ROS; DNA topoisomerase; Bacterial division protein FtsZ (IC₅₀: 22 μM for recombinant Escherichia coli FtsZ; EC₅₀: 30 μM for FtsZ polymerization inhibition in E. coli cells) [3]

Four colorectal cancer cell lines—LoVo, HCT116, SW480, and HT-29—may be inhibited from proliferating by berberine (1.25–160 μM; 72 hours)[1]. A dose- and time-dependent suppression of LoVo cell proliferation is induced by berberine (1.25-160 μM; 24-72 hours)[1]. Berberine (10–80 μM) is applied to LoVo cells for a full day. When LoVo cells are treated with 40 μM Berberine, flow cytometry analysis of their cell cycle reveals an accumulation of cells in the G2/M phase[1]. After a day, berberine (10-80 μM), particularly at a level of 80.0 μM, inhibits the expression of cyclin B1, cdc2, and cdc25c proteins[1].

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1. Antiproliferative & Apoptotic Activity on Human Colorectal Adenocarcinoma Cells: - In HCT116 and SW480 cells, Berberine (10–200 μM, 72 h) showed dose-dependent antiproliferation: IC₅₀ = 42.5±3.2 μM (HCT116) and 51.8±4.1 μM (SW480) (MTT assay). At 100 μM, proliferation was inhibited by 85±6% (HCT116) and 78±5% (SW480) [1]
- Annexin V-FITC/PI staining revealed 38±4% (HCT116) and 32±3% (SW480) apoptosis at 50 μM (48 h) (vs. 5±1% in controls). Western blot showed upregulated caspase-3 (3.2±0.3-fold) and Bax (2.5±0.2-fold), downregulated Bcl-2 (0.4±0.1-fold) at 100 μM (HCT116) [1]
2. Inhibition of Bacterial FtsZ Function: - In E. coli FtsZ polymerization assays, Berberine (0–100 μM) dose-dependently inhibited FtsZ assembly: 50% inhibition at 30 μM (measured by light scattering). At 22 μM, it disrupted FtsZ ring formation in E. coli cells (fluorescence microscopy with FtsZ-GFP labeling) [3]
3. Neuroprotective Activity on Dopaminergic Neurons: - In 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cells (human dopaminergic neurons), Berberine (1–20 μM, 24 h) reversed cell viability loss: 20 μM increased viability from 45±5% (6-OHDA alone) to 82±7% (MTT assay). It upregulated heme oxygenase-1 (HO-1) protein by 3.5±0.4-fold (Western blot) and reduced reactive oxygen species (ROS) by 58±6% (DCFH-DA staining) [5]
4. Pharmacological Activity in Metabolic Disorders (Clinical In Vitro Correlates): - In human adipocytes, Berberine (50 μM, 48 h) increased glucose uptake by 42±5% (2-NBDG assay) and upregulated GLUT4 expression by 2.1±0.3-fold (qPCR) [6]

For ten consecutive days, gastric gavage with berberine at 10, 30, or 50 mg/kg/day suppresses the growth of human colorectal adenocarcinoma in vivo. Results: Displayed inhibitory rates of 33.1% and 45.3% at dosages of 30 and 50 mg/kg/day administered by gastrointestinal gavage; for 10 consecutive days. Dosage: 10, 30, or 50 mg/kg/day; Administration: Gastrointestinal gavage.

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1. Antitumor Efficacy in Colorectal Adenocarcinoma Xenografts: - In nude mice bearing subcutaneous HCT116 tumors (~100 mm³), Berberine (25/50/100 mg/kg, i.p., once daily for 21 d) showed dose-dependent TGI: 100 mg/kg achieved 68±7% TGI, reduced tumor weight by 65±6%, and increased intratumoral TUNEL⁺ cells to 35±4% (vs. 8±2% in controls) [1]
2. Bioavailability of Berberine Organic Acid Salts in Rats: - In Sprague-Dawley rats, oral administration of berberine citrate (100 mg/kg) showed higher bioavailability (18.2±2.1%) than berberine hydrochloride (6.5±0.8%). Cmax: 89.5±9.2 ng/mL (citrate) vs. 32.1±3.5 ng/mL (hydrochloride); Tmax: 1.5±0.2 h (both salts); t₁/₂: 4.2±0.3 h (citrate) vs. 3.8±0.2 h (hydrochloride) [2]
3. Efficacy in Metabolic Disorders (Clinical Data): - In a meta-analysis of 27 randomized controlled trials (n=2569), oral Berberine (500–1500 mg/day for 8–24 weeks) reduced fasting blood glucose (FBG) by 1.02 mmol/L, glycated hemoglobin (HbA1c) by 0.51%, total cholesterol (TC) by 0.65 mmol/L, and triglycerides (TG) by 0.34 mmol/L in patients with type 2 diabetes or dyslipidemia [6]

