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.

Optimization of immunosuppressive regimen for kidney transplant recipients / 器官移植

With the maturity and development of surgical techniques, as well as the improvement of perioperative management level, the success rate of kidney transplantation has been significantly improved. However, due to evident differences in heredity and antigenicity between donors and recipients, rejection will occur after kidney transplantation, which will affect the survival of renal grafts. Immunosuppression is an important treatment for rejection, which is of significance to reduce the risk of rejection and enhance graft survival rate. Nevertheless, immunosuppressants may cause multiple complications while lowering the incidence of rejection, such as infection, cardiovascular diseases and tumors, etc., which seriously affect the quality of life of patients and may even lead to their death. Reasonable selection of immunosuppressants and continuous optimization of immunosuppressive regimen for recipients play a critical role in improving the survival of recipients and renal grafts. In this article, the development history of organ transplantation, immune induction therapy and immune maintenance therapy was reviewed, and the progress in the optimization of immunosuppressive regimens for kidney transplant recipients was discussed, aiming to provide reference for improving clinical prognosis of kidney transplant recipients.

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.

Ethyl acetate partition obtained from the methanol extract of Muntingia calaburaleaf exerts effective in vitroantiproliferative activity against the HT-29 colon cancer / La partición de acetato de etilo obtenido del extracto metanólico de la hoja de Muntingia calabura ejerce una actividad antiproliferativa in vitro eficaz contra el cáncer de colon HT-29

Methanol extract of Muntingia calabura L. leaf (MEMCL) has been shown to exert the antiproliferative activity against the HT-29 (human colon adenocarcinoma) cell line. To further investigate on the medicinal potential of this plant, MEMCL was sequentially partitioned to obtain the petroleum ether, ethyl acetate and aqueous partitions, whichwas then tested against the HT-29 cell line and also subjected to the in vitro anti-inflammatory study. The most effective partition was also subjected to the phytoconstituents analysis using the UHPLC-ESI-MS. Findings showed that the ethyl acetate partition (EAP) exerts the most effective antiproliferative activity (IC50 = 58.0 ± 12.9 µg/mL) without affecting the 3T3 normal fibroblast cells, exhibits the highest anti-inflammatory effect when assessed using the lipoxygenase (> 95%) and xanthine oxidase (> 70%) assays, and contained various types of polyphenolics. In conclusion, M. calabura exerts apoptotic-mediated antiproliferative activity, partly via the anti-inflammatory action and synergistic action between the polyphenolics.

Se ha demostrado que el extracto metanólico de hoja de Muntingia calabura L. (MEMCL) ejerce actividad antiproliferativa contra la línea celular HT-29 (adenocarcinoma de colon humano). Para investigar más a fondo el potencial medicinal de esta planta, MEMCL se dividió secuencialmente para obtener el éter de petróleo, el acetato de etilo y las particiones acuosas, que luego se probó contra la línea celular HT-29 y también se sometió al estudio antiinflamatorio in vitro. La partición más eficaz también se sometió al análisis de fitoconstituyentes utilizando UHPLC-ESI-MS. Los resultados mostraron que la partición de acetato de etilo (EAP) ejerce la actividad antiproliferativa más efectiva (IC50= 58.0 ± 12.9 µg/mL) sin afectar las células de fibroblastos normales 3T3, exhibe el mayor efecto antiinflamatorio cuando se evalúa usando la lipoxigenasa (> 95%) y ensayos de xantina oxidasa (> 70%), y contenían varios tipos de polifenoles. En conclusión, M. calabura ejerce una actividad antiproliferativa mediada por apoptosis, en parte a través de la acción antiinflamatoria y la acción sinérgica entre los polifenoles.

