Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.

Dietary flavonoids may have a protective and therapeutic effect in Parkinson disease: A systematic review.

Parkinson disease (PD) is characterized by the loss of dopaminergic neurons because of oxidative stress and neuroinflammation. Polyphenols in vegetables, known for their high antioxidant capacity, may prevent the onset, or delay the progression of the disease; among these, flavonoids are the most abundant class of polyphenols in foods. Clinical and cohort studies have evaluated the effect of polyphenol consumption on the risk of developing PD or of attenuating the symptoms after diagnosis; therefore, it is necessary to integrate the scientific evidence into making dietary recommendations. The objective of this study was to perform a systematic review of randomized controlled trials and cohort studies that have investigated the use of polyphenols in PD. The studies were identified through the PubMed, Science Direct, Scielo, and Web of Science databases. A total of 1100 studies were found; these were analyzed and filtered by 2 independent reviewers. After completion, 5 studies were included (3 randomized controlled trials and 2 cohort studies). The consumption of flavonoids, anthocyanins, or 2-5 servings/week of specific foods (apples, red wine, blueberries, and strawberries) reduces the risk of PD and associated mortality. Treatment with licorice, curcumin, or cocoa, which are rich in flavonoids and other polyphenols, improves motor function in PD patients. No statistically significant differences were found in quality of life, disease progression or nonmotor symptoms such as cognitive ability and mood. Although cohort studies suggest a neuroprotective effect, further clinical studies are urgently needed to evaluate the effect of specific flavonoids and other polyphenols in PD.

Anthocyanin supplementation improves obesity-related inflammatory characteristics: A systematic review and meta-analysis of randomized controlled trials.

The relationship between anthocyanin intake and obesity-related inflammatory markers remains unclear in existing research. To investigate this, we hypothesized that anthocyanin supplementation could reduce plasma concentrations of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1, and other cytokines in obesity. We conducted a systematic search of PubMed, Web of Science, Scopus, SinoMed, and other related literature and identified 16 randomized controlled trials that met our inclusion criteria. Our findings showed that anthocyanin intake was significantly associated with a reduction in vascular cell adhesion molecule-1 mean plasma concentrations (-53.56 ng/mL; 95% confidence interval [CI], -82.10 to -25.03). We also observed a modest decrease in CRP (-0.27 ng/mL; 95% CI, -0.58 to 0.05), TNF-α (-0.20 ng/mL; 95% CI, -0.54 to 0.15), and IL-6 (-0.53 ng/mL; 95% CI, -1.16 to 0.10) mean plasma concentrations. Subgroup analysis revealed that anthocyanin intake tended to decrease CRP and IL-6 concentrations in overweight or dyslipidemic individuals. Additionally, the intervention duration subgroup analysis showed that anthocyanin supplementation had a stronger effect on plasma IL-6 and TNF-α in participants after 8 to 12 weeks of intervention. In conclusion, our meta-analysis indicated that anthocyanin supplementation can effectively reduce obesity-related inflammatory markers associated with chronic low-grade inflammation.

Recent insights into the hepatoprotective potential of medicinal plants and plant-derived compounds.

Liver problems are a worldwide concern, and conventional medicinal therapies are ineffective. Hence, safeguarding the healthy liver is vital for good health and well-being. Infections due to virus, immune problems, cancer, alcohol abuse, and an overdose of drugs are some of the causes of liver diseases. Antioxidants derived from medicinal plants and conventional dietary sources can protect the liver from damages caused by oxidative stress system and various chemicals. Plants and plant-derived phytochemicals are appealing hepatoprotective agents since they have less side effects and still there is a lot of interest shown in using herbal tonics for treating liver disorders. This review therefore primarily focuses on newly discovered medicinal plants and compounds produced from plants that fall under the classifications of flavonoids, alkaloids, terpenoids, polyphenolics, sterols, anthocyanins, and saponin glycosides, all of which have the potential to be hepatoprotective. Hosta plantaginea, Ligusticum chuanxiong, Daniella oliveri, Garcinia mangostana, Solanum melongena, Vaccinium myrtillus, Picrorhiza kurroa, and Citrus medica are some potential plants having hepatoprotective effects. We conclude that these phytochemicals and the plant extracts listed above are used in the future to treat a variety of liver diseases, additional research is still needed to develop safer and more potent phytochemical drugs.

