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Frontiers in Medical Technology 2024The regulation and use of herbal medicines is a topic of debate due to concerns about their quality, safety, and efficacy. EU Directive 2004/24/EC on Herbal Medicinal... (Review)
Review
The regulation and use of herbal medicines is a topic of debate due to concerns about their quality, safety, and efficacy. EU Directive 2004/24/EC on Herbal Medicinal Products was a significant step towards establishing a regulatory framework for herbal medicinal products in the EU, and bridging the gap between conventional and herbal medicines. This Directive allows herbal medicinal products to be marketed in the EU through full marketing authorisation, well-established use, and traditional use of herbal medicinal products. The framework relies on the correlation between the therapeutic claims of herbal medicine and the scientific evidence backing them up: the greater the claims made regarding medicinal benefits, the more evidence is required to substantiate its efficacy and safety. This regulatory framework acknowledges and incorporates traditional knowledge when evaluating herbal medicines, showcasing a balanced approach that values cultural traditions while mandating monographs for traditional herbal medicinal products. Excluding herbal medicines completely limits access to affordable treatment, particularly when they serve as the only alternative for some, and protects consumer autonomy. This EU framework could therefore serve as a practical guidance for the use and regulation of herbal medicines, even outside the EU. In conclusion, it is argued that the same moral imagination and courage shown by regulators in the case of herbal medicines could perhaps be used in the regulatory frameworks of other healthcare products.
PubMed: 38948354
DOI: 10.3389/fmedt.2024.1358956 -
Regulatory Toxicology and Pharmacology... Jun 2024Potentially mutagenic impurities are likely to be formed in any drug substance, since their synthesis requires reactive intermediates which may also react with DNA. The...
Potentially mutagenic impurities are likely to be formed in any drug substance, since their synthesis requires reactive intermediates which may also react with DNA. The ICH M7 guideline, which defines how to risk assess and control mutagenic impurities, was first published in 2014 and is not to be applied retrospectively; however, some impurities have been found above the permitted limits in drug products which were already on the market. This study assessed the implications of applying ICH M7 retrospectively to anti-hypertensive drugs marketed in Brazil by performing a risk assessment and establishing control strategies. The manufacturing processes of 15 drug substances were evaluated and 262 impurities were identified, from which 21% were classified as potentially mutagenic. Most of the impurities were identified below ICH M7 acceptable limits, except for impurities described in a pharmacopoeial monograph. Compendial specifications are defined based on scientific evidence and play an important role in setting quality and safety standards for pharmaceuticals, however there are opportunities for further alignment with ICH guidelines, aiming for a holistic assessment of the impurities profile to ensure the safety of medicines.
PubMed: 38936796
DOI: 10.1016/j.yrtph.2024.105669 -
Hospital Pharmacy Aug 2024Each month, subscribers to receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to... (Review)
Review
Each month, subscribers to receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of publishes selected reviews in this column. For more information about , contact Wolters Kluwer customer service at 866-397-3433.
PubMed: 38919758
DOI: 10.1177/00185787241236439 -
Gualou-Xiebai-Banxia-Tang regulates liver-gut axis to ameliorate Metabolic Syndrome in HFD-fed mice.Phytomedicine : International Journal... Jan 2024Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases....
BACKGROUND
Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases. Gualou-Xiebai-Banxia-Tang decoction (GT) was first described in the Synopsis of the Golden Chamber, the earliest traditional Chinese medicine (TCM) monograph on diagnosis and treatment of miscellaneous diseases in China. According to TCM precepts, based on its ability to activate yang to release stagnation, activate qi to reduce depression, remove phlegm, and broaden the chest, GT has been used for more than 2,000 years to treat cardiovascular ailments. However, the molecular bases of its therapeutic mechanisms remain unclear.
PURPOSE
The aim of this study was to identify lipid- and glucose-related hepatic genes differentially regulated by GT, and to assess GT impact on gut microbiota composition, in mice with high-fat diet (HFD)-induced MetS.
STUDY DESIGN AND METHODS
ApoE/ mice were fed with an HFD for 24 weeks, with or without concurrent GT supplementation, to induce MetS. At the study's end, body weight, visceral fat weight, blood lipid levels, and insulin sensitivity were measured, and histopathological staining was used to evaluate hepatosteatosis and intestinal barrier integrity. Liver transcriptomics was used for analysis of differentially expressed genes in liver and prediction of relevant regulatory pathways. Hepatic lipid/glucose metabolism-related genes and proteins were detected by RT-qPCR and western blotting. Gut microbial composition was determined by 16S rRNA gene sequencing.
