Antidiabetic Effect of Fig Seed Oil in Rats with Diabetes Induced by Streptozotocin.

The anti-diabetic effect of Ficus carica (Fig) seed oil was investigated. 4 groups with 6 rats in each group were used in the experiment as control, diabetes (45 mg/kg streptozotocin), fig seed oil (FSO) (6 mL/ kg/day/rat by gavage) and diabetes+FSO groups. Glucose, urea, creatinine, ALT, AST, GSH, AOPP and MDA analyses were done. Pancreatic tissues were examined histopathologically. When fig seed oil was given to the diabetic group, the blood glucose level decreased. In the diabetes+FSO group, serum urea, creatinine, AOPP, MDA levels and ALT and AST activities decreased statistically significantly compared to the diabetes group, while GSH levels increased significantly, histopathological, immunohistochemical, and immunofluorescent improvements were observed. It has been shown for the first time that FSO has positive effects on blood glucose level and pancreatic health. It can be said that the protective effect of fig seed oil on tissues may be due to its antioxidant activity.

Antioxidant Activity and Effectiveness of Fig Extract in Counteracting Carbon Tetrachloride-Induced Oxidative Damage in Rats.

Figs are the edible fruits of the fig tree, Ficus carica L., that have been used for centuries for human consumption and in traditional medicine, to treat skin problems, inflammation, and gastrointestinal disorders. Our previous study investigated the presence of phenolic compounds in aqueous extracts of two Algerian popular fig varieties, azendjar (Az) and taamriouth (Ta), as well as their in vitro antioxidant activity. In this study, we assessed hydroethanolic extracts of these fig varieties. The total phenolic content was measured, along with the phenolic profile. Rutin was determined to be the dominant phenolic compound, followed by vanillic acid, 3,4-dihydroxybenzoic acid, quercetin, 4-hydroxybenzoic acid, rosmarinic acid (in Az only), and cinnamic acid. The antioxidant activity of the extracts was evaluated both in vitro (DPPH and FRAP assays) and in vivo, in rats intoxicated with carbon tetrachloride. In all assays, the fig extract-especially the dark-peeled fig variety azendjar-showed antioxidant potency. The administration of fig extract resulted in a reduction in liver damage, expressed by both different biochemical markers and histopathological study (less degraded liver architecture, reduced fibrosis, and only mild inflammation). A dose-dependent therapeutic effect was observed. The extract from the dark-peeled fig variety, Az, was characterized by a higher phenolic content and a stronger antioxidant activity than the extract from the light-peeled variety-Ta. Our study justifies the use of figs in traditional healing and shows the potential of using fig extracts in natural medicines and functional foods.

Enhancing nutritional status, growth, and fruit quality of dried figs using organic fertilizers in rain-fed orchards: A case study in Estahban, Iran.

The majority of Iranian fig production is exported, making it one of the world's most well-known healthy crops. Therefore, the main objective of the current experiment was to investigate the effects of various types of organic fertilizers, such as animal manure (cow and sheep), bird manure (partridge, turkey, quail, and chicken), and vermicompost, on the nutritional status of trees, vegetative and reproductive tree characteristics, fruit yield, and fruit quality traits in dried fig cultivar ("Sabz"). According to the findings, applying organic fertilizers, particularly turkey and quail, significantly improves vegetative and reproductive characteristics. However, other manures such as sheep, chicken, and vermicompost had a similar effect on the growth parameters of fig trees. Additionally, the findings indicated that except for potassium, use of all organic fertilizers had an impact on macro and microelements such as phosphorus, nitrogen, and sodium amount in fig tree leaves. Also, based on fruit color analysis in dried figs, the use of all organic fertilizers improved fruit color. Moreover, the analyses fruit biochemical showed that the use of some organic fertilizers improved that TSS and polyphenol compounds such as coumarin, vanillin, hesperidin gallic acid and trans frolic acid. In general, the results indicated that the addition of organic fertilizers, especially turkey manure, led to increased vegetative productivity and improvement in the fruit quality of the rain-fed fig orchard.

Molecular interplay between phytoconstituents of Ficus Racemosa and neurodegenerative diseases.

