Hien-Trung Trinh

Anti-pruritic effect of baicalin and its metabolites, baicalein and oroxylin A, in mice

AbstractAim:To explore whether intestinal microflora plays a role in anti-pruritic activity of baicalin, a main constituent of the rhizome of Scutellaria baicalensis (SB).Methods:Baicalin was anaerobically incubated with human fecal microflora, and its metabolites, baicalein and oroxylin A, were isolated. The inhibitory effect of baicalin and its metabolites was accessed in histamine- or compound 48/80-induced scratching behavior in mice.Results:Baicalin was metabolized to baicalein and oroxylin A, with metabolic activities of 40.2±26.2 and 1.2±1.1 nmol·h−1·mg−1 wet weight of human fecal microflora, respectively. Baicalin (20, 50 mg/kg) showed more potent inhibitory effect on histamine-induced scratching behavior when orally administered than intraperitoneally. In contrast, baicalein and oroxylin A had more potent inhibitory effect when the intraperitoneally administered. The anti-scratching behavior activity of oral baicalin and its metabolites was in proportion to their inhibition on histamine-induced increase of vascular permeability with oroxylin A more potent than baicalein and baicalin. In Magnus test using guinea pig ileum, oroxylin A is more potent than baicalein and baicalin in inhibition of histamine-induced contraction. The anti-scratching behavioral effect of oral baicalin was significantly reduced when oral antibiotics were simultaneously administered, whereas the effect of baicalein and oroxylin A were not affected.Conclusion:Oral baicalin may be metabolized by intestinal microflora into baicalein and oroxylin A, which ameliorate pruritic reactions through anti-histamine action.

Metabolism of Cyanidin‐3‐O‐β‐D‐Glucoside Isolated from Black Colored Rice and Its Antiscratching Behavioral Effect in Mice

Black-colored rice (BCR), the main constituent of which is cyanidin-3-O-beta-D-glucoside (C3G), exhibits an anti-allergic effect, and orally administered C3G is mainly metabolized to protocatechuic acid in rats. Therefore, to understand the relationship between the metabolism of C3G and its pharmacological effect, we isolated C3G from BCR, anaerobically incubated it with fecal microflora, investigated its metabolite(s) by LC-MS/MS, and measured the antiscratching behavioral effects of C3G and its metabolites. C3G was metabolized to protocatechuic acid via cyanidin. Protocatechuic acid and cyanidin were identified as the metabolites. The activities transforming C3G to protocatechuic acid and cyanidin were 28.2 +/- 11.7 and 21.8 +/- 5.2 nmol/h/mg fecal microflora, respectively. C3G and its metabolites showed inhibitory effects against histamine- or compound 48/80-induced scratching behaviors in mice. C3G more potently inhibited scratching behaviors following oral administration than following intraperitoneal administration. However, protocatechuic acid and cyanidin showed more potent inhibition when administered intraperitoneally than when administered orally. These metabolites also inhibited the expression of allergic cytokines, IL-4 and TNF-alpha, and the activation of their transcription factor, NF-kappaB, in RBL-2H3 cells stimulated with IgE-antigen. These findings suggest that C3G-rich BCR may be a beneficial food for diseases involving scratching behaviors, such as chronic dermatitis, rhinitis, and psoriasis.

Artemisia princeps Pamp. Essential Oil and Its Constituents Eucalyptol and α-terpineol Ameliorate Bacterial Vaginosis and Vulvovaginal Candidiasis in Mice by Inhibiting Bacterial Growth and NF-κB Activation

To investigate the inhibitory effects of Artemisia princeps Pamp. (family Asteraceae) essential oil (APEO) and its main constituents against bacterial vaginosis and vulvovaginal candidiasis, their antimicrobial activities against Gardnerella vaginalis and Candida albicans in vitro and their anti-inflammatory effects against G. vaginalis-induced vaginosis and vulvovaginal candidiasis were examined in mice. APEO and its constituents eucalyptol and α-terpineol were found to inhibit microbe growths. α-Terpineol most potently inhibited the growths of G. vaginalis and C. albicans with MIC values of 0.06 and 0.125 % (v/v), respectively. The antimicrobial activity of α-terpineol was found to be comparable to that of clotrimazole. Intravaginal treatment with APEO, eucalyptol, or α-terpineol significantly decreased viable G. vaginalis and C. albicans numbers in the vaginal cavity and myeloperoxidase activity in mouse vaginal tissues compared with controls. These agents also inhibited the expressions of proinflammatory cytokines (IL-1 β, IL-6, TNF- α), COX-2, iNOS, and the activation of NF- κB and increased expression of the anti-inflammatory cytokine IL-10. In addition, they inhibited the expressions of proinflammatory cytokines and the activation of NF- κB in lipopolysaccharide-stimulated peritoneal macrophages, and α-terpineol most potently inhibited the expressions of proinflammatory cytokines and NF- κB activation. Based on these findings, APEO and its constituents, particularly α-terpineol, ameliorate bacterial vaginosis and vulvovaginal candidiasis by inhibiting the growths of vaginal pathogens and the activation of NF- κB.

