Future Journal of Pharmaceutical Sciences最新文献

Background

Traditional medicine claims that Anodendron parviflorum has benefits for treating various human diseases. The present study seeks to understand better the phytochemical and LC–MS/MS-QTOF profiling of A. parviflorum's ethanolic extract and to investigate the properties of the different solvents of A. parviflorum for anti-inflammatory, antioxidant, antimicrobial, toxicity, and cytotoxic effects.

Results

The quantitative methods exhibited higher total phenolics (327.16 ± 2.4 mg GAE/g dw), total flavonoid (109.82 ± 1.9 mg QE/g dw), and total alkaloid (14.13 ± 0.09%) content in ethanol extract. In contrast, a higher total extraction value (22.8 ± 0.6%) and total terpenoid (57.23 ± 0.06 mg LL/g dw) content was shown in the methanol extract of A. parviflorum. LC–MS/MS-QTOF analysis of its ethanolic extract revealed a notable occurrence of phenols and flavonoids. The ethanolic extract of A. parviflorum exhibited significant antioxidant activities with lower IC₅₀ values in DPPH, phosphomolybdenum, and metal chelating and reducing power assay. The methanolic extract of A. parviflorum had the more significant anti-inflammatory property (94.55 ± 0.1%) in the bovine serum albumin assay. The extracts also demonstrated a higher inhibition zone against pathogenic bacteria. The ethanolic extract of A. parviflorum demonstrated substantial cytotoxicity against A549 cells.

Conclusion

Consequently, these findings validate the use of A. parviflorum in traditional medical practices due to its bioactive compounds, which may have potential therapeutic value in various biomedical applications.

Highlights

• A. parviflorum leaves extract showed the presence of significant levels of alkaloids, flavonoids, phenols, and terpenoids.

• LC–MS/MS-QTOF analysis revealed notable bioactive compounds of A. parviflorum.

• The different extracts showed remarkable antioxidant and antimicrobial activities.

• The extracts exhibited less hemolytic and higher thrombolytic activities.

• It demonstrated significant cytotoxicity against A549 cell lines.

Graphical abstract

Background

Emerging evidence links vitamin D deficiency to oxidative stress (OS) and inflammation, posing ongoing risks to cardiovascular outcomes in hemodialysis (HD) patients. Despite this, current data are lacking regarding the optimal approach or schedule for administering vitamin D in this population. This study investigated the effectiveness of oral weekly versus oral monthly cholecalciferol supplementation on 25-hydroxy vitamin D (25(OH)D) levels, oxidative stress, inflammatory indicators, and secondary hyperparathyroidism in HD population. HD patients (N = 50) were randomly allocated to Group A (oral weekly 50,000 IU cholecalciferol) or Group B (oral monthly 200,000 IU cholecalciferol) for a 3 months duration. Serum levels of 25(OH)D, malondialdehyde (MDA), superoxide dismutase (SOD), high sensitivity C-reactive protein (HsCRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and intact parathyroid hormone (iPTH) were assessed at baseline and upon completion of the study.

Results

A notable increase in serum 25(OH)D levels observed in both groups, with Group A showing a notably greater increase (p = 0.003). Group A demonstrated significant reductions in serum MDA and increases in SOD, along with declines in hsCRP and NLR levels, which were not observed in Group B. Moreover, Group A exhibited a greater drop in iPTH (ΔiPTH = − 30 pg/mL vs. − 3 pg/mL) compared to Group B. Clinicaltrial.gov: NCT05460338, registered 13/07/2022.

Conclusions

Weekly oral 50,000 IU cholecalciferol supplementation emerges as a tolerable, safe and effective approach for restoring vitamin D levels in HD patients, while concurrently mitigating inflammation, OS, and secondary hyperparathyroidism. This finding suggests that the more frequent the administration of oral cholecalciferol, the higher the efficiency observed.

