Moringa oleifera : Recent Insights for Its Biochemical and Medicinal Applications

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Introduction
1.1.History of Moringa oleifera.Medicinal plants and their extracts are widely used for multiple medicinal purposes all over the world [1][2][3].Due to their huge extracts and bioactive ingredients, they could be utilized in the management, control, and treatment of many disorders [4][5][6][7][8].A medicinal plant could be defned as any plant that contains bioactive ingredients used in therapy or contains a precursor for drug manufacture [9].Moringa oleifera Lam.(MO) is a medicinal plant belonging to the Moringaceae family (Table 1).Its bioactive material is utilized in the treatment of a huge number of disorders with magical and amazing results to the extent that it is called a miracle tree [10].Its bioactive components have antipyretic, antioxidant, anti-infammatory, antiaging, antidiabetic, antihypertensive, immunomodulatory, hepatoprotective, and diuretic as shown in Table 2. Furthermore, recently, the plant has been approved to have antiparasitic activity [67], neuroprotective and cerebroprotective [68,69], and antiproliferative activity against cancers [70].On the other hand, the plant has a potential use in regenerative dentistry [71] and has the ability to control and attenuate osteoporosis [72].Nowadays, its anticonstipation [73], anti-infammatory [74], antioxidant [75], and neuroplasticity activities [76] have been confrmed.Te plant is natively discovered in Indian forests and was consumed as a food additive [77].Te medicinal applications of MO were recorded in ancient medical books in many countries.In China, the frst record of Moringa back to the bower script (volume II), about the 4 th -6 th century A.D. Tousands of years old, the medicinal purposes of Moringa plant parts have been recorded in the Ayurvedic Pharmacopoeia of India (API) [78].Te ancient Egyptians used Moringa oil as a sunscreen.Ancient Greeks discovered many medicinal applications for Moringa, and they introduced it to Romans where it spread everywhere in Europe while, in modern history in 1817, the Jamaican introduced Moringa oil for many food purposes till it reached to British Empire from where Moringa has been expanded all over the world [79].Although the plant has great medicinal purposes, there is a need for further studies to elaborate and explore more details about its isolated compounds of synergistic action [80].We and authors recommended further studies and advised us to continue research in this feld.
1.2.Taxonomy, Synonyms, and Distribution.Moringaceae family is globally distributed especially in tropical areas.Te plant is distributed in subtropical and tropical areas and includes about 13 species [81].Globally, MO is widely distributed over Africa, Asia, Central America, and the Caribbean islands [82,83].MO in English is called the horseradish tree and drumstick tree; in Hindi, it is called Saijan; in Sanskrit, it is called Shigru [84].Te taxonomical classifcation and plant tree synonyms are illustrated in Tables 1 and 3 [85].

Bioactive Components and Their Medicinal Importance of Moringa oleifera
Te tree of MO has many medicinal importance.It contains a huge number of bioactive compounds that could be used as it is or included in the formulation of drugs [86].Organic agents such as protein, lipids, minerals, vitamins, tannin, favonoids, saponins, phenolic acids, isothiocyanate, and others are active components isolated from MO illustrated in Figure 1.Te pharmacological and medicinal aspects of these compounds are listed in Table 2. Te cultivation processes and storage of plant parts have a great infuence on the contents of these bioactive compounds which may afect its application and use [87].
Tese components are illustrated in Table 4. Te plant parts contain a high amount of sulphur-containing amino acids, and they contain higher amounts of β-carotenes than carrots, higher amounts of L-ascorbate than oranges, higher levels of calcium than milk, higher potassium levels than that in bananas, nine times more iron than that in spinach, and four times more fber than that in oats [110].Other functional chemical groups have been extracted from leaves such as aldehydes, acids, amides, alcohols, phenols, vitamins, and phytosterols [111].Due to their great nutritional properties, plant parts have been included in the formulation of both animal and human diets.Laboratory studies on the blood of models fed on MO investigated an increase in serum levels of calcium, proteins, phosphorus, and antioxidants but a decrease in glucose, triglycerides, and cholesterol levels [112].

Moringa oleifera as a Source for Animal Diets.
Dietary preparations from MO were included in many animal diets such as chicken [113], fshes [114,115], sheep [116], cows [117], and rabbits [118].For chicken, Moringa diets formulated from leaves and stems improved the growth performance and carcass trait [119], and productivity and the quality of egg production [120].MO extracts added to chicken diets lead to support and potentiate the immune response and introduce protection against infectious diseases [121].MO diets are introduced to cows to improve colostrum quality, immunity, and milk production [117], protect the mammary epithelium from oxidants [122], and increase milk yield, rumen fermentation, and digestibility [123].Diets supplemented with MO for pigs improved the reproduction performances, increased the protein contents of colostrum, and improved the antioxidant activities [124].

Moringa oleifera as a
Source for Human Diets.MO has been also included in the formulation of human diets for many nutritional and medicinal purposes [125].Moringa plant parts have been used as a natural agent for food fortifcation which is used to improve various aspects of food defciencies, especially in children with micronutrient malnutrition [126].It has been used to supplement humans with proteins and lipids of high biological values as well as a potent source for supplementation of iron, zinc, copper, and calcium [127].It has been included in the diets of young women (teenagers) to improve their nutritional status and educational performance [128].Te addition of MO leaves powder to cookies or as an herbal drink improved the glycemic index, lowered blood glucose, improved appetite, and gastrointestinal health, and lowered both diastolic and systolic high pressure in highly consumed salt models [49,129,130].MO dried leaves have been added to the

Leaves
Prevented memory impairment and errors [62] Radioprotective Leaves Prevented the electromagnetic and gamma radiation deleterious consequences [63][64][65][66] Journal of Food Biochemistry dishes and snacks of children to compete their malnutrition and defciencies of β-carotenes or/and minerals and improve energy, iron, and zinc requirements [131][132][133].In the same line, MO was efective to compete malnutrition in a clinical study performed on malnourished girls [134].MO leaf powder could be added to cereals meals or sprinkled on infants' foods for improving micronutrient contents and competing vitamin A defciency [135,136].Interestingly, Moringa was added to the diets of healthy overweight human models lead to improve the overweight and their lipid profles [137].

