Glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammation: A randomized placebo-controlled clinical trial

Cao, Zhiyong; Liu, Yun-Zi; Li, Jiamei; Ruan, Yijun; Yan, Wenjie; Zhong, Shi-Yang; Zhang, Ting; Liu, Linlin; Wu, Ran; Wang, Bo; Wang, Wei; Bi, Xiaoying; Wang, Yunxia; Su, Wen‐Jun; Jiang, Chun‐Lei

doi:10.1016/j.jad.2020.01.048

Cited by 62 publications

(38 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As already mentioned in the introduction, the antagonist of 11betaHSD2 and of TLR4, glycyrrhizin, was therefore hypothesized to overcome treatment refractoriness. Indeed, the results of a recent double-blind placebo-controlled study are consistent with our hypothesis, as it demonstrated a superior outcome of glycyrrhizin adjunct to citalopram in comparison to citalopram alone (19). A preferential benefit of patients with higher levels of inflammation, as expressed by C-reactive protein levels > 3 mg/l, was observed in that study.…”

Section: Discussionsupporting

confidence: 87%

“…A recent study demonstrated in a placebo-controlled randomized trial the added benefit of glycyrrhizin as an adjunct treatment to SSRI (19). Interestingly, glycyrrhizin targets exactly the biological pattern, which we identified in our bottom up approach to define therapy refractory depression (TRD): it reduces circulating aldosterone (and vasopressin) levels (20)(21)(22)(23) and also increases blood pressure (24) in a dose-dependent manner.…”

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Adjunct Therapy With Glycyrrhiza Glabra Rapidly Improves Outcome in Depression—A Pilot Study to Support 11-Beta-Hydroxysteroid Dehydrogenase Type 2 Inhibition as a New Target

et al. 2020

View full text Add to dashboard Cite

Mineralocorticoid-receptor (MR) dysfunction as expressed by low systolic blood pressure and a high salivary aldosterone/cortisol ratio predicts less favorable antidepressant treatment outcome. Inhibition of peripheral 11-beta-hydroxysteroid-dehydrogenase type 2 (11betaHSD2) reverses these markers. We therefore tested the hypothesis that the 11betaHSD2 inhibitor glycyrrhizin affects treatment outcome via this mechanism. We administered Glycyrrhiza glabra (GG) extract containing 7–8 % of glycyrrhizin at a dose of 2 × 700 mg daily adjunct to standard antidepressants in hospitalized patients with major depression. These subjects were compared in an open-label fashion with patients, who did not receive GG (treatment as usual, TAU). Assessments were done at baseline and approximately 2 weeks after. Twelve subjects were treated with GG and compared to 55 subjects with TAU. At week 2, the Hamilton Depression Rating Scale (HAMD-21) change from baseline as well as the CGI-S change showed a significant time × treatment interaction (p < 0.03), indicating a possible therapeutic benefit of GG. Clinical benefit seems to be more pronounced in subjects with lower systolic blood pressure and significantly correlated with reduced sleep duration in the GG group. Our preliminary data show that treatment with the 11betaHSD2 inhibitor glycyrrhizin may possess a beneficial effect on antidepressant response, which may be specific to a defined depression subtype.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 90%

Adjunct Therapy With Glycyrrhiza Glabra Rapidly Improves Outcome in Depression—A Pilot Study to Support 11-Beta-Hydroxysteroid Dehydrogenase Type 2 Inhibition as a New Target

