Modulating Effects of Zingiberaceae Phenolic Compounds on Neurotrophic Factors and Their Potential as Neuroprotectants in Brain Disorders and Age-Associated Neurodegenerative Disorders: A Review.

The Zingiberaceae family possess various phenolic compounds that have significant systemic bioactivities in the brain, including in age-related neurodegenerative diseases. Neurotrophins are growth factors that protect neurons from oxidative stress, and dysregulation of the neurotrophic system may result in neurocognitive disease. Phenolic compounds from the Zingiberaceae family have been used in traditional and complementary medicine (TCM) to improve cognitive functions. These compounds may affect the expression of neurotrophic agents, but their underlying molecular mechanisms require further investigation. Therefore, the goal of this review is to determine the expression and functional roles of phenolic compounds from the Zingiberaceae family in brain disorders and age-related neurodegenerative disorders. While previous studies have proposed various mechanisms for the neuroprotective activity of these compounds, their precise mechanism of action remains complex and poorly understood. Despite some promising findings, there are still shortcomings in the therapeutic use of these herbs, and current interventions involving the Zingiberaceae family appear to be clinically insufficient. This article aims to summarize recent discoveries of phenolic compounds from several Zingiberaceae family members and their use as neuroprotectants and provide the first review of evidence-linked neuroprotective activity of bioactive ingredients from prominent members of the Zingiberaceae family.

Inspecting Histamine Isolated from Fish through a Highly Selective Molecularly Imprinted Electrochemical Sensor Approach.

Numerous analytical approaches have been developed to determine histamine levels in food samples due to its health consequences. Consuming histamine over the Food and Drug Administration (FDA)-regulated 50 mg kg-1 limit would result in chronic toxicity. Consequently, the present study discusses a novel electrochemical approach to evaluate histamine levels in fish products via a molecularly imprinted polymer (MIP) on an electrode surface. The film was produced with electropolymerized polyurethane (PU), which maintained the histamine compound. Fourier-transform infrared (FTIR) spectroscopy was applied to verify the MIP manufactured in this study. The capability of the polymer was measured by assessing its electron shifts with cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Differential pulse voltammetry (DPV) was also employed to validate the sensing method. The MIP/screen-printed electrode (SPE) and non-imprinted polymer (NIP)/SPE recorded a linear response ranging from 1 to 1000 nmol L-1 at the 1.765 and 709 nmol L-1 detection limits. The sensing technique was subsequently utilized to determine the histamine levels in selected samples at room temperature (25 °C). Generally, the sensor allowed the accurate and precise detection of histamine in the fish samples. Furthermore, the approach could be categorized as a simple technique that is low-cost and suitable for on-site detections.

Polyurethane Application to Transform Screen-Printed Electrode for Rapid Identification of Histamine Isolated from Fish.

The toxicity of histamine has attracted numerous researchers to develop a method for histamine determination purposes. The Food and Drug Administration (FDA) unequivocally prohibits the consumption of histamine above 50 mg·kg-1. Thus, an innovation in histamine detection in fish has been developed in this research. The investigation of the histamine level in fish has been conducted by using an electrochemical sensor approach and producing a polymer via molecularly imprinted polymer (MIP) on a screen-printed electrode. The technique was validated by assessing the shifts in electron shifting using the cyclic voltammetry (CV) approach and electrochemical impedance spectroscopy (EIS), whereas differential pulse voltammetry (DPV) was applied to validate the sensor method. The instruments showed a linear response ranging from 1-1000 nmol·L-1, with a detection limit of MIP/SPE at 1.765 nmol·L-1 and 709 nmol·L-1 for the NIP/SPE, respectively. The sensing technique was employed to determine the histamine level in selected samples at room temperature (25°C). The outcomes of this study indicated that the validated chemical sensor allowed accurate and precise detection of fish samples and can be categorized as a simple approach. The instrument is inexpensive and suitable for on-site detection.

A subcritical water extract of soil grown Zingiber officinale Roscoe: Comparative analysis of antioxidant and anti-inflammatory effects and evaluation of bioactive metabolites.

