Xanthorrhizol, a potential anticancer agent, from Curcuma xanthorrhiza Roxb.

BACKGROUND: Xanthorrhizol (XTZ), a bisabolene sesquiterpenoid, is abundantly found in the plant Curcuma xanthorrhiza Roxb. Traditionally, C. xanthorrhiza is widely used for the treatment of different health conditions, including common fever, infection, lack of appetite, fatigue, liver complaints, and gastrointestinal disorders. XTZ exhibits wide-ranging pharmacological activities, including anticancer, antioxidative, anti-inflammatory, antimicrobial, and antidiabetic activities, in addition to a protective effect on multiple organs. The present review provides detailed findings on the anticancer activities of XTZ and the underlying cellular and molecular mechanisms. METHODS: Literature was searched systematically in main databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with keywords "tumor AND xanthorrhizol" or "cancer AND xanthorrhizol". RESULTS: Studies show that XTZ has preventive and therapeutic activities against different types of cancer, including breast, cervical, colon, liver, lung, oral and esophageal, and skin cancers. XTZ regulates multiple signaling pathways that block carcinogenesis and proliferation. In vitro and in vivo studies showed that XTZ targets different kinases, inflammatory cytokines, apoptosis proteins, and transcription factors, leading to the suppression of angiogenesis, metastasis, and the activation of apoptosis and cell cycle arrest. CONCLUSION: The potential anticancer benefits of XTZ recommend further in vivo studies against different types of cancer. Further, XTZ needs to be confirmed for its toxicity, bioavailability, protective, antifatigue, and energy booster activities. Future studies for the therapeutic development of XTZ may be directed to cancer-related fatigue.

Isolation, Characterization and in Silico Studies of Secondary Metabolites from Jurinea macrocephala DC. with Antiproliferative Activity.

In the present work, cytotoxic potential of Jurinea macrocephala DC. (Asteraceae) was evaluated on A549 lung cancer and MCF-7 breast cancer cell lines. Isolation studies were carried out using various and repetitive chromatographic methods in order to determine the phytochemical profile of the extracts. These studies led to the identification of twelve compounds; four triterpenes (1-4) and eight flavonoids (5-12). Spectroscopic examination (1D and 2D NMR, ESI-MS) and comparison with relevant literature data were used to deduce the structures of all isolated molecules. To rationalize the obtained cytotoxicity data against breast cancer cell lines, the isolated compounds were docked into the binding site of aromatase, an important target enzyme for the treatment of breast cancer. Molecular docking studies revealed that flavonoids without sugar moieties (5-8) showed the best binding affinities. Overall, these mentioned compounds turned out to be also the most appropriate oral drug candidates after the calculation of their Lipinski parameters.

Role of Hypericum perforatum oil and pomegranate seed oil in wound healing: an in vitro study.

This study aimed to investigate the wound-healing efficacy of Hypericum perforatum and pomegranate seed extract oil combined with curcumin as an anti inflammatory agent. A series of experiments were carried out to determine effective concentrations for H. perforatum oil, pomegranate seed extract oil, and curcumin. Ibuprofen was used as a positive control. The wound-healing effects of the applied compounds were tested according to the migration experiment model performed in HaCaT cells. A real-time cell analyzer (xCELLigence) was used to determine the cytotoxic/proliferative effects of H. perforatum, pomegranate seed oil, ibuprofen, and curcumin in HaCaT cells alone and their combined use at specified concentrations. After examining the noncytotoxic concentrations of H. perforatum oil, pomegranate seed oil, curcumin, and ibuprofen, migration experiments were performed to examine the wound healing properties. According to the results, the wound-healing efficacy of curcumin and H. perforatum combination was better than ibuprofen combinations. Also, according to the results, the wound-healing efficacy of curcumin and pomegranate seed oil combination was better than ibuprofen combinations. It was concluded that both oils had improved wound-healing properties in combination with curcumin or Ibuprofen.

Natural product-based nanoformulations for cancer therapy: Opportunities and challenges.

