The therapeutic effects of berberine for gastrointestinal cancers.

Cancer is one of the most serious human health issues. Drug therapy is the major common way to treat cancer. There is a growing interest in using natural compounds to overcome drug resistance, adverse reactions, and target specificity of certain types of drugs that may affect several targets with fewer side effects and be beneficial against various types of cancer. In this regard, the use of herbal medicines alone or in combination with the main anticancer drugs is commonly available. Berberine (BBR), a nature-driven phytochemical component, is a well-known nutraceutical due to its wide variety of pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiparasitic, antidiabetic, antihypertensive, and hypolipidemic. In addition, BBR exerts anticancer activities. In present article, we summarized the information available on the therapeutic effects of BBR and its mechanisms on five types of the most prevalent gastrointestinal cancers, including esophageal, gastric, colorectal, hepatocarcinoma, and pancreatic cancers.

Melatonin and cisplatin co-treatment against cancer: A mechanistic review of their synergistic effects and melatonin's protective actions.

Combination chemotherapy appears to be a preferable option for some cancer patients, especially when the medications target multiple pathways of oncogenesis; individuals treated with combination treatments may have a better prognosis than those treated with single agent chemotherapy. However, research has revealed that this is not always the case, and that this technique may just enhance toxicity while having little effect on boosting the anticancer effects of the medications. Cisplatin (CDDP) is a chemotherapeutic medicine that is commonly used to treat many forms of cancer. However, it has major adverse effects such as cardiotoxicity, skin necrosis, testicular toxicity, and nephrotoxicity. Many research have been conducted to investigate the effectiveness of melatonin (MLT) as an anticancer medication. MLT operates in a variety of ways, including decreasing cancer cell growth, causing apoptosis, and preventing metastasis. We review the literature on the role of MLT as an adjuvant in CDDP-based chemotherapies and discuss how MLT may enhance CDDP's antitumor effects (e.g., by inducing apoptosis and suppressing metastasis) while protecting other organs from its adverse effects, such as cardio- and nephrotoxicity.

Potential of natural products in osteosarcoma treatment: Focus on molecular mechanisms.

Osteosarcoma is the most frequent type of bone cancer found in children and adolescents, and commonly arises in the metaphyseal region of tubular long bones. Standard therapeutic approaches, such as surgery, chemotherapy, and radiation therapy, are used in the management of osteosarcoma. In recent years, the mortality rate of osteosarcoma has decreased due to advances in treatment methods. Today, the scientific community is investigating the use of different naturally derived active principles against various types of cancer. Natural bioactive compounds can function against cancer cells in two ways. Firstly they can act as classical cytotoxic compounds by non-specifically affecting macromolecules, such as DNA, enzymes, and microtubules, which are also expressed in normal proliferating cells, but to a greater extent by cancer cells. Secondly, they can act against oncogenic signal transduction pathways, many of which are activated in cancer cells. Some bioactive plant-derived agents are gaining increasing attention because of their anti-cancer properties. Moreover, some naturally-derived compounds can significantly promote the effectiveness of standard chemotherapy drugs, and in certain cases are able to ameliorate drug-induced adverse effects caused by chemotherapy. In the present review we summarize the effects of various naturally-occurring bioactive compounds against osteosarcoma.

Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.

Silymarin contains a group of closely-related flavonolignan compounds including silibinin, and is extracted from Silybum marianum species, also called milk thistle. Silymarin has been shown to protect the liver in both experimental models and clinical studies. The chemopreventive activity of silymarin has shown some efficacy against cancer both in vitro and in vivo. Silymarin can modulate apoptosis in vitro and survival in vivo, by interfering with the expression of cell cycle regulators and apoptosis-associated proteins. In addition to its anti-metastatic activity, silymarin has also been reported to exhibit anti-inflammatory activity. The chemoprotective effects of silymarin and silibinin (its major constituent) suggest they could be applied to reduce the side effects and increase the anti-cancer effects of chemotherapy and radiotherapy in various cancer types, especially in gastrointestinal cancers. This review examines the recent studies and summarizes the mechanistic pathways and down-stream targets of silymarin in the therapy of gastrointestinal cancer.

An Update on the Effects of Probiotics on Gastrointestinal Cancers.

Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.

Nanomicellar-curcumin exerts its therapeutic effects via affecting angiogenesis, apoptosis, and T cells in a mouse model of melanoma lung metastasis.

