Antibacterial Activities of Methanolic Seeds Extract of Black pepper (Piper nigrum L.) against Gram Positive Staphylococcus aureus & Gram-Negative Escherichia coli.

Evaluation of the in vitro antibacterial activity of Methanolic extracts isolated from Black pepper seeds (Piper nigrum L.) against two infection causing pathogens, Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Between July 2022 and June 2023, this experimental study was conducted at the Mymensingh Medical College's Department of Pharmacology and Therapeutics in conjunction with the Department of Microbiology. Using the disc diffusion and broth dilution methods, the antibacterial activity of methanolic extract of black pepper seeds (MBPE) was evaluated at various doses. The solvents Methanol and 10.0% Di Methyl Sulfoxide (DMSO) were used to make the extract. Using the broth dilution procedure, the conventional antibiotic Ciprofloxacin was utilized and the outcome was contrasted with that of Methanol extracts. Methanolic extract of black pepper seeds (MBPE) at seven distinct concentrations (100, 80, 60, 40, 20, 10 and 5 mg/ml) were utilized, then later in chosen concentrations as needed to confirm the extracts' more precise margin of antimicrobial sensitivity. At 80 mg/ml and above doses of the MBPE, it had an inhibitory impact against the aforementioned microorganisms. For Staphylococcus aureus and Escherichia coli the MIC were 60 and 75 mg/ml in MBPE respectively. As of the MIC of Ciprofloxacin was 1µg/ml against Staphylococcus aureus and Escherichia coli. In comparison to MICs of MBPE for the test organisms, the MIC of Ciprofloxacin was the lowest. This study clearly shows that Staphylococcus aureus and Escherichia coli are sensitive to the methanolic extract of black pepper seeds' antibacterial properties.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Identification and characterization of silver nanoparticles from Erythrina indica and its antioxidant and Uropathogenic antimicrobial properties.

The plant Erythrina indica comes under Fabaceae family, mainly used for used in traditional medicine as nervine sedative, antiepileptic, antiasthmatic, collyrium in opthalmia, antiseptic. Current study focused synthesize of silver nanoparticles (AgNPs) by E. indica leaf ethanol extract. The green-synthesized AgNPs underwent characterization using multiple analytical techniques, including UV-visible, FTIR, DLS, SEM, TEM, XRD, and EDX, and estimation of their antioxidant activity and antimicrobial activity. Phytochemical analysis identified alkaloids, tannins, saponins, flavonoids, and phenols as secondary metabolites. The Total Phenol Content (TPC) was determined to be 237.35 ± 2.02 mg GAE-1, indicating a substantial presence of phenolic compounds. The presence of AgNPs was verified through UV-Visible analysis at 420 nm, and FT-IR revealed characteristic phenolic functional groups. DLS analysis indicated a narrow size distribution (polydispersity index - PDI: 3.47%), with SEM revealing spherical AgNPs of approximately 20 nm. TEM showed homogeneous, highly polycrystalline AgNPs with lattice spacing at 0.297. XRD analysis demonstrated crystallinity and purity, with distinct reflection peaks corresponding to miller indices of JCPDS card no. 01 087 1473. In vitro, AgNPs exhibited robust antioxidant activity like; DPPH, ABTS, and H2O2, surpassing E. indica-assisted synthesis. ABTS assay indicated higher antioxidant activity (81.94 ± 0.05%) for AgNPs at 734 nm, while E. indica extraction showed 39.67 ± 0.07%. At 532 nm, both E. indica extraction (57.71 ± 0.11%) and AgNPs (37.41 ± 0.17%) exhibited H2O2 scavenging. Furthermore, AgNPs displayed significant antimicrobial properties, inhibiting Staphylococcus aureus (15.7 ± 0.12 mm) and Candida albicans (10.7 ± 0.17 mm) byfor the concentration of 80 µg/mL. Through the characterizations underscore of the potential of Erythrina indica-synthesized AgNPs, rich in polyphenolic compounds, for pharmacological, medical, biological applications and antipyretic properties.

Effect of Laurus nobilis on bacteria and human transforming growth factor-ß1.

