Beneficial Effects of Natural Alkaloids from Berberis glaucocarpa as Antidiabetic Agents: An In Vitro, In Silico, and In Vivo Approach.

Diabetes, also known as diabetes mellitus (DM), is a metabolic disorder characterized by an abnormal rise in blood sugar (glucose) levels brought on by a complete or partial lack of insulin secretion along with corresponding changes in the metabolism of lipids, proteins, and carbohydrates. It has been reported that medicinal plants play a pivotal role in the treatment of various ailments such as diabetes mellitus, dyslipidemia, and hypertension. The current study involved exploring the acute toxicity and in vivo antidiabetic activity of berberine (WA1), palmatine (WA2), and 8-trichloromethyl dihydroberberine (WA3) previously isolated from Berberis glaucocarpa Stapf using a streptozotocin (STZ)-induced diabetic rat model. Body weight and blood glucose level were assessed on a day interval for 4 weeks. Biochemical parameters, antioxidant enzymes, and oxidative stress markers were also determined. In an acute toxicity profile, the WA1, WA2, and WA3 were determined to be nontoxic up to 500 mg/kg (b.w). After the second and third weeks of treatment (14 and 21 days), the blood glucose levels in the WA1-, WA2-, and WA3-treated groups were significantly lower than those in the diabetic control group (476.81 ± 8.65 mg/dL, n = 8, P < 0.001). On the 21st day, there was a decrease in the blood glucose level and the results obtained were 176.33 ± 4.69, 197.21 ± 4.80, and 161.99 ± 4.75 mg/dL (n = 8, P < 0.001) for WA1, WA2, and WA3 at 12 mg/kg, respectively, as opposed to the diabetic control group (482.87 ± 7.11 mg/dL, n = 8, P < 0.001). Upon comparison with the diabetic group at the end of the study (28 days), a substantial drop in the glucose level of WA3 at 12 mg/kg (110.56 ± 4.11 mg/dL, n = 8, P < 0.001) was observed that was almost near the values of the normal control group. The treated groups (WA1, WA2, and WA3) treated with the samples displayed a significant decline in the levels of HbA1c. Treatment of the samples dramatically lowered the lipid level profile. In groups treated with samples, plasma levels of triglycerides, total cholesterol, and LDL were significantly lowered [F (5, 42) = 100.6, n = 8, P < 0.001]; these levels were also significantly decreased [F (5, 42) = 129.6 and 91.17, n = 8, P < 0.001]. In contrast to the diabetes group, all treated groups had significantly higher HDL levels [F (5, 42) = 15.46, n = 8, P < 0.001]. As a result, hypolipidemic activity was anticipated in the samples. In addition to that, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was considerably elevated in the groups treated with the sample compared to the diabetic control group (n = 8, P < 0.001).

Chemical insights into the synthetic chemistry of five-membered saturated heterocycles-a transition metal-catalyzed approach.

Drug design and delivery is primarily based on the hunt for new potent drug candidates and novel synthetic techniques. Recently, saturated heterocycles have gained enormous attention in medicinal chemistry as evidenced by the medicinal drugs listed in the FDA Orange Book. Therefore, the demand for novel saturated heterocyclic syntheses has increased tremendously. Transition metal (TM)-catalyzed reactions have remained the prime priority in heterocyclic syntheses for the last three decades. Nowadays, TM catalysis is well adorned by combining it with other techniques such as bio- and/or enzyme-catalyzed reactions, organocatalysis, or using two different metals in a single catalysis. This review highlights the recent developments of the transition metal-catalyzed synthesis of five-membered saturated heterocycles.

Bioenergy Generation and Phenol Degradation through Microbial Fuel Cells Energized by Domestic Organic Waste.

