Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.

AREAS COVERED: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. EXPERT OPINION: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.

Use of Aloe Vera Gel as Media to Assess Antimicrobial Activity and Development of Antimicrobial Nanocomposites.

Antimicrobial resistance is a menace to public health on a global scale. In this regard, nanomaterials exhibiting antimicrobial properties represent a promising solution. Both metal and metal oxide nanomaterials are suitable candidates, even though their mechanisms of action vary. Multiple antimicrobial mechanisms can occur simultaneously or independently; this includes either direct contact with the pathogens, nanomaterial uptake, oxidative stress, ion release, or any of their combinations. However, due to their specific properties and more particularly fast settling, existing methods to study the antimicrobial properties of nanoparticles have not been specifically adapted in some cases. The development of methodologies that can assess the antimicrobial properties of metallic nanomaterials accurately is necessary. A cost-effective methodology with a straightforward set-up that enables the easy and quick assessment of the antimicrobial properties of metal nanoparticles with high accuracy has been developed. The methodology is also capable of confirming whether the killing mechanism involves ionic diffusion. Finally, Aloe Vera gel showed good properties for use as a medium for the development of antimicrobial ointment.

Antivirulence and antipathogenic activity of Mayan herbal remedies against Pseudomonas aeruginosa.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yucatan Peninsula has a privileged wealth of vascular plants with which various Mayan herbal formulations have been developed. However, studies on their antipathogenic and antivirulence properties are scarce. AIM OF THE STUDY: Identify antivirulence properties in Mayan herbal remedies and determine their antipathogenic capacity in burn wounds infected with Pseudomonas aeruginosa. MATERIALS AND METHODS: An ethnobotanical study was conducted in Mayan communities in central and southern Quintana Roo, Mexico. Furthermore, the antipathogenic capacity of three Mayan herbal remedies was analyzed using an animal model of thermal damage and P. aeruginosa infection. Antivirulence properties were determined by inhibiting phenotypes regulated by quorum sensing (pyocyanin, biofilm, and swarming) and by the secretion of the ExoU toxin. The chemical composition of the most active herbal remedy was analyzed using molecular network analysis. RESULTS: It was found that topical administration of the remedy called "herbal soap" (HS) for eleven days maintained 100% survival of the animals, reduced establishment of the bacteria in the burn and prevented its systemic dispersion. Although no curative effect was recorded on tissue damaged by HS treatment, its herbal composition strongly reduced swarming and ExoU secretion. Through analysis of Molecular Networks, it was possible to carry out a global study of its chemical components, and identify the family of oxindole monoterpenoid alkaloids and carboline and tetrahydropyrididole alkaloids. In addition, flavonols, flavan-3-ols, and quinic acid derivatives were detected. CONCLUSIONS: The antipathogenic and antivirulence capacity of ancient Mayan remedies makes them a potential resource for developing new antibacterial therapies to treat burns infected by P. aeruginosa.

Evidence for the efficacy of anti-inflammatory plants used in Brazilian traditional medicine with ethnopharmacological relevance.

ETHNOPHARMACOLOGICAL RELEVANCE: When exacerbated, inflammatory processes can culminate in physical and emotional disorders and, if not stopped, can be lethal. The high prevalence of inflammation has become a public health problem, and the need for new drugs to treat this pathology is imminent. The use of medicinal plants has emerged as an alternative, and a survey of data that corroborates its application in inflammatory diseases is the starting point. Furthermore, Brazil harbors a megadiversity, and the traditional use of plants is relevant and needs to be preserved and carefully explored for the discovery of new medicines. AIM OF THE STUDY: This review sought to survey the medicinal plants traditionally used in Brazil for the treatment of inflammatory processes and to perform, in an integrative way, a data survey of these species and analysis of their phytochemical, pharmacological, and molecular approaches. MATERIALS AND METHODS: Brazilian plants that are traditionally used for inflammation (ophthalmia, throat inflammation, orchitis, urinary tract inflammation, ear inflammation, and inflammation in general) are listed in the DATAPLAMT database. This database contains information on approximately 3400 native plants used by Brazilians, which were registered in specific documents produced until 1950. These inflammatory disorders were searched in scientific databases (PubMed/Medline, Scopus, Web of Science, Lilacs, Scielo, Virtual Health Library), with standardization of DECS/MESH descriptors for inflammation in English, Spanish, French, and Portuguese, without chronological limitations. For the inclusion criteria, all articles had to be of the evaluated plant species, without association of synthesized substances, and full articles free available in any of the four languages searched. Duplicated articles and those that were not freely available were excluded. RESULTS: A total of 126 species were identified, culminating in 6181 articles in the search. After evaluation of the inclusion criteria, 172 articles representing 40 different species and 38 families were included in the study. Comparison of reproducibility in intra-species results became difficult because of the large number of extraction solvents tested and the wide diversity of evaluation models used. Although the number of in vitro and in vivo evaluations was high, only one clinical study was found (Abrus precatorius). In the phytochemical analyses, more than 225 compounds, mostly phenolic compounds, were identified. CONCLUSION: This review allowed the grouping of preclinical and clinical studies of several Brazilian species traditionally used for the treatment of many types of inflammation, corroborating new searches for their pharmacological properties as a way to aid public health. Furthermore, the large number of plants that have not yet been studied has encouraged new research to revive traditional knowledge.

