Search Results (700)

Recent years have seen growing medical interest in the influence of crosstalk between the gut microbiota and the endocannabinoidome (eCBome) on inflammation and pain modulation. Growing evidence indicates that gut microbiota can modify the effects of several marketed drugs, including analgesics. Cannabigerol (CBG) is an overlooked phytocannabinoid with a broad pharmacological spectrum and no psychotropic effects, which has anti-inflammatory and antinociceptive properties. This review aims to provide a comprehensive exploration of CBG and its role at the intersection of gut microbiota and eCBome, detailing the pharmacological mechanisms by which it acts as a promising therapeutic agent to modulate chronic inflammation and pain. Our data review suggests that CBG could act on the eCBome by activating CB2, PPARs, TRPV1, TRPA1, and α2-adrenergic receptors, while suppressing cellular and molecular mechanisms of inflammation, such as TNFα, COX-2, iNOS, IL-1β, and IL-6, and increasing antioxidant factors. These receptors and enzymes are distributed across neurons, glial, immune, and epithelial cells, which can also positively modulate gut microbiota and its metabolites, producing neurotransmitters, cytokines, and enzymes that regulate eCBome tone, and generating cannabinoid-mimetic compounds as part of pleiotropic functions. Nevertheless, CBG may exert direct effects on gut microbiota, promoting eubiosis and symbiotic bacteria. Moreover, there are no specific preclinical assays that demonstrate how CBG modulates the bidirectional communication between the gut microbiota and eCBome, addressing the specific mechanism involved in eCBome activation, and determining whether its anti-inflammatory and analgesic effects are dependent on gut microbiota type. Therefore, studies are required to evaluate this hypothesis to achieve translational medicine impact. Full article

The quinazoline/quinazolinone ring is known as a unique scaffold, and its derivatives possess a broad biological activity profile, including antibacterial, antifungal, anticonvulsant, anti-inflammatory, anti-HIV, and analgesic activity, primarily focusing on anticancer activity. In this study, the synthesis of 2-[[4-oxo-3-(substituted phenyl)-3,4-dihydro-(substituted quinazolin-2-yl)]thio]-N′-(aryl/heteroaryl methylene)acetohydrazide (4a–4x) derivatives and their potential anticancer activities were investigated on the lung cancer A549 cell line, the breast cancer MCF-7 cell line, and healthy fibroblast L929 cell line. Compounds 4c, 4i, 4m, and 4u were identified as the most cytotoxic and selective molecules on the A549 cell line (IC₅₀: 44.75–78.13 µM), while 4i, 4l, 4m, and 4u were identified as the most cytotoxic and selective molecules on the MCF-7 cell line (IC₅₀: 14.43–29.39 µM). The mechanisms of action of their anticancer activities were examined and studied. It was determined that these compounds induced strong apoptosis and significantly activated caspase-3 activation in both cell types and that they interrupted the cell cycle in the pre-G (sub G0) phase. Compounds 4m and 4u exhibited EGFR inhibition (IC₅₀: 4.80 µM, IC₅₀: 5.40 µM, respectively) at a level similar to the standard drug gefitinib (IC₅₀: 1.86 ± 0.43 µM). Based on the results of the biological activity assays, molecular docking, and molecular dynamics simulation studies, the 4-quinazolinone–acetyl hydrazone scaffold can be considered a promising structural framework with potential anticancer activity. More specifically, the findings of this study indicate that the acetyl moiety may function as an important pharmacophoric group, while the trisubstituted quinazolinone core may represent a favorable structural feature for caspase-3 activation. However, the same structural framework appears to be less favorable for EGFR inhibition, possibly due to steric constraints within the EGFR binding pockets. Full article

