PMID: 

Int Immunopharmacol. 2018 Feb ;55:120-127. Epub 2017 Dec 22. PMID: 29248792

Abstract Title: 

Crocin alleviates coronary atherosclerosis via inhibiting lipid synthesis and inducing M2 macrophage polarization.

Abstract: 

Atherosclerosis is a chronic inflammatory disease arising from an imbalance in lipid levels and the accumulation of cholesterol-laden macrophages in the artery wall. Crocin is an active ingredient of Crocus sativus L. This study established a rat coronary atherosclerosis model induced by vitamin D3 (VD3), to explore the effect of Crocin on lipid metabolism, macrophage polarization and the activity of inflammatory proteins. The results revealed that Crocin decreased blood lipid levels by decreasing the levels of endothelin (ET), total cholesterol (TC), triglyceridelow (TG) and low-density lipoprotein cholesterol (LDL-c), elevating the level of high-density lipoprotein cholesterin (HDL-c). Crocin also inhibited lipogenesis by suppressing the expression of lipogenesis-related proteins and elevating lipid catabolism-related proteins. Moreover, Crocin effectively alleviated inflammation by suppressing the expression of pro-inflammatory cytokines and increasing levels of anti-inflammatory cytokines. We further found that Crocin promoted macrophage polarization to the M2 phenotype by reducing M1 markers (CD40and CD11c) and elevating M2 markers (CD68and CD206). Finally, Crocin strongly inhibited the expression of NF-κB p65 and its translocation into the nucleus. Crocin partially counteracted nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 expression and the nuclei accumulation caused by NF-κB p65 overexpression. Taken together, our research indicated that Crocin inhibited lipogenesis and alleviated the inflammation in a VD3-induced rat coronary atherosclerosis model by promoting M2 macrophage polarization and maybe by inhibiting NF-κB p65 nuclear translocation. This study implicates Crocin as a potential therapeutic strategy for coronary atherosclerosis.

read more

PMID: 

Arch Gynecol Obstet. 2018 03 ;297(3):717-724. Epub 2018 Jan 13. PMID: 29332222

Abstract Title: 

Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder associated with post-menopausal hot flashes: a double-blind, randomized, placebo-controlled trial.

Abstract: 

PURPOSE: Due to concerns regarding the side effects of hormone therapy, many studies have focused on the development of non-hormonal agents for treatment of hot flashes. The aim of this study was to evaluate the efficacy and safety of saffron (stigma of Crocus sativus) in treatment of major depressive disorder associated with post-menopausal hot flashes.METHODS: Sixty women with post-menopausal hot flashes participated in this study. The patients randomly received either saffron (30 mg/day, 15 mg twice per day) or placebo for 6 weeks. The patients were assessed using the Hot Flash-Related Daily Interference Scale (HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist at baseline and also at the second, fourth, and sixth weeks of the study.RESULTS: Fifty-six patients completed the trial. Baseline characteristics of the participants did not differ significantly between the two groups. General linear model repeated measures demonstrated significant effect for time × treatment interaction on the HFRDIS score [F (3, 162) = 10.41, p = 0.0001] and HDRS score [F (3, 162) = 5.48, p = 0.001]. Frequency of adverse events was not significantly different between the two groups.CONCLUSIONS: Results from this study revealed that saffron is a safe and effective treatment in improving hot flashes and depressive symptoms in post-menopausal healthy women. On the other hand, saffron, with fewer side effects, may provide a non-hormonal and alternative herbal medicine option in treatment of women with hot flashes.

read more

PMID: 

Avicenna J Phytomed. 2018 Jan-Feb;8(1):14-23. PMID: 29387570

Abstract Title: 

Protective effect of crocin against d-galactose-induced aging in mice.

