Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Cell Biochem Biophys. 2024 Aug 31. doi: 10.1007/s12013-024-01489-1. Online
ahead  of print.

Molecular Dynamics Simulation Studies of Beta-Glucogallin and Dihydro Dehydro 
Coniferyl Alcohol from Syzygium cumini for its Antimicrobial Activity on 
Staphylococcus aureus.

Bhavyashree N(1), Vaishnavi MS(1), Shravani P(1), Sabat S(2).

Author information:
(1)Department of Biotechnology, People's Education Society University, 
Bangalore, 560085, Karnataka, India.
(2)Department of Biotechnology, People's Education Society University, 
Bangalore, 560085, Karnataka, India. sasmitasabat@pes.edu.

With the escalating threat of antimicrobial resistance (AMR), discovering novel 
therapeutic agents against resistant pathogens like Staphylococcus aureus is 
crucial. This study explores phytochemicals from Syzygium cumini for their 
potential efficacy against AMR S. aureus infections, elucidating their 
mechanisms through in silico methods. We investigated 83 compounds from S. 
cumini, sourced from PubMed, using rigorous docking analysis against the ATP 
binding domain AgrC of S. aureus with AMdock with Autodock Vina v1.5.2. 
Drug-likeness predictions were assessed using SwissADME v2023 and Pass online 
v2.0. Molecular dynamics (MD) simulations identified promising compounds, 
focusing on stability and interaction dynamics. Beta-Glucogallin (BEG) and 
Dihydro Dehydro Coniferyl alcohol (DIH) emerged as significant hits. MD 
simulations with GROMACS v2020.6 revealed stable BEG and DIH complexes with 
AgrC, forming six hydrogen bonds with six key amino acids (Arg-303, Asp-338, 
Glu-342, Glu-384, Lys-389, Gly-396), indicating strong and stable bonding. The 
binding affinities for DIH and BEG are -73.474 ± 11.104 kJ/mol and 
-6.319 ± 18.823 kJ/mol with 4BXI, respectively. Our findings highlight BEG and 
DIH as promising candidates against AMR S. aureus infections, showing favourable 
binding affinities and stable interactions with AgrC. This study underscores the 
importance of natural products in combating AMR and demonstrates the utility of 
computational methodologies in drug discovery. Further experimental validation 
is warranted to fully exploit these phytochemicals' therapeutic potential.

© 2024. The Author(s), under exclusive licence to Springer Science+Business 
Media, LLC, part of Springer Nature.

DOI: 10.1007/s12013-024-01489-1
PMID: 39214923


2. Biotechnol Bioeng. 2024 Nov;121(11):3527-3536. doi: 10.1002/bit.28820. Epub
2024  Jul 30.

Microbial synthesis of gallic acid and its glucoside β-glucogallin.

Guo J(1), Ren X(1), Lu L(1), An N(1), Li S(1), Geng M(1), Li G(1), Shen X(1), 
Sun X(1), Wang J(1), Yuan Q(1).

Author information:
(1)State Key Laboratory of Chemical Resource Engineering, Beijing University of 
Chemical Technology, Beijing, China.

Gallic acid (GA) and β-glucogallin (BGG) are natural products with diverse uses 
in pharmaceutical, food, chemical and cosmetic industries. They are valued for 
their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, 
and anticancer properties. Despite their significant importance, microbial 
production of GA and BGG faces challenges such as limited titers and yields, 
along with the incomplete understanding of BGG biosynthesis pathways in 
microorganisms. To address these challenges, we developed a recombinant 
Escherichia coli strain capable of efficiently producing GA. Our approach 
involved screening efficient pathway enzymes, integrating biosynthetic pathway 
genes into the genome while balancing carbon flux via adjusting expression 
levels, and strengthening the shikimate pathway to remove bottlenecks. The 
resultant strain achieved impressive results, producing 51.57 g/L of GA with a 
carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, 
we extended this microbial platform to biosynthesize BGG by screening GA 
1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. 
This work establishes an efficient chassis for producing GA at an industrial 
level and provides a microbial platform for generating GA derivatives.

© 2024 Wiley Periodicals LLC.

DOI: 10.1002/bit.28820
PMID: 39081029 [Indexed for MEDLINE]


3. J Food Drug Anal. 2024 Mar 15;32(1):54-64. doi: 10.38212/2224-6614.3494.

Effect of Indian gooseberry extract on improving methylglyoxal-associated leptin 
resistance in peripheral tissues of high-fat diet-fed rats.

