Antidiabetic and Antioxidant Effects of Acteoside from Jacaranda mimosifolia Family Biognoniaceae in Streptozotocin–Nicotinamide Induced Diabetes in Rats

BACKGROUND: Acteoside is a phenylethanoid compound isolated from Jacaranda mimosifolia D. Don leaves with a potential antidiabetic effect. OBJECTIVES: This study was designed to investigate the antidiabetic and antioxidant effects of acteoside in streptozotocin-nicotinamide (STZ-NA)-induced Type 2 diabetes in rats. METHODS: Diabetes was induced by intraperitoneal (i.p.) injection of a single dose of STZ (52.5 mg/kg), 15 min following i.p. administration of NA (25 mg/kg). Rats were divided into six groups; Group I: Normal rat group received the vehicle, Group II: Diabetic control group, and Groups III-IV: Diabetic rat groups were treated by either oral acteoside (10, 20, and 40 mg/kg) or pioglitazone (30 mg/kg) for 21 consecutive days. Biochemical parameters were assessed in the serum and liver homogenates. Examination of liver sections for histopathology was also carried out. RESULTS: Acteoside treated rats showed significant lower levels of blood glucose, glycosylated hemoglobin, total cholesterol, triglycerides, and increased serum insulin compared to control diabetic rats. Furthermore, acteoside treated rats, in comparison to the diabetic control, demonstrated significantly reduced malondialdehyde, increased reduced glutathione liver contents, and attenuated pathological alterations in the liver. These effects were comparable to those caused by the standard antidiabetic drug, pioglitazone. In vitro, acteoside scavenged stable free radical 1,1-diphenyl-2-picrylhydrazyl. CONCLUSION: Acteoside could be considered as a potential therapeutic agent for type 2 diabetes mellitus. However, studying further mechanisms underlying its antidiabetic effect is recommended

Anti-prostate cancer metabolites from the soil-derived Aspergillus neoniveus

Prostate cancer (PCa) ranks as one of the most commonly diagnosed malignancies worldwide. Toxicity, lack of clinical efficacy, and development of resistance phenotypes are the main challenges in the control of prostate malignancies. Notably, castration-resistance prostate cancer (CRPCa) is a highly aggressive and metastatic phenotype of the disease with a poor prognosis and very limited therapeutic options. Herein, we report the isolation and genotypic identification of a soil-derived fungus Aspergillus neoniveus using the PCR-based internal transcribed spacer (ITS) region amplification approach. HPLC/MS investigation of the metabolic profile of the ethyl acetate extract from the fungal biomass revealed tentative identification of forty-five compounds belonging to various chemical classes including γ-butyrolactones, alkaloids, phenolics, and quinoids. Furthermore, the chromatographic purification of microbial extract enabled the identification of nervonic acid methyl ester (1) for the first time from endophytic fungi, as well as acetyl aszonalenin (2), and butyrolactone II (3) for the first time from A. neoniveus. The chemical frameworks of the isolated compounds were identified via extensive spectral analysis including 1 and 2D NMR and MS. The X-ray crystal structure and absolute configuration of acetyl aszonalenin (2) were also determined. Additionally, screening of in vitro anticancer activity of the fungal extract revealed its potential antiproliferative and anti-migratory activities against five different prostate cancer cells (PC3, PC-3M, DU-145, CWR-R1ca, and 22Rv1), including different cells with the castration-resistance phenotype. Moreover, the isolated metabolites significantly inhibited the proliferation, migration, and colonization of human prostate cancer cells at low micromolar levels, thus providing credence for future investigation of these metabolites in relevant anti-prostate cancer animal models. Furthermore, computational target prediction tools identified the cannabinoid G-protein coupled receptors type 1 (CB1) as a potential biological target mediating, at least in part, the anticancer effects of acetylaszonalenin (2). Moreover, molecular modeling and docking studies revealed a favorable binding pose at the CB1 receptor orthosteric ligand pocket aided by multiple polar and hydrophobic interactions with critical amino acids. In conclusion, the Aspergillus neoniveus-derived prenylated indole alkaloid acetylaszonalenin has promising anticancer activity and is amenable to further hit-to-lead optimization for the control of prostate malignancies via modulating CB1 receptor

