18β-glycyrrhetinic Acid Research Articles

The protective effects of 18β-glycyrrhetinic acid against inflammation microenvironment in gastric tumorigenesis targeting PGE2-EP2 receptor-mediated arachidonic acid pathway

Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for gastrointestinal diseases. Glycyrrhiza glabra, a traditional Chinese medicine, has been shown to safely suppress gastric cancer; however, the anti-inflammatory mechanisms in gastric tumorigenesis have been poorly investigated. Therefore, this study is committed to demonstrate the in vivo anti-inflammatory effect of 18β-glycyrrhetinic acid (GRA), the main active component of G. glabra. The lymphocytes and macrophages were heavily infiltrated in the transgenic mice that highly expressed cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1; however, a significant reduction was observed after treatment with GRA. In addition, GRA downregulated the protein levels of COX-2, GαS, EP2, and β-catenin, which were involved in the arachidonic acid pathway. In conclusion, our study showed the potential protective effects of GRA against inflammatory environment that might be involved in gastric tumorigenesis in vivo through the PGE2-EP2 receptor-mediated arachidonic acid pathway.

Inhibitory effect of 18β-glycyrrhetinic acid on the biofilm formation of Streptococcus mutans

Inhibitory effect of 18β-glycyrrhetinic acid on the biofilm formation of <i>Streptococcus mutans</i>

Effects of 18β-Glycyrrhetinic Acid on Fungal Protease-Induced Airway Inflammatory Responses.

Airway epithelial cells secrete diverse inflammatory mediators in response to various stimuli. Thus, early regulation of immune responses in the airway epithelium is likely critical for the control of chronic inflammatory diseases. The purpose of the present study was to evaluate the effects of 18β-glycyrrhetinic acid (GA) on inflammatory responses generated in response to a fungal protease allergen that induces epithelial damage. To understand the underlying mechanisms, we also investigated the inhibitory effects of GA on the production of mitochondrial reactive oxygen species (ROS) in the human bronchial epithelial cell line BEAS2B. In this study, GA treatment reduced cytokine production and the human neutrophil cell line HL60 migration through decreased mitochondrial ROS production. In addition, GA significantly reduced inflammatory cell infiltration and cytokine levels in the bronchoalveolar lavage (BAL) fluid of fungal allergen-administered mice. Inhibitory effects of GA are dependent on the mitochondrial ROS/MAPK axis. Moreover, the effect of GA on the regulation of mitochondrial ROS depends on the expression of uncoupling protein-2 (UCP-2). Taken together, GA might represent a potential therapeutic agent for blocking inflammatory responses in airways.

In vitro effects of glycyrrhetinic acid and hyaluronic acid on the growth of vulvovaginal Candida albicans and other yeasts

Aims. The present study aimed to test the in vitro activity against Candida albicans and non-albicans strains of 18-β glycyrrhetinic acid (18-β GA) and hyaluronic acid (HA), both alone and in combination. This antimicrobial activity was assessed using the National Committee for Clinical Laboratory Standards (NCCLS) method on Candida strains that were isolated from patients with recurrent vulvovaginal candidiasis (RVVC). Results. Our results demonstrate that the anti-Candida activity is independent from antifungal susceptibility level and the fact that the growth inhibition is stronger at acidic pH level makes the two drugs a promising biological alternative for the topical treatment of vulvovaginal candidiasis (VVC) and RVVC. Conclusions. Furthermore, the reduction of both budding cells formation and germ tube elongation, on mammalian cell monolayers, may explain the observed growth inhibition and suggest a decreased virulence, respectively.

Evaluation of effectiveness of the use of toothpastes in treatment of non-carious teeth diseases

Aim. To assess the effectiveness of the use of therapeutic and prophylactic toothpastes containing hydroxyapatite nanoparticles or sodium fluoride in patients with non-carious lesions. Methods. Mixed saliva was studied in 40 individuals. All subjects were divided into three groups. Group 1 (n=15) used toothpaste №1 containing zinc citrate and sodium fluoride for tooth brushing, group 2 (n=15) brushed teeth with a paste №2 with hydroxyapatite nanoparticles which contained materials removing dental plaque due to antioxidant β-glycyrrhetinic acid possessing anti-inflammatory activity. The control group included 10 subjects with healthy oral cavity. Hyperesthesia of teeth was assessed using Shiff air sensitivity scale, indices of prevalence of tooth hyperesthesia and intensity of tooth hyperesthesia in %, periodontal condition (papillary marginal alveolar index) in % and the oral hygiene score were determined. The activity of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase (U/l) before and after tooth brushing with toothpastes containing hydroxyapatite particles or sodium fluoride, was also measured. Results. After tooth brushing with both pastes for three months, a decrease of tooth hyperesthesia was observed, as evidenced by the values of Shiff test, index of prevalence of hyperesthesia and intensity of tooth hyperesthesia. Oral hygiene and periodontal state improved. The best effect was observed with a paste №2, containing anti-inflammatory and abrasive components and hydroxyapatite nanoparticles. This is confirmed by a decrease of the activity of lactate dehydrogenase present in anaerobic bacteria, as well as activity of aspartate aminotransferase and alanine aminotransferase, reflecting a decrease of inflammation in the periodontal tissues. Conclusion. Use of toothpastes containing hydroxyapatite nanoparticles or sodium fluoride reduces hyperesthesia of the enamel and inflammation in the periodontium and is accompanied by decreased activity of enzymes in mixed saliva.

18β-glycyrrhetinic acid inhibits migration and invasion of human gastric cancer cells via the ROS/PKC-α/ERK pathway.

18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice root which exerts pharmacological activities including anti-inflammatory, antiviral, anti-oxidative and anti-cancer effects. The current study further investigated the molecular mechanisms associated with the inhibitory effects of 18β-GA on tumor metastasis in human gastric cancer cells. The results indicated that 18β-GA significantly reduced invasion and migration activities and suppressed MMP-2 and 9 activities on SGC-7901cells in a dose-dependent manner. Further study showed 18β-GA upregulated E-cadherin expression but downregulated vimentin expression. The results also showed that 18β-GA inhibited ROS formation, PKC-α expression and the phosphorylation of ERK in a dose-dependent manner. In conclusion, this study revealed that 18β-GA inhibits migration and invasion via the ROS/PKC-α/ERK signaling pathway in gastric cancer cells. This suggests that 18β-GA has the potential to be used as an effective chemopreventive agent for the prevention of gastric cancer metastasis.

Fabrication of Chitosan‐18β‐Glycyrrhetinic Acid Modified Titanium Implants with Nanorod Arrays for Suppression of Osteosarcoma Growth and Improvement of Osteoblasts Activity

AbstractSurgery has been combined with chemotherapy to treat osteosarcoma. However, the recovery rate of osteosarcoma patients is still low. To prevent post‐operative recurrence of the osteosarcoma, developing an alternative biomaterial is essential. 18β‐Glycyrrhetinic acid (GA) has shown potential anticancer activity in various malignancies. Here it is proposed that GA can induce osteosarcoma cell apoptosis, and a polydopamine‐mediated titanium oxide nanorod (TiO2NR) surface is functionalized by covalently grafting the chitosan‐18β‐glycyrrhetinic acid conjugate (CS–GA). In vitro and in vivo biological tests indicate that the CS–GA modified surface shows significant antiproliferation and apoptosis in osteosarcoma cells (MG63). Additionally, this modified surface with nanoarray structure stimulation and chitosan supplementation significantly promotes osteoblast (MC3T3‐E1) adhesion and proliferation in vitro. This dual‐functional, Ti‐based implant with balanced antitumor and biocompatibility properties represents an effective strategy for the surgical treatment of osteosarcoma.

Blocking autophagy enhances the apoptotic effect of 18\u03b2-glycyrrhetinic acid on human sarcoma cells via endoplasmic reticulum stress and JNK activation

Sarcoma, a rare form of cancer, is unlike the much more common carcinomas as it occurs in a distinct type of tissue. The potent antitumor effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, have been demonstrated in various cancers. However, the effect of GA on human sarcoma, and the underlying mechanisms, remain to be elucidated. In the current study, we show that GA inhibits sarcoma cell proliferation by inducing G0/G1-phase arrest. Exposure to GA resulted in the activation of caspase-3, -8, and -9, indicating that GA induced apoptosis through both extrinsic and intrinsic pathways. In addition, the autophagy pathway, characterized by the conversion of LC3-I to LC3- II, was activated, resulting in increased Beclin-1 protein levels, decreased p62 expression, and stimulation of autophagic flux. The present findings showed that GA stimulated autophagy by inducing endoplasmic reticulum (ER) stress via the IRE1–JNK pathway. Our data supported the prosurvival role of GA-induced autophagy when the autophagy pathway was blocked with specific chemical inhibitors. Finally, GA markedly reduced sarcoma growth, with little organ-related toxicity, in vivo. The present results suggest that the combination of GA with a specific autophagy inhibitor represents a promising therapeutic approach for the treatment of sarcoma.

