ABSTRACT
AIM OF THE STUDY: The growing resistance of helminth parasites to currently available commercial anthelmintic drugs, combined with apprehensions regarding detrimental chemical residues in livestock products, has sparked an interest in exploring medicinal plants as an alternative strategy for treating helminthiasis. As a result, this study was designed to investigate the anthelmintic activity of crude methanolic extracts (CME) of Saussurea costus root on Ascaridia.galli, a pathogenic nematode of poultry. MATERIALS AND METHODS: In vitro, the anthelmintic effect of Saussurea costus root was evaluated in comparison to commercial anthelmintic, levamisole on the adult nematode parasites, A.galli using worm motility inhibition (WMI) test. The CME of S.costus was also evaluated for in vivo anthelmintic activity in chickens experimentally infected with Ascaridia galli. For the in vivo study, one hundred-day-old chickens were orally infected with embryonated eggs of A. galli worms. The efficacy of the plant extract as an anthelmintic was assessed through two tests: faecal egg count reduction (FECR) test and worm count reduction (WCR) test. The study investigated three distinct doses of plant extract under in vivo setup: 500 mg kg-1 body weight (bw), 1000 mg kg-1 bw, and 2000 mg kg-1 bw. RESULTS: In vitro, all the tested concentrations of S.costus (25 mg/ml, 50 mg/ml, and 100 mg/ml) showed a significant (P < 0.001) anthelmintic effects on live adult A. galli worms in terms of inhibition of worm motility at different hours post-treatment. At the highest concentration of the extract, we observed worm motility inhibition of 100% at 24 h post-exposure. On day 14 post-treatment, all birds were slaughtered, and adult A. galli worms were subsequently retrieved from their small intestines. Birds treated with CME extract of S. costus root exhibited a significant (P < 0.001) reduction in faecal egg count. However, the administration of the extract at the dosage of 500 mg kg-1bw to the birds did not reveal any significant (P > 0.05) differences in the worm count compared to the negative control group. The CME of S. costus at a dose of 2000 mg kg-1bw showed the highest anthelmintic activity by inducing 83.10% FECR and 76.47% WCR. CONCLUSION: In conclusion, the root extract of S. costus has a promising anthelmintic activity on A. galli as demonstrated by the results of the present experiment.
Subject(s)
Anthelmintics , Ascaridia , Ascaridiasis , Chickens , Plant Extracts , Poultry Diseases , Saussurea , Animals , Ascaridia/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Poultry Diseases/parasitology , Poultry Diseases/drug therapy , Anthelmintics/pharmacology , Chickens/parasitology , Saussurea/chemistry , Ascaridiasis/veterinary , Ascaridiasis/drug therapy , Ascaridiasis/parasitology , Parasite Egg Count , Feces/parasitology , Plant Roots/chemistry , Levamisole/pharmacology , Levamisole/therapeutic useABSTRACT
The interest in Pickering emulsions is based on the possibility of replacing classical emulsifiers with solid particles. These emulsions are very attractive in the pharmaceutical field for their stability virtues and as a vehicle to deliver active ingredients. The study aimed to analyze the properties of the residual film of the Pickering emulsions on the human skin compared to conventional systems. For this project, three types of solid particles were used: titanium dioxide, zinc oxide and silicon dioxide. All of them are capable of stabilizing the oil/water interface and thus forming totally emulsified systems. To create an emulsion of reference, a classical surfactant was used as an excipient. Complementary systems containing both particles and the emulsifier were also analyzed. Then, a combined approach between physicochemical and biometrological in vivo analysis was employed. The study proved that Pickering emulsions stabilized by the metal oxides were distinct from the reference emulsion in terms of droplet sizes and organization, rheological and textural responses. Consequently, it impacted the properties of the residual film once the product was applied to the skin. The particle-stabilized emulsions formed a hydrophobic film counter to conventional excipients. Also, the Friction parameter (or the roughness of the film) was directly linked to the quantity of the particles used in the formulation and their perception on the skin surface. The use of the particles blurs the glossy effect of the oil phase. Finally, it was observed that the appearance of the residual film was impacted by the type of the particle, namely TiO2 and ZnO particles.
Subject(s)
Emulsions , Excipients , Silicon Dioxide , Skin , Titanium , Zinc Oxide , Humans , Excipients/chemistry , Skin/metabolism , Titanium/chemistry , Zinc Oxide/chemistry , Silicon Dioxide/chemistry , Particle Size , Adult , Surface-Active Agents/chemistry , Rheology , Administration, Cutaneous , Hydrophobic and Hydrophilic Interactions , Female , Chemistry, Pharmaceutical/methodsABSTRACT
The bioactive extracts of traditional medicinal plants are rich in polyphenols and help to rejuvenate skin. The study was designed to assess the skin rejuvenating effects of a stable cream enriched with 4% I. argentea (IaMe) extract. The quantity of polyphenols by spectrophotometric methods was TPC, 101.55 ± 0.03 mg GAE/g and total flavonoid content; 77.14 ± 0.13 mg QE/g, while HPLC-PDA revealed gallic acid; 4.91, chlorogenic acid 48.12, p-coumaric acid 0.43, and rutin 14.23 µg/g. The significant results of biological activities were observed as DPPH; 81.81% ± 0.05%, tyrosinase; 72% ± 0.23% compared to ascorbic acid (92.43% ± 0.03%), and kojic acid (78.80% ± 0.19%) respectively. Moreover, the promising sun protection effects Sun protection factor of extract (20.53) and formulation (10.59) were observed. The active cream formulation (w/o emulsion) was developed with liquid paraffin, beeswax, IaMe extract, and ABIL EM 90, which was stable for 90 days as shown by various stability parameters. The rheological results demonstrated the active formulation's non-Newtonian and pseudo-plastic characteristics and nearly spherical globules by SEM. The IaMe loaded cream was further investigated on human trial subjects for skin rejuvenating effects and visualized in 3D skin images. Herein, the results were significant compared to placebo. IaMe formulation causes a substantial drop in skin melanin from -1.70% (2 weeks) to -10.8% (12 weeks). Furthermore, it showed a significant increase in skin moisture and elasticity index from 7.7% to 39.15% and 2%-30%, respectively. According to the findings, Indigofera argentea extract has promising bioactivities and skin rejuvenating properties, rationalizing the traditional use and encouraging its exploitation for effective and economical cosmeceuticals.
ABSTRACT
This study explored the existence forms(original constituents and metabolites) of Tiantian Capsules, Aloe, and Tiantian Capsules without Aloe in rats for the first time, aiming to clarify the contribution of Aloe to the existence form of Tiantian Capsules. Rats were administrated with corresponding drugs by gavage once a day for seven consecutive days. All urine and feces samples were collected during the seven days of administration, and blood samples were collected 0.5, 1, and 1.5 h after the last administration. UHPLC-Q-TOF-MS was employed to detect and identify the original constituents and metabolites in the samples. A total of 34, 28, and 2 original constituents and 64, 94, and 0 metabolites were identified in the samples of rats administrated with Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe, respectively. The main metabolic reactions were methylation, hydrogenation, hydroxylation, dehydroxylation, glucuronidation, and sulfation. This study clarified for the first time the existence forms and partial metabolic pathways of Aloe, Tiantian Capsules, and Tiantian Capsules without Aloe in rats, laying a foundation for revealing their effective forms. The findings are of great significance to the research on the functioning mechanism and quality control of Aloe and Tiantian Capsules.
Subject(s)
Aloe , Drugs, Chinese Herbal , Rats , Animals , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/metabolism , Administration, Oral , Feces , CapsulesABSTRACT
Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons. VIP neurons are important for light entrainment and synchronization of suprachiasmatic nucleus neurons, whereas AVP neurons are important for circadian period determination. Output targets of the suprachiasmatic nucleus include the hypothalamus (subparaventricular zone, paraventricular hypothalamic nucleus, preoptic area, and medial hypothalamus), the thalamus (paraventricular thalamic nuclei), and lateral septum. The suprachiasmatic nucleus also sends information through several brain regions to the pineal gland. The olfactory bulb is thought to be able to generate a circadian rhythm without the suprachiasmatic nucleus. Some reports indicate that circadian rhythms of the olfactory bulb and olfactory cortex exist in the absence of the suprachiasmatic nucleus, but another report claims the influence of the suprachiasmatic nucleus. The regulation of circadian rhythms by sensory inputs other than light stimuli, including olfaction, has not been well studied and further progress is expected.
