Cytotoxicity, Anti-diabetic, and Hepato-protective Potential of Ajuga bracteosa-conjugated Silver Nanoparticles in Balb/c Mice.

BACKGROUND: Ajuga bracteosa is a traditional herb used against various diseases. OBJECTIVES: Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu). METHODS: In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration. RESULTS: In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepatoprotective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity. CONCLUSION: It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepatoprotective phytoconstituents, which could be used in the prevention of diseases.

Therapeutic Potential of Novel Mastoparan-Chitosan Nanoconstructs Against Clinical MDR Acinetobacter baumannii: In silico, in vitro and in vivo Studies.

PURPOSE: Acinetobacter baumannii antibiotic resistant infections in high-risk patients are a great challenge for researchers and clinicians worldwide. In an effort to achieve potent bactericidal outcomes, a novel chitosan-mastoparan nanoconstruct (Mast-Cs NC) was designed and assessed for its therapeutic potential through in silico, in vitro and in vivo experimentation against clinical multidrug-resistant (MDR) A. baumannii. METHODS: Optimized 3D structures of mastoparan and chitosan were coupled computationally through an ionic cross-linker to generate a circular ring of chitosan encasing mastoparan. The complex was assessed for interactions and stability through molecular dynamic simulation (MDS). Binding pocket analysis was used to assess the protease-peptide interface. Mast-Cs NC were prepared by the ionic gelation method. Mast-Cs NC were evaluated in vitro and in vivo for their therapeutic efficacy against drug-resistant clinical A. baumannii. RESULTS: MDS for 100 ns showed stable bonds between chitosan and mastoparan; the first at chitosan oxygen atom-46 and mastoparan isoleucine carbon atom with a distance of 2.77 Å, and the second between oxygen atom-23 and mastoparan lysine nitrogen atom with a distance of 2.80 Å, and binding energies of -3.6 and -7.4 kcal/mol, respectively. Mast-Cs complexes approximately 156 nm in size, with +54.9 mV zeta potential and 22.63% loading capacity, offered >90% encapsulation efficiency and were found to be geometrically incompatible with binding pockets of various proteases. The MIC90 of Mast-Cs NC was significantly lower than that of chitosan (4 vs 512 µg/mL, respectively, p<0.05), with noticeable bacterial damage upon morphological analysis. In a BALB/c mouse sepsis model, a significant reduction in bacterial colony count in the Mast-Cs treated group was observed compared with chitosan and mastoparan alone (p<0.005). Mast-Cs maintained good biocompatibility and cytocompatibility. CONCLUSION: Novel mastoparan-loaded chitosan nanoconstructs signify a successful strategy for achieving a synergistic bactericidal effect and higher therapeutic efficacy against MDR clinical A. baumannii isolates. The Mast-Cs nano-drug delivery system could work as an alternative promising treatment option against MDR A. baumannii.

Synergistic Antibacterial Efficacy of Biogenic Synthesized Silver Nanoparticles using Ajuga bractosa with Standard Antibiotics: A Study Against Bacterial Pathogens.

BACKGROUND: Multi-drug resistance in bacterial pathogens is a major concern of today. Green synthesis technology is being used to cure infectious diseases. OBJECTIVES: The aim of the current research was to analyze the antibacterial, antioxidant, and phytochemical screening of green synthesized silver nanoparticles using Ajuga bracteosa. METHODS: Extract of A. bracteosa was prepared by maceration technique. Silver nanoparticles were synthesized using A. bracteosa extract and were confirmed by UV-Vis spectrophotometer, Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, TLC-Bioautography, TLC-Spot screening, antioxidant, and phytochemical screening were also investigated. RESULTS: UV-Vis spectrum and Scanning electron microscopy confirmed the synthesis of green nanoparticles at 400 nm with tube-like structures. FTIR spectrum showed that functional groups of nanoparticles have a role in capping and stability of AgNP. Agar well diffusion assay represented the maximum antibacterial effect of ABAgNPs against Escherichia coli, Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Pseudomonas aeruginosa at 0.10 g/mL concentration compared to ABaqu. Two types of interactions among nanoparticles, aqueous extract, and antibiotics (Synergistic and additive) were recorded against tested pathogens. Crystal violet, MTT, TLC-bio-autography, and spot screening supported the findings of the antibacterial assay. Highest antioxidant potential effect in ABaqu was 14.62% (DPPH) and 13.64% (ABTS) while 4.85% (DPPH) and 4.86% (ABTS) was recorded in ABAgNPs. Presence of phytochemical constituents showed pharmacological importance. CONCLUSION: It was concluded that green synthesis is an innovative technology in which natural products are conjugated with metallic particles and are used against infectious pathogens. The current research showed the significant use of green nanoparticles against etiological agents.

Phyto-Therapeutic and Nanomedicinal Approaches to Cure Alzheimer's Disease: Present Status and Future Opportunities.

Alzheimer's disease (AD) is characterized by cognitive inability manifested due to the accumulation of ß-amyloid, formation of hyper phosphorylated neurofibrillary tangles, and a malfunctioned cholinergic system. The degeneration integrity of the neuronal network can appear long after the onset of the disease. Nanotechnology-based interventions have opened an exciting area via theranostics of AD in terms of tailored nanomedicine, which are able to target and deliver drugs across the blood-brain barrier (BBB). The exciting interface existing between medicinal plants and nanotechnology is an emerging marvel in medicine, which has delivered promising results in the treatment of AD. In order to assess the potential applications of the medicinal plants, their derived components, and various nanomedicinal approaches, a review of literature was deemed as necessary. In the present review, numerous phytochemicals and various feats in nanomedicine for the treatment of AD have been discussed mechanistically for the first time. Furthermore, recent trends in nanotechnology such as green synthesis of metal nanoparticles with reference to the treatment of AD have been elaborated. Foreseeing the recent progress, we hope that the interface of medicinal plants and nanotechnology will lead to highly effective theranostic strategies for the treatment of AD in the near future.

In vitro Studies on Cytotoxic, DNA Protecting, Antibiofilm and Antibacterial Effects of Biogenic Silver Nanoparticles Prepared with Bergenia ciliata Rhizome Extract.

BACKGROUND: Many health hazardous diseases are caused by clinical pathogens. Drugresistant microbes are one of the major health problems in the world. To overcome the effect of infectious diseases new antimicrobial agent from nature has been explored which is environmentally friendly, less costly and more effective for the development of next-generation drugs. Bergenia ciliata and silver nitrate both have medicinal properties. OBJECTIVES: The aim of the current research was to evaluate the cytotoxic, and antibacterial effect of green synthesized nanoparticles using Bergenia ciliata rhizome against clinical bacterial pathogens. METHODS: Extract of Bergenia ciliata was prepared by maceration technique. Silver nanoparticles were synthesized using Bergenia ciliata rhizome extract. Synthesized silver nanoparticles were confirmed by UV-vis spectrophotometer, Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The antibacterial, anti-biofilm, cell proliferation inhibition, DNA protection, brine shrimp lethality effects of synthesized nanoparticles were investigated. RESULTS: UV-vis spectrophotometer indicated the prelaminar synthesis of silver nanoparticles at 400 nm. The spherical shape of synthesized nanoparticles with 35 nm size was confirmed using SEM. Greatest zone of inhibition (6.0 ± 0.0 mm to 8.3 ± 0.57 mm) was recorded against all tested pathogens compared with the B. ciliata aqueous extract. Anti-biofilm analysis and MTT assay supported the results of the antibacterial activity. Silver nanoparticles protect the DNA degradation. CONCLUSION: Green synthesized nanoparticles had potent antibacterial activity and may provide a basis for the development of the new antibacterial drug.

Multifunctional theranostic applications of biocompatible green-synthesized colloidal nanoparticles.

Phytochemicals offer immense promise for sustainable development and production of nanotechnology-enabled products. In the present study, Olax nana Wall. ex Benth. (family: Olacaceae) aqueous extract was used as an effective stabilizing agent to produce biogenic silver (ON-AgNPs) and gold nanoparticles (ON-AuNPs), which were investigated for biocompatibility and prospective biomedical applications (antibacterial, anticancer, antileishmanial, enzyme inhibition, antinociceptive, and anti-inflammatory activities). Various characterization techniques (XRD, FTIR, SEM, TEM, DLS, EDX, and SAED) revealed efficient biosynthesis of ON-AgNPs (26 nm) and ON-AuNPs (47 nm). In the toxicological assessment, ON-AgNPs and ON-AuNPs were found biocompatible towards human RBCs and macrophages (IC50 > 200 µg/mL). In a concentration range of 62.5-2000 µg/mL, a strong antibacterial effect was produced by ON-AgNPs against Staphylococcus epidermidis (MIC = 7.14 µg/mL) and Escherichia coli (8.25 µg/mL), while ON-AuNPs was only active against Staphylococcus aureus (9.14 µg/mL). At a concentration of 3.9-500 µg/mL, a dose-dependant inhibition of HepG2 cancer cells was produced by ON-AgNPs (IC50 = 14.93 µg/mL) and ON-AuNPs (2.97 µg/mL). Both ON-AgNPs and ON-AuNPs were found active against Leishmania tropica (KMH23) promastigotes (IC50 = 12.56 and 21.52 µg/mL) and amastigotes (17.44 and 42.20 µg/mL), respectively, after exposure to a concentration range of 1-200 µg/mL for 72 h. Preferential enzyme inhibition against urease and carbonic anhydrase II were noted for ON-AgNPs (39.23 and 8.89%) and ON-AuNPs (31.34 and 6.34%), respectively; however, these were found inactive against xanthine oxidase at 0.2 mg/mL. In the in vivo antinociceptive (acetic acid-induced abdominal constrictions) and anti-inflammatory (carrageenan-induced paw edema) activities, ON-AgNPs and ON-AuNPs at doses of 40 and 80 mg/kg, significantly attenuated the tonic nociception (P < 0.001) and ameliorated the carrageenan-induced inflammation (P < 0.01, P < 0.001). The results of in vitro and in vivo activities indicated that the biogenic nanoparticles can be used as valuable theranostic agents for further exploration of diverse biomedical applications.

