SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway

Pulsatilla koreana has been used as a traditional medicine for the treatment of several diseases. The purpose of this study was to determine if SB365, Pulsatilla saponin D isolated from the root of P. koreana inhibits the progression of colon cancer. We found that SB365 strongly suppressed the growth and proliferation of colon cancer cells and induced their apoptosis. Also, SB365 showed anti-angiogenic activity by decreasing the expression of HIF-1α and VEGF. These results were confirmed by an in vivo study showing that SB365 significantly inhibited tumor growth by the induction of apoptosis and inhibition of angiogenesis with stronger anticancer activity than 5-FU. When further examined for its anticancer mechanism, SB365 effectively suppressed the AKT/mTOR pathway both in vitro and in vivo. Taken together, our study demonstrated that SB365 inhibits the AKT/mTOR pathway, leading to the suppression of tumor growth and angiogenesis together with induction of apoptosis. Therefore, SB365 is a good candidate as a natural product for use in the treatment of colon cancer.     

Polysaccharides derived from Lycium barbarum suppress IGF-1-induced angiogenesis via PI3K/HIF-1α/VEGF signalling pathways in MCF-7 cells

Lycium barbarum (LB) is a berry-type fruit. Lycium barbarum polysaccharides (LBPs), derived from LB, has anti-tumour properties and exhibits potent anti-angiogenic effects. The aim of this study was to elucidate possible signal transduction pathways functioning to mediate the breast cancer-suppressive effects of LBPs. Using MCF-7 cells, we determined that a 90 h treatment with 0.50 mg/ml of LBPs resulted in significant inhibition of cell proliferation. Using this same system, we observed that LBPs could also affect insulin-like growth factor (IGF)-1 protein accumulation, suppress phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated-PI3K (p-PI3K) protein levels, inhibit hypoxia-inducible factor-1 (HIF-1α) protein accumulation without altering HIF-1α mRNA levels, and suppress VEGF mRNA expression and protein production. Our results demonstrate that LBPs may inhibit tumour cell growth by suppressing IGF-1-induced angiogenesis via PI3K/HIF-1α/VEGF signalling pathways.     

The modulation of endothelial cell gene expression by green tea polyphenol-EGCG

Human and animal studies have shown that green tea consumption is associated with a reduced risk of some cancers. This has been attributed to its polyphenol components, in particular (-)-epigallocatechin gallate (EGCG). In addition to be a cancer chemopreventive agent, EGCG inhibits angiogenesis, thus reducing tumor growth and metastasis. We tested EGCG modulation on the gene expression profile of endothelial cells stimulated by VEGF using Affymetrix microarrays. A total of 421 genes were up-regulated and 72 genes were down-regulated at the false discovery rate of 5% by VEGF, EGCG, and EGCG pretreatment followed by VEGF stimulation. The changes in the expression of several pivotal genes were validated by real-time PCR. Furthermore, we have identified two signaling pathways (Wnt and Id) involved in cell proliferation were inhibited by EGCG treatment, suggesting the negative regulation of EGCG on cell proliferation. Our results also indicate that the antiangiogenesis effect of EGCG is partially mediated through its broad inhibition on endothelial cell proliferation. Our data further support earlier observations that the anticancer effect of EGCG is mediated through changes in the expression of genes that are associated with cell proliferation.     

