Research Article

A Bioactive Component from Aconitum pendulum Attenuates Rheumatoid Arthritis-Related Inflammation in Rats via PI3K/Akt Pathway Regulation

DOI:

10.3791/70473

⸱

April 21st, 2026

 ,  ,  ,  ,  ,  , 
1School of Pharmacy, Qinghai MinZu University, 2Qinghai Modern Plateau Biomedical Industry Institute, 3Qinghai Institute of Tibetan Medicine, 4Qinghai Provincial Key Laboratory of Plant Resource Chemistry on the Tibetan Plateau

In This Article

Summary

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Using network pharmacology and molecular docking, anti- rheumatoid arthritis (RA) components from A. pendulum were identified. In vivo studies showed diterpene alkaloids, especially smirnotine A, alleviate RA symptoms in rats via the PI3K/Akt pathway.

Abstract

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

In traditional Chinese medicine and various ethnic medical practices, the roots of Aconitum pendulum N. Busch are commonly used for their ability to dredge meridians, dispel rheumatism, promote blood circulation, and alleviate arthralgia. As a result, this medicinal plant has become a well-regarded treatment for sprains and rheumatic diseases across different ethnic medical systems. This study investigated the mechanisms by which six previously isolated compounds from A. pendulum ameliorate rheumatoid arthritis (RA)-related inflammation using both in vitro and in vivo approaches. A combination of techniques, including network pharmacology, molecular docking, enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E) staining, quantitative real-time polymerase chain reaction (q-PCR), and western blot (WB), was employed. Results demonstrated that smirnotine A, one of the six compounds, alleviates RA symptoms by targeting the PI3K/Akt signaling pathway and suppressing the inflammatory response. These findings provide a scientific basis for understanding the material foundation and mechanistic action underlying the traditional use of A. pendulum in treating RA.

Introduction

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by synovial inflammation, hyperplasia of the synovial lining, infiltration of immune cells, formation of invasive pannus tissue, and consequent joint destruction1,2,3. With a global prevalence of 0.5%–1%, RA poses a significant public health burden and severely impacts patients' quality of life4,5,6,7. Conventional therapies—such as methotrexate (MTX), glucocorticoids, ....

Access restricted. Please log in or start a trial to view this content.

Protocol

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Fifty specific pathogen-free (SPF) male Sprague-Dawley rats (weighing 180–200 g) were supplied by the Hubei Provincial Center for Disease Control and Prevention (Hubei Provincial Academy of Preventive Medicine) (Wuhan, China; Animal License Certificate No. SCXK(JB) 2023-0005). All experimental procedures involving animals were conducted in strict accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (8th edition, 2011). The study protocol was reviewed and approved by the Experimental Animal Ethics Committee of Tianjin Genink Biological Technology Co., Ltd. (Approval No. GENINK-20250074). Key reagents and equipment used in t....

Access restricted. Please log in or start a trial to view this content.

Results

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

Effects of A. pendulum derivatives on anti-RA target
The 3D structures of the six compounds were retrieved in SDF format, and the SMILES numbers were uploaded to the SwissTargetPrediction database for target prediction. Targets with a probability greater than 0 were retained, and the results were exported as a CSV file. After removing duplicates, a total of 97 potential compound-related targets were identified.

Disease targets associated with rheumatoid arthritis .......

Access restricted. Please log in or start a trial to view this content.

Discussion

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

This integrated study provides novel mechanistic insights into the anti-rheumatoid arthritis activity of smirnotine A, a C19-diterpenoid alkaloid from Aconitum pendulum N. Busch. Our findings demonstrate that smirnotine A ameliorates RA inflammation through targeted inhibition of the PI3K/Akt signaling pathway, representing a distinct mechanism from previously reported diterpenoid alkaloids.

The combination of network pharmacology prediction and molecular docking validation successful.......

Access restricted. Please log in or start a trial to view this content.

Disclosures

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

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.

Acknowledgements

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

This research was financially supported by the Qinghai Science and Technology Department Natural Science Fund youth project (No. 2022-ZJ-950Q) and the National Natural Science Foundation of China (NSFC) (No. 82460845).

....

Access restricted. Please log in or start a trial to view this content.

Materials

List of materials used in this article
NameCompanyCatalog NumberComments
AceQ qPCR SYBR Green Master MixVazymeQ111
AKT (60 kDa) monoclonal mouse antibodyWuhan Sanying Biotechnology60203-2-Ig
BCA Protein Assay KitGuangzhou Jiebeisi BiotechnologyG3522
BSA StandardGuangzhou Jiebeisi BiotechnologyG8532
Complete Medium for MH7A cellsShanghai Fuheng BiotechnologyFH-MH7A
ELISA Kit for IL-10Lunchangshuo BiotechnologyED-13626
ELISA Kit for IL-17ALunchangshuo BiotechnologyED-10344
ELISA Kit for IL-1βLunchangshuo BiotechnologyED-10351
ELISA Kit for IL-6Lunchangshuo BiotechnologyED-10377
ELISA Kit for TNF-αLunchangshuo BiotechnologyED-11776
Fluorescence Quantitative PCR SystemApplied BiosystemsViiA-7
GAPDH monoclonal mouse antibodyWuhan Sanying Biotechnology60004-1-Ig
High-Speed Refrigerated CentrifugeHunan Kecheng Instrument EquipmentHI-16KR
HiScript II Q Select RT SuperMix for qPCRVazymeR223
HRP-labeled goat anti-mouse secondary antibodyWuhan Sanying BiotechnologySA00001-1
HRP-labeled goat anti-rabbit secondary antibodyBeyotime BiotechnologyA0208
Human rheumatoid arthritis fibroblast-like synoviocyte line MH7AQisai BiotechnologyQS-H075
Microplate ReaderBioTekMQX200
MicroscopeLeicaFLEXACAM C1
Multimode Microplate ReaderMolecular DevicesFlexStation 3
P-AKT (60 kDa) polyclonal rabbit antibodyWuhan Sanying Biotechnology28731-1-AP
Paraffin MicrotomeLeicaRM 2016
PCR AmplifierApplied BiosystemsproFlex
Phosphate Buffered Saline (1× PBS)Qisai BiotechnologyQS-S001
PI3K (85 kDa) polyclonal rabbit antibodyAffinityAF6241
P-PI3K (85 kDa) polyclonal rabbit antibodyAffinityAF3242
Smirnotine Aisolated and identified by our laboratoryC39H49NO11
Tissue DehydratorWuhan Junjie ElectronicJT-12J
Tissue Embedding MachineWuhan Junjie ElectronicJB-L6
Tissue Spreading and Baking MachineWuhan Junjie ElectronicJK-6
TrizolAmbion15596-026
Trypsin Cell Digestion Solution (0.25% trypsin,  with EDTA, without phenol red)Qisai BiotechnologyQS-S401

References

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,
  1. Perera, J., Delrosso, C. A., Nerviani, A., Pitzalis, C. Clinical phenotypes, serological biomarkers, and synovial features defining seropositive and seronegative rheumatoid arthritis: a literature review. Cells. 13 (9), 743(2024).
  2. Jiang, N., Tian, X. P., Zeng, X. F.

Access restricted. Please log in or start a trial to view this content.

Reprints and Permissions

Request permission to reuse the text or figures of this JoVE article

Request Permission

Tags

Aconitum PendulumRheumatoid ArthritisPI3K Akt PathwayInflammatory ResponseNetwork PharmacologyMolecular DockingEnzyme Linked ImmunosorbentWestern BlotReal Time PCRTraditional Chinese Medicine
Video Coming Soon

Related Articles