Background

Since December 2019, a global crisis has unfolded with the emergence of a new strain of coronavirus known as SARS-CoV-2. This pandemic has afflicted hundreds of millions of people worldwide, resulting in millions of fatalities. In response to this urgent healthcare crisis, extensive efforts have been made to discover inhibitors of the COVID-19 virus. Given the structural similarities between SARS-CoV-2 and HCV, drugs approved by the FDA for treating HCV were selected and subjected to in silico testing against the SARS-CoV-2 virus, with Remdesivir used as the standard for validation. Drug repurposing and phytochemical testing have also been conducted to identify potential candidates capable of inhibiting or suppressing the infection caused by the coronavirus. The time constraints imposed by the pandemic necessitated the in silico analysis of existing drug molecules against the coronavirus. Eleven HCV drugs approved by the FDA, along with one RNA synthesis inhibitor antibiotic drug, were tested using the in silico method due to their structural similarities with HCV and the SARS-CoV-2 virus.

Results

Molecular docking and MD simulation studies were performed for all selected compounds. Binding energies, root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and molecular mechanics generalized born surface area were calculated. Based on docking and MD simulation studies all the selected compounds have shown good binding energy values with Mpro (PDB ID: 6LU7). No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA.

Conclusions

This study shows that FDA-approved HCV drugs can be used as for SARS-COVID-19 inhibitors.

Background

Sea buckthorn (Hippophae rhamnoides), a deciduous species plant, is widely distributed around the globe, and native to the cold-temperate regions of Europe and Asia. This medicinal herb contains several bioactive constituents including chlorogenic acid. The conventional methods used for the extraction of phenolic antioxidants from natural herbs often result in low yields, high toxicity, and pose environmental hazards limiting their effectiveness and scalability. Therefore, green extraction techniques using deep eutectic solvents, composed of natural, non-toxic, and biodegradable components were applied for extraction of chlorogenic acid from sea buckthorn weed. Fourteen deep eutectic solvent mixtures were prepared and evaluated for extraction yield of chlorogenic acid. Parameters such as hydrogen bond donor-to-hydrogen bond acceptor ratio, liquid-to-solid ratio, shaking speed, and shaking time were optimized for the best mixture.

Results

The combination of lactic acid and maltose (1:1) was found to give best extraction yield using response surface methodology. The deep eutectic solvent system under optimum conditions produced 12.2 g/100 g of crude extract sea buckthorn containing 174.7 mg gallic acid equivalents (mg GA)/g) of extract. Moreover, the optimized extract exhibited appreciable radical scavenging capacity (91%), trolox equivalent antioxidant capacity (11.2% of extract), and inhibition of peroxide in linoleic acid (80.6%). High-performance liquid chromatography-based characterization revealed the extracts contained chlorogenic acid (20.1 mg/g of extract) as the major constituent.

Conclusions

In summary, the adoption of DES for the extraction of bioactive phenolic constituents from sea buckthorn offers multiple benefits, including economic efficiency, enhanced extraction performance, and environmental sustainability. The findings of this study not only advance the understanding of DES in phytochemical extraction but also pave the way for broader application of green solvents in the natural products industry. Future research should focus on further optimizing DES formulations and scaling up the extraction process to fully realize the potential of this innovative extraction method in commercial applications.

Background

Bala is an important Ayurvedic drug used for the treatment of many diseases. Sida cordifolia (L.), Malvaceae family, is the genuine source drug of Bala as per Ayurvedic Pharmacopeia of India. The other species of Sida like Sida acuta, Sida rhombifolia, Sida alnifolia and Sida cordata are also used as adulterants or substitutes of Bala. The objective of the present study is to identify a scientifically validated substitute for Bala (Sida cordifolia) by detailed phytochemical evaluation of its allied species.

Results

Preliminary analysis showed that all the selected species contain similar class of compounds like alkaloids, phenolics, flavonoids, etc. Quantitative estimation of major class of compounds such as total alkaloids, total phenolics and total flavonoids was done by spectrophotometric methods. Polyphenolic contents of selected species are almost comparable. In the case of alkaloids, variations have been observed among the species. Chemical profiles of selected species were compared by HPTLC and HPLC analysis. Major chemical constituents are found to be common for the selected species. HPLC profiles also showed similarity in their peak pattern.