Background/Objectives: Excessive inflammation is a critical contributor to impaired oral mucosal wound healing, yet effective therapeutic strategies are still lacking. Although dehydrocorydaline (DHC) has been reported to exhibit anti-inflammatory and analgesic properties, its role in wound healing and the underlying mechanisms have not been fully elucidated. This study aimed to investigate whether DHC accelerates palatal wound healing and to elucidate the role of the p38 mitogen-activated protein kinase (MAPK)/CCL2 signaling axis in DHC-mediated regulation of macrophage chemotaxis. Methods:In vitro, macrophages were stimulated with 1 μg/mL lipopolysaccharide (LPS) and treated with DHC at 0.1, 1, and 10 μM. The chemotactic response and inflammatory function of macrophages were assessed using real-time PCR, ELISA, Western blotting, and Transwell assays. Molecular docking simulations and Western blotting analyses were performed to examine the regulatory effect of DHC on MAPK signaling pathway. In vivo, a full-thickness palatal mucoperiosteal wound extending from the left maxillary first to third molars was established in mice by scalpel scraping. The effects of topical 10 μM DHC gel on wound healing were evaluated using stereomicroscopy, histological staining, and real-time PCR at 0, 3, and 5 days post-modeling. Results:In vitro, DHC effectively downregulated the expression of chemokines, including C-C motif chemokine ligand 2 (Ccl2), Ccl5, Ccl22, C-X-C motif chemokine ligand 10 (Cxcl10), and Ccl24, with the most significant inhibitory effect on Ccl2 (70.8% inhibition). In Transwell assays, DHC reduced macrophage migration by 68.2%. Mechanistically, DHC prominently inhibited the activation of the MAPK signaling pathway. In vivo, DHC treatment accelerated wound healing and markedly reduced macrophage infiltration in mouse palatal wound tissues. Conclusions: These findings demonstrated that DHC accelerated palatal wound healing 1.6-fold in mice. DHC suppressed macrophage chemotaxis by 68.2% through modulation of the MAPK signaling pathway. Full article

Phytol, an acyclic diterpene alcohol and a key lipophilic side-chain moiety of chlorophyll, is widely distributed in nature. It exhibits potent antioxidant, anti-inflammatory, analgesic and broad-spectrum antibacterial activities. Notably, phytol can also effectively inhibit melanin production, repair the skin barrier, and exert profound anti-aging effects, making it a highly promising ingredient for daily skincare with substantial industrial application value. The skincare benefits of phytol are primarily achieved by constructing a multi-dimensional regulatory network involving defense, modulation and repair. Compared to conventional retinol-based skincare ingredients, phytol exhibits superior biocompatibility, mild irritation, and remarkable safety advantages. Nevertheless, its application is hindered by inherent limitations, including strong hydrophobicity, spontaneous aggregation tendency, and poor photothermal stability. These drawbacks severely restrict its dispersibility, storage stability and percutaneous bioavailability in aqueous cosmetic formulations. To address these deficiencies, nanodrug delivery systems (NDDS), such as liposomes, nanoemulsions, solid lipid nanoparticles and PLGA nanoparticles, have been widely employed. These nanocarriers can penetrate the skin barrier via the size effect, enabling targeted skin delivery and long-term controlled release of phytol. This review systematically summarizes the biological sources and metabolic fate of phytol, as well as its multi-mechanistic pharmacological effects on the skin. Furthermore, we outline the current application status and industrial development trends of phytol in mainstream cosmetics worldwide. This work aims to provide theoretical basis and forward-looking references for the development of high-efficiency, safe and stable phytol-derived skincare raw materials and topical formulations. Highlights: (1) Phytol, a natural acyclic diterpene alcohol, exerts multi-dimensional skincare effects including antioxidant, anti-inflammatory, whitening, anti-aging, and skin barrier repair activities via a defense–modulation–repair regulatory network. (2) Phytol may act as a mild, non-irritating functional alternative to retinoids, targeting PPAR/RXR pathways and avoiding TRPV1-mediated irritation, making it suitable for sensitive skin. (3) Poor water solubility and instability hinder phytol’s translation; nanodelivery systems effectively improve solubility, permeability, and sustained release. Full article

