Abstract

Moringa oleifera Lam. hailed as the "tree of life" or "miracle tree," has become a widely distributed plant in tropical and a subtropical regions, that resides to the Moringaceae family. Its numerous pharmacological characteristics encompass antidiabetic, antioxidant, antimicrobial, anti-inflammatory, anticancer, hepatoprotective, neuroprotective actions and among others. Rich in alkaloids, flavonoids, vitamins, and terpenes and have active constituents like as isothiocyanates, zeatin, glucosinolates, quercetin, rhamnose, ?-sitosterol, rhamnetin ,caffeoylquinic acid, Isoquercitrin , kaempferol , kaempferitrin , aspartic acid, glutamic acid, glycine, threonine, alanine, valine, leucine, isoleucine, lysine, arginine, phenylalanine, tryptophan, cysteine methionine , arachidic acid , linoleic and linolenic acid , this plant exhibits a broad spectrum of medicinal benefits. Safety studies indicate its benign nature, making it a promising candidate for therapeutic use and revealed no negative effects on the organisms and organs under study, indicating that M. oleifera is safe to use. This review offers a comprehensive overview of M. oleifera plant morphology, phytochemistry, pharmacological activities and safety profiles.

Keywords

Introduction

The Moringa oleifera Lam. plant is a member of the Moringaceae family of trees that evolves rapidly and resists dryness. Many names are widely associated with it, such as moringa, drumstick tree, horseradish tree, ben oil tree, and miracle tree. [1] Since M. oleifera is an essential medicinal plant itself, phytochemicals extracted from it may be helpful in creating lead chemicals for the creation of novel natural remedies. Native to tropical and subtropical areas, the moringa plant has a special combination of phytochemicals, including sitosterol, zeatin, quercetin, kaempferom, and caffeolquinic. [2,3] The bioactive substances known as phytocompounds are extracted from plants and resembles vitamin a, vitamin c, carotenoids, polyphenols, phenolic acids, flavonoids, flavone glycosides, alkaloids, tannins, saponins, oxalates, amino acids, fatty acids, terpenes, sucrose, vanillin, carbohydrates, beta-carotene, methionine, cysteine, glucosinolates, isothiocyanates, thiocarbonates and other secondary metabolites. [4] According to data from the World Health Organization (WHO), 80% of people in poor nations receive their primary medical care from traditional practitioners. Considering the high cost of conventional pharmaceuticals medicinal plants like M. Oleifera portray the essential product for rural as well as urban populations for their health care needs. Furthermore it has been discovered that these herbs offer significant medicinal value in the treatment of serious health issues. [5]

Taxonomy and Morphology

Moringa oleifera Lam. is classified within the kingdom of Plantae, Tracheobionta subkingdom, along with Spermatophyta superdivision. It resides to the Magnoliophyta division, Magnoliopsida class, and Dilleniidae subclass. Further classification involves the Capparales order, Moringaceae family, Moringa genus, and oleifera species. [6] It's a small, quickly developing evergreen or deciduous tree that may attain heights of up to nine meters. Its bark is corky and slippery, and its roots taste like horseradish. Its wood is soft and white. The main axis of the leaves, which are 30-75 cm long and have branch joins that are glandular at the joints, are longitudinally cracked, and the leaflets are glabrous and whole. The leaflets have whole (non-toothed) borders, are green, nearly hairless, and finely hairy on their upper surface. The lower surface is paler and hairless, with reddish-tinged mid-veins that are bluntly or roundedly pointed at the bottom. The twigs are green and slightly hairy. Large axillary hanging panicles of fragrant, white flowers hold pendulous, ribbed pods with three-angled seeds. [7, 8] M. Oleifera is a very adaptable plant that does well in hot, semiarid climates with yearly rainfalls as little as 500 mm. [9] It can withstand yearly rainfall ranging from 250 mm to more than 3000 mm. [10] Originally from the sub-Himalayan mountains of India's northern region, M. Oleifera is currently grown throughout the world's tropical and even subtropical climates for a number of uses. [11] It thrives in temperatures between 25 and 35 degrees Celsius in direct sunlight at 500 meters above sea level within fairly acidic to alkaline ( pH 5.0 to 9.0) soil. Even yet, it can withstand extreme heat up to 48 degrees Celsius in the winter, altitude, and a wide range of soil conditions. [12] The leading producer in India, both in terms of area and output, is the state of Andhra Pradesh, followed by Tamil Nadu and Karnataka. [13] With a yearly output of 1.1–1.3 million tons from a land area of 38,000 ha, India is globally the largest producer of M. Oleifera fruits (pods). [14] Indonesia, Malaysia, Mexico, Central, South America, and Sri Lanka as well as Africa, Cambodia and Nepal are among the other continents where it is extensively grown. [15]

PHYTOCHEMISTRY

More than ninety substances with considerable medicinal potential have been identified in the genus Moringa. [16] Proteins, amino acids alongside phenolic acids, carotenoids, alkaloids, glucosinolates, flavonoids, sterols, terpenes, tannins, saponins, in addition to this fatty acids, glycosides, and polysaccharides are just a few of the many categories that these isolated synthetic substances fall under. [17,18] Numerous phytochemicals, including isothiocyanates, zeatin, glucosinolates, quercetin as well as rhamnose, ?-sitosterol, rhamnetin, caffeineoylquinic acid, isoquercitrin, kaempferol, and kaempferitrin, are abundant in the Moringa family. [19] Citations for M. oleifera leaves as significant providers of vitamins have also been made, with reports indicating that they have high vitamin C than conventional sources like oranges. [20] Also the primary source of catechins, specifically epicatechin, catechin, and pyrocatechin, is found in M. oleifera leaves. [21] The polyphenols benzyl isothiocyanate, 3-caffeoylquinic acid, 5-caffeoylquinic acid, and niazimicin have also been found in studies on M. oleifera leaves. [22] (1-6)-ß-D-galactopyranosyl (1-6)-D-galactose, O-(ß-D-glucopyranosyluronic acid), as well as aspartic acid, glutamic acid, glycine, threonine, phenylalanine, tryptophan, cysteine,  alanine, valine, leucine, isoleucine, lysine, arginine and methionine in M. oleifera leaves, are the constituents of aldotriouronic acid, that derived from the acid hydrolysis of gum. [23] It has been found that 4-(?-L-rhamnopyranosyloxy)-benzylglucosinolate is present in bark. [24] A sterol glycoside called ß-sitosterol-3-O--D-galactopyranoside is isolated from M. Oleifera's bark. [25] The stem of the plant is also known to contain the alkaloids moringin and moringinine. It turns out to be a rich source of glucosinolates, with the highest concentration seen in glucomoringin. [26, 27] As a result, the major components of immature seeds are isothiocyanates, while seeds and pods have methionine, cysteine, 4-(alpha-L- rhamnopyranosyloxy) benzylglucosinolate, Moringine, benzylglucosinolate, niazimicin, niazirin in aqueous and hydroalcoholic extrac as well as isothiocyanate, nitrites, thiocarbamates,O-(1-heptenyloxy) propyl undecanoate, O-ethyl-4-(alpha-L-rhamnosyloxy) benzyl carbamate, methyl-p-hydroxybenzoate, and niazimicin are also present. [28,29] High amounts of 4-(alpha-l-rhamnopyranosyloxy)-benzylglucosinolate and benzyl glucosinolate are found in M. oleifera roots. For the first time from this species, chemicals aurantiamide acetate 4 and 1, 3-dibenzyl urea were extracted and identified from the roots of M. oleifera. [30] However, the seeds and seed oil have higher levels of oleic (18:1, 70–80%), palmitoleic (16:1, 6–10%), stearic (18:0, 4–10%), and arachidic acid (20:0, 2-4%) and less linoleic and linolenic acid. [31, 32] Further study demonstrates that M. oleifera gum includes aldotriouronic acid, which is identified as O-(?-D-glucopyranosyluronic acid) (1,6)-?-D-galactopyranosyl (1,6)-D-galactose and is produced by the gum's acid hydrolysis. [33]

Table 1 – Phytoconstituents and structures of Moringa Oleifera Lam.

PHARMACOLOGICAL  ACTIVITIES

1. Antidiabetic activity

Diabetes, marked by high blood sugar levels, leads to complications like retinopathy and atherosclerosis. Moringa Oleifera Lam. shows promise in treating both Type 1 and Type 2 diabetes. With diabetes prevalence rising, there's heightened attention on prevention and treatment efforts to reduce its impact. [43] A variety of antioxidants like flavonoids, quercetin, kaempferol, and other polyphenols and vitamins in various plant sections may be the cause of M. oleifera's hypoglycemic activity. [44] The ethanol extracts of Moringa oleifera seeds, stems, flowers, leaves, and roots were compared for their in vivo and in vitro antidiabetic potentials. The results indicated that the extracts from the seeds, followed by those from the leaves, produced greater enzyme inhibition and glucose-lowering activities. [45] In diabetic rats, M. oleifera leaf extract dramatically lowered glucose, insulin, and cytokine levels. This suggests that M. oleifera leaf extract modulates hyperinsulinemia, PPAR?, and inflammatory cytokines to attenuate hyperglycemia in type 2 diabetes. [46] In another study, moringa seed powder was shown to effectively lower fasting blood sugar levels in rats of STZ-induced diabetes. [47] Similarly, methanolic pod extract of M. oleifera was discovered to have anti-diabetic activities in a study on diabetic albino rats produced by streptozotocin (STZ). [48] According to studies, M. oleifera's ethyl acetate fraction and leaf extracts can raise the production of insulin in pancreatic beta cells, which could bring blood glucose levels to normal. Also, it has been shown to greatly decrease the level of glycosylated hemoglobin in patients with elevated Streptozotocin-induced diabetes (STZ) [49] Specifically, the study investigated the effects of M. oleifera leaves in the alloxan induced diabetic rats which showed decrease in blood glucose level at the end of 21days. [50] M. Oleifera has a hypoglycemic and hypolipidemic effect, and its leaves water extraction may improve blood glucose levels in people with diabetes. Overall, the extract or powder from its leaves improved insulin secretion, glycogen production and absorption of glucose in the liver and muscles, hence influencing type I and type II diabetes. [51]

2. Antioxidant activity

revealed that M. Oleifera leaves have higher antioxidant activity than stems. [52] Additionally, M. oleifera leaves and roots extracts, both aqueous and alcoholic (methanolic & ethanolic), indicate potent in vitro antioxidant and radical scavenging activity. [53] It has investigated that the antioxidant activity of methanol extract of M. oleifera in diabetes-induced nephritic male wistar rats and concluded that M. oleifera has excellent ability to protect against oxidative damage and was also able to enhance antioxidant status and reduced lipid peroxidation. [54] In a study using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical technique, M. oleifera also shown excellent antioxidant activity from the majority of isolated chemicals within several in vitro bioassays. [55] Moreover, an in vivo investigation carried out on normal and obese male mice showed that the intracellular anti-inflammatory and antioxidant effects of Moringa seed extract could improve metabolic health. [56] Phenolic chemicals found in M. Oleifera were shown to have antioxidant properties this was verified by phytochemical screening of the hydro-ethanolic extract. Also various bioactive substances are found in its pods, these substances chelate metal ions, quench reactive oxygen species, and replenish antioxidants that are membrane-bound. [57]

3. Antimicrobial And Antifungal Activity

Different components of M. Oleifera have been utilized to treat different human illnesses, according to pharmacological reports. The extracts displayed diverse levels of antibacterial and antifungal activity on the tested microorganism. The leaf ethanol extract of Moringa oleifera exhibited the widest range of action against the test bacterium, according to antibacterial activity of the extracts on bacterial isolates. [58] Alkaloids, amino acids, cardiglycosides, flavonoids, saponins, steroids, terpenoids, and tannins are among the plant's antibacterial constituents. Notable antibacterial qualities are also shown by the antibiotic chemical pterygospermine, which is produced from flowers. [59] According to a different study, M. oleifera leaves have inhibitory qualities, making them a viable alternative treatment for several fungal diseases and wounds. [60] The growth of E. Coli, P. aeruginosa, and S. aureus bacteria is negatively impacted by moringa root extracts, whereas M. oleifera leaves, in both juice and hydroalcoholic extracts, show antibacterial ability against both Gram-positive and Gram-negative bacteria. [61,62,63] The numerous parts of this plant can be utilized as a herbal remedy to combat infectious disorders brought on by different bacteria that are quickly developing treatment resistance it also shows that the antibacterial activity of the leaves, however, was superior to that of the roots. [64]