An updated overview of cyanidins for chemoprevention and cancer therapy.

Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-ß-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration.

Cornelian Cherry (Cornus mas L.) Iridoid and Anthocyanin-Rich Extract Reduces Various Oxidation, Inflammation, and Adhesion Markers in a Cholesterol-Rich Diet Rabbit Model.

Atherogenesis leads to the development of atherosclerosis, a progressive chronic disease characterized by subendothelial lipoprotein retention and endothelial impairment in the arterial wall. It develops mainly as a result of inflammation and also many other complex processes, which arise from, among others, oxidation and adhesion. Cornelian cherry (Cornus mas L.) fruits are abundant in iridoids and anthocyanins-compounds with potent antioxidant and anti-inflammatory activity. This study aimed to determine the effect of two different doses (10 mg and 50 mg per kg of body weight, respectively) of iridoid and anthocyanin-rich resin-purified Cornelian cherry extract on the markers that are important in the progress of inflammation, cell proliferation and adhesion, immune system cell infiltration, and atherosclerotic lesion development in a cholesterol-rich diet rabbit model. We used biobank blood and liver samples that were collected during the previous original experiment. We assessed the mRNA expression of MMP-1, MMP-9, IL-6, NOX, and VCAM-1 in the aorta, and the serum levels of VCAM-1, ICAM-1, CRP, PON-1, MCP-1, and PCT. The application of the Cornelian cherry extract at a dose of 50 mg/kg bw resulted in a significant reduction in MMP-1, IL-6, and NOX mRNA expression in the aorta and a decrease in VCAM-1, ICAM-1, PON-1, and PCT serum levels. The administration of a 10 mg/kg bw dose caused a significant decrease in serum ICAM-1, PON-1, and MCP-1. The results indicate the potential usefulness of the Cornelian cherry extract in the prevention or treatment of atherogenesis-related cardiovascular diseases, such as atherosclerosis or metabolic syndrome.

Anthocyanins: Potential Therapeutic Approaches towards Obesity and Diabetes Mellitus Type 2.

Overweight and obesity are present in about three-quarters of the adult population in Mexico. The inflammatory mechanisms subjacent to visceral white adipose tissue are accountable for the initiation and development of cardiometabolic alterations, including type 2 diabetes. Lifestyle changes are pillars within its therapeutics and, thus, current dietary modifications should include not only hypocaloric prescriptions with balanced macronutrient intake, preferably by increasing the amount of whole grains, fruits, vegetables, nuts and legumes, but in concomitance, bioactive substances, such as anthocyanins, have been correlated with lower incidence of this disease.

Anthocyanins-rich interventions on oxidative stress, inflammation and lipid profile in patients undergoing hemodialysis: meta-analysis and meta-regression.