Neurodegenerative diseases (NDs) are a significant global health concern, primarily affecting middle and older populations. Recently, there has been growing interest in herbal therapeutics as a potential approach to address diverse neuropathological conditions. Despite the widespread prevalence of NDs, limited phytochemical has been reported for their promising therapeutic potential with distinct underlying mechanisms. Additionally, the intricate molecular pathways influenced by herbal phytoconstituents, particularly in neurodegenerative disorders, are also not well documented. This report explores the phytoconstituents of Ficus racemosa (F. racemosa), an unfamiliar plant of the Moraceae family, for their potential interactions with pathological pathways of NDs. The influential phytoconstituents of F. racemosa, including polyphenols, glycosides, terpenoids, and furocoumarin, have been reported for targeting diverse pathological states. We proposed the most convincing molecular interplay between leading phytoconstituents and detrimental signalling cascades. However, extensive research is required to thoroughly understand the phytochemical persuaded intricate molecular pathway. The comprehensive evidence strongly suggests that F. racemosa and its natural compounds could be valuable in treating NDs. This points towards an exciting path for future research and the development of potential treatments based on a molecular level.

Four undescribed coumarin derivatives, with ten amides from the roots of Ficus hirta and their cytotoxic activities.

Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a/3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer.

Skin hydration modulatory activities of Ficus deltoidea extract.

Ficus deltoidea was known for its potent antioxidant, anti-melanogenic and photoprotective skin barrier activities. These properties are contributed by its biomarkers which are vitexin and isovitexin. This study aims to optimize the yield of methanolic extraction of Ficus deltoidea leaves (EFD) and evaluate their effects on skin barrier function and hydration. For optimization, Box-Behnken design was utilized to investigate the effects of methanol concentration, sonication time, and solvent-to-sample ratio on the yields of vitexin and isovitexin in EFD. The optimal yields obtained were 32.29 mg/g for vitexin and 35.87 mg/g for isovitexin. The optimum extraction conditions were 77.66% methanol concentration, 20.03 min sonication time, and 19.88 mL/g solvent-to-sample ratio. The quantitative real-time polymerase chain reaction was utilized to measure variant marker genes of transglutaminase-1, caspase 14, ceramide synthase 3, involucrin, and filaggrin of EFD-induced keratinocyte differentiation by in vitro study. Exposure to EFD has elevated the mRNA levels of all tested marker genes by 0.7-9.2 folds. Then, in vivo efficacy study was conducted on 20 female subjects for 14 days to evaluate skin biophysical assessment of hydration. EFD topical formulation treatment successfully increased skin hydration on day 7 (43.74%) and day 14 (47.23%). In silico study by molecular docking was performed to identify intermolecular binding interactions of vitexin and isovitexin with the interested proteins of tested marker genes. The result of molecular docking to the interested proteins revealed a similar trend with real-time PCR data. In conclusion, EFD potentially enhanced the skin barrier function and hydration of human skin cells.

Bioactive compound composition and cellular antioxidant activity of fig (Ficus carica L.).

BACKGROUND: Fig (Ficus carica L.) fruit is consumed worldwide as a functional food. It contains phytochemicals that have been related to health benefits. However, the characteristic chemicals remain unclear. In this work, phytochemicals were prepared from figus by ultrasound-assisted extraction under optimized conditions. The chemical composition of fig fruit and leaves was characterized by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: One hundred and fifty-seven compounds were identified, including 58 flavonoids, 29 coumarins, 19 acids, 15 terpenoids, 11 alkaloids, and 25 other compounds. The mass spectrum (MS) fragmentation pathways of representative chemicals were elucidated. Flavonoid glycosides and prenylated flavonoids were mainly present in fig fruit, whereas coumarins were abundant in leaves. Both fig fruit and leaf extracts showed good cellular antioxidant activity. CONCLUSION: The full phytochemical profile of fig was revealed by UPLC-MS/MS. Prenylated flavonoids and prenylated coumarins were the characteristic phytochemicals. These data provided useful information for the extensive utilization of fig fruit in functional food. © 2023 Society of Chemical Industry.

Ficus carica polysaccharide extraction via ultrasound-assisted technique: Structure characterization, antioxidant, hypoglycemic and immunomodulatory activities.