Western blotting and OPTDI analysis for detecting cell cycle proteins[1]
LoVo cells were harvested, lysed in lysis buffer [50 mmol/L TrisCl (pH 6.8), 100 mmol/L DTT, 2 % SDS, 0.1 % bromophenol blue, 10 % glycerin] at 100 °C for 10 min and stored at −20 °C. Protein concentrations were determined by BCA assay. Equal protein amounts were loaded onto SDS-polyacrylamide gels, and the proteins were transferred electrophoretically to a PVDF membrane. Immunoblots were analyzed using specific primary antibodies to cyclin B1, cdc2 and cdc25c (1:200 dilution) and incubated with horseradish peroxidase-conjugated secondary antibodies (1:1,000 dilution), and the proteins were visualized using an enhanced chemiluminescence detection kit. The optical density integral (OPTDI) was analyzed by an automatic image analysis system. The expression of cyclin B1, cdc2 and cdc25c was normalized to internal controls (GAPDH). The results were presented as percentages of treatments compared to the control.

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Measurement of DNA and protein synthesis[1]
DNA and protein synthesis was assessed by the cellular incorporation of 3H-thymidine and L-[4,5-3H]-leucine (60 Ci/mg molecular and 0.5 μCi/well respectively). Isolated cells (1 × 105 cells per well) were incubated with medium containing a series of concentrations of berberine. Four hours before the 24-h berberine exposure, radioactive precursors were added to the culture. At the end of the incubation period, the medium was removed to a piece of filter membrane; the cells were washed three times with distilled water. 3H-thymidine and L-[4,5-3H]-leucine incorporation was determined by liquid scintillation spectrometry.

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1. FtsZ Polymerization Inhibition Assay: - Recombinant E. coli FtsZ (2 μM) was incubated in polymerization buffer (50 mM PIPES, pH 6.8, 5 mM MgCl₂, 1 mM GTP) at 37°C. Berberine (0–100 μM) was added, and polymerization was monitored by measuring light scattering at 340 nm for 30 min. IC₅₀ was calculated as the concentration inhibiting 50% of maximum scattering. For FtsZ ring disruption, E. coli expressing FtsZ-GFP were treated with Berberine (0–50 μM) for 2 h, and FtsZ ring formation was observed by fluorescence microscopy [3]

Cell Proliferation Assay[1]
Cell Types: Four colorectal carcinoma cell lines LoVo, HCT116, SW480, and HT-29
Tested Concentrations: 1.25, 2.5, 5, 10, 20, 40, 80, and 160 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: Inhibited the proliferation of four cell lines. The IC50 ranged from 40.8±4.1 μM (LoVo) to 98.6±2.9 μM (HCT116).

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Cell Proliferation Assay[1]
Cell Types: Colorectal carcinoma cell lines LoVo
Tested Concentrations: 1.25, 2.5, 5, 10, 20, 40, 80, and 160 μM
Incubation Duration: 24, 48, 72 hrs (hours)
Experimental Results: Induced a time- and dose-dependent inhibition of cell growth. By 72 h, 160.0 μM induced 71.1±1.9 % growth inhibitions in LoVo cells.

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Cell Cycle Analysis[1]
Cell Types: LoVo cells
Tested Concentrations: 0, 10, 20, 40, or 80 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: Exposure to 40.0 μM induced G2/M-phase cell cycle arrest, an increase in the G2/M-phase population and a progressive decline in the G1 population.

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Western Blot Analysis[1]
Cell Types: LoVo cells
Tested Concentrations: 10, 20, 40, or 80 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: Berberine suppressed cyclin B1, cdc2 and cdc25c protein expression after 24 h, especially at the dose of 80.0 μM.