Moringa oleifera and Glucose Status
(1) Te Action of Moringa oleifera to Control Blood Glucose Level.MO were widely used to control blood glucose and its metabolism through multiple mechanisms (Figure 2).First, the plant extracts have been approved to inhibit many enzymes that could control glucose absorption or advanced glycation as intestinal α-glucosidase and pancreatic α-amylase [130,[138][139][140]. Another mechanism includes its ability to inhibit Na + -dependent glucose uptake [141,142].Te plant's high fber led to a delay in gastric emptying [142].Also, its contents of favonoids and many phenolic compounds induce hypoglycemic action [143,144].Te plants contain a huge amount of hypoglycemic bioactive agents such as catechin, cyanidin, ellagic acid, luteolin, kaempferol, quercetin, rosmarinic acid, and rutin [145].Te potential hypoglycemic power of MO has been approved in many clinical and laboratory studies for both animals and human diabetic models [146][147][148][149].A majority of these studies' results showed a signifcant improvement in fasting blood glucose levels or glucose tolerance.Te plant action revealed the normalization of the gene expressions of enzymes of insulin signaling, glycolytic mechanisms, glycogen storage, and decline in hepatic gluconeogenesis [150][151][152].Aqueous extract of MO has been approved to increase the expression levels of glycogen synthase, hexokinase, and pyruvate kinase and lower pyruvate carboxylase expression in the liver of diabetic mice model [153] while seed extract activated glycogen synthase kinase-3beta (GSK-3β) [154].Te insulinlike proteins isolated from the MO plant contributed to the improvement of glucose uptake, and induced blood glucose reduction could be another way for its hypoglycemic action [155,156].MO stimulated insulin secretion through the activation of the insulin-dependent Akt pathway and increased GLUT-4 in skeletal muscle [157].
(2) Moringa oleifera as a Diabetic Control Plant.Some animal studies provided evidence for the potential use of MO as a hypoglycemic plant in diabetics and prediabetics [158].
While there is an existing viewpoint that these studies remain inconclusive and necessitate additional clarifcation and refnement [159].Regarding human clinical studies, it is difcult to obtain scientifc consensus about the antidiabetic action of MO as there are only few approvals with variable results [160].Te plant has been approved to improve blood glucose levels through its ability to increase insulin secretion sensitivity with a noticed inhibition of β-glucosidase and α-amylase activities and increases muscles and liver glucose uptake with noticed inhibition in intestinal uptake and decreases liver gluconeogenesis [161].
(3) Te Hypoglycemic Evidences for Moringa oleifera.Prediabetics supplemented with MO showed an improvement in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels [162], while, postprandial blood glucose levels (PBG) declined in diabetics [130], the same results obtained from studies on diabetic rats [163].Fermented MO improved the glucose tolerance in obese mice [164].MO leaves enhanced the insulin release, glucose uptake in the liver, and glycogen biosynthesis in alloxan-induced diabetic models [165].In the same way, the leaf aqueous extract ameliorated the insulin resistance in mice [166].Methanolic extract of MO leaves improved both glycogen synthesis and glucose tolerance in rats [151].Moringa aqueous leaf extract showed a remarkable reduction in blood glucose concentration in rats [167].Systemic and topical applications of MO leaf aqueous extract positively improved wound healing in  4 Journal of Food Biochemistry diabetic rats [168].MO enhanced the regulation of circulating glucose through the regulation of Hsp70 and ILP2 (insulin-like peptide 2) [169] and enhanced the uptake of glucose in adipocytes [170].It has been approved that the favonoids and polysaccharides isolated from MO leaves had synergistic action to delay glucose difusion, dialysis, and delaying starch digestion [171].In the same line, MO polysaccharides improved glucose levels and metabolism in diabetic models [172].Te supplementation of leaves and seeds potentially activated monoamine oxidase (MAO), adenosine triphosphatase (ATPase), adenosine deaminase (ADA), acetylcholinesterase (AChE), arginase, lactate dehydrogenase (LDH), and angiotensin-I converting enzyme (ACE) activities in diabetics [173].Leaves potentially control both insulin levels and blood glucose levels in rats with polycystic ovaries [144].

Moringa oleifera and Lipids.
Te potential role of MO extracts in lipids metabolism has been illustrated in Figure 3.
It has been approved that MO supplementation leads to an improvement in the metabolic status of obese mice [89,174].Moreover, it controlled hypertriglyceridemia and hypercholesterolemia in rodent models [175].Its fermented leaf extracts have the ability to decrease hepatic accumulation of lipids in obese mice [164], and it alleviated the metabolic syndrome in rats inducing an improvement in lipid profle and adipokines such as adiponectin and leptin [176].Furthermore, rats that received MO leaf extract showed great resistance against consequences resulting from metabolic syndrome induced by high fructose and fat diets [177].Te leaves reduced lipids absorption in obese rats [42].Leaf extract lowered levels of TC, HDL-C, LDL-C, and TAGs through an invitro inhibition of pancreatic lipase and α-glucosidase [178].Te same results were obtained when MO was added to ice cream introduced to rats [179].In adipocytes, MO has the ability to increase glucose uptake, promote lipolysis, and attenuate adipogenesis by controlling the cell cycle genes [170,180].
Seed oil extracts reduced leptin and resistin indicating antiobesity activity [181].Serum examinations indicated that dietary polysaccharides extracted from MO leaves reduced TC, TAGs, and LDL-C in rabbits stressed with heat and modulated their lipid metabolism [182].Similarly, the administration of MO polysaccharides to mice induced protection against high-fat diet-induced obesity [183].MO prevented the progression of liver damage and inhibited de novo lipogenesis in the liver [184].In a similar study, it protected liver damage in ethanol-induced liver damage and reduced TAG levels in mice [185].Seed extracts upregulated the AMPK and PPARα and downregulated mTOR and SREBP-1 [44].Moringa also downregulated the expression of PPARc, C/EBPα, and FAS and upregulated the expression and phosphorylation of ACCl and AMPKα [186].

