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.

Antiviral Potentialities of Chemical Characterized Essential Oils of Acacia nilotica Bark and Fruits against Hepatitis A and Herpes Simplex Viruses: In Vitro, In Silico, and Molecular Dynamics Studies.

Acacia nilotica (synonym: Vachellia nilotica (L.) P.J.H.Hurter and Mabb.) is considered an important plant of the family Fabaceae that is used in traditional medicine in many countries all over the world. In this work, the antiviral potentialities of the chemically characterized essential oils (EOs) obtained from the bark and fruits of A. nilotica were assessed in vitro against HAV, HSV1, and HSV2. Additionally, the in silico evaluation of the main compounds in both EOs was carried out against the two proteins, 3C protease of HAV and thymidine kinase (TK) of HSV. The chemical profiling of the bark EOs revealed the identification of 32 compounds with an abundance of di- (54.60%) and sesquiterpenes (39.81%). Stachene (48.34%), caryophyllene oxide (19.11%), and spathulenol (4.74%) represented the main identified constituents of bark EO. However, 26 components from fruit EO were assigned, with the majority of mono- (63.32%) and sesquiterpenes (34.91%), where trans-caryophyllene (36.95%), Z-anethole (22.87%), and γ-terpinene (7.35%) represented the majors. The maximum non-toxic concentration (MNTC) of the bark and fruits EOs was found at 500 and 1000 µg/mL, respectively. Using the MTT assay, the bark EO exhibited moderate antiviral activity with effects of 47.26% and 35.98% and a selectivity index (SI) of 2.3 and 1.6 against HAV and HSV1, respectively. However, weak activity was observed via the fruits EO with respective SI values of 3.8, 5.7, and 1.6 against HAV, HSV1, and HSV2. The in silico results exhibited that caryophyllene oxide and spathulenol (the main bark EO constituents) showed the best affinities (ΔG = -5.62, -5.33, -6.90, and -6.76 kcal/mol) for 3C protease and TK, respectively. While caryophyllene (the major fruit EO component) revealed promising binding capabilities against both proteins (ΔG = -5.31, -6.58 kcal/mol, respectively). The molecular dynamics simulation results revealed that caryophyllene oxide has the most positive van der Waals energy interaction with 3C protease and TK with significant binding free energies. Although these findings supported the antiviral potentialities of the EOs, especially bark EO, the in vivo assessment should be tested in the intraoral examination for these EOs and/or their main constituents.

Phytochemical Profiling of the Leaf Extract of Ximenia americana var. caffra and Its Antioxidant, Antibacterial, and Antiaging Activities In Vitro and in Caenorhabditis elegans: A Cosmeceutical and Dermatological Approach.

We previously annotated the phytochemical constituents of a root extract from Ximenia americana var. caffra and highlighted its hepatoprotective and hypoglycemic properties. We here extended our study on the leaf extract and identified its phytoconstituents using HPLC-PDA-ESI-MS/MS. In addition, we explored its antioxidant, antibacterial, and antiaging activities in vitro and in an animal model, Caenorhabditis elegans. Results from HPLC-PDA-ESI-MS/MS confirmed that the leaves contain 23 secondary metabolites consisting of condensed tannins, flavonol glycosides, flavone glycosides, and flavonol diglycosides. The leaf extract demonstrated significant antioxidant activity in vitro with IC50 value of 5 µg/mL in the DPPH assay and 18.32 µg/mL in the FRAP assay. It also inhibited four enzymes (collagenase, elastase, hyaluronidase, and tyrosinase) crucially involved in skin remodeling and aging processes with comparable activities to reference drugs along with four pure secondary metabolites identified from the extract. In accordance with the in vitro result, in vivo tests using two transgenic strains of C. elegans demonstrated its ability to reverse oxidative stress. Evidence included an increased survival rate in nematodes treated with the prooxidant juglone to 68.9% compared to the 24.8% in untreated worms and a reduced accumulation of intracellular reactive oxygen species (ROS) in a dose-dependent manner to 77.8%. The leaf extract also reduced levels of the expression of HSP 16.2 in a dose-dependent manner to 86.4%. Nuclear localization of the transcription factor DAF-16 was up to 10 times higher in worms treated with the leaf extract than in the untreated worms. The extract also inhibited the biofilm formation of Pseudomonas aeruginosa (a pathogen in skin infections) and reduced the swimming and swarming mobilities in a dose-dependent fashion. In conclusion, leaves of X. americana are a promising candidate for preventing oxidative stress-induced conditions, including skin aging.

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.

Pea (Pisum sativum) peel extract attenuates DOX-induced oxidative myocardial injury.