Regulation of Gut Microbiota by Herbal Medicines.

Preserving host health and homeostasis is largely dependent on the human gut microbiome, a varied and ever-changing population of bacteria living in the gastrointestinal tract. This article aims to explore the multifaceted functions of the gut microbiome and shed light on the evolving field of research investigating the impact of herbal medicines on both the composition and functionality of the gut microbiome. Through a comprehensive overview, we aim to provide insights into the intricate relationship between herbal remedies and the gut microbiome, fostering a better understanding of their potential implications for human health.The gut microbiota is composed of trillions of microorganisms, predominantly bacteria, but also viruses, fungi, and archaea. It functions as a complex ecosystem that interacts with the host in various ways. It aids in nutrient metabolism, modulates the immune system, provides protection against pathogens, and influences host physiology. Moreover, it has been linked to a range of health outcomes, including digestion, metabolic health, and even mental well-being. Recent research has shed light on the potential of herbal medicines to modulate the gut microbiome. Herbal medicines, derived from plants and often used in traditional medicine systems, contain a diverse array of phytochemicals, which can directly or indirectly impact gut microbial composition. These phytochemicals can either act as prebiotics, promoting the growth of beneficial bacteria, or possess antimicrobial properties, targeting harmful pathogens. Several studies have demonstrated the effects of specific herbal medicines on the gut microbiome. For example, extracts from herbs have been shown to enhance the abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, while reducing potentially harmful microbes. Moreover, herbal medicines have exhibited promising antimicrobial effects against certain pathogenic bacteria. The modulation of the gut microbiome by herbal medicines has potential therapeutic implications. Research suggests herbal interventions could be harnessed to alleviate gastrointestinal disorders, support immune function, and even impact metabolic health. However, it is important to note that individual responses to herbal treatments can vary due to genetics, diet, and baseline microbiome composition. In conclusion, the gut microbiome is a critical player in maintaining human health, and its modulation by herbal medicines is a burgeoning area of research. Understanding the complex interactions between herbal compounds and gut microbiota will pave the way for innovative approaches to personalized healthcare and the development of herbal-based therapeutics aimed at promoting gut health and overall well-being.

A Comprehensive Review on Potential Chemical and Herbal Permeation Enhancers Used in Transdermal Drug Delivery Systems.

Using skin patches to deliver drugs is dependable and doesn't have the same issues as permeation enhancers, which help drugs get through the skin but struggle because of the skin's natural barrier. Strategies are required to increase topical bioavailability to enhance drug absorption. Natural compounds offer a promising solution by temporarily reducing skin barrier resistance and improving drug absorption. Natural substances allow a wider variety of medications to be distributed through the stratum corneum, offering a dependable approach to enhancing transdermal drug delivery. Natural substances have distinct advantages as permeability enhancers. They are pharmacologically effective and safe, inactive, non-allergenic, and non-irritating. These characteristics ensure their suitability for use without causing adverse effects. Natural compounds are readily available and well tolerated by the body. Studies investigating the structure-activity relationship of natural chemicals have demonstrated significant enhancer effects. By understanding the connection between chemical composition and enhancer activity, researchers can identify effective natural compounds for improving drug penetration. In conclusion, current research focuses on utilizing natural compounds as permeability enhancers in transdermal therapy systems. These substances offer safety, non-toxicity, pharmacological inactivity, and non-irritation. Through structure-activity relationship investigations, promising advancements have been made in enhancing drug delivery. Using natural compounds holds enormous potential for improving the penetration of trans-dermally delivered medications.