Moringa oleifera and Proteins
(1) Proteins and Enzymes from Moringa oleifera.Qualitative analysis of plant parts indicated the presence of many important proteins and enzymes which are included in the synthesis of vitamins, iron transporters, and calcium storage proteins [187].MO provides proteins for people of low income in consequence, and the plant has been expected to help to reduce kwashiorkor symptoms and its related consequences [188].Te studies approved also that the plant parts could be an alternative resource of proteins used for the preparation of animal diets [189].It has been approved that MO supplementation enhanced animal reproduction and elevated the protein contents in their milk [124].Seed oil extracts regulated and enhanced plasma proteins, and reduced the hepatic and renal as well as infammatory parameters in rats [41].Polysaccharides isolated from MO also upregulated the expression of enzymes included in protein digestion and absorption in rabbits [118].Recently, many isolated proteins from MO leaves could improve protein digestibility [190,191].In the same way, cysteine peptidase derived from MO seeds is considered a promising alternative to rennet [192].Milk-clotting peptidase and protease have been isolated and purifed from MO seeds and could be used in the dairy industry due to their thermostability [193].
Bioactive compounds like quercetin could target many proteins of high biological functions like p53.Isolated compounds showed great binding afnity to p53 in a molecular docking model the matter which opens the window to apply MO as an active agent in cancer research [194].
Coagulant protein isolated from MO possessed a great antimicrobial action against many isolates of bacteria isolated from water [195].Leaf extract could modulate the diferentiation of brown adipose tissue through the upregulation of bone morphogenetic protein 7 (BMP7) levels in obese mice [196].Te ethanolic extracts were associated with signifcant normalization of proteins of antioxidant, antiinfammatory, and antiapoptotic activities [197].Mass spectrometric results revealed that there was a modulation in the expression of about 125 proteins included in metabolism, signal transduction, transcription, and translation in models supplemented with pods [198].MO extracts also have been shown to introduce protection against apoptosis and oxidative stress induced in human neuroblastoma cells through their ability to activate caspase-3 [199].Leaf extracts protected cells from peroxidative damage and stimulated osteogenic induction in stem cells through the activation of phosphatidylinositol 3-kinase (PI3K/Akt/Foxo1 pathway [200]).MO decreased the infammatory cytokines as IL-6, IL-1β, TNF-α, and IFN-β, inhibited the nuclear transfer and expression of the cellular protein transcription factor EB (TFEB), and declined the cellular autophagy [201].Leaves extracts also alleviated infammation in colorectal cancer models through the downregulation of TNF-α, IL-2, and IL-6 [202].Polysaccharides extracted from MO-elevated total proteins and increased protease and amylase activities in early pregnant goats [203].MO extracts given to laying hens lead to an increase in total proteins and albumin and reduced urea [204].MO polysaccharides signifcantly improved the plasma proteins and enhanced protease and amylase activities in goats [103].MO increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor beta-1 (TGF-β1) leading to the contraction of wounds, reduction of epithelization time, increasing antioxidant activities, and reduction of capillary density [205].
(2) Peptides and Peptide Fractions of Moringa oleifera.Many peptides isolated from MO are illustrated in Table 5.Furthermore, hydrolysis of MO seeds globulin with trypsin produced many peptides that have potential antioxidant and antihypertensive action [214].Peptides of hypotensive efect were isolated from MO as angiotensin-converting enzyme (ACE), Gly-Leu-Phe-Phe (GLFF), and renin peptides Leu-Gly-Phe-Phe (LGF) [51].Many peptides of antimicrobial agents have been purifed from MO proteins [215].Another peptide (<7.5 kDa) has been isolated from MO and possessed an efcient antimicrobial activity [216].An antimicrobial peptide (AMP) has been also, isolated from MO seeds with an inhibitory action against S. aureus through inhibition of DNA gyrase and dihydrofolate reductase [96].
Another peptide of hypoglycemic action has been isolated from MO and interacted with α-glucosidase through hydrogen bonding and hydrophobic interactions [217].
(3) Moringa oleifera, Uric Acid, Urea, and Creatinine.Many studies shed light on the potential infuence of MO extracts on protein metabolites such as urea, uric acid, and creatinine.Methanolic extracts of MO decreased both BUN and creatinine in renal ischemic rats' models [218].Leaves supplementation reduced both serum uric acid and creatinine [219], ameliorated serum uric acid levels [220], improved the hematological indices, and reduced uric acid levels in stressed models [221] in consequence, and MO returned the uric acid to its normal level in diabetic rats and mice [222,223].Also, MO seeds reduced the uric acid level in the blood of diabetic rats [224] providing evidence of the hypouricemic power of leaf extracts [225].

