Inhibitory Effects of Raw-Extract Centella asiatica (RECA) on Acetylcholinesterase, Inflammations, and Oxidative Stress Activities via In Vitro and In Vivo
Open accessAbstract
Centella asiatica (C. asiatica) is one of the medicinal plants that has been reported to exert comprehensive neuroprotection in vitro and in vivo. In view of this, the present study was performed to investigate the effect of ethanolic extract of C. asiatica, designated as raw-extract of C. asiatica (RECA) in reducing the acetylcholinesterase (AChE), inflammations, and oxidative stress activities via both in vitro (SH-SY5Y and RAW 264.7 cells) and in vivo (Sprague Dawley rats). Quantitative high-performance liquid chromatography analysis reveals that RECA contains a significantly high proportion of glycosides than the aglycones with madecassoside as the highest component, followed by asiaticoside. Treatment of SH-SY5Y cells with RECA significantly reduced the AChE activity in a concentration-dependent manner with an IC50 value of 31.09 ± 10.07 µg/mL. Furthermore, the anti-inflammatory and antioxidant effects of RECA were evaluated by lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. Our results elucidated that treatment with RECA significantly suppressed the level of pro-inflammatory cytokine/mediators and oxidative stress released in a concentration-dependent manner. Interestingly, these patterns of inhibition were consistent as observed in the LPS-induced neuroinflammation Sprague Dawley rats’ model. The highest concentration used in the two models presented the most significant results. Herein, our findings strongly suggest that RECA may offer therapeutic potential for the treatment of Alzheimer’s disease through inhibiting the AChE, inflammation, and oxidative stress activities.
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C. asiatica has an anti-inflammatory effect observed by reduction in IL-1β, IL-6, TNFα, PGE2, and COX-2.
“C. asiatica has shown an anti-inflammatory effect observed by the reduction in Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumour Necrosis Factor α (TNFα) [33,36,37], as well as prostaglandin E2 (PGE2) [36,38], and cyclooxygenase-2 (COX-2) [39].”
From A systematic review of the effect of Centella asiatica on wound healing (2022) · cites this paper as [36]
Results §§2.4 and 2.7 report that raw-extract C. asiatica reduced TNF-α and PGE2 in LPS-stimulated cells and rats. The paper does not report reductions in IL-1β or IL-6, which appear in the same citation cluster. The sentence cites a different source for COX-2. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThis enhancement might result from the anti-inflammatory effect of C. asiatica due to reduction in IL-1β, IL-6, TNFα, PGE2, and COX-2.
“This might result from the anti-inflammatory effect caused by C. asiatica due to the reduction in IL-1β, IL-6 and TNFα [33,36,37], as well as prostaglandin E2 (PGE2) [36,38] and cyclooxygenase-2 (COX-2) [39].”
From A systematic review of the effect of Centella asiatica on wound healing (2022) · cites this paper as [36]
Results §§2.4 and 2.7 report reduced TNF-α and PGE2 after raw-extract C. asiatica treatment in LPS-stimulated cells and rats. Our copy does not report reductions in IL-1β or IL-6, which the citing sentence also attributes to this source. COX-2 is cited separately to [39], not to this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe anti-inflammatory action of RECA in LPS-stimulated microglial cells is attributed to its comparatively lower madecassic acid content, not to its highest triterpene constituents madecassoside and asiaticoside.
“however, despite the highest triterpene constituent of RECA being characterized to be madecassoside, followed by asiaticoside, the anti‐inflammatory action seen in this study was instead attributed to the comparatively lower madecassic acid content.”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [61]
The HPLC Results (section 2.1; page unavailable) identify madecassoside as RECA’s highest component and report more glycosides than aglycones. The Discussion (section 3; page unavailable) assigns madecassic acid an important anti-inflammatory role relative to the glycosides, but says the extract’s *moderate* effect may be due to its smaller amount of madecassic acid. The claim overstates that tentative explanation as an attribution of the anti-inflammatory action itself; the retrieved passage also does not establish that asiaticoside ranks second. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRECA displays strong anti-inflammatory activity by suppressing inflammatory mediators in a concentration-dependent manner in LPS-stimulated microglial cells.
“RECA displayed strong anti‐inflammatory activity by suppressing the inflammatory mediators in a concentration‐dependent manner; however, despite the highest triterpene constituent of RECA being characterized to be madecassoside, followed by asiaticoside, the anti‐inflammatory action seen in this study was instead attributed to the comparatively lower madecassic acid content.”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [61]
RECA exhibits curative and protective properties against AD by attenuating acetylcholinesterase activity both in vitro and in LPS-injected rodent models of AD.
“In addition, RECA exhibited curative and protective properties against AD by attenuating acetylcholinesterase activity both in vitro as well as in the LPS‐injected rodent models of AD. 61”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [61]
Administration of RECA significantly prohibits or restores oxidative stress and neuroinflammation in LPS-treated Sprague Dawley rats.
“Similar properties were observed in vivo using LPS‐treated Sprague Dawley rats, where administration of RECA significantly prohibited or restored oxidative stress and neuroinflammation.”
From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [61]
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References 79 · Cited by 64
- Authors
- Hafiz, Z. Z., Amin, M. ‘. M., Johari James, R. M., Teh, L. K., Salleh, M. Z., & Adenan, M. I.
- Affiliations
- Universiti Teknologi MARA System (MY)
- Universiti Teknologi MARA (MY)
- Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA Selangor Branch, Puncak Alam Campus, 42300 Puncak Alam, Selangor Darul Ehsan, Malaysia
- Corresponding author
- Adenan, Mohd Ilham
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2020-02-17
- Volume
- 25
- Issue
- 4
- Pages
- 892
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC7070982
- OpenAlex
- W3006578543
- Cited by
- 64
- References
- 79
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 11 · 2023: 19 · 2022: 6 · 2021: 11 · 2020: 4
- FWCI
- 11.08
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Kementerian Pertanian dan Industri Asas Tani Malaysia (100-RMI/MOA 16/6/2(5/2015).)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- Centella asiatica, acetylcholinesterase inhibition, neuroinflammation, oxidative stress, neuroprotection, madecassoside, asiaticoside, glycosides, LPS-induced neuroinflammation, Alzheimer's disease, SH-SY5Y cells, RAW 264.7 macrophages, inflammatory cytokines
- MeSH terms
- RAW 264.7 Cells, Acetylcholinesterase, Animals, Anti-Inflammatory Agents, Antioxidants, Cell Survival, Chromatography, High Pressure Liquid, Glutathione, Humans, Inflammation, Nitrites, Plant Extracts, Triterpenes, Tumor Necrosis Factor-alpha, Dinoprostone, Cell Death, Rats, Sprague-Dawley, Reactive Oxygen Species, Oxidative Stress, Centella, Mice
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