The aim of this systematic review and meta-analysis was to evaluate the effects of anthocyanins-interventions on oxidative stress, inflammation, and lipid profile in patients undergoing hemodialysis. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO CRD42020209742). The primary outcome was anthocyanins-rich intervention on OS parameters and secondary outcome was anthocyanins-rich intervention on inflammation and dyslipidemia. RevMan 5.4 software was used to analyze the effect size of anthocyanins-rich intervention on OS, inflammation and dyslipidemia. Meta-analysis effect size calculations incorporated random-effects model for both outcomes 1 and 2. Eight studies were included in the systematic review (trials enrolling 715 patients; 165 men and 195 women; age range between 30 and 79 years). Anthocyanin intervention in patients undergoing hemodialysis decrease the oxidant parameters (std. mean: -2.64, 95% CI: [-3.77, -1.50], P ≤ 0.0001, I2 = 97%). Specially by reduction of malondialdehyde products in favor of anthocyanins-rich intervention (std. mean: -14.58 µmol.L, 95% CI: [-26.20, -2.96], P ≤ 0.0001, I2 = 99%) and myeloperoxidase (std. mean: -1.28 ηg.mL, 95% CI: [-2.11, -0.45], P = 0.003, I2 = 77%) against placebo group. Decrease inflammatory parameters (std. mean: -0.57, 95% CI: [-0.98, -0.16], P = 0.007, I2 = 79%), increase HDL cholesterol levels (std. mean: 0.58 mg.dL, 95% CI: [0.23, 0.94], P = 0.001, I2 = 12%) against placebo group. Anthocyanins-rich intervention seems to reduce oxidative stress, inflammatory parameters and improve lipid profile by increasing HDL cholesterol levels in patients with chronic kidney disease undergoing hemodialysis.

Cyanidin as potential anticancer agent targeting various proliferative pathways.

A natural compound cyanidin, which is a type of anthocyanin present in pigmented leaves, fruits, and flowers; distributed widely in berries, apples, and oranges possess anticancer activities, thus curing various types of cancer such as breast, liver, lung, prostate, and thyroid cancer. The article provides an insight into the potential of using a single phytochemical, cyanidin to treat various cancer types including breast, liver, lung, prostate, and thyroid cancer. Information about cyanidin and its pharmacological impact on cancer was collected from books, scientific journals, and reports through electronic data search (Web of Science, Scifinder, PubMed, Scopus, Google Scholar, Elsevier, Springer, Wiley, ACS, Science Direct, CNKI as well as Kew Plants of the Word Online) and library. Cyanidin produces its effects against cancer probably by inhibiting (RAS, MAPK) and activating (caspases-3 and P-38) innovative molecular pathways. It may cause cell cycle arrest, cell differentiation processes and changes in redox status which trigger the cytotoxic chemotherapeutic effects. However, it also optimizes the chemotherapeutic targets which are cancer cells less responsive to chemotherapy. Cancer is considered the most widely spread disease and cyanidin from natural origin provides an essential role in treatment of cancer by approaching various mechanistic pathways.

Dried Bilberry (Vaccinium myrtillus L.) Alleviates the Inflammation and Adverse Metabolic Effects Caused by a High-Fat Diet in a Mouse Model of Obesity.

Obesity is an increasing problem worldwide. It is often associated with co-morbidities such as type II diabetes, atherosclerotic diseases, and non-alcoholic fatty liver disease. The risk of these diseases can be lowered by relieving the systemic low-grade inflammation associated with obesity, even without noticeable weight loss. Bilberry is an anthocyanin-rich wild berry with known antioxidant and anti-inflammatory properties. In the present study, a high-fat-diet-induced mouse model of obesity was used to investigate the effects of air-dried bilberry powder on weight gain, systemic inflammation, lipid and glucose metabolism, and changes in the gene expression in adipose and hepatic tissues. The bilberry supplementation was unable to modify the weight gain, but it prevented the increase in the hepatic injury marker ALT and many inflammatory factors like SAA, MCP1, and CXCL14 induced by the high-fat diet. The bilberry supplementation also partially prevented the increase in serum cholesterol, glucose, and insulin levels. In conclusion, the bilberry supplementation alleviated the systemic and hepatic inflammation and retarded the development of unwanted changes in the lipid and glucose metabolism induced by the high-fat diet. Thus, the bilberry supplementation seemed to support to retain a healthier metabolic phenotype during developing obesity, and that effect might have been contributed to by bilberry anthocyanins.

Can Nutrition Play a Role in Ameliorating Digital Eye Strain?

Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.

