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[This corrects the article DOI: 10.3389/fphar.2023.1194578.].
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Inhalable microparticle-based anti TB drug delivery systems are being investigated extensively for Tuberculosis [TB] treatment as they offer efficient and deep lung deposition with several advantages over conventional routes. It can reduce the drug dose, treatment duration and toxic effects and optimize the drug bioavailability. Yeast derived ß-glucan is a ß-[1-3/1-6] linked biocompatible polymer and used as carrier for various biomolecules. Due to presence of glucan chains, particulate glucans act as PAMP and thereby gets internalized via receptor mediated phagocytosis by the macrophages. In this study, ß-glucan microparticles were prepared by adding l-leucine as excipient, and exhibited 70% drug [Rifabutin] loading efficiency. Further, the sizing and SEM data of particles revealed a size of 2-4 µm with spherical dimensions. The FTIR and HPLC data confirmed the ß-glucan composition and drug encapsulations efficiency of the particles. The mass median aerodynamic diameter [MMAD] and geometric standard deviation [GSD] data indicated that these particles are inhalable in nature and have better thermal stability as per DSC thermogram. These particles were found to be non-toxic upto a concentration of 80 µg/ml and were found to be readily phagocytosed by human macrophage cells in-vitro as well as in-vivo by lung alveolar macrophage. This study provides a framework for future design of inhalable ß-glucan particle based host-directed drug delivery system against pulmonary TB.
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Sistemas de Liberación de Medicamentos , Rifabutina , beta-Glucanos , Rifabutina/administración & dosificación , Rifabutina/farmacocinética , Rifabutina/química , beta-Glucanos/química , Humanos , Administración por Inhalación , Tuberculosis Pulmonar/tratamiento farmacológico , Tamaño de la Partícula , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Portadores de Fármacos/química , Antituberculosos/administración & dosificación , Antituberculosos/farmacocinética , Antituberculosos/químicaRESUMEN
[This corrects the article DOI: 10.3389/fcimb.2023.1295593.].
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BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.
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Antineoplásicos , Ácido Oleanólico , Plectranthus , Antioxidantes/uso terapéutico , Factor de Necrosis Tumoral alfa , Interleucina-6 , Ácido Oleanólico/uso terapéutico , Antiinflamatorios/uso terapéutico , Extractos Vegetales/uso terapéutico , Inflamación/tratamiento farmacológico , Citocinas , Antineoplásicos/uso terapéutico , Óxido Nítrico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Lipopolisacáridos/farmacologíaRESUMEN
Dia/betes is a serious health concern in many countries with high blood glucose, obesity, and multiple organ failures in late stages. Treating diabetes with effective drugs is still a challenging issue since most of the available diabetic drugs are not effective in combating diabetes, especially in secondary disease complications like obesity, retinopathy, and nephropathy associated with diabetes. Hence search for effective antidiabetic medication, especially from natural sources is mandatory with no adverse side effects. In the present study, a combined herbal aqueous extract of Tribulus terrestris and Curcuma amada was administered to diabetic-induced rats for 37 days. During experimentation, the mean blood glucose level was estimated and at the end of the experiment on the 37th day, the animal was sacrificed and observed for weight gain, plasma insulin, glycogen, glycated hemoglobin, urea, and creatinine level. The results revealed that TT and CA extract-treated diabetic groups significantly lowered the mean blood glucose level followed by increased glycogen and insulin level. Urea, creatinine, and HbA1c levels were considerably reduced in TT and CA-treated diabetic animals as compared to that of antidiabetic drug Glibenclamide-treated groups. TT and CA-treated diabetic animals showed considerable net body weight gain at the end of the experimental day. A concluding remark of the study shows that TT and CA herbal extract is effective against diabetes and it can be considered as an antidiabetic agent in ayurvedic medicine practice.
