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Received : 20-10-2023

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Get Permission Darekar, Patil, Bathe, and Doke: Moringa oleifera: A comprehensive review on pharmacology, phytochemistry, and clinical applications


Introduction

Moringa oleifera, recognized as the "miracle tree," commonly found in tropical and subtropical regions worldwide, with its presumed origin in Asian countries including Afghanistan, Bangladesh, India, and Pakistan. The Moringa family encompasses 13 species, and M. oleifera, in particular, has gained prominence for its multifaceted uses in nutrition, biogas production, and fertilizer. Notably, Moringa exhibits a unique resilience to drought. Research indicates that M. oleifera stands out as an economical and dependable option for achieving optimal nutrition. Virtually all parts of the tree are utilized for their essential nutrients. 1, 2 The leaves of M. oleifera are rich in β-carotene, minerals, calcium, and potassium. Dried leaves, boasting an oleic acid content of approximately 70%, which having application in the formulation of moisturizers. The powdered leaves use for the production of various beverages, with "Zija" being particularly popular in India. 3, 4 The tree's bark is esteemed for its efficacy in addressing diverse ailments such as ulcers, toothaches, and hypertension. Roots play a role in treating toothaches, helminthiasis, and paralysis. Moringa flowers are utilized in the treatment of ulcers, enlarged spleens, and the production of aphrodisiac substances. The tree is renowned for its remarkable properties in addressing malnutrition in infants and lactating mothers.5

The current review aims to present a comprehensive summary of current understanding of M. oleifera's pharmacological activity, worldwide research analysis, toxicological characteristics, phytochemical composition, and ethnomedicinal attributes.

Morphology and Taxonomy

The tree displays rapid growth in loamy and well-drained sandy soils, with a preference for elevations around 500 meters above sea level. Typically, it attains a small to medium size, featuring naturally trifoliate leaves and flowers borne on an inflorescence measuring 10–25 cm in length. The fruits, commonly referred to as "pods," are usually trifoliate. While the trunk typically grows straight, occasional poor formation is observed. Branches tend to be disorganized, forming an umbrella-shaped canopy. The brown seeds possess a semi-permeable hull, and each tree yields approximately 15,000–25,000 seeds annually. 6, 7

Table 1

Taxonomical classification

1.

Kingdom

Plantae

2.

Sunkingdom

Tracheobionta

3.

Super division

Spermatophyte

4.

Division

Magnoliophyta

5.

Class

Magnoliopsida

6

Subclass

Dilleniidae

7.

Order

Capparales

8.

Family

Moringaceae

9.

Genus

Moringa

10.

Species

Oleifera

M. oleifera has been a staple in diets worldwide since ancient times due to its significant therapeutic values. Various medicines derived from the plant have been recognized for their ethnomedicinal properties and have been utilized for centuries in treating various diseases. Practically every part of the plant, including leaves, pods, bark, gum, flowers, seeds, seed oil, and roots, has been employed in the treatment of different ailments. The plant's uses extend to addressing conditions such as antihypertension, anti-anxiety, anti-diarrhea, and diuresis. Moringa has proven effective in treating dysentery and colitis, with poultices made from its leaves providing quick relief for inflammatory conditions like glandular inflammation, headaches, and bronchitis. 8

The pods are utilized to treat hepatitis and alleviate joint pain, while the roots conventionally address concerns such as kidney stones, liver diseases, inflammation, ulcers, and ear and tooth pain. Stem bark is applied to wounds and skin infections. In Indian traditional medicine, gum extracted from the plant is used to treat fever and induce abortions. The seeds function as a laxative and find application in treating tumors, prostate issues, and bladder problems. Their potential in treating arthritis by modifying oxidative stress and reducing inflammation is recognized. Preparations from the plants leaves benefit nursing mothers, malnourished infants, and contribute to the overall health of the population. Historically, the leaves have been used to address insomnia and wound treatment. In contemporary times, Moringa is extensively utilized in the cosmetic industry, a practice reminiscent of its use in ancient Egyptian history for preparing dermal ointments. 9

Phytochemistry Overview

Extensive research has been conducted on various parts of Moringa oleifera, as well as its isolated synthetic compounds. The genus Moringa boasts the identification of over 90 compounds with significant therapeutic potential. These isolated synthetic compounds possess a diverse array of categories, including proteins and amino acids, phenolic acids, carotenoids, alkaloids, glucosinolates, flavonoids, sterols, terpenes, tannins, saponins, fatty acids, glycosides, and polysaccharides. 10, 11, 12

Moringa oleifera leaves, in particular, exhibit a notable concentration of phenolic acids and flavonoids. Phenolic acids such as cinnamic acid, sinapic acid, syringic acid, gentisic acid, gallic acid, ferulic acid, protocatechuic acid, vanillin, caffeic acid, o-coumaric acid, p-coumaric acid, and epicatechin are present, while flavonoids including quercetin, catechin, myricetin, and kaempferol demonstrate excellent therapeutic activity.11 Lutein, a carotenoid, is found in substantial quantities in M. oleifera leaves. The therapeutic efficacy of the plant is attributed to the active constituents present in its leaves, as revealed by gas chromatography–mass spectrometry analysis, identifying key compounds like palmitoyl chloride, cis-vaccenic acid, 5-O-acetyl-thio-octyl, pregna-7-dien 3-ol-20-one, γ-sitosterol, β-l-rhamnofuranoside, and tetradecanoic acid. 13

The leaves also yield two new alkaloids, marumoside A and marumoside B, along with aurnatiamide acetate from the roots. Moringin and moringinine, two alkaloids, are identified in the plant's stem. M. oleifera emerges as a rich source of glucosinolates, with glucomoringin being the most abundant. β-sitosterol, a sterol isolate, is found in both seeds and leaves, while β-sitosterol-3-O-β-D-galactopyranoside, another sterol glycoside, is extracted from the bark. The leaves contain diterpenes and terpenes, with phytol being a major diterpene alcohol. Trace amounts of terpenes and their derivatives are also present. 14, 15

