Potential Effects of Boldine on Oxidative Stress, Apoptosis, and Inflammatory Changes Induced by the Methylprednisolone Hepatotoxicity in Male Wistar Rats

Abstract

Background Synthetic glucocorticoid therapeutic agent methylprednisolone (MPL), when used for an extended period of time at high dose, promotes the development of reactive oxygen species (ROS)-induced liver toxicity. This study investigated the role of boldine, a natural antioxidant with anti-apoptotic and anti-inflammatory properties, against MPL-induced hepatoxicity in male Wistar rats. Methods 120 rats were divided into eight equal groups: G1 (control), G2, 3, and 4 (rats orally administered 5, 10, and 50 mg boldine/kg b.w./day; respectively, for 28 days), G5 (rats intramuscularly injected with 100 mg MPL/kg b.w. only on the last three days), G6, 7, and 8 (rats administered boldine + MPL). After the last MPL injection, rats were sacrificed at intervals of 1, 24, and 48 h. Results There was a significant decrease in WBCs, RBCs count, and HGB levels, as well as an increase in PLT count, ALT, AST, TG, and LDL levels, and a decrease in HDL level in serum. Oxidative stress markers levels increased at all times, and gene expression of antioxidant enzymes increased at 24h. Immunohistochemical analysis revealed that cytochrome c levels significantly increased after MPL treatment. The COMET assay revealed detectable DNA lesions. There was no immune reactivity of IL-6 expressions as an inflammatory response marker. Conclusions Oral administration of boldine has a modulatory protective, antioxidant, and anti-apoptotic effect against free radicals.

Boldine protects against carbon tetrachloride‐induced chronic liver injury by regulating NF‐κB signaling pathway

“…In methylprednisolone-induced rats, boldine treatment reduced triglyceride and low-density lipoprotein levels. [22] Boldine suppressed CCl 4 -induced hepatic steatosis by decreasing hepatic lipid accumulation due to its antilipidemic properties and our present results are in agreement with these reports. The probable hepatoprotective mechanism of boldine is presented in Figure 10.…”

“…Previous studies have also shown that both boldine and SIL have antioxidant and membrane stabilizing properties against various drugs and chemical induced liver injuries. [22,48,49] Therefore, it can be stated that boldine could have nullified CCl 4 mediated free radicals and reduced oxidative stress due to its inherent antioxidant and free radical quenching properties.…”

“…[20] Methylprednisolone and acetaminophen-induced hepatotoxicities were significantly alleviated after boldine administration due to its antioxidant, anti-inflammatory and antiapoptotic effects. [21,22] Therefore, it is reasonable to assume that boldine concurrent administration may protect against carbon tetrachloride (CCl 4 )-induced chronic liver injury in rats. Hence, this study explores the protective effect of boldine against CCl 4 -induced chronic liver disease in rats.…”

Boldine Alkaloid: Holistic Overview on Potential Health Benefits and Medicinal Merits a comprehensive review

“…Also, treatment with boldine significantly increased the levels of SOD, GSHPx, and GR, in contrast to treated groups with MPL. Also cytochrome c protein expressed in treated rats with MPL, meanwhile it was reduced with rats treated with boldine and MPL [22]…”

Biotransformation of Modified Benzylisoquinoline Alkaloids: Boldine and Berberine and In Silico Molecular Docking Studies of Metabolites on Telomerase and Human Protein Tyrosine Phosphatase 1B

“…Furthermore, boldine has gastroprotective effect and is useful in gastric ulcer treatment [ 6 ]. As an effective antioxidant, boldine can act as anti-apoptotic agent and protect the liver from damage induced by methylprednisolone [ 7 ]. Boldine showed anti-inflammatory activity in Guinea pig Paw edema and reduced hyperthermia in rabbits due to bacterial pyrogens and inhibited prostaglandin biosynthesis [ 8 ].…”