Microbial fuel cells (MFCs) seem to have emerged in recent years to degrade the organic pollutants from wastewater. The current research also focused on phenol biodegradation using MFCs. According to the US Environmental Protection Agency (EPA), phenol is a priority pollutant to remediate due to its potential adverse effects on human health. At the same time, the present study focused on the weakness of MFCs, which is the low generation of electrons due to the organic substrate. The present study used rotten rice as an organic substrate to empower the MFC's functional capacity to degrade the phenol while simultaneously generating bioenergy. In 19 days of operation, the phenol degradation efficiency was 70% at a current density of 17.10 mA/m2 and a voltage of 199 mV. The electrochemical analysis showed that the internal resistance was 312.58 Ω and the maximum specific capacitance value was 0.00020 F/g on day 30, which demonstrated mature biofilm production and its stability throughout the operation. The biofilm study and bacterial identification process revealed that the presence of conductive pili species (Bacillus genus) are the most dominant on the anode electrode. However, the present study also explained well the oxidation mechanism of rotten rice with phenol degradation. The most critical challenges for future recommendations are also enclosed in a separate section for the research community with concluding remarks.

An insight into recent developments of copper, silver and gold carbon dots: cancer diagnostics and treatment.

Cancer is one of the most fatal diseases globally, however, advancement in the field of nanoscience specifically novel nanomaterials with nano-targeting of cancer cell lines has revolutionized cancer diagnosis and therapy and has thus attracted the attention of researchers of related fields. Carbon Dots (CDs)-C-based nanomaterials-have emerged as highly favorable candidates for simultaneous bioimaging and therapy during cancer nano-theranostics due to their exclusive innate FL and theranostic characteristics exhibited in different preclinical results. Recently, different transition metal-doped CDs have enhanced the effectiveness of CDs manifold in biomedical applications with minimum toxicity. The use of group-11 (Cu, Ag and Au) with CDs in this direction have recently gained the attention of researchers because of their encouraging results. This review summarizes the current developments of group-11 (Cu, Ag and Au) CDs for early diagnosis and therapy of cancer including their nanocomposites, nanohybrids and heterostructures etc. All The manuscript highlights imaging applications (FL, photoacoustic, MRI etc.) and therapeutic applications (phototherapy, photodynamic, multimodal etc.) of Cu-, Ag- and Au-doped CDs reported as nanotheranostic agents for cancer treatment. Sources of CDs and metals alogwith applications to give a comparative analysis have been given in the tabulated form at the end of manuscript. Further, future prospects and challenges have also been discussed.

Efficacy Evaluation of 10-Hydroxy Chondrofoline and Tafenoquine against Leishmania tropica (HTD7).

Leishmaniasis is affirmed as a category one disease (most emerging and unmanageable) by the World Health Organization (WHO), affecting 98 countries with an annual global incidence of ~1.2 million cases. Options for chemotherapeutic treatment are limited due to drug resistance and cytotoxicity. Thus, the search for new chemical compounds is instantly desirable. In this study, we used two compounds, i.e., 10-hydroxy chondrofoline and tafenoquine, for their antileishmanial activity against L. tropica (HTD7). First, the cytotoxicity assay of the test compounds against THP-1 cells was carried out, and these compounds were found safe. Intra-THP-1 amastigote activity (in vitro) was performed, which was then followed by the in vivo activity of 10-hydroxy chondrofoline in the murine cutaneous leishmaniasis (CL) model. A total of three concentrations were used, i.e., 25, 50, and 100 µM, to check the in vitro activity of the test compounds against the amastigotes. 10-hydroxy chondrofoline was found to be the most potent compound in vitro (and thus was selected for in vivo studies) with an LD50 value of 43.80 µM after 48 h incubation, whilst tafenoquine had an LD50 value of 53.57 µM. In vivo activity was conducted by injecting 10-hydroxy chondrofoline in the left hind foot of the infected BALB/c mice, where it caused a statistically significant 58.3% (F = 14.18; p = 0.002) reduction in lesion size (0.70 ± 0.03 mm) when compared with negative control (1.2 ± 0.3 mm).

Fluorinated triazoles as privileged potential candidates in drug development-focusing on their biological and pharmaceutical properties.

