Effect of Endogenous Lipids and Proteins on the Antioxidant, in vitro Starch Digestibility, and Pasting Properties of Sorghum Flour

This study evaluated the effect of endogenous lipids and proteins on the antioxidants, starch digestibility, and pasting properties of sorghum (Sorghum bicolor) flour (SF). Endogenous lipids and/or proteins were removed from different portions of SF to obtain defatted (DF), deproteinized (DP), and defatted and deproteinized (DF-DP) flours. Bioactive constituents (total phenolics, tannins, flavonoids, saponins, and anthocyanins), antioxidant activities [2,2-Azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation (ABTS*+) and 2, 2-Diphenyl-2-picrylhydrazyl radical (DPPH*) scavenging activities, reducing power, and Fe2+ chelating capacity], starch, amylose, starch hydrolysis index (HI), estimated glycemic index (eGI), and pasting properties of treated and control (untreated) flours were determined. The control flour (SF) had significantly higher (p < 0.05) levels of all the bioactive constituents and antioxidant activity tested than the DF, DP, and DF-DP flours, while the DF-DP flour had the least levels of bioactive constituents and antioxidant activity. In contrast, the starch, amylose, HI, and eGI were consistently in the order of DF-DP > DF > DP > control flour (p < 0.05). The control flour had the highest (p < 0.05) peak viscosity, and the least peak time and pasting temperature, while the DF flour had the highest final viscosity. Therefore, endogenous lipids and proteins contribute to the antioxidant, starch digestibility, and pasting properties of sorghum flour.

Effect of Coix Seed Extracts on Growth and Metabolism of Limosilactobacillus reuteri

Coix seed (Coix lachryma-jobi L.) is an important nourishing food and traditional Chinese medicine. The role of their bioactive constituents in physiology and pharmacology has received considerable scientific attention. However, very little is known about the role of coix seed bioactive components in the growth of Limosilactobacillus reuteri (L. reuteri). This study aimed to evaluate the effects of coix seed extract (CSE) on the growth, acidifying activity, and metabolism of L. reuteri. The results showed that CSE can increase the growth and acidifying activity of L. reuteri compared with the control group. During the stationary phase, the viable bacteria in the medium supplemented with coix seed oil (CSO, 13.72 Log10 CFU/mL), coix polysaccharide (CPO, 12.24 Log10 CFU/mL), and coix protein (CPR, 11.91 Log10 CFU/mL) were significantly higher (p < 0.05) than the control group (MRS, 9.16 Log10 CFU/mL). CSE also enhanced the biosynthesis of lactic acid and acetic acid of L. reuteri. Untargeted metabolomics results indicated that the carbohydrate metabolism, amino acid metabolism, and nucleotide metabolism activities of L. reuteri were increased after adding CSE. Furthermore, CSE increased the accumulation of bioactive metabolites, such as phenyl lactic acid, vitamins, and biotin. Overall, CSE may have prebiotic potential and can be used to culture L. reuteri with high viable bacteria.

Safety, Stability, and Therapeutic Efficacy of Long-Circulating TQ-Incorporated Liposomes: Implication in the Treatment of Lung Cancer

Thymoquinone (TQ), which is one of the main bioactive constituents of Nigella sativa seeds, has demonstrated its potential against various cancer models. The poor solubility of TQ in aqueous solution limits its uses in clinical application. The present study aimed to develop a novel formulation of TQ to increase its bioavailability and therapeutic potential with minimal toxicity. Polyethylene glycol (PEG)-coated DSPC/cholesterol comprising TQ liposomes (PEG-Lip-TQ) were prepared and characterized on various aspects. A computational investigation using molecular docking was used to assess the possible binding interactions of TQ with 12 prospective anticancer drug targets. The in vitro anticancer activity was assessed in A549 and H460 lung cancer cells in a time- and dose-dependent manner, while the oral acute toxicity assay was evaluated in silico as well as in vivo in mice. TQ docked to the Hsp90 target had the lowest binding energy of −6.05 kcal/mol, whereas caspase 3 was recognized as the least likely target for TQ with a binding energy of −1.19 kcal/mol. The results showed 96% EE with 120 nm size, and −10.85 mv, ζ-potential of PEG-Lip-TQ, respectively. The cell cytotoxicity data demonstrated high sensitivity of PEG-Lip-TQ and a several fold decrease in the IC50 while comparing free TQ. The cell cycle analysis showed changes in the distribution of cells with doses. The in vivo data revealed an ~9-fold increase in the LD50 of PEG-Lip-TQ on free TQ as an estimated 775 and 89.5 mg/kg b.w, respectively. This study indicates that the pharmacological and efficacy profile of PEG-lip-TQ is superior to free TQ, which will pave the way for an exploration of the effect of TQ formulation in the treatment of lung cancer in clinical settings.

