Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology

Wahab, Shadma; Annadurai, Sivakumar; Abullais, Shahabe Saquib; Das, Gotam; Ahmad, Wasim; Ahmad, Faruque; Kandasamy, Geetha; Vasudevan, Rajalakshimi; Ali, Sajid; Amir, Mohd

doi:10.3390/plants10122751

Cited by 154 publications

(138 citation statements)

References 221 publications

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“…Over 50% of all pharmaceutical drugs are still natural ingredients [ 129 , 130 ]. Currently, natural sources such as plants, microorganisms, and sea creatures account for more than 60% of commercially accessible anticancer medicines [ 131 , 132 , 133 , 134 ]. A total of 3000 plant species have been utilized to treat various kinds of cancer [ 132 , 135 ].…”

Section: Pharmacological Efficacy Of Tamarix Aphyllamentioning

confidence: 99%

Pharmacological Efficacy of Tamarix aphylla: A Comprehensive Review

Alshehri

Wahab

Abullais

et al. 2021

Plants

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Tamarix aphylla is a well-known species of the genus Tamarix. T. aphylla (Tamaricaceae) is a perennial tree in Asia, the Middle East, and Central Africa. It is used as a carminative diuretic in tuberculosis, leprosy, and hepatitis. Various pharmacological properties have been shown by T. aphylla, such as antidiabetic, anti-inflammatory, antibacterial, antifungal, anticholinesterase, and wound-healing activity. However, T. aphylla has not received much attention for its secondary metabolites and bioactive constituents. Research has shown that this plant has hidden potential that needs to be explored. This review aims to cover botanical classification, geographical distribution, taxonomy, ethnobotanical uses, and the phytochemical compounds found in T. aphylla. The toxicology and pharmacological effects of T. aphylla are also discussed. We examined various scholarly resources to gather information on T. aphylla, including Google Scholar, Scopus, Science Direct, Springer Link, PubMed, and Web of Science. The finding of this work validates a connection between T. aphylla in conventional medicine and its antidiabetic, antibacterial, anti-inflammatory, wound-healing, antifungal, anticholinesterase, and other biological effects. T. aphylla’s entire plant (such as bark, leaves, fruits) and root extracts have been used to treat hypertension, stomach discomfort, hair loss, cough and asthma, abscesses, wounds, rheumatism, jaundice, fever, tuberculosis, and gum and tooth infection. The phytochemical screening revealed that noticeably all extracts were devoid of alkaloids, followed by the presence of tannins. In addition, different parts have revealed the existence of steroids, flavonoids, cardiac glycosides, and byproducts of gallic acid and ellagic acid. T. aphylla has shown many valuable activities against different diseases and supports its traditional uses. Therefore, high-quality preclinical research and well-designated clinical trials are needed to establish the efficacy and safety of this plant in humans.

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Section: Pharmacological Efficacy Of Tamarix Aphyllamentioning

confidence: 99%

Pharmacological Efficacy of Tamarix aphylla: A Comprehensive Review

Alshehri

Wahab

Abullais

et al. 2021

Plants

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“…Enoxolone is a pentacyclic triterpenoid aglycone metabolite of glycyrrhizin that is found in licorice. It exhibits a range of pharmacological properties including antitumor, anti-inflammatory, and anti-viral activities (22). We decided to focus on enoxolone due its greater potency, chemical tractability, and reports of related pentacyclic triterpenoids that show anti-virulence against various bacteria (23).…”

Section: Resultsmentioning

confidence: 99%

“…From screening of structurally diverse phytochemicals, we identified that the triterpenoid enoxolone (18β-glycyrrhetinic acid) inhibits toxin biosynthesis by perturbing multiple metabolic pathways in C. difficile . Enoxolone is an aglycone metabolite of glycyrrhizin, the main bioactive component of licorice root extracts ( Glycyrrhiza [sweet root]) (22). Licorice has a long history of use as a traditional Chinese medicine and is widely consumed in dietary supplements, herbal tea, confectionaries, beverages and cosmetics in the USA, Middle East, Asia, and Europe (22).…”

Section: Discussionmentioning

confidence: 99%

“…Enoxolone is an aglycone metabolite of glycyrrhizin, the main bioactive component of licorice root extracts ( Glycyrrhiza [sweet root]) (22). Licorice has a long history of use as a traditional Chinese medicine and is widely consumed in dietary supplements, herbal tea, confectionaries, beverages and cosmetics in the USA, Middle East, Asia, and Europe (22). Glycyrrhizin is hydrolyzed by intestinal bacteria to 18β-glycyrrhetinic acid that may undergo hepatic transformation to glucoronidated and sulfated conjugates that enter entero-hepatic circulation prior to renal excretion.…”

Section: Discussionmentioning

confidence: 99%

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The licorice metabolite enoxolone attenuates Clostridioides difficile pathophysiology by corrupting its metabolic and toxin production networks

