Therapeutic Effects Of Crocin Research Articles

Therapeutic Effects of Crocin Alone or in Combination with Sorafenib against Hepatocellular Carcinoma: In Vivo & In Vitro Insights.

This study investigated the therapeutic effects of the phytochemical crocin alone or in combination with sorafenib both in rats chemically induced with hepatocellular carcinoma (HCC) and in human liver cancer cell line (HepG2). Male rats were randomly divided into five groups, namely, control group, HCC induced group, and groups treated with sorafenib, crocin or both crocin and sorafenib. HCC was induced in rats with a single intraperitoneal injection of diethylnitrosamine (DEN), then 2-acetylaminofluorene (2-AAF). The HCC-induced rats showed a significant decrease in body weight compared to animals treated with either or both examined drugs. Serum inflammatory markers (C-reactive protein (CRP); interleukin-6 (IL-6); lactate dehydrogenase (LDH), and oxidative stress markers were significantly increased in the HCC group and were restored upon treatment with either or both of therapeutic molecules. Morphologically, the HCC-induced rats manifested most histopathological features of liver cancer. Treatment with either or both of crocin and sorafenib successfully restored normal liver architecture. The expression of key genes involved in carcinogenesis (TNFα, p53, VEGF and NF-κB) was highly augmented upon HCC induction and was attenuated post-treatment with either or both examined drugs. Treatment with both crocin and sorafenib improved the histopathological and inflammation parameters as compared to single treatments. The in vivo anti-cancer effects of crocin and/or sorafenib were supported by their respective cytotoxicity on HepG2 cells. Crocin and sorafenib displayed an anti-tumor synergetic effect on HepG2 cells. The present findings demonstrated that a treatment regimen with crocin and sorafenib reduced liver toxicity, impeded HCC development, and improved the liver functions.

Therapeutic Effect of Crocin on the NASH Model by Targeting the Fas Receptor Signaling Pathway.

The role of hepatocyte apoptosis and inflammation has been implicated in the progression of nonalcoholic steatohepatitis (NASH). Overproduction of reactive oxygen species (ROS) appears to accelerate these pathways through the activation of Fas receptor signaling. Therefore, we explored the hepatoprotective effects of crocin as a strong free radical scavenger against oxidative damages leading to NASH development. Thirty-two male mice were randomly divided into control, NASH, NASH + crocin, and crocin groups. They received an intraperi- toneal injection of crocin twice a week, for 3 weeks. For NASH model induction, the animals were fed with a Western diet and exposed to cigarette smoke for 8 weeks. At the end of the experiment, liver histology, biochemical, and biomolecular analyses were done to evaluate the antioxidant, anti-inflammatory, and anti-apoptotic activities of crocin in the NASH model. Evaluation of the features of the NASH model revealed steatosis, inflammatory infiltrate, and ballooning degeneration. Metabolic dysfunction was associated with elevated serum levels of the lipid profile and decreased hepatic liver enzymes. The increased content of malondialdehyde (MDA) and reduced antioxidant activities confirmed hepatotoxicity induction. There was a significant increase in expression level of Fas, caspase 3, and NF-κB genes that was also associated with elevation in hepatic TNF-α content. Moreover, expression the of Fas receptor protein was significantly detected on the hepatocyte membrane. Treatment with crocin effectively improved NASH-related parameters, and the histopathological findings were also parallel with the resulting changes. Crocin can be introduced as a candidate hepatoprotective agent against NASH by virtue of its anti-inflammatory, antioxi- dant, and anti-apoptotic properties, possibly through regulation of the Fas death receptor pathway.

Administering crocin ameliorates anxiety-like behaviours and reduces the inflammatory response in amyloid-beta induced neurotoxicity in rat.