In this research, the ultrasound-assisted extraction (UAE) conditions of the water-soluble polysaccharide (FCPS) from Ficus carica fruits were optimized using the response surface methodology. The optimal FCPS yield was 7.97 % achieved by conducting ultrasound-assisted extraction four times at a solid-liquid ratio of 1:20 (g/mL) and an ultrasound temperature of 70 °C. Then, the structure, antioxidant properties, hypoglycemic effects, and immunomodulatory activities of FCPS were evaluated. FCPS was characterized as irregular, rough-surfaced, flaky materials consisting of pyran-type polysaccharides with α- and ß-glycosidic linkages, and composed of multiple monosaccharides and only one homogeneous concentrated polysaccharide component (FCPS1) with a molecular weight of 4.224 × 104 Da. The results suggested FCPS exhibited remarkable antioxidant activity in vitro, as evidenced by improved cell viability and reduced the reactive oxygen species (ROS) levels. Meanwhile, FCPS effectively improved liver-related insulin resistance by promoting glucose consumption in hepatocytes and activated the immune response through activation of murine bone marrow-derived dendritic cells (DCs) and upregulation of interleukin 6 (IL6) and interleukin 12 (IL-12) expression. The findings demonstrate the efficacy of the UAE technique in isolating FCPS with biological functionality and FCPS could potentially serve as a beneficial organic antioxidant source and functional food, carrying important implications for future studies.

Synthesis and Bioactivity of Isoflavones from Ficus carica and Some Non-Natural Analogues.

Ficucaricone D (1) and its 4'-demethyl congener 2 are isoflavones isolated from fruits of Ficus carica that share a 5,7-dimethoxy-6-prenyl-substituted A-ring. Both natural products were, for the first time, obtained by chemical synthesis in six steps, starting from 2,4,6-trihydroxyacetophenone. Key steps are a microwave-promoted tandem sequence of Claisen- and Cope-rearrangements to install the 6-prenyl substituent and a Suzuki-Miyaura cross coupling for installing the B-ring. By using various boronic acids, non-natural analogues become conveniently available. All compounds were tested for cytotoxicity against drug-sensitive and drug-resistant human leukemia cell lines, but were found to be inactive. The compounds were also tested for antimicrobial activities against a panel of eight Gram-negative and two Gram-positive bacterial strains. Addition of the efflux pump inhibitor phenylalanine-arginine-ß-naphthylamide (PAßN) significantly improved the antibiotic activity in most cases, with MIC values as low as 2.5 µM and activity improvement factors as high as 128-fold.

The inhibitory potential of chemical constituents of Ficus carica targeting interleukin-6 (IL-6) mediated inflammation.

Inflammation is an innate reaction of the body of an individual when subjected to the noxious factors repeatedly. Pharmacological approaches focused at disrupting cytokine signaling networks have become significant therapeutic alternatives for the treatment of inflammatory illnesses, cancer and autoimmune disorders. High levels of inflammatory mediators, particularly interleukin IL-1, IL-6, IL-18, IL-12, and tumor necrosis factor alpha leads to a cytokine storm in the body. Among all the released cytokines in a patient suffering from inflammatory disorder, IL-6 mediator has a pivotal role in this inflammatory cascade which progresses to a cytokine storm. Therefore, the blockage of the IL-6 inflammatory mediator could be a promising treatment option for the patients with hyper inflammatory conditions. The phytochemicals could provide the new lead compounds against the IL-6 mediator. Ficus carica has been the ideal plant of research and investigation due to its commercial, economic and medical importance. The anti-inflammatory properties of F. carica were further investigated by in silico and in vivo approaches. The docking scores of Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin are -9.231, -8.921, -8.840, and -8.335 Kcal/mole respectively. The free energy of binding and stability of the docked complexes of these top four phytochemicals with the IL-6 were further analyzed by Molecular Mechanics-Generalized Born Surface Area and Molecular Dynamic simulations, respectively. The in vivo anti-inflammatory carrageenan-induced rat paw edema model was used for the validation of in silico results. The maximum percentage paw edema inhibition with petroleum ether and ethyl acetate was 70.32% and 45.05%, respectively. The in vivo anti-inflammatory activity confirms the anti-inflammatory potential of F. carica. Therefore, it is predicted that Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin have the potential to inhibit the IL-6 mediator which will aid in mitigating the cytokine storm in patients with acute inflammations.

Purification and characterization of a serine protease from the fruit of Ficus carica cultivar Masui Dauphine.

