Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM.

With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one of the most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug-disease pair discovery without relying on drug- or disease-specific prior knowledge, which has been widely used in modern medicine. However, profile-based systematic screening of active ingredients of traditional Chinese medicine (TCM) has been scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop the largest-to-date online TCM active ingredients-based pharmacotranscriptomic platform integrated traditional Chinese medicine (ITCM) for the effective screening of active ingredients. First, we performed unified high-throughput experiments and constructed the largest data repository of 496 representative active ingredients, which was five times larger than the previous one built by our team. The transcriptome-based multi-scale analysis was also performed to elucidate their mechanism. Then, we developed six state-of-art signature search methods to screen active ingredients and determine the optimal signature size for all methods. Moreover, we integrated them into a screening strategy, TCM-Query, to identify the potential active ingredients for the special disease. In addition, we also comprehensively collected the TCM-related resource by literature mining. Finally, we applied ITCM to an active ingredient bavachinin, and two diseases, including prostate cancer and COVID-19, to demonstrate the power of drug discovery. ITCM was aimed to comprehensively explore the active ingredients of TCM and boost studies of pharmacological action and drug discovery. ITCM is available at http://itcm.biotcm.net.

Biological activities of drug inactive ingredients.

In a drug formulation (DFM), the major components by mass are not Active Pharmaceutical Ingredient (API) but rather Drug Inactive Ingredients (DIGs). DIGs can reach much higher concentrations than that achieved by API, which raises great concerns about their clinical toxicities. Therefore, the biological activities of DIG on physiologically relevant target are widely demanded by both clinical investigation and pharmaceutical industry. However, such activity data are not available in any existing pharmaceutical knowledge base, and their potentials in predicting the DIG-target interaction have not been evaluated yet. In this study, the comprehensive assessment and analysis on the biological activities of DIGs were therefore conducted. First, the largest number of DIGs and DFMs were systematically curated and confirmed based on all drugs approved by US Food and Drug Administration. Second, comprehensive activities for both DIGs and DFMs were provided for the first time to pharmaceutical community. Third, the biological targets of each DIG and formulation were fully referenced to available databases that described their pharmaceutical/biological characteristics. Finally, a variety of popular artificial intelligence techniques were used to assess the predictive potential of DIGs' activity data, which was the first evaluation on the possibility to predict DIG's activity. As the activities of DIGs are critical for current pharmaceutical studies, this work is expected to have significant implications for the future practice of drug discovery and precision medicine.

Determination of an Anti-Parasitic Active Pharmaceutical Ingredient in Wastewater Effluents Using Capillary Zone Electrophoresis.

Ireland has a successful pharmaceutical industry with over 100 pharmaceutical manufacturing sites across the island. Although this success has many benefits, the irreversible effects emissions from pharmaceutical manufacturing can have on the environment are a major drawback. Although known pollutants are regularly monitored with limits set out by the Environmental Protection Agency, one significant pollutant has been overlooked: pharmaceutical pollution. Detecting these pollutants and ensuring they are at a safe concentration for the environment is of utmost importance. In recent years, capillary electrophoresis is being recognised as a suitable alternative to high-performance liquid chromatography due to its many benefits such as faster analysis, water-based buffers and smaller sample volumes. In this paper, a capillary zone electrophoresis (CZE) method with a preconcentration step of solid-phase extraction was developed for an anti-parasitic active pharmaceutical ingredient (API) called ZB23. The API was successfully detected in a wastewater sample in less than 10 min using the CZE parameters of 25 mM borate buffer with a pH of 10.5, 15% MeOH, 10 kV voltage, 25 mbar for 5 s injection size, an Lt of 40 cm, an Ld of 31.5 cm and a detection wavelength of 214 nm.

Protein Ingredient Quality within Infant Formulas Impacts Plasma Amino Acid Concentrations in Neonatal Minipiglets.

