Complete Genome of Vibrio neocaledonicus CGJ02-2, An active Compounds Producing Bacterium Isolated from South China Sea.

Strain CGJ02-2 was isolated from the coral reefs in South China sea and deposited in South China Sea Institute of Oceanology, Chinese Academy of Sciences. Active compounds including indole, ρ-hydroxybenzaldehyde were isolated from this strain. To explore the biosynthetic way of these compounds and search gene clusters, the complete genome of this strain was sequenced by Single Molecule, Real-Time (SMRT) technology. It was de novo assembled to two circular chromosomes of 3,400,283 bp with GC% 44.77 and 1,845,572 bp with GC% 44.59 respectively and classified as Vibrio alginolyticus. In silico phenotype features of Vibrio alginolyticus CGJ02-2 were also analyzed. The biosynthetic pathway of ρ-hydroxybenzaldehyde and indole in this strain were postulated. Gene clusters of four secondary metabolites including bacteriocin, ectoine, siderophore, arylpolyene were identified. This study provides helpful information for further utilizing Vibrio alginolyticus CGJ02-2 as a source of valuable bioactive compounds.

Perspective on the Therapeutics of Anti-Snake Venom.

Snakebite envenomation is a life-threatening disease that was recently re-included as a neglected tropical disease (NTD), affecting millions of people in tropical and subtropical areas of the world. Improvement in the therapeutic approaches to envenomation is required to palliate the morbidity and mortality effects of this NTD. The specific therapeutic treatment for this NTD uses snake antivenom immunoglobulins. Unfortunately, access to these vital drugs is limited, principally due to their cost. Different ethnic groups in the affected regions have achieved notable success in treatment for centuries using natural sources, especially plants, to mitigate the effects of snake envenomation. The ethnopharmacological approach is essential to identify the potential metabolites or derivatives needed to treat this important NTD. Here, the authors describe specific therapeutic snakebite envenomation treatments and conduct a review on different strategies to identify the potential agents that can mitigate the effects of the venoms. The study also covers an increased number of literature reports on the ability of natural sources, particularly plants, to treat snakebites, along with their mechanisms, drawbacks and future perspectives.

Bioactive Compounds Isolated from Marine Bacterium Vibrio neocaledonicus and Their Enzyme Inhibitory Activities.

Marine organisms are recognized as a source of compounds with interesting biological activities. Vibrio neocaledonicus has been reported on for its high effectiveness against corrosion in metals but it has been little studied for its chemical and biological activities. In this study, four compounds were isolated from V. neocaledonicus: indole (1); 1H-indole-3-carboxaldehyde (2); 4-hydroxybenzaldehyde (3) and Cyclo (-Pro-Tyr) (4); using a bioassay-guided method, since in a previous study it was found that the ethyl acetate extract was active on the enzymes acetylcholinesterase (AChE), alpha-glucosidase (AG) and xanthine oxidase (XO). The inhibitory activities of the three compounds against AChE, AG and XO was also evaluated. In addition, the enzymatic inhibitory activity of indole to the toxins from the venom of Bothrops asper was tested. Results showed that indole exhibited strong inhibitory activity to AG (IC50 = 18.65 ± 1.1 µM), to AChE, and XO (51.3% and 44.3% at 50 µg/mL, respectively). 1H-indole-3-carboxaldehyde displayed strong activity to XO (IC50 = 13.36 ± 0.39 µM). 4-hydroxybenzaldehyde showed moderate activity to XO (50.75% at 50 µg/mL) and weak activity to AChE (25.7% at 50 µg/mL). Furthermore, indole showed a significant in vitro inhibition to the coagulant effect induced by 1.0 µg of venom. The findings were supported by molecular docking. This is the first comprehensive report on the chemistry of V. neocaledonicus and the bioactivity of its metabolites.

Interactions of Desmethoxyyangonin, a Secondary Metabolite from Renealmia alpinia, with Human Monoamine Oxidase-A and Oxidase-B.

Renealmia alpinia (Zingiberaceae), a medicinal plant of tropical rainforests, is used to treat snakebites and other injuries and also as a febrifuge, analgesic, antiemetic, antiulcer, and anticonvulsant. The dichloromethane extract of R. alpinia leaves showed potent inhibition of human monoamine oxidases- (MAOs-) A and B. Phytochemical studies yielded six known compounds, including pinostrobin 1, 4'-methyl ether sakuranetin 2, sakuranetin 3, pinostrobin chalcone 4, yashabushidiol A 5, and desmethoxyyangonin 6. Compound 6 displayed about 30-fold higher affinity for MAO-B than MAO-A, with Ki values of 31 and 922 nM, respectively. Kinetic analysis of inhibition and equilibrium-dialysis dissociation assay of the enzyme-inhibitor complex showed reversible binding of desmethoxyyangonin 6 with MAO-A and MAO-B. The binding interactions of compound 6 in the active site of the MAO-A and MAO-B isoenzymes, investigated through molecular modeling algorithms, confirmed preferential binding of desmethoxyyangonin 6 with MAO-B compared to MAO-A. Selective reversible inhibitors of MAO-B, like desmethoxyyangonin 6, may have important therapeutic significance for the treatment of neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease.

