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Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats

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Pakdeechote, Poungrat, Bunbupha, Sarawoot, Kukongviriyapan, Upa, Prachaney, Parichat, Khrisanapant, Wilaiwan, Kukongviriyapan, Veerapol·2014·Nutrients
DOI 10.3390/nu6010355PMC PMC3916866
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Abstract

Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α) levels (p<0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p<0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p<0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

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Figure 1 Chemical structure of asiatic acid (from Sigma-Aldrich).
Figure 1 Chemical structure of asiatic acid (from Sigma-Aldrich).CC BY · PubMed Central
Figure 2 Effect of asiatic acid on systolic blood pressure in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group (n = 8/group).
Figure 2 Effect of asiatic acid on systolic blood pressure in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group (n = 8/group).CC BY · PubMed Central
Figure 3 Effect of asiatic acid on vascular superoxide production (A) and plasma MDA (B) in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group (n = 8/group).
Figure 3 Effect of asiatic acid on vascular superoxide production (A) and plasma MDA (B) in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group (n = 8/group).CC BY · PubMed Central
Figure 4 Effect of asiatic acid on plasma nitric oxide metabolites (NOx) in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group (n = 8/group).
Figure 4 Effect of asiatic acid on plasma nitric oxide metabolites (NOx) in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group (n = 8/group).CC BY · PubMed Central
Figure 5 Effect of asiatic acid on plasma TNF-α in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group, † p < 0.05 vs. MS + AA 10 mg/kg group (n = 8/group).
Figure 5 Effect of asiatic acid on plasma TNF-α in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group, † p < 0.05 vs. MS + AA 10 mg/kg group (n = 8/group).CC BY · PubMed Central
Figure 6 Effect of asiatic acid on iNOS protein expression (A) and eNOS protein expression (B) in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group, † p < 0.05 vs. MS + AA 10 mg/kg group (n = 4/group).
Figure 6 Effect of asiatic acid on iNOS protein expression (A) and eNOS protein expression (B) in all experimental groups. Results are expressed as mean ± SEM. AA represents asiatic acid. * p < 0.05 vs. control group, # p < 0.05 vs. MS group, † p < 0.05 vs. MS + AA 10 mg/kg group (n = 4/group).CC BY · PubMed Central

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Metadata

Authors
Pakdeechote, P., Bunbupha, S., Kukongviriyapan, U., Prachaney, P., Khrisanapant, W., & Kukongviriyapan, V.
Affiliations
Khon Kaen University (TH)
Corresponding author
Pakdeechote, Poungrat
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2014-01-16
Volume
6
Issue
1
Pages
355-370
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu6010355
PMC
PMC3916866
OpenAlex
W2071030426
Cited by
109
References
44
Citations by year
2026: 4 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 6 · 2021: 15 · 2020: 4 · 2019: 11 · 2018: 16 · 2017: 7 · 2016: 12 · 2015: 6 · 2014: 5
FWCI
8.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords
asiatic acid, Centella asiatica, triterpenoids, metabolic syndrome, high-fat high-carbohydrate diet, fructose-induced obesity, endothelial nitric oxide synthase, inducible nitric oxide synthase, nitric oxide, oxidative stress, inflammation, TNF-α, malondialdehyde, insulin resistance, glucose tolerance, hemodynamics, lipid profile, cardiovascular complications
MeSH terms
Animals, Anti-Inflammatory Agents, Antioxidants, Blood Glucose, Diet, Glucose Tolerance Test, Hemodynamics, Inflammation, Insulin, Insulin Resistance, Male, Malondialdehyde, Nitrates, Nitrites, Triglycerides, Tumor Necrosis Factor-alpha, Gene Expression, Rats, Sprague-Dawley, Oxidative Stress, Metabolic Syndrome, Rats, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Pentacyclic Triterpenes, Diet, High-Fat

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