Modulación por Passiflora edulis de triglicéridos y colesterol intracelulares en líneas celulares de cáncer colorrectal SW480 y sus derivadas metastásicas (SW620) / Modulation by Passiflora edulis of intracellular triglycerides and cholesterol in SW480 col orectal cancer cell lines and their metastatic derivatives (SW620)

Cancer cells modify lipid metabolism to proliferate, Passiflora edulis ( P. edulis ) fruit juice (ZuFru) has antitumor activity, but whether a mechanism is through modulation of cell lipids is unknown. T o establish if ZuFru modifies cholesterol and triglycerides in SW480 and SW620. ZuFru composition was studied by phytochemical march; antiproliferative activity by sulforhodamine B, cholesterol , and triglycerides by Folch method. Z ufru contains anthocyanins, flavonoids, alkaloids , and tannins. Cell lines showed differences in their growth rate ( p =0.049). At 39.6 µg/m L of ZuFru, cell viability was decreased: SW480 (45.6%) and SW620 (45.1%). In SW480, cholesterol (44.6%) and triglycerides (46.5%) decreased; In SW620, cholesterol decreased 14.8% and triglycerides increased 7%, with significant differences for both lines. A ntiproliferative activity of ZuFru could be associated with the inhibition of intracellular biosynthesis of cholesterol and triglycerides in SW480. Action mechanisms need to be further investigated.

Las células cancerosas modifican el metabolismo lipídico para proliferar; el zumo de fruta (ZuFru) de Passiflora edulis ( P. edulis ) tiene activida d antitumoral, sin embargo, se desconoce si se involucran los lípidos celulares. E stablecer si ZuFru modifica colesterol y triglicéridos en células SW480 y SW620. C omposición del ZuFru, actividad antiproliferativa, colesterol y triglicéridos. Se encontraro n antocianinas, flavonoides, alcaloides y taninos. Las líneas celulares mostraron diferencias en su tasa de crecimiento ( p =0 . 049); ZuFru 39,6 µg/ml se disminuyó la viabilidad celular; SW480 (45,6%) y SW620 (45,1%); en SW480 colesterol (44,6%) y triglicérid os (46,5%) en SW620, colesterol (14,8%) y los triglicéridos aumentaron 7%, con diferencias significativas para ambas líneas. La actividad antiproliferativa del ZuFru podría estar asociada a la inhibición de la biosíntesis intracelular de colesterol y de tr iglicéridos en SW480, pero no en SW620. Estos mecanismos de acción deben ser fuertemente investigados.

Identification of antarctic soil bacteria exhibiting antiproliferative activity against a colon cancer cell line / Identificación de bacterias de suelo antártico que presentan actividad antiproliferativa sobre una línea celular de cáncer de colon

SUMMARY: Cancer is the second leading cause of death in the world and colorectal cancer is the only cancer that has shown a sustained increase in mortality in the last decade. In the search for new chemotherapeutic agents against cancer, extremophilic microorganisms have shown to be a potential source to obtain molecules of natural origin and with selective cytotoxic action towards cancer cells. In this work we analyzed the ability of a collection of Antarctic soil bacteria, isolated on Collins Glacier from the rhizosphere of Deschampsia antarctica Desv plant, to secrete molecules capable of inhibiting cell proliferation of a colorectal cancer tumor line. Our results demonstrated that culture supernatants from the Antarctic bacteria K2I17 and MI12 decreased the viability of LoVo cells, a colorectal adenocarcinoma cell line. Phenotypic and genotypic characterization of the Antarctic bacteria showed that they were taxonomically related and nucleotide identity analysis based on the 16S rRNA gene sequence identified the bacterium K2I17 as a species belonging to the genus Bacillus.

