Moringa oleifera: a systematic review of its botany, traditional uses, phytochemistry, pharmacology and toxicity

Abstract

Objectives

Moringa oleifera (M. oleifera) Lam (Moringaceae) is a perennial plant broadly used in South Asia and Africa as a traditional folk medicine to treat many ailments such as paralysis, helminthiasis, sores and skin infections. The review provides a critical and comprehensive evaluation of the botany, traditional uses, phytochemistry, pharmacology, toxicity, agricultural economy and dietary benefit of M. oleifera and its future perspectives.

Key findings

In this review, the entire plant of M. oleifera, containing diverse phytochemicals, is summarized. The 163 chemical components, included flavonoids, carbamates, glucosinolates, phenols, and so on with various bioactivities, such as anti-tumour, antioxidant, anti-inflammatory, and so on. Additionally, M. oleifera is toxic at certain doses; and overuse can cause genotoxicity.

Summary

Although M. oleifera has been widely used in traditional medicine, the pharmacological studies that have been conducted so far are not sufficient for its use in the setting of evidence-based medicine. Little relevant data from clinical trials of M. oleifera have been reported. The majority of studies of its constituents, such as carbamates and glucosinolates, have been conducted only in vitro. Owing to a lack of available data, the pharmacology, toxicity, agricultural economy and dietary benefit of its constituents and extracts require further evaluation.

Moringa oleifera Lam, ethnobotany, carbamates, glucosinolates, pharmacological activity, toxicity

Introduction

Ethnobotany of Moringa oleifera Lam

Moringa oleifera Lam (Moringaceae) is a member of the genus, Moringa, which has 14 other species.^[1] According to ‘The Plant List’ (http://www.theplantlist.org), M. oleifera is the only acceptable name for this plant; and no synonyms have been reported for it.

The height of the tree ranges from 5 to 10 m. It consists of three-pinnate compound leaves with leaflets 12–18 mm long and petiole yellow, which is yellow or white without red stripes. The flowers of M. oleifera are bisexual, which is white or milky white. Its pods and seeds are nearly spherical (Figure 1). The optimum growth temperature of M. oleifera is from 25 to 35°C. It is hardly affected by drought, which accounts for the adaption of a variety of soil types.^[2–4]

Figure 1

M. oleifera leaves, flowers, fruits and seeds.

M. oleifera is also known as drumstick tree or horseradish tree, dandalonbin, Mulangay, Mlonge, Benzolive, Sajna, Kelor, Punjabese, Sujna, Marango and Saijihan.^[5] It is native to the Himalayas of north-western India^[4] and currently, it is widely distributed in India, the Philippines, Ceylon, Thailand, Malaysia, Myanmar, Pakistan, Singapore, the West Indies, Cuba, Jamaica and Nigeria,^[2] and still spreading to other areas.

Traditional uses

Since ancient times, M. oleifera has been consumed as food or as a folk medicine in Oriental countries.^[6] It is nutritious and almost all parts of the plant are edible.^{[6, 7]} According to a report, it was consumed as a nutrient during pregnancy and breastfeeding in Africa, India and Nicaragua for many years.^[3]

In addition to being a rich source of mineral nutrients, M. oleifera also contains various amino acids and trace elements necessary for the human body. Its nutritional value is equivalent to that provided by spirulina.^[8]

In India, Pakistan, the Philippines, Hawaii and in African countries, such as Nigeria, the leaves, fruits, flowers and immature pods of this tree are used as food.^[9–11] In Malaysia, M. oleifera seeds are directly consumed, while in other countries, young leaves are used in salads, vegetable curries, or made into seasonings for daily use.^[3]

The seeds of M. oleifera have significant cohesive and antibacterial properties.^[12] Traditionally, they are used for water purification in Asia, Africa and rural areas of India, the Philippines, Sudan and Malawi.^{[10, 13–15]}M. oleifera seeds are used as biodiesel, which is ascribed to the high yield of M. oleifera Lam and Moringa seed oil. It is also used as animal feed owing to its high nutrient levels.^[16–18