Abstract: 

Objective: Aging is a multifactorial phenomenon, which attribute to different diseases and abnormalities in living systems. Oxidative stress, which is an important factor in aging, exacerbates this process via different mechanisms. Crocin (CR), one of the active components of saffron showed strong antioxidant effects. In the present study, anti-aging property of crocin was investigated in mice.Materials and Methods: The model of aging was induced using administration of d-galactose (500 mg/kg, s. c.) for 42 days. Animals were treated with crocin (10, 20, 40 mg/kg, i.p.) during treatment with d-galactose. At the end of treatment, levels of malondialdehyde (MDA) as a lipid peroxidation marker and glutathione content (GSH) in the liver and brain were measured. Also, biochemical factors including liver enzymes (ALT and AST), male sex hormones including testosterone and dehydroepiandrosterone-sulfate (DHEA-SO) and pro-inflammatory markers such as tumor necrosis factor -α (TNF-α) and interlukine-6 (IL-6) in serum, were evaluated.Results: Administration of d-galactose led to induction of lipid peroxidation in liver and brain tissues, as well as elevation of AST, ALT, and pro-inflammatory cytokines and reduction of male sex hormones levels in serum. Interestingly, treatment of animals with crocin (10, 20 and 40 mg/kg) diminished lipid peroxidation in the liver and brain tissues while elevated GSH content. Also, a decline in serum levels of TNF-α and IL-6 and an elevation of male sex hormones were observed following treatment with crocin.Conclusion: Administration of crocin reduced d-galactose-induced aging in mice through inhibition of oxidative stress, reduction of inflammation and elevation of sex hormones.

read more

PMID: 

Avicenna J Phytomed. 2018 Jan-Feb;8(1):43-50. PMID: 29387573

Abstract Title: 

Saffron improved depression and reduced homocysteine level in patients with major depression: A Randomized, double-blind study.

Abstract: 

Objectives: A correlation between hyperhomocysteinemia, and depression has been reported. Saffron () is recommended for treatment of depression; hence, in this study the effect of co-administration of saffron and fluoxetine on plasma homocysteine and depression was evaluated.Material and methods: This was a 4-week randomized and double-blind clinical trial which was conducted from March 2013 to February 2014. In this trial, 40 male and females (20-55 years old) diagnosed with severe depression were selected and following filing the Beck form, were randomly divided into two groups. Experimental group was treated with fluoxetine 20 mg/day and saffron 30 mg /day and the control group received placebo and fluoxetine 20 mg/day for four weeks. Before treatment and at the end of the study, fasting blood samples were collected. For females, blood samples were collected on the third day of their menstrual cycle.Results: A significant reduction of homocysteine levels was observed in both sex in the experimental group compared to before treatment (p

read more

PMID: 

Zhonghua Xin Xue Guan Bing Za Zhi. 2019 Aug 24 ;47(8):647-652. PMID: 31434437

Abstract Title: 

[Protective effects of berberine against exhaustion exercise induced myocardial injury in rats].

Abstract: 

To investigate the effect and possible mechanism of berberine (Ber) on myocardial injury induced by exhaustion exercise (Ee).Forty healthy male SPF Sprague-Dawley rats were randomly divided into 5 groups using the random unit group design method: control group, Ee group and Ee plus Ber group (low: 50 mg·kg(-1)·d(-1), medium: 100 mg·kg(-1)·d(-1) and high dose: 150 mg·kg(-1)·d(-1),8 each). Ber (1.5 ml) or equal volume saline was given per gavage for 14 days. Rats assigned to Ee groups underwent Ee swimming once daily and rats in control group remain sedentary. After 14 days, echocardiographic measurements were performed and left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular diastolic diameter (LVIDd) and left ventricular systolic diameter (LVIDs) were obtained. The morphological structure of heart was detected by HE and Masson staining. Serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Cardiomyocytes apoptosis was detected by TUNEL method. The protein expression of myocardial hypertrophy marker protein B-type natriuretic peptide (BNP) and apoptotic marker protein (Bcl-2, Bax) in rat myocardial tissue was detected by Western blot.(1) Both LVFS and LVEF were significantly lower, and LVIDs and LVIDd were significantly larger in Ee group than those in control group (all0.01). The LVFS and LVEF in medium dose of Ber and high-dose Ber groups were significantly higher, and the LVIDs and LVIDd were significantly smaller than those in Ee group (all0.01). (2) The results of HE staining showed that the myocardial cells in control group were closely arranged, regular, normal in morphology, clear in structure, and uniform in staining. The myocardial cells of rats in Ee group were disarranged, cell staining was uneven, and vacuoles appeared in the cytoplasm. The disorder of myocardial cell arrangement and unequal staining in the medium dose of Ber were attenuated than in Ee group. The Masson staining results showed that the myocardial cells in control group were closely arranged, regular, normal in shape, clear in structure, and rarely blue-stained (fibrosis). Myocardial cells in rats in Ee group showed obvious fibrosis. The myocardial cell fibrosis in rats with medium dose of Ber was significantly reduced than exercise group. (3) MDA content in myocardial tissue of rats in Ee group was significantly higher than that of control group, and MDA content in myocardial tissue of rats in medium dose of Ber group was significantly lower than in Ee group (0.01). The SOD activity of myocardial tissue in rats was significantly lower than that of control group, while that of rats with medium dose of Ber was significantly higher than that of rats in Ee group (0.01). (4) TUNEL staining results showed that only a small amount of apoptosis myocardial cells were seen in control group, and a large number of apoptosis myocardial cells were seen in rats in Ee group. However, the number of apoptotic cardiomyocytes in medium dose of Ber was significantly lower than that in Ee group. The AI of rat cardiomyocytes was significantly higher than that of control group (0.01), and the AI of rat cardiomyocytes in median dose of Ber group was significantly lower than in Ee group (0.01). (5) BNP and Bax protein expression in the myocardial tissues of rats in Ee group were significantly higher than in control group (0.01). BNP and Bax protein expression in the myocardial tissues in median dose of Ber group were significantly lower than that of Ee group (0.01). The myocardial protein expression level of Bax was significantly higher, and the myocardial protein level of Bcl-2 was significantly lower in Ee group than in control group (both0.01), treatment with median dose of Ber could partly reverse above changes (both0.01).Ber can attenuate exhaustion exercise induced myocardial injury and remodeling in rats, and the beneficial effects of Ber might possibly be mediated by reducing free radical release and cardiomyocytes apoptosis.