The goal of this work aimed to evaluate the protective effects of pea (Pisum sativum) peels extract versus doxorubicin-induced oxidative myocardial injury in male mice. The mice were divided into seven groups (n = 7): (I) control group; (II) P. sativum 250 group; (III) P. sativum 500 group; (IV) DOX (3 times alternately of 2.5 mg/kg/week, i.p. for a continuous two-week period) group; (V) Vit. E 100 + DOX group; (VI) P. sativum 250 + DOX group, and (VII) P. sativum 500 + DOX group). Twenty polyphenolic compounds, mainly flavonoid glycosides such as quercetin, kaempferol apigenin, and phenolics compounds were characterized by LC-MS/MS analysis in the examined extract. DOX administration elevated the activities of serum biomarkers of myocardial dysfunction (ALT, AST, ALP, LDH, troponin, CPK, and CK-MB), lipid profile, and proinflammatory cytokines. Also, it decreased cardiac antioxidants (GSH, SOD, GPX, CAT) and increased myocardial markers of oxidative stress (NO and MDA) and inflammatory marker (MPO). As well as it downregulated and upregulated the Bcl-2 (anti-apoptotic gene) and the Bax (pro-apoptotic gene) expressions, respectively. Pre-treatment of DOX-exposed mice with P. sativum or vitamin E (as a reference protective antioxidant) alleviated the changes dose-dependently via DOX-induced cardiotoxicity. These data show that P. sativum has a cardio-protective impact against DOX-induced cardiomyocyte damage in mice via boosting endogenous antioxidants, decreasing inflammation, and regulating BcL-2 and Bax apoptosis pathway, which might be related to the presence of flavonoid glycosides. P. sativum peels are a by-product that could be suggested for further screening as a possible new candidate for therapeutic use.

Chemical Composition, Allelopathic, Antioxidant, and Anti-Inflammatory Activities of Sesquiterpenes Rich Essential Oil of Cleome amblyocarpa Barratte & Murb.

The integration of green natural chemical resources in agricultural, industrial, and pharmaceutical applications allures researchers and scientistic worldwide. Cleome amblyocarpa has been reported as an important medicinal plant. However, its essential oil (EO) has not been well studied; therefore, the present study aimed to characterize the chemical composition of the C. amblyocarpa, collected from Egypt, and assess the allelopathic, antioxidant, and anti-inflammatory activities of its EO. The EO of C. amblyocarpa was extracted by hydrodistillation and characterized via gas chromatography-mass spectrometry (GC-MS). The chemometric analysis of the EO composition of the present studied ecospecies and the other reported ecospecies was studied. The allelopathic activity of the EO was evaluated against the weed Dactyloctenium aegyptium. Additionally, antioxidant and anti-inflammatory activities were determined. Forty-eight compounds, with a prespondence of sesquiterpenes, were recorded. The major compounds were caryophyllene oxide (36.01%), hexahydrofarnesyl acetone (7.92%), alloaromadendrene epoxide (6.17%), myrtenyl acetate (5.73%), isoshyobunone (4.52%), shyobunol (4.19%), and trans-caryophyllene (3.45%). The chemometric analysis revealed inconsistency in the EO composition among various studied ecospecies, where it could be ascribed to the environmental and climatic conditions. The EO showed substantial allelopathic inhibitory activity against the germination, seedling root, and shoot growth of D. aegyptium, with IC50 values of 54.78, 57.10, and 74.07 mg L-1. Additionally, the EO showed strong antioxidant potentiality based on the IC50 values of 4.52 mg mL-1 compared to 2.11 mg mL-1 of the ascorbic acid as standard. Moreover, this oil showed significant anti-inflammation via the suppression of lipoxygenase (LOX) and cyclooxygenases (COX1, and COX2), along with membrane stabilization. Further study is recommended for analysis of the activity of pure authentic materials of the major compounds either singularly or in combination, as well as for evaluation of their mechanism(s) and modes of action as antioxidants or allelochemicals.

Chemical Profiles, Anticancer, and Anti-Aging Activities of Essential Oils of Pluchea dioscoridis (L.) DC. and Erigeron bonariensis L.

Plants belonging to the Asteraceae family are widely used as traditional medicinal herbs around the world for the treatment of numerous diseases. In this work, the chemical profiles of essential oils (EOs) of the above-ground parts of Pluchea dioscoridis (L.) DC. and Erigeron bonariensis (L.) were studied in addition to their cytotoxic and anti-aging activities. The extracted EOs from the two plants via hydrodistillation were analyzed by gas chromatography-mass spectroscopy (GC-MS). GC-MS of EO of P. dioscoridis revealed the identification of 29 compounds representing 96.91% of the total oil. While 35 compounds were characterized from EO of E. bonariensis representing 98.21%. The terpenoids were found the main constituents of both plants with a relative concentration of 93.59% and 97.66%, respectively, including mainly sesquiterpenes (93.40% and 81.06%). α-Maaliene (18.84%), berkheyaradulen (13.99%), dehydro-cyclolongifolene oxide (10.35%), aromadendrene oxide-2 (8.81%), ß-muurolene (8.09%), and α-eudesmol (6.79%), represented the preponderance compounds of EO of P. dioscoridis. While, trans-α-farnesene (25.03%), O-ocimene (12.58%), isolongifolene-5-ol (5.53%), α-maaliene (6.64%), berkheyaradulen (4.82%), and α-muurolene (3.99%), represented the major compounds EO of E. bonariensis. A comparative study of our results with the previously described data was constructed based upon principal component analysis (PCA) and agglomerative hierarchical clustering (AHC), where the results revealed a substantial variation of the present studied species than other reported ecospecies. EO of P. dioscoridis exhibited significant cytotoxicity against the two cancer cells, MCF-7 and A-549 with IC50 of 37.3 and 22.3 µM, respectively. While the EO of the E. bonariensis showed strong cytotoxicity against HepG2 with IC50 of 25.6 µM. The EOs of P. dioscoridis, E. bonariensis, and their mixture (1:1) exhibited significant inhibitory activity of the collagenase, elastase, hyaluronidase, and tyrosinase comparing with epigallocatechin gallate (EGCG) as a reference. The results of anti-aging showed that the activity of mixture (1:1) > P. dioscoridis > E. bonariensis against the four enzymes.

