Current knowledge and pharmacological profile of berberine: An update

Kumar, Anil; Ekavali,; Chopra, Kanwaljit; Mukherjee, Madhurima; Pottabathini, Raghavender; Dhull, Dinesh K.

doi:10.1016/j.ejphar.2015.05.068

Cited by 435 publications

(268 citation statements)

References 85 publications

Supporting

Mentioning

255

Contrasting

Unclassified

Order By: Relevance

“…[13]. In recent years, BBR has been demonstrated its beneficial effect in neurodegenerative and neuropsychiatric disorders because of its dual antioxidant and anti-apoptotic activities [14], [15], [16].…”

Section: Introductionmentioning

confidence: 99%

Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways

et al. 2017

View full text Add to dashboard Cite

Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways.

show abstract

Section: Introductionmentioning

confidence: 99%

Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways

et al. 2017

View full text Add to dashboard Cite

show abstract

“…To this end, in the present study, we assessed 12 pure natural compounds with the potential to modulate iron metabolism. All these compounds are extracts from traditional Chinese herbal medicinal plants, and many of them have been reported to be effective therapeutically for multiple disorders, including inflammation, oxidative injuries and cardiovascular diseases (12)(13)(14)(15)(16)(17)(18)(19)(20). According to the Chinese Pharmacopoeia (21), all of these compounds are capable of improving microcirculation and have the potential to modulate blood cell formation.…”

Section: Introductionmentioning

confidence: 99%

Icariin regulates systemic iron metabolism by increasing hepatic hepcidin expression through Stat3 and Smad1/5/8 signaling

Zhang

Liu

Guo

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Systemic iron homeostasis is strictly controlled under normal conditions to ensure a balance between the absorption, utilization, storage and recycling of iron. The hepcidin-ferroportin (FPN) axis is of critical importance in the maintenance of iron homeostasis. Hepcidin deficiency gives rise to enhanced dietary iron absorption, as well as to increased iron release from macrophages, and this in turn results in iron accumulation in the plasma and organs, and is associated with a range of tissue pathologies. Low hepcidin levels have been demonstrated in most forms of hereditary hemochromatosis (HH), as well as in β-thalassemia. Therapies that increase hepcidin concentrations may potentially play a role in the treatment of these iron overload-related diseases. To date, natural compounds have not been extensively investigated for this purpose, to the best of our knowledge. Thus, in the present study, we screened natural compounds that have the potential to regulate hepcidin expression. By performing hepcidin promoter-luciferase assay, RT-qPCR and animal experiments, we demonstrated that icariin and berberine were potent stimulators of hepcidin transcription.Mechanistic experiments indicated that icariin and berberine increased hepcidin expression by activating the signal transducer and activator of transcription 3 (Stat3) and Smad1/5/8 signaling pathways. The induction of hepcidin was confirmed in mice following icariin administration, coupled with associated changes in serum and tissue iron concentrations. In support of these findings, the icariin analogues, epimedin A, B and C, also increased hepatic hepcidin expression. However, these changes were not observed in hepcidin-deficient [Hamp1 -/-or Hamp1-knockout (KO)] mice following icariin administration, thereby verifying hepatic hepcidin as the target of icariin. Although berberine exhibited a robust capacity to promote hepcidin expression in vitro, it failed to alter hepcidin expression in mice. Taken together, the findings of the present study suggest that icariin exhibits a robust capacity to increase hepatic hepcidin expression and to modulate systemic iron homeostasis. The present study therefore highlights the significance of using natural compounds to ameliorate iron disorders through the regulation of hepcidin expression. IntroductionIron is an essential metal involved in a large array of biological processes, such as energy metabolism, DNA replication and other important cellular functions (1-3). Systemic iron homeostasis is accurately and strictly governed to ensure a balance between iron absorption, utilization and storage in mammals (4). Hepcidin is the central hormone secreted by hepatocytes that plays a fundamental role in the regulation of iron flow through limiting dietary iron absorption from the duodenum and reducing iron egress from macrophages (5). Hepcidin achieves this effect by binding to its receptor, ferroportin (FPN; the only known iron exporter thus far), on the plasma membrane of target cells and inducing its internalization ...

show abstract

“…All of these actions of BBR lead to an enhanced bile flow. In addition to goldenseal, BBR is also found in many other medicinally important plants such as Berberis aquifolium (Oregon grape) and Berberis vulgaris (barberry) (18). These plants have been used for over 3000 years in human history to treat various diseases (19).…”

Section: Discussionmentioning

confidence: 99%

Berberine-induced Inactivation of Signal Transducer and Activator of Transcription 5 Signaling Promotes Male-specific Expression of a Bile Acid Uptake Transporter

Zhang

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Jeffrey E. PessinSodium-taurocholate co-transporting polypeptide (Ntcp/ NTCP) is the major uptake transporter of bile salts in mouse and human livers. In certain diseases, including endotoxemia, cholestasis, diabetes, and hepatocarcinoma, Ntcp/NTCP expression is markedly reduced, which interferes with enterohepatic circulation of bile salts, impairing the absorption of lipophilic compounds. Therefore, normal Ntcp/NTCP expression in the liver is physiologically important. Berberine is an herbal medicine used historically to improve liver function and has recently been shown to repress STAT signaling. However, berberine effects on Ntcp/NTCP expression are unknown, prompting use to investigate this possible connection. Our results showed that berberine dose-dependently increased Ntcp expression in male mouse liver and decreased taurocholic acid levels in serum but increased them in the liver. In mouse and human hepatoma cells, berberine induced Ntcp/NTCP mRNA and protein expression and increased cellular uptake of [3H] taurocholate. Mechanistically, berberine decreased nuclear protein levels of phospho-JAK2 and phospho-STAT5, thus disrupting the JAK2-STAT5 signaling. Moreover, berberine stimulated luciferase reporter expression from the mouse Ntcp promoter when one putative STAT5 response element (RE) (؊1137 bp) was deleted and from the human NTCP promoter when three putative STAT5REs (؊2898, ؊2164, and ؊691 bp) were deleted. Chromatin immunoprecipitation demonstrated that berberine decreased binding of phospho-STAT5 protein to the؊2164 and ؊691 bp STAT5REs in the human NTCP promoter. In summary, berberine-disrupted STAT5 signaling promoted mouse and human Ntcp/NTCP expression, resulting in enhanced bile acid uptake. Therefore, berberine may be a therapeutic candidate compound for maintaining bile acid homeostasis.

show abstract

Current knowledge and pharmacological profile of berberine: An update

Cited by 435 publications

References 85 publications

Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways

Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways

Icariin regulates systemic iron metabolism by increasing hepatic hepcidin expression through Stat3 and Smad1/5/8 signaling

Berberine-induced Inactivation of Signal Transducer and Activator of Transcription 5 Signaling Promotes Male-specific Expression of a Bile Acid Uptake Transporter

Contact Info

Product

Resources

About