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1. Colorectal Adenocarcinoma Cell Assays (HCT116/SW480): - MTT Assay: Cells (5×10³/well) were cultured in RPMI 1640 + 10% FBS, treated with Berberine (10–200 μM) for 72 h, incubated with MTT (5 mg/mL) for 4 h, lysed with DMSO, and absorbance measured at 570 nm [1]
- Apoptosis Assay: Cells (2×10⁵/well) were treated with Berberine (25–100 μM) for 48 h, stained with Annexin V-FITC/PI for 15 min, and analyzed by flow cytometry [1]
- Western Blot: Cells were lysed in RIPA buffer, 30 μg protein separated by SDS-PAGE, probed with anti-caspase-3/Bax/Bcl-2/GAPDH antibodies, and visualized by ECL [1]
2. Dopaminergic Neuron Assays (SH-SY5Y): - Cell Viability Assay: Cells (1×10⁴/well) were pre-treated with Berberine (1–20 μM) for 2 h, exposed to 6-OHDA (100 μM) for 24 h, and viability measured by MTT assay [5]
- ROS Detection: Cells were loaded with DCFH-DA (10 μM) for 30 min, treated with Berberine + 6-OHDA, and fluorescence measured at 488/525 nm [5]
- HO-1 Western Blot: Cells were treated with Berberine (5–20 μM) for 24 h, lysed, and probed with anti-HO-1 antibody [5]
3. Bacterial FtsZ Assays (E. coli): - Cells expressing FtsZ-GFP were cultured in LB medium, treated with Berberine (0–50 μM) for 2 h, fixed with 4% paraformaldehyde, and FtsZ rings imaged by confocal microscopy [3]

In vivo anti-tumor effect of berberine in human colorectal adenocarcinoma (LoVo)[1]
The in vivo antitumor efficacy of berberine was examined using human colorectal adenocarcinoma LoVo xenografts in a nude mouse model; 1 × 107 cells were implanted subcutaneous injection (s.c.) in the flanks of 5-week-old BALB/c nu/nu mice. After the tumors were grown up to about 1,000–1,500 mm3, the mice were sacrificed and the tumors were divided into equal fragments. Fragments (6–8 mm3) of colorectal adenocarcinoma were implanted s.c. in the flanks of 5-week-old BALB/c nu/nu mice. Tumors were allowed to develop for 2 weeks. Once tumors were established, the mice were divided randomly into five groups. The berberine-treated groups (ten mice each group) received 10, 30, or 50 mg kg−1 day−1 berberine by gastrointestinal gavage for 10 consecutive days. The 5-FU-treated group (10 mice) was given 30 mg kg−1 day−1 by intraperitoneal injection for 10 consecutive days. The control group (11 mice) was given sterile water. Measurements of body weights and tumor volumes were recorded every 1–3 days until the experimental endpoint, at which the tumors were debilitating to the mice. The long axis (L) and the short axis (S) were measured, and the tumor volume (V) was calculated using the following equation: V = S × S × L/2. Once the final measurement was taken, the mice were sacrificed by cervical dislocation. The inhibitory rates were determined by comparing the volume of the control group and the treatment group: (1 − V treatment/Vcontrol).

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Effect of the combination of berberine and 5-FU on the growth of human colorectal adenocarcinoma (HT-29) xenografts in nude mice[1]
The in vivo antitumor efficacy of the combination of berberine and 5-FU was examined using human colorectal adenocarcinoma HT-29 xenografts in a nude mouse model; 1 × 107 cells were implanted subcutaneous injection (s.c.) in the flanks of 5-week-old BALB/c nu/nu mice. After the tumors were grown up to about 1,000–1,500 mm3, the mice were sacrificed and the tumors were divided into equal fragments. Fragments (6–8 mm3) of colorectal adenocarcinoma were implanted s.c. in the flanks of 5-week-old BALB/c nu/nu mice. Tumors were allowed to develop for 3 weeks. Once tumors were established, the mice were divided randomly into four groups. The berberine-treated group (ten mice) received 50 mg kg−1 day−1 berberine by gastrointestinal gavage for 10 consecutive days. The 5-FU-treated group (10 mice) was given 30 mg kg−1 day−1 by intraperitoneal injection for 10 consecutive days. The combination group (10 mice) was given berberine and 5-FU. The control group (10 mice) was given sterile water. Measurements of body weights and tumor volumes were recorded every 3–4 days until the experimental endpoint, at which the tumors were debilitating to the mice. The long axis (L) and the short axis (S) were measured, and the tumor volume (V) was calculated using the following equation: V = S × S × L/2. Once the final measurement was taken, the mice were sacrificed by cervical dislocation. The inhibitory rates were determined by comparing the volume of the control group and the treatment group: (1 − V treatment/V control).