El cáncer es la segunda causa de muerte en el mundo y el cáncer colorrectal es el único que presenta un aumento sostenido de la mortalidad en la última década. En la búsqueda de nuevos agentes quimioterapeúticos contra el cáncer, se ha propuesto a los microorganismos extremófilos como una fuente potencial para obtener moléculas de origen natural y con acción citotóxica selectiva hacia las células cancerígenas. En este trabajo analizamos la capacidad de una colección de bacterias de suelo antártico, aisladas en el glaciar Collins desde rizosfera de la planta de Deschampsia antarctica Desv, de secretar moléculas capaces de inhibir la proliferación celular de una línea tumoral de cáncer colorrectal. Nuestros resultados demostraron que los sobrenadantes de cultivo de las bacterias antárticas K2I17 y MI12 disminuyeron la viabilidad de la línea celular de adenocarcinoma colorrectal LoVo, en un ensayo de reducción metabólica de MTT. La caracterización fenotípica y genotípica de las bacterias antárticas, demostró que estaban relacionadas taxonómicamente y el análisis de la identidad nucleotídica en base a la secuencia del gen ARNr 16S identificó a la bacteria K2I17 como una especie perteneciente al género Bacillus.

In vitro Antiproliferative Studies of Selected Medicinal Plants on Cancerous and Normal Cells

Globally, approximately 13% of all deaths annually are attributed to cancer. Surgery, radiation and chemotherapy are the current treatment techniques for cancer; however, these methods are expensive, have high failure rates and have been associated with detrimental side effects. Plant derived products could be good candidates in alleviating challenges being experienced with these current methods. This study aimed at evaluating the phytochemistry, antiproliferation potential, and probable mechanism of action of Albizia gummifera, Rhamnus staddo and Senna didymobotrya plant extracts. The 3– (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium (MTT) assay dye was used in the determination of the antiproliferative activity of the extracts. Extracts induction potential of p53 (apoptosis) and VEGF (angiogenesis) genes’ expression was evaluated using Real Time PCR. Phytochemical screening was done as per standard procedures. Several plant extracts exhibited antiproliferative activity against the cancerous cell lines tested showing selective toxicity to cancer cells while sparing the normal cells (SI ? 3). An upregulation of p53 and down-regulation VEGF genes was observed. Phytochemical screening revealed presence of pharmacologically important phytochemicals in the plant’s extracts. The study findings suggest exploitation of these plant extracts as potential candidates for development of drugs for the management of breast and prostate cancer.

Plantas medicinales utilizadas en la región de Teziutlán, Puebla, México / Medicinal plants used in the region of Teziutlán, Puebla, México

The objective of this work was to collect information on the curative use of plants in the municipality of Teziutlán, Puebla through semi-structured interviews. Thus, 78 plants used for medicinal purposes were identified, of which 40 are native to Mexico and 38 introduced; The value of use (UV) of each one and the Informant's Consensus Factor (FCI) of 10 categories of diseases were calculated. The five most frequently used plants are Ruta chalepensis L., Rosmarinus officinalis, Arnica montana, Loeselia mexicana (Lam.) Brandegee and Sambucus cerulea var., Neomexicana, which underwent a chemical and pharmacological review. On the other hand, the most frequent preparations are infusion and decoction, using mainly leaves (49.34%) and flowers (19.51%). It is concluded that the inhabitants of Teziutlán have a fairly homogeneous ethnomedical knowledge, setting the standard for research on its pharmacological properties.

El objetivo del presente trabajo fue recopilar información sobre el uso curativo de las plantas del municipio de Teziutlán, Puebla por medio de entrevistas semiestructuradas. Así, se identificaron 78 plantas utilizadas con fines medicinales, de las cuales 40 son propias de México y 38 introducidas; se calculó el valor de uso (UV) de cada una y el Factor de Consenso del Informante (FCI) de 10 categorías de padecimientos. Las cinco plantas utilizadas con mayor frecuencia son Ruta chalepensis L., Rosmarinus officinalis, Arnica montana, Loeselia mexicana (Lam.) Brandegee y Sambucus cerulea var., neomexicana, a las que se les hizo una revisión química y farmacológica. Por otro lado, las preparaciones más frecuentes son infusión y decocción, utilizando principalmente hojas (49.34 %) y flores (19.51 %). Se concluye que los habitantes de Teziutlán cuentan con un conocimiento etnomédico bastante homogéneo, dando la pauta para investigaciones sobre sus propiedades farmacológicas.

