☯ TCM Properties

Category: clearing heat

Temperature: cool

Taste: sweet, bitter

Meridians: lung, liver, stomach

Functions:

Clears Heat and Resolves Toxicity; Inhibits cancer; Stops Bleeding; Dispels Wind-Dampness; Promotes Urination and Drains Damp-Heat

Traditional Chinese Uses

Shi Shang Bai (selaginella doederleinii herb, rock cypress herb) is a bitter, neutral herb used in Chinese medicine to clear Heat toxin, eliminate Dampness, and stop coughing. It is applied for Lung Heat cough and wheezing with phlegm, urinary tract infections from Damp-Heat, jaundice, and inflammatory conditions involving Heat toxin and Dampness. Modern Chinese herbal oncology has explored its use as a supportive herb for certain types of cancer due to its Heat-toxin-clearing and immune-modulating effects.

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Botanical Description

Selaginella doederleinii is a perennial evergreen spikemoss (lycophyte) of the family Selaginellaceae, native to shaded, humid forested slopes and stream banks in southern China, Taiwan, Japan, and parts of Southeast Asia. It forms loose mats with creeping primary stems that root at the nodes, giving rise to erect or ascending, repeatedly branched leafy shoots 15 to 45 cm tall. The shoots bear two ranks of larger lateral leaves and two ranks of smaller appressed median leaves, all bright green and finely toothed. Tetragonal strobili up to 1 cm long terminate the upper branches, containing both megaspores and microspores, which is characteristic of the heterosporous Selaginella. The entire aerial plant is collected year-round for medicinal use.

Active Constituents

Amentoflavone

Biflavonoid (C3'-C8'' linked apigenin dimer)

Concentration: 13.65% w/w of the ethyl acetate extract of the herb, the single most abundant constituent of that fraction

The dominant biflavone of the drug and the compound that drives both its cytotoxicity and its interaction risk. It is among the most potent natural inhibitors of human CYP3A4 and CYP2C9 reported, with IC50 values of 0.07 and 0.03 microM respectively in one polyphenol screen, and it also shows time-dependent (mechanism-based) inhibition of CYP2C19, CYP2D6 and CYP3A.

Delicaflavone

Biflavonoid

Concentration: 2.21% w/w of the ethyl acetate extract

The second most abundant biflavone of the extract and one of the compounds carrying its antitumour activity. Unlike amentoflavone it showed no time-dependent CYP inhibition, so it contributes less to the interaction profile.

Apigenin

Flavone

Concentration: 0.024% w/w of the ethyl acetate extract

The monomeric flavone corresponding to the biflavone units. Present only in trace amounts, so it contributes little to the activity of the whole drug relative to the dimers.

Palmatine

Protoberberine alkaloid

Concentration: 0.019% w/w of the ethyl acetate extract

A trace alkaloid of the drug, quantified alongside the biflavones in the CYP inhibition study. At this level it is not expected to contribute meaningfully to activity.

Total biflavonoids of Selaginella doederleinii

Biflavonoid fraction (C-C and C-O-C linked apigenin dimers)

Concentration: 22.26 mg/g of the dried herb by optimised ultrasound-assisted extraction; twenty biflavonoids identified in the total fraction, of which eight were new to this species, including a rare class linked by direct C-3-O-C-4''' bonds

This fraction is the pharmacologically relevant part of the drug. Isolated members inhibit non-small-cell lung cancer cell proliferation with IC50 values of 2.3 to 8.4 microM while sparing non-cancerous MRC-5 fibroblasts, and the fraction shows antitumour activity in mouse xenograft models.

⚠ Drug Interactions

CYP2C9 substrates (warfarin, phenytoin, losartan, glimepiride, NSAIDs)

Major Evidence: Possible

The ethyl acetate extract of Selaginella doederleinii inhibits human CYP2C9 with an IC50 of 1.06 micrograms/mL, the most potently affected isoform tested. The responsible constituent is amentoflavone, reported at an IC50 of 0.03 microM against CYP2C9 in a separate polyphenol screen, and present at 13.65% of the extract. Evidence is entirely in vitro in human liver microsomes and recombinant enzymes; no human pharmacokinetic study of this herb exists, so the in vivo magnitude is unquantified but the potency of the inhibition makes it a real concern.

Clinical note: Avoid in patients on warfarin. If it is used anyway, check INR within one week of starting and one week of stopping. Watch for hypoglycaemia in patients on sulfonylureas.

CYP3A4/CYP3A substrates (statins, calcium channel blockers, ciclosporin, tacrolimus, midazolam, many kinase inhibitors and taxanes)

Major Evidence: Possible

The extract inhibits CYP3A with IC50 values of 5.18 micrograms/mL (testosterone probe) and 7.97 micrograms/mL (dextromethorphan probe), and both the extract and amentoflavone show time-dependent inhibition: after 35 minutes of NADPH pre-incubation, residual CYP3A activity fell from 98.5% to 63%. Time-dependent inhibition matters clinically because the enzyme must be resynthesised, so the effect accumulates with repeated dosing and persists after the herb is stopped. Amentoflavone inhibited recombinant CYP3A4 at an IC50 of 0.07 microM in a polyphenol screen. This is particularly important because Shi Shang Bai is given as an anticancer folk drug and many cytotoxic and targeted oncology agents are CYP3A4 substrates with narrow therapeutic windows.

Clinical note: Do not co-prescribe with chemotherapy, targeted oncology agents or transplant immunosuppressants. Where a patient is already taking it alongside cancer treatment, this should be disclosed to the treating oncologist rather than managed in the clinic.

CYP2C8 substrates (repaglinide, paclitaxel, montelukast)

Moderate Evidence: Possible

CYP2C8 was inhibited by the ethyl acetate extract with an IC50 of 1.04 micrograms/mL, essentially equal to CYP2C9 and the joint most sensitive isoform in the panel. As with the other isoforms, the data are in vitro only.

Clinical note: Relevant mainly to repaglinide and paclitaxel; separate the herb from these drugs rather than dose-adjusting empirically.

CYP2C19 and CYP2D6 substrates (clopidogrel, proton pump inhibitors, many antidepressants, tamoxifen)

Moderate Evidence: Possible

CYP2C19 was inhibited by the extract with an IC50 of 2.22 micrograms/mL. CYP2D6 was not inhibited in the direct assay (IC50 above 10 micrograms/mL) but both the extract and amentoflavone showed time-dependent inhibition of CYP2D6 as well as CYP2C19, so a single-timepoint IC50 understates the risk on repeated dosing. Clopidogrel and tamoxifen depend on CYP2C19 and CYP2D6 respectively for conversion to their active metabolites, so inhibition reduces rather than increases their effect.

Clinical note: Avoid alongside clopidogrel or tamoxifen, where the consequence of inhibition is treatment failure rather than toxicity.

Evidence Tier

Moderate evidence · 6 studies

Recorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.

Systematic review / meta-analysis

0

Randomized controlled trial

0

Other clinical trial

0

Observational / case report

0

In vitro / animal

6

1 verified · 5 unverified

Show 6 studies

Inhibitory effect of Selaginella doederleinii hieron on human cytochrome P450
Ethyl acetate extract from Selaginella doederleinii Hieron inhibits the growth of human lung cancer cells A549 via caspase-dependent apoptosis pathway
Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects
Biflavonoids from Selaginella doederleinii as Potential Antitumor Agents for Intervention of Non-Small Cell Lung Cancer
A Biflavonoid-Rich Extract from Selaginella doederleinii Hieron. against Throat Carcinoma via Akt/Bad and IKKβ/NF-κB/COX-2 Pathways
Antidiabetic and Antigout Properties of the Ultrasound-Assisted Extraction of Total Biflavonoids from Selaginella doederleinii Revealed by In Vitro and In Silico Studies

Other / unclassified

0

Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description

Clinical Studies

Inhibitory effect of Selaginella doederleinii hieron on human cytochrome P450

Lin F, Lin X, Wang X, Mei G, Chen B, Yao H, Huang L (2023) Frontiers in Pharmacology in vitro

The ethyl acetate extract and four quantified constituents were tested against a panel of human CYP isoforms. Extract IC50 values were 1.04 micrograms/mL for CYP2C8, 1.06 for CYP2C9, 2.22 for CYP2C19, 5.18 and 7.97 for CYP3A (testosterone and dextromethorphan probes), 8.90 for CYP2E1, and above 10 for CYP1A2 and CYP2D6. Both the extract and amentoflavone produced time-dependent inhibition of CYP2C19, CYP2D6 and CYP3A, with CYP3A activity falling from 98.5% to 63% after 35 minutes of NADPH pre-incubation; delicaflavone did not. Amentoflavone made up 13.65% of the extract, delicaflavone 2.21%, apigenin 0.024% and palmatine 0.019%. This is the single most clinically consequential study on the herb.

DOI: 10.3389/fphar.2023.1108867 Link

Ethyl acetate extract from Selaginella doederleinii Hieron inhibits the growth of human lung cancer cells A549 via caspase-dependent apoptosis pathway

Sui Y, Li S, Shi P, Wu Y, Li Y, Chen W, Huang L, Yao H, Lin X (2016) Journal of Ethnopharmacology animal

The ethyl acetate extract, containing mainly eight biflavonoids, caused loss of mitochondrial membrane potential in A549 lung cancer cells, upregulated Bax, downregulated Bcl-2, activated caspase-9 and caspase-3 and arrested cells in S phase. In A549 xenograft mice it reduced tumour growth, Ki67 expression and microvascular density. An acute oral toxicity test in healthy mice showed no apparent toxicity. This is the best animal evidence behind the traditional anticancer use, and it is still preclinical.

