Cattleianal and Cattleianone: Two New Meroterpenoids from Psidium cattleianum Leaves and Their Selective Antiproliferative Action against Human Carcinoma Cells.

The Myrteacae family is known as a rich source of phloroglucinols, a group of secondary metabolites with notable biological activities. Leaves of Psidium cattleianum were extracted with chloroform: methanol 8:2 to target the isolation of phloroglucinol derivatives. Isolated compounds were characterized using different spectroscopic methods: nuclear magnetic resonance (NMR), ultra-violet (UV) and mass spectrometry (MS). Two new phloroglucinols were evaluated for cytotoxicity against a panel of six human cancer cell lines, namely colorectal adenocarcinoma cells (HT-29 and HCT-116); hepatocellular carcinoma cells (HepG-2); laryngeal carcinoma (Hep-2); breast adenocarcinoma cells (MCF7 and MDA-MB231), in addition to normal human melanocytes HFB-4. Additionally, cell cycle analysis and annexin-V/FITC-staining were used to gain insights into the mechanism of action of the isolated compounds. The new phloroglucinol meroterpenoids, designated cattleianal and cattleianone, showed selective antiproliferative action against HT-29 cells with IC50's of 35.2 and 32.1 µM, respectively. Results obtained using cell cycle analysis and annexin-V/FITC-staining implicated both necrosis and apoptosis pathways in the selective cytotoxicity of cattleianal and cattleianone. Our findings suggest that both compounds are selective antiproliferative agents and support further mechanistic studies for phloroglucinol meroterpenoids as scaffolds for developing new selective chemotherapeutic agents.

Combination of pomegranate extract and curcumin ameliorates thioacetamide-induced liver fibrosis in rats: impact on TGF-ß/Smad3 and NF-κB signaling pathways.

Protection against liver injury and its consequences is considered an essential issue to minimize the number of annual deaths caused by liver diseases. The present study was designed to evaluate the potential role of pomegranate extract (PE) and/or curcumin in the regression of thioacetamide (TAA)-induced liver fibrosis, focusing on their modulatory effects on Nrf2/HO-1, NF-κB, and TGF-ß/Smad3 signaling pathways. Liver fibrosis was induced in male Wistar rats by intraperitoneal injection of TAA (100 mg/kg) three times a week, for 8 weeks. To assess the protective effects of PE and/or curcumin against TAA-induced liver fibrosis, rats were treated on a daily basis with oral doses of PE (200 mg/kg) and/or curcumin (200 mg/kg) for 8 weeks. The results indicated that PE and/or curcumin attenuated TAA-induced liver fibrogenesis, as evidenced by a significant improvement in the liver function tests (AST, ALT, ALP, and albumin), oxidative stress biomarkers (MDA, SOD, and GSH), and inflammatory biomarkers (NF-ĸB, TNF-α, IL-1ß, iNOS, TGF-ß, and MPO), compared to TAA group. Moreover, treatment with PE and/or curcumin exerted a significant upregulation of Nrf2/HO-1 gene expressions along with significant downregulation of NF-ĸB, TGF-ß, and phospho-Smad3 protein expressions, as well as α-SMA and collagen-1 gene expressions. The histopathological examination has corroborated these findings. In conclusion, hepatoprotective activities of PE and/or curcumin could be linked to their abilities to modulate Nrf2/HO-1, NF-κB, and TGF-ß/Smad3 signaling pathways. It is worth noting that the combination of PE and curcumin exerted superior hepatoprotective effects against TAA-induced liver fibrosis, as compared to monotherapy.

Randomized double-blinded pilot clinical study of the antidiabetic activity of Balanites aegyptiaca and UPLC-ESI-MS/MS identification of its metabolites.

CONTEXT: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are traditionally known for the treatment of hyperglycaemia. Several in vitro and in vivo studies proposed some mechanisms of action. However, clinical trials in human beings were never reported to date. OBJECTIVES: To investigate the antidiabetic efficacy of the 70% ethanol extract of the pericarps of B. aegyptiaca (BE) within a nutritional intervention in elderly people. MATERIALS AND METHODS: Ultra-performance electrospray ionization-mass spectroscopy (UPLC-ESI-MS/MS) analysis was used for metabolic profiling of BE which was incorporated in hard gelatine capsules (400 mg/day) and tested on 30 type 2 diabetes (T2D) Egyptian patients for 8 weeks. According to sex, age and body mass index participants were divided into two equivalent groups, placebo and treatment. RESULTS: Thirteen compounds were identified in BE using UPLC-ESI-MS/MS analysis among which five steroidal saponins, seven phenolic compounds and a sterol glucoside. At the end of the 8-week treatment, the treated group showed 26.88% decrease in 2 h postprandial plasma glucose relative to 2.6% increase in the placebo group, while fasting plasma glucose was reduced to 10.3%. Treatment with BE capsules for 8 weeks produced significant reduction in the plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol by 9.0, 12.76 and 21.35%, respectively, with 29.8% increase in the high-density lipoprotein cholesterol. Plasma alanine transaminase and aspartate transaminase were reduced by 42.6 and 43.3%, respectively. DISCUSSION AND CONCLUSION: Administration of the BE capsules to T2D resulted in significant improvements in the glycaemic markers and the lipid profile, without adverse effects or hypoglycaemia.

Use of Random Amplified Polymorphic DNA (RAPD) Technique to Study the Genetic Diversity of Eight Aloe Species.

The genus Aloe comprises over 400 species of flowering succulent plants. Aloe leaves are used in the treatment of asthma, gastrointestinal ulcers, cardiovascular disease, tumors, burns, and diabetes. They are rich in anthraquinones, such as aloin, aloe-emodin, chrysophanol, aloinoside A, and aloinoside B. The various species of Aloe show chemical and morphological similarity and diversity, which depend on the genotype and environmental conditions. In a continuity to our interest in the genus Aloe, this study targets the authentication of eight different Aloe species, Aloe vera (A1), Aloe arborescens (A2), Aloe eru (A3), Aloe grandidentata (A4), Aloe perfoliata (A5), Aloe brevifolia (A6), Aloe saponaria (A7), and Aloe ferox (A8), grown in Egypt by using the technique of random amplified polymorphic DNA. Twelve decamer primers were screened in amplification with genomic DNA extracted from all species, of which five primers yielded species-specific reproducible bands. Out of 156 loci detected, the polymorphic, monomorphic, and unique loci were 107, 26, and 23, respectively. Based on a dendrogram and similarity matrix, the eight Aloe species were differentiated from each other and showed more divergence. Aloe species prevailed similarity coefficients of 54-70 % by which they could be classified into three major groups. Thus, this technique may contribute to the identification of these Aloe species that have great morphological similarity in the Egyptian local markets.

Anti-acetylcholinesterase activity of essential oils and their major constituents from four Ocimum species.

Ocimum is a genus of considerable importance in traditional medicine worldwide. The goal of this study was to examine the anti-acetylcholinesterase activity of Ocimum essential oils and to correlate the activity with their chemical profiles using a metabolome based GC-MS approach coupled to chemometrics. Further, molecular docking was adopted to rationalize the activity of some essential oil isolates. Essential oil prepared from the four species O. basilicum, O. africanum, O. americanum, and O. minimum exhibited significant anti-acetylcholinesterase activity with (IC50 0.22, 0.175, 0.57 and 0.152 mg/mL, respectively) comparable to that of physostigmine (IC50 0.27 mg/mL). The phenylpropanoids (i.e. estragole) constituted the most dominant chemical group in O. basilicum (sweet basil) and O. minimum, whereas camphor (a ketone) was the most abundant in O. africanum and O. americanum. Supervised and unsupervised multivariate data analyses clearly separated O. africanum and O. americanum from other accessions, with estragole, camphor and, to less extent, ß-linalool contributing to species segregation. Estragole was found the most active AchE inhibitor (IC50 0.337 µM) followed by cineole (IC50 2.27 µM), camphor (IC50 21.43 µM) and eugenol (IC50 40.32 µM). Molecular docking revealed that these compounds bind to key amino acids in the catalytic domain of AchE, similar to standard drugs.

Metabolic profile and hepatoprotective activity of the anthocyanin-rich extract of Hibiscus sabdariffa calyces.