Propriedades Químicas e Farmacológicas do Gênero Copaifera no Tratamento de Lesões/feridas: Revisão Integrativa / Chemical and Pharmacological Properties of the Genus Copaifera in the Treatment of Injuries/wounds: Integrative Review / Propiedades Químicas y Farmacológicas del Género Copaifera en el Tratamiento de Lesiones/heridas: Revisión Integradora

Objetivo:Identificar propriedades químicas e farmacológicas do gênero Copaifera no tratamento de lesões e feridas. Método: Revisão integrativa da literatura realizada nas bases de dados LILACS, MEDLINE, PubMed, Taylor & Francis e Scopus, em janeiro de 2022, por meio da estratégia de busca: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Foram incluídos artigos originais, de texto completo, identificados de acordo nível de evidência, redigidos em português, inglês ou espanhol. Resultados: Na busca primária foram encontrados 261 artigos. Após a seleção sistematizada, 12 estudos foram selecionados para análise qualitativa. Espécies do gênero Copaifera apresentam propriedades farmacológicas favoráveis ao tratamento de feridas: controle da dor inflamatória, diminuição da reação inflamatória, reepitelização e reparo tecidual, angiogênese, retração da ferida e remodelagem de cicatrizes. Dentre as propriedades químicas associadas ao tratamento de lesões, destacam-se presença de compostos bioativos: diterpenos, 3-hidroxi-copálico, sesquiterpenos, éster kolavic-15-metílico. Entre os diterpenos testados, o caurenoico e os ácidos copálicos mostraram atividades hemolíticas significativas. Apenas o ácido copálico e o ácido hardwíckiico inibiram a produção de óxido nítrico em macrófagos ativados por lipopolissacarídeos. Conclusão: As plantas do gênero Copaifera apresentam propriedades químicas e farmacológicas favoráveis ao tratamento de lesões e feridas

Objective:To identify chemical and pharmacological properties of Copaifera in the treatment of injuries and wounds. Method: Integrative literature review conducted in the LILACS, MEDLINE, PubMed, Taylor & Francis and Scopus databases in January 2022, using the search strategy: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" and "Pharmacology" AND "Copaifera" AND "Wounds and Injuries." Original articles, full text, identified according to level of evidence, written in Portuguese, English or Spanish, were included. Results: In the primary search 261 articles were found. After systematized selection, 12 studies were selected for qualitative analysis. Species of the genus Copaifera have pharmacological properties favorable for wound treatment: control of inflammatory pain, reduction of inflammatory reaction, tissue reepithelialization and repair, angiogenesis, wound retraction and scar remodeling. Among the chemical properties associated with the treatment of injuries, the presence of bioactive compounds stand out: diterpenes, 3-hydroxy-copalic, sesquiterpenes, kolavic-15-methyl ester. Among the tested diterpenes, kaurenoic and copalic acids showed significant hemolytic activities. Only copalic acid and hardwickiic acid inhibited nitric oxide production in lipopolysaccharide-activated macrophages. Conclusion: Plants of the genus Copaifera have chemical and pharmacological properties favorable for the treatment of injuries and wounds.

Objetivo:Identificar las propiedades químicas y farmacológicas del género Copaifera en el tratamiento de lesiones y heridas. Método: Revisión integradora de la literatura realizada en las bases de datos LILACS, MEDLINE, PubMed, Taylor & Francis y Scopus, en enero de 2022, mediante la estrategia de búsqueda: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Se incluyeron artículos originales, a texto completo, identificados según el nivel de evidencia, escritos en portugués, inglés o español. Resultados: En la búsqueda primaria se encontraron 261 artículos. Tras una selección sistematizada, se seleccionaron 12 estudios para el análisis cualitativo. Las especies del género Copaifera presentan propiedades farmacológicas favorables para el tratamiento de las enfermedades: control del dolor inflamatorio, disminución de la reacción inflamatoria, reepitelización y reparación tecidual, angiogénesis, retracción de la piel y remodelación de las cicatrices. Entre las propiedades químicas asociadas al tratamiento de las lesiones, destaca la presencia de compuestos bioactivos: diterpenos, 3-hidroxicopálico, sesquiterpenos, éster kolavico-15-metilo. Entre los diterpenos probados, los ácidos kaurenoico y copálico mostraron actividades hemolíticas significativas. Sólo el ácido copálico y el ácido hardwickiico inhibieron la producción de óxido nítrico en macrófagos activados por lipopolisacáridos. Conclusión: Las plantas del género Copaifera presentan propiedades químicas y farmacológicas favorables para el tratamiento de lesiones y heridas.