OBJECTIVE: In this study, we aimed to determine the phenolic compounds, the antibacterial activity of extract from Laurus nobilis leaves, and its possible effect on transforming growth factor-ß1 expression level in peripheral blood mononuclear cells. METHODS: The phenolic components of Laurus nobilis were identified by the high-performance liquid chromatography method. The antibacterial activity of this extract was determined by disk diffusion and broth microdilution methods. The transforming growth factor-ß1 expression was analyzed using the RT-qPCR method. RESULTS: Epicatechin was found in the highest amount and o-coumaric acid in the lowest amount. The half-maximal inhibitory concentration (IC50) was determined to be 55.17 µg/mL. The zones of inhibition and minimum inhibitory concentration for Staphylococcus aureus, Enterococcus faecalis, and Klebsiella pneumoniae were 15, 14, and 8 mm and 125, 250, and 1000 µg/mL, respectively. The change in transforming growth factor-ß1 expression levels was found to be statistically significant compared with the control groups (p<0.0001). CONCLUSION: Laurus nobilis extract was found to be effective against bacteria and altered the expression level of transforming growth factor-ß1 in peripheral blood mononuclear cells.

Untargeted metabolomics and molecular docking studies on green silver nanoparticles synthesized by Sarocladium subulatum: Exploring antibacterial and antioxidant properties.

The biological synthesis of silver nanoparticles (Ag-NPs) with fungi has shown promising results in antibacterial and antioxidant properties. Fungi generate metabolites (both primary and secondary) and proteins, which aid in the formation of metal nanoparticles as reducing or capping agents. While several studies have been conducted on the biological production of Ag-NPs, the exact mechanisms still need to be clarified. In this study, Ag-NPs are synthesized greenly using an unstudied fungal strain, Sarocladium subulatum AS4D. Three silver salts were used to synthesize the Ag-NPs for the first time, optimized using a cell-free extract (CFE) strategy. Additionally, these NPs were assessed for their antimicrobial and antioxidant properties. Various spectroscopic and microscopy techniques were utilized to confirm Ag-NP formation and analyze their morphology, crystalline properties, functional groups, size, stability, and concentrations. Untargeted metabolomics and proteome disruption were employed to explore the synthesis mechanism. Computational tools were applied to predict metabolite toxicity and antibacterial activity. The study identified 40 fungal metabolites capable of reducing silver ions, with COOH and OH functional groups playing a pivotal role. The silver salt type impacted the NPs' size and stability, with sizes ranging from 40 to 52 nm and zeta potentials from -0.9 to -30.4 mV. Proteome disruption affected size and stability but not shape. Biosynthesized Ag-NPs using protein-free extracts ranged from 55 to 62 nm, and zeta potentials varied from -18 to -27 mV. Molecular docking studies and PASS results found no role for the metabolome in antibacterial activity. This suggests the antibacterial activity comes from Ag-NPs, not capping or reducing agents. Overall, the research affirmed the vital role of specific reducing metabolites in the biosynthesis of Ag-NPs, while proteins derived from biological extracts were found to solely affect their size and stability.

Copper selenide nanosheets with photothermal therapy-related properties and multienzyme activity for highly effective eradication of drug resistance.

Bacterial infections are among the most significant causes of death in humans. Chronic misuse or uncontrolled use of antibiotics promotes the emergence of multidrug-resistant superbugs that threaten public health through the food chain and cause environmental pollution. Based on the above considerations, copper selenide nanosheets (CuSe NSs) with photothermal therapy (PTT)- and photodynamic therapy (PDT)-related properties have been fabricated. These CuSe NSs possess enhanced PDT-related properties and can convert O2 into highly toxic reactive oxygen species (ROS), which can cause significant oxidative stress and damage to bacteria. In addition, CuSe NSs can efficiently consume glutathione (GSH) at bacterial infection sites, thus further enhancing their sterilization efficacy. In vitro antibacterial experiments with near-infrared (NIR) irradiation have shown that CuSe NSs have excellent photothermal bactericidal properties. These experiments also showed that CuSe NSs exerted excellent bactericidal effects on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) and significantly promoted the healing of infected wounds. Because of their superior biological safety, CuSe NSs are novel copper-based antimicrobial agents that are expected to enter clinical trials, serving as a modern approach to the major problem of treating bacterially infected wounds.

Phytochemical screening of Podocarpus lambertii Klotzch ex Endl. leaf extracts and potential antimicrobial, antioxidant and antibiofilm activity.