DOI: 10.1016/j.jep.2016.06.029 Link

Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects

Yao H, Chen B, Zhang Y, Ou H, Li Y, Li S, Shi P, Lin X (2017) Molecules animal Verified: In vitro / animal

Twenty biflavonoids were identified or tentatively characterised in the total biflavonoid extract, eight of them found in this species for the first time, spanning four linkage types. The extract was active in MTT assays and reduced tumour growth in a Lewis lung carcinoma xenograft model in C57BL/6 mice.

DOI: 10.3390/molecules22020325 Link

Biflavonoids from Selaginella doederleinii as Potential Antitumor Agents for Intervention of Non-Small Cell Lung Cancer

Kang F, Zhang S, Chen D, Tan J, Kuang M, Zhang J, Zeng G, Xu K, Zou Z, Tan G (2021) Molecules in vitro

Four previously undescribed biflavonoids with a rare direct C-3-O-C-4''' linkage were isolated alongside a known analogue. All inhibited non-small-cell lung cancer cell proliferation with IC50 values of 2.3 to 8.4 microM while showing low toxicity to non-cancerous MRC-5 cells, outperforming cisplatin in the same assay. The most active compound suppressed XIAP and survivin, increased cleaved caspase-3, and induced apoptosis and cell cycle arrest in A549 cells.

DOI: 10.3390/molecules26175401 Link

A Biflavonoid-Rich Extract from Selaginella doederleinii Hieron. against Throat Carcinoma via Akt/Bad and IKKβ/NF-κB/COX-2 Pathways

Wang S, Wan D, Liu W, Kang X, Zhou X, Sefidkon F, Hosseini MZ, Zhang T (2022) Pharmaceuticals in vitro

A biflavonoid-rich extract acted against throat carcinoma cells through the Akt/Bad and IKKbeta/NF-kappaB/COX-2 pathways, giving a mechanism for the folk use of the herb in Guangxi for throat cancer. As with all the antitumour work on this species, the evidence is cellular and animal only.

DOI: 10.3390/ph15121505 Link

Antidiabetic and Antigout Properties of the Ultrasound-Assisted Extraction of Total Biflavonoids from Selaginella doederleinii Revealed by In Vitro and In Silico Studies

Gao Q, Qiao L, Hou Y, Ran H, Zhang F, Liu C, Kuang J, Deng S, Jiang Y, Wang G, Zhang X (2024) Antioxidants in vitro

Optimised ultrasound extraction gave a total biflavonoid content of 22.26 mg/g of herb, purified with a transfer rate of 82.12%. The fraction inhibited alpha-glucosidase, alpha-amylase and xanthine oxidase in vitro. This is the source of the best available figure for how much biflavonoid a given weight of the crude drug actually contains.

DOI: 10.3390/antiox13101184 Link

Historical Texts

Quan Guo Zhong Cao Yao Hui Bian (A Compendium of Chinese Herbal Medicine)

Modern, People's Republic of China, 1975

The first standard reference to record Shi Shang Bai. It defines the drug as the whole plant of Selaginella doederleinii, gives it as sweet and neutral, and lists the indications as cancer, pneumonia, acute tonsillitis, conjunctivitis and mastitis. Shi Shang Bai has no pre-modern textual record: it entered the materia medica from Chinese folk practice during the twentieth-century anticancer herb surveys.

Zhong Hua Ben Cao (Chinese Materia Medica)

Modern, People's Republic of China, 1999

Gives the drug as sweet, slightly bitter, astringent and cool, clearing heat and resolving toxicity and dispelling wind-damp, for sore swollen throat, red swollen painful eyes, Lung-heat cough, mastitis, damp-heat jaundice, wind-damp painful obstruction and traumatic bleeding. Internal dose 10 to 30 g of the dried herb, double for fresh.

Shen Nong Ben Cao Jing

Han dynasty

Recorded here only to prevent a common conflation. The Juan Bai of the classic, listed in the upper grade, is Selaginella tamariscina, a different species with a different drug profile. It is not Selaginella doederleinii, and none of the classical Juan Bai indications should be carried across to Shi Shang Bai.

References

Kimura Y, Ito H, Ohnishi R, Hatano T. Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity . Food and Chemical Toxicology (2010) [DOI]
Liang H, Fang C, Qiu M. The multi-target mechanism of action of Selaginella doederleinii Hieron in the treatment of nasopharyngeal carcinoma: a network pharmacology and multi-omics analysis . Scientific Reports (2025) [DOI]

Shi Shang Bai

Traditionally used for

Cautions & contraindications