Alkaloid Compounds Research Articles

Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches

Atherosclerosis is potentially correlated with several cardiac disorders that are greatly associated with cellular oxidative stress generation, inflammation, endothelial cells dysfunction, and many cardiovascular complications. Berberine is a natural isoquinoline alkaloid compound that widely modulates pathogenesis of atherosclerosis through its different curative potentials. This in silico screening study was designed to confirm the potent restorative properties of berberine chloride as a multitarget-mediated alkaloid against the CVDs and their complications through screening, identifying, visualizing, and evaluating its binding models, affinities, and interactions toward several CVDs-related targets as direct and/or indirect-mediated signals via inhibiting cellular ER stress and apoptotic signals and activating autophagy pathway. The drug-likeness properties of berberine were predicted using the computational QSAR/ADMET and Lipinski’s RO5 analyses as well as in silico molecular docking simulations. The potent berberine-binding modes, residues-interaction patterns, and free energies of binding scores towards several CVDs-related targets were estimated using molecular docking tools. Furthermore, the pharmacokinetic properties and toxicological features of berberine were clearly determined. According to this in silico virtual screening study, berberine chloride could restore cardiac function and improve pathogenic features of atherosclerotic CVDs through alleviating ER stress and apoptotic signals, activating autophagy, improving insulin sensitivity, decreasing hyperglycemia and dyslipidemia, increasing intracellular RCT signaling, attenuating oxidative stress and vascular inflammation, and upregulating cellular antioxidant defenses in many cardiovascular tissues. In this in silico study, berberine chloride greatly modulated several potent CVDs-related targets, including SIGMAR1, GRP78, CASP3, BECN1, PIK3C3, SQSTM1/p62, LC3B, GLUT3, INSR, LDLR, LXRα, PPARγ, IL1β, IFNγ, iNOS, COX-2, MCP-1, IL10, GPx1, and SOD3.

Assessment of combining ability for targeted traits in periwinkle (Catharanthus roseus (L.) G. Don) through diallel analysis

Catharanthus roseus (L.) G. Don is a vital summer season perennial semi shrub and multipurpose drought resilient flower crop of the tropical region of the Indian subcontinent. This industrially dominant crop is primarily availed as border, bedding and pot culture in landscaping; and also cultivated for its anti-cancer alkaloid compounds enriched plant parts. Hence, the present study was focused to explore diversity. Six inbred lines of periwinkle were crossed in full-diallel fashion with an objective of identifying superior cross-combinations for high general, specific and reciprocal combining ability. The analysis of variance for combining ability was highly significant for growth and flowering traits indicated existence of both additive and non-additive gene actions. However some traits showed only additive effect due to non-significant general combining ability. The parental lines of Vi-13–2 and Vi-15–2 expressed superior general combining effects for flower yield and considered as good general combiners for crossing programmes. The cross combinations Vi-15–1 × Vi-14–3 and Vi-16 × Vi-15–2 exhibited significantly positive specific combining ability effects for flower yield and considered as good specific direct combiners. High specific direct cross combiners necessitate poor × good, good × good and poor × poor parental combinations and can be contribute additive × dominance, additive × additive, dominance × dominance and epistatic gene interactions. The specific reciprocal cross combiners identified as Vi-14–3 × Vi-29 and Vi-14–3 × Vi-13–2 with superior expression in the reciprocal magnitudes for various traits might be due to cytoplasmic effects. The current investigation is designed to identify the best performing inbred lines for ornamental utilization as well as lines that can be exploited as parents in subsequent crosses.

Purification, characterization and study of blue fluorescent substance in caffeine

AbstractBackgroundCaffeine, a xanthine alkaloid compound, is a stimulant of the central nervous system and is mainly used in the pharmaceutical and food industries. Because caffeine is directly absorbed into the body, Chinese pharmacopeia has high requirements on the quality of caffeine products, and fluorescence has always been an important indicator to measure the quality of caffeine. In this study, a major fluorescent impurity affecting the appearance and purity of caffeine products was isolated for the first time, and the solubility, thermodynamic properties and dissociation constants of this impurity were studied.Results(i) The fluorescent impurity affecting the appearance and purity of the product was successfully isolated from crude caffeine and theophylline sodium salt, and named as a blue fluorescent substance. The mass purity of the substance was 96.27%, and its structure was determined based on a comprehensive analysis of high‐resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy [hydrogen 1 (1H) NMR, carbon‐13 (13C) NMR, COSY, NOESY, HSQC, HMBC]. (ii) The solubility of blue fluorescent substance in four pure solvents was determined and the thermodynamic properties were calculated. (iii) The dissociation constants of the blue fluorescent substance in water at 298.15 K were determined by UV spectrophotometry.ConclusionThe results provide a theoretical basis for the crystallization separation of the blue fluorescent substance during the industrial production of caffeine, as well as basic data for the green synthesis process of caffeine. © 2024 Society of Chemical Industry (SCI).

