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Multitude of diseases and side effects from conventional drugs have surged the use of herbal remedies. Thus, the current study aimed to appraise various pharmacological attributes of Artemisia brevifolia Wall. ex DC. Extracts prepared by successive solvent extraction were subjected to phytochemical and multimode antioxidant assays. Various polyphenolics and artemisinin derivatives were detected and quantified using RP-HPLC analysis. Compounds present in methanol (M) and distilled water (DW) extracts were identified using high resolution mass spectrometry (HRMS). Extracts were pharmacologically evaluated for their antibacterial, antifungal, antimalarial, antileishmanial and antidiabetic potentials. Moreover, cytotoxicity against Artemiasalina, human cancer cell lines and isolated lymphocytes was assessed. Genotoxicity was evaluated using comet, micronucleus and chromosomal aberration assays. Lastly, anti-inflammatory potential was determined through a series of in vitro and in vivo assays using BALB/c mice. Maximum extract recovery (5.95% w/w) was obtained by DW extract. Highest phenolics and flavonoids content, total antioxidant capacity, total reduction potential, percentfree radical scavenging, β-carotene scavenging and iron chelating activities were exhibited by M extract. RP-HPLC analysis revealed significant amounts of various polyphenolic compounds (vanillic acid, syringic acid, emodin and luteolin), artemisinin, dihydro artemisinin, artesunate and artemether in ethyl acetate (EA) extract. Total 40 compounds were detected through HRMS. A noteworthy antimicrobial activity (MIC 22.22 µg/ml) was exhibited by EA extract against A. fumigatus and several bacterial strains. Maximum antimalarial, antileishmanial, brine shrimp lethality and cytotoxic potential against cancer cells was manifested by EA extract. None of the extracts exhibited genotoxicity and toxicity against isolated lymphocytes. Highest α-amylase and α-glucosidase inhibition capacities were demonstrated by DW extract. Various in-vivo anti-inflammatory models revealed significant (p < 0.05) anti-inflammatory potential of M and DW extracts. In conclusion, present findings divulged theremarkable pharmacological potential of A. brevifolia and endorse its richness in artemisinin. [ABSTRACT FROM AUTHOR]

Withanolides are natural medicinal agents whose safety and therapeutic profiles make them valuable to mankind. Among multiple withanolides, withametelin is underexplored. The present study was aimed to create a general biological profile of isolated withametelin from Datura innoxia Mill. targeting different biological models. In-silico studies include drug-likeliness, pharmacokinetics, toxicity, molecular targets and cytotoxicity to cancer cell lines predictions. In silico directed preliminary in-vitro evaluation comprised of cancer/normal cell cytotoxicity, DPPH and protein kinase inhibition assays while in-vivo bioactivities include antiinflammatory, analgesic, antidepressant and anticoagulant assays. Pharmacological findings were strengthened by molecular docking studies to check interactions with various proteins and to propose the future path of studies. Results indicated compliance with Lipinski drug-likeliness rule (score −0.55). ADMET prediction showed strong plasma protein binding, GI absorption (Caco-2 cells permeability = 46.74 nm/s), blood brain barrier penetration (Cbrain/Cblood = 0.31), efflux by P-glycoprotein, metabolism by CYP1A2, CYP2C19 and CYP3A4, medium hERG inhibition and non-carcinogenicity in rodents. Predicted molecular targets included mainly receptors (glucocorticoid, kappa opioid, delta opioid, adrenergic and dopamine), oxidoreductase (arachidonate 5-lipoxygenase and cyclooxygenase-2), enzymes (HMG-CoA reductase) and kinase (NFκb). Withametelin was more cytotoxic to cancer cells (DU145 IC 50 7.67 ± 0.54 µM) than normal lymphocytes (IC 50 33.55 ± 1.31 µM). It also showed good antioxidant and protein kinase inhibition potentials. Furthermore, withametelin (20 mg/kg) significantly reduced inflammatory paw edema (68.94 ± 5.55%), heat-induced pain (78.94 ± 6.87%) and immobility time (50%) in animals. Molecular docking showed hydrogen bonding interactions (binding energies: −11.3 to −7.8 kcal/mol) with arachidonate 5 lipoxygenase, NFκb and glucocorticoid receptor. Withametelin has potential for advance investigations for its cytotoxic, anti-inflammatory, analgesic and antidepressant activities. [ABSTRACT FROM AUTHOR]

The rol genes have been shown to enhance the production of secondary metabolites in plants. This report examines the effect of trans-genes (rol ABC) on possible high production of biologically important phytochemicals and enhanced pharmacological activities. Three transgenic lines (1, 2 and 3) of Artemisia dubia WALL (transformed with Agrobacterium tumefaciens harboring rol ABC genes) were subjected to phytochemical analysis and pharmacological studies. A great variation in phytochemistry and the pharmacological activities was observed not only between the transgenic and non-transgenic control plants but also among the transgenic lines itself. Comparative chemical profile obtained via HPLC, TLC and spectrophotometry showed high degree of variations in the quantity of phytochemicals. An increased production of total flavonoids (71.1% in transgenic line 2) and total phenolics (110.8% in transgenic line 1), increase in caffeic acid and catechin and a decrease in gallic acid content in the extracts of transformed plants compared to the untransformed control plants was decreased. In case of pharmacological activities, moderate to high level increase in antimicrobial (antibacterial and antifungal) activities, cytotoxicity (14.1%), antitumor (29%) and antioxidant activities (23.9%) was observed (in transgenic line 2). In general all the three transgenic lines under study showed improvement in their pharmacological activities in the order of transgenic line 2 > 1 > 3 > control. The implication of these findings will help to meet the increasing demand of pharmacologically important compounds. [ABSTRACT FROM AUTHOR]

CoFe 2 O 4 are important magnetic NPs with high coercivity and moderate magnetization. These properties of CoFe 2 O 4 NPs show variation when doped with various metals. Recent studies explained that Cobalt ferrites doped with metal ion like Mn+2, have attracted increasing attention in many applications, particularly in biomedical applications. A relatively simple way is employing plants and their extracts as precursors instead of toxic chemicals to produce NPs with desirable characteristic. In current study we report green synthesis and characterization of magnetic (CoFe 2 O 4 , MnCoFe 2 O 4 , CoFe 2 O 4 @S.C, MnCoFe 2 O 4 @S.C) nanoparticles using ethanolic extract of Swertia Chirata. To enhance application as biocompatible magnetic nano drug delivery vector and cell targeting efficacy of drugs, Glimepiride (GLM), Dexamethasone (DXM), Fexofenadine (FEX) and Levofloxacin (LVX) 1were loaded on synthesized NPs. Synthesized CFNPs has been broadly characterized and applied for in vitro anticancer, antidiabetic and antibacterial potential. For synthesis of CoFe 2 O 4 (CF), CoMnFe 2 O 4 (CFM), CoFe 2 O 4 @S.C (SCF) & CoMnFe 2 O 4 @S.C (SCFM), stochiometric amounts 5 mmol of CoCl 2 ·6 H 2 O (0.284 g) and 10 mmol FeCl 3 ·6 H 2 O (0.378 g) were dissolved in 13 mL of deionized water. To this sodium acetate (3.05 g) and urea (0.6 g) were added until complete dissolution. Afterward n-heptane was added, and contents were then transferred to Teflon lining autoclave at 180 °C for 4 h. Black powder CoFe 2 O 4 NPs after washing, were dried and calcined at 450 oC for 2 h. XRD diffractogram of CF have proved the single-phase cubic spinel structure formation for all samples. Swertia Chirata formulations were shown to have effective in vitro antidiabetic activity. CF, CFM & SCFM showed good inhibition of α -glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. SCF showed that the value slightly higher than 16 µg/mL compared to standard. Drug loaded CFNPs (L -CFNPs, F-CFNPs, D -CFNPs & G-CFNPs) also effectively inhibited α -glucosidase. IC50 value for CFNPs inhibition of α -glucosidase was 12.4 µg/mL. All synthesized CF NPs showed cytotoxic potential against breast cancer cells MCF-7. About 50–60% cell viability and cytotoxicity 40% were observed for bare CFNPs as compare to Doxorubicin with related toxicity 80% and 20% cell viability. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain. CFM, SCF, SCFM were active against S. aureus at concentration 100 µg/mL, 100 µg/mL, and 50 µg/mL respectively. The synthesized CF NPs showed significant cytotoxic potential against MCF-7 breast cancer cell line. Further, drug loaded samples displayed lesser cell viability and slightly increased cytotoxicity in range of 40–50% in comparison with bare CFNPs. However, higher toxicity was observed for CFMGS towards MCF-7 cells with results nearly equal to Doxorubicin with significant decrease in viability. CF, CFM & SCFM showed good inhibition of α -glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain. [ABSTRACT FROM AUTHOR]