Anxiety, hippocampus synaptic plasticity deficit, as well as pro-inflammatory cytokines, are involved in Alzheimer's disease (AD). The present study is designed to evaluate the possible therapeutic effect of crocin on anxiety-like behaviours, hippocampal synaptic plasticity and neuronal shape, as well as pro-inflammatory cytokines in the hippocampus using in vivo amyloid-beta (Aβ) models of AD. The Aβ peptide (1-42) was bilaterally injected into the frontal-cortex. Five hours after the surgery, the rats were given intraperitoneal (IP) crocin (30mg/kg) daily up to 12days. Elevated plus maze results showed that crocin treatment after bilateral Aβ injection significantly increased the percentage of spent time into open arms, frequency of entries, and percentage of entries into open arms as compared with the Aβ group. In the open field test, the Aβ+crocin group showed a higher percentage of spent time in the centre and frequency of entries into central zone as compare with the Aβ treated animals. Administering crocin increased the number of soma, dendrites and axonal arbores in the CA1 neurons among the rats with Aβ neurotoxicity. Cresyl violet (CV) staining showed that crocin increased the number of CV-positive cells in the CA1 region of the hippocampus compared with the Aβ group. Silver-nitrate staining indicated that crocin reduced neurofibrillary tangle formation induced by Aβ. Crocin treatment attenuated the expression of TNF-α and IL-1β mRNA in the hippocampus compared with the Aβ group. Our results suggest that crocin attenuated Aβ-induced anxiety-like behaviours and neuronal damage, and synaptic plasticity loss in hippocampal CA1 neurons may via its anti-inflammatory effects.

Prevention of toxic effects of orally administered tartrazine by crocin in Wistar rats

Tartrazine is used in the pharmaceutical, cosmetic, and food industries worldwide, despite its many toxic effects. The therapeutic effects of crocin (50 mg/kg/day) against tartrazine-induced (500 mg/kg/day) oxidative damage in ileum and colon tissues in rats have been investigated. Malondialdehyde and total oxidant status levels elevated by tartrazine within the ileum and colon tissues were reduced with crocin treatment, while tartrazine decreased antioxidative parameters (glutathione, total antioxidant status, superoxide dismutase, and catalase) were reverted. Tartrazine-induced histopathological changes of ileum and colon tissues were ameliorated following crocin treatment. In conclusion, Tartrazine consumption elicited tissue injury via lipid peroxidation, and crocin ameliorated oxidative injury by its antioxidant and free radical scavenger properties.

Crocin attenuates CCl4-induced liver fibrosis via PPAR-γ mediated modulation of inflammation and fibrogenesis in rats.

Liver fibrosis is a chronic pathological condition with a leading cause of liver-related mortality worldwide. In the present study, we have evaluated the antifibrotic effect of crocin, a carotenoid present in the stigma of Crocus sativus, and also explored its putative mechanism of action. Liver fibrosis was induced by intraperitoneal administration of 30% carbon tetrachloride (CCl4). The crocin was administered orally at 20, 40 and 80 mg/kg body weight along with CCl4 up to 8 weeks. Chronic exposure to CCl4 resulted in elevated levels of liver enzymes and reduced cytochrome P450 2E1 (CYP2E1) activity in the liver. The liver tissue showed cellular swelling, vacuolization, necrosis, infiltration of inflammatory cells and fibrotic changes. The crocin treatment significantly lowered the levels of liver enzymes in serum and improved the liver CYP2E1 mRNA levels. The pathological changes in the liver were also lowered by crocin treatment. The level of pro-inflammatory cytokines, nuclear factor-kappa B, interleukin-6 and tumor necrosis factor α and fibrogenic factor, transforming growth factor β, and α-smooth muscle actin were elevated by the CCl4 in the liver tissue. However, crocin treatment at different doses significantly reduced the expression of these factors. The increased caspase 3/7 activity was also lowered by crocin. CCl4 administration decreased the expression of peroxisome proliferator-activated receptor γ (PPAR-γ) in liver tissue. The improved PPAR-γ expression in the liver by crocin treatment indicates its role in the therapeutic effect of crocin. Crocin attenuated the various events in the progression of liver fibrosis via PPAR-γ mediated modulation of inflammatory and fibrogenic pathways.

Effects of crocin in reducing DNA damage, inflammation, and oxidative stress in multiple sclerosis patients: A double-blind, randomized, and placebo-controlled trial.

Multiple sclerosis (MS) is an autoimmune disease in which the immune system attacks the nerve cells, resulting in neurological disorders. Oxidative stress, free radicals, and neuritis have important roles in MS pathogenesis. Here, we aim to evaluate the effect of crocin on inflammatory markers, oxidative damage, and deoxyribonucleic acid (DNA) damage in the blood of patients with MS. A total of 40 patients were divided into two groups, drug and placebo-treated groups, using random assignment. Participants of the intervention and control groups received two crocin capsules or placebo per day for 28 days, respectively. Findings revealed a significant decrease in the level of important pathogenic factors in MS, including lipid peroxidation, DNA damage, tumor necrosis factor-alpha, and interleukin 17 as well as a significant increase in the total antioxidant capacity in the serum of patients treated with crocin compared with the placebo group. Our results suggest the beneficial and therapeutic effects of crocin in MS.