Reducing myocardial infarction by combination of irisin and Dendrobium nobile Lindl through inhibiting nod-like receptor protein-3-related pyroptosis and activating PINK1/Parkin-mitophagy during aging.

Aging, a crucial risk factor for ischemic heart disease, has negative impacts on cardioprotective mechanisms. As such, there is still an unmet requirement to explore potential therapies for improving the outcomes of myocardial ischemia/reperfusion (IR) injury in elderly subjects. Here, we aimed to confirm the cardioprotective function of irisin/Dendrobium nobile Lindl (DNL) combination therapy against myocardial IR injury in aged rats, with a focus on the involvement of pyroptosis and mitophagy. Male aged Wistar rats (22-24 months old, 400-450 g; n = 54) underwent myocardial IR or sham surgery. Before IR operation, rats were pretreated with irisin (0.5 mg/kg, intraperitoneally) and/or DNL (80 mg/kg, orally) for 1 or 4 weeks, respectively, at corresponding groups. Cardiac function, lactate dehydrogenase (LDH) and cardiac-specific isoform of troponin-I (cTn-I) levels, the expression of proteins involved in pyroptosis (nod-like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein, c-caspase-1, and GSDMD-N) and mitophagy (PINK1 and Parkin), and pro-inflammatory cytokines levels were evaluated after 24 h of reperfusion. Irisin/DNL combined therapy significantly restored cardiac function and decreased LDH and cTn-I levels. It also downregulated pyroptosis-related proteins, upregulated PINK1 and Parkin, and decreased pro-inflammatory cytokines secretion. Pretreatment with Mdivi-1, as mitophagy inhibitor, abolished the cardioprotective action of dual therapy. This study revealed the cardioprotective effects of irisin/DNL combination therapy against IR-induced myocardial injury in aged rats, and also showed that the mechanism might be associated with suppression of NLRP3-related pyroptosis through enhancing the activity of the PINK1/Parkin mitophagy. This combination therapy is worthy of further detailed studies due to its potential to alleviate myocardial IR injury upon aging.

Gleditsiae fructus regulates osteoclastogenesis by inhibiting the c­Fos/NFATc1 pathway and alleviating bone loss in an ovariectomy model.

Medical and economic developments have allowed the human lifespan to extend and, as a result, the elderly population has increased worldwide. Osteoporosis is a common geriatric disease that has no symptoms and even a small impact can cause fractures in patients, leading to a serious deterioration in the quality of life. Osteoporosis treatment typically involves bisphosphonates and selective estrogen receptor modulators. However, these treatments are known to cause severe side effects, such as mandibular osteonecrosis and breast cancer, if used for an extended period of time. Therefore, it is essential to develop therapeutic agents from natural products that have fewer side effects. Gleditsiae fructus (GF) is a dried or immature fruit of Gleditsia sinensis Lam. and is composed of various triterpenoid saponins. The anti­inflammatory effect of GF has been confirmed in various diseases, and since the anti­inflammatory effect plays a major role in inhibiting osteoclast differentiation, GF was expected to be effective in osteoclast differentiation and menopausal osteoporosis; however, to the best of our knowledge, it has not yet been studied. Therefore, the present study was designed to examine the effect of GF on osteoclastogenesis and to investigate the mechanism underlying inhibition of osteoclast differentiation. The effects of GF on osteoclastogenesis were determined in vitro by tartrate­resistant acid phosphatase (TRAP) staining, pit formation assays, filamentous actin (F­actin) ring formation assays, western blotting and reverse transcription­quantitative PCR analyses. Furthermore, the administration of GF to an animal model exhibiting menopausal osteoporosis allowed for the analysis of alterations in the bone microstructure of the femur using micro­CT. Additionally, assessments of femoral tissue and serum were conducted. The present study revealed that the administration of GF resulted in a reduction in osteoclast levels, F­actin rings, TRAP activity and pit area. Furthermore, GF showed a dose­dependent suppression of nuclear factor of activated T­cells cytoplasmic, c­Fos and other osteoclastogenesis­related markers.