Appraisal on the Wound Healing Potential of Deverra tortuosa DC. and Deverra triradiata Hochst Essential Oil Nanoemulsion Topical Preparation

Deverra tortuosa (Desf.) DC. and Deverra. triradiata Hochst. ex Bioss are perennial desert shrubs widely used traditionally for many purposes and they are characteristic for their essential oil. The objective of the present study was to investigate the in vivo wound healing activity of the essential oil (EO) of D. tortuosa and D. triradiata through their encapsulation into nanoemulsion. EO nanoemulsion was prepared using an aqueous phase titration method, and nanoemulsion zones were identified through the construction of phase diagrams. The EO was prepared by hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and supercritical fluid extraction (SFE) and analyzed using GC/MS. D. tortuosa oil is rich in the non-oxygenated compound, representing 74.54, 73.02, and 41.19% in HD, MADH, and SFE, respectively, and sabinene represents the major monoterpene hydrocarbons. Moreover, D. triradiata is rich in oxygenated compounds being 69.77, 52.87, and 61.69% in HD, MADH, and SFE, respectively, with elemicin and myristicin as major phenylpropanoids. Topical application of the nanoemulsion of D. tortuosa and D. triradiata (1% or 2%) exhibited nearly 100% wound contraction and complete healing at day 16. Moreover, they exhibit significant antioxidant and anti-inflammatory effects and a significant increase in growth factors and hydroxyproline levels. Histopathological examination exhibited complete re-epithelialization accompanied by activated hair follicles and abundant collagen fibers, especially at a concentration of 2%. Therefore, the incorporation of the two Deverra species into nanoemulsion could professionally endorse different stages of wound healing

Chemical and biological characterization of Melaleuca subulata (Cheel) Craven leaves’ volatile constituents supported by chemometric analysis and molecular docking

Abstract Background The genus Melaleuca (Myrtaceae) comprises dozens of essential oil (EO)-rich species that are appreciated worldwide for their various medicinal values. Additionally, they are renowned in traditional medicine for their antimicrobial, antifungal, and other skin-related activities. The current study investigated the chemical profile and skin-related activities of volatile constituents derived from M. subulata (Cheel) Craven (Synonym Callistemon subulatus) leaves cultivated in Egypt for the first time. Methods The volatile components were extracted using hydrodistillation (HD), headspace (HS), and supercritical fluid (SF). GC/MS and Kovat’s retention indices were implemented to identify the volatile compounds, while the variations among the components were assessed using Principal Component Analysis and Hierarchical Cluster Analysis. The radical scavenging activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and β-carotene assays. Moreover, the anti-aging effect was evaluated using anti-elastase, and anti-collagenase, while the antimicrobial potential was deduced from the agar diffusion and broth microdilution assays. Lastly, the molecular docking study was executed using C-docker protocol in Discovery Studio 4.5 to rationalize the binding affinity with targeted enzymes. Results The SF extraction approach offered the highest EO yield, being 0.75%. According to the GC/MS analysis, monoterpene hydrocarbons were the most abundant volatile class in the HD oil sample (54.95%), with α-pinene being the most copious component (35.17%). On the contrary, the HS and SF volatile constituents were pioneered with oxygenated monoterpenes (72.01 and 36.41%) with eucalyptol and isopulegone being the most recognized components, representing 67.75 and 23.46%, respectively. The chemometric analysis showed segregate clustering of the three extraction methods with α-pinene, eucalyptol, and isopulegone serving as the main discriminating phytomarkers. Concerning the bioactivity context, both SF and HD-EOs exhibited antioxidant effects in terms of ORAC and β-carotene bleaching. The HD-EO displayed potent anti-tyrosinase activity, whereas the SF-EO exhibited significant anti-elastase properties. Moreover, SF-EO shows selective activity against gram-positive skin pathogens, especially S. aureus. Ultimately, molecular docking revealed binding scores for the volatile constituents; analogous to those of the docked reference drugs. Conclusions M. subulata leaves constitute bioactive volatile components that may be indorsed as bioactive hits for managing skin aging and infection, though further in vivo studies are recommended

