Natural anti-inflammatory agent

Compared to the acetic acid control, both Diammonium Glycyrrhizinate (DG) and dexamethasone showed a significant anti-inflammatory effect (P < 0.01). The expression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa was significantly lower in the Diammonium Glycyrrhizinate group and dexamethasone group than in the acetic acid group. Conclusion: Diammonium Glycyrrhizinate could reduce inflammatory injury in a rat model of ulcerative colitis. This may occur via suppression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa. [1]

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DAI, morphologic injury, histological changes, and MPO activity [1]
1-2 d after colonic infusion of acetic acid, rats displayed diarrhea, pyemic stool, and reduced body weight. Morphologically, a dilated lumen, thickened wall, and brown or black color was observed continuously in the injured bowel. Edema, erosions, necrosis, superficial ulcerations, crypt abscesses, and inflammatory infiltration into the lamina propria were observed in the injured segment by light microscopy. In Table 3, according to DAI, scores of morphological and histological changes, and MPO activity, the colon showed significant pathogenic changes in the Diammonium Glycyrrhizinate (DG), dexamethasone, and acetic acid control groups compared to the normal control group that received saline alone (P < 0.01), which demonstrated that acetic acid infusion results in injuries that are comparable to those seen in humans with ulcerative colitis. These inflammatory indices were significantly improved by DG and dexamethasone (P < 0.01). The anti-inflammatory effect of DG was significantly lower than that of dexamethasone (P < 0.01).

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Expression of NF-κB p65, TNF-α and ICAM-1 in injured colon [1]
In rats that received acetic acid, NF-κB p65 was positive mainly in nuclei of most endothelial cells, epithelial cells and mononuclear cells, especially in the mucosa and submucosa. TNF-α and ICAM-1 were positive mainly in the cytoplasm, membrane and rarely in nuclei. ICAM-1 was positive in most endothelial cells and macrophages. TNF-α positive cells, including mononuclear cells, macrophages and neutrophils, were located densely in lamina propria and in proximity to the muscularis. The percentage of cells positive for these three molecules was significantly correlated with the degree of inflammatory injury (Table 4), and these markers were rarely expressed in samples taken from the normal control group. The positive percentage and density of NF-κB p65, TNF-α and ICAM-1 in injured colon was significantly higher than that in normal control. After Diammonium Glycyrrhizinate (DG) or dexamethasone treatment, the positive percentage and density of these molecules were reduced significantly, which indicates that both DG and dexamethasone may inhibit the expression of these molecules. Also, the expression of these molecules was significantly lower in DG treated samples than in dexamethasone treated samples (P < 0.01).

Spragur-Dawley female rats were divided into four groups: Diammonium Glycyrrhizinate (DG) group, dexamethasone group, acetic acid control and normal control group. Colonic inflammation was evaluated by disease activity index, gross morphologic damage, histological injury and colonic myeloperoxidase activity. Immunohistochemistry was used to detect the expression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa. [1]

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Preparation of animal model: Forty SD rats were divided into four groups: Diammonium Glycyrrhizinate (DG) group, dexamethasone group, acetic acid control and normal control group. All rats were fasted for twenty-four hour. Before the colonic infusion of acetic acid, 0.3 mL (30 mg/kg) Natrium pentobarbital was injected peritoneally. A polyethylene catheter was put into the colon extending a distance of eight centimeters beyond the anus. For DG, dexamethasone, and the acetic acid control groups, 1 mL of 10% (v/v) acetic acid was infused into the colon through this catheter, held in place for 30 s, and then flushed with 5 mL normal saline. Only normal saline was infused into the colon in the normal control group. In the DG group, 40 mg/kg DG was injected intraabdominally every day for one week; in dexamethasone group, 0.2 mg/kg dexamethasone was injected intraabdominally cavity daily for one week; in the acetic acid control and normal control groups, equal volumes of normal saline were injected into the abdominal cavity daily for one week. [1]

Absorption, Distribution and Excretion
GLYCYRRHIZIN WAS ABSORBED IN RAT SMALL INTESTINE; THERE WAS NO DETECTABLE AMT OF GLYCYRRHETINIC ACID IN BLOOD AFTER BOLUS INJECTION OF GLYCYRRHIZIN INTO PORTAL VEIN; GLYCYRRHETINIC ACID WAS PRESENT IN DETECTABLE AMT IN BLOOD AFTER ORAL ADMIN. SAKIYA ET AL; CHEM PHARM BULL 27(5) 1125 (1979)

Glycyrrhizic acid (GZA) and glycyrrhetinic acid (GRA) can be determined rapidly and precisely by high-performance liquid chromatography (HPLC) in biological fluids and tissues from experimental animals and humans. From plasma and tissues, glycyrrhizic acid and glycyrrhetinic acid are extracted by organic solvents and the extracts can directly be used for HPLC. From bile or urine, extraction and determination of glycyrrhizic acid and glycyrrhetinic acid are more difficult due to interfering endogenous compounds and conjugation of glycyrrhetinic acid with glucuronides or sulfates. Extraction of glycyrrhizic acid and glycyrrhetinic acid from urine or bile can be performed by ion-pairing followed by extraction with organic solvents or by solid phase extraction. Glycyrrhetinic acid conjugates can be determined by chromatographic separation or by pretreatment with beta-glucuronidase. The pharmacokinetics of glycyrrhetinic acid and glycyrrhizic acid can be described by a biphasic elimination from the central compartment with a dose-dependent second elimination phase. Depending on the dose, the second elimination phase in humans has a half-life of 3.5 hours for glycyrrhizic acid and between 10-30 hours for glycyrrhetinic acid. The major part of both glycyrrhetinic acid or glycyrrhizic acid is eliminated by the bile. While glycyrrhizic acid can be eliminated unmetabolized and undergoes enterohepatic cycling, Glycyrrhetinic acid is conjugated to glycyrrhetinic acid glucuronide or sulfate prior to biliary excretion. Orally administered glycyrrhizic acid is almost completely hydrolyzed by intestinal bacteria and reaches the systemic circulation as glycyrrhetinic acid. PMID:8191540

Glycyrrhizic acid is currently of clinical interest for treatment of chronic hepatitis. It is also applied as a sweetener in food products and chewing tobacco. In some highly exposed subgroups of the population, serious side effects such as hypertension and electrolyte disturbances have been reported. In order to analyze the health risks of exposure to this compound, the kinetics of glycyrrhizic acid and its active metabolites were evaluated quantitatively. Glycyrrhizic acid and its metabolites are subject to complex kinetic processes, including enterohepatic cycling and presystemic metabolism. In humans, detailed information on these processes is often difficult to obtain. Therefore, a model was developed that describes the systemic and gastrointestinal tract kinetics of glycyrrhizic acid and its active metabolite glycyrrhetic acid in rats. Due to the physiologically based structure of the model, data from earlier in vitro and in vivo studies on absorption, enterohepatic cycling, and presystemic metabolism could be incorporated directly. The model demonstrates that glycyrrhizic acid and metabolites are transported efficiently from plasma to the bile, possibly by the hepatic transfer protein 3-alpha-hydroxysteroid dehydrogenase. Bacterial hydrolysis of the biliary excreted metabolites following reuptake of glycyrrhetic acid causes the observed delay in the terminal plasma clearance of glycyrrhetic acid. These mechanistic findings, derived from analysis of experimental data through physiologically based pharmacokinetic modeling, can eventually be used for a quantitative health risk assessment of human exposure to glycyrrhizic acid containing products. Copyright 2000 Academic Press. PMID:10652246

To assess the multiplicity for the biliary excretion of xenobiotic conjugates, glycyrrhizic acid (glycyrrhizin) was studied in rats after intravenous (IV) injection of 10 mg/kg glycyrrhizic acid and IV infusion of inhibitors, dibromosulfophthalein and indocyanine green. Indocyanine green did not affect the biliary excretion of glycyrrhizic acid, whereas dibromosulfophthalein reduced it significantly. The plasma level of glycyrrhizic acid was increased by dibromosulfophthalein, but not by indocyanine green. In Eisai hyperbilirubinemic rats, the biliary excretion of glycyrrhizic acid was severely impaired, resulting in an increased plasma level. The findings suggested that the biliary excretion of glycyrrhizic acid is mediated by the system shared by liquiritigenin glucuronides and dibromosulfophthalein, but not by indocyanine green, and that the system is hereditarily defective in Eisai hyperbilirubinemic rats. PMID:8987080

