Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Fitoterapia. 2024 Oct;178:106196. doi: 10.1016/j.fitote.2024.106196. Epub 2024 Aug 30.
Withania somnifera (W. somnifera) has a long history of safety in the amelioration of neuro-active ailments. The current study aims to explore Withania somnifera phyto-active principle anti-microbial, ant-neuropathic, and anti-inflammatory activities, and to modify these activities utilizing nano-cubosomes exploiting their mechanisms of action. Bio-guided fractionation technique was utilized, to identify the most phyto-active compound, using LC-MS-NMR online technique and biological models of diabetes, neuropathy, and inflammation. In-vitro antibacterial activity was also monitored. The HbA1c, in-vivo antioxidant (serum-catalase, TBARS, and GSH), serum insulin, and pro-inflammatory serum cytokines (TNF alpha, IL-six, and IL-ten) levels have been assessed to establish the anti-neuropathic and anti-inflammatory mechanisms. The nano-cubosomal formulations (CUB 1-3) were utilized to improve the W. somnifera most active compound efficacy. W. somnifera has shown ten major peaks; coagulin Q (10.2 %), dihydrowithanolide A (2.4 %), dihydrowithaferin D (1.8 %), physagulin D (7.6 %), withanoside V (2.3 %), withanolide A (WDA, 10.3 %), withafrin A (4.9 %), withaferin D (7.7 %), withanone 9 (9.9 %), withanolide D (4.8 %). The bio-guided fractionation technique utilizing LC-MS-NMR technique has proved that withanolide A (WDA) is the most phyto-active compound in W. somnifera. The latter has shown better results than WDA, which might be due to other effective compounds in Ws. However, CUB 3 (WDA nano-cubosomes dispersion) has shown more prominent anti-diabetic, anti-neuropathic, anti-inflammatory, and anti-bacterial potentials than Ws and WDA. Thus, CUB 3 modified WDA activity, and improved its efficacy. The normalization of HbA1c levels, increased insulin secretagogue potential, and the amelioration of the oxidative-stress may be the underlying Ws, WDA, and CUB 3 antidiabetic neuropathy mechanism. Moreover, the Ws, WDA, and CUB 1-3 anti-inflammatory mechanism might be due to the amelioration of the pro-inflammatory serum cytokines (decreasing TNF alpha and IL-six levels and increasing IL-ten). Thus, CUB 3 might be a powerful tool in augmenting Withania somnifera activity as an oral drug-delivery system and improving its efficacy against neuropathy and inflammation.
睡茄（W. somnifera）具有改善神经活性疾病的安全性的悠久历史。本研究旨在探索睡茄植物活性成分的抗微生物、抗神经病变和抗炎活性，并利用纳米立方脂质体（nano-cubosomes）来修饰这些活性，探索其作用机制。利用 LC-MS-NMR 在线技术和糖尿病、神经病变和炎症的生物模型，采用生物导向的分步分离技术，鉴定最具植物活性的化合物。还监测了体外抗菌活性。评估了 HbA1c、体内抗氧化剂（血清过氧化氢酶、TBARS 和 GSH）、血清胰岛素和促炎血清细胞因子（TNF alpha、IL-six 和 IL-ten）水平，以确定抗神经病变和抗炎机制。利用纳米立方脂质体（CUB 1-3）制剂来提高睡茄最有效化合物的功效。睡茄显示出十个主要峰；凝脂素 Q（10.2%）、二氢醉茄醇 A（2.4%）、二氢醉茄醇 D（1.8%）、薯蓣皂素 D（7.6%）、缬草皂甙 V（2.3%）、醉茄皂甙 A（WDA，10.3%）、醉茄呋喃 A（4.9%）、醉茄呋喃 D（7.7%）、胡椒酮 9（9.9%）、醉茄醇 D（4.8%）。利用 LC-MS-NMR 技术的生物导向分步分离技术证明，睡茄皂甙 A（WDA）是睡茄中最具植物活性的化合物。后者的效果优于 WDA，这可能是由于睡茄中的其他有效化合物。然而，CUB 3（WDA 纳米立方脂质体分散体）在抗糖尿病、抗神经病变、抗炎和抗细菌方面显示出比睡茄和 WDA 更显著的潜力。因此，CUB 3 改变了 WDA 的活性，提高了其疗效。HbA1c 水平的正常化、胰岛素分泌刺激潜力的增加以及氧化应激的改善可能是睡茄、WDA 和 CUB 3 抗糖尿病神经病变的潜在机制。此外，睡茄、WDA 和 CUB 1-3 的抗炎机制可能是由于促炎血清细胞因子（降低 TNF alpha 和 IL-six 水平，增加 IL-ten）的改善。因此，CUB 3 可能是增强睡茄作为口服药物递送系统活性和提高其对神经病变和炎症疗效的有力工具。
