Betulinic Acid: Triterpenoid Derivative Induced NADPH-d Expression in the Urinary System with a Possible Renal Protective Role of Nitric Oxide

Soo Yue Yin; Siddiqua Ayesha; Chellasamy Panneerselvam; Adel Ibrahim Alalawy; Fahad Mohamed Almutairi; Mohamed Ali Seyed

doi:10.3390/ddc2010004

journal article Open Access Feb 02, 2023

Betulinic Acid: Triterpenoid Derivative Induced NADPH-d Expression in the Urinary System with a Possible Renal Protective Role of Nitric Oxide

Soo Yue Yin Siddiqua Ayesha Chellasamy Panneerselvam

Adel Ibrahim Alalawy

Fahad Mohamed Almutairi Mohamed Ali Seyed

Drugs and Drug Candidates Vol. 2 No. 1 pp. 52-68 · MDPI AG

View at Publisher Save 10.3390/ddc2010004

Abstract

The birch tree-derived pentacyclic lupine type-triterpenoid Betulinic acid has demonstrated a variety of biological activities BetA is known for its harmlessness on normal healthy cells. However, recent investigations have indicated that BetA can cause cellular changes in mouse normal embryonic fibroblasts even with a minimal concentration. This report cautioned the use of BetA at the clinical level, which encouraged us to examine whether BetA could produce any key effect on normal healthy cells of any organs in mice. The present study extended its investigation to evaluate whether BetA could induce any changes in the renal system and the expression pattern of NADPH-diaphorase an indirect marker of the enzyme nitric oxide synthase in mice. Our results indicated that BetA exposure induced NADPH-d expression in both organs without causing any significant morphological changes. Moreover, NADPH-d activity patterns in the organs of BetA-treated animals tremendously increased (from day 4 until day 12) when compared to controls. The expression of NADPH-d in both the kidney and bladder implies that NADPH-d-mediated nitric oxide signaling could be a mechanism involved in BetA-induced nephroprotection. These outcomes are of direct clinical importance and could pay the way for the improvement of BetA as an important pharmaceutical product.

Topics

No keywords indexed for this article. Browse by subject →

References

152

[1]

Ali "Nitric oxide mediated photo-induced cell death in human malignant cells" Int. J. Oncol. (2003)

[2]

Vijayaraghavan "Phytochemical screening, free radical scavenging, and antimicrobial potential of Chromolaena odorata leaf extracts against pathogenic bacterium in wound infections—A multispectrum perspective" Biocatal. Agric. Biotech. (2008) 10.1016/j.bcab.2018.05.014

[3]

Phaniendra "Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases" Indian J. Clin. Biochem. (2015) 10.1007/s12291-014-0446-0

[4]

Griendling "NAD(P)H oxidase: Role in cardiovascular biology and disease" Circ. Res. (2000) 10.1161/01.res.86.5.494

[5]

Vaziri "Oxidative stress and dysregulation of superoxide dismutase and NADPH oxidase in renal insufficiency" Kidney Int. (2003) 10.1046/j.1523-1755.2003.00702.x

[6]

Moncada "Nitric oxide: Physiology, pathophysiology, and pharmacology" Pharm. Rev. (1991)

[7]

Nitric oxide synthases in mammals

R G Knowles, S Moncada

Biochemical Journal 1994 10.1042/bj2980249

[8]

Pang "Betulinic acid-induced expression of nicotinamide adenine dinucleotide phosphate-diaphorase in the immune organs of mice: A role of nitric oxide in immunomodulation" Mol. Med. Rep. (2018)

[9]

Khorashadi, M., Bokoch, M.P., and Legrand, M. (2020). Is nitric oxide the forgotten nephroprotective treatment during cardiac surgery?. Ann. Intensive Care, 10. 10.1186/s13613-020-0631-7

[10]

Ali "Localization of nitrergic neuronal and non-neuronal cells in the ultimobranchial glands of the chicken" Anat. Embryol. (1996) 10.1007/bf00214706

[11]

Akbari "NADPH-d/NOS reactivity in the lumbar dorsal horn of congenitally hypothyroid pups before and after formalin pain induction" Int. J. Dev. Neurosci. (2009) 10.1016/j.ijdevneu.2009.08.012

[12]

