Characterizing environmental contamination by plant protection products along the land-to-sea continuum:a focus on France and French overseas territories.

Environmental compartments are contaminated by a broad spectrum of plant protection products (PPPs) that are currently widely used in agriculture or, for some of them, whose use was banned many years ago. The aim of this study is to draw up an overview of the levels of contamination of soils, continental aquatic environments, seawaters and atmosphere by organic PPPs in France and the French overseas territories, based on data from the scientific publications and the grey literature. It is difficult to establish an exhaustive picture of the overall contamination of the environment because the various compartments monitored, the monitoring frequencies, the duration of the studies and the lists of substances are not the same. Of the 33 PPPs most often recorded at high concentration levels in at least one compartment, 5 are insecticides, 9 are fungicides, 15 are herbicides and 4 are transformation products. The PPP contamination of the environment shows generally a seasonal variation according to crop cycles. On a pluriannual scale, the contamination trends are linked to the level of use driven by the pest pressure, and especially to the ban of PPP. Overall, the quality of the data acquired has been improved thanks to new, more integrative sampling strategies and broad-spectrum analysis methods that make it possible to incorporate the search for emerging contaminants such as PPP transformation products. Taking into account additional information (such as the quantities applied, agricultural practices, meteorological conditions, the properties of PPPs and environmental conditions) combined with modelling tools will make it possible to better assess and understand the fate and transport of PPPs in the environment, inter-compartment transfers and to identify their potential impacts. Simultaneous monitoring of all environmental compartments as well as biota in selected and limited relevant areas would also help in this assessment.

Individual use of self-medication and other remedies in COVID-19 outpatients in Western-Pomerania.

We analyzed data from positively tested COVID-19 outpatients to describe self-medication with OTC drugs and use of other remedies against symptoms of SARS-CoV-2 infection. We specifically considered their type and frequency, as well as associations with patient characteristics, and reasons for use. Data were collected between May 1, 2020 and February 22, 2021 with two questionnaires in an observational cohort study with PCR-confirmed SARS-CoV-2-positive adult outpatients in the district of Western Pomerania in Germany. 523 out of 710 outpatients (74%; 340 women and 183 men) reported using drugs and other remedies to relieve COVID-19-symptoms. Overall, participants reported utilization of 1282 finished dosage products or remedies, including 213 different ingredients. In the population of 710 outpatients, utilization of ibuprofen (26%), acetaminophen (21%), metamizole (14%), and acetylsalicylic acid (10%) was most commonly reported. Phytopharmaceuticals, herbal and animal products as well as vitamins and minerals were also frequently reported. Among the 523 participants who used drugs and other remedies, most commonly mentioned reasons for use were headache (40%), other kinds of pain (e.g. myalgia; 37%), fever (24%) and cough (16%). Our analysis showed that a majority of the participants tried to alleviate COVID-19-symptoms using drugs and other remedies. Especially analgesic and antipyretic agents, followed by herbal medicines, were used very frequently.Trial registration: German Register for Clinical Studies DRKS00021672, first registration on December 1st, 2020.

Quality by design approach of apocynin loaded clove oil based nanostructured lipid carrier as a prophylactic regimen in hemorrhagic cystitis in vitro and in vivo comprehensive study.

Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (23 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

Salvia verticillata (L.)-Biological Activity, Chemical Profile, and Future Perspectives.

Species belonging to the genus Salvia, Lamiaceae, have been deeply involved in the folk medicine of different nations since ancient times. Lilac sage, or Salvia verticillata L. (S. verticillata) is a less studied species from the genus. However, it seems to have a prominent potential for the future drug discovery strategies of novel phytopharmaceuticals. This review aims to summarise the data on the biological activity and the phytochemical profile of extracts and essential oils derived from S. verticillata. This review is based on data from 57 in vitro and in vivo studies. The chemical profile of S. verticillata includes different synergic compounds like phenolic acids, flavonoids, terpenes, and salvianolic acids. Although some small amounts of salvianolic acid B were found in S. verticillata extracts, the major compound among the salvianolic acids is salvianolic acid C, a compound associated with the potential for improving liver fibrosis, cardio- and hepatoprotection, and the inhibition of SARS-CoV-2 infection. The cannabinoid type 2 receptor agonist ß-caryophyllene is one of the major compounds in S. verticillata essential oils. It is a compound with a prominent potential in regenerative medicine, neurology, immunology, and other medical fields. The in vivo and the in vitro studies, regarding S. verticillata highlighted good antioxidant potential, anti-inflammatory, antibacterial, and antifungal activity. S.verticillata was also reported as a potential source of drug candidates for the treatment of neurodegenerative diseases such as Alzheimer's disease, because of the inhibitory activity on the acetylcholinesterase. However, the number of studies in this direction is limited.