Moringa oleifera and Minerals.
MO is characterized by its huge content of many macro and microelements.Its seeds are rich in iron (Fe), zinc (Zn), phosphorus (P), magnesium (Mg), copper (Cu), and manganese (Mn) [226] while its leaves are full of calcium (Ca), potassium (K), sulphur (S), and Fe [92,227,228].Selenium (Se) and iodide (I) are also present in high concentrations in many parts of edible plants [229].Its richness of minerals made it a great nutritional supportive plant of high biological value and could be used in the control, management, and treatment of micronutrient malnutrition in both humans and animals, help in bone growth and strength, and competing anemia [126,134,188,[230][231][232].
(1) Moringa oleifera and Calcium.MO is approved to contain higher Ca than milk and more potassium (K) than that in bananas [110,233].Many methods could be used for the formulation and extraction of MO to increase its bioaccessibility and bioavailability of Ca [234].Ca contents of leaf extract promoted the growth and development of rats exposed to Ca defciency, stimulated deposition of Ca in bones, promoted bone growth and strength, and declined resorption of bone [188,235].MO has been demonstrated to modulate the Ca signals in tissues, the matter that approved its hypotensive action [236].Its extracts also were approved to block the entrance and mobilization of Ca +2 in sarcolemma [237].
Recently, the plant extracts were used to modify the amorphous/crystallization status of Ca and P the matter which opens the way for its use in drug delivery and nutraceutical applications [238].Additionally, MO regulates the Ca levels in mitochondria enabling its ability to prevent mitochondrial dysfunction increasing the potentiality of mitochondrial membranes [105].
(2) Moringa oleifera, Iron, and Zinc.On a wide scale, MO has been added to formulate diets to compete anemia and bone problems due to its high content of Fe included in its leaves [239].It is incorporated into the diets of children, pregnant, and lactating women to overcome iron defciency and malnutrition [227,240].Leaves powder has been used as a fortifed food for iron supplementation and to increase its bioaccessibility [241].Te addition of lime juice, ascorbic acid, and citric acid to MO-fortifed diets increased iron and zinc bioavailability and bioaccessibility [242].Fermented leaves also could be another way to increase Fe bioavailability in MO enabling its use to control anemia in children [243].Tere are many forms to add MO for animal and human diets; MO leaf four as a source of Fe and Zn could be added to biscuits to improve pregnant mothers' health who have anemia [244].
For potentiation of children's health and protecting them from the consequences and development of anemia, MO leaf powders have been added to their formulated diets.Tere is a proportional relationship between the time of using MO in diets and reduction of anemia among children [132,245].

Moringa oleifera and
Vitamins.β-Carotenes, α-tocopherols, and L-ascorbic acid, along with vitamins B1, B2, and B3, were identifed in many plant parts of MO especially leaves [85,[246][247][248].Te amount of vitamin A in MO is greater than that in carrots, and the amount of Lascorbic acid is greater than that in orange [110].It has been approved also that the recommended daily allowance of vitamins A and C could be covered by the daily use of Moringa seeds and leaves [243,249].Clinical studies also approved the ability of MO to improve vitamin A (retinol) kinetics and store with an ameliorated malnutrition status in children [250,251], improvement of vitamin A levels in postmenopausal women [252], and improved the serum retinol levels in adolescent girls.[253].

