Isolation of Myricitrin and 3,5-di-O-Methyl Gossypetin from Syzygium samarangense and Evaluation of their Involvement in Protecting Keratinocytes against Oxidative Stress via Activation of the Nrf-2 Pathway

The wax apple (Syzygium samarangense) is traditionally employed as an antibacterial and immunostimulant drug in traditional medicine. This plant is rich in different flavonoids and tannins. In this study, we isolated two compounds from S. samarangense leaves: myricitrin and 3,5-di-O-methyl gossypetin. Then, we investigated the mechanisms of action of the two compounds against oxidative stress (induced by sodium arsenite) and inflammation (induced by UV light) on human keratinocytes. We could clearly demonstrate that the pre-treatment of cells with both compounds was able to mitigate the negative effects induced by oxidative stress, as no alteration in reactive oxygen species (ROS) production, glutathione (GSH) level, or protein oxidation was observed. Additionally, both compounds were able to modulate mitogen-activated protein kinase (MAPK) signaling pathways to counteract oxidative stress activation. Finally, we showed that 3,5-di-O-methyl gossypetin exerted its antioxidant activity through the nuclear transcription factor-2 (Nrf-2) pathway, stimulating the expression of antioxidant proteins, such as HO-1 and Mn-SOD-3

GLC-MS profiling of non-polar extracts from Phlomis bucharica and P. salicifolia and their cytotoxicity

Phlomis species (Phlomis bucharica Regel and P. salicifolia Regel) have been traditionally used by Uzbek people as stimulant, tonic, diuretic, and in the treatment of ulcers, hemorrhoids, wounds and gynecological problems. In the present study, we characterized the chemical composition of non-polar extracts from P. bucharica and P. salicifolia by high resolution GLC-MS and evaluated their cytotoxicity. Concentrations of hexadecanoic acid in hexane and chloroform extracts were higher in P. bucharica than in P. salicifolia. 1,8- Cineol, camphor, borneol, α-terpinol, thymol, and isobornyl acetate were detected in P. bucharica but not in P. salicifolia. About 45 components were identified in P. bucharica and 40 in P. salicifolia. The chloroform extract from P. bucharica showed cytotoxicity in HeLa and HL-60 cells, with IC50 values of 26.07 and 29.42 μg/ml, respectively

Mentha rotundifolia (L.) Huds. and Salvia officinalis L. hydrosols mitigate aging related comorbidities in rats

IntroductionAging is often linked to oxidative stress, where the body experiences increased damage from free radicals. Plants are rich sources of antioxidants, playing a role in slowing down aging and supporting the proper functioning and longevity of cells. Our study focuses on exploring the impact of Mentha rotundifolia (MR) and Salvia officinalis (SO) hydrosols on aging-related comorbidities.MethodsThe chemical composition of MR and SO hydrosols was analyzed by gas chromatography coupled to mass spectrometry. 2,2-Diphenyl 1-picrylhydrazyl and 2,20-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid radicals scavenging assays were used to assess their in vitro antioxidant activity, and heat induced albumin denaturation test was used to evaluate their anti-inflammatory activity. Subsequently, we administered 5% of each plant hydrosol in the drinking water of 18-month-old rats for six months. We then conducted behavioral tests, including open field, dark/light box, rotarod, and Y-maze assessments, and measured biochemical parameters in plasma, liver and brain tissues.Results and discussionAt two years old, animals treated with MR and SO hydrosols displayed fewer physical and behavioral impairments, along with well-preserved redox homeostasis in comparison with animals in the control group. These results highlighted the significance of MR and SO hydrosols in addressing various aspects of age-related comorbidities. The study suggests that these plant-derived hydrosols may have potential applications in promoting healthy aging and mitigating associated health challenges

Syzygium aqueum: A polyphenol- rich leaf extract exhibits antioxidant, hepatoprotective, pain-killing and anti-inflammatory activities in animal models

