3.1.4. Safety Profile

Baicalein is considered safe and has a good tolerability profile in humans, as per se it did not have adverse reports in VigiBase [95], the WHO global database of potential side effects of medicinal products.

Mild side effects were reported in a placebo-controlled study in which 68 healthy subjects were treated with a single dose of baicalein orally, 100 to 800 mg [94]. The most common side effects were increased levels of the C-reactive protein and triglycerides, and proteinuria; these undesirable effects did not depend on the dose of baicalein administered [94]. In a clinical trial, multiple doses of baicalein (200, 400 or 800 mg twice daily) in healthy volunteers produced various adverse effects, such as abdominal pain, constipation, and increased alanine transaminase and aspartate aminotransferase levels [96].

In fact, some concerns arose from reports on the possible liver toxicity of the use of plant extracts rich in flavonoids. Recently, it was shown in vitro that baicalein can inhibit human UDP-glucuronosyltransferases1A1, the enzyme that is primarily responsible for glucuronidation and the elimination of bilirubin [97], which can cause jaundice and severe liver disease. In general, further clinical trials involving a higher number of enrolled subjects are needed to produce a clearer picture of the safety profile of baicalein in humans.

#### *3.2. Curcumin*

#### 3.2.1. Chemistry and Sources

Curcumin, also known as diferuloylmethane [(1*E*,6*E*)-1,7-bis(4-hydroxy-3-methoxyphenyl) hepta-1,6-diene-3,5-dione], is a diarylheptanoid that represents the main component of the turmeric rhizome (*Curcuma longa* L. and other *Curcuma* spp.), and has caused extensive investigations from biological and chemical points of view [98]. Turmeric is a widely used medicinal plant in Asian countries, appreciated for its antioxidant and anti-inflammatory activities, as well as for other multiple properties [99].