Ficus carica produces, in addition to the cysteine protease ficin, a serine protease (FSP). Here, we purified FSP to homogeneity from the fruit of F. carica cultivar Masui Dauphine. An 81-fold enrichment in specific activity of FSP with 2.1% recovery was attained. Three protein bands (70, 62, and 60 kDa) were identified on SDS-PAGE. Each band was identified as a subtilisin-like protease (661 amino acids) by trypsin digestion, LC-MS/MS analysis, and the partial N-terminal amino acid sequence analysis. Gelatin zymography revealed that the active FSP exists as a dimer. The optimum hydrolysis pH of FSP was 7.5, and the pHs at which the enzyme retained its initial activity by 70% in 24 h were 8.0-11.0. The optimum hydrolysis temperature of FSP was 50-60 °C, and the temperature required to reduce the initial activity by 50% in 15 min was 70 °C. These results will inform the industrial use of FSP.

Industrial Application and Health Prospective of Fig (Ficus carica) By-Products.

The current review was carried out on the industrial application of fig by-products and their role against chronic disorders. Fig is basically belonging to fruit and is botanically called Ficus carica. There are different parts of fig, including the leaves, fruits, seeds and latex. The fig parts are a rich source of bioactive compounds and phytochemicals including antioxidants, phenolic compounds, polyunsaturated fatty acids, phytosterols and vitamins. These different parts of fig are used in different food industries such as the bakery, dairy and beverage industries. Fig by-products are used in extract or powder form to value the addition of different food products for the purpose of improving the nutritional value and enhancing the stability. Fig by-products are additive-based products which contain high phytochemicals fatty acids, polyphenols and antioxidants. Due to the high bioactive compounds, these products performed a vital role against various diseases including cancer, diabetes, constipation, cardiovascular disease (CVD) and the gastrointestinal tract (GIT). Concussively, fig-based food products may be important for human beings and produce healthy food.

Chemical constituents from Ficus sur Forssk (Moraceae).

Phytochemical investigation of the aerial roots of Ficus sur, a Cameroonian medicinal plant, resulted in a previously undescribed cerebroside, suroside (1), in addition to its aglycon congener suramide (2). Moreover, six known natural products including alpinumisoflavone (3), wighteone metabolite (4), oleanolic acid (5), ß-sitosterol (6), ß-sitosterol-3-O-ß-D-glucopyranoside (7), and epi-ѱ-taraxastanolone (8) were identified. The structures of the previously undescribed compounds were determined by analysis of 1D and 2D-NMR (One and two dimensional nuclear magnetic resonance), mass spectrometry, chemical conversion, and by comparison of these data with those from the literature. Wighteone metabolite (4) exhibited a weak cytotoxic activity against the human HepG2 hepatocellular carcinoma cells with an IC50 value of 51.9 µM.

Thermostable ficin from jelly fig (Ficus pumila var. awkeotsang) latex: purification, identification and characterization.

BACKGROUND: The achenes/seeds of endemic jelly fig (Ficus pumila var. awkeotsang) fruit have been applied to prepare a traditional beverage in Taiwan. Upon fruit harvest, jelly fig latex exuded from stalks was discarded. Protease activity was monitored in its latex. Proteases capable of hydrolyzing proteins have many application aspects based on diverse characteristics. Commercial plant proteases are frequently from latex. RESULTS: The latex protease of jelly fig, termed FaFicin, was purified to homogeneity with a molecular mass of ~32 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. According to liquid chromatographic-tandem mass spectrometric analyses, the expected protein band of protease was matched to ficin A, ficin B or chymopapain from common fig or papaya. Iodoacetamide, an inhibitor of cysteine protease, inhibited its protease activity completely. Hence FaFicin was identified as a papain-like cysteine protease (PLCP), exhibiting more than 80% and 70% activity as assayed at pH 5-8 and 40-70 °C, respectively. It maintained ~89% of initial activity after 120 min at 55 °C and pH 7. Moreover, FaFicin could degrade the myosin and actin of meat, and clot milk. CONCLUSION: The ficin FaFicin was obtained, purified and identified as a PLCP member from agricultural waste: jelly fig latex. It possessed activity under a wide range of pH values and temperature, and exhibited excellent thermostability. Based on its initial evaluation as a meat tenderizer and milk clotting reagent, the application of FaFicin was possible, which may extend utilization of jelly fig. © 2022 Society of Chemical Industry.

Mechanistic Insights into the Neuroprotective Potential of Sacred Ficus Trees.

Ficus religiosa (Bo tree or sacred fig) and Ficus benghalensis (Indian banyan) are of immense spiritual and therapeutic importance. Various parts of these trees have been investigated for their antioxidant, antimicrobial, anticonvulsant, antidiabetic, anti-inflammatory, analgesic, hepatoprotective, dermoprotective, and nephroprotective properties. Previous reviews of Ficus mostly discussed traditional usages, photochemistry, and pharmacological activities, though comprehensive reviews of the neuroprotective potential of these Ficus species extracts and/or their important phytocompounds are lacking. The interesting phytocompounds from these trees include many bengalenosides, carotenoids, flavonoids (leucopelargonidin-3-O-ß-d-glucopyranoside, leucopelargonidin-3-O-α-l-rhamnopyranoside, lupeol, cetyl behenate, and α-amyrin acetate), flavonols (kaempferol, quercetin, myricetin), leucocyanidin, phytosterols (bergapten, bergaptol, lanosterol, ß-sitosterol, stigmasterol), terpenes (α-thujene, α-pinene, ß-pinene, α-terpinene, limonene, ß-ocimene, ß-bourbonene, ß-caryophyllene, α-trans-bergamotene, α-copaene, aromadendrene, α-humulene, alloaromadendrene, germacrene, γ-cadinene, and δ-cadinene), and diverse polyphenols (tannin, wax, saponin, leucoanthocyanin), contributing significantly to their pharmacological effects, ranging from antimicrobial action to neuroprotection. This review presents extensive mechanistic insights into the neuroprotective potential, especially important phytochemicals from F. religiosa and F. benghalensis. Owing to the complex pathophysiology of neurodegenerative disorders (NDDs), the currently existing drugs merely alleviate the symptoms. Hence, bioactive compounds with potent neuroprotective effects through a multitarget approach would be of great interest in developing pharmacophores for the treatment of NDDs.

Systematical Ingredient Investigations of Ficus tikoua Bur. Fruit and Immunoregulatory and Antioxidant Effects of Different Fractions.

Although the fruit of Ficus tikoua Bur. has been consumed by montanic people in China for centuries, its chemical and biological composition was still unclear. A series of comprehensive investigations on its chemical constituents and bioactivities were carried out for the first time. As a result, six compounds were isolated and identified as the main components in this fruit. GC-MS analysis of the lipid components demonstrated that Ficus tikoua Bur. fruit contains some wholesome constituents such as fatty acids, vitamins, triterpenoids, and phytosterols. The fatty acids are mainly composed of linolenic acid (61.27%) and linoleic acid (22.79%). Furthermore, this fruit contains a relative high content of crude protein (9.41 ± 0.03%), total amino acids (9.28%), and total polyphenols (0.86 ± 0.01 g/100 g). The analysis of monosaccharide composition showed that the total polysaccharide mainly consists of glucose, glucuronic acid, xylose, arabinose, mannose, galactose, galacturonic acid, and rhamnose. The polysaccharide, polyphenol, water, ethanol, and flavonoid extracts exhibited prominent antioxidant activity determined by ABTS, DPPH, and FRAPS methods. Meanwhile, the total polysaccharide exhibited significant immunomodulatory effect by enhancing the release of cytokines and expression of iNOS and COX-2 in RAW264.7 cells, significantly decreasing the expression of c-Jun and p65 proteins in the cytoplasm; increasing the translocation of c-Jun and p65 to the nucleus; and regulating the phosphorylation level of Akt, PI3K, and PDK1 in the PI3K/AKT signaling pathway. This study proved that the fruit of F. tikoua is a reliable source of functional food.

In Vitro and In Vivo Evaluation of Antidiabetic Properties and Mechanisms of Ficus tikoua Bur.

In folk medicine, Ficus tikoua (F. tikoua) has been used to treat diabetes for a long time, but there is a rare modern pharmacological investigation for its antidiabetic effect and mechanisms. Our study aimed to evaluate its hypoglycemic effect using in vitro and in vivo experimental models and then explore the possible mechanisms. In the ethanol extracts and fractions of F. tikoua, n-butanol fraction (NBF) exhibited the most potent effect on inhibiting α-glucosidase activity (IC50 = 0.89 ± 0.04 µg/mL) and promoting glucose uptake in 3T3-L1 adipocytes. Further animal experiments showed that NBF could play an antidiabetic role by ameliorating random blood glucose, fasting blood glucose, oral glucose tolerance, HbA1c level, and islets damage in diabetic mice. Then, the activities of the five subfractions of NBF (NBF1-NBF5) were further evaluated; NBF2 showed stronger α-glucosidase inhibition activities (IC50 = 0.32 ± 0.05 µg/mL) than NBF. Moreover, NBF2 also possessed the ability to promote glucose uptake, which was mediated via P13K/AKT and AMPK pathways. This study demonstrated that F. tikoua possesses antidiabetic efficacy in vitro and in vivo and provided a scientific basis for its folk medicinal use. NBF2 might be potential natural candidate drugs to treat diabetes mellitus. It is the first time the antidiabetic activity and the potential mechanisms of NBF2 were reported.

