Baicalein

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1. What Baicalein Is

Flavonoids are secondary plant metabolites; baicalein therefore belongs to the same substance class as the compounds galangin, isorhamnetin and apigenin mentioned in the adjacent studies. The reviews classify it as a natural flavonoid and discuss it for chronic liver diseases, cancer prevention and treatment, neurodegenerative diseases and hepatocyte protection. Some of the studies examine baicalein as an isolated substance, others in mixtures with additional flavonoids. This distinction is decisive for evaluation, because no effect of the single substance can be inferred from mixture studies.

One point is central to understanding all studies: the great majority of investigations are not conducted in humans. The studies span basic research, cell culture and animal and human cell models; only observational studies exist in humans. Consequently, an open question stands between the described molecular mechanisms and any application in humans: whether the concentrations at which effects are reported in cell studies are attained in the human organism at all. This question is not answered in the available studies. Hypothesis: It is likely the principal reason why clinical testing is still pending.

2. What the Studies Show in Detail

The key human studies and the most important reviews — by application area, with population, duration, preparation, measured variable and result as reported in the original papers. Numbers appear only where the study states them.

Inflammatory Processes

In a mouse model of acute-on-chronic liver failure (ACLF), baicalein was administered intraperitoneally; the model was created by chronic liver damage with carbon tetrachloride followed by acute inflammatory induction with lipopolysaccharide 1. Baicalein markedly reduced acute inflammation and liver damage, assessed by histopathological evaluation, liver-function analysis and inflammatory markers. Transcriptomics and molecular-biological experiments showed that baicalein up-regulates surface expression of the TREM2 receptor on macrophages via activation of the TrkB-CREB1 signalling axis, promotes M2 polarisation and activates efferocytosis. The macrophage cell line iBMDM served for mechanistic clarification in vitro; peripheral blood from clinical ACLF patients was additionally used for validation. The results rest essentially on animal and cell models and are therefore preclinical.

One study combined network pharmacology, molecular docking, bulk RNA sequencing of macrophages and single-cell RNA sequencing of peripheral blood from sepsis patients 5. JAK2, SRC, TP53, MAPK3, AKT1, HSP90AA1 and ESR1 were identified as potential core targets of baicalein in macrophages; the JAK2-STAT3 and NF-κB signalling pathways emerged as possible downstream regulatory axes of the anti-inflammatory effect. On the basis of the single-cell expression patterns, baicalein could modulate the inflammatory phenotype of several peripheral-blood immune-cell populations, including monocytes, T cells, B cells and granulocyte-monocyte progenitors. The authors themselves classify this as a potential systemic effect that still requires experimental verification in human cells.

A 2023 review summarises findings on the root extract of Scutellaria baicalensis, to which hepatoprotective, sedative, antiallergic and anti-inflammatory properties are attributed; baicalein, the 5,6,7-trihydroxyflavone, is described therein as one of the principal aglycones with strong antiradical activity 32. A 2025 narrative review places baicalein alongside galangin and isorhamnetin in chronic liver diseases and cites hepatoprotective effects via attenuation of oxidative stress, inhibition of fibrogenesis and modulation of lipid metabolism 33. A further 2025 review lists hepatoprotective effects against various toxicity models (acetaminophen, cisplatin, doxorubicin, CCl4, monocrotalin, D-galactosamine) as well as activities in neurotoxicity, inflammation (arthritis, pulmonary fibrosis, LPS-induced sepsis), cancer and diabetes 31; it therefore addresses several agents and not baicalein alone.

Three further reviews address adjacent fields. A 2024 paper summarises data on cancer prevention and treatment and states that baicalein is said to inhibit cancer progression via induction of apoptosis, autophagy and genomic instability as well as to exert chemopotentiation and antimetastatic effects; traditionally it is used, among other indications, for hypertension, cardiovascular diseases, inflammation and infections 26. A 2024 review on gastrointestinal tumours deals with chemistry, pharmacokinetics, nanotechnology and synergisms. A 2025 paper discusses modulation of Nrf2/ARE, NFĸB and MAPK, mitochondrial protection, apoptosis regulation, autophagy and excitotoxicity for Huntington’s disease; the preclinical evidence derives from in-vitro and in-vivo studies, and the authors name bioavailability and clinical translation as open questions 30.

