Compounds isolation from Syzygium cumini leaf extract against the Vibrio species in shrimp through bioassay-guided fractionation.

This study was conducted to isolate and identify the bioactive compounds from the ethanolic extract of Syzygium cumini leaf against Vibrio species through a bioassay-guided fractionation. The ethanol extract was exposed to silica gel chromatography followed by reversed phase HPLC to isolate the most effective fraction against V. parahaemolyticus. Using further UHPLC-orbitrap-ion trap mass spectrometry, five compounds were isolated with broad-spectrum potency against a range of Vibrio species viz. V. parahaemolyticus, V. alginolyticus, V. harveyi, V. vulnificus and V. anguillarum. The IC50 values for the compounds ranged from 8 to 48 µg/mL against the most sensitive species V. vulnificus and 58 to >400 µg/mL against V. alginolyticus. The results of the toxicity tests demonstrated that the compounds were not harmful for shrimp. The study's findings indicate that S. cumini leaf extract may contain bioactive molecules that are able to be substituted for antibiotics to treat vibriosis in shrimp farming.

Compound isolation through bioassay-guided fractionation of Tectona grandis leaf extract against Vibrio pathogens in shrimp.

Tectona grandis Linn, commonly known as teak, is traditionally used to treat a range of diseases, including the common cold, headaches, bronchitis, scabies, diabetes, inflammation, and others. The present study was conducted with the purpose of isolating and identifying the active compounds in T. grandis leaf against a panel of Vibrio spp., which may induce vibriosis in shrimp, using bioassay-guided purification. The antimicrobial activity was assessed using the microdilution method, followed by the brine shrimp lethality assay to determine toxicity. Following an initial screening with a number of different solvents, it was established that the acetone extract was the most effective. The acetone extract was then exposed to silica gel chromatography followed by reversed-phase HPLC and further UHPLC-orbitrap-ion trap mass spectrometry to identify the active compounds. Three compounds called 1-hydroxy-2,6,8-trimethoxy-9,10-anthraquinone, deoxyanserinone B, and khatmiamycin were identified with substantial anti-microbial action against V. parahaemolyticus, V. alginolyticus, V. harveyi, V. anguillarum, and V. vulnificus. The IC50 values of the three compounds viz. 1-hydroxy-2,6,8-trimethoxy-9,10-anthraquinone, deoxyanserinone B, and khatmiamycin varied between 2 and 28, 7 and 38, and 7 and 56 µg/mL, respectively, which are as good as the standard antibiotics such as amoxicillin and others. The in vivo toxicity test revealed that the compounds were non-toxic to shrimp. The results of the study suggest that T. grandis leaf can be used as a source of bioactive compounds to treat Vibrio species in shrimp farming.

Promising applications of phyto-fabricated silver nanoparticles: Recent trends in biomedicine.

The prospective contribution of phyto-nanotechnology to the synthesis of silver nanomaterials for biomedical purposes is attracting increasing interest across the world. Green synthesis of silver nanoparticles (Ag-NPs) through plants has been extensively examined recently, and it is now seen to be a green and efficient path for future exploitation and development of practical nano-factories. Fabrication of Ag-NPs is the process involves use of plant extracts/phyto-compounds (e.g.alkaloids, terpenoids, flavonoids, and phenolic compounds) to synthesise nanoparticles in more economical and feasible. Several findings concluded that in the field of medicine, Ag-NPs play a major role in pharmacotherapy (infection and cancer). Indeed, they exhibits novel properties but the reason is unclear (except some theoretical interpretation e.g. size, shape and morphology). But recent technological advancements help to address these questions by predicting the unique properties (composition and origin) by characterizing physical, chemical and biological properties. Due to increased list of publications and their application in the field of agriculture, industries and pharmaceuticals, issues relating to toxicity are unavoidable and question of debate. The present reviews aim to find out the role of plant extracts to synthesise Ag-NPs. It provides an overview of various phytocompounds and their role in the field of biomedicine (antibacterial, antioxidant, anticancer, anti-inflammatory etc.). In addition, this review also especially focused on various applications such as role in infection, oxidative stress, application in medical engineering, diagnosis and therapy, medical devices, orthopedics, wound healing and dressings. Additionally, the toxic effects of Ag-NPs in cell culture, tissue of different model organism, type of toxic reactions and regulation implemented to reduce associated risk are discussed critically. Addressing all above explanations, this review focus on the detailed properties of plant mediated Ag-NPs, its impact on biology, medicine and their commercial properties as well as toxicity.

Potential use of the Asteraceae family as a cure for diabetes: A review of ethnopharmacology to modern day drug and nutraceuticals developments.

