitro exposure.

Full Safety & Interactions Detail

SSd is best characterized as a dose-dependent hepatotoxin, and this is the defining feature of the entry. It activates the Fas death-receptor pathway and Bid in hepatocytes to cause apoptosis ^{4Reference 4Zhang F et al. · 2016Activation of the Fas death-receptor pathway and Bid in hepatocytes is involved in saikosaponin-D induction of hepatotoxicityView study →}, and it sensitizes the liver to other insults — it exacerbates acetaminophen-induced injury by sabotaging GABARAP–SNARE assembly in protective autophagy, i.e. disabling a hepatoprotective repair mechanism ^{3Reference 3Fan G et al. · 2025Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP–SNARE complex assembly in protective autophagyView study →}.

The paradox is intrinsic: the same molecule that reduced CCl₄ fibrosis at 1–2 mg/kg ^{1Reference 1Dang SS et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in ratsView study →} worsens drug-induced hepatocyte death, with no safe-margin consensus — which is why traditional vinegar/wine processing of Bupleurum, which lowers saikosaponin content, functions as a safety step. On top of this, SSd is estrogenic (ER-agonist, MCF-7 proliferation) ^{5Reference 5Wang P et al. · 2010In vitroEstrogen-like activities of saikosaponin-d in vitro: a pilot studyView study →} and a CYP3A4 inducer ^{6Reference 6Li H et al. · 2021Effects of saikosaponin-d on CYP3A4 in HepaRG cells and a protein-ligand docking studyView study →}, so it can lower plasma levels of CYP3A4-substrate drugs and adds an endocrine caution — the combined hepatotoxic, endocrine and interaction profile is well above the bar used for benign dietary constituents.

This section is the hepatotoxicity reference for both epimers. Saikosaponin A differs only in the orientation of one hydroxyl at C-16 ^{8Reference 8Lu CN et al. · 2012In vitroSaikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of the NF-κB signalling pathway — in vitroView study →}, occurs in the same root tissues, and is lowered by the same vinegar processing ^{9Reference 9Wang S et al. · 2017AnimalContent decline of the SERCA inhibitors saikosaponin a and d attenuates the cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri — animal modelView study →}; both are also SERCA inhibitors, which is the activity implicated in the cardiotoxicity of Bupleurum preparations ^{9Reference 9Wang S et al. · 2017AnimalContent decline of the SERCA inhibitors saikosaponin a and d attenuates the cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri — animal modelView study →}. The mild third sibling saikosaponin C is neither.

Dosage

There is no established or safe human dose for saikosaponin D, and nothing here is a recommendation. Antifibrotic rat studies used 1–2 mg/kg ^{1Reference 1Dang SS et al. · 2007AnimalInhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in ratsView study →}, and anticancer/mechanistic work used micromolar in-vitro concentrations that are cytotoxic ranges overlapping the hepatotoxic mechanism, not a therapeutic target ^{2Reference 2Manoharan S et al. · 2022Chemotherapeutic potential of saikosaponin D: experimental evidenceView study →}. Poor oral bioavailability plus dose-dependent hepatotoxicity means the preclinical doses do not translate to human use.

References

1. Dang SS, Wang BF, Cheng YA, et al. (2007). Inhibitory effects of saikosaponin-d on CCl₄-induced hepatic fibrogenesis in rats. World Journal of Gastroenterology. https://pubmed.ncbi.nlm.nih.gov/17278221/
2. Manoharan S, Deivendran B, Perumal E (2022). Chemotherapeutic potential of saikosaponin D: experimental evidence. Journal of Xenobiotics. https://pubmed.ncbi.nlm.nih.gov/36547471/
3. Fan G, Li X, Li F, et al. (2025). Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP–SNARE complex assembly in protective autophagy. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/39874796/
4. Zhang F, Chen L, Jin H, et al. (2016). Activation of the Fas death-receptor pathway and Bid in hepatocytes is involved in saikosaponin-D induction of hepatotoxicity. Environmental Toxicology and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/26645133/
5. Wang P, Ren J, Tang J, et al. (2010). Estrogen-like activities of saikosaponin-d in vitro: a pilot study. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/19819234/
6. Li H, Tang Y, Wei W, et al. (2021). Effects of saikosaponin-d on CYP3A4 in HepaRG cells and a protein-ligand docking study. Basic & Clinical Pharmacology & Toxicology. https://pubmed.ncbi.nlm.nih.gov/33369126/
7. Gao T, Wang T, Wu L, et al. (2024). Saikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activation. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/38070467/
8. Lu CN, Yuan ZG, Zhang XL, et al. (2012). Saikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of the NF-κB signalling pathway — in vitro. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/22728095/
9. Wang S, Zhang Y, Zhang Q, et al. (2017). Content decline of the SERCA inhibitors saikosaponin a and d attenuates the cardiotoxicity and hepatotoxicity of vinegar-baked Radix Bupleuri — animal model. Environmental Toxicology and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/28412648/
10. Li XQ, Gao QT, Chen XH, et al. (2005). High-performance liquid chromatographic assay of saikosaponins from Radix Bupleuri in China. Biological and Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/16141550/
11. Liang Z, Oh K, Wang Y, et al. (2014). Cell type-specific qualitative and quantitative analysis of saikosaponins in three Bupleurum species using laser microdissection and liquid chromatography-quadrupole/time-of-flight mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. https://pubmed.ncbi.nlm.nih.gov/24863374/
12. Shibata S, Kitagawa I, Fujimoto H (1966). The chemical studies on oriental plant drugs. XV. On the constituents of Bupleurum spp. (2). The structure of saikogenin A, a sapogenin of Bupleurum falcatum L. Chemical and Pharmaceutical Bulletin. https://doi.org/10.1248/cpb.14.1023
13. Shimaoka A, Seo S, Minato H (1975). Saponins isolated from Bupleurum falcatum L.; components of saikosaponin b. Journal of the Chemical Society, Perkin Transactions 1. https://doi.org/10.1039/p19750002043
14. Ashour ML, Wink M (2011). Genus Bupleurum: a review of its phytochemistry, pharmacology and modes of action — review. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/21749378/
15. Yang Y, Chen H, Sun J, et al. (2025). Research progress on the extraction, purification, biotransformation, pharmacological effects, toxicity, combined therapy and new dosage forms of saikosaponins — review. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/40639699/
16. Wu M, Wang M, Zhang Y, et al. (2020). Efficient and clean preparation of rare prosaikogenin D by enzymatic hydrolysis of saikosaponin B2 and response surface methodology optimization — in vitro. Enzyme and Microbial Technology. https://pubmed.ncbi.nlm.nih.gov/33220869/
17. Abe H, Sakaguchi M, Odashima S, et al. (1982). Protective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat — animal model. Naunyn-Schmiedeberg’s Archives of Pharmacology. https://doi.org/10.1007/bf00510139

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