Protective Action Mechanisms of Launaea mucronata Extract and Its Nano-Formulation against Nephrotoxicity in Rats as Revealed via Biochemical, Histopathological, and UPLC-QTOF-MS/MS Analyses.

Plants belonging to the Launaea genus have been extensively utilized ethnopharmacologically to treat a variety of diseases, including kidney disorders. Chromium is a common industrial pollutant that has been linked to kidney disease. The present work was designed for the investigation of the UPLC-QTOF-MS/MS metabolite profile of the L. mucronate ethanolic extract (LME), along with assessing the mechanistic protective actions of LME and its nano-silver formulation (LMNS) against K2Cr2O7-induced nephrotoxicity in rats. LMNE was successfully biosynthesized and confirmed using UV-Visible (UV-Vis) spectroscopy and transmission electron microscopy (TEM). The nephroprotective effects of LME and LMNE was assessed in rats exposed to potassium dichromate (K2Cr2O7, 15 mg/kg BW) to cause nephrotoxicity. LME and LMNS, separately, were administered twice daily for 14 days at doses of 200 and 400 mg/kg BW, respectively. The kidney function, catalase, UGT, Nrf2, PGE2, Cox-2, ERK, and MAPK levels in renal tissue were all assessed, along with histopathological examinations for exploring their ameliorative effects. Forty-five bioactive metabolites were annotated belonging to flavonoids, phenolic and organic acids, coumarins, and fatty acids. Metabolite profiling revealed that chlorogenic acid, apigenin, and luteolin glycosides were the main phenolics, with chlorogenic acid-O-hexoside reported for the first time in LME. The findings revealed that the serum kidney function indicators (urea and creatinine) were markedly elevated in K2Cr2O7-intoxicated rats. Furthermore, inflammatory indicators (COX-2 and PGE2), MAPK, and ERK were all markedly elevated in kidney tissue, whereas catalase, UGT, and Nrf2 levels were downregulated. Histological and immunohistochemical assays confirmed the toxic effects of K2Cr2O7 in the kidneys. In contrast, the administration of LME and LMNS prior to K2Cr2O7 considerably improved the architecture of the renal tissue, while also restoring levels of most biochemical markers. Functioning via the inhibition of the MAPK/ERK pathway, activating Nrf2, and modifying the antioxidant and metabolic enzymes, LME and LMNS exerted their nephroprotective effects against K2Cr2O7-induced toxicity.

Effect of electromagnetic therapy versus low-level laser therapy on diabetic patients with trigeminal neuralgia: a randomized control trial.

BACKGROUND: Trigeminal neuralgia (TN) is defined as intense, abrupt, often unilateral, stabbing, short, repeated episodes of pain in one or more distributional branches of the trigeminal nerve. AIM: To see how electromagnetic therapy (EMT) compared to low-level laser therapy (LLLT) affect TN in diabetes patients. DESIGN: This is a randomized controlled trial. SETTING: Physical therapy and Neurology Outpatients Clinics at Faculty of Physical Therapy. POPULATION: One hundred and forty diabetic patients with TN were evaluated for eligibility. As a result, 126 diabetic patients with TN were included in this trial. They were randomly divided into three equal-sized groups using random allocation software. Due to travel to another country, two patients did not complete the treatment protocol, and four opted out of the post-therapy evaluation. So, 120 volunteer diabetic patients with TN of both sexes were diagnosed for the participation in this study by a neurologist (N.=40 in each group). METHODS: For two months, participants in the control group A received the medication only (oral hypoglycemic drugs, Analgesics, vitamin B12), participants in the study group B received the medications as in group A in addition to LLLT, and participants in the study group C received medication as in group A in addition to electromagnetic therapy (EMT). The primary outcome was the amplitude of compound muscle action potentials of temporalis and masseter muscles by using NEXUS 10 (Mind media). The secondary outcome was pain intensity by using the Visual Analog Scale (VAS). RESULTS: According to the results of this study, there is a statistically significant difference in visual analog scale scores and the amplitude of compound muscle action potentials of the temporalis and masseter muscles among groups in favor of group B. CONCLUSIONS: After treatment, all groups improved significantly, with the laser group outperforming the electromagnetic group by a large margin. For irradiation, LLLT was more effective than EMT in reducing diabetic patients' trigeminal pain, and increasing masseter and temporalis muscles compound action potential amplitude in diabetic patients with TN. CLINICAL REHABILITATION IMPACT: LLLT was more effective than EMT at reducing diabetic patient's trigeminal pain, and increasing masseter and temporalis muscles compound action potential amplitude in diabetic patients with TN patients after two months of interventions.