Moringa oleifera and Hormones
(1) Moringa oleifera and Reproductive Hormones.Many biochemical studies have demonstrated the possible efect of MO on both males and females.Its efect tended to be dosedependent.In females, MO reduced serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen while in males, there was an increase in serum concentration of FSH, LH, and testosterone [197,[254][255][256]. Tis illustrated its efect on male fertility, enhancement of semen quality, and sex hormones.Terefore, MO is more benefcial for male reproduction than that for female reproduction [256][257][258].Furthermore, MO extracts improved male fertility through elevation of serum testosterone and gonadotrophin levels in obese rats [259], improved sperm functions, decreased FSH and increased inhibin B levels in mice [260], and normalized the level of testosterone in rats [261].For its androgenic efect on testosterone chemistry and reserve, MO leaf extracts have been reported to inhibit β-hydroxylation of testosterone by cytochrome P450 3A4 (CYP3A4) [262], increased the testosterone productivity in Leydig TM3 cells [263], and reduced the level of testosterone in prostatic hyperplastic rats [264].Te combination of MO leaves with nanoparticles like zinc oxide nanoparticles Journal of Food Biochemistry Journal of Food Biochemistry (ZnONPs) could potentiate the biogenic synthesis of LH, FSH, and testosterone through the regulation of the hypothalamus-pituitary-testicular axis [265].Contrary to the previously mentioned, MO seed extracts have been reported to potentiate male reproductive toxicity as they decreased testosterone, LH, sperm motility, and sperm in rats [266].
(2) Moringa oleifera and Tyroid Hormones.In related to its efect on thyroid hormones, MO induced a signifcant decline in serum levels of thyroid-stimulating hormone (TSH) and an elevation in T3 and T4 in patients with primary hypothyroidism [267].Furthermore, it inhibited the peripheral conversion of T4 to T3 illustrating its potent role in conserving T4.It should be noted that this inhibitory efect was signifcant in females than in males [268,269].On the contrary, the consumption of Moringa more than twice a day may be associated with the induction of goiter in human [270].
(3) Moringa oleifera and Metabolic Hormones.It has been recorded that the MO has a direct efect on β-cells of the pancreas, stimulating insulin secretion [144,157].Clinically, high doses of leaf powder in the form of capsules induced a considerable increase in insulin secretion in healthy populations suggesting its role as an agent in the controlling of blood glucose [146].Invitro studies approved its infuence on direct and/or indirect increases in insulin signaling and sensitivity [152].Accordingly, it provided a protection against the consequences of insulin resistance, hyperinsulinemia, increased low-density lipoprotein (LDL), increased visceral fat, and high liver weight [177].Te isolated agents from MO opened the window for innovative formulation of drugs against diabetes mellitus [148].On the other hand, MO leaves have been recorded to elevate the plasma insulin such as growth factor I (IGF-I) [271] insulin [144] and leptin hormones [42,184] leading to inhibiting adipogenesis [180,272].On the contrary, others recorded its ability to reduce serum leptin [152,181,273,274] leading to an increase in the energy expenditure and controlling obesity [275].
(4) Moringa oleifera, Prolactin, and Progesterone.Phytohormones such as auxins, cytokinins, and gibberellins have been approved to be contained in signifcant amounts in MO leaf extracts [276].Due to the presence of these phytohormones, consumption of MO during pregnancy may be unuseful as the plant could change the hormonal profle of pregnant women.Phytochemical contents and their metabolites may induce uterine contractility leading to abortion, afecting the conception rate, inducing teratogenicity, and producing congenital anomalies [277].Regardless of its harmful use during pregnancy, the plant could be used as a galactagogue increasing milk letdown in lactating females and improving milk volume and infant weight better than other pharmacological galactagogues [278].A strange point here has been reported; MO could be used to initiate and establish lactation even in nongestational women [279].Its leaf extract has been recorded to resist the negative efect of stress on hormonal balance during pregnancy [280] while consumption of seed extract induced a decrease in serum progesterone in heat-stressed females [281].
(5) Moringa oleifera, Serotonin (5-Hydroxytryptamine), and Melatonin.It has been recorded that the brain level of serotonin is elevated in aged rats administered aqueous extract of MO [282] while the aqueous extract from its roots signifcantly elevated the serotonin levels in the cerebral cortex, cerebellum, midbrain, and caudate nucleus [283].Serotonin release also has been potentiated through the efect of MO 5hydroxytryptamine 3 (5-HT3) receptors in experimental ulcer models [284].Te MO seed extract was able to ameliorate the level of serotonin in the cerebellum of titanium oxide nanoparticles induced damaged brain in rats [285].In depressed rats, it increased serotonin release through the noradrenergic-serotonergic neurotransmission pathway [286] and recovered the serotonin levels in rats afected with Alzheimer's disease [287].It has a protective efect against gastric ulceration through increasing 5-HT levels and enterochromafn cell count [288].It also potentiated the sleep time induced by pentobarbitone and increased serotonin levels in rats [289].Up to this moment, there were no studies on the efect of MO on melatonin levels in experimental animals or humans.As well as, phytochemical studies revealed the absence of melatonin in MO extracts [290].