Evaluation of Antipruritic Effects of Red Ginseng and Its Ingredients in Mice

The anti-pruritic effect of red ginseng (the steamed root of Panax ginseng C.A. Meyer, Araliaceae), a traditional medicine in Asian countries, was investigated in mouse scratching behavior models induced by either compound 48/80 or histamine. Red ginseng and its saponin fraction, but not its polysaccharide fraction, showed an anti-pruritic effect. Representative constituents in the saponin fraction, ginsenosides Rg3 and Rh2, inhibited scratching behavior and vascular permeability. These ginsenosides also inhibited the expression of TNF-alpha and IL-4 induced by IgE-antigen complex in RBL-2H3 cells, as well as acetic acid-induced writhing in mice. These results suggest that red ginseng and its ingredients, ginsenosides Rg3 and Rh2, may inhibit scratching behavior by inhibiting IL-4 and TNF-alpha expression, promoting membrane stability, and inhibiting Ca (++) influx.

Anti-scratching behavioral effect of Lactobacillus plantarum PM008 isolated from kimchi in mice

To isolate antipruritic lactic acid bacteria (LAB) from kimchi, a traditional Korean food, we investigated the interleukin (IL)-4 production-inhibitory effect in the colon of mice for previously isolated LAB. Orally administered Lactobacillus plantarum PM008 potently inhibited the expression of IgE-switching cytokine, IL-4, and of proinflammatory cytokines, IL-1β and TNF-α, in the colon of mice. Its inhibitory effect was dependent on the dosage and administration period. When PM008 was orally administered to mice, the number of PM008 detected in the intestine and feces by polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) methods was dependent on the administration dosage and period. The number of PM008 attached in the intestine was gradually decreased with increasing time after completion of its oral administration. PM008 dose-dependently inhibited the scratching behavior induced by histamine or compound 48/80. PM008 treated at a dose of 1 × 1010 CFU for 14 days inhibited the histamine- and compound 48/80-induced scratching behaviors by 32.8% and 48.6%, respectively. This inhibitory effect continued, although reduced, at 7 days after stopping the oral administration of PM008 attached in the intestine. Based on these findings, L. plantarum PM008 may improve pruritus by inhibiting IL-4 expression.

Antiallergic effect of ginseng fermented with Ganoderma lucidum

Ginseng (the root of Panax ginseng CA Meyer, family Araliacease), which is used in Korea, China and Japan as a herbal medicine, was fermented with Ganoderma lucidum (GL) and their antiallergic effects were investigated. Of GLs used for fermentation, KCTC 6283 potently produced ginsenoside Rh2, followed by KFRI M101. KCTC 6532, and ginsenoside Rd, followed by KFRI M101. Oral administration of these fermented ginseng extracts inhibited allergic reactions, passive cutaneous anaphylaxis reaction induced by IgE and scratching behaviors induced by compound 48/80. Of them, the ginseng extract fermented by KCTC 6532 and KFRI M101 potently inhibited allergic reactions compared to that fermented by KCTC 6283. These findings suggest that the fermentation of ginseng with GL can increase its antiallergic activity and the increment of its antiallergic effect may be due to the biotransformation of ginseng saponins to ginsenosides Rd and Rh2.

Inhibitory effect of Lactobacillus plantarum K-1 on passive cutaneous anaphylaxis reaction and scratching behavior in mice.

