Betulinic acid, natural pentacyclic triterpenoid prevents arsenic-induced nephrotoxicity in male Wistar rats

Binu, Prakash; Abhilash, S; Chandraprabha, Vineetha Radhakrishnan; Arathi, P; Nair, Harikumaran

doi:10.1007/s00580-017-2548-6

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…The apoptotic inducing activity of BA as an anti-cancer agent is enhanced by the ability to inhibit cell growth and metastasis in various cancer cells, including PC, selectively [ 11 , 19 , 20 , 21 , 22 , 23 , 24 ] and to reverse nephrotoxicity [ 25 ]. However, BA has the disadvantages of poor aqueous solubility [ 26 ] and reduced plasma half-life, the Achilles heel of many potential drug candidates [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells

Fru

Nweke

Mthimkhulu

et al. 2021

Life

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Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct of polyethylene glycol (PEG), (PEG–BA), on PC cells (MIA PaCa-2), a normal cell line (Vero) and on peripheral blood mononuclear cells (PBMCs). PEG–BA, was tested for its effect on cell death, immunomodulation and chemoresistance-linked signalling pathways. The conjugate was significantly more toxic to PC cells (p < 0.001, IC50 of 1.35 ± 0.11 µM) compared to BA (IC50 of 12.70 ± 0.34 µM), with a selectivity index (SI) of 7.28 compared to 1.4 in Vero cells. Cytotoxicity was confirmed by increased apoptotic cell death. PEG–BA inhibited the production of IL-6 by 4–5.5 fold compared to BA-treated cells. Furthermore, PEG–BA treatment of MIA PaCa-2 cells resulted in the dysregulation of crucial chemoresistance genes such as WNT3A, TXNRD1, SLC2A1 and GATA3. The dysregulation of chemoresistance-associated genes and the inhibition of cytokines such as IL-6 by the model polymer construct, PEG–BA, holds promise for further exploration in PC treatment.

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Section: Introductionmentioning

confidence: 99%

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells

Fru

Nweke

Mthimkhulu

et al. 2021

Life

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“…In this regard, we have evaluated the protective effects of a medicinal plant and its compounds against cisplatin-induced kidney cell toxicity to investigate the use of natural products that are effective but less toxic. Several studies have shown that kidney damage is reduced by treatment with triterpenoids such as betulinic acid [ 19 , 20 ], total triterpenoids from Psidium guajava leaves [ 21 ], oleanolic acid [ 22 , 23 , 24 ], and the synthetic triterpenoids RTA 405 [ 25 ] and RTA 408 [ 26 ]. Results indicate that the use of triterpenoids is an effective approach to reducing kidney injury.…”

Section: Introductionmentioning

confidence: 99%

Multiple Targets of 3-Dehydroxyceanothetric Acid 2-Methyl Ester to Protect Against Cisplatin-Induced Cytotoxicity in Kidney Epithelial LLC-PK1 Cells

et al. 2019

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Chronic exposure to cisplatin, a potent anticancer drug, causes irreversible kidney damage. In this study, we investigated the protective effect and mechanism of nine lupane- and ceanothane-type triterpenoids isolated from jujube (Ziziphus jujuba Mill., Rhamnaceae) on cisplatin-induced damage to kidney epithelial LLC-PK1 cells via mitogen-activated protein kinase (MAPK) and apoptosis pathways. Cisplatin-induced LLC-PK1 cell death was most significantly reduced following treatment with 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME). Additionally, apoptotic cell death was significantly reduced. Expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 was markedly suppressed by 3DC2ME, indicating inhibition of the MAPK pathway. Treatment with 3DC2ME also significantly reduced expression of active caspase-8 and -3, Bcl-2-associated X protein (Bax), and B cell lymphoma 2 (Bcl-2), indicating the inhibition of apoptosis pathways in the kidneys. We also applied the network pharmacological analysis and identified multiple targets of 3DC2ME related to MAPK signaling pathway and apoptosis.

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“…Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. Potential of plant-derived triterpenes as new nephroprotective agents has been demonstrated using various animal models [ 13 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…The results served as an indication of the hypouricemic and nephroprotective potential of the triterpene. Substantial experimental evidence has also demonstrated the significant nephroprotective properties of some other plant-derived triterpenes [ 13 , 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

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A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats

et al. 2020

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Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.

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Betulinic acid, natural pentacyclic triterpenoid prevents arsenic-induced nephrotoxicity in male Wistar rats

Cited by 10 publications

References 23 publications

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells

Multiple Targets of 3-Dehydroxyceanothetric Acid 2-Methyl Ester to Protect Against Cisplatin-Induced Cytotoxicity in Kidney Epithelial LLC-PK1 Cells

A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats

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