As a medicinal plant, the leaves, fruits, roots and seeds of M. oleifera have been traditionally used to treat paralysis, helminthiasis, sores and skin infections.^[19] Traditionally, it has been used in India in the holistic system of Ayurveda, owing to its pharmacological properties.^[20] In Thailand, the leaves and pods are used as antipyretics and antidotes,^[21] while in South Asia and India, it is used for its anti-aging properties.^[22]

This review reveals the possible relationship between traditional use and modern pharmacological activity, summarizes the efficacy of the chemical components of M. oleifolia, especially the value of agricultural economy and nutrition and also summarizes the potential toxicity of M. oleifolia. This provides new insights into the development of potential new drugs, agricultural products or health products.

Phytochemistry of M. oleifera

According to the literature, the chemical constituents of M. oleifera, including those in its leaves, seeds, roots, flowers, gum, barks and fruit pods, have been extensively studied and can be broadly divided into flavonoids, carbamates, glucosinolates, phenols, steroids and carotenoids. The levels of the phytoconstituents of M. oleifera are summarized in Table 1.

Table 1

Chemical constituents of M. oleifera Lam

No.	Compound name(s)	Tissue(s)	Ref.
Flavonoids
1	Astragalin	Leaves	[23]
2	Quercetin-3-O-(6″-malonylglucoside)	Leaves	[24]
3	Quercetin-3-O-rhamnosylglucoside	Seeds, Leaves	[24]
4	Kaempferol-3-O-(6″-malonylglucoside)	Leaves	[24]
5	Quercetin-3-O-β-d-(6″-O-3-hydroxy-3-methylglutaryl)-glucoside	Leaves	[25]
6	Kaempferide-3-O-2″,3″-diacetylglucoside	Leaves	[26]
7	Kaempferol-3-O-[β-glucosyl-(1→2)]-[α-rhamnosyl-(1→6)-O-β-glucoside-7-O-arhamnoside	Leaves	[26]
8	Kaempferide-3-O-(2″-O-galloylrhamnoside)	Leaves	[26]
9	Kaempferide-3-O-(2″-O-galloylrutinoside)-7-O-α-rhamnoside	Leaves	[26]
10	Kaempferol-3-O-[α-rhamnosyl-(1→2)]-[α-rhamnosyl-(1→4)-β-glucoside-7-O-α-rhamnoside	Leaves	[26]
11	Quercetin 3-O-rutinoside	Pods	[27]
12	Quercetin 3-O-glucoside	Seeds, leaves	[27]
13	Kaempferol 3-O-rutinoside	Pods	[27]
14	Isorhamnetin 3-O-(6″-malonylglucoside)	Pods	[27]
15	Quercetin	Seeds	[27]
16	Kaempferol	Seeds	[19]
17	Kaempferol-3-O-β-d-glucopyranoside	Leaves	[28]
18	Quercetin-3-O-β-d-glucopyranoside	Leaves	[28]