Species of the genus Podocarpus L'Hér. ex Pers.present biological activities, such as analgesic, antioxidant, antifungal, acting in the fight against anemia, depurative and fortifying. Podocarpus lambertii Klotzch ex Endl. is a Brazilian native species popularly known as maritime pine and lacks information about its phytochemical profile and possible biological activities. The study was conducted to determine the phytochemical composition of soluble plant extracts of acetone (EA), ethyl acetate (EAE) and hexane (HE) from leaves of P. lambertii; evaluate the antimicrobial potential by the broth microdilution technique; antioxidant potential by the DPPH method, as well as to evaluate the biofilm inhibition capacity by the crystal violet assay and reduction of the yellow tetrazolium salt (MTT). Phytochemical screening detected the presence of flavonoids, triterpenoids, steroids, tannins, alkaloids and saponins. All extracts showed antimicrobial activity on the microorganisms tested, and the EA showed the best results. High free radical scavenging potential was observed only in EAE (96.35%). The antibiofilm potential was observed in the EAE extract. The results contribute to the knowledge of the species and indicate the potential of P. lambertii extracts as a source of plant bioactives for the development of new alternative strategies to control resistant microorganisms.

New pimarane diterpenoids with antibacterial activity from fungus Arthrinium sp. ZS03.

A comprehensive chemical study of the endophytic fungus Arthrinium sp. ZS03, associated with Acorus tatarinowii Schott, yielded eleven pimarane diterpenoids (compounds 1-11), including seven novel compounds designated arthrinoids A-G (1-7). The determination of their structures and absolute configurations was achieved through extensive spectroscopic techniques, quantum chemical calculations of electronic circular dichroism (ECD), and single-crystal X-ray diffraction analysis. Furthermore, 7 demonstrated inhibitory activity against Klebsiella pneumoniae, comparable to the reference antibiotic amikacin, with a minimum inhibitory concentration (MIC) of 8 µg·mL-1.

Comprehensive antifungal investigation of natural plant extracts against Neosartorya spp. (Aspergillus spp.) of agriculturally significant microbiological contaminants and shaping their metabolic profile.

Fungi belonging to the genus Neosartorya (teleomorph of Aspergillus spp.) are of great concern in the production and storage of berries and fruit-based products, mainly due to the production of thermoresistant ascospores that cause food spoilage and possible secretion of mycotoxins. We initially tested the antifungal effect of six natural extracts against 20 isolates of Neosartorya spp. using a traditional inhibition test on Petri dishes. Tested isolates did not respond uniformly, creating 5 groups of descending sensitivity. Ten isolates best representing of the established sensitivity clusters were chosen for further investigation using a Biolog™ MT2 microplate assay with the same 6 natural extracts. Additionally, to test for metabolic profile changes, we used a Biolog™ FF microplate assay after pre-incubation with marigold extract. All natural extracts had an inhibitory effect on Neosartorya spp. growth and impacted its metabolism. Lavender and tea tree oil extracts at a concentration of 1000 µg mL-1 presented the strongest antifungal effect during the inhibition test, however all extracts exhibited inhibitory properties at even the lowest dose (5 µg mL-1). The fungal stress response in the presence of marigold extract was characterized by a decrease of amino acids and carbohydrates consumption and an uptake of carboxylic acids on the FF microplates, where the 10 studied isolates also presented differences in their innate resilience, creating 3 distinctive sensitivity groups of high, average and low sensitivity. The results confirm that natural plant extracts and essential oils inhibit and alter the growth and metabolism of Neosartorya spp. suggesting a possible future use in sustainable agriculture as an alternative to chemical fungicides used in traditional crop protection.

Seriphidium herba-alba (Asso): A comprehensive study of essential oils, extracts, and their antimicrobial properties.

Seriphidium herba-alba (Asso), a plant celebrated for its therapeutic qualities, is widely used in traditional medicinal practices throughout the Middle East and North Africa. In a detailed study of Seriphidium herba-alba (Asso), essential oils and extracts were analyzed for their chemical composition and antimicrobial properties. The essential oil, characterized using mass spectrometry and retention index methods, revealed a complex blend of 52 compounds, with santolina alcohol, α-thujone, ß-thujone, and chrysanthenone as major constituents. Extraction yields varied significantly, depending on the plant part and method used; notably, methanol soaking of aerial parts yielded the most extract at 17.75%. The antimicrobial analysis showed that the extracts had selective antibacterial activity, particularly against Staphylococcus aureus, and broad-spectrum antifungal activity against organisms such as Candida albicans and Aspergillus spp. The methanol-soaked extract demonstrated the strongest antimicrobial properties, indicating its potential as a natural antimicrobial source. This study not only underscores the therapeutic potential of Seriphidium herba-alba (Asso) in pharmaceutical applications but also sets a foundation for future research focused on isolating specific bioactive compounds and in vivo testing.