Metabolomics approach of Symphyotrichum squamatum ethanol extract and its nano-Ag formulation protective effect on gastric ulcer via bio-chemical and pathological analyses.

ContextGastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.Materials and MethodsChemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analysed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.ResultsUPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signalling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.ConclusionPresent results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.

Cytoprotective potentialities of carvacrol and its nanoemulsion against cisplatin-induced nephrotoxicity in rats: development of nano-encasulation form.

Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.

Oral and Topical Anti-Inflammatory and Antipyretic Potentialities of Araucaria bidiwillii Shoot Essential Oil and Its Nanoemulsion in Relation to Chemical Composition.

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC-MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), ß-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1ß and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κß levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer's yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.

Renoprotective and therapeutic effects of newly water, ethanol, and butanol ginseng fractions in hypertensive and chronic kidney disease with L-NAME.

The present study investigated the protective and treatment effects of different ginseng fractions against L-NAME-induced renal toxicity in rats. The data obtained demonstrated that L-NAME significantly increased creatinine, urea, KIM-1, and lipocalin-2 levels in serum; and also increased renal MDA and eNOS levels compared with the control group. Three bioactive fractions were newly extracted from ginseng, analyzed by GC-MS analysis, and were examined for antimicrobial, prebiotic, and histological activities. All ginseng fractions improved such histological changes, as reflected by significant reductions in creatinine, urea, KIM-1, and LCN-2 levels in serum, and renal MDA and eNOS contents in tissue homogenate. The water ginseng fraction (WGF) has the highest prebiotic index of 4.7 toward Lactobacillus reuteri, and can improve the renal functions more than butanol ginseng fraction (BGF) and ethanol ginseng fraction (EGF). These three ginseng fractions significantly reversed L-NAME-induced depletion in the TNF-α gene expression level. Interestingly, WGF was able to improve the renal functions more than BGF and EGF. L-NAME led to alterations in the histological structure and functions of renal tissue of rats and ginseng supplementation could offer greater protection against these changes. Moreover, the WGF exhibited superior renoprotection properties when compared with the other two fractions: BGF and EGF, and the reference drug losartan.

A Completely Polyherbal Conditioning and Antioxidant Shampoo: A Phytochemical Study and Pharmaceutical Evaluation.

AIM: A recent approach in shampoo research has been to find a natural alternative for synthetic detergents that have deteriorative effects on hair follicles. This study aimed at the formulation of a completely herbal shampoo containing a natural foaming agent, in addition to having conditioning, antioxidant, and antimicrobial effects. MATERIAL AND METHODS: The leaves of Salix babylonica L., Ziziphus spina-christi L. (Willd), and Glycyrrhiza glabra rhizomes were extracted with 70% methanol then quantified for their phenolic and flavonoid contents using colorimetric assays that were qualitatively identified by Ultra-performance liquid chromatography (UPLC) with tandem mass spectrometry (MS-MS). The mineral content was also estimated. The radical scavenging activity was estimated using 1,1-diphenyl-2-Picrylhydrazyl (DPPH) and the half maximal inhibitory concentration (IC50) was determined. Additionally, the antimicrobial activity was tested using agar diffusion assay and compared to vancomycin and ketoconazole. Four formulations, consisting of the different plant extracts and a combination of the extracts, were prepared and evaluated for several physicochemical properties. The best formula was evaluated for its conditioning effects using scanning electron microscope and blind touch tests by asking volunteers for grading the formulations. RESULTS AND DISCUSSION: UPLC-MS-MS analysis of S. babylonica and Z. spina-christi allowed tentative identification of 12 phytoconstituents in each. Z. spina-christi showed the highest phenolic content and a high copper, zinc, and manganese content beside the best antioxidant activity, whereas G. glabra had a high potency against Bacillus cereus and Candida albicans. The polyherbal shampoo formulation (F4) was selected as an optimized formulation because of a high foam stability after 4 min, low wetting time (2 s), surface tension reduction, and comparable results for percent solid content. F4 showed good conditioning effect and consumer contentment. CONCLUSION: The formulated polyherbal shampoo is chemical free, extra-nourishing shampoo with excellent conditioning, cleansing, and antimicrobial effects.