Anthocyanin Encapsulated Nanoparticles as a Pulmonary Delivery System.

Anthocyanins are known for their therapeutic efficacy for many human diseases, including cancer. After ingestion, anthocyanins degrade due to oxidation and enzymatic breakdown, resulting in reduced therapeutic efficacy. Direct delivery to target tissues and entrapment of anthocyanins increases their stability, bioavailability, and therapeutic efficacy. The objective of the present study was to develop a direct delivery system of anthocyanins into pulmonary tissues via encapsulated nanocarriers. A cyanidin-3-O-glucoside (C3G)-rich anthocyanin extract was prepared from well-ripened haskap (Lonicera caerulea L.) berries (HB) and encapsulated in three different polymeric nanocarrier systems: polyethylene glycol-poly(lactide-co-glycolide), maltodextrin, and carboxymethyl chitosan (CMC). The anthocyanin encapsulation efficiency was significantly higher in CMC (10%) than in the other two polymers. The cytotoxicity and cytoprotective effect of HB anthocyanin-encapsulated CMC (HB-CMC, 4 µg of C3G equivalent anthocyanin in 2 mg/mL nanoparticle) and anthocyanin-free CMC (E-CMC, 2 mg/mL) were tested for cytotoxicity using human normal lung epithelial BEAS-2B cells. The CMC nanoparticles were not cytotoxic for BEAS-2B cells. The HB-CMC nanoparticles reduced carcinogen-induced oxidative stress in BEAS-2B cells and restored the expression of superoxide dismutase and glutathione peroxidase enzymes. The HB-CMC nanoparticles also reduced carcinogen-induced DNA single-strand breaks and alkaline-labile sites but not the double-strand breaks. The E-CMC, HB-CMC (28 µg C3G equivalent/mouse/day for six days), or the same dose of free HB anthocyanin was administered to A/JCr mice through a nose-only passive inhalation device. C3G and its metabolites, cyanidin, peonidin-3-O-glucoside, and cyanidin-3-O-glucuronide, were detected by UPLC/ESI/Q-TOF-MS in the lungs of mice after one hour of exposure. Therefore, the CMC could be a promising noncytotoxic candidate to encapsulate HB anthocyanin. Direct delivery of anthocyanin to lung tissues enhances tissue retention, slows phase 2 metabolism, and improves therapeutic efficacy.

Consumption of oils and anthocyanins may positively modulate PPAR-γ expression in chronic noncommunicable diseases: A systematic review.

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) plays a central role in health and is an essential cardioprotective factor because of its effect on lipid and glucose metabolism, inflammation, and oxidative stress. We hypothesized that nutritional strategies positively regulate PPAR-γ expression in patients with noncommunicable diseases (NCDs). A systematic search was conducted using PubMed, Scientific Electronic Library Online (SciELO), and LILACS databases from May 2020 to January 2021. Eligibility criteria included placebo-controlled randomized clinical trials in adults with chronic diseases involving nutritional strategies, which performed PPAR-γ analysis (majority on mononuclear cells) before and after the intervention. The exclusion criteria included studies published more than 10 years ago, studies not published in English or Spanish, theses, reviews, and other study designs. The review was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological quality was assessed based on 7 criteria obtained from the Cochrane Handbook. A total of 7 studies were included that reported the effects of different nutritional strategies (such as anthocyanins, fish oil, Berberis vulgaris juice, ketogenic diet, flaxseed oil, olive oil) on 346 patients with NCDs (such as type 2 diabetes, hypertension, obesity, and cancer) between 18 and 85 years of age. These results suggest that anthocyanins, flaxseed oil, and olive oil may function as putative PPAR-γ agonists.

Blueberry Anthocyanins Extract Attenuates Acrylamide-Induced Oxidative Stress and Neuroinflammation in Rats.