Subject(s)
Hypothalamus , Suprachiasmatic Nucleus , Animals , Suprachiasmatic Nucleus/metabolism , Hypothalamus/metabolism , Circadian Rhythm/physiology , Vasoactive Intestinal Peptide/metabolism , Sleep , Arginine Vasopressin/metabolismABSTRACT
Photobiomodulation (PBM) has attracted attention as a treatment for chronic pain. Previous studies have reported that PBM of the sciatic nerve inhibits neuronal firing in the superficial layers (lamina I-II) of the spinal dorsal horn of rats, which is evoked by mechanical stimulation that corresponds to noxious stimuli. However, the effects of PBM on the deep layers (lamina III-IV) of the spinal dorsal horn, which receive inputs from innocuous stimuli, remain poorly understood. In this study, we examined the effect of PBM of the sciatic nerve on firing in the deep layers of the spinal dorsal horn evoked by mechanical stimulation. Before and after PBM, mechanical stimulation was administered to the cutaneous receptive field using 0.6-26.0 g von Frey filaments (vFFs), and vFF-evoked firing in the deep layers of the spinal dorsal horn was recorded. The vFF-evoked firing frequencies were not altered after the PBM for any of the vFFs. The inhibition rate for 26.0 g vFF-evoked firing was approximately 13 % in the deep layers and 70 % in the superficial layers. This suggests that PBM selectively inhibits the transmission of pain information without affecting the sense of touch. PBM has the potential to alleviate pain while preserving the sense of touch.
Subject(s)
Low-Level Light Therapy , Rats , Animals , Rats, Sprague-Dawley , Spinal Cord Dorsal Horn , Neurons , Sciatic Nerve , Pain , Spinal Cord/physiologyABSTRACT
Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.
Subject(s)
Fatty Acids, Omega-3 , Geographic Atrophy , Wet Macular Degeneration , Humans , Fatty Acids, Unsaturated/therapeutic use , Fatty Acids , Fatty Acids, Omega-3/therapeutic useABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: This research substantiates the traditional use of Glycyrrhiza uralensis Fisch. for liver health, with scientific evidence of the non-toxic and lipid-lowering properties of licorice sprout extracts. The sprouts' rich mineral and amino acid content, along with their strong antioxidant activity, reinforce their value in traditional medicine. These findings bridge ancient herbal practices with modern science, highlighting licorice's potential in contemporary therapeutic applications. AIM OF THE STUDY: The study aimed to investigate the dietary and medicinal potential of G. uralensis sprouts by assessing their safety, nutritional content, and antioxidant properties using both plant and animal models. Specifically, the study sought to determine the effects of different sizes of licorice sprouts on lipid metabolism in human liver cancer cells and their overall impact on rat health indicators. MATERIALS AND METHODS: The study examined the effects of aqueous and organic extracts from G. uralensis sprouts of varying lengths on the cytotoxicity, lipid metabolism, and antioxidant activity in HepG2 cells, alongside in vivo impacts on Sprague-Dawley rats, using MTT, ICP, and HPLC. It aimed to assess the potential health benefits of licorice sprouts by analyzing their protective effects against oxidative stress and their nutritional content. RESULTS: Licorice sprout extracts from G. uralensis demonstrated no cytotoxicity in HepG2 cells, significantly reduced lipid levels, and enhanced antioxidant activities, with the longest sprouts (7 cm) showing higher mineral, sugar, and arginine content as well as increased glycyrrhizin and liquiritigenin. In vivo studies with Sprague-Dawley rats revealed weight gain and improved antioxidant enzyme activities in blood plasma and liver tissues after consuming the extracts, highlighting the sprouts' dietary and therapeutic potential. CONCLUSIONS: This study is the first to demonstrate that G. uralensis sprouts, particularly those 7 cm in length, have no cytotoxic effects, reduce lipids, and have high mineral and antioxidant contents, offering promising dietary and therapeutic benefits.
Subject(s)
Glycyrrhiza uralensis , Glycyrrhiza , Rats , Humans , Animals , Glycyrrhiza uralensis/chemistry , Glycyrrhiza/chemistry , Antioxidants/pharmacology , Antioxidants/analysis , Rats, Sprague-Dawley , Plant Roots/chemistry , Plant Extracts/chemistry , Minerals/analysis , LipidsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis. MATERIALS AND METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects. RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index RCOX-2/COX-1 lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < damnacanthol < rubiadin < damnacanthol-3-O-ß-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with RCOX2/COX1 ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands. CONCLUSION: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.
