Diammonium glycyrrhizinate

Antiviral Res. 2010 Feb;85(2):346-53.

Antiviral effect of diammonium glycyrrhizinate and lithium chloride on cell infection by pseudorabies herpesvirus.[Pubmed: 19879899 ]

Diammonium glycyrrhizin (Diammonium glycyrrhizinate, DG), a salt from glycyrrhizinate (GL) that is a major active component of licorice root extract with various pharmacological activities was investigated for its inhibitory effect on pseudorabies virus (PrV) infection. In parallel, lithium chloride (LiCl), a chemical reagent with potential antiviral activity was compared with DG for their inhibitory ability against PrV infection in vitro. Virus plaque-reduction assays, PCR and RT-PCR analysis indicated that both drugs inhibited cell infection by PrV. Moreover, addition of the drugs resulted in fewer apoptotic cells during PrV infection.

Int Immunopharmacol. 2007 Oct;7(10):1292-8.

Diammonium glycyrrhizinate, a component of traditional Chinese medicine Gan-Cao, prevents murine T-cell-mediated fulminant hepatitis in IL-10- and IL-6-dependent manners.[Pubmed: 17673144]

Diammonium glycyrrhizinate (DG), a traditional Chinese medicine (TCM), is extracted and purified from liquorices (Radix glycyrrhizae). The liquorices exert an important function in the treatment of hepatitis because of its anti-inflammatory effects based upon the clinical practice, but the underlying mechanism is unclear.
METHODS AND RESULTS:
In this study, we investigated the mechanisms of DG in protecting mice from ConA-induced hepatitis. The results showed that intraperitoneal administration of DG protected mice against ConA-induced elevation of serum ALT levels and apoptosis of hepatocytes; at the same time, the absolute amount of hepatic NKT cells and T cells was significantly decreased, indicating that DG can inhibit the recruitment of lymphocytes into the liver. In addition, the production of IL-6 and IL-10 was improved by DG pretreatment, suggesting that DG may possibly protect the liver from injury via two pathways: direct protection of hepatocytes from apoptosis through an IL-6-dependent way and indirect inhibition of T-cell-mediated inflammation through an IL-10-dependent way.

Nan Fang Yi Ke Da Xue Xue Bao. 2013 Oct;33(10):1416-20.

Diammonium glycyrrhizinate inhibits airway smooth muscle proliferation in a murine model of chronic asthma.[Pubmed: 24144738]

To investigate the therapeutic value and possible mechanism of Diammonium glycyrrhizinate (DG) in treatment of airway remodeling in a murine model of chronic asthma.
METHODS AND RESULTS:
Thirty male BALB/C mice were randomly divided into control group, OVA DG group and OVA group (n=10). HE staining was used to observe the pathological changes, and Masson's staining was used to detect and measure collagen deposition. Alpha-SMA and PPARγ mRNA expressions were analyzed by RT-PCR, and the protein expressions of α-SMA and PPARγ were measured by Western blotting. After 75 days of OVA sensitization and challenge, obvious pathological changes occurred in the lung tissues, which was more severe in OVA group than in OVA DG group. Collagen deposition was significantly increased after OVA stimulation, but was obviously milder in OVA DG group than in OVA group. OVA-induced up-regulation of α-SMA was notably attenuated by DG injection. The expression of PPARγ was markedly down-regulated after OVA stimulation but was substantially enhanced after DG intervention.
CONCLUSIONS:
DG can inhibit airway smooth muscle proliferation possibly through up-regulation of PPARγ in a murine model of chronic asthma.

PLoS One. 2012;7(4):e35823.

Diammonium glycyrrhizinate upregulates PGC-1α and protects against Aβ1-42-induced neurotoxicity.[Pubmed: 22540007 ]

Mitochondrial dysfunction is a hallmark of beta-amyloid (Aβ)-induced neurotoxicity in Alzheimer's disease (AD), and is considered an early event in AD pathology. Diammonium glycyrrhizinate (DG), the salt form of Glycyrrhizin, is known for its anti-inflammatory effects, resistance to biologic oxidation and membranous protection.
METHODS AND RESULTS:
In the present study, the neuroprotective effects of DG on Aβ(1-42)-induced toxicity and its potential mechanisms in primary cortical neurons were investigated. Exposure of neurons to 2 µM Aβ(1-42) resulted in significant viability loss and cell apoptosis. Accumulation of reactive oxygen species (ROS), decreased mitochondrial membrane potential, and activation of caspase-9 and caspase-3 were also observed after Aβ(1-42) exposure. All these effects induced by Aβ(1-42) were markedly reversed by DG treatment. In addition, DG could alleviate lipid peroxidation and partially restore the mitochondrial function in Aβ(1-42)-induced AD mice. DG also significantly increased the PGC-1α expression in vivo and in vitro, while knocking down PGC-1α partially blocked the protective effects, which indicated that PGC-1α contributed to the neuroprotective effects of DG. Furthermore, DG significantly decreased the escape latency and search distance and increased the target crossing times of Aβ(1-42)-induced AD mice in the Morris water maze test.
CONCLUSIONS:
Therefore, these results demonstrated that DG could attenuate Aβ(1-42)-induced neuronal injury by preventing mitochondrial dysfunction and oxidative stress and improved cognitive impairment in Aβ(1-42)-induced AD mice, indicating that DG exerted potential beneficial effects on AD.

World J Gastroenterol. 2006 Jul 28;12(28):4578-81.

Anti-inflammatory effect of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis.[Pubmed: 16874877 ]

To explore the anti-inflammatory mechanism of Diammonium glycyrrhizinate in a rat model of ulcerative colitis induced by acetic acid.
METHODS AND RESULTS:
Spragur-Dawley female rats were divided into four groups: Diammonium glycyrrhizinate 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. Compared to the acetic acid control, both Diammonium glycyrrhizinate 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.
CONCLUSIONS:
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.