Soft hydrogel based on modified chitosan containing P. granatum peel extract and its nano-forms: Multiparticulate study on chronic wounds treatment.

Punica granatum peel (PGP) is widely used in traditional medicinal purposes for chronic wounds owing to containing natural phenolics active components. In current study, active wound dressing hydrogel for chronic wound healing was prepared based on P. granatum peel crude extract (PGPC), ethyl acetate fraction (PGPEA) and their silver nanoforms (Ag-NPs). Methacrylated chitosan was synthesized as precursor to hydrogel and crosslinked by divinyl sulfone (DVS) in mild condition. Hydrogel was fully characterized by spectral morphological, mechanical and physical analyses. The integration of PGPEA silver nanoforms was formed with particle size of 15-56 nm to show minimum inhibitory concentration (MIC) equal 63 for Staphylococcus aureus and 125 for Pseudomonas aeruginosa. The hydrogel-based wound dressing with/without the active ingredients showed acceptable cytotoxicity against fibroblast human cells for PGPC and PGPEA fraction over the silver nanoforms. Rat as animal model was considered to show the impact of the active wound dressing on diabetic wounds which was proved by histopathological examination. In addition, the significant intensity of immunopositivity signals of the transforming growth factor beta (TGF-ß1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the epidermal cells have revealed the efficiency of Ag NPs-PGPEA-chitosan hydrogel for chronic wound curing.

New applied pharmacological approach/trend on utilization of agro-industrial wastes.

This study aimed to transform the locally available lignocellulosic residual palm frond (PF) and rice straw (RS) wastes into multifunction added products like methylated cellulose and sulfated and phosphorylated hemicelluloses by simple processes. Hydrolysis with 2 N sulfuric acid was the most suitable reaction for microcrystalline cellulose production. The characteristics of the prepared products were studied to obtain the optimum reaction conditions. Palm frond hemicellulose (PFHC) recorded the highest antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans (22, 22, 26 mm), respectively, and phosphorylated palm frond hemicellulose (PPFHC) exhibited the highest potential antioxidant activity of approximately 60%, suggesting a possible correlation between the two bioactivities. Most of extracted celluloses and their derivatives had a variety of promising probiotic activities which are expected to reduce the side effects of the gastric mucosa and possibly play a role in curing the gastric ulcer. Accordingly, the determination of anti-inflammatory and gastroprotective activity results revealed that methylcellulose, sulfated and phosphorylated hemicelluloses showed anti-inflammatory and gastroprotective activities and the capability of all tested compounds to ameliorate the ethanol-induced gastric ulcer in rats' stomach. All results recommended PF and RS and their derivatives to be used as a medicinal food.

Combined protocol of cell therapy for chronic spinal cord injury. Report on the electrical and functional recovery of two patients.

BACKGROUND: This is a preliminary report on successful results obtained during treatment of two patients with chronic spinal cord injury. The therapeutic approach was based on the generation of controlled inflammatory activity at the injury site that induced a microenvironment for the subsequent administration of autologous, BM-driven transdifferentiated neural stem cells (NSC). METHODS: BM mesenchymal stem cells (MSC) were cocultured with the patient's autoimmune T (AT) cells to be transdifferentiated into NSC. Forty-eight hours prior to NSC implant, patients received an i.v. infusion of 5 x 10(8) to 1 x 10(9) AT cells. NSC were infused via a feeding artery of the lesion site. Safety evaluations were performed everyday, from the day of the first infusion until 96 h after the second infusion. After treatment, patients started a Vojta and Bobath neurorehabilitation program. RESULTS: At present two patients have been treated. Patient 1 was a 19-year-old man who presented paraplegia at the eight thoracic vertebra (T8) with his sensitive level corresponding to his sixth thoracic metamere (T6). He received two AT-NSC treatments and neurorehabilitation for 6 months. At present his motor level corresponds to his first sacral metamere (S1) and his sensitive level to the fourth sacral metamere (S4). Patient 2 was a 21-year-old woman who had a lesion that extended from her third to her fifth cervical vertebrae (C3-C5). Prior to her first therapeutic cycle she had severe quadriplegia and her sensitive level corresponded to her second cervical metamere (C2). After 3 months of treatment her motor and sensitive levels reached her first and second thoracic metameres (T1-T2). No adverse events were detected in either patient. DISCUSSION: The preliminary results lead us to think that this minimally invasive approach, which has minor adverse events, is effective for the repair of chronic spinal cord lesions.