Aconitum L. species are widely recognized for their highly bioactive diterpenoid alkaloids, which contribute to their therapeutic potential and substantial toxicity. While Asian and European Aconitum species have been extensively studied in traditional medicine, phytochemistry, pharmacology, and toxicology, North American species remain comparatively underexplored. This review examines the ethnobotanical records, phytochemical data, toxicological mechanisms, and reported biological activities of North American Aconitum species, with emphasis on A. delphiniifolium and A. columbianum, the only native North American species with published alkaloid characterization. The literature was collected from scientific databases and ethnobotanical sources, with comparisons made to the better-studied Asian medicinal species, A. carmichaelii. Available research indicates that North American Aconitum species have limited documented medicinal use, although Alaskan Native groups historically used Aconitum-derived poisons in whale hunting. Phytochemical studies identified at least fifteen diterpenoid alkaloids in A. delphiniifolium and A. columbianum, including several compounds also found in A. carmichaelii with reported analgesic, anti-inflammatory, neuroprotective, and cytotoxic activities. However, direct pharmacological studies on North American species are lacking. These findings suggest that limited exploration of North American Aconitum reflects historical and research bias rather than the absence of therapeutic potential and highlights a significant research gap to support further metabolomic, pharmacological, and toxicological investigations of North American Aconitum species. Full article

Background/Objectives: Heracleum millefolium Diels (HMD) is a traditional Tibetan medicinal herb that has been reported to possess analgesic, anti-edematous, and anti-inflammatory activities. However, its chemical composition and anti-inflammatory mechanisms remain unclear. Methods: In this study, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS), combined with database searching and “seed”-based molecular networking, was used to systematically characterize the chemical constituents of HMD. Furthermore, an integrated strategy combining network pharmacology, molecular docking, and cellular validation was applied to explore potential anti-inflammatory mechanisms associated with HMD. Results: A total of 472 compounds were identified or tentatively identified from HMD. Network pharmacology analysis predicted five key targets, namely TNF, IL-6, IL-1β, GAPDH, and AKT1, together with four potential bioactive constituents, including velutin, artemitin, kaempferol, and naringenin. Pathway enrichment analysis indicated that the potential anti-inflammatory effects of HMD were mainly associated with lipid and atherosclerosis and the AGE-RAGE signaling pathway. Molecular docking suggested potential favorable interactions between the selected constituents and key targets. Moreover, cellular experiments demonstrated that the four compounds significantly inhibited inflammatory responses in LPS-stimulated RAW264.7 macrophages. Conclusions: This study systematically characterized the chemical profile of HMD and preliminarily explored its potential anti-inflammatory mechanisms, providing a scientific basis for further investigation of its bioactive constituents and pharmacological properties. Full article

Solanum elaeagnifolium has been utilized for its analgesic, anti-inflammatory, and antioxidant properties to treat a range of conditions, including pain and inflammation. It possesses antibacterial, insecticidal, and molluscicidal properties as well. To investigate the pharmacological potential of the S. elaeagnifolium extract, in vitro, in vivo, and in silico studies were used. Albumin denaturation, heat-induced anti-haemolytic action, and lipooxygenase inhibition were the three techniques used to test anti-inflammatory effectiveness. The phenolic chemicals utilized were identified through the use of high-performance liquid chromatography (HPLC). The effectiveness of the extract in lowering problems connected to diabetes was further evaluated by evaluating fructosamines, carbonyl groups, and β-amyloid formations in albumin glycation. Regarding in vivo studies, the Writhing test and the tail flick test were the two techniques used to evaluate analgesic activity. For docking analysis, we used the following identifiers: cyclooxygenase (PDB ID: 6COX), lipooxygenase (PDB ID: 3V99) and VC1 domain of the receptor for advanced glycation products (PDB ID: 7LMW). The most prevalent phenolic chemicals, according to HPLC analysis, were 3,4-dihydroxybenzoic acid (4.78%), caffeic acid (1.28%), gallic acid (8.18%), ursolic acid (2.6%), syringic acid (1.78%), quercetin (24.09%), catechin (6.67%), and p-coumaric acid (20.49%). Significant suppression of albumin glycation and fructosamine production was demonstrated by the extract, indicating that it may help lessen difficulties associated with diabetes. Furthermore, the extract demonstrated a strong anti-inflammatory impact, with an IC₅₀ of 146 ± 1.17 μg/mL for lipooxygenase inhibition, 87.64 ± 5.35 μg/mL for anti-haemolytic action, and 86.94 ± 1.63 μg/mL for albumin denaturation inhibition. A similar analgesic effect to those of analgesic medications was also demonstrated by SEFE extract. Reinforcing the relevance of the observed effects, the in silico study of the tested activities validated these findings. These findings indicate significant pharmacological promise in the management of diabetes consequences, including inflammation and protein glycation, as well as an analgesic. Full article