Syed "Localization of NADPH-diaphorase reactivity in the chick and mouse thyroid gland" Thyroid (1994) 10.1089/thy.1994.4.475

[13]

Gulati "Ontogeny of NADPH-d expression in the thymic microenvironment of the chick embryo" Cell Tissue Res. (1998) 10.1007/s004410051183

[14]

Kerschbaum "NADPH-diaphorase activity and nitric oxide synthase activity in the kidney of the clawed frog, Xenopus laevis" Cell Tissue Res. (2000) 10.1007/s004410000244

[15]

Vaziri "Enhanced nitric oxide inacti vation and protein nitration by reactive oxygen species in chronic renal insufficiency" Hypertension (2002) 10.1161/hy0102.100540

[16]

Deng "Increased tyrosine nitration of the brain in chronic renal insufficiency: Reversal by antioxidant therapy" J. Am. Soc. Nephrol. (2001) 10.1681/asn.v1291892

[17]

Dorko, F., Špakovská, T., Lovasová, K., Patlevič, P., and Kluchová, D. (2012). NADPH-d activity in rat thymus after the application of retinoid acid. Eur. J. Histochem., 56. 10.4081/ejh.2012.e7

[18]

Nitric oxide synthases: regulation and function

U. Forstermann, W. C. Sessa

European Heart Journal 2012 10.1093/eurheartj/ehr304

[19]

Andronowska "Expression, and cellular distribution of NADPH-diaphorase and nitric oxide synthases in the porcine uterus during early pregnancy" Folia Histochem. Cytobiol. (2007)

[20]

Lee "Nitric oxide in the kidney: Its physiological role and pathophysiological implications" Electrolyte Blood Press. (2008) 10.5049/ebp.2008.6.1.27

[21]

Ahmad, A., Dempsey, S.K., Daneva, Z., Azam, M., Li, N., Li, P.L., and Ritter, K.J. (2018). Role of Nitric Oxide in the Cardiovascular and Renal Systems. Int. J. Mol. Sci., 19. 10.3390/ijms19092605

[22]

Martin "Evaluation of inducible nitric oxide synthase inhibition on kidney function and structure in high-fat diet-induced kidney disease" Exp. Physiol. (2018) 10.1113/ep086594

[23]

Vermeulen, W.I.C., de Wit, N.C.J., Sertorio, J.T.C., van Bijnen, A.A., Ganushchak, Y.M., Heijmans, J.H., Tanus-Santos, J.E., Jacobs, M.J., Maessen, J.G., and Buurman, W.A. (2014). Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage. Front. Physiol., 5. 10.3389/fphys.2014.00340

[24]

Legrand "Renal hypoxia and dysoxia after reperfusion of the ischemic kidney" Mol. Med. (2008) 10.2119/2008-00006.legrand

[25]

Choi "Expression, and cellular localization of inducible nitric oxide synthase in lipopolysaccharide-treated rat kidneys" J. Histochem. Cytochem. (2012) 10.1369/0022155411436131

[26]

Goligorsky "Nitric oxide in acute renal failure: NOS versus NOS" Kidney Int. (2002) 10.1046/j.1523-1755.2002.00233.x

[27]

Bank "Role of EDRF (nitric oxide) in diabetic renal hyperfiltration" Kidney. Int. (1993) 10.1038/ki.1993.183

[28]

Komers "Role of endothelium-derived nitric oxide in the pathogenesis of the renal hemodynamic changes of experimental diabetes" Diabetes (1993) 10.2337/diab.43.10.1190

[29]

Musabayane "The effects of medicinal plants on renal function and blood pressure in diabetes mellitus" Cardiovasc. J. Afr. (2012) 10.5830/cvja-2012-025

[30]

Zubair, M., Ahmad, J., Malik, A., and Talluri, M.R. (2021). Diabetic Foot Ulcer, Springer. 10.1007/978-981-15-7639-3

[31]

Disis "Immune regulation of cancer" J. Clin. Oncol. (2010) 10.1200/jco.2009.27.2146

[32]

Geetha "Immunomodulatory effects of seabuckthorn (Hippophae rhamnoides L.) against chromium (VI) induced immunosuppression" Mol. Cell. Biochem. (2005) 10.1007/s11010-005-7095-9

[33]

"Anti-inflammatory plant natural products for cancer therapy" Planta Med. (2010) 10.1055/s-0030-1249859

[34]

Winkler "In vitro effects of two extracts and two pure alkaloid preparations of Uncaria tomentosa on peripheral blood mononuclear cells" Planta Med. (2004) 10.1055/s-2004-815536

[35]

"Botanical immunodrugs: Scope and opportunities" Drug Discov. Today (2005) 10.1016/s1359-6446(04)03357-4

[36]

Oveissi "Medicinal plants and their isolated phytochemicals for the management of chemotherapy-induced neuropathy: Therapeutic targets and clinical perspective" Daru (2019) 10.1007/s40199-019-00255-6

[37]

Schepetkin "Botanical polysaccharides: Macrophage immunomodulation and therapeutic potential" Int. Immunopharmacol. (2006) 10.1016/j.intimp.2005.10.005

[38]

Seyed, M.A., and Siddiqua, A. (2020). Calotropis—A multi-potential plant to humankind: Special focus on its wound healing efficacy. Biocatal. Agric. Biotechnol., 28. 10.1016/j.bcab.2020.101725

[39]

Lahlou "The Success of Natural Products in Drug Discovery" Pharmacol. Pharm. (2013) 10.4236/pp.2013.43a003

[40]

Bruce "The role of natural products in evolution" Recent Advances in Phytochemisty (2022)

[41]

Yogeeswari "Betulinic acid and its derivatives: A review on their biological properties" Curr. Med. Chem. (2005) 10.2174/0929867053202214

[42]

McChesney "Plant natural products: Back to the future or into extinction?" Phytochemistry (2007) 10.1016/j.phytochem.2007.04.032

[43]

James "Pentacyclic Triterpenoids from the Medicinal Herb, Centella asiatica (L.) Urban" Molecules (2009) 10.3390/molecules14103922

[44]

Perveen, S., and Al-Taweel, A. (2018). Terpenes and Terpenoids, IntechOpen. 10.5772/intechopen.71175

[45]

Hordyjewska "Betulin and betulinic acid: Triterpenoids derivatives with a powerful biological potential" Phytochem. Rev. (2019) 10.1007/s11101-019-09623-1

[46]

Trojan "Pentacyclic triterpene distribution in various plants—Rich sources for a new group of multi-potent plant extracts" Molecules (2009) 10.3390/molecules14062016

[47]

Laszczyk "Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy" Planta Med. (2009) 10.1055/s-0029-1186102

[48]

Dehelean "Betulin as an antitumor agent tested in vitro on A431, HeLa and MCF7, and as an angiogenic inhibitor in vivo in the CAM assay" Nat. Prod. Commun. (2012)

[49]

Dehelean, C.A., Soica, C., Ledeţi, I., Aluaş, M., Zupko, I.G., Luşcan, A., Cinta-Pinzaru, S., and Munteanu, M. (2012). Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation. Chem. Cent. J., 6. 10.1186/1752-153x-6-137

[50]

Kovalenko "Immunotoxicity and allergenic properties of betulin-containing birch bark dry extract" Pharm. Chem. J. (2007) 10.1007/s11094-007-0005-6

Showing 50 of 152 references

Metrics

3

Citations

152

References

Details

Published: Feb 02, 2023
Vol/Issue: 2(1)
Pages: 52-68
License: View

Authors

S

Soo Yue Yin

Faculty of Pharmacy, The National University of Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia

S

Siddiqua Ayesha

School of Public Health, SRM University, Kattankulathur, Chennai 603203, India

C

Chellasamy Panneerselvam

Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia

A

Adel Ibrahim Alalawy

Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia

F

Fahad Mohamed Almutairi

Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia

M

Mohamed Ali Seyed

Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia

Cite This Article

Soo Yue Yin, Siddiqua Ayesha, Chellasamy Panneerselvam, et al. (2023). Betulinic Acid: Triterpenoid Derivative Induced NADPH-d Expression in the Urinary System with a Possible Renal Protective Role of Nitric Oxide. Drugs and Drug Candidates, 2(1), 52-68. https://doi.org/10.3390/ddc2010004

Betulinic Acid: Triterpenoid Derivative Induced NADPH-d Expression in the Urinary System with a Possible Renal Protective Role of Nitric Oxide

You May Also Like