Viral Infections

The XueBiJing injection (XBJ) is associated with immunomodulatory, antithrombotic and antioxidant effects in severe infections such as sepsis and COVID-19 2. In the zebrafish model, XBJ reduced the numbers of neutrophils and macrophages in a dose-dependent manner. Through network pharmacology, molecular docking and kinetic simulation, baicalein was identified as one of the key compounds targeting KEAP1; binding to the target protein was verified by cellular thermal shift assay–Western blot and surface plasmon resonance, and the central signalling pathways were confirmed by gene silencing. The study examines a multi-substance mixture; no effect of baicalein alone can be inferred from it. Which binding affinity and which effect on KEAP1-mediated antioxidant activity were measured individually remains an open question that a targeted investigation with baicalein alone would clarify.

Metabolism

In a study on diabetic cardiomyopathy, baicalein was tested for inhibition of ferroptosis induced by high glucose and sodium palmitate concentrations (HG + PA) in cardiomyocytes 3. Baicalein markedly improved viability of H9c2 and AC16 cells, reduced cell death and lowered LDH release under HG + PA. Network pharmacology and data analysis assigned the protection to ferroptosis regulation; molecular docking predicted favourable binding geometries of baicalein with Nrf2, SLC7A11 and GPX4, and molecular-dynamics simulations indicated stability of the modelled complexes. The ferroptosis inhibitor ferrostatin-1 abolished the effects. The findings derive from cell culture and data analysis and are therefore preclinical.

A study on the hepatotoxic effect of tuberculosis drugs (ATB-DILI) combined network pharmacology, animal models and cell assays 6. Baicalein alleviated liver damage and hepatocyte injury in vivo and in vitro; the reactive-oxygen-species production, lipid accumulation and cellular ferroptosis triggered by the anti-TB drugs were attenuated. Baicalein reduced excessive ferritinophagy via the NCOA4/FTH1 signalling pathway. YAP1 knockdown abolished the protective effect: the increase in NCOA4, the decrease in FTH1, iron overload and the subsequent ferroptosis and lipid peroxidation in rat liver and hepatocytes did not occur. These are again animal and cell findings; testing in humans is still pending.

Oncology

In cell lines and human-derived xenograft models (cell-derived xenograft), baicalein showed stronger activity against microsatellite-unstable (MSI) colorectal cancer than against microsatellite-stable (MSS) colorectal cancer 4. Adenosylhomocysteinase was identified as a binding target via baicalein affinity purification conjugated to Sepharose 4B; several biochemical assays characterised the binding affinity. Histone methylation and stem-cell-gene expression were analysed by Western blot. Relevance of target and signalling pathway was validated on clinical patient tissue samples and patient-derived xenograft models (PDX). The work therefore rests on cell and animal models with human tissue for validation; clinical testing of the MSI-specific effect is the next open question.

Overall Picture

Across the fields runs a mechanistic thread: baicalein is linked to the modulation of Nrf2, NF-κB and MAPK, to the inhibition of ferroptosis and ferritinophagy, and to the shift of macrophages towards M2 polarisation 1 3 5 6 30. The studies repeatedly employ network pharmacology, molecular docking and pathway analyses and subsequently test the predicted targets in cell and animal models. The review articles collate these findings for liver, nervous system, cancer and metabolism 31 26 32 33; one of them covers baicalein together with galangin and isorhamnetin. Taken together, the studies present a consistent preclinical picture that justifies further testing in humans.

What remains outstanding across all fields is clinical testing. The cited mechanistic studies report results from cell culture, zebrafish, mouse and rat; human material in these studies served to validate individual targets or pathways 1 4 5. For Huntington’s disease the authors explicitly name bioavailability and clinical translation as open questions 30. Hypothesis: Should the preclinical mechanisms be confirmed, controlled studies with clear dose specifications and defined endpoints would be the next step; which dose is effective and tolerable in humans has not yet been examined.

3. How Robust the Research Is

Research on baicalein is broad but unevenly distributed. The largest block consists of cell-culture studies, followed by mechanism reviews. Animal studies and investigations on human cells are markedly rarer; studies in humans form a small group. In terms of content, four areas dominate: inflammation and oxidative stress, neurodegenerative diseases, oncology and liver diseases; metabolic topics such as insulin resistance are also present. Individual studies address environmental and agricultural questions, for example the influence of cadmium in carp. The most frequently cited study overall is a basic-science investigation of Nrf2 and NF-κB in neurodegenerative diseases.

The methodological strength of the field lies in its mechanistic detail: several studies consistently describe pathways such as Nrf2/ARE, NF-κB and MAPK, and the reviews collate these findings. The citation counts indicate high scientific interest. The weakness lies in transferability. Cell-culture and animal findings are preclinical; they do not support any statement about the course of a disease in humans. The observational human studies describe associations and mechanisms, not a tested effect. No conclusion about baicalein alone can be drawn from combination studies with other flavonoids. A clinical assessment therefore rests, for the time being, on preclinical findings.