CONTEXT: Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological activities. OBJECTIVES: To evaluate the hepatoprotective effect and study the metabolic profile of the anthocyanin-rich extract of H. sabdariffa calyces (HSARE). MATERIALS AND METHODS: The hepatoprotective activity of HSARE was assessed (100 mg/kg/d for 4 weeks) by examining the hepatic, inflammatory, oxidative stress markers and performing a histopathological examination in rats with thioacetamide (TAA)-induced hepatotoxicity. HSARE was analyzed using ultra-performance liquid chromatography-quadrupole-time-of-flight-photodiode array-mass spectrometry (UPLC-qTOF-PDA-MS). RESULTS: The UPLC-qTOF-PDA-MS analysis of HSARE enabled the identification of 25 compounds represented by delphinidin and its derivatives, cyanidin, kaempferol, quercetin, myricetin aglycones and glycosides, together with hibiscus lactone, hibiscus acid and caffeoylquinic acids. Compared to the TAA-intoxicated group, HSARE significantly reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and hepatic malondialdehyde by 37.96, 42.74 and 45.31%, respectively. It also decreased hepatic inflammatory markers, including tumour necrosis factor alpha, interleukin-6 and interferon gamma (INF-γ), by 85.39, 14.96 and 70.87%, respectively. Moreover, it decreased the immunopositivity of nuclear factor kappa-B and CYP2E1 in liver tissue, with an increase in the effector apoptotic marker (caspase-3 positive cells), restoration of the altered hepatic architecture and increases in the activities of superoxide dismutase (SOD) and glutathione by 150.08 and 89.23%, respectively. DISCUSSION AND CONCLUSION: HSARE revealed pronounced antioxidant and anti-inflammatory potential where SOD and INF-γ were significantly improved. HSARE possesses the added value of being more water-soluble and of natural origin with fewer side effects expected compared to silymarin.

Chemical composition and bioactivity of the volatile oil from leaves and stems of Eucalyptus cinerea.

CONTEXT: Eucalyptus cinerea F. Muell. ex Benth. (Myrtaceae) is a medium-sized tree cultivated in Egypt. OBJECTIVE: First, to determine the chemical composition of the volatile oil of the juvenile leaves and stems of E. cinerea to identify its chemotype. Second, to study the in vivo antioxidant activity and in vitro antimicrobial activity of the studied volatile oils against selected Gram-positive, Gram-negative bacteria, yeast, and mycelia fungi. MATERIALS AND METHODS: The volatile oil was prepared by hydrodistillation and then identified by GC/MS analysis. Broth microdilution and agar dilution methods were applied for determining the MIC. The antioxidant activity was studied by determination of glutathione level in blood of alloxan-induced diabetic rats. RESULTS: The yield of the volatile oil hydrodistilled from the juvenile leaves and stems of E. cinerea was 4.5 and 0.5%, respectively. 1,8-Cineole was the major identified oxygenated monoterpenoid (84.55% and 60.15% in the juvenile leaves and stems, respectively). The antibacterial activity of the oil of the juvenile leaves was more potent against all the tested organisms than that of the stems. The (MIC) of volatile oil of the juvenile leaves against Escherichia coli, Pseudomonas aeruginosa, Streptococcus faecalis, Candida albicans, and Aspergillus flavus were 5.2, 5.6, 4, 4.8, and 12.8 µg/ml, respectively. Also, the juvenile leaves' oil was more active as an antioxidant than that of the stems. They restored glutathione level by 33.7 ± 1.1 and 29.6 ± 0.7 mg/dl, respectively, compared with vitamin E (35.9 ± 1.2 mg/dl) which was used as a reference. DISCUSSION AND CONCLUSION: RESULTS suggest that the volatile oil is 1,8-cineole chemotype. Moreover, the oil of the juvenile leaves of E. cinerea might find usefulness as a therapeutic agent following further development.

Rosemary and neem: an insight into their combined anti-dandruff and anti-hair loss efficacy.

Dandruff, a common scalp disorder characterized by flaking dead skin, is often treated with conventional topical products. However, limitations exist due to potential side effects and high costs. Therefore, searching for natural, cost-effective solutions for dandruff and hair loss is crucial. Rosemary herb and neem tree, both cultivated in Egypt, possess well-documented anti-inflammatory properties derived from their rich phenolic phytoconstituents. This study formulated a standardized combined extract of rosemary and neem (RN-E 2:1) into hair gel and leave-in tonic formats. This extract demonstrated superior efficacy against Malassezia furfur (a causative agent of dandruff) and Trichophyton rubrum (associated with scalp disorders) compared to the conventional antifungal agent, ketoconazole. The combined extract (RN-E 2:1) also exhibited potent anti-inflammatory activity. Additionally, the suppression of iNOS expression is considered concentration-dependent. Quality control verified formulation stability, and ex-vivo studies confirmed effective ingredient penetration into the epidermis, the primary site of fungal presence. Remarkably, both formulations outperformed the standard treatment, minoxidil in hair growth trials. These findings highlight the potential of natural extracts for scalp and hair health.