19	Isoquercitrin	Leaves	[21]
20	7-O-(β-d-glucopyranosyl)-5-O-Menaringenin-4′-[α-l-rhamnopyranosyl-(1→2)]-β-d-glucopyranoside	Stems	[29]
21	Quercetin-3-O-β-d-(6″-O-malonyl)-glucoside	Leaves	[21]
22	Kaempferol-3-O-β-d-(6″-O-malonyl)-glucoside	Leaves	[21]
23	Myricetin	Leaves	[30]
24	Isorhamnetin	Leaves	[31]
25	Apigenin	Leaves	[31]
26	Daidzein	Leaves	[32]
27	Genistein	Leaves	[32]
28	Luteolin	Leaves	[31]
29	Quercetin-O-3,7-diglucoside	Leaves	[33]
30	Apigenin-O-8-glucoside	Leaves	[33]
31	Quercetin-O-3-glucoside	Leaves	[33]
32	Apigenin-7-C-glucoside	Leaves	[33]
33	Kaempferol-O-3,7-diglucoside	Leaves	[33]
34	Quercetin-3-acetylglucoside	Leaves	[33]
35	Kaempferol-O-3-glucoside	Leaves	[33]
36	Kaempferol-O-7-glucoside	Leaves	[33]
Carbamates
37	Niazinin A	Pods, Leaves	[34]
38	Niazinin B	Leaves	[35]
39	Niazimicin	Leaves	[35]
40	Niazimimin A	Leaves	[35]
41	Niazimimins B	Leaves	[35]
42	O-methyl-4-[(2′,3′,4′-tri-O-acetyl-α-L-rhamnosyloxy) benzyl] carbamate (E)	Leaves	[36]
43	O-methyl-4-[(2′,3′,4′-tri-O-acetyl-α-L-rhamnosyloxy) benzyl] carbamate (Z)	Leaves	[36]
44	O-ethyl-4-[(2′,3′,4′-tri-O-acetyl-α-L-rhamnosyloxy) benzyl] carbamate (E)	Leaves	[36]
45	O-methyl-4-[(4′-O-acetyl-α-L-rhamnosyloxy) benzyl] carbamate (E)	Leaves	[36]
46	O-methyl-4-[(2′,3′,4′-tri-O-acetyl-α-L-rhamnosyloxy) benzyl] thiocarbamate(E)	Leaves	[36]
47	O-methyl-4-[(2′,3′,4′-tri-O-acetyl-α-L-rhamnosyloxy)benzyl] thiocarbamate (Z)	Leaves	[36]
48	O-ethyl-4-[(2′,3′,4′-tri-O-acetyl-α-L-rhamnosyloxy) benzyl] thiocarbamate (E)	Leaves	[36]
49	Niazidin	Pods	[37]
50	O-ethyl-p-hydroxy benzyl thiocarbamate	Pods	[37]
51	O-ethyl-4-[(α-L-rhamnosyloxy)-benzyl] carbamate	Pods	[38]
52	O-n-butyl-4-[(α-l-rhamnopyranosyloxy) benzyl]thiocarbamate	Seeds	[39]
53	O-ethyl-4-[(α-l-rhamnopyranosyloxy)-3-hydroxybenzyl]thiocarbamate	Seeds	[39]
54	S-methyl-N-thiocarbamate	Pods	[39]
55	Niazicin A	Pods	[39]
56	Marumoside A	Leaves	[21]
57	Marumoside B	Leaves	[21]
58	Methyl-4-(α-l-rhamnopyranosyloxy)benzyl carbamate	Leaves	[21]
59	N-benzylcarbamic acid	Root barks	[40]
60	4-Aminobenzoic acid	Root barks	[40]
61	Aurantiamide acetate	Root barks	[40]
62	Pterygospermin	Root barks, leaves, pods	[41]
63	Me-N-4-(α-l-rhamnopyranosyloxy)-benzyl carbamate	Seeds	[42]
64	S-methyl-N-{4-[(α-l-rhamnopyranosyloxy)benzyl]} thiocarbamate	Leaves	[34]
65	N-[4-(β-l-rhamnopyranosyl)benzyl]-1-O-α-d-glucopyranosyl-thiocarboxamide	Seeds	[43]
66	Methyl-N-{4-[(4′-O-acetyl-α-l-rhamnopyranosyl)benzyl]} carbamate	Seeds	[43]
67	4-(β-d-glucopyranosyl-1→4-α-l-rhamnopyranosyl)benzyl thiocarboxamide	Seeds	[42]
68	O-ethyl,4-[(2′,3′,4′-tri-O-acetyl-α-l-rhamnosyloxy)benzyl] thiocarbamate (Z)	Leaves	[36]
69	O-ethyl-4-[α-l-rhamnosyloxy)benzyl] thiocarbamate(Z)	Leaves	[36]
70	Aglycon of deoxy-niazimicine (N-benzyl, S-ethylthioformate)	Root barks	[44]
71	1,3-Dibenzyl urea	Roots	[45]
Phenols
72	Cryptochlorogenic acid	Leaves	[46]
73	4-O-(4′-O-α-d-glucopyranosyl)-caffeoyl quinic acid	Leaves	[47]
74	4-O-(3′-O-α-d-glucopyranosyl)-caffeoyl quinic acid	Leaves	[47]
75	Methyl 2-[4-(α-l-rhamnopyranosyl)phenyl]acetate	Seeds	[43]
76	1-O-phenyl-α-L-rhamnopyranoside	Seeds	[43]
77	Gallic acid	Seeds	[19]
78	p-Coumaric acid	Seeds	[48]
79	Ferulic acid	Seeds	[48]
80	Vanillin	Seeds	[49]
81	Caffeic acid	Seeds	[48]
82	Protocatechuic acid	Seeds	[48]
83	Cinnamic acid	Seeds	[48]
84	Ellagic acid	Seeds	[19]
85	4-Hydroxymellein	Stems	[49]
86	Moringyne	Seeds	[50]
87	Benzoic acid 4-O-α-rhamnosyl-(1→2)-β-glucoside	Leaves	[26]
88	Benzoic acid-4-O-β-glucoside	Leaves	[26]
89	Benzaldehyde-4-O-β-glucoside	Leaves	[26]
90	Benzyl β-d-xylopyranosyl-(1→6)-β-d-glucopyranoside	Leaves	[21]
91	Benzyl-β-d-glucopyranoside	Leaves	[21]
92	4-(α-l-rhamnopyranosyloxy) Benzaldehyde	Root barks	[40]
93	Methyl vanillate	Root barks	[40]
94	De-O-methyllasiodiplodin	Root barks	[40]
95	Methylparaben	Root barks	[40]
96	p-Hydroxybenzaldehyde	Stems, Rootbarks	[40]
97	Methyl ferulate	Stems	[40]
98	Trans-ferulic acid	Stems	[40]
99	Epicatechin	Leaves	[32]
100	Catechin	Seeds	[48]
101	Lasiodiplodin	Stems	[40]
102	p-Hydroxybenzoic acid	Stems	[40]
103	Benzyl β-d-arabinopyranosyl-(1→6)-β-d-glucopyranoside	Stems	[40]
104	Benzoic acid	Stems	[40]
105	Methyl-p-hydroxybenzoate	Pods	[45]
106	α-Tocopherol	Leaves	[45]
107	γ-Tocopherol	Leaves	[45]
108	2-Hydroxylcoumaric acid	Leaves	[51]
109	Sinapic acid	Leaves	[51]
110	Gentistic acid	Leaves	[51]
111	Syringic acid	Leaves	[51]
112	4-O-(4′-O-α-d-glucopyranosyl)-caffeoyl quinic acid	Leaves	[47]
113	4-O-(3′-O-α-d-glucopyranosyl)-caffeoyl quinic acid	Leaves	[47]
114	Chlorogenic acid	Leaves	[47]
115	4-O-caffeoyl quinic acid	Leaves	[47]
116	5-O-caffeoyl quinic acid	Leaves	[47]
