*Review* **Prospects for Protective Potential of** *Moringa oleifera* **against Kidney Diseases**

**Tanzina Akter 1,† , Md Atikur Rahman 1,† , Akhi Moni <sup>1</sup> , Md. Aminul Islam Apu <sup>1</sup> , Atqiya Fariha <sup>1</sup> , Md. Abdul Hannan 1,2 and Md Jamal Uddin 1,3,\***


**Abstract:** Kidney diseases are regarded as one of the major public health issues in the world. The objectives of this study were: (i) to investigate the causative factors involved in kidney disease and the therapeutic aspects of *Moringa oleifera*, as well as (ii) the effectiveness of *M. oleifera* in the anti-inflammation and antioxidant processes of the kidney while minimizing all potential side effects. In addition, we proposed a hypothesis to improve *M. oleifera* based drug development. This study was updated by searching the key words *M. oleifera* on kidney diseases and *M. oleifera* on oxidative stress, inflammation, and fibrosis in online research databases such as PubMed and Google Scholar. The following validation checking and scrutiny analysis of the recently published articles were used to explore this study. The recent existing research has found that *M. oleifera* has a plethora of health benefits. Individual medicinal properties of *M. oleifera* leaf extract, seed powder, stem extract, and the whole extract (ethanol/methanol) can up-increase the activity of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while decreasing the activity of inflammatory cytokines such as TNF-α, IL-1β, IL-6, and COX-2. In our study, we have investigated the properties of this plant against kidney diseases based on existing knowledge with an updated review of literature. Considering the effectiveness of *M. oleifera*, this study would be useful for further research into the pharmacological potential and therapeutic insights of *M. oleifera*, as well as prospects of *Moringa*-based effective medicine development for human benefits.

**Keywords:** *Moringa oleifera*; antioxidant; anti-aging; fibrosis; inflammation; kidney disease

### **1. Introduction**

Kidney diseases are considered among the major health problems worldwide. Acute kidney injury (AKI) is closely connected with chronic kidney diseases (CKD). Since 1990, CKD has been included in the list of non-communicable conditions investigated by the global burden of disease study. As the disease's growth rate accelerates, it has become a global concern. The majority of incidents occur in low and lower-middle income countries [1–3]. The kidneys gradually lose their ability to function in CKD patients, and the glomerular filtration rate (GFR) falls below 60 mL/min per 1.73 m<sup>2</sup> [1,2]. Mainly people who have been already suffering from diabetes, heart disease, or high blood pressure are at a high risk of developing CKD. Few drugs, such as prolyl hydroxylase domain inhibitors against anemia in CKD [3], can be used to treat CKD complications. The main pathologies involved in kidney complications are inflammation, oxidative stress, apoptosis, and fibrosis [4]. Unfortunately, no potential drug for treating kidney diseases exists at

**Citation:** Akter, T.; Rahman, M.A.; Moni, A.; Apu, M.A.I.; Fariha, A.; Hannan, M.A.; Uddin, M.J. Prospects for Protective Potential of *Moringa oleifera* against Kidney Diseases. *Plants* **2021**, *10*, 2818. https:// doi.org/10.3390/plants10122818

Academic Editors: Juei-Tang Cheng, I-Min Liu and Szu-Chuan Shen

Received: 27 November 2021 Accepted: 16 December 2021 Published: 20 December 2021

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this time. Therefore, the search for a potential drug with fewer side effects to combat this disease is becoming increasingly important. *M. oleifera* Lam., also known as drumstick tree, is a *Moringaceae* family member that grows in the Indian subcontinent. This plant's various parts have medicinal applications, such as antifungal, antiviral, anti-inflammatory, etc. [5–8]. *Moringa* leaves also have a low calorific value and can be included in the diet of obese individuals [9]. Furthermore, it contains numerous bioactive phytochemicals such as flavonoids, saponin, vanillin, omega fatty acids, carotenoids, ascorbates, tocopherols, beta-sitosterol, moringine, kaempferol, and quercetin that have been reported in its flowers, roots, fruits, and seeds, and can play a variety of roles in medicine [10–13]. In general, the choice of the most suitable bioactive substance for therapeutic purposes necessarily depends on the chemical formula of that specific compound, its structure giving its unique properties, and implicitly its mode of action [14]. Kaempferol has been shown to promote cancer cell apoptosis, such as MCF-7 and A549 cells [15]. Due to its anti-inflammatory and antioxidant properties, quercetin has the potential to be hepatoprotective, hypocholesterolemic, hypolipidemic, and anti-atherosclerotic [16]. *Moringa* has an anti-hyperglycemic effect, according to researchers who studied it in vivo on mice models [17].