Conclusion

Based on the phytochemical studies, the species like S. alnifolia, S. acuta and S. rhombifolia contain almost similar types of phytochemicals. However, the chemical constituents of Sida cordata are found to be different from other allied species. Further studies including pharmacological evaluation are required to ensure the therapeutic properties of allied species to confirm the substitute.

Background

Carbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited.

Results

In this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs.

To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively.

Conclusion

This research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy.

Graphical abstract

Background

Bacterial ghost cells (BGCs) are cell envelopes that devoid of cytoplasmic and genetic contents in purpose of variable applications, including their great potential as vaccine candidates and their effectiveness as delivery systems for drugs and proteins. To our knowledge, this is the first study to produce Gram-positive BGCs by treating Streptococcus pyogenes (S. pyogenes) ATCC 19615 with Tween80 (TW80) or TritonX-100 (TX100), followed by preliminary testing of their antigenicity and safety in NIH/Ola-Hsd mice. The produced BGCs were confirmed by the presence of intact cells under a light microscope, the absence of growth signs upon re-cultivation. The transmembrane tunnels were visualized using a scanning electron microscope, and subsequently, considerable quantities of released DNA and protein were detected in the culture supernatant of the BGCs. The antigenicity of the produced BGCs was tested through three intra-nasal immunization doses followed by infection. Afterward, the opsonic activity and the IgG levels were measured, followed by a comprehensive histopathological examination for selected tissues and organs.

Results

The sera of immunized mice exhibited a significant rise in both opsonic activity (TW80 produced BGC = 68% and TX100 produced BGC = 75%) and IgG levels (TW80 produced BGC = a threefold increase and TX100 produced BGC = a fourfold increase) when compared to the positive control group "non-immunized challenged with ATCC 19615." Histopathological analysis revealed that the BGCs produced by TW80 are relatively safer and have a less severe impact than those produced by TX100.

Conclusion

The study's findings suggest that Sp-BGC/TW80 is initially effective and safe in vivo. However, further pre-clinical studies are necessary to confirm its effectiveness and ensure complete safety, specifically in terms of the absence of autoimmunity and antibody cross-reactivity with myosin proteins in human cardiac tissues.

Background

Nyctanthes arbor-tristis Linn. is a small, sacred ornamental tree used in prayer. It is renowned throughout India for its aromatic white blossoms. The entire plant was widely used for several health applications particularly root and bark were used to treat fever and cough, respectively. Also, the leaf was used for managing fever and diabetes, and its cholagogue, diaphoretic, and anthelmintic properties.

Main text

The current review aimed to comprehensively analyze the botanical characteristics, phytochemistry, and pharmacology of N. arbor-tristis essential oil (NAEO) and extracts. Additionally, it wants to emphasize the latest advancements in phytochemistry and pharmacology related to this aromatic plant. Depending on the variety, origin, and plant parts used, the NAEO yield ranged from 0.002 to 0.10% on a dry basis. The NAEO has been investigated in only a few research studies and resulted, in the predominant levels of phytol and methyl palmitate chemical compounds. Furthermore, the NAEO was found to have significant volatile chemical constituents, including geranylgeraniol, phytoene, nonadecane, linalool, and various other miscellaneous chemical components. The plant extracts and NAEO have numerous biological properties, including antioxidant, antimicrobial, anticancer, anti-inflammatory, analgesic, larvicidal, and other miscellaneous activities.

Conclusion

This paper analyzes and summarizes the diverse research potential associated with N. arbor-tristis. The results of the present study suggested that most of the biological and pharmacological investigations were carried out without including dosage, positive controls, and negative controls. Furthermore, several pharmacological investigations were exclusively carried out using cell lines and animal models. Hence, the following research endeavors aimed at assessing the medicinal properties of NAEO and extracts in human subjects would broaden the scope of its utilization.