Constructing Interfacial Charge Transfer Channels and Electric Field in Violet Phosphorus-Based van der Waals Heterojunction for Phototherapy of Periodontitis.

Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti3C2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport "bridge" (P-Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti3C2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O2 and H2O on the surfaces of Ti3C2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti3C2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli, respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti3C2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.

Plackett-Burman screening of physico-chemical variables affecting Citrus peel-mediated synthesis of silver nanoparticles and their antimicrobial activity.

With the growing resistance of pathogenic microbes to traditional drugs, biogenic silver nanoparticles (SNPs) have recently drawn attention as potent antimicrobial agents. In the present study, SNPs synthesized with the aid of orange (Citrus sinensis) peel were engineered by screening variables affecting their properties via Plackett-Burman design. Among the variables screened (temperature, pH, shaking speed, incubation time, peel extract concentration, AgNO3 concentration and extract/AgNO3 volume ratio), pH was the only variable with significant effect on SNPs synthesis. Therefore, SNPs properties could be enhanced to possess highly regular shape with zeta size of 11.44 nm and zeta potential of - 23.7 mV. SNPs purified, capped and stabilized by cloud point extraction technique were then checked for their antimicrobial activity against Bacillus cereus, Listeria innocua, Listeria monocytogenes, Staphylococcus aureus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium and Candida albicans. The maximum antimicrobial activity of SNPs was recorded against E. coli, L. monocytogenes and C. albicans with clear zone diameter of 33.2, 31.8 and 31.7 mm, respectively. Based on minimum inhibition concentration and minimum bactericidal concentration of SNPs (300 mg/l) as well as their effect on respiratory chain dehydrogenases, cellular sugar leakage, protein leakage and lipid peroxidation of microbial cells, E. coli was the most affected. Scanning electron microscopy, protein banding and DNA fragmentation proved obvious ultrastructural and molecular alterations of E. coli treated with SNPs. Thus, biogenic SNPs with enhanced properties can be synthesized with the aid of Citrus peel; and such engineered nanoparticles can be used as potent antimicrobial drug against E. coli.

Longistylin A from Cajanus cajan (L.) Millsp. disturbs glycerophospholipid metabolism and cytokinin biosynthesis of Nocardia seriolae.

ETHNOPHARMACOLOGICAL RELEVANCE: Nocardiosis is an uncommon infectious disease that bears certain similarities to tuberculosis, with a continuous increase in its incidence and a poor prognosis. In traditional Chinese medicine, the leaves of Cajanus cajan (L.) Millsp. are employed to treat wounds, malaria, coughs, and abdominal pain. AIM OF THE STUDY: In this study, we investigated the effects and mechanisms of longistylin A (LGA), a natural stilbene isolated from C. cajan, as a potential antibiotic against nocardiosis. MATERIALS AND METHODS: LGA was isolated from the leaves of C. cajan and assessed using a minimum bactericidal concentration (MBC) determination against Nocardia seriolae. Multi-omics analysis encompassing genes, proteins, and metabolites was conducted to investigate the impact of LGA treatment on N. seriolae. Additionally, quantitative analysis of 40 cytokinins in N. seriolae mycelium was performed to assess the specific effects of LGA treatment on cytokinin levels. Cryo-scanning electron microscopy was utilized to examine morphological changes induced by LGA treatment, particularly in the presence of exogenous trans-zeatin-O-glucoside (tZOG). The therapeutic effect of LGA was investigated by feeding N. seriolae-infected largemouth bass. RESULTS: LGA exhibited significant efficacy against N. seriolae, with MBC value of 2.56 µg/mL. Multi-omics analysis revealed that LGA disrupted glycerophospholipid metabolism and hormone biosynthesis by notably reducing the expression of glycerol-3-phosphate dehydrogenase and calmodulin-like protein. Treatment with LGA markedly disrupted 12 distinct cytokinins in N. seriolae mycelium. Additionally, the addition of exogenous tZOG counteracted the inhibitory effects of LGA on filamentous growth, resulting in mycelial elongation and branching. Furthermore, LGA treatment improved the survival rate of largemouth bass infected with N. seriolae. CONCLUSIONS: We found for the first time that LGA from C. cajan exhibited significant efficacy against N. seriolae by interfering with glycerophospholipid metabolism and cytokinin biosynthesis.