Development and validation of a high-performance liquid chromatography method for standardization of the bioactive ethyl acetate fraction of Alstonia scholaris (Linn.) R. Br. growing in Egypt.

Bio-guided fractionation of the ethanolic extract of the leaves of Alstonia scholaris (Apocynaceae) growing in Egypt was carried out to evaluate its antihyperglycemic activity in alloxan-induced diabetic rats and its hepatoprotective activity against CCl4-induced hepatotoxicity in rats. The ethyl acetate fraction of the ethanolic extract showed the highest antihyperglycemic [(133.6 +/- 4.2) mg/mL, relative to metformin with (92.3 +/- 2.7) mg/mL] and hepatoprotective [(37.9 +/- 1.4) U/L, relative to silymarin with (29.7 +/- 0.8) U/L] activities. Four compounds were isolated from this fraction, and identified by spectroscopic techniques and by comparison with reported data: caffeic acid and isoquercitrin for the first time from this plant, in addition to quercetin 3-O-beta-D-xylopyranosyl (1''' --> 2")-beta-D-galactopyranoside (major compound) and chlorogenic acid. A validated reversed phase-high-performance liquid chromatography (RP-HPLC) method was developed for the standardization of the bioactive ethyl acetate fraction. The calibration curve showed good linearity (r2 > 0.999) within tested ranges. The relative standard deviation of the method was less than 3% for intra- (0.4-2.0%) and inter-day (1.9-2.8%) assays. Mean recovery of the method was within the range of 98.5-102.5%. The minimum detectable concentration of the analyte (LOD) was found to be 0.04 microg/mL. This developed HPLC method was shown to be simple, rapid, precise, reproducible, robust, specific, and accurate for quality assessment of the bioactive fraction.

New bioactive metabolites from a crown gall induced on an Eucalyptus tereticornis Sm. tree.

Applying a bioactivity-guided isolation strategy for the ethanolic extract of crown gall tumours induced on an Eucalyptus tereticornis tree, two new compounds in addition to a known one were isolated. The new compounds were identified as an amino acid derivative named 1-ethyl-6-(1'-methyl-1'-phenylethyl) piperidin-2-one (1) and a lanostane tetracyclic triterpene named 3beta-hydroxy-24-methyllanosta-8,17(20),24(28)-trien-22-oic acid (2), together with stigmasterol-3-O-glucoside (3). The three compounds exhibited significant cytotoxic activity against two human cell lines, breast (MCF7) and colon (HCT116), with IC50 values of 1.01, 1.54, and 2.15 microg/ml, respectively, against MCF7 and 3.49, 3.83, and 3.39 microg/ ml, respectively, against HCT116. Furthermore, in rats elevated levels of blood cholesterol, triglycerides, and low-density lipoprotein (LDLc) were significantly reduced, while the level of high-density lipoprotein (HDLc) was significantly increased by administration of the ethanolic extract as well as of 3. These results support a correlation between the reduction of blood cholesterol levels and improvement of colorectal cancer.

A novel lupene derivative from Thymus capitatus possesses an apoptosis-inducing effect via Let-7 miRNA/Cyclin D1/VEGF cascade in the A549 cell line.