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Introduction: Zinc oxide nanoparticles (ZnO-NPs) have garnered considerable interest in biomedical research primarily owing to their prospective therapeutic implications in combatting pathogenic diseases and microbial infections. The primary objective of this study was to examine the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) using chicken egg white (albumin) as a bio-template. Furthermore, this study aimed to explore the potential biomedical applications of ZnO NWs in the context of infectious diseases. Methods: The NWs synthesized through biological processes were observed using electron microscopy, which allowed for detailed examination of their characteristics. The results of these investigations indicated that the NWs exhibited a size distribution ranging from approximately 10 to 100 nm. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) mapping analyses successfully corroborated the size, dimensions, and presence of biological constituents during their formation. In this study, XTT assay and confocal imaging were employed to provide evidence of the efficacy of ZnO-NWs in the eradication of bacterial biofilms. The target bacterial strains were Staphylococcus aureus and Escherichia coli. Furthermore, we sought to address pertinent concerns regarding the biocompatibility of the ZnO-NWs. This was achieved through comprehensive evaluation of the absence of cytotoxicity in normal HEK-293T and erythrocytes. Results: The findings of this investigation unequivocally confirmed the biocompatibility of the ZnO-NWs. The biosynthesized ZnO-NWs demonstrated a noteworthy capacity to mitigate the dermatitis-induced consequences induced by Staphylococcus aureus in murine models after a therapeutic intervention lasting for one week. Discussion: This study presents a comprehensive examination of the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) derived from chicken egg whites. These findings highlight the considerable potential of biosynthesized ZnO-NWs as a viable option for the development of therapeutic agents targeting infectious diseases. The antibacterial efficacy of ZnO-NWs against both susceptible and antibiotic-resistant bacterial strains, as well as their ability to eradicate biofilms, suggests their promising role in combating infectious diseases. Furthermore, the confirmed biocompatibility of ZnO-NWs opens avenues for their safe use in biomedical applications. Overall, this research underscores the therapeutic promise of ZnO-NWs and their potential significance in future biomedical advancements.
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Enfermedades Transmisibles , Dermatitis , Nanopartículas del Metal , Óxido de Zinc , Animales , Ratones , Óxido de Zinc/farmacología , Óxido de Zinc/química , Pollos , Clara de Huevo , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus , Espectroscopía Infrarroja por Transformada de Fourier , Extractos Vegetales/farmacologíaRESUMEN
In the current study, we report the synthesis of methotrexate-conjugated zinc oxide nanoparticles (MTX-ZnONPs) and their high efficacy against lung cancer cells. Conjugation of MTX with ZnONPs was authenticated by UV-vis spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). This drug-nanoconjugate also showed high drug-loading efficiency. The therapeutic efficacy of MTX-ZnONPs was further tested in vitro against A549 cells, and the results of MTT and LDH release assays showed that MTX-ZnONPs, in addition to free MTX, were efficient in exerting cytotoxic effect on A549 cells; however, the effectiveness of MTX-ZnONPs was found to be considerably enhanced at very low doses compared to that of free MTX. Moreover, ZnONPs alone significantly inhibited the cell viability of A549 cells at a much higher concentration compared to MTX-ZnONPs and MTX. Furthermore, the cytomorphology of A549 cells was characterized by cellular shrinkage and detachment from the surface in all the treatment groups. Similarly, A549 cells, in all the treatment groups, showed fragmented and condensed nuclei, indicating the initiation of apoptosis. Mitochondrial membrane potential (ψm) in A549 cells showed a gradual loss in all the treatment groups. Results of the qualitative and quantitative analyses depicted increased reactive oxygen species (ROS) levels in A549 cells. The results of the caspase activity assay showed that MTX-ZnONPs andfree MTX caused significant activation of caspase-9, -8, and -3 in A549 cells; however, the effect of MTX-ZnONPs was more profound at very low doses compared to that of free MTX. Thus, our results showed high efficacy of MTX-ZnONPs, suggesting efficient intracellular delivery of the drug by ZnONPs as nanocarriers.
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Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1',2'-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.