The Invasive Alien Plant Solidago canadensis: Phytochemical Composition, Ecosystem Service Potential, and Application in Bioeconomy.

Solidago canadensis L. (Canadian goldenrod) is a widely distributed invasive herb from the Asteraceae family. It contains compounds that can change the soil structure and its nutritional components and thus affect indigenous species' growth, germination, and survival. Consequently, it can pose a major ecological threat to biodiversity. On the other hand, many studies show that this species, due to its chemical properties, can be used for many positive purposes in pharmacy, agriculture, medicine, cosmetic industry, etc. S. canadensis contains a diverse array of bioactive compounds that may be responsible for antioxidant, antimicrobial, and anticancer activities. Many studies have discussed the invasiveness of S. canadensis, and several chemical and genetic differences between this plant in native and introduced environments have been discovered. Previous ecological and environmental evaluations of the potential of S. canadensis as an ecosystem services provider have come out with four promising groups of its products: active extracts, essential oil, fuel, and others. Although identified, there is a need for detailed validation and prioritisation of ecosystem services. This article aims to overview the S. canadensis invasive features, emphasising chemical characterisation and its potential for providing ecosystem services. Moreover, it identifies scenarios and proposes a methodology for estimating S. canadensis use in bioeconomy.

Exploring the Potential Role of Phytopharmaceuticals in Alleviating Toxicities of Chemotherapeutic Agents.

BACKGROUND: Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments. AIM: The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations. MATERIALS AND METHODS: The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals. RESULTS: Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities. CONCLUSION: The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy.

Genus Echinophora-Biological Activity, Chemical Composition, and Future Perspectives.

Species belonging to the genus Echinophora (Apiaceae) have been used by humanity since ancient times as flavoring agents, preservatives, and medicines for the treatment of a broad spectrum of conditions, including respiratory, digestive and kidney disorders, fungi infections, wounds, and gastric ulcers. Phytochemical studies on this botanical genus mainly investigate the essential oil composition and reveal the species as a rich source of volatile compounds, including monoterpenes and phenylpropanoids. Among the non-volatile secondary metabolites, flavonoids, coumarins, phenolic acids, phytosterols, and polyacetylenes have been identified. Pharmacological studies revealed Echinophora extracts and essential oils exhibit different biological properties, including antibacterial, antifungal, anticancer, insecticidal, anti-inflammatory, and hepatoprotective activities. However, compared to other genera, the biological activity and chemical diversity of this genus are not well studied. In future decades, it is highly likely that the small genus Echinophora will play an important role in drug discovery and drug development.

Comparing Cancer Risks and Mortality between Phytopharmaceuticals and Estrogen-Progestogen Medications for Menopausal Women: A Population-Based Cohort Study.

We evaluated the long-term risks of overall cancer and all-cause mortality associated with five types of phytopharmaceuticals and the most commonly used estrogen-progestogen medications for the treatment of postmenopausal syndrome in women. Using data from Taiwan's National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2018, we conducted a 1:2 matched cohort study with 12,087 eligible patients. We compared phytopharmaceuticals -only users (n = 4029, phytopharmaceuticals group) with HRT-only users (n = 8058, HRT group) with a washout period of ≥6 months. The phytopharmaceuticals group had significantly lower risks of overall cancer and all-cause mortality than the HRT group (adjusted hazard ratio [95% confidence interval]: 0.60 [0.40-0.9] and 0.40 [0.16-0.99], respectively) after over 180 days of use. Bupleurum and Peony Formula were associated with lower risks of overall cancer and all-cause mortality (aHR: 0.57 [0.36-0.92] and 0.33 [0.11-1.05], respectively). In conclusion, phytopharmaceuticals may serve as an alternative therapy to HRT for alleviating menopausal symptoms and reducing health risks, leading to more favorable long-term health outcomes. Further randomized control trials are necessary to validate the findings of this study.

Harnessing controlled environment systems for enhanced production of medicinal plants.