Introduction: Ginger (Zingiber officinale Roscoe) can scavenge free radicals, which cause oxidative damage and inflamm-ageing. This study aimed to evaluate the antioxidant and anti-inflammatory effects of soil ginger's sub-critical water extracts (SWE) on different ages of Sprague Dawley (SD) rats. The antioxidant properties and yield of SWE of soil- and soilless-grown ginger (soil ginger and soilless ginger will be used throughout the passage) were compared and evaluated. Methods: Three (young), nine (adult), and twenty-one (old) months old SD rats were subjected to oral gavage treatments with either distilled water or the SWE of soil ginger at a concentration of 200 mg/kg body weight (BW) for three months. Results: Soil ginger was found to yield 46% more extract than soilless ginger. While [6]-shogaol was more prevalent in soilless ginger, and [6]-gingerol concentration was higher in soil ginger (p < 0.05). Interestingly, soil ginger exhibited higher antioxidant activities than soilless ginger by using 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay. With ginger treatment, a reduced levels of tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) but not interleukin-6 (IL-6) were observed in young rats. In all ages of SD rats, ginger treatment boosted catalase activity while lowering malondialdehyde (MDA). Reduction of urine 15-isoprostane F2t in young rats, creatine kinase-MM (CK-MM) in adult and old rats and lipid peroxidation (LPO) in young and adult rats were also observed. Discussion: The findings confirmed that the SWE of both soil and soilless grown ginger possessed antioxidant activities. Soil ginger produced a higher yield of extracts with a more prominent antioxidant activity. The SWE of soil ginger treatment on the different ages of SD rats ameliorates oxidative stress and inflammation responses. This could serve as the basis for developing a nutraceutical that can be used as a therapeutic intervention for ageing-related diseases.

Authentication of Marantodes pumilum (Blume) Kuntze: A Systematic Review.

Botanical drug products consist of complex phytochemical constituents that vary based on various factors that substantially produce different pharmacological activities and possible side effects. Marantodes pumilum (Blume) Kuntze (Primulaceae) is one of the most popular Malay traditional botanical drugs and widely recognized for its medicinal use. Many studies have been conducted focusing on the identification of bioactive substances, pharmacological and toxicological activities in its specific varieties but less comprehensive study on M. pumilum authentication. Lack of quality control (QC) measurement assessment may cause different quality issues on M. pumilum containing products like adulteration by pharmaceutical substances, substitution, contamination, misidentification with toxic plant species, which may be detrimental to consumers' health and safety. This systematic literature review aims to provide an overview of the current scenario on the quality control of botanical drug products as determined by pharmacopoeia requirements specifically for M. pumilum authentication or identification. A systematic search for peer-reviewed publications to document literature search for M. pumilum authentication was performed using four electronic databases: Web of Science, PubMed, Scopus and ScienceDirect for related studies from January 2010 to December 2021. The research studies published in English and related articles for identification or authentication of M. pumilum were the main inclusion criteria in this review. A total 122 articles were identified, whereby 33 articles met the inclusion criteria. Macroscopy, microscopy, chemical fingerprinting techniques using chromatography, spectroscopy and hyphenated techniques, and genetic-based fingerprinting using DNA barcoding method have been used to identify M. pumilum and to distinguish between different varieties and plant parts. The study concluded that a combination of approaches is necessary for authenticating botanical drug substances and products containing M. pumilum to assure the quality, safety, and efficacy of marketed botanical drug products, particularly those with therapeutic claims.

Surface-engineered liposomes for dual-drug delivery targeting strategy against methicillin-resistant Staphylococcus aureus (MRSA).

This study focused on the encapsulation of vancomycin (VAN) into liposomes coated with a red blood cell membrane with a targeting ligand, daptomycin-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, formed by conjugation of DAPT and N-hydroxysuccinimidyl-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine. This formulation is capable of providing controlled and targeted drug delivery to the bacterial cytoplasm. We performed MALDI-TOF, NMR and FTIR analyses to confirm the conjugation of the targeting ligand via the formation of amide bonds. Approximately 45% of VAN could be loaded into the aqueous cores, whereas 90% DAPT was detected using UV-vis spectrophotometry. In comparison to free drugs, the formulations controlled the release of drugs for > 72 h. Additionally, as demonstrated using CLSM and flow cytometry, the resulting formulation was capable of evading detection by macrophage cells. In comparison to free drugs, red blood cell membrane-DAPT-VAN liposomes, DAPT liposomes, and VAN liposomes reduced the MIC and significantly increased bacterial permeability, resulting in > 80% bacterial death within 4 h. Cytotoxicity tests were performed in vitro and in vivo on mammalian cells, in addition to hemolytic activity tests in human erythrocytes, wherein drugs loaded into the liposomes and RBCDVL exhibited low toxicity. Thus, the findings of this study provide insight about a dual antibiotic targeting strategy that utilizes liposomes and red blood cell membranes to deliver targeted drugs against MRSA.

Pharmacological activities and mechanisms of action of hypophyllanthin: A review.

Hypophyllanthin is a major lignan present in various Phyllanthus species and has been used as one of the bioactive chemical markers for quality control purposes as it contributes to their diverse pharmacological activities. The objective of this study is to compile up-to-date data on the pharmacological actions and mechanisms of hypophyllanthin. This review also includes the extracts of Phyllanthus species whose pharmacological actions have been partially attributed to hypophyllanthin. The scientific findings on the compound are critically analyzed and its potential as a lead molecule for the discovery of drug candidates for the development of therapeutics to treat diverse diseases is highlighted. Data collection was mainly through the exploration of Ovid-MEDLINE, Scopus, Science Direct, and Elsevier databases. Studies conducted in vitro and in vivo showed that hypophyllanthin had potent immunomodulating properties as well as a variety of other pharmacological properties, including anti-inflammatory, hepatoprotective, anti-tumor, anti-allergic, anti-hypertensive, and phytoestrogenic properties. Several mechanisms of action on the effects of hypophyllanthin on the immune system, in cancer and other disease states, were presented to provide some insights into its pharmacological effects. Before being submitted to clinical investigations, additional animal studies utilising different animal models are necessary to analyse its bioavailability, pharmacokinetics, and pharmacodynamic properties, as well as its toxicity, to determine its efficacy and safety. Understanding its potential as a lead molecule for the discovery of therapeutic candidates, particularly for the development of therapies for inflammatory and immune-related disorders, requires an understanding of its pharmacological activities and mechanisms of action. An insight into its pharmacological activities and mechanisms of action will provide an understanding of its potential as a lead compound for the discovery of drug candidates, especially for the development of therapies for inflammatory and immune related diseases.

Anti-Allergic Rhinitis Effects of Medicinal Plants and Their Bioactive Metabolites via Suppression of the Immune System: A Mechanistic Review.

Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa and it is an immunoglobulin E-mediated disease. The incidence and prevalence of AR globally have been escalating over recent years. Antihistamines, intranasal corticosteroids, decongestants, intranasal anticholinergics, intranasal cromolyn, leukotriene receptor antagonists and immunotherapy have been used in the treatment of AR. However, there is a need to search for more effective and safer remedies as many of the current treatments have reported side effects. Medicinal plants have been used traditionally to relief symptoms of AR but their efficacy and safety have not been scientifically proven. In this review, up-to-date reports of studies on the anti-allergic rhinitis of several medicinal plants and their bioactive metabolites through suppression of the immune system are compiled and critically analyzed. The plant samples were reported to suppress the productions of immunoglobulin E, cytokines and eosinophils and inhibit histamine release. The suppression of cytokines production was found to be the main mechanistic effect of the plants to give symptomatic relief. The prospect of these medicinal plants as sources of lead molecules for development of therapeutic agents to treat AR is highlighted. Several bioactive metabolites of the plants including shikonin, okicamelliaside, warifteine, methylwarifteine, luteolin-7-O-rutinoside, tussilagone, petasin, and mangiferin have been identified as potential candidates for development into anti-allergic rhinitis agents. The data collection was mainly from English language articles published in journals, or studies from EBSCOHOST, Medline and Ovid, Scopus, Springer, and Google Scholar databases from the year 1985-2020. The terms or keywords used to find relevant studies were allergic rhinitis OR pollinosis OR hay fever, AND medicinal plant OR single plant OR single herb OR phytotherapy. This comprehensive review serves as a useful resource for medicinal plants with anti-allergic rhinitis potential, understanding the underlying mechanisms of action and for future exploration to find natural product candidates in the development of novel anti-allergic rhinitis agents.

Rapid Discrimination of Halal and Non-halal Pharmaceutical Excipients by Fourier Transform Infrared Spectroscopy and Chemometrics.