The diabetes-associated mortality rate is increasing annually, along with the severity of its accompanying disorders that impair human health. Worldwide, several medicinal plants are frequently urged for the management of diabetes. Reports are available on the use of medicinal plants by traditional healers for their blood-sugar-lowering effects, along with scientific evidence to support such claims. The Asteraceae family is one of the most diverse flowering plants, with about 1,690 genera and 32,000 species. Since ancient times, people have consumed various herbs of the Asteraceae family as food and employed them as medicine. Despite the wide variety of members within the family, most of them are rich in naturally occurring polysaccharides that possess potent prebiotic effects, which trigger their use as potential nutraceuticals. This review provides detailed information on the reported Asteraceae plants traditionally used as antidiabetic agents, with a major focus on the plants of this family that are known to exert antioxidant, hepatoprotective, vasodilation, and wound healing effects, which further action for the prevention of major diseases like cardiovascular disease (CVD), liver cirrhosis, and diabetes mellitus (DM). Moreover, this review highlights the potential of Asteraceae plants to counteract diabetic conditions when used as food and nutraceuticals. The information documented in this review article can serve as a pioneer for developing research initiatives directed at the exploration of Asteraceae and, at the forefront, the development of a botanical drug for the treatment of DM.

Dark or light? Preference of anuran tadpoles to background illumination in response to food and predators.

Background illumination and its intensity are crucial factors in visual interaction among organisms. In the present study, we used tadpoles of eight sympatric anuran species (Duttaphrynus melanostictus, Microhyla ornata, Uperodon globulosus, Kaloula taprobanica, Euphlyctis cyanophlyctis, Fejervarya orissaensis, Polypedates maculatus, and Polypedates teraiensis) to examine species-specific responses towards background illumination (shade and light), combined with four treatments [without food and predator (F-P-), with food and without predator (F+P-), without food and with predator (F-P+), and with food and with predator (F+P+)], with four coloured backgrounds (green, red, brown, and black) during different hours of a day (early morning, late morning, noon, and afternoon). Anuran tadpoles choose shaded sides over lighter sides, as such microhabitats are used as an effective means of camouflage, but most of the M. ornata tadpoles preferred the opposite. The observations were similar for red, green, and brown backgrounds simulating different natural conditions. The developmental stage and co-occurrence of tadpoles of multiple species do not affect their behavioural responses. These results draw attention to the importance of low illuminated/shaded backgrounds for behavioural responses of anuran tadpoles to environmental changes.

Metabolic profiling of Chimonanthus grammatus via UHPLC-HRMS-MS with computer-assisted structure elucidation and its antimicrobial activity.

Chimonanthus grammatus is used as Hakka traditional herb to treat cold, flu, etc. So far, the phytochemistry and antimicrobial compounds have not been well investigated. In this study, the orbitrap-ion trap MS was used to characterize its metabolites, combined with a computer-assisted structure elucidation method, and the antimicrobial activities were assessed by a broth dilution method against 21 human pathogens, as well as the bioassay-guided purification work to clarify its main antimicrobial compounds. A total of 83 compounds were identified with their fragmentation patterns, including terpenoids, coumarins, flavonoids, organic acids, alkaloids, and others. The plant extracts can strongly inhibit the growth of three Gram-positive and four Gram-negative bacteria, and nine active compounds were bioassay-guided isolated, including homalomenol C, jasmonic acid, isofraxidin, quercitrin, stigmasta-7,22-diene-3ß,5α,6α-triol, quercetin, 4-hydroxy-1,10-secocadin-5-ene-1,10-dione, kaempferol, and E-4-(4,8-dimethylnona-3,7-dienyl)furan-2(5H)-one. Among them, isofraxidin, kaempferol, and quercitrin showed significant activity against planktonic Staphylococcus aureus (IC50 = 13.51, 18.08 and 15.86 µg/ml). Moreover, their antibiofilm activities of S. aureus (BIC50 = 15.43, 17.31, 18.86 µg/ml; BEC50 = 45.86, ≥62.50, and 57.62 µg/ml) are higher than ciprofloxacin. The results demonstrated that the isolated antimicrobial compounds played the key role of this herb in combating microbes and provided benefits for its development and quality control, and the computer-assisted structure elucidation method was a powerful tool for chemical analysis, especially for distinguishing isomers with similar structures, which can be used for other complex samples.

Recent advances to combat ESKAPE pathogens with special reference to essential oils.

