bims-antpol 2023-06-18 papers

Issue of 2023–06–18
five papers selected by
Rick Sheridan, EMSKE Phytochem

Biochem Biophys Res Commun. 2023 Jun 03. pii: S0006-291X(23)00736-2. [Epub ahead of print]671 116-123

Flavonoid quercetin and its glucuronide and sulfate conjugates bind to 67-kDa laminin receptor and prevent neuronal cell death induced by serum starvation.

Rayudu Gopalakrishna, Andrew Oh, Lucas Hou, Emily Lee, Jennifer Aguilar, Andrew Li, William J Mack.

Quercetin, a dietary flavonoid, has been shown to protect against various neurodegenerative diseases with mechanisms largely unknown. After oral administration, quercetin is rapidly conjugated, and the aglycone is not detectable in the plasma and brain. However, its glucuronide and sulfate conjugates are present only at low nanomolar concentrations in the brain. Since quercetin and its conjugates have limited antioxidant capability at low nanomolar concentrations, it is crucial to determine whether they induce neuroprotection by binding to high-affinity receptors. Previously we found that (-)-epigallocatechin-3-gallate (EGCG), a polyphenol from green tea, induces neuroprotection by binding to the 67-kDa laminin receptor (67LR). Therefore, in this study, we determined whether quercetin and its conjugates bind 67LR to induce neuroprotection and compared their ability with EGCG. Based on the quenching of intrinsic tryptophan fluorescence of peptide G (residues 161-180 in 67LR), we found quercetin, quercetin-3-O-glucuronide, and quercetin-3-O-sulfate bind to this peptide with a high affinity comparable to EGCG. Molecular docking using the crystal structure of 37-kDa laminin receptor precursor supported the high-affinity binding of all these ligands to the site corresponding to peptide G. A pretreatment with quercetin (1-1000 nM) did not effectively protect Neuroscreen-1 cells from death induced by serum starvation. Contrarily, a pretreatment with low concentrations (1-10 nM) of quercetin conjugates better protected these cells than quercetin and EGCG. The 67LR-blocking antibody substantially prevented neuroprotection by all these agents, suggesting the role of 67LR in this process. Collectively, these studies reveal that quercetin induces neuroprotection primarily through its conjugates via high affinity binding to 67LR.

Keywords: 67-kDa laminin receptor; Epigallocatechin-3-gallate; Neuroprotection; Quercetin; Quercetin-3-O-glucuronide; Quercetin-3-O-sulfate

DOI: https://doi.org/10.1016/j.bbrc.2023.06.007

Chem Biodivers. 2023 Jun 12. e202300547

Chemical characterization of different extracts from Artemisia annua and their antioxidant, enzyme inhibitory and anti-inflammatory properties.

Alessandra Acquaviva, Nilofar Nilofar, Abdelhakim Bouyahya, Gokhan Zengin, Simonetta Cristina Di Simone, Lucia Recinella, Sheila Leone, Luigi Brunetti, Abdullahi Ibrahim Uba, Ugur Cakilcioğlu, Rıdvan Polat, Ekrem Darendelioglu, Luigi Menghini, Claudio Ferrante, Giustino Orlando, Maria Loreta Libero, Annalisa Chiavaroli.

Artemisia annua L. (Asteraceae Family) is a plant endemic in Asia that has been used by Chinese herbalists for centuries for treating different diseases, including fever due to malaria, wounds, tubercolisis, scabues, pain, convulsions, diabetes, and inflammation. In this study we aimed to evaluate the effects of different polarity extracts from A. annua against the burden of inflammation and oxidative stress occurring in colon tissue exposed to LPS. In parallel, chemical composition, antiradical, and enzyme inhibition effects against α-amylase, α-glucosidase, tyrosinase, and cholinesterases were evaluated. All extracts revealed effective as antioxidants, enzyme inhibitors, and anti-inflammatory agents, as demonstrated by the blunting effects on COX-2 and TNFα gene expression. These effects seemed to be not related to the only phenolic content. However, it is worthy of interest to highlight how the higher potency against LPS-induced gene expression was shown by the water extract ; thus suggesting a potential phytotherapy application in the management of clinical symptoms related to inflammatory colon diseases, although future in vivo studies are needed to confirm such in vitro and ex vivo observations.