Pharmacological/Therapeutic activities:

Figure 1

Therapeutic potential of moringa oleifera plant

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Antimicrobial and antifungal activity

Moringa, abundant in bioactive compounds, demonstrates the capacity to hinder the proliferation of pathogenic bacteria and fungi, especially those producing toxins. The plant encompasses antimicrobial components like alkaloids, amino acids, cardiglycosides, flavonoids, saponins, steroids, terpenoids, and tannins. Pterygospermine, an antibiotic compound derived from flowers, exhibits notable antimicrobial properties. 16 Root extracts of moringa adversely affect the growth of E. coli, P. aeruginosa, and S. aureus bacteria. The fresh leaves of M. oleifera, in both juice and hydroalcoholic extracts, exhibit antimicrobial potential against both Gram-negative and Gram-positive bacteria. 17, 18, 19 Alcoholic extracts also demonstrate biological activity against Candida albicans. Methanolic extracts significantly inhibit the growth of Aspergillus flavus fungi and Trichoderma harzianum. Extracts of M. oleifera's leaves, seeds, and stems have been proven to suppress a number of fungus species, including Fusarium solani, Aspergillus niger, Aspergillus flavus, Aspergillus terreus, and Aspergillus nidulans. M. oleifera fruit contains alkaloids, flavonoids, and steroids that inhibit Candida albicans growth by either denaturing proteins or blocking spore germination via the steroid ring.20 Moringa seed kernel extract exhibits substantial inhibitory effects against Bacillus cereus, Staphylococcus aureus, Mucor species, and Aspergillus species, but is less efficient against P. aeruginosa and E. coli. A recent study highlights that single extract from M. oleifera seeds demonstrates antimicrobial potential over Gram +ve bacteria.18, 19

Anti-inflammatory activity

Various components of M. oleifera, including leaves, pods, flowers, and roots, demonstrated a noteworthy anti-inflammatory effect. Specifically, an isolated compound, 4-[2-o-Acetyl-alpha-l-rahamnoslyloxy) benzyl] thiocynate from Moringa, exhibited inhibitory activity on nitric oxide and proved effective in Raw264.7. The study explores the anti-inflammatory properties of the Moringa oleifera ethyl acetate fraction in RAW264.7 cells. It found that the fraction downregulated iNOS, COX-2, and NF-κB expression, while increasing IκBα levels. This suggests a potential therapeutic avenue, as agents that disrupt NF-κB activation have shown efficacy in treating inflammation-associated diseases. The study also found that the ethyl acetate fraction's anti-inflammatory potential is linked to suppressing NF-κB activation, preventing IκBα degradation and NF-κB p65 protein translocation. 21 Aurnatiamide acetate and 1, 3-dibenzylurea, derived from the roots of Moringa oleifera, were identified as supplementary compounds with inhibitory effects on tumor necrosis factor (TNF-α) production. Tannins, phenols, alkaloids, flavonoids, carotenoids, β-sitosterol, vanillin, and moringin forms the active chemical constituents were identified for their anti-inflammatory properties.. 22

The extract from M. oleifera fruit was observed to impede the translocation of nuclear factor kappa B (NF κB), and the chloroform extract exhibited cytotoxicity at higher concentrations (500–1000 µg/mL). 23 In an experimental mice model, the application of Moringa oleifera leaf extract emerged as an efficacious treatment strategy for atopic dermatitis in human keratinocytes. This treatment strategy was accompanied by a significant decrease in the ear tissues' expression levels of retinoic acid-related orphan receptor γT, thymic stromal lymphopoietin, and mannose receptor mRNA. 24, 25

In addressing urinary tract infections, Moringa oleifera bark extract has exhibited notable efficacy, achieving a complete cure rate of 66.67% within three weeks. When lipopolysaccharide (LPS) and cigarette smoke extract (CSE) are added to human monocyte-derived macrophages (MDM), the extract shows modulatory effects. Its effect is demonstrated by the control it exerts on the inflammatory markers TNF-α, IL-6, and IL-8, as well as the inhibition of RelA expression, a crucial gene involved in the NF-κB p65 signaling cascade. 26 In rat models with acetic acid-induced acute colitis, oral administration of M. oleifera seeds results in a reduction in distal colon weight, ulcer severity, and thus themucosal inflammation, 27 This underscores the potential of M. oleifera in mitigating inflammation-related conditions through a multifaceted approach.

Neuroprotective and antioxidant effect in neurodegenerative disorders

Moringa is recognized for its neuroprotective effects, attributed to its ability to enhance blood supply to the brain. This is crucial in preventing cerebral ischemia and reducing the ROS formation. The plant significantly reduces ROS, inducing an antioxidant response that protects the brain. Notably, Moringa reduces brain infarct volume in cortical and subcortical areas significantly. 28 It also increases superoxide dismutase (SOD) activity in rodent hippocampus and striatum. The ethyl acetate fraction of Moringa has been studied for its impact on the molecular mechanisms of inflammation. Treatment with this fraction results in the downregulation of iNOS, COX-2, and NF-κB expression, while upregulating IκBα levels. These findings suggest a potential therapeutic strategy, as interference with NF-κB activation has shown efficacy in treating inflammation-associated diseases. Studies further reveal that Moringa seed extract effectively manages cognitive impairment by improving the cholinergic system and neuron synthesis in the hippocampus. 21 Moringa administration reverses scopolamine-induced reductions in phosphorylated extracellular signal-regulated protein kinase (ERK1/2), AK strain transforming (Akt), and cAMP response element-binding protein (CREB) in the hippocampus. 29

