Acute toxicity of berberine and its correlation with the blood concentration in mice
Abstract
The aim of this study was to investigate the LD(50) (median lethal dosage) of berberine (BBR) through three different routes of injection in mice: intravenous (i.v.) injection, intraperitoneal (i.p.) injection, and intragastric (i.g.) oral administration. The concentration of BBR in blood from their i.g. doses (10.4, 20.8, 41.6, and 83.2 g/kg) and the content relationship of BBR among different injections were analyzed by high-performance liquid chromatography (HPLC). The LD(50) of BBR from i.v. and i.p. injections is 9.0386 and 57.6103 mg/kg, respectively; but no LD(50) was found in the i.g. group. A significant difference in bioavailability was observed between the different routes. Furthermore, the concentration of BBR in the blood from different i.g. doses was also significantly different. However, we discovered an interesting phenomenon indicating that the absorption of BBR by oral administration has a limit, therefore, explaining the difficulty in obtaining an LD(50) of BBR for i.g. injection. From the analysis of BBR content in blood after various administrations, we hypothesized that not only does the concentration of BBR in blood contribute to its acute toxicity, but also the routes of administration may be an important facet that affects this toxicity evaluation.
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The toxicity of berberine and related alkaloids depends on dose and formulation.
“The toxicity of berberine and related alkaloids also depends on dose and formulation [33,111]”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [111]
Berberine is not a harmless "natural" product but an active pharmacological perpetrator, with an interaction profile predictable from its pharmacology.
“Berberine is not a harmless “natural” product but an active pharmacological perpetrator, with an interaction profile predictable from its pharmacology [35,37,111].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [111]
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“The toxicity of berberine and related alkaloids also depends on dose and formulation [33,111], and the gastrointestinal safety profile is documented in dedicated syntheses [112].”
- Authors
- Kheir, M. M., Wang, Y., Hua, L., Hu, J., Li, L., Lei, F., & Du, L.
- Affiliations
- University of Michigan (US)
- Tsinghua University (CN)
- Corresponding author
- Du, Lijun
- Venue
- Food and Chemical Toxicology
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 48
- Issue
- 4
- Pages
- 1105-1110
- ISSN
- 0278-6915 (ISSN-L)
- OpenAlex
- W2016184231
- Cited by
- 235
- References
- 21
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 21 · 2023: 20 · 2022: 20 · 2021: 22 · 2020: 16 · 2019: 10 · 2018: 11 · 2017: 14 · 2016: 21 · 2015: 11 · 2014: 8 · 2013: 12 · 2012: 7
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Food and Chemical Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Plant-based Medicinal Research
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Keywords
- berberine, acute toxicity, LD50, route of administration, bioavailability, blood concentration, oral absorption, intravenous injection, intraperitoneal injection, intragastric administration, mice
- MeSH terms
- Animals, Berberine, Biological Availability, Chromatography, High Pressure Liquid, Drug Administration Routes, Drugs, Chinese Herbal, Female, Lethal Dose 50, Male, Mice, Inbred ICR, Toxicity Tests, Acute, Mice
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