18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts.

Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.

Characterisation of the cancer-associated glucocorticoid system: key role of 11\u03b2-hydroxysteroid dehydrogenase type 2

Background:Recent studies have shown that production of cortisol not only takes place in several non-adrenal peripheral tissues such as epithelial cells but, also, the local inter-conversion between cortisone and cortisol is regulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). However, little is known about the activity of this non-adrenal glucocorticoid system in cancers.Methods:The presence of a functioning glucocorticoid system was assessed in human skin squamous cell carcinoma (SCC) and melanoma and further, in 16 epithelial cell lines from 8 different tissue types using ELISA, western blotting and immunofluorescence. 11β-HSD2 was inhibited both pharmacologically and by siRNA technology. Naïve CD8+ T cells were used to test the paracrine effects of cancer-derived cortisol on the immune system in vitro. Functional assays included cell–cell adhesion and cohesion in two- and three-dimensional models. Immunohistochemical data of 11β-HSD expression were generated using tissue microarrays of 40 cases of human SCCs as well as a database featuring 315 cancer cases from 15 different tissues.Results:We show that cortisol production is a common feature of malignant cells and has paracrine functions. Cortisol production correlated with the magnitude of glucocorticoid receptor (GR)-dependent inhibition of tumour-specific CD8+ T cells in vitro. 11β-HSDs were detectable in human skin SCCs and melanoma. Analyses of publicly available protein expression data of 11β-HSDs demonstrated that 11β-HSD1 and -HSD2 were dysregulated in the majority (73%) of malignancies. Pharmacological manipulation of 11β-HSD2 activity by 18β-glycyrrhetinic acid (GA) and silencing by specific siRNAs modulated the bioavailability of cortisol. Cortisol also acted in an autocrine manner and promoted cell invasion in vitro and cell–cell adhesion and cohesion in two- and three-dimensional models. Immunohistochemical analyses using tissue microarrays showed that expression of 11β-HSD2 was significantly reduced in human SCCs of the skin.Conclusions:The results demonstrate evidence of a cancer-associated glucocorticoid system and show for the first time, the functional significance of cancer-derived cortisol in tumour progression.

Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability

Twenty-six conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80μM and 3.52μM, respectively. The enzyme inhibition ratio of nine compounds at 10μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition.

Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents

The potential of licorice dietary supplements to interact with drug metabolism was evaluated by testing extracts of three botanically identified licorice species (Glycyrrhiza glabra L., Glycyrrhiza uralensis Fish. ex DC. and Glycyrrhiza inflata Batalin) and 14 isolated licorice compounds for inhibition of 9 cytochrome P450 enzymes using a UHPLC-MS/MS cocktail assay. G. glabra showed moderate inhibitory effects against CYP2B6, CYP2C8, CYP2C9, and CYP2C19, and weak inhibition against CYP3A4 (testosterone). In contrast, G. uralensis strongly inhibited CYP2B6 and moderately inhibited CYP2C8, CYP2C9 and CYP2C19, and G. inflata strongly inhibited CYP2C enzymes and moderately inhibited CYP1A2, CYP2B6, CYP2D6, and CYP3A4 (midazolam). The licorice compounds isoliquiritigenin, licoricidin, licochalcone A, 18β-glycyrrhetinic acid, and glycycoumarin inhibited one or more members of the CYP2C family of enzymes. Glycycoumarin and licochalcone A inhibited CYP1A2, but only glycycoumarin inhibited CYP2B6. Isoliquiritigenin, glabridin and licoricidin competitively inhibited CYP3A4, while licochalcone A (specific to G. inflata roots) was a mechanism-based inhibitor. The three licorice species commonly used in botanical dietary supplements have varying potential for drug-botanical interactions as inhibitors of cytochrome P450 isoforms. Each species of licorice displays a unique profile of constituents with potential for drug interactions.

Binding effect of fluorescence labeled glycyrrhetinic acid with GA receptors in hepatocellular carcinoma cells

Glycyrrhetinic acid (GA) is a natural active component from licorice, which is broadly used in traditional Chinese medicine. Lots of glycyrrhetinic acid receptors (GA-R) are proved to locate on the surface of liver cells. Many reports about the hepatocellular carcinoma (HCC) treatment were dependent on GA modified carriers. However, the reality of GA-R in HCC cells was not clear. In this paper, 18β-glycyrrhetinic acid (18β-GA) was labeled with fluorescence (FITC) by chemical synthesis. Together with the binding effect of fluorescence labeled glycyrrhetinic acid (FITC-GA), the competitive action of 18β-GA with GA-R was investigated in HCC cells. The results showed that in HepG2 cells, 18β-GA and FITC-GA presented similar cytotoxicity. The specific binding saturation of GA showed the dissociation constant (Kd) was 7.457±2.122pmol/L and the maximum binding counts (Bmax) was 2.385±0.175pmol/2.5×106 cells, respectively. FITC-GA bound to cytomembrane specifically and 18β-GA competed to bind the sites significantly in HepG2 cells. Therefore, there is binding effect between fluorescence labeled GA and GA-R. The GA-R on HCC cells is confirmed as expected, which provides a useful reference of active target modified by GA and a novel approach for receptors and ligands study.Keywords: Glycyrrhetinic acid; fluorescence labeled; receptor saturation; completive effect; hepatocellular carcinoma cells.

18β-glycyrrhetinic acid exhibits potent antitumor effects against colorectal cancer via inhibition of cell proliferation and migration.

Accumulating evidence shows that 18β-glycyr-rhetinic acid (GRA) has antitumor activities in breast, ovarian cancer and leukemia, while its role in colorectal cancer remains unknown. In the present study, we investigated the effect of GRA in colorectal cancer cells LoVo, SW480 and SW620 and studied the underlying molecular mechanisms. Results showed that GRA had potent inhibitory effects on colorectal cancer cell proliferation in a dose- and time-dependent manner invitro and invivo. Growth inhibition was mediated by pro-apoptosis, as evident from AnnexinV-FITC staining, the reduced expression of survivin and the induced expression of cleaved PARP. Furthermore, GRA treatment resulted in marked reduction of cell migration, invasion and wound healing capability, accompanying by the downregulated MMP expression. Moreover, GRA decreased the protein levels of p-PI3K, p-AKT, p-STAT3, p-JNK, p-p38 and p-NF-κB p65, of which the phosphorylation of PI3K and STAT3 decreased as early as 2h after the GRA treatment. These results suggest that regulation of the apoptosis, invasion and migration of colorectal cancer cells by GRA might be through suppressing PI3K and STAT3 signaling pathways. the present study indicated that GRA could be a potential effective therapy for patients with colorectal cancer.

Properties of synchronous spontaneous Ca2+ transients in the mural cells of rat rectal arterioles.

Synchrony of spontaneous Ca2+ transients among venular mural cells (smooth muscle cells and pericytes) in visceral organs relies on the intercellular spread of L-type voltage-dependent Ca2+ channel (LVDCC)-dependent depolarisations. However, the mechanisms underlying the synchrony of spontaneous Ca2+ transients between arteriolar mural cells are less understood. The spontaneous intracellular Ca2+ dynamics of arteriolar mural cells in the rat rectal submucosa were visualised by Cal-520 Ca2+ imaging to analyse their synchrony. The mural cells in fine arterioles that had a rounded cell body with several extended processes developed spontaneous 'synchronous' Ca2+ transients arising from Ca2+ released from sarcoendoplasmic reticulum Ca2+ stores. Gap junction blockers (3μM carbenoxolone, 10μM 18β-glycyrrhetinic acid), a Ca2+-activated Cl- channel (CaCC) blocker (100μM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) or lowering extracellular Cl- concentration (from 134.4 to 12.4mM) disrupted the synchrony of Ca2+ transients between arteriolar mural cells. Blockers of T-type voltage-dependent Ca2+ channels (TVDCCs, 1μM mibefradil or ML218) or LVDCCs (1μM nifedipine) reduced the Ca2+ transient frequency or their area under curve (AUC), respectively. However, neither TVDCC nor LVDCC blockers disrupted the synchrony of Ca2+ transients among arteriolar mural cells. This is in contrast with rectal venules in which nifedipine disrupted the synchrony of spontaneous Ca2+ transients. Thus, spontaneous transient depolarisations arising from the opening of CaCCs may effectively spread to neighbouring arteriolar mural cells via gap junctions to maintain the Ca2+ transient synchrony. Activation of TVDCCs appears to accelerate spontaneous Ca2+ transients, while LVDCCs predominantly contribute to the duration of Ca2+ transients.

Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPARγ and Nrf2: Protective effect of 18β-Glycyrrhetinic acid

18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice with promising hepatoprotective activity. However, its protective mechanism on methotrexate (MTX) hepatotoxicity in not well defined. We investigated the hepatoprotective effect of 18β-GA, pointing to the role of peroxisome proliferator activated receptor gamma (PPARγ) and the redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2). Wistar rats were orally administered 18β-GA (50 and 100 mg/kg) 7 days either before or after MTX injection. MTX induced significant increase in circulating liver function marker enzymes and bilirubin with concomitant declined albumin levels. Serum pro-inflammatory cytokines, and liver malondialdehyde and nitric oxide were significantly increased in MTX-induced rats. Treatment with 18β-GA significantly reduced serum enzymes of liver function, bilirubin and pro-inflammatory cytokines. 18β-GA attenuated MTX-induced oxidative stress and restored the antioxidant defenses. In addition, 18β-GA improved liver histological structure and decreased the expression of Bax whereas increased Bcl-2 expression. MTX-induced rats showed significant down-regulation of Nrf2, hemoxygenase-1 and PPARγ, an effect that was markedly reversed by 18β-GA supplemented either before or after MTX. In conclusion, 18β-GA protected against MTX-induced liver injury, possibly by activating Nrf2 and PPARγ, and subsequent attenuation of inflammation, oxidative stress and apoptosis. Therefore, 18β-GA can provide protection against MTX-induced hepatotoxicity.

Multiple Psychopharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan, and the Brain Regions it Affects.

Yokukansan (YKS), a traditional Japanese Kampo medicine, has indications for use in night crying and irritability in children, as well as neurosis and insomnia. It is currently also used for the remedy of the behavioral and psychological symptoms of dementia (BPSD), such as aggressiveness, agitation, and hallucinations. In parallel with clinical evidence, a significant amount of fundamental researches have been undertaken to clarify the neuropsychopharmacological efficacies of YKS, with approximately 70 articles, including our own, being published to date. Recently, we reviewed the neuropharmacological mechanisms of YKS, including its effects on glutamatergic, serotonergic, and dopaminergic neurotransmission, and pharmacokinetics of the ingredients responsible for the effects. This review is aimed to integrate the information regarding the psychopharmacological effects of YKS with the brain regions known to be affected, to facilitate our understanding of the clinical efficacy of YKS. In this review, we first show that YKS has several effects that act to improve symptoms that are similar to BPSDs, like aggressiveness, hallucinations, anxiety, and sleep disturbance, as well as symptoms like tardive dyskinesia and cognitive deficits. We next provide the evidence showing that YKS can interact with various brain regions, including the cerebral cortex, hippocampus, striatum, and spinal cord, dysfunctions of which are related to psychiatric symptoms, cognitive deficits, abnormal behaviors, and dysesthesia. In addition, the major active ingredients of YKS, geissoschizine methyl ether and 18β-glycyrrhetinic acid, are shown to predominantly bind to the frontal cortex and hippocampus, respectively. Our findings suggest that YKS has multiple psychopharmacological effects, and that these are probably mediated by interactions among several brain regions. In this review, we summarize the available information about the valuable effects of a multicomponent medicine YKS on complex neural networks.

18β-Glycyrrhetinic acid, the major bioactive component of Glycyrrhizae Radix, attenuates airway inflammation by modulating Th2 cytokines, GATA-3, STAT6, and Foxp3 transcription factors in an asthmatic mouse model.

