Title:Fangchinoline Inhibited Proliferation of Neoplastic B-lymphoid Cells and
Alleviated Sjögren’s Syndrome-like Responses in NOD/Ltj Mice via the
Akt/mTOR Pathway
Volume: 15
Author(s): Yanxiong Shao*, Jiayao Fu, Tianle Zhan, Lei Ye and Chuangqi Yu*
Affiliation:
- Department of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center of Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Department of Oral Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center of Oral Disease, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
Keywords:
Fangchinoline, Akt/mTOR pathway, B cells, lymphocytic focus, Sjögren’s syndrome, LY294002, wild-type ICR mice.
Abstract:
Background: Fangchinoline is a bisbenzylisoquinoline alkaloid extracted from Stephania
tetrandra S. Moore that is conventionally used as an analgesic, antirheumatic, and antihypertensive drug
in China. However, the application of Fanchinoline in Sjögren syndrome (SS) remains unreported.
Objective: This study aimed to identify the potential role of Fangchinoline in the treatment of SS via
altering Akt/mTOR signaling.
Methods: First, we examined levels of p-Akt and p-mTOR in infiltrating lymphocytes of labial glands
from SS patients by immunohistochemistry. Then, the effects of Fangchinoline on Raji cells and Daudi
cells were investigated using the CCK-8 assay, propidium iodide (PI)/RNase, and Annexin V/PI staining.
Western blotting was used to identify the levels of Akt, p-Akt(ser473), mTOR, and p-mTOR. For in vivo
analyses, NOD/Ltj and wild-type ICR mice were treated with a Fangchinoline solution, an LY294002
solution (an inhibitor of the PI3K/Akt/mTOR pathway), or their solvent for 28 days. Then, salivary flow
assays and hematoxylin and eosin staining of submandibular glands were performed to determine the
severity of SS-like responses in the mice.
Results: Immunohistochemical staining of labial glands from SS patients showed that activation of p-Akt
and p-mTOR in infiltrating lymphocytes might be correlated with SS development. In vitro, Fangchinoline
and LY294002 inhibited proliferation, induced cell cycle arrest, and promoted apoptosis in Raji and
Daudi cells by altering Akt/mTOR signaling. In vivo, Fangchinoline and LY294002 significantly improved
the salivary secretion by NOD/Ltj mice and reduced the number of lymphocytic foci in the submandibular
glands.
Conclusion: These results indicated that Fangchinoline could effectively inhibit the proliferation of neoplastic
B-lymphoid cells and reduce SS-like responses in NOD/Ltj mice. Our study highlights the potential
value of the clinical application of Fangchinoline for SS treatment.