Chen SY(1), Huang YN(1), Lin JA(2), Yen GC(1).

Author information:
(1)Department of Food Science and Biotechnology, National Chung Hsing 
University, 145 Xingda Road, Taichung 40227, Taiwan.
(2)Graduate Institute of Food Safety, National Chung Hsing University, 145 
Xingda Road, Taichung 40227, Taiwan.

Increased leptin resistance and methylglyoxal (MG) levels are observed in obese 
patients. However, whether MG deposits contribute to leptin resistance, 
oxidative stress, and inflammation in peripheral tissues remains unclear. In 
addition, the edible fruit of Indian gooseberry (Phyllanthus emblica L.) 
contains abundant bioactive components such as vitamin C, β-glucogallin (β-glu), 
gallic acid (GA), and ellagic acid (EA). Water extract of Indian gooseberry 
fruit (WEIG) and GA has been shown to improve cognitive decline by suppressing 
brain MG-induced insulin resistance in rats administered a high-fat diet (HFD). 
Accordingly, this study investigated the functions of WEIG and GA in inhibiting 
MG-induced leptin resistance, oxidative stress, and inflammation in the 
peripheral tissues of HFD-fed rats. The results showed that MG, advanced 
glycation end products (AGEs), and leptin resistance accumulation in the liver, 
kidney, and perinephric fat were effectively restored by elevated glyoxalase-1 
(Glo-1) activity after WEIG and GA administration comparable to that of 
alagebrium chloride (positive control) treatment in HFD-fed rats. Furthermore, 
WEIG and GA supplementation increased adiponectin and antioxidant enzymes 
(glutathione peroxidase, superoxide dismutase, catalase) and decreased 
inflammatory cytokines (IL-6, IL-1β, TNF-α) in the peripheral tissues of HFD-fed 
rats. In conclusion, these findings demonstrated that MG may trigger leptin 
resistance, oxidative stress, and inflammation in peripheral tissues, which 
could be abolished by WEIG and GA treatment. These results show the potential of 
P. emblica for functional food development and improving obesity-associated 
metabolic disorders.

DOI: 10.38212/2224-6614.3494
PMCID: PMC10962648
PMID: 38526590 [Indexed for MEDLINE]

Conflict of interest statement: Conflicts of interest: There are no conflicts to 
declare.


4. New Phytol. 2024 Jun;242(6):2702-2718. doi: 10.1111/nph.19711. Epub 2024 Mar
21.

Genomic basis of the distinct biosynthesis of β-glucogallin, a biochemical 
marker for hydrolyzable tannin production, in three oak species.

Yang Q(#)(1)(2), Li J(#)(1)(2), Wang Y(#)(3), Wang Z(4), Pei Z(1)(2), Street 
NR(5)(6), Bhalerao RP(7), Yu Z(1)(2), Gao Y(8), Ni J(8), Jiao Y(8), Sun M(1)(2), 
Yang X(1)(2), Chen Y(1)(2), Liu P(1)(2), Wang J(1)(2), Liu Y(1)(2), Li G(1)(2).

Author information:
(1)State Key Laboratory of Efficient Production of Forest Resources, Beijing 
Forestry University, Beijing, 100083, China.
(2)Research Center of Deciduous Oaks, Beijing Forestry University, Beijing, 
100083, China.
(3)College of Horticulture, China Agricultural University, Beijing, 100193, 
China.
(4)Co-Innovation Center for Sustainable Forestry in Southern China, College of 
Ecology and Environment, Nanjing Forestry University, Nanjing, 210037, China.
(5)Umeå Plant Science Centre, Department of Plant Physiology, Umeå University, 
Umeå, 90754, Sweden.
(6)SciLifeLab, Umeå University, Umeå, 90754, Sweden.
(7)Umeå Plant Science Centre, Department of Forest Genetics and Plant 
Physiology, Swedish University of Agricultural Sciences, 90187, Umeå, Sweden.
(8)College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 
310058, China.
(#)Contributed equally

Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in 
grape wine aging, feed additives, and human healthcare. However, the limited 
availability of a high-quality reference genome of oaks greatly hampered the 
recognition of the mechanism of HT biosynthesis. Here, high-quality reference 
genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and 
Quercus dentata) that have different HT contents were generated. Multi-omics 
studies were carried out to identify key genes regulating HT biosynthesis. 
In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast 
one-hybrid assays were used to reveal the transcriptional regulation. Our 
results revealed that β-glucogallin was a biochemical marker for HT production 
in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme 
for β-glucogallin biosynthesis. The differential expression of UGT84A13, rather 
than enzyme activity, was the main reason for different β-glucogallin and HT 
accumulation. Notably, sequence variations in UGT84A13 promoters led to 
different trans-activating activities of WRKY32/59, explaining the different 
expression patterns of UGT84A13 among the three species. Our findings provide 
three high-quality new reference genomes for oak trees and give new insights 
into different transcriptional regulation for understanding β-glucogallin and HT 
biosynthesis in closely related oak species.

© 2024 The Authors New Phytologist © 2024 New Phytologist Foundation.

DOI: 10.1111/nph.19711
PMID: 38515244 [Indexed for MEDLINE]


5. Appl Microbiol Biotechnol. 2024 Dec;108(1):69. doi:
10.1007/s00253-023-12895-5.  Epub 2024 Jan 6.

Enzymatic synthesis of phenolic acid glucosyl esters to test activities on 
cholangiocarcinoma cells.

Suyanto E(1)(2)(3), Gorantla JN(1)(2), Santi M(1)(2), Fatchiyah F(3), 
Ketudat-Cairns M(2)(4), Talabnin C(5), Ketudat Cairns JR(6)(7)(8).

Author information:
(1)School of Chemistry, Institute of Sciences, Suranaree University of 
Technology, Nakhon Ratchasima, Thailand.
(2)Center for Biomolecular Structure, Function and Application, Suranaree 
University of Technology, Nakhon Ratchasima, Thailand.
(3)Biology Department, Faculty of Mathematics and Natural Sciences, Brawijaya 
University, Malang, Indonesia.
(4)School of Biotechnology, Institute of Agricultural Technology, Suranaree 
University of Technology, Nakhon Ratchasima, Thailand.
(5)School of Chemistry, Institute of Sciences, Suranaree University of 
Technology, Nakhon Ratchasima, Thailand. chutima.sub@sut.ac.th.
(6)School of Chemistry, Institute of Sciences, Suranaree University of 
Technology, Nakhon Ratchasima, Thailand. cairns@sut.ac.th.
(7)Center for Biomolecular Structure, Function and Application, Suranaree 
University of Technology, Nakhon Ratchasima, Thailand. cairns@sut.ac.th.
(8)Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand. 
cairns@sut.ac.th.

While glycoside hydrolase family 1 (GH1) enzymes mostly catalyze hydrolysis 
reactions, rice Os9BGlu31 preferentially catalyzes transglycosylation to 
transfer a glucosyl moiety to another aglycone moiety to form a new glycosylated 
compound through a retaining mechanism. In this study, Os9BGlu31 was used to 
synthesize eight phenolic acid glucosyl esters, which were evaluated for 
activities in cholangiocarcinoma cells. The transglycosylation products of 
Os9BGlu31 wild type and its mutant variants were detected, produced on a 
milligram scale, and purified, and their structures were characterized by NMR 
spectroscopy. The transglycosylation products were evaluated by antioxidant and 
anti-proliferative assays, followed by an anti-migration assay for the selected 
phenolic acid glucosyl ester. Os9BGlu31 mutants produced higher yield and 
activity than wild-type enzymes on phenolic acids to produce phenolic acid 
glucosyl esters. Among these, gallic acid glucosyl ester (β-glucogallin) had the 
highest antioxidant activity and anti-proliferative activity in 
cholangiocarcinoma cells. It also inhibited the migration of cholangiocarcinoma 
cells. Our study demonstrated that rice Os9BGlu31 transglucosidase is a 
promising enzyme for glycosylation of bioactive compounds in one-step reactions 
and provides evidence that β-glucogallin inhibits cell proliferation and 
migration of cholangiocarcinoma cells. KEY POINTS: • Os9BGlu31 transglucosidases 
produced phenolic acid glucosyl esters for bioactivity testing. • Phenolic acid 
glucosyl esters were tested for cytotoxicity in cholangiocarcinoma cells. • 
β-Glucogallin displayed the highest inhibition of cholangiocarcinoma cell 
growth.

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
part of Springer Nature.

DOI: 10.1007/s00253-023-12895-5
PMID: 38183488 [Indexed for MEDLINE]