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Extracted from the roots of Glycyrrhiza glabra, glycyrrhizin (GA) has been reported to possess numerous pharmacological effects, including anti-inflammatory and anti-viral activities (13). Furthermore, it has recently been demonstrated that GA has a markedly hepatoprotective effect (13)(14)(15); however, the association between GA and the regulation of cellular metabolism in LC remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin

et al. 2021

View full text Add to dashboard Cite

Glycyrrhizin (GA) is the most essential active ingredient in licorice root, and has a wide range of biological and pharmacological activities. The present study aimed to conduct a detailed analysis of the effects of GA on liver cancer (LC) cell proliferation and the Warburg effect. Hexokinase-2 (HK2) is a glycolytic enzyme that catalyzes the Warburg effect. To this end, the LC HepG2 cell line was transfected with small interfering RNA-HK2 or pCDNA3.1-HK2, followed by GA treatment. A Cell Counting Kit-8 assay and EdU staining were employed to evaluate the proliferation rate of LC cells. The expression levels of HK2 and the phosphorylation level of AKT were measured by reverse transcription-quantitative PCR and western blotting, respectively. Furthermore, the glucose uptake capacity and lactic acid content were assessed by kits, and the glycolysis level was evaluated by assessing the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). A pronounced increase in the OCR, and decreases in the cell proliferation, glucose uptake capacity, lactic acid content, ECAR and HK2 expression were detected in LC cells subjected to GA treatment or HK2-knockdown. Conversely, overexpression of HK2 reversed these trends, indicating that glycyrrhizin may inhibit LC cell proliferation and the Warburg effect through suppression of HK2. In addition, it was revealed that the PI3K/AKT signaling pathway was associated with LC cell proliferation and the Warburg effect; notably, treatment of LC cells with the AKT agonist SC79 induced elevation of the ECAR, cell proliferation, glucose uptake capacity, lactic acid content, phosphorylated-AKT and HK2 expression, and suppressed the OCR. In conclusion, GA may inhibit the Warburg effect and cell proliferation in LC by suppressing HK2 through blockade of the PI3K/AKT signaling pathway.

show abstract

“…However, as mentioned above, strokes may lead to the massive disruption of the BBB and interestingly, ischemic brain regions have also shown greater penetration through the BBB [10]. Glycyrrhizic acid has been evaluated as an adjunctive anti-inflammatory agent to treat depression in a randomized-placebo-controlled clinical trial [64], but similar studies in aSAH could be possible. There is a need to characterize the pharmacokinetics and bioavailability of the drugs at the CNS level (e.g., in the CSF), particularly in patients who underwent extraventricular drain placement.…”

Section: Discussionmentioning

confidence: 99%

Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

Muhammad

Chaudhry

Kahlert

et al. 2020

IJMS

View full text Add to dashboard Cite

Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate ruptured aneurysms in almost every case. However, despite successful interventions, the clinical outcomes of aSAH patients are often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. This review emphasizes the importance of pharmacological interventions targeting high mobility group box 1 (HMGB1)-mediated brain damage after subarachnoid hemorrhage (SAH) and CVS. We searched Pubmed, Ovid medline and Scopus for “subarachnoid hemorrhage” in combination with “HMGB1”. Based on these criteria, a total of 31 articles were retrieved. After excluding duplicates and selecting the relevant references from the retrieved articles, eight publications were selected for the review of the pharmacological interventions targeting HMGB1 in SAH. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The discussed evidence suggested that HMGB1, an important DAMP, contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.

show abstract

Glycyrrhizic acid as an adjunctive treatment for depression through anti-inflammation: A randomized placebo-controlled clinical trial

Cited by 62 publications

References 39 publications

Adjunct Therapy With Glycyrrhiza Glabra Rapidly Improves Outcome in Depression—A Pilot Study to Support 11-Beta-Hydroxysteroid Dehydrogenase Type 2 Inhibition as a New Target

Adjunct Therapy With Glycyrrhiza Glabra Rapidly Improves Outcome in Depression—A Pilot Study to Support 11-Beta-Hydroxysteroid Dehydrogenase Type 2 Inhibition as a New Target

HK2 is associated with the Warburg effect and proliferation in liver cancer: Targets for effective therapy with glycyrrhizin

Targeting High Mobility Group Box 1 in Subarachnoid Hemorrhage: A Systematic Review

Contact Info

Product

Resources

About