Effect of berberine on barrier function in a human retinal pigment epithelial cell line.

PURPOSE: To examine the effects of berberine, an alkaloid isolated from some medicinal herbs, on the disruption of the barrier function in a human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin-1beta (IL-1beta). METHODS: ARPE-19 cells were cultured to confluence. Berberine and IL-1beta were added to the medium. Barrier functions were evaluated by measuring transepithelial electrical resistance (TER) and the permeability to horseradish peroxidase (HRP) and sodium fluorescein (SF). RESULTS: Berberine dose-dependently inhibited decreased TER and increased the permeability to HRP and SF in the cells stimulated with IL-1beta. CONCLUSIONS: Berberine dose-dependently inhibited the disruption of the barrier function in the ARPE-19 cell line induced by IL-1beta.

Effect of berberine on monocyte chemotactic protein-1 and cytokine-induced neutrophil chemoattractant-1 expression in rat lipopolysaccharide-induced uveitis.

PURPOSE: The aims of this study were to examine the in vivo effects of berberine, an alkaloid isolated from some medicinal herbs, on monocyte chemotactic protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) expression in rat lipopolysaccharide (LPS)-induced uveitis. METHODS: LPS was injected intraperitoneally. Berberine was orally administered. MCP-1 mRNA and CINC-1 mRNA were measured by semiquantitative reverse-transcription polymerase chain reaction and real-time polymerase chain reaction. MCP-1 and CINC-1 protein concentration in the aqueous humor were measured by enzyme-linked immunosorbent assay. Histopathologic study was performed in the anterior ocular segments. RESULTS: Berberine dose-dependently inhibited LPS-induced MCP-1 mRNA and CINC-1 mRNA expression of the iris-ciliary body. The alkaloid inhibited chemokines, protein and cell levels in the aqueous humor in rats stimulated with LPS. On histopathologic study, the inflammatory cell infiltration was diminished by the berberine treatment. CONCLUSIONS: These findings indicate that berberine dose-dependently inhibited the expression of MCP-1 and CINC-1 induced by LPS and diminished the anterior uveitis.

Vitreous Chemokines and Sho (Zheng in Chinese) of Chinese-Korean-Japanese medicine in patients with diabetic vitreoretinopathy.

We examined the levels of vitreous chemokines and Sho (Zheng in Chinese) of Chinese-Korean-Japanese medicine in diabetic patients. Patients undergoing vitrectomy were classified into Group 1 (no diabetic retinopathy), Group 2 (diabetic retinopathy with no or a few new vessels), and Group 3 (diabetic retinopathy with many new vessels). The levels of IL-8, MCP-1, MIP-1alpha, MIP-1beta, and RANTES in the vitreous fluid were measured using cytometric bead array method. Sho was determined by the standard diagnostic method of Chinese-Korean-Japanese medicine. Vitreous levels of IL-8 and MCP-1 in Groups 2 and 3 were higher than those in Group 1. MIP-1alpha, MIP-1beta, and RANTES levels in Groups 2 and 3 were almost the same as those in Group 1. The percentage of patients with Keishibukuryo-gan (Guizhifuling-wan in Chinese) sho in Group 3 was higher than that in Group 1. In conclusion, vitreous levels of IL-8 and MCP-1 were high in patients with diabetic vitreoretinopathy. Keishibukuryo-gan sho may be associated with diabetic vitreoretinopathy.

Effect of berberine on interleukin 8 and monocyte chemotactic protein 1 expression in a human retinal pigment epithelial cell line.