Fluorinated heterocycles have attracted extensive attention not only in organic synthesis but also in pharmaceutical and medicinal sciences due to their enhanced biological activities than their non-fluorinated counterparts. Triazole is a simple five-membered heterocycle with three nitrogen atoms found in both natural and synthetic molecules that impart a broad spectrum of biological properties including but not limited to anticancer, antiproliferative, inhibitory, antiviral, antibacterial, antifungal, antiallergic, and antioxidant properties. In addition, incorporation of fluorine into triazole and its derivatives has been reported to enhance their pharmacological activity, making them promising drug candidates. This mini-review explores the current developments of backbone-fluorinated triazoles and functionalized fluorinated triazoles with established biological activities and pharmacological properties.

Spectral, Anti-Inflammatory, Anti-Pyretic, Leishmanicidal, and Molecular Docking Studies, Against Selected Protein Targets, of a New Bisbenzylisoquinoline Alkaloid.

A new bisbenzylisoquinoline named as chondrofolinol (1) and four reported compounds (2-5) were isolated and characterized from the roots of Berberis glaucocarpa Stapf. Anti-inflammatory, anti-pyretic, and leishmanicidal studies were performed against carrageenan-induced paw edema, yeast-induced pyrexia, and the promastigotes of Leishmania tropica, respectively. The new compound significantly reduced the paw volume in carrageenan-induced paw edema and rectal temperature in yeast-induced pyrexia at 10 and 20 mg/ kg of body weight. Chondrofolinol caused almost 100% inhibition of the promastigotes of Leishmania tropica. All the compounds displayed minimal cytotoxicity against THP-1 monocytic cells. In order to ascertain the potential macromolecular targets of chondrofolinol responsible for the observed anti-inflammatory and anti-leishmanial activities, a molecular docking study was carried out on relevant protein targets of inflammation and Leishmania. Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of N-myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for Leishmania major were selected after thorough literature search about protein targets responsible for inflammation and Leishmania major. Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The Leishmania major protein targets with the most favorable docking scores to chondrofolinol were NMT, TyrRS, and UGPase. The study indicated that bisbenzylisoquinoline and isoquinoline alkaloids possess anti-pyretic, anti-inflammatory, and anti-leishmanial properties with minimal cytotoxicity and therefore, need to be further explored for their therapeutic potential.

Effect of Temperature on 1H NMR Spectra, Antitrypanosomal Activity, Conformational Analysis, and Molecular Docking of Curine Derivatives from Berberis brevissima.

The ethanolic root extract of Berberis brevissima afforded a new bisbenzylisoquinoline alkaloid, 13-nitrochondrofoline (2), and two known bisbenzylisoquinoline alkaloids, chondrofoline (1) and curine (4). The acetylation of chondrofoline (1) gave O-acetylchondrofoline (3). The dimeric structures of 1 and 2 were studied through variable-temperature 1H NMR spectroscopy at 25, 40, 60, and 80 °C and conformational analysis, using density functional theory employing the M06-2X functional and the 6-31G* basis set. The in vitro antitrypanosomal activity of compounds 1, 2, 3, and 4 against Trypanosoma brucei showed significant potential with MIC values of 2.6, 2.2, 2.3, and 3.8 µM, respectively. Molecular docking evaluation of alkaloids 1, 2, 3, and 4 against known T. brucei protein targets revealed T. brucei phosphodiesterase B1 to be the preferred target. The docking energies of the alkaloids with Tb6PGL (PDB 3EB9) ranged from -88.8 to -106.0 kJ/mol and was comparable to the cocrystallized ligand, citrate (Edock = -78.3 kJ/mol). It seems reasonable that the curine alkaloids may compete with the natural substrates for these protein targets and serve as leads in designing and developing more potent and selective drugs against T. brucei.

Electrical, Photocatalytic, and Humidity Sensing Applications of Mixed Metal Oxide Nanocomposites.

