Greener approach for the isolation of oleanolic acid from Nepeta leucophylla Benth. Its derivatization and their molecular docking as antibacterial and antiviral agents.

In the present study bioactive methanolic extract along with chloroform and hexane extracts obtained from shade dried leaves of the Himalayan aromatic medicinal plant Nepeta leucophylla Benth. Were screened for the presence of triterpenoids, especially oleanolic acid (OA). Total three compounds oleanolic acid, squalene and linoleic methyl ester were isolated from methanol extract. The percentage yield of OA was 0.11%. Out of these three, OA is more bioactive and was further subjected to derivatization using greener Ultrasonication method. Total three derivatives (3-Acetyl oleanolic acid, 3-Phthaloyl oleanolic acid and 3-Oxo oleanolic acid) were synthesized with 91.16%, 93.98%, and 83.6% respectively. Further, the antioxidant potential of OA and its derivatives were evaluated using DPPH assay which suggested that the 3-Phthaloyl oleanolic acid exhibits highest antioxidant potential with 40.83 ± 1.14% inhibition. OA and its derivatives were screened in-silico antibacterial potential against three bacterial pathogens (E-coli, M. tuberculosis and S. aureus) and antiviral potential against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), Human immunodeficiency virus (HIV) and H1N1 influenza virus. The in-silico results suggested that 3-phthaloyl oleanolic acid showed best H-bonding with FtsA (Staphylococcus aureus), enoyl acyl reductase (E. coli) and arabinosyl transferase (Mycobactrium tuberculosis). 3-Phthaloyl oleanolic acid also showed best H-Bond interactions with the target proteins hemagglutinin (H1N1) and reverse transcriptase (HIV), whereas, oleanolic acid exhibited the best interactions with RNA dependent RNA polymerase (SARS-CoV-2) and thus could be considered for further in vitro studies.

Review of Shikonin and Derivatives: Isolation, Chemistry, Biosynthesis, Pharmacology and Toxicology.

Shikonin and its derivatives, isolated from traditional medicinal plant species of the genus Lithospermum, Alkanna, Arnebia, Anchusa, Onosma, and Echium belonging to the Boraginaceae family, have numerous applications in foods, cosmetics, and textiles. Shikonin, a potent bioactive red pigment, has been used in traditional medicinal systems to cure various ailments and is well known for its diverse pharmacological potential such as anticancer, antithrombotic, neuroprotective, antidiabetic, antiviral, anti-inflammatory, anti-gonadotropic, antioxidants, antimicrobial and insecticidal. Herein, updated research on the natural sources, pharmacology, toxicity studies, and various patents filed worldwide related to shikonin and approaches to shikonin's biogenic and chemical synthesis are reviewed. Furthermore, recent studies to establish reliable production systems to meet market demand, functional identification, and future clinical development of shikonin and its derivatives against various diseases are presented.

The genus Nepeta: Traditional uses, phytochemicals and pharmacological properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Nepeta is a multiregional genus of the "Lamiaceae" (Labiatae or Mint) family. Species of Nepeta are a valuable part of traditional medicine and used extensively, particularly in the Himalayan region of India (Uttarakhand, Himachal Pradesh, Jammu and Kashmir, Leh-Ladakh), Pakistan (Khyber Pakhtunkhwaand Pakistani Kashmir), Nepal (Baglund district), also in China and hilly regions of Turkey and Iran. Nepeta species are extensively used as a remedy against a variety of ailments and conditions like chicken pox, tuberculosis, malaria, pneumonia, influenza, measles, stomach disorders, eye complaints, respiratory disorders, asthma, colds, coughs etc. AIM OF THE REVIEW: The main aim of this review is to present a comprehensive and detailed study on traditional uses, pharmacology, phytochemistry, toxicology of Nepeta species and suggest future direction on the design and conduct of various preparations, either alone or in blends with prevailing conventional remedies. The review also emphasizes encouraging researchers towards the wide range of pharmaceutical applications of the various species of Nepeta for their better use and exploration in the future. MATERIAL AND METHODS: All the relevant data and information on different species of Nepeta were assembled using different databases, such as Science Direct, Springer, PubMed, Taylor and Francis imprints, Chemspider, Google scholar, review and research articles from peer-reviewed journals and unpublished data. Some select 'grey literature' sources viz. ethnobotanical books, chapters, Wikipedia and webpages were also studied. RESULTS: A variety of bioactive secondary metabolites and nutraceuticals has been isolated from various species of Nepeta. These bioactive compounds belong to different classes of secondary metabolites, such as phenolic acids and their glycosides (rosmarinic acid, gallic acid, caffeic acid), flavonoids and their glycosides (cirsimaritin, salvigenin, luteolin, apigenin), iridoids (nepetalactones and their derivatives), terpenoids (1,8-cineole, linalool, ß-caryophyllene, germacrene D, parnapimaro, ß-amyrin, oleanolic acid, ursolic acid), steroids (ß-sitosterol, stigmasterol), lignans, amino acids, carbohydrates, volatile oils, etc. The species of the genus Nepeta possess a variety of pharmacological activities namely anti-inflammatory, anti-nociceptive, anti-alzheimer, anticancer and cytotoxic, antioxidant, immunomodulatory, antimicrobial, antifungal, insecticidal and along with other biological activities. CONCLUSION: The species of the genus Nepeta contains a rich source of various bioactive compounds, which are well tolerated as traditional medicines. In fact, different species of Nepeta are widely used in a variety of traditional medicinal systems all around the world. Owing to the variety of pharmacological properties of Nepeta species, more comprehensive and inclusive clinical trials are necessary for the utilization of different Nepeta species against the treatment of a wide range of ailments. There are also various other uses such as food, cosmetic and agriculture that can be investigated or explored in future. Some of the major domains that can be explored within this genus are the investigation of different species for their unexplored biological potential, isolation and characterization of new bioactive constituents and finally, investigation of new applications and possible commercialization of these bioactive leads. No doubt, there are various viable research domains outside those discussed above, but presently for the purposes of this review we will only emphasize the activities herein.