Bioactive metabolites identified from Aspergillus terreus derived from soil

Abstract Aspergillus terreus has been reported to produce many bioactive metabolites that possess potential activities including anti-inflammatory, cytotoxic, and antimicrobial activities. In the present study, we report the isolation and identification of A. terreus from a collected soil sample. The metabolites existing in the microbial ethyl acetate extract were tentatively identified by HPLC/MS and chemically categorized into alkaloids, terpenoids, polyketides, γ-butyrolactones, quinones, and peptides. In addition, a new triglyceride (1) and a diketopiperazine derivative namely asterrine (4), together with two known butyrolactone (2–3) were purified from the extract. The chemical skeleton of the purified compounds was established by comprehensive analysis of their ESI/MS, 1 and 2D-NMR data. The extract and compounds 3,4 exhibited a strong inhibitory activity for the binding of ACE2 to SARS-CoV-2 spike-protein receptor with IC50 7.4, 9.5, and 8.5 µg/mL, respectively. In addition, the extract, 1 and 2 displayed a potent anti-inflammatory effect with IC50 51.31 and 37.25 pg/mL (Il-6) and 87.97, 68.22 pg/mL (TNF-α), respectively, in comparison to LPS control. In addition, the extract and compound 4 displayed an antimicrobial effect towards S. aureus by MIC 62.5 and 125 μg/mL, while the extract exhibited a potent effect against C. albicans (MIC of 125 μg/mL). Collectively, our data introduce novel bioactivities for the secondary metabolites produced by the terrestrial fungus Aspergillus terreus. 

Article Polyphenolic Profile and Bioactivity Study of Oenothera speciosa Nutt. Aerial Parts

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Polyphenolic Profile of Callistemon viminalis Aerial Parts: Antioxidant, Anticancer and In Silico 5-LOX Inhibitory Evaluations

Five new compounds viz kaempferol 3-O-(4″-galloyl)-β-d-glucopyranosyl-(1‴→6″)-O-β-d-glucopyranoside (1), kaempferol 3-O-β-d-mannuronopyranoside (2), kaempferol 3-O-β-d-mannopyranoside (3), quercetin 3-O-β-d-mannuronopyranoside (4), 2, 3 (S)- hexahydroxydiphenoyl]-d-glucose (5) along with fifteen known compounds were isolated from 80% aqueous methanol extract (AME) of C. viminalis. AME and compounds exerted similar or better antioxidant activity to ascorbic acid using DPPH, O2−, and NO inhibition methods. In addition, compounds 16, 4, and 7 showed cytotoxic activity against MCF-7 cell lines while 3, 7 and 16 exhibited strong activity against HepG2. An in silico analysis using molecular docking for polyphenolic compounds 2, 3, 7, 16 and 17 against human stable 5-LOX was performed and compared to that of ascorbic acid and quercetin. The binding mode as well as the enzyme-inhibitor interactions were evaluated. All compounds occupied the 5-LOX active site and showed binding affinity greater than ascorbic acid or quercetin. The data herein suggest that AME, a source of polyphenols, could be used against oxidative-stress-related disorders

Phenolic profile, anti-inflammatory, antinociceptive, anti-ulcerogenic and hepatoprotective activities of Pimenta racemosa leaves