Bioactive Lipids in Pathological Retinopathy

Diabetic retinopathy is a common condition that occurs in patients with diabetes with long-standing hyperglycemia that is characterized by inappropriate angiogenesis. This pathological angiogenesis could be a sort of physiological proliferative response to injury by the endothelium. Recent studies suggested that reactive oxygen species (ROS) play a significant role in this angiogenesis. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that plays a significant role in diabetic retinopathy. The interaction between VEGF and ROS, and theirs in turn with pro- and anti-inflammatory cytokines and anti-inflammatory bioactive lipid molecules such as lipoxins, resolvins, protectins, and maresins is particularly relevant to understand the pathophysiology of diabetic retinopathy and develop future therapeutic interventions.     

l‐Citrulline Supplementation‐Increased Skeletal Muscle PGC‐1α Expression Is Associated with Exercise Performance and Increased Skeletal Muscle Weight

Scope

l ‐citrulline has recently been reported as a more effective supplement for promoting intracellular nitric oxide (NO) production compared to l ‐arginine. Here, the effect of l ‐citrulline on skeletal muscle and its influence on exercise performance were investigated. The underlying mechanism of its effect, specifically on the expression of skeletal muscle peroxisome proliferator‐activated receptor‐gamma coactivator‐1α (PGC‐1α), was also elucidated.

Methods and results

Six‐week‐old ICR mice were orally supplemented with l ‐citrulline (250 mg kg^?1) daily, and their performance in weight‐loaded swimming exercise every other day for 15 days, was evaluated. In addition, mice muscles were weighed and evaluated for the expression of PGC‐1α and PGC‐1α‐regulated genes. Mice orally supplemented with l ‐citrulline had significantly higher gastrocnemius and biceps femoris muscle mass. Although not statistically significant, l ‐citrulline prolonged the swimming time to exhaustion. PGC‐1α upregulation was associated with vascular endothelial growth factor α (VEGFα) and insulin‐like growth factor 1 (IGF‐1) upregulation. VEGFα and IGF‐1 are important for angiogenesis and muscle growth, respectively, and are regulated by PGC‐1α. Treatment with NG‐nitro‐l ‐arginine methyl ester hydrochloride (l ‐NAME), a nitric oxide synthesis inhibitor, suppressed the l ‐citrulline‐induced PGC‐1α upregulation in vitro.

Conclusion

Supplementation with l ‐citrulline upregulates skeletal muscle PGC‐1α levels resulting in higher skeletal muscle weight that improves time to exhaustion during exercise.

     

Human endometrial angiogenesis

Angiogenesis is the development of new microvessels from existing vessels, a process that involves microvascular endothelial cells. Physiological angiogenesis rarely occurs in adults except in the ovary and endometrium during the reproductive life of females. Angiogenesis occurs by sprouting and non-sprouting mechanisms. Since endothelial sprouts are not observed in human endometrium, we hypothesized that non-sprouting mechanisms such as intussusception and elongation are involved in endometrial angiogenesis. The demand for angiogenesis differs spatially and temporally in the endometrium: angiogenesis occurs in the basalis layer during menstruation and in the functionalis and subepithelial capillary plexus during the proliferative and early secretory stages. Most studies have failed to demonstrate a link between expression of endometrial angiogenic factors and new vessel growth. However, we demonstrated recently a strong relationship between vascular endothelial growth factor (VEGF) immunolocalized in in-travascular neutrophils and endothelial cell proliferation in each of the subepithelial capillary plexus, functionalis and basalis regions of the human endometrium. Our data also indicate that focal neutrophil VEGF has a role in the development of the subepithelial capillary plexus and functionalis microvessels during the proliferative phase of the menstrual cycle. We propose that neutrophils are an intravascular source of VEGF for vessels that undergo angiogenesis by intussusception and elongation.     

Health functionality of apigenin: A review

Apigenin is being used by humans in the form of plant extract for the treatment of a number of disorders and inflammatory conditions, until its discovery as a core compound. Apigenin, chemically known as 4′, 5, 7,-trihydroxyflavone is a yellow crystalline powder belonging to the flavone class, that is the aglycone of several naturally occurring glycosides. It is insoluble in water but soluble in organic solvents. Numerous pharmacological activities, including anti-inflammatory, anti-toxicant, anti-cancer, etc., are attributed to apigenin. Research has shown that apigenin has numerous molecular targets involved in inflammation. Based on the in vivo, in vitro, and clinical trial studies suggested that apigenin is a potent therapeutic agent to overcome diseases such as rheumatoid arthritis, autoimmune disorders, Parkinson’s disease, Alzheimer’s disease, and various type of cancers. Delayed plasma clearance and slow decomposition in liver increases its systemic bioavailability, and makes it a strong therapeutic agent in pharmaceutical studies. In the present review, detailed accounts of the properties of apigenin have been discussed.     