4. Anti-inflammatory  Activity

Inflammation is one of the most prevalent symptoms of many chronic illnesses. [65] The crude ethanol extract of dried seeds decreased the inflammation in the hind paw of mice that was brought on by carrageenan. Additionally, the crude ethanol extract of dried seeds' hexane fractions, together with the butanol and water fractions, inhibited inflammation. [66] When P. gingivalis bacteria was used to cause inflammation, M. oleifera leaf extract demonstrated anti-inflammatory properties. Additionally, in cases of periodontitis, the extract can lessen the synthesis of the pro-inflammatory cytokine IL-6 brought on by the P. gingivalis bacteria. [67] According to reports, the pod extract alleviated inflammatory-related disorders such as atopic dermatitis, asthma, rheumatoid arthritis, cancer, and allergic rhinitis. [68] Additionally, nitric oxide inhibitory action was identified in 4-[2-o-Acetyl-alpha-l-rahamnoslyloxy) benzyl] thiocynate, an isolated chemical from Moringa, which was later confirmed to be efficacious in Raw264.7 cell lines. [69] TNF-alpha production was suppressed by a substance called aurnatiamide acetate and 1,3-dibenzylurea, which were obtained from M. oleifera roots. [70] Additional research demonstrates M. oleifera's capacity to suppress cytokines (TNF, IL-6) that cause tissue illness and damage as well as cytokines (IL-8) that encourage neutrophil infiltration into the lungs. [71] The active chemical ingredients, which include tannins, phenols, alkaloids, flavonoids, carotenoids, b-sitosterol, vanillin, and moringin, were found to have anti-inflammatory effect. [72]

5. Anticancer Activity and Antitumar Activity

Cancer is a noncommunicable illness with an extremely high mortality rate. M. oleifera includes bioactive 4-(-L-rhamnosyloxy) benzyl isothiocyanate, nizimicin, b-sitosterol-3-O-D-glucopyranoside, and ITC type MIC-1, which can stop the growth and multiplication of cancer cells. halt tumor angiogenesis and slow carcinogenesis to induce apoptosis. [73] An M. oleifera leaf extract impairs the growth of all types of cancer cells.. This implies that it can be applied to treat different kinds of cancer. [74] Rather than being caused by a single phytoconstituent, the anticancer activity of M. oleifera leaves is most likely the result of many phytoconstituents working together. [75] According to recent research, M. oleifera root extract efficiently destroys all forms of cancer cells, including HepG2, MCF7, Caco-2 cells, and HCT 116. Aside from that, this extract significantly kills cancer cells that were the focus of those studies. [76,77]  Human cancer cells that include breast cancer cell type MDA-MB-231, HCT-8 cells and A549 lung cancer cells have also been used to illustrate the plant's potential anticancer activity utilizing the ethanolic extracts from its leaves. [78] It contains a range of bioactive compounds with anticancer effects, such as thiocarbamate, which has been hailed as a potent anticancer drug, and niazimicin, which suppresses tumour promoter teleocidin B-4-incited Epstein-Barr virus activation. [79] Fruit and leaf extracts, both alcoholic and hydro-methanolic, have demonstrated a important reduction in tumor growth in a mouse model of melanoma. The most affinity for binding to BRCA-1 is exhibited by rutin in M. oleifera, according to a recent computational modeling study. [80] M. oleifera leaf extracts have demonstrated consistent anti-tumor and anti-cancer properties in Ehrlich's solid tumor implanted mice, as demonstrated by the stimulation of apoptosis and inhibition of tumor growth. [81]

6. Antiallergic Activity

Rat basophilic leukemia (RBL-2H3) cells were used to test the anti-allergic activity of the extracts of the leaves, seeds, and pods of the identified compounds for both early and late phases of allergic reactions and Ketotifen fumarate was used as a positive control. Inhibitions were seen in both the extract and the pure chemicals, suggesting a possible application as an anti-allergic medication candidate. [82] A positive skin-prick test on fresh M. oleifera leaves can still be seen in the context of IgE sensitization, and it is verified as the causative allergen by prick testing with fresh leaves, despite claims that M. oleifera reduces histamine release from mast cells. [83] It has been proposed that M. Oleifera aqueous extract reduces mast cell activation and enhances the Th1/Th2 (skewed T helper type 1/2) balance to Th1 dominance in allergic mice, hence mitigating allergy symptoms. Clarifying mode of anti-allergy activity could offer fresh perspectives on its potential as a reliable aliments for the relief of type 1 allergy. [84]

7. Antiviral Activity

The public's health can be seriously jeopardized by viral infections, hence treatment and prevention are crucial. Investigation demonstrates the antiviral properties of M. oleifera leaves by showing that the ethanolic extract of the leaves prevented plaque development in herpes simplex virus type 1 (HSV-1) infections and decreased the mortality of HSV-1 infected mice. [85] Additionally, the aqueous extract dramatically lowers the amount of HBV cccDNA by inhibiting the hepatitis B virus. [86] Aqueous extract of M. oleifera leaves has been found to have significant antiviral activity against Foot and Mouth disease (FMD), one of the deadliest animal diseases. [87] Moreover, a daily treatment dose of 750 mg/kg of M. oleifera ethanol extract prevented the formation of skin lesions, decreased mice mortality, and lengthened the life period of mice infected with herpes simplex virus type 1 (HSV-1). [88] M. Oleifera is widely utilized to treat HIV-related secondary infections and AIDS. It shown notable antiviral activity against viruses such as NDV, FMDV, HSV, HBV, and HIV. [89] According to a study, M. oleifera seed works well against IAVs because it prevents the virus from replicating and shields the host cells from its cytopathic effects. Additionally, several viral infections, including the Newcastle disease virus (NDV) and the influenza A virus (IAV), were effectively inhibited by its extracts. [90,91,92] Additional research reveals that the crude ethanolic extract of M. oleifera exhibited virucidal activity against over 80% of H1N1 and SARS-CoV-2 viruses. [93]

8. Anti-ulcer Activity

It has been demonstrated that M. Oleifera extract considerably lowers free radicals, balances the acidic nature of gastric juice, and prevents the development of stomach ulcers. [94] It has been found that the plant's flavonoids prevent ulcer formation by enhancing microcirculation and capillary resistance, which reduces cell damage. [95] Because M. oleifera leaf aqueous extracts have anti-inflammatory and antioxidant properties, they provide gastroprotection against acid-alcohol-induced ulcers. [96] According to reports, the leaf extract significantly decreased the ulcer index in both the pyloric ligation test and the stomach ulcer model created by ibuprofen. [97] The another results represents that M. oleifera's ethanolic root-bark extract significantly reduced ulceration in albino Wistar rats. It showed promise as an antiulcer medication by lowering gastric acidity, lessening the severity of ulcers, and raising gastric pH. As a result, it has beneficial cytoprotective, antisecretory, and antiulcer properties. [98]

9. Hepatoprotective Activity

Current studies indicate that liver problems can be effectively treated with Moringa oleifera. The methanol extract of Moringa oleifera has hepatoprotective properties because it contains quercetin. [99] The results of the investigation clearly show that M. Oleifera extract protected the rats' livers against the negative effects of paracetamol. By raising antioxidant enzymes and anti-inflammatory mediators while lowering pro-inflammatory mediators, M. Oleifera extract, at a dose of 300 mg/kg/day, demonstrated protective activity that was very similar to silymarin, at a dose of 100 mg/kg, according to hepatotoxicity indicators. [100] Crude extracts from M. oleifera seeds have shown promise as a herbal treatment for liver illnesses in vitro, with HepG2 cells showing promise as both a preventative and therapeutic agent for liver damage. [101] A study found that the stem, leaves, flowers, and seeds of M. oleifera all have hepatoprotective qualities. Additionally, the study shows that antitubercular medications such isoniazid, rifampicin, and pyrazinamide can harm rat liver. Nonetheless, a hepatoprotective effect of the ethanolic extract made from Moringa oleifera leaves suggests that it can be able to lessen the liver damage that these drugs cause. [102] The study was to evaluated the hepatoprotective role of M. oleifera extract on acetaminophen-induced liver fibrosis in albino rats and results showed a significant decrease in liver enzymes, TNF-?, and TGF-? in the treated and prophylactic groups. [103] Also M. oleifera leaves may inhibit hepatic steatosis by influencing the expression of genes linked to the synthesis of hepatic lipids, which lowers triglyceride and cholesterol levels and reduces liver inflammation. [104]

10. Analgesic/antipyretic Activity

Several pre-clinical studies conducted on rats have confirmed Moringa Oleifera's analgesic effects. Study on alcoholic extract of moringa seed and leaves showed a comparative analgesic efficacy between aspirin and indomethacin. [105] According to a different investigation, the alcoholic extract and the M. oleifera seed extract both exhibited strong analgesic action that was comparable to aspirin at a dosage of 25 mg/kg of body weight. Similarly, a number of studies have demonstrated that M. oleifera seeds have strong analgesic efficacy in conjunction with the common medication aspirin, establishing the use of M. oleifera seeds as a regular analgesic. [106]

