Orthosiphon aristatus (Blume) Miq. Extracts attenuate Alzheimer-like pathology through anti-inflammatory, anti-oxidative, and β-amyloid inhibitory activities

J Ethnopharmacol. 2024 Feb 10:320:117132. doi: 10.1016/j.jep.2023.117132. Epub 2023 Sep 11.

Abstract

Ethnopharmacological relevance: Orthosiphon aristatus (Blume) Miq. (OA) is a traditional folk-herb, which is usually used to treat acute and chronic nephritis, epilepsy, cystitis, and other diseases. Phenols and flavonoids are the main active compound compounds of OA, with proven anti-inflammatory and antioxidant activities.

Aims of this study: Based on evidenced therapeutic activities, we aimed to investigate the impact of OA on Alzheimer's disease (AD) which is the most common age-related neurodegenerative disease, and the pathological features include accumulation of beta-amyloid (Aβ) and neurofibrillary tangles (NFT).

Materials and methods: OA was extracted with water, methanol, chloroform, and ethyl acetate, and determined its total flavonoid and phenolic contents. Initially, Aβ1-42 based cytotoxicity was induced in BV2 cells and C6 cells to investigate the therapeutic impact of OA therapy by MTT, RT-PCR, Western blot, and ELISA. Further, Aβ1-42 Oligomer (400 pmol)-induced AD mice model was established to evaluate the impact of OA extract on improving learning and memory impairment.

Results: The results showed that the extract of OA could increase cell survival, inhibit the expression of TNF-α, IL-6, IL-1β, COX-2, and iNOS, and increase BDNF levels. We infer that the OA extract may attenuate Aβ-induced cytotoxicity by retarding the production of inflammatory-related factors. In the animal behavior test, the number of mice entering darkroom and the time of arriving at the platform were significantly reduced, indicating the learning and memory-improving ability of OA extract.

Conclusions: These findings imply that the OA ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.

Keywords: Alzheimer's disease (AD); Beta-amyloid (Aβ); Neurofibrillary tangles (NFT); Orthosiphon aristatus (OA).

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Disease Models, Animal
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Mice
  • Neurodegenerative Diseases* / drug therapy
  • Orthosiphon* / metabolism
  • Plant Extracts / analysis
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use

Substances

  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents
  • Plant Extracts
  • Flavonoids