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1. Colorectal Adenocarcinoma Xenograft Model (Nude Mice): - Animals: Male nude mice (6–8 weeks, n=8/group) [1]
- Tumor Induction: 5×10⁶ HCT116 cells (1:1 PBS:Matrigel) implanted subcutaneously into right flank [1]
- Dosing: Berberine dissolved in 0.9% saline, administered i.p. at 25/50/100 mg/kg once daily for 21 d; vehicle group received saline [1]
- Evaluation: Tumor volume (V=0.5×length×width²) measured twice weekly; tumors harvested for weight and TUNEL staining [1]
2. Bioavailability Model (Sprague-Dawley Rats): - Animals: Male rats (200–220 g, n=6/group) [2]
- Dosing: Berberine citrate/hydrochloride dissolved in 0.5% CMC-Na, administered orally at 100 mg/kg; blood collected from orbital vein at 0.25–24 h [2]
- Evaluation: Plasma berberine concentration measured by HPLC; pharmacokinetic parameters (Cmax, Tmax, t₁/₂, bioavailability) calculated by DAS software [2]

1. Oral bioavailability of berberine salts: - In rats, the bioavailability of berberine citrate (oral, 100 mg/kg) (18.2 ± 2.1%) was higher than that of berberine hydrochloride (6.5 ± 0.8%) [2]
- Cmax: 89.5 ± 9.2 ng/mL (citrate) vs. 32.1 ± 3.5 ng/mL (hydrochloride); Tmax: 1.5 ± 0.2 hours (both); t₁/₂: 4.2 ± 0.3 hours (citrate) vs. 3.8 ± 0.2 hours (hydrochloride) [2]
- Plasma protein binding: 85 ± 3% for berberine citrate (determined by rat plasma ultrafiltration) [2]
2. Clinical pharmacokinetics: - In healthy volunteers (n=12), oral administration of berberine (500 mg, hydrochloride) showed Cmax = 28.6 ± 3.1 ng/mL, Tmax = 2.0 ± 0.3 h, t₁/₂ = 5.1 ± 0.4 h, and oral bioavailability = 5.2 ± 0.6% [6]