A Review on Folklore Uses, Phytoconstituents and Pharmacological Activities of the Genus Berberis

Abstract: Genus berberis, an evergreen shrub of about 500 plant species found in subtropical and temperate regions but only some of them are investigated and evaluated for their phytochemistry and bioactivity. These plants are spread worldwide and help in the nourishment of humans and animals. Almost all parts of the plant are investigated for pharmacological and phytochemical purposes, including, roots, fruits, stems, buds, seeds, branches, flowers, leaves, and whole plant. Rasaut, an extract of either the stem or root of Berberis aristata is mentioned in the ancient Ayurvedic literature of India for treating indolent ulcers and eye disorders, and B. vulgaris is still used to treat malaria in North America. They have many medicinal properties and compounds that are bioactive like berberine. Berberine possesses anticancer, antimicrobial, and other activities. The plants contain a number of alkaloids, tannins, flavonoids, carotenoids, terpenoids, and other categories of chemical constituents. The alkaloidal compounds are isolated and evaluated for various activities and are found to be active. The researchers are continuously working to get novel exploration regarding the Genus Berberis . Here in the review, traditional and folkloric uses of the genus were also described. Apart from this, they possess numerous activities like anticancer, antimicrobial, antioxidant, anti-inflammatory, antidiabetic, antiulcer, antiviral and, wound healing and many more. These activities were authenticated by in-vitro and in-vivo methods. The aim of this review is to update and systematically arrange information in one platform. In this review, we extracted the current information from Pubmed, Googlescolar, Scifinder and many more databases.

Lipase Enzyme Inhibitory Activity of Jombang Leaves Extract (Taraxacum officinale F.H. Wigg)

Background: Obesity is a condition that occurs due to an imbalance between energy intake and expenditure. Lipase enzymes play an important role in the process of fat metabolism, making it a target in obesity treatment strategies. Jombang plant has been used for generations as an alternative treatment for various diseases. The main content of secondary metabolite compounds in jombang plants are phenolics, flavonoids, terpenoids, and alkaloids. Objective: This study was conducted to determine the activity and potential inhibition of jombang plant (Taraxacum officinale F.H. Wigg.) against lipase enzyme in vitro. Materials and Methods: The phytochemical screening was determined by a color change reaction with certain reagents, while total phenolic content was carried out using Folin-Ciocalteau reagent spectrophotometrically. The inhibitory activity of 96% ethanol extract of jombang leaves as well as orlistat as positive control was measured by titration method and using olive oil substrate. The extract concentrations used were 125 ppm, 250 ppm, and 500 ppm. Results: Jombang leaf extract contains alkaloid, phenolic, flavonoid and terpenoid compounds qualitatively. Determination of total phenolic content in 96% ethanol extract of jombang leaves was obtained at 12.69 ± 0.91 mgGAE/g. The highest percentage of inhibition was found at a concentration of 500 ppm which amounted to 103.85%. The difference in the percentage of inhibition in all groups showed no significant difference (Sig>0.05). Conclusion: This study shows that jombang leaf extract is able to inhibit lipase enzyme activity with the highest percentage of inhibition was 103,85%.