Biofilm-associated bacteria, especially ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), are a serious challenge worldwide. Due to the lack of discovery of novel antibiotics, in the past two decades, it has become necessary to search for new antibiotics or to study synergy with the existing antibiotics so as to counter life-threatening infections. Nature-derived compounds/based products are more efficient than the chemically synthesized ones with less resistance and lower side effects. In this descriptive review, we discuss the most promising therapeutics for the treatment of ESKAPE-related biofilms. The first aspect includes different types of natural agents [botanical drugs, essential oils (EOs), antimicrobial peptides, bacteriophages, and endolysins] effective against ESKAPE pathogens. The second part of the review deals with special references to EOs/essential oil components (EOCs) (with some exclusive examples), mode of action (via interfering in the quorum-sensing pathways, disruption of biofilm and their inhibitory concentrations, expression of genes that are involved, other virulence factors), existing in literature so far. Moreover, different essential oils and their major constituents were critically discussed using in vivo models to target ESKAPE pathogens along with the studies involving existing antibiotics.

Essential Oils as Novel Anthelmintic Drug Candidates.

Helminths, with an estimated 1.5 billion annual global infections, are one of the major health challenges worldwide. The current strategy of the World Health Organization to prevent helminth infection includes increasing hygienic awareness, providing better sanitation and preventative anthelmintic drug therapy in vulnerable populations. Nowadays, anthelmintic drugs are used heavily in livestock, both in case of infection and as a preventative measure. However, this has led to the development of resistance against several of the most common drugs, such as levamisole, ivermectin and thiabendazole. As many as 70% of the livestock in developed countries now has helminths that are drug resistant, and multiple resistance is common. Because of this, novel anthelmintics are urgently needed to help combat large-scale production losses. Prior to this review, no comprehensive review of the anthelmintic effects of essential oils and their components existed. Multiple review articles have been published on the uses of a single plant and its extracts that only briefly touch upon their anthelmintic activity. This review aims to provide a detailed overview of essential oils and their components as anthelmintic treatment against a wider variety of helminths.

Leaf Extract and Active Fractions of Dillenia pentagyna Roxb. Reduce In Vitro Human Cancer Cell Migration Via NF-κB Pathway.

BACKGROUND: Different parts of Dillenia pentagyna have long been used in traditional medicines to cure several diseases including cancer. However, the mechanism(s) of anti-cancer effects are still unknown. We aimed to elucidate the anti-metastatic potential of ethanolic extracts of leaves of D. pentagyna (EELDP) and active fractions of it in highly metastatic human cancer cells. METHODS: We screened different HPLC fractions of EELDP based on their anti-metastatic effect. We used TLC and ESI-MS for determining the presence of various phytochemicals in EELDP and fractions. We monitored in vitro anti-metastasis effect of EELDP (0-0.6 mg/ml) and active fractions (0-0.050 mg/ml) on various human cancer cells like A549, HeLa, and U2OS. RESULTS: EELDP significantly reduced cell viability and cell migration in A549, HeLa, and U2OS cells. However, higher sensitivity was observed in A549 cells. We screened 2 active HPLC fractions F6 and F8 having anti-MMPs activity. EELDP and active fractions reduced metastasis via the NF-κB pathway, decreased the expression of Vimentin, N-cadherin, and increased the expression of Claudin-1. CONCLUSION: Significant reduction of metastasis by EELDP at a dose of 0.1 mg/ml or by active fractions at 0.050 mg/ml implicates that the active compound(s) present in crude or fractions are extremely potent to control highly metastatic cancer.

Ethnobotanical study of Hakka traditional medicine in Ganzhou, China and their antibacterial, antifungal, and cytotoxic assessments.

BACKGROUND: Traditional herbs played a crucial role in the health care of the Hakka people. However, studies to identify these traditional herbs are few. Here we document and assess the potential of these plants for treating microbial infections. Many herbs used by the Hakka people could potentially be a novel medicinal resource. METHODS: Local herb markets were surveyed via semi-structured interviews, complemented by direct observations to obtain information on herbal usage. For each herb selected for this study, extracts in four different solvents were prepared, and tested for activity against 20 microorganisms, as well as cancerous and noncancerous cells. All data were subjected to cluster analysis to discover relationships among herbs, plant types, administration forms, solvents, microorganisms, cells, etc., with the aim to discern promising herbs for medicine. RESULTS: Ninety-seven Hakka herbs in Ganzhou were documented from 93 plants in 62 families; most are used for bathing (97%), or as food, such as tea (32%), soup (12%), etc. Compared with the Chinese Pharmacopoeia and Chinese Materia Medica, 24 Hakka medicines use different plant parts, and 5 plants are recorded here for the first time as traditional medicines. The plant parts used were closely related with the life cycle: annual and perennial herbs were normally used as a whole plant, and woody plants as (tender) stem and leaf, indicating a trend to use the parts that are easily collected. Encouragingly, 311 extracts (94%) were active against one or more microorganisms. Most herbs were active against Gram-positive bacteria, such as Staphylococcus aureus (67%), Listeria innocua (64%), etc. Cytotoxicity was often observed against a tumor cell, but rarely against normal cells. Considering both antimicrobial activity and cytotoxicity, many herbs reported in this study show promise as medicine. CONCLUSION: Hakka people commonly use easily-collected plant parts (aerial parts or entire herb) as medicine. External use of decoctions dominated, and may help combating microbial infections. The results offer promising perspectives for further research since little phytopharmacology and phytochemistry has been published to date.