Distribution of observational human studies by application area — the figures are not additive, as one study may be assigned to several areas:

4. What Is Frequently Claimed — and What the Data Support

5. Profile: Molecule and Charge

baicalein is not a single molecule but a mixture — there is no molecular formula and no fixed molecular mass. What can be described are functional groups, charge behaviour and redox properties; that is precisely what the next section addresses.

6. Charge, Electrons, Radicals

Radicals and redox stand at the centre of the available findings. DPPH radical-scavenging capacity has been examined in human tissue. For immunogenic cell death triggered by baicalein, a review shows that inhibition of ER stress or reactive oxygen species (ROS) attenuated this process, pointing to an ROS-dependent mechanism 18. In cell culture, ROS levels decreased under a hydrogel formulation 21, whereas a combination treatment produced a pro-oxidative shift with an increase in ROS of 78 % to 144 % 20. Single substance and combination must be read separately.

Little has yet been measured in humans. One human observation reports that ROS formation, lipid accumulation and cellular ferroptosis under anti-TB medication were reduced after treatment with Bai both in vivo and in vitro 6. Further studies — human tissue, review and cell culture — classify ROS as accompanying keratinocyte damage by particulate matter 16, as a driver of dopaminergic neuron degeneration 19 and as a signalling pathway in acute myeloid leukaemia 22. Charge, cation exchange and electron transfer are not measured in the cited studies. What remains to be clarified is whether radical-scavenging capacity and ROS modulation can be reproduced in humans.

7. Interactions with Other Substances

With which other substances on the platform this substance has been jointly examined or discussed in human studies and reviews — combination, comparison or shared pathway. The number indicates studies in which both appear.

Regarding absorption, a pharmacokinetic study in rats reports a relative bioavailability of 236,4 % for a solid dispersion (BAC-SD) compared with BAC 14. The formulation thus markedly influences absorption; whether this applies to humans remains open. Hypothesis: The anti-inflammatory mechanism of baicalein may be associated with interactions at target structures of the CYP450 family in HaCaT cells 25. An observation in humans shows that baicalein upregulates PLAU gene expression, but the increased PLAU protein is bound and inhibited 10.

A review names baicalein as an option alone or with established cancer therapeutics 26. In the animal experiment, BAI was combined with TNF-α to downregulate the TNF-α/TNFR1-AP-1 signalling pathway 27. In HaCaT cells, baicalein lowered inflammatory factors after induction with TNF-α and IFN-γ, without influencing the Th1/Th17 shift 24. For PMP@ED/Ba with NIR irradiation, a review describes synergistic inhibition of T24 tumour growth 23. For a representative from TQG (HQA004), synergistic Mpro inhibition was described with arbidol 28 28. Which combinations hold in humans remains open.

8. Overdosage, Tolerability, Limits

Regarding the tolerability of baicalein, one study reports that preclinical investigations show a good safety profile and that few adverse effects occurred at therapeutic doses 8; the evidence sentence contains no dose specification. A review summarises the hepatoprotective effect of baicalein against various toxicity models (acetaminophen, cisplatin, doxorubicin, CCl4, monocrotalin, d-galactosamine) 31. In human cell lines, normal liver cells (THLE-2) and liver cancer cells (HepG2) were tested for cytotoxicity in the MTT assay 17; for BC a selective effect on HepG2 cells with a high selectivity index is described 17.

A comparator preparation (UNI110) achieved a sevenfold higher potency than baicalein in MMR-deficient cell lines, with lower IC50 values and stronger cytotoxic effect 29. The cytotoxic and immunogenic effects of baicalein were investigated in murine (ID8) and human (SKOV3) ovarian carcinoma cell lines 18. For a combination of a baicalein-containing system and NIR irradiation, tumour suppression with extensive apoptosis and necrosis without significant organ toxicity was described 23; no conclusion about baicalein alone is possible from this. Upper limits and contraindications in humans would need to be clarified in dose-escalation studies.

9. The Most Robust Studies

Ordered by strength of evidence, not by familiarity: reviews and studies with many participants first. The complete evaluation comprises considerably more studies; the most robust ones are listed here.