Acrylamide (AA) is a widespread environmental and dietary-derived neurotoxin, which can induce oxidative stress and associated inflammation in the brain. Anthocyanins widely occur as natural antioxidant and anti-inflammatory phytochemicals. Herein, the protective effects of blueberry anthocyanins extract (BAE) against AA-induced neurotoxicity were investigated in rats. The rats were pretreated with BAE (175 mg/kg body weight/day) by oral gavage for the first 7 days, followed by the co-administration of BAE and AA (35 mg/kg body weight/day) by oral gavage for the next 12 days. Results showed that BAE significantly decreased the malondialdehyde (MDA) production, and increased glutathione (GSH) and antioxidant enzyme levels; and it also suppressed microglial activation, astrocytic reaction, and pro-inflammatory cytokine expressions. Furthermore, BAE elevated the extracellular signal-related kinase (ERK)/cAMP response elements binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway, and relieved the accumulation of amyloid beta (Aß) 1-42 and 1-40 after AA exposure. Consequently, AA-induced neuronal necrosis and downregulation of synaptosomal-associated protein 25 (SNAP-25) were attenuated by BAE in the hippocampus and cerebral cortex. In conclusion, BAE can exert a protective function on neurons and synapses against AA-induced oxidative stress and neuroinflammation.

In vitro anticancer properties of anthocyanins: A systematic review.

Anthocyanins have been associated with beneficial effects on human health. Cancer has been one of the main public health issues due to its aggressiveness and high mortality rate. This systematic review aimed to address recent research (from January 2000 to September 2021) on the anticancer activity of anthocyanins assessed by in vitro assays. The selected studies revealed that anthocyanins have anticancer potential by inhibiting cancer cell viability and proliferation, controlling cell cycle, and promoting apoptosis.

Maternal AA/EPA Ratio and Triglycerides as Potential Biomarkers of Patients at Major Risk for Pharmacological Therapy in Gestational Diabetes.

Gestational diabetes mellitus (GD) is characterized by glycemic and lipid metabolism alterations in an environment of low-grade inflammation. Our trial aimed to assess the effect of nutraceutical supplements (omega-3 fatty acids, anthocyanins, and alpha-cyclodextrins) in GD patients and evaluate the role of anthropometric, metabolic, and inflammatory parameters as biomarkers to identify subjects who require pharmacological hypoglycemic treatment during gestation. Pregnant women with GD at 24-28 weeks of gestation were enrolled in a double-blind trial and randomized to receive either nutraceutical supplements or a placebo for 12 weeks. No statistically significant differences were observed between the two groups in blood and urine measurements of metabolic, inflammatory, and antioxidant parameters. In the whole cohort, pre-pregnancy BMI and anthropometric measurements were significantly different in patients who required pharmacological intervention. These patients showed higher triglycerides, CRP, and insulin levels and gave birth to newborns with significantly higher weights. Subjects with a greater AA/EPA ratio had higher PAF levels and gave birth four days earlier. In conclusion, one-to-one nutritional coaching and poor compliance with nutraceutical supplementation might have outweighed the impact of this intervention. However, triglyceride concentration and the AA/EPA ratio seems to be a biomarker for higher inflammatory levels and GD candidates for pharmacological treatment. An adequate assumption of omega-3 in women with GD, either by a controlled diet or by nutraceutical supplementation, reduces the need for pharmacological therapy.

The anticancer effects of cyanidin 3-O-glucoside combined with 5-fluorouracil on lung large-cell carcinoma in nude mice.