Application of natural product-based nanoformulations for the treatment of different human diseases, such as cancer, is an emerging field. The conventional cancer therapeutic modalities, including surgery, chemotherapy, immunotherapy, radiotherapy has limited achievements. A larger number of drawbacks are associated with these therapies, including damage to proliferating healthy tissues, structural deformities, systemic toxicity, long-term side effects, resistance to the drug by tumor cells, and psychological problems. The advent of nanotechnology in cancer therapeutics is recent; however, it has progressed and transformed the field of cancer treatment at a rapid rate. Nanotherapeutics have promisingly overcome the limitations of conventional drug delivery system, i.e., low aqueous solubility, low bioavailability, multidrug resistance, and non-specificity. Specifically, natural product-based nanoformulations are being intentionally studied in different model systems. Where it is found that these nanoformulations has more proximity and reduced side effects. The nanoparticles can specifically target tumor cells, enhancing the specificity and efficacy of cancer therapeutic modalities which in turn improves patient response and survival. The integration of phytotherapy and nanotechnology in the clinical setting may improve pharmacological response and better clinical outcome of patients.

Recent Advances Regarding the Phytochemical and Therapeutic Uses of Populus nigra L. Buds.

Populus nigra L. (Salicaceae family) is one of the most popular trees that can be found in deciduous forests. Some particularities that characterize the Populus genus refer to the fact that it includes more than 40 species, being widespread especially in Europe and Asia. Many residues, parts of this tree can be used as a bioresource for different extracts as active ingredients in pharmaceuticals next to multiple benefits in many areas of medicine. The present review discusses the latest findings regarding the phytochemical composition and the therapeutic properties of Populus nigra L. buds. The vegetal product has been described mainly to contain phenolic compounds (phenols, phenolic acids and phenylpropanoids), terpenoids (mono and sesquiterpenoids), flavones (e.g., apigenol and crysin), flavanones (e.g., pinocembrin and pinostrombin), caffeic/ferulic acids and their derivates, and more than 48 phytocompounds in the essential oils. The resinous exudates present on the buds have been the major plant source used by bees to form propolis. Several studies depicted its antioxidant, anti-inflammatory, antibacterial, antifungal, antidiabetic, antitumor, hepatoprotective, hypouricemic properties and its effects on melanin production. All these lead to the conclusion that black poplar buds are a valuable and important source of bioactive compounds responsible for a wide range of therapeutic uses, being a promising candidate as a complementary and/or alternative source for a large number of health problems. The aim of the review is to gather the existing information and to bring an up to date regarding the phytochemical and therapeutic uses of Populus nigra L. buds.

Molecular Mechanisms of Action of Tocotrienols in Cancer: Recent Trends and Advancements.

Tocotrienols, found in several natural sources such as rice bran, annatto seeds, and palm oil have been reported to exert various beneficial health promoting properties especially against chronic diseases, including cancer. The incidence of cancer is rapidly increasing around the world not only because of continual aging and growth in global population, but also due to the adaptation of Western lifestyle behaviours, including intake of high fat diets and low physical activity. Tocotrienols can suppress the growth of different malignancies, including those of breast, lung, ovary, prostate, liver, brain, colon, myeloma, and pancreas. These findings, together with the reported safety profile of tocotrienols in healthy human volunteers, encourage further studies on the potential application of these compounds in cancer prevention and treatment. In the current article, detailed information about the potential molecular mechanisms of actions of tocotrienols in different cancer models has been presented and the possible effects of these vitamin E analogues on various important cancer hallmarks, i.e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed.

Anti-inflammatory Effects of Pelargonium endlicherianum Fenzl. Extracts in Lipopolysaccharide-stimulated Macrophages.