Keywords: Artemisia annua; anti-inflammatory effects; antioxidant effects; enzyme inhibition; specialized metabolites

DOI: https://doi.org/10.1002/cbdv.202300547

Molecules. 2023 May 31. pii: 4476. [Epub ahead of print]28(11):

Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Ting-Ting Tang, Su-Mei Li, Bo-Wen Pan, Jun-Wei Xiao, Yu-Xin Pang, Shou-Xia Xie, Ying Zhou, Jian Yang, Ying Wei.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).

Keywords: HIV-1 protease; Scutellaria barbata D. Don; cathepsin L protease; flavonoids; structure–activity relationships

DOI: https://doi.org/10.3390/molecules28114476

Bioorg Med Chem. 2023 Jun 02. pii: S0968-0896(23)00210-9. [Epub ahead of print]90 117362

Isolation and identification of the new baicalin target protein to develop flavonoid structure-based therapeutic agents.

Yoshio Kusakabe, Shun-Suke Moriya, Toru Sugiyama, Yoshiki Miyata.

Proteins are vital constituents of all living organisms. As many therapeutic agents alter the activity of functional proteins, identifying functional target proteins of small bioactive molecules isessential for the rational design of stronger medicines. Flavonoids with antioxidant, anti-allergy, and anti-inflammatory effects are expected to have preventive effects for several diseases closely related to oxidation and inflammation, including heart disease, cancer, neurodegenerative disorders, and eye diseases. Therefore, identifying the proteins involved in the pharmacological actions of flavonoids, and designing a flavonoid structure-based medicine that strongly and specifically inhibits flavonoid target proteins, could aid the development of more effective medicines for treating heart disease, cancer, neurodegenerative disorders, and ocular diseases with few side effects. To isolate the flavonoid target protein, we conducted a novel affinity chromatography in a column wherein baicalin, a representative flavonoid, was attached to Affi-Gel 102. Through affinity chromatography and nano LC-MS/MS, we identified GAPDH as a flavonoid target protein. Then, we performed fluorescence quenching and an enzyme inhibition assay to experimentally confirmbaicalin's binding affinity for, and inhibition of, GAPDH. We also conducted in silico docking simulations to visualize the binding modes of baicalin and the newly identified flavonoid target protein, GAPDH. From the results of this study, it was considered that one of the reasons why baicalin exhibits the effects on cancer and neurodegenerative diseases is that it inhibits the activity of GAPDH. In summary, we showed that Affi-Gel102 could quickly and accurately isolate the target protein for bioactive small molecules, without the need for isotopic labeling or a fluorescent probe. By using the method presented here, it was possible to easily isolate the target protein of a medicine containing a carboxylic acid.

Keywords: And cell biology; Flavonoid target protein; In silico study; Inhibition assay

DOI: https://doi.org/10.1016/j.bmc.2023.117362

Microorganisms. 2023 Apr 28. pii: 1156. [Epub ahead of print]11(5):

Insights into Antimicrobial and Anti-Inflammatory Applications of Plant Bioactive Compounds.

Gregoria Mitropoulou, Elisavet Stavropoulou, Natalia Vaou, Zacharias Tsakris, Chrysa Voidarou, Arsenis Tsiotsias, Christina Tsigalou, Birce Mercanoglou Taban, Yiannis Kourkoutas, Eugenia Bezirtzoglou.

Plants have long been thought to contribute to health promotion due to their fiber and phenolic content, as well as their inherent biological potential. The bioactive derivatives of medicinal plants are a valuable resource in the fight against serious diseases all around the world. The present review focuses on the current state of knowledge on the usage and medicinal applications of plant bioactives. Issues concerning the effect of aromatic plant derivatives on human gut microbiota and their antimicrobial and anti-inflammatory potentials are discussed and worth further exploring.

Keywords: antibiotics; antimicrobial activity; antioxidants; bioactive compounds; human microbiota; inflammatory diseases; medicinal plants; new antimicrobials; plant derivatives

DOI: https://doi.org/10.3390/microorganisms11051156