Non-small-cell lung carcinoma (NSCLC) is a type of epithelial lung cancer accounting for about 85% of all lung cancers. In our research, a novel lupene derivative namely acetoxy-lup-5(6), 20(29)-diene (ALUP), as well as two known triterpenes; lupeol (LUP) and betulinic acid (BA) were isolated through the chromatographic purification of the 95% ethanolic extract of Thymus capitatus. Identification of the compounds was carried out by physicochemical properties as well as spectral 1D and 2D NMR analysis. The anti-cancer activity of the three triterpenes was assessed on non-small cell lung cancer cell line; A549 using MTT assay and cell cycle analysis using annexin V/propidium iodide. The molecular mechanism underlying anti-apoptotic effects was determined by analyzing Let-7 miRNA and miRNA-21 expression, the mRNA gene expression level of Bax, CASP-8, CD95, Bcl2, KRAS, VEGF, Cyclin D1 using qRT-PCR. Our results revealed that the three isolated compounds ALUP, LUP, and BA caused cell cycle arrest at the G2/M phase with an increase in the apoptosis which may be attributed to their significant effect on raising Bax, CASP-8, and CD95 and reducing the mRNA expression levels of Bcl-2, KRAS, VEGF, and Cyclin D1 compared to control cells. RT-PCR results showed that the ALUP, LUP, and BA significantly downregulated miRNA-21 expression. Meanwhile, the three compounds caused significant overexpression of Let-7 miRNA. This is the first report on the anti-cancer activity of acetoxy-lup-5(6), 20(29)-diene (ALUP) in reducing the proliferation and differentiation of the A549 cell line through inducing apoptosis. Finally, by targeting the Let-7 miRNA/Cyclin D1/VEGF cascade, acetoxy-lup-5(6), 20(29)-diene could be a potential therapeutic agent for lung cancer.

Nanotechnology in leukemia: diagnosis, efficient-targeted drug delivery, and clinical trials.

Leukemia is a group of malignant disorders which affect the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Many types of leukemia exist; thus, their diagnosis and treatment are somewhat complicated. The use of conventional strategies for treatment such as chemotherapy and radiotherapy may develop many side effects and toxicity. Hence, modern research is concerned with the development of specific nano-formulations for targeted delivery of anti-leukemic drugs avoiding toxic effects on normal cells. Nanostructures can be applied not only in treatment but also in diagnosis. In this article, types of leukemia, its causes, diagnosis as well as conventional treatment of leukemia shall be reviewed. Then, the use of nanoparticles in diagnosis of leukemia and synthesis of nanocarriers for efficient delivery of anti-leukemia drugs being investigated in in vivo and clinical studies. Therefore, it may contribute to the discovery of novel and emerging nanoparticles for targeted treatment of leukemia with less side effects and toxicities.

Anti-Obesity Effect of a Tea Mixture Nano-Formulation on Rats Occurs via the Upregulation of AMP-Activated Protein Kinase/Sirtuin-1/Glucose Transporter Type 4 and Peroxisome Proliferator-Activated Receptor Gamma Pathways.

White, green, and oolong teas are produced from the tea plant (Camellia sinensis (L.) Kuntze) and are reported to have anti-obesity and hypolipidemic effects. The current study aims to investigate the anti-obesity effects of a tea mixture nano-formulation by targeting the AMPK/Sirt-1/GLUT-4 axis in rats. In vitro lipase and α-amylase inhibition assays were used to determine the active sample, which was then incorporated into a nanoparticle formulation subjected to in vivo anti-obesity testing in rats by measuring the expression level of different genes implicated in adipogenesis and inflammation using qRT-PCR. Moreover, metabolomic analysis was performed for each tea extract using LC/ESI MS/MS coupled to chemometrics in an attempt to find a correlation between the constituents of the extracts and their biological activity. The in vitro pancreatic lipase and α-amylase inhibition assays demonstrated more effective activity in the tea mixture than the standards, orlistat and acarbose, respectively, and each tea alone. Thus, the herbal tea mixture and its nanoparticle formulation were evaluated for their in vivo anti-obesity activity. Intriguingly, the tea mixture significantly decreased the serum levels of glucose and triglycerides and increased the mRNA expression of GLUT-4, P-AMPK, Sirt-1, and PPAR-γ, which induce lipolysis while also decreasing the mRNA expression of TNF-α and ADD1/SREBP-1c, thereby inhibiting the inflammation associated with obesity. Our study suggests that the tea mixture nano-formulation is a promising therapeutic agent in the treatment of obesity and may also be beneficial in other metabolic disorders by targeting the AMPK/Sirt-1/Glut-4 pathway.

Non-polar metabolites of green beans (Phaseolus vulgaris L.) potentiate the antidiabetic activity of mesenchymal stem cells in streptozotocin-induced diabetes in rats.