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In this study, we successfully synthesized selenium nanoparticles (P-SeNPs) using an environment-friendly approach. This method involves utilizing the aqueous peel extract of Benincasa hispida (ash gourd) in combination with selenium salt. Through our innovative procedure, we harnessed the impressive bio-reduction capabilities, therapeutic potential, and stabilizing attributes inherent in B. hispida. This results in the formation of P-SeNPs with distinct and noteworthy qualities. Our findings were thoroughly substantiated through comprehensive characterizations employing various techniques, including ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, and Fourier transform infrared spectroscopy (FTIR). The nanoparticles exhibited a spherical shape, considerable size (22.32 ± 2 nm), uniform distribution, and remarkable stability (-24 mV), all of which signify the effective integration of the phytoconstituents of B. hispida. Furthermore, P-SeNPs displayed robust antibacterial efficacy against pathogenic bacterial strains, as indicated by their low minimum inhibitory concentration values. Our research also revealed the remarkable ability of P-SeNPs to fight cancer, as demonstrated by their impressive IC50 value of 0.19 µg/mL against HeLa cells, while showing no harm to primary human osteoblasts, while simultaneously demonstrating no toxicity toward primary human osteoblasts. These pivotal findings underscore the transformative nature of P-SeNPs, which holds promise for targeted antibacterial treatment and advancements in cancer therapeutics. The implications of these nanoparticles extend to their potential applications in therapies, diagnostics, and various biomedical contexts. Notably, the environmentally sustainable synthesis process and exceptional properties established this study as a significant milestone in the field of nanomedicine, paving the way for a more promising and health-enhancing future.
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The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.
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Alternative and modified therapeutic approaches are key elements in culminating antibiotic resistance. To this end, an experimental trial was conducted to determine the cytotoxicity and antibacterial potential of composites of magnesium oxide (MgO) nanoparticles and antibiotics stabilized in sodium alginate gel against multi-drug-resistant Staphylococcus aureus isolated from a houbara bustard. The characterization of preparations was carried out using X-ray diffraction (XRD), scanning transmissible electron microscopy (STEM), and Fourier-transform infrared spectroscopy (FTIR). The preparations used in this trial consisted of gel-stabilized MgO nanoparticles (MG), gel-stabilized tylosin (GT), gel-stabilized ampicillin (GA), gel-stabilized cefoxitin (GC), gel-stabilized MgO and tylosin (GMT), gel-stabilized MgO and cefoxitin (GMC), and gel-stabilized MgO and ampicillin (GMA). The study presents composites that cause a lesser extent of damage to DNA while significantly enhancing mitotic indices/phases compared to the other single component preparations with respect to the positive control (methyl methanesulphonate). It was also noted that there was a non-significant difference (p > 0.05) between the concentrations of composites and the negative control in the toxicity trial. Studying in parallel trials showed an increased prevalence, potential risk factors, and antibiotic resistance in S. aureus. The composites in a well diffusion trial showed the highest percentage increase in the zone of inhibition in the case of GT (58.42%), followed by GMT (46.15%), GC (40.65%), GMC (40%), GMA (28.72%), and GA (21.75%) compared to the antibiotics alone. A broth microdilution assay showed the lowest minimum inhibitory concentration (MIC) in the case of GMA (9.766 ± 00 µg/mL), followed by that of GT (13.02 ± 5.64 µg/mL), GMC (19.53 ± 0.00 µg/mL), GA (26.04 ± 11.28 µg/mL), GMT (26.04 ± 11.28 µg/mL), MG (39.06 ± 0.00 µg/mL), and GC (39.06 ± 0.00 µg/mL). The study thus concludes the effective tackling of multiple-drug-resistant S. aureus with sodium-alginate-stabilized MgO nanoparticles and antibiotics, whereas toxicity proved to be negligible for these composites.
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Psidium guajava fruits are highly appreciated for their nutrients and bioactive compounds content, which contribute to their antioxidant and antimicrobial capacities. The purpose of this study was to determine bioactive compound (phenolic, flavonoids, and carotenoid contents), antioxidant activity (DPPH, ABTS, ORAC, and FRAP), and antibacterial potential against MDR and food-borne pathogenic strains of Escherichia coli, and Staphylococcus aureus during different stages of fruit ripening.The results elucidated that ripe fruits (methanolic extract) contain the highest total phenolic, flavonoids, and carotenoid contents (417.36 ± 2.63 µg GAE/gm of FW, 711.78 ± 0.70 µg QE/gm of FW and 0.683 ± 0.06 µg/gm of FW) followed by hexane, ethyl acetate, and aqueous. Methanolic extract of the ripe fruits showed the highest antioxidant activity when measured by DPPH (61.55 ± 0.91%), FRAP (31.83 ± 0.98 mM Fe(II)/gm of FW), ORAC (17.19 ± 0.47 mM TE/ gm of FW), and ABTS (41.31 ± 0.99 µmol Trolox/gm of FW) assays. In the antibacterial assay, the ripe stage had the highest antibacterial activity against MDR and food-borne pathogenic strains of Escherichia coli, and Staphylococcus aureus. The methanolic ripe extract was found to possess maximum antibacterial activity ZOI, MIC, and IC50 18.00 ± 1.00 mm, 95.95 ± 0.05%, and 0.58 µg/ml; 15.66 ± 0.57 mm, 94.66 ± 0.19%, and 0.50 µg/ml, respectively, against pathogenic and MDR strains of E. coli and 22.33 ± 0.57 mm, 98.97 ± 0.02%, and 0.26 µg/ml; 20.33 ± 1.15 mm, 96.82 ± 0.14%, and 0.39 µg/ml, respectively, against pathogenic and MDR strains of S. aureus. Considering the bioactive compounds and beneficial effects, these fruit extracts could be promising antibiotic alternatives, avoiding antibiotic overuse and its negative effects on human health and the environment, and can be recommended as a novel functional food.
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It is yet unknown what causes cardiovascular disease (CVD), but we do know that it is associated with a high risk of death, as well as severe morbidity and disability. There is an urgent need for AI-based technologies that are able to promptly and reliably predict the future outcomes of individuals who have cardiovascular disease. The Internet of Things (IoT) is serving as a driving force behind the development of CVD prediction. In order to analyse and make predictions based on the data that IoT devices receive, machine learning (ML) is used. Traditional machine learning algorithms are unable to take differences in the data into account and have a low level of accuracy in their model predictions. This research presents a collection of machine learning models that can be used to address this problem. These models take into account the data observation mechanisms and training procedures of a number of different algorithms. In order to verify the efficacy of our strategy, we combined the Heart Dataset with other classification models. The proposed method provides nearly 96 percent of accuracy result than other existing methods and the complete analysis over several metrics has been analysed and provided. Research in the field of deep learning will benefit from additional data from a large number of medical institutions, which may be used for the development of artificial neural network structures.
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The Wnt signaling pathway is reported to be associated with lung cancer progression, metastasis and drug resistance, and thus it is an important therapeutic target for lung cancer. Plants have been shown as reservoirs of multiple potential anticancer agents. In the present investigation, the ethanolic leaf extract of Artemisia vulgaris (AvL-EtOH) was initially analyzed by means of gas chromatography-mass spectrometry (GC-MS) to identify the important phytochemical constituents. The GC-MS analysis of AvL-EtOH exhibited 48 peaks of various secondary metabolites such as terpenoids, flavonoids, carbohydrates, coumarins, amino acids, steroids, proteins, phytosterols, and diterpenes. It was found that the treatment with increasing doses of AvL-EtOH suppressed the proliferation and migration of lung cancer cells. Furthermore, AvL-EtOH induced prominent nuclear alteration along with a reduction in mitochondrial membrane potential and increased ROS (reactive oxygen species) generation in lung cancer cells. Moreover, AvL-EtOH-treated cells exhibited increased apoptosis, demonstrated by the activation of caspase cascade. AvL-EtOH also induced downregulation of Wnt3 and ß-catenin expression along with cell cycle protein cyclin D1. Thus, the results of our study elucidated the potential of bioactive components of Artemisia vulgaris in the therapeutic management of lung cancer cells.
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The present research is focused on developing floating matrix tablets of mitiglinide to prolong its gastric residence time for better absorption. Gastroretentive tablets were prepared using a direct compression technique with hydroxypropyl methylcellulose K15M (HPMC K15M) and sodium alginate as matrix-forming polymers and sodium bicarbonate as the gas-forming agent. A 32 full factorial design was adopted to optimize the flotation and release profile of the drug. The concentration of HPMC K15M and sodium alginate were taken as the independent variables, and the floating lag time, time required for 50% drug release, and time required for 90% drug release were taken as dependent variables. The compatibility between drug and excipients was assessed by Fourier transform infrared (FTIR) spectroscopy. The prepared tablets were evaluated for different parameters such as hardness, friability, drug content, floating time, in vitro dissolution, and stability. Dissolution data were analyzed using various kinetic models to ascertain the mechanism of drug release. Finally, a radiographic study was conducted to estimate the retention time of the optimized floating matrix tablets of mitiglinide inside the body. The results revealed that all the physical properties of the developed formulations were within standard limits. The formulation M3, with the maximum amount of both independent variables, was considered to be the optimized formulation based on the desirability value. In addition, the optimized M3 formulation showed stability for over 6 months, as evidenced by insignificant changes in lag time, drug release pattern, and other physical properties. Furthermore, radiographic examination indicated that the tablets remained afloat in gastric fluid for up to 12 h in the rabbit's stomach. In conclusion, the developed floating matrix tablet of mitiglinide could be regarded as a promising formulation that could release the drug in the stomach at a controlled rate and, hence, offer better management of type II diabetes.
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In this particular research study, a unique three-dimensional mixing technique was used to incorporate multi-walled carbon nanotubes (MWCNTs) into polymethyl methacrylate (PMMA), and the KB cell line was used in the analysis of cytotoxicity, apoptosis detection, and cell viability using the MTT assay protocol. At low concentrations (0.001 to 0.1 g/mL), these results showed that the CNT did not seem to cause cell death or apoptosis directly. It increased lymphocyte-mediated cytotoxicity against KB cell lines. This was demonstrated by the fact that the CNT increased the time it took for KB cell lines to die. In the end, the unique three-dimensional mixing method solves problems such as clumping and uneven mixing that have been written about in the relevant literature. Phagocytic uptake of MWCNT-reinforced PMMA nanocomposite by KB cells leads to oxidative stress and apoptosis induction in a dose-dependent manner. The cytotoxicity of the generated composite and the ROS (reactive oxygen species) it produces may be controlled by adjusting the MWCNT loading. The conclusion that can be drawn from the studies to date is that it could be possible to treat some types of cancer using PMMA that has MWCNTs incorporated into it.
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Medicinal plants are an essential source of traditional curatives for numerous skin diseases. Polyalthia longifolia (Sonn.) Thwaites (Annonaceae family) is a medicinal plant used to cure skin illnesses. P. longifolia is usually applied in folkloric therapeutical systems to treat skin diseases. The methicillin-resistant Staphylococcus aureus (MRSA) bacteria is among the essential bacteria contributing to skin diseases. Hence, to verify the traditional medicinal claim of P. longifolia usage in skin disease treatment, the current research was performed to study the synergistic antibacterial activity of standardized Polyalthia longifolia methanol leaf extract (MEPL) against MRSA bacteria. The synergistic antimicrobial activity result of ceftriaxone, when mixed with MEPL, against MRSA was investigated by the disc diffusion method, broth microdilution method, checkerboard dilution test, and modulation of mecA gene expression by multiplex polymerase chain reaction (multiplex PCR). The MEPL extract exhibited good synergistic antimicrobial activity against MRSA. Using the checkerboard method, we confirmed the synergistic effect of MEPL from P. longifolia and ceftriaxone (2:1) for MRSA with a marked reduction of the MIC value of the ceftriaxone from 8000 µg/mL to 1000 µg/mL. Moreover, the combination of MEPL with ceftriaxone significantly (p < 0.05) inhibited the presence of the resistant mecA gene in the tested strain. The LC-ESI-MS/MS analysis identified compounds that were reported to exhibit antimicrobial activity. Conclusively, the MEPL extract, an important etiological agent for skin diseases, showed worthy synergistic antimicrobial action against MRSA bacteria, thus supporting the traditional use of P. longifolia.
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Though there are several advancements and developments in cancer therapy, the treatment remains challenging. In recent years, the antimicrobial peptides (AMPs) from traditional herbs are focused for identifying and developing potential anticancer molecules. In this study, AMPs are identified from Sphaeranthus amaranthoides, a natural medicinal herb widely used as a crucial immune stimulant in Indian medicine. A total of 86 peptide traces were identified using liquid-chromatography-electrospray-ionisation mass spectrometry (LC-ESI-MS). Among them, three peptides were sequenced using the manual de novo sequencing technique. The in-silico prediction revealed that SA923 is a cyclic peptide with C-N terminal interaction of the carbon atom of ASP7 with the nitrogen atom of GLU1 (1ELVFYRD7). Thus, SA923 is presented under the orbitides class of peptides, which lack the disulfide bonds for cyclization. In addition, SA923, steered with the physicochemical properties and support vector machine (SVM) algorithm mentioned for the segment, has the highest in silico anticancer potential. Further, the in vitro cytotoxicity assay revealed the peptide has anti-proliferative activity, and toxicity studies were demonstrated in Danio rerio (zebrafish) embryos.
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Despite the existence of modern antidiabetic medications, diabetes still affects millions of individuals worldwide, with a high death and disability rate. There has been a concerted search for alternative natural medicinal agents; luteolin (LUT), a polyphenolic molecule, might be a good choice, both because of its efficacy and because of it having fewer side effects, compared to conventional medicines. This study aims to explore the antidiabetic potential of LUT in diabetic rats, induced by streptozotocin (STZ; 50 mg/kg b.w.), intraperitoneally. The level of blood glucose, oral glucose tolerance test (OGTT), body weight, glycated hemoglobin A1c (HbA1c), lipidemic status, antioxidant enzymes, and cytokines were assessed. Also, its action mechanism was explored through molecular docking and molecular dynamics simulations. Oral supplementation of LUT for 21 days resulted in a significant decrease in the blood glucose, oxidative stress, and proinflammatory cytokine levels, and modulated the hyperlipidemia profile. LUT also ameliorated the tested biomarkers of liver and kidney function. In addition, LUT markedly reversed the damage to the pancreas, liver, and kidney cells. Moreover, molecular docking and molecular dynamics simulations revealed excellent antidiabetic behavior of LUT. In conclusion, the current investigation revealed that LUT possesses antidiabetic activity, through the reversing of hyperlipidemia, oxidative stress, and proinflammatory status in diabetic groups. Therefore, LUT might be a good remedy for the management or treatment of diabetes.
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Ilimaquinone (IQ), a metabolite found in marine sponges, has been reported to have a number of biological properties, including potential anticancer activity against colon cancer. However, no clear understanding of the precise mechanism involved is known. The aim of this study was to examine the molecular mechanism by which IQ acts on HCT-116 cells. The anticancer activity of IQ was investigated by means of a cell viability assay followed by the determination of induction of apoptosis by means of the use of acridine orange-ethidium bromide (AO/EB) staining, Annexin V/PI double staining, DNA fragmentation assays, and TUNEL assays. The mitochondrial membrane potential (ΔΨm) was detected using the JC-1 staining technique, and the apoptosis-associated proteins were analyzed using real-time qRT-PCR. A molecular docking study of IQ with apoptosis-associated proteins was also conducted in order to assess the interaction between IQ and them. Our results suggest that IQ significantly suppressed the viability of HCT-116 cells in a dose-dependent manner. Fluorescent microscopy, flow cytometry, DNA fragmentation and the TUNEL assay in treated cells demonstrated apoptotic death mode. As an additional confirmation of apoptosis, the increased level of caspase-3 and caspase-9 expression and the downregulation of Bcl-2 and mitochondrial dysfunction were observed in HCT-116 cells after treatment with IQ, which was accompanied by a decrease in mitochondrial membrane potential (ΔΨm). Overall, the results of our studies demonstrate that IQ could trigger mitochondria-mediated apoptosis as demonstrated by a decrease in ΔΨm, activation of caspase-9/-3, damage of DNA and a decrease in the proportion of Bcl-2 through the mitochondrial-mediated apoptosis pathway.