Bioactive Components and Health-Promoting Properties of Yuzu (Citrus ichangensis × C. reticulate)

Yuzu (Citrus ichangensis × C. reticulate) fruit is an important functional food that possesses several health-promoting properties. It has been widely used in commercial medical products, healthy foods, and cosmetics in many countries. Yuzu is a rich source of wide variety of non-nutritive compounds, such as flavonoids, anthocyanins, phenolic acids, carotenoids, and tannins; as well as nutritive compounds such as sugars, proteins, vitamins, fibers, and minerals. Yuzu fruit (juice, peel, and seeds) and its bioactive compounds have been demonstrated to have numerous functional properties, such as antioxidant, anti-inflammatory, anticancer, antiplatelet, angiogenesis, and antimicrobial properties, both in vitro and in vivo. These diverse applications provided by the yuzu fruit (juice, peel, and seeds) and its bioactive compounds are of great industrial importance. This review summarizes the composition, nutritional values, and functional properties of yuzu fruit, and their biological activity in relation to their potential impact on human health.     

Anti-cancer properties and mechanisms of action of thymoquinone,the major active ingredient of Nigella sativa

Over the past two decades, studies have documented the wide-range anti-cancer effects of Nigella sativa, known as black seed or black cumin. Thymoquinone (TQ), its major active ingredient, has also been extensively studied and reported to possess potent anti-cancer properties. Herein, we provide a comprehensive review of the findings related to the anti-cancer activity of TQ. The review focuses on analyzing experimental studies performed using different in vitro and in vivo models to identify the anti-proliferative, pro-apoptotic, anti-oxidant, cytotoxic, anti-metastatic, and NK-dependent cytotoxic effects exerted by TQ. In addition, we pinpoint the molecular mechanisms underlying these effects and the signal transduction pathways implicated by TQ. Our analysis show that p53, NF-κB, PPARγ, STAT3, MAPK, and PI3K/AKT signaling pathways are among the most significant pathways through which TQ mediates its anti-cancer activity. Experimental findings and recent advances in the field highlight TQ as an effective therapeutic agent for the suppression of tumor development, growth and metastasis for a wide range of tumors.     

抗血管生成药物的研究进展与临床应用

血管生成(angiogenesis)在恶性肿瘤和视网膜病变等疾病过程中发挥着重要作用.随着血管新生的调节机制逐渐被揭示,抗血管生成药物的研发也取得新的突破,目前成功获批上市的抗血管生成靶向药物已达十余种,主要包括小分子多靶点血管靶向药物、大分子单靶点血管靶向药物、内源性泛靶点血管靶向药物3类.本文对抗血管生成策略的理论...     

Chemotherapy of fascioliasis. II. 4-cyano-2-iodo-6-nitrophenol (nitroxynil) and related compounds

A series of halogenated nitro- and cyano-phenols has been synthesised for structure-activity studies against the liver fluke, Fasciola hepatica. Hie functional groups of the most effective compound, 4-cyano- 2-iodo-6-nitrophenol (nitroxynil), have been modified in several ways.     

Health Benefits of Purple Corn (Zea mays L.) Phenolic Compounds

Purple corn (Zea mays L.), a grain with one of the deepest shades in the plant kingdom, has caught the attention of the food industry as it could serve as a source for alternatives to synthetic colorants. Also being rich in phenolic compounds with potential health‐promoting properties, purple corn is becoming a rising star in the novel ingredients market. Although having been widely advertised as a “healthy” food, the available information on purple corn health benefits has not yet been well reviewed and summarized. In this review, we present compositional information focused on the potential functional phenolic compounds correlated to health‐promoting effects. Studies evaluating potential health‐benefitting properties, including in vitro tests, cell models, animal and human trials, are also discussed. This paper emphasizes research using purple corn, or its extracts, but some other plant sources with similar phenolic composition to purple corn are also mentioned. Dosage and toxicity of purple corn studies are also reviewed. Purple corn phenolic compounds have been shown in numerous studies to have potent antioxidant, anti‐inflammatory, antimutagenic, anticarcinogenic, and anti‐angiogenesis properties. They were also found to ameliorate lifestyle diseases, such as obesity, diabetes, hyperglycemia, hypertension, and cardiovascular diseases, based on their strong antioxidant power involving biochemical regulation amelioration. With promising evidence from cell and animal studies, this rich source of health‐promoting compounds warrants additional attention to better understand its potential contributions to human health.     

Probiotic Lactic Acid Bacteria and Skin Health

Human skin is the first defense barrier against the external environment, especially microbial pathogens and physical stimulation. Many studies on skin health with Lactic acid bacteria (LAB) have been published for many years, including prevention of skin disease and improvement of skin conditions. LAB, a major group of gram-positive bacteria, are known to be beneficial to human health by acting as probiotics. Recent studies have shown that LAB and their extracts have beneficial effects on maintenance and improvement of skin health. Oral administration of Lactobacillus delbrueckii inhibits the development of atopic disease. In addition, LAB and LAB extracts are known to have beneficial effects on intestinal diseases, with Lactobacillus plantarum having been shown to attenuate IL-10 deficient colitis. In addition to intestinal health, L. plantarum also has beneficial effects on skin. pLTA, which is lipoteichoic acid isolated from L. plantarum, has anti-photoaging effects on human skin cells by regulating the expression matrix meralloprotionase-1 (MMP-1) expression. While several studies have proposed a relationship between diseases of the skin and small intestines, there are currently no published reviews of the effects of LAB for skin health through regulation of intestinal conditions and the immune system. In this review, we discuss recent findings on the effects of LAB on skin health and its potential applications in beauty foods.     

Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, has garnered attention for its anticancer properties. This review synthesizes existing research on PEITC, focusing on its mechanisms of action in combatting cancer. PEITC has been found to be effective against various cancer types, such as breast, prostate, lung, colon, and pancreatic cancers. Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and reduction of metastasis (spread of cancer cells to new areas). PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways. These findings suggest PEITC's potential as a therapeutic agent against cancer. However, further research is necessary to determine the optimal dosage, understand its bioavailability, and assess potential side effects. This will be crucial for developing PEITC-based treatments that are both effective and safe for clinical use in cancer therapy.     

Phytic Acid: From Antinutritional to Multiple Protection Factor of Organic Systems

Several studies have shown the benefits of natural antioxidants on health and food preservation. Phytic acid (IP6) is a natural antioxidant that is found mainly in cereals and vegetables and, for a long period of time, was considered an antinutritional factor. However, in vitro and in vivo studies have demonstrated its beneficial effects in the prevention and treatment of several pathological conditions and cancer. Despite the numerous benefits of IP6, the signs and intracellular interactions mediated by this antioxidant remain poorly understood. This review describes the main chemical and biological aspects of IP6, as well as its actions in the prevention and treatment of various diseases.     