OBJECTIVES: This study was designed to investigate the anti-inflammatory effects of Pelargonium endlicherianum Fenzl. and Pelargonium quercetorum Agnew. root extracts compared with the effects of commercial Pelargonium sidoides root extract by production of pro-inflammatory substances and inflammatory signal transduction on LPS-stimulated macrophages. MATERIALS AND METHODS: To measure the effects of root extracts on pro-inflammatory mediators, we used the following methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (cell viability or cytotoxcicity), enzyme-linked immunosorbent assay (cytokine production, prostoglandin E2 production), reverse transcriptase-polymerase chain reaction (COX-2, iNOS mRNA), Western blotting analysis [MAPK activation and NF-κB (p65) traslocation] and the Griess reaction (NO production). RESULTS: Stimulation of the RAW 264.7 cells with LPS (0.5 µg/mL, 6 hrs treatment) caused an elevated production of pro-inflammatory cytokines (TNF-α and IL-6), increased mRNA expression of COX-2 and inducible NO synthase with release of PGE2 and NO, activated MAPK (phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, P38) signalling pathway, and nuclear translocation of NF-κB (p65), which were markedly inhibited by the pre-treatment with 11% ethanol and 70% methanol root extracts of P. endlicherianum without causing any cytotoxic effects. P. quercetorum root extract only decreased TNF-α production and P. sidoides root extract alleviated P38/MAPK activation and COX-2 mRNA expression with PGE2 production. CONCLUSION: Our data indicate that especially 11% ethanol root extract of P. endlicherianum targets the inflammatory response of macrophages via inhibition of COX-2, IL-6, and TNF-α through inactivation of the NF-κB signalling pathway, supporting the pharmacologic basis of P. endlicherianum as a traditional herbal medicine for the treatment of inflammation and its associated disorders.

Chemical composition and biological investigation of Pelargonium endlicherianum root extracts.

CONTEXT: Pelargonium endlicherianum Fenzl. (Geraniaceae) roots and flowers are traditionally used in Turkey as a decoction treatment against intestinal parasites. Neither the chemical composition nor the potential bioactivity of the plant roots has been studied before. OBJECTIVES: The phenolic content and effects of P. endlicherianum root extracts on antioxidant enzyme levels on A549 cells were studied for the first time. MATERIALS AND METHODS: The chemical composition was analyzed via spectrophotometric and chromatographic (HPLC MS/MS and HPLC) techniques. The antioxidant activity was determined at different concentrations ranging from 0.001 to 2 mg/mL using DPPH• and ABTS•+ radical scavenging activity, ß-carotene-linoleic acid co-oxidation assay, protection of 2-deoxyribose and bovine brain-derived phospholipids against a hydroxyl radical-mediated degradation assay. Glutathione peroxidase and superoxide dismutase activities were also studied as well as the effects of the extracts on nitric oxide levels on IL-1ß stimulated A549 cells. RESULTS: The key parameters for the most active ethyl acetate extract included the following: DPPH• IC50: 0.23 mg/mL, TEAC/ABTS: 2.17 mmol/L Trolox, reduction: 0.41 mmol/g AsscE, and protection of lipid peroxidation IC50: 0.05 mg/mL. Furthermore, the ethyl acetate extract increased the SOD level significantly compared to control group (4.48 U/mL) at concentrations of 100 and 200 µg/mL SOD, 5.50 and 5.67 U/mL, respectively. Apocynin was identified as the major component, and the ethyl acetate fraction was found to be rich in phenolic compounds. DISCUSSION AND CONCLUSION: Pelargonium endlicherianum root extracts displayed antioxidant activity and increased the antioxidant enzyme levels in IL-1ß stimulated A549 cells, while decreasing the NO levels.

Effects of propolis on fracture healing: an experimental study.

Propolis is a substance of honeybee origin with known antioxidant effects. The purpose of this study was to examine the effects of propolis on fracture healing and the antioxidant system in an experimental setting. Thirty-two rats that underwent experimental femur fracture and then fixation were randomly allocated in one of four groups: two control groups (Control-3w and Control-6w) and two treatment groups (Propolis-3w and Propolis-6w). Treatment groups received propolis until killing (at 3 or 6 weeks). X-ray, histological, bone mineral density measurement findings and endogenous antioxidant levels were examined. The bone mineral density was higher, radiological and histological evaluation scores were better, and superoxide dismutase, total glutathione and myeloperoxidase levels were lower among the rats that received oral propolis treatment compared with the controls. In addition, bone mineral density and histological assessment scores showed time-dependent improvement in the treatment group. In conclusion, the findings of this study suggest that propolis has some time-dependent beneficial effects on fracture healing.