Investigation of the nephroprotective activity of Moringa peregrina leaves aqueous extract in mice

Pharmacia 69(4): 1095–1102 DOI 10.3897/pharmacia.69.e90506 Research Article Investigation of the nephroprotective activity of Moringa peregrina leaves aqueous extract in mice Abdulhakeem Hasan1, Reem Issa1, Lidia Al-Halaseh2, Manal A. Abbas3, Nariman Al-Jawabri2, Rawan Al-Suhaimat2 1 Department of Pharmaceutical Sciences, Pharmacological and Diagnostic Research Center (PDRC), Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University, Zipcode (61710), Al-Karak, Jordan 3 Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman19328, Jordan Corresponding author: Reem Issa () Received 18 July 2022 ♦ Accepted 21 September 2022 ♦ Published 21 December 2022 Citation: Hasan A, Issa R, Al-Halaseh L, Abbas MA, Al-Jawabri N, Al-Suhaimat R (2022) Investigation of the nephroprotective activity of Moringa peregrina leaves aqueous extract in mice. Pharmacia 69(4): 1095–1102. https://doi.org/10.3897/pharmacia.69.e90506 Abstract Traditional remedies for Moringa peregrina leaves have a variety of uses with confirmed biological and therapeutic effects, as per published reports. The current study aims to evaluate the ability of the leaves aqueous extract to protect from nephrotoxicity in gentamicin-treated mice. Phytochemical analysis for the aqueous extract was performed using DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay for antioxidants, Folin-Ciocalteu, AlCl3 and HPLC- MS/MS analysis, focusing on phenol and flavonoid content. The nephroprotective activity of the prepared extract was evaluated by means of variable biochemical parameters including Creatinine (Cr), Uric Acid (UA), and Urea (Ur). In addition, histological examination of renal tissues was performed in all mice groups (control, gentamicin-induced (150 mg/Kg i.p) and aqueous extract-orally treated groups (500 and 1000 mg/Kg)). Findings reveal that the prepared extract has total phenols (555.57±0.92mg/g, equivalent to gallic acid), flavonoids (40.08±1.56 mg/g, equivalent to quercetin), and DPPH IC50 (3.10 µg/ml). HPLC-MS/MS analysis revealed the presence of 10 phenols and flavonoids compounds. In vivo studies showed a significant (P < 0.05) reducing effect for the high-dose treatment, on serum and urine concentrations for UA, Cr, and U, among the nephrotoxicity induced mice. Low-dose treated group showed significant reduction on serum concentration of UA, Cr and U, but only for Cr concentration in urine. The histological examination showed an improvement in the image of the renal tissue among the induced-nephrotoxicity mice, which was treated with high-dose extract. In conclusion, leaves aqueous extract of M. peregrina have shown potential protective effect to counteract some of the gentamicin consequences on kidney functions. Keywords Moringa peregrina, nephroprotective, anti-oxidants, traditional medicine, kidney function test, phenols, flavonoids Copyright Hasan A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 1096 Hasan A et al.: Nephroprotective activity of Moringa peregrina extract Introduction Herbal Medicine, often known as Ethnic Medicine, a branch of the Complementary and Alternative Medicine, is an old form of health care used to prevent and treat physical and mental disorders around the world (Kpobi et al. 2019; Randeepraj et al. 2020). Nowadays, using natural products, in particular herbal, for treating either mild or serious illnesses is in an increasing global trend (Tabatabaee 2011). Acute and chronic nephrotoxicity might result after exposure to hazardous substances, medication, or simply a reflection of an unbalanced diet (Wimalawansa 2015). The renal proximal tubule is highly vascularized thus; it would be more susceptible to drug-induced nephrotoxicity (Cohen et al. 2021). Globally, more than 5 million people die each year due to a lack of access to crucial kidney disease therapies (Luyckx et al. 2021). Variable drugs could induce nephrotoxicity. Reports confirmed that around 20% of renal complaints have been induced by drugs side effects. The elderly is the most affected with a 66% prevalence rate of nephrotoxicity was recorded (Kim et al. 2012). Aminoglycoside antibiotics have confirmed nephrotoxic effects. That’s why their use is limited to treating life-threatening Gram-negative infections (Ali 2005; Al-Azzam et al. 2010; Tavafi 2013). Recently, the nephroprotective activity of variable herbal remedies was clinically approved (Khatoon et al. 2019). Examples of these remedies include Cryptocoryne auriculata and Annona reticulata. The extracts, of these medicinal plants, were investigated in in-vivo study against the nephrotoxic effects of gentamicin and cisplatin. The medicinal effect was related to the antioxidant activity of the extracts, that was determined by the phenols content (Negi et al. 2020). The Moringaceae family of flowering plants includes only one genus “Moringa” with 13 species native to tropical and subtropical climates. The two most studied species are Moringa peregrina and Moringa oleifera (Al Khateeb et al. 2013). Generally, Moringa species contain large amounts of flavonoids, phenols, vitamins, amino acids and minerals (Mansour et al. 2014). These compounds are well known for their role as antioxidants and as nutrients (Mir et al. 2022). The crude extract of M. peregrina leaves was found rich in antioxidants such as phenolic compounds and flavonoids (Al-Owaisi et al. 2014). Accordingly, confirmed activities against microbes, inflammation, hyperglycemia, hypertension, hyperlipidemia, and cytotoxicity were reported (Said-Al Ahl et al. 2017; Senthilkumar et al. 2018; Dhanalekshmi et al. 2022). The spasmolytic and memory enhancement properties were also approved (Senthilkumar et al. 2018). Additionally, the hepatotoxicity induced by doxorubicin, was alleviated with M. peregrina extracts in experimental animals (Sliai et al. 2016). Previous studies have shown that M. oleifera has a nephroprotective effect, when tested in animal experiments with gentamicin and acetaminophen-induced nephrotoxicity (Ouédraogo et al. 2013; Sheikh et al. 2014). Therefore, the overall aim of the current study is to evaluate the nephroprotective activity of M. peregrina leaves extract based on the well-known antioxidant rich components. This in-vivo study lines up with the justification purpose of the use of this herbal drug by people in Jordan for the biological activity of interest. Materials and methods Chemicals Gentamicin was purchased from Medscheme (Cyprus), Quercetin, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and gallic acid were purchased from Sigma-Aldrich, USA. Folin- Ciocalteu reagent was obtained from Merck, Germany. All other chemicals and solven (...truncated)