In vitro and in vivo evaluation of the anti-infective potential of the essential oil extracted from the leaves of Plectranthus amboinicus (lour.) spreng against Klebsiella pneumoniae and elucidation of its mechanism of action through proteomics approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Members of Plectranthus genus such as Plectranthus amboinicus (Lour.) Spreng is a well-known folkloric medicine around the globe in treating several human ailments such as cardiovascular, respiratory, digestive, urinary tract, skin and infective diseases. Its therapeutic value is primarily attributed to its essential oil. Although several properties of Plectranthus amboinicus essential oil have been documented, its mechanism of action and safety has not been completely elucidated. AIM OF THE STUDY: To investigate the anti-infective potential of Plectranthus amboinicus essential oil against Klebsiella pneumoniae using in vitro and in vivo bioassays and identify its mode of action. The study was conducted to scientifically validate the traditional usage of Plectranthus amboinicus oil and propose it as a complementary and alternative medication to combat Klebsiella pneumoniae infections due to emerging antibiotic resistance problem. MATERIALS AND METHODS: Plectranthus amboinicus essential oil was extracted through steam distillation and was chemically characterized using Gas Chromatography Mass Spectrometry (GC-MS). The antibacterial activity was assessed using microbroth dilution assay, metabolic viability assay and growth curve analysis. The mode of action was elucidated by the proteomics approach using Nano-LC-MS/MS followed by in silico analysis. The results of proteomic analysis were further validated through several in vitro assays. The cytotoxic nature of the essential oil was also confirmed using adenocarcinomic human alveolar basal epithelial (A549) cells. Furthermore, the safety and in vivo anti-infective efficacy of Plectranthus amboinicus essential oil was evaluated through survival assay, CFU assay and histopathological analysis of vital organs using zebrafish as a model organism. RESULTS: The chemical characterization of Plectranthus amboinicus essential oil revealed that it is predominantly composed of thymol. Thymol rich P. amboinicus essential oil demonstrated potent inhibitory effects on Klebsiella pneumoniae growth, achieving a significant reduction at a concentration of 400 µg/mL within 4 h of treatment The nano-LC-MS/MS approach unveiled that the essential oil exerted its impact by disrupting the antioxidant defense system and efflux pump system of the bacterium, resulting in elevated cellular oxidative stress and affect the biosynthesis of biofilm. The same was validated through several in vitro assays. Furthermore, the toxicity of Plectranthus amboinicus essential oil determined using A549 cells and zebrafish survival assay established a non-toxic concentration of 400 µg/mL and 12.5 µg/mL respectively. The results of anti-infective potential of the essential oil using Zebrafish as a model organism demonstrated significantly improved survival rates, reduced bacterial load, alleviated visible signs of inflammation and mitigated the adverse effects of infection on various organs, as evidenced by histopathological analysis ensuring its safety for potential therapeutic application. CONCLUSION: The executed in vitro and in vivo assays established the effectiveness of essential oil in inhibiting bacterial growth by targeting key proteins associated with the bacterial antioxidant defense system and disrupted the integrity of the cell membrane, highlighting its critical role in addressing the challenge posed by antibiotic-resistant Klebsiella pneumoniae.

Antimicrobial activity of Southern African medicinal plants on Helicobacter pylori and Lactobacillus species.