The genus Glaucium (Papaveraceae), comprising approximately 30 species, is widely distributed across the Mediterranean region, Europe, North Africa, and Central and Southwest Asia. In the flora of Türkiye, the genus is represented by 11 taxa and is commonly known as “boynuzlu gelincik” and “çömlek çatlatan”. The aim of this study is to explore the analgesic and anti-inflammatory properties of Glaucium corniculatum (L.) Rud subsp. refractum (NAB) Cullen, and Glaucium leiocarpum Boiss., which are found in Türkiye and are known for their high alkaloid content. Traditionally, G. leiocarpum has been used for wound care, cuts, bruises, acne, hemorrhoids, headache, and diarrhea, while G. corniculatum subsp. refractum has been employed as an antitussive and for external applications against ocular inflammations. Ethanolic extracts and crude alkaloid fractions from the aerial parts were evaluated in vivo in anti-inflammatory and antinociceptive test models. Anti-inflammatory activity was assessed by the carrageenan-induced paw edema model, while antinociceptive activity was determined using tail-flick and hot-plate tests. G. leiocarpum ethanolic extract (200 mg/kg) showed the highest anti-inflammatory activity, effectively suppressing carrageenan-induced edema (1.58 ± 0.30–1.73 ± 0.51 mL), and displayed the strongest antinociceptive activity, with tail-flick latencies reaching 23.91 ± 2.08 s (90 min) and 22.23 ± 1.97 s (150 min) and hot-plate latencies of 22.27 ± 4.76 s (30 min) and 23.00 ± 4.61 s (90 min). Bioactivity-guided fractionation of the most active extract was carried out using various chromatographic techniques. Thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analyses were employed throughout the isolation process to monitor fractions and determine their phytochemical profiles. As a result, two compounds were obtained and subsequently evaluated for their biological activities. The chemical structures of the isolated compounds were elucidated by spectroscopic methods, including ¹H-NMR, ¹³C-NMR, 2D-NMR, and LC-MS analyses as kaempferol-3-O-glucorhamnoside and quercetin-3-O-glucorhamnoside. Biological activity evaluation demonstrated that these compounds significantly contributed to the observed antinociceptive activity. These findings confirm that Glaucium species are traditionally used and highlight their potential to provide bioactive compounds with anti-inflammatory and pain-relieving effects. Full article

Gymnaconitum gymnandrum, a Tibetan medicinal herb, is distributed across high-altitude regions of China. Despite its high toxicity, it exhibits analgesic, anti-inflammatory, antitumor, and other pharmacological activities. It is used topically for skin conditions and orally for rheumatism. Its main bioactive components are alkaloids. A new organic amine alkaloid has been isolated from the plant and structurally identified using HRMS, NMR, and X-ray diffraction. Full article

Background: Doyerea emetocathartica (Cucurbitaceae) is endemic to the Brazilian Caatinga, commonly known as “cabeça-de-negro”, and is traditionally used to treat various conditions, including pain. Previous studies have demonstrated that the aqueous stem extract exhibits anti-inflammatory activity, which may be associated with the presence of cayaponoside D2, a major component of this extract. Given this, the aim of this study was to characterize the aqueous extract of D. emetocatharthica stems in terms of its Cayaponoside D2 content and to evaluate its antinociceptive activity using in vivo models, as well as to assess the involvement of the opioid pathway in the observed effect. Methods: For this purpose, the extract was analyzed by HPLC to quantify cayaponoside D2, and formalin- and acetic acid-induced nociception models were used to evaluate antinociceptive activity; the rats were divided into six groups (n = 6). The test groups received the aqueous extract of the D. emetocathartica stem (DEAQ) at doses of 25, 50, and 100 mg/kg; the control group received 0.9% saline; and morphine and indomethacin were used as positive controls. To investigate the mechanism of action involved in the antinociceptive effect, an evaluation was conducted of the role of the opioid pathway and the involvement of opioid receptors in the antinociceptive effect in the presence of specific antagonists: naloxone, CTOP, naltrindole, and Nor-BNI. Results: The analgesic activity of DEAQ was demonstrated in acetic acid-induced abdominal writhing and formalin-induced nociception models, with the most pronounced effects observed at doses of 50 and 100 mg kg⁻¹. In the formalin test, DEAQ showed a predominant effect during the inflammatory phase. Mechanistic investigations revealed that the antinociceptive activity involves the opioid system, mainly through μ-opioid receptors, with additional participation of δ-opioid receptors, as evidenced by the partial reversal of the effect by selective antagonists. These findings suggest that DEAQ may exert a multimodal analgesic effect involving both opioid and non-opioid pathways. This activity can be attributed to the presence of cayaponoside D2, which was quantified in the extract at a concentration of 108 mg g⁻¹ of dry extract. Conclusions: These findings demonstrate that the aqueous stem extract from D. emetocathartica exhibits promising analgesic activity mediated by the opioid pathway, reinforcing its pharmacological potential and supporting its traditional use in pain management. Full article