The haskap (Lonicera caerulea L., Caprifoliaceae) berry has been widely used in traditional medicine in Kuril Islands, Russia, Japan, and China. Cyanidin-3-O-glucoside (C3G) is the most abundant anthocyanin in haskap berries, and C3G induces antiproliferative pharmacological activity in various cancer cells. However, no study has investigated its anti-lung large-cell carcinoma (LCC) pharmacological role. Therefore, this study determined whether C3G alone or C3G combined with 5-fluorouracil (5-FU) inhibits human lung LCC. We determined the tumor growth, apoptosis, inflammation, and metastasis in the H661 lung LCC lines xenografted into BALB/c nude mice. The mice were administered saline (control), 5-FU, C3G, or both C3G and 5-FU. Relative to the control mice, those treated with C3G alone or both C3G and 5-FU exhibited impaired tumor growth; increased tumor apoptosis; decreased inflammatory cytokine levels (e.g., IL-1ß, TNF-α, C-reactive protein, and IL-6); decreased inflammation-related factors, including cyclooxygenase-2 protein and nuclear factor-κB (NF-κB) mRNA; increased inhibition of NF-κB kinase α mRNA; and downregulated metastasis-related factors, such as transforming growth factor-ß, CD44, epidermal growth factor receptor, and vascular endothelial growth factor. In addition, C3G alone or combined with 5-FU affected the expression of the tumor microenvironment-related factors Ki67, CD45, PDL1, and CD73. Compared with the mice treated with 5-FU or C3G alone, those treated with both C3G and 5-FU exhibited significantly impaired tumor growth, decreased tumor sizes, and increased tumor inhibition. This in vivo study demonstrated that C3G alone or combined with 5-FU may impair the growth of lung LCC and inhibit tumorigenesis. The findings indicate that C3G alone or C3G combined with 5-FU may be beneficial for treating human lung LCC.

The Promising Therapeutic and Preventive Properties of Anthocyanidins/Anthocyanins on Prostate Cancer.

As water-soluble flavonoid derivatives, anthocyanidins and anthocyanins are the plants pigments mostly rich in berries, pomegranate, grapes, and dark color fruits. Many bioactivity properties of these advantageous phytochemicals have been reported; among them, their significant abilities in the suppression of tumor cells are of the promising therapeutic features, which have recently attracted great attention. The prostate malignancy, is considered the 2nd fatal and the most distributed cancer type in men worldwide. The present study was designated to gather the preclinical and clinical studies evaluating potencies of anthocyanidins/anthocyanins for the treatment and prevention of this cancer type for the first time. In general, findings confirm that the anthocyanins (especifically cyanidin-3-O-glucoside) indicated higher activity against prostatic neoplasms compared to their correlated anthocyanidins (e.g., delphinidin); in which potent anti-inflammatory, apoptosis, and anti-proliferative activities were analyzed. Complementary anti-prostate cancer assessment of diverse naturally occurred anthocyanidins/anthocyanins and their synthetically optimized derivatives through preclinical experiments and eventually confirmed by clinical trials can promisingly lead to discover natural-based chemotherapeutic drug options.

Recent Advances in the Antiproliferative and Proapoptotic Activity of Various Plant Extracts and Constituents against Murine Malignant Melanoma.

Although conventional medicine, chemical drug synthesis and pharmaceutical research are advancing at a rapid pace, nature remains a major supplier of biological molecules. Natural bioactive compounds are studied closely especially as an alternative to the limitations of conventional therapy in many diseases, melanoma being one of them. Malignant melanoma is a highly aggressive type of cancer, and the current methods of treatment used are cryotherapy, external surgery, radiation therapy, chemotherapy, photodynamic therapy, biological therapy, and targeted drug therapy. Unfortunately, these treatment methods are often inefficient, extremely expensive and cause many side effects, which is why focusing on melanoma chemoprevention and adjuvant therapy with natural herbal phytoconstituents is an emerging strategy to prevent, cure or treat melanoma. This review aims to examine the latest discoveries in terms of potential natural bioactive compounds that possess important activity against the development and spread of murine melanoma cancer. In particular, the use of different phytochemicals such as phenolic acids, flavonoids, anthocyanins, terpenoids, essential oils and carotenoids in vitro and in vivo models will be discussed. These data are helpful in guiding researchers in the direction of studying phytonutrients with important effects in the prevention and treatment of melanoma.