11. Antihypertensive Activity

All-cause morbidity and mortality globally are mostly associated with one major modifiable risk factor, which is hypertension. Of the 8 billion people on the planet, about 33% have hypertension. [107] The anti-hypertensive properties of M. oleifera indicate that consuming raw leaves or extracts of the plant is positively correlated with the animals' reduced blood pressure. [108] Rats with high salt diet-induced hypertension showed an antihypertensive effect from the hydroalcoholic extract of M. oleifera seeds. It also dilates the aorta, which is constricted by norepinephrine, and greatly increases salt excretion and diuresis. [109] The study examined the effects of root extracts on hypertension in normotensive Sprague Dawley rats. The results indicated that the extracts, when extracted with dichloromethane and petroleum ether, decreased mean arterial blood pressure to a point camparable to the control group. [110] The in vitro investigations suggest that the M. Oleifera leaves methanolic extract  inhibit the Angiotensin converting enzyme and could be useful in hypertention. [111] Furthermore, it was observed that the chemicals naacicin-A, naacimin-A, and naaciminin-B from the ethanolic leaf extract have strong antihypertensive effect by inhibiting angiotensin converting enzyme. [112] Other in vivo studies showed that the systolic blood pressure of N-nitro l-arginine methyl ester (l-NAME)-induced hypertension mice was considerably reduced in animals fed with crude methanol and ethyl acetate extracts of M. oleifera. [113] Additionally, M. oleifera leaf extract used in vitro has a smooth muscle relaxant effect on blood vessels. This effect is most likely caused by inhibiting calcium influx, which is mediated by the Gq-signalling pathway and depolarization-dependent voltage-operated calcium channels. [114] The finding state that the extract from M. oleifera leaves improves the haematological parameters in hypertensive Wistar rats. According to this, the leaf extract may be utilized to treat hypertension because it possesses antihypertensive qualities. [115]

12. Hypolipidemic Activity

The study's findings indicate that the methanolic root extract and column-fractions of the Moringa oleifera plant exhibit antihyperlipidemic effect, as indicated by a decrease in triacylglyceride and total cholesterol. Furthermore, the plant's ability to modify the lipid profile for a healthy cardiovascular state is indicated by the  decreasing effect on atherogenic risk predictors. [116] M. oleifera leaf extract for its hypolipidemic effect in adult Wistar rats exposed to cadmium. Both hyperlipidemia and hypercholesterolemia were seen in response to cadmium exposure, and treatment with M. oleifera leaf extract resulted in a significant reduction in triglyceride, total cholesterol, high density lipoprotein(HDL), low density lipoprotein(LDL), and very low density lipoprotein levels(VLDL). [117] Additionally, the potential of mulberry and moringa as possible useful dietary ingredients for reducing the risk of obesity and hyperlipidemia is supported by the antiobesity and antihyperlipidemic effects of M. oleifera leaf, mulberry leaf as well as mulberry fruit. [118] Numerous chemical substances, including flavonoids and other phenolic entities, may have an impact on lipid control and contribute to these effects. [119]

13. Neuroprotective Activity

In PC-12 cells, the concentrated polyphenols and phenolic extract from moringa leaves have shown potent neuroprotective effects against H2O2-induced oxidative stress. [120] The primary method deployed to evaluate M. oleifera's neuroprotective properties was in vitro and in vivo tests with the crude extracts.. There has been evidence of neuropharmacological activity for both known and isolated M. oleifera components, including phenolic acids and flavonoids, as well as for moringin, astragalin, and isoquercitrin. [121] According to a study, M. oleifera's di-ethyl-ether root extract can change amount of norepinephrine and epinephrine in the brain and serum of rats that appear to be in better health. This finding raises potential that the extract can protect animals against depressive and neurodegenerative symptoms. [122] Long-term use of moringa can restore acetylcholine levels, slow the progression of Alzheimer's disease (AD), improve spatial memory, reduce escape latency, and minimize oxidative stress. It also reverses dementia-like diseases by boosting glutathione levels and inhibiting MDA, cholinesterase, nitric oxide, and amyloid levels. [123] Moringa has been linked to a decrease in mitochondrial damage, apoptosis oxidative stress and reactive oxygen species production in relation to Parkinson's disease (PD). A constituent of moringa called sulforaphane has been demonstrated to guard against Parkinson's disease (PD) by targeting transcription factor Nrf2 in an effort to prolong dopaminergic neuron life. [124] Recent findings shows that the M. Oleifera extract might have pharmacological characteristics that prevent MPTP-induced neuronal injury in mice. It may therefore be employed as a therapeutic drug to shield dopaminergic neurons from the neuronal damage caused by PARP1. [125]

