Effect Of Glycyrrhetinic Acid Research Articles

Effects of glycyrrhetinic acid β on growth and virulence of Aeromonas hydrophila.

Aeromonas hydrophila is a significant pathogen to freshwater farmed animals, and antibiotics are usually used to control the bacterial septicemia caused by A. hydrophila. Due to the severe situation of development and spread of antibiotic resistance, there are stricter restrictions on antibiotics used in aquaculture. To evaluate the feasibility of glycyrrhetinic acid β (GA) as an alternative therapy against bacterial infection, in this study, an A. hydrophila isolated from diseased fish is used to test the antibacterial, anti-virulence activity and therapeutic effect of GA in vitro and in vivo, respectively. Results showed that GA did not affect the growth of A. hydrophila in vitro, while it could down-regulate (p < 0.05) the mRNA expression of the hemolysis-related genes hly and aerA, and significantly inhibited (p < 0.05) hemolytic activity of A. hydrophila. In addition, in vivo test showed that oral administration of GA was ineffective in controlling acute infections caused by A. hydrophila. In conclusion, these findings suggested that GA was a potential anti-virulence candidate against A. hydrophila, but the application of GA for the prevention and treatment of A. hydrophila-related diseases was still a long way.

The effect of glycyrrhetinic acid on the proliferation and inva-sion of colorectal cancer LoVo cells

目的:研究不同浓度的甘草次酸对大肠癌LoVo细胞增殖和侵袭的影响。方法:将大肠癌LoVo细胞分为对照组,甘草次酸低、中、高剂量组(甘草次酸浓度分别为50, 100, 200 μmol/L)和5氟尿嘧啶组(5氟尿嘧啶浓度为100 μmol/L ),各组细胞经过药物孵育24和48 h后进行检测。通过四氮唑蓝试验检测甘草次酸对各组细胞增殖率的影响;通过Annexin V/PI双标流式细胞术检测各组细胞的凋亡率;Transwell 小室法检测各组细胞的侵袭能力;通过蛋白质印迹法检测检各组细胞的NF-κB蛋白表达。结果:与对照组相比,甘草次酸中、高剂量组和5氟尿嘧啶组中细胞抑制率均显著降低(P＜0.05);甘草次酸中、高剂量组和5氟尿嘧啶组中细胞凋亡率均显著升高(P＜0.05);甘草次酸中、高剂量组和5氟尿嘧啶组中大肠癌LoVo 细胞侵袭能力显著降低(P＜ 0.05);甘草次酸中、高剂量组和5氟尿嘧啶组中NF-κB相对表达量均显著降低(P＜0.05)。结论:浓度为100 μmol/L和200 μmol/L甘草次酸可以抑制大肠癌LoVo细胞的增殖,降低侵袭能力,这些作用的机制与抑制NF-κB蛋白的表达有关。.

Effect of glycyrrhetinic acid on apoptosis of thyroid cancer cell line SW579 and its mechanism

Effect of glycyrrhetinic acid on apoptosis of thyroid cancer cell line SW579 and its mechanism