Medicinal plants (MPs) are valued for their contributions to human health. However, the growing demand for MPs and the concerns regarding their quality and sustainability have prompted the reassessment of conventional production practices. Controlled environment cropping systems, such as vertical farms, offer a transformative approach to MP production. By enabling precise control over environment factors, such as light, carbon dioxide, temperature, humidity, nutrients, and airflow, controlled environments can improve the consistency, concentration, and yield of bioactive phytochemicals in MPs. This review explores the potential of controlled environment systems for enhancing MP production. First, we describe how controlled environments can overcome the limitations of conventional production in improving the quality of MP. Next, we propose strategies based on plant physiology to manipulate environment conditions for enhancing the levels of bioactive compounds in plants. These strategies include improving photosynthetic carbon assimilation, light spectrum signalling, purposeful stress elicitation, and chronoculture. We describe the underlying mechanisms and practical applications of these strategies. Finally, we highlight the major knowledge gaps and challenges that limit the application of controlled environments, and discuss future research directions.

Development of phytosterol-loaded silver nanoparticles for ameliorating haemorrhoidal complications via the AMPK pathway-a mechanistic approach.

The aim of the current study was to synthesize silver nanoparticles (PLSNPs) using green technology by means of phytosterol-enriched fractions fromBlumea laceraextracts (EAF) and evaluate their toxicological and anti-haemorrhoidal potential. The average size of the synthesized particles was found to be 85.64 nm by scanning electron microscopy and transmission electron microscopy. Energy dispersive spectroscopy showed the elemental composition of PLSNPs to be 12.59% carbon and 87.41% silver, indicating the capping of phytochemicals on the PLSNPs. The PLSNPs were also standardized for total phytosterol content using chemical methods and high-perfromance liquid chromatography. The PLSNPs were found to be safe up to 1000 mg kg-1as no toxicity was observed in the acute and sub-acute toxicity studies performed as per OECD guidelines. After the induction of haemorrhoids, experimental animals were treated with different doses of EAF, PLSNPs and a standard drug (Pilex) for 7 d, and on the eighth day the ameliorative potential was assessed by evaluating the haemorrhoidal (inflammatory severity index, recto-anal coefficient) and biochemical (tumour necrosis factor-alpha and interleukin-6) parameters and histology of the recto-anal tissue. The results showed that treatment with PLSNPs and Pilex significantly (p< 0.05) reduced haemorrhoidal and biochemical parameters. This was further supported by restoration of altered antioxidant status. Further, a marked reduction in the inflammatory zones along with minimal dilated blood vessels was observed in the histopathological study. The results of molecular docking studies also confirmed the amelioration of haemorrhoids via AMP-activated protein kinase (AMPK)-mediated reduction of inflammation and endothelin B receptor modification by PLSNPs. In conclusion, PLSNPs could be a good alternative for the management of haemorrhoids.

Neglected impacts of plant protection products on invertebrate aquatic biodiversity: a focus on eco-evolutionary processes.

The application of plant protection products (PPPs) may have delayed and long-term non-intentional impacts on aquatic invertebrates inhabiting agricultural landscapes. Such effects may induce population responses based on developmental and transgenerational plasticity, selection of genetic resistance, as well as increased extirpation risks associated with random genetic drift. While the current knowledge on such effects of PPPs is still scarce in non-target aquatic invertebrate species, evidences are accumulating that support the need for consideration of evolutionary components of the population response to PPPs in standard procedures of risk assessment. This mini-review, as part of a contribution to the collective scientific assessment on PPP impacts on biodiversity and ecosystem services performed in the period 2020-2022, presents a brief survey of the current results published on the subject, mainly in freshwater crustaceans, and proposes some research avenues and strategies that we feel relevant to fill this gap.

Nanovesicular ultraflexible invasomes and invasomal gel for transdermal delivery of phytopharmaceuticals.

Tweetable abstract Invasomes and invasomal gel are ultraflexible, soft vesicular, phospholipid based nanocarriers with deeper skin penetration ability for transdermal applications of drugs and phytopharmaceuticals.

Lipids Fortified Nano Phytopharmaceuticals: A Breakthrough Approach in Delivering Bio-actives for Improved Therapeutic Efficacy.