In vitro anticancer activity of ethanolic extract of Stoechospermum marginatum against HT-29 human colon adenocarcinoma cells

Colorectal cancer is a one of the leading causes of death globally and its clinical management of cancer involves chemotherapy. Increase in the development of resistance to the drugs used in the cancer treatment and serious side effects associated with chemotherapeutic drugs are the major limitations in cancer therapy. Hence, there exists a huge need to develop safer natural therapeutic products for cancer therapy. In this study, ethanolic extract of Stoechospermum marginatum was evaluated for its anticancer activity. The cytotoxicity of S. marginatum extract was evaluated on HT-29 cells by MTT assay. Trypan blue cell viability was also carried out to evaluate cytotoxicity and antiproliferative effect. The apoptosis-inducing potential of the extract was analyzed by acridine orange and ethidium bromide dual staining method, mitochondrial membrane potential assay and FITC Annexin V-Propidium iodide staining method. The ethanolic extract of S. marginatum showed significant dose-dependent cytotoxicity in HT-29 cells Treatment with S. marginatum extract increased number of apoptotic cells in HT-29 cells and caused damage to mitochondrial membrane potential. The findings of the present study confirmed in vitro anticancer activity of ethanolic extract S. Marginatum

Phytochemical and biological attributes of Bauhinia variegata L. (Caesalpiniaceae) / Atributos fitoquímicos e biológicos de Bauhinia variegata L. (Caesalpiniaceae)

Bauhinia variegata plant is a very popular and traditionally potent ethnomedicine. Therefore, it is need of hour to study ameliorative characteristics of B. variegata for novel secondary metabolites. The current study was designed to explore antiproliferative potential of B. variegata due to scant reports on this aspect. Extracts of various parts (flowers, leaves, bark, stem, and roots) were prepared by successive maceration using organic solvents in increasing order of polarity (n-hexane, ethyl acetate, methanol, and water). The determination of polyphenolic contents was done by using colorimetric methods while antioxidant potential was measured using reducing power assay. Brine shrimp lethality assay was performed for determining preliminary cytotoxicity and antiproliferative activity against breast cancer MCF-7 cell line using MTT protocols. Moreover, antimicrobial activities were detected by using disc diffusion assay. The alpha-amylase assay was performed to monitor the antidiabetic potential of the plant. In case of phytochemical analysis methanolic extract of leaves and bark showed highest phenolic and flavonoids contents. n-Hexane and ethyl acetate extracts of stem and roots exhibited more than 90% mortality with LD50 ranges between 1-25 µg/mL when studied by brine shrimp lethality assay. n-Hexane and ethyl acetate extracts of roots and stem also showed antiproliferative activity against human breast cancer MCF-7 cell line with IC50 values ranges between 12.10-14.20 µg/mL. Most of the extracts displayed moderately high antibacterial and antifungal activities. The n-hexane extract of roots showed antidiabetic activity with 60.80 ± 0.20% inhibition of alpha-amylase. In sum, these preliminary results will be useful for further compound isolation from selected plant parts for the discovery of antibacterial, antidiabetic, and anticancer lead candidates.