甘草次酸对银屑病患者角质形成细胞增殖、凋亡及miR-21表达的影响

Objective To preliminarily evaluate the effect of glycyrrhetinic acid on the proliferation and apoptosis of keratinocytes in patients with psoriasis, and to explore its possible mechanisms. Methods Keratinocytes were isolated from patients with psoriasis, and subjected to a primary culture in vitro. After 2-3 passages, the keratinocytes were divided into several groups to be treated with glycyrrhetinic acid at final concentrations of 0 (control group) , 1, 2, 4, 8 and 10 mg/L (glycyrrhetinic acid groups) , respectively. After 24-72 hours of treatment, MTS assay was performed to evaluate the effect of glycyrrhetinic acid on the proliferation of keratinocytes, and flow cytometry was conducted to detect the apoptosis of keratinocytes after 24-hour treatment with glycyrrhetinic acid at different concentrations. Real-time fluorescence-based PCR was performed to determine the expression of miR-21 in keratinocytes. Results After 24-72 hours of treatment with 1-10 mg/L glycyrrhetinic acid, the proliferation activity of keratinocytes significantly decreased along with the increase in the treatment duration and concentrations of glycyrrhizinic acid. After 24-hour treatment with 1, 2, 4, 8, 10 mg/L glycyrrhetinic acid, the apoptosis rates of keratinocytes increased to (9.64 ± 0.86) %, (25.24 ± 2.93) %, (27.68 ± 3.70) %, (35.55 ± 4.23) % and (38.89 ± 2.31) % respectively. As LSD-t test showed, the apoptosis rates of keratinocytes were significantly higher in all the glycyrrhetinic acid groups than in the control group (10.09% ± 0.69%, all P < 0.01) , except the 1 mg/L glycyrrhetinic acid group. After 24-hour treatment with 1, 2 and 4 mg/L glycyrrhetinic acid, the miR-21 expression (2-ΔΔCt) significantly decreased (0.24 ± 0.04, 0.22 ± 0.07, 0.17 ± 0.05, respectively) compared with the control group (0.92 ± 0.12, F= 213.10, P < 0.05) . After 18-, 24-and 48-hour treatment with 2 mg/L glycyrrhetinic acid, the miR-21 expression significantly decreased (0.55 ± 0.02, 0.22 ± 0.06 and 0.15 ± 0.06 respectively) compared with the control group (0.98 ± 0.02, F= 238.10, P < 0.05) . Conclusion Glycyrrhetinic acid can inhibit the proliferation of keratinocytes from psoriatic patients, but promote the apoptosis, likely by down-regulation of miR-21 expression. Key words: Psoriasis; Glycyrrhetinic acid; Keratinocytes; Cell proliferation; Apoptosis; MicroRNAs; miR-21

Glycyrrhetinic acid selectively inhibits proliferation of hepatocellular carcinoma cells in vitro

To investigate the selective inhibitory effect of glycyrrhetinic acid on 4 hepatocellular carcinoma (HCC) cells with different proliferation rates and explore the underlying mechanisms. MTT method was used to detect the proliferation rates of 4 HCC cell lines, namely SMMC-7721, SK-HEP1, HEPG2 and HEP3B. Following treatment of the cells with glycyrrhetinic acid (5, 10, 20, 30, 40, and 60 µmol/L), the cell viability was analyzed using MTT assay and the expressions of total ERK protein, p-ERK protein and topoisomerase IIα were detected using Western blotting. Among the 4 cell lines, SMMC-7721 had the lowest and SK-HEP1 had the highest proliferation rate. Treatment with glycyrrhetinic acid for 48 h dose-dependently inhibited the proliferation of all the 4 cell lines in vitro and produced the strongest inhibitory effect in SMMC-7721 cells with the IC50 of 28.04 µmol/L. The proliferation rate of the cells was positively correlated with the expression levels of p-ERK and topoisomerase IIα, which were the lowest in SMMC-7721 cells and the highest in SK-HEP1 cells. Treatment with 50 µmol/L glycyrrhetinic acid significantly down-regulated the expressions of p-ERK and topoisomerase IIα in the 4 HCC cell lines (P<0.05), while 25 µmol/L glycyrrhetinic acid significantly reduced the expression of topoisomerase IIα and p-ERK in SMMC-7721, HEPG2 and HEP3B cells (P<0.05) but not in SK-HEP1 cells. Glycyrrhetinic acid can inhibit the proliferation of different HCC cells particularly in cells with a low proliferation rate. The inhibitory effect of glycyrrhetinic acid might be mediated by reducing the expressions of topoisomerase IIα and inhibiting the ERK pathway.

