A review on pharmacokinetics of sinomenine and its anti-inflammatory and immunomodulatory effects

Wang, Siwei; Zhang, Lvzhuo; Zhou, Yanhua; Huang, Jiangrong; Zhou, Zushan; Liu, Zhenzhen

doi:10.1016/j.intimp.2023.110227

Cited by 11 publications

(7 citation statements)

References 147 publications

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“…In recent years, numerous studies have investigated the benefits of SIN, which have been reported to include potent antioxidant, antiapoptotic, anti‐inflammatory, and immune regulatory activities. 31 , 32 SIN has been found to exert protective roles against I/R injury in multiple organs. For instance, SIN has been shown to protect the brain against cerebral I/R injury in ischemic rats via the anti‐inflammatory effect, which relieves acidosis, enhances energy metabolism, and reduces ASIC1a expression.…”

Section: Discussionmentioning

confidence: 99%

High‐dose sinomenine attenuates ischemia/reperfusion‐induced hepatic inflammation and oxidative stress in rats with diabetes mellitus

Hui,

Zhang,

Dong

et al. 2024

Immunity Inflam & Disease

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IntroductionIschemia‐reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a crucial organ for carbohydrate and lipid metabolism, exhibits decreased tolerance to hepatic I/R in patients with diabetes mellitus (DM), resulting in a significant increase in hepatic dysfunction following surgery. This may be attributed to elevated oxidative stress and inflammation. Our prior research established sinomenine's (SIN) protective role against hepatic I/R injury. Nevertheless, the impact of SIN on hepatic I/R injury in DM rats remains unexplored.Objective and MethodsThis study aimed to investigate the therapeutic potential of SIN in hepatic I/R injury in DM rats and elucidate its mechanism. Diabetic and hepatic I/R injury models were established in rats through high‐fat/sugar diet, streptozotocin injection, and hepatic blood flow occlusion. Liver function, oxidative stress, inflammatory reaction, histopathology, and Nrf‐2/HO‐1 signaling pathway were evaluated by using UV spectrophotometry, biochemical assays, enzyme‐linked immunosorbent assay, hematoxylin‐eosin staining, and Western blot analysis.ResultsHigh‐dose SIN (300 mg/kg) significantly attenuated hepatic I/R injury in DM rats, reducing serum activities of ALT and AST, decreasing the AST/ALT ratio, enhancing tissue contents of SOD and GSH‐Px, suppressing the levels of TNF‐α and IL‐6, improving the liver histopathology, and activating Nrf‐2/HO‐1 signaling by promoting Nrf‐2 trans‐location from cytoplasm to nucleus. Low‐dose SIN (100 mg/kg) was ineffective.ConclusionsThis study demonstrates that high‐dose sinomenine's mitigates hepatic I/R‐induced inflammation and oxidative stress in diabetes mellitus (DM) rats via Nrf‐2/HO‐1 activation, suggesting its potential as a preventive strategy for hepatic I/R injury in DM patients.

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Section: Discussionmentioning

confidence: 99%

High‐dose sinomenine attenuates ischemia/reperfusion‐induced hepatic inflammation and oxidative stress in rats with diabetes mellitus

Hui,

Zhang,

Dong

et al. 2024

Immunity Inflam & Disease

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“…The clinical application of sinomenine is constrained by its short half-life, high required concentration and low drug utilization [ 10 , 14 , 232 ]. Efforts to enhance sinomenine’s absorption rate and sustained release performance, such as incorporating it into hydrogels, are still in the nascent stages and require further validation [ 215 ].…”

Section: Conclusion or Concluding Remarksmentioning

confidence: 99%

“…In subsequent research, P. Teng et al reported on the synthesis and evaluation of SIN derivatives. Compound 2a (14) was found to be highly effective in inhibiting LPS-induced NO production in mouse macrophage Mouse mononuclear macrophage leukemia cells Raw264.7 with an IC 50 value of 9.5 µM and an inhibition rate of 41.6% at 6.25 µM [137]. W. Meng et al discovered that SIN derivative 8h (15) significantly reduced TNFα production in LPS-stimulated mouse macrophages (J774) with an inhibition rate of 73% [138].…”

Section: Anti-inflammatory Activity and Analgesic Activity Of Compoun...mentioning

confidence: 99%

“…Sinomenine exhibits low water solubility [ 10 ], leading to the development of sinomenine hydrochloride (SH) to enhance its water solubility and drug-like properties. Numerous biological studies have confirmed a wide array of biological activities for these compounds, including antitumor [ 11 ], anti-inflammatory [ 12 ], analgesic [ 13 ], immunomodulatory [ 14 ], neuroprotective [ 15 ], and cardioprotective effects [ 16 ], as summarized in Figure 2 . These properties render them potential candidates for clinical medications.…”

Section: Introductionmentioning

confidence: 99%

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Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

Hou,

Huang,

Huang

et al. 2024

Molecules

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Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of approximately 121.4 nM against PC-3 and DU-145 cells, primarily through the PI3K/Akt/mTOR, NF-κB, MAPK, and JAK/STAT signaling pathways. Additionally, they manifest anti-inflammatory and analgesic effects predominantly via the NF-κB, MAPK, and Nrf2 signaling pathways. Utilized in treating rheumatic arthritis, these alkaloids also play a significant role in cardiovascular and cerebrovascular protection, as well as organ protection through the NF-κB, Nrf2, MAPK, and PI3K/Akt/mTOR signaling pathways. This review concludes with perspectives and insights on this topic, highlighting the potential of sinomenine-related compounds in clinical applications and the development of medications derived from natural products.

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“…Sinomenine (SIN, ) is an alkaloid extracted from the vine stems of Sinomenium acutum ( S. acutum ) and S. acutum var. cinerum[ 11 ] that has analgesic, sedative, anti-inflammatory and antioxidant effects, as well as few adverse effects on the digestive system, and is clinically used to treat various conditions such as acute and chronic arthritis, rheumatoid arthritis, osteoarthritis, synovitis, and neuropathic pain[ 12 ]. In addition, SIN was reported to affect bone metabolism through multiple mechanisms[ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy

Xiao,

Yu,

Xia

et al. 2024

World J Stem Cells

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BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells (BMSCs) has been suggested to be an important cause of decreased osteogenic differentiation. A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis. AIM To explore the effects of sinomenine (SIN) on the osteogenic differentiation of BMSCs and the underlying mechanisms. METHODS For in vitro experiments, BMSCs were extracted from sham-treated mice and ovariectomized mice, and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concentrations of SIN and the autophagy inhibitor 3-methyladenine. In vivo , the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur. RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, inhibited mTOR activity, and increased autophagy ability of BMSCs, thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo . CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis, bone homeostasis disorders, and autophagy-related diseases.

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A review on pharmacokinetics of sinomenine and its anti-inflammatory and immunomodulatory effects

Cited by 11 publications

References 147 publications

High‐dose sinomenine attenuates ischemia/reperfusion‐induced hepatic inflammation and oxidative stress in rats with diabetes mellitus

High‐dose sinomenine attenuates ischemia/reperfusion‐induced hepatic inflammation and oxidative stress in rats with diabetes mellitus

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy

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