Graphical abstract

Background

Echinometra mathaei (family Echinometridae), is one of the sea urchins widely distributed on the Egyptian coasts in the Red Sea. This organism contains edible and non-edible parts. The present study was carried out to analyze and identify the metabolites present in the non-edible parts (Aristotle's lantern and viscera) using LC/MS. Also, the cytotoxic activity on Vero cell line and antiviral activity against herpes simplex virus type 1 were evaluated using MTT colorimetric assay.

Results

Chemical profiling of the crude extracts of Aristotle's lantern and viscera using LC/MS indicated the presence of 51 and 59 compounds, respectively. The main metabolites present in both non-edible parts were phospholipids, amino acids, peptides, fatty acids and glycerol derivatives. However, the characteristic difference was the presence of carotenoid pigments only in viscera. The crude extract of Aristotle's lantern and viscera showed no cytotoxic activity on Vero cell line and significant antiviral activity against herpes simplex virus with an IC₅₀ value equal to 115.48 ± 1.20 and 122.4 ± 0.50 µg/mL, respectively.

Conclusions

In the present study, the crude extracts of the non-edible parts of E. mathaei were analyzed using LC.MS.MS.QTOF and indicated the existence of 110 chemical compounds, with significant antiviral activity against HSV-1 and no cytotoxic activity. The diversity of the identified compounds with two main categories of compounds, phospholipids and peptides, may contribute to the antiviral activity of Aristotle's lantern and viscera. Additionally, this research focused on clarification of nutritive, pharmaceutical and economic values of these parts. As future prospects, further studies are required to isolate the metabolites and assess the detailed mechanism of antiviral activity via in vitro, in vivo and in silico studies.

Background

Neurodegenerative disorders (NDs), primarily affecting the elderly, are marked by complex pathophysiological processes and are projected to become the second leading cause of death. Parkinson’s disease (PD), one of the most common NDs, is characterized by motor impairments due to reduced dopamine levels in the substantia nigra (SN), a crucial midbrain region involved in motor control and reward mechanisms. PD also impacts cognitive functions, potentially leading to depression and sleep disturbances. Recent research highlights the importance of MAO-B inhibitors in PD management, as these enzymes play a critical role in regulating neurotransmitter levels by catalyzing the oxidative deamination of intracellular amines and monoamine neurotransmitters.

Result

Computational virtual screening of several quinoline-based ligands against the target protein MAO-B (PDB ID: 1OJA) was performed using molecular docking simulation and ADMET studies to identify promising inhibitors for neurodegenerative disease treatment. The most active hit, Compound PA001, exhibited a MolDock score of − 207.76 kcal/mol. Subsequent investigation of 6-methoxy-2-(4-phenylpiperazin-1-yl)quinoline (Compound PA001) using molecular dynamics (MD) simulations with GROMACS revealed potent inhibition and significant interactions at key active site residues. MD simulations confirmed the stability of the Compound PA001-MAO-B complex under physiological conditions. Additionally, ADMET analysis demonstrated that Compound PA001 possesses favorable drug-like properties, including absorption, distribution, metabolism, excretion, and toxicity profiles. These findings underscore 6-methoxy-2-(4-phenylpiperazin-1-yl)quinoline (Compound PA001) as a promising candidate for developing new MAO-B inhibitors to treat neurodegenerative diseases.

Conclusion

The research highlighted 6-methoxy-2-(4-phenylpiperazin-1-yl)quinoline (Compound PA001) as a promising MAO-B inhibitor, exhibiting strong binding affinity, stability, and desirable drug-like characteristics for the treatment of neurodegenerative diseases. Among the top ten molecules, Compound PA001 was selected for molecular dynamics (MD) simulation using GROMACS. The compound showed potent inhibition, significant interactions with key active site residues, and stable complex formation under physiological conditions. ADMET analysis further confirmed its favorable pharmacokinetic profile.