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Schematic drawing of the pathogenesis of the patient. The patient was heterozygous for a mutation in HSD11B2 (“normal/mutant" alleles in the figure), suggesting that her 11βHSD2 enzyme activity in the kidney was reduced. Without licorice loading, she was able to keep her healthy condition. However, with licorice loading, she showed serious hypertension.
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Licorice ingestion, as well as mutations in the HSD11B2 gene, inhibits 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) enzyme activity, causing the syndrome of apparent mineral corticoid excess (AME). However, the combined effect of licorice ingestion and an HSD11B2 mutation has never been reported, until now. In this study, we demonstrated that...
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... Interestingly, some individuals are more prone to licorice or glycyrrhizin-induced intoxication even if they consume very low amounts compared to normal individuals. This happens due to a partial deficiency of 11β-HSD2 that appeared as a result of a mutation in the HSD11B2 gene (Edwards et al., 1993;Harahap et al., 2011). The regular prescription of glycyrrhizin drugs (Neo-Minophagen ® -C and Glycyron ® ) may also induce hypertensive crisis with targeted organ impairment, especially eyes and kidneys (J. ...
Since the beginning, human beings have consistently been using plants and their components for the prevention and treatment of various ailments. However, in the last few decades, plant-based medicines and health supplements are gaining more acceptability and rapid popularity. Licorice (Glycyrrhiza sp.) is a terrestrial herb belonging to the family Fabaceae and primarily cultivated in European, Middle Eastern, and South Asian countries. Ethnomedicinal uses of licorice have frequently been described in the world's renowned medical systems, including Ayurveda, Unani, Chinese, Korean, Japanese, African, and European traditional medical systems. To date, 30 species of licorice are known, and among them, G. glabra, G. inflata, and G. uralensis are significantly explored for nutritional and pharmacological benefits. The wide range of commercially available products, including herbal preparations, health supplements, cosmetics, and food and feeds preparations use licorice as active ingredient. Glabridin, licochalcone A, glycyrrhizin, and 18-glycyrrhetinic acid are the notable phytochemicals isolated from licorice and immensely explored for biological and pharmacological activities. Nevertheless, the excessive intake of licorice has also been associated with a wide spectrum of adverse effects on human health. Among them, several are reported to be mediated by modulation of drug-metabolizing cytochrome P-450 enzymes. In the present review, we provide a comprehensive description of the current knowledge of licorice, including historical development, phytoconstituents, species-specific marker metabolites, herb–drug interaction, pharmacological uses, food additive application, and toxicities. We believe this review will provide excellent information to physicians, researchers, and personnel of different scientific regulatory bodies.
... [15] Harahap et al found that licorice ingestion and mutations in HSD11B2 inhibit 11β-hydroxysteroid dehydrogenase type 2 enzyme activity and cause the syndrome of apparent mineralocorticoid excess. [16] They speculated that licorice ingestion may be an environmental risk factor for hypertension or an apparent mineralocorticoid excess state in patients with a mutation in HSD11B2. In our patient, the exact dose of glycyrrhizic acid could not be known because she took the licorice in the herbal medicine shop without a prescription. ...
A 60-year-old woman presented with polymorphic ventricular tachycardia secondary to hypokalemia, which necessitated dozens of DC cardioversions. She was not taking any other medication and denied any vomiting or diarrhea. Further investigation for hypokalemia suggested a hypermineralocorticoid state. Repeated inquiry prompted the patient to admit to taking herbal medicine containing licorice. She was treated with magnesium sulfate, potassium infusion, and intravenous lidocaine. A potassium-sparing diuretic was also prescribed. On the seventh day, the patient was discharged from the hospital with advice to discontinue taking herbal medicines containing licorice. She has been followed up at our outpatient clinic without further symptoms for 3 years. This case highlights the potential for cardiovascular complications associated with consumption of herbal medicines such as licorice. Clinicians should be aware that patients presenting to the emergency department with ventricular arrhythmia and uncertain hypokalemia should be questioned about licorice intake. Obtaining a detailed history from patients admitted to the hospital for electrical storm is essential.
... Russo et al. [161] proposed that some people could be susceptible to low doses of GC because of an 11β-hydroxysteroid dehydrogenase deficiency. Harahap et al. [162] believed that licorice ingestion, as well as mutations in the HSD11B2 gene, inhibited 11β-hydroxysteroid dehydrogenase type 2 enzyme activity and caused the syndrome of apparent mineral corticoid excess, which supposed that licorice ingestion was an environmental risk factor for hypertension or an apparent mineral corticoid excess state in patients with a mutation in HSD11B2. ...
