Ashwagandha-loaded nanocapsules improved the behavioral alterations, and blocked MAPK and induced Nrf2 signaling pathways in a hepatic encephalopathy rat model

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Khalil H.M.A.; Khalil I.A.; Al-Mokaddem A.K.; Hassan M.; El-Shiekh R.A.; Eliwa H.A.; Tawfek A.M.; El-Maadawy W.H.

Journal: Drug Delivery and Translational Research

Publisher: Springer

Publication Date: 7 June 2022

Volume / Issue: Volume 13 / Issue 1

Pages: 252–274

ISSN: 2190393X

DOI: 10.1007/s13346-022-01181-y

Scopus: View on Scopus

PubMed: 35672652

Document Type: Article

Access: All Open Access; Green Open Access; Hybrid Gold Open Access

Authors and Affiliations

Khalil H.M.A., Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; Khalil I.A., Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University of Science and Technology (MUST), 6th of October, Giza, 12582, Egypt; Al-Mokaddem A.K., Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza Square, Giza, 12211, Egypt; Hassan M., Department of Immunology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba, P.O. 30, Giza, 12411, Egypt; El-Shiekh R.A., Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini st., Cairo, 11562, Egypt; Eliwa H.A., Department of Pharmacology and Toxicology, College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology (MUST), 6th October, Giza, 12566, Egypt; Tawfek A.M., Department of Clinical Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; El-Maadawy W.H., Department of Pharmacology, Theodor Bilharz Research Institute, Kornaish El Nile, Warrak El-Hadar, Imbaba, P.O. 30, Giza, 12411, Egypt

Abstract

Ashwagandha (ASH), a vital herb in Ayurvedic medicine, demonstrated potent preclinical hepato- and neuroprotective effects. However, its efficacy is limited due to low oral bioavailability. Accordingly, we encapsulated ASH extract in chitosan–alginate bipolymeric nanocapsules (ASH-BPNCs) to enhance its physical stability and therapeutic effectiveness in the gastrointestinal tract. ASH-BPNC was prepared by emulsification followed by sonication. The NCs showed small particle size (< 220 nm), zeta-potential of 25.2 mV, relatively high entrapment efficiency (79%), physical stability at acidic and neutral pH, and in vitro release profile that extended over 48 h. ASH-BPNC was then investigated in a thioacetamide-induced hepatic encephalopathy (HE) rat model. Compared with free ASH, ASH-BPNC improved survival, neurological score, general motor activity, and cognitive task-performance. ASH-BPNC restored ALT, AST and ammonia serum levels, and maintained hepatic and brain architecture. ASH-BPNC also restored GSH, MDA, and glutathione synthetase levels, and Nrf2 and MAPK signaling pathways in liver and brain tissues. Moreover, ASH-BPNC downregulated hepatic NF-κB immunohistochemical expression. Moreover, the in vivo biodistribution studies demonstrated that most of the administered ASH-BPNC is accumulated in the brain and hepatic tissues. In conclusion, chitosan–alginate BPNCs enhanced the hepatoprotective and neuroprotective effects of ASH, thus providing a promising therapeutic approach for HE. Graphical abstract: [Figure not available: see fulltext.] © 2022, The Author(s).

Keywords

Ashwagandha; Bipolymeric nanocapsules; Cognition; Hepatic encephalopathy; MAPK pathway; Nrf2 pathway; Animals; Chitosan; Nanocapsules; Neuroprotective Agents; Plant Extracts; Rats; Signal Transduction; Tissue Distribution; alanine aminotransferase; ammonia; aspartate aminotransferase; glutathione synthase; malonaldehyde; nanocapsule; transcription factor Nrf2; Withania somnifera extract; neuroprotective agent; plant extract; animal experiment; animal model; animal tissue; Article; ash; Ayurveda; bioassay; chronic liver disease; controlled study; dispersity; liver toxicity; male; MAPK signaling; morphological trait; motor activity; nanopharmaceutics; nonhuman; Nrf2 signaling; particle size; practice guideline; rat; real time reverse transcription polymerase chain reaction; Withania somnifera; animal

Citation Information

Scopus Citations: 28

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