Investigation of high optical gain in complex type-II InGaAs/InAs/GaAsSb nano-scale heterostructure for MIR applications.

This paper reports a comprehensive theoretical study of W-shaped complex type-II InGaAs/InAs/GaAsSb nano-scale heterostructure consisting of two quantum wells of InAs material using the six-band k.p theory. The entire structure has been supposed to be grown on InP substrate. In order to optimize the optical gain, the probability densities of electrons and holes were optimized in the heterostructure. Following these calculations, dispersion relations for electron and hole energies, and transverse electric and transverse magnetic polarizations dependent dipole matrix elements and momentum matrix elements were calculated and, finally, the optical gain in both polarization modes was calculated. For this optimized complex heterostructure, a very high optical gain of the order of ∼4500 cm-1 in the regime of mid-infrared wavelength ∼3.2 µm has been achieved. The results suggest that the designed nano-heterostructure may be utilized for mid-infrared region (MIR) applications such as chemical and bio-molecular sensing of molecules, for the applications of spectroscopy in the "fingerprint region" of molecular science, and for detection of atmospheric gases that respond to 3.2 µm wavelength.

Antibacterial properties of PEKK for orthopedic applications.

Orthopedic implant infections have been steadily increasing while, at the same time, antibiotics developed to kill such bacteria have proven less and less effective with every passing day. It is clear that new approaches that do not rely on the use of antibiotics are needed to decrease medical device infections. Inspired by cicada wing surface topographical features, nanostructured surfaces represent a new approach for imposing antibacterial properties to biomaterials without using drugs. Moreover, new chemistries with altered surface energetics may decrease bacterial attachment and growth. In this study, a nanostructured surface was fabricated on poly-ether-ketone-ketone (PEKK), a new orthopedic implant chemistry, comprised of nanopillars with random interpillar spacing. Specifically, after 5 days, when compared to the orthopedic industry standard poly-ether-ether-ketone (PEEK), more than 37% less Staphylococcus epidermidis were found on the PEKK surface. Pseudomonas aeruginosa attachment and growth also decreased 28% after one day of culture, with around a 50% decrease after 5 days of culture when compared to PEEK. Such decreases in bacteria function were achieved without using antibiotics. In this manner, this study demonstrated for the first time, the promise that nanostructured PEKK has for numerous anti-infection orthopedic implant applications.

Reduced bacterial growth and increased osteoblast proliferation on titanium with a nanophase TiO2 surface treatment.