Glucosinolates
117	4-[(2′,3′,4′-tri-O-actyl-α-l-rhamnosyloxy)benzyl] nitrile	Leaves	[36]
118	Niazirinin	Leaves	[39]
119	Methyl-1-aminopentasulfide-5-sulfinate	Pods	[37]
120	Phenylacetonitrile	Root barks	[40]
121	Niazirin	Seeds, leaves	[34]
122	4-[(β-d-glucopyranosyl)-(1→3)-(α-l-rhamnopyranosyl)] phenylacetonitrile	Fruits	[43]
123	4-[(2′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate	Pods	[34]
124	4-[(3′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate	Pods	[34]
125	4-[(4′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate	Pods	[34]
126	4-[(α-l-rhamnosyloxy)benzyl]isothiocyanate	Pods	[34]
127	Sulforaphane	Pods	[52]
128	Glucomoringin	Seeds	[53]
129	Glucosinalbin	Seeds	[53]
130	4′-O-acetyl-4-(α-l-rhamnosyloxy)-benzyl glucosinolates	Seeds	[54]
131	3-hydroxy-4-(α-l-rhamnosyloxy)-benzyl glucosinolates	Seeds	[53]
132	4-(2′-acetyl-α-l-rhamnosyloxy)-benzyl glucosinolates	Seeds	[53]
133	4-(3′-acetyl-α-l-rhamnosyloxy)-benzyl glucosinolates	Seeds	[53]
134	4-(4′-acetyl-α-l-rhamnosyloxy)-benzyl glucosinolates	Seeds	[53]
135	Glucoraphanin	Seeds	[53]
136	Glucoiberin	Seeds	[53]
137	Benzyl glucosinolate	Seeds	[53]
138	Glucotropaedlin	Seeds	[53]
139	Glucobarbarin	Seeds	[53]
140	Glucoraphenin	Seeds	[53]
141	4-O-(α-l-acetylrhamnopyranosyloxy)-benzyl glucosinolate isomer 3	Roots	[24]
142	4-O-(α-l-acetylrhamnopyranosyloxy)-benzyl glucosinolate isomer 1	Roots	[24]
143	4-O-(α-l-acetylrhamnopyranosyloxy)-benzyl glucosinolate isomer 2	Roots	[24]
Steroids
144	β-Sitosterol	Seeds	[22]
145	3-O-(6′-O-oleoyl-β-d-glucopyranosyl)-β-sitosterol	Seeds	[55]
146	β-Sitosterol-3-O-β-d-glucopyranoside	Seeds	[22]
147	β-Sitosterone	Roots	[45]
Carotenoids
148	β-Carotene	Leaves	[56]
149	Lutein	Leaves	[56]
Others
150	Glycerol-1-(9-octadecanoate)	Seeds	[22]
151	O-[2′-Hydroxy-3′-(2″-heptenyloxy)-propyl undecanoate	Pods	[38]
152	α-Phellandrene	Roots	[45]
153	p-Cymene	Roots	[45]
154	O-(1-heptenyloxy) propyl undecanoate	Pods	[45]
155	Mthionine	Seeds	[56]
156	Cysteine	Seeds	[56]
157	Phytates	Leaves	[57]
158	Methyl-1-aminopentasulfide-5-sulfinate	Pods	[37]
159	d-mannose	Flowers	[45]
160	N,N′-bis{4-[(α-l-rhamnosyloxy) benzyl]} thiourea	Seeds	[58]
161	Moringine	Seeds	[59]
162	Pyrrolemarumine-4’’-O-α-L-rhamnopyranoside	Leaves	[21]
163	N,α-L-rhamnopyranosyl vincosamide	Leaves	[60]

Flavonoids

Flavonoids have a wide spectrum of pharmacological effects that have attracted the interest of scholars. Almost all flavonoids (1~36) are found in the leaves, with quercetin (15) and kaempferol (16) being the representative compounds.^{[19, 27, 48]} They are mainly in the bound form of glucosides. To date, 36 flavonoids (Figure 2) have been isolated from M. oleifera and classified as flavonols (1–25, 28–36) and isoflavones (26, 27).

Figure 2

Structures of 36 flavonoids of M. oleifera.

Astragalin (1) was detected using HPLC and its quantitative analysis was successfully performed using a Hypersil BDS C18 column.^[46] Several studies have suggested the radical scavenging activity of astragalin (1), isoquercitrin (19), isorhamnetin (24) and rutin (3).^{[61, 62]}

Five flavonol glycosides (6–10) were isolated in a study,^[26] and quercetin-3-O-rutinoside (11), quercetin-3-O-glucoside (12), kaempferol 3-O-rutinoside (13), isorhamnetin-3-O-(6″-malonylglucoside) (14) were detected exactly in stems, leaves, flowers and pods of M. oleifera, respectively.^[27]

Previous studies have demonstrated the antioxidant properties of kaempferol (16) and quercetin (15).^[19] Additionally, quercetin-O-3,7-diglucoside (29), apigenin-O-8-glucoside (30), quercetin-O-3-glucoside (31), apigenin-7-C-glucoside (32), kaempferol-O-3,7-diglucoside (33), quercetin-3-acetylglucoside (34), kaempferol-O-3-glucoside (35), kaempferol-O-7-glucoside (36) isolated from M. oleifera leaves exhibited antioxidant activity.^[33]

The presence of these compounds can be attributed to the pharmacological properties ascribed to M. oleifera and existing studies can improve our knowledge on flavonoids and provide a basis for further research for the biosynthesis and mechanism of flavonoids.

Carbamates

Carbamates are bioactive compounds and are also present in M. oleifera (37~71) (Figure 3). Compounds 38–51 were isolated in studies.^[35] Niazinin A (37), niazimicin (39), niazimimin A (40) and niazimimin B (41) were found to be effective in managing hypertension.^[35]O-methyl-4-[(2′,3′,4′-tri-O-acetyl-α-l-rhamnosyloxy)benzyl]thiocarbamate (E) (46), O-methyl-4-[(2′,3′,4′-tri-O-acetyl-α-l-rhamnosyloxy)benzyl]thiocarbamate (Z) (47), O-ethyl-4-[(2′,3′,4′-tri-O-acetyl-α-l-rhamnosyloxy)benzyl]thiocarbamate (E) (48) and O-ethyl-4-[α-l-rhamnosyloxy)benzyl]thiocarbamate (Z) (49) have been shown to reduce arterial blood pressure in normotensive anaesthetized rats.^[36] In 2006, a research group isolated compounds 52~54 and found that S-methyl-N-thiocarbamate (54) was a novel carbamate compound exhibiting anti-inflammatory activity.^[39]

Figure 3

Structures of 35 carbamates of M. oleifera.

4-(β-d-Glucopyranosyl-1→4-α-l-rhamnopyranosyloxy)-benzylthiocarboxamide (67) and methyl-N-4-(α-l-rhamnopyranosyloxy)benzylcarbamate (63) have been shown to have significant antibacterial activity at 5 mg/L.^[42] Additionally, pterygospermin (62), with appreciable antibacterial properties, was isolated from the roots of M. oleifera.^[41]

Phenols

To date, 45 phenols (72~116) (Figure 4), including their esters and glycosides, have been isolated from the leaves and seeds of M. oleifera. The basic skeleton of these phytochemicals comprises a phenolic hydroxyl substituted aromatic ring.

Figure 4

Structures of 45 phenols of M. oleifera.

Phenols, which act as free radical scavengers or chelating agents as antioxidants, are the predominant chemical constituents of M. oleifera leaves. The structure of 4-O-(4′-O-α-d-glucopyranosyl)-caffeoylquinic acid (73) and 4-O-(3′-O-α-d-glucopyranosyl)-caffeoylquinic acid (74) isolated from its leaves were elucidated using spectroscopic analyses. These compounds were found to inhibit neuraminidase and found to have antioxidant properties in the 1,1-diphenyl-2-picrylhydrazyl (DPHH)-free radical scavenging assay.^[47] Epicatechin (99) and catechin (100) were reported to possess antioxidant and bactericidal activities.^[48] Cryptochlorogenic acid (72), chlorogenic acid (114), 4-O-caffeoyl quinic acid (115) and 5-O-caffeoyl quinic acid (116) were the other compounds that have been found in M. oleifera leaves. Studies report that chlorogenic acids (114) have several biological activities and have been used for their antibacterial, antioxidant, cancer suppression activities and for the regulation of glucose and lipid metabolism.^[63] Methyl-2-[4-(α-l-rhamnopyranosyl)phenyl]acetate (75) and 1-O-phenyl-α-l-rhamnopyranoside (76) were found in M. oleifera fruits, with cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibition assays, the later have significantly stimulated insulin release.^[43]