PURPOSE: The aims of this study were to examine the effects of berberine, an alkaloid isolated from some medicinal herbs, on interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) expression in a human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin 1beta (IL-1beta) or tumor necrosis factor alpha (TNF-alpha). METHODS: ARPE-19 cells were cultured to confluence. Berberine and IL-1beta or TNF-alpha were added to the medium. IL-8 mRNA and MCP-1 mRNA were measured by semiquantitative reverse-transcription polymerase chain reaction and real-time polymerase chain reaction. IL-8 and MCP-1 protein concentrations in the media were measured using enzyme-linked immunosorbent assay. RESULTS: Berberine dose-dependently inhibited IL-8 mRNA and MCP-1 mRNA expression of the cells and protein levels in the media stimulated with IL-1beta or TNF-alpha. CONCLUSION: These findings indicate that berberine dose-dependently inhibited the expression of IL-8 and MCP-1 induced by IL-1beta or TNF-alpha.

Effects of oral administration of Gardeniae fructus extract and intravenous injection of crocetin on lipopolysaccharide- and prostaglandin E2-induced elevation of aqueous flare in pigmented rabbits.

The purpose of this study was to evaluate the effects of extracts of Coptidis rhizoma, Phellodendri cortex and Gardeniae fructus, which are medicinal herbs in Orengedoku-to (Huanglin-Jie-Du-Tang in Chinese), and crocetin (a major component of Gardeniae fructus) on experimental elevation of aqueous flare in pigmented rabbits. To produce aqueous flare elevation, 0.5 microg/kg lipopolysaccharide (LPS) was injected into the ear vein, or prostaglandin E2 (PGE2) 25 microg/ml, was applied to the cornea by means of a glass cylinder. Animals were pretreated by oral administration of 150 g/day of food containing 0.15% (w/w) extract powder of Coptidis rhizoma, 0.10% (w/w) extract powder of Phellodendri cortex or 0.15% (w/w) extract powder of Gardeniae fructus for 4 days, or by intravenous injection of crocetin, 0.3, 3, 30 or 300 microg/kg, 30 minutes before aqueous flare elevation. Aqueous flare was measured with a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. The AUC of LPS- and PGE2-induced aqueous flare elevation was 4685 and 1386 arbitrary units, respectively. Pretreatment by oral administration of 0.15% (w/w) extract of Coptidis rhizoma or 0.10% (w/w) extract of Phellodendri cortex did not inhibit LPS-induced aqueous flare elevation. Pretreatment by oral administration of 0.15% extract of Gardeniae fructus suppressed LPS-induced aqueous flare elevation (AUC: 1411 arbitrary units). Pretreatment by intravenous injection of 3, 30 or 300 microg/kg of crocetin-inhibited LPS-induced aqueous flare elevation in a dose-dependent manner. Pretreatment with 3 or 30 microg/kg of crocetin did not inhibit PGE2-induced aqueous flare elevation, but 300 microg/kg of crocetin inhibited PGE2-induced aqueous flare elevation (AUC: 918 arbitrary units).

Effects of topical instillation of traditional herbal medicines, herbal extracts, and their components on prostaglandin E2-induced aqueous flare elevation in pigmented rabbits.

PURPOSE: To evaluate the effect of topical instillation of traditional herbal medicines, herbal extracts, and their components on the elevation of aqueous flare induced by prostaglandin E(2) (PGE(2)) in pigmented rabbits. METHODS: Transcorneal diffusion of 25 micro g/mL of PGE(2) was carried out through a glass cylinder placed on the cornea to induce aqueous flare elevation in pigmented rabbits. Traditional herbal medicines, herbal extracts, and their components were topically instilled before the PGE(2) application. Aqueous flare was measured with a laser flare-cell meter. RESULTS: Two instillations, 60 and 30 minutes before PGE(2), of Kakkon-to, Sairei-to, Orengedoku-to, Senkanmeimoku-to, Scutellariae radix extract, Coptidis rhizoma extract, Gardeniae fructus extract, Phellodendri cortex extract, baicalein, baicalin, wogonin, crocetin, berberine, or glycyrrhizine did not inhibit the elevation induced by PGE(2). Two instillations, 60 and 30 minutes before PGE(2), of a Ligusticum wallichii extract (100 mg/mL) inhibited the elevation by 20%. Two instillations (5 and 3 hours before PGE(2)) of baicalein (1 mg/mL) or baicalin (5 mg/mL) inhibited the elevation by 16% and 24%, respectively. Two instillations, 5 and 3 hours before PGE(2), of wogonin, crocetin, berberine, or glycyrrhizine did not inhibit the elevation. CONCLUSION: Two instillations of Ligusticum wallichii extract 60 and 30 minutes before the PGE(2), and two instillations of baicalein or baicalin, 5 and 3 hours before the PGE(2), inhibited the PGE(2)-induced aqueous flare elevation in pigmented rabbits.