Long-term Moringa treatment improves spatial memory, decreases escape latency, and lowers oxidative stress, restoring acetylcholine levels and halting the progression of Alzheimer's disease (AD). The neuroprotective effects extend to dementia, where Moringa treatment reverses dementia-like conditions via decreasing MDA, cholinesterase, nitric oxide (NO), and amyloid levels while increasing glutathione levels. Moringa has a positive influence on neuronal health by promoting neurite outgrowth and neuronal differentiation in embryonic neurons. Research demonstrates its efficacy in restoring spatial memory and neurodegeneration in various hippocampal regions. Additionally, Moringa exhibits neuroprotective effects in models of Alzheimer's disease, restoring neurotransmitter levels and monoamine balance in the brain. 30

Parkinson's disease (PD) is a hypokinetic neurological illness caused by dopaminergic neuron degeneration in the substantia nigra pars compacta. 31 In the context of Parkinson's disease (PD), Moringa is implicated in reducing oxidative stress, ROS formation, mitochondrial damage, and apoptosis. Sulforaphane, a component of Moringa, has been shown to protect against PD by directing interventions towards the transcription factor Nrf2 with the aim of enhancing the longevity of dopaminergic neurons. 32 Moringa's anti-inflammatory properties extend to the reduction of proinflammatory cytokines in PD models. 33

For Huntington's disease (HD), Moringa treatment preserves normal parameters and prevents the elevation of glutamate and dopamine levels observed in the HD group. However, its effectiveness is limited against specific induced demyelination and protein aggregations in certain brain areas of the HD rodent model. 34

Figure 2

Neuroprotective mechanism of moringa oleifera

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Neuronal degeneration is a significant contributor to oxidative stress, a leading factor in neurological disorders like mitochondrial dysfunction. Mitochondria, vital for cellular functions such as energy metabolism, synthesis regulation, ATP production, and ROS scavenging, become dysfunctional in various neurodegenerative disorders. Non-mitochondrial ROS generation leads to mitochondrial ROS and disrupts chelation balance within cells. 35 The study conducted by Muhammed et al. in 2020 revealed that Moringa exerted a protective influence against mitochondrial dysfunction by modulating the activities of mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase and ATPase enzymes. This underscores the plant's intrinsic neuroprotective activity, which plays a key role in averting ROS generation and mitigating oxidative damage. 36

Antidiabetic activity

Moringa leaves exhibited notable efficacy in augmenting glucose tolerance in Wistar and Goto-Kakizaki rats, concurrently eliciting a reduction in blood glucose levels. The aqueous extract demonstrated pronounced antidiabetic effects by modulating key parameters, including blood glucose levels, protein, sugar, and haemoglobin, in rat models. 37 Consumption of the plant's leaves resulted in a discernible reduction in glucose levels within a three-hour timeframe, although without surpassing the efficacy exhibited by the standard drug glibenclamide. Orally administered Moringa were found to harbor insulin-like proteins possessing antigenic epitopes to insulin, thereby manifesting notable antihyperglycemic activity. 38

Administration of the aqueous extract obtained from M. oleifera leaves at a dose of 100 mg/kg resulted in improvements in insulin sensitivity, an increase in total antioxidant capacity, and enhancements in immune tolerance. These findings align with concurrent research suggesting the ameliorative potential of M. oleifera in addressing glucose intolerance. Noteworthy antidiabetic properties inherent in the plant's leaf extracts were evidenced by heightened levels of catalase and malondialdehyde, coupled with diminished fasting plasma glucose, hemoglobin, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol in individuals with type 2 diabetes. 39 Most notably, these extracts induced elevated insulin levels in healthy subject. Furthermore, the seed extract from M. oleifera demonstrated a reduction in lipid peroxidation levels, concomitant with an augmentation of the antioxidant effect in mice subjected to streptozotocin-induced conditions. This seed extract was also effective in diminishing parameters such as immunoglobulin G, immunoglobulin A, and interleukin-6, along with mitigating pancreatic β-cell activity. The compounds deemed responsible for these effects were proposed to include quercetin, kaempferol, glucomoringin, chlorogenic acid, and isothiocyanates. 40 Furthermore, recent investigations underscored the pivotal role of M. oleifera leaf extract administration over a six-week period in alleviating diabetic complications. This encompassed a protective effect against diabetes-induced renal damage and inflammation in a streptozotocin-induced diabetes rat model. Administration of M. oleifera seed powder exhibited ameliorative potential for diabetic nephropathy, culminating in the restoration of normal histology in both renal and pancreatic tissues, particularly in comparison with a diabetic-positive control group. 41

These findings suggest that M. oleifera leaf extract and seed powder may have therapeutic potential in managing diabetic complications, particularly in terms of renal and pancreatic health. Further research is warranted to elucidate the underlying mechanisms and explore their potential as adjunct therapies for diabetes management.

Anticancer activity

Cancer is a major cause of death globally and the second leading cause of death in the United States. Several epidemiological studies have found a link between cruciferous vegetable consumption and an increased risk of developing breast, lung, and colon cancer. 42 Extracts obtained from leaves and bark of M. oleifera downregulate the tumor growth in pancreatic, breast, and colorectal cancer cell proliferation. Alsamari and colleagues conducted gas chromatography-mass spectroscopy analysis, identifying 12 distinct compounds in M. oleifera extract, with three potentially possessing anticancer properties. 43 The precursor form of the potent anticancer compound isothiocyanates, glucosinolates, naturally occurs in the intact plant. 44 Extensive research has focused on their anticancer efficacy, revealing that both androgen-dependent and androgen-independent human prostate cancer cells are inhibited in development by allyl isothiocyanates. When benzyl isothiocyanates were administered to mice harboring BxPC-3 tumor xenografts, it shows a significant 43% decrease in tumor development. By blocking AKT, phenyethyl isothiocyanates have shown promise in slowing the progression of cancer. 45