Subject(s)
Methyl Ethers , Morinda , Rubiaceae , Humans , Mice , Animals , Morinda/chemistry , Rubiaceae/chemistry , Molecular Docking Simulation , Cyclooxygenase 2 , Quercetin/analysis , Plant Roots/chemistry , Anthraquinones/pharmacology , Anthraquinones/therapeutic use , Plant Extracts/therapeutic use , Plant Extracts/toxicity , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/analysis , Glycosides/chemistry , Inflammation/drug therapy , Methyl Ethers/analysis , Phytochemicals/therapeutic use , Phytochemicals/toxicityABSTRACT
The low efficiency of in vivo transfection of a few fibres revealed a novel tissue network that temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibres began to grow after complete fibre degradation, synchronous inflammation, myoblast and myotube formation. Neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) was first detected in this system. The neonatal, fast and slow SERCA isoforms displayed consequent changes with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that expression of the slow myosin heavy chain and the slow muscle type SERCA2a are differentially regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SERCA1b shRNA stimulated fibre size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished by co-transfection of Cain or with perimuscular injection of IL4 antibody. This revealed a novel signalling network resembling scale-free networks which, starting from transfected fibre myonuclei as "hubs", can amplify growth stimulation uniformly in the entire regenerating muscle.
Subject(s)
Acupuncture Therapy , Muscle, Skeletal , Rats , Animals , Muscle, Skeletal/metabolism , Muscle Fibers, Skeletal/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , TransfectionABSTRACT
The drug efficacy evaluation of tumor-selective photosensitive substances was expected to be enabled by imaging the fluorescence intensity in the tumor area. However, fluorescence observation is difficult during treatments that are performed during gastrointestinal endoscopy because of the challenges associated with including the fluorescence filter in the camera part. To address this issue, this study developed a device that integrates a narrow camera and a laser diffuser to enable fluorescence imaging through a forceps port. This device was employed to demonstrate that a laser diffuser with an NIR fluorescence imaging sensor could be delivered through a 3.2 mm diameter port. In addition, fluorescence images of Cetuximab-IR700 were successfully observed in two mice, and the fluorescence intensity confirmed that the fluorescence decayed within 330 s. This device is expected to have practical application as a tool to identify the optimal irradiation dose for tumor-selective photosensitive substances under endoscopy.
Subject(s)
Light , Phototherapy , Mice , Animals , Cell Line, Tumor , Phototherapy/methods , Optical Imaging/methods , Endoscopy, GastrointestinalABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Liriope spicata Lour., a species listed in the catalogue of 'Medicinal and Edible Homologous Species', is traditionally used for the treatment of fatigue, restlessness, insomnia and constipation. AIM OF THE STUDY: This study is aimed to evaluate the sedative and hypnotic effect of the saponins from a natural plant L. spicata Lour. in vivo. MATERIALS AND METHODS: The total saponin (LSTS) and purified saponin (LSPS) were extracted from L. spicata, followed by a thorough analysis of their major components using the HPLC-MS. Subsequently, the therapeutic efficacy of LSTS and LSPS was evaluated by the improvement of anxiety and depression behaviors of the PCPA-induced mice. RESULTS: LSTS and LSPS exhibited similar saponin compositions but differ in their composition ratios, with liriopesides-type saponins accounting for a larger proportion in LSTS. Studies demonstrated that both LSTS and LSPS can extend sleep duration and immobility time, while reducing sleep latency in PCPA-induced mice. However, there was no significant difference in weight change among the various mice groups. Elisa results indicated that the LSTS and LSPS could decrease levels of NE, DA, IL-6, and elevate the levels of 5-HT, NO, PGD2 and TNF-α in mice plasma. LSTS enhanced the expression of neurotransmitter receptors, while LSPS exhibited a more pronounced effect in regulating the expression of inflammatory factors. In conclusion, the saponins derived from L. spicata might hold promise as ingredients for developing health foods with sedative and hypnotic effects, potentially related to the modulation of serotonergic and GABAAergic neuron expression, as well as immunomodulatory process.
Subject(s)
Saponins , Sleep Initiation and Maintenance Disorders , Animals , Mice , Hypnotics and Sedatives/pharmacology , Hypnotics and Sedatives/therapeutic use , Sleep Initiation and Maintenance Disorders/chemically induced , Sleep Initiation and Maintenance Disorders/drug therapy , Saponins/pharmacology , Saponins/therapeutic use , Plants, Edible , AnxietyABSTRACT
BACKGROUND: Siwu Decoction (SWD) is a well-known classical TCM formula that has been shown to be effective as a basis for preventing and reducing liver metastases (LM). However, the active ingredients and potential molecular mechanisms remain unclear. OBJECTIVE: This study aimed to systematically analyze the active ingredients and potential molecular mechanisms of SWD on LM and validate mechanisms involved. MATERIALS AND METHODS: The active ingredients in SWD were extracted by UHPLC-MS/MS in a latest study. Protox II was retrieved to obtain toxicological parameters to detect safety. Swiss Target Prediction database was exploited to harvest SWD targets. Five databases, Gene Cards, DisGeNET, Drugbank, OMIM, and TTD, were employed to filter pathogenic targets of LM. STRING database was utilized to construct the protein-protein interaction network for therapeutic targets, followed by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. GEPIA database and the Human Protein Atlas were taken to observe the expression of core genes and proteins. ImmuCellAI algorithm was applied to analyze the immune microenvironment and survival relevant to core genes. Molecular docking was performed to verify the affinity of SWD effective ingredients to core targets. In vivo experiments were carried out to validate the anti-LM efficacy of SWD and verify the pivotal mechanisms of action. RESULTS: Eighteen main bioactive phytochemicals identified were all non-hepatotoxic. PPI network acquired 118 therapeutic targets, of which VEGFA, CASP3, STAT3, etc. were identified as core targets. KEGG analysis revealed that HIF-1 pathway and others were critical. After tandem targets and pathways, HIF-1/VEGF was regarded as the greatest potential pathway. VEGFA and HIF-1 were expressed differently in various stages of cancer and normal tissues. There was a negative regulation of immunoreactive cells by VEGFA, which was influential for prognosis. Molecular docking confirmed the tight binding to VEGFA. This study revealed the exact effect of SWD against LM, and identified significant inhibition the expression of HIF-1α, VEGF, and CD31 in the liver microenvironment. CONCLUSION: This study clarified the active ingredients of SWD, the therapeutic targets of LM and potential molecular mechanisms. SWD may protect against LM through suppressing HIF-1/VEGF pathway.
Subject(s)
Drugs, Chinese Herbal , Liver Neoplasms , Humans , Molecular Docking Simulation , Network Pharmacology , Tandem Mass Spectrometry , Vascular Endothelial Growth Factor A , Liver Neoplasms/drug therapy , Drugs, Chinese Herbal/pharmacology , Tumor MicroenvironmentABSTRACT
BACKGROUND: Cisplatin (DDP) is one of the important chemotherapy drugs for patients with advanced gastric cancer and metastasis, but its resistance is a bottleneck problem that affects clinical efficacy and patient survival. Eremias multiocellata (EM) is a traditional Chinese herbal medicine, which has been used in the treatment of precancerous lesions, gastric cancer, liver fibrosis, and other digestive diseases. However, the mechanism of reducing chemotherapy resistance to gastric cancer is still unclear. METHODS: We used the MTT assay to evaluate the proliferative viability of gastric cancer parental cell line MKN45 and its drug-resistant cell line MKN45/DDP, and compared their drug-resistance indices. The migration and invasion abilities of MKN45/DDP drug-resistant cells were evaluated using the Transwell assay. Apoptosis in MKN45/DDP drug-resistant cells was detected using flow cytometry. The effect of a combination of EM and cisplatin on the levels of reactive oxygen species (ROS) and lipid peroxides (LPO) in cisplatin-resistant gastric cancer cells was detected using ROS fluorescent probes and a lipid peroxidation assay kit in conjunction with flow cytometry. The effect of EM combined with cisplatin on the level of iron ions was detected by fluorescence probe and confocal laser technique. Hematoxylin-eosin staining (HE staining) was used to detect the histopathologic morphology of drug-resistant gastric cancer in nude mice. Ferroptosis-related proteins were measured using immunohistochemistry. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect tumor drug resistance-related genes. The NF-κB/Snail pathway-related proteins, PI3K/AKT/mTOR pathway-related proteins, and drug resistance-related proteins were detected by Western blot. RESULTS AND CONCLUSIONS: The results of in vitro and in vivo experiments showed that EM combined with DDP could effectively inhibit the migration and invasive ability of MKN45/DDP cells, as well as induce apoptosis of MKN45/DDP cells; the combination of the two drugs could significantly increase the levels of ROS, lipid peroxidation and divalent ferric ions in MKN45/DDP cells, at the same time reducing the levels of Ferroptosis-related proteins, which could induce Ferroptosis. In addition, EM combined with DDP can also exert the effect of reversing DDP resistance and increasing the sensitivity of gastric cancer drug-resistant cells to DDP by regulating the NF-κB/Snail signaling pathway, PI3K/AKT/mTOR signaling pathway, and the expression of drug resistance-related proteins and genes.