An Antimicrobial Fabric Using Nano-Herbal Encapsulation of Essential Oils.

Lab coats are widely used in biohazard laboratories and healthcare facilities as protective garments to prevent direct exposure to pathogens, spills, and burns. These cotton-based protective coats provide ideal conditions for microbial growth and attachment sites due to their porous nature, moisture-holding capacity, and retention of warmth from the user's body. Several studies have demonstrated the survival of pathogenic bacteria on hospital garments and lab coats, acting as vectors of microbial transmission. A common approach to fix these problems is the application of antimicrobial agents in textile finishing, but concerns have been raised due to the toxicity and environmental effects of many synthetic chemicals. The ongoing pandemic has also opened a window for the investigation of effective antimicrobials and eco-friendly and toxic-free formulations. This study uses two natural bioactive compounds, carvacrol and thymol, encapsulated in chitosan nanoparticles, which guarantee effective protection against four human pathogens with up to a 4-log reduction (99.99%). These pathogens are frequently detected in lab coats used in biohazard laboratories. The treated fabrics also resisted up to 10 wash cycles with 90% microbial reduction, which is sufficient for the intended use. We made modifications to the existing standard fabric tests to better represent the typical scenarios of lab coat usage. These refinements allow for a more accurate evaluation of the effectiveness of antimicrobial lab coats and for the simulation of the fate of any accidental microbial spills that must be neutralized within a short time. Further studies are recommended to investigate the accumulation of pathogens over time on antimicrobial lab coats compared to regular protective coats.

Impact of Alpinia galanga and zinc on semen quality and some reproductive hormone constituents in California rabbit bucks.

The objective of the current study was to investigate the influence of synergism of the dry powder of Alpinia galanga rhizomes (AGR) and/or zinc sulfate in the diet on semen quality and reproductive traits of California rabbit bucks. The study was conducted in two stages. First stage: appreciation of semen characteristics, 36 California rabbit bucks (aged 5 months) with average body weights of 2980 g were divided randomly into six treatments (six individuals each). The treatment groups were: first group, control fed basal diet (C); second group, fed basal diet plus 1 g AGR/kg dry matter (DM) (AGR1); third group, fed basal diet plus 2 g AGR/kg DM (AGR2); fourth group, fed basal diet plus 200 mg Zn/litre drinking water (Zn); fifth group, fed basal diet plus 1 g AGR/kg DM and 200 mg Zn/litre drinking water (AGR1 + Zn); sixth group, fed basal diet plus 2 g AGR/kg DM and 200 mg Zn/litre drinking water (AGR2 + Zn). Second stage: the previous bucks were used to determine the efficiency of semen on reproductive fertility traits, 48 mature does (aged 6 months, nulliparous) with an average body weight of 3050 ± 20.7 g were divided randomly into six treatments and inseminated with previous groups of treated bucks. The results of the first stage, recorded high activity on gonadotropins hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH), free testosterone (FT), progesterone (P4) and oestrogen (E217ß) concentrations for AGR1 + Zn and AGR2 + Zn compared with the control group. Groups AGR1, AGR2, AGR1 + Zn and AGR2 + Zn had significantly lowered concentrations of triglycerides, total cholesterol, low-density lipoprotein, and malondialdehyde (MDA), whereas high-density lipoprotein and total antioxidant capacity (TAC) were increased significantly compared with the control group. The group supplemented with AGR with or without Zn had significantly improved ejaculate volume, advanced motility, sperm concentration, and cell integrity. Fertility rate and litter size were improved in all groups compared with the control. It was concluded that supplementing diets with Alpinia galanga and Zn significantly increased sperm percentage, motility and reproductive hormones (testosterone, FSH, LH, E217ß, P4). This suggested that this plant when used may be favourable for improved sperm quality and fertility parameters.

Molecular Docking Analysis of Adhatoda vasica with Thromboxane A2 Receptor (TXA2R) (6IIU) and Antiviral Molecules for Possible Dengue Complications.