Mixed metal oxide nanocomposites (NCs) comprising Cu-Sr (CS), Sr-Cd (SC), and Cd-Cu (CC) were fabricated via a sol-gel method. Structural investigations of fabricated samples were carried out via X-ray diffraction (XRD), scanning electron microscopy (SEM), diffuse reflectance spectroscopy (DRS), and X-ray photoelectron spectroscopy (XPS). The Maxwell-Wagner model, attributing to poor conducting layers around the conducting grains, was indicated to be followed by all of the NCs while investigating the dielectric properties. The Space-charge polarization and hoping mechanism contributed to low AC conductivity at lower frequencies and high AC conductivity at higher frequencies. The as-synthesized NCs effectively degraded two toxic water contaminants, such as crystal violet (CV) and Congo red (CR). Furthermore, the NCs were also evaluated for humidity sensing measurements. All of the NCs indicated efficient response/recovery time with better stability. The extensive investigation suggested the synthesized NCs, well suited for various optical and microelectronic applications.

Viscosine as a Potent and Safe Antipyretic Agent Evaluated by Yeast-Induced Pyrexia Model and Molecular Docking Studies.

The antipyretic potential of viscosine, a natural product isolated from the medicinal plant Dodonaea viscosa, was investigated using yeast-induced pyrexia rat model, and its structure-activity relationship was investigated through molecular docking analyses with the target enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1). The in vivo antipyretic experiments showed a progressive dose-dependent reduction in body temperatures of the hyperthermic test animals when injected with viscosine. Comparison of docking analyses with target enzymes showed strongest bonding interactions (binding energy -17.34 kcal/mol) of viscosine with the active-site pocket of mPGES-1. These findings suggest that viscosine shows antipyretic properties by reducing the concentration of prostaglandin E2 in brain through its mPGES-1 inhibitory action and make it a potential lead compound for developing effective and safer antipyretic drugs for treating fever and related pathological conditions.

The chemistry and pharmacology of alkaloids and allied nitrogen compounds from Artemisia species: A review.

Several reviews have been published on Artemisia's derived natural products, but it is the first attempt to review the chemistry and pharmacology of more than 80 alkaloids and allied nitrogen compounds obtained from various Artemisia species (covering the literature up to June 2018). The pharmacological potential and unique skeleton types of certain Artemisia's alkaloids provoke the importance of analyzing Artemisia species for bioactive alkaloids and allied nitrogen compounds. Among the various types of bioactive Artemisia's alkaloids, the main classes were the derivatives of rupestine (pyridine-sesquiterpene), lycoctonine (diterpene), pyrrolizidine, purines, polyamine, peptides, indole, piperidine, pyrrolidine, alkamides, and flavoalkaloids. The rupestine derivatives are Artemisia's characteristic alkaloids, whereas the rest are common alkaloids found in the family Asteraceae and chemotaxonomically links the genus Artemisia with the tribes Anthemideae. The most important biological activities of Artemisia's alkaloids are including hepatoprotective, local anesthetic, ß-galactosidase, and antiparasitic activities; treatment of angina pectoris, opening blocked arteries, as a sleep-inducing agents and inhibition of HIV viral protease, CYP450, melanin biosynthesis, human carbonic anhydrase, [3H]-AEA metabolism, kinases, and DNA polymerase ß1 . Some of the important nitrogen metabolites of Artemisia include pellitorine, zeatin, tryptophan, rupestine, and aconitine analogs, which need to be optimized and commercialized further.

Green nanotechnology: a review on green synthesis of silver nanoparticles - an ecofriendly approach.

