In the competition for nutrients, members of the Bacillus genus often produce a vast array of biologically active molecules that potentially inhibit the development of competing organisms. The Gram-positive bacterium Bacillus subtilis has an average of 4 to 5% of its genome devoted to antibiotic synthesis and is able to produce more than two dozen antibiotics with an amazing variety of structures (1). Many of these compounds, which have a peptide origin, are synthesized either ribosomally or nonribosomally. Among the nonribosomally generated amphipathic cyclic lipopeptides, surfactins, iturins, and fengycins have well-recognized potential applications in biotechnology and biopharmaceutical products due to their antagonistic activities and surfactant properties (2, 3). Furthermore, the mechanisms behind the observed biocontrol efficacy of different Bacillus strains have also been well described (4-6). Lipopeptides are able to induce systemic resistance in plants and to facilitate the multicellular behaviors of the producing strains, such as swarming motility, biofilm formation, and colony morphology (5-7).Surfactins, iturins, and fengycins are synthesized by nonribosomal peptide synthetases (NRPSs) which exhibit a distinct modular architecture (2, 8-10). A module is typically composed of three core domains, with each domain responsible for a certain biochemical reaction (11). Specifically, the amino acid adenylation domain (A domain) controls the entry of substrates into the peptide structure by recognizing and activating a specific amino acid. The thiolation domain (T domain), also referred to as the peptidyl carrier protein (PCP), contains an invariant serine residue which is essential for the binding of a 4=-phosphopantetheine cofactor. The N-terminal condensation domain (C domain) is required for the coupling of two consecutively bound amino acids (12, 13). These three domains constitute a minimal elongation module, the basic repetitive unit of a multimodular NRPS. Furthermore, modules can be supplemented with domains that catalyze modifications of the activated amino acid, such as N-methylation and epimerization. In some cases, when the first module of an NRPS complex lacks a C domain, the last module contains a termination thioesterase domain (TE domain) to release the end product (14). The order and specificity of the modules within the protein template determine the sequence of the product (for type A, linear NRPSs) (8, 11). Genetic and biochemical analyses have revealed that the modular arrangement of most lipopeptide synthetases is colinear with the amino acid sequences of lipopeptides (1, 2). This assembly line arrangement of the conserved catalytic modules and domains provides the means to construct hybrid NRPSs for use in the synthesis of new lipopeptide compounds (15-18). The prospect of creating numerous bioactive lipopeptides by engineering existing lipopeptide synthetases has stimulated the search for new NRPSs responsible for lipopeptide synthesis (19-24).To date, only two reported kinds of bios...

BackgroundAge is the leading risk factor for acute and chronic neurodegenerative diseases. The Shen Nong Ben Cao Jing, the oldest known compendium of Chinese materia media, lists herbal medicines that were believed to exert neither fast acting pharmacological effects nor discernible toxicity, but to promote general health and longevity. In modern terms, these herbal medicines could be considered as complementary health care products for prevention rather than treatment of diseases. In the present study, we examined whether a selection of 13 such herbal medicines exhibited neuroprotective activity.MethodsThe antioxidant capacity of the herbal extracts was determined using three non-cellular assays measuring the total phenol content (FCR assay), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity and oxygen radical absorbance capacity (ORAC). Cytotoxic effects of the herbal extracts were assayed in cultured mouse cortical neurons and their neuroprotective activities were studied using staurosporine-induced apoptosis of the cultured neurons.ResultsMost of the herbal extracts showed negligible toxic effects at 100 μg/ml. However, Polygonum multiflorum and Rhodiola rosea exhibited some neurotoxicity at this concentration. Extracts of Ganoderma lucidum, Glycyrrhiza glabra, Schizandra chinensis, and Polygonum cuspidatum inhibited staurosporine-induced apoptosis by 30 – 50% in a dose-dependent manner. The neuroprotective effects of Polygonum cuspidatum were predominantly due to its major ingredient, resveratrol. The effective herbal extracts showed various levels of reactive oxygen species (ROS) scavenging capacity, which was significantly correlated with their neuro- protective activity. However, P. multiflorum and R. rosea extracts proved to be the exception as they exhibited a high level of antioxidant capacity, but did not exhibit neuroprotective effects in cell-based assay.ConclusionsThis in vitro study provides evidence for neuroprotective activity of some Chinese herbal medicines traditionally used to promote healthy ageing and longevity. Our results provide a justification for further study of these herbal extracts in neurodegenerative animal models to assess their safety and effectiveness as a basis for subsequent clinical trials. These herbal medicines might potentially offer a novel preemptive neuroprotective approach in neurodegenerative diseases and might be developed for use in persons at risk.