Licorice is one of the oldest and most frequently used herbs in traditional Chinese medicine. It contains more than 20 triterpenoids and 300 flavonoids. In recent years, a lot of studies have reported that the active compounds isolated from licorice possess antitumor, antimicrobial, antiviral, anti-inflammatory, immunoregulatory, and several other activities that contribute to the recovery and protection of the nervous, alimentary, respiratory, endocrine, and cardiovascular systems. In this paper, nine different pharmacological activities of licorice are summarized. The active compounds responsible for these pharmacological activities, the molecular mechanisms, and in vivo and in vitro studies are listed in detail. Furthermore, the clinical therapeutics and toxicity studies of licorice are also discussed. We hope this work can provide a basis for further studies concerning with the safe and effective use of licorice.
Georg Thieme Verlag KG Stuttgart · New York.
The beneficial effects of liquorice in treating chills, colds, and coughs have been fully discussed in Ayurveda, as well as in the texts of ancient Egyptians, Greeks, and Romans. The plant has been prescribed for dropsy during the period of famous Hippocrates. The reason being that it was quite helpful as thirst-quenching drugs (Biondi et al. in J Nat Prod 68:1099–1102, 2005; Mamedov and Egamberdieva in Herbals and human health-phytochemistry. Springer Nature Publishers, 41 pp, 2017). No doubt, the clinical use of liquorice in modern medicine started around 1930; Pedanios Dioscorides of Anazarba (Adana), first century AD-Father of Pharmacists, mentions that it is highly effective in the treatment of stomach and intestinal ulcers. In Ayurveda, people in ancient Hindu culture have used it for improving sexual vigor.
Context: Increasing incidence and impact of inflammatory diseases have encouraged the search of new pharmacological strategies to face them. Licorice has been used to treat inflammatory diseases since ancient times in China.
Objective: To summarize the current knowledge on anti-inflammatory properties and mechanisms of compounds isolated from licorice, to introduce the traditional use, modern clinical trials and officially approved drugs, to evaluate the safety and to obtain new insights for further research of licorice.
Methods: PubMed, Web of Science, Science Direct and ResearchGate were information sources for the search terms ‘licorice’, ‘licorice metabolites’, ‘anti-inflammatory’, ‘triterpenoids’, ‘flavonoids’ and their combinations, mainly from year 2010 to 2016 without language restriction. Studies were selected from Science Citation Index journals, in vitro studies with Jadad score less than 2 points and in vivo and clinical studies with experimental flaws were excluded.
Results: Two hundred and ninety-five papers were searched and 93 papers were reviewed. Licorice extract, 3 triterpenes and 13 flavonoids exhibit evident anti-inflammatory properties mainly by decreasing TNF, MMPs, PGE2 and free radicals, which also explained its traditional applications in stimulating digestive system functions, eliminating phlegm, relieving coughing, nourishing qi and alleviating pain in TCM. Five hundred and fifty-four drugs containing licorice have been approved by CFDA. The side effect may due to the cortical hormone like action.
Conclusion: Licorice and its natural compounds have demonstrated anti-inflammatory activities. More pharmacokinetic studies using different models with different dosages should be carried out, and the maximum tolerated dose is also critical for clinical use of licorice extract and purified compounds.
Resistant hypertension (RH) is defined as failure to achieve goal blood pressure while receiving a 3 drug regimen at optimal doses that includes a diuretic. The exact prevalence of resistant hypertension is unknown which may vary from 5% to 50%. Patient or clinician-related factors contributing to resistant hypertension include patient's non-adherence to antihypertensive therapy, White-coat effect and pseudo-hypertension and life style factors (Obesity, alcohol, smoking, dietary sodium etc). Several drugs may induce pre-existing hypertension where non-steroidal anti-inflammatory drugs are usually the most common due to their frequent use; whereas oral contraceptives, sympathomimetics (decongestants, anorectics), adrenal steroids and antineoplastic drugs targeting the vascular endothelial growth factor (VEGF) pathway has a good deal of contribution to resistant hypertension. Most common secondary causes of resistant hypertension are obstructive sleep apnea, renal artery stenosis, renal parenchymal disease, and primary aldosteronism while some uncommon causes such as pheochromocytoma, Cushing's disease, thyroid and parathyroid dysfunction; and aortic coarctation also contribute to resistant hypertension. Both pharmacological and non-pharmacological treatments are available for the management of resistant hypertension. This article reviews the prevalence, symptoms, causes and treatment of resistant hypertension.