Green beans (Phaseolus vulgaris L.) are consumed as pods or mature seeds (common beans). The pods were extracted with 95% ethanol and processed to prepare non-polar and polar fractions. Comparing the antihyperglycemic activity of both fractions, non-polar fraction (NPF, 200 mg kg-1  day-1 ) lowered blood glucose in streptozotocin diabetic rats by 65% compared to 57% for the polar fraction at the same dose. When NPF treatment was combined with injection of mesenchymal stem cells (MSC) a 4.4-fold increase in serum insulin and a 73.6% reduction in blood glucose were observed compared to untreated control. Additionally, a significant decrease in malondialdehyde (76.2%), nitric oxide (68.2%), cholesterol (76.1%), and triglycerides (69.5%) and a 1.75-fold increase in HDL concentrations were observed in the group treated with this combination compared to diabetic animals. Interestingly, NPF increased homing of MSC in pancreas potentiating their antidiabetic activity. Finally, 26 compounds were identified in NPF using LC/MS analysis and four were isolated in pure form. The isolated compounds namely calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol showed good inhibitory activity against pancreatic lipase with IC50 at 1.93, 1.07, 1.34 and 1.44-1 µg/ml, respectively. Additionally, these compounds inhibited α-amylase, albeit at higher concentration, with IC50 at 248, 212, 254, and 155 µg/ml for calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol, respectively. Our results suggest that green beans extract can potentiate effect of MSC in diabetes directly due to its own antidiabetic effect and indirectly by increasing MSC homing in pancreatic tissues. PRACTICAL APPLICATIONS: It has been suggested in this study that green beans can improve hyperglycemia, oxidative balance in diabetes, so green beans can be promoted as a healthy nutrient for diabetic patients. Green beans also can enhance homing and differentiation of mesnchymal stem cells in the pancreas for future stem cell therapy of type I diabetes.

Comparative metabolite profiling of four polyphenol rich Morus leaves extracts in relation to their antibiofilm activity against Enterococcus faecalis.

Enterococci are a common cause of urinary tract infections. The severity of enterococcal infections is associated with their ability to form biofilms. Morus leaves are known as a natural antibacterial, however, their antibiofilm activity against Enterococcus remains unveiled. This study aimed to evaluate the ability of four polyphenol-rich Morus leaves extracts (Morus nigra, M. rubra, M. macroura, and M. alba) to inhibit biofilm formed by enterococcal clinical isolates in relation to their metabolic profiling. Results revealed that 48% of the isolates formed strong biofilm, 28% formed moderate biofilm, 20% formed weak biofilm, and only 4% did not form a biofilm. The strong biofilm-forming isolates were E. faecalis, and hence were chosen for this study. The antibiofilm activity of the four polyphenol-rich Morus leaves extracts revealed that the M. nigra extract exhibited the highest percentage of biofilm inhibition followed by M. rubra then M. macroura and the least inhibition was detected in M. alba, and these results were in accordance with the phenolic and flavonoid contents of each extract. UPLC-ESI-MS/MS identified 61 polyphenolic compounds in the four extracts. Further, multivariate analysis confirmed clear segregation of M. nigra from the other species suggesting disparity in its metabolome, with accumulation of flavonoids, anthocyanidins, phenolic acids and coumarin derivatives. Quercetin and kaempferol glycosides were found to be positively and significantly correlated to the antibiofilm activity. In conclusion, M. nigra ethanolic extracts showed the highest phenolic content and antibiofilm activity and they could be developed as a complementary treatment for the development of antimicrobial agents.

A new hepatoprotective flavone glycoside from the flowers of Onopordum alexandrinum growing in Egypt.

A bioactivity-guided fractionation of the ethyl acetate fraction of the flowers of Onopordum alexandrinum L. (Asteraceae) yielded a new flavonoidal glycoside designated as acacetin-7-O-galacturonide (9), alongside with nine known flavonoids; 6-methoxy-apigenin (hispidulin) (1), acacetin (2), apigenin (3), luteolin (4), kaempferol (5), eriodictyol (6), apigenin-7-O-glucoside (7), luteolin-7-O-glucoside (8), and kaempferol-3-O-rutinoside (10). The compounds were assayed for their hepatoprotective activity against CCl4-induced hepatic cell damage in rats and free radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 4, 6, 9, and 10 have not been previously reported from flowers of O. alexandrinum L., and this is the first report of acacetin-7-O-galacturonide (9) in nature which has also shown significant hepatoprotective and free radical scavenging effects. The isolated compounds were identified using different spectroscopic methods (UV, 1H NMR, 13C NMR, HMQC, HMBC, and COSY).

Phenolics from Physalis peruviana fruits ameliorate streptozotocin-induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression.