Subject(s)
Cisplatin , Stomach Neoplasms , Animals , Mice , Humans , Cisplatin/pharmacology , Cisplatin/therapeutic use , Stomach Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , NF-kappa B , Proto-Oncogene Proteins c-akt/metabolism , Mice, Nude , Phosphatidylinositol 3-Kinases , Reactive Oxygen Species , Apoptosis , TOR Serine-Threonine Kinases , Ions/pharmacology , Ions/therapeutic use , Cell Line, Tumor , Cell ProliferationABSTRACT
Capsicum annuum (L.) is one of the essential spices most frequently used in our daily routine and has remarkable ethnobotanical and pharmacological properties. Its fruits are rich in vitamins, minerals, carotenoids, and numerous other phenolic metabolites with a well-known antioxidant activity. Regular consumption of chili fruits may have a positive influence on human health. Therefore, we investigated a commercially available chili fruit powder in the present study, extracting it with 50% ethanol. The dried hydro-ethanolic extract (CAE) was thoroughly analyzed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS/MS), and 79 bioactive phenolic constituents were identified. Then, we quantified the main phenolic compounds and found a polyphenol content of 4.725 ± 1.361 mg Eq tannic acid/100 g extract and a flavonoid amount of 1.154 ± 0.044 mg Eq rutin/100 g extract. Phenolic secondary metabolites are known for their dual redox behavior as antioxidants/pro-oxidants, underlying their numerous benefits in health and disease. Thus, the antioxidant potential of CAE was evaluated using three methods; our results could explain the protective effects of chili fruits: IC50DPPH = 1.669 mg/mL, IC50ABTS = 0.200 mg/mL, and EC50FRAP = 0.561 mg/mL. The pro-oxidant potential of phenolic compounds could be a basis for CAE cytotoxicity, investigated in vitro on tumor cell lines and in vivo on Daphnia sp. Results demonstrated the dose- and time-dependent CAE's cytotoxic activity; the highest antiproliferative activity was recorded on colon (LoVo) and breast (MDA-MB-231) cancer cell lines after 48 h of exposure (IC50 values < 200 µg/mL). In vivo testing on Daphnia sp. reported a potent CAE cytotoxicity after 48 h and embryonic developmental delays. Extensive data analyses support our results, showing a significant correlation between the CAE's concentration, phenolic compound content, antioxidant activity, exposure time, and the viability rate of different tested cell lines.
ABSTRACT
Colorectal cancer (CRC) is the third most common neoplasia in the world. Its mortality rate is high due to the lack of specific and effective treatments, metastasis, and resistance to chemotherapy, among other factors. The natural products in cancer are a primary source of bioactive molecules. In this research, we evaluated the antitumor activity of an acetogenin (ACG), laherradurin (LH), isolated from the Mexican medicinal plant Annona macroprophyllata Donn.Sm. in a CRC murine model. The CRC was induced by azoxymethane-dextran sulfate sodium (AOM/DSS) in Balb/c mice and treated for 21 days with LH or cisplatin. This study shows for the first time the antitumor activity of LH in an AOM/DSS CRC model. The acetogenin diminished the number and size of tumors compared with cisplatin; the histologic studies revealed a recovery of the colon tissue, and the blood toxicity data pointed to less damage in animals treated with LH. The TUNEL assay indicated cell death by apoptosis, and the in vitro studies exhibited that LH inhibited cell migration in HCT116 cells. Our study provides strong evidence of a possible anticancer agent for CRC.
