A Comprehensive Approach to Derivatization: Elemental Composition, Biochemical, and In Silico Studies of Metformin Derivatives Containing Copper and Zinc Complexes.

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.

Comprehensive Biological Potential, Phytochemical Profiling Using GC-MS and LC-ESI-MS, and In-Silico Assessment of Strobilanthes glutinosus Nees: An Important Medicinal Plant.

Plants of the genus Strobilanthes have notable use in folklore medicines as well as being used for pharmacological purposes. The present work explored the biological predispositions of Strobilanthes glutinosus and attempted to accomplish a comprehensive chemical profile through GC-MS of different fractions concerning polarity (chloroform and n-butanol) and LC-ESI-MS of methanolic extract by both positive and negative ionization modes. The biological characteristics such as antioxidant potential were assessed by applying six different methods. The potential for clinically relevant enzyme (α-amylase, α-glucosidase, and tyrosinase) inhibition was examined. The DPPH, ABTS, CUPRAC, and FRAP results revealed that the methanol fraction presented efficient results. The phosphomolybdenum assay revealed that the n-hexane fraction showed the most efficient results, while maximum metal chelation potential was observed for the chloroform fraction. The GC-MS profiling of n-butanol and chloroform fractions revealed the existence of several (110) important compounds presenting different classes (fatty acids, phenols, alkanes, monoterpenes, diterpenes, sesquiterpenoids, and sterols), while LC-ESI-MS tentatively identified the presence of 44 clinically important secondary metabolites. The n-hexane fraction exhibited the highest potential against α-amylase (497.98 mm ACAE/g extract) and α-glucosidase (605.85 mm ACAE/g extract). Significant inhibitory activity against tyrosinase enzyme was displayed by fraction. Six of the prevailing compounds from the GC-MS study (lupeol, beta-amyrin, stigmasterol, gamma sitosterol, 9,12-octadecadienoic acid, and n-hexadecanoic acid) were modelled against α-glucosidase and α-amylase enzymes along with a comparison of binding affinity to standard acarbose, while three compounds identified through LC-ESI-MS were docked to the mushroom tyrosinase enzyme and presented with significant biding affinities. Thus, it is assumed that S. glutinosus demonstrated effective antioxidant and enzyme inhibition prospects with effective bioactive molecules, potentially opening the door to a new application in the field of medicine.

Multifaced Assessment of Antioxidant Power, Phytochemical Metabolomics, In-Vitro Biological Potential and In-Silico Studies of Neurada procumbens L.: An Important Medicinal Plant.

This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules ß-amyrin, campesterol, ergosta-4,6,22-trien-3ß-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications.

Evaluation of the anti-inflammatory, antioxidant, and cytotoxic potential of Cardamine amara L. (Brassicaceae): A comprehensive biochemical, toxicological, and in silico computational study.

Introduction: Cardamine amara L. (Brassicaceae) is an important edible plant with ethnomedicinal significance. This study aimed at evaluating the phytochemical composition, anti-inflammatory, antioxidant and cytotoxicity aspects of the hydro-alcoholic extract of C. amara (HAECA). Methods: The phytochemical composition was evaluated through total phenolic contents (TPC), total flavonoid contents (TFC) determination and UPLC-QTOF-MS profiling. Anti-inflammatory evaluation of HAECA was carried out through the carrageenan induced paw edema model. Four in vitro methods were applied in the antioxidant evaluation of HAECA. MTT assay was used to investigate the toxicity profile of the species against human normal liver cells (HL7702), human liver cancer cell lines (HepG2) and human breast cancer cell lines (MCF-7). Three major compounds (Gentisic acid, skullcapflavone and conidendrine) identified in UPLC-Q-TOF-MS analysis were selected for in silico study against cyclooxygenase (COX-I and COX-II). Results and Discussion: The findings revealed that HAECA is rich in TPC (39.32 ± 2.3 mg GAE/g DE) and TFC (17.26 ± 0.8 mg RE/g DE). A total of 21 secondary metabolites were tentatively identified in UPLC-Q-TOF-MS analysis. In the MTT cytotoxicity assay, the extract showed low toxicity against normal cell lines, while significant anticancer activity was observed against human liver and breast cancer cells. The carrageenan induced inflammation was inhibited by HAECA in a dose dependent manner and showed a marked alleviation in the levels of oxidative stress (catalase, SOD, GSH) and inflammatory markers (TNF-α, IL-1ß). Similarly, HAECA showed maximum antioxidant activity through the Cupric reducing power antioxidant capacity (CUPRAC) assay (31.21 ± 0.3 mg TE/g DE). The in silico study revealed a significant molecular docking score of the three studied compounds against COX-I and COX-I. Conclusively the current study encourages the use of C. amara as a novel polyphenolic rich source with anti-inflammatory and antioxidant potential and warrants further investigations on its toxicity profile.

Revisiting the Effects of Different Dietary Sources of Selenium on the Health and Performance of Dairy Animals: a Review.

Selenium (Se) is one of the most important essential trace elements in livestock production. It is a structural component in at least 25 selenoproteins such as the iodothyronine deiodinases and thioredoxin reductases as selenocysteine at critical positions in the active sites of these enzymes. It is also involved in the synthesis of the thyroid hormone and influences overall body metabolism. Selenium being a component of the glutathione peroxidase enzyme also plays a key role in the antioxidant defense system of animals. Dietary requirements of Se in dairy animals depend on physiological status, endogenous Se content, Se source, and route of administration. Most of the dietary Se is absorbed through the duodenum in ruminants and also some portion through the rumen wall. Inorganic Se salts such as Na-selenate and Na-selenite have shown lower bioavailability than organic and nano-Se. Selenium deficiency has been associated with reproductive disorders such as retained placenta, abortion, early embryonic death, and infertility, together with muscular diseases (like white muscle disease and skeletal and cardiac muscle necrosis). The deficiency of Se can also affect the udder health particularly favoring clinical and subclinical mastitis, along with an increase of milk somatic cell counts in dairy animals. However, excessive Se supplementation (5 to 8 mg/kg DM) can lead to acute toxicity including chronic and acute selenosis. Se is the most vital trace element for the optimum performance of dairy animals. This review focuses to provide insights into the comparative efficacy of different forms of dietary Se (inorganic, organic, and nano-Se) on the health and production of dairy animals and milk Se content.

Phytogenic Additives Can Modulate Rumen Microbiome to Mediate Fermentation Kinetics and Methanogenesis Through Exploiting Diet-Microbe Interaction.

Ruminants inhabit the consortia of gut microbes that play a critical functional role in their maintenance and nourishment by enabling them to use cellulosic and non-cellulosic feed material. These gut microbes perform major physiological activities, including digestion and metabolism of dietary components, to derive energy to meet major protein (65-85%) and energy (ca 80%) requirements of the host. Owing to their contribution to digestive physiology, rumen microbes are considered one of the crucial factors affecting feed conversion efficiency in ruminants. Any change in the rumen microbiome has an imperative effect on animal physiology. Ruminal microbes are fundamentally anaerobic and produce various compounds during rumen fermentation, which are directly used by the host or other microbes. Methane (CH4) is produced by methanogens through utilizing metabolic hydrogen during rumen fermentation. Maximizing the flow of metabolic hydrogen in the rumen away from CH4 and toward volatile fatty acids (VFA) would increase the efficiency of ruminant production and decrease its environmental impact. Understanding of microbial diversity and rumen dynamics is not only crucial for the optimization of host efficiency but also required to mediate emission of greenhouse gases (GHGs) from ruminants. There are various strategies to modulate the rumen microbiome, mainly including dietary interventions and the use of different feed additives. Phytogenic feed additives, mainly plant secondary compounds, have been shown to modulate rumen microflora and change rumen fermentation dynamics leading to enhanced animal performance. Many in vitro and in vivo studies aimed to evaluate the use of plant secondary metabolites in ruminants have been conducted using different plants or their extract or essential oils. This review specifically aims to provide insights into dietary interactions of rumen microbes and their subsequent consequences on rumen fermentation. Moreover, a comprehensive overview of the modulation of rumen microbiome by using phytogenic compounds (essential oils, saponins, and tannins) for manipulating rumen dynamics to mediate CH4 emanation from livestock is presented. We have also discussed the pros and cons of each strategy along with future prospective of dietary modulation of rumen microbiome to improve the performance of ruminants while decreasing GHG emissions.

Potential of Mulberry Leaf Biomass and Its Flavonoids to Improve Production and Health in Ruminants: Mechanistic Insights and Prospects.

Leaf biomass from the mulberry plant (genus Morus and family Moraceae) is considered a potential resource for livestock feeding. Mulberry leaves (MLs) contain high protein (14.0-34.2%) and metabolizable energy (1130-2240 kcal/kg) with high dry matter (DM) digestibility (75-85%) and palatability. Flavonoid contents of MLs confer unique antioxidant properties and can potentially help alleviate oxidative stress in animals during stressful periods, such as neonatal, weaning, and periparturient periods. In addition, mulberry leaf flavonoids (MLFs) possess antimicrobial properties and can effectively decrease the population of ruminal methanogens and protozoa to reduce enteric methane (CH4) production. Owing to its rich flavonoid content, feeding MLs increases fiber digestion and utilization leading to enhanced milk production in ruminants. Dietary supplementation with MLFs alters ruminal fermentation kinetics by increasing total volatile fatty acids, propionate, and ammonia concentrations. Furthermore, they can substantially increase the population of specific cellulolytic bacteria in the rumen. Owing to their structural homology with steroid hormones, the MLFs can potentially modulate different metabolic pathways particularly those linked with energy homeostasis. This review aims to highlight the potential of ML and its flavonoids to modulate the ruminal microbiome, fermentation, and metabolic status to enhance productive performance and health in ruminants while reducing CH4 emission.

Development of herbal formulation of medicinal plants and determination of its antihyperuricemic potential in vitro and in vivo rat's model.

Hyperuricemia is a common metabolic disorder and several herbal formulations are being used for its treatment. The study aimed to develop herbal formulation (Urinil B) and find its hypouricemic effects in vitro and in vivo. Urinil B was prepared by taking Trachyspermum ammi, Piper nigrum and Berberis vulgaris equally. In vitro Dissolution test and xanthine oxidase inhibition assay was performed for checking capsule absorbance and IC50 calculation respectively. For in vivo experimentation, the study comprised of 14 groups of rats (n=6). Results showed that significant xanthine oxidase inhibition was shown by herbal formulation with IC50 of 586±1.5µg/mL. Oral administration of Urinil B 250, 500 and 1000 mg/kg decreased serum and liver uric acid levels of hyperuricemic rats in dose and time dependent manner. 3 day and seven day administration of Urinil B reduced serum and liver uric acid level more significantly as compared to one day administration. However, allopurinol normalized serum and liver uric acid levels in all study groups. The present study indicated marked hypouricemic effects of Urinil B in hyperuricemia induced by potassium oxonate in rats. However, due to caveat of small sample size in this study, clear conclusion regarding hypouricemic potential of Urinil B can't be made.

Pharmacological and nutritive potential of Euphorbia granulata.

Background Euphorbia granulata is herb of family Euphorbiaceae having several traditional uses. The aim of the study is to summarize reported nutritional and medicinal value along with ethnomedical records. Methods The papers on nutritional and medicinal value of E. granulata are collected from electronic search engines (Google Scholar, PubMed). Synonyms are confirmed from "The plant List." Results Pharmacological studies suggest that the extracts of E. granulata possess antioxidant, antibacterial, antifungal, diuretic, antiulcerative colitis and spasmolytic properties. Moreover, it is rich with nutritive components such as carbohydrates, lipid contents (saturated and unsaturated fatty acids), minerals and protein (amino acids). Toxicological data of E. granulata showed that it may be poisonous and toxic at higher doses. Conclusion Research studies suggest that E. granulata has sufficient pharmacological potential against several diseases including infections, gastric ulcers, anuria, oliguria and spasmodic disorders; however, more research is required to confirm its pharmacological potential. Moreover, dose fixation studies should be carried out to avoid its toxicity.

Plant derived anticancer agents: A green approach towards skin cancers.

Plants have been used as medicinal agents since the origin of mankind. High cost and severe side effects associated with conventional chemotherapy has limited their general acceptability and fuel up the search for alternate options. The alternative treatment options like phytochemicals have come up with ease of availability and cost effectiveness. Owing to their general acceptance, safety, low side effects and multistep targeting in signal transduction pathways, plant derived phyto-constituents have promising anti-carcinogenic potential for skin related cancers. This leads to the surge in research of new phytochemicals for the prevention and cure of a variety of skin cancers which are major cause of morbidity and mortality in present world. Although very limited clinical data involving humans is available in literature to demonstrate favorable eff ;ects of phyto-constituents on various types of skin carcinomas yet the topical treatment with these plant derived anticancer phytochemicals is very promising. There are various mechanisms and pathways responsible for antitumor activity of plant derived medicinal compounds such as loss of mitochondrial membrane potential, release of cytochrome-c, Down regulation of Anti-apoptotic proteins and Up regulation of pro-apoptotic proteins, Activation of Caspase, Fas, FADD, p53 and c-Jun signaling pathway, Inhibition of Akt signaling pathway, phosphorylation of ERK, P13K, Raf, survivin gene, STAT 3 and NF-kB. In-vitro testing of skin cancer cell lines models offers the opportunity for identifying mechanisms of action of compounds from plant origin against variety of skin related cancers. This review thus aims at providing an overview of plant derived anti-cancer compounds which have been reported to show promising anti-carcinogenic effects against various skin cancer cell lines and on animal models. Phytochemicals that are discussed in this review include steroids, coumarines, trepenes, essential oils, alkaloids, esters, ethers, resins, phenols and flavonoids. This review also provides information about marketed formulations developed so far from plant derived compounds for skin cancer prevention and treatment.