OBJECTIVE: The present study is an in silico model of platelet amplification potential of Adhatoda vasica, which can be used to treat thrombocytopenia in dengue complications. METHODS: Docking studies have proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In the present study, vasicine containing natural anti-dengue potential was subjected to docking studies using Schrodinger glides software (ver.11.1). The docking study was carried out to find out the potential molecular targets for selected protein. The docking was carried out on different ligands, like vasicine, ramatroban, chloroquine, celgosivir, and standard eltrombopag downloaded from PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Docking was performed using the ligand docking wizard of Glide-maestro 2018. RESULTS: The docking score of vasicine (-5.27) is nearly identical to the standard eltrombopag (-6.08), and both ligands bind with one hydrogen bond. The validation score of ramatroban is -12.39, binding with five hydrogen bonds, Celgosivir exhibited a docking score of -7.3 with three hydrogen bonds, and chloroquine displayed no hydrogen bond but had a docking score of -4.6. CONCLUSION: Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary, and it has been indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue; experimental evaluation will be carried out in the near future.

Atractylodes lancea for cholangiocarcinoma: Modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice.

Atractylodes lancea (Thunb.) DC. (A. lancea: AL) is a promising candidate for the treatment of cholangiocarcinoma (bile duct cancer). The study investigated (i) the propensity of capsule formulation of the standardized extract of AL (formulated AL) to modulate mRNA and protein expression and activities of CYP1A2 and CYP3A1 in rats after long- and short-term exposure, (ii) the pharmacokinetics of atractylodin (ATD: active constituent) after long-term administration of formulated AL, and (iii) the biodistribution of atractylodin-loaded polylactic-co-glycolic acid (ATD-PLGA-NPs) in mice. To investigate CYP1A2 and CYP3A1 modulatory activities following long-term exposure, rats of both genders received oral doses of the formulated AL at 1,000 (low dose), 3,000 (medium dose), and 5,000 (high dose) mg/kg body weight daily for 12 months. For short-term effects, male rats were orally administered the formulated AL at the dose of 5,000 mg/kg body weight daily for 1, 7, 14 and 21 days. The pharmacokinetic study was conducted in male rats after administration of the formulated AL at the dose of 5,000 mg/kg body weight daily for 9 months. The biodistribution study was conducted in a male mouse receiving ATD-PLGA-NPs at the equivalent dose to ATD of 100 mg/kg body weight. The high dose of formulated AL produced an inducing effect on CYP1A2 but an inhibitory effect on CYP3A1 activities in male rats. The low dose, however, did not inhibit or induce the activities of both enzymes in male and female rats. ATD reached maximum plasma concentration (Cmax) of 359.73 ng/mL at 3 h (tmax). Mean residence time (MRT) and terminal phase elimination half-life (t1/2z) were 3.03 and 0.56 h, respectively. The extent of biodistribution of ATD in mouse livers receiving ATD-PLGA-NPs was 5-fold of that receiving free ATD. Clinical use of low-dose AL should be considered to avoid potential herb-drug interactions after long-term use. ATD-PLGA-NPs is a potential drug delivery system for cholangiocarcinoma treatment.

Hangekobokuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus through its anti-inflammatory action.

BACKGROUND/AIMS: Gastroprokinetic agents are used for patients with postoperative ileus (POI), and the Japanese traditional herbal medicine daikenchuto (DKT) is one such agent used in the clinical setting. POI is caused by inflammation. DKT and rikkunshito have anti-inflammatory abilities in addition to their gastroprokinetic effects. The efficacy of Kampo formulations, including hangekobokuto (HKT), in patients with POI has been reported recently. Several authors have described the efficacy of honokiol, the primary component of Magnoliae Cortex, in HKT in mouse models of POI. We therefore analyzed the effect of HKT on POI model mice to determine the similarities in the mechanism of action between HKT and DKT. METHODS: HKT was administered orally to each mouse before and after intestinal manipulation was performed on the distal ileum. The gastrointestinal transit in vivo, leukocyte infiltration, and levels of inflammatory mediators, such as cytokines and chemokines, were analyzed. RESULTS: HKT significantly inhibited the infiltration of neutrophils and macrophages and led to the recovery of delayed intestinal transit. In addition, it significantly decreased inducible nitric oxide synthase (iNOS) as well as honokiol levels, suggesting anti-inflammatory activity. However, it did not inhibit the increase in levels of interleukin (IL)-1beta and IL-6, which are related to iNOS induction. In contrast, HKT increased levels of nerve growth factor (NGF) and suppressed those of nuclear factor-κB (NFκB), which are related to iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism. CONCLUSIONS: HKT exerted a POI-relieving effect similar to DKT in a murine POI model, and findings suggest that it may exert its anti-inflammatory activity through NGF.