The role of progesterone in endometrial angiogenesis in pregnant and ovariectomised mice

The role of progesterone (and oestrogen) in endometrial angiogenesis remains controversial. The aims of this study were to quantify endometrial angiogenesis in pregnant mice and to investigate the role of progesterone in promoting endothelial cell proliferation in ovariectomized mice. Uteri were collected on days 1 to 4 of pregnancy when circulating progesterone concentrations were increasing, prior to implantation. Before dissection, mice were injected with bromodeoxyuridine (BrdU) enabling proliferating endothelial cells to be quantified with CD31/BrdU double-immunohistochemistry. There was a significant increase in proliferating endothelial cells on day 3 of pregnancy when plasma progesterone also increased. To determine if this endothelial cell proliferation was due to progesterone, an experiment was performed on ovariectomised mice. One group was treated with a single oestradiol injection on day 8 after ovariectomy, followed by a no-treatment day and three consecutive daily injections of progesterone. Other groups were treated with either the vehicle, oestradiol or progesterone injections only; all were dissected on day 13 following ovariectomy. Unexpectedly, mice treated with progesterone-only had the highest amount of endothelial cell proliferation and oestrogen priming was found to significantly reduce this progesterone-induced endothelial cell proliferation. To determine if this proliferation is mediated by vascular endothelial growth factor (VEGF), a further experiment in which VEGF anti-serum was administered concurrently with the progesterone injections was performed. Endothelial cell proliferation was reduced but not abolished suggesting progesterone-induced endometrial angiogenesis is only partly mediated by VEGF. Results indicate that oestrogen priming is not required for progesterone to stimulate endometrial endothelial cell proliferation and that oestrogen inhibits progesterone-induced angiogenesis in ovariectomised mice.     

A critical review of the relationship between dietary components,the gut microbe Akkermansia muciniphila,and human health

Abstract

The human gut contains trillions of microorganisms with a great diversity that are associated with various health benefits. Recent studies have reported an increasing correlation between diet, gut microbiota, and human health, indicating rapid development in the field of gut health. Diet is an important factor that determines the gut microbiota composition. The gut comprises great diversities of microbes involved in immune modulation and other functions. In particular, Akkermansia muciniphila is a mucin-degrading bacterium is believed to have several health benefits in humans. Several studies have evaluated the prebiotic effects of various dietary components on A. muciniphila and their association with various ailments, such as diabetes mellitus, atherosclerosis, and cancer. Hence, this review aims to provide a plausible mechanistic basis for the interactions between dietary components, and A. muciniphila and for the therapeutic benefits of this interaction on various illnesses.     

Production of nutritious precooked foods in developing countries by low‐cost extrusion technology

Medicinal plants represent one approach in the management of liver injuries due to various factors such as infection, toxification, and immune damage in Oriental society. One of these plants, Ganoderma (Ling Zhi, Reishi mushroom; Aphyllophoromycetideae), has been widely used for the treatment of hepatopathy of various etiologies. This article highlights the hepatoprotective activity of Ganoderma mushroom, with an emphasis on the possible biochemical mechanisms. Preclinical studies demonstrated that Ganoderma extracts, which mainly contain polysaccharides or triterpenoids, protected the liver against injury caused by exposure to toxic chemicals (e.g., CCl₄) or Bacillus Calmette-Guerin (BCG) plus lipopolysaccharide (LPS). Interestingly, Ganoderma extracts showed antihepatitis B virus (HBV) in a duckling model. A randomized placebo-controlled clinical trial by our group showed that treatment with Ganoderma polysaccharides for 12 weeks significantly decreased hepatitis B e antigen (HbeAg) and HBV DNA levels in 25% (13/52) patients with HB. The underlying mechanisms for the hepatoprotective effects of Ganoderma are largely unclear, but several potential biochemical pathways have been implicated. For example, the hepatoprotective effect of Ganoderma has been ascribed to its antioxidant and radical-scavenging activity, inhibition of β-glucuronidase, modulation of nitric oxide production, modulation of hepatic phase I and II enzymes, antifibrotic and antiviral activity, maintenance of hepatocellular calcium homeostasis, and immunomodulating effect. Given that Ganoderma has shown promising efficacy and was well tolerated for the management of various hepatic injuries, further studies are needed to explore the kinetics and mechanisms of action of Ganoderma constituents with hepatoprotective activity.