Previous studies indicate that the juice of the super food *M. oleifera* enhances antimicrobial defense [18] and regulates insulin level, as well as glucose uptake in muscles [19,20]. Interestingly, *M. oleifera* showed a significant reduction of hyperglycemia, low-density lipoprotein (LDL) cholesterol, total cholesterol, fatty substances, FPG, and VLDL-cholesterol [21]. *M. oleifera* is also beneficial for skin, hair, liver, eye, blood pressure, treating anemia, kidney disease, and diabetes [22]. Several recent studies have documented the beneficial impacts of *M. oleifera* in alleviating renal diseases in animal model. Nafiu et al. [23] marked that gentamicin-induced impairment and oxidative stress significantly reduced by ethanolic extract of *Moringa oleifera* seeds in plasma, urine and kidney homogenate of rats. Akinrinde et al. [24] observed that *M. oleifera* extract attenuates the deleterious effects of renal ischemia-reperfusion through alleviation of oxidative stress. Soliman et al. [25] explored the ameliorative effects of *M. oleifera* against oxidative stress and methotrexate-induced hepato–renal dysfunction. Recently, Abu-Zeid et al. [26] discovered that the ecofriendly selenium nanoparticle using *M. oleifera* and/or *M. oleifera* ethanolic leaf extract reduces melamine-induced nephrotoxicity by alleviating of renal function impairments, oxidative stress, and apoptosis in rat kidney. Despite the great progress of *M. oleifera* in this field in recent years, less attention has been given to the effectiveness of *M. oleifera*, particularly against kidney related diseases. Therefore, there are still some issues which need further exploration, such as the protective effects of *M. oleifera* in kidney related disease difficulties and its prospects in drug development for human benefits.

This review updates the existing knowledge concerning the causative factors involved in kidney disease, as well as the therapeutic aspects of *M. oleifera*. Furthermore, this study provides a hypothesis on how *M. oleifera* would be effective in the anti-inflammation and antioxidant processes of the kidney, with the least amount of side effects.

### **2. Methods**

This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [27]. Databases such as Scopus, PubMed, and Google Scholar were accessed to retrieve information using the keywords 'MeSH terms', on 'kidney diseases' and 'oxidative stress' and 'inflammation', and 'fibrosis' and '*Moringa oleifera*'. The information was retrieved from 2011 to 15 June 2021. Automatic search tools were used to exclude some of the articles, while others were screened manually. Articles published in languages other than English were excluded. Reviews, book chapters, expert opinions, conference papers, and letters to editors were also excluded from this review. A total of 151 research articles were retrieved from the databases and discussed in this study (Figure 1). All information compiled in the table was obtained from these research articles.

databases and discussed in this study (Figure 1). All information compiled in the table

**Figure 1.** PRISMA 2020 flow diagram for the systematic review. **Figure 1.** PRISMA 2020 flow diagram for the systematic review.

was obtained from these research articles.

### **3. Phytochemical Content and Pharmacological Potential of** *M. oleifera* **on Kidney Dis-3. Phytochemical Content and Pharmacological Potential of** *M. oleifera* **on Kidney Diseases**

**eases**  *M. oleifera* contains several bioactive phytochemicals including flavonoids and isothiocyanates [10]; polyphenols, carotenoids, alkaloids, and terpenoids [11]; and triterpenoids, moringyne, monopalmitic, di-oleic triglyceride, campesterol, stigmasterol, β-sitosterol, avenasterol, and vitamin A [12]. These bioactive phytochemicals are found in *M. oleifera* roots, fruits, and seeds. These phytochemicals have medicinal properties which *M. oleifera* contains several bioactive phytochemicals including flavonoids and isothiocyanates [10]; polyphenols, carotenoids, alkaloids, and terpenoids [11]; and triterpenoids, moringyne, monopalmitic, di-oleic triglyceride, campesterol, stigmasterol, β-sitosterol, avenasterol, and vitamin A [12]. These bioactive phytochemicals are found in *M. oleifera* roots, fruits, and seeds. These phytochemicals have medicinal properties which have been shown to be effective antioxidant, antimicrobial, inflammatory, and anti-carcinogenic agents [28]. More studies are required to explore the role of bioactive phytochemicals specially in kidney diseases.