Marrubium vulgare L. aerial parts are a rich source of polyphenols with recognized antioxidant and anti-inflammatory properties; however, their therapeutic potential is limited due to poor stability and bioavailability. To enhance its pharmacological efficacy, a liposomal formulation of M. vulgare polyphenolic extract (MV-Lipos) was developed in this study by employing the thin-film hydration method. Before encapsulating, the free-extract (MV-Ext) was analyzed using LC-MS, and the resultant nanoliposomes were tested for physicochemical qualities, biological activity, and safety. MV-Lipos exhibited particle sizes ranging from 127 to 200 nm, an 84% encapsulation efficiency, and high colloidal stability (zeta potential −29.58 ± 0.40 mV). In vitro evaluations revealed anti-inflammatory and antioxidant activities without cytotoxic effects. In vivo, MV-Lipos significantly improved analgesic and anti-inflammatory responses. Specifically, a dose of 100 mg/kg lowered acetic acid induced writhing by up to 75.9% and carrageenan induced paw edema by 72%, with efficacy comparable to ibuprofen. A 28-day subacute toxicity assessment found no treatment-related adverse effects. Furthermore, molecular docking analyses validated the experimental results by revealing possible interactions with inflammation-related targets. Overall, liposomal encapsulation improved the biological efficacy and safety profile of M. vulgare polyphenols, highlighting their potential as natural agents for the management of pain and inflammatory conditions. Full article

Cannabis sativa contains more than 120 phytocannabinoids, with Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being the best characterized. This review synthesizes preclinical and clinical evidence on hemp-derived extracts, cannabinoids, and active compounds. THC primarily acts as a partial agonist at cannabinoid receptor type 1 (CB1) and type 2 (CB2), producing psychoactive, appetite-stimulating, antiemetic, and analgesic effects. CBD is non-intoxicating and has a multimodal profile involving CB1 negative allosteric modulation, CB2 inverse agonism or antagonism, inhibition of anandamide inactivation, and activity at 5-HT1A receptors, transient receptor potential channels, GPR55, and peroxisome proliferator-activated receptor gamma. Preclinical models of Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, epilepsy, and pain support anti-inflammatory, antioxidant, anti-excitotoxic, and glial-modulating mechanisms, but clinical translation remains uneven. The strongest evidence supports FDA-approved cannabidiol for Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex, and THC-based agents for refractory chemotherapy-induced nausea and vomiting and AIDS-related anorexia. Moderate-certainty evidence supports nabiximols for multiple sclerosis spasticity and small benefits in selected chronic neuropathic pain populations. Evidence remains insufficient or negative for acute pain, insomnia, most psychiatric disorders, and many promoted indications. Key risks include cannabis use disorder, cognitive and psychiatric effects, cardiovascular events, sedation, high-dose CBD hepatotoxicity, and drug interactions. Rigorous, long-term, product-standardized trials are needed. Full article