Therapeutic effects of Crocin in autoimmune diseases: A review.

The immune system when acts against selfmolecules results in an imbalance in immunologic tolerance leading to the development of several autoimmune diseases (ADs) such as rheumatoid arthritis, asthma, ulcerative colitis, type 1 diabetes, and multiple sclerosis. Improved recognition of the mechanisms of ADs has led to the advancement of the management of these diseases. The principal mediators of ADs are inflammatory molecules. The herbal medicines due to their antioxidant and antiinflammatory properties have an important role in the management of ADs. Crocin is the principal chemical component extracted from saffron, which is a medicinal plant. This review focuses on the therapeutic effects of Crocin in various ADs.

Possible Therapeutic Effect of Crocin on Thioacetamide-Induced Liver Injury in Male Albino Rats

AbstractBackground: Thioacetamide is an experimentally used hepatotoxic substance. Its hepatotoxicity is mainly due to increased cellular oxidative stress.Aim: To evaluate the possible hepatoprotective effects of crocin on the damage induced by Thioacetamide in liver of male rats.Methods: 50 male Wister rats were divided into 5 groups, 10 rats in each group; control group; given intraperitoneal injection of 1ml normal saline daily, thioacetamide group; received intraperitoneal injection of thioacetamide in a single dose (300mg/kg), and three (Crocin + Thioacetamide) groups, received crocin in doses of 12.5, 25 and 50mg/kg respectively after thioacetamide intoxication, as in group 2. Then the animals were anaesthetized, blood samples were taken by cardiac puncture. Serum levels of aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phos-phatase (ALP) were determined. Moreover, the tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were measured in liver tissue.Results: Compared to control group, thioacetamide group, showed significant increase in serum levels of AST, ALT, ALP, and tissue levels of MDA, with significant decrease in tissue GSH and GPx. Crocin treatment significantly decreased serum levels of AST, ALT, ALP, and tissue levels of MDA and significantly increased tissue GSH and GPx, in a dose dependant manner.Conclusion: Crocin treatment attenuated the liver injury caused by thioacetamide and its clinical application might be a new therapeutic approach in the liver diseases due to its anti-inflammatory and antioxidant properties.

The Effect of Crocin on Endocrine Functions of the Testes before and after Testicular Damage in Rats

AbstractAim of the Work: The aim of this work is to study the effect of crocin on endocrine functions of testes before and after testicular damage in rats.Methods: The present work will be carried on 40 male albino rats. The rats will be divided into four groups, (10 rats for each). Control group (group I): Rats received 1ml normal saline intraperitoneally. Cadmium-treated group (group II): Rats received intraperitoneal injection of a single dose of 1 mg/kg cadmium chloride dissolved in saline. Crocin-pretreated group (group III): Rats received crocin in a dose of 50mg/kg intra-peritoneally once daily for 4 weeks, then they received cadmium chloride as in group II. Crocin-treated group (group IV): Rats received cadmium chloride as in group II, then they treated with crocin as in group III. At the end of the experiment, the animals were anesthetized, then the animals were sacrificed by cervical decapitation. The collected blood samples were collected.Results: At the end of the experimental period, the results of the present work revealed that in Cd-treated group, there was significant decrease of serum levels of testosterone, FSH and LH. On the other hand, there was significant increase of testicular caspase-3 and testicular MDA with concomitant significant decrease of testicular GSH level compared to normal control group. In both the crocin-pretreated group and crocin-treated groups, there was significant increase of serum levels of testosterone, FSH and LH, significant decrease of testicular MDA levels associated with significant increase of testicular GSH levels as compared to cadmium-treated group. Testicular caspase-3 significanlty decreased in the crocin-treated group, but insignificanlty changed in crocin-pretreated as compared to cadmium-treated group. Also, all studied parameters significantly improved in crocin-treated group as compared to the crocin-pretreated group.Conclusion: We conclude that crocin can improve testicular toxicity induced by cadmium via its anti-apoptotic and anti-oxidant effects. Moreover, our results showed that the thera-peutic effect of crocin is more effective than its protective effect on testicular toxicity induced by Cd.