BACKGROUND: Curcumin is a natural phytochemical polyphenol with significant anti-cancer effects and negligible side effects. In this study, the therapeutic capacity of nanomicellar-curcumin for treating lung metastasis was evaluated in an immunocompetent mouse model of metastatic melanoma. MARTIALS AND METHODS: Two doses of nanomicellar-curcumin (i.e. 10 and 20 µM) were used to induce cytotoxicity in 3 melanoma cell lines. A total of 60 mice were allocated to 20 mice in each of three groups (10 for survival and 10 for assays). Groups were no treatment control, PBS control, nanomicellar-curcumin 20 mg/kg IP 4 times a week, for three weeks). Immunohistochemistry, TUNEL assay, and Western blots were used on lung samples. RESULTS: Nanomicellar-curcumin inhibited the in vitro growth of B16 F10 melanoma cells at 20 µM over 72 h. In vivo, 20 mg/kg nanomicellar-curcumin injected IP, delayed tumor cell growth and significantly extended mouse survival rate. Tumor infiltration of regulatory T cells and angiogenesis were reduced, while IFN-γ and CXCL10 were increased. CONCLUSION: Nanomicellar-curcumin can inhibit lung metastasis and growing melanoma via activation of apoptosis, activated T cells and inhibition of angiogenesis, tumor growth and regulatory T cells.

Quercetin as an anticancer agent: Focus on esophageal cancer.

Esophageal cancer (EC) is regarded as the sixth highest contributor to all cancer-related mortality, worldwide. In spite of advances in the treatment of EC, currently used methods remain ineffective. Quercetin, as a dietary antioxidant, is a plant flavonol from the flavonoid group of polyphenols, and can be found in numerous vegetables, fruits, and herbs. Quercetin can affect the processes of cancer-related diseases via cell proliferation inhibitory effects, potential apoptosis effects, and antioxidant properties. Of the various types of cancer, the use of quercetin has now become prominent in the treatment of EC. In this review, we discuss how quercetin may be an important supplement for the prevention, treatment, and management of EC, owing to its natural origin, and low-cost relative to synthetic cancer drugs. However, most findings cited in the current study are based on in vitro and in vivo studies, and thus, further human-based research is necessitated. PRACTICAL APPLICATIONS: In spite of advances in the treatment of esophageal cancer, currently used methods remain ineffective, therefore, an alternative or complementary therapy is required. Quercetin, as a dietary antioxidant, can affect the processes of cancer-related diseases via cell proliferation inhibitory effects, potential proapoptotic functions, and antioxidant properties. Quercetin may be an important supplement for the prevention, treatment, and management of EC, owing to its natural origin. The low cost of quercetin as supplement or dietary intake, relative to synthetic cancer drugs, is an advantage of the compound which should be considered.

Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt Signaling Pathways.

Glioblastoma (GBM) is the most serious brain tumor and shows a high rate of drug resistance. Wnt signaling is a very important pathway in GBM that can activate/inhibit other pathways, such as apoptosis and autophagy. In this study, we evaluated the efficacy of a combination of temozolomide (TMZ) plus curcumin or nanomicellar-curcumin on the inhibition of GBM growth in vitro, via effects on autophagy, apoptosis, and the Wnt signaling pathway. Two concentrations of curcumin and nanomicellar-curcumin (i.e., 20 µM and 50 µM) alone, and in combination with TMZ (50 µM) were used to induce cytotoxicity in the U87 GBM cell line. Wnt signaling-, autophagy-, and apoptosis-related genes were assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blots. All treatments (except 20 µM curcumin alone) significantly decreased the viability of U87 cells compared to controls. Curcumin (50 µM), nanomicellar-curcumin alone and in combination with TMZ significantly decreased the invasion and migration of U87 cells. Autophagy-related proteins (Beclin 1, LC3-I, LC3-II) were significantly increased. Apoptosis-related proteins (Bcl-2 and caspase 8) were also significantly increased, while Bax protein was significantly decreased. The expression levels of Wnt pathway-associated genes (ß-catenin, cyclin D1, Twist, and ZEB1) were significantly reduced.

Effect of Lactobacillusplantarum containing probiotics on blood pressure: A systematic review and meta-analysis.

Previous studies have recommended that probiotics may have blood pressure (BP)-lowering effects. However, they examined all probiotic strains (multi/single probiotics) simultaneously. In respect to strain specificity properties of probiotic, the aim of the present study was to systematically investigate the role of Lactobacillus plantarum as an anti-hypertensive agent by performing a meta-analysis of randomized controlled trials. PubMed, Scopus, Cochrane Library and Google Scholar were used from inception until October 2018 to identify eligible trials. We used random-effects model as the preferable method to assess the combined treatment effect. We further conducted sensitivity analysis and stratified analysis. Seven studies with 653 participants were included in the meta-analysis. The pooled weighted mean difference (WMD) with the random effects model showed a significant effects of Lactobacillus plantarum supplementation on improvement of SBP with no statistically significant heterogeneity (WMD: -1.58 mmHg, 95 % CI: -3.05 to 0.11) (heterogeneity P = 0.14; I² = 36 %). The overall effect in the DBP showed significant pooled estimates (WMD: -0.92 mmHg, 95 % CI: -1.49 to -0.35) with a complete homogeneity between the studies (heterogeneity P = 0.46; I² = 0 %). The findings of the present meta-analysis study support the use of Lactobacillus plantarum supplementation for lowering systolic and diastolic blood pressure. The clinical significance of blood pressure-lowering effect of Lactobacillus Plantarum supplementation is not considerable; however, given the overarching benefits evident and concurrent lack of specific side effects, further trials are warranted to clarify the effects of Lactobacillus Plantarum probiotics particularly for hypertensive patients.