Lactobacillus plantarum K-1 (LP) inhibiting AP-1 (c-Jun) and NF-κB activations was isolated from kimchi, and its inhibitory activity against scratching behavior and passive cutaneous anaphylaxis reaction in mice was investigated. Heat-inactivated LP (heated at 60°C for 30 min) potently inhibited the expression of TNF-α and IL-4 as well as the activation of their transcription factors, NF-κB and c-jun, in phorbol 12′-myristate 13′-acetate-stimulated RBL-2H3 cells. LP (1 ×1010 CFU per mouse) showed a potent inhibition against passive cutaneous anaphylaxis reaction induced by the IgE-antigen complex in mice, inhibiting it by 87.5%. LP (1 × 1010 CFU/mouse) inhibited histamine-induced scratching behavior by 58.9% compared to the control group. LP significantly inhibited vascular permeability induced by histamine. The inhibitory activity of LP against vascular permeability was in proportion to its inhibition against scratching behavior. LP potently inhibited histamine-induced cytokine production: it (1 × 1010 CFU per mouse) inhibited IL-4, IL-1β, and TNF-α expression by 88.9%, 88.6%, and 98.9%, respectively. LP also inhibited IgE level increased by histamine by 85.3%. It inhibited histamine-induced the activations of their transcription factors, NF-κB and c-Jun. Based on these findings, LP may improve allergic diseases, such as anaphylaxis, atopic dermatitis, rhinitis, and pruritus by inhibiting the expression of IgE-switching cytokine IL-4 and proinflammatory cytokines IL-1β and TNF-α via NF-κB and AP-1 signaling pathways.

Inhibitory effects of curcuminoids on passive cutaneous anaphylaxis reaction and scratching behavior in mice

To understand anti-allergic effect of Curcuma aromatica (family Zingerberaceae), which inhibited passive cutenous anaphylaxis (PCA) reaction in preliminary study, we isolated its main constituents, curcumin, demethoxycurcumin and bisdemethoxycurcumin, and investigated their inhibitory effects against PCA reaction and scratching behavior. These curcuminoids inhibited the PCA reaction induced by the IgE-antigen complex (IAC) and the scratching behavior induced by compound 48/80. These curcuminoids also inhibited degranulation, protein expression of TNF-α and IL-4, and transcription factor NF-κB activation in IAC-induced RBL-2H3 cells. Of these curcuminoids, curcumin exhibited the most potent inhibition, followed by demethoxycurcumin and bisdemethoxycurcumin. These findings suggest that curcuminoids, particularly curcumin, can improve the symptoms of allergic diseases, such as anaphylaxis and itching.

Anti-allergic effect of Petasites japonicus fermented with lactic acid bacteria in mice

Abstract Petasites japonicus (PJ, family Asteraceae) was fermented with lactic acid bacteria (LAB), Bifidobacterium breve (BB) or Lactobacillus acidophilus (LA), and its allergic effect was investigated. LAB-fermented PJs more potently inhibited IgE–antigen-stimulated degranulation of RBL-2H3 cells than non-fermented PJ, with BB-fermented PJ more potent than LA-fermented PJ. Fermented PJ more potently inhibited TNF-α and IL-4 cytokine expression and transcription factor NF-κB activation in IgE-induced RBL-2H3 cells. PJ and BB-fermented PJ also inhibited IgE–antigen-induced passive cutaneous anaphylaxis (PCA) reactions as well as compound 48/80-induced scratching behaviours in mice, with fermented PJ more potent than non-fermented PJ. These findings suggest that PJ may show anti-allergic effects by inhibiting degranulation, and TNF-α and IL-4 expression and its anti-allergic effects can be enhanced by LAB fermentation.

Inhibitory Effect of Fermented Red Ginseng against Passive Cutaneous Anaphylaxis Reaction and Scratching behaviors in Mice

To evaluate the antiatopic effect of Korea red ginseng (RG, steamed root of Panax ginseng CA Meyer, Family Araliaceae) fermented by Bifidobacterium longum H-1 (FRG), its inhibitory effect on passive cutaneous anaphylaxis (PCA) reaction and itching in mice was measured. FRG and its ingredient saponin fraction (FSF) potently inhibited PCA reaction and scratching behaviors. FRG at a dose of 200 ㎎/㎏ and FSF at a dose of 50 ㎎/㎏ significantly inhibited the scratching frequency by 45% and 47%, respectively. FRG and FSF also inhibited the degranulation and protein expression of tumor-necrosis factor-α and interleukin-4 of RBL-2H3 cells induced by IgE-complex. However, polysaccharide fraction of FRG (FPF) weakly inhibited it, compared with FSF. The inhibitory effect of FRG against PCA reaction and scratching behaviors more potently inhibited than that of RG. Based on these findings, FRG can improve allergic skin disorders atopic dermatitis by the regulation of TNF-α, and IL-4 produced by mast cells and basophils and its degranulation.