RESULTS
GT administration reduced MetS-related liver steatosis and weight gain, promoted insulin sensitivity and lipid metabolism, and beneficially modulated gut microbiota composition by decreasing the relative abundance of g_Lachnospiraceae_NK4A136_group and increasing the relative abundance of g_Alistipes. Liver transcriptomics revealed that GT regulated the expression of genes related to lipid and glucose metabolism (Pparγ, Igf1, Gpnmb, and Trem2) and of genes encoding chemokines/chemokine receptors (e.g. Cxcl9 and Cx3cr1). Significant, positive correlations were found for Ccr2, Ccl4, Ccr1, and Cx3cr1 and the g_Lachnospiraceae_NK4A136_group, and between Cxcl9, Ccr2, Ccl4, and Cx3cr1 and g_Desulfovibrio. GT treatment downregulated the protein expressions of SCD1 and CX3CR1 and upregulated the expression of PCK1 protein.
CONCLUSION
GT supplementation alleviates HFD-induced MetS in mice by improving hepatic lipid and glucose metabolism. The anti-metabolic syndrome effects of GT may be related to the regulation of the gut-liver axis.
PubMed: 38901285
DOI: 10.1016/j.phymed.2023.155320 -
Studies in Mycology Jun 2023(, ) species are common soil-borne fungi, endophytes, epiphytes, and saprotrophs. Sexual morphs of spp were placed in the genus , which was further segregated into the...
(, ) species are common soil-borne fungi, endophytes, epiphytes, and saprotrophs. Sexual morphs of spp were placed in the genus , which was further segregated into the six subgenera , , , , , and . However, with the end of dual nomenclature, became the single depository for sexual and asexual morph-typified species. Species of are typically characterised by penicillate, sporodochial, and, in many cases, dimorphic conidiophores (primary and secondary conidiophores). Primary conidiophores are mononematous, either verticillium-like or narrowly penicillate. The secondary conidiophores generally form imbricate conidial chains that can collapse to slimy masses, particularly on sporodochia. In the present study, we investigated the species diversity within a collection of 420 strains of from the culture collection of, and personal collections at, the Westerdijk Fungal Biodiversity Institute in Utrecht, the Netherlands. Strains were analysed based on their morphological characters and molecular phylogeny. The latter used DNA sequence data of the nuclear ribosomal internal transcribed spacer regions and intervening 5.8S nrDNA (ITS) and partial 28S large subunit (LSU) nrDNA and partial protein encoding genes including the RNA polymerase II second largest subunit (), translation elongation factor 1-alpha () and β-tubulin (). Based on these results, the subgenera , , and are supported within . Furthermore, the genus is resurrected to accommodate the former subgenera and . The close relationship of and is strongly supported as both are inferred phylogenetically as sister-genera. New taxa include 24 new species and 10 new combinations. Recognition of distinguishes species typically forming a reduced perithecial stroma superficially on plant tissue from species in often forming well-developed, through bark erumpent stromata. The patterns of observed perithecial wall anatomies, perithecial wall and stroma interfaces, and asexual morph diversifications described in a previously compiled monograph are used for interpreting ancestral state reconstructions. It is inferred that the common ancestor of and may have formed perithecia superficially on leaves, possessed a perithecial wall consisting of a single region, and formed intercalary phialides in penicilli of conidiophores. Character interpretation may also allow hypothesising that diversification of morphs occurred then in the two genera independently and that the frequently stroma-linked morphs evolved together with the occupation of woody host niches and mycoparasitism. L. Zhao & Crous, L. Zhao & Crous, L. Zhao & Crous, L. Zhao & Crous, L. Zhao & Crous, L. Zhao & Crous, L. Zhao, Crous & Schroers, L. Zhao & Crous, L. Zhao, Crous & Schroers, L. Zhao & Crous, L. Zhao & Crous, L. Zhao, Crous & Schroers, , L. Zhao & Crous, L. Zhao, Crous & Schroers, L. Zhao & Crous, L. Zhao, Crous & Schroers, L. Zhao & Crous, L. Zhao, Crous & Schroers, L. Zhao, Crous & Schroers, L. Zhao & Crous, L. Zhao & Crous, L. Zhao & Crous, L. Zhao & Crous, L. Zhao & Crous. (J.A. Stev.) L. Zhao & Crous, (Y.P. Tan .) L. Zhao & Crous, (Y.P. Tan .) L. Zhao & Crous, (Samuels) L. Zhao, Crous & Schroers, (Schroers) L. Zhao, Crous & Schroers, (Schroers) L. Zhao, Crous & Schroers, (Lechat & J. Fourn.) L. Zhao & Crous, (Samuels) L. Zhao, Crous & Schroers, (Lechat & J. Fourn.) L. Zhao & Crous, (Höhn.) Schroers. W.H. Chen ., H. Yu & Y. Wang, R.H. Perera & K.D. Hyde, (Starbäck) Forin & Vizzini, Prasher & R. Chauhan, R.H. Perera ., (Sacc.) Forin & Vizzini, (J. Luo & W.Y. Zhuang) Z.Q. Zeng & W.Y. Zhuang. J.C. Schmidt ex Link, Bonord. Zhao L, Groenewald JZ, Hernández-Restrepo M, Schroers H-J, Crous PW (2023). Revising and allied genera in . : 205-266. doi: 10.3114/sim.2023.105.03.