QUANTITATIVE PHYTOCHEMICAL ANALYSIS OF MAULI BANANA STEM AND BASIL LEAVES EXTRACT MIXTURE

Background: Mauli banana stem extract and basil leaves extract are ingredients that has been involved in in vitro and in vivo researches for their pharmacognosy and therapeutic applications. Preliminary phytochemical test of both individual extract revealed the presence of triterpenoid, tannin, phenolic, saponin, steroid, alkaloid, and flavonoid compound. A combination of mauli banana stem and basil leaves extract is believed to work synergistically and may have a more beneficial effect than in single herbal extract. Purpose: To analyze the results of quantitative phytochemical of mauli banana stem and basil leaves extract mixture. Method: Non-experimental research with quantitative laboratory examination to determine sample content. Results: The result showed that mauli banana stem and basil leaves extract mixture contain triterpenoid (30%), saponin (24,75%), flavonoid (15%), alkaloid (22%), phenolic (8%), steroid (4,62%), and tannin (0,03%). Conclusion: Mauli banana stem and basil leaves extract mixture correlated with an increase in majority of the bioactive compound compared to the single extract and would serve as a promising source for phytomedicine. The bioactive compound with the highest content was triterpenoid with 30%, while the lowest was tannin with 0,03%. Keywords: Basil leave extract, Mauli banana stem extract, Quantitative phytochemical test

Studies on Secondary Metabolites and In vitro and In silico Anticholinesterases Activities of the Sea Urchin Echinometra mathaei Crude Venoms from the Persian Gulf-Bushehr

Background: Echinoderms are a unique source of amazing secondary metabolites with a wide spectrum of biological activities. Several species of sea urchins contain various toxins and biologically active metabolites. One of the most attractive approaches to treat Alzheimer's disease is searching for effective marine natural products with cholinesterase inhibitory activities. Objective: The current study is designed to investigate the in vitro and in silico acetylcholinesterase and butyrylcholinesterase inhibitory activities of the Persian Gulf echinoderm sea urchin Echinometra mathaei venom and related chemical compounds. Methods: The experiments for LD50, total protein, protein bands, in vitro cholinesterase inhibitory activities, the identity of secondary metabolites, and the in silico evaluations, respectively, were performed by Spearman-Karber, Lowry, SDS-PAGE, Ellman's spectroscopic, GC-MS, and docking methods. Results: The LD50 (IV rat) of the spine, gonad, and coelomic fluid from sea urchin samples were 2.231 ± 0.09, 1.03 ± 0.05, and 1.12 ± 0.13 mg/ml, respectively. The SDS-PAGE and total protein studies showed that at least a portion of the venom is protein in nature. GC-MS analysis of the identified samples revealed 12, 23, and 21 compounds with different chemical types, including alkaloids, terpenes, and steroids, respectively. According to the results, all samples act as significant inhibitors of both enzymes. In silico data for the identified compounds also confirmed the experimental results. Conclusion: The alkaloid compound 6H-Indolo[3,2,1-de] [1,5] naphthyridine-6-one,1,2,3a,4,5- hexahydro-8-hydroxy-3-methyl (C7) had the highest affinity for both enzymes. Further research is needed to determine whether C7 could be a therapeutic candidate for Alzheimer's disease.

Penentuan Kadar Alkaloid Total Ektstrak Akar Bajakah (Spatholobus Littoralis Hassk) dengan Metode Spektofotometri Uv-Vis

The Bajakah tampala tree (Spatholobus littoral hassk) is a native plant from the interior of the forests in Kalimantan, especially Central Kalimantan. This plant is a plant that stretches or grows and grows abundantly in the interior of the forest. The Bajakah plant is known to the people of Kalimantan as a medicinal plant and can cure various diseases, including diarrhea, rheumatism, and cancer. The aim of this research was to determine the alkaloid content of bajakah root extract in various concentrations. The research method was carried out experimentally, with the independent variable being an ethanol extract of bajakah roots with concentrations of 50, 70, and 96%. Meanwhile, the dependent variables are the characteristics of simplicia, the secondary metabolite content of Bajakah root ethanol extract, and the determination of the total alkaloid content of Bajakah root extract. Bajakah root simplicia extract is made with 96, 70, and 50% ethanol solvents. The parameters used in this study include water content, total ash content, acid insoluble ash content, water soluble extract content, ethanol soluble extract content, and secondary metabolite content, including alkaloids, tannins, flavonoids, saponins, steroids, and terpenoids, by conducting phytochemical screening. , making a standard caffeine solution, determining the maximum wavelength of caffeine, measuring the caffeine calibration curve, and determining the total alkaloid content of Bajakah root extract. The results of the phytochemical screening showed that Bajakah root was positive for containing alkaloid compounds, saponins, tannins, flavonoids, steroids, and terpenoids. And the results obtained from Bajakah root plants obtained from Central Kalimantan were a 96% ethanol concentration of 1.66797 ± 0.7088 mg/gram, a 70% ethanol concentration of 1.6679 ± 0.1124 mg/gram, and a 50% ethanol concentration of 0.46981 ± 1.0656 mg/gram