Chronic pain affects hundreds of millions of people and remains poorly managed, as the most effective drugs, including opioids, carry side effects that limit long-term use. Because inflammation drives both the initiation and maintenance of chronic pain, anti-inflammatory mechanisms are an attractive analgesic target. We investigated human alpha-1 antitrypsin (hAAT), a serine proteinase inhibitor with potent anti-inflammatory activity and established protection across disease models, as a candidate analgesic, using Aralast NP^®, a clinical-grade, already-approved formulation that makes findings directly translatable. Using calcium imaging and patch-clamp electrophysiology in mouse dorsal root ganglion (DRG) neurons, we found that hAAT reduced activation of low-voltage-activated Ca²⁺ channels and dampened intrinsic excitability. Veratridine-evoked Ca²⁺ responses, a sodium-channel-dependent readout of nociceptor activity, were suppressed by hAAT to a degree comparable to the selective sodium channel inhibitors ProTx-II (Na_V1.7) and VX-548 (Na_V1.8), driven by loss of the nociceptor-associated response profiles. In vivo, hAAT decreased pain sensitivity and pain-associated behaviors in both inflammatory and neuropathic models. Together, these findings reveal a mechanism by which hAAT suppresses nociceptor activity and position Aralast NP^® as a safe, effective candidate for treating chronic pain. Full article

Petiveria alliacea L. (commonly known as “anamu,” “guiné,” “hierba de zorro,” and “tipi”) has been widely used in Mesoamerican traditional medicine to treat pain and inflammation. However, scientific evidence supporting its efficacy in diabetic neuropathy remains limited. This study evaluated the antinociceptive potential of a methanolic leaf extract of P. alliacea in a murine model of alloxan-induced diabetic neuropathy and investigated its possible mechanisms of action. Diabetic CD-1 mice were evaluated for mechanical allodynia and hyperalgesia using the Von Frey test and for tonic pain using the formalin test. Pharmacological antagonists were administered to assess the involvement of opioid, nitric oxide, serotonergic, and GABAergic pathways. Phytochemical profiling was performed by LC-ESI-MS/MS, and potential pharmacological and pharmacokinetic properties of the identified metabolites were predicted using in silico tools (PASS online, SwissTargetPrediction, SwissADME, and pkCSM). The methanolic extract significantly reduced mechanical allodynia and hyperalgesia in diabetic mice and attenuated nociceptive responses in both phases of the formalin test, showing an effect comparable to gabapentin. Antinociceptive activity was not altered by naloxone or L-NAME but was significantly attenuated by methiothepin and bicuculline, suggesting that serotonergic and GABAergic pathways contribute, at least in part, to the observed antinociceptive effects. LC-ESI-MS/MS analysis identified 38 metabolites, including flavonoids, alkaloids, and terpenes, with in silico predictions supporting their potential analgesic and anti-inflammatory activities. The methanolic leaf extract of P. alliacea exhibits significant antinociceptive activity in diabetic neuropathy, partially likely to involve serotonergic and GABAergic mechanisms, supporting its ethnomedicinal use and its potential as a source of novel analgesic agents. Full article

Prospero autumnale L. is a Mediterranean medicinal plant traditionally employed for inflammatory and neurological disorders. Nonetheless, its safety profile, toxicity, and application for treating inflammation and pain are yet to be comprehensively established. This investigation aimed to assess the bioactivity and toxicity of extracts derived from its aerial (AgP) and underground (UgP) parts. The phytochemical constituents of various P. autumnale extracts were analyzed using LC-MS/MS, and their phenolic content was quantified. The biological activities were evaluated through in vitro assays—including antioxidant, anti-inflammatory, acetylcholinesterase-inhibitory, and photoprotection assessments—and in vivo experiments, including evaluations of acute oral toxicity, anti-inflammatory, and analgesic effects. UgP extracts demonstrated significant antioxidant activity, with the methanolic extract exhibiting the highest reducing and superoxide scavenging capacities. Dichloromethane and ethyl acetate extracts performed exceptionally well in ABTS and DPPH assays. The aqueous extract from AgP exhibited noteworthy anti-inflammatory and analgesic effects, surpassing diclofenac in vitro and demonstrating efficacy in vivo. It also showed considerable acetylcholinesterase inhibition, while the ethyl acetate extract displayed high photoprotective potential. The acute toxicity was moderate (LD₅₀: 300–400 mg/kg), indicating dose-dependent risks. LC-MS/MS analysis revealed diverse phenolics potentially contributing to both therapeutic and adverse effects. This research enhances the medicinal prospects of P. autumnale, provides new perspectives on plant utilization, and suggests its potential as a natural anti-inflammatory agent. However, due to moderate toxicity and dose-dependent effects, cautious application is advised. These findings underscore the importance of toxicological evaluation alongside bioactivity screening in ethnopharmacology to ensure safety. Full article