Saffron extract and crocin exert anti-inflammatory and anti-oxidative effects in a repetitive mild traumatic brain injury mouse model

Abstract

Saffron Crocus sativus L. (C. sativus) is a flower from the iridaceous family. Crocin, saffron’s major constituent, and saffron have anti-oxidative and anti-inflammatory activities. In this work, the neuroprotective effects of saffron and crocin are being investigated in a repetitive mild traumatic brain injury (rmTBI) mouse model. A weight drop model setup was employed to induce mild brain injury in male albino BABL/c mice weighing 30–40 g. Saffron (50 mg/kg) and crocin (30 mg/kg) were administrated intraperitoneally 30 min before mTBI induction. Behavioral tests were conducted to assess behavioral deficits including the modified neurological severity score (NSS), Morris water maze (MWM), pole climb test, rotarod test, and adhesive test. The levels of TNF alpha (TNF-α), interferon-gamma (IFN-γ), myeloperoxidase activity (MPO), malonaldehyde (MDA), and reduced glutathione (GSH) were measured. Histological analysis of different brain parts was performed. Both saffron and crocin demonstrated marked improved neurological, cognitive, motor, and sensorimotor functions. Besides, both compounds significantly reduced the oxidative stress and inflammatory processes. No abnormal histological features were observed in any of the injured groups. Saffron extract and crocin provide a neuroprotective effect in a mouse model of rmTBI by decreasing oxidative stress, inflammatory responses, and behavioral deficits.

An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines

“…Intraperitoneal treatment with saffron stigma extract or petal extract was associated with an LD50 value of 1.6 g/kg and 6 g/kg, respectively [ 26 , 160 , 175 , 176 , 177 ]. The LD50 of CRCs is estimated at >3 g/kg [ 26 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

“…Saffron and its metabolites did not cause any significant hematological or biochemical toxic effects, nor were associated with histotoxicity in heart, liver, spleen and kidney, or genotoxic and mutagenic effects [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. CRCs in preclinical mice models were well tolerated in doses up to 3 g/kg, in intraperitoneal or oral administration for acute exposure and 400 mg/kg in intraperitoneal administration for subacute exposure (3–4 weeks) [ 26 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Saffron Extract Attenuates Anxiogenic Effect and Improves Cognitive Behavior in an Adult Zebrafish Model of Traumatic Brain Injury

“…Both aqueous and ethanolic saffron extracts were shown to exert anti-inflammatory effects in induced chronic inflammation in mice [ 61 ]. A recent study in a repetitive mild non-invasive traumatic brain injury mouse model showed that saffron extract and crocin suppress TBI-induced inflammatory and oxidative responses by decreasing the levels of IFN-γ, TNF-α, MPO, GSH, and MDA [ 31 ]. Furthermore, dysregulation in both excitatory and inhibitory neurotransmission has been shown after TBI [ 62 ].…”

“…Studies have shown that saffron has a broad spectrum of pharmacological properties, including anti-hyperglycemic [ 28 ], anti-depressive [ 29 ], anti-tumor [ 27 ], and anti-oxidant [ 30 ] effects that have been identified in rodent disease models. Specifically, administration of crocin in a controlled cortical impact (CCI) model of TBI in mice showed a decrease in brain edema and neurological motor severity score [ 31 ]. Apoptotic cell death and neuroinflammation were inhibited in a TBI-induced mouse model treated with crocin, through the Notch signaling pathway [ 17 ].…”

The Effect of Triptolide Combined With Crocin on Arthritis in Mice: From Side Effect Attenuation to Therapy

“…Modern pharmacological studies of saffron and its main constituents have revealed a wide spectrum of biological activities (i.e., anti-inflammatory, antinociceptive, antioxidant, immunoregulatory effects, neurodegenerative diseases, cardiovascular diseases, anticancer, anti-arthritic effects and protection against natural and chemical toxins) ( Attia et al, 2021 ; Xing et al, 2021 ). Crocin, mono, and diglycosyl esters of a polyene dicarboxylic acid are some of the main active components that are responsible for the pharmacological effects of saffron ( Abdi et al, 2022 ; Salem et al, 2022 ; Xu et al, 2022 ).…”