18β-Glycyrrhetinic acid (18Gly), the major bioactive component of Glycyrrhizae Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological properties. Although 18Gly is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic inflammatory lung disease have not been examined. Moreover, there are no in vivo studies on the anti-asthmatic effects of 18Gly in allergic asthma. We investigated its effect and mechanism of action in airway inflammation in a BALB/c mouse model of allergic asthma. Interestingly, 18Gly strongly suppressed airway hyperresponsiveness, accumulation of inflammatory cells, and levels of T helper type 2 (Th2) cytokines (interleukin (IL)-5 and IL-13) in bronchoalveolar lavage fluid (BALF). It also attenuated lung IL-5, IL-13, and IL-4 expression, but it upregulated peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression in lungs. Moreover, it exerted immunomodulatory effects by suppressing Th2 cytokines (IL-5, IL-13) production through upregulation of forkhead box p3 (Foxp3), and downregulation of signal transducer and activator of transcription (STAT6), GATA-binding protein 3 (GATA-3), and retinoic acid-related orphan receptor γ t (RORγt) expression. These results suggest that the anti-asthmatic activity of 18Gly may occur by the suppression of IL-5, IL-13, and OVA-specific Immunoglobulin E (IgE) production through inhibition of the RORγt, STAT6, GATA-3 pathways and upregulation of the Foxp3 transcription pathway. Also, 18Gly treatment was protective against the oxidative stress by inducing significant decrease of reactive oxygen species (ROS) generation in MH-S alveolar macrophage cells. Our results suggest that 18Gly can improve allergic asthma and can be a novel therapeutic component for the treatment of allergic asthma.

Partial protection by 18β Glycrrhetinic acid against Cisplatin induced oxidative intestinal damage in wistar rats: Possible role of NFkB and caspases.

Cisplatin (CP) is a potent chemotherapeutic agent commonly used for the treatment of various malignancies. It has varied undesirable effects such as nephrotoxicity, intestinal toxicity which limit its wide and extensive clinical usage. 18β-Glycyrrhetinic acid (GA) is a pentacyclic triterpenoid derivative, obtained from the herb liquorice having pharmacological properties such as anti-inflammatory, hepatoprotective and antioxidant. The present study was designed to investigate in vivo efficacy of GA against CP induced small intestinal toxicity. Rats were subjected to prophylactic oral treatment of GA (50 and 100mg/kg body weight) for 21days against intestinal toxicity induced by single intra peritoneal injection of CP (10mg/kg body weight) on day 18th and sacrificed on 21st day. The plausible mechanism of CP induced small intestinal toxicity is via deficit in anti-oxidant armory, induction of oxidative stress; TNF-α, NFkB, activation of apoptotic pathway proteins by up regulation of caspases. However prophylactic treatment of GA diminished oxidative stress markers, TNF-α, NFkB expression and enhanced anti-oxidant status, down regulated apoptosis, recovered histopatholgical alterations in small intestine. Therefore, results of the present finding provide strong evidence that GA may be a useful modulator in alleviating CP induced intestinal toxicity.

Protective Effect of 18β-Glycyrrhetinic Acid against Triptolide-Induced Hepatotoxicity in Rats.

Triptolide (TP) is the major active component of Tripterygium wilfordii Hook F (TWHF) and possesses multiple pharmacological effects. However, hepatotoxicity of TP which is one of the toxic properties slows its progression in clinical application. 18β-Glycyrrhetinic acid (GA) is the main bioactive ingredient of Licorice (Glycyrrhiza glabra L.), a herbal medicine famous for its detoxification. This study aims to investigate whether GA possesses protective effect against TP-induced hepatotoxicity in rats. TP interference markedly elevated serum levels of ALT, AST, and ALP, caused evident liver histopathological changes, and elevated hepatic TNF-α, IL-6, IL-1β, and IFN-γ as well as nuclear translocation of NF-κB. TP also significantly elevated liver MDA and declined hepatic activities of SOD, CAT, and GSH-Px. Assay of TUNEL and apoptosis proteins (Bax, Bcl-2, and active caspase-3) showed that TP induced severe hepatocellular apoptosis. In contrast, low-dose GA (50 mg/kg) significantly reversed TP-induced changes above. However, high-dose GA (100 mg/kg) had no such effect. Overall, these findings indicated that low-dose GA but not high-dose GA exhibited a protective effect against TP-induced hepatotoxicity in rats by anti-inflammation, antioxidation, and antiapoptosis, which suggests that the doses of GA/Licorice should be carefully considered when used together with TWHF or TWHF preparations.