Direct action of leptin, obestatin and ginkgo on hormone release by luteinised human ovarian granulosa cells.

CONTEXT: The role of metabolic hormones, medicinal plants and their interrelationships in the control of human reproductive processes are poorly understood. AIMS: To examine how leptin, obestatin and ginkgo (Ginkgo biloba L.) affect human ovarian hormone release. METHODS: We analysed the influence of leptin and obestatin alone and in combination with ginkgo extract on cultured human ovarian granulosa cells. The release of progesterone (P), insulin-like growth factor I (IGF-I), oxytocin (OT) and prostaglandin F (PGF) were analysed by enzyme immunoassay and enzyme-linked immunosorbent assay. KEY RESULTS: Leptin addition promoted the release of all the measured hormones. Obestatin stimulated the release of P, IGF-I and OT and inhibited PGF output. Ginkgo suppressed P, IGF-I and OT and promoted PGF release. Furthermore, ginkgo changed the stimulatory action of leptin on PGF to an inhibitory one. CONCLUSIONS: Leptin and obestatin are involved in the control of human ovarian hormone release and ginkgo influences their function. IMPLICATIONS: Leptin and obestatin could be useful as stimulators of human ovarian cell functions. The suppressive influence of ginkgo on ovarian function should lead to the development of ginkgo-containing drugs.

Efficacy and Mechanism of Pueraria lobata and Pueraria thomsonii Polysaccharides in the Treatment of Type 2 Diabetes.

Diabetes is called a "wasting and thirsting disorder" in Chinese traditional medicine because there is a depletion of vital substances in the body independent of the intake of food or water and an inability to reintroduce fluids through drinking. Pueraria lobata (Willd.) Ohwi (GG) and Pueraria thomsonii Benth. (FG) are traditional Chinese herbal medicines used in the treatment of wasting-thirst that reduce blood glucose levels. Flavonoids are the main pharmacodynamic components of GG and FG, and they are also the most studied components at present, but polysaccharides are also active components of GG and FG, which, however, are less studied. Therefore, this study aimed to investigate the effect of Pueraria polysaccharides (GG and FG polysaccharides) on type 2 diabetes (T2D), as well as their related mechanisms of action in terms of both intestinal flora and metabolomics. The C57BL/KsJ-db/db mouse model, a well-established model of obesity-induced T2D, was used in this study. The metabolomic analysis showed that Pueraria polysaccharides improved the metabolic profile of diabetic mice and significantly regulated metabolites and metabolic pathways. Both GG and FG polysaccharides regulated insulin resistance in mice by regulating PPAR signaling pathway so as to treat T2D. Additionally, Pueraria polysaccharides regulated the structure of gut microbiota and improved the diabetes-related metabolic pathway. Therefore, this study discovered the antidiabetic effects and potential mechanisms of Pueraria polysaccharides through multiple pathways involving gut microbiota and metabolites, providing a theoretical basis for further studies on their effects in the treatment of T2D.

Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-α, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1ß, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS.

The Novel Role of Crocus sativus L. in Enhancing Skin Flap Survival by Affecting Apoptosis Independent of mTOR: A Data-Virtualized Study.