Background: Nanotechnology explores a variety of promising approaches in the area of material sciences on a molecular level, and silver nanoparticles (AgNPs) are of leading interest in the present scenario. This review is a comprehensive contribution in the field of green synthesis, characterization, and biological activities of AgNPs using different biological sources. Methods: Biosynthesis of AgNPs can be accomplished by physical, chemical, and green synthesis; however, synthesis via biological precursors has shown remarkable outcomes. In available reported data, these entities are used as reducing agents where the synthesized NPs are characterized by ultraviolet-visible and Fourier-transform infrared spectra and X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Results: Modulation of metals to a nanoscale drastically changes their chemical, physical, and optical properties, and is exploited further via antibacterial, antifungal, anticancer, antioxidant, and cardioprotective activities. Results showed excellent growth inhibition of the microorganism. Conclusion: Novel outcomes of green synthesis in the field of nanotechnology are appreciable where the synthesis and design of NPs have proven potential outcomes in diverse fields. The study of green synthesis can be extended to conduct the in silco and in vitro research to confirm these findings.

Thermodynamic and kinetic insights into plant-mediated detoxification of lead, cadmium, and chromium from aqueous solutions by chemically modified Salvia moorcroftiana leaves.

Thermodynamic and kinetic aspects for the biosorptive removal of Pb, Cd, and Cr metals from water using Chemically Modified Leaves of Salvia moorcroftiana (CMSML) were determined. Different parameters including pH, temperature, metal's initial concentration, biomass dosage, and contact time were optimized. Optimum biosorptions of Pb, Cd, and Cr were attained at pH values of 6.0, 7.0, and 3.0 respectively. Batch experiments showed maximum removal of both Pb and Cd at 40 °C and that of Cr at 30 °C. Biosorption capability of CMSML was observed to decrease with raising temperature. Optimal equilibrium times for Pb, Cd, and Cr uptake were 120, 60, and 120 min respectively. Based on the values of regression correlation coefficients (R2), the current data is explained better by applying Langmuir isotherms than the Freundlich model. Maximum biosorbent capabilities (qmax) for Pb, Cd, and Cr were approximately 270.27, 100.00, and 93.45 mg/g respectively. Thermodynamically, removal of all the three metal ions was shown to be exothermic and spontaneous.

NMR, Novel Pharmacological and In Silico Docking Studies of Oxyacanthine and Tetrandrine: Bisbenzylisoquinoline Alkaloids Isolated from Berberis glaucocarpa Roots.

Urease enzyme is responsible for gastric cancer, peptic ulcer, hepatic coma, and urinary stones in millions of people across the world. So, there is a strong need to develop new and safe antiurease drugs, particularly from natural sources. In search for new and effective drugs from natural sources bioassay-guided fractionation and isolation of Berberis glaucocarpa Stapf roots bark resulted in the isolation and characterization, on the basis of 1D and 2D NMR data, of two bisbenzylisoquinoline alkaloids, oxyacanthine (1) and tetrandrine (2), followed by urease inhibition studies. Crude extract, all the subfractions and the isolated compounds 1 and 2 displayed excellent urease enzyme inhibition properties in vitro. The antiurease nature and possible mode of action for compounds 1 and 2 were verified and explained through their molecular docking studies against jack-bean urease enzyme. Half-maximum inhibitory concentration (IC50) was calculated for compounds 1 and 2. The IC50 value was found to be 6.35 and 5.51 µg/mL for compounds 1 and 2, respectively. Both compounds 1 and 2 have minimal cytotoxicity against THP-1 monocytic cells.

A new irregular monoterpene acetate along with eight known compounds with antifungal potential from the aerial parts of Artemisia incisa Pamp (Asteraceae).

A new compound named as santolinylol-3-acetate (4-(2-hydroxypropan-2-yl)-2-methylhexa-1,5-dien-3-yl acetate) (3), along with seven known compounds; linoleic acid (1), benzoic acid (2), santolinylol (4), ethyl-(E)-p-hydroxy cinnamate (5), scopoletin (6), esculetin (7) isofraxidin (8) and eupatorin (9), were isolated from the aerial parts (ethanolic extract) of endangered species: Artemisia incisa Pamp (Asteraceae). The compounds' structures were determined through modern spectroscopic techniques, and comparison of data (physicochemical constants) with the literature. The relative stereochemistry of santolinylol-3-acetate (3) was determined by comparing its data of NOESY, and specific rotation with its diol analogue; santolinylol (4), isolated from the same plant; A. incisa. The results of the antifungal activity showed that coumarins are as whole less active compounds. Compounds 3 (25 and 300 µg/mL), and 4 (12.5 and 300 µg/mL), showed good activities against Candida albicans, and Aspergillus flavus, respectively, which justifies A. incisa as a traditional medicine for curing the said fungal infections.