PubMed: 38895704
DOI: 10.3114/sim.2023.105.03 -
Molecules (Basel, Switzerland) Jun 2024Kostel. is a species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical...
Kostel. is a species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical and chemical quality criteria for leaf and bark as herbal substances and to evaluate their in vitro antioxidant potential. Macroscopic and microscopic qualitative and quantitative analyses, chemical LC-UV/DAD-ESI/MS profiling, and the quantification of key chemical classes were performed. Antioxidant activity was evaluated by DPPH and FRAP assays. Macroscopically, the leaf is asymmetrical with an emarginated apex and cuneate base. Microscopically, it shows features such as two-layered adaxial palisade parenchyma, vascular bundles surrounded by 3-6 layers of sclerenchyma, prismatic calcium oxalate crystals (5.89 ± 1.32 μm) along the fibers, paracytic stomata only on the abaxial epidermis (stomatal index-20.15), and non-glandular trichomes only on petiolules. The microscopic features of the bark include a broad cortex with large lignified sclereids, prismatic calcium oxalate crystals (8.24 ± 1.57 μm), and secondary phloem with distinct 2-5 seriated medullary rays without crystals. Chemical profile analysis revealed that phenolic derivatives, mainly condensed tannins and flavonoids, are the main classes identified. A total of 22 marker compounds were tentatively identified in both plant parts. The major compounds identified in the leaf were quercetin-3--glucoside and taxifolin pentoside and in the bark were B-type dimeric proanthocyanidins and taxifolin 3--rhamnoside. The total phenolics content was higher in the leaf (1521 ± 4.71 mg GAE/g dry weight), while the total flavonoids and condensed tannins content were higher in the bark (82 ± 0.58 mg CE/g and 1021 ± 5.51 mg CCE/g dry weight, respectively). A total of 70% of the hydroethanolic extracts of leaf and bark showed higher antioxidant activity than the ascorbic acid and concentration-dependent scavenging activity in the DPPH assay (IC 23.95 ± 0.93 and 23.63 ± 1.37 µg/mL, respectively). A positive and statistically significant ( < 0.05) correlation between the phenol content and antioxidant activity was found. The results obtained will provide important clues for the quality control criteria of leaf and bark, as well as for the knowledge of their pharmacological potential as possible anti-inflammatory agents with antioxidant activity.
Topics: Plant Bark; Plant Leaves; Antioxidants; Plant Extracts; Plants, Medicinal; Flavonoids; Phytochemicals; Herbal Medicine; Phenols; Proanthocyanidins
PubMed: 38893505
DOI: 10.3390/molecules29112629 -
EClinicalMedicine Jul 2024The International Agency for Research on Cancer (IARC) recently classified opium consumption as carcinogenic to humans. This study aimed to estimate the potential...
BACKGROUND
The International Agency for Research on Cancer (IARC) recently classified opium consumption as carcinogenic to humans. This study aimed to estimate the potential reduction in incident cancers by 2035 in Iran, which accounts for 42% of global opium consumption, through decreasing opium use prevalence.
METHODS
The population attributable fraction (PAF) of opium-related cancers was projected using national cancer incidence, age- and gender-specific opium use prevalence, relative cancer risks associated with opium use, and annual percentage changes in cancer incidence rates in Iran. Opium-related cancers were defined based on IARC monographs as cancers of lung, larynx, bladder, esophagus, stomach, pancreas, and pharynx. The number of preventable cancer cases under different opium prevalence scenarios was determined by subtracting attributable cases in each year based on current prevalence from those in alternative scenarios.
FINDINGS
By 2035, an estimated 3,001,421 new cancer cases are expected in Iran, with 904,013 (30.1%) occurring in opium-related sites. Maintaining the current opium prevalence (5.6%) is projected to cause 111,130 new cancer cases (3.7% of all cancers, 12.3% of opium-related). A 10%, 30%, and 50% reduction in opium prevalence could prevent 9,016, 28,161, and 49,006 total incident cancers by 2035 in Iran, respectively. Reducing opium use prevalence by 10%-50% is projected to have the highest impact on lung cancer (prevention of 2,946-15,831 cases), stomach cancer (prevention of 2,404-12,593 cases), and bladder cancer (prevention of 1,725-9,520 cases).