ABSTRACT
Coelogyne suaveolens has been used as a traditional medicine for many years, and its potential as a natural source of antibacterial agents is of great interest. This investigation aimed to identify the bioactive compounds in the plant extract and assess their antibacterial properties. To achieve this, we identified the bioactive compounds using Gas chromatography mass spectrometry (GCMS) analysis on the extract's ethyl acetate fraction and used the disc diffusion method to determine the antibacterial effect. Additionally, molecular docking were performed to predict the binding affinities of selected phytochemicals against specific proteins in order to identify the root cause of bacterial inhibition. Our results revealed that the extract exhibited significant antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae, which are common and problematic pathogens. Furthermore, molecular docking studies identified eight best-selected compounds, of which {androstan-17-one, oxime, (5.alpha.)-}, diethofencarb, tetraconazole, {3,6-dimethyl-2,3,3a,4,5,7a-hexahydrobenzofuran}, and geranyl acetate showed a significant binding affinity with best binding interaction with the target enzymes. This suggests that binding to these specific proteins might lead to the mechanism of action of the evaluated antibacterial action. In conclusion, the present study contributes to the growing body of knowledge on natural antimicrobial agents and could have significant implications for the development of new and effective antibacterial agents.
ABSTRACT
There are numerous medicinal benefits from herbal plants, with many herbal medicines being used as 'Jamu', 'standardized herbal medicines' and phytopharmaceuticals. Physalis angulata Linn. (P. angulata L.), a plant utilized for both medicinal and food consumption purposes in a number of tropical and subtropical nations, is widely studied for its beneficial properties. The present review summarized the scientific evidence which suggested that P. angulata L. possesses antibacterial, anticancer, antiparasitic, anti-inflammatory, antifibrotic and antidiabetic properties. Furthermore, the various pharmacological studies that have been conducted utilizing in vivo and in vitro models, as well as the identification of phytochemical components with therapeutic value are described. In addition, the present review explained the solvents and the toxicity tests that were used for the investigation of P. angulata L. The authors aspire that this literature review will provide an overview for researchers regarding the scientific progress of P. angulata L. over the past ten years and the potential areas of future research.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu (HCS) is a traditional Chinese medicine obtained from the dried skin glands of Bufo gargarizans and clinical uses of HCS have been approved in China to treat malignant tumors. The traditional Chinese medicine theory states that HCS relieves patients with cancer by promoting blood circulation to remove blood stasis. Clinical observation found that local injection of HCS given to pancreatic cancer patients can significantly inhibit tumor progression and assist in enhancing the efficacy of chemotherapy. However, the material basis and underlying mechanism have not yet been elucidated. AIM OF THE STUDY: To investigate the therapeutic potential of HCS for the treatment of pancreatic cancer in in situ transplanted tumor nude mouse model. Furthermore, this study sought to elucidate the molecular mechanisms underlying its efficacy and assess the impact of HCS on the microenvironment of pancreatic cancer. To identify the antitumor effect of HCS in in situ transplanted tumor nude mouse model and determine the Chemopreventive mechanism of HCS on tumor microenvironment (TME). METHODS: Using the orthotopic transplantation nude mouse model with fluorescently labeled pancreatic cancer cell lines SW1990 and pancreatic stellate cells (PSCs), we examined the effect of HCS on the pancreatic ductal adenocarcinoma (PDAC) microenvironment based on the transforming growth factor ß (TGF-ß)/Smad pathway. The expression of TGF-ß, smad2, smad3, smad4, collagen type-1 genes and proteins in nude mouse model were detected by qRT-PCR and Western blot. RESULTS: HCS significantly reduced tumor growth rate, increased the survival rate, and ameliorated the histopathological changes in the pancreas. It was found that HCS concentration-dependently reduced the expression of TGF-ß1 and collagen type-1 genes and proteins, decreased the expression of Smad2 and Smad3 genes, and downregulated the phosphorylation level of Smad2/3. Additionally, the gene and protein expression of Smad4 were promoted by HCS. Further, the promoting effect gradually enhanced with the rise of HCS concentration. CONCLUSIONS: The results demonstrated HCS could regulate the activity of the TGF-ß/Smad pathway in PDAC, improved the microenvironment of PDAC and delayed tumor progression. This study not only indicated that the protective mechanism of HCS on PDAC might be attributed partly to the inhibition of cytokine production and the TGF-ß/Smad pathway, but also provided evidence for HCS as a potential medicine for PDAC treatment.
Subject(s)
Amphibian Venoms , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Mice , Animals , Humans , Transforming Growth Factor beta/metabolism , Mice, Nude , Pancreatic Neoplasms/genetics , Transforming Growth Factor beta1/metabolism , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Collagen , Tumor MicroenvironmentABSTRACT
Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.