Phytopharmaceuticals, derived from natural sources, manifest tremendous potential for therapeutic applications. Nevertheless, effective delivery of these bio-actives presents significant challenges. A breakthrough in fortifying phytopharmaceuticals within phosphatidylcholine is a promising remedy to overcome solubility, permeability, and other related drawbacks. This intrinsic lipid, which is obtained from both natural and synthetic sources, confers numerous benefits, encompassing heightened solubility, augmented bioavailability, and enhanced stability. The conjugation of phytopharmaceuticals with phosphatidylcholine enables improved dermal permeation, absorption, targeted distribution, and the possibility of synergistic results, eventually improving therapeutic efficacy. Additionally, the use of phytopharmaceuticals enriched with phosphatidylcholine presents a promising route for overcoming the limitations imposed by conventional delivery techniques, encouraging more effective treatments. The review provides a thorough analysis of phosphatidylcholine- incorporated phytopharmaceuticals as nanomedicine with variables that significantly affect their therapeutic efficacy. Moreover, the review elaborates on how phosphatidylcholine improves solubility, permeability, and tissue distribution and boosts the potential of phytopharmaceuticals. Further, the review underscores the significance of nano-formulation strategies, analytical methodologies, and forthcoming prospects to propel this field forward. Furthermore, the review emphasizes the potential inherent in this innovative approach while highlighting the importance of additional research endeavors and collaborative initiatives to unlock the therapeutic benefits of phosphatidylcholinefortified phytopharmaceuticals, enhancing patient well-being.

Free radical scavenging polyphenols isolated from Phyllanthus niruri L. ameliorates hyperglycemia via SIRT1 induction and GLUT4 translocation in in vitro and in vivo models.

Type 2 diabetes milletus (T2DM) is a complex multifaceted disorder characterized by insulin resistance in skeletal muscle. Phyllanthus niruri L. is well reported sub-tropical therapeutically beneficial ayurvedic medicinal plant from Euphorbiaceae family used in various body ailments such as metabolic disorder including diabetes. The present study emphasizes on the therapeutic potential of Phyllanthus niruri L. and its phytochemical(s) against insulin resistance conditions and impaired antioxidant activity thereby aiding as an anti-hyperglycemic agent in targeting T2DM. Three compounds were isolated from the most active ethyl acetate fraction namely compound 1 as 1-O-galloyl-6-O-luteoyl-ß-D-glucoside, compound 2 as brevifolincarboxylic acid and compound 3 as ricinoleic acid. Compounds 1 and 2, the two polyphenols enhanced the uptake of glucose and inhibited ROS levels in palmitate induced C2C12 myotubes. PNEAF showed the potent enhancement of glucose uptake in palmitate-induced insulin resistance condition in C2C12 myotubes and significant ROS inhibition was observed in skeletal muscle cell line. PNEAF treated IR C2C12 myotubes and STZ induced Wistar rats elevated SIRT1, PGC1-α signaling cascade through phosphorylation of AMPK and GLUT4 translocation resulting in insulin sensitization. Our study revealed an insight into the efficacy of marker compounds isolated from P. niruri and its enriched ethyl acetate fraction as ROS scavenging agent and helps in attenuating insulin resistance condition in C2C12 myotubes as well as in STZ induced Wistar rat by restoring glucose metabolism. Overall, this study can provide prospects for the marker-assisted development of P. niruri as a phytopharmaceutical drug for the insulin resistance related diabetic complications.

Changes in the Prescription of Antibiotics and Phytopharmaceuticals in Children Treated for Acute Upper and Lower Respiratory Tract Infections in Pediatric Practices in Germany in 2013, 2018, and 2022.

Background: Little is known about the recent trends in antibiotic and phytopharmaceutical prescribing for acute upper (URIs) and lower respiratory tract infections (LRIs) in children and adolescents. Therefore, this study investigated changes in the prescription of antibiotics and phytopharmaceuticals in children diagnosed with acute URIs and LRIs in pediatric practices in Germany in 2013, 2018, and 2022. Methods: The present retrospective study included children aged 2-12 years diagnosed with acute URIs or LRIs in one of 180 pediatric practices in 2013, 2018, and 2022. The URIs included nasopharyngitis, sinusitis, pharyngitis, tonsillitis, laryngitis and tracheitis, and upper respiratory infections of multiple and unspecified sites, while the LRIs corresponded to bronchitis. The primary outcomes were the proportion of children being prescribed antibiotics and the proportion of those being prescribed phytopharmaceuticals. Results: A total of 120,894 children were diagnosed with acute URIs or LRIs in 2013 compared to 116,844 in 2018 and 127,821 in 2022. The prevalence of antibiotic prescription decreased for all diagnoses between 2013 and 2022. This decrease was statistically significant for both 2013-2018 and 2018-2022 for nasopharyngitis, pharyngitis, and bronchitis. Meanwhile, there was a significant increase in the use of phytopharmaceuticals for all diagnoses between 2013 and 2018. The prevalence of phytopharmaceutical prescription decreased slightly between 2018 and 2022, but this decrease was generally not statistically significant. Conclusions: The prescription of antibiotics has decreased and that of phytopharmaceuticals has increased in children diagnosed with acute URIs and LRIs in Germany over the last decade. More data are needed to corroborate these findings in other settings.

