JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Xin Chen,Duanxiu Li,Yanwen Duan,Yong Huang
Drug co-amorphization is an emerging technology to improve the pharmacokinetic properties of drugs and overcome their side effects. Herein co-amorphization of sinomenine (SIN), an anti-rheumatoid arthritis alkaloid, and an antihistamine drug tranilast (TRA) was investigated for the sustained release of SIN and alleviating its histamine-release adverse reactions. The full co-amorphization of SIN-TRA was determined by powder X-ray diffraction and modulated temperature differential scanning calorimetry , while their CO 2 − and N + –H stretching vibrations in FTIR and protonated nitrogen signals in N 1s X-ray photoelectron spectra suggest the proton transfer between SIN and TRA. These intermolecular interactions could also be observed in their 1D and 2D NMR spectra. All co-amorphous samples exhibited sustained SIN release and excellent physical stability. Therefore, our study not only characterized the strong intermolecular interactions between SIN and TRA, but also discovered a promising drug combination strategy for the sustained release of SIN and reduction of its side effects.
研究领域:
药剂学
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药物化学
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DOI
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2016
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IF 1.566
Wenqiang Ba,Zhou Li,Lisheng Wang,Ding Wang,Weiguo Liao,Wentao Fan,Yinai Wu,Fengyun Liao,Jianye Yu
The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box–Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN from PLO was 146.55 ± 2.93 μg/cm2/h, significantly higher than that of gel (120.39 μg/cm2/h) and the amount of SIN deposited in skin from the PLO was 10.08 ± 0.86 μg/cm2, significantly larger than that from gel (6.01 ± 0.04 μg/cm2). In vivo skin microdialysis studies showed that the maximum concentration (Cmax) of SIN from PLO in “permeation study” and “drug-deposition study” were 150.27 ± 20.85 μg/ml and 67.95 μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73 μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.
研究领域:
药剂学
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药物递送系统
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生物医学工程
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DOI
PubMed
高影响因子
Scientific Reports
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2014
·Vol. 4
·期 1
·1-5
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IF 5.078
Zhu Qing,Sun Yuehua,Zhu Jie,Fang Tian,Zhang Wei,Li Jun-Xu
Sinomenine is a principal ingredient of traditional Chinese medicine, Sinomenium Acutum , which has been reported to have various pharmacological effects including anti-rheumatism and immunomodulation. This study examined the effects of sinomenine in rats that received chronic constriction injury (CCI), a model of peripheral neuropathic pain. CCI injury on the right sciatic nerve led to long-lasting mechanical hyperalgesia. Acute sinomenine treatment (10–40 mg/kg, i.p.) significantly and dose-dependently reversed mechanical hyperalgesia. In addition, the antinociceptive effects of sinomenine remained stable during repeated daily treatment for up to 2 weeks. Although sinomenine did not alter the duration of immobility in the forced swimming test in healthy animals, it dose-dependently reversed the increased immobility time in rats receiving CCI, suggesting that sinomenine attenuated chronic pain-induced depressive-like behavior. The antinociceptive effects of sinomenine were blocked by the GABAa receptor antagonist bicuculine. The doses of sinomenine studied here did not significantly alter the spontaneous locomotor activity. Together, these results suggested that sinomenine exerts significant antinociceptive effects for neuropathic pain via GABAa-mediated mechanism, which suggests that sinomenine may be useful for the management of chronic painful conditions such as neuropathic pain.
研究领域:
药理学
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疼痛研究
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神经科学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2017
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IF 2.759
Biao Zhou,Xiaolong Lu,Zhi Tang,Dan Liu,Youliang Zhou,Peng Zeng,Hui Xiong
With the advent of aging, the morbidity rates of such diseases as osteoarthritis , rheumatoid arthritis , and osteoporosis has witnessed a significant increase. As a common rattan drug , sinomenine (SIN) has been widely applied for the treatment of various arthritic diseases in traditional Chinese medicine (TCM) clinics. Given that SIN has been reported to inhibit the expression of Prostaglandin E2 (PGE2) in several types of cells, in this study, the influence of SIN treatment on PGE2 expression in mesenchymal stem cells (MSCs), thereby changing the osteoprotegerin (OPG) receptor/activator for the nuclear factor-κ B ligand (RANKL) ratio, was investigated. Our results showed that, when compared with the untreated cells, treatment with 0.25 mM SIN can down-regulate the mRNA and protein expression levels of the Prostaglandin E synthase 3 (PTGES3) or PGE2 and RANKL , while the OPG was up-regulated. After being cultured with SIN treated MSC-conditioned medium (stMSC-CM), the amount of TRAP-positive multinucleated osteoclasts differentiated from RAW264.7 cells was reduced. Also, the expression levels of specific markers for active osteoclasts were decreased when incubated with stMSC-CM. Moreover, these changes were able to be recovered when the exogenous RANKL was added to the MSC-CM culture . This indicates that the increased OPG/RANKL ratio can reduce the osteoclastogenesis of RAW264.7 cells. Our results demonstrated that SIN has an inhibitory effect on osteoclast differentiation through mechanisms involving the inhibition of the PGE2-induced OPG/RANKL ratio. SIN can also serve as a proinflammatory mediator to regulate the MSC immunosuppressive effects. Our findings suggest that SIN can be useful for the treatment of bone diseases associated with over-activity of osteoclasts.