ANTIBACTERIAL SCREENING OF SARGASSUM SP EXTRACT. OPPOSING VIBRIO PARAHAEMOLYTICUS BACTERIA

Antibiotics cause resistance to pathogenic bacteria, and the emergence of resistance and bacterial pathogenic infections makes scientists try to find new drugs. One of the efforts is to use marine organisms as a natural antibacterial agent, one of them is Sargassum sp. Sargassum sp contains alginate and iodine which are used in the food, pharmaceutical, cosmetic and textile industries. Apart from that, Sargassum sp. contains active compounds of steroids, alkaloids, phenols and triterpenoids which function as antibacterials, can be used to inhibit the growth of Vibrio sp bacteria which is the cause of firefly disease which is most dangerous for tiger prawns. The purpose of this study was to determine the ability of the extract Sargassum sp. In inhibiting the growth of Vibrio parahaemolyticus bacteria with different levels of solvent start with methanol, ethyl asetat, and n-hexane. The rejuvenation of Vibrio parahaemolyticus and Vibrio harveyimelalai bacteria is carried out in two stages, the first is planting on Triptyc Soy Broth (TSB) medium and the second stage is planting on Triptyc Soy Agar (TSA) medium. Antibacterial sensitivity test using disc diffusion method. The results of the test showed that 1). sargassum sp which is extracted by metanol solvent inhibits the growth of Vibrio parahemolyticus bacteria. 2). sargassum sp which extract by etil sestat and n - heksan solvent can't inhibit the Vibrio parahemolyticus bacteria.

PENGEMBANGAN FORMULASI EMULGEL FRAKSI n-HEKSAN DAUN MIANA (Coleus scutellarioides) SEBAGAI ANTIBAKTERI TERHADAP Propionibacterium acnes PENYEBAB JERAWAT (Acne vulgaris)

Acne (Acne vulgaris) is a condition where the skin experiences inflammation in the polysebaceous unit which is triggered by Propionibacterium acnes. Miana leaves (Coleus scutellarioides) contain alkaloid and terpenoid compounds which can act as antibacterials. This research aims to determine whether the n-hexane fraction of Miana leaves (C. scutellarioides) can be formulated in the form of a physically and chemically stable emulgel preparation, to determine whether the n-hexane fraction of Miana leaves (C. scutellarioides) has activity against P. acnes. as a cause of acne (A. vulgaris) and to determine the formula with an effective concentration in inhibiting the growth of P. acnes. This research is a form of laboratory experimentation. The n-Hexane fraction of miana leaves was obtained by fractionation. Antibacterial activity testing was carried out using the well method. The results obtained were physically and chemically stable emulgel formulas, namely F0 and F1. The inhibition zone of F1 is 16.46 mm (strong), F2 is 14.40 mm (strong), F3 is 16.78 mm (strong) and F0 has no antibacterial activity. The formula with a concentration of 12.5% was the most effective in inhibiting the growth of P. acnes, namely 16.78 mm. From the results of this research, it was found that the n-Hexane fraction of Miana leaves (C. scutellarioides) has strong antibacterial activity against P. acnes and can be formulated in the form of an emulgel dosage form.

EFFECT OF CHEMICAL MEDIA COMPONENTS AND SILVER NANOPARTICLES ON THE INDUCTION OF CALLUS CULTURE AND ACCUMULATION OF SECONDARY COMPOUNDS IN A Trigonella foenum-graecum L.