[Conservative and pharmacological treatment of benign prostatic hyperplasia : The German S2e-guideline 2023-part2]. / Konservative und medikamentöse Therapie des benignen Prostatasyndroms : Die deutsche S2e-Leitlinie 2023 ­ Teil 2.

BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH, in German guidelines: benign prostatic syndrome [BPS]) is considered the most common disease of the lower urinary tract in men and can have a tremendous impact on the quality-of-life of affected patients. Conservative and pharmacological therapy of this disease are of great importance, both in improving LUTS and reducing progression-related complications. OBJECTIVES: Presentation of the conservative and pharmacological treatment options according to the current German S2e guideline on BPS. MATERIALS AND METHODS: Summary and overview of chapters 9 and 10 of the current German S2e guideline on BPS. RESULTS: In addition to a controlled watchful waiting for BPS patients without an absolute indication for prostate surgery, a variety of phytopharmacological formulations and synthetic drugs according to the symptomatology and clinical progress are available. Phytotherapy should, due to inconsistent study data, only be considered for mild to moderate symptoms. Synthetic drugs include alpha-blockers, 5α-reductase inhibitors, phosphodiesterase inhibitors, antimuscarinics and, more recently, the ß3-agonist mirabegron in the current guideline. In addition, various combination therapies are listed and evaluated according to their indications, effects and side effects. CONCLUSIONS: The current German S2e guideline on the diagnosis and treatment of BPS provides an evidence-based foundation for finding the best possible and most effective medication.

Chemical occurrence of pesticides and transformation products in two small lentic waterbodies at the head of agricultural watersheds and biological responses in caged Gasterosteus aculeatus.

Recent monitoring campaigns have revealed the presence of mixtures of pesticides and their transformation products (TP) in headwater streams situated within agricultural catchments. These observations were attributed to the use of various agrochemicals in surrounding regions. The aim of this work was to compare the application of chemical and ecotoxicological tools for assessing environmental quality in relation to pesticide and TP contamination. It was achieved by deploying these methodologies in two small lentic water bodies located at the top of two agricultural catchments, each characterized by distinct agricultural practices (ALT: organic, CHA: conventional). Additionally, the results make it possible to assess the impact of contamination on fish caged in situ. Pesticides and TP were measured in water using active and passive samplers and suspended solid particles. Eighteen biomarkers (innate immune responses, oxidative stress, biotransformation, neurotoxicity, genotoxicity, and endocrine disruption) were measured in Gasterosteus aculeatus encaged in situ. More contaminants were detected in CHA, totaling 25 compared to 14 in ALT. Despite the absence of pesticide application in the ALT watershed for the past 14 years, 7 contaminants were quantified in 100 % of the water samples. Among these contaminants, 6 were TPs (notably atrazine-2-hydroxy, present at a concentration exceeding 300 ng·L-1), and 1 was a current pesticide, prosulfocarb, whose mobility should prompt more caution and new regulations to protect adjacent ecosystems and crops. Regarding the integrated biomarker response (IBRv2), caged fish was similarly impacted in ALT and CHA. Variations in biomarker responses were highlighted depending on the site, but the results did not reveal whether one site is of better quality than the other. This outcome was likely attributed to the occurrence of contaminant mixtures in both sites. The main conclusions revealed that chemical and biological tools complement each other to better assess the environmental quality of wetlands such as ponds.

Antimicrobial Activity of Psidium guajava Aqueous Extract against Sensitive and Resistant Bacterial Strains.