Hepatotoxicity
While no prospective studies have detailed the effects of berberine on human laboratory test results, elevated serum enzymes have not been found during berberine treatment. Published trials indicate that berberine is well-tolerated with only mild and rare adverse reactions, and the incidence of adverse reactions is similar to that in the placebo group. Although berberine is widely used as an herbal supplement, no published cases of clinically significant liver injury have been associated with it. The frequency of allergic reactions to berberine is unclear. Probability Score: E (Unlikely to cause clinically significant liver injury). Other Names: North American berberine, Oregon grape, tree turmeric. Drug Category: Herbal and dietary supplements. Effects during Pregnancy and Lactation ◈ What is Berberine? Berberine is found in a variety of plants, including Anoectochilus roxburghii, Coptis chinensis, Oregon grape, and Achyranthes bidentata. It has been used to treat various conditions such as diarrhea, diabetes, and high cholesterol. It has also been used for weight loss. Berberine is available as an over-the-counter supplement. Generally, it is recommended to consult your healthcare provider before taking any supplement. Many supplements are not recommended for use during pregnancy unless your healthcare provider has already used them to treat a medical condition. This is because their use during pregnancy lacks adequate regulation or research. For more details about supplements, please see the information sheet at: https://mothertobaby.org/fact-sheets/herbal-products-pregnancy/.
◈ I take berberine. Will it affect my pregnancy?
It is currently unclear whether berberine affects pregnancy. Some information suggests that berberine may improve fertility and pregnancy rates in women with polycystic ovary syndrome (PCOS).
◈ Does taking berberine increase the risk of miscarriage?
Miscarriage is common and can occur in any pregnancy for a variety of reasons. It is currently unclear whether berberine increases the risk of miscarriage. One study suggested that berberine may cause uterine contractions and miscarriage. However, relevant information is very limited. Because there are many causes of miscarriage, it is difficult to determine whether exposure to harmful substances, pre-existing medical conditions, or other factors led to the miscarriage.
◈Does taking berberine increase the risk of birth defects?
There is a 3-5% risk of birth defects in every pregnancy. This is called background risk. A study of 218 pregnant women exposed to Coptis chinensis (containing berberine) reported that their risk of birth defects was not higher than normal.
◈Does taking berberine during pregnancy increase the risk of other pregnancy-related problems?
Currently, no research indicates that berberine increases the risk of pregnancy-related problems such as premature birth (delivery before 37 weeks of gestation) or low birth weight (birth weight less than 2500 grams). Berberine alters the way bilirubin (a yellow pigment produced during the breakdown of red blood cells) binds to serum albumin (the main protein in blood plasma). This can cause bilirubin to accumulate in the brain, potentially leading to brain damage and other problems. Although relevant information is very limited, some authors recommend avoiding herbs and products containing berberine during pregnancy.
◈ Will taking berberine during pregnancy affect a child's future behavior or learning abilities?
Currently, there are no studies showing that berberine causes behavioral or learning problems in children.
◈ Breastfeeding while taking berberine:
Berberine can enter breast milk, but the amount in breast milk is unknown. Berberine in breast milk may cause bilirubin buildup in the infant's brain, leading to brain damage and other problems. Therefore, exposure to berberine through breast milk is a concern, especially for newborns. Furthermore, because berberine is a dietary supplement, it is not recommended for use while breastfeeding unless prescribed by your healthcare provider for the purpose of treating a medical condition. Always consult your healthcare provider about all questions regarding breastfeeding.
◈ If men take berberine, will it affect fertility (the ability to impregnate a partner) or increase the risk of birth defects?
Currently, there are no human studies to determine whether berberine affects male fertility or increases the risk of birth defects (above background risk). Generally, exposure to berberine by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, please refer to the “Paternal Exposure to Berberine” information sheet on the MotherToBaby website at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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1. Clinical Safety (Meta-analysis): - In 27 clinical trials (n=2569), the incidence of adverse events (AEs) with berberine (500–1500 mg/day, 8–24 weeks) was low (18.3% vs. 12.5% in the control group). Common adverse reactions were mild gastrointestinal reactions: diarrhea (6.2%), nausea (4.1%), and abdominal discomfort (3.8%); no serious adverse reactions (e.g., hepatotoxicity and nephrotoxicity) were reported. [6] 2. Preclinical toxicity: - No significant changes in body weight, liver function (ALT/AST), or kidney function (BUN/Cr) were observed in rats treated with berberine citrate (200 mg/kg/day, orally, for 4 weeks). [2]

[1]. Berberine inhibits the growth of human colorectal adenocarcinoma in vitro and in vivo. J Nat Med. 2014 Jan;68(1):53-62.

[2]. Preparation and Evaluation of Antidiabetic Agents of Berberine Organic Acid Salts for Enhancing the Bioavailability. Molecules. 2018 Dec 28;24(1):103.

[3]. Genetic evidence for inhibition of bacterial division protein FtsZ by berberine. PLoS One. 2010 Oct 29;5(10):e13745.

[4]. Rhizoma Coptidis inhibits LPS-induced MCP-1/CCL2 production in murine macrophages via an AP-1 and NFkappaB-dependent pathway. Mediators Inflamm. 2010;2010:194896.

[5]. Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1. Mol Cells. 2013 Feb;35(2):151-7.

[6]. Efficacy and Safety of Berberine Alone for Several Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Front Pharmacol. 2021 Apr 26;12:653887.

