Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Plant J. 2024 Jul;119(2):927-941. doi: 10.1111/tpj.16807. Epub 2024 Jun 14.

Functional characterization of polyphenol oxidase OfPPO2 supports its 
involvement in parallel biosynthetic pathways of acteoside.

Liu Y(#)(1), Han X(#)(1), Zhao M(#)(2), Liu L(1), Deng Z(1), Zhao Q(1), Yu 
Y(1)(3).

Author information:
(1)Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Hubei 
Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, School 
of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, Wuhan, P.R. 
China.
(2)Department of Gynecologic Oncology, Zhongnan Hospital of Wuhan University; 
Women and Children's Hospital Affiliated to Zhongnan Hospital of Wuhan 
University, 185 East Lake Road, Wuhan, P.R. China.
(3)State Key Laboratory of Non-Food Biomass and Enzyme Technology, Guangxi 
Academy of Sciences, Nanning, 530007, China.
(#)Contributed equally

Acteoside is a bioactive phenylethanoid glycoside widely distributed throughout 
the plant kingdom. Because of its two catechol moieties, acteoside displays a 
variety of beneficial activities. The biosynthetic pathway of acteoside has been 
largely elucidated, but the assembly logic of two catechol moieties in acteoside 
remains unclear. Here, we identified a novel polyphenol oxidase OfPPO2 from 
Osmanthus fragrans, which could hydroxylate various monophenolic substrates, 
including tyrosine, tyrosol, tyramine, 4-hydroxyphenylacetaldehyde, salidroside, 
and osmanthuside A, leading to the formation of corresponding 
catechol-containing intermediates for acteoside biosynthesis. OfPPO2 could also 
convert osmanthuside B into acteoside, creating catechol moieties directly via 
post-modification of the acteoside skeleton. The reverse 
transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and 
subcellular localization assay further support the involvement of OfPPO2 in 
acteoside biosynthesis in planta. These findings suggest that the biosynthesis 
of acteoside in O. fragrans may follow "parallel routes" rather than the 
conventionally considered linear route. In support of this hypothesis, the 
glycosyltransferase OfUGT and the acyltransferase OfAT could direct the flux of 
diphenolic intermediates generated by OfPPO2 into acteoside. Significantly, 
OfPPO2 and its orthologs constitute a functionally conserved enzyme family that 
evolved independently from other known biosynthetic enzymes of acteoside, 
implying that the substrate promiscuity of this PPO family may offer 
acteoside-producing plants alternative ways to synthesize acteoside. Overall, 
this work expands our understanding of parallel pathways plants may employ to 
efficiently synthesize acteoside, a strategy that may contribute to plants' 
adaptation to environmental challenges.

© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.

DOI: 10.1111/tpj.16807
PMID: 38872484 [Indexed for MEDLINE]


2. Plant Commun. 2023 Jul 10;4(4):100592. doi: 10.1016/j.xplc.2023.100592. Epub 
2023 Mar 20.

Complete biosynthesis of the phenylethanoid glycoside verbascoside.

Yang Y(1), Xi D(2), Wu Y(2), Liu T(3).

Author information:
(1)Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin 
Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 
300308, China; National Center of Technology Innovation for Synthetic Biology, 
Tianjin 300308, China; University of Chinese Academy of Sciences, Beijing 
100049, China.
(2)Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin 
Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 
300308, China; National Center of Technology Innovation for Synthetic Biology, 
Tianjin 300308, China.
(3)Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin 
Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 
300308, China; National Center of Technology Innovation for Synthetic Biology, 
Tianjin 300308, China. Electronic address: liu_t@tib.cas.cn.

Verbascoside, which was first discovered in 1963, is a well-known phenylethanoid 
glycoside (PhG) that exhibits antioxidant, anti-inflammatory, antimicrobial, and 
neuroprotective activities and contributes to the therapeutic effects of many 
medicinal plants. However, the biosynthetic pathway of verbascoside remains to 
be fully elucidated. Here, we report the identification of two missing enzymes 
in the verbascoside biosynthesis pathway by transcriptome mining and in vitro 
enzymatic assays. Specifically, a BAHD acyltransferase 
(hydroxycinnamoyl-CoA:salidroside hydroxycinnamoyltransferase [SHCT]) was shown 
to catalyze the regioselective acylation of salidroside to form osmanthuside A, 
and a CYP98 hydroxylase (osmanthuside B 3,3'-hydroxylase [OBH]) was shown to 
catalyze meta-hydroxylations of the p-coumaroyl and tyrosol moieties of 
osmanthuside B to complete the biosynthesis of verbascoside. Because SHCTs and 
OBHs are found in many Lamiales species that produce verbascoside, this pathway 
may be general. The findings from the study provide novel insights into the 
formation of caffeoyl and hydroxytyrosol moieties in natural product 
biosynthetic pathways. In addition, with the newly acquired enzymes, we achieved 
heterologous production of osmanthuside B, verbascoside, and ligupurpuroside B 
in Escherichia coli; this work lays a foundation for sustainable production of 
verbascoside and other PhGs in micro-organisms.

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.xplc.2023.100592
PMCID: PMC10363510
PMID: 36935606 [Indexed for MEDLINE]


3. Molecules. 2022 Oct 31;27(21):7390. doi: 10.3390/molecules27217390.

Phenylethanoid and Phenylmethanoid Glycosides from the Leaves of Ligustrum 
robustum and Their Bioactivities.

Lu SH(1), Zuo HJ(2), Huang J(3), Chen R(4), Pan JP(1), Li XX(5).

