Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Ethnopharmacol. 2024 Oct 28;333:118394. doi: 10.1016/j.jep.2024.118394. Epub
 2024 May 30.

Yangonin, one of the kavalactones isolated from Piper methysticum G. Forst, acts 
through cannabinoid 1 (CB(1)) receptors to induce an intrathecal 
anti-hyperalgesia.

Chow LH(1), Lin PC(2), Chen YJ(3), Chen YH(4), Huang EY(5).

Author information:
(1)Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, 
Taiwan; Department of Anesthesiology, School of Medicine and Institute of 
Clinical Nursing, School of Nursing, National Yung Ming Chiao Tung University, 
Taipei, Taiwan; Department of Anesthesiology, Tri-Service General Hospital, 
National Defense Medical Center, Taipei, Taiwan; Department of Pharmacology, 
National Defense Medical Center, Taipei, Taiwan. Electronic address: 
chowlh96@gmail.com.
(2)Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. 
Electronic address: 404040005@mail.ndmctsgh.edu.tw.
(3)Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. 
Electronic address: aprile431@yahoo.com.tw.
(4)Department of Neurological Surgery, Tri-Service General Hospital, National 
Defense Medical Center, Taipei, Taiwan. Electronic address: chenyh178@gmail.com.
(5)Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. 
Electronic address: eyh58@mail.ndmctsgh.edu.tw.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst (Piperaceae) is 
traditionally consumed in Polynesian culture. The roots are used to produce an 
entheogenic drink and traditional medicine with sedative and anxiolytic 
properties. There is also evidence that it functions as a pain reliever. 
Kavalactones, its main active ingredients, exhibit psychoactive effects on the 
central nervous system. However, the active ingredients and pharmacological 
mechanisms underlying the analgesic effect of kavalactones are unclear.
AIM OF THE STUDY: This study investigated the effects of kavain and yangonin on 
nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at 
the spinal level.
MATERIALS AND METHODS: Male Sprague-Dawley rats were administered kavain and 
yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests 
were performed to evaluate the anti-nociceptive properties. The efficacy of 
kavain and yangonin on inflammatory hyperalgesia was examined using a plantar 
test in rats with carrageenan-induced paw inflammation. The von Frey test was 
used to assess mechanical allodynia induced by partial sciatic nerve ligation.
RESULTS: Intrathecal injection of yangonin demonstrated a relatively potent 
anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These 
effects were completely reversed by the co-administration of PF 514273, a 
cannabinoid 1 (CB1) receptor antagonist. However, yangonin did not affect 
mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, 
did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal 
level.
CONCLUSIONS: Overall, our study demonstrated that yangonin exerts 
anti-nociception and anti-inflammatory hyperalgesia effects via CB1 receptors at 
the spinal level. We identified a single kavalactone, yangonin, extracted from 
kava as a promising treatment for pain.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jep.2024.118394
PMID: 38823663 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


2. J AOAC Int. 2024 Jul 4;107(4):663-678. doi: 10.1093/jaoacint/qsae025.

Development of Certified Reference Material Solutions for Phytochemicals in 
Ginger and Kava.

Aijaz SM(1), Ruan Z(1), Leija C(1), Lytwak LA(1), Waddell S(1), Kuszak AJ(2), 
Wise SA(2), Sreenivasan U(1).

Author information:
(1)MilliporeSigma, 811 Paloma Drive Suite A, Round Rock, TX 78665-2402, United 
States.
(2)U.S. Department of Health and Human Services, National Institutes of Health, 
Office of Dietary Supplements, 6705 Rockledge Drive, Bethesda, MD 20817, United 
States.

BACKGROUND: Dietary supplements derived from botanicals are commonly consumed 
and investigated in biomedical studies for their potential health benefits. 
Accurate identification and quantification of key chemical constituents from 
botanical ingredients is necessary for consistent product preparations and 
reproducible research results. Manufacturers need quantitative reference 
materials of the chemical constituents of interest to verify the content of 
ingredients and products. The rigor and reproducibility of biomedical research 
is enhanced through thorough characterization of the interventions used in 
mechanistic, clinical, and safety investigations. Quantitative reference 
materials enable reliable product quality assessments and reproducible research 
results.
OBJECTIVE: Solution-based certified reference material (CRM) mixes were 
developed as calibrants for phytochemicals in ginger and kava. The kava CRM 
contained yangonin, desmethoxyyangonin, dihydrokavain, DL-kavain, methysticin, 
dihydromethysticin, flavokawain A, flavokawain B, and flavokawain C. The ginger 
CRM contained 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, and 
10-shogaol.
METHODS: Each phytochemical was sourced as an isolated compound and assigned a 
purity factor by a mass balance approach accounting for residual impurities. The 
solution standard mixes were formulated by gravimetric addition of each 
phytochemical incorporating the purity factor and diluting with acetonitrile to 
the target concentrations of 500 µg/mL for the gingerols and shogaols, 250 µg/mL 
for the kavalactones, and 25 µg/mL for the flavokawains.
RESULTS: The concentration accuracy of each component in the solution mixes was 
analytically verified by ultra high performance liquid chromatography with 
ultraviolet detection (UHPLC-UV) assay comparison to an independently prepared 
calibration solution. Each component in the ginger and kava CRMs were within 5 
and 7% of the target concentrations, respectively.
CONCLUSION: Homogeneous kava and ginger phytochemical solution mixes were 
produced with accurate constituent concentrations and demonstrated good 
stability over 2 years. These solution mixes were launched as commercially 
available CRMs.
HIGHLIGHTS: These mixes can be used as accurate concentration stock solutions to 
prepare calibrators and controls for botanical dietary supplement product 
testing and standardization.

© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC 
INTERNATIONAL. All rights reserved. For permissions, please email: 
journals.permissions@oup.com.

DOI: 10.1093/jaoacint/qsae025
PMID: 38530970 [Indexed for MEDLINE]


3. Eur J Gastroenterol Hepatol. 2023 Feb 1;35(2):133-152. doi: 
10.1097/MEG.0000000000002483. Epub 2022 Dec 8.

A review of edible plant-derived natural compounds for the therapy of liver 
fibrosis.

Xu W(1)(2), Wang L(3), Niu Y(1), Mao L(3), Du X(1), Zhang P(1), Li Z(1), Li 
H(4), Li N(4).

Author information:
(1)Gansu University of Chinese Medicine.
(2)Gansu Provincial Hospital of Traditional Chinese Medicine.
(3)Affiliated Hospital, Gansu University of Chinese Medicine.
(4)School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.

Liver fibrosis has a high incidence worldwide and is the common pathological 
basis of many chronic liver diseases. Liver fibrosis is caused by the excessive 
deposition of extracellular matrix and concomitant collagen accumulation in 
livers and can lead to the development of liver cirrhosis and even liver cancer. 
A large number of studies have provided evidence that liver fibrosis can be 
blocked or even reversed by appropriate medical interventions. However, the 
antifibrosis drugs with ideal clinical efficacy are still insufficient. The 
edible plant-derived natural compounds have been reported to exert effective 
antifibrotic effects with few side-effects, representing a kind of promising 
source for the treatment of liver fibrosis. In this article, we reviewed the 
current progress of the natural compounds derived from dietary plants in the 
treatment of liver fibrosis, including phenolic compounds (capsaicin, 
chlorogenic acid, curcumin, ellagic acid, epigallocatechin-3-gallate, 
resveratrol, sinapic acid, syringic acid, vanillic acid and vitamin E), 
flavonoid compounds (genistein, hesperidin, hesperetin, naringenin, naringin and 
quercetin), sulfur-containing compounds (S-allylcysteine, ergothioneine, lipoic 
acid and sulforaphane) and other compounds (betaine, caffeine, cucurbitacin B, 
lycopene, α-mangostin, γ-mangostin, ursolic acid, vitamin C and yangonin). The 
pharmacological effects and related mechanisms of these compounds in in-vivo and 
in-vitro models of liver fibrosis are focused.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

DOI: 10.1097/MEG.0000000000002483
PMID: 36574304 [Indexed for MEDLINE]


4. Foods. 2022 Dec 1;11(23):3889. doi: 10.3390/foods11233889.

Isolation and Identification of Constituents Exhibiting Antioxidant, 
Antibacterial, and Antihyperuricemia Activities in Piper methysticum Root.

Minh TN(1), Van TM(2), Khanh TD(3)(4), Xuan TD(2)(5).

Author information:
(1)Center for Research and Technology Transfer, Vietnam Academy of Science and 
Technology (VAST), Hanoi 122100, Vietnam.
(2)Transdisciplinary Science and Engineering Program, Graduate School of 
Advanced Science and Engineering, Hiroshima University, Hiroshima 739-8529, 
Japan.
(3)Agricultural Genetic Institute, Pham Van Dong Street, Hanoi 122000, Vietnam.
(4)Center for Agricultural Innovation, Vietnam National University of 
Agriculture, Hanoi 131000, Vietnam.
(5)Center for the Planetary Health and Innovation Science (PHIS), The IDEC 
Institute, Hiroshima University, Higashi-Hiroshima 739-8529, Japan.