研究领域:
药理学
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免疫学
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细胞生物学
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干细胞研究
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骨病治疗
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DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
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2022
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IF 3.898
Dandan Ren,Shanshan Xiang,Yuwen Yan,Ruiying Kong,Xingchu Gong
Sinomenine hydrochloride is generally produced from Caulis Sinomenii . At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine hydrochloride yield. In this study, a new purification process for sinomenine hydrochloride was proposed by using the extract obtained from acid extraction of Caulis Sinomenii as the starting material. The process included the following steps: alkalization, extraction, water washing, acid–water stripping, drying, and crystallization. 1-Heptanol was used as the extractant. The distribution coefficients of sinomenine and sinomenine hydrochloride in 1-heptanol–water system were 27.4 and 0.0167, respectively. The dissociation constants of sinomenine hydrochloride were 8.27 and 11.24, respectively. Process parameters of the new purification process were optimized with experimental design. The extractant 1-heptanol and sinomenine hydrochloride in the crystallization mother solution can be recycled in the new process. The purity of the obtained sinomenine hydrochloride crystals exceeded 85%, and the yield was about 70%. Compared with current industrial processes, safer extractant, less solid waste, and higher sinomenine hydrochloride yield can be achieved using the new purification process of sinomenine hydrochloride provided in this study.
研究领域:
中药化学
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制药工程
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DOI
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2016
·Vol. 173
·期 10
·1693-1702
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IF 5.259
Qing Zhu,Yuehua Sun,Lina Mao,Chengpeng Liu,Bo Jiang,Wei Zhang,Jun-Xu Li
Background and Purpose This study examined the antinociceptive effects of sinomenine in a rat model of postoperative pain. Experimental Approach Male and female rats were subjected to a surgical incision in the right hind paw, and the von Frey filament test was used to measure mechanical hypersensitivity after drug or vehicle treatment (p.o. or i.p.). Rats were treated daily with sinomenine before or after the surgery and the AUCs of the antinociceptive effects measured during a 4 h period were calculated to determine the ED 50 values of sinomenine. The anti-hyperalgesic effects of different doses of a combination of sinomenine and acetaminophen (paracetamol) were assessed in another group of rats. Dose combinations were determined by using a fixed ratio dose-addition analysis method. Key Results Sinomenine (5–80 mg·kg −1 ) produced dose-dependent antinociceptive effects in rats that had been subjected to surgery and this effect lasted for 4 h. The potency of sinomenine, given i.p. or p.o., did not differ between male and female rats. However, sinomenine was fourfold more potent when given i.p. than p.o. The GABA A receptor antagonist bicuculline blocked the antinociceptive effects of sinomenine. The antinociceptive effect of a daily treatment with sinomenine remained stable throughout the course of postoperative pain. Pretreatment with sinomenine did not alter the mechanical hypersensitivity post-surgery. The combination of sinomenine with acetaminophen produced an infra-additive interaction. Conclusions and Implications Sinomenine demonstrated significant antinociceptive activity against postoperative pain and may be a useful novel pharmacotherapy for the management of postoperative pain.
研究领域:
药理学
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疼痛研究
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DOI
PubMed
高影响因子
INFLAMMATION
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2026
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IF 5.4
Yan Jie,Li Wenjuan,Qin Tian,Ye Haimin,Chen Congling,Li Ling,Liu Yehui
Sinomenine (SIN) has been established to exert neuroprotective effects in ischemic stroke (IS), yet its specific molecular targets and detailed mechanisms remain incompletely understood. This study identified Fermt2 as a critical target through which SIN exerted its neuroprotective effects in IS. In a rat model of cerebral ischemia-reperfusion injury, overexpression of Fermt2 improved neurological deficits, reduced cerebral infarct volume by nearly one-third, and significantly decreased neuronal apoptosis in the ischemic penumbra. In vitro and in vivo experiments demonstrated that upregulation of Fermt2 promoted a shift in microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby suppressing pro-inflammatory cytokines and restoring anti-inflammatory factors. Mechanistic investigations revealed that Fermt2 functioned by inhibiting the RhoA/ROCK/NF-κB signaling pathway. Crucially, knockdown of Fermt2 reversed the beneficial effects of SIN in IS rats. In conclusion, Fermt2 is a master regulator of microglia-dependent neuroinflammation and a promising therapeutic target for IS.