have been shown to be effective antioxidant, antimicrobial, inflammatory, and anti-carcinogenic agents [28]. More studies are required to explore the role of bioactive phytochemicals specially in kidney diseases. *M. oleifera* also possesses a variety of pharmacological properties, which are closely associated with the presence of its bioactive compounds. Therefore, in the following section we highlighted the pharmacological potential of *M. oleifera*. *M. oleifera* showed phar-*M. oleifera* also possesses a variety of pharmacological properties, which are closely associated with the presence of its bioactive compounds. Therefore, in the following section we highlighted the pharmacological potential of *M. oleifera*. *M. oleifera* showed pharmacological potential against some plausible factors such as oxidative stress, inflammation, fibrosis, and other pathologies responsible for kidney diseases. The potential effects of *M. oleifera* against risk factors associated with kidney disease in the following sections as shown in Figures 2 and 3.

macological potential against some plausible factors such as oxidative stress, inflammation, fibrosis, and other pathologies responsible for kidney diseases. The potential effects of *M. oleifera* against risk factors associated with kidney disease in the following sections

as shown in Figures 2 and 3.

**Figure 2.** Renoprotective effects of *M. oleifera* against oxidative stress. Stress stimuli (streptozotocin, CoCl2, methotrexate, tilmicosin, TiO2NPs, acetaminophen (APAP), glycerol, and *Salmonella*) increased malondialdehyde (MDA), lipid peroxidation products (LPP), total protein carbonyl content (TPCC), blood urea nitrogen (BUN), creatinine, and nitric oxide (NO) production via triggering reactive oxygen species (ROS), H2O2, glutathione disulfide (GSSG), and lactoperoxidase (LPO). Oxidative stress emerged as a result of these events. MO—induced models, on the other hand, increased the expression of catalase (CAT); superoxide dismutase (SOD); glutathione peroxidase (GPx); glutathione (GSH), total antioxidant capacity (TAC); delta-amino levulinic acid dehydratase (ALAD), and G-6-Pase, which then activates glutathione (GSH). These stressors inhibit the expression of oxidative stress suppressive factors. ROS, H2O2, GSSG, and LPO, all related to oxidative stress, were **Figure 2.** Renoprotective effects of *M. oleifera* against oxidative stress. Stress stimuli (streptozotocin, CoCl<sup>2</sup> , methotrexate, tilmicosin, TiO2NPs, acetaminophen (APAP), glycerol, and *Salmonella*) increased malondialdehyde (MDA), lipid peroxidation products (LPP), total protein carbonyl content (TPCC), blood urea nitrogen (BUN), creatinine, and nitric oxide (NO) production via triggering reactive oxygen species (ROS), H2O<sup>2</sup> , glutathione disulfide (GSSG), and lactoperoxidase (LPO). Oxidative stress emerged as a result of these events. MO—induced models, on the other hand, increased the expression of catalase (CAT); superoxide dismutase (SOD); glutathione peroxidase (GPx); glutathione (GSH), total antioxidant capacity (TAC); delta-amino levulinic acid dehydratase (ALAD), and G-6- Pase, which then activates glutathione (GSH). These stressors inhibit the expression of oxidative stress suppressive factors. ROS, H2O<sup>2</sup> , GSSG, and LPO, all related to oxidative stress, were decreased by GSH. GSH is also capable of reducing oxidative stress.

decreased by GSH. GSH is also capable of reducing oxidative stress.

**Figure 3.** Renoprotective effects of *M. oleifera* against inflammation. The expression of C-reactive protein (CRP), which activates NF-kB in the cytosol, is linked to stress factors. TNF-, Il-6, Il-1B, iNOS, and COX-2 are all activated when NF-kB enters the nucleus and binds to DNA. All of these elements have been linked to the development of inflammation. NO is activated even more by iNOS. NO is thought to be a pro-inflammatory mediator that causes inflammation. In the cytosol, *M. oleifera* suppressed the expression of CRP and NF-kB. It also boosted cortisol, adrenaline, NK, and Treg cells, which helped reduce inflammation. Anti-inflammatory hormones Cortisol and Adrenaline Both NK cells and Treg cells are anti-inflammatory regulators. **Figure 3.** Renoprotective effects of *M. oleifera* against inflammation. The expression of C-reactive protein (CRP), which activates NF-kB in the cytosol, is linked to stress factors. TNF-, Il-6, Il-1B, iNOS, and COX-2 are all activated when NF-kB enters the nucleus and binds to DNA. All of these elements have been linked to the development of inflammation. NO is activated even more by iNOS. NO is thought to be a pro-inflammatory mediator that causes inflammation. In the cytosol, *M. oleifera* suppressed the expression of CRP and NF-kB. It also boosted cortisol, adrenaline, NK, and Treg cells, which helped reduce inflammation. Anti-inflammatory hormones Cortisol and Adrenaline Both NK cells and Treg cells are anti-inflammatory regulators.