INTERPRETATION
Our results highlight the significant benefits that can be achieved through effective cancer prevention policies targeting opium use in Iran. Neglecting this risk factor is estimated to pose a significant burden on cancer incidence in the next decade in this population.
FUNDING
None.
PubMed: 38881571
DOI: 10.1016/j.eclinm.2024.102650 -
Current Topics in Medicinal Chemistry Jun 2024Osteoarthritis (OA) is a common chronic articular degenerative disease characterized by articular cartilage degradation, synovial inflammation/immunity, and subchondral...
Osteoarthritis (OA) is a common chronic articular degenerative disease characterized by articular cartilage degradation, synovial inflammation/immunity, and subchondral bone lesions. Recently, increasing interest has been devoted to treating or preventing OA with herbal medicines. The mechanism of action of plant raw materials used in osteoarthrosis treatment is well documented. They are sought after because of the high frequency of inflammation of the knee joint among both elderly and young people engaged in sports in which their knee joints are often exposed to high-stress conditions. The purpose of this work was to present some most effective and safe plant medicines with proven mechanisms of action that can help to alleviate the growing social problem of osteoarthrosis caused in recent years. A review of the available literature based primarily on the latest editions of ESCOP and EMA monographs and the latest scientific papers has made it possible to select and propose medical management of osteoarthrosis by ranking plant medicines according to their effectiveness. Clinical studies of raw plant materials, such as Harpagophyti radix, Olibanum indicum, and Urticae foliumet herba have indicated that these drugs should be considered the first choice in osteoarthrosis treatment. The efficacy of Rosae pseudo-fructus, Salicis cortex, Filipendulae ulmariae flos et herba, Ribis nigri folium, and externally applied Capsici fructus and Symphyti radix, has also been proven by pharmacological studies. All the plant medicines mentioned in the paper have been studied in detail in terms of their phytochemistry, which can help doctors in their decision-- making in the treatment of osteoarthrosis.
PubMed: 38867521
DOI: 10.2174/0115680266297662240527105450 -
Biophysical Journal Jun 2024Tight junctions are cell-cell adhesion complexes that act as gatekeepers of the paracellular space. Formed by several transmembrane proteins, the claudin family performs... (Review)
Review
Tight junctions are cell-cell adhesion complexes that act as gatekeepers of the paracellular space. Formed by several transmembrane proteins, the claudin family performs the primary gate-keeping function. The claudin proteins form charge and size-selective diffusion barriers to maintain homeostasis across endothelial and epithelial tissue. Of the 27 known claudins in mammals, some are known to seal the paracellular space, while others provide selective permeability. The differences in permeability arise due to the varying expression levels of claudins in each tissue. The tight junctions are observed as strands in freeze-fracture electron monographs; however, at the molecular level, tight junction strands form when multiple claudin proteins assemble laterally (cis assembly) within a cell and head-on (trans assembly) with claudins of the adjacent cell in a zipper-like architecture, closing the gap between the neighboring cells. The disruption of tight junctions caused by changing claudin expression levels or mutations can lead to diseases. Therefore, knowledge of the molecular architecture of the tight junctions and how that is tied to tissue-specific function is critical for fighting diseases. Here, we review the current understanding of the tight junctions accrued over the last three decades from experimental and computational biophysics perspectives.
PubMed: 38859584
DOI: 10.1016/j.bpj.2024.06.010 -
Journal of Pharmaceutical Sciences Jun 2024In this monograph, the potential use of methods based on the Biopharmaceutics Classification System (BCS) framework to evaluate the bioequivalence of solid...
In this monograph, the potential use of methods based on the Biopharmaceutics Classification System (BCS) framework to evaluate the bioequivalence of solid immediate-release (IR) oral dosage forms containing fexofenadine hydrochloride as a substitute for a pharmacokinetic study in human volunteers is investigated. We assessed the solubility, permeability, dissolution, pharmacokinetics, pharmacodynamics, therapeutic index, bioavailability, drug-excipient interaction, and other properties using BCS recommendations from the ICH, FDA and EMA. The findings unequivocally support fexofenadine's classification to BCS Class IV as it is neither highly soluble nor highly permeable. Further impeding the approval of generic equivalents through the BCS-biowaiver pathway is the reference product's inability to release ≥ 85 % of the drug substance within 30 min in pH 1.2 and pH 4.5 media. According to ICH rules, BCS class IV drugs do not qualify for waiving clinical bioequivalence studies based on the BCS, even though fexofenadine has behaved more like a BCS class I/III than a class IV molecule in pharmacokinetic studies to date and has a wide therapeutic index.
PubMed: 38857646
DOI: 10.1016/j.xphs.2024.06.002