Medicinal Plants As Natural Polarizers of Macrophages: Phytochemicals and Pharmacological Effects.

Macrophages are one of the crucial mediators of the immune response in different physiological and pathological conditions. These cells have critical functions in the inflammation mechanisms that are involved in the inhibition or progression of a wide range of diseases including cancer, autoimmune diseases, etc. It has been shown that macrophages are generally divided into two subtypes, M1 and M2, which are distinguished on the basis of their different gene expression patterns and phenotype. M1 macrophages are known as pro-inflammatory cells and are involved in inflammatory mechanisms, whereas M2 macrophages are known as anti-inflammatory cells that are involved in the inhibition of the inflammatory pathways. M2 macrophages help in tissue healing via producing anti-inflammatory cytokines. Increasing evidence indicated that the appearance of different macrophage subtypes is associated with the fate of diseases (progression versus suppression). Hence, polarization of macrophages can be introduced as an important venue in finding, designing and developing novel therapeutic approaches. Albeit, there are different pharmacological agents that are used for the treatment of various disorders, it has been shown that several natural compounds have the potential to regulate M1 to M2 macrophage polarization and vice versa. Herein, for the first time, we summarized new insights into the pharmacological effects of natural compounds on macrophage polarization.

Anti-cancer effects of cinnamon: Insights into its apoptosis effects.

Cancer is known as a leading cause of death worldwide. In the last two decades, the incidence of cancer has been dramatically increased mostly due to lifestyle changes. The importance of this issue has attracted further attention to discover novel therapies to prevent and treat cancers. According to previous studies, drugs used to treat cancer have shown significant limitations. Therefore, the role of herbal medicines alone or in combination with chemotherapy drugs has been extensively studied in cancer treatment. Cinnamon is a natural component showing a wide range of pharmacological functions including anti-oxidant, anti-microbial and anti-cancer activities. Impaired apoptosis plays critical roles in the initiation and progression of cancer. Increasing evidence indicates that cinnamon, as a therapeutic agent, has anti-cancer effects via affecting numerous apoptosis-related pathways in cancer cells. Here, we highlighted anticancer properties of cinnamon, particularly through targeting apoptosis-related mechanisms.

Effect of cinnamon (Cinnamomum Zeylanicum) supplementation on serum C-reactive protein concentrations: A meta-analysis and systematic review.

OBJECTIVE: The effect of cinnamon (Cinnamomum Zeylanicum) on serum C-reactive protein (CRP), an acute phase protein commonly used as a marker of inflammation, is uncertain. Therefore, the objective of the present study was to conduct a systematic review and meta-analysis of published randomised controlled trials (RCTs) of cinnamon to determine the effect on levels of serum CRP, relative to controls. DESIGN: Studies were identified by a search of electronic databases including PubMed, Cochrane Library, Google Scholar and Scopus before August 2018. Combined and stratified analyses were used. Weighted mean differences (WMD) and its 95% confidence interval were estimated for net change in serum CRP by using random-effects model. The heterogeneity of meta-analysis was assessed by χ2 and I2 test. RESULTS: Six studies were identified, and data from 285 participants were included. Pooled analysis showed significant reductions in serum CRP (WMD: -0.81 mg/L, 95% CI: -1.36 to -0.26, p = 0.004), with significant heterogeneity between selected studies. Improvements in sub-group analysis were observed when baseline CRP levels were greater than 3 mg/dL, and in trials of >12 weeks duration. Doses <1500 mg/day and ≥1500 mg/day were effective in lowering serum CRP (WMD: -0.56 mg/dL, 95% CI: -1.01 to -0.10, p = 0.02 and WMD: -2.13 mg/dL, 95% CI: -4.08 to -0.19, p = 0.03), respectively, with significantly reduced heterogeneity in trials with lower doses of cinnamon <1500 mg/day (test for heterogeneity: P = 0.22 and I2 = 33%). No changes were found in controls. CONCLUSION: Cinnamon supplementation improves levels of serum CRP, particularly in chronic conditions, where basal CRP levels are raised. Further well-designed studies are warranted to confirm or not the above-mentioned findings.