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  2. Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic-Oleic Acid-Induced Steatosis in HepG2 Cells

Orthosiphon aristatus (Blume) Miq Alleviates Non-Alcoholic Fatty Liver Disease via Antioxidant Activities in C57BL/6 Obese Mice and Palmitic-Oleic Acid-Induced Steatosis in HepG2 Cells

  • Pharmaceuticals (Basel). 2023 Jan 11;16(1):109. doi: 10.3390/ph16010109.
Salah Abdalrazak Alshehade 1 2 Raghdaa Hamdan Al Zarzour 1 3 Michael Mathai 4 Nelli Giribabu 5 Atefehalsadat Seyedan 6 Gurjeet Kaur 7 Fouad Saleih Resq Al-Suede 8 9 Amin Malik Shah Abdul Majid 8 10 Vikneswaran Murugaiyah 1 11 Hassan Almoustafa 6 Mohammed Abdullah Alshawsh 6 12
Affiliations

Affiliations

  • 1 Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia.
  • 2 Faculty of Bioeconomic & Health Sciences, Universiti Geomatika Malaysia, Kuala Lumpur 54200, Malaysia.
  • 3 Department of Pharmacology, Faculty of Pharmacy, Arab International University, Damascus 16180, Syria.
  • 4 College of Health and Biomedicine, Victoria University, Melbourne, VIC 3011, Australia.
  • 5 Department of Physiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
  • 6 Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
  • 7 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia.
  • 8 Eman Research Ltd., Level 3/81 Flushcombe Rd, Blacktown, NSW 2148, Australia.
  • 9 Eman Biodiscoveries Sdn. Bhd., A1-4, Halal Park, Sungai Petani 08000, Kedah, Malaysia.
  • 10 ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
  • 11 Centre for Drug Research, Universiti Sains Malaysia, Gelugor 11800, Penang, Malaysia.
  • 12 School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia.
Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease. Orthosiphon aristatus (Blume) Miq, a traditional plant in South Asia, has previously been shown to attenuate obesity and hyperglycaemic conditions. Eight weeks of feeding C57BL/6 mice with the standardized O. aristatus extract (400 mg/kg) inhibited the progression of NAFLD. Liver Enzymes including alanine aminotransferase and aspartate transaminase were significantly reduced in treated mice by 74.2% ± 7.69 and 52.8% ± 7.83, respectively. Furthermore, the treated mice showed a reduction in serum levels of glucose (50% ± 5.71), Insulin (70.2% ± 12.09), total Cholesterol (27.5% ± 15.93), triglycerides (63.2% ± 16.5), low-density lipoprotein (62.5% ± 4.93) and atherogenic risk index relative to the negative control. Histologically, O. aristatus reversed hepatic fat accumulation and reduced NAFLD severity. Notably, our results showed the antioxidant activity of O. aristatus via increased superoxide dismutase activity and a reduction of hepatic malondialdehyde levels. In addition, the levels of serum pro-inflammatory mediators (IL-6 and TNFα) decreased, indicating anti-inflammatory activity. The aqueous, hydroethanolic and ethanolic fractions of O. aristatus extract significantly reduced intracellular fat accumulation in HepG2 cells that were treated with palmitic-oleic acid. Together, these findings suggest that antioxidant activities are the primary mechanism of action of O. aristatus underlying the anti-NAFLD effects.

Keywords

Orthosiphon aristatus; atherosclerosis; high-fat diet; medicinal plant; non-alcoholic fatty liver disease; rosmarinic acid.

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