Butyrate Emerges as a Crucial Effector of Zhi-Zi-Chi Decoctions to Ameliorate Depression via Multiple Pathways of Brain-gut Axis

Background: Gut microbiota has emerged as a crucial target of gut-brain axis to influence brain and behavior and also has been closely connected with depression. Zhi-Zi-Chi decoctions (ZZCD), as a classic oral formula in clinic prescribed to clear heat and relieve restlessness traditionally, is widely applied in depression treatment nowadays. However, the underlying mechanism in the antidepressant activity of ZZCD remains largely unknown. Our previous study revealed that isoflavones, the bioactive constituents of Semen Sojae Praeparatum, benefited health by regulating the gut microbiota, which introduced the gut microbiota into understanding the mechanism of Traditional Chinese Medicine (TCM). Hence, in the present study, we aimed to investigate the antidepressant mechanism of ZZCD by focusing on the gut microbiota. Results: A classic depression model of chronic mild unpredictable stress (CUMS) was established in rats based on the results of behavioral tests and hippocampal histomorphology. 16S rRNA sequencing analysis indicated that ZZCD could increase short-chain fatty acid-producing and anti-inflammatory bacteria and reduce inflammatory and tryptophan-metabolizing bacteria, which reflected the changes of short-chain fatty acids (SCFAs), inflammation and tryptophan metabolism from the perspective of the gut microbiota. Furthermore, ZZCD reversed the alterations of BDNF, TNF-α, pro-inflammatory cytokines and neurotransmitters in the gut, blood and brain along the brain-gut axis and restored the decrease of butyrate in cecal content caused by CUMS. Then, butyrate was utilized to validate its ameliorative effect on pathological characteristics of depressive rats. Conclusions: Taken together, these results show that ZZCD exhibits antidepressant effect through modulating gut microbiota to facilitate the production of butyrate, which further regulate anti-inflammation, neurotransmitters, endocrine and BDNF along the gut-brain axis. Hence, this study fills the gap of the antidepressive mechanism of ZZCD in the light of the brain-gut axis and established a multi-targets and multi-levels platform eventually for further research into the mechanism of other TCM efficacy.

Macrofilaricidal Activity, Acute and Biochemical Effects of Three Lichen Species Found on Mount Cameroon

Onchocerciasis is a parasitic infection affecting a relatively small population globally but has very devastating pathological outcomes. Ivermectin and recently moxidectin are the only drugs approved for clinical management of the disease, both of which have several limitations. In particular, they are efficacious against microfilariae (microfilaricidal) with no activity against adult worms (nonmacrofilaricidal). Promising anthelmintic activity has been reported in some lichens. This study investigated three lichens, Usnea articulata, Parmotrema tinctorum, and Heterodermia obscurata, found on Mount Cameroon, for potential macrofilaricidal activity. Organic extracts were screened for anti-Onchocerca activity against Onchocerca ochengi isolated from cattle skin using worm motility and MTT formazan assays. Toxicity of highly active extracts was investigated on monkey kidney epithelial (LLCMK2) cells and in BALB/c mice (2000 mg/kg body weight) including effects on liver enzymes. The methanol extract of P. tinctorum (Pammet) was the most active against adult male worms ( I C 50 = 8.1 μg/mL) with the highest selectivity index ( SI = 21.3 ). U. articulata was the most active against the adult female ( I C 50 = 36.3 μg/mL) but had a low SI value (3.4). No mortality and no adverse effects were recorded in the acute toxicity test. These two most active extracts had no significant effect on liver enzymes, alanine aminotransferase, and aspartate ( P values < 0.05), but a high AST : ALT ratio (2.59) for Pammet indicates likely reversible adverse hepatic toxicity. The high macrofilaricidal activity and selectivity of P. tinctorum suggest it is a potential source of new macrofilaricides which should be further investigated to identify its bioactive constituents.