Destabilizing effect of glycyrrhetinic acid on pre-formed biofilms ofStreptococcus mutans

Objectives: In this study, the destabilizing effect of glycyrrhetinic acid on pre-formed biofilms of Streptococcus mutans (S. mutans) was observed. Methods: Alamar blue assay was used to determine the toxicity of glycyrrhetinic acid on pre-formed biofilms of S. mutans. Four different concentrations (0, 3.75, 7.5, 15 g/ml) of glycyrrhetinic acid were tested. Changes in the biofilm architecture after exposure to glycyrrhetinic acid were analyzed by scanning electron microscopy (SEM). Moreover, the role of glycyrrhetinic acid in enhancing the antimicrobial activity of cetylpyridinium chloride (CPC), an antimicrobial agent commonly used in oral health care products, was evaluated. Results: Glycyrrhetinic acid concentration of up to 15 g/ml had little cytotoxic effect but significantly changed the biofilm architecture. SEM analysis revealed destabilized biofilm structure after the preformed biofilms were exposed to glycyrrhetinic acid. Supplementing 2.5 g/ml CPC with 15 g/ml glycyrrhetinic acid significantly enhanced the bactericidal effect of CPC on the pre-formed biofilms than that in the non-supplemented CPC treated control. This indicates that glycyrrhetinic acid enhanced the antimicrobial activity of CPC by modifying the structure, thus facilitating the penetration of CPC into the biofilm. Conclusions: Glycyrrhetinic acid could be a potential agent to effectively control S. mutans biofilms responsible for dental caries.

Effect of glycyrrhetinic acid on lipid raft model at the air/water interface

To investigate an interfacial behavior of the aglycon of glycyrrhizin (GC), glycyrrhetinic acid (GA), with a lipid raft model consisting of equimolar ternary mixtures of N-palmitoyl sphingomyelin (PSM), dioleoylphosphatidylcholine (DOPC), and cholesterol (CHOL), Langmuir monolayer techniques were systematically conducted. Surface pressure (π)–molecular area (A) and surface potential (ΔV)–A isotherms showed that the adsorbed GA at the air/water interface was desorbed into the bulk upon compression of the lipid monolayer. In situ morphological analysis by Brewster angle microscopy and fluorescence microscopy revealed that the raft domains became smaller as the concentrations of GA in the subphase (CGA) increased, suggesting that GA promotes the formation of fluid networks related to various cellular processes via lipid rafts. In addition, ex situ morphological analysis by atomic force microscopy revealed that GA interacts with lipid raft by lying down at the surface. Interestingly, the distinctive striped regions were formed at CGA=5.0μM. This phenomenon was observed to be induced by the interaction of CHOL with adsorbed GA and is involved in the membrane-disrupting activity of saponin and its aglycon. A quantitative comparison of GA with GC (Sakamoto et al., 2013) revealed that GA interacts more strongly with the raft model than GC in the monolayer state. Various biological activities of GA are known to be stronger than those of GC. This fact allows us to hypothesize that differences in the interactions of GA/GC with the model monolayer correlate to their degree of exertion for numerous activities.

Mechanisms underlying the inhibitory effect of glycyrrhetinic acid on epidermal growth factor-induced proliferation of HaCaT cells

Objective To estimate the effect of glycyrrhetinic acid on epidermal growth factor (EGF)-induced proliferation of HaCaT cells,and to investigate its possible mechanism.Methods Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of HaCaT cells treated with different concentrations of EGF (0,1,5,10,25,50,100 μg/L) and glycyrrhetinic acid (0,0.1,1.0,10,25,50,100μmol/L) alone,or the combination of 25 μg/L EGF with 25 μ mol/L glycyrrhetinic acid or 10 μ mol/L U0126 (an inhibitor of MEK1/2).Western blot was carried out to measure the protein expression of proliferating cell nuclear antigen (PCNA),Notch-1,ERK 1/2 and phosphorylated ERK 1/2 in HaCaT cells treated with 25 μg/L EGF,10 μmol/L U0126,25μmol/L glycyrrhetinic acid alone or in combination.Data were statistically analyzed by using t test,analysis of variance and correlation analysis with SPSS 17.0 software.Results EGF of 0-100 μg/L promoted the proliferation of HaCaT cells in a dose-dependent manner (r =0.798,P ＜ 0.05),and there was a linear correlation between the effect and concentration within the concentration range 0-50 μg/L (r =0.859,P ＜ 0.05).However,glycyrrhetinic acid of 10-100 μmol/L inhibited the proliferation of HaCaT cells in a dose-dependent manner (r =-0.945,P ＜0.01),and 10 μmol/L glycyrrhetinic acid could suppress the EGF (25 μg/L)-induced proliferation and phosphorylation of ERK1/2 in HaCaT cells.Also,both 25 μmol/L glycyrrhetinic acid and 10 μmol/L U0126 could attenuate the increase in PCNA and Notch-1 expression in HaCaT cells induced by 25 μg/L EGF.Conclusion Glycyrrhetinic acid can inhibit the EGF-induced proliferation of HaCaT cells,likely by suppressing the activation of ERK1/2 signaling pathway.

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel.

The Effect of Glycyrrhetinic Acid on Pharmacokinetics of Cortisone and Its Metabolite Cortisol in Rats

The purpose of this paper is to study pharmacokinetics of cortisone (E) and its metabolite cortisol (F) in rats after administration of glycyrrhetinic acid (GA) and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC(0−t), AUC(0−∞), and Cmax for E in the group of E + GA were significantly higher than those in the group of E (P < 0.01); the half-time (t1/2β) was extended compared to E (P < 0.05) and CL/F was dropped obviously (P < 0.01). The rise in AUC(0−t), AUC(0−∞), and Cmax for cortisol in the group of E + GA was significantly compared to the group of E (P < 0.01). CL/F was lower than E (P < 0.01) and the half-time (t1/2β) was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t1/2β, and Cmax of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD).

Novel effects of glycyrrhetinic acid on the central nervous system tumorigenic progenitor cells: Induction of actin disruption and tumor cell-selective toxicity

Licorice extracts are used worldwide in foods and medicines, and glycyrrhetinic acid (GA) is a licorice component that has been reported to induce various important biological activities. In the present study, we show that GA induces actin disruption and has tumor cell-selective toxic properties, and that its selectivity is superior to those of all the clinically available antitumor agents tested. The cytotoxic activity of GA and the tested antitumor agents showed better correlation with the partition coefficient (log P) values rather than the polar surface area (PSA) values. For selective toxicity against tumor cells, GA was most effective at 10 μM that was the same concentration as the previously reported maximum plasma GA level reached in humans ingesting licorice. These results suggest that GA could be utilized as a promising chemopreventive and therapeutic antitumor agent. The underlying mechanisms involved in the selective toxicity to tumor cells by GA are also preliminarily discussed.

Synthesis of glycyrrhetinic acid derivatives for the treatment of metabolic diseases

The effect of glycyrrhetinic acid (GA) and GA-derivatives towards 11β-hydroxysteroid dehydrogenase (11β-HSD) was investigated. Novel compounds with modifications at positions C-3, C-11 and C-29 of the GA skeleton were prepared. Single crystal X-ray diffraction data of selected substances are reported and discussed.

Effect of glycyrrhetinic acid on membrane band 3 in human erythrocytes

Glycyrrhetinic acid (GA) is a hydrolytic product of the triterpene glycoside of glycyrrhizic acid, one of the main constituents of licorice root, which has long been studied, due to its several biological and endocrine properties. In this paper, GA was tested on human erythrocytes, and GA-induced alterations were compared with those caused by diamide, a mild oxidant inducing well-characterized cell/membrane alterations, and n-ethylmaleimide (NEM), as alkylating agent. In order to verify the biochemical steps underlying the action of GA, band 3 Tyr-phosphorylation level, enzyme recruitment and band 3 clustering in cells pre-incubated with GA before diamide treatment were all examined. Results show that GA, in a dose-dependent manner, prevents both diamide and NEM-induced band 3 Tyr-phosphorylation, but not GSH decrease caused by both compounds. In addition, diamide-induced band 3 clustering and IgG binding to altered cells were also completely reversed by GA pre-treatment. Also, when membrane sensitivity toward proteolytic digestion was tested, GA-treated cells showed high resistance to proteolysis. In conclusion, in human erythrocytes, GA is proposed to strengthen membrane integrity against both oxidative and proteolytic damage.

Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells

Glycyrrhetinic acid (GA) is the active metabolite of glycyrrhizic acid, one of the components of liquorice extract. It has been shown to possess anti-inflammatory activity and to inhibit hepatic tumour growth. In this preliminary study, we have shown that GA could significantly reduce the rate of proliferation of LNCaP androgen dependent prostate cancer cells, whereas it had no effect on proliferation of PC3 and DU145 androgen-independent prostate cancer cells. Additionally, GA could significantly reduce the production of prostate-specific antigen by LNCaP cells maintained in-vitro. This study provides a sound platform for further investigation.

Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application

Cortisol is involved in the distribution and deposition of fat, and its action is regulated by the activity of 11β-hydroxysteroid dehydrogenase. Glycyrrhetinic acid, the active principle of licorice root, blocks 11β-hydroxysteroid dehydrogenase type 1, thus reducing the availability of cortisol at the level of adipocytes. We evaluated the effect of topical application of a cream containing glycyrrhetinic acid in the thickness of fat at the level of the thigh. Eighteen healthy women (age range 20–33 years) with normal BMI were randomly allocated to treatment, at the level of the dominant thigh, with a cream containing 2.5% glycyrrhetinic acid ( n = 9) or with a placebo cream containing the excipients alone ( n = 9). Before and after 1 month of treatment both the circumference and the thickness of the superficial fat layer of the thighs (by ultrasound analysis) were measured. The circumference and the thickness of the superficial fat layer were significantly reduced in comparison to the controlateral untreated thigh and to control subjects treated with the placebo cream. No changes were observed in blood pressure, plasma renin activity, plasma aldosterone or cortisol. The effect of glycyrrhetinic acid on the thickness of subcutaneous fat was likely related to a block of 11β-hydroxysteroid dehydrogenase type 1 at the level of fat cells; therefore, glycyrrhetinic acid could be effectively used in the reduction of unwanted local fat accumulation.

Effect of glycyrrhetinic acid on 11β-hydroxysteroid dehydrogenase activity in normotensive and hypertensive subjects

The 11β-hydroxysteroid dehydrogenase (11β-HSD) isoenzymes catalyse the interconversion of cortisol and cortisone. Type 1 11β-HSD mainly converts cortisone into active cortisol. Type 2 11β-HSD inactivates cortisol in mineralocorticoid target tissues, and its activity can be inhibited by glycyrrhetinic acid (GA). Inactivation of cortisol to cortisone is impaired in a subgroup of patients with primary hypertension. To study where this defect is located, we measured cortisol and cortisone concentrations in arterial plasma, in saliva and across the forearm at baseline and after administration of GA in normotensive and hypertensive subjects. GA (500mg) or placebo was administered orally to 20 normotensive subjects in a placebo-controlled double-blind fashion. Further, we compared the effect of GA in 20 patients with primary hypertension with that in 20 normotensive subjects. Cortisol and cortisone were measured in plasma from the brachial artery and vein and in saliva. Samples were obtained at 0, 90 and 150min. Forearm blood flow (FBF) was measured simultaneously. Forearm production of corticosteroid hormones was assessed by multiplying the arteriovenous difference in corticosteroid concentration by FBF. The cortisol/cortisone ratio in arterial plasma remained at baseline levels after placebo (4.9±1.2; mean±S.D.), while after GA the ratio increased similarly in normotensive subjects (12.3±3.4) and in hypertensive patients (12.2±3.7). A similar effect of GA on the salivary cortisol/cortisone ratio was found. In both normotensive subjects and hypertensive patients no forearm production of cortisol or cortisone could be demonstrated, either at baseline or after administration of GA. Thus, both before and after GA administration, we did not find any difference in systemic and salivary 11β-HSD type 2 activity between subjects with primary hypertension and normotensive controls. Further, both at baseline and after GA administration we were not able to demonstrate net inactivation or re-activation of cortisol and cortisone by the 11β-HSD isoenzymes in the forearm in either normotensive or primary hypertensive subjects.

Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats.

Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats

Effect of glycyrrhetinic acid on the viability of human gingival fibroblasts

Some therapeutic agents and medicines such as phenytoin(PHT), nifedipine and cyclosporine may lead to adverse effects causing pathologic changes in tissue, especially on the gingivae1-8). The common histological finding is a marked gingival hyperplasia, with proliferation of gingival fibroblasts and an increase of collagen fibers in connective tissue. PHT-induced human gingival overgrowth may be genetically programmed for increased synthesis of collagen9). PHT-induced gingival overgrowth was preceded by the inflammation of gingivae10-11). Previous studies reported that PHT, nifedipine and cyclosporine increased the cell activity of human gingival fibroblasts12-17). Some differentiation factors such as glycyrrhetinic acid(GA), retinoic acid, ursolic acid and oleanolic acid inhibited18-25). Previous studies reported that GA inhibited intercellular communication between human fibroblasts26-27). Glycyrrhizin(GL), a major component of licorice (Glycyrrhiza glabra L.), is ingested orally as a sweetener or as an ingredient in oriental medicine. GL has a steroid-like action and anti-viral activity (Pompei et al., 1979). Indeed, use of GL to treat chronic viral hepatitis has shown that it can reduce hepatocellular injury by immunopathologic mechanisms and hepatotoxins, possibly through its ability to inhibit phospholipase A2 activity preventing liver lysosome labilization29-30). GL is metabolized to GA, and then 3-epi-18-GA via 3-keto-18-GA by human intestinal flora31). GA shows pronounced antiinflammatory activity and anti-estrogenic action via alteration of cortisol metabolism32-35). GA inhibits the growth and stimulates melanogenesis in cultured melanoma cells36). There are many reports about the use of differentiation factors for the resolution of uncontrolled growth such as in tumors, but there are few report about its use in the dental field including gingival hyperplasia. The purpose of this study was to investigate the 대한치주과학회지 : Vol. 28, No. 3, 1998

Effect of glycyrrhetinic acid on histamine synthesis and release

The effect of glycyrrhetinic acid (18β-glycyrrhetinic acid, GA) on histarnine synthesis and release was investigated in cocultured mast cells with Swiss 3T3 fibroblasts. GA has strong dose dependent inhibitory activity for histamine synthesis and release in cocultured mast cells. GA (50 μM) inhibited about 85% of histidine decarboxylase (HDC) activity. The appearance of cells staining positively with berberine sulfate was also decreased in the presence of GA. It indicates that transdifferentiation of cultured mast cells (CMCs) was also inhibited.

Inhibition of histamine synthesis by glycyrrhetinic acid in mast cells cocultured with Swiss 3T3 fibroblasts.

The effect of glycyrrhetinic acid (18-O-beta-glycyrrhetinic acid, GA) on histamine metabolism was investigated in cultured mast cells (CMCs) cocultured with Swiss 3T3 fibroblasts. GA strongly inhibited histamine synthesis in the cocultured CMCs. Since 50 microM GA inhibited about 80% of histidine decarboxylase (HDC) activity, the inhibitory activity of GA for histamine synthesis was considered to be derived from the inhibition of HDC activity. The number of berberine-sulfate-positive cells also decreased in the presence of GA, which indicated that maturation of CMCs was inhibited by GA. Furthermore, we examined the effect of GA on the mRNA expression of novel protein kinase C delta (nPKC delta), a major isoform of CMCs, by northern blot analysis. The expression of nPKC delta mRNA in the presence of GA was significantly lower than in the absence of GA. These results suggest the possibility that the inhibition of histamine synthesis by GA is regulated by nPKC delta.