The objective of our study was to evaluate the effect of Physalis peruviana L. fruits in the management of diabetes and diabetic nephropathy in relation to its metabolic profile. In-vitro α-amylase, ß-glucosidase, and lipase inhibition activities were assessed for the ethanolic extract (EtOH) and its subfractions. Ethyl acetate (EtOAc) fraction showed the highest α-amylase, ß-glucosidase, and lipase inhibition effect. In vivo antihyperglycemic testing of EtOAc in streptozotocin (STZ)-induced diabetic rats showed that it decreased the blood glucose level, prevented the reduction in body weight, improved serum indicators of kidney injury (urea, uric acid, creatinine), and function (albumin and total protein). EtOAc increased autophagic parameters (LC3B, AMPK) and depressed mTOR contents. Histopathology revealed that EtOAc ameliorated the pathological features and decreased the glycogen content induced by STZ. The immunohistochemical analysis showed that EtOAc reduced P53 expression as compared to the STZ-diabetic group. UPLC-ESI-MS/MS metabolite profiling of EtOAc allowed the identification of several phenolic compounds. Among the isolated compounds, gallic acid, its methylated dimer and the glycosides of quercetin had promising α-amylase and ß-glucosidase inhibition activity. The results suggest that the phenolic-rich fraction has a protective effects against diabetic nephropathy presumably via enhancing autophagy (AMPK/mTOR pathway) and prevention of apoptosis (P53 suppression).

Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer.

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.

Downregulation of MMP1 expression mediates the anti-aging activity of Citrus sinensis peel extract nanoformulation in UV induced photoaging in mice.

Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine metabolites. CSPE was standardized to a hesperidin content of 15.53 ± 0.152 mg% using RP-HPLC. It was suggested that the optimized formulation (F7) had (245 nm) particle size, (91.065%) EE, and (91.385%) occlusive effect with a spherical and smooth surface. The visible appearance of UV-induced photoaging in mice was significantly improved after topical application on CSPE-NLC cream for 5 weeks, levels of collagen and SOD were significantly increased in CSPE- NLC group, while levels of PGE2, COX2, JNK, MDA, and elastin was reduced. Finally, The prepared anti-aging CSPE-NLC cream represents a safe, convenient, and promising skincare cosmetic product.

A Novel Biochemical Study of Anti-Ageing Potential of Eucalyptus Camaldulensis Bark Waste Standardized Extract and Silver Nanoparticles.

Eucalyptus camaldulensis Dehnh belongs to family Myrtaceae. They are massive in Egypt. Although reputed for high phenolic content, barks are considered waste. Ageing is a natural phenomenon caused by apoptosis and senescence resulting in wrinkles. The phytochemical analysis of the 70% ethanolic Eucalyptus camaldulensis bark extract (EBE) and evaluation of its anti-ageing potential and as silver nanoparticles (AgNPs) were conducted in this study. Ultra performance liquid chromatography / electrospray ionization mass spectrometry of EBE fingerprint revealed twenty compounds, where Rutin was major. EBE was standardized to contain 1.26 % Rutin. AgNPs synthesized by green synthesis, were characterized by transmission electron microscope and zeta potential measurement. Both EBE and AgNPs were subjected to MTT assay in HFB4 cells and cell cycle arrest. Flow cytometry was used to assess apoptosis and p16 INK4a. Genetic expression of p53 and p21 and telomerase level were determined. Anti-wrinkle enzyme assays were done. AgNps were spherical, 468.7 nm in size and with Poly dispersity index of 0.817 ± 0.129. EBE and AgNPs with IC50 0.156 mg/mL ± 0.05 and 2.315 ± 0.07 µg/mL expressed significant difference in % of cells (DNA content) at G2/M, apoptotic cells numbers, p53 and p21expression and p16INK4a vs aged cells (P < 0.0001). Both expressed significant increase in telomerase (P < 0.0001). They exhibited elastase, collagenase and tyrosinase inhibition (75 ± 4.3 and 75.9 ± 6.8 % at 300 µg/mL, 58 ± 4.8 and 63 ± 2.3, at 500 µg/mL, 51 ± 4.8 and 65 ± 5.87, at 500 µg/mL, respectively. Although it is considered waste, EBE and Ag NPs are anti-ageing candidates as they inhibit apoptosis, senescence and prevent wrinkles formation.