Cited by 29Medicinal Plant ResearchPhytochemical Studies and BioactivitiesPhytochemistry Medicinal Plant Applications

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Cytotoxicity against Human Hepatocellular Carcinoma (HepG2) Cells and Anti-Oxidant Activity of Selected Endemic or Medicinal Plants in Sri Lanka

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Abstract

Hepatocellular carcinoma (HCC) is the most fatal cancer globally with limited treatment options. Plants and herbs have been used to treat cancer and other diseases for a long time by traditional practitioners in Sri Lanka. In the present study, leaf and bark extracts of selected plants were investigated for cytotoxic properties on HepG2 cells. Anti-oxidant activity and total phenolic and flavonoid contents were also determined. Plant extracts that exerted cytotoxic effects on the HepG2 cell line with IC50 <100 μg/mL were tested on normal liver epithelial cells (THLE-3). Out of the 56 extracts, 21 exhibited potent cytotoxic effects (IC50 < 100 µg/mL) on HepG2 cells after 48 h exposure, and 12 were less toxic (IC50 > 100 μg/mL) to THLE-3 normal liver cells. Six extracts exhibited potent radical scavenging activity with EC50 < 100 μg/mL against 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, while 17 extracts showed potent anti-oxidant activity (Trolox equivalents > 100 mg/g) against ferric reducing anti-oxidant power (FRAP) assay. Out of the 56 extracts, 15 had total phenolic content above 100 mg/g of gallic acid equivalents, and 4 had flavonoid content above 100 mg/g of quercetin equivalents. Among the extracts screened, hexane, dichloromethane, ethyl acetate, and methanol extracts of Allophylus cobbe leaves (IC50 – 9.388, 6.8, 19.95, and 11.3 μg/mL, respectively), Madhuca longiflora bark (IC50 – 14.42 μg/mL), methanol extract of Munronia pinnata bark (IC50 – 52.06 μg/mL), and hexane, dichloromethane, ethyl acetate, and methanol extracts of Adenanthera bicolor (IC50 – 45.86, 27.35, 24.56, and 61.83 μg/mL, respectively) exerted potent cytotoxicity against HepG2 with less toxicity (IC50 > 100 μg/mL) to THLE-3 cells after 48 h of incubation. These findings provide a direction to isolate possible anti-cancer compounds for hepatocellular carcinoma.

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Figure 1 Cytotoxicity of selected active plant extracts against HepG2 cells after 48 h of incubation (dose concentration range: 12.5‐200 μg/mL) (a) A. cobbe leaves - hexane extract, (b) A. cobbe leaves - dichloromethane extract, (c) A. cobbe leaves ‐ ethyl acetate extract, (d) A. cobbe leaves - methanol extract, (e) A. bicolor leaves - hexane extract, (f) A. bicolor leaves - dichloromethane extract, (g) A. bicolor leaves - ethyl acetate extract, (h) A. bicolor bark ‐ dichloromethane extract, (i) M. pinnata leaves - ethyl acetate extract, S. castaneifolia leaves extracts, (j) dichloromethane, and (k) ethyl acetate and S. castaneifolia bark extracts (l) hexane, (m) dichloromethane, (n) ethyl acetate, and (o) methanol extracts.
Figure 1 Cytotoxicity of selected active plant extracts against HepG2 cells after 48 h of incubation (dose concentration range: 12.5‐200 μg/mL) (a) A. cobbe leaves - hexane extract, (b) A. cobbe leaves - dichloromethane extract, (c) A. cobbe leaves ‐ ethyl acetate extract, (d) A. cobbe leaves - methanol extract, (e) A. bicolor leaves - hexane extract, (f) A. bicolor leaves - dichloromethane extract, (g) A. bicolor leaves - ethyl acetate extract, (h) A. bicolor bark ‐ dichloromethane extract, (i) M. pinnata leaves - ethyl acetate extract, S. castaneifolia leaves extracts, (j) dichloromethane, and (k) ethyl acetate and S. castaneifolia bark extracts (l) hexane, (m) dichloromethane, (n) ethyl acetate, and (o) methanol extracts.CC BY · PubMed Central
Figure 2 Microscopic observations of HepG2 cells (magnification = ×100) treated with selected active plant extracts (IC50 < 50 μg/mL) after 48 h incubation; 50 μg/mL and 200 μg/mL of (1A) A. cobbe leaves – hexane, (1B) A. cobbe leaves – dichloromethane, and (1C) A. cobbe leaves – ethyl acetate; (2A) A. cobbe – methanol, (2B) A. bicolor leaves – hexane, and (2C) A. bicolor leaves – dichloromethane; (3A) A. bocolor leaves – ethyl acetate, (3B) A. bicolor bark – dichloromethane, and (3C) M. pinnata leaves – ethyl acetate; S. castaneifolia leaves extracts (4A) dichloromethane and (4B) ethyl acetate and S. castaneifolia barks (4C) hexane; and S. castaneifolia barks (5A) dichloromethane, (5B) ethyl acetate, and (5C) methanol. Scale bar 400 μm.
Figure 2 Microscopic observations of HepG2 cells (magnification = ×100) treated with selected active plant extracts (IC50 < 50 μg/mL) after 48 h incubation; 50 μg/mL and 200 μg/mL of (1A) A. cobbe leaves – hexane, (1B) A. cobbe leaves – dichloromethane, and (1C) A. cobbe leaves – ethyl acetate; (2A) A. cobbe – methanol, (2B) A. bicolor leaves – hexane, and (2C) A. bicolor leaves – dichloromethane; (3A) A. bocolor leaves – ethyl acetate, (3B) A. bicolor bark – dichloromethane, and (3C) M. pinnata leaves – ethyl acetate; S. castaneifolia leaves extracts (4A) dichloromethane and (4B) ethyl acetate and S. castaneifolia barks (4C) hexane; and S. castaneifolia barks (5A) dichloromethane, (5B) ethyl acetate, and (5C) methanol. Scale bar 400 μm.CC BY · PubMed Central

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Authors
Thusyanthan, J., Wickramaratne, N. S., Senathilake, K. S., Rajagopalan, U., Tennekoon, K. H., Thabrew, I., & Samarakoon, S. R.
Affiliations
Institute of Biochemistry, Molecular Biology and Biotechnology (LK)
Corresponding author
Samarakoon, Sameera Ranganath
Venue
Advances in Pharmacological and Pharmaceutical Sciences
Publisher
Wiley
Published
2022-03-30
Volume
2022
Pages
1-9
ISSN
  • 2633-4690 (ISSN-L)
  • 2633-4682
OpenAlex
W4221119921
Cited by
29
References
1
Citations by year
2026: 5 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 4
FWCI
3.30
Type
journal article
Language
en
Open access
Locations
  • Advances in Pharmacological and Pharmaceutical Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Science Foundation (RPHS/2016/C 07)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
  • Physical Sciences › Chemistry › Organic Chemistry › Phytochemical Studies and Bioactivities
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry Medicinal Plant Applications
Keywords
hepatocellular carcinoma, HepG2 cells, plant extracts, cytotoxicity, antioxidant activity, phenolic content, flavonoids, Allophylus cobbe, medicinal plants, Sri Lanka, liver cancer, free radical scavenging, hepatotoxicity, traditional medicine

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