Neutral berberine sulfate
[CAS# 316-41-6]

Identification

• Classification: Biochemical >> Natural biochemical product
• Name: Neutral berberine sulfate
• Synonyms: 7,8,13,13a-Tetradehydro-9,10-dimethoxy-2,3-(methylenedioxy)-berbinium sulfate; 5,6-Dihydro-9,10-dimethoxy-benzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium sulfate
• Molecular Formula: 2(C₂₀H₁₈NO₄)^.SO₄
• Molecular Weight: 768.79
• CAS Registry Number: 316-41-6
• EC Number: 206-258-2
• SMILES: COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC5=C(C=C4CC3)OCO5)OC.COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC5=C(C=C4CC3)OCO5)OC.[O-]S(=O)(=O)[O-]

Safety Data

• Hazard Symbols: GHS06 Danger
• Hazard Statements: H301-H311-H331
• Precautionary Statements: P261-P262-P264-P270-P271-P280-P301+P316-P302+P352-P304+P340-P316-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301

Discovory and Applicatios

Neutral berberine sulfate is a quaternary ammonium salt derivative of berberine, a naturally occurring isoquinoline alkaloid predominantly found in plants of the Berberidaceae and Ranunculaceae families, such as *Berberis* species. Chemically, it is formed by combining berberine with sulfate anions to produce a neutral salt, which improves its solubility, stability, and bioavailability compared to berberine hydrochloride or other berberine salts. These modifications facilitate its use in pharmaceutical and experimental applications while retaining the pharmacological activities of the parent compound.

The discovery of neutral berberine sulfate stems from early investigations into the pharmacological potential of berberine, which has been used in traditional medicine for centuries to treat gastrointestinal infections, liver disorders, inflammation, and metabolic conditions. Researchers identified that the sulfate salt form could address some limitations of berberine, particularly its poor water solubility and limited absorption in the gastrointestinal tract, thereby enhancing its therapeutic potential.

Pharmacologically, neutral berberine sulfate retains the broad spectrum of bioactivities associated with berberine. It exhibits antimicrobial effects against a variety of bacterial, fungal, and protozoal pathogens, making it valuable for addressing infections. In addition, it has been shown to possess anti-inflammatory properties by modulating pro-inflammatory cytokines and enzymes, contributing to the reduction of inflammation in various tissues. Its antioxidant activity enables it to scavenge reactive oxygen species, protecting cells from oxidative stress and related damage.

Neutral berberine sulfate also demonstrates potential benefits in metabolic disorders, including hyperlipidemia, hyperglycemia, and insulin resistance. Studies indicate that it can modulate lipid and glucose metabolism, improve insulin sensitivity, and exert cardioprotective effects. These properties have prompted its investigation in preclinical models of diabetes, obesity, and cardiovascular diseases, highlighting its potential as a therapeutic agent for metabolic syndrome.

The sulfate form facilitates enhanced pharmacokinetics, with improved solubility allowing for more consistent absorption and distribution in vivo. This makes neutral berberine sulfate more suitable for oral administration and practical use in medicinal formulations. The compound’s improved bioavailability allows it to achieve effective plasma concentrations and exert its pharmacological effects more reliably than poorly soluble berberine salts.

Clinically, neutral berberine sulfate is employed as a bioactive supplement or therapeutic agent in experimental and pharmaceutical contexts. Its safety profile is generally favorable, with low toxicity reported in preclinical studies, although further clinical evaluations are necessary to fully establish its efficacy and safety in humans. Its ability to combine the pharmacological benefits of berberine with enhanced solubility makes it a promising candidate for future drug development.

In summary, neutral berberine sulfate is a bioactive derivative of berberine with enhanced solubility, stability, and pharmacokinetic properties. Its antimicrobial, anti-inflammatory, antioxidant, and metabolic effects make it a versatile compound with potential applications in infectious, inflammatory, and metabolic disorders. Continued research into its mechanisms of action, therapeutic applications, and clinical potential will be important in translating its benefits into practical medical use.

References

2020. Botanical Sources, Chemistry Aspects and Biological Functions of Berberine: An Updated Critical Review. Botanical Leads for Drug Discovery.
DOI: 10.1007/978-981-15-5917-4_20

2018. A new triple system DNA-Nanosilver-Berberine for cancer therapy. Applied Nanoscience, 8(3).
DOI: 10.1007/s13204-018-0688-x

2017. In Vitro Activity of Berberine Alone and in Combination with Antifungal Drugs Against Planktonic Forms and Biofilms of Trichosporon Asahii. Mycopathologia, 182(7-8).
DOI: 10.1007/s11046-017-0119-7