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The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop

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Chinese Journal of Natural Medicines 2021年第11期19卷 815-824页

作者： CHEN Yao-Dong CAI Fang-Yu MAO Yu-Ze YANG Yong-Sheng XU Kun LIU Xiao-Fang FAN Wen-Wen CHEN Wu JIANG Feng-Qi ZHANG Hui Department of Ultrasonic Imaging the First Hospital of Shanxi Medical UniversityTaiyuan 030001China Department of Radiology the First Clinical Medical CollegeShanxi Medical UniversityTaiyuan 030001China Department of Thoracic Surgery the General Hospital of Heilongjiang Province Land Reclamation BureauHarbin 150088China Department of Cardio-Thoracic Surgery the First Affiliated Hospital of Jiamusi UniversityJiamusi 154000China Department of General Surgery Heilongjiang Provincial HospitalHarbin 150001China

Cervical cancer(CC)is recognized as the most common neoplasm in the female reproductive system *** lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of ***(ALO)is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation,allergies and ***,its therapeutic efficacy and underlying mechanism in CC are still *** the current study,MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in ***,the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry,respectively,while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell ***,nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in *** molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical *** study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle ***,ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ***,the migration and invasion of HeLa cells were attenuated by ALO treatment,which was considered to result from inhibition of epithelial-to-mesenchymal *** molecular mechanisms,the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO *** study indicated that ALO markedly suppresses the proliferation,migration and invasion and enhances the apoptosis of HeLa *** addition,these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

关键词： Cervical cancer Chemotherapy aloperine Epithelial-mesenchymal transition IL-6-JAK1-STAT3 feedback loop

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Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1

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Chinese Chemical Letters 2024年第5期35卷 201-206页

作者： Yulong Shi Fenbei Chen Mengyuan Wu Xin Zhang Runze Meng Kun Wang Yan Wang Yuheng Mei Qionglu Duan Yinghong Li Rongmei Gao Yuhuan Li Hongbin Deng Jiandong Jiang Yanxiang Wang Danqing Song Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacy Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJining 272000China

Thirty-one new 10,12-disubstituted aloperine derivatives were subtly constructed through a selective oxidation on the 10-α-C-H induced by sulfonyl and a nucleophilic substitution with the stereoselectivity and *** them,compound 6b displayed a moderate anti-human coronavirus OC43(HCoV-OC43)potency and blocked the viral entry stage through a host mechanism of *** chemoproteomic techniques,both transmembrane serine protease 2(TMPRSS2)and scavenger receptor class B type 1(SR-B1)proteins,which act as host cofactors of viral entry,were identified to be the direct targets of 6b against ***,6b may deactivate the TMPRSS2 by inducing a change in protein conformation,rather than binding to its catalytic center,thus suppressing the viral membrane ***,our study provided key scientific data for the development of aloperine derivatives into a new class of antiviral candidates against humanβ-coronavirus,including severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

关键词： aloperine SARS-CoV-2 TMPRSS2 SR-B1 Synthesis

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Inhibition of aloperine on Dextran Sulphate Sodium-induced Chronic Colitis in C57BL/6 Mice

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Chinese Herbal Medicines 2012年第3期4卷 218-223页

作者： SONG Li-jun 1 , ZHAO Wen-chang 1 , DENG Hong-zhu 2 1. School of Pharmacy, Guangdong Medical College, Dongguan 523808, China 2. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China School of Pharmacy Guangdong Medical College Dongguan 523808 China School of Traditional Chinese Medicine Southern Medical University Guangzhou 510515 China

Objective To investigate the effects of aloperine (ALO) on a model of dextran sulphate sodium (DSS)-induced chronic colitis in C57BL/6 mice. Methods Repeated colitis was induced by administration of four cycles of 4% DSS. The severity of colitis was assessed on the basis of clinical signs, ratio of colon weight and colon length, and histological grading scores. Moreover, secretory immunoglobulin A (S-IgA) and plasma haptoglobin (HP) were analyzed by enzyme-linked immunosorbent assay, and the changes of mRNA expression of ICAM-1 and MIF gene in colorectal tissue were detected by quantitative reverse transcriptase real-time polymerase chain reaction using SYBR Green I. Results ALO administration significantly attenuated the colon damage, caused substantial reductions of the rise in HP, and maintained the level of cecum S-IgA. ALO inhibited the ICAM-1 mRNA expression and had no effect on MIF mRNA expression. Conclusion The effect of ALO on DSS-induced chronic colitis in mice is investigated for the first time, which suggests that ALO could be an attractive therapeutic candidate in the treatment of inflammatory bowel disease.

关键词： aloperine dextran sulphate sodium haptoglobin inflammatory bowel disease secretory immunoglobulin A

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aloperine attenuate mice symptoms from colitis by regulating PI3K/AKT/m TOR signaling pathway and Foxp3+CD4+ Tregs

Aloperine attenuate mice symptoms from colitis by regulating...

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第十届全国免疫学学术大会

作者： Xiaoxia Fu Guangdong Medical College

aloperine has been recognized with the potential capacity to treat inflammatory and allergic diseases as well as *** plays a key role in ***,there is limited evidence indicating aloperine can regulate Treg function in *** found that treatment with aloperine attenuated mice symptoms from colitis in DSS-induced colitis *** can up-regulate Foxp3+CD4+Tregs number in lamina propria mononuclear cells(LPMCs),spleen and mesenteric lymph nodes cell,and prevented the development of colitis induced by the adoptive transfer of lamina propria(LP)colitogenic effectors memory CD4+T cells(low CD44 high CD62L).In vitro study shown that aloperine inhibited proliferation and induced apoptosis in Jurkat cells in a dose-and time-dependent *** findings indicate that aloperine may be involved in the control of inflammatory responses through down-regulating PI3K/AKT/m TOR signaling in DSSinduced ***2A and FOXO3 may be the target in the treatment of aloperine.

关键词： Colitis aloperine Tregs PI3K/AKT/mTOR

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Development and Validation of a Novel Reverse Phase HPLC for Determination of aloperine in aloperine Tablets

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Journal of Chinese Pharmaceutical Sciences 2003年第4期12卷 211-214页

作者： WANGHua ZHENGLi WANGZhan ZHANGYong-qiang] WUFeng-lan DepartmentofPharmaceutics SchoolofPharmaceuticolSciencesPekingUnitersityBeiting100083China

Aim To develop a reverse phase HPLC method for the determination of aloperine, an alkaloid that is newly extracted from Sophora alopecuraides and has shown wide pharmacological effects including antibacterial and antiinflammatory actions. Methods The samples were analyzed on a ODS column with methanol water triethylamine (3∶97∶0 1 V/V) as a mobile phase. The flow rate was 1 0 mL·min -1 , and UV detection wavelength 205 nm. Results Linear regression equation was A=1 6920C+1 7455 (r 2=0 9999, n =5) in concentratins ranging from 20 to 120 μg·mL -1 . The recoveries were 101 2±1 46 % at 80 μg·mL -1 , 100 5±0 75% at 100 μg·mL -1 , and 100 7±1 10% at 120 μg·mL -1 , respectively, and the precisions of aloperine within or between run were from 0 80% to 1 98% ( n =5). The relative contents of aloperine in three lots of tablets were 101 59±1 38%, 98 46±0 23%, and 99 41±1 09% ( n =3). Conclusion The newly developed reverse phase HPLC method is simple and useful for daily assay of aloperine tablets and can overcome the interference from excipient and other alkaloids in titration and UV detection.

关键词： aloperine aloperine tablets RP HPLC

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