MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

Li, Jianzhong; Xu, Jing; Lu, Yiming; Qiu, Lei; Xu, Wei-Heng; Lü, Bin; Hu, Zhenlin; Chu, Zun-hua; Chai, Yifeng; Zhang, Junping

doi:10.3390/molecules21050649

Cited by 14 publications

(4 citation statements)

References 61 publications

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“…Traditional Chinese herbs provide abundant sources for anti-osteoporosis medicine ( Li et al, 2014 ). Matrine is the major component of traditional Chinese herb Sophora flavescens Ait and exhibited significant anti-inflammatory and anti-fibrotic pharmacological effects ( Qian et al, 2015 ; Li J. Z. et al, 2016 ; Sun et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

et al. 2018

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Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, PI3K/AKT, and MAPKs pathways activity in vitro, and prevent ovariectomy-induced bone loss in vivo. Our previous study has proved that ribosomal protein S5 (RPS5) was a direct target of M19, based on which M54 was synthesized. Thus we deduced that M54 also targeted RPS5. During osteoclastogenesis, the RPS5 level in RAW264.7 cells was significantly down-regulated while M54 could maintain its level. After RPS5 was silenced, the inhibitory effects of M54 on osteoclastogenesis were partially compromised, indicating that M54 took effects through targeting RPS5. In summary, M54 was a potential clinical medicine for post-menopause osteoporosis treatment, and RPS5 is a possible key protein in PMOP.

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Section: Introductionmentioning

confidence: 99%

A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

et al. 2018

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“…The mechanism of action of MASM observed in this study may be related to the RPS5-mediated suppression of NF-κB and MAPK activation and the decrease in the expression of proinflammatory mediators, indicating that MASM may be further used in the treatment of sepsis. Li et al 124 found a protective effect of MASM against rats with lethal total body irradiation (TBI), and that MASM pretreatment reduced the symptoms of radiation sickness and increased the survival of rats before or after lethal TBI, which may be mainly or partly by modulating multiple MAPK pathways. These results suggested that MASM has the potential to serve as an effective therapeutic or radioprotective agent to minimize radiation damages and improve the efficacy of combined oncology radiotherapy.…”

Section: Matrine Exerts Pharmacological Effects Through the Mapk Sign...mentioning

confidence: 99%

Matrine Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review

Lin¹,

He²,

Wu³

et al. 2022

DDDT

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As The main effective monomer of the traditional Chinese medicine Sophora flavescens Ait , matrine has a broad scope of pharmacological activities such as anti-tumor, anti-inflammatory, analgesic, anti-fibrotic, anti-viral, anti-arrhythmia, and improving immune function. These actions explain its therapeutic effects in various types of tumors, cardiopathy, encephalomyelitis, allergic asthma, rheumatoid arthritis (RA), osteoporosis, and central nervous system (CNS) inflammation. Evidence has shown that the mechanism responsible for the pharmacological actions of matrine may be via the activation or inhibition of certain key molecules in several cellular signaling pathways including the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), transforming growth factor-β/mothers against decapentaplegic homolog (TGF-β/Smad), nuclear factor kappa B (NF-κB), Wnt (wingless/ integration 1)/β-catenin, mitogen-activated protein kinases (MAPKs), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. This review comprehensively summarizes recent studies on the pharmacological mechanisms of matrine to provide a theoretical basis for molecular targeted therapies and further development and utilization of matrine.

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“…Aer cleavage from the resin with triuoroethanol, full protected intermediates Asp(OtBu) 6 -PEG n -Leu-Arg(Pbf) (6-8) were coupled with 4-aminobenzyl alcohol by 1H-1,2,3-benzotriazole (HOBt) and N,N 0 -diisopropylcarbodiimide to construct 1,6-self-immolative p-aminobenzyloxycarbonyl (PABC) linker containing intermediates Asp(OtBu) 6 -PEG n -Leu-Arg(Pbf)-PABC (9)(10)(11). The following reaction between 9-11 with triphosgene and M19 in the presence of DIPEA given protected PDCs Asp(OtBu) 6 -PEG n -Leu-Arg(Pbf)-PABC-M19 (12)(13)(14). Finally, global deprotection of compounds 12-14 with K reagent obtained the target PDCs (BTM19-1, BTM19-2 and BTM19-3).…”

Section: Synthesis Of M19-based Bone Targeting Pdcsmentioning

confidence: 99%

“…First of all, the excessively broad pharmacological activity of M19 may bring the risk of off-target effects. [13][14][15] Besides, the biological particularity of bone tissue, such as high tissue density and poor permeability, brought great difficulties to drug delivery. 16 More importantly, the druggability of M19 was not satisfactory owing to its poor chemical stability and strong alkalinity.…”

Section: Introductionmentioning

confidence: 99%

Development of novel bone targeting peptide–drug conjugate of 13-aminomethyl-15-thiomatrine for osteoporosis therapy

et al. 2022

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MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

Cited by 14 publications

References 61 publications

A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

Matrine Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review

Development of novel bone targeting peptide–drug conjugate of 13-aminomethyl-15-thiomatrine for osteoporosis therapy

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