Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation

Abstract

BACKGROUND Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported. AIM To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation. METHODS Male albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections. RESULTS Fluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels. CONCLUSION These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress a...

Protective effects of baicalin magnesium on non-alcoholic steatohepatitis rats are based on inhibiting NLRP3/Caspase-1/IL-1β signaling pathway

“…Clinically, Scutellaria baicalensis as the active ingredient of Shenqin compounded formulations and Shuganning injection can play a role in liver protection by increasing the secretion of hepatocyte growth factor, stimulating hepatocyte regeneration, scavenging oxygen free radicals and regulating immunity [ 4 ]. Baicalin is the primary effective component of Scutellaria baicalensis , which has been shown to have anti-inflammatory, antioxidant, anti-lipid deposition, and hepatoprotective effects in modern medical research [ 5 – 7 ]. Clinically, baicalin tablets or capsules can be used to treat chronic liver disease [ 8 ].…”

Baicalin promotes random‐pattern skin flap survival by inducing autophagy via AMPK‐regulated TFEB nuclear transcription

“…Though BA treatment significantly improved the survival rate in Area II, it would be better to have a positive control group in this study. Moreover, there are many studies choose BA 50 mg/kg as their therapeutic dose (Ganguly et al, 2022) and only treated rats with BA 200 mg/kg rats 7 times/day, 6 times/ week, showed the body weight and kidney coefficient were lower (Zhang et al, 2021). Actually, we did not use such high dose and high frequency of BA and also there were no rat has weight loss in our study.…”

Role of baicalin as a potential therapeutic agent in hepatobiliary and gastrointestinal disorders: A review

“…The clinical application of baicalin in pharmacology has been challenging, due to its low solubility and bioavailability. In the last decade, many researchers have designed novel delivery strategies for baicalin that include phospholipid complex, liposomes, solid baicalin nanocrystals, and micelle formation[ 123 ]. The dissolution and solubility of baicalin is considerably enhanced when administered in combination with other molecules in complex form.…”

“…For instance, baicalin has exhibited improved oral bioavailability, distribution, targeting, and therapeutic efficacy when combined with polyethylene glycol and folic acid in the form of liposomes. β-Cyclodextrin complex has also been used as an effective formulation to facilitate the effective delivery of baicalin with wide range of therapeutic outcomes[ 123 , 124 ]. Moreover, baicalin is commonly used as adjuvant therapy for hepatitis.…”