Syzygium aqueum is widely used in folk medicine. A polyphenol-rich extract from its leaves demonstrated a plethora of substantial pharmacological properties. The extract showed solid antioxidant properties in vitro and protected human keratinocytes (HaCaT cells) against UVA damage. The extract also reduced the elevated levels of ALT, AST, total bilirubin (TB), total cholesterol (TC) and triglycerides (TG) in rats with acute CCl4 intoxication. In addition to reducing the high MDA level, the extract noticeably restored GSH and SOD to the normal control levels in liver tissue homogenates and counteracted the deleterious histopathologic changes in liver after CCl4 injection. Additionally, the extract exhibited promising anti-inflammatory activities in vitro where it inhibited LOX, COX-1, and COX-2 with a higher COX-2 selectivity than that of indomethacin and diclofenac and reduced the extent of lysis of erythrocytes upon incubation with hypotonic buffer solution. S. aqueum extract also markedly reduced leukocyte numbers with similar activities to diclofenac in rats challenged with carrageenan. Additionally, administration of the extract abolished writhes induced by acetic acid in mice and prolonged the response latency in hot plate test. Meanwhile, the identified polyphenolics from the extract showed a certain affinity for the active pockets of 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and cyclooxygenase- 2 (COX-2) explaining the observed anti-inflammatory activities. Finally, 87 secondary metabolites (mostly phenolics) were tentatively identified in the extract based on LCMS/ MS analyses. Syzygium aqueum displays good protection against oxidative stress, free radicals, and could be a good candidate for treating oxidative stress related diseases

Chemical composition, antioxidant and hepatoprotective activities of methanol extracts from leaves of Terminalia bellirica and Terminalia sericea (Combretaceae)

Background Plants belonging to the genus Terminalia such as Terminalia bellirica and Terminalia sericea are used traditionally to treat several diseases and health disorders. Up to this date, the roots of Terminalia sericea and the fruits of Terminalia bellirica are the mostly studied plant parts. The phytochemical composition and the biological activities of the leaves of both species are not well identified so far. Methods The secondary metabolites of Terminalia bellirica and Terminalia sericea leaves were identified using HPLC-PDA-MS/MS. The antioxidant activities of the leaves extracts were determined by DPPH and FRAP assays. The hepatoprotective potential was evaluated in rats with D-galactosamine induced liver damage. The effect of the extracts on the expression of the anti-apoptotic marker Bcl-2 was measured in an immunohistochemical study. The most abundant compounds identified in the studied extracts were docked into Bcl-2: Bim (BH3) interaction surface using molecular operating environment software. Results A total of 85 secondary metabolites were identified in the leaf extracts of both species. Ellagitannins such as corilagin, chebulagic acid, galloylpunicalagin, and digalloyl-hexahydroxydiphenoyl-hexoside were found to be the major components in Terminalia bellirica whereas flavonoid glycosides including quercetin rutinoside and quercetin galloyl-glucoside were highly abundant in Terminalia sericea. The studied extracts exhibited pronounced antioxidant activities, moderate anti-apoptotic and hepatoprotective potential. In silico docking experiments revealed that the compounds abundant in the extracts were able to bind to Bcl-2: Bim (BH3) interaction surface with an appreciable binding free energy. Discussion The antioxidant and hepatoprotective activities exhibited by the studied extracts might be attributed to the high content of the polyphenols. The anti-apoptotic activity could be due to the interference with the apoptotic pathway mediated by Bcl-2: Bim interaction. These findings support the medicinal relevance of Terminalia bellirica and Terminalia sericea and provide a rational base for their utilization in folk medicine

Bioactive strawberry fruit (Arbutus unedo L.) extract remedies paraquat-induced neurotoxicity in the offspring prenatally exposed rats