ETHNOPHARMACOLOGICAL RELEVANCE: Numerous medicinal plants have been used traditionally in South Africa for gastric ulcer treatment. Helicobacter pylori is known for causing inflammation and the onset of gastric ulcers. While several studies explored medicinal plants against H. pylori, investigation of medicinal plants used for gastric ulcers has been neglected, as well as the effects these plants would have on bacteria occurring naturally in the gut microbiome. AIM OF THE STUDY: This study aimed to investigate Southern African medicinal plants used traditionally for treating gastric ulcers against H. pylori , as well as the effects that these plants have when combined with Lactobacillus species and tested against H. pylori. METHODOLOGY: Based on evidence from the ethnobotanical literature, 21 plants were collected. Their antimicrobial activity was assessed against five clinical H. pylori strains, and in combination with each of three Lactobacillus species, using the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) broth microdilution assays. Toxicity was assessed using the brine shrimp lethality assay. RESULTS: Noteworthy activity was observed against at least one H. pylori strain for 12 plant species. The lowest mean MICs were from organic extracts of Carissa edulis Vahl (0.18 mg/mL) and Chironia baccifera L. (0.20 mg/mL), and aqueous extracts of Sansevieria hyacinthoides (L.) Druce (0.26 mg/mL) and Dodonaea viscosa Jacq. (0.30 mg/mL). Aqueous extracts of the investigated plants were combined with Lactobacillus species, and the majority of combinations showed increased antimicrobial activity compared with the extracts alone. Combinations of Lactobacillus rhamnosus with 18 of the 21 aqueous plant extracts showed at least a two-fold decrease in the mean MBC against all H. pylori strains tested. Lactobacillus acidophilus combined with either Protea repens L., Carpobrotus edulis (L.) L. Bolus or Warburgia salutaris (Bertol.f.) Chiov. aqueous extracts had the best anti-H. pylori activity (mean MBCs of 0.10 mg/mL for each combination). Only four organic and one aqueous extract(s) were considered toxic. CONCLUSION: These results highlight the potential of medicinal plants to inhibit H. pylori growth and their role in traditional treatments for the management of ulcers. The results also indicate that aqueous extracts of these plants do not hinder the growth of bacteria that occur naturally in the gut microbiome and play a role in maintaining gut health, as well as show the potential benefit of including Lactobacillus species as potentiators of H. pylori activity.

Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

Antimicrobial Potential of Polyphenols: An Update on Alternative for Combating Antimicrobial Resistance.

The last decade has encountered an increasing demand for plant-based natural antibiotics. This demand has led to more research-based investigations for natural sources of antimicrobial agents and published reports demonstrating that plant extracts are widely applied in modern medicine, reporting potential activity that may be due to polyphenol compounds. Interestingly, the effects of polyphenols on the sensitivity of bacteria to antibiotics have not been well-studied. Hence, the current review encompasses the prospective application of plant-based phenolic extracts from plants of Indian origin. The emergence of resistance to antimicrobial agents has increased the inefficacy of many antimicrobial drugs. Several strategies have been developed in recent times to overcome this issue. A combination of antimicrobial agents is employed for the failing antibiotics, which restores the desirable effect but may have toxicity-related issues. Phytochemicals such as some polyphenols have demonstrated their potent activity as antimicrobial agents of natural origin to work against resistance issues. These agents alone or in combination with certain antibiotics have been shown to enhance the antimicrobial activity against a spectrum of microbes. However, the information regarding the mechanisms and structure-activity relationships remains elusive. The present review also focuses on the possible mechanisms of natural compounds based on their structure- activity relationships for incorporating polyphenolic compounds in the drug-development processes. Besides this work, polyphenols could reduce drug dosage and may diminish the unhidden or hidden side effects of antibiotics. Pre-clinical findings have provided strong evidence that polyphenolic compounds, individually and in combination with already approved antibiotics, work well against the development of resistance. However, more studies must focus on in vivo results, and clinical research needs to specify the importance of polyphenol-based antibacterials in clinical trials.

Identification and characterization of a novel antifungal compound tubeimoside I targeting cell wall.