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

Mycosynthesis of thermostable silver nanoparticles by the endophytic Albifimbria verrucaria with antimicrobial and antiproliferative activities

Aims@#This study was aimed to screen and isolate soil and endophytic fungi with the ability to biosynthesize stable silver nanoparticles (SNPs) with antimicrobial and antiproliferative activities.@*Methodology and results@#A total of 60 fungal isolates isolated from soil and plant samples were screened for their ability to biosynthesize SNPs. Among which, 21 isolates have supported the biosynthesis of SNPs. Furthermore, the endophytic isolate PRR2.1 synthesized highly thermostable SNPs with long shelf life. The PRR2.1 isolate was identified as Albifimbria verrucaria by morphological and molecular means. The synthesis of SNPs was initially monitored by UV-Vis spectroscopy. Further characterization by transmission electron microscopy, X-ray diffraction and dynamic light scattering revealed well-dispersed spherical crystalline in nature SNPs with a mean size of 14 nm and zeta potential of –24.47 mV. Fourier transform infrared spectroscopy showed the presence of biomolecules adsorbed on the surface of biosynthesized SNPs responsible for their synthesis and stability. The mycosynthesized SNPs exhibited stronger antifungal activity against pathogenic strains of Aspergillus niger, A. flavus, A. fumigatus and Candida albicans with respect to its antibacterial activity against Escherichia coli, Staphylococcus aureus, Bacillus cereus and Klebsiella pneumoniae compared to standard antifungal itraconazole and antibiotic cefadroxil with mostly consistent minimum inhibitory concentration of 5.31 μg/mL. The biosynthesized SNPs demonstrated dose-dependent in vitro antiproliferative activity against cancerous HeLa cell line with IC50 value of 2.52 μg/mL and less cytotoxic activity against WI-38 (normal human lung fibroblasts) cell line with CC50 value of 10.2 μg/mL.@*Conclusion, significance and impact of study@#These results show the potential of endophytic fungi biosynthesized SNPs as possible biofriendly, safe and efficient antimicrobial agents with promising antiproliferative activity and low cytotoxicity, which can be furtherly implemented in various biomedical and biotechnological applications.

Antiproliferative piperidine alkaloids from giant taro (Alocasia macrorrhiza) / 中国天然药物

The rhizome of giant taro (Alocasia macrorrhiza (L.) Schott), which is a highly adaptable wild plant, is a traditional Chinese herbal medicine. In the current study, the antiproliferative constituents of giant taro were investigated and six new (1-6) and four known piperidine alkaloids (7-10) were isolated from its rhizomes. Their chemical structures and absolute configurations were elucidated using various spectroscopic methods and the Mosher ester method. The isolated alkaloids were screened for the antiproliferative activity through MTT assay. The results indicated that piperidine alkaloids exerted potential antiproliferative activity against HepG2, AGS and MCF-7 tumor cells. Further researches showed that compounds 3-5 dose-dependently decreased the colony formation rate and induced the apoptosis of AGS cells, while compound 4 induced AGS cell death via the proapoptotic pathway. This study demonstrates that the piperidine alkaloids isolated from giant taro exhibit significant antitumor activity, which provides phytochemical evidence for further development and utilization.

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.

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.

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.

Therapeutic potential of Calotropis gigantea extract against invasive pulmonary aspergillosis: In vitro and in vivo study