Abstract Background Pimenta racemosa tree has many traditional uses where its leaves are used as herbal tea for treatment of flatulence, gastric disorder, osteoarthritis, colds and fever in addition to its analgesic and anti-inflammatory activities. So, this study aimed to isolate phenolic constituents of 80% aqueous methanol extract (AME) of leaves and evaluate its biological activities. Methods The defatted AME was chromatographed and structures of the isolated compounds were elucidated using UV, NMR spectroscopy and UPLC-ESI-MS analysis. Antioxidant activity was investigated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity. Anti-inflammatory activity was evaluated using carrageenan - induced paw oedema, while antinociceptive activity was determined by chemical and thermal stimuli. Anti-ulcerogenic effect of AME against gastric damage induced by ethanol in Wister male albino rats was evaluated. Also, hepatoprotective activity was investigated through determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) following oral administration of paracetamol. Both of Anti-ulcerogenic and hepatoprotective activities (125, 250 and 500 mg/kg b.wt.) were supported by histopathological examinations. Results Gallic acid (1), methyl gallate (2), avicularin (3), quercetin 3-O-β-D-arbinopyranoside (4), quercetin 3-O-β-D-glucopyranoside (5), quercetrin (6), cynaroside (7), strictinin (8), castalagin (9), grandinin (10) quercetin (11) and ellagic acid (12) were isolated. AME showed significant radical scavenging activity (SC50 = 4.6 μg/mL), promising anti-inflammatory effect through inhibition of oedema and antinociceptive activity by reduction in number of writhes after acetic acid injection and prolongation of reaction time towards the thermal stimulus. AME reduced the gastric mucosal lesions compared with ethanol control and ranitidine groups, ALT at the three doses and AST only at 125 and 250 mg/kg b.wt., when compared with paracetamol group. The results were confirmed by histopathological studies. Conclusion P. racemosa leaves are rich in phenolic compounds and showed significant biological activities

Cytotoxicity, Antimicrobial, and In Silico Studies of Secondary Metabolites From Aspergillus sp. Isolated From Tecoma stans (L.) Juss. Ex Kunth Leaves

Elsayed HE, Kamel RA, Ibrahim RR, et al. Cytotoxicity, Antimicrobial, and In Silico Studies of Secondary Metabolites From Aspergillus sp. Isolated From Tecoma stans (L.) Juss. Ex Kunth Leaves. Frontiers in Chemistry. 2021;9: 760083.Endophytes are prolific producers of privileged secondary metabolites with diverse therapeutic potential, although their anticancer and antimicrobial potential still have a room for further investigation. Herein, seven known secondary metabolites namely, arugosin C (1), ergosterol (2), iso-emericellin (3), sterigmatocystin (4), dihydrosterigmatocystin (5), versicolorin B (6), and diorcinol (7) were isolated from the rice culture ofAspergillus sp.retrieved fromTecoma stans(L.) Juss. ex Kunth leaves. Their anticancer and antimicrobial activities were evaluated in MTT and agar well diffusion assays, respectively. The cytotoxicity results showed that metabolite3displayed the best viability inhibition on the MCF-7 breast cancer cells with IC50= 225.21 µM, while5on the HepG2 hepatocellular carcinoma cells with IC50= 161.81 µM.5demonstrated a 60% apoptotic mode of cell death which is virtually correlated to its high docking affinity to Hsp90 ATP binding cleft (binding score −8.4 Kcal/mol). On the other side, metabolites4and5displayed promising antimicrobial activity especially onPseudomonas aeruginosawith MIC = 125 μg/ml. The observed effect may be likely related to their excellentin silicoinhibition of the bacterial DNA-gyrase kinase domain (binding score −10.28 Kcal/mol). To the best of our knowledge, this study is the first to report the promising cytotoxic and antibacterial activities of metabolites 3, 4, and 5 which needs further investigation and renovation to therapeutic leads

UHPLC-MS profiles and antidiarrheal activity for two Quercus species grown in Egypt

 Quercus L. genus (Oak) belongs to the family Fagaceae and their galls are used commercially in leather tanning, dyeing, and ink preparation. Several Quercus species were used traditionally in the management of wound healing, acute diarrhea, hemorrhoid, and inflammatory diseases. The present study aims to investigate the phenolic content of the 80% aqueous methanol extract (AME) of Q. coccinea and Q. robur leaves as well as to assess their anti-diarrheal activity. Twenty-five and twenty-six polyphenolic compounds were tentatively identified in Q. coccinea and Q. robur AME, respectively using UHPLC/MS. The identified compounds are related to quercetin, kaempferol, isorhamnetin, and apigenin glycosides and their aglycones. In addition, hydrolyzable tannins, phenolic acid, phenyl propanoides derivatives, and cucurbitacin F were also identified in both species.  </p