Fragaria × ananassa leaves extracts prepared in different solvents were subject for antioxidative, cytotoxicity, protein kinase inhibition and antibacterial activities. The extracts showed varying activities depending upon solvent used for extraction. Combined effect of methanol and ethyl acetate showed maximum antioxidant and reducing power potential (207.65±6μg AAE/mg and 88.58±20μg AAE/mg, respectively). Maximum DPPH (2,2-diphenyl-1-picryl hydrazyl) free radical scavenging activity was calculated by when methanol: chloroform and acetate fractions were used (87.68% and 86.88% inhibition, respectively). Total phenolics varied from 186 to 1.91μg AAE/mg while total flavonoids also significantly varied among the extracts. The extracts also showed significant activities against brine shrimp larvae and bacterial strains tested. The study concludes that Fragaria × ananassa leaves can be a good source for isolation of active phytochemicals to be used in different industries. [ABSTRACT FROM AUTHOR]

Low yields of isolated natural compounds halt the drug discovery process as they can only be used for structure elucidation studies and basic biological screening. Metabolite profiling via chromatographic means for optimized selection of biomass and extraction medium can help resolve the issue. In line with this, the project is focused on metabolite profiling of Datura innoxia regarding its two bioactive principals i.e., withametelin and daturaolone. Samples (8 4 0) were prepared via collection of five parts (leaves, stem, fruit, root, flowers) from two geographically different regions of Pakistan i.e., Islamabad and Muzaffargarh for six months (May-October) and extraction in fourteen solvent systems of varied polarity range, respectively. Six months agroclimatology data (temperature, humidity, soil wetness, UV irradiance) was also obtained. TLC co-detection method (n-hexane: ethyl acetate; 7:3) of withametelin and daturaolone was developed and analysis was performed on all samples. RP HPLC method was developed for withametelin (Linearity = R2;0.9) and daturaolone (linearity: R2;0.9) and 118 samples which showed detections in TLC analysis were quantified. Withametelin was mostly detected in leaves with a maximum quantified value of 5.12 ± 0.28 µg/mg dry plant powder when collected in June from arid Muzaffargarh region and extracted with Ethyl acetate + Ethanol (1:1). Distribution of daturaolone is mostly found in fruits with a maximum quantified value of 5.18 ± 0.45 µg/mg dry plant powder when collected in August from mountainous Islamabad region and extracted with Ethyl acetate + Ethanol (1:1). The study states that the presence and quantitative variations of withametelin and daturaolone depend on the plant's part, extraction medium, geographical location, weather conditions and soil wetness. Use of a controlled environment research to determine the quantitative relationship between different parameters is proposed. [ABSTRACT FROM AUTHOR]