Chemical Profile of Launaea nudicaulis Ethanolic Extract and Its Antidiabetic Effect in Streptozotocin-Induced Rats.

Launaea nudicaulis is used in folk medicine worldwide to treat several diseases. The present study aimed to assess the antidiabetic activity of L. nudicaulis ethanolic extract and its effect on diabetic complications in streptozotocin-induced hyperglycemic rats. The extract was orally administrated at 250 and 500 mg/kg/day for 5-weeks and compared to glibenclamide as a reference drug at a dose of 5 mg/kg/day. Administration of the extract exhibited a potential hypoglycemic effect manifested by a significant depletion of serum blood glucose concurrent with a significant elevation in serum insulin secretion. After 5-weeks, extract at 250 and 500 mg/kg/day decreased blood glucose levels by about 53.8 and 68.1%, respectively, compared to the initial values (p ≤ 0.05). The extract at the two dosages prevented weight loss of rats from the 2nd week till the end of the experiment, compared to diabetic control rats. The extract further exhibited marked improvement in diabetic complications including liver, kidney and testis performance, oxidative stress, and relative weight of vital organs, with respect to diabetic control. Histopathological examinations confirmed the previous biochemical analysis, where the extract showed a protective effect on the pancreas, liver, kidney, and testis that degenerated in diabetic control rats. To characterize extract composition, UPLC-ESI-qTOF-MS identified 85 chromatographic peaks belonging to flavonoids, phenolics, acyl glycerols, nitrogenous compounds, and fatty acids, with four novel phenolics reported. The potential anti-diabetic effect warrants its inclusion in further studies and or isolation of the main bioactive agent(s).

Essential Oil of Calotropis procera: Comparative Chemical Profiles, Antimicrobial Activity, and Allelopathic Potential on Weeds.

Plants are considered green resources for thousands of bioactive compounds. Essential oils (EOs) are an important class of secondary compounds with various biological activities, including allelopathic and antimicrobial activities. Herein, the present study aimed to compare the chemical profiles of the EOs of the widely distributed medicinal plant Calotropis procera collected from Saudi Arabia and Egypt. In addition, this study also aimed to assess their allelopathic and antimicrobial activities. The EOs from Egyptian and Saudi ecospecies were extracted by hydrodistillation and analyzed via GC-MS. The correlation between the analyzed EOs and those published from Egypt, India, and Nigeria was assessed by principal component analysis (PCA) and agglomerative hierarchical clustering (AHC). The allelopathic activity of the extracted EOs was tested against two weeds (Bidens pilosa and Dactyloctenium aegyptium). Moreover, the EOs were tested for antimicrobial activity against seven bacterial and two fungal strains. Ninety compounds were identified from both ecospecies, where 76 compounds were recorded in Saudi ecospecies and 33 in the Egyptian one. Terpenes were recorded as the main components along with hydrocarbons, aromatics, and carotenoids. The sesquiterpenes (54.07%) were the most abundant component of EO of the Saudi sample, while the diterpenes (44.82%) represented the mains of the Egyptian one. Hinesol (13.50%), trans-chrysanthenyl acetate (12.33%), 1,4-trans-1,7-cis-acorenone (7.62%), phytol (8.73%), and myristicin (6.13%) were found as the major constituents of EO of the Saudi sample, while phytol (38.02%), n-docosane (6.86%), linoleic acid (6.36%), n-pentacosane (6.31%), and bicyclogermacrene (4.37%) represented the main compounds of the Egyptian one. It was evident that the EOs of both ecospecies had potent phytotoxic activity against the two tested weeds, while the EO of the Egyptian ecospecies was more effective, particularly on the weed D. aegyptium. Moreover, the EOs showed substantial antibacterial and antifungal activities. The present study revealed that the EOs of Egyptian and Saudi ecospecies were different in quality and quantity, which could be attributed to the variant environmental and climatic conditions. The EOs of both ecospecies showed significant allelopathic and antimicrobial activity; therefore, these EOs could be considered as potential green eco-friendly resources for weed and microbe control, considering that this plant is widely grown in arid habitats.