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产品关联
DOI
高影响因子
PHYTOTHERAPY RESEARCH
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2025
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IF 6.3
Yichao Du,Junjie Bai,Tingting Ma,Ziming Wu,Pengru Wang,Xiaolin Zhong,Wenguang Fu,Shuixiang He
Liver fibrosis, a pivotal pathological feature in the progression of chronic liver injury, currently lacks effective therapies. Sinomenine (SIN), a bioactive alkaloid derived from traditional Chinese medicine, demonstrates diverse pharmacological properties. However, its therapeutic potential and mechanisms in liver fibrosis remain inadequately characterized. This study investigates the anti-fibrotic effects of SIN and its underlying molecular mechanisms. The anti-fibrotic efficacy of SIN was evaluated in two murine models of liver fibrosis induced by carbon tetrachloride (CCl 4 ) or bile duct ligation (BDL), along with transforming growth factor-beta 1 (TGF-β1)-stimulated rat hepatic stellate cells (HSC-T6). Serum biochemical markers, histopathological analyses (Hematoxylin–Eosin, Sirius red, and Masson's trichrome staining), immunofluorescence, and immunohistochemistry were employed to assess hepatic injury and collagen deposition. Western blotting elucidated molecular mechanisms. SIN administration significantly attenuated hepatic injury in CCl 4 - or BDL-induced mice, as evidenced by reduced transaminase levels and improved histopathological features. In both in vivo and in vitro models, SIN suppressed fibrogenesis by decreasing collagen deposition and downregulating expression of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP2), and collagen I. Mechanistically, SIN inhibited the TGF-β/SMAD pathway through reduced phosphorylation of SMAD2/3 and attenuated c-JUN signaling via diminished phosphorylated c-JUN levels. Pretreatment with TP0427736 (a SMAD2/3 inhibitor) or SP600125 (a c-JUN inhibitor) synergistically enhanced SIN-mediated α-SMA suppression in HSC-T6 cells. SIN ameliorates liver fibrosis through inhibition of TGF-β/SMAD and c-JUN signaling pathways. These findings position SIN as a promising therapeutic candidate for liver fibrotic disorders.
研究领域:
药理学
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肝脏病学
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DOI
PubMed
高影响因子
Metabolites
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2022
·Vol. 12
·期 10
·946
·
IF 5.581
Jing Zhang,Dan Huang,Yue Dai,Yu-Feng Xia
Colitis-associated cancer (CAC), arising from long-lasting intestinal inflammation, is a common type of colorectal cancer. Sinomenine (SIN), the major active compound ofSinomenium acutum, displays excellent antitumor activity. In modern pharmacological research, SIN has been proved to arrest proliferation of human colon cancer cells in vitro, but its functional role and specific mechanism in CAC were still elusive. This study explored the molecular mechanism of SIN on CAC. The results showed that orally administered SIN could decrease the occurrence and development of CAC. Metabolomics results revealed SIN could reprogram metabolism in CAC mice by reversing 34 endogenous metabolites. Importantly, the most prominent metabolic alteration was lipid metabolism. Mechanistically, SIN improved lipid metabolism by enhancing the expression of CPT1A in CAC mice. Moreover, the inhibitory effect of SIN on the proliferation of human colon cancer cells was blunted via CPT1A inhibitor. The results of this study added further evidence of the molecular mechanisms that allow SIN to exert anti-CAC effect by facilitating lipid metabolism and reaffirmed its potential and distinctive role as a chemopreventive agent in CAC.Keywords:sinomenine;colitis-associated cancer;lipid metabolism;UPLC-QTOF-MS/MS;cell proliferation
研究领域:
药理学
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肿瘤学
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代谢组学
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DOI
PubMed
高影响因子
Journal of Oleo Science
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2013
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IF 1.242
Xin Liu,Teng Chen,Xuesong Liu,Yong Chen,Longhu Wang
