Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Anal Methods. 2024 Feb 15;16(7):1083-1092. doi: 10.1039/d3ay01803b.

Serum-based metabolomics reveals the mechanism of action of isorhynchophylline 
in the intervention of atherosclerosis in ApoE(-/-) mice.

Wang L(1), Li H(1), Zhang H(1), Song X(1), Jiang H(1)(2)(3), Wang D(1), Wang 
Y(4).

Author information:
(1)Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of 
Traditional Chinese Medicine, Jinan 250355, China. xibeiadan@126.com.
(2)Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of 
Education, Shandong University of Traditional Chinese Medicine, Jinan 250355, 
China.
(3)Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic 
Research, Shandong University of Traditional Chinese Medicine, Jinan 250355, 
China.
(4)Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 
Jinan 250011, China. wangyutcm.jinan@foxmail.com.

Atherosclerosis (AS) is a chronic inflammatory disease with disorders of lipid 
metabolism. Metabolic disorders, inflammation and lipid deposition are prominent 
pathological features of atherosclerosis. Isorhynchophylline (IRN) has 
pharmacological effects such as protection of vascular endothelial cells, 
anti-inflammatory, anti-thrombotic, and anti-smooth muscle cell proliferation. 
However, it is unclear whether IRN is efficacious in atherosclerosis. In the 
present study, we verified the pharmacological efficacy and hepatoprotective 
effects of IRN in intervening in AS. LC-MS-based serum untargeted metabolomics 
was performed to search for potential biomarkers and related pathways in 
IRN-treated AS in ApoE-/- mice. Fifty-eight biomarkers were metabolically 
disturbed in the model mice compared to controls. Thirteen biomarkers showed 
optimal recovery methods after IRN-40 mg ml-1 intervention. We identified three 
metabolic pathways involved in IRN: glycerophospholipid metabolism, linoleic 
acid metabolism, and alpha-linolenic acid metabolism. These findings provide a 
research basis for the intervention of IRN in atherosclerosis.

DOI: 10.1039/d3ay01803b
PMID: 38284158 [Indexed for MEDLINE]


2. Org Lett. 2024 Feb 2;26(4):824-828. doi: 10.1021/acs.orglett.3c03938. Epub
2024  Jan 18.

Total Synthesis of Tetracyclic Spirooxindole Alkaloids via a Double Oxidative 
Rearrangement/Cyclization Cascade.

Wang X(1)(2), Zhang M(1)(3), Liu X(4), Lou M(1), Li G(1), Qi X(1)(3)(5).

Author information:
(1)National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun 
Life Science Park, Beijing 102206, China.
(2)School of Life Sciences, Tsinghua University, Beijing 100084, China.
(3)Chinese Academy of Medical Sciences & Union Medical College, Beijing 100730, 
China.
(4)Institute for Smart Materials & Engineering, School of Chemistry and Chemical 
Engineering, University of Jinan, Jinan 250022 Shandong, China.
(5)Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua 
University, Beijing 100084, China.

Skeleton rearrangement could rapidly transfer simple molecules to complex 
structures and has significant potential in the total synthesis of natural 
products. We developed a one-pot reaction cascade of double oxidative 
rearrangement of furan and indole followed by a nucleophilic cyclization that 
was successfully applied for the formal synthesis of 
rhynchophylline/isorhynchophylline and the first total synthesis of 
(±)-7(R)-geissoschizol oxindole/(±)-7(S)-geissoschizol oxindole. In addition, 
the geissoschizol oxindoles were revised to their C3 epimers, and the mechanism 
for the reversed stereochemistry through the retro-Mannich/Mannich cascade was 
proposed and supported by density functional theory calculations.

DOI: 10.1021/acs.orglett.3c03938
PMID: 38237069


3. Pak J Pharm Sci. 2023 Nov;36(6):1743-1747.

Simultaneous determination of seven toxic components in ShenFuTuoDu capsules by 
HPLC-MS/MS.

Zhou Z(1), Zheng L(2).

Author information:
(1)Zhejiang Police College, Hangzhou, Zhejiang, China/Zhejiang University of 
Technology, Hangzhou, Zhejiang, China.
(2)Jinhua Institute for Food and Drug Control, Jinhua, Zhejiang, China.

An accurate and reliable HPLC-MS/MS method has been established for the 
simultaneous determination of seven toxic components in the Chinese medicine 
ShenFuTuoDu capsules. The seven toxic components were separated on a Shimadzu 
Shim-pack GIST C18 column (3.0 mm×50 mm, 3.0 μm) with methanol and water 
(containing 0.1% formic acid) as the mobile phase by gradient elution. The flow 
rate was 0.5 mL•min-1. The column temperature was 25°C and the injection volume 
was 5μL. An ESI+ scan combined with MRM was adopted and the instrument 
parameters were as follows: ion source voltage, 5.5 kV; ion source temperature, 
600oC; curtain gas, 68.95 kPa; atomized gas, 344.75 kPa; auxiliary gas, 344.75 
kPa. The linear relationships of the seven components were good (R2>0.9937). The 
average recoveries were 95.2%-106.7% with RSD of 0.79%-5.27% (n=6). The seven 
toxic components of scopolamine, atropine, rhynchophylline, isorhynchophylline, 
benzoylaconine, benzoylmesaconine and benzoylhypaconine in six batches of 
ShenFuTuoDu capsules were 5.99-18.48μg•g-1, 6.36-14.79μg•g-1, 3.71-15.45μg•g-1, 
7.90-15.08μg•g-1, 19.05-44.58μg•g-1, 117.38-248.26μg•g-1 and 19.74-79.49μg•g-1, 
respectively. Precision, stability and repeatability test RSDs were less than 
7.17% (n=6). The method is suitable for the simultaneous determination of 
scopolamine, atropine, rhynchophylline, isorhynchophylline, benzoylaconine, 
benzoylmesaconine and benzoylhypaconine. It can be used for the quality control 
of ShenFuTuoDu capsules.

