**6.1** *Nigella sativa* **in COVID-19**

*N. sativa* is a plant native to South East Asia with several pharmacological effects including bronchodilation, antitussive, and anti-inflammatory and used as treatments of respiratory conditions, diabetes, cardiovascular diseases, among others [89, 90]. For example, in a clinical trial with 90 obese women, 3 g/day of *N. sativa* oil for 8 weeks reduced serum levels of TNFα and hsCRP in comparison to placebo with no adverse events reported [91]. In patients with asthma, 1 g *N. sativa* oil per day for 4 weeks reduced several inflammatory markers and improved pulmonary function [92]. Preclinical studies have shown that constituents in the methanolic extract of *N. sativa* seeds are responsible for the bronchodilator effect [93]. Recently, *N. sativa* has been regarded as a potential therapy for COVID-19 [13, 18, 94, 95]. For example, in a molecular docking-based study *N. sativa* inhibited SARS-CoV2 [94].

#### **6.2** *Nigella sativa* **in diabetes**

Several clinical trials have been conducted to evaluate *N. sativa* in patients with type 2 diabetes [96]. For example, three controlled studies investigated the adjuvant use of 1–3 g/day *N. sativa* seeds powder or 2.5 ml/day *N. sativa* oil for 12 weeks in patients with type-2 diabetes. Significant and similar effects were observed with doses of 2 and 3 g/d on the reductions in fasting blood glucose, 2-hour postprandial glucose, HbA1C levels, and insulin resistance. Treatments were not associated with any adverse renal or hepatic functions throughout the study period. Patients were concomitantly taking oral hypoglycemic drugs (glibenclamide, metformin, rosiglitazone) but not insulin. Patients with coronary artery disease, valvular heart disease, heart failure, uncontrolled hypertension, renal failure and hepatic failure were excluded [97–99].

#### **6.3** *Nigella sativa* **in heart disease**

In a meta-analysis including 11 randomized clinical trials with 860 hypertensive or normotensive individuals, *N. sativa* seeds versus placebo and one versus standard treatment significantly reduced systolic blood pressure by −3.60 mmHg and diastolic blood pressure by −2.80 mmHg. [100]. A similar meta-analysis including 17 randomized clinical trials with 1185 individuals with hyperlipidemia, obesity, hypertension, type 2 diabetes, or others, found that *N. sativa* seed powder or oil 1–3 g/day for up to 3 months reduces total cholesterol, LDL-cholesterol, and

triglycerides [101]. No adverse events were reported by the subjects [102, 103]. One study in elderly with hypertension reported mild adverse events including dyspepsia in 6 subjects (15.7%), nausea in 3 subjects (7.8%), and constipation in 2 subjects (5.2%). No electrolyte abnormalities, liver and renal toxicities, or orthostatic hypotension were observed [104].
