Dihydroberberine

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Cat Number

PIPE-0252

CAS Number

483-15-8

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CAS Number

483-15-8

EINECS

683-111-2

Storage

Store at 2-8°C

Synonyms

Dihydroumbellatine; 7,8-Dihydroberberine; DTXSID70197476

Molecular Formula

C20H19NO4

Molecular Weight

337.4

Smiles

COC1=C(C2=C(C=C1)C=C3C4=CC5=C(C=C4CCN3C2)OCO5)OC

Appearance

Light yellow to yellow solid powder

Melting Point

223-224°C (dec.)

Boiling Point

557.8±50.0°C (Predicted)

Relative Density

1.37±0.1

General Description

Dihydroberberine (DHB) is an alkaloid derivative of berberine (BBR) with significantly better bioavailability. This reduced form of berberine is considered a potent, bioavailable compound. It exhibits similar, and in some cases superior, pharmacological effects compared to its parent molecule.

Mechanism of Action

Dihydroberberine acts through multiple pathways. It has been shown to normalize insulin secretion by regulating glucokinase, a key enzyme in glucose metabolism. It can also regulate hepatic glucose production, reducing glucose release when blood glucose is high. Furthermore, dihydroberberine is a highly effective inhibitor of H-PGDS, a pivotal enzyme in the biosynthesis of the pro-inflammatory mediator PGD2. Similar to berberine, it is likely metabolized by the gut microbiota to exert some of its effects.

Application

Dihydroberberine is being clinically evaluated for its effects on glycemic control, appetite, and mood in adults with pre-diabetes. It shows significant hypoglycemic activity and plays a positive role in regulating blood glucose balance through improving insulin sensitivity and promoting glucose metabolism. It has also demonstrated protective effects in models of ulcerative colitis and cholestatic liver disease.

In hyperuricemic mice, dihydroberberine (DHB) – a hydrogenated derivative of berberine – exhibited significant hypouricemic and renoprotective effects. DHB inhibited xanthine oxidase (XOD) with an IC₅₀ of 34.37 µM, lowered serum uric acid and XOD, suppressed hepatic XOD and adenosine deaminase, and downregulated renal XOD, URAT1, GLUT9, and NLRP3 inflammasome components (NLRP3, ASC, caspase‑1, IL‑1β). It also reduced inflammatory cytokines and ameliorated renal histopathology. DHB acts through multiple pathways including XOD inhibition, urate transporter downregulation, and NLRP3 suppression.

Fig. 1 Effect of DHB on serum UA and serum markers of kidney damage in PO/HX-induced hyperuricemic mice. (Xu L, et al., 2021)

References

Xu L, et al. Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice. Front Pharmacol. 2021;12:645879.

Dihydroberberine combined with sunitinib (DCS) showed synergistic antitumor effects in non‑small cell lung cancer (NSCLC) cell lines (A549, NCI‑H460, NCI‑H1299) and xenografts. DCS downregulated phosphorylated JNK, p38, NF‑κB, IκB, and COX‑2, and reduced IL‑1 secretion in tumors. Inhibition of p38 contributed to IL‑1 and COX‑2 downregulation. Microarray analysis revealed DCS‑induced changes in cell cycle signaling molecules, leading to downregulation of JNK and p38. DCS is an efficacious strategy in NSCLC therapy.

Fig. 2 Effects of dihydroberberine and/or sunitinib on the growth of lung cancer cells. (Dai B, et al., 2017)

References

Dai B, et al. Dihydroberberine exhibits synergistic effects with sunitinib on NSCLC NCI-H460 cells by repressing MAP kinase pathways and inflammatory mediators. J Cell Mol Med. 2017;21(10):2573-2585.

Does Dihydroberberine require protection from oxygen and light during storage?

Yes, the reduced form is highly sensitive to oxidation, reverting to berberine. Store in airtight, light-resistant containers under inert gas (nitrogen) at 2-8°C.

Is Dihydroberberine less stable than berberine, and how is this managed?

Yes, due to the labile dihydropyridine ring, it oxidizes more readily. Antioxidants (e.g., ascorbic acid) may be added to formulations to improve stability.

What is the recommended packaging for Dihydroberberine to prevent oxidation?

Use amber glass vials with PTFE-lined caps, filled to minimize headspace, and sealed under nitrogen. Store in refrigerated conditions with oxygen absorbers.

How is the impurity berberine (oxidation product) monitored during stability?

This primary degradation product is specifically quantified using a stability-indicating HPLC method, ensuring oxidation levels remain within acceptable limits.