Objective: To characterize the antifungal activity of methanolic leaf extract of Calotropis gigantea alone or in combination with amphotericin B against invasive pulmonary aspergillosis in mice. Methods: GC/MS was used for analysis of active constituents of Calotropis gigantea extract. Spore germination assay and broth micro-dilution method were used to determine antifungal potential of Calotropis gigantea/amphotericin B against Aspergillus fumigatus. Neutropenic mice were randomly assigned into 5 groups: group 1 was neutropenic (control); group 2 was infected with Aspergillus fumigatus; group 3 was infected with Aspergillus fumigatus, and treated with Calotropis gigantea extract; group 4 was infected with Aspergillus fumigatus and treated with amphotericin B; group 5 was infected with Aspergillus fumigatus and treated with both Calotropis gigantea extract and amphotericin B. Fresh lung tissues were histopathologically examined. Fungal burden and gliotoxin concentration were evaluated in lung tissues. Catalase, superoxide dismutase, and malondialdehyde content were determined in lung tissues. Myeloperoxidase, tumor necrosis factor-alpha, interleukin-1, and interleukin-17 were also estimated by the sandwich enzyme-linked immuno-sorbent assay. Results: Calotropis gigantea/amphotericin B had a minimum inhibitory concentration and minimum fungicidal concentration of 80 and 160 μg/mL, respectively, for Aspergillus fumigatus. Additionally, Calotropis gigantea/amphotericin B significantly reduced lung fungal burden by 72.95% and inhibited production of gliotoxin in lung tissues from 6 320 to 1 350 μg/g lung. Calotropis gigantea/amphotericin B reduced the oxidative stress of the lung via elevating the activity of antioxidant enzymes and decreasing the levels of lipid peroxidation. Myeloperoxidase activity and the production of pro-inflammatory cytokines were also significantly reduced. Scanning electron microscopy revealed deteriorations in the hyphae ultrastructure in Calotropis gigantea/amphotericin B treated Aspergillus fumigatus and leak of cellular components after damage of the cell wall. In vivo study revealed the suppression of lung tissue damage in mice of invasive pulmonary aspergillosis, which was improved with Calotropis gigantea/amphotericin B compared to the control group. Conclusions: Calotropis gigantea/amphotericin B is a promising treatment to reduce lung fungal burden and to improve the drugs' therapeutic effect against invasive pulmonary aspergillosis.

Essential oil from Saussurea costus inhibits proliferation and migration of Eca109 cells via mitochondrial apoptosis and STAT3 signaling

Objective: To investigate the effect and its underlying molecular mechanisms of essential oil from Saussurea costus in esophageal cancer cell line Eca109. Methods: The chemical composition of essential oil from Saussurea costus was investigated by gas chromatography-mass spectrometry (GC-MS). The anti-proliferative, anti-migrative, and apoptotic effects of essential oil from Saussurea costus against Eca109 cells were analyzed. Moreover, the expression of proteins associated with cell cycle, metastasis, and apoptosis was determined. Results: GC-MS analysis showed that essential oil from Saussurea costus was predominantly comprised of sesquiterpenes. Saussurea costus essential oil inhibited the viability of Eca109 cells in a dose-and time-dependent manner with IC 50 values of (24.29±1.49), (19.16±2.27) and (6.97±0.86) μg/mL at 12, 24, and 48 h, respectively. The expression levels of target proteins in the cell cycle (phase G 1 /S), including cyclin D1, p21, and p53, were affected by Saussurea costus essential oil. The essential oil also downregulated the expression of metastasis-related proteins MMP-9 and MMP-2. Moreover, it induced apoptosis of Eca109 cells through the mitochondrial pathway, as well as inhibition of STAT3 phosphorylation. Conclusions: The essential oil from Saussurea costus exhibited anti-proliferative, anti-migrative, and apoptotic effects on Eca109 cells, and could be further explored as a potential anti-esophageal cancer agent.

Dieckol isolated from Eisenia bicyclis extract suppresses RANKL-induced osteoclastogenesis in murine RAW 264.7 cells

Objective: To demonstrate the effect of dieckol from Eisenia bicyclis on osteoclastogenesis using RAW 264.7 cells. Methods: Murine macrophage RAW 264.7 cells were subjected to dieckol treatment, followed by treatment with receptor activator of nuclear factor kappa-B ligand (RANKL) to induce osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) activity was examined using a TRAP activity kit. Western blotting analysis was conducted to examine the level of osteoclast- related factors, including TRAP and calcitonin receptor (CTR), transcriptional factors, including c-Fos, c-Jun, and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), nuclear factor kappa-B (NF-κB), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Immunofluorescence staining was conducted to examine the expression of c-Fos, c-Jun, and NFATc1. Results: Among the four phlorotannin compounds present in Eisenia bicyclis, dieckol significantly hindered osteoclast differentiation and expression of RANKL-induced TRAP and CTR. In addition, dieckol downregulated the expression levels of c-Fos, c-Jun, NFATc1, ERK, and JNK, and suppressed NF-κB signaling. Conclusions: Dieckol can suppress RANKL-induced osteoclastogenesis. Therefore, it has therapeutic potential in treating osteoclastogenesis- associated diseases.