Isolation, structure elucidation and enzyme inhibition studies of a new hydroxy ester and other compounds from Berberis jaeschkeana Schneid stem.

Bioassay-guided isolation and fractionation of Berberis jaeschkeana Schneid var. jaeschkeana stem resulted in the isolation and characterisation of a new long chain hydroxy ester named as berberinol (1) along with six known compounds (2-7). All the structures were established from 1D and 2D spectroscopic data. Crude extract, sub-fractions and all the isolated compounds were evaluated for their anti-fungal and urease enzyme inhibition properties. All of the sub-fractions and compounds showed good anti-fungal and urease enzyme inhibition properties. Minimum inhibitory concentrations (MICs) were calculated for all active samples in case of urease enzyme inhibition. MICs values were found to be in the range of 39.03-49.78 µg/mL for urease enzyme inhibition.

A new isoquinoline alkaloid with anti-microbial properties from Berberis jaeschkeana Schneid. var. jaeschkeana.

One new isoquinoline alkaloid named berberidione (1) along with four new source alkaloids berberine (2), palmatine (3), jatrorrhizine (4) and chondrofoline (5) and three new source non-alkaloids syringic acid (6), ß-sitosterol (7) and stigmasterol (8) was isolated and characterised from different fractions of Berberis jaeschkeana Schneid var. jaeschkeana. All the structures were determined from 1D and 2D spectroscopic data. Crude extract, sub-fractions and isolated compounds showed excellent anti-microbial properties. The toxicity level for the alkaloids was found to be very low on THP-1 cells.

Phytochemical and antitrypanosomal investigation of the fractions and compounds isolated from Artemisia elegantissima.

CONTEXT: Trypanosoma brucei brucei (T.b. brucei) infection causes death in cattle, while the current treatments have serious toxicity problems. However, natural products can be used to overcome the problems associated with parasitic diseases including T.b. brucei. OBJECTIVE: Artemisia elegantissima Pamp (Asteraceae) was evaluated phytochemically for its constituents and antitrypanosomal potential against T.b. brucei for the first time. Scopoletin isolated from A. elegantissima has shown better potential then the standard drug suramin, used against T.b. brucei. MATERIALS AND METHODS: The ethanol extract of the aerial parts of A. elegantissima was fractionated by column and preparative thin-layer chromatography into six fractions (A-F) yielding 13 compounds, these were evaluated for their antitrypanosomal activity against T.b. brucei at different concentrations. RESULTS: Thirteen compounds were isolated from A. elegantissima: (Z)-p-hydroxy cinnamic acid, stigmasterol, ß-sitosterol, betulinic acid, bis-dracunculin, dracunculin, scopoletin, apigenin, dihydroluteolin, scoparol, nepetin, bonanzin, and 3',4'-dihydroxy bonanzin. The fractions D-F were found to be active at the concentration of 20 µg/ml and three compounds isolated from these fractions, scopoletin (MIC ≤0.19 µg/ml), 3',4'-dihydroxy bonanzin (MIC = 6.25 µg/ml) and bonanzin (MIC = 20 µg/ml), were found to be highly active. DISCUSSION AND CONCLUSION: Artemisia elegantissima was phytochemically and biologically explored for its antitrypanosomal potential against T.b. brucei. The number and orientation of phenolic hydroxyl groups play an important role in the antitrypanosomal potential of coumarins and flavonoids. The compounds 3',4'-dihydroxy bonanzin and scopoletin with low MIC values, hold potential for use as antitrypanosomal drug leads.