Berberine Chloride Hydrate

Neurodegenerative diseases (NDs), including Alzheimer's, Amyotrophic lateral sclerosis, Huntington's, and Parkinson's, present an increasingly widespread health burden globally with limited curative or treatment modalities, mostly having symptomatic attenuation. Berberine (BBR) is an isoquinoline alkaloid that occurs naturally and has been proposed as a potential neuroprotectant, since it has been found to exert multiple effects to modulate most of the pathological hallmarks of NDs, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and protein aggregation. Although it shows promise, the practical utilization of BBR is marred by low oral bioavailability, high rate of oxidation, and low blood-brain barrier permeability. To combat these issues, recent developments in nanotechnology, especially in the use and creation of lipidic, inorganic, and polymeric nano-particles, have dramatically altered the pharmacokinetics and pharmacodynamics of BBR. This article summarizes recent advances in BBR-based nanoformulations and emphasizes the translational potential of BBR-based nanopreparations to improve treatment response in NDs. It also describes the molecular foundation of the neuroprotective effects of BBR and its possible place in clinical practice. Future nanocarrier development and investigation of BBR mechanisms will be essential to the development of the next generations of therapeutics in NDs.

A series of eighteen berberine derivatives were designed and synthesized via molecular hybridization, introducing boronic acid/ester pharmacophores at the C-9 position to improve the selectivity of the natural product against breast cancer. The in vitro antiproliferative activities against MDA-MB-468 and MCF-7 cell lines identified several promising leads. Notably, compounds 4c, 5d, 5f, and 8b demonstrated good activity coupled with high selectivity indices over the normal human embryonic kidney (HEK-293) cell line, outperforming berberine and 5-fluorouracil. Computational ADME profiling highlighted 8b and 5f as oral leads and 4c as a BBB-penetrant agent. Molecular docking provided a plausible hypothesis for a proteasome inhibition mechanism for 8b through interaction with the β5 subunit.