BackgroundParaquat (1,1′-dimethyl-4-4′-bipyridinium dichloride) exposure is well-established as a neurotoxic agent capable of causing neurological deficits in offspring. This study aimed to investigate therapeutic effects of Arbutus unedo L. aqueous extract (AU) against paraquat (PQ) exposure.MethodsFor that the phytoconstituents of AU was determined by LC/MS, and then its antioxidant potential was assessed by DPPH and ABTS assays. The assessment included its impact on cell viability and mitochondrial metabolism using N27 dopaminergic cells. Additionally, we evaluated the effects of prenatal PQ exposure on motor coordination, dopamine levels, trace element levels, and total antioxidant capacity (TAC) in rat progeny.ResultsThe phytochemical profile of AU extract revealed the presence of 35 compounds, primarily phenolic and organic acids, and flavonoids. This accounted for its strong in vitro antioxidant activities against DPPH and ABTS radicals, surpassing the activities of vitamin C. Our findings demonstrated that AU effectively inhibited PQ-induced loss of N27 rat dopaminergic neural cells and significantly enhanced their mitochondrial respiration. Furthermore, daily post-treatment with AU during the 21 days of the rat's pregnancy alleviated PQ-induced motor deficits and akinesia in rat progeny. These effects inhibited dopamine depletion and reduced iron levels in the striatal tissues. The observed outcomes appeared to be mediated by the robust antioxidant activity of AU, effectively counteracting the PQ-induced decrease in TAC in the blood plasma of rat progeny. These effects could be attributed to the bioactive compounds present in AU, including phenolic acids such as gallic acid and flavonoids such as quercetin, rutin, apigenin, glucuronide, and kaempferol, all known for their potent antioxidant capacity.DiscussionIn conclusion, this preclinical study provided the first evidence of the therapeutic potential of AU extract against PQ-induced neurotoxicity. These findings emphasize the need for further exploration of the clinical applicability of AU in mitigating neurotoxin-induced brain damage

The first comprehensive chemical profiling of Vachellia gummifera (Willd.) Kyal. & Boatwr., a plant with medicinal value

Vachellia gummifera (Willd.) Kyal. & Boatwr. is a medicinal plant endemic to Morocco that has no documented studies on its chemical composition. In this study, the chemical composition of the water/methanol (4 : 1) extracts of air-dried leaf and stem samples of Moroccan V. gummifera was determined using UHPLC-MS and NMR. In total, over 100 metabolites were identified in our study. Pinitol was the major compound in both the leaf and stem extracts, being significantly more abundant in the former. Asparagine and 3-hydroxyheteroendrin were the second most abundant compounds in the stem and leaf extracts, respectively, though both compounds were present in each tissue. The other compounds included flavonoids based on quercetin, and phenolic derivatives. Eucomic acid, only identified in the stems and was the major aromatic compound distinguishing the leaf and stem profiles. Quercetin 3-O-(6′′-O-malonyl)-β-D-glucopyranoside was identified as the major flavonoid in the leaves but was also present in the stems. Other malonylated derivatives that were all flavonol glycosides based on myricetin, kaempferol, and isorhamnetin in addition to quercetin were also identified. This is the first report of eucomic acid and malonylated compounds in Vachellia species. This report provides valuable insights into the chemotaxonomic significance of the Vachellia genus.OCP Morocco.FP05is a collaboration between Mohammed VI Polytechnic University, Rothamsted Research and Cranfield Universit

Therapeutic efficacy of β-sitosterol treatment on Trypanosoma congolense infection, anemia development, and trans-sialidase (TconTS1) gene expression

BackgroundAfrican animal trypanosomiasis hinders sustainable livestock productivity in sub-Saharan Africa. About 17 million infected cattle are treated with trypanocides annually but most of the drugs are associated with drawbacks, necessitating the search for a promising chemotherapeutic agent.ObjectivesIn this study, the effects of β-sitosterol on Trypanosoma congolense infection were investigated along with its effect on the trans-sialidase gene expressions.ResultsOral treatment with β-sitosterol at 15 and 30 mg/kg body weight (BW) for 14 days significantly (p < 0.05) reduced parasitemia and ameliorated the parasite-induced anemia. Also, the parasite-induced increase in serum urea level and renal histopathological damage scores in addition to renal hypertrophy was significantly (p < 0.05) reverted following treatment with 30 mg/kg BW β-sitosterol. The compound also significantly (p < 0.05) down-regulated the expression of TconTS1 but not TconTS2, TconTS3, and TconTS4. Correlation analysis between free serum sialic acid with the TconTS1 and TconTS2 gene variants revealed negative correlations in the β-sitosterol-treated groups although they were non-significant (p > 0.05) in the group treated with 15 mg/kg BW β-sitosterol. Similarly, a non-significant negative (p > 0.05) correlation between the biomolecule and the TconTS3 and TconTS4 gene variants was observed in the β-sitosterol-treated groups while positive correlations were observed in the infected untreated control group.ConclusionThe observed effect of β-sitosterol on T. congolense infection could make the compound a possible template for the design of novel trypanocides