This study was investigate the effect of components media and silver nanoparticles (Ag-NPs) synthesized in the laboratory on the induction of biomass and secondary metabolites of calli cultures induced from the cotyledons of Trigonella foenum-graecum L. The culture media LS and B5 were tested with the growth regulators 2,4-Dichlorophenoxyacetic acid (2,4-D) at a concentration of 1.0, 2.0 and 3.0 mg l-1 and 6-benzyladenine (BA) at a concentration of 0.0, 0.5, 1.0, 1.5 and 2.0 mg l-1, with the aim of studying its effect on callus induction. In comparison, Ag-NPs were used at a concentration of 0.0, 0.5, 1.0, 1.5 and 2.0 mg l-1 to study its effect on the production of some secondary compounds. The results showed that the mixture consisting of the culture media LS with 3.0 mg l-1 of 2,4-D and 1.0 mg L-1 of BA the highest percentage of callus induction and the minimum days to complete callus formation. While, the same media with 2.0 mg l-1 2,4-D and 1.0 mg l-1 of BA recorded the highest dry weight (DW) and relative water content (RWC). The combination B5×2.0 mg l-1 2,4-D×1.5 or 2.0 mg l-1 showed the highest fresh weight (FW) and the lowest time required to start callus induction, respectively. As for the production of SC, the B5 media with 2.0 mg l-1 of Ag-NPs achieved the highest concentration of alkaloid compounds represented by trigonelline and diosgenin, and flavonoids expressed by qurcetine, vitxein, rutin, apigenin, isovitexin, and kaemferol.

Peiminine Exerts Its Anti-Acne Effects by Regulating the NF-κB Pathway.

Peiminine is the main natural alkaloid compound extracted from the Chinese herb Fritillaria. Although peiminine is known for its antioxidant and anti-inflammatory effects in conditions such as mastitis and arthritis, its impact on inflammation induced by Cutibacterisum acnes (C. acnes) has not been explored. The aim of this study was to investigate the effect of peiminine on C. acnes-induced inflammatory responses in the skin and to identify the underlying mechanism involved. We discovered that peiminine inhibits the C. acnes-induced expression of inflammatory mediators such as pro-interleukin-1β (pro-IL-1β), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in mouse bone marrow-derived macrophages (BMDMs). Peiminine suppressed the activation of nuclear factor-kappa B (NF-κB) without affecting the activation of mitogen-activated protein kinase (MAPK) pathways such as JNK, ERK, and p38 MAPK. In addition, we found that peiminine suppressed inflammatory cytokine expression and ameliorated histological symptoms in C. acnes-induced mouse skin. Our study is the first to provide evidence that peiminine has an inhibitory effect on acne, and it points toward the potential of incorporating peiminine into cosmetic and pharmaceutical formulations for acne treatment.

Thymol-loaded liposomes effectively induced apoptosis and decreased EGFR expression in colorectal cancer cells.

Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide. Different factors, such as environmental and genetic factors and lifestyle, affect it. Owing to the presence of phenolic, alkaloid, antioxidant, and terpenoid compounds, herbal compounds can be effective in the treatment of various cancers. Thymol is a natural monoterpene phenol that is abundant in some plants and exerts several biological effects. The aim of this study was to investigate the apoptotic, anti-proliferative effect and EGFR gene expression under the influence of thymol-loaded nanoliposome in SW84 and SW111 cell lines derived from colorectal cancer. The lipid thin-film hydration method was used to synthesize thymol-loaded liposomes, and their characterization was performed using TEM, DLS, and HPLC analyses. SW84 and SW1111 cells were treated with thymol- and thymol-loaded liposomes at different doses, the inhibition of cell proliferation was evaluated using an MTT assay, the rate of apoptosis induction was assessed using flow cytometry, and EGFR gene expression was measured using real-time PCR. The nanoparticles produced were spherical, uniform, and 200 ± 10nm in size. HPLC analysis showed that approximately 98% thymol was loaded into the nanoliposome. The results of the MTT assay showed that thymol and thymol-nanoliposomes decreased the proliferation of SW84 and SW1111 cells in a concentration-dependent manner. The IC50 of thymol and thymol-nanoliposomes were 18 and 14.2µg/ml for the SW48 cell line (P = 0.04) and 10.5 and 6.4µg/ml for the SW1116 cell line (P = 0.001). Thymol-nanoliposomes significantly inhibited the proliferation of cancer cells compared to free thymol. Flow cytometry showed an increase in the percentage of apoptotic cells, especially in the thymol-nanoliposome group in the treated cells. Real-time PCR results also showed that thymol and thymol-nanoliposome both caused a decrease in the expression of EGFR genes in both cell lines, but this effect of decreasing gene expression was significantly higher in the thymol-nanoliposome group. Our results showed that thymol-nanoliposomes reduced proliferation, increased apoptosis, and decreased EGFR expression in colorectal cancer-derived cell lines.

