Anticancer potential of oroxylin A: from mechanistic insight to synergistic perspectives.

Oroxylin A (OA), a well-known constituent of the root of Scutellariae plants, has been used in ethnomedicine already for centuries in treating various neoplastic disorders. However, only recent molecular studies have revealed the different mechanisms behind its action, demonstrating antiproliferative, anti-inflammatory, and proapoptotic effects, restricting also the spread of cancer cells to distant organs. A variety of cellular targets and modulated signal transduction pathways regulated by OA have been determined in diverse cells derived from different malignant tissues. In this review article, these anticancer activities are thoroughly described, representing OA as a potential lead structure for the design of novel more potent anticancer medicines. In addition, co-effects of this natural compound with conventional anticancer agents are analyzed and the advantages provided by nanotechnological methods for more efficient application of OA are discussed. In this way, OA might represent an excellent example of using ethnopharmacological knowledge for designing modern medicines.

Evaluation of analgesic and anti-inflammatory activities and molecular docking analysis of steroidal lactones from Datura stramonium L.

BACKGROUND: Datura stramonium L. is widely used across the world for its therapeutic potential to treat inflammatory disorders. The current work was designed to isolate and identify steroidal lactones from D. stramonium leaves and evaluate their anti-inflammatory and analgesic properties. METHODS: Several compounds were isolated from D. stramonium leaves and characterized by nuclear magnetic resonance and high-resonance electron spray ionization mass spectrometry techniques. Further, anti-inflammatory properties of these compounds were evaluated by in vitro assays, such as release of NO and pro-inflammatory cytokines by lipopolysaccharide (LPS)-activated J774A.1 macrophages. Using in vivo models, anti-inflammatory and analgesic effects were examined by mouse tail-flick, carrageenan-induced inflammation in rat paw model, vascular permeability in rats, and acetic acid-induced writhing in mice. The docking studies were performed for assessing the binding efficiency of the test compounds with cyclooxygenase-1 (COX-1) and COX-2, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), inducible nitric oxide synthases (iNOS) and nuclear factor-κB (NF-κB). RESULTS: Three lactones were isolated and confirmed as daturalactone (D1), 12-deoxywithastramonolide (D23), and daturilin (D27). Further, the isolated compounds showed nitric oxide inhibition and pro-inflammatory cytokines released by LPS-activated J774A.1 macrophages. The in vivo results suggest that D1, D23 and D27 (20 mg/kg) were able to reduce the pain and inflammation in various animal models. The docking analysis showed that these three compounds actively bind with COX-1, COX-2, LOX-1, NF-κB, and iNOS, validating the anti-inflammatory effects of the lactones. CONCLUSION: These findings demonstrate substantial anti-inflammatory and analgesic properties of D. stramonium-derived lactones and their potential as anti-inflammatory agents to treat chronic inflammatory ailments.

Metal-doped and hybrid carbon dots: A comprehensive review on their synthesis and biomedical applications.

Carbon dots (CDs) are the most promising candidates of the carbon family with superior properties like ultra-small size, high aqueous solubility, low cytotoxicity, and inherent photoluminescence which makes them suitable for diverse biomedical applications. Methods have been developed to enhance their applications. Doping/surface passivation of CDs improves their physicochemical properties, visible light absorption probability, and quantum yield by controlling their size, morphology, structure, and band-gap energy. Recently, metal-doped CDs have emerged as an important class of nanomaterials with numerous biomedical applications. Additionally, the conjugation of CDs with semiconductor metal-oxide nanoparticles (NPs) enhances their free radical production rates under visible light irradiation. Conjugation of fluorescent CDs with magnetic NPs leads to the development of multimodal imaging platforms. Similarly, ternary conjugates composed of fluorescent CDs, near-infrared (NIR) responsive, and magnetic NPs are useful for multi-modal imaging-guided, and NIR-responsive synergistic chemo-phototherapy. However, no comprehensive review is published yet which covers metal-doped and hybrid CDs. Therefore, herein we provide detailed information about their synthesis and important biomedical applications. Firstly, we have covered various synthesis methods for CD conjugation including the critical analysis of the effects of the reaction conditions and doping/conjugation on the structure and properties of the CDs. Then we have extensively reviewed their biomedical applications as antimicrobial, antioxidant, and bioimaging agents, and in the field of cancer phototherapy with special emphasis on their mechanisms of actions. Finally, the future directions of research and the applications of the metal-doped and hybrid CDs have been discussed. We believe that this review article will enrich the understanding of different synthetic routes of CD-nanocomposites and their biomedical applications.

Bioactive constituents of Emblica officinalis overcome oxidative stress in mammalian cells by inhibiting hyperoxidation of peroxiredoxins.

Emblica officinalis (Amla) is a renowned fruit having nutritional and medicinal traits mostly linked to its antioxidants content. In the current study, the methanolic crude extract of amla fruit is subjected to sequential fractionation to get its partially purified fractions. The ethyl acetate (EA) and butanol (BUT) fractions of amla showed maximum antioxidant potential. The ferric reducing capability and nitric oxide scavenging activity were highest in EA fraction. One of the highlights of the study is the cellular antioxidant assay conducted in HeLa cells. Additionally, HeLa cells pre-treated with EA and BUT fractions were able to combat oxidative stress via total reduction in hyperoxidation of intracellular peroxiredoxin enzyme. Gallic acid, ascorbic acid, ellagic acid, rutin, quercetin, and catechol are the major compounds present in these fractions as identified by LC-ESI-MS followed by their quantification by HPLC. These findings indicate that components of E. officinalis can protect intracellular oxidative stress-mediated degeneration. PRACTICAL APPLICATIONS: The study highlighted that E. officinalis is a promising source of phenolics and flavonoids acting as natural antioxidants, which showed varied potential to scavenge ROS. Also, the plant fractions were able to fight intracellular oxidative stress via total reduction in hyperoxidation of the human peroxiredoxin. In conclusion, we can say that the regular intake of such food supplements that affect important antioxidant enzymes can be of special interest in the management of oxidative stress-mediated human ailments.