Compounds 77~83 were identified using HPLC by comparison with the retention times of the standard compounds. They were found to have antioxidant activities as well as antibacterial effects against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Yersinia enterocolitica.^[48] A series of phenol glycosides (87–89) were isolated from the methanol extract of M. oleifera leaves.^[26] Besides, 4-O-(4′-O-α-d-glucopyranosyl)-caffeoyl quinic acid (112), 4-O-(3′-O-α-d-glucopyranosyl)-caffeoyl quinic acid (113), chlorogenic acid (114), 4-O-caffeoyl quinic acid (115), 5-O-caffeoyl quinic acid (116) are also found from the leaves of M. oleifera.^[51]

Glucosinolates (117~143)

4-[(2′,3′,4′-tri-O-actyl-α-l-rhamnosyloxy)benzyl] nitrile (117) was isolated from M. oleifera leaves and identified using chemical and spectroscopic methods of analysis.^[36] The structure of methyl-1-aminopentasulfide-5-sulfinate (119), isolated from the fresh pods of M. oleifera, was identified using gas chromatography–mass spectrometry (GS-MS).^[37] In 2014, niazirin (121), isolated from the fruits of M. oleifera, was reported to possess anti-inflammatory activities.^[40] 4-[(β-d-Glucopyranosyl)-(1→3)-(α-l-rhamnopyranosyl)] phenylacetonitrile (122) isolated from M. oleifera fruits has potential as an antimicrobial^[43] agent (Figure 5).

Figure 5

Structures of 27 glucosinolates of M. oleifera.

Four isothiocyanates, including 4-[(2′-O-acetyl-α-l-rhamnosyloxy) benzyl]isothiocyanate (123), 4-[(3′-O-acetyl-α-l-rhamnosyloxy) benzyl]isothiocyanate (124), 4-[(4′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate (125) and 4-[(α-l-rhamnosyloxy)benzyl]isothiocyanate (126) have been isolated. Studies reveal that these compounds have anti-inflammatory effects and the mechanism of action is attributed to the inhibition of nitric oxide (NO) activity and decreasing the expression of inducible nitric oxide synthase (iNOS).^[34] Additionally, the antibacterial activities of these compounds have also been reported.^[42] Subsequently, in 2016, sulforaphane (127) was shown to have potential as a cancer chemopreventive, which is changing the growth of cells that mediated by oncogenic signal transducer and activator of transcription 5 (STAT5).^[52]

Compounds 128, 129 and 131~140 were isolated and their structures were elucidated using different MS approaches.^[53] Three monoacetyl isomers of 4-(α-l-rhamnopyranosyloxy)-benzyl glucosinolate (141~143) were reported to be present in high concentrations in the roots of M. oleifera.^[24]

Steroids (144~147)

3-O-(6′-O-oleoyl-β-d-glucopyranosyl)-β-sitosterol (146) and β-sitosterone (147) were isolated from M. oleifera seeds and roots, respectively.^{[45, 55]} β-sitosterol (144), which is isolated from the seeds of M. oleifera^[22] was found to have hypotensive activity^[38] (Figure 6).

Figure 6

Structures of 4 steroids of M. oleifera.

Carotenoids (148~149)

Carotenoids, as a micronutrient, exist in many plants and also play an important role in preventing diseases and improving immunity.^[64] β-Carotene (148) and lutein (149) were isolated from the leaves of M. oleifera (Figure 7).^[56]

Figure 7

Structures of 2 carotenoids of M. oleifera.

β-Carotene (148) is a precursor of vitamin A. Several studies suggest that this compound has anticancer and antioxidant activities and is also known to enhance immune responses.^[64–66]

Lutein (149) has anticancer and antioxidant activities and has also been shown to be useful in cardiovascular disease. Additionally, it protects the eyes and prevents macular degeneration.^[67]

Others (150~163)

In addition to the aforementioned components, some other components of M. oleifera have also been identified. In 1997, methyl-1-aminopentasulfide-5-sulfinate (159), the only polysulfide compound, was isolated from the pods of M. oleifera.^[37] The following year, O-[2′-hydroxy-3′-(2″-heptenyloxy)-propyl undecanoate (151) was isolated from the whole pods of M. oleifera and its structure has been deduced.^[38] In 2001, the amino acids, methionine (155) and cysteine (156), were isolated from M. oleifera seeds, which are important for human health (Figure 8).^[56]

Figure 8

Structures of 14 others ingredients of M. oleifera.