Phytochemistry, biological activities, industrial and traditional uses of fig (Ficus carica): A review.

This review describes the traditional and industrial use of fig (Ficus carica) in medicine as remedies for health problems and its biological activities. It describes various ways of traditional use to treat various ailments like, inflammation, gastric problems and cancer. Phytochemical studies on fruits and leaves of fig plant have explored that they are rich in phenolics, organic acids and volatile compounds. Owing to rich and diversified presence of biologically active compounds, they possess various biological activities such as antioxidant, anti-inflammatory, antibacterial, anticancer, hepatoprotective, antidiabetic, antifungal, antiviral, antimutagenic, antipyretic, antituberculosis, anti-angiogenic, antiparisitic, hematostatis, anticonstipation and antiwarts activities.

The Cytotoxic and Anti-Migratory Properties of Caesalpinia sappan and Ficus septica, in Combination with Doxorubicin on 4T1 TNBC Cells with Nephroprotective Potential.

OBJECTIVE: To evaluate the anti-cancer properties of Caesalpinia sappan and Ficus septica in combination with doxorubicin on 4T1 cells, confirm their nephroprotective activities, and predict the molecular targets of the underlying mechanisms. METHODS: The cytotoxic activities of all extracts and doxorubicin were determined by MTT assay followed by cell cycle and apoptosis analysis using flow cytometry. Immunoblotting was used to determine the protein expressions. The proteins involved in the cell proliferation and migration were analyzed through bioinformatics approaches, whereas, the interaction between compounds and protein targets was observed through molecular docking. Furthermore, the effect of the extracts on cell migration was analyzed by scratch wound healing assay. The intracellular ROS after treatment with extracts was observed using DCFDA staining flow cytometry. RESULTS: Both ECS and EFS performed cytotoxic properties and significantly enhanced doxorubicin's cytotoxic effects against 4T1 cells. However, these cytotoxic activities did not correlate with the cell cycle progression. On the contrary, the combination treatment caused apoptosis that may correlate with the decreasing of IκBα phosphorylation, indicating that all agents targeted the inhibition of NF-κB activation. The combination treatments also inhibited cell migration and decreased MMP-9 expression. TNBC proliferation and metastasis needed at least 54 proteins to be activated, some of them are related to NF-κB activation. The inhibitory effect of ECS correlated with the interaction of brazilin and brazilein to IKK, a kinase protein that plays a role in IκBα phosphorylation. In addition, ECS and EFS reduced ROS expression in Vero cells caused by doxorubicin. CONCLUSION: In conclusion, ECS and EFS effectively enhanced the cytotoxic effect of doxorubicin and inhibit cell migration on 4T1 cells and these activities may correlate to the inhibitory effect of NF-κB activation. ECS and EFS also exhibit ROS suppressing effect on Vero cells that may be beneficent to reduce nephrotoxicity of chemotherapeutic treatment.

Lignans and phenylpropanoids from the roots of Ficus hirta and their cytotoxic activities.

One undescribed lignan, one new natural product, along with fourteen known compounds, were isolated from the roots of Ficus hirta. The structures of the isolates were elucidated by comprehensive spectroscopic technologies, including UV, IR, HRESIMS, and NMR. The absolute configuration of 1 was determined by comparison of experimental and calculated ECD data. The cytotoxicity of all the compounds against HeLa and HepG2 cell lines was evaluated and compound 7 showed considerable cytotoxic effect towards HepG2 cells. Also, the apoptotic effect of 7 on HepG2 cells and the effect of 7 on the key proteins (p-JNK and p-p38) in MAPK (Mitogen-activated protein kinases) pathways were studied by flow cytometry and western blotting experiment. As a result, compound 7 induced the apoptosis of HepG2 cells, and dose-dependently increased the phosphorylation of JNK and p38. Thus, 7 might trigger HepG2 cells apoptosis via JNK/p38 MAPK signaling pathway.