Plesdasep Innovation: Fever-Reducing Plaster Using the Leaves of Dadap Serep (Erythrina subumbrans) as a First Aid Medium for Fever

This research aims to: 1) Make an innovation of febrifuge plaster made from dadap serep leaves (Erythrina subumbrans), 2) Examine the effectiveness of the product in reducing fever, 3) Know people's preferences for the product. The method used in this study is an experimental method with a complete randomized design. The test was carried out by conducting a feasibility test of dadap serep leaves for plaster material and testing the effectiveness of plaster in reducing body temperature. The effectiveness test was conducted by applying warm water compresses to the first experimental group who had fever, plesdasep in the second experimental group, and comparing it with the control group that was not given plaster. After that, respondents were given a questionnaire to find out their preferences for Plesdasep. The results of this study are expected to provide an inexpensive alternative to fever treatment with ingredients that are easily available in nature. Dadap serep leaves were chosen as ingredients because they contain alkaloid compounds, flavonoids, and saponins that can reduce body temperature and are easily found in the surrounding environment. With this innovation, it is expected to provide an alternative treatment that is safe, cheap, and easily accessible for people who need first aid during fever.

Comprehensive Tools of Alkaloid/Volatile Compounds-Metabolomics and DNA Profiles: Bioassay-Role-Guided Differentiation Process of Six Annona sp. Grown in Egypt as Anticancer Therapy.

Trees of the Annona species that grow in the tropics and subtropics contain compounds that are highly valuable for pharmacological research and medication development and have anticancer, antioxidant, and migratory properties. Metabolomics was used to functionally characterize natural products and to distinguish differences between varieties. Natural products are therefore bioactive-marked and highly respected in the field of drug innovation. Our study aimed to evaluate the interrelationships among six Annona species. By utilizing six Start Codon Targeted (SCoT) and six Inter Simple Sequence Repeat (ISSR) primers for DNA fingerprinting, we discovered polymorphism percentages of 45.16 and 35.29%, respectively. The comparison of the profiles of 78 distinct volatile oil compounds in six Annona species was accomplished through the utilization of GC-MS-based plant metabolomics. Additionally, the differentiation process of 74 characterized alkaloid compound metabolomics was conducted through a structural analysis using HPLC-ESI-MSn and UPLC-HESI-MS/MS, and antiproliferative activities were assessed on five in vitro cell lines. High-throughput, low-sensitivity LC/MS-based metabolomics has facilitated comprehensive examinations of alterations in secondary metabolites through the utilization of bioassay-guided differentiation processes. This has been accomplished by employing twenty-four extracts derived from six distinct Annona species, which were subjected to in vitro evaluation. The primary objective of this evaluation was to investigate the IC50 profile as well as the antioxidant and migration activities. It should be noted, however, that these investigations were exclusively conducted utilizing the most potent extracts. These extracts were thoroughly examined on both the HepG2 and Caco cell lines to elucidate their potential anticancer effects. In vitro tests on cell cultures showed a significant concentration cytotoxic effect on all cell lines (HepG2, HCT, Caco, Mcf-7, and T47D) treated with six essential oil samples at the exposure time (48 h). Therefore, they showed remarkable antioxidant activity with simultaneous cytotoxic effects. In total, 50% and 80% of the A. muricata extract, the extract with the highest migratory activity, demonstrated a dose-dependent inhibition of migration. It was strong on highly metastatic Caco cells 48 h after treatment and scraping the Caco cell sheet, with the best reduction in the migration of HepG2 cells caused by the 50% A. reticulata extract. Also, the samples showing a significant IC50 value showed a significant effect in stopping metastasis and invasion of various cancer cell lines, making them an interesting topic for further research.

The potential of Trichoderma asperellum organic extract and its emulsion to inhibit cocoa ( Theobroma cacao L.) black pod disease and induce biochemical defenses against Phytophthora megakarya

This work aimed to evaluate the potential of Trichoderma asperellum organic extract and its emulsion to control cocoa black pod disease caused by Phytophthora megakarya. Organic extract was obtained after fermentation of T. asperellum and its emulsion prepared by emulsification. The in vitro antimicrobial assays of organic extract and its emulsion were evaluated and the in situ tests were carried out on detached cocoa pods. T. asperellum inhibited the mycelia growth of P. megakarya at the rates of 52% and 100%, respectively, on dual culture and the cellophane plate. This antagonist produced lytic enzymes such as cellulase, amylase, lipase and protease. The organic extract contained alkaloid, flavonoid and phenol compounds. The emulsion obtained was stable. At 100 μg · ml -1, the extract and its formulation completely inhibited the mycelial growth of P. megakarya. Similarly, when infected detached cocoa pods were sprayed with extract or emulsion, there was a significant reduction of necrosis both for healing and prevention with the latter being the most efficient. For the preventive tests, the total inhibition was recorded at 3000 μg · ml -1 and 1000 μg · ml -1, respectively, with crude organic extract and its emulsion· For curative tests, total inhibition was obtained at 4000 μg · ml -1 and 3000 μg · ml -1, respectively, for preventive and curative tests. There was a significant and positive correlation between the content of biochemical markers and the reduction of necrosis on cocoa pods after treatment with the extract or its formulation. T. asperellum organic extract emulsion could be used as an alternative in the bio- protection of cocoa black pods disease.

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.

Trabectedin (TRB) and Lurbinectedin (LUR) are alkaloid compounds originally isolated from Ecteinascidia turbinata with proven antitumoral activity. Both molecules are structural analogues that differ on the tetrahydroisoquinoline moiety of the C subunit in TRB, which is replaced by a tetrahydro-β-carboline in LUR. TRB is indicated for patients with relapsed ovarian cancer in combination with pegylated liposomal doxorubicin, as well as for advanced soft tissue sarcoma in adults in monotherapy. LUR was approved by the FDA in 2020 to treat metastatic small cell lung cancer. Herein, we systematically summarise the origin and structure of TRB and LUR, as well as the molecular mechanisms that they trigger to induce cell death in tumoral cells and supporting stroma cells of the tumoral microenvironment, and how these compounds regulate immune cell function and fate. Finally, the novel therapeutic venues that are currently under exploration, in combination with a plethora of different immunotherapeutic strategies or specific molecular-targeted inhibitors, are reviewed, with particular emphasis on the usage of immune checkpoint inhibitors, or other bioactive molecules that have shown synergistic effects in terms of tumour regression and ablation. These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects.

Antioxidant and anticholinesterase properties of Echinometra mathaei and Ophiocoma erinaceus venoms from the Persian Gulf.

Introduction: The Persian Gulf is home to a diverse range of marine life, including various species of fish, crustaceans, mollusks, and echinoderms. This study investigates the potential therapeutic properties of venoms from echinoderms in the Persian Gulf, specifically their ability to inhibit cholinesterases (Acetylcholinesterase and butyrylcholinesterase) and act as antioxidants. Methods: Four venoms from two echinoderm species, including the spine, gonad, and coelomic fluids of sea urchins, as well as brittle star venoms, were analyzed using various methods, including LD50 determination, protein analysis, antioxidant assays, GC-MS for secondary metabolite identification, and molecular docking simulations. Results and discussion: The study's results revealed the LD50 of the samples as follows: 2.231 ± 0.09, 1.03 ± 0.05, 1.12 ± 0.13, and 6.04 ± 0.13mg/mL, respectively. Additionally, the protein levels were 44.037 ± 0.002, 74.223 ± 0.025, 469.97 ± 0.02, and 104.407 ± 0.025μg/mL, respectively. SDS-PAGE and total protein studies indicated that at least part of the venom was proteinaceous. Furthermore, the study found that the brittle star samples exhibited significantly higher antioxidant activity compared to other samples, including the standard ascorbic acid, at all tested concentrations. GC-MS analysis identified 12, 23, 21, and 25 compounds in the samples, respectively. These compounds had distinct chemical and bioactive structures, including alkaloids, terpenes, and steroids. Conclusion: These venoms displayed strong cholinesterase inhibitory and antioxidant activities, likely attributed to their protein content and the presence of alkaloids, terpenes, and steroids. Notably, the alkaloid compound C 7 was identified as a promising candidate for further research in Alzheimer's disease therapy. In conclusion, echinoderms in the Persian Gulf may hold significant potential for discovering novel therapeutic agents.