Observational Studies in Humans

• 1 Baicalein upregulates macrophage TREM2 expression via TrKB-CREB1 pathway to attenuate acute inflammatory injury in acute-on-chronic liver failure (2024)
• 2 Identifying Baicalein as a Key Bioactive Compound in XueBiJing Targeting KEAP1: Implications for Antioxidant Effects (2025)
• 3 Baicalein Attenuates High Glucose and Sodium Palmitate-Induced Ferroptosis in Cardiomyocytes via the Nrf2/SLC7A11/GPX4 Signaling Pathway (2026)
• 4 Baicalein specifically suppresses microsatellite instability colorectal cancer by targeting adenosylhomocysteinase to inhibit histone H3 lysine 4 … (2025)
• 5 Potential targets of baicalein in macrophages revealed by bulk and single cell RNA sequencing analysis (2026)
• 6 Baicalein mitigates anti-tuberculosis-induced liver injury via inhibition of lipid peroxidation mediated by ferritinophagy and ferroptosis … (2026)
• 7 Baicalein alleviates anxiety symptom in Parkinson's disease by targeting Sema3A-mediated parvalbumin interneuron dysfunction (2026)
• 8 Promising Anti-Cancer Effects and Mechanisms of Baicalin and Baicalein in the Treatment of Oral Cancer: A Comprehensive Review (2026)
• 9 Baicalein inhibits DDX60 to suppress pancreatic cancer growth and regulate the tumor microenvironment (2025)
• 10 Baicalein inhibits the progression of thyroid cancer by suppressing the TPL2/MEK2/ERK2 pathway (2026)
• 11 Therapeutic effects and mechanisms of action of Baicalein on stomach cancer: a comprehensive systematic literature review (2025)
• Targeting MMR-deficient colorectal cancer with a potent small molecule UNI110 (2025)
• 12 Mechanisms of Jisheng-Wumei tablet in laryngeal cancer treatment: a network pharmacology analysis of baicalein's targeting of cytochrome C for … (2025)

Investigations on Human Tissue

• 13 Ligand- and tissue-specific differences in the activation of the aryl hydrocarbon receptor by flavonoids: A focus on baicalein and scutellarein (2025)
• 14 Baicalein solid dispersion prepared by solvent evaporation enhances oral bioavailability and alleviates ulcerative colitis (2026)
• 15 A multifunctional eutectogel loaded with baicalein and MXene for diabetic infected wound healing under mild photothermal conditions (2026)
• A Novel Series of Flavone-Cinnamic Acid Hybrid Derivatives as Hypoglycemic Agents: Design, Synthesis, and Activity Studies (2026)
• 16 Baicalein protects human keratinocytes against PM_2.5-induced apoptosis by suppressing oxidative stress, endoplasmic reticulum … (2026)
• 17 Inhibition of Antioxidant Genes Expression in Echinococcus Granulosus by Baicalein: Implications for Novel Antiparasitic Strategies (2026)
• Antidiabetic Properties of Polyalthia longifolia: A Comprehensive In Vitro Study of Leaf and Stem Extracts (2025)

10. Summary

The research is strongly mechanistic in character and focuses on signalling pathways such as Nrf2, NF-κB and MAPK. Preclinical findings show anti-inflammatory, antioxidant and hepatoprotective effects in cell and animal models. In cell lines and xenograft models, baicalein acted more strongly against colorectal cancer with microsatellite instability than against microsatellite-stable colorectal cancer. A review from 2023 describes baicalein as one of the most important aglycones with strong antiradical activity. These results are preclinical and carry no statement about the course of a disease in humans.

It is plausible that the repeatedly described mechanisms – modulation of Nrf2, NF-κB and MAPK, inhibition of ferroptosis and ferritinophagy as well as M2 polarisation of macrophages – justify further testing in humans. Hypothesis: Should these preclinical mechanisms be confirmed, controlled investigations with clear dose specifications and defined endpoints would be the next step. Which dose is effective and tolerable in humans has not yet been tested.

A study would have to test baicalein as a single substance in a sufficiently large group of humans, with predefined endpoints and clear dose specifications. For the MSI-specific effect in colorectal cancer, a clinical trial is the next open question. Such controlled investigations in humans with a clearly defined preparation are still lacking. The abundance of mechanisms does not replace a study in humans: high citation numbers measure attention in the scientific community, not the robustness of an application.

11. What Remains Open

• Absorption: Are the concentrations at which effects are described in cell experiments even reached in the human organism?
• Single Substance: Can a finding from studies that combine baicalein with apigenin, galangin or isorhamnetin be attributed to baicalein alone at all?
• Endpoints: Which clinical endpoints would a controlled study in humans have to define in advance in order to make an effect testable?

12. Further Paths

Topics, mechanisms of action and chains in which this substance occurs — for all those who wish to look beyond the substance.

• Interaction Network