Inhibitory effect of pinostrobin from Renealmia alpinia, on the enzymatic and biological activities of a PLA2.

Pinostrobin is a flavanone isolated from Renealmia alpinia, a plant used in folk medicine to treat snakebites. We tested the inhibitory ability of pinostrobin on the enzymatic, anticoagulant, myotoxic and edema-inducing activities of a PLA2 isolated from Crotalus durissus cumanensis venom. The compound displayed IC50 values of 1.76mM and 1.85mM (95% Confidence intervals: 1.34-2.18 and 1.21-2.45) on the PLA2 enzymatic activity, when either aggregated or monodispersed substrates were used, respectively. When mice were injected with PLA2 preincubated with 0.4, 2.0 and 4.0mM of pinostrobin, myotoxic activity induced by the PLA2 was inhibited up to 87%. Nevertheless, these values decreased up to 56% when the pinostrobin was injected into muscle after PLA2. Pinostrobin inhibited edema-forming and anticoagulant activities of the PLA2. In order to have insights on the mode of action of pinostrobin, intrinsic fluorescence and ultraviolet studies were performed. Results suggest that pinostrobin interacts directly with the PLA2. These findings were supported by molecular docking results, which suggested that pinostrobin forms hydrogen bonds with residues His48 and Asp49 of PLA2, besides, a π-π stacking interactions with those of residues Phe5 and Trp31, and rings C of flavanone and Tyr52 of the toxin.

Neuropharmacological effects of the ethanolic extract of Sida acuta

ABSTRACT Sida acuta Burm. f., Malvaceae, is regarded as astringent, tonic and useful in treating urinary diseases and blood disorders, bile, liver and as treatment for nervous diseases. Different methods were developed: sodium pentobarbital-induced sleeping time, anxiolytic activity, test for muscle-effects, pentylenetetrazole (PTZ)-induced seizures, effect on normal body temperature. All experiments were performed in an isolated room with 12/12 h light/dark cycles at 22 ± 1 ºC. The effects described in this work for Sida acuta are according to what is known in traditional medicine, where is used as sedative agent. At the higher doses used in this work (500 and 1000 mg/kg), the Sida acuta extract reduced the latency time (T1) and increased the sleeping time (T2) induced by pentobarbital, indicating a sedative and hypnotic effect of the plant's extract. The extract of Sida acuta shows an increase in open arm exploration (anxiolytic activity). Results obtained in the rota-rod test showed that only the elevated dose (750 mg/kg) of Sida acuta extract, acutely administered, promotes significant changes, at 60 and 120 min post-administration, in the time of permanence in the rod. The ethanolic extract from the leaves and stems of Sida acuta, causes effects on the central nervous system in experimental animals.

Main plants used in traditional medicine for the treatment of snake bites n the regions of the department of Antioquia, Colombia.

ETHNOPHARMACOLOGY RELEVANCE: In Colombia, more than 4.000 ophidian accidents occur per year and due to the scarce distribution and limited availability of antivenom, the use of traditional medicine has been perpetuated in some of its rural communities, in which initially, those affected are treated by healers and shamans using medicinal plants in different ways. METHODS: Research was conducted with renowned healers or connoisseurs of plants on the ethnobotany of ophidian accidents in five different areas and their municipalities of Antioquia: Magdalena Medio (Caracolí, Puerto Berrío); Bajo Cauca (Caucasia, Zaragoza); Nordeste (San Roque, Yalí); Norte (Gómez Plata, Valdivia); Suroeste (Ciudad Bolívar, Salgar); collecting information related to experience and time of use of plants in the treatment of these poisonings, amounts used, ways of use (beverage, bathing, ointment, chupaderas, vapors), preparation types (maceration or decoction) and treatment duration. RESULTS: 71 plant species were identified and collected, 49.29% of them without previous reports as antiophidian and 38.0% employed for the same purpose in other geographical areas. The leaves (24.82%), stems (11.68%) and flowers (10.95%) were found to be the most frequently employed structures in the preparation of the extracts, which are usually prepared by decoction (83.94%), maceration (6.57%). CONCLUSIONS: In this work, specimens lacking previous ethnobotanical reports have been found, plants used by ethnic groups from other regions of Antioquia and the world to treat snake bites; and herbaceous plants whose inhibitory activity of symptoms produced by some snake venoms, has been experimentally verified by in vivo and in vitro tests.

Antinociceptive activity of extracts and secondary metabolites from wild growing and micropropagated plants of Renealmia alpinia.