Phytochemical compounds of Guibourtia ehie and their antioxidant, urease and α-glucosidase inhibitory activities

Thirteen compounds (<b>1</b>‒<b>13</b>) were isolated and identified during phytochemical analysis of the leaves and stem bark of <i>Guibourtia ehie</i> (A. Chev) J. Leonard. Spectroscopic and spectrometric methods and the comparison of their results with those given in the literature were used to ascertain their structures. Furthermore, the acetylation of 3,3′-di-<i>O</i>-methylellagic acid 4′-<i>O</i>-β-D-xylopyranoside (<b>2</b>) afforded a new derivative 3,3′-di-<i>O</i>-methylellagic acid 4′-<i>O</i>-β-D-(4,2′′,4′′-triacetyl)-xylopyranoside (<b>2a</b>). Extracts, fractions, and isolated compounds were assessed for their antioxidant, urease, and α-glucosidase inhibitory activities. Compound <b>1</b> demonstrated potent antioxidant activity in the DPPH with an IC₅₀ value of 36.4 ± 0.2 µM, while rhaponticin (<b>3</b>), 2,6-dimethoxybenzoquinone (<b>4</b>), and taraxerol (<b>6</b>) exhibited a strong α-glucosidase inhibitory activity with the IC₅₀ values of 35.5 ± 0.1, 25.5 ± 0.2 and 43.4 ± 0.3 µM, respectively. The present study enriches the chemistry of <i>Guiboutia ehie</i> and provides further evidence on its bioactive constituents, which might help in the development of hypoglycaemic drugs.

Molecular Dynamics Free Energy Simulation study to Investigate Binding Pattern of Isoliquiritigenin as PPAR𝛾 Agonist

Phytochemicals are rich source of bioactive constituents and can be used as another alternative to currently used drugs for diseases like Diabetes mellitus. The potential of Isoliquiritigenin (a constituent of Pterocarpus marsupium) as PPAR𝛾 agonist was evaluated by in silico technique. Autodock results showed that Tyr327, and Tyr473 of the PPARγ forms H-bonds with Isoliquiritigenin (binding energy of -7.46 kcal/mol) and Troglitazone (known drug) showed H bond with Tyr327, Ser289, with binding energy of -11.01 kcal/mol. Isoliquiritigenin, binding energy in Extra precision (XP) was -6.74 kcal/mol while Troglitazone docking, gave binding energy in XP mode as -9.59 kcal/mol. The best Induced fit docking (IFD) score of the optimised PPARγ- Isoliquiritigenin complexes was -9.39 Kcal/mol. The important residues in IFD forming H bond were Cys 285, Arg 288, Tyr 327 and Leu 340. The post docking MM/GBSA free energy for PPARγ with Isoliquiritigenin and Troglitazone was -49.29 and -71.48 Kcal/mol respectively. Binding interaction in MD simulation and Principal Component Analysis studies revealed stable binding throughout 100 ns simulation. Post Simulation MM/PBSA free energy was calculated. The results indicated that compound possessed a negative binding free energy with -114.37KJ/mol. It was observed that van der Waals, electrostatic interactions and non-polar solvation energy negatively contributed to the total interaction energy while only polar solvation energy positively contributed to total free binding energy. The Isoliquiritigenin fulfils the criteria of drug-likeness property. Thus, study presents a systematic analysis on molecular mechanism of action of Isoliquiritigenin as PPARγ agonist in controlling Diabetes mellitus.

Therapeutic and Pharmaceutical Potential of Cinnamon

Cinnamon has been used as a spice, condiment, and aromatic plant since centuries ago. Cinnamon is a small evergreen tree belonging to the genus Cinnamomum in the family Lauraceae. There are more than 250 species of cinnamon worldwide. In India, Cinnamomum verum and Cinnamomum cassia are the most common species grown in the Himalaya region. They have been used as folk medicine for the treatment of nausea, flatulent dyspepsia, coughs, diarrhea, malaria, gastric disorder, and to alleviate pain and inflammation in rheumatic arthritis. Therapeutic properties of cinnamon are due to the presence of bioactive constituents such as p-coumaric, cinnamaldehyde, cinnamic acid, and eugenol. Cinnamaldehyde and eugenol are the major active constituents responsible for its characteristic flavor, aroma, and therapeutic properties. Pharmacological studies found that it could be a promising candidate with potential for designing new drugs. This review is aimed to summarize the ethanomedicinal importance, phytochemistry, and wide spectrum of pharmacological and therapeutic applications of cinnamon.