Although investigations into Moringa isothiocyanates are limited, existing studies on other isothiocyanates suggest the potential for this compound to usher in novel avenues in cancer therapeutics. The Moringa plant has been shown to have anti-cancer properties in several portions of the plant; specific chemicals such as isothiocyanate and thiocarbamate have been shown to inhibit tumor cells. In a mouse model of melanoma, alcoholic and hydro-methanolic extracts from fruits and leaves have shown a substantial reduction in tumor development. According to a recent computational modeling research, rutin in M. oleifera has the highest affinity for binding to BRCA-1. 46

Analgesic/antipyretic activity

Numerous pre-clinical investigations on rats have documented the analgesic and anti-inflammatory properties of Moringa, and it has been suggested that Moringa reduces inflammatory indicators. An alcoholic extract of moringa seed and leaves showed a comparative analgesic efficacy between aspirin and indomethacin. 47 According to these researches, Moringa is equivalent to the common medication’s aspirin and indomethacin, which is widely recognized to have an analgesic effect. 48 In a carrageenan-induced model of paw edema, Anti-inflammatory activities of moringa leaf extract have been demonstrated and it is might be mediated via neutrophils and the c-Jun N-terminal kinase pathway. 22, 49 Moringa's anti-inflammatory active ingredients include vanillin, hydroxymellein, moringine, moringinine, -sitostenone, and 9-octadecenoic acid. 50 Moringa leaf extract's antipyretic effectiveness was shown in experimental albino rats, where it decreased pyrexia caused by yeast and, in a dose-dependent way, maintained normal body temperature. Moringa leaf extract was shown to be an excellent antipyretic in experimental albino rats by significantly reducing fever caused by yeast. Moreover, the extract exhibited a dose-dependent response, effectively maintaining normal body temperature in the tested subjects. 51

Hepatoprotective

M. oleifera's hepatoprotective activity is associated to the abundance of bioactive substances found in its aqueous leaf extracts, which include high quantities of phytochemicals such as flavonoids, phenolic acids, and carotenoids. These chemicals work together to provide therapeutic effect and for its possible health advantages, M. oleifera should be consumed on a daily basis. 52 However, excessive intake may lead to iron accumulation, causing gastrointestinal distress and hemochromatosis. To prevent nutrient over-accumulation, a daily dose of 70 g of M. oleifera is suggested. 53

The antioxidant-rich characteristics of M. oleifera aqueous leaf extract are demonstrated in in vivo experiments, and this is an important defense against illnesses brought on by oxidative stress. According to in vitro studies, M. oleifera hepatoprotective qualities against a range of medications, including acetaminophen, pyrazinamide, gentamicin, and rifampicin, are mostly ascribed to its leaves. 54 Determining a half-maximal inhibitory concentration is frequently necessary in order to assess the efficacy M. oleifera as a protective agent in vitro. In vitro models such as the HepG2 cell line are often used to evaluate hepatatoxicity and the protective effects of aqueous leaf extracts by mimicking the natural in vivo environment. 55

The hepatoprotective properties of M. oleifera against oxidative stress are remarkable. M. oleifera's antioxidant action reacts to elevated ROS. M. oleifera releases Nrf2 via activating the Nrf2-Keap1 complex in the presence of oxidative stress. Antioxidant response elements (ARE) are bound by the phosphorylated version of Nrf2 (p-Nrf2), which then translocates to the nucleus and stimulates the transcription of antioxidant genes. By upregulating antioxidants and downregulating ROS, this cascade efficiently reduces oxidative stress. 56

Immunomodulatory Activity

The extract derived from Moringa oleifera leaves, particularly rich in isothiocyanates, has exhibited the ability to impede both gene and protein expression of interleukins IL-1β and IL-6 in lipopolysaccharide stimulated RAW 264.7 cells. 57 Furthermore, the ethyl acetate fraction of M. oleifera, characterized by its phenolic content, demonstrated inhibition of macrophage activation induced by LPS or cigarette smoke. This resulted in a notable decrease in gene and protein expression of pro-inflammatory cytokines, including IL-6, IL-8, and TNF-α. 58, 59

Active ingredients such isothiocyanate and glycoside cyanide, which have immunostimulatory action and efficiently boost immunity, are present in the plant's methanolic extract. According to a recent review study, a number of bioactive substances have been employed to treat immune-related conditions like diabetes, cancer, and hypertension, which has improved host immunity. Several substances obtained from M. oleifera, such as the polysaccharide isolated from the root of M. oleifera and the isothiocyanates-enriched seed extract showed similar anti-inflammatory properties. These substances were discovered to inhibit phosphorylation of Rel A(p65), phosphorylation of Iκβ, and nuclear translocation of NF-κβ, resulting in decreased mRNA expression of COX-2, TNF-α, iNOS, IL-1, and IL-6. 60 Furthermore, it has been demonstrated that extracts from Moringa oleifera leaves boost unstimulated macrophage proliferation and pinocytic activity in addition to secreting more ROS. Certain elements, such Moringa oleifera seed resistant protein, stimulated the growth of murine splenocytes and the macrophages' generation of nitric oxide (NO). Peripheral blood mononuclear cells were exposed to water-soluble lectins, which caused the production of several cytokines TNF-α, IL-2, IL-6, IL-10 and NO. 2

These findings underscore the versatile the efficacy of plant extracts from Moringa oleifera in reducing inflammation in activated immune cells, suggesting therapeutic applications in immunity disorders, organ transplantation and immunocompromised conditions like acquired immune deficiency syndrome (AIDS) and HIV/AIDS. In summary, Moringa oleifera has context-dependent immunomodulatory effects on immune cells that activate resting or unstimulated cells while suppressing stimulated cells. Furthermore, it has been shown that the ethanolic leaf extract of Moringa oleifera can protect immune cells from the cytotoxicity caused by melamine, a common food adulterant and contaminant. 60, 61

Table 2

Phytopharmaceutical applications of moringa oleifera

Sr.no

Type of extract

Formulation

Therapeutic Application

References

1

Ethanolic extract of Leaves

Lozenges

Anti-inflammatory

62

2

Ethanolic extract of Leaves

Effervescent Tablets

Anti-anemia

63

3

Seed Oil

Cream

Anti-inflammatory

64

4

Ethanolic extract of Leaves

Ag-Nps (Silver nanoparticles

antimicrobial

  65

5

Hydro-alcoholic extract of Leaves + Fruits

In-Situ Nasal Gel

Allergic rhinitis

66

6

Ethanolic extract of Leaves

Suspension

Hepato-protection against Isoniazid

67

7

Ethanolic extract of Leaves

Granules

Anti-inflammatory and anti-arthritic

68

8

Seed Oil

Suppositories

Hemorrhoids

69

9

Aqueous, ethanolic extract of Leaves

Film Dressing

Wound healing

70

10

Hydro-alcoholic extract of Leaves

In-Situ Gel

Allergic rhinitis

66

11

Hydro-alcoholic extract of Leaves

Micro-Particles

Exuding wound treatment

71

12

Aqueous extract from Leaves

Film Dressing

Wound healing in diabetic condition

72

13

Aqueous/methanolic extract from Leaves

Ointments

Edema

73

14

Seed Oil

Nano-Micelle

Mitochondrial cancer cell apoptosis

74

15

Leaves

Nanorods

Anti-bacterial property

75

16

Seed Oil

Micro-Dispersion

Anti-inflammatory

76

Toxicity and Phytopharmaceutical Formulations

Moringa oleifera, recognized for its nutritional and medicinal properties, has undergone extensive scrutiny to elucidate its toxicological aspects. In a particular investigation, the oral administration of an aqueous methanol solution from Moringa, at a dosage of 2000 mg/kg, manifested no lethal effects in female rats. 77 Similarly, a parallel examination involving Sprague-Dawley rats revealed an absence of deleterious or lethal consequences associated with the consumption of Moringa leaves. The seeds of Moringa oleifera exhibited acute toxicity at a dose of 4000 mg/kg, with observed mortality at 5000 mg/kg. 78 Despite this, the seed extract was determined to be suitable for nutritional purposes. Subsequent subacute toxicity tests conducted at diverse dosage levels unveiled a lethal dose of 1585 mg/kg, which, notably, did not induce significant deviations in sperm quality, biochemical parameters, or hematological indices. 79 Findings from an acute toxic study at 5000 mg/kg and subacute investigations ranging from 40 to 1000 mg/kg indicated an absence of adverse reactions. However, heightened levels of ALT and ALP, coupled with decreased creatinine levels, prompted the recommendation that daily Moringa consumption should not surpass 70 gm/day to avert cumulative toxicity.80

The collective data underscore the importance of adhering to recommended daily limits, given the generally safe nature of Moringa consumption, even though potential adverse effects were observed at higher doses. To augment the current understanding of Moringa's safety profile, further scientific inquiry is warranted. Below are the list of Phytopharmaceutical formulations prepared using M. oleifera extract.

Conclusion, Current Status, and Future Prospects

Moringa stands out as a versatile plant, offering a myriad of benefits across diverse applications. The current assessment of its status indicates its potential in various pharmacological activities, biomedical applications, and animal husbandry, as evidenced by extensive research conducted in key regions like India, Nigeria, Brazil, and China between 2019 and 2022. This wealth of research serves as a valuable repository for global researchers.

The comprehensive study of M. oleifera reveals its multifaceted contributions to human well-being. Rich in nutrients and phytoconstituents, the plant is not only suitable for human consumption but also finds applications in various formulations owing to its potent antioxidant properties. These formulations range from wound healing to anti-cancer and anti-aging solutions. Moreover, M. oleifera extracts serve as effective fertilizers. Despite its numerous benefits, it is crucial to note potential toxic and abortifacient effects associated with excessive consumption. The comprehensive review delves into various facets of Moringa oleifera, spanning global research, ethnopharmacology, pharmacological activities, phytochemistry, phytopharmaceutical formulations, clinical studies, toxicology, and miscellaneous parameters. Noteworthy compounds like alkaloids, phenolic acids, glycosides, sterols, glucosinolates, flavonoids, terpenes, and fatty acids contribute significantly to the medicinal properties of M. oleifera. Furthermore, the plant emerges as a prolific source of vitamins, micronutrients, and carotenoids, augmenting its medicinal worth and positioning it as a superfood.

Pharmacological studies underscore the plant's effectiveness in treating various diseases, including neuropathic pain, cancer, hypertension, and diabetes. However, there is a need for further exploration of phytochemicals for potential therapeutic benefits. Beyond clinical applications, M. oleifera serves as a cost-effective biostimulant for farmers. While preclinical research has been prolific, future endeavors should prioritize extensive clinical studies, particularly in addressing life-threatening diseases such as coronavirus outbreaks, AIDS, and various cancers. Mechanistic studies are also recommended to unravel the plant's active or synergistic compounds. In summary, M. oleifera, aptly named the "Miracle tree," emerges as a promising phytopharmaceutical and functional food. Regular consumption holds the potential to address a spectrum of chronic diseases, presenting itself as a safer alternative for medical practitioners in diverse therapeutic applications.

Source of Funding

None.

Conflict of Interest

None.

References

1 

GJ Chand AV Babu U Spandana A review on meracle tree: Moringa oleiferaJ Pharmacogn Phytochem20165618991

2 

S Anudeep VK Prasanna SM Adya C Radha Characterization of soluble dietary fiber from Moringa oleifera seeds and its immunomodulatory effectsInt J Biol Macromol20169165662

3 

PM Aja N Nwachukwu UA Ibiam IO Igwenyi CE Offor UO Orji Chemical constituents of Moringa oleifera leaves and seeds from Abakaliki, NigeriaAm J Phytomed Clin Ther20142331031

4 

W Salama A Salem E Yousef Development of Innovative Beverage Based on Milk Permeate Fortified With Dried Leaves of Moringa OleiferaArab Univ J Agric Sci2014221312

5 

B Koul N Chase Moringa oleifera Lam: panacea to several maladiesJ Chem Pharm Res201576687707

6 

HPS Makkar K Becker Nutrients and antiquality factors in different morphological parts of the Moringa oleifera treecJ Agricul Sci2009128331122

7 

M Singh S Singh D Verma Morphological and Pharmacognostical Evaluation of Moringa oleifera Lam. (Moringaceae): A Plant with High Medicinal Value in Tropical and Subtropical Parts of the WorldPharmacogn Rev2020142813883

8 

GC Stevens KP Baiyeri O Akinnnagbe Ethno-medicinal and culinary uses of Moringa oleifera Lam. in NigeriaJ Med Plants Res2013713799804

9 

S Dixit A Tripathi P Kumar Medicinal Properties of Moringa oleifera: A ReviewInt J Educ Sci Res Rev 20163217385

10 

N Masarkar SK Ray Z Saleem S Mukherjee Potential anti-cancer activity of Moringa oleifera derived bio-active compounds targeting hypoxia-inducible factor-1 alpha in breast cancerJ Complement Integr Med20231810.1515/jcim-2023-0182

11 

BK Paikra HKJ Dhongade B Gidwani Phytochemistry and pharmacology of Moringa oleifera LamJ Pharmacopuncture2017203194200

12 

M Krawczyk I Burzynska-Pedziwiatr LA Wozniak M Bukowiecka-Matusiak Evidence from a Systematic Review and Meta-Analysis Pointing to the Antidiabetic Effect of Polyphenol-Rich Plant Extracts from Gymnema montanum, Momordica charantia and Moringa oleiferaCurr Issues Mol Biol2022442699717

13 

A Bhattacharya G Ghosh D Agrawal PK Sahu S Kumar SS Mishra GC-MS profiling of ethanolic extract of Moringa oleifera leafInt J Pharma Bio Sci20145426375

14 

P Sahakitpichan C Mahidol W Disadee S Ruchirawat T Kanchanapoom Unusual glycosides of pyrrole alkaloid and 4′-hydroxyphenylethanamide from leaves of Moringa oleiferaPhytochemistry20117287916

15 

Nza Rani K Husain E Kumolosasi Moringa genus: A review of phytochemistry and pharmacologyFront Pharmacol20189

16 

P Jayasri M Sreeja N Keerthi J Yeshashwini J Praveen Moringa oleifera: A review on nutritive importance and its potential use as nutraceutical plantJ Med Plants Stud2021921522

17 

P Sharma J Wichaphon W Klangpetch Antimicrobial and antioxidant activities of defatted Moringa oleifera seed meal extract obtained by ultrasound-assisted extraction and application as a natural antimicrobial coating for raw chicken sausagesInt J Food Microbiol20203322 10877010.1016/j.ijfoodmicro.2020.108770

18 

A Anzano B De Falco M Ammar A Ricciardelli L Grauso M Sabbah Chemical Analysis and Antimicrobial Activity of Moringa oleifera LamLeaves and Seeds. Mol20222724892010.3390/molecules27248920

19 

BL Dinesha U Nidoni CT Ramachandra N Naik KB Sankalpa Effect of extraction methods on physicochemical, nutritional, antinutritional, antioxidant and antimicrobial activity of Moringa (Moringa oleifera Lam.) seed kernel oilJ Appl Nat Sci201810128795

20 

JS Moodley SBN Krishna K Pillay P Govender Green synthesis of silver nanoparticles from Moringa oleifera leaf extracts and its antimicrobial potentialAdv Nat Sci Nanosci Nanotechnol20189119

21 

EJ Park S Cheenpracha LC Chang TP Kondratyuk JM Pezzuto Inhibition of lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression by 4-[(2’-O-acetyl-α-L-rhamnosyloxy) benzyl]isothiocyanate from moringa oleiferaNutr Cancer201163697182

22 

A Bhattacharya P Tiwari PK Sahu S Kumar A review of the phytochemical and pharmacological characteristics of moringa oleiferaJ Pharm Bioallied Sci201810418191

23 

S Sugiharto S Ramadany H Handayani H Achmad A Gani M Tanumihardja Ethanolic Extract of Moringa oleifera Leaves Influences NF-κB Signaling Pathway for periodontal tissue regeneration in ratsJ Popul Ther Clin Pharmacol202330132432

24 

KM Kim SY Kim TJ Mony HJ Bae SH Choi YY Choi Moringa concanensis L. Alleviates DNCB-Induced Atopic Dermatitis-like Symptoms by Inhibiting NLRP3 Inflammasome-Mediated IL-1β in BALB/c MicePharmaceuticals20221010121710.3390/ph15101217

25 

EJ Choi T Debnath Y Tang YB Ryu SH Moon EK Kim Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balanceBiomed Pharmacother201684870710.1016/j.biopha.2016.09.085

26 

X Kou B Li JB Olayanju JM Drake N Chen Nutraceutical or pharmacological potential of Moringa oleifera LamNutrients201810334310.3390/nu10030343

27 

M Minaiyan G Asghari D Taheri M Saeidi S Nasr-Esfahani Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in ratsAvicenna J Phytomed20144212763

28 

W Kirisattayakul J Wattanathorn T Tong-Un S Muchimapura P Wannanon J Jittiwat Cerebroprotective effect of Moringa oleifera against focal ischemic stroke induced by middle cerebral artery occlusionOxid Med Cell Longev201395141510.1155/2013/951415