Dodonaea viscosa Jacq. is an ethnomedicinal plant that has been extensively used for the treatment of gout, rheumatism and pain. Current study was undertaken to mine its antioxidant, antimicrobial, cytotoxic and antidiabetic potential. Chromogenic assays were employed to establish plant's multimode antioxidant profile whereas HPLC fingerprinting was performed to quantify polyphenols. Standard brine shrimp lethality, MTT and SRB assays proved its cytotoxicity potential. Among all the extracts (flower, leaf, stem and root), maximum extract recovery (22% w/w), gallic acid equivalent total phenolic content (20.11 ± 0.11 ug GAE/mg DW), ascorbic acid equivalent total antioxidant capacity (22.5 ± 0.07 µg/mg DW) and total reducing power (31.1 ± 1.13 µg/mg DW) were recorded in the distilled water + acetone extract of leaf. The acetone extract of leaf showed maximum quercetin equivalent total flavonoid content (4.78 ± 0.13 µg/mg DW). HPLC-DAD analysis revealed significant amount of rutin, vanillic acid, coumaric acid, ferulic acid, gallic acid, syringic acid, cinnamic acid, gentisic acid, catechin, caffeic acid, apigenin and myricetin in the different plant parts. Maximum scavenging potential was exhibited by methanol + ethyl acetate stem extract (IC 50 = 23.8 µg/ml). The highest antibacterial potential was found in flower (85.7%) and root (71.4%) extracts. The ethanol + ethyl acetate (1:1) leaf extract showed noteworthy toxicity against brine shrimps (LC 50 = 95.46 µg/ml) while a notable antiproliferative activity against THP-1 (IC 50 = 3.4 µg/ml) and Hep G2 (IC 50 = 20 µg/ml) cell lines was shown by ethanol + ethyl acetate extracts (1:1) of stem and root, respectively. A moderate inhibition of α-amylase enzyme was observed in all parts of the plant. The results of the present study suggest D. viscosa as a potential source of antioxidant, anticancer and α-amylase inhibitory phytochemicals. [ABSTRACT FROM AUTHOR]

• Imidazoline is a promising bioactive compound in medicinal chemistry. • A series of novel derivatives of 2-phenyl-2-imidazoline (SP1-SP13) were synthesized and their structural characterization was done by spectroanalytical techniques. • A diverse spectrum of biological activities has been presented and synthesized molecules are evaluated for their antioxidant, α-amylase inhibitory, antimicrobial, cytotoxic, in vitro and in vivo anti-inflammatory activities. • SwissADME software and the BOILED-Egg method was used to evaluate the compound's pharmacokinetic parameters. A series of N-Mannich base derivatives of 2-phenyl-2-imidazoline with substituted amines (1 – 13) were designed, synthesized, and characterized by spectroanalytical techniques. The newly synthesized compounds (SP1-SP13) were evaluated biologically for their antioxidant, α-amylase enzyme inhibition, antimicrobial, cytotoxic, and anti-inflammatory activities. Compounds were analyzed to predict their drug-likeliness behavior SP11 showed good activity in % FRSA against DPPH free radical at IC 50 of 148.16 ± 2.81 µg/mL. SP11 and SP13 exhibited good antioxidant responses in TAC and TRP assays, respectively. SP2 has shown maximum % inhibition against α-amylase enzyme to 94.02 ± 0.2% at 200 µg/mL. SP2 , SP8 , and SP12 exhibited potent effect against α-amylase enzyme at IC 50 value of 9.20 ± 0.48, 10.25 ± 0.43, and 13.81 ± 0.90 µg/mL, respectively. Compounds showed good to moderate activity against all bacterial and fungal strains. The compounds were selected for further analysis against hepatocellular carcinoma cell line (HepG2) based on LD 50 and IC 50 values obtained in brine shrimp cytotoxicity and biocompatibility assay, respectively. SP3 , SP12 , and SP13 were evaluated at 24, 48, and 72 h against HepG2 cells. Maximum response was observed at 72 h. A dose-optimization study was conducted and in vivo anti-inflammatory activity was performed on SP3 , SP12 , and SP13 based on results obtained from in vitro NO assay. The results are compared to that of standard (acetylsalicylic acid). [ABSTRACT FROM AUTHOR]