BACKGROUND: Infant formulas (IFs), the only adequate substitute to human milk, are complex matrices that require numerous ingredients and processing steps that may impact protein digestion and subsequent amino acid (AA) absorption. OBJECTIVES: The objective was to understand the impact of the protein ingredient quality within IFs on postprandial plasma AA profiles. METHODS: Four isonitrogenous and isocaloric IFs were produced at a semi-industrial scale using whey proteins from different origins (cheese compared with ideal whey) and denaturation levels (IF-A, -B, -C), and caseins with different supramolecular organizations (IF-C, -D). Ten Yucatan minipiglets (12- to 27-d-old) were used as a human infant model and received each IF for 3 d according to a Williams Latin square followed by a 2-d wash-out period. Jugular plasma was regularly sampled from 10 min preprandial to 4 h postprandial on the third day to measure free AAs, urea, insulin, and glucose concentrations. Data were statistically analyzed using a mixed linear model with diet (IFs), time, and sex as fixed factors and piglet as random factor. RESULTS: IFs made with cheese whey (IF-A and -B) elicited significantly higher plasma total and essential AA concentrations than IFs made with ideal whey (IF-C and -D), regardless of the pre- and postprandial times. Most of the differences observed postprandially were explained by AA homeostasis modifications. IFs based on cheese whey induced an increased plasma concentration of Thr due to both a higher Thr content in these IFs and a Thr-limiting degrading capability in piglets. The use of a nonmicellar casein ingredient led to reduced plasma content of AA catabolism markers (IF-D compared with IF-C). CONCLUSIONS: Overall, our results highlight the importance of the protein ingredient quality (composition and structure) within IFs on neonatal plasma AA profiles, which may further impact infant protein metabolism.

A systematic review of herbicide safener toxicity.

Herbicide safeners are agrochemicals added to herbicide formulations to protect crops from herbicide damage without reducing the effectiveness of the herbicide against weeds. While safeners are typically structurally similar to their co-formulated herbicides, they are classified as "inert" in the United States, meaning they are not held to the same regulatory standards as the herbicides. This review systematically examines the toxicity of safeners, which is important given their large-scale global use and potential for exposure to wildlife, livestock, and humans. A systematic review of peer-reviewed literature identified only seven studies examining safener toxicity. Regulatory toxicity data, compiled from the European Chemicals Agency (ECHA) database, included data for 9 of the 18 commercial safeners. Most safeners have low acute ecotoxicity and mammalian toxicity; however, chronic effects and the underlying mechanism are less clear. Benoxacor showed enantioselective metabolism and depletion by drug-metabolizing enzymes. In conclusion, despite the widespread use of safeners, significant knowledge gaps exist regarding their toxicity. More research is needed to fully characterize the potential risks of safeners to human health and the environment. Regulatory agencies should consider reclassifying safeners as active ingredients to ensure adequate toxicity testing and risk assessment.

Antilisterial and antioxidant exopolysaccharide from Enterococcus faecium PCH.25 isolated from cow butter: characterization and probiotic potential.

Exopolysaccharides produced by lactic acid bacteria have gained attention for their potential health benefits and applications in functional foods. This study explores the isolation and characterization of a novel exopolysaccharide-producing strain from dairy products. The aim was to evaluate its probiotic potential and investigate the properties of the produced exopolysaccharide. A strain identified as Enterococcus faecium PCH.25, isolated from cow butter, demonstrated exopolysaccharide production. The study's novelty lies in the comprehensive characterization of this strain and its exopolysaccharide, revealing unique properties with potential applications in food, cosmetic, and pharmaceutical industries. The E. faecium PCH.25 strain exhibited strong acid tolerance, with a 92.24% viability rate at pH 2 after 2 h of incubation. It also demonstrated notable auto-aggregation (85.27% after 24 h) and co-aggregation abilities, antibiotic sensitivity, and absence of hemolytic activity, suggesting its probiotic potential. The exopolysaccharide produced by this strain showed bactericidal activity (MIC and MBC = 1.8 mg/ml) against Listeria monocytogenes and antioxidant properties (22.8%). Chemical analysis revealed a heteropolysaccharide composed of glucose and fructose monomers, with various functional groups contributing to its bioactivities. Physical characterization of the exopolysaccharide indicated thermal stability up to 270 °C, a negative zeta-potential (-27 mV), and an average particle size of 235 nm. Scanning electron microscopy and energy dispersive X-ray analysis revealed a smooth, nonporous structure primarily composed of carbon and oxygen, with an amorphous nature. These findings suggest that the exopolysaccharide from E. faecium PCH.25 has potential as a natural antibacterial and antioxidant polymer for use in functional foods, cosmetics, and pharmaceuticals.