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Metabolism / Metabolites
BOLUS INJECTION OF GLYCYRRHIZIN GIVEN RATS IN PORTAL VEIN, GAVE RISE IN BLOOD LEVEL OF SUBSTANCE WHICH APPEARS TO BE GLUCURONIC ACID CONJUGATE FORMED AS METABOLITE OF GLYCYRRHETINIC ACID. SAKIYA ET AL; CHEM PHARM BULL 27(5) 1125 (1979)

Interactions
ADDITION OF 10-6 M GLYCYRRHETINIC ACID IN PRESENCE OF 10-8 M ALDOSTERONE STIMULATED SHORT-CIRCUIT SIGNIFICANTLY AS COMPARED WITH CONTROL SKIN TREATED WITH ALDOSTERONE ALONE. PMID:6973465

ADMIN OF GLYCYRRHIZIN DEPRESSED EFFECT OF INJECTED CORTISONE ON GLYCOGEN STORAGE AND ENHANCED IMMUNOSUPPRESSIVE ACTION OF CORTISONE. KUMAGAI A; TAISHA 10 632 (1973)

The pharmacokinetics of total and free prednisolone (PSL) in six healthy men, with or without pretreatment with oral glycyrrhizin (GL), was investigated to confirm whether oral administration of GL influences the metabolism of prednisolone in man. Each subject received an intravenous administration of 0.096 mg/kg of prednisolone hemisuccinate (PSL-HS) with or without pretreatment with 50 mg of oral glycyrrhizin four times. Blood samples were taken from a peripheral vein at 5, 10, 15, 30, 45 min and 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after the start of prednisolone-HS infusion. The concentrations of total prednisolone in plasma were analyzed by high-performance liquid chromatography, and the free prednisolone was measured by an isocolloidosmolar equilibrium dialysis method. The pharmacokinetic parameters of prednisolone were determined by non-compartment analysis. Oral administration of glycyrrhizin was found to significantly increase the concentrations of total prednisolone at 6, 8 hr, and of free prednisolone at 4, 6 and 8 hr after prednisolone-hemisuccinate infusion. Moreover, oral administration of glycyrrhizin was also found to modify the pharmacokinetics of both total and free prednisolone. After oral administration of glycyrrhizin, the area under the curve (AUC) was significantly increased, the total plasma clearance (CL) was significantly decreased, and the mean residence time (MRT) was significantly prolonged. However, the volume of distribution (Vdss) showed no evident change. This suggests that oral administration of glycyrrhizin increases the plasma prednisolone concentrations and influences its pharmacokinetics by inhibiting its metabolism, but not by affecting its distribution. PMID:1752235

To clarify whether glycyrrhizin, the aqueous extract of licorice root and a drug for treatment of chronic active hepatitis, prevents the development of hepatic injury induced by carbon tetrachloride, allyl formate, and endotoxin, the present study was undertaken in rats. The treatment with glycyrrhizin 20 hr before carbon tetrachloride administration protected the development of the pericentral hepatocellular necrosis. Glycyrrhizin treatment 2 hr prior to the administration of allyl formate also inhibited the development of the periportal hepatocellular necrosis. However, glycyrrhizin did not protect the development of endotoxin-induced focal and random hepatocellular necrosis. These experimental results suggest that glycyrrhizin has no protective effect on hepatic injury following sinusoidal circulatory disturbance as seen in the case of endotoxin and that glycyrrhizin can protect against hepatotoxicity induced by the direct action on the hepatocytes due to hepatotoxins, such as carbon tetrachloride and allyl formate. PMID:2767217

To investigate the effects of Potenlini on nuclear factor-kappa B (NF-kappa B) binding activity in the livers of animals models with liver cirrhosis, and to delineate the molecular mechanism of the bioactivities of Potenlini. METHODS: Male SD rats were randomly allocated into a normal control group, a model control group, and a Potenlini group. Rats in the latter two groups were treated with CCl4 and Ethanol solution in order to induce chronic liver injury. Rats in Potenlini group were given Potenlini treatment at the same time. All rats were killed at the 9th week after CCl4 administration. Serum and liver specimens were collected, serum ALT activities and histological findings were assessed. Nuclear extracts from liver tissues were prepared and gel retardation assays were performed for the evaluation of NF-kappa B activity. RESULTS: (1) Serum ALT levels were significantly reduced in rats treated with Potenlini compared with those in rats of the model control group, which had dramatically increased ALT levels. (2) Histologically, liver steatosis and fibrosis were severe in the rats of the model group, but were significantly improved in rats of the Potenlini group. (3) NF-kappa B binding activity was markedly increased in the liver specimens taken from the rats of the model control group in comparison with the binding of normal livers, but the binding levels were nearly normal in the livers of the Potenlini group. CONCLUSION: Potenlini can inhibit the NF-kappa B binding activity in CCl4 and ethanol induced chronic liver injury, and that may partially be the mechanism by which Potenlini protects liver from hepatotoxin-induced liver injury and cirrhosis. PMID:10366987

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Human Toxicity Excerpts
14 VOLUNTEERS ATE DAILY DOSES OF 100-200 G LIQUORICE, EQUIV TO O.7-1.4 G GLYCYRRHIZINIC ACID FOR 1-4 WK. PLASMA K CONCN FELL; PLASMA RENIN & URINARY ALDOSTERONE DEPPRESSED IN ALL SUBJECTS.

...TOXICITY OF THIS COMPOUND & ITS DERIVATIVES BY MOUTH IS PRESUMED TO BE LOW. /GLYCYRRHIZA AND ITS DERIVATIVES/

POTENTIAL SERIOUS METABOLIC EFFECTS MAY OCCUR IN SOME PEOPLE WHO EAT MODEST AMT OF LIQUORICE DAILY FOR LESS THAN A WEEK.

GLYCYRRHIZIC ACID COMPLETELY INHIBITED GROWTH & CYTOPATHIC EFFECTS OF VACCINIA, HERPES SIMPLEX TYPE 1, NEWCASTLE DISEASE & VESICULAR STOMATITIS VIRUSES IN CULTURES OF HUMAN ANEUPLOID HEP2 CELLS. POMPEI R ET AL; NATURE (LONDON) 281 (5733): 689 (1979)

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Non-Human Toxicity Excerpts
IN 10-WK DIETARY EXPOSURE, BODY WT GAIN OF RATS SHOWED DOSE-RESPONSE EFFECT. SIGNIFICANT INCR IN DEAD IMPLANTS DURING 1ST WK OF BREEDING AFTER 40,000 PPM IN DIET OF RATS.

GLYCYRRHIZIN PROMOTED SODIUM RETENTION BY INHIBITING CORTICOIDS IN LIVER AND INHIBITED METABOLISM OF PROGESTERONE AND ALDOSTERONE.

GLYCYRRHETINIC ACID & ITS DERIVATIVES INHIBITED 5BETA-REDUCTION OF CORTISOL, ALDOSTERONE, & TESTOSTERONE BY RAT LIVER PREPN IN VITRO TO GREATER EXTENT THAN 5ALPHA-REDUCTION.

A single parenteral and oral administration of ammonium glycyrrhizinate in rat and mice experiments showed that the compound is related to practically nontoxic drugs. Its repeated administration (30 times) into the stomach in a maximum daily therapeutic dose (7 mg/kg) and in a four-fold dose (28 mg/kg) did not cause signs of intoxication, essential changes in the hematological and integral parameters, shifts in the activity of serum enzymes, morphological changes in the cell structures of the internal organs. Administration of the drug in a dose of 28 mg/kg for a second time led to changes in the activity of some enzymes in the brain, the development of parenchymatous dystrophy of the liver which changed to acidophilic necrosis attended with signs of regeneration. Under conditions of a subacute experiment the maximum daily therapeutic dose of ammonium glycyrrhizinate may be considered practically nontoxic.

[1]. Anti-inflammatory effect of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis. World J Gastroenterol. 2006 Jul 28;12(28):4578-81.

Diammonium Glycyrrhizinate is the diammonium salt of glycyrrhizin and the active constituent in the traditional Chinese medicinal herb Glycyrrhiza uralensis (Chinese liquorice or Gan-Cao) with anti-inflammatory, antioxidant and hepatoprotective properties. Diammonium glycyrrhizinate (DG) is slowly metabolized within the cells into glycyrrhetic acid, which inhibits enzymes that control cortisol metabolism and contributes to this agent's anti-inflammatory effect. Although the exact mechanism of action remains to be fully elucidated, DG may prevent or reduce hepatotoxicity via the scavenging of free radicals. This agent also upregulates the expression of transcription coactivator PGC-1alpha and modulates hepatic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase and glutathion peroxidase.
A widely used anti-inflammatory agent isolated from the licorice root. It is metabolized to GLYCYRRHETINIC ACID, which inhibits 11-BETA-HYDROXYSTEROID DEHYDROGENASES and other enzymes involved in the metabolism of CORTICOSTEROIDS. Therefore, glycyrrhizic acid, which is the main and sweet component of licorice, has been investigated for its ability to cause hypermineralocorticoidism with sodium retention and potassium loss, edema, increased blood pressure, as well as depression of the renin-angiotensin-aldosterone system.
See also: Glycyrrhizin (annotation moved to).

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Therapeutic Uses
DEMULCENT, MILD LAXATIVE; EXPECTORANT; USED TO DISGUISE TASTE OF MEDICATIONS

SNMC (stronger Neominophagen C), whose active component is glycyrrhizin (a saponin extracted from licorice) has been utilized to improve the liver function in Japan. To assess the effectiveness of interferon (IFN), stronger Neominophagen C combination therapy in patients, who did not respond to interferon therapy alone, we investigate 28 patients with histology of CAH 2B at 12 weeks after interferon administration. 15 patients received interferon alone continuously (group A), and 13 patients received interferon with stronger Neominophagen C (group B) for 12 weeks thereafter. Normalization of serum ALT level was observed in 33.3% of group A and in 64.3% of group B. Disappearance of serum HVC RNA was 13.3% in group A and 38.5% in group B. But these data were not significant statistically. Histological improvement was not significant, between group A and B by Knodel's HAI score, but reversal of histological grade (Europe classification) was noted more frequently in group B. A case of post transfusion hepatitis type C, exacerbated by interferon therapy is reported. HLA class I antigen was strongly expressed in the liver tissue after administration of interferon. In this case, potentiation of cellular immunity was thought to be the cause of the exacerbation and interferon, stronger Neominophagen C combination therapy was useful in improving liver function. PMID:7521424

Licorice (Glycyrrhiza glabra), a Mediterranean plant, has been used as an antidote, demulcent, and elixir folk medicine for generations in China. The main water-soluble constituent of licorice is glycyrrhizin (GL), which has been shown to possess several pharmacological properties. In this study, we show that oral feeding of glycyrrhizin to Sencar mice resulted in substantial protection against skin tumorigenesis caused by 7,12-dimethyl-benz [a]anthracene (DMBA) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. The latent period prior to the onset of tumor development was considerably prolonged in glycyrrhizin-fed animals compared with animals not fed glycyrrhizin and resulted in significant decrease in the number of tumors per mouse, during and at the termination of the experiment. Oral feeding of glycyrrhizin in drinking water also resulted in inhibition in the binding of topically applied [3H]benzo[a]pyrene and [3H]DMBA to epidermal DNA. The possible mechanism(s) of the antitumor-initiating activity may be due to the involvement of glycyrrhizin as inhibitor of the carcinogen metabolism followed by DNA adduct formation. Our results suggest that glycyrrhizin possesses considerable antitumorigenic activity and could prove useful in protecting some forms of human cancer. PMID:1907733

Hepatocellular carcinoma (HCC) occurs in patients with hepatitis C virus-RNA positive chronic liver disease. It is important to prevent Hepatocellular carcinoma with drug administration. METHODS: A retrospective study was undertaken to evaluate the long term preventive effect of Stronger Neo-Minophagen C (SNMC) on Hepatocellular carcinoma development. Stronger Neo-Minophagen C is a Japanese medicine that is commonly administered to patients with chronic hepatitis C to improve the serum alanine aminotransferase (ALT) level. Of 453 patients diagnosed with chronic hepatitis C retrospectively in the study hospital between January 1979 and April 1984, 84 patients (Group A) had been treated with Stronger Neo-Minophagen C; Stronger Neo-Minophagen C was given at a dose of 100 mL daily for 8 weeks, then 2-7 times a week for 2-16 years (median, 10.1 years). Another group of 109 patients (Group B) could not be treated with Stronger Neo-Minophagen C or interferon for a long period of time (median, 9.2 years) and were given other herbal medicine (such as vitamin K). The patients were retrospectively monitored, and the cumulative incidence of Hepatocellular carcinoma and risk factors for Hepatocellular carcinoma were examined. RESULTS: The 10th-year rates of cumulative Hepatocellular carcinoma incidence for Groups A and B were 7% and 12%, respectively, and the 15th-year rates were 12% and 25%. By Cox regression analysis, the relative risk of Hepatocellular carcinoma incidence in patients not treated with Stronger Neo-Minophagen C (Group B) was 2.49 compared with that of patients treated with Stronger Neo-Minophagen C (Group A). CONCLUSIONS: In this study, long term administration of Stronger Neo-Minophagen C in the treatment of chronic hepatitis C was effective in preventing liver carcinogenesis.

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As reported previously, NF-κB is a key molecule in both the initiation and progression phase of the inflammatory reaction. Activated NF-κB translocates into the nucleus and induces the expression of proinflammatory cytokines, adhesive molecules and chemokines. In this rat model, the expression of NF-κB was inhibited by both DG and dexamethasone, which means that the anti-inflammatory mechanism of DG may be similar to that of dexamethasone. Though the efficacy of DG was less than that of dexamethasone, its side-effects are expected to be less severe. In summary, DG was efficacious in experimental ulcerative colitis induced in rats, and associated with insignificant side effects. This result suggests that DG may be a promising drug candidate for the treatment of ulcerative colitis. [1]

C42H68N2O16

856.9931

856.456

79165-06-3

656656

White to off-white solid powder

1021.4ºC at 760 mmHg

2.893

10

18

7

60

1730

19

C[C@]12CC[C@](C[C@H]1C3=CC(=O)[C@@H]4[C@]5(CC[C@@H](C([C@@H]5CC[C@]4([C@@]3(CC2)C)C)(C)C)O[C@@H]6[C@@H]([C@H]([C@@H]([C@H](O6)C(=O)O)O)O)O[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)C(=O)O)O)O)O)C)(C)C(=O)O.N.N

SPPIIOPGDLITJE-VLQRKCJKSA-N

InChI=1S/C42H62O16.2H3N/c1-37(2)21-8-11-42(7)31(20(43)16-18-19-17-39(4,36(53)54)13-12-38(19,3)14-15-41(18,42)6)40(21,5)10-9-22(37)55-35-30(26(47)25(46)29(57-35)33(51)52)58-34-27(48)23(44)24(45)28(56-34)32(49)50;;/h16,19,21-31,34-35,44-48H,8-15,17H2,1-7H3,(H,49,50)(H,51,52)(H,53,54);2*1H3/t19-,21-,22-,23-,24-,25-,26-,27+,28-,29-,30+,31+,34-,35-,38+,39-,40-,41+,42+;;/m0../s1

(2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid;azane

Diammonium glycyrrhizinate; 79165-06-3; UNII-A9ZZD585U6; A9ZZD585U6; Glycyrrhizic acid, diammonium salt; 18beta-Glycyrrhizic acid diammonium salt; glycyrrhizin; (2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid;azane;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~116.69 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.92 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (2.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)