A planta Bauhinia variegata é uma etnomedicina muito popular e tradicionalmente potente. Portanto, as características de melhoria de B. variegata foram estudadas. Foi avaliada a determinação dos teores antioxidantes e polifenólicos. O ensaio de letalidade do camarão de salmoura foi realizado para determinar a citotoxicidade preliminar e a atividade antiproliferativa contra linhas de células de câncer de mama MCF-7 usando protocolos de MTT. Além disso, foram detectadas atividades antimicrobianas. O ensaio da alfa-amilase foi realizado para monitorar o potencial antidiabético da planta. Dentre vinte amostras diferentes, o extrato metanólico (EM) da casca apresentou os maiores teores fenólicos totais. A EM das folhas apresentou excelente conteúdo de flavonoides, atividade antioxidante significativa foi exibida pelo extrato hexânico do caule. O extrato do caule de hexano exibe 77,40% como citotóxico em DL50 10,50 µg/mL quando avaliado através do ensaio de letalidade de artêmia. Extratos de hexano e acetato de etila de raiz e caule mostraram atividade antiproliferativa contra a linhagem celular MCF7 de câncer de mama humano (IC50 12,10-14,20 µg/mL). Para potencial antimicrobiano importante, vários extratos exibiram excelentes atividades antibacteriana e antifúngica, enquanto o extrato de n-hexano da raiz mostrou atividade antidiabética (60,80 ± 0,20% na concentração de 200 µg/mL). Em suma, estes resultados preliminares serão úteis para isolamento adicional de compostos a partir de partes de plantas selecionadas para a descoberta de candidatos a antibacterianos, antidiabéticos e anticâncer.

Phytochemical and biological attributes of Bauhinia variegata L. (Caesalpiniaceae)

Abstract Bauhinia variegata plant is a very popular and traditionally potent ethnomedicine. Therefore, it is need of hour to study ameliorative characteristics of B. variegata for novel secondary metabolites. The current study was designed to explore antiproliferative potential of B. variegata due to scant reports on this aspect. Extracts of various parts (flowers, leaves, bark, stem, and roots) were prepared by successive maceration using organic solvents in increasing order of polarity (n-hexane, ethyl acetate, methanol, and water). The determination of polyphenolic contents was done by using colorimetric methods while antioxidant potential was measured using reducing power assay. Brine shrimp lethality assay was performed for determining preliminary cytotoxicity and antiproliferative activity against breast cancer MCF-7 cell line using MTT protocols. Moreover, antimicrobial activities were detected by using disc diffusion assay. The alpha-amylase assay was performed to monitor the antidiabetic potential of the plant. In case of phytochemical analysis methanolic extract of leaves and bark showed highest phenolic and flavonoids contents. n-Hexane and ethyl acetate extracts of stem and roots exhibited more than 90% mortality with LD50 ranges between 1-25 µg/mL when studied by brine shrimp lethality assay. n-Hexane and ethyl acetate extracts of roots and stem also showed antiproliferative activity against human breast cancer MCF-7 cell line with IC50 values ranges between 12.10-14.20 µg/mL. Most of the extracts displayed moderately high antibacterial and antifungal activities. The n-hexane extract of roots showed antidiabetic activity with 60.80 ± 0.20% inhibition of alpha-amylase. In sum, these preliminary results will be useful for further compound isolation from selected plant parts for the discovery of antibacterial, antidiabetic, and anticancer lead candidates.

Resumo A planta Bauhinia variegata é uma etnomedicina muito popular e tradicionalmente potente. Portanto, as características de melhoria de B. variegata foram estudadas. Foi avaliada a determinação dos teores antioxidantes e polifenólicos. O ensaio de letalidade do camarão de salmoura foi realizado para determinar a citotoxicidade preliminar e a atividade antiproliferativa contra linhas de células de câncer de mama MCF-7 usando protocolos de MTT. Além disso, foram detectadas atividades antimicrobianas. O ensaio da alfa-amilase foi realizado para monitorar o potencial antidiabético da planta. Dentre vinte amostras diferentes, o extrato metanólico (EM) da casca apresentou os maiores teores fenólicos totais. A EM das folhas apresentou excelente conteúdo de flavonoides, atividade antioxidante significativa foi exibida pelo extrato hexânico do caule. O extrato do caule de hexano exibe 77,40% como citotóxico em DL50 10,50 µg/mL quando avaliado através do ensaio de letalidade de artêmia. Extratos de hexano e acetato de etila de raiz e caule mostraram atividade antiproliferativa contra a linhagem celular MCF7 de câncer de mama humano (IC50 12,10-14,20 µg/mL). Para potencial antimicrobiano importante, vários extratos exibiram excelentes atividades antibacteriana e antifúngica, enquanto o extrato de n-hexano da raiz mostrou atividade antidiabética (60,80 ± 0,20% na concentração de 200 µg/mL). Em suma, estes resultados preliminares serão úteis para isolamento adicional de compostos a partir de partes de plantas selecionadas para a descoberta de candidatos a antibacterianos, antidiabéticos e anticâncer.

