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

Pakdeechote, Poungrat; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Prachaney, Parichat; Khrisanapant, Wilaiwan; Kukongviriyapan, Veerapol

doi:10.3390/nu6010355

Cited by 109Natural Antidiabetic Agents StudiesNitric Oxide and Endothelin EffectsMedicinal Plants and Neuroprotection

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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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 [37]
Results §3.5 reports reduced plasma TNF-α after asiatic acid treatment in metabolic-syndrome rats. The Discussion reports reductions in IL-1β, IL-6, and COX-2 from other asiatic-acid studies; PGE2 appears only in the title of a cited study in the References. The source concerns isolated asiatic acid, not C. asiatica as a whole, and does not itself report reductions in all five markers. (LLM, conf=0.85)
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This 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 [37]
The Discussion reports reduced TNF-α in rats treated with asiatic acid and describes prior studies reporting reductions in IL-1β and IL-6. The source studies asiatic acid isolated from C. asiatica, not C. asiatica itself. In the printed sentence, this citation supports the cytokine portion; PGE2 and COX-2 have separate citations. (LLM, conf=0.84)
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“asiatica has shown an anti-inflammatory effect observed by the reduction in Interleukin1β (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].”
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Protective effects of asiatic acid in a spontaneous type 2 diabetic mouse model
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A Pivotal Role of the Nrf2 Signaling Pathway in Spinal Cord Injury: A Prospective Therapeutics Study
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Centella asiatica (L.) Urb. Prevents Hypertension and Protects the Heart in Chronic Nitric Oxide Deficiency Rat Model
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Asiatic acid rescues intestinal tissue by suppressing molecular, biochemical, and histopathological changes associated with the development of ulcerative colitis
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The protective effect of asiatic acid on podocytes in the kidney of diabetic rats.
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Asiatic acid alleviates Ang-II induced cardiac hypertrophy and fibrosis via miR-126/PIK3R2 signaling
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Severe Malarial Anemia (SMA) Pathophysiology and the Use of Phytotherapeutics as Treatment Options
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Network Pharmacology Analysis and Experimental Validation to Explore the Anti-inflammatory Mechanism of Asiatic Acid on Alcoholic Steatohepatitis
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Cardiovascular complications are resolved by tuna protein hydrolysate supplementation in rats fed with a high-fat diet
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Modulatory Effect of Pyrus pyrifolia Fruit and its Phenolics on Key Enzymes against Metabolic Syndrome: Bioassay-Guided Approach, HPLC Analysis, and In Silico Study
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Mitigation effect of galangin against aortic dysfunction and hypertrophy in rats with metabolic syndrome
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Cardiac remodeling and higher sensitivity to ischemia–reperfusion injury in female rats submitted to high-fat high-sucrose diet: An in vivo/ex vivo longitudinal follow-up
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Cratoxylum formosum dyer extract alleviates testicular damage in hypertensive rats
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Impact of Plant-Derived Compounds on Amyotrophic Lateral Sclerosis
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Synergistic Effect of Asiatic Acid and Madecassic Acid against Antioxidant Deficit in Rat Peripheral Nervous System
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Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats
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Biochanin-A Protects Rats from Diabetes-associated Cardiorenal Damage by Attenuating Oxidative Stress through Activation of Nrf-2/HO-1 Pathway
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Exploring the Mechanism of Asiatic Acid against Atherosclerosis Based on Molecular Docking, Molecular Dynamics, and Experimental Verification
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Prevention of Hypertension and Arterial Stiffness by Combination of Centella asiatica and Curcuma longa in Rats
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Optimization of ethanolic extraction of asiaticoside and asiatic acid: A stability study and correlation of dielectric constant
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Asiatic acid potentiates the activity of common antidepressant drugs in mice
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Antihypertensive activity of spray-dried nanoemulsion containing Asiatic acid-Palm oil in high salt diet-fed rats
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Dietary Triterpenoids
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The Effect of Combined Extracts of Sappan Wood (Caesalpinia sappan L.) and Gotu Kola (Centella asiatica L.) in Improving Diabetic Condition in Rats
Putri, B. M., Wasita, B., & Febrinasari, R. P. (2022) · Jurnal Gizi dan Pangan · doi:10.25182/jgp.2022.17.1.37-46 · Cited by 3 · see citing works
Anti-Inflammatory Effect of Centella asiatica Extract on Prevented Aortic Intima-Media Thickening in Diabetic Rats
Hawas, A. A., Nugrahaningsih, D. A. A., Sholikhah, E. N., Syarifuddin, S., Wijayaningsih, R. A., & Ngatidjan (2018) · The Thai Journal of Pharmaceutical Sciences · doi:10.56808/3027-7922.2381 · Cited by 3 · see citing works
Centella Asiatica Effect in A High Fat and Fructose Diet-Induced Model of Metabolic Disorder in Rats
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Charting the Phytopharmacological Frontier of Centella asiatica: A Quarter-Century Bibliometric Atlas Unlocking Translational Potential
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Pharmacology of Anti-obesity and Antidiabetic Phytochemicals Isolated from Various Natural Sources (Plants, Seaweeds, Mushrooms, Marine Animals, and Microorganisms)
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Self Nano Emulsifying Drug Delivery System (SNEDDS) Activity of Pegagan (Centella asiatica L) Extraction on Zebrafish Caudal Fins Regeneration
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Asiatic acid alleviates vascular remodeling in BAPN ‐induced aortic dissection through inhibiting NF‐κB p65/ CX3CL1 signaling
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Antiarthritic activity of asiaticoside against the Freund's complete adjuvant-induced rheumatoid arthritis in experimental wistar rats
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Antidiabetic properties of centella asiatica in type II diabetic rats.
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Asiatic acid attenuates renin-angiotensin system activation and improves vascular function in high-carbohydrate, high-fat diet fed rats
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Asiatic acid alleviates metabolic and hemodynamic alterations in high-fat, high-carbohydrate diet-induced metabolic syndrome rats
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Asiatic acid alleviates cardiovascular remodelling in rats with L‐ NAME ‐induced hypertension
Bunbupha, S., Prachaney, P., Kukongviriyapan, U., Kukongviriyapan, V., Welbat, J. U., & Pakdeechote, P. (2015) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12472 · Cited by 63 · see citing works
Effects of asiatic acid, an active constituent in Centella asiatica (L.): restorative perspectives of streptozotocin-nicotinamide induced changes on lipid profile and lipid metabolic enzymes in diabetic rats
Swapna, K., Uddandrao, V. V. S., Parim, B., Ravindarnaik, R., Suresh, P., Ponnusamy, P., Balakrishnan, S., Vadivukkarasi, S., Harishankar, N., Kallamadi, P. R., et al. (2019) · Comparative Clinical Pathology · doi:10.1007/s00580-019-02955-6 · Cited by 16 · see citing works
Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate, High-Fat Diet
Senaphan, K., Kukongviriyapan, U., Sangartit, W., Pakdeechote, P., Pannangpetch, P., Prachaney, P., Greenwald, S. E., & Kukongviriyapan, V. (2015) · Nutrients · doi:10.3390/nu7085283 · Cited by 99 · see citing works

Authors: Pakdeechote, P., Bunbupha, S., Kukongviriyapan, U., Prachaney, P., Khrisanapant, W., & Kukongviriyapan, V.
Affiliations: Khon Kaen University (TH)
Corresponding author: Pakdeechote, Poungrat
ORCID: Pakdeechote, Poungrat
Bunbupha, Sarawoot
Kukongviriyapan, Upa
Prachaney, Parichat
Khrisanapant, Wilaiwan
Kukongviriyapan, Veerapol
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: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/3.0/ (vor)
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 › 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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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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