Wound healing applications of biogenic colloidal silver and gold nanoparticles: recent trends and future prospects.

Nanotechnology has emerged as a prominent scientific discipline in the technological revolution of this millennium. The scientific community has focused on the green synthesis of metal nanoparticles as compared to physical and chemical methods due to its eco-friendly nature and high efficacy. Medicinal plants have been proven as the paramount source of various phytochemicals that can be used for the biogenic synthesis of colloidal silver and gold nanoparticles as compared to other living organisms, e.g., microbes and fungi. According to various scientific reports, the biogenic nanoparticles have shown promising potential as wound healing agents. However, not a single broad review article was present that demonstrates the wound healing application of biogenic silver and gold nanoparticles. Foreseeing the overall literature published, we for the first time intended to discuss the current trends in wound healing via biogenic silver and gold nanoparticles. Furthermore, light has been shed on the mechanistic aspects of wound healing along with futuristic discussion on the faith of biogenic silver and gold nanoparticles as potential wound healing agents.

HPLC-DAD finger printing, antioxidant, cholinesterase, and α-glucosidase inhibitory potentials of a novel plant Olax nana.

BACKGROUND: The medicinal importance of a novel plant Olax nana Wall. ex Benth. (family: Olacaceae) was revealed for the first time via HPLC-DAD finger printing, qualitative phytochemical analysis, antioxidant, cholinesterase, and α-glucosidase inhibitory assays. METHODS: The crude methanolic extract of O. nana (ON-Cr) was subjected to qualitative phytochemical analysis and HPLC-DAD finger printing. The antioxidant potential of ON-Cr was assessed via 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS) and hydrogen peroxide (H2O2) free radical scavenging assays. Furthermore, acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities were performed using Ellman's assay, while α- glucosidase inhibitory assay was carried out using a standard protocol. RESULTS: The qualitative phytochemical analysis of ON-Cr revealed the presence of secondary metabolites like alkaloids, flavonoids, tannins, sterols, saponins and terpenoids. The HPLC-DAD finger printing revealed the presence of 40 potential compounds in ON-Cr. Considerable anti-radical activities was revealed by ON-Cr in the DPPH, ABTS and H2O2 free radical scavenging assays with IC50 values of 71.46, 72.55 and 92.33 µg/mL, respectively. Furthermore, ON-Cr showed potent AChE and BChE inhibitory potentials as indicated by their IC50 values of 33.2 and 55.36 µg/mL, respectively. In the α-glucosidase inhibition assay, ON-Cr exhibited moderate inhibitory propensity with an IC50 value of 639.89 µg/mL. CONCLUSIONS: This study investigated Olax nana for the first time for detailed qualitative phytochemical tests, HPLC-DAD finger printing analysis, antioxidant, anticholinesterase and α-glucosidase inhibition assays. The antioxidant and cholinesterase inhibitory results were considerable and can provide scientific basis for further studies on the neuroprotective and anti-Alzheimer's potentials of this plant. ON-Cr may further be subjected to fractionation and polarity guided fractionation to narrow down the search for isolation of bioactive compounds.

Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions.

Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol-induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta-1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.

Biosynthesized colloidal silver and gold nanoparticles as emerging leishmanicidal agents: an insight.

Many recent key innovations in nanotechnology have greatly fascinated scientists to explore new avenues in treatment and diagnosis of emerging diseases. Due to extensive utilization of metallic nanoparticles (NPs) in diverse biomedical applications, scientists are looking forward to green synthesis of NPs as safer, simple, fast, and low-cost method over chemical and physical methods. Due to enriched phytochemistry, no need for maintenance and ready availability, plants are preferred for green synthesis of silver (AgNPs) and gold NPs (AuNPs). Recently, several researchers have exploited these biogenic NPs as potential antileishmanial agents. The current article is focused to mechanistically explain the antileishmanial activity of biogenic AuNPs and AgNPs with a futuristic discussion on the faith of these particles as emerging antileishmanial agents.

Green synthesis of silver nanoparticles via plant extracts: beginning a new era in cancer theranostics.

With the development of the latest technologies, scientists are looking to design novel strategies for the treatment and diagnosis of cancer. Advances in medicinal plant research and nanotechnology have attracted many researchers to the green synthesis of metallic nanoparticles due to its several advantages over conventional synthesis (simple, fast, energy efficient, one pot processes, safer, economical and biocompatibility). Medicinally active plants have proven to be the best reservoirs of diverse phytochemicals for the synthesis of biogenic silver nanoparticles (AgNPs). In this review, we discuss mechanistic advances in the synthesis and optimization of AgNPs from plant extracts. Moreover, we have thoroughly discussed the recent developments and milestones achieved in the use of biogenic AgNPs as cancer theranostic agents and their proposed mechanism of action. Anticipating all of the challenges, we hope that biogenic AgNPs may become a potential cancer theranostic agent in the near future.