Prodigiosin from Serratia: Synthesis and potential applications

Prodigiosin is a red pigment with a pyrrolylpyrromethane skeleton. It is mainly produced by bacterial strains belonging to the Serratia genus, but also by some other genera, including Streptomyces and Vibrio. Within the genus Serratia, the pigment is generally produced as a virulence factor. However, it also has many important beneficial biological activities such as immunosuppressive and anti- proliferative activities. Moreover, the pigment has many industrial applications in textile and cosmetics. In this mini-review, we discuss the genetic and molecular mechanisms supporting prodigiosin synthesis and production from the Serratia genus, as well as its potential applications.

Piperine suppresses growth and migration of human breast cancer cells through attenuation of Rac1 expression

Objective: To investigate the effect of piperine on human breast cancer cells. Methods: The effect of piperine on proliferation and migration of human breast cancer cells, MCF-7 and MDA-MB-231, was investigated using colony formation assays, wound healing assays, Matrigel migration assays, flow cytometry, RT-qPCR, and Western blotting assays. Results: Piperine inhibited the growth of MCF-7 and MDA-MB-231 cells and suppressed colony formation. Cell reduction at the G 0 / G 1 phase and cell arrest at the G 2 /M phase were observed in breast cancer cells. However, the significant effect was only demonstrated in MDA-MB-231 cells. Moreover, cancer cell migration was suppressed by piperine at low concentration. RT-qPCR and Western blotting assays showed that piperine downregulated Rac1 gene and protein expression. Conclusions: Piperine could inhibit growth and migration of breast cancer cells by reducing Rac1 gene and protein expression.

Enhancing pharmaceutical potential and oral bioavailability of Allium cepa nanosuspension in male albino rats using response surface methodology

Objective: To enhance the pharmaceutical potential and oral bioavailability of quercetin contents of Allium cepa peel extract by novel nanosuspension technology. Methods: Nanoprecipitation approach was successfully used for the formulation of nanosuspension. To obtain pharmaceutical-grade nanosuspension with minimum particle size and polydispersity index, sodium lauryl sulphate was selected as a stabilizer. Important formulation parameters were statistically optimized by the response surface methodology approach. The optimized nanosuspension was subjected to stability and in vitro dissolution testing and characterized by scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and zeta sizer. To evaluate the preeminence of nanosuspension over coarse suspension, comparative bioavailability studies were carried out in male albino rats. The pharmaceutical potential of developed nanosuspension was evaluated by antioxidant, antimicrobial, and toxicity studies. Results: The optimized nanosuspension showed an average particle size of 275.5 nm with a polydispersity index and zeta potential value of 0.415 and -48.8 mV, respectively. Atomic force microscopy revealed that the average particle size of nanosuspension was below 100 nm. The formulated nanosuspension showed better stability under refrigerated conditions. Nanosuspension showed an improved dissolution rate and a 2.14-fold greater plasma concentration of quercetin than coarse suspension. Moreover, the formulated nanosuspension exhibited enhanced antioxidant and antimicrobial potential and was non-toxic. Conclusions: Optimization of nanosuspension effectively improves the pharmaceutical potential and oral bioavailability of Allium cepa extract.