Yoga as an intervention to manage multiple sclerosis symptoms.

Multiple sclerosis (MS) is an autoimmune, demyelinating, inflammatory disease of central nervous system (CNS) which is characterized by spasticity, fatigue, depression, anxiety, bowel and bladder dysfunction, impaired mobility, cognitive impairment etc. and affects approximately 2.5 million people worldwide. Disease modifying therapies for MS which help in preventing accumulation of lesions in white matter of CNS are costly and have significant adverse effects. Therefore, patients with MS are using complementary and alternative medicine (CAM) and Yoga is one of the most popular form of CAM which is being used immensely to reduce or overcome the symptoms of MS. In the current review attempted to present the potential impact of yoga practices on reducing MS related symptoms.

Deciphering the in vivo redox behavior of human peroxiredoxins I and II by expressing in budding yeast.

Peroxiredoxins (Prxs), scavenge cellular peroxides by forming recyclable disulfides but under high oxidative stress, hyperoxidation of their active-site Cys residue results in loss of their peroxidase activity. Saccharomyces cerevisiae deficient in human Prx (hPrx) orthologue TSA1 show growth defects under oxidative stress. They can be complemented with hPRXI but not by hPRXII, but it is not clear how the disulfide and hyperoxidation states of the hPrx vary in yeast under oxidative stress. To understand this, we used oxidative-stress sensitive tsa1tsa2Δ yeast strain to express hPRXI or hPRXII. We found that hPrxI in yeast exists as a mixture of disulfide-linked dimer and reduced monomer but becomes hyperoxidized upon elevated oxidative stress as analyzed under denaturing conditions (SDS-PAGE). In contrast, hPrxII was present predominantly as the disulfide in unstressed cells and readily converted to its hyperoxidized, peroxidase-inactive form even with mild oxidative stress. Interestingly, we found that plant extracts containing polyphenol antioxidants provided further protection against the growth defects of the tsa1tsa2Δ strain expressing hPrx and preserved the peroxidase-active forms of the Prxs. The extracts also helped to protect against hyperoxidation of hPrxs in HeLa cells. Based on these findings we can conclude that resistance to oxidative stress of yeast cells expressing individual hPrxs requires the hPrx to be maintained in a redox state that permits redox cycling and peroxidase activity. Peroxidase activity decreases as the hPrx becomes hyperoxidized and the limited protection by hPrxII compared with hPrxI can be explained by its greater sensitivity to hyperoxidation.

Biological markers for the effects of yoga as a complementary and alternative medicine.

From the last few decades, there are increasing incidences of disorders like premature aging, cardiovascular disease, multiple sclerosis, fibromyalgia, and Alzheimer's disease In addition to medication, researchers have found that yoga, a mind-body therapy, can be used as an alternative medicine. Yoga combines specific physical postures, breathing techniques, relaxation and meditation that improve mental and physical health of the body. The purpose of this review is to collate the research evidences claiming health benefits of performing traditional yogic practices. What are the biological and other reliable indicators to suggest that doing asanas, pranayama, and meditation could reduce or treat wide range of life style disorders are discussed. Importantly, these indicators are otherwise used to assess the severity of disorders. In many of the study it has been shown that yoga improves the redox health of body whose imbalance has been well proven to cause many health complications. The impact of yoga on neurodegenerative diseases have revealed that it reverses memory loss, reduce anxiety, depression and stress, the biological indicators of disease. However, most studies have several limitations and therefore further research into yoga is needed to validate these findings.

Pectin-guar gum-zinc oxide nanocomposite enhances human lymphocytes cytotoxicity towards lung and breast carcinomas.

Pectin-guar gum-zinc oxide (PEC-GG-ZnO) nanocomposite was prepared by precipitation technique. The composite was characterized by using FT-IR, XRD, HRTEM, SAED, EDS, and SEM. TEM images showed the hexagonal shape of nanocomposite with the size range of 50-70 nm. Further, PEC-GG-ZnO was used as an immunomodulator for the first time to improve the cancer cells killing capabilities of human peripheral-blood lymphocytes (PBL). The lymphocyte proliferation assay proved the immunostimulatory property of the PEC-GG-ZnO which increased with the increase in concentration (25 µg/ml to 200 µg/ml). ELISA detection confirmed a significant increase in the release of IFN-γ, IL-2 and TNF-α cytokines and flow cytometry analysis revealed enhanced expression of CD3, CD8, and CD56 after treating PBL with PEC-GG-ZnO as compared to PEC and GG treatment. Moreover, we also found that nanocomposite pretreated human PBL displayed enhanced cytotoxicity towards lung (A549) and breast carcinoma (MCF-7) cells as compared to untreated PBL. The microcytotoxicity assay also demonstrated that with increase in effector: target ratios from 2.5:1 to 20:1, there was an increase in the cancer cell death. Taken together, the current data corroborates the immunostimulatory activities of PEC-GG-ZnO, a novel nanocomposite, hence it can serve as a promising cancer therapeutic agent.