Glycyrrhizic Acid: A Natural Plant Ingredient as a Drug Candidate to Treat COVID-19

Sun, Zhong; He, Guozhong; Huang, Ninghao; Thilakavathy, Karuppiah; Lim, Jonathan Chee Woei; Kumar, Sanjeev; Xiong, Chenglong

doi:10.3389/fphar.2021.707205

Cited by 24 publications

(15 citation statements)

References 98 publications

(101 reference statements)

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“…Therefore, anti-inflammatory drugs and immunomodulatory drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm (Rabaan et al 2021 ; Reyes et al 2021 ). The antioxidant, anti-inflammatory and immunomodulatory effects of GR and BA have been confirmed in several articles (Baram et al 2019 ; Eltahir et al 2020 ; Efferth and Oesch 2020 ; Murck 2020 ; Gomaa and Abdel-Wadood 2021 , Gomaa et al 2021 ; Sun et al 2021 ; Renda et al 2021 ; Zheng et al 2021 , Zhang et al 2021b ). Moreover, GR and BA have strong inhibitory effect against NLRP3 inflammasome and NF-κB3 (Beghelli et al 2017 ; Roy et al 2019 ; Ding et al 2020 ; Majeed et al 2021 ).…”

Section: Discussionmentioning

confidence: 77%

Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial

et al. 2022

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Recent evidence points to a potential therapeutic role for glycyrrhizin(GR) and boswellic acids (BA) in the treatment of COVID-19 but conclusive evidence is lacking. Our aim is to investigate the efficacy of GR + BA versus placebo for the treatment of hospitalized patients with moderate SARS-CoV-2 or COVID-19 variants infection. The current study is a randomized, double-blind, placebo-controlled, single-center trial. Patients with SARS-CoV-2 or COVID-19 variants diagnosed by PCR test who were admitted to Sohag University hospital were eligible if they were at least 18 years of age and had moderate symptoms. Patients were randomly assigned to receive oral GR capsule (60 mg) and BA (200 mg) twice daily for 14 days or a matching placebo. All patients also received treatment with the institutional protocol for COVID-19. The primary outcome was mortality and time to recovery. Secondary outcome was clinical status score, 14 days after receiving study drugs. Adverse events from use of study drugs have been evaluated for up to 14 days. The trial is registered at ClinicalTrials.gov (Identifier NCT04487964). During the 6-month enrollment period (June-November, 2021) only 50 patients (54% women; median age 60 years, IQR 54–65) met eligibility and were randomly assigned. Evaluation of the primary outcome at 14 days showed that there were five deaths in the placebo group and no deaths in the GR + BA group. With regard to recovery time, it was significantly shorter (p = 0.0001) in the group receiving GR + BA capsule compared to the placebo group (median 7.0; IQR 6.0–8.0 days vs. median 12.5; IQR 12–20 days). Clinical status on the ordinal score scale as a secondary outcome showed a significant difference between the GR + BA group (median (IQR) score, 2 [2–3]) and placebo groups (mean (IQR) score, 3 [3–5.5]). There was a significant decrease in CRB (p = 0.000041) in GR + BA compared with the placebo group. In conclusion, this safe, inexpensive, antiviral, immunomodulating and anti-inflammatory combination may be considered for use in mild to moderate infections of SARS-CoV-2 or COVID-19 variants. The study is limited by the small sample size; therefore, larger randomized trials are required.

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Section: Discussionmentioning

confidence: 77%

Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial

et al. 2022

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“…The pharmacological bases for the use of GR/licorice and BAs/Boswellia extract in clinical trials have been attributed to their anti-inflammatory, antioxidant and immunomodulatory properties. Since the outbreak of COVID-19, there have been few clinical studies on GR/licorice or BAs/Boswellia extract as a potential treatment for COVID-19, and there are many studies on Chinese prescriptions with licorice as a major ingredient (Sun et al 2021 ). Only seven clinical trials with a rigorous design regarding the usefulness of GR, BAs and their combinations have been published through July 2022.…”

Section: Resultsmentioning

confidence: 99%

Glycyrrhizin and boswellic acids, the golden nutraceuticals: multitargeting for treatment of mild–moderate COVID-19 and prevention of post-COVID cognitive impairment

2022

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Breakthrough infections have been reported in fully vaccinated persons. Furthermore, rebound symptoms have been reported following the new FDA granted emergency use to combat SARS-CoV-2. Glycyrrhizin (GR) and boswellic acids (BAs) combination has been shown to have highly successful actions against COVID-19 in our recent clinical trial. However, the study is limited by the small sample size, and therefore, the aim of this article is to comprehensively evaluate recent evidence on the efficacy of GR and BAs in preventing the development of COVID-19 in patients with mild and moderate infections and in preventing post-COVID-19 cognitive impairment, which is the most important symptom after recovery from Covid-19 disease. We have reviewed and discussed information published since the outbreak of the COVID-19 pandemic until July 2022 on preclinical (in vivo, in vivo and bioinformatics) and clinical studies related to the antiviral, anti-inflammatory and immunomodulatory activity of Gr and BAs. Sixteen studies were performed to determine the efficacy of GR against SARS-CoV-2. Ten studies were used primarily for in vitro and in vivo assays and six used molecular docking studies. However, the antiviral activity of BAs against SARS-CoV-2 was determined in only five studies using molecular modeling and bioinformatics. All these studies confirmed that GR n and BAs have strong antiviral activity and can be used as a therapeutic agent for COVID-19 and as a protective agent against SARS-CoV-2. They may act by inhibiting the main protease SARS-CoV-2 (Mpro) responsible for replication and blocking spike protein-mediated cell entry. Only seven rigorously designed clinical trials regarding the usefulness of GR, BAs or their combinations in the treatment of COVID-19 have been published as of July 2022. Although there is no clinical study regarding the treatment of cognitive impairment after COVID-19 that has been published so far, several preclinical and clinical studies have demonstrated the potential effect of GR and BAs in the prevention and treatment of cognitive impairment by inhibiting the activity of several molecules that activate inflammatory signaling pathway. In conclusion, the findings of our study documented the beneficial use of GR and BAs to treat SARS-CoV-2 and its variants and prevent post-COVID cognitive impairment. However, it warrants further studies with a larger randomized sample size to ensure that the studies have sufficient evidence of benefits against COVID-19 and post-COVID-19 symptoms.

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“…These two trials used the same nanomicellar formulation, named SinaCurcumin®, previously developed by Hatamipour et al [ 73 ] to enhance the oral bioavailability of curcuminoids. Glycyrrhizic (GA) acid is another naturally derived agent proposed for COVID-19 treatment owing to its ability to impede SARS-CoV-2 replication and undesired inflammatory responses [ 74 ]. Besides its therapeutic benefits, GA per se is a potential drug carrier due to its ability of self-association in aqueous solutions and complexation with other drugs [ 75 ].…”

Section: Implications Of Inflammation In Covid-19 Therapies and Drug ...mentioning

confidence: 99%

COVID-19 inflammation and implications in drug delivery

Zoulikha

Huang

et al. 2022

Journal of Controlled Release

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Glycyrrhizic Acid: A Natural Plant Ingredient as a Drug Candidate to Treat COVID-19

Cited by 24 publications

References 98 publications

Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial

Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial

Glycyrrhizin and boswellic acids, the golden nutraceuticals: multitargeting for treatment of mild–moderate COVID-19 and prevention of post-COVID cognitive impairment

COVID-19 inflammation and implications in drug delivery

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