ETHNOPHARMACOLOGICAL RELEVANCE: Renealmia alpinia is native to the American continent and can be found from Mexico to Brazil, and in the Caribbean islands. It is known as "matandrea" in Colombia, and it has been commonly used in traditional medicine to treat painful diseases and ailments. Based on its traditional uses, it is of interest to evaluate the pharmacologic effects of this plant and its secondary metabolites. MATERIALS AND METHODS: Methanol and aqueous extracts of wild and micropropagated R. alpinia (leaves) were obtained and chemically compared by High Performance Thin Layer Chromatography (HPTLC). The antinociceptive activity of these extracts was examined using an in vivo assay (Siegmund test). Additionally, the dichloromethane extract of R. alpinia was fractionated and pure compounds were isolated by chromatographic methods. The structure elucidation of isolated compounds was performed by NMR experiments and spectroscopic techniques and comparison with the literature data. Purified compounds were evaluated for their in vitro binding affinity for opioids and cannabinoids receptors. RESULTS: The dichloromethane extract of the plant's aerial part afforded sinostrobin (1), naringenin 7,4'-dimethyl ether (2), 2',6'-dihydroxy-4'-methoxychalcone (3), 4-methoxy-6-(2-phenylethenyl)-2H-pyran-2-one (4), naringenin 7-methyl ether (5) and 3,5-heptanediol, 1,7-diphenyl (6), which were isolated using chromatographic methods. Their chemical structures were established by physical and spectroscopic techniques. The antinociceptive effects observed in mice by extracts of wild and micropropagated plants were similar. The compounds isolated from R. alpinia do not show affinity to opioid or cannabinoid receptors. CONCLUSION: Aqueous and methanol extracts of R. alpinia provide antinociceptive and analgesic effects in an in vivo model. These results contribute additional insight as to why this plant is traditionally used for pain management. Also, this is the first comprehensive report of a phytochemical study of R. alpinia.

Traditional use of the genus Renealmia and Renealmia alpinia (Rottb.) Maas (Zingiberaceae)-a review in the treatment of snakebites.

Renealmia alpinia (R. alpinia) typically occurs in the tropical rainforests of Mexico to Peru, Brazil through the Antilles, Guyana, Suriname, Colombia and Venezuela. It has traditionally been used against snakebite in Colombia. In addition to the common local use for pain, R. alpinia has been used as an antipyretic and antiemetic to treat wounds, malignant ulcers, epilepsy and fungal infections. The species of the Zingiberaceae family are famous for their use as spices and herbs. This review provides information on the traditional use of plants in the Zingiberaceae family, Renealmia genus, and specifically R. alpinia. We conducted a narrative review in English and Spanish in electronic databases, such as ScienceDirect, Napralert, PubMed, ScFinder, SciElo, during August 2011 to March 2013. We were interested in their applications in ethnomedicine and their chemical components, providing a major and methodical revision. We found 120 sources, 98 of which were selected as they contained essential information. This study has stimulated the development of a new work, which aims to isolate and evaluate metabolites from R. alpinia leads toward the development of a phytotherapeutic product, which might be accessible to the population. Studies on the toxicity and safety of R. alpinia are insufficient to provide information on the ethnomedical use of this species. Thus, the present review summarizes information about R. alpinia and proposes possible scope of future research to fill gaps identified in this narrative review.

Inhibition of the toxic effects of Bothrops asper venom by pinostrobin, a flavanone isolated from Renealmia alpinia (Rottb.) MAAS.

ETHNOPHARMACOLOGICAL RELEVANCE: Renealmia alpinia has been traditionally used to treat snakebites by indigenous Embera-Katíos tribes belonging to the regions of Antioquia and Chocó, Colombia, and it has been shown to inhibit the enzymatic and biological activities of Bothrops venoms and their purified phospholipase A2 (PLA2) toxins. In addition to its common local usage against snakebites, Renealmia alpinia is commonly used to treat pain. To evaluate the inhibitory ability of pinostrobin, the main compound in the dichloromethane extract of Renealmia alpinia, on the toxic effects of Bothrops asper venom through in vitro and in vivo models and to evaluate its activity against pain and edema. MATERIALS AND METHODS: Pinostrobin was isolated from the dichloromethane extract of Renealmia alpinia leaves. The protective properties of the extract and of pinostrobin against the indirect hemolytic, coagulant and proteolytic effects of Bothrops asper venom were evaluated in vitro, and the anti-hemorrhagic and anti-inflammatory activity were evaluated in vivo. RESULTS: Renealmia alpinia extract significantly inhibited the proteolytic activity and indirect hemolytic activity of Bothrops asper venom at a venom:extract ratio of 1:20. Moreover, the present data demonstrate that pinostrobin may mitigate some venom-induced local tissue damage due to hemorrhagic effects, and the compound is also responsible for the analgesic and anti-inflammatory activity of the extract from Renealmia alpinia. This is the first report to describe pinostrobin in the species Renealmia alpinia and its properties in vitro against Bothrops asper venom. CONCLUSION: Our studies of the activity of Renealmia alpinia against the venom of Bothrops asper have confirmed that this species possesses inhibitory effects against Bothrops asper venom in both in vitro and in vivo models and that these effects may be due to pinostrobin, supporting the traditional usage of the plant. Additionally, pinostrobin may be responsible for the anti-hemorrhagic and analgesic activity (peripheral analgesic activity) of Renealmia alpinia.