Glinus lotoides ethanolic extract alleviates LPS-induced anxiety and depression-like behavior by modulating antioxidant and inflammatory biomarkers in rats

Objective: To explore the protective role of Glinus lotoides ethanolic extract in a depression model through modulating oxidant/antioxidant enzyme system and inflammatory status. Methods: Phytochemical constituents of Glinus lotoides ethanolic extract were evaluated qualitatively and quantitatively along with HPLC. Rats were divided into six groups. The normal control and the intoxicated groups received normal saline, and the standard group received imipramine, while the remaining groups received 100, 300, and 500 mg/kg Glinus lotoides ethanolic extract. All groups received treatments for 14 d. Lipopolysaccharides (LPS) were then administered i.p. (0.83 mg/kg) to all groups except the normal control group. After 24 h, anxiety and depression-like behaviors were evaluated by performing behavioral analysis (open field, tail suspension, forced swim, sucrose preference test), and determining total oxidant status, total antioxidant capacity, catalase, and biochemical parameters [malondialdehyde, glutathione, superoxide dismutase, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6]. Results: Phytochemical studies confirmed the presence of phenols and flavonoids and HPLC analysis showed the presence of gallic acid, quercetin, chlorogenic, and caffeic acid. Total oxidant status was significantly decreased, while total antioxidant capacity was significantly increased in the Glinus lotoides ethanolic extract treated groups. Moreover, Glinus lotoides ethanolic extract diminished malondialdehyde, IL-6, and TNF-alpha levels, while increasing superoxide dismutase, catalase, and glutathione activities. Conclusions: Glinus lotoides ethanolic crude extract shows significant antidepressant activity by modulating oxidative and biochemical parameters that supports its folkloric use in traditional systems of medicine.

Anti-tumor effects and cellular mechanisms of Pistacia atlantica methanolic extract against Ehrlich solid tumor in mice

Objective: To assess the anti-tumor effects of Pistacia atlantica methanolic extract (PAME) compared with cyclophosphamide against Ehrlich solid tumors in mice. Methods: Swiss albino mice (n=40) were divided into five groups: normal control mice, mice with Ehrlich solid tumors treated with normal saline, mice with Ehrlich solid tumors treated with cyclophosphamide intraperitoneally once a day for 14 d, or 50 mg/kg or 100 mg/kg PAME orally once a day for 14 d. Tumor growth inhibition, body weight, tumor markers, liver and kidney enzymes, oxidative stress markers, antioxidant enzymes, tumor necrosis factor-alpha level (TNF-α), and apoptosis-regulatory gene expression were evaluated. Results: Treatment of mice bearing Ehrlich solid tumors with PAME at 50 and 100 mg/kg orally significantly decreased tumor volume, body weight, tumor markers, liver and kidney enzymes, oxidative stress markers and TNF-α level in comparison with mice with Ehrlich solid tumors receiving normal saline. whereas PAME at 50 and 100 mg/kg/day significantly elevated the level of antioxidant enzymes (P<0.05). Conclusions: Pistacia atlantica methanolic extract has potent antitumor activity in mice. Therefore, the extract might be considered as an alternative anticancer agent against tumors, however, additional studies especially in the clinical setting are required to confirm this finding.

Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

Protein extract of kenaf seed exhibits anticoagulant, antiplatelet and antioxidant activities

Objective: To explore the anticoagulant, antiplatelet and antioxidant activities of protein extract of kenaf seed (PEKS). Methods: Sodium dodecyl sulphate polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography techniques were employed for protein characterization. Antioxidant activity of PEKS was assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The protective effect of PEKS on sodium nitrite (NaNO 2) induced oxidative stress was evaluated using the in vitro red blood cell model, while the effect of PEKS on diclofenac-induced oxidative stress was examined in vivo in rats. Platelet-rich plasma and platelet-poor plasma were used for anticoagulant and antiplatelet activities of PEKS. Results: PEKS revealed similar protein bands on SDS-PAGE under reduced and non-reduced conditions. Several acidic proteins were present in native PAGE. PEKS showed antioxidant properties by scavenging DPPH with an IC 50 of 24.58 μg. PEKS exhibited a protective effect on NaNO 2 induced oxidative stress in red blood cells by restoring the activity of stress markers. In addition, PEKS alleviated diclofenac-induced tissue damage of the liver, kidney, and small intestine. PEKS showed an anticoagulant effect in both in vivo and in vitro experiments by enhancing normal clotting time. PEKS did not affect prothrombin time but increase activated partial thromboplastin time. Furthermore, PEKS inhibited adenosine diphosphate and epinephrine-induced platelet aggregation. Conclusions: PEKS protects tissues from oxidative stress and exhibits antithrombotic activity.

