Therapeutic effects of crocin: A review of recent studies

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.

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.

Nanoencapsulation of saffron (Crocus sativus L.) extract in zein nanofibers and their application for the preservation of sea bass fillets

An updated consensus statement from the European Menopause and Andropause Society noted that a woman's quality of life may decline during peri- and post-menopause as a result of various menopausal symptoms and age-related comorbidities. The purpose of the work was to assess the possibility of using bioactive compounds in periand postmenopausal women to prevent the development of menopausal complications and chronic diseases associated with aging. Material and methods. Literature search was carried out using PubMed, Google Scholar, ResearchGate, RSCI databases mainly over the past 10 years, with the exception of works of fundamental importance, according to the keywords "perimenopause", "postmenopause", "Affron® saffron extract", "special extract ERr 731". Results. The use of diet, dietary supplements including those containing extracts of saffron (Affron®) and Siberian rhubarb (ERr 731) and their biologically active substances, has a versatile effect on the correction of menopausal disorders due to the impact on various pathogenetic pathways of their development and can be used in women in this period as a phytonutrient support. Conclusion. The combined use of saffron and Siberian rhubarb extracts is promising from the point of view of correcting the female state during peri- and postmenopause, taking into account the pathogenetic moments of the development of menopausal complications and chronic diseases associated with aging.

Skin whitening body lotions are the cosmetics products which work on human skin by reducing a pigment called melanin in the skin. It also lightens naturally dark skin and dark spots. It is giving a moisturizing effect to the skin as a natural cosmetics body lotion. This study was aimed on a reduction of skin melanin by tyrosine inhibitory with plant extracts by formulating a stable whitening body lotion containing the plant extracts of Psidium guajava L. leaves and also the extract of Crocus sativus (Saffron). Two plants were extracted in a different way; the method of extraction for Crocus sativus was reflux method and for Psidium guajava leaves was maceration method. The phytochemical screening and tyrosinase inhibition activity of extracts were evaluated. The various types of lotion namely F1 to F5 were formulated by incorporating different concentrations of extracts and evaluated for different parameters. The findings of tyrosinase inhibitory study exhibited that the IC50 value of tyrosine inhibitory of combined extract of Psidium guajava and Crocus sativus was lower compared to Crocus sativus extract. The formulation F3 with the mixture 0.5 g of Crocus sativus and 0.5 g of Psidium guajava leaves showed the best results among several formulations. The result which obtained from formulation F3 was compatible to pass all the evaluation tests. As a conclusion, the mixture of Psidium guajava and Crocus sativus extract possesses a strong tyrosine inhibition activity, and it was formulated as a stable whitening natural body lotion, and it can be safely used on the skin.

Background: Vancomycin, a glycopeptide antibiotic, is commonly used against methicillin-resistant Gram-positive cocci. However, the nephrotoxic side-effects of Vancomycin results in dose restriction and reduces the duration of administration. Objectives: The present study was designed to evaluate the protective effects of aqueous saffron (Crocus sativus) extract on vancomycin-induced nephrotoxicity in rats. Materials and methods: In this study 32 adult male Wistar rats were randomly divided into 4 groups of 8 rats; (i) control (ii) saffron (80 mg/kg, I.P.), (iii) vancomycin (200 mg/kg/BD, I.P.) and (iv) vancomycin plus saffron. The saffron treatment began 24 hours before the administration of the vancomycin therapy and lasted 8 days, while the duration of the vancomycin therapy was 7 days. Serum creatinine and blood urea nitrogen (BUN), renal malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity and histopathological changes of renal tissue were analyzed. Results: Administration of vancomycin caused a significant increase in serum creatinine, BUN and renal MDA levels, whereas, SOD activity was decreased, when compared to the control group. Aqueous saffron extract, on the other hand, decreased serum creatinine, BUN concentration and renal MDA levels but increased the level of renal SOD activity. Substantial histopathological alterations including destruction of kidney tubules, interstitial edema, epithelia vacuolization and epithelial desquamation, were observed with the vancomycin-only treatment group. However, the administration of saffron extract resulted in a significant reduction of damage to the kidneys. Conclusion: The present study demonstrated that oxidative stress plays an important role in vancomycin induced nephrotoxicity and saffron extract has a potent renoprotective effect against vancomycin induced lipid peroxidation and nephrotoxicity.