The present study investigated the feasibility of ostrich oil utilizing as a promising vehicle for improved skin permeation of sinomenine with reference to vaseline matrix containing different content of chemical enhancers. The fatty acid composition of ostrich oil was analyzed by GC-MS. Penetration enhancing potential of ostrich oil on permeation of sinomenine across rat abdominal skin in vitro was studied using an automatic diffusion cell apparatus. The content of sinomenine percutaneous absorbed was determined by HPLC. Various parameters viz. steady-state skin flux (Jss), permeability coefficient (kP), cumulative amount of sinomenine (Q) and enhancement ratios (ER) were calculated from the permeation data. Fick’s law of diffusion and Scheuplein kinetic were used to evaluate the transdermal absorbent enhancement of ostrich oil to sinomenine. Ostrich oil showed significant penetration effect on sinomenine compared with vaseline matrix containing different content of chemical enhancers, the density sequence as follow: 2% Azone > ostrich oil > 1% Azone plus 1% propylene glycol > 1% Azone > 3% Azone > 1% propylene glycol. The percutaneous endosmic rate constant (Jss) and permeability coefficient (kP) of sinomenine in ostrich oil through rat skin were 10.01 μg/cm2/h and 0.087, respectively. Ostrich oil produced stronger enhancement (ER = 24.31) with greater cumulative amount of drug permeated (255.53 μg/cm2) up to 24 h and caused no skin irritation. The drug release of sinomenine was coincided with Fick’s equation. In summary, ostrich oil containing fatty acids is proposed as a promising adjuvant for use in cosmetics and pharmaceuticals for improved permeation of drug.
研究领域:
药剂学
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皮肤科学
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DOI
高影响因子
JOURNAL OF MICROENCAPSULATION
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2024
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IF 3
Mengyao Cui,Yaqing Li,Jing Li,Nini Jia,Wenxuan Cao,Zhengguang Li,Xiang Li,Xiaoqin Chu
Objective To investigate the transdermal mechanisms and compare the differences in transdermal delivery of Sinomenine hydrochloride (SN) between solid lipid nanoparticles (SLN), liposomes (LS), and nanoemulsions (NE).Methods SN-SLN, SN-LS and SN-NE were prepared by ultrasound, ethanol injection and spontaneous emulsification, respectively. FTIR, DSC, in vitro skin penetration, activation energy (Ea) analysis were used to explore the mechanism of drug penetration across the skin.Results The particle size and encapsulation efficiency were 126.60 nm, 43.23 ± 0.48%(w/w) for SN-SLN, 224.90 nm, 78.31 ± 0.75%(w/w) for SN-LS, and 83.22 nm, 89.01 ± 2.16%(w/w) for SN-LS. FTIR and DSC showed the preparations had various levels of impacts on the stratum corneum’s lipid structure which was in the order of SLN > NE > LS. Ea values of SN-SLN, SN-LS, and SN-NE crossing the skin were 2.504, 1.161, and 2.510 kcal/mol, respectively.Conclusion SLN had a greater degree of alteration on the skin cuticle, which allows SN to permeate skin more effectively.
研究领域:
药剂学
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皮肤科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2018
·Vol. 18
·期 4
·3691-3698
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IF 1.922
Yan Zhou,Hanyang Liu,Jun Song,Liang Cao,Liming Tang,Chunjian Qi
Sinomenine (SIN), a pure alkaloid isolated from Sinomenium acutum, has been widely used in arthritis for its anti‑inflammatory effect, but little is known about the effect of SIN on human ulcerative colitis (UC). In the present study, the effect and mechanism of SIN was examined in a dextran sulfate sodium (DSS)‑induced murine colitis model, which mimics human UC. Oral administration of SIN significantly suppressed the elevated disease activity index and ameliorated colonic histological damage in a DSS‑induced colitis model. Tumor necrosis factor‑α, interleukin‑6 and inducible nitric oxide synthase levels were also reduced as detected by reverse transcription‑quantitative polymerase chain reaction. In addition, SIN reversed the decreased colon length and colonic superoxide dismutase activity. Furthermore, western blot analysis revealed that nuclear factor‑erythroid 2‑related factor 2 (Nrf2) and its downstream genes, heme oxygenase‑1 and NADP(H) quinone oxidoreductase 1 (NQO‑1), were markedly activated by SIN. The current results indicated that SIN alleviated DSS‑induced colitis in mice, which may be due to its antioxidant properties and was at least in part dependent on the Nrf2/NQO‑1 signaling pathway. Therefore, SIN may have potential applications as a protective drug for patients with UC.
研究领域:
药理学
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免疫学
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胃肠病学
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DOI
PubMed
高影响因子
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