BACKGROUND: Despite the improvements to enhance skin flap viability, the effects of ischemia-reperfusion (IR), oxidative stress, necrosis, and apoptosis are still challenging. Crocus sativus L. (Saffron) is highly noticeable due to its tissue-protective and antioxidant properties. So, we aimed to investigate its effects on skin flap viability, oxidative stress, apoptosis markers, histopathological changes, and mTOR/p-mTOR expression. MATERIALS AND METHODS: 40 Sprauge-Dawley rats, weighting 200-240 g, were divided into four groups including: (1) Sham (8 × 3 cm skin cut, without elevation); (2) Flap Surgery (8 × 3 cm skin flap with elevation from its bed); (3) Saffron 40 mg/kg + Flap Surgery; and (4) Saffron 80 mg/kg + Flap Surgery. Saffron was administrated orally for 7 days. At day 7, flap necrosis percentage, histopathological changes, malondialdehyde level, Myeloperoxidase and superoxide dismutase activity, Bax, Bcl-2, mTOR, and p-mTOR expression were measured. Protein expressions were controlled by ß-Actin. RESULTS: Saffron administration decreased flap necrosis percentage (p < 0.01), which was not dose-dependent. Treatment groups showed significant histological healing signs (Neovascularization, Fibroblast migration, Epithelialization, and Epithelialization thickness), decreased MDA content (p < 0.01), increased SOD (p < 0.01) and decreased MPO activity (p < 0.01). Bax and Bcl-2 expression, decreased and increased respectively in treated groups (p < 0.0001). mTOR and p-mTOR expression were not changed significantly in Saffron treated groups. CONCLUSION: Saffron could increase skin flap viability, alleviate necrosis, decrease oxidative stress and decrease apoptotic cell death, after skin flap surgery, but it acts independent of the mTOR pathway. So, Saffron could potentially be used clinically to enhance skin flap viability. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. https://www.springer.com/00266.

Premna microphylla Turcz pectin protected UVB-induced skin aging in BALB/c-nu mice via Nrf2 pathway.

Excessive exposure to ultraviolet B (UVB) irradiation is one of the major risk factors for skin photoaging. The aim of this study was to investigate the protective effect of Premna microphylla Turcz pectin (PMTP) against UVB-induced skin aging in BALB/c-nu mice. PMTP was characteristic of a low methoxyl RG-I pectin with Mw was 26.60 kDa, mainly composed of galacturonic acid. PMTP-containing cream efficiently inhibited the water loss, epidermal hyperplasia, matrix metalloproteinases-1 (MMP-1), and collagen destruction in UVB-induced skin injury mice. Additionally, topical administration of PMTP-containing cream significantly increased protein levels of the nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), macrophage-activating factor (Maf), and heme oxygenase 1 (HO-1), and the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). In contrast, application of PMTP-containing cream on mice skin decreased the protein levels of nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase ß (IKKß), and cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines. Taken togethmier, these findings suggest that PMTP might protect UVB-induced skin aging via activating Nrf2 pathway and suppressing NF-κB pathway.

Nephroprotective role of Echinacea purpurea against potassium dichromate-induced oxidative stress, inflammation, and apoptosis in rats.

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with the overproduction of free radicals, which induces oxidative damage. Echinacea purpurea (L.) Moench is an herbaceous perennial plant rich in phenolic components and frequently used for its medicinal benefits. The current work evaluated the effectiveness of E. purpurea (EP) against oxidative stress and nephrotoxicity induced by potassium dichromate in male rats. Male Wistar rats were divided into four groups: control, E. purpurea (EP; 50 mg/kg; once daily for 3 weeks), hexavalent chromium (Cr(VI); 15 mg/kg; single intraperitoneal dose), and EP + Cr(VI) where rats were pretreated with EP for 3 weeks before receiving CrVI, respectively. Results revealed that rats exposed to Cr(VI) showed a significant increase in PC, TBARS, and H2 O2 , kidney function biomarkers (Urea, creatinine, and uric acid), lactate dehydrogenase activity (LDH), TNF-α, IL-18, nuclear factor kappa B (NFκB), and IGF-1 (Insulin-like growth factor-1) levels as well as a considerable decline in metallothionein (MT), glutathione (GSH) content, enzymatic antioxidants (SOD, CAT, GPx, GR, and GST), alkaline phosphatase (ALP) activities, and protein content. Cr(VI) induced apoptosis in kidney tissues as revealed by upregulation of Bax and caspase 3 and downregulation of Bcl-2. Furthermore, EP treatment ameliorated the Cr(VI)-induced histopathological and ultrastructure variations of kidney tissue, which was confirmed by the biochemical and molecular data. It is clear from the results of this study that EP exerts nephroprotective effects by improving the redox state, suppressing inflammatory reaction and cell apoptosis as well as ameliorating the performance of kidney tissue architecture, which is eventually reflected by the improvement of kidney function in rats.