The aqueous extract of kava (Piper methysticum) root is known as a traditional 
beverage for daily intake in the Western Pacific Islands, such as Fiji, Tonga, 
and Vanuatu, to induce relaxation and health-beneficial effects. In this study, 
the antioxidant, anti-hyperuricemia, and antibacterial properties of kava root 
were investigated through the isolation and purification of bioactive compounds 
in ten fractions separated by column chromatography (CC). They included six 
flavonoids, 5-hydroxy-4',7-dimethoxyflavanone (C1), matteucinol (C2), 
isosakuranetin (C3), 5,7- dimethoxyflavanone (C4), 
2',4'-dihydroxy-6'-methoxydihydrochalcone (in MC5) and alpinetin (C10), and 
seven kavalactones, 5,6-dehydrokawain (DK) (in MC5 and C6), kavain (in MC7), 
yangonin (in MC7 and C8), dihydro-5,6-dehydrokavain (DDK) (in MC9), 
7,8-dihydromethysticin (in MC9), dihydromethysticin (in MC9), methysticin (in 
MC9). The chemical structures of the compounds were illustrated by the analyses 
of gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass 
spectrometry (ESI-MS), nuclear magnetic resonance (1H and 13C-NMR), and X-ray 
diffraction. The evaluation of the free radical scavenging activity of the 
isolated substances via the DPPH and ABTS assays revealed that C3 (IC50: ABTS = 
76.5; DPPH = 74.8 µg/mL) possessed the strongest antioxidant property. In terms 
of anti-hyperuricemia activity evaluated via the xanthine oxidase inhibitory in 
vitro assay, the compound C10 was the most promising inhibitor, revealing an 
IC50 of 134.52 µg/mL. The two kavalactone mixtures in MC5 and a pure compound C6 
inhibited the growth of bacteria Listeria monocytogenes, while MC7 can constrain 
the development of Klebsiella pneumoniae. This is the first study to isolate, 
purify, and identify the flavonoids isosakuranetin, 
2',4'-dihydroxy-6'-methoxydihydrochalcone and alpinetin in kava root and report 
their pharmaceutical potential. The identified bioactive compounds showed potent 
antioxidant, anti-hyperuricemia, and antibacterial activity and thus can enhance 
the value of beverages and foods derived from kava root.

DOI: 10.3390/foods11233889
PMCID: PMC9739624
PMID: 36496697

Conflict of interest statement: The authors declare no conflict of interest.


5. Front Microbiol. 2022 Sep 23;13:994188. doi: 10.3389/fmicb.2022.994188. 
eCollection 2022.

Integration of metagenomic and metabolomic insights into the effects of 
microcystin-LR on intestinal microbiota of Litopenaeus vannamei.

Duan Y(1)(2)(3), Xing Y(1), Zeng S(3), Dan X(3), Mo Z(3), Zhang J(1), Li Y(3).

Author information:
(1)Key Laboratory of South China Sea Fishery Resources Exploitation and 
Utilization, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key 
Laboratory of Fishery Ecology and Environment, South China Sea Fisheries 
Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.
(2)Key Laboratory of Efficient Utilization and Processing of Marine Fishery 
Resources of Hainan Province, Sanya Tropical Fisheries Research Institute, 
Sanya, China.
(3)University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region 
on Marine Bioresource Conservation and Exploitation, Guangdong Laboratory for 
Lingnan Modern Agriculture, College of Marine Sciences, South China Agricultural 
University, Guangzhou, China.

Microcystin-LR (MC-LR) is a hazardous substance that threaten the health of 
aquatic animals. Intestinal microbes and their metabolites can interact with 
hosts to influence physiological homeostasis. In this study, the shrimp 
Litopenaeus vannamei were exposed to 1.0 μg/l MC-LR for 72 h, and the toxic 
effects of MC-LR on the intestinal microbial metagenomic and metabolomic 
responses of the shrimp were investigated. The results showed that MC-LR stress 
altered the gene functions of intestinal microbial, including ABC transporter, 
sulfur metabolism and riboflavin (VB2) metabolism, and induced a significant 
increase of eight carbohydrate metabolism enzymes. Alternatively, intestinal 
metabolic phenotypes were also altered, especially ABC transporters, protein 
digestion and absorption, and the biosynthesis and metabolism of amino acid. 
Furthermore, based on the integration of intestinal microbial metagenomic and 
metabolome, four bacteria species (Demequina globuliformis, Demequina sp. NBRC 
110055, Sphingomonas taxi and Sphingomonas sp. RIT328) and three metabolites 
(yangonin, α-hederin and soyasaponin ii) biomarkers were identified. Overall, 
our study provides new insights into the effects of MC-LR on the intestinal 
microbial functions of L. vannamei.

Copyright © 2022 Duan, Xing, Zeng, Dan, Mo, Zhang and Li.

DOI: 10.3389/fmicb.2022.994188
PMCID: PMC9537473
PMID: 36212851

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest.