Evaluation of the efficacy of oral nano‐silymarin formulation in hospitalized patients with COVID‐19: A double‐blind placebo‐controlled clinical trial

Abstract

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID‐19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID‐19. The participants were assigned to the nano‐silymarin ( n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups ( n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow‐up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration ( p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group ( p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.

Effects of silymarin supplementation on liver and kidney functions: A systematic review and dose–response meta‐analysis

“…In addition, 1607 titles and abstracts were reviewed, and then 1595 studies were removed. Finally, 41 eligible studies were considered in this meta‐analysis after a full‐text review (Abbasirad et al, 2021; Ahmed et al, 2022; Anushiravani et al, 2019; Aryan et al, 2022; Bárcena et al, 2013; Darvishi‐Khezri et al, 2017; Di Pierro et al, 2013; Ebrahimpour Koujan et al, 2015; Elgarf et al, 2015; Fallah Huseini et al, 2005; Fallahzadeh et al, 2012; Firuzi et al, 2016; Fried et al, 2012; Gharagozloo et al, 2009; Gordon et al, 2006; Hajaghamohammadi et al, 2008; Hashemi et al, 2009; Heo et al, 2017; Huseini et al, 2004, 2006; Kheong et al, 2017; Luangchosiri et al, 2015; Lucena et al, 2002; Masoodi et al, 2013; Mirhashemi et al, 2022; Mirnezami et al, 2020; Mirzaei et al, 2021; Moayedi et al, 2013; Moezian et al, 2022; Mohaghegh et al, 2015; Momeni et al, 2015; Palasciano et al, 1994; Parés et al, 1998; Ramezani et al, 2008; Razzaq et al, 2011; Rendina et al, 2014; Salmi & Sarna, 1982; Simanek et al, 2001; Solhi et al, 2014; Taghvaei et al, 2013; Valentová et al, 2008).…”

“…These were published between 1982 and 2022. Thirty‐nine studies were parallel trials (Abbasirad et al, 2021; Ahmed et al, 2022; Anushiravani et al, 2019; Aryan et al, 2022; Bárcena et al, 2013; Di Pierro et al, 2013; Ebrahimpour Koujan et al, 2015; Elgarf et al, 2015; Fallah Huseini et al, 2005; Fallahzadeh et al, 2012; Firuzi et al, 2016; Fried et al, 2012; Gharagozloo et al, 2009; Hajaghamohammadi et al, 2008; Hashemi et al, 2009; Heo et al, 2017; Huseini et al, 2004, 2006; Kheong et al, 2017; Luangchosiri et al, 2015; Lucena et al, 2002; Masoodi et al, 2013; Mirhashemi et al, 2022; Mirnezami et al, 2020; Mirzaei et al, 2021; Moayedi et al, 2013; Moezian et al, 2022; Mohaghegh et al, 2015; Momeni et al, 2015; Palasciano et al, 1994; Parés et al, 1998; Ramezani et al, 2008; Razzaq et al, 2011; Rendina et al, 2014; Salmi & Sarna, 1982; Simanek et al, 2001; Solhi et al, 2014; Taghvaei et al, 2013; Valentová et al, 2008) and two were crossover studies (Darvishi‐Khezri et al, 2017; Gordon et al, 2006). The duration of the trials and sample sizes varied from 2 to 96 weeks and from 16 to 200 participants, respectively.…”

“…The average age of the participants was between 18 and 67 years. The studies were conducted in Iran (Abbasirad et al, 2021; Anushiravani et al, 2019; Aryan et al, 2022; Darvishi‐Khezri et al, 2017; Ebrahimpour Koujan et al, 2015; Fallah Huseini et al, 2005; Fallahzadeh et al, 2012; Firuzi et al, 2016; Gharagozloo et al, 2009; Hajaghamohammadi et al, 2008; Hashemi et al, 2009; Huseini et al, 2004, 2006; Masoodi et al, 2013; Mirhashemi et al, 2022; Mirnezami et al, 2020; Mirzaei et al, 2021; Moayedi et al, 2013; Moezian et al, 2022; Mohaghegh et al, 2015; Momeni et al, 2015; Ramezani et al, 2008; Solhi et al, 2014; Taghvaei et al, 2013), Australia (Gordon et al, 2006), Finland (Salmi & Sarna, 1982), the United States (Fried et al, 2012), Spain (Bárcena et al, 2013; Lucena et al, 2002; Parés et al, 1998), Italy (Palasciano et al, 1994; Rendina et al, 2014), the Czech Republic (Simanek et al, 2001; Valentová et al, 2008), Malaysia (Kheong et al, 2017), Thailand (Luangchosiri et al, 2015), Egypt (Elgarf et al, 2015), Italy (Di Pierro et al, 2013), South Korea (Heo et al, 2017), Iraq (Razzaq et al, 2011), and Pakistan (Ahmed et al, 2022).…”

“…The trials enrolled patients with liver disease (Salmi & Sarna, 1982), hepatitis C (Ahmed et al, 2022; Bárcena et al, 2013; Fried et al, 2012; Gordon et al, 2006; Rendina et al, 2014), or B (Fallah Huseini et al, 2005), NAFLD (Anushiravani et al, 2019; Hajaghamohammadi et al, 2008; Masoodi et al, 2013; Mirhashemi et al, 2022), liver cirrhosis (Lucena et al, 2002; Parés et al, 1998), type 2 diabetes (T2DM) (Di Pierro et al, 2013; Ebrahimpour Koujan et al, 2015; Elgarf et al, 2015; Fallahzadeh et al, 2012; Huseini et al, 2004, 2006; Ramezani et al, 2008), metabolic syndrome (Valentová et al, 2008), β‐thalassemia (Darvishi‐Khezri et al, 2017; Gharagozloo et al, 2009; Moayedi et al, 2013), NASH (Hashemi et al, 2009; Kheong et al, 2017; Solhi et al, 2014; Taghvaei et al, 2013), breast cancer (Moezian et al, 2022; Mohaghegh et al, 2015; Razzaq et al, 2011), malignancy (Momeni et al, 2015), tuberculosis (TB) (Luangchosiri et al, 2015), end‐stage renal disease (Firuzi et al, 2016), hepatotoxicity of anti‐tuberculosis (anti‐TB) drugs (Heo et al, 2017), acne (Mirnezami et al, 2020), trauma (Mirzaei et al, 2021), multiple sclerosis (MS) (Abbasirad et al, 2021), and COVID‐19 (Aryan et al, 2022). The remaining two studies were performed with healthy participants (Simanek et al, 2001) and patients who received chronic psychotropic drug therapy (Palasciano et al, 1994).…”

“…Thirty RCTs with 2152 participants (SIL‐treated group, n = 1084 and placebo group, n = 1068) were selected for the meta‐analysis of AST values following SIL intake (Abbasirad et al, 2021; Ahmed et al, 2022; Anushiravani et al, 2019; Aryan et al, 2022; Di Pierro et al, 2013; Fallah Huseini et al, 2005; Gharagozloo et al, 2009; Hashemi et al, 2009; Heo et al, 2017; Huseini et al, 2004, 2006; Kheong et al, 2017; Luangchosiri et al, 2015; Lucena et al, 2002; Masoodi et al, 2013; Mirhashemi et al, 2022; Mirnezami et al, 2020; Mirzaei et al, 2021; Moayedi et al, 2013; Moezian et al, 2022; Mohaghegh et al, 2015; Palasciano et al, 1994; Parés et al, 1998; Ramezani et al, 2008; Razzaq et al, 2011; Salmi & Sarna, 1982; Simanek et al, 2001; Solhi et al, 2014; Taghvaei et al, 2013; Valentová et al, 2008) (Figure 1). The pooled analysis of 32 trial arms indicated that serum levels of AST were significantly reduced in SIL users compared with controls (WMD: −6.53 IU/L, 95% CI: −8.60, −4.46; p < 0.001).…”