29 

J Zhou WS Yang DQ Suo Y Li L Peng LX Xu Moringa oleifera seed extract alleviates scopolamine-induced learning and memory impairment in miceFront Pharmacol2018938910.3389/fphar.2018.00389

30 

M Mundkar A Bijalwan D Soni P Kumar Neuroprotective potential of Moringa oleifera mediated by NF-kB/Nrf2/HO-1 signaling pathway: A reviewJ Food Biochem20224612e1445110.1111/jfbc.14451

31 

RR Doke PA Pansare SR Sainani VM Bhalchim KR Rode SR Desai The Counteracting Performance of Phytoconstituents Against Neurodegeneration Involved in Parkinson’s DiseaseJ Sci Res2021650114658

32 

A F Wright Role of the transcription factor Nrf2 and Redox Balance in Parkinson ’ s Disease Role of the transcription factor Nrf2 and redox balance in Parkinson ’ s diseaseFront Pharmacol20201391923310.3389/fphar.2022.919233

33 

S Giacoppo TS Rajan De Nicola GR Iori R Rollin P Bramanti The isothiocyanate isolated from moringa oleifera shows potent anti-inflammatory activity in the treatment of murine subacute Parkinson’s diseaseRejuvenation Res20172015063

34 

OF Akinpelu PD Shalli OJ Ogundipe AA Akande FE Oladipupo SO Jimoh Neurobehavioural investigation of the role/s of Moringa oleifera on 3-nitropropionic acid model of Huntington’s disease.Int J Res Sci Innov20196910935

35 

RR Doke A Prajakta M Vrushali R Shivani Natural products: An emerging tool in parkinson’s diseaseIP Indian J Neurosci20195395105

36 

RE Muhammed MA El-Desouky SB Abo-Seda AA Nahas H Elhakim MI Alkhalaf The protecting role of Moringa oleifera in cypermethrin-induced mitochondrial dysfunction and apoptotic events in rats brainJ King Saud Univ Sci2020326271739

37 

CM Sena C Barosa E Nunes R Seiça JG Jones Sources of endogenous glucose production in the Goto-Kakizaki diabetic ratDiab Metab2007334296302

38 

P Carvalho de Moringa oleifera Lam.: uma fonte vegetal de proteínas hipoglicemiantes e hipolipemiantesDoutorado em Bioquímica2017134

39 

MJ Tuorkey Effects of Moringa oleifera aqueous leaf extract in Alloxan induced diabetic miceInterv Med Appl Sci20168310926

40 

EI Omodanisi YG Aboua OO Oguntibeju RM Lamuela-Raventós Assessment of the anti-hyperglycaemic, anti-inflammatory and antioxidant activities of the methanol extract of moringa oleifera in diabetes-induced nephrotoxic male wistar ratsMolecules201722443910.3390/molecules22040439

41 

AL Al-Malki El Rabey The antidiabetic effect of low doses of moringa oleifera lam. Seeds on streptozotocin induced diabetes and diabetic nephropathy in male ratsBiomed Res Int2015381040 10.1155/2015/381040

42 

DA Boggs JR Palmer LA Wise D Spiegelman MJ Stampfer L Adams-Campbell Fruit and vegetable intake in relation to risk of breast cancer in the black women’s health studyAm J Epidemiol201017211126879

43 

JH Fowke FL Chung JF Qi D Cai Q Conaway Urinary isothiocyanate levels, Brassica, and human breast cancerCancer Res2003631439806

44 

JW Fahey AT Zalcmann P Talalay The chemical diversity and distribution of glucosinolates and isothiocyanates among plantsPhytochemistry2001561551

45 

D Xiao SK Srivastava KL Lew Y Zeng P Hershberger CS Johnson Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosisCarcinogenesis20032458918

46 

N Gao A Budhraja S Cheng EH Liu J Chen Z Yang Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathwaysCell Death Dis201124e14010.1038/cddis.2011.22

47 

HB Mabrok MS Mohamed Induction of COX-1, suppression of COX-2 and pro-inflammatory cytokines gene expression by moringa leaves and its aqueous extract in aspirin-induced gastric ulcer ratsMol Biol Rep2019464421337

48 

SK Biswas A Chowdhury J Das RA Hosen Pharmacological potentials of Moringa oleifera lam.: A ReviewInt J Pharm Sci Res20123230515

49 

D Meireles J Gomes L Lopes M Hinzmann J Machado A review of properties, nutritional and pharmaceutical applications of Moringa oleifera: integrative approach on conventional and traditional Asian medicineAdv Tradit Med2020204495515

50 

KA Ansari Moringa oleifera), pharmacognosy and pharmacology: A reviewJ Pharmacogn Phytochem2017614427

51 

A Pandey MO Lam Moringa Oleifera Lam. (Sahijan) - A Plant with a Plethora of Diverse Therapeutic Benefits: An Updated RetrospectionMed Aromat Plants20121118

52 

N Chhikara A Kaur S Mann MK Garg SA Sofi A Panghal Bioactive compounds, associated health benefits and safety considerations of Moringa oleifera L.: an updated reviewNutr Food Sci202151225577

53 

P Pagadala V Shankar Moringa olifera: Constituents and protective effects on organ systemsPhysiol Pharmacol20202428290

54 

RSN Brilhante JA Sales VS Pereira S Castelo-Branco D De A Cordeiro R De CM De Souza Sampaio Research advances on the multiple uses of Moringa oleifera: A sustainable alternative for socially neglected populationAsian Pac J Trop Med201710762151

55 

M Saki D Villiers H Ntsapi C Tiloke The Hepatoprotective Effects of Moringa oleifera against Antiretroviral-Induced Cytotoxicity in HepG2 Cells: APlants20231218323510.3390/plants12183235