Effects of goshajinkigan on corneal sensitivity, superficial punctate keratopathy and tear secretion in patients with insulin-dependent diabetes mellitus.

Goshajinkigan (niu-che-shen-qi-wan in Chinese), a traditional herbal medicine, has been used in Japan to treat clinical symptoms of diabetic neuropathy. A double-masked study was performed to evaluate its effects on corneal sensitivity, superficial punctate keratopathy and tear production in patients with insulin-dependent diabetes mellitus. Fifty diabetic patients were randomized into two groups: Group A, in which 25 patients received goshajinkigan orally, 7.5 g/day for 3 months; Group B, in which 25 patients were orally administered placebo, 6.0 g/day for 3 months; and in Group C, 25 non-diabetic subjects were orally administered goshajinkigan, 7.5 g/day for 3 months. Corneal sensitivity was measured with an aesthesiometer. The area of superficial punctate keratopathy was expressed as a fluorescein staining score. Reflex tearing was determined with a Schirmer test without anesthesia goshajinkigan was analyzed by high-performance liquid chromatography. Corneal thresholds after treatment with goshajinkigan (2.03 g/mm2) in Group A were significantly lower than those before treatment (2.47 g/mm2). Those in Groups B and C did not change after treatment. Fluorescein staining scores after administration of Goshajinkigan (0.64) in Group A were significantly lower than those before treatment (1.32). Those in Groups B and C did not change after treatment. Schirmer test results after goshajinkigan administration (11.0 mm/5 min) in Group A were significantly higher than those before treatment (9.3 mm/5 min). Those in Groups B and C did not change after treatment. Hemoglobin A1c levels in Groups A, B,and C did not change after treatment. Several components in goshajinkigan were found on high performance liquid chromatography. In conclusion, goshajinkigan improved ocular surface disorders in patients with insulin-dependent diabetes mellitus.

Effects of kakkon-to and sairei-to on aqueous flare elevation after complicated cataract surgery.

We evaluate prospectively the effects of traditional herbal medicines on elevation of aqueous flare after complicated cataract surgery. Twenty-seven patients with bilateral complicated cataract undergoing phacoemulsification with intraocular lens implantation were studied. The patients received no herbal medicine when the right eyes underwent cataract surgery. Fifteen patients were given kakkon-to (ge-gen-yang in Chinese) granules (7.5 g daily) and 12 patients were given sairei-to (cai-ling-tang in Chinese) granules (9.0 g daily), for 3 days before surgery, the day of surgery, and for 7 days after surgery when the left eyes underwent cataract surgery. Diclofenac eyedrops were instilled in all patients. Aqueous flare was measured before and after surgery. The differences in preoperative flare intensities between groups treated with Kakkon-to and Sairei-to were not significant. In the untreated right eyes of the kakkon-to and Sairei-to groups, the flare was 99.1 and 89.6 photon counts/msec, respectively, on day 1, and then gradually decreased. The flare intensities on days 1, 3, and 5 in the kakkon-to treated left eyes were significantly lower than in those of the untreated right eyes (Fig. 1). The flare intensities in the Sairei-to treated left eyes were the same as those in the untreated right eyes. Kakkon-to contributed to a reduction of aqueous flare elevation after surgery for complicated cataract.