14. Immunomodulatory Activity

M. oleifera leaf extract demonstrated both immunostimulatory and immunosuppressive properties for immunomodulatory action. [126] The results highlight the adaptable effectiveness of M. oleifera plant extracts in decreasing inflammation in activated immune cells, implying potential therapeutic uses in immune system disorders, organ transplantation, and immunocompromised conditions such as HIV or acquired immune deficiency syndrome (AIDS). In conclusion, M. oleifera stimulates activated cells while inhibiting resting or unstimulated cells through context-dependent immunomodulatory effects on immune cells. Additionally, research has demonstrated that the ethanolic leaf extract of M. oleifera can shield immune cells from the cytotoxicity of melamine, a frequent contaminant and adulterant in food. [127,128] Additionally, it is advised to supplement with M. Oleifera leaf powder to improve the immune system and defense against A. hydrophila infection in rainbows, which in turn promotes immunostimulation and accelerates growth performance. [129] Furthermore, the plant used animal models of immunity in experiments to activate the immune system through humoral and cellular immunity. [130]

TOXICITY  AND SAFETY STUDIES

Several investigations unequivocally showed that M. oleifera bark extracts are non-toxic to rats and did not cause any casualties. [131] besides revealed no negative effects on the organisms and organs under study, indicating that M. oleifera may be safe to use in experimental animals. [132] Furthermore, it is mentioned that in low- and middle-income nations, the seed powder might enhance the quality of the supernatant and may be utilized as an easily accessible, reasonably priced conditioner for home wastewater sludge thickening. [133] Through the use of melanoma cells (A375, A2058) and usual human dermal fibroblasts (NHDF, WS1), M. oleifera leaf extracts was evaluated using the WST-1 test. These findings proved that M. oleifera extract could, via a dose-dependent manner, stop the growth of both melanoma cells. However the maximum concentration (200 mg mL?1), M. oleifera extract did not significantly inhibit either normal human somatic cell (IC50 > 200 mg mL?1), and after 48 hours, it only mildly cytotoxically affected normal cells. [134,135] The extract might be safe up to 2,000 mg/kg alone dose, according to findings of an acute toxicity study that showed zero mortality at 2,000 mg/kg dose and subchronic toxicity, whereas 150, 300, and 600 mg/kg extract has been given in both sexes for a period of ninety days in order to assess toxicity of M. oleifera leaf methanol extract in Wistar rats and cytotoxic abilities. [136] In both acute and subchronic experiments, the toxic effect of M. oleifera water extract was examined. Mice were administered extract orally at doses of 6400, 250, 500 and 1500 mg/kg, respectively, and via intraperitoneally(IP) at a dose of 1500 mg/kg. The results of these studies indicated that the extract was safe. [137] For the purpose of determining acute toxicity (LD50), 100 g of ethanol extract concentrate and thirty (30) mature mice (30–40 g) were utilized. The results indicated that an LD50 of 3900 mg/kg resulted in mice mortality. Thus, M. Oleifera can be safely consumed in moderation to support health. [138] However, a repeated dose of 1000 mg/kg of the plant extract is deemed hazardous and should not be used as an alternative medicine or food supplement. On the other hand, shorter periods of delivery and lower doses could be utilized safely for medicinal purposes. [139] Hydroalcoholic Moringa seed extract enhanced with isothiocyanate-1 has recently been shown to be safe in mid to low rat groups without causing harmful responses on that organs. [140] Therefore, M. oleifera are safe to use within a particular dose range.

CONCLUSION

Moringa oleifera Lam. is an essential medicinal plant, and one of the most widely cultivated species. This review highlighted the multifaceted pharmacological activities of various extracts of M. oleifera on in-vitro and in addition on animal models also. Review also summarized the  phytochemicals , toxicity and safety of M. oleifera as a multi-purpose medicinal plant.

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