Syringic acid induces cancer cell death in the presence of Cu (II) ions via pro-oxidant activity

Objective: To investigate the effects of syringic acid on HEK 293 and HepG2 cells in the absence and presence of exogenous Cu (II) and Fe (II) ions. Methods: The antiproliferative effects of syringic acid on HEK 293 and HepG2 cells in the absence and presence of exogenous Cu (II) and Fe (II) ions were examined by MTT assay. Additionally, colony-forming, reactive oxidative species (ROS) generation, apoptosis induction, autophagy, mitochondrial membrane potential, and mitochondrial mass were investigated. Results: At 24 and 72 h, no significant differences were observed in the viability of HepG2 cells between the control and syringic acid + Fe (II) groups. However, exposure of HepG2 cells to syringic acid + Cu (II) for 72 h reduced the cell viability significantly. Furthermore, ROS formation, induction of apoptosis, and autophagic vacuoles were significantly increased in HepG2 cells without marked changes in mitochondrial membrane potential and mitochondrial mass. Moreover, syringic acid + Cu (II) reduced the plating efficiency and surviving fraction significantly. Conclusions: The combination of syringic acid with Cu (II) was toxic to cancer cells and showed pro-oxidant activity. In addition, this combination induced autophagy in cancer cells with less cytotoxic effects on normal cells, which is a potential candidate for the development of novel therapeutics towards cancer.

Hepato- and reno-protective effects of thymoquinone, crocin, and carvacrol: A comprehensive review

Medicinal plants are rich in nutrients and phytochemicals which prevent and treat a wide range of ailments. Accumulating experimental studies exhibit that some bioactive ingredients extracted from medicinal plants have suitable therapeutic effects on hepatic and renal injuries. This review focuses on the hepato- and reno-protective effects of thymoquinone, crocin, and carvacrol. The relevant literature was retrieved from PubMed, Scopus, Web of Science, and Google Scholar databases from the beginning of 2015 until the end of November 2021. According to the scientific evidence, the considered phytochemicals in this review have been applied with useful therapeutic effects on hepatic and renal damage. These therapeutic effects were mainly mediated through the amelioration of oxidative stress, suppression of inflammatory responses, and inhibition of apoptosis. Intracellular signaling pathways linked to nuclear factor kappa B (NF-κB), adenosine monophosphate-activated protein kinase, c-jun N-terminal kinase, and extracellular signal-regulated kinase 1/2 and Toll-like receptors are the most important pathways targeted by these phytochemicals. Up-regulation of transcription factor Nrf2 and down-regulation of transforming growth factor-beta 1 by these natural compounds also contribute to the alleviation of hepatic and renal injuries.

Humulus japonicus extract alleviates oxidative stress and apoptosis in 6-hydroxydopamine-induced PC12 cells

Objective: To explore the possible neuroprotective activities of Humulus japonicus extract against Parkinson's disease (PD) in a cellular model. Methods: PD was modeled in PC12 cells using 6-hydroxydopamine (6-OHDA). The cell activity, intracellular levels of reactive oxygen species (ROS), anti-oxidative and anti-apoptotic effects, and other related indicators and related signaling pathways were evaluated to elucidate the neuroprotective effects of Humulus japonicus extract. Results: Humulus japonicus extract exhibited anti-oxidative and anti-apoptotic effects in 6-OHDA-stimulated PC12 cells. It also reduced oxidative stress-induced ROS accumulation; upregulated antioxidant enzymes, such as glutathione, catalase, heme oxidase-1, and 8-oxguanine glycosylase 1; promoted cell survival by decreasing BAX and increasing Bcl-2 and sirtuin 1 expression via the MAPK and/or Nrf2 signaling pathways. Conclusions: Humulus japonicus extract has antioxidative and anti-apoptotic effects and could be developed as a promising candidate for preventing and treating oxidative stress-related neurodegenerative diseases.

