Inhibitory Effect Of Berberine Research Articles

Effect of berberine on Staphylococcus epidermidis biofilm formation

Staphylococcus epidermidis is one of the main causes of medical device-related infections owing to its adhesion and biofilm-forming abilities on biomaterial surfaces. Berberine is an isoquinoline-type alkaloid isolated from Coptidis rhizoma (huang lian in Chinese) and other herbs with many activities against various disorders. Although the inhibitory effects of berberine on planktonic bacteria have been investigated in a few studies, the capacity of berberine to inhibit biofilm formation has not been reported to date. In this study, we observed that berberine is bacteriostatic for S. epidermidis and that sub-minimal inhibitory concentrations of berberine blocked the formation of S. epidermidis biofilm. Using viability assays and berberine uptake testing, berberine at a concentration of 15–30 μg/mL was shown to inhibit bacterial metabolism. Data from this study also indicated that modest concentrations of berberine (30–45 μg/mL) were sufficient to exhibit an antibacterial effect and to inhibit biofilm formation significantly, as shown by the tissue culture plate (TCP) method, confocal laser scanning microscopy and scanning electron microscopy for both S. epidermidis ATCC 35984 and a clinical isolate strain SE243. Although the mechanisms of bacterial killing and inhibition of biofilm formation are not fully understood, data from this investigation indicated a potential application for berberine as an adjuvant therapeutic agent for the prevention of biofilm-related infections.

Inhibitory effect of berberine on the TNF‐α‐induced Expression of IL‐8 and MCP‐1 is mediated through suppression of NF‐κB activation in HT29 Human Colon Epithelial Cells

Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti‐inflammation. In this study, we examined the effects of berberine on the TNF‐α‐induced chemokine expression in HT29 human colon adenocarcinoma cells that were used as an in vitro model of inflammatory bowel disease (IBD). Since the activation and recruitment of leukocytes to the inflamed tissue is an important step initiating IBD, we evaluated the effect of berberine on the adhesion of U937 monocytic cells to HT29 colon epithelial cells. Berberine significantly inhibited the TNF‐α‐induced monocyte adhesion to HT29 cells in a concentration‐dependent manner. Co‐treatment of the TNF‐α‐stimulated HT29 cells with berberine concentration‐dependently inhibited the mRNA expression of IL‐8 and MCP‐1, important mediators involved in the pathologic process of IBD. In addition, the ratio of the firefly and renilla luciferase activities (F/R) was used as an indicator of the NF‐κB activity in the cells. TNF‐α significantly increased the F/R ratio in the cells, and this was significantly inhibited by berberine in a concentration‐dependent manner. The results suggest that berberine may be a potential candidate to suppress the colon inflammation by inhibiting TNF‐α‐induced pro‐inflammatory cytokines.

Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice

We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl- d-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D 1 and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance.

Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats

Berberine is the major active constituent of Rhizoma coptidis. The present study was carried out to investigate the effect of berberine on diabetes in rats and its possible mechanisms. Diabetes was induced by tail vein injection with alloxan in Wistar rats. The amount of alloxan administered was 55 mg/kg. Diabetic rats were fed with a high-cholesterol diet. The fasting blood glucose, total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-c), high density lipoprotein-cholesterol (HDL-c), nitric oxide (NO) levels in serum and malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-px) contents in heart tissue were assayed by spectrophotometry. Pancreas samples collected after 3 weeks of alloxan treatment were stained with hematoxylin–eosin (HE) and examined under a light microscope, and scored. Intragastric administration of berberine (100 and 200 mg/kg) significantly decreased fasting blood glucose levels, serum content of TC, TG, LDL-c, and effectively increased HDL-c, NO level in diabetic rats. Furthermore, berberine treatment significantly blocked the increase of MDA, increased SOD and GSH-px levels in diabetic rats. Histopathological scores showed that berberine had restored the damage of pancreas tissues in rats with diabetes mellitus. The results showed berberine significantly inhibited the progression of diabetes induced by alloxan, and the inhibitory effect of berberine on diabetes might be associated with its hypoglycemic effect, modulating lipids metabolic effects and its ability to scavenge free radical.

Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-kappaB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.

Inhibitory effects of berberine on ion channels of rat hepatocytes

To examine the effects of berberine, an isoquinoline alkaloid with a long history used as a tonic remedy for liver and heart, on ion channels of isolated rat hepatocytes. Tight-seal whole-cell patch-clamp techniques were performed to investigate the effects of berberine on the delayed outward potassium currents (I(K)), inward rectifier potassium currents (I(K1)) and Ca(2+) release-activated Ca(2+) currents (I(CRAC)) in enzymatically isolated rat hepatocytes. Berberine 1-300 micromol/L reduced I(K) in a concentration-dependent manner with EC(50) of 38.86+/-5.37 micromol/L and n(H) of 0.82+/-0.05 (n = 8). When the bath solution was changed to tetraethylammonium (TEA) 8 mmol/L, I(K) was inhibited. Berberine 30 micromol/L reduced I(K) at all examined membrane potentials, especially at potentials positive to +60 mV (n = 8, P<0.05 or P<0.01 vs control). Berberine had mild inhibitory effects on I(K1) in rat hepatocytes. Berberine 1-300 micromol/L also inhibited I(CRAC) in a concentration-dependent fashion. The fitting parameters were EC(50) = 47.20+/-10.86 micromol/L, n(H) = 0.71+/-0.09 (n = 8). The peak value of I(CRAC) in the I-V relationship was decreased by berberine 30 micromol/L at potential negative to -80 mV (n = 8, P<0.05 vs control). But the reverse potential of I(CRAC) occurred at voltage 0 mV in all cells. Berberine has inhibitory effects on potassium and calcium currents in isolated rat hepatocytes, which may be involved in hepatoprotection.

Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat liver.

Berberine, a main protoberberine component of Coptidis Rhizoma, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver. In the preliminary study, berberine expressed an antioxidant property by its capacity for quenching the free radicals of 1,1-diphenyl-2-picrylhydrazyl (DPPH). Further investigations were conducted using t-BHP-induced cytotoxicity in rat primary hepatocytes and hepatotoxicity in rats to evaluate the antioxidative bioactivity of berberine. The results in rat primary hepatocytes demonstrated that berberine, at the concentrations of 0.01-1.0 mM, significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and the formation of malondialdehyde (MDA) induced by 30 min treatment of t-BHP (1.5 mM). Berberine also attenuated the t-BHP-induced depletion of glutathione (GSH) and induced a high level of DNA repair synthesis. The in vivo study showed that the intraperitoneal pretreatment with berberine (0.5 and 5 mg/kg) for 5 days before a single dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of hepatic enzyme markers (ALT and aspartate aminotransferase) and reduced oxidative stress in the liver. The histopathological evaluation of the livers revealed that berberine reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltrations, and necrosis induced by t-BHP. These results lead us to speculate that berberine may play a chemopreventive role via reducing oxidative stress in living systems.

Inhibitory effect of berberine on the mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma

We examined the effect of berberine, a major component with anti-fungal properties contained in Coptidis Rhizoma and Phellodendri Cortex, on the lymph node metastasis of murine lung cancer. Oral administration of berberine for 14 days significantly inhibited the spontaneous mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma (LLC) into the lung parenchyma in a dose-dependent manner, but did not affect the tumor growth at the implantation site of the lung. Combined treatment with berberine and an anti-cancer drug, CPT-11, resulted in a marked inhibition of tumor growth at the implantation site and of lymphatic metastasis, as compared with either treatment alone. Anti-activator protein-1 (anti-AP-1) transcriptional activity of non-cytotoxic concentrations of berberine caused the inhibition of the invasiveness of LLC cells through the repression of expression of urokinase-type plasminogen activator (u-PA).

Inhibitory effects of berberine on voltage- and calcium-activated potassium currents in human myeloma cells

The effects of berberine, an isoquinoline alkaloid, were investigated in human myeloma cells. In cells with intracellular Ca 2+ concentration ([Ca 2+] i) = 10 nM, the depolarizing square pulses from −80 mV elicited an instantaneous outward current with an inactivation. This outward current was voltage dependent, activating at −30 mV and showed inactivation with repetitive depolarization, and was hence believed to be n type voltage-activated K + current (i k(v)). Berberine (30 μM) produced a prolongation in the recovery of i k(v) inactivation. In cells with [Ca 2+] i = 1 μM, berberine also inhibited A23187-induced I K(Ca) Berberine (1–300 μM) caused the inhibition of i k(v) and I K(Ca) in the concentration-dependent manners. The IC 50 values of berberine-induced inhibition of i k(v) and i k(ca) were approximately 15 μM and 50 μM, respectively. In inside-out configurations, berberine inside the pipette suppressed the activity of k ca channels without changing the single channel conductance. Berberine also inhibited the proliferation of this cell line and the IC 50 value of berberine-induced inhibition of cell proliferation was 5 μM. Thus, the cytotoxic effect of berberine in cancer cells may be partially explained by its direct blockade of these K + channels.

Inhibitory effects of berberine on ATP-sensitive K + channels in cardiac myocytes

The effects of berberine on cardiac action potentials were measured in isolated guinea-pig papillary muscles exposed to hypoxia and cromakalim using the standard microelectrode technique. In addition, the patch clamp technique was used to determine the effects of berberine on cromakalim-induced outward currents in isolated ventricular myocytes and on ATP-sensitive K + (K ATP) channels in inside-out membrane patches. Berberine, at 3 μM significantly inhibited, while at 100 μM completely blocked the shortening of action potential duration and effective refractory period induced by hypoxia or cromakalim (100 μM). Under the whole-cell voltage clamp conditions, berberine (3–100 μM) attenuated or even abolished the cromakalim-elicited outward K + currents. Berberine (3–100 μM) inhibited K ATP channel activity in a concentration-dependent fashion in inside-out membrane patches exposed to 0.1 mM ATP. This inhibition appeared to be mainly due to a decrease in the open channel probability without affecting unitary conductance or the time constants for open and closed channel times. Glibenclamide (10 μM) partially blocked the hypoxia-evoked but fully reversed the cromakalim-evoked abbreviation of action potential duration and effective refractory period. Both the whole-cell outward K + currents induced by cromakalim and the opening of single K ATP channels induced by the low intracellular ATP concentration were also completely abolished by 10 μM glibenclamide. We conclude that berberine is a blocker of the cardiac K ATP channel. The reported beneficial effect of berberine on ischemia-induced arrhythmias is likely attributed to its inhibition of K ATP channel activation and subsequent shortening of action potential duration and effective refractory period during ischemia.

Inhibitory effect of berberine on agonist-induced contraction of guinea-pig aortic strips

Inhibitory effect of berberine on agonist-induced contraction of guinea-pig aortic strips