Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis.
Naringin in Combination with Isothiocyanates as Liposomal Formulations Potentiates the Anti-inflammatory Activity in Different Acute and Chronic Animal Models of Rheumatoid Arthritis.
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DOI：
10.1021/acsomega.0c04300
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发表时间：
2020-11-03
期刊：
影响因子：
4.1
通讯作者：
Si SC
中科院分区：
文献类型：
--
作者：
Mohanty S;Sahoo AK;Konkimalla VB;Pal A;Si SC
联合用药被广泛用于治疗慢性炎症性疾病。柚皮苷（NAR）、萝卜硫素（SFN）和异硫氰酸苯乙酯（PEITC）是具有良好抗炎特性的营养品。然而，由于其水溶性低和生物利用度差，其临床有效性受到阻碍。在本研究中，制备了两种脂质体组合（NAR + SFN和NAR + PEITC），并在急性和慢性炎症模型的不同体内模型中进行了彻底研究。用1，2-二棕榈酰-sn-甘油基-3-磷酸胆碱/胆固醇/1，2-二硬脂酰-sn-甘油基-3-磷酸乙醇胺-020CN（15：4：1 M比率）制备的组合脂质体制剂（CLF）中NAR、SFN和PEITC的包封率分别测定为79.8 ± 4.2%、46.5 ± 3.6%和78.5 ± 3.2%。采用差示扫描量热法、X射线衍射法、动态光散射法和傅里叶变换红外光谱法对CLF进行了表征。物理化学结果表明，该制剂在水中是单分散的（PDI 0.062 - 0.248），平均粒径为140.5 - 165.6 nm，zeta电位为− 47.3-− 53.3 mV。体外溶出研究显示，与SFN的释放（3小时）相比，PEITC的释放（> 90%，6小时）较慢。在此，我们首次报道了NAR + SFN和NAR + PEITC的CLF在弗氏完全佐剂（FCA）诱导的关节炎模型中的抗关节炎活性。在腹膜内剂量（375 ± 375 μ g/mL）下持续3周，在FCA大鼠中，与其游离药物组合相比，NAR + PEITC脂质体显著改善了%爪水肿和关节炎评分。最重要的是，血液学和生化结果显示贫血状况改善，SGOT、SGPT和ALP水平显著变化。ELISA结果显示，细胞因子（IL-10）升高和炎症标志物（TNF-α、IL-6、IFN-γ）降低的趋势相似。组织学评价显示细胞浸润、血管翳形成以及骨和软骨破坏减少，进一步证实和验证了CLF的抗关节炎活性。这项全面的研究揭示了难溶性抗炎分子（NAR，SFN，PEITC）组合脂质体治疗关节炎的有效性。
Combination of drugs is extensively used to treat chronic inflammatory disease. Naringin (NAR), sulforaphane (SFN), and phenethyl isothiocyanate (PEITC) are nutraceuticals with promising anti-inflammatory properties. However, their clinical effectiveness gets hindered because of low aqueous solubility and poor bioavailability. In the current study, two combinations of liposome (NAR + SFN and NAR + PEITC) were prepared and studied thoroughly in different in vivo models of acute and chronic models of inflammation. The encapsulation efficiency of NAR, SFN, and PEITC in the combination liposomal formulations (CLFs) prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine -020CN (15:4:1 M ratio) was determined to be 79.8 ± 4.2, 46.5 ± 3.6, and 78.5 ± 3.2%, respectively. The CLFs were characterized by differential scanning calorimetry, X-ray diffraction, dynamic light scattering, and Fourier transform infrared spectroscopy. The physicochemical results showed that the preparations were monodisperse (PDI 0.062–0.248) in water with an average size from 140.5 to 165.6 nm and a zeta potential of −47.3 to −53.3 mV. Dissolution studies in vitro showed a slower release of PEITC (>90%, 6 h) in comparison to that of SFN (3 h). Here, we are the first to report the antiarthritic activity of CLF of NAR + SFN and NAR + PEITC in the Freund’s complete adjuvant (FCA)-induced arthritic model. At an intraperitoneal dose (375 + 375 μg/mL) for 3 weeks, the NAR + PEITC liposome significantly improves both % paw edema and arthritic score compared to their free drug combinations in FCA rats. Most importantly, hematological and biochemical results showed improved anemic conditions with significant changes in the SGOT, SGPT, and ALP levels. The ELISA results showed similar trends of increased cytokine (IL-10) and decreased inflammation markers (TNF-α, IL-6, IFN-γ). Histological evaluations showing reduction in cell infiltration, pannus formation, and bone and cartilage destruction further confirm and validate the antiarthritic activity of the CLF. This comprehensive study reveals the effectiveness of combination liposomes of poorly soluble anti-inflammatory molecules (NAR, SFN, PEITC) in the treatment of arthritis.
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影响因子：
4.9
作者：
Fragoulis A;Laufs J;Müller S;Soppa U;Siegl S;Reiss LK;Tohidnezhad M;Rosen C;Tenbrock K;Varoga D;Lippross S;Pufe T;Wruck CJ
通讯作者：
Wruck CJ
DOI：
10.1166/mat.2014.1161
发表时间：
2014-06-01
期刊：
MATERIALS FOCUS
影响因子：
--
作者：
Gupta, Ujval;Singh, Vivek K.;Khajuria, Yugal
通讯作者：
Khajuria, Yugal
影响因子：
4.3
作者：
Ahmad, Sheikh Fayaz;Zoheir, Khairy M. A.;Abd-Allah, Adel R. A.
通讯作者：
Abd-Allah, Adel R. A.
DOI：
10.2174/1872214809666150505164138
发表时间：
2015-01-01
期刊：
RECENT PATENTS ON ENDOCRINE METABOLIC & IMMUNE DRUG DISCOVERY
影响因子：
--
作者：
de Figueiredo, Sonia M.;Binda, Nancy S.;Caligiorne, Rachel B.
通讯作者：
Caligiorne, Rachel B.
影响因子：
--
作者：
Datta, Poulami;Sarkar, Amrita;Gomes, Antony
通讯作者：
Gomes, Antony