Non-alcoholic fatty liver disease: Epidemiology, pathophysiology and an update on the therapeutic approaches

Non-alcoholic fatty liver disease (NAFLD) denotes a spectrum of fatty liver disease in individuals without significant alcohol consumption. NAFLD is set to be the most common etiology of serious liver diseases in numerous nations when accompanied by obesity and type 2 diabetes. It is further histologically categorized into the non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and non-alcoholic steatohepatitis (NASH) which is characterized by the coexistence of hepatic steatosis and inflammation and is accompanied by hepatocyte injury (ballooning), either with or without fibrosis. NAFL is considered the benign and reversible stage arising from the excessive accumulation of triglycerides in hepatocytes. However, NASH is a more progressive stage of NAFLD, due to the increased risks of evolving more serious diseases such as cirrhosis, hepatocellular carcinoma. This concept, however, has been lately challenged by a hypothesis of multiple parallel hits of NAFLD, in which steatosis and NASH are separate entities rather than two points of the NAFLD spectrum, not only from a set of histological patterns but also from a pathophysiological perspective. The current review highlights the epidemiology and pathophysiology of NAFLD, and its progression towards steatohepatitis, with special focus on the novel imminent therapeutic approaches targeting the molecular aspects and the pathogenic pathways involved in the development, and progression of NAFLD.

Hexadecanoic acid-enriched extract of Halymenia durvillei induces apoptotic and autophagic death of human triple-negative breast cancer cells by upregulating ER stress

Objective: To investigate the effect of the hexane solvent fraction of Halymenia durvillei (HDHE) on triple-negative breast cancer. Methods: The phytochemical profile of HDHE was investigated by GC-MS. The cytotoxicity of HDHE against MDA-MB-231 cells was determined. The apoptotic and autophagic effects of HDHE were analyzed. The expression of molecular markers controlling apoptosis, autophagy, DNA damage, and endoplasmic reticulum (ER) stress was determined. Results: HDHE contains a mixture of fatty acids, mainly hexadecanoic acid. HDHE at a cytotoxic concentration induced apoptotic death of MDA-MB-231 cells through mitochondrial membrane dysfunction, and induction of apoptosis markers, and increased the expression of proteins related to DNA damage response. HDHE also induced the expression of LC-3, a marker of autophagic cell death at a cytotoxic concentration. Moreover, HDHE modulated the expression of ER stress genes. Conclusions: The hexadecanoic acid-enriched extract of Halymenia durvillei promotes apoptosis and autophagy of human triple-negative breast cancer cells. This extract may be further explored as an anticancer agent for triple-negative breast cancer.

Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Objective: To compare the cardioprotective efficacy of equimolar doses (50 mM/kg, p.o.) of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg. This study included four treatment groups of rats (n=6): the control group (0.5% carboxymethyl cellulose solution-treated), the doxorubicin- treated group (0.5% carboxymethyl cellulose solution along with doxorubicin), the genistein-treated group (50 mM/kg/day; p.o. along with doxorubicin) and phloretin-treated group (50 mM/kg/day; p.o. along with doxorubicin). On the 10th day of dosing, rats were anesthetized for recording ECG, mean arterial pressure, and left ventricular function. Oxidative stress, nitric oxide levels, and inflammatory cytokines were estimated in the cardiac tissue. Cardiac function parameters (creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase) were estimated in the serum samples. Results: Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats. Phloretin administration attenuated doxorubicin- induced alterations in hemodynamic parameters (heart rate, mean arterial blood pressure, and left ventricular function) and suppressed the expression of pro-inflammatory cytokines. The cardiac injury markers like creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase were reduced by both genistein and phloretin. All these effects of phloretin were more prominent than genistein. Conclusions: Phloretin offers cardioprotection that is comparable to genistein, a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity. Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