The inappropriate use of antimicrobials, along with environmental conditions, can lead to the emergence of resistant microorganisms. The use of phytopharmaceuticals and herbal medicines has a positive impact and represents a promising alternative. Psidium guajava extracts have been widely reported to have antimicrobial potential; however, studies reporting their activity against resistant bacterial strains are scarce. Because of the emerging resistance, the aim of this study was to analyze the antimicrobial capacity of the aqueous extract of guava leaves against wild-type and resistant bacterial strains. The aqueous extract obtained from the leaves of P. guajava was evaluated by HPLC for the content of total phenolics and tannins, antioxidant activity, and chemical composition. The antimicrobial activity of the extracts was analyzed by the disk diffusion and broth microdilution methods. The results of the chemical analysis of the extracts showed total phenolics content of 17.02 ± 6.87 mg/g of dry extract, total tannin content of 14.09 ± 1.20 mg of tannic acid equivalents/g of dry extract, and moderate antioxidant capacity with an EC50 value of 140 µg/mL. Flavonoids are the major compounds (rutin, hesperidin, and quercetin), followed by phenolic acids. Disk diffusion test results showed the presence of inhibition halos for Gram-positive bacteria (Staphylococcus aureus, sensitive and resistant; Staphylococcus pseudintermedius, sensitive and resistant; and Streptococcus spp., beta-hemolytic), while for Gram-negative bacteria (Escherichia coli, sensitive and resistant), there was no inhibition in the tested concentration range. The Minimal Inhibitory Concentration was 6.8 mg/mL for all Gram-positive strains evaluated. The present study demonstrated the antimicrobial activity of the aqueous extract of P. guajava against sensitive and resistant Gram-positive bacteria. The better antimicrobial activity found in the present study compared with previously reported activity should be highlighted and may be related to the higher concentration of total phenolics present in the tested extract. Moreover, the content of tannins found suggests a species with high quality that produces tannins. These new findings suggest an innovative profile regarding therapeutic resources that can be adopted to combat resistant microbial strains.

Natural product-derived therapies for treating drug-resistant epilepsies: From ethnopharmacology to evidence-based medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy is one of the most prevalent neurological human diseases, affecting 1% of the population in all age groups. Despite the availability of over 25 anti-seizure medications (ASMs), which are approved in most industrialized countries, approximately 30% of epilepsy patients still experience seizures that are resistant to these drugs. Since ASMs target only limited number of neurochemical mechanisms, drug-resistant epilepsy (DRE) is not only an unmet medical need, but also a formidable challenge in drug discovery. AIM: In this review, we examine recently approved epilepsy drugs based on natural product (NP) such as cannabidiol (CBD) and rapamycin, as well as NP-based epilepsy drug candidates still in clinical development, such as huperzine A. We also critically evaluate the therapeutic potential of botanical drugs as polytherapy or adjunct therapy specifically for DRE. METHODS: Articles related to ethnopharmacological anti-epileptic medicines and NPs in treating all forms of epilepsy were collected from PubMed and Scopus using keywords related to epilepsy, DRE, herbal medicines, and NPs. The database clinicaltrials.gov was used to find ongoing, terminated and planned clinical trials using herbal medicines or NPs in epilepsy treatment. RESULTS: A comprehensive review on anti-epileptic herbal drugs and natural products from the ethnomedical literature is provided. We discuss the ethnomedical context of recently approved drugs and drug candidates derived from NPs, including CBD, rapamycin, and huperzine A. Recently published studies on natural products with preclinical efficacy in animal models of DRE are summarized. Moreover, we highlight that natural products capable of pharmacologically activating the vagus nerve (VN), such as CBD, may be therapeutically useful to treat DRE. CONCLUSIONS: The review highlights that herbal drugs utilized in traditional medicine offer a valuable source of potential anti-epileptic drug candidates with novel mechanisms of action, and with clinical promise for the treatment of drug-resistant epilepsy (DRE). Moreover, recently developed NP-based anti-seizure medications (ASMs) indicate the translational potential of metabolites of plant, microbial, fungal and animal origin.

Multiple Protein Biomarkers and Different Treatment Strategies for Colorectal Carcinoma: A Comprehensive Prospective.

In this review, we emphasized important biomarkers, pathogenesis, and newly developed therapeutic approaches in the treatment of colorectal cancer (CRC). This includes a complete description of small-molecule inhibitors, phytopharmaceuticals with antiproliferative potential, monoclonal antibodies for targeted therapy, vaccinations as immunotherapeutic agents, and many innovative strategies to intervene in the interaction of oncogenic proteins. Many factors combine to determine the clinical behavior of colorectal cancer and it is still difficult to comprehend the molecular causes of a person's vulnerability to CRC. It is also challenging to identify the causes of the tumor's onset, progression, and responsiveness or resistance to antitumor treatment. Current recommendations for targeted medications are being updated by guidelines throughout the world in light of the growing number of high-quality clinical studies. So, being concerned about the aforementioned aspects, we have tried to present a summarized pathogenic view, including a brief description of biomarkers and an update of compounds with their underlying mechanisms that are currently under various stages of clinical testing. This will help to identify gaps or shortfalls that can be addressed in upcoming colorectal cancer research.