Due to fungal diseases that threaten immunocompromised patients, along with the limited availability of antifungal agents, there is an urgent need for new antifungal compounds to treat fungal infections. Here, we aimed to identify potential antifungal drugs from natural products using the fission yeast Schizosaccharomyces pombe as a model organism since it shares many features with some pathogenic fungi. Here, we identified tubeimoside I (TBMS1), an extract from Chinese herbal medicine, that showed strong antifungal activity against S. pombe. To gain insight into the underlying mechanism, we performed transcriptomics analyses of S. pombe cells exposed to TBMS1. A significant proportion of the differential expressed genes were involved in cell wall organization or biogenesis. Additionally, TBMS1 treatment of S. pombe cells resulted in pleiotropic phenotypes, including increased sensitivity to ß-glucanase, enhanced calcineurin activity, translocation of GFP-Prz1 to the nucleus, as well as enhanced dephosphorylation of Prz1, suggesting that TBMS1 disrupted cell wall integrity of S. pombe cells. Notably, calcofluor staining showed that abnormal deposits of cell wall materials were observed in the septum and cell wall of the TBMS1-treated cells, which were further corroborated by electron microscopy analysis. We also found that oxidative stress might be involved in the antifungal action of TBMS1. Moreover, we confirmed the antifungal activities of TBMS1 against several clinical isolates of pathogenic fungi. Collectively, our findings suggest that TBMS1, a novel antifungal compound, exerts its antifungal activity by targeting cell walls, which may pave the way for the development of a new class of antifungals. IMPORTANCE: Fungal infections pose a serious threat to public health and have become an emerging crisis worldwide. The development of new antifungal agents is urgently needed. Here, we identified compound tubeimoside I (TBMS1) for the first time showing strong antifungal activity, and explored the underlying mechanisms of its antifungal action by using the model yeast Schizosaccharomyces pombe. Notably, we presented multiple evidence that TBMS1 exerts its antifungal activity through targeting fungal cell walls. Moreover, we verified the antifungal activities of TBMS1 against several pathogenic fungi. Our work indicated that TBMS1 may serve as a novel antifungal candidate, which provides an important foundation for designing and developing new cell wall-targeting agents for combating life-threatening fungal infections.

Synergistic activity of crocin and crocin loaded in niosomes alone and in combination with fluconazole against Candida albicans isolates: In vitro and in silico study.

INTRODUCTION: Since the drug resistance in Candida species is becoming a serious clinical challenge, novel alternative therapeutic options, particularly herbal medicine, have attracted increasing interest. This study aimed to pinpoint the potential antifungal activity of crocin (Cro), the efficacy of the niosomal formulation of Cro (NCro), and the synergistic activity of both formulations in combination with fluconazole (FLC) against susceptible and resistant C. albicans isolates. MATERIAL AND METHODS: NCro was formulated using the heating method. The in vitro antimycotic activity of Cro, NCro, and FLC was evaluated. Checkerboard and isobologram assays evaluated the interaction between both formulations of Cro and FLC. Necrotic and apoptotic effects of different agents were analyzed using the flow cytometry method. In silico study was performed to examine the interactions between Lanosterol 14 alpha-demethylase and Cro as a part of our screening compounds with antifungal properties. RESULTS: NCro exhibited high entrapment efficiency up to 99.73 ± 0.54, and the mean size at 5.224 ± 0.618 µm (mean ± SD, n = 3). Both formulations of Cro were shown to display good anticandidal activity against isolates. The synergistic effect of the NCro in combination with FLC is comparable to Cro (P-value =0.03). Apoptotic indicators confirmed that tested compounds caused cell death in isolates. The docking study indicated that Cro has interactivity with the protein residue of 14α-demethylase. CONCLUSION: The results showed a remarkable antifungal effect by NCro combined with FLC. Natural compounds, particularly nano-sized carrier systems, can act as an effective therapeutic option for further optimizing fungal infection treatment.

Antibacterial Activities of the Algal Bromophenol Methylrhodomelol Against Pseudomonas aeruginosa.

Methylrhodomelol (1: ) is a bromophenol from the red alga Vertebrata lanosa that has been associated with antimicrobial properties. The aim of the current study was, therefore, to assess the antimicrobial potential of this compound in more detail against the gram-negative pathogen Pseudomonas aeruginosa. 1: exerted weak bacteriostatic activity against different strains when grown in minimal medium, whereas other phenolics were inactive. In addition, 1: (35 and 10 µg/mL) markedly enhanced the susceptibility of multidrug-resistant P. aeruginosa toward the aminoglycoside gentamicin, while it did not affect the viability of Vero kidney cells up to 100 µM. Finally, pyoverdine release was reduced in bacteria treated at sub-inhibitory concentration, but no effect on other virulence factors was observed. Transcriptome analysis of treated versus untreated P. aeruginosa indicated an interference of 1: with bacterial carbon and energy metabolism, which was corroborated by RT-qPCR and decreased ATP-levels in treated bacteria. In summary, the current study characterized the antibacterial properties of methylrhodomelol, revealed its potential as an adjuvant to standard antibiotics, and generated a hypothesis on its mode of action.