Ethnomedicinal, Phytochemical and Pharmacological Investigations of Tetradenia riparia (Hochst.) Codd (Lamiaceae).

Tetradenia riparia Hochsteter codd. (Lamiaceae) in its native African continent, is considered one of the most popular aromatic medicinal plants. In folk medicine it may be used as an infusion to treat respiratory problems, cough, headache, stomach pain, diarrhea, fever, malaria, and dengue; and in the form of compresses it is applied for the relief of headaches and toothaches. The species T. riparia has been researched for decades to isolate and identify chemical constituents present in extracts or essential oil obtained from the leaves, floral buds, or stems of this plant. The present study reviews the scientific literature on ethnomedicinal, phytochemical, and pharmacological aspects of T. riparia. We discuss issues related to the botanical and geographical description of the species, ethnobotanical uses, phytochemical studies on its essential oil and extracts, and biological activities of T. riparia. Several compounds have already been isolated from leaves, such as ibozol, 7α-hydroxyroileanone, 1',2'-dideacetylboronolide, 8(14),15-sandaracopimaradiene-7α,18-diol; 5,6-dihydro-α-pyrone and α-pyrone. Terpenes predominated in the essential oil, comprising monoterpenes, sesquiterpenes, diterpenes, hydrocarbons, and oxygenates. Most phytocompounds were isolated from the leaves and flower buds, namely fenchone, 14-hydroxy-9-epi (E)-caryophyllene, 9ß, 13ß-epoxy-7-abietene, and 6,7-dehydroroileanone. These compounds provide the species a high pharmacological potential, with antimicrobial, antioxidant, antitumor, analgesic, anti-leishmania, anti-tuberculosis, and anti-parasitic activities. Therefore, this species is a promising herbal medicine.

Optimization of a locomotion-based zebrafish seizure model.

BACKGROUND: Locomotor assays in zebrafish have emerged as a screening test in early drug discovery for antiseizure compounds. However, parameters differ considerably between published studies, which may explain some discrepant results with (candidate) antiseizure medications. NEW METHOD: We optimized a locomotor-based seizure assay in zebrafish with pentylenetetrazol (PTZ) as the pharmacological proconvulsant to generate a therapeutic window in which proconvulsant-treated zebrafish larvae could be discriminated from a non-treated control. To generate a reliable control, exposure time and concentration of valproate (VPA, anticonvulsant) was optimized. RESULTS: Wells with one or three larvae show a similar PTZ dose-dependent increase in locomotion with less variability in motility for the latter. Zebrafish immersed in 10 mM PTZ showed a significant increase in movement with a sustained effect, without any indication of toxicity. Animals treated with 3 mM VPA showed the strongest reduction of PTZ-induced movement without toxicity. The decrease in PTZ-induced locomotion was greater after 18 h versus 2 h. COMPARISON WITH EXISTING METHOD(S): For the larval zebrafish PTZ-induced seizure model, varying experimental parameters have been reported in literature. Our results show that PTZ is often used at toxic concentrations, and we provide instead reliable conditions to quantify convulsant behaviour using an infrared-beam motility assay. CONCLUSIONS: We recommend using three zebrafish larvae per well to quantify locomotion in 96-multiwell plates. Larvae should preferably be exposed to 10 mM PTZ for 1 h, consisting of 30 min acclimation and 30 min subsequent recording. As positive control for anticonvulsant activity, we recommend exposure to 3 mM VPA for 18 h before administration of PTZ.

Anticancer Activities of Mushrooms: A Neglected Source for Drug Discovery.