read more

PMID: 

Front Pharmacol. 2019 ;10:857. Epub 2019 Aug 6. PMID: 31447670

Abstract Title: 

An Insight Into the Molecular Mechanism of Berberine Towards Multiple Cancer Types Through Systems Pharmacology.

Abstract: 

Over the past several decades, natural products with poly-pharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Berberine (PubChem CID: 2353), a soliloquies quaternary alkaloid, has been validated to exert powerful effects in many cancers. However, the underlying molecular mechanism is not yet fully elucidated. In this study, we summarized the molecular effects of berberine against multiple cancers based on current available literatures. Furthermore, a systems pharmacology infrastructure was developed to discover new cancer indications of berberine and explore their molecular mechanisms. Specifically, we incorporated 289 high-quality protein targets of berberine by integrating experimental drug-target interactions (DTIs) extracted from literatures and computationally predicted DTIs inferred by network-based inference approach. Statistical network models were developed for identification of new cancer indications of berberine through integration of DTIs and curated cancer significantly mutated genes (SMGs). High accuracy was yielded for our statistical models. We further discussed three typical cancer indications (hepatocarcinoma, lung adenocarcinoma, and bladder carcinoma) of berberine with new mechanisms of actions (MOAs) based on our systems pharmacology framework. In summary, this study systematically provides a powerful strategy to identify potential anti-cancer effects of berberine with novel mechanisms from a systems pharmacology perspective.

read more

PMID: 

Biosci Biotechnol Biochem. 2019 Aug 29:1-13. Epub 2019 Aug 29. PMID: 31462179

Abstract Title: 

Berberine and palmatine inhibit the growth of human rhabdomyosarcoma cells.

Abstract: 

A natural isoquinoline alkaloid, berberine, has been known to exhibit anti-tumor activity in various cancer cellsinducing cell cycle arrest. However, it has not been investigated whether berberine and its analogs inhibit the growth of rhabdomyosarcoma (RMS), which is the most frequent soft tissue tumor in children. The present study examined the anti-tumor effects of berberine and palmatine on expansions of three human embryonal RMS cell lines; ERMS1, KYM1, and RD. Intracellular incorporation of berberine was relatively higher than that of palmatine in every RMS cell line. Berberine significantly inhibited the cell cycle of all RMS cells at Gphase. On the other hand, palmatine only suppressed the growth of RD cells. Both of berberine and palmatine strongly inhibited the growth of tumorsphere of RD cells in three-dimensional culture. These results indicate that berberine derivatives have the potential of anti-tumor drugs for RMS therapy.: ARMS: alveolar rhabdomyosarcoma; ERMS: embryonal rhabdomyosarcoma; RMS: rhabdomyosarcoma.

read more

PMID: 

Int Heart J. 2018 Mar 30 ;59(2):387-393. Epub 2018 Feb 23. PMID: 29479012

Abstract Title: 

Crocin Attenuates Oxidative Stress and Myocardial Infarction Injury in Rats.