56 

CG Kim SN Chang SM Park BS Hwang SA Kang KS Kim Moringa oleifera mitigates ethanol-induced oxidative stress, fatty degeneration and hepatic steatosis by promoting Nrf2 in micePhytomedicine202210015403710.1016/j.phymed.2022.154037

57 

KH Shah MJ Oza Comprehensive Review of Bioactive and Molecular Aspects of Moringa Oleifera LamFood Rev Int2022387142760

58 

N Kooltheat P Sranujit R Chumark P Potup PL Lewin N Usuwanthim An ethyl acetate fraction of Moringa oleifera Lam. inhibits human macrophage cytokine production induced by cigarette smokeNutrients201462697710

59 

T Luetragoon RP Sranujit C Noysang Y Thongsri P Potup N Suphrom Bioactive compounds in moringa oleifera Lam. Leaves inhibit the pro-inflammatory mediators in lipopolysaccharide-induced human monocyte-derived macrophagesMolecules202025119110.3390/molecules25010191

60 

UM Adamu H Lawal R Ramasamy Immunomodulatory functions of moringa oleifera (Lam.)Malaysian J Med Heal Sci2021175463

61 

YM Abd-Elhakim KM El Bohi SK Hassan S El Sayed SM Abd-Elmota Palliative effects of Moringa olifera ethanolic extract on hemato-immunologic impacts of melamine in ratsFood Chem Toxicol201811411010.1016/j.fct.2018.02.020

62 

AA Abd-Rabou KMA Zoheir MS Kishta AB Shalby MI Ezzo Nano-micelle of moringa oleifera seed oil triggers mitochondrial cancer cell apoptosisAsian Pacific J Cancer Prev20161711492962

63 

CY Isimi LB John-Africa KE Ekere OJ Olayemi OI Aremu MO Emeje Formulation, evaluation and anti-hemorroidal activity of suppositories containing moringa oleifera lam. Seed oilActa Pharm Sci202159164765

64 

CY Chin SF Ng Development of Moringa oleifera Standardized Leaf Extract Nanofibers Impregnated onto Hydrocolloid Film as A Potential Chronic Wound Dressing. Fibers Polym20202111246272

65 

T Luetragoon RP Sranujit C Noysang Y Thongsri P Potup J Somboonjun Evaluation of anti-inflammatory effect of moringa oleifera lam. And cyanthillium cinereum (less) h. rob. lozenges in volunteer smokersPlants2021107133610.3390/plants10071336

66 

C Pagano L Perioli C Baiocchi A Bartoccini T Beccari F Blasi Preparation and characterization of polymeric microparticles loaded with Moringa oleifera leaf extract for exuding wound treatmentInt J Pharm202058711970010.1016/j.ijpharm.2020.119700

67 

CY Chin PY Ng SF Ng Moringa oleifera standardised aqueous leaf extract-loaded hydrocolloid film dressing: in vivo dermal safety and wound healing evaluation in STZ/HFD diabetic rat modelDrug Deliv Transl Res20199245368

68 

JS Yadav BN Shah A Gupta DP Shah Development and evaluation of polyherbal ointments for anti-inflammatory therapyInt J Pharm Res20146311423

69 

E MH T MB Moringa oleifera Lam . -Based Effervescent Tablets : Design , Formulation and Physicochemical EvaluationInt J Drug Deliv Technol20188422230

70 

SO Aisida N Madubuonu MH Alnasir I Ahmad S Botha M Maaza Biogenic synthesis of iron oxide nanorods using Moringa oleifera leaf extract for antibacterial applicationsAppl Nanosci202010130520

71 

S Vibhute V Kasture S Kasture P Kendre S Rupnar V Pande Design and characterization of Moringa oleifera seed oil impregnated antiinflammatory topical micro-dispersionDer Pharm Lett201573716

72 

V Suryadevara S Doppalapudi S Reddivallam AR Mudda Formulation and evaluation of anti-inflammatory cream by using Moringa oleifera seed oilPharmacognosy Res2018102195204

73 

K Labh A Rajeshkumar S Roy A Santhoshkumar J Lakshmi Herbal formulation mediated synthesis of silver nanoparticles and its antifungal activity against candida albicansIndian J Public Heal Res Dev20191011345462

74 

R Srivastava S Srivastava SP Singh Comparative study of anti-allergic activity of two poly-herbal formulations in ova-challenged allergic rhinitis mice modelOrient Pharm Exp Med20191913747

75 

A Aristianti N Nurkhaeri VY Tandiarrang A Awaluddin L Muslimin Formulation and pharmacological studies of leaves of moringa (Moringa oleifera), a novel hepatoprotection in oral drug formulations. Open Access MacedJ Med Sci20219A1517

76 

HJM Alsammarraie NAK Khan R Mahmu Formulation, evaluation, and in vivo anti-inflammatory and anti-arthritic activities of moringa granulesInt J Appl Pharm202113311232

77 

Y Kim A Jaja-Chimedza D Merrill O Mendes I Raskin A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in ratsToxicol Reports201854182610.1016/j.toxrep.2018.02.012

78 

TO Ajibade R Arowolo FO Olayemi Phytochemical screening and toxicity studies on the methanol extract of the seeds of moringa oleiferaJ Complement Integr Med201310120125

79 

O Igado The ameliorative effects of a phenolic derivative of Moringa oleifera leave against vanadium-induced neurotoxicity in miceIBRO Rep201891648210.1016/j.ibror.2020.07.004

80 

IJ Asiedu-Gyekye S Frimpong-Manso C Awortwe DA Antwi AK Nyarko Micro-and Macroelemental Composition and Safety Evaluation of the Nutraceutical Moringa oleifera LeavesJ Toxicol201478697910.1155/2014/786979



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