Physical and insecticidal durability of Interceptor®, Interceptor® G2, and PermaNet® 3.0 insecticide-treated nets in Burkina Faso: results of durability monitoring in three sites from 2019 to 2022.

BACKGROUND: National Malaria Programmes (NMPs) monitor the durability of insecticide-treated nets (ITNs) to inform procurement and replacement decisions. This is crucial for new dual active ingredients (AI) ITNs, for which less data is available. Pyrethroid-only ITN (Interceptor®) and dual AI (Interceptor® G2, and PermaNet® 3.0) ITNs were assessed across three health districts over 36 months in southern Burkina Faso to estimate median ITN survival, insecticidal efficacy, and to identify factors contributing to field ITN longevity. METHODS: Durability was monitored through a prospective study of a cohort of nets distributed during the 2019 mass campaign. Three health districts were selected for their similar pyrethroid-resistance, environmental, epidemiological, and population profiles. Households were recruited after the mass campaign, with annual household questionnaire follow-ups over three years. Each round, ITNs were withdrawn for bioassays and chemical residue testing. Key measures were the percentage of cohort ITNs in serviceable condition, insecticidal effectiveness, and chemical residue content against target dose. Cox proportional hazard models were used to identify determinants influencing ITN survival. RESULTS: At endline, the median useful life was 3.2 (95% CI 2.5-4.0) years for PermaNet® 3.0 ITNs in Orodara, 2.6 (95% CI 1.9-3.2) years for Interceptor® G2 ITNs in Banfora and 2.4 (95% CI 1.9-2.9) years for Interceptor® ITNs in Gaoua. Factors associated with ITN survival included cohort ITNs from Orodara (adjusted hazard ratio (aHR) = 0.58, p = 0.026), households seeing less rodents (aHR = 0.66, p = 0.005), female-headed households (aHR = 0.66, p = 0.044), exposure to social behavior change (SBC) messages (aHR = 0.52, ≤ 0.001) and folding nets when not in use (aHR = 0.47, p < 0.001). At endline, PermaNet® 3.0 ITN recorded 24-h mortality of 26% against resistant mosquitos on roof panels, with an 84% reduction in PBO content. Interceptor® G2 ITN 72-h mortality was 51%, with a 67% reduction in chlorfenapyr content. Interceptor® ITN 24-h mortality was 71%, with an 84% reduction in alpha-cypermethrin content. CONCLUSION: Only PermaNet® 3.0 ITNs surpassed the standard three-year survival threshold. Identified protective factors should inform SBC messaging. Significant decreases in chemical content and resulting impact on bioefficacy warrant more research in other countries to better understand dual AI ITN insecticidal performance.

The relative nature of the standards for proof of safety: a review of FDA's safety standards for various consumer products.

Are all food ingredients, dietary supplement ingredients and even foods, required to meet the same safety standards? Are they all equally safe? If so, then why do the various categories have different expressions describing their safety, such as "reasonable certainty of no harm" for food ingredients and "reasonable expectation of no harm" for dietary supplement ingredients? The basis for these different expressions is that they are not standards of safety, but standards of proof of safety. Just as in criminal vs. civil courts, the threshold for proving guilt or fault is different, so too are there differences between various categories of consumer products regulated by the US Food and Drug Administration. This manuscript describes the threshold requirements for each standard, as well as to the identity of the decision makers on what is safe, their credentials as decision makers and the databases mandated for their use.

Knowledge-Based Design of Multifunctional Polymeric Nanoparticles.