BACKGROUND: The attachment and initial growth of bacteria on an implant surface dictates the progression of infection. Treatment often requires aggressive antibiotic use, which does not always work. To overcome the difficulties faced in systemic and local antibiotic delivery, scientists have forayed into using alternative techniques, which includes implant surface modifications that prevent initial bacterial adhesion, foreign body formation, and may offer a controlled inflammatory response. OBJECTIVE: The current study focused on using electrophoretic deposition to treat titanium with a nanophase titanium dioxide surface texture to reduce bacterial adhesion and growth. Two distinct nanotopographies were analyzed, Ti-160, an antimicrobial surface designed to greatly reduce bacterial colonization, and Ti-120, an antimicrobial surface with a topography that upregulates osteoblast activity while reducing bacterial colonization; the number following Ti in the nomenclature represents the atomic force microscopy root-mean-square roughness value in nanometers. RESULTS: There was a 95.6% reduction in Staphylococcus aureus (gram-positive bacteria) for the Ti-160-treated surfaces compared to the untreated titanium alloy controls. There was a 90.2% reduction in Pseudomonas aeruginosa (gram-negative bacteria) on Ti-160-treated surfaces compared to controls. For ampicillin-resistant Escherichia coli, there was an 81.1% reduction on the Ti-160-treated surfaces compared to controls. Similarly for surfaces treated with Ti-120, there was an 86.8% reduction in S. aureus, an 82.1% reduction in P. aeruginosa, and a 48.6% reduction in ampicillin-resistant E. coli. The Ti-120 also displayed a 120.7% increase at day 3 and a 168.7% increase at day 5 of osteoblast proliferation over standard titanium alloy control surfaces. CONCLUSION: Compared to untreated surfaces, Ti-160-treated titanium surfaces demonstrated a statistically significant 1 log reduction in S. aureus and P. aeruginosa, whereas Ti-120 provided an additional increase in osteoblast proliferation for up to 5 days, criteria, which should be further studied for a wide range of orthopedic applications.

XanoMatrix surfaces as scaffolds for mesenchymal stem cell culture and growth.

Stem cells are being widely investigated for a wide variety of applications in tissue engineering due to their ability to differentiate into a number of cells such as neurons, osteoblasts, and fibroblasts. This ability of stem cells to differentiate into different types of cells is greatly based on mechanical and chemical cues received from their three-dimensional environments. All organs are formed by a number of cells linked together via an extracellular matrix (ECM). The ECM is a complex network of proteins and carbohydrates, which occupies intercellular spaces and regulates cellular activity by controlling cell adhesion, migration, proliferation, and differentiation. The ECM is composed of two main types of macromolecules, namely, polysaccharide glycosaminoglycans, which are covalently attached to proteins in the form of proteoglycans and fibrous proteins belonging to two functional groups, structural (collagen and elastin) and adhesive (fibronectin, laminin, vitronectin, etc). Tissue engineering is a multidisciplinary field that aims to develop biomimetic scaffolds that emulate properties of the ECM to help repair or regenerate diseased or damaged tissue. This study introduces one of these matrices, XanoMatrix, as an optimal scaffold for tissue engineering applications, in particular, for stem cell research, based on its composition, nanofibrous structure, and porosity. Results of this study suggest that XanoMatrix scaffolds are promising for stem cell tissue engineering applications and as improved cell culture inserts for studying stem cell functions (compared to traditional Corning and Falcon cell culture plates) and, thus, should be further studied.

Enhanced chondrocyte culture and growth on biologically inspired nanofibrous cell culture dishes.

Chondral and osteochondral defects affect a large number of people in which treatment options are currently limited. Due to its ability to mimic the natural nanofibrous structure of cartilage, this current in vitro study aimed at introducing a new scaffold, called XanoMatrix™, for cartilage regeneration. In addition, this same scaffold is introduced here as a new substrate onto which to study chondrocyte functions. Current studies on chondrocyte functions are limited due to nonbiologically inspired cell culture substrates. With its polyethylene terephthalate and cellulose acetate composition, good mechanical properties and nanofibrous structure resembling an extracellular matrix, XanoMatrix offers an ideal surface for chondrocyte growth and proliferation. This current study demonstrated that the XanoMatrix scaffolds promote chondrocyte growth and proliferation as compared with the Corning and Falcon surfaces normally used for chondrocyte cell culture. The XanoMatrix scaffolds also have greater hydrophobicity, three-dimensional surface area, and greater tensile strength, making them ideal candidates for alternative treatment options for chondral and osteochondral defects as well as cell culture substrates to study chondrocyte functions.

Increased NIH 3T3 fibroblast functions on cell culture dishes which mimic the nanometer fibers of natural tissues.

Traditional flat tissue cell culture dishes have consisted of polystyrene treated with plasma gases for growing, subculturing, and studying cell behavior in vitro. However, increasingly it has been observed that mimicking natural tissue properties (such as chemistry, three-dimensional structure, mechanical properties, etc) in vitro can lead to a better correlation of in vitro to in vivo cellular functions. The following studies compared traditional NIH 3T3 fibroblasts' functions on XanoMatrix scaffolds to standard tissue culture polystyrene. Results found significantly greater fibroblast adhesion and proliferation on XanoMatrix cell culture dishes which mimic the nanoscale geometry of natural tissue fibers with true, tortuous fiber beds creating a robust, consistent, and versatile growth platform. In this manner, this study supports that cell culture dishes which mimic features of natural tissues should be continually studied for a wide range of applications in which mimicking natural cellular functions are important.

Reducing bacteria and macrophage density on nanophase hydroxyapatite coated onto titanium surfaces without releasing pharmaceutical agents.

Reducing bacterial density on titanium implant surfaces has been a major concern because of the increasing number of nosocomial infections. Controlling the inflammatory response post implantation has also been an important issue for medical devices due to the detrimental effects of chronic inflammation on device performance. It has recently been demonstrated that manipulating medical device surface properties including chemistry, roughness and wettability can control both infection and inflammation. Here, we synthesized nanophase (that is, materials with one dimension in the nanoscale) hydroxyapatite coatings on titanium to reduce bacterial adhesion and inflammatory responses (as measured by macrophage functions) and compared such results to bare titanium and plasma sprayed hydroxyapatite titanium coated surfaces used clinically today. This approach is a pharmaceutical-free approach to inhibit infection and inflammation due to the detrimental side effects of any drug released in the body. Here, nanophase hydroxyapatite was synthesized in sizes ranging from 110-170 nm and was subsequently coated onto titanium samples using electrophoretic deposition. Results indicated that smaller nanoscale hydroxyapatite features on titanium surfaces alone decreased bacterial attachment in the presence of gram negative (P. aeruginosa), gram positive (S. aureus) and ampicillin resistant gram-negative (E. coli) bacteria as well as were able to control inflammatory responses; properties which should lead to their further investigation for improved medical applications.

Decreased Staphylococcus aureus and increased osteoblast density on nanostructured electrophoretic-deposited hydroxyapatite on titanium without the use of pharmaceuticals.

BACKGROUND: Plasma-spray deposition of hydroxyapatite on titanium (Ti) has proven to be a suboptimal solution to improve orthopedic-implant success rates, as demonstrated by the increasing number of orthopedic revision surgeries due to infection, implant loosening, and a myriad of other reasons. This could be in part due to the high heat involved during plasma-spray deposition, which significantly increases hydroxyapatite crystal growth into the nonbiologically inspired micron regime. There has been a push to create nanotopographies on implant surfaces to mimic the physiological nanostructure of native bone and, thus, improve osteoblast (bone-forming cell) functions and inhibit bacteria functions. Among the several techniques that have been adopted to develop nanocoatings, electrophoretic deposition (EPD) is an attractive, versatile, and effective material-processing technique. OBJECTIVE: The in vitro study reported here aimed to determine for the first time bacteria responses to hydroxyapatite coated on Ti via EPD. RESULTS: There were six and three times more osteoblasts on the electrophoretic-deposited hydroxyapatite on Ti compared with Ti (control) and plasma-spray-deposited hydroxyapatite on Ti after 5 days of culture, respectively. Impressively, there were 2.9 and 31.7 times less Staphylococcus aureus on electrophoretic-deposited hydroxyapatite on Ti compared with Ti (control) and plasma-spray-deposited hydroxyapatite on Ti after 18 hours of culture, respectively. CONCLUSION: Compared with uncoated Ti and plasma-sprayed hydroxyapatite coated on Ti, the results provided significant promise for the use of EPD to improve bone-cell density and be used as an antibacterial coating without resorting to the use of antibiotics.

Utilization of oleo-chemical industry by-products for biosurfactant production.

Biosurfactants are the surface active compounds produced by micro-organisms. The eco-friendly and biodegradable nature of biosurfactants makes their usage more advantageous over chemical surfactants. Biosurfactants encompass the properties of dropping surface tension, stabilizing emulsions, promoting foaming and are usually non- toxic and biodegradable. Biosurfactants offer advantages over their synthetic counterparts in many applications ranging from environmental, food, and biomedical, cosmetic and pharmaceutical industries. The important environmental applications of biosurfactants include bioremediation and dispersion of oil spills, enhanced oil recovery and transfer of crude oil. The emphasis of present review shall be with reference to the commercial production, current developments and future perspectives of a variety of approaches of biosurfactant production from the micro-organisms isolated from various oil- contaminated sites and from the by-products of oleo-chemical industry wastes/ by-products viz. used edible oil, industrial residues, acid oil, deodorizer distillate, soap-stock etc.