Aqueous extract of freeze-dried Protaetia brevitarsis larvae promotes osteogenesis by activating β-catenin signaling

Objective: To investigate the effect of an aqueous extract of Protaetia brevitarsis (AEPB) on osteogenesis using preosteoblast MC3T3-E1 cells and zebrafish larvae. Methods: Flow cytometric analysis was used to measure the cytotoxicy. Alkaline phosphatase activity was detetmined using p-nitrophenyl phosphate as a substrate. Calcium deposition was detected using alizarin red staining along with osteogenic marker expression in preosteoblast MC3T3E1 cells. In addition, vertebral formation in zebrafish larvae was detected using calcein staining and osteogenic gene expression. Results: AEPB highly promoted the expression of osteogenic markers including runt-related transcription factor 2, osterix, and alkaline phosphatase, along with elevated levels of mineralization in MC3T3-E1 cells. Moreover, AEPB accelerated vertebral formation in zebrafish larvae accompanied by upregulated expression of osteogenic genes. FH535, an inhibitor of Wnt/β-catenin, suppressed AEPB-induced osteogenic gene expression and vertebral formation, indicating that AEPB stimulates osteogenesis by activating the Wnt/β-catenin signaling pathway. Conclusions: AEPB stimulates osteoblast differentiation and bone formation by activating β-catenin. Therefore, AEPB is a promising material that induces osteogenesis, and is useful for the treatment of bone resorption diseases.

Methyl gallate isolated from Mangifera pajang kernel induces proliferation inhibition and apoptosis in MCF-7 breast cancer cells via oxidative stress

Objective: To determine the lead bioactive compound in kernel extract of Mangifera pajang and its anti-cancer activity against human breast cancer cell lines with positive estrogen receptor (MCF-7). Methods: The methanolic extract of dried powder kernel of Mangifera pajang was exposed to column chromatography for isolation. The structural elucidation of the isolated compound was characterized using infrared, nuclear magnetic resonance, mass spectrometry. Furthermore, cytotoxicity, morphological changes, flow cytometry and cell cycle arrest analyses were performed to examine the mechanism of anti-proliferation and apoptosis induced by methyl gallate against MCF-7. Results: One compound was isolated from the methanolic extract of Mangifera pajang kernel and identified as methyl gallate. The flow cytometric results demonstrated induction of apoptosis in MCF-7 cells by three concentrations of methyl gallate. The cell cycle arrest showed a significant (P<0.05) decrease in cell progression at G 2/M phase of MCF-7 after treatment with 100 μM of methyl gallate. The cell percentage of early and late apoptosis was significant at 10 and 100 μM of methyl gallate. Also, methyl gallate treatment induced up-regulation of reactive oxygen species levels in MCF-7 cells with a reduction in superoxide dismutase levels. Conclusions: These findings indicate that isolated methyl gallate from Mangifera pajang kernel extracts induces growth inhibition and apoptosis in MCF-7 cells via up-regulating oxidative stress pathway.

Anti-obesity effect and UHPLC-QTOF-MS/MS based metabolite profiling of Solanum nigrum leaf extract

Objective: To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum. Methods: Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties. The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum. Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds. The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet. Results: The 80% hydroethanolic extract exhibited the highest extract yield, total phenolic contents, total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity, total antioxidant power, and pancreatic lipase inhibitory properties. The 80% hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver, kidney, and heart. The 80% hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum. The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat. Conclusions: Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.