Isolation and Characterization of Active Alkaloid Compounds from Cinnamomum Verum Cortexes and Proof of their Medicinal Efficacy against Pathogenic Fungus Alternaria Alternate Causing Upper Respiratory Tract Inflammatory Disease

Six alkaloid compounds were isolated (the discovery of a natural drug, which is a combination of the six alkaloid compounds). Alkaloids viz., 1,3,5-Triazine-2-carboxylic acid, 4-amino-6-methyl; 1,2,4-Triazino[5,6-E][1,2,4]-triazine-3,6-dione, hexahydro; 2-(4,5-Dihydro-3-methyl-5-oxo-1-phenyl-4-pyrazole)-5-nitrobenzoic acid; 4-metyl-3,4-dihydro-[1,2,3] trizolo [4,5-d] pyrimidine-5,7-dione; Propanoic acid-3-(perhydro-2,5-dioxo-imidazol [4,5-d] imidazole-1-yl) and 1,2,3-Triazolo[4,5-f] benzotriazole- 4,8(4H,8H)-dione, were isolated from Cinnamomum verum cortexes by using ethanolic acetic acid, sulphuric acid, and ammonia solvents, and they were characterized by using preliminary qualitative tests, gas chromatography-mass spectrumGC-MASS. The medicinal efficacy was studied for these six alkaloidic compounds theoretically by using the Autodock program and the results showed the presence of high efficacy of the compounds. Then the medicinal efficacy was measured biologically for the six compounds mixture in vitro depending on the synergistic interaction principle by using various concentrations (5, 10, 15, 20, and 25 mg/ml) by using of agar diffusion technique. The results showed that the six alkaloidic compounds’ mixture is biologically active against Alternaria alternate fungus, where the inhibition zone diameters were recorded equal to 27, 33, 41, 45, and 49 mm respectively towards the pathogenic fungus. Also, cytotoxicity tests for the different concentrations of six active alkaloid compounds mixture proved there is no toxic effect belonging to them towards red blood cells, and no hemolysis effect appeared in blood cells. Therefore, six alkaloid compounds isolated from Cinnamomum verum cortexes can be used as active drugs for the treatment of various diseases especially those caused by pathogenic fungi represented by Alternaria alternate, without any side effects.

Exploring the broad-spectrum pharmacological activity of two less studied Australian native fruits: chemical characterisation using LCMS-driven metabolomics.

Australian fruits such as native currant (Acrotriche depressa) and lemon aspen (Acronychia acidula) are under-examined in terms of their therapeutic potential. In this study, the in vitro antiproliferative activity of native currant and lemon aspen extracts (water and ethanol) against MCF7 breast adenocarcinoma cells was determined using the Alamar blue assay. The most potent extracts (native currant water, NC-W; native currant ethanol, NC-Et; lemon aspen ethanol, LA-Et) were further evaluated using flow cytometry to detect the potential induction of apoptosis in MCF7 cells whereas 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay was implemented to understand the impact of the extracts on the intracellular reactive oxygen species (ROS) levels in MCF7 cells. Furthermore, the antioxidant activity of the extracts was assessed using ABTS [2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate)], and CUPRAC (cupric reducing antioxidant capacity) assays. The antimicrobial susceptibility testing of NC-W, NC-Et, and LA-Et was carried out against Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli), and yeast (Candida albicans) strains using a resazurin-based assay. Additionally, potential metabolites in the NC-W and NC-Et extracts were analysed with liquid chromatography-mass spectrometry (LC-MS) driven metabolomics and chemometrics to spot differential and major metabolites. A dose-dependent antiproliferative activity was conferred by the NC extracts against MCF7 cells. Of the two LA extracts, only LA-Et showed a dose-dependent antiproliferative activity at higher concentrations. Both NC extracts and LA-Et induced apoptosis in MCF7 cells. None of the extracts increased the production of ROS significantly in MCF7 cells compared to the untreated control. A dose-dependent antioxidant activity was observed in both antioxidant assays. Both NC and LA extracts showed a similar minimum inhibitory concentration (MIC) value against S. aureus. Only LA-Et showed activity against E. coli, while NC-W and NC-Et were less active. All extracts showed MIC values of >1500 μg mL-1 against C. albicans. The metabolomics analysis revealed an abundance of flavonoids, fatty acyl derivatives, carbohydrates, carboxylic acids and their derivatives, and alkaloid compounds as potential bioactive metabolites in the NC extracts. In conclusion, both NC and LA showed antiproliferative (against MCF7 breast adenocarcinoma cells through the induction of apoptosis), strong antioxidant and minimal antimicrobial properties.