Marreddy

Picker

Phelps

et al. 2022

Preprint

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Toxins TcdA and TcdB are the main virulence factors of Clostridioides difficile, a leading cause of hospital-acquired diarrhea. We investigated the therapeutic potential of inhibiting the biosynthesis of TcdA and TcdB. Accordingly, screening of structurally diverse phytochemicals with medicinal properties identified 18β-glycyrrhetinic acid (enoxolone) as an inhibitor of TcdA and TcdB biosynthesis. Enoxolone also inhibited sporulation. In a CDI colitis model, enoxolone when combined with vancomycin protected mice from becoming moribund and the combination was more effective than vancomycin alone, a standard of care antibiotic for CDI. While enoxolone alone reduced the in vivo load of toxins, the monotherapy did not protect mice from CDI. Affinity based proteomics identified ATP synthase subunit alpha (AtpA) and adenine deaminase (Ade) as possible molecular targets for enoxolone. Silencing of mRNA for Ade and AtpA also reduced toxin biosynthesis, while molecular interaction analysis showed that enoxolone directly bound to Ade. Ade converts adenine to hypoxanthine as an early step in the purine salvage pathway. Metabolomics revealed enoxolone caused cells to accumulate adenosine and deplete hypoxanthine and ATP. Accordingly, supplementation with hypoxanthine partly restored toxin production. Enoxolone also impacted phosphate metabolism by reducing the amounts of cellular phosphate. Thus, supplementation with triethyl phosphate as a source of phosphate also partly restored toxin production. When hypoxanthine and triethyl phosphate were combined, toxin production was fully restored in the presence of enoxolone. Taken together, studies with enoxolone revealed metabolic pathways that affect C. difficile toxin production and could represent potential anti-virulence drug targets.IMPORTANCEClostridioides difficile, a leading cause of hospital-acquired diarrhea, produces two co-regulated toxins (TcdA and TcdB) that are the focus of most anti-virulence discovery efforts for C. difficile infection (CDI). Exploration of an alternate anti-virulence strategy led to the discovery that the licorice metabolite enoxolone inhibits C. difficile virulence by blocking the cellular biosynthesis of TcdA and TcdB. Blockage of toxin production by enoxolone was associated with multiple effects on cells, including inhibiting adenine deaminase and ATP synthase leading to disruption of purine biosynthesis and phosphate metabolism. In mice infected with C. difficile, the efficacy of enoxolone in combination with vancomycin was superior to vancomycin alone. These findings contribute to establishing toxin biosynthesis inhibition as a newer therapeutic concept for CDI.

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“…Liquorice (Glycyrrhizae radix et rhizome), the roots of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L. or Glycyrrhiza inflate Bat., has long been used as a tonic herbal medicine in traditional Chinese medicine (TCM) due to its ability to harmonize unpleasant characteristics of other herbs or reduce the toxicities of certain herbs when used together in the herbal formulas ( Wang et al, 2013 ; Wahab et al, 2021 ). In China, although there are no reports on the scientific rationale, liquorice is presented with PA-containing herbs in TCM compound formulas, yet no PA-poisoning cases have been reported with this combinational use.…”

Section: Introductionmentioning

confidence: 99%

Liquorice Extract and 18β-Glycyrrhetinic Acid Protect Against Experimental Pyrrolizidine Alkaloid-Induced Hepatotoxicity in Rats Through Inhibiting Cytochrome P450-Mediated Metabolic Activation

Wang

Yao

et al. 2022

Front. Pharmacol.

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Misuse of pyrrolizidine alkaloid (PA)-containing plants or consumption of PA-contaminated foodstuffs causes numerous poisoning cases in humans yearly, while effective therapeutic strategies are still limited. PA-induced liver injury was initiated by cytochrome P450 (CYP)-mediated metabolic activation and subsequent formation of adducts with cellular proteins. Liquorice, a hepato-protective herbal medicine, is commonly used concurrently with PA-containing herbs in many compound traditional Chinese medicine formulas, and no PA-poisoning cases have been reported with this combination. The present study aimed to investigate hepato-protective effects of liquorice aqueous extract (EX) and 18β-glycyrrhetinic acid (GA, the primary bioactive constituent of liquorice) against PA-induced hepatotoxicity and the underlying mechanism. Histopathological and biochemical analysis demonstrated that both single- and multiple-treatment of EX (500 mg/kg) or GA (50 mg/kg) significantly attenuated liver damage caused by retrorsine (RTS, a representative hepatotoxic PA). The formation of pyrrole-protein adducts was significantly reduced by single- (30.3% reduction in liver; 50.8% reduction in plasma) and multiple- (32.5% reduction in liver; 56.5% reduction in plasma) treatment of GA in rats. Single- and multiple-treatment of EX also decreased the formation of pyrrole-protein adducts, with 30.2 and 31.1% reduction in rat liver and 51.8 and 53.1% reduction in rat plasma, respectively. In addition, in vitro metabolism assay with rat liver microsomes demonstrated that GA reduced the formation of metabolic activation-derived pyrrole-glutathione conjugate in a dose-dependent manner with the estimated IC50 value of 5.07 µM. Further mechanism study showed that GA inhibited activities of CYPs, especially CYP3A1, the major CYP isoform responsible for the metabolic activation of RTS in rats. Enzymatic kinetic study revealed a competitive inhibition of rat CYP3A1 by GA. In conclusion, our findings demonstrated that both EX and GA exhibited significant hepato-protective effects against RTS-induced hepatotoxicity, mainly through the competitive inhibition of CYP-mediated metabolic activation of RTS.

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Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology

Cited by 154 publications

References 221 publications

Pharmacological Efficacy of Tamarix aphylla: A Comprehensive Review

Pharmacological Efficacy of Tamarix aphylla: A Comprehensive Review

The licorice metabolite enoxolone attenuates Clostridioides difficile pathophysiology by corrupting its metabolic and toxin production networks

Liquorice Extract and 18β-Glycyrrhetinic Acid Protect Against Experimental Pyrrolizidine Alkaloid-Induced Hepatotoxicity in Rats Through Inhibiting Cytochrome P450-Mediated Metabolic Activation

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