Abstract: 

Oxidative stress and excessive nitric oxide (NO) production play considerable roles in infarction-induced injury impairing cardiac functions. Crocin is the active constituent of Crocus sativus (saffron) with antioxidant properties and has protective effects against disturbances induced by ischemia in many organs. The present study aimed to investigate the protective effects and the underlying mechanisms of crocin on myocardial infarction (MI)-induced injury in rats in vivo. MI rats were intraperitoneally injected with crocin at different doses for seven successive days after coronary ligation. Infarct size, hemodynamic studies, and capillary density were evaluated. Levels of oxidative stress, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and their corresponding phosphorylation expressions were then measured. Crocin decreased infarct size, left ventricular (LV) end-diastolic pressure, and LV minimum dP/dt while increased LV maximum dP/dt and percentage of LV fractional shortening dose dependently. Capillary density was markedly increased after crocin treatment. Crocin enhanced superoxide dismutase activity and reduced malondialdehyde levels as well as inhibited excessive production of NO through downregulating iNOS as well as upregulating eNOS during MI-induced injury. This study reveals that crocin improves MI-induced impairments in cardiac function, which is associated with its antioxidant properties.

read more

PMID: 

Biomed Pharmacother. 2018 May ;101:174-180. Epub 2018 Feb 24. PMID: 29486335

Abstract Title: 

Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system.

Abstract: 

Chemotherapy induced testicular toxicity is an emerging reason for azoospermia and impotency in males. Cyclophosphamide (CP) is a widely used chemotherapeutic agent to manage neoplastic and non-neoplastic autoimmune diseases. Testicular toxicity along with bladder and hepatotoxicity are its widely reported adverse effects. Crocin (CR) is the digentiobiosyl ester of crocetin, found in the fruits of gardenia (Gardenia jasminoides E.) and dried stigmas of saffron (Crocus sativus L.) possess antioxidant, anti-depressant, anti-tumor and aphrodisiac properties. In the light of these reports, the present study aimed to investigate protective effect of CR administration (10 mg/kg and 20 mg/kg per day for eight weeks) on CP induced (15 mg/kg per week for eight weeks) testicular toxicity in male Sprague dawley rats by analysing the Glutathione redox cycle, Sperm quality, spermatogenic and steroidogenesis hormonal axis, caspase 3 activity and histological investigations. Administration of CR preserved the glutathione redox cycle, sperm quality, hormonal mediators associated with sperm production. It also decreased testicular apoptosis as evident from the reduction of caspase 3 activity. These biochemical findings were well reflected on the histo-pathologicalinvestigation. Conclusively, the results of this study indicate that administration of CR can dose dependently attenuate the toxic effects of CP on testis.

read more

PMID: 

Microvasc Res. 2018 07 ;118:82-89. Epub 2018 Mar 7. PMID: 29524452

Abstract Title: 

Protective effects of saffron and its active components against oxidative stress and apoptosis in endothelial cells.

Abstract: 

In this study, we investigated the role of mitogen-activated protein kinase (MAPK) signaling pathways in mediation of the protective effects of saffron extract, saffron essential oil, safranal and crocin on bovine aortic endothelial cells against oxidative injury. The viability of cells in response to HO-induced toxicity (0.4, 2 and 10 mM) was measured using resazurin assay in the presence or absence of saffron extract (2-40 μg/ml), saffron oil (2-40 μg/ml), safranal (2-40 μM) and crocin (2-40 μM). Dichlorodihydrofluorescin diacetate was used as an indicator for the amount of reactive oxygen species (ROS) in cells at the same concentrations of samples as the former test. In addition, propidium iodide staining of the fragmented DNA was performed to measure the level of apoptotic cells by the application of 2-10 μM of crocin and safranal. Finally, the proteins involved in apoptosis were detected using westernblotting at the concentration of 0, 2, 10 μM for crocin and safranal. The results indicated that all tested moieties improved viability and reduced ROS production in HO-treated cells (p 

read more