Author information:
(1)College of Pharmacy, Youjiang Medical University for Nationalities, Baise 
533000, China.
(2)Department of Laboratory Science of Public Health, West China School of 
Public Health, Sichuan University, Chengdu 610041, China.
(3)Key Laboratory of Drug Targeting, Ministry of Education, West China School of 
Pharmacy, Sichuan University, Chengdu 610041, China.
(4)Institute of Life Science, Youjiang Medical University for Nationalities, 
Baise 533000, China.
(5)Nursing School, Youjiang Medical University for Nationalities, Baise 533000, 
China.

The phytochemical study on the leaves of Ligustrum robustum, which have been 
used as Ku-Ding-Cha, led to the isolation and identification of three new 
phenylethanoid glycosides and three new phenylmethanoid glycosides, named 
ligurobustosides R1 (1b), R2-3 (2), R4 (3), S1 (4b), S2 (5), and S3 (6), and 
five reported phenylethanoid glycosides (7-11). In the bioactivity test, 
(Z)-osmanthuside B6 (11) displayed strong fatty acid synthase (FAS) inhibitory 
activity (IC50: 4.55 ± 0.35 μM) as the positive control orlistat (IC50: 4.46 ± 
0.13 μM), while ligurobustosides R4 (3) and S2 (5), ligupurpuroside B (7), 
cis-ligupurpuroside B (8), ligurobustoside N (9), osmanthuside D (10), and 
(Z)-osmanthuside B6 (11) showed stronger ABTS radical scavenging activity (IC50: 
2.68 ± 0.05~4.86 ± 0.06 μM) than the positive control L-(+)-ascorbic acid (IC50: 
10.06 ± 0.19 μM). This research provided a theoretical basis for the leaves of 
L. robustum as a tea with function in treating obesity and diabetes.

DOI: 10.3390/molecules27217390
PMCID: PMC9657303
PMID: 36364215 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest. The 
funders had no role in the design of the study; in the collection, analyses, or 
interpretation of data; in the writing of the manuscript, or in the decision to 
publish the results.


4. Org Lett. 2021 Oct 15;23(20):7851-7854. doi: 10.1021/acs.orglett.1c02873. Epub
 2021 Oct 5.

Discovery of Glycosyltransferases Involved in the Biosynthesis of 
Ligupurpuroside B.

Yang Y(1)(2), Wu Y(1)(3), Zhuang Y(1), Liu T(1).

Author information:
(1)Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of 
Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
(2)University of Chinese Academy of Sciences, Beijing 100049, China.
(3)College of Biotechnology, Tianjin University of Science & Technology, Tianjin 
300457, China.

In this study, we report the characterization of three glycosyltransferases 
involved in the biosynthesis of ligupurpuroside B, a complex acylated phenolic 
glycoside in Ligustrum robustum. UGT85AF8 catalyzed the formation of salidroside 
from tyrosol. UGT79G7, an osmanthuside A 1,3-rhamnosyltransferase, and UGT79A19, 
an osmanthuside B 1,4-rhamnosyltransferase, sequentially converted osmanthuside 
A into ligupurpuroside B. Orthologs of UGT79G7 were also discovered from other 
plants producing verbascoside. These rhamnosyltransferases expand the toolbox 
for the biosynthesis of natural products with various sugar chains.

DOI: 10.1021/acs.orglett.1c02873
PMID: 34609151 [Indexed for MEDLINE]


5. Evid Based Complement Alternat Med. 2019 Mar 17;2019:2167947. doi: 
10.1155/2019/2167947. eCollection 2019.

The Difference of Chemical Components and Biological Activities of the Raw 
Products slices and the Wine Steam-Processed Product from Cistanche deserticola.

Zhang Y(1)(2), Wang Y(3), Yang S(1), Xiao Y(3), Guan H(2), Yue X(2), Wang X(2), 
Li X(1).

Author information:
(1)School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
Liangxiang Higher Education Park, Beijing 102488, China.
(2)School of Pharmacy, Inner Mongolia Medical University, Jinshan Development 
Zone, Hohhot, Inner Mongolia 010110, China.
(3)The Center for New Drug Safety Evaluation and Research of Inner Mongolia 
Medical University, Jinshan Development Zone, Hohhot, Inner Mongolia 010110, 
China.

As a well-known Chinese herb medicine, the Cistanche deserticola has been used 
for the treatment of kidney deficiency syndrome in China for thousands of years. 
Both the raw product of Cistanche deserticola slices (RCD) and its Wine 
Steam-Processed Product (WSCD) are used clinically for different effects. In 
this study, the influences of steaming process with wine (SPW) from Cistanche 
deserticola on chemical compositions and biological effects were investigated. 
The principal component analysis (PCA) and quantitative analysis were used to 
study the differences of the chemical compositions. The effects of nourishing 
kidney were also investigated to compare the differences between the RCD and the 
WSCD. The PCA results indicated that the obvious separation was achieved in the 
RCD and WSCD. The results of quantitative analysis showed that the WSCD has 
higher amounts of total polysaccharides, total PhGs, isoacteoside, and 
osmanthuside B than RCD, while the content of 2'-acetylacteoside and acteoside 
decreased after the SPW. The comparison of RCD and WSCD on biological activities 
showed that both could restore the level of sex hormone in the model of 
kidney-yang deficiency and improve the antioxidant effect. The WSCD were much 
better in increasing the viscera weight of kidney and seminal vesicle. The 
results indicated that SPW changed its chemical components and enhanced its 
biological activities.

DOI: 10.1155/2019/2167947
PMCID: PMC6441511
PMID: 31007699