**4.** *Glycyrrhiza sp.* **root (licorice) – Antiviral and respiratory support**

#### **4.1 Licorice in COVID-19**

Licorice root is used as a flavoring agent in food in many countries. In the United States, anise oil is often used for this purpose. Licorice is promoted as a dietary supplement for digestion, cough, infections, and others [40]. Frequently recommended by herbalists, licorice has recently shown to be the herb most frequently used for COVID-19 treatment [41, 42]. Several review articles have discussed the potential effectiveness of licorice in treating COVID-19 for its antiviral, anti-inflammatory, spasmolytic, and expectorant effects [9, 10, 12–14]. Some in vitro studies showed that the active component glycyrrhizin inhibits the replication of SARS-coronavirus (SARS-CoV) [43, 44]. Other in vitro studies showed that glycyrrhizin may prevent SARS-CoV-2 entry by binding to ACE2 receptors and other protein targets [45, 46]. Clinical trials of licorice use during COVID-19 are ongoing. Daily doses range from 250 mg 25% extract (62.5 mg glycyrrhizin) for 10 days to 2.28 g 3% extract (70 mg glycyrrhizin) for 7 days [47, 48].

#### **4.2 Licorice in diabetes**

Not many studies have investigated the effects of licorice in diabetes. In a clinical trial with 58 overweight and obese but otherwise healthy volunteers, 1.5 g licorice extract (<0.01% glycyrrhizin) for 8 weeks decreased insulin and HOMA-IR without side effects [49]. In cell cultures, de-glycyrrhizinated or regular licorice showed to be a potential therapeutic target in diabetic nephropathy [50]. In diabetic mice, licorice hydrophobic flavonoids demonstrated abdominal fat-lowering and hypoglycemic effects [51].