INTRODUCTION: The appendage of "halal" to a product is not just a guarantee that the product is permitted for Muslims, but it has also become favorable lifestyle choice globally. However, the expansion of halal pharmaceutical market was hindered by lack of global halal standards for pharmaceutical ingredients and product integrity analytical methodology. OBJECTIVE: This work aimed to explore the possibility of using Fourier-transform infrared (FTIR) spectroscopy and chemometrics to develop multivariate models to authenticate the "halal-ity" of pharmaceutical excipients with controversial halal status (e.g., magnesium stearate). MATERIALS AND METHODS: The FTIR spectral fingerprints of the substance were used to build principal component analysis (PCA) models. The effects of different spectral pretreatment processes such as auto-scaling, baseline correction, standard normal variate (SNV), first, and second derivatives were evaluated. The optimization of the model performance was established to ensure the sensitivity, specificity, and accuracy of the predicted models. RESULTS: Significant peaks corresponding to the properties of the compound were identified. For both bovine and plant-derived magnesium stearate, the peaks associated can be seen within the regions 2900cm-1 (C-H), 2800cm-1 (CH3), 1700cm-1 (C=O), and 1000-1300cm-1 (C-O). There was not much difference observed in the FTIR raw spectra of the samples from both sources. The quality and accuracy of the classification models by PCA and soft independent modeling classification analogy (SIMCA) have shown to improve using spectra optimized by first derivative followed by SNV smoothing. CONCLUSION: This rapid and cost-effective technique has the potential to be expanded as an authentication strategy for halal pharmaceuticals.

Rapid detection of sildenafil analogue in Eurycoma longifolia products using a new two-tier procedure of the near infrared (NIR) spectra database.

A simple and cost-effective two-tier drug screening procedure comprises a 'dedicated' NIR spectral database of common medicines and a 'unified' database was developed to detect the sildenafil analogue in Eurycoma longifolia products. Diffuse reflectance spectra of ten commercial herbal products containing E. longifolia were obtained over the wavelength range of 1100-2500 nm. The spectral search of two products purchased via the internet against a dedicated database of reputable E. longifolia products have resulted in the similarity index of more than 0.1 which indicated significantly different spectra. Further searches against the unified database showed a close match to the spectra of drug containing sildenafil citrate suggesting the presence of a sildenafil analogue. This finding was supported by clustering of these spectra in the PCA score plot within 5% significance level. This approach has alleviated the use of reference product or standard active for direct comparison and has a potential to be used for adulterated food and drugs detection.

A phytochemical comparison of saw palmetto products using gas chromatography and (1) H nuclear magnetic resonance spectroscopy metabolomic profiling.

OBJECTIVES: Preparations containing saw palmetto berries are used in the treatment of benign prostatic hyperplasia (BPH). There are many products on the market, and relatively little is known about their chemical variability and specifically the composition and quality of different saw palmetto products notwithstanding that in 2000, an international consultation paper from the major urological associations from the five continents on treatments for BPH demanded further research on this topic. Here, we compare two analytical approaches and characterise 57 different saw palmetto products. METHODS: An established method - gas chromatography - was used for the quantification of nine fatty acids, while a novel approach of metabolomic profiling using (1) H nuclear magnetic resonance (NMR) spectroscopy was used as a fingerprinting tool to assess the overall composition of the extracts. KEY FINDINGS: The phytochemical analysis determining the fatty acids showed a high level of heterogeneity of the different products in the total amount and of nine single fatty acids. A robust and reproducible (1) H NMR spectroscopy method was established, and the results showed that it was possible to statistically differentiate between saw palmetto products that had been extracted under different conditions but not between products that used a similar extraction method. Principal component analysis was able to determine those products that had significantly different metabolites. CONCLUSIONS: The metabolomic approach developed offers novel opportunities for quality control along the value chain of saw palmetto and needs to be followed further, as with this method, the complexity of a herbal extract can be better assessed than with the analysis of a single group of constituents.

Near-infrared spectroscopy (NIRS) and chemometric analysis of Malaysian and UK paracetamol tablets: a spectral database study.

The influx of medicines from different sources into healthcare systems of developing countries presents a challenge to monitor their origin and quality. The absence of a repository of reference samples or spectra prevents the analysis of tablets by direct comparison. A set of paracetamol tablets purchased in Malaysian pharmacies were compared to a similar set of sample purchased in the UK using near-infrared spectroscopy (NIRS). Additional samples of products containing ibuprofen or paracetamol in combination with other actives were added to the study as negative controls. NIR spectra of the samples were acquired and compared by using multivariate modeling and classification algorithms (PCA/SIMCA) and stored in a spectral database. All analysed paracetamol samples contained the purported active ingredient with only 1 out of 20 batches excluded from the 95% confidence interval, while the negative controls were clearly classified as outliers of the set. Although the substandard products were not detected in the purchased sample set, our results indicated variability in the quality of the Malaysian tablets. A database of spectra was created and search methods were evaluated for correct identification of tablets. The approach presented here can be further developed as a method for identifying substandard pharmaceutical products.