Objective: Oxidative stress plays an important role in the pathogenesis of diabetic retinopathy. The aim of the present study was to investigate the effect of Crocus sativus L. styles (saffron) extract on oxidative stress indices of retina in streptozotocin (STZ)-induced diabetic rats. Methods: Adult male Wistar rats (n=20) were randomized into the following 4 groups (n=6-7/ group): Control group (C): normal, Control + Saffron group (CS): non-diabetic rats treated with 60 mg/ kg of saffron extract, Diabetic group (D) and Diabetic + Saffron group (DS): diabetic rats treated with 60 mg/ kg saffron extract. We determined the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as markers of antioxidant response, as well as malondialdehyde (MDA) as a marker of lipid peroxidation. Results: Induction of diabetes caused a significant decline in the activities of CAT (76.43%), SOD (53.43%) and GPx (77.58%). MDA levels were significantly lower in the DS group (0.878 ± 0.375 nmol MDA/ mg protein) as compared to D group (1.950 ± 0.299 nmol MDA/ mg protein, p<0.01) and in the CS group (0.503 ± 0.221) in comparison to C group (1.699 ± 0.454, p<0.01). Moreover, SOD and GPx activities were significantly higher (more than 1.5 and 3.5-fold respectively) after treatment with saffron (p<0.01). Regarding the retinas of non-diabetic animals, the administration of the extract caused an > 1.8-fold increase in the activity of CAT (p<0.05) and a 3-fold decrease in MDA levels (p<0.01). Conclusions: This study showed that saffron extract has a protective antioxidant action in retinas of diabetic rats. Abbreviations: C = Control group, CS = non-diabetic rats diabetic rats treated with 60 mg/ kg saffron extract, D = diabetic group, DS = diabetic rats treated with 60 mg/ kg saffron extract, SOD = superoxide dismutase, GPx = glutathione peroxidase, CAT = catalase, MDA = malondialdehyde, DM = diabetes mellitus, DR = diabetic retinopathy, ROS = reactive oxygen species, STZ = streptozotocin, GSH = reduced glutathione

Arbutus unedo L.: From traditional medicine to potential uses in modern pharmacotherapy

Herein, we have advanced a green process for the synthesis and characterization of hybrid nanoflowers using saffron extract, crocin and safranal which were involved as organic components in the creating formation of the nanoflowers, and Cu+2 ions which were involved as the inorganic component. The antimicrobial activities of saffron extract, crocin, safranal, and their Nfs were tested against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Candida albicans ATCC 1023, and the percentages of inhibition were calculated by minimum inhibitory concentration as well. The activities of nanoflowers were highly effective against all microorganisms than the saffron extract and its components, while only the crocin and crocin nanoflowers were ineffective against C. albicans. Similarly, 2,2-diphenyl-1picrylhydrazyl scavenging and catalytic activities of the nanoflowers were found to be more active than extracts and components. In the study, successful synthesis with saffron and its active components showed that they are promising antimicrobial and antioxidant agents.

Caffeic Acid Phenethyl Ester Possessing Various Immunomodulatory Effects Is a Potentially Effective Therapy for Asthma

Resveratrol (RSV) is a naturally occurring polyphenol that has been found to exert antioxidant, anti-inflammatory, and neuroprotective properties. However, how RSV exerts its beneficial health effects remains largely unknown. Here, we show that RSV inhibits insulin- and leucine-stimulated mTOR signaling in C2C12 fibroblasts via a Sirt1-independent mechanism. Treating C2C12 cells with RSV dramatically inhibited insulin-stimulated Akt, S6 kinase, and 4E-BP1 phosphorylation but had little effect on tyrosine phosphorylation of the insulin receptor and activation of the p44/42 MAPK signaling pathway. RSV treatment also partially blocked mTOR and S6 kinase phosphorylation in TSC1/2-deficient mouse embryonic fibroblasts, suggesting the presence of an inhibitory site downstream of TSC1/2. Knocking out PDK1 or suppressing AMP-activated protein kinase had little effect on leucine-stimulated mTOR signaling. On the other hand, RSV significantly increased the association between mTOR and its inhibitor, DEPTOR. Furthermore, the inhibitory effect of RSV on leucine-stimulated mTOR signaling was greatly reduced in cells in which the expression levels of DEPTOR were suppressed by RNAi. Taken together, our studies reveal that RSV inhibits leucine-stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity.

Cross-talk between SARS-CoV-2 infection and the insulin/IGF signaling pathway: Implications for metabolic diseases in COVID-19 and for post-acute sequelae of SARS-CoV-2 infection

Background: 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 phosphatase (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 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.

Discoidin domain receptors (DDRs) DDR1 and DDR2 are receptor tyrosine kinases with the unique ability among receptor tyrosine kinases to respond to collagen. Several signaling molecules have been implicated in DDR signaling, including Shp-2, Src, and MAPK pathways, but a detailed understanding of these pathways and their transcriptional targets is still lacking. Similarly, the regulation of the expression of DDRs is poorly characterized with only a few inflammatory mediators, such as lipopolysaccharide and interleukin-1β identified as playing a role in DDR1 expression. DDRs have been reported to induce the expression of various genes including matrix metalloproteinases and bone morphogenetic proteins, but the regulatory mechanisms underlying DDR-induced gene expression remain to be determined. The aim of the present work was to elucidate the molecular mechanisms implicated in the expression of DDRs and to identify DDR-induced signaling pathways and target genes. Our data show that collagen I induces the expression of DDR1 in a dose- and time-dependent manner in primary human lung fibroblasts. Furthermore, activation of DDR2, JAK2, and ERK1/2 MAPK signaling pathways was essential for collagen I-induced DDR1 and matrix metalloproteinase 10 expression. Finally, inhibition of the ERK1/2 pathway abrogated DDR1 expression by blocking the recruitment of the transcription factor polyoma enhancer A-binding protein 3 to the DDR1 promoter. Our data provide new insights into the molecular mechanisms of collagen I-induced DDR1 expression and demonstrate an important role for ERK1/2 activation and the recruitment of polyoma enhancer-A binding protein 3 to the DDR1 promoter.