Alkaloids are a class of naturally occurring nitrogen-containing basic compounds and have several pharmacological activities, such as anticancer, anti-tumour, cardiovascular and central nervous system (CNS) effects. The rarely found glycosides of the pyrrole alkaloid, pyrrolemarumine-4″-O-α-l-rhamnopyranoside (162) and N,α-l-rhamnopyranosyl vincosamide (163), were isolated from the leaves of M. oleifera; the latter shows promise as a cardioprotective agent in an in-vivo study.^[68]

Pharmacological Activities

Some of the phytochemicals of M. oleifera show anti-inflammatory and immune-regulation effects and also anti-tumour, antioxidant, antibacterial and antiviral activities (Table 2). They have also been reported to be effective in diabetes, renal calculi, ulcers, hypertension and in maintaining appropriate cholesterol levels.^{[20, 60]}

Table 2

Pharmacology activities of extracts and compounds of M. oleifera

Pharmacology activities	Sample	Ref.
Antioxidant	The MeOH extract of roots	[69]
	The MeOH extract of leaves	[69]
	The MeOH extract of stems bark	[69]
	The 90% (90 : 10 ethanol : water) hydro-ethanolic gradient extract of leaves	[70]
	The phenols of aqueous extract of leaves	[71]
	The aqueous extract of seeds	[72]
	The flavones and polysaccharides of MeOH extract of leaves	[73]
	The MeOH extract of fruit	[43]
	Compd 1	[61, 62]
	Compd 3	[61, 62]
	Compd 15	[19]
	Compd 16	[19]
	Compd 19	[61, 62]
	Compd 24	[61, 62]
	Compd 29	[33]
	Compd 30	[33]
	Compd 31	[33]
	Compd 32	[33]
	Compd 33	[33]
	Compd 34	[33]
	Compd 35	[33]
	Compd 36	[33]
	Compd 73	[47]
	Compd 74	[47]
	Compd 77	[48]
	Compd 78	[48]
	Compd 79	[48]
	Compd 80	[48]
	Compd 81	[48]
	Compd 82	[48]
	Compd 83	[48]
	Compd 99	[48]
	Compd 100	[48]
	Compd 114	[63]
Anti-tumour	The aqueous extract of pods	[74]
	The ethanol extract of fruit	[75]
	The aqueous extract of leaves	[76]
	The ethanol extracts of the leaf and bark	[77].
	The crude residue aqueous extracts of leaves	[78]
	The ethanol extract of drumsticks	[79]
	Compd 39	[80]
	Compd 126	[22]
	Compd 145	[22]
	Compd 146	[22]
Anti-hypertension and cholesterol	Thiocarbamates and isothiocyanate glycosides	[38, 81]
	Compd 37	[82]
	Compd 38	[82]
	Compd 39	[22]
	Compd 40+41	[82]
	Compd 46	[36]
	Compd 47	[36]
	Compd 48	[36]
	Compd 144	[36]
	Compd 147	[83]
Antibacterial and antifungal	The acetone fraction extract of leaves	[84]
	Endophytic fungus	[85]
	Compd 56	[86]
	Compd 62	[41]
	Compd 63	[42]
	Compd 67	[42]
	Compd 77	[48]
	Compd 78	[48]
	Compd 79	[48]
	Compd 80	[48]
	Compd 81	[48]
	Compd 82	[48]
	Compd 83	[48]
	Compd 99	[48]
	Compd 100	[48]
	Compd 114	[48]
	Compd 121	[86]
	Compd 126	[87]
Antiviral	The ethanol extract of leaves	[88].
	