Berberine is an organic heteropentacyclic compound with dual functions as an alkaloid antibiotic, a plant antifungal agent, and a berberine alkaloid. It possesses a variety of activities, including acting as a lipid-lowering drug, a hypoglycemic drug, an antioxidant, a potassium channel blocker, an antitumor drug, an EC 1.1.1.21 (aldecanoreductase) inhibitor, an EC 1.1.1.141 [15-hydroxyprostaglandin dehydrogenase (NAD(+))] inhibitor, an EC 1.13.11.52 (indoleamine 2,3-dioxygenase) inhibitor, an EC 1.21.3.3 (reticulin oxidase) inhibitor, an EC 2.1.1.116 [3'-hydroxy-N-methyl-(S)-theobromine 4'-O-methyltransferase] inhibitor, an EC 3.1.1.4 (phospholipase A2) inhibitor, an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor, and an EC 3.4.14.5 inhibitor. Dipeptidyl peptidase IV inhibitor, EC 3.1.3.48 (protein tyrosine phosphatase) inhibitor, EC 3.1.1.7 (acetylcholinesterase) inhibitor, EC 3.1.1.8 (cholinesterase) inhibitor, EC 2.7.11.10 (IκB kinase) inhibitor, EC 2.1.1.122 [(S)-tetrahydroproberberine N-methyltransferase] inhibitor, anti-aging agent, and metabolite. Berberine is an alkaloid from Hydrastis canadensis L. (Berberidaceae). It is also found in many other plants. Berberine is relatively highly toxic when injected, but can be used orally to treat various parasitic and fungal infections as well as as an antidiarrheal. Berberine is a quaternary ammonium compound found in a variety of plant products, including Hydrastis canadensis, Berberis, and Vitis davidiana. Berberine is claimed to possess antioxidant and antibacterial properties and can be used to treat various diseases, including obesity, diabetes, hyperlipidemia, heart failure, Helicobacter pylori infection, and prevention of colonic adenomas. No elevation of serum transaminases or clinically significant liver damage was observed during berberine treatment. Berberine has been reported to be found in Stephania tetrandra, Coptis chinensis, and other organisms with relevant data. Berberine is a quaternary ammonium salt of isoquinoline alkaloids and an active ingredient in many traditional Chinese medicines, possessing potential antitumor, radiosensitizing, anti-inflammatory, lipid-lowering, and antidiabetic activities. Although the mechanism of action of berberine is not fully elucidated, after administration, the drug appears to inhibit the activation of a variety of proteins and/or regulate the expression of a variety of genes involved in tumorigenesis and inflammation, including but not limited to the transcription factors nuclear factor-κB (NF-κB), myeloid leukemia 1 (Mcl-1), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-superlarge (Bcl-xl), cyclooxygenase (COX)-2, tumor necrosis factor (TNF), interleukin (IL)-6, IL-12, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), CXC motif chemokine 2 (CXCL2), cyclin D1, and activator protein (AP-1). Hypoxia-inducible factor 1 (HIF-1), signal transducer and activator of transcription 3 (STAT3), peroxisome proliferation-activating receptor (PPAR), aromatic amine N-acetyltransferase (NAT), and DNA topoisomerases I and II. Regulation of gene expression may induce cell cycle arrest and apoptosis, and inhibit cancer cell proliferation. Furthermore, berberine can regulate lipid and glucose metabolism. Berberine is an alkaloid extracted from Hydrastis canadensis L. (Berberidaceae). It is also found in many other plants. Injection administration is relatively toxic, but oral administration is used to treat various parasitic and fungal infections, as well as as an antidiarrheal. See also: Hydrastis canadensis (part); Berberis bristlenoides stem (part).

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1. Mechanism of action: - Antitumor: induces apoptosis of colorectal adenocarcinoma cells by activating caspase-3 and Bax/Bcl-2 imbalance[1]
- Antibacterial: inhibits bacterial cell division by targeting FtsZ polymerization and cyclization[3]
- Neuroprotective: protects dopaminergic neurons from 6-OHDA damage by upregulating HO-1 and reducing ROS[5]
- Metabolic regulation: improves insulin sensitivity by upregulating GLUT4 and reduces blood lipids by inhibiting cholesterol synthesis[6]
2. Dosage optimization principle: - The development of berberine organic acid salts (e.g., citrate) aims to enhance oral bioavailability (18.2% compared to 6.5% of hydrochloride) by improving water solubility and reducing intestinal metabolism[2]

C20H18NO4

336.3612

336.123

2086-83-1

Berberine chloride hydrate;68030-18-2;Berberine chloride;633-65-8;Berberine sulfate;633-66-9

2353

Solid

204-206ºC (dec.)

Chinese herb Huanglian

-0.99

0

4

2

25

488

0

O1C([H])([H])OC2=C1C([H])=C1C(=C2[H])C2C([H])=C3C([H])=C([H])C(=C(C3=C([H])[N+]=2C([H])([H])C1([H])[H])OC([H])([H])[H])OC([H])([H])[H]

YBHILYKTIRIUTE-UHFFFAOYSA-N

InChI=1S/C20H18NO4/c1-22-17-4-3-12-7-16-14-9-19-18(24-11-25-19)8-13(14)5-6-21(16)10-15(12)20(17)23-2/h3-4,7-10H,5-6,11H2,1-2H3/q+1

16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaene

Natural Yellow 18; Umbellatine; Berberin; Berbericine; Majarine; Thalsine; Umbellatin;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: > 10 mM

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)