Conventional drug delivery systems (DDS) today still face several drawbacks and obstacles. High total doses of active pharmaceutical ingredients (API) are often difficult or impossible to deliver due to poor solubility of the API or undesired clearance from the body caused by strong interactions with plasma proteins. In addition, high doses lead to a high overall body burden, in particular if they cannot be delivered specifically to the target site. Therefore, modern DDS must not only be able to deliver a dose into the body, but should also overcome the hurdles mentioned above as examples. One of these promising devices are polymeric nanoparticles, which can encapsulate a wide range of APIs despite having different physicochemical properties. Most importantly, polymeric nanoparticles are tunable to obtain tailored systems for each application. This can already be achieved via the starting material, the polymer, by incorporating, e.g., functional groups. This enables the particle properties to be influenced not only specifically in terms of their interactions with APIs, but also in terms of their general properties such as size, degradability, and surface properties. In particular, the combination of size, shape, and surface modification allows polymeric nanoparticles to be used not only as a simple drug delivery device, but also to achieve targeting. This chapter discusses to what extent polymers can be designed to form defined nanoparticles and how their properties affect their performance.

In silico evaluation of the potential allergenicity of a fungal biomass from Rhizomucor pusillus for use as a novel food ingredient.

The world's hunger for novel food ingredients drives the development of safe, sustainable, and nutritious novel food products. For foods containing novel proteins, potential allergenicity of the proteins is a key safety consideration. One such product is a fungal biomass obtained from the fermentation of Rhizomucor pusillus. The annotated whole genome sequence of this strain was subjected to sequence homology searches against the AllergenOnline database (sliding 80-amino acid windows and full sequence searches). In a stepwise manner, proteins were designated as potentially allergenic and were further compared to proteins from commonly consumed foods and from humans. From the sliding 80-mer searches, 356 proteins met the conservative >35% Codex Alimentarius threshold, 72 of which shared ≥50% identity over the full sequence. Although matches were identified between R. pusillus proteins and proteins from allergenic food sources, the matches were limited to minor allergens from these sources, and they shared a greater degree of sequence homology with those from commonly consumed foods and human proteins. Based on the in silico analysis and a literature review for the source organism, the risk of allergenic cross-reactivity of R. pusillus is low.

Detailed aggregate exposure analysis shows that exposure to fragrance ingredients in consumer products is low: Many orders of magnitude below thresholds of concern.

The Research Institute for Fragrance Materials (RIFM) and Creme Global Cremeglobal.com partnered to develop an aggregate exposure model for fragrance ingredients. The model provides a realistic estimate of the total exposure of fragrance ingredients to individuals across a population. The Threshold of Toxicological Concern (TTC) and Dermal Sensitization Threshold (DST) were used to demonstrate the magnitude of low exposure to fragrance materials. The total chronic systemic, inhalation, and dermal 95th percentile exposures on approximately 3000 fragrance ingredients in RIFM's inventory were compared to their respective TTC or DST. Additionally, representative fragrance ingredients were randomly selected and analyzed for exposure distribution by product type (i.e., cosmetic/personal care, household care, oral care, and air care) and route of exposure. It was found that 76 % of fragrance ingredients fall below their respective TTC limits when compared to 95th percentile systemic exposure, while 99 % are below inhalation TTC limits. The lowest 95th percentile aggregate exposure by product type was from household care products, then air care, and oral care products. The highest exposure was from personal care/cosmetic products. The volume of use for most fragrance ingredients (63 %) was <1 metric ton, estimating that environmental exposure to fragrance ingredients is likely low.

Comparison of permitted daily exposure (PDE) values for active pharmaceutical ingredients (APIs) - Evidence of a robust approach.

Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in shared facilities. With the lack of official PDE lists for pharmaceuticals, PDEs have to be set by each company separately. Although general rules and guidelines for the setting of PDEs exist, inter-company variations in the setting of PDEs occur and are considered acceptable within a certain range. To evaluate the robustness of the PDE approach between different pharmaceutical companies, data on PDE setting of five marketed APIs (amlodipine, hydrochlorothiazide, metformin, morphine, and omeprazole) were collected and compared. Findings show that the variability between PDE values is within acceptable ranges (below 10-fold) for all compounds, with the highest difference for morphine due to different Point of Departures (PODs) and Adjustment Factors (AFs). Factors of PDE variability identified and further discussed are: (1) availability of data, (2) selection of POD, (3) assignment of AFs, (4) route-to-route extrapolation, and (5) expert judgement and differences in company policies. We conclude that the investigated PDE methods and calculations are robust and scientifically defensible. Additionally, we provide further recommendations to harmonize PDE calculation approaches across the pharmaceutical industry.

Bacillus subtilis ZB423: 90-Day repeat dose oral (gavage) toxicity study in Wistar rats.

The novel genetically modified probiotic Bacillus subtilis ZB423 was assessed in a 90-day repeated-dose oral toxicity study adhering to Good Laboratory Practice (GLP) and Organization for Economic Cooperation and Development (OECD) guidelines. Spray-dried spores at a concentration of 1.1E12 CFU/g were administered at doses of 130, 260, and 519 mg/kg body weight/day correlating to 1.43 × 1011, 2.86 × 1011, and 5.71 × 1011 CFU/kg/day, respectively, by oral gavage to Wistar rats for a period of 90 consecutive days. Results showed no toxicologically relevant findings for B. subtilis ZB423 from measured parameters. The no observed adverse effect level (NOAEL) of B. subtilis ZB423 is 519 mg/kg body weight/day corresponding to 5.71 × 1011 CFU/kg/day for lyophilized B. subtilis ZB423 spores under the test conditions employed.

Presence of 2-hydroxyethyl methacrylate (HEMA) and other (meth)acrylates in nail cosmetics, and compliance with EU legislation: An online market survey.

BACKGROUND: During the last 15-20 years, allergic contact dermatitis from acrylates-containing nail cosmetics (acrylic nails, gel nails, gel nail polish) has been increasingly reported. 2-Hydroxyethyl methacrylate (HEMA) is considered to be the major allergenic culprit; few data on its presence in nail cosmetics are available. OBJECTIVES: To investigate (1) the frequency in which HEMA and di-HEMA trimethylhexyl dicarbamate are present in nail cosmetics; (2) whether nail cosmetics comply with EU regulations; (3) which other (meth)acrylates are present in nail cosmetics and how often. METHODS: One-line market survey. RESULTS: HEMA was present in nearly 60% of 394 cosmetic nail products and di-HEMA trimethylhexyl dicarbamate in 34%. Mandatory warnings on the packages of products containing HEMA were absent in 35% ('For professional use only') resp. 55% ('Can cause an allergic reaction'). Forty-five other (meth)acrylates were identified, of which the most frequent were hydroxypropyl methacrylate (25%), isobornyl methacrylate (16%) and trimethylolpropane triacrylate (12%). Some ingredient lists mentioned non-INCI names or non-specific names. CONCLUSIONS: HEMA was by far the most common ingredient of nail cosmetics, being present in nearly 60% of the products. Violations of EU legislation occurred in >30% (mandatory warnings missing) resp. 10% (mislabelling) of nail cosmetics.

Counts of mesophilic aerobic, mesophilic anaerobic, thermophilic aerobic sporeforming bacteria and persistence of Bacillus cereus spores throughout cocoa powder processing chain.

Sporeforming bacteria are a concern in some food raw materials, such as cocoa powder. Samples (n = 618) were collected on two farms and at several stages during cocoa powder manufacture in three commercial processing lines to determine the impact of each stage on bacterial spore populations. Mesophilic aerobic, mesophilic anaerobic, thermophilic aerobic, and Bacillus cereus spore populations were enumerated in all the samples. Genetic diversity in B. cereus strains (n = 110) isolated from the samples was examined by M13 sequence-based PCR typing, partial sequencing of the panC gene, and the presence/absence of ces and cspA genes. The counts of different groups of sporeforming bacteria varied amongst farms and processing lines. For example, the counts of mesophilic aerobic spore-forming (MAS) populations of cocoa bean fermentation were lower than 1 log spore/g in Farm 1 but higher than 4 log spore/g in Farm 2. B. cereus isolated from cocoa powder was also recovered from cocoa beans, nibs, and samples after roasting, refining, and pressing, which indicated that B. cereus spores persist throughout cocoa processing. Phylogenetic group IV was the most frequent (73%), along with processing. Strains from phylogenetic group III (14 %) did not show the ces gene's presence.

An Eco-Friendly Extraction and Purification Approach for Obtaining Active Ingredients for Cosmetics from Two Marine Brown Seaweeds.

Brown seaweeds are attracting attention due to their richness in bioactive compounds, in particular, their phlorotannins. We present here a case study of two Fucales, Ascophyllum nodosum and Halidrys siliquosa, sustainably collected, to produce active polyphenols for the cosmetics sector. Phenolic contents of crude extracts, obtained by Accelerated Solvent Extraction (ASE), were more elevated in H. siliquosa at 100.05 mg/g dry weight (DW) than in A. nodosum (29.51 mg/g DW), considering 3 cycles with cell inversion. The temperature of extraction for a high phenolic content and high associated antioxidant activities close to positive controls was 150 °C for both algae and the use of only one cycle was enough. A semi-purification process using Solid-phase Extraction (SPE) was carried out on both ASE crude extracts (one per species). The majority of phlorotannins were found in the ethanolic SPE fraction for A. nodosum and the hydroethanolic one for H. siliquosa. The SPE process allowed us to obtain more concentrated fractions of active phenolic compounds (×1.8 and 2 in A. nodosum and H. siliquosa, respectively). Results are discussed in regard to the exploitation of seaweeds in Brittany and to the research of sustainable processes to produce active natural ingredients for cosmetics.

Preparation of milk fat globule membrane ingredients enriched in polar lipids: Composition characterization and digestive properties.

In this study, milk fat globule membrane (MFGM) ingredients enriched in polar lipids were prepared using membrane filtration, including microfiltration, diafiltration, and ultrafiltration from butter serum powder. Polar lipids (phospholipids, sterols, and gangliosides) in prepared MFGM ingredients were analyzed by 31P nuclear magnetic resonance spectroscopy, GC-MS, and ultra-performance liquid chromatography (UPLC)-MS/MS, respectively. The lipolysis degree and microstructure of MFGM ingredient and soybean lecithin (SL) emulsions during in vitro digestion were also analyzed. Microfiltration showed higher concentration efficiency than ultrafiltration, which increased by 2.16% and 2.73% in phospholipids, respectively. Moreover, diafiltration concentrated more polar lipids (6.39% of phospholipids) than microfiltration. Milk fat globule membrane ingredients had high levels of sphingomyelin (1.27%-1.36%) and ratio of GD3 to GM3 is 9.25- to 9.88-fold. The different lipolysis behaviors between MFGM ingredient emulsions and SL emulsions were correlated with their different polar lipid compositions. Phospholipids from both MFGM ingredients and SL could help maintain the initial structure during the gastric digestion. These results could provide a scientific basis for developing high-polar-lipids food, particularly infant formulas and special functional foods.

Effect of CeO2, TiO2 and SiO2 nanoparticles on the growth and quality of model medicinal plant Salvia miltiorrhiza by acting on soil microenvironment.

In this study, a six-month pot experiment was conducted to explore the effects of nanoparticles (NPs), including CeO2, TiO2 and SiO2 NPs at 200 and 800 mg/kg, on the growth and quality of model medicinal plant Salvia miltiorrhiza. A control group was implemented without the application of NPs. Results showed that NPs had no significant effect on root biomass. Treatment with 200 mg/kg of SiO2 NPs significantly increased the total tanshinone content by 44.07 %, while 200 mg/kg of CeO2 NPs were conducive to a 22.34 % increase in salvianolic acid B content. Exposure to CeO2 NPs induced a substantial rise in the MDA content in leaves (176.25 % and 329.15 % under low and high concentration exposure, respectively), resulting in pronounced oxidative stress. However, TiO2 and SiO2 NPs did not evoke a robust response from the antioxidant system. Besides, high doses of CeO2 NP-amended soil led to reduced nitrogen, phosphorus and potassium contents. Furthermore, the NP amendment disturbed the carbon and nitrogen metabolism in the plant rhizosphere and reshaped the rhizosphere microbial community structure. The application of CeO2 and TiO2 NPs promoted the accumulation of metabolites with antioxidant functions, such as D-altrose, trehalose, arachidonic acid and ergosterol. NPs displayed a notable suppressive effect on pathogenic fungi (Fusarium and Gibberella) in the rhizosphere, while enriching beneficial taxa with disease resistance, heavy metal antagonism and plant growth promotion ability (Lysobacter, Streptomycetaceae, Bacillaceae and Hannaella). Correlation analysis indicated the involvement of rhizosphere microorganisms in plant adaptation to NP amendments. NPs regulate plant growth and quality by altering soil properties, rhizosphere microbial community structure, and influencing plant and rhizosphere microbe metabolism. These findings were beneficial to deepening the understanding of the mechanism by which NPs affect medicinal plants.

Topical and transdermal botanical formulations of the Chinese pharmacopoeia-A review.

In pharmaceutics, ingredients are classified as active ingredients and excipients. In topical/transdermal phytomedicines, an ingredient may serve both functions. Published information on these dual-purpose ingredients and their pharmacological relevance is limited. An intriguing scenario arises in traditional Chinese medicine (TCM) formulations, where active ingredients and excipients are undifferentiated. This study analyzes ingredients in TCM topical/transdermal formulations, aiming at harmonization of understanding of TCMs. The most commonly recorded ingredients from such formulations in the Chinese pharmacopoeia 2020 (ChP 2020) are reviewed, aiming at developing innovative topical/transdermal phytomedicines. Current editions of Chinese historical documents were reviewed to explore the principles underlying the use of these ingredients. TCM formulations containing botanical drugs for topical/transdermal application were selected from the ChP 2020. The use of botanical materials in TCM formulations is guided by the "Jun-Chen-Zuo-Shi" principle rooted in Yin-Yang and the five elements' theories. In the ChP 2020, 155 botanical drugs, along with 40 excipients (from the "procedure" section, focusing on processing and technical parameters), were identified from 34 botanical formulations intended for topical/transdermal application. Pungent and aromatic botanical materials were the most frequently recorded. Adhesive plasters were the most commonly recorded TCM dosage form, employing specific matrix blends. This new perspective of study reveals the prevalence of pungent and aromatic botanical materials, the common use of adhesive plasters, multifunctional properties of botanical oils, and formulation adaptability in TCM topical/transdermal products. These insights should inform novel formulation designs for both pharmaceutical and phytopharmacological research.

In Silico Prediction of N-Nitrosamine Formation Pathways of Pharmaceutical Products.

The recent discovery of N-nitrosodimethylamine (NDMA), a mutagenic N-nitrosamine, in pharmaceuticals has adversely impacted the global supply of relevant pharmaceutical products. Contamination by N-nitrosamines diverts resources and time from research and development or pharmaceutical production, representing a bottleneck in drug development. Therefore, predicting the risk of N-nitrosamine contamination is an important step in preventing pharmaceutical contamination by DNA-reactive impurities for the production of high-quality pharmaceuticals. In this study, we first predicted the degradation pathways and impurities of model pharmaceuticals, namely gliclazide and indapamide, in silico using an expert-knowledge software. Second, we verified the prediction results with a demonstration test, which confirmed that N-nitrosamines formed from the degradation of gliclazide and indapamide in the presence of hydrogen peroxide, especially under alkaline conditions. Furthermore, the pathways by which degradation products formed were determined using ranitidine, a compound previously demonstrated to generate NDMA. The prediction indicated that a ranitidine-related compound served as a potential source of nitroso groups for NDMA formation. In silico software is expected to be useful for developing methods to assess the risk of N-nitrosamine formation from pharmaceuticals.