Approximately 270 species of mushrooms have been reported as potentially useful for human health. However, few mushrooms have been studied for bioactive compounds that can be helpful in treating various diseases. Like other natural regimens, the mushroom treatment appears safe, as could be expected from their long culinary and medicinal use. This review aims to provide a critical discussion on clinical trial evidence for mushrooms to treat patients with diverse types of cancer. In addition, the review also highlights the identified bioactive compounds and corresponding mechanisms of action among the explored mushrooms. Furthermore, it also discusses mushrooms with anticancer properties, demonstrated either in vitro and/or in vivo models, which have never been tested in clinical studies. Several mushrooms have been tested in phase I or II clinical trials, mostly for treating breast cancer (18.6%), followed by colorectal (14%) and prostate cancer (11.6%). The majority of clinical studies were carried out with just 3 species: Lentinula edodes (22.2%), Coriolus versicolor, and Ganoderma lucidum (both 13.9%); followed by two other species: Agaricus bisporus and Grifola frondosa (both 11.1%). Most in vitro cell studies use breast cancer cell lines (43.9%), followed by lung (14%) and colorectal cancer cell lines (13.1%), while most in vivo animal studies are performed in mice tumor models (58.7%). Although 32 species of mushrooms at least show some promise for the treatment of cancer, only 11 species have been tested clinically thus far. Moreover, most clinical studies have investigated fewer numbers of patients, and have been limited to phase III or IV. Therefore, despite the promising preclinical and clinical data publication, more solid scientific efforts are required to clarify the therapeutic value of mushrooms in oncology.

Disease Burden and Current Therapeutical Status of Leprosy with Special Emphasis on Phytochemicals.

BACKGROUND: Leprosy (Hansen's disease) is a neglected tropical disease affecting millions of people globally. The combined formulations of dapsone, rifampicin and clofazimine (multidrug therapy, MDT) is only supportive in the early stage of detection, while "reemergence" is a significant problem. Thus, there is still a need to develop newer antileprosy molecules either of natural or semi-synthetic origin. OBJECTIVES: The review intends to present the latest developments in the disease prevalence, available therapeutic interventions and the possibility of identifying new molecules from phytoextracts. METHODS: Literature on the use of plant extracts and their active components to treat leprosy was searched. Selected phytoconstituents were subjected to molecular docking study on both wild and mutant types of the Mycobacterium leprae. Since the M. leprae dihydropteroate synthase (DHPS) is not available in the protein data bank (PDB), it was modelled by the homology model method and validated with the Ramachandran plot along with other bioinformatics approaches. Two mutations were introduced at codons 53 (Thr to Ile) and 55 (Pro to Leu) for docking against twenty-five selected phytoconstituents reported from eight plants that recorded effective anti-leprosy activity. The chemical structure of phytochemicals and the standard dapsone structure were retrieved from the PubChem database and prepared accordingly for docking study with the virtual-screening platform of PyRx-AutoDock 4.1. RESULTS: Based on the docking score (kcal/mol), most of the phytochemicals exhibited a higher docking score than dapsone. Asiaticoside, an active saponin (-11.3, -11.2 and -11.2 kcal/mol), was proved to be the lead phytochemical against both wild and mutant types DHPS. Some other useful phytoconstituents include echinocystic acid (-9.6, -9.5 and -9.5 kcal/mol), neobavaisoflavone (-9.2, -9.0 and -9.0 kcal/mol), boswellic acid (-8.90, -8.90 and -8.90 kcal/mol), asiatic acid (-8.9, -8.8 and -8.9 kcal/mol), corylifol A (-8.8, 8.0, and -8.0), etc. Overall, the computational predictions support the previously reported active phytoextracts of Centella asiatica (L.) Urban, Albizia amara (Roxb.) Boivin, Boswellia serrata Roxb. and Psoralea corylifolia L. to be effective against leprosy. CONCLUSION: A very small percentage of well-known plants have been evaluated scientifically for antileprosy activity. Further in vivo experiments are essential to confirm anti-leprosy properties of such useful phytochemicals.

Medicinal mushrooms: Clinical perspective and challenges.

Mushrooms are valued by humans worldwide as food, but also for their medicinal properties. Over 130 medicinal effects of mushrooms have been reported, including anti-diabetic, antioxidant, antimicrobial, anticancer, prebiotic, immunomodulating, anti-inflammatory and cardiovascular benefits. Several mushrooms have been tested in phase I, II, or III clinical trials for various diseases, including cancers, as well as to modulate immunity. Here, we review clinical studies on medicinal mushrooms or preparations (but not pure compounds) derived thereof. Overall, few phase III trials have been performed, and in many cases, these trials included a relatively small number of patients. Therefore, despite the promising published clinical data, especially on immune modulation, more work is required to clarify the therapeutic value of mushrooms.