Moringa oleifera and Antioxidants.
Te ingredients isolated from many plant parts such as leaves, seeds, or buds have been examined for their antioxidant power in many animals' models.Plant extracts have been reported to elevate antioxidant enzyme activities and decrease hydroperoxides (HP) and thiobarbituric acid reactive substances (TBARS) [291].
Active ingredients such as niazirin and isothiocyanate have been isolated form MO and have been approved for their potent antioxidant activity and could be used to control many oxidant-related stresses [292,293], while its polysaccharides signifcantly lead to enhancement of CAT, SOD, and GPx activities and declined malondialdehyde (MDA) and reactive oxygen species (ROS) levels [294].MO supplementation enhanced the activity of SOD, CAT, GPx, and lower MDA [124,295].MO also could compete with the heat stress in birds through its power to modulate the antioxidant system in heat-stressed broilers.Te birds fed on MO showed better antioxidant profles and low lipid peroxide markers [113].Te leaf extract of MO has been approved also to increase TAC and improve tolerance of immunity [154,166].Notably, leaf extract also showed an ability to strength the intracellular antioxidant defense system (SOD, CAT, and GSH) and lowered MDA in many experimental models [296].Leaf extracts of MO could be also used to improve the health of muscles through its ability to infuence the redox state in myotubes against hydrogen peroxide oxidant stresses.It elevated the activity of thioredoxin (Trx), SOD, CAT, GPx, and GST.It also mitigated lipids and protein peroxidation by lowering the levels of TBARS and protein carbonyls [297].Te methanolic extract of MO Journal of Food Biochemistry improved the semen quality in rams through its ability to lower the MDA and elevate SOD, GPx, and ascorbic acid in ram frozen semen [298].Interestingly, supplementation of MO could protect gastric mucosa in ulcerated stomach by increasing the activities of CAT, SOD, and GPx in rats' stomach [33].In the same prospect, alcoholic extract from MO has been approved to protect the stomach from ulcers induced by bisphenol via its antioxidant activities [32].
Leaves extracts have been approved to improve ulcerative colitis pathological consequences through their antioxidant power, and they elevated CAT and SOD and lowered MDA in rat's serum [299].
(2) Antioxidant Power of Moringa oleifera at Molecular Level.At molecular levels, MO tended to reduce the oxidative stress via activation of a basic leucine zipper transcription factor that links to the promoter domain of the antioxidant response element (Nrf2-ARE) signaling, elevating the expression of Nrf2 target genes and declining the expression of transforming growth factor beta-1 (TGF-β1) signaling [300].

Conclusion
Due to its huge content of bioactive compounds and ingredients, Moringa oleifera has been approved for its medicinal and nutritional value.Further studies are recommended to discover promising active compounds with therapeutic and synergistic efects for chronic and serious disorders.Furthermore, the molecular efect of MO should be studied on a wide range to explore more molecular mechanisms for understanding its role as a medicinal plant.

Figure 1 :
Figure 1: Bioactive compounds isolated from diferent plant parts of Moringa oleifera.

Table 5 :
Medicinal signifcances of bioactive components in diferent parts of Moringa oleifera.