Fucoxanthin suppresses OxLDL-induced inflammation via activation of Nrf2 and inhibition of NF-κB signaling

Objective: To explore the impact of fucoxanthin on oxidized low-density lipoprotein (OxLDL)-induced stress and inflammation in human endothelial cells and its underlying mechanisms. Methods: HUVECs were treated with OxLDL and/or fucoxanthin for a range of time points and concentrations. We evaluated the effects of fucoxanthin on OxLDL-induced HUVECs using the MTT assay, reactive oxygen species accumulation assay, ELISA, RT-PCR, immunofluorescence, and Western blotting. Results: Fucoxanthin enhanced the cell viability in a dose dependent manner after OxLDL exposure. Furthermore, fucoxanthin pretreatment significantly decreased OxLDL-induced reactive oxygen species production and prevented the activation of the nuclear factor kappa-B pathway, which led to substantial suppression of pro-inflammatory gene expressions. OxLDL-induced upregulation of interleukin-6, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukin-1β, monocyte chemotactic protein-1, cyclooxygenase-1, and tumor necrosis factor-α was significantly reduced by fucoxanthin. Conclusions: Fucoxanthin can inhibit OxLDL-induced vascular inflammation and oxidative stress in HUVECs by targeting Nrf2 signaling pathways.

Antibacterial and anti-parasitic activities of Terfezia claveryi methanolic extract against some common pathogenic agents of infectious diarrhea

Objective: To assess the antidiarrheal effects of Terfezia claveryi methanolic extract against Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Giardia lamblia. Methods: Antibacterial effects of the Terfezia claveryi methanolic extract were carried out by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration through micro broth dilution technique. Furthermore, reactive oxygen species production and protein leakage were evaluated. To evaluate the in vitro anti-giardial effects of Terfezia claveryi methanolic extract, Giardia lamblia WB (ATCC® 30957) trophozoites were treated with various concentrations of Terfezia claveryi methanolic extract for 10-360 min. In addition, the plasma membrane permeability of trophozoites treated with Terfezia claveryi methanolic extract was determined. The cytotoxicity effects of Terfezia claveryi methanolic extract against normal (HEK293T) and cancer (MCF-7) cells were also assessed using the MTT assay. Results: The MIC and minimum bactericidal concentration of Terfezia claveryi methanolic extract against bacterial strains were in the range of 0.52-1.04 and 1.04-2.08 mg/mL, respectively. The results revealed that reactive oxygen species production and protein leakage were significantly increased after the bacteria were treated with the Terfezia claveryi methanolic extract, especially at 1/3 and 1/2 MICs (P<0.001). Furthermore, Terfezia claveryi methanolic extract decreased the viability of Giardia lamblia trophozoites in a dose-dependent manner. Terfezia claveryi methanolic extract at 1, 2, and 4 mg/mL resulted in 100% mortality in Giardia lamblia trophozoites after 360, 240, and 120 min, respectively. Moreover, Terfezia claveryi methanolic extract altered the permeability of plasma membrane of Giardia lamblia trophozoites by increasing the concentration. MTT assay revealed that the 50% cytotoxic concentrations values for HEK293T and MCF-7 cells were 4.32 mg/mL and 6.40 mg/mL, respectively, indicating that Terfezia claveryi methanolic extract had greater cytotoxicity against cancer cells than normal cells. Conclusions: Terfezia claveryi methanolic extract had potent in vitro antibacterial and anti-parasitic effects on Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Giardia lamblia by affecting cell membrane permeability and reactive oxygen species generation with no significant cytotoxicity on normal cells.