Munch, G. (2013). Cytoprotective properties of traditional Chinese medicinal herbal extracts in hydrogen peroxide challenged human U373 astroglia cells. Neurochemistry International: the journal for the publication of cellular and molecular aspects of neurochemistry, 62 (5), 522-529. Cytoprotective properties of traditional Chinese medicinal herbal extracts in hydrogen peroxide challenged human U373 astroglia cells AbstractAge is the leading risk factor for many of the most prevalent and devastating diseases including neurodegenerative diseases. A number of herbal medicines have been used for centuries to ameliorate the deleterious effects of ageing-related diseases and increase longevity. Oxidative stress is believed to play a role in normal ageing as well as in neurodegenerative processes. Since many of the constituents of herbal extracts are known antioxidants, it is believed that restoring oxidative balance may be one of the underlying mechanisms by which medicinal herbs can protect against ageing and cognitive decline. Based on the premise that astrocytes are key modulators in the progression of oxidative stress associated neurodegenerative diseases, 13 herbal extracts purported to possess anti-ageing properties were tested for their ability to protect U373 human astrocytes from hydrogen peroxide induced cell death. To determine the contribution of antioxidant activity to the cytoprotective ability of extracts, total phenol content and radical scavenging capacities of extracts were examined. Polygonum multiflorum, amongst others, was identified as possessing potent antioxidant and cytoprotective properties. Not surprisingly, total phenol content of extracts was strongly correlated with antioxidant capacity. Interestingly, when total phenol content and radical scavenging capacities of extracts were compared to the cytoprotective properties of extracts, only moderately strong correlations were observed. This finding suggests the involvement of multiple protective mechanisms in the beneficial effects of these medicinal herbs. AbstractAge is the leading risk factor for many of the most prevalent and devastating diseases including neurodegenerative diseases. A number of herbal medicines have been used for centuries to ameliorate the deleterious effects of ageing-related diseases and increase longevity. Oxidative stress is believed to play a role in normal ageing as well as in neurodegenerative processes. Since many of the constituents of herbal extracts are known antioxidants, it is believed that restoring oxidative balance may be one of the underlying mechanisms by which medicinal herbs can protect against ageing and cognitive decline. Based on the premise that astrocytes are key modulators in the progression of oxidative stress associated neurodegenerative diseases, 13 herbal extracts purported to possess antiageing properties were tested for their ability to protect U373 human astrocytes from hydrogen peroxide induced cell death. To determine the contribution of antioxidant activity to the cytoprotective ab...

Purpose: Acute spinal cord injury (SCI) triggers multiple cellular and molecular pathways; therapy aimed at only one pathway is unlikely to succeed. Anecdotal reports indicate that a novel herbal formulation (JSK-Ji-Sui-Kang) may enhance recovery in humans with SCI. We investigated whether JSK's therapeutic effects could be verified in a well-established SCI model in rats. Methods: Therapeutic effects of JSK were tested using a standard behavioral assessment, histological, immunochemical and microarray analysis. Phytochemical fingerprinting of JSK was performed using high performance liquid chromatography coupled with photodiode array detection and electrospray ionization-mass spectrometry. JSK or vehicle was gavaged to rats 24 hours after SCI and daily thereafter for 3 weeks. Results: Locomotor function significantly improved (n = 12; p < 0.05), tissue damage was reduced (p < 0.01; n = 6) and more axons and myelin were observed in JSK-treated compared with vehicle control animals. JSK significantly enhanced expression of neuroglobin, vascular endothelial growth factor and growth-associated protein 43, and reduced the expression of caspase 3, cyclooxygenase-2, RhoA (p < 0.05; n = 6) and fibrinogen (p < 0.01; n = 6). RNA microarray indicated that JSK altered transcription of genes involved in ischemic and inflammatory/immune responses and apoptosis (p < 0.05; n = 3).Conclusions: JSK appears to target multiple biochemical and cellular pathways to enhance functional recovery and improve outcomes of SCI. The results provide a basis for further investigation of JSK's effects following SCI.

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