PMID: 38124414 [Indexed for MEDLINE]


4. Food Funct. 2023 Apr 3;14(7):3208-3219. doi: 10.1039/d2fo02939a.

Rhynchophylline alleviates neuroinflammation and regulates metabolic disorders 
in a mouse model of Parkinson's disease.

Zhang C(1)(2), Xue Z(1)(2), Zhu L(1)(2), Zhou J(1)(2), Zhuo L(1)(2), Zhang 
J(1)(2), Zhang X(1)(2), Liu W(1)(3), Han L(1)(2), Liao W(1)(2).

Author information:
(1)Key Laboratory of Drug Quality Control and Pharmacovigilance, China 
Pharmaceutical University, Ministry of Education, Nanjing 210009, China. 
lwting84@163.com.
(2)Department of Pharmaceutical Analysis, China Pharmaceutical University, 
Nanjing 210009, China.
(3)Zhejiang Center for Safety Study of Drug Substances (Industrial Technology 
Innovation Platform), Hangzhou, 310018, China.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder 
with limited therapeutic agents. Rhynchophylline (RIN), a tetracyclic oxindole 
alkaloid isolated from Uncaria rhynchophylla, has multiple neuropharmacological 
activities, including anti-inflammatory, anti-depression, anti-neurodegenerative 
disease, and anti-drug addiction. Though it is reported that RIN exerts a 
neuroprotective effect against PD, the underlying protective mechanism remains 
obscure. In this study, a mass spectrometry-based metabolomic strategy combined 
with neurobehavioral tests, serum biochemical assays, and immunohistochemistry 
were employed to decipher the protective mechanism of RIN against 
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced 
subacute PD in mice. Our results indicated that RIN significantly improved the 
MPTP-induced behavioral abnormalities, reduced the loss of dopaminergic neurons, 
and reversed the secretion of inflammatory cytokines and oxidative stress 
indicators. Further studies showed that RIN significantly suppressed the 
expression of toll-like receptor 4, NOD-like receptor protein 3, and 
cyclooxygenase 2 in the mouse striatum. The results of serum metabolomics showed 
that RIN could ameliorate metabolic disorders in PD mainly through the 
regulation of retinol metabolism, arachidonic acid metabolism, 
glycerophospholipid metabolism, and purine metabolism. These pieces of evidence 
revealed that RIN is a promising drug candidate for PD by alleviating 
neuroinflammation and maintaining metabolic homeostasis.

DOI: 10.1039/d2fo02939a
PMID: 36919954 [Indexed for MEDLINE]


5. BMC Complement Med Ther. 2023 Mar 11;23(1):80. doi:
10.1186/s12906-023-03902-3.

Isorhynchophylline inhibits inflammatory responses in endothelial cells and 
macrophages through the NF-κB/NLRP3 signaling pathway.

Wang LH(1), Gu ZW(1), Li J(1), Yang WQ(1), Li YL(2), Qi DM(2), Wang DY(3), Jiang 
HQ(4).

Author information:
(1)Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of 
Traditional Chinese Medicine, Jinan, 250000, China.
(2)Shandong University of Traditional Chinese Medicine, Jinan, 250000, China.
(3)Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of 
Traditional Chinese Medicine, Jinan, 250000, China. xibeiadan@126.com.
(4)Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of 
Traditional Chinese Medicine, Jinan, 250000, China. jhq12723@163.com.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease of arterial wall, 
which is closely related to inflammatory reaction. In this study, the 
anti-inflammatory effect of isorhynchophylline was studied by NF- κB / NLRP3 
pathway.
METHODS: (1) ApoE-/- mice were fed with high-fat diet to establish 
atherosclerotic model, while C57 with the same genetic background was fed with 
common diet as control group. Body weight was recorded and blood lipids were 
detected. The expression of NLRP3, NF-κB, IL-18 and Caspase-1 in aorta was 
detected by Western-Blot and PCR, and plaque formation was detected by HE and 
oil red O staining. (2) Lipopolysaccharide interfered with Human Umbilical Vein 
Endothelial Cells (HUVECs) and RAW264.7 to form inflammatory model, and was 
treated with isorhynchophylline. The expression of NLRP3, NF-κB, IL-18 and 
Caspase-1 in aorta was detected by Western-Blot and PCR, and the ability of cell 
migration was detected by Transwell and scratch test.
RESULTS: (1) the expression of NLRP3, NF- κB, IL-18 and Caspase-1 in aorta of 
model group was higher than that of control group, and plaque formation was 
obvious. (2) the expressions of NLRP3, NF- κB, IL-18 and Caspase-1 in HUVECs and 
RAW264.7 model groups were higher than those in control group, while 
isorhynchophylline decreased their expression and enhanced cell migration 
ability.
CONCLUSION: Isorhynchophylline can reduce the inflammatory reaction induced by 
lipopolysaccharide and promote the ability of cell migration.

© 2023. The Author(s).

DOI: 10.1186/s12906-023-03902-3
PMCID: PMC10007741
PMID: 36906555 [Indexed for MEDLINE]

Conflict of interest statement: The authors have declared that no conflict of 
interest exists.