Nano-cubosomes of the phyto-active principle in Withania somnifera: LC-MS-NMR, anti-microbial, and insights of the anti-neuropathic and anti-inflammatory mechanism.

Autor: Raafat KM; Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt. Electronic address: karim.raafat@pua.edu.eg., Abdelwahab IA; Department of Microbiology and Immunology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt., El-Zahaby SA; Department of Pharmaceutics and Industrial Pharmacy, PharmD Program, Egypt-Japan University of Science and Technology (E-JUST), Alexandria, Egypt.
Jazyk: angličtina
Zdroj: Fitoterapia [Fitoterapia] 2024 Oct; Vol. 178, pp. 106196. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1016/j.fitote.2024.106196
Abstrakt: 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.
Competing Interests: Declaration of competing interest The three authors declare no conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: