Comparison and correlation of in vitro, in vivo and in silico evaluations of alpha, beta and gamma cyclodextrin complexes of curcumin

In the present study investigated the effect of curcumin (CUR) alpha (α), beta (β) and gamma (γ) cyclodextrin (CD) complexes on its solubility and bioavailability. CUR the active principle of turmeric is a natural antioxidant agent with potent anti-inflammatory activity along with chemotherapeutic and chemopreventive properties. Poor solubility and poor oral bioavailability are the main reasons which preclude CUR use in therapy. Extent of complexation was β-CD complex (82 %) > γ-CD (71 %) > α-CD (65 %). Pulverization method resulted in significant enhancement of CUR (0.002 mg/ml) solubility with CUR α-CD complex (0.364 mg/ml) > CUR β-CD complex (0.186 mg/ml) > CUR γ-CD complex (0.068 mg/ml). Gibbs-free energy and in silico molecular docking studies favour formation of α-CD complex > β-CD complex > γ-CD complex. With reference to CUR, relative bioavailability of CUR α-CD, CUR β-CD and CUR γ-CD complexes were 460, 365 and 99 % respectively. CUR–CD complexes exhibited increased bioavailability with an increase in t_½, tmax, Cmax, AUC, Ka, and MRT; and a decrease in Ke, clearance and Vd values. AUC increase was CUR α-CD complex > CUR β-CD complex > CUR γ-CD complex. Significant difference (p < 0.05) was observed between CUR α-CD complex and CUR γ-CD complex by one-way ANOVA and Dunnett’s post hoc test for multiple comparison analysis. Correlation observed between in vitro, in vivo and in silico methods indicates potential of in silico and in vitro methods in CD selection.     

Reaction between ellagic acid and an ultimate carcinogen

The reaction coordinate between a typical ultimate carcinogen benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) and ellagic acid, a proven chemopreventive agent active against cancers caused by polycyclic aromatic hydrocarbons (PAHs), was examined by density functional theory (DFT) and semiempirical MO calculations, and activation energy was calculated. The effect of a polar environment was included using Tomasi and the Langevin dipoles methods. The calculated BPDE/ellagic acid reaction free energy of activation is found to be in decent agreement with experimental data [Sayer, J. M. et al. J. Am. Chem. Soc. 1982, 104, 5562-5564]. This work sheds light on the mechanism of action of ellagic acid. Quantum chemical calculations of this kind are valuable for the design of ellagic acid derivatives with even lower activation energy and increased reactivity toward ultimate carcinogens as well as controlled reactivity toward DNA.     

Polarity Directed Appraisal of Pharmacological Potential and HPLC-DAD Based Phytochemical Profiling of Polygonum glabrum Willd

The present study was designed to evaluate polarity-dependent extraction efficiency and pharmacological profiling of Polygonum glabrum Willd. Crude extracts of leaves, roots, stems, and seeds, prepared from solvents of varying polarities, were subjected to phytochemical, antioxidant, antibacterial, antifungal, antidiabetic, and cytotoxicity assays. Maximum extraction yield (20.0% w/w) was observed in the case of an acetone:methanol (AC:M) root extract. Distilled water:methanol (W:M) leaves extract showed maximum phenolic contents. Maximum flavonoid content and free radical scavenging potential were found in methanolic (M) seed extract. HPLC-DAD quantification displayed the manifestation of substantial quantities of quercetin, rutin, gallic acid, quercetin, catechin, and kaempferol in various extracts. The highest ascorbic acid equivalent total antioxidant capacity and reducing power potential was found in distilled water roots and W:M leaf extracts, respectively. Chloroform (C) seeds extract produced a maximum zone of inhibition against Salmonella typhimurium. Promising protein kinase inhibition and antifungal activity against Mucor sp. were demonstrated by C leaf extract. AC:M leaves extract exhibited significant cytotoxic capability against brine shrimp larvae and α-amylase inhibition. Present results suggest that the nature of pharmacological responses depends upon the polarity of extraction solvents and parts of the plant used. P. glabrum can be considered as a potential candidate for the isolation of bioactive compounds with profound therapeutic importance.     

DABCO-catalyzed multi-component domino reactions for the one-pot efficient synthesis of diverse and densely functionalized benzofurans in water

Research on Chemical Intermediates - An efficient, three-component strategy for the improved synthesis of a pharmaceutically interesting diverse kind of multi-functionalized benzofurans via one-pot...     

Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5–6 and 8a–8b. The compound 5 exhibits an exceptional IC₅₀ value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.     

Effects of Aloe vera Flower Extract and Its Active Constituent Isoorientin on Skin Moisturization via Regulating Involucrin Expression: In Vitro and Molecular Docking Studies

Skin moisturization is very crucial for maintaining the flexibility, viscoelasticity, and differentiation of the epidermis and its deprivation causes several diseases from dry skin to dermatitis. Aloe vera, a miracle plant having diverse medicinal properties including skin moisturization effects. This study investigated for the first time the molecular mechanism targeting skin moisturization effects of the Aloe vera flower and its major active constituent. By treating human epidermal keratinocytes (HaCaT cells) with Aloe vera flower water extract (AFWE), we found that AFWE upregulated epidermal involucrin by activating the expression of protein kinase C, p38, and ERK 1/2. Additionally, it modulated filaggrin, increased aquaporin expression, and hyaluronan synthesis via a balanced regulation of HAS1 and HYAL1 protein. Similarly, it was able to protect UVB-induced photodamage. Western blot analysis, ELISA, and qRT- PCR were performed to evaluate various epidermal differentiation markers and moisturization-related factors on human epidermal keratinocytes (HaCaT cells). TLC and HPLC were used to detect and analyze the chemical constituents. Among them, we found that an active component of Aloe vera flower, isoorientin (IO) has a high binding affinity to all of its targeted proteins such as involucrin, PKC, P38, etc. through molecular docking assay. This study indicated that the Aloe vera flower and its active constituent, IO can be used as a prominent ingredient to enhance skin barrier function and improve its related pathologies.     

Ferrite Nanocomposite Based Electrochemical Sensor: Characterization,Voltammetric and Amperometric Studies for Electrocatalytic Detection of Formaldehyde in Aqueous Media

Development of nanocomposite based electrochemical sensors for detection of toxic chemicals describes an environmentally benign strategy for monitoring the health of ecosystem. Herein, we reported in situ preparation of graphitic carbon nitride (g-C₃N₄) decorated Ag₂S/NiFe₂O₄ nanocomposite sensor by facile precipitation method. The electrochemical studies demonstrated efficient electrocatalytic activity of ternary nanocomposite pasted glassy carbon electrode (g-C₃N₄@Ag₂S/NiFe₂O₄/GCE) for selective detection of formaldehyde. Moreover, fabricated sensor exhibit rapid amperometric response with excellent selectivity, remarkable sensitivity (1681 μA mmol L⁻¹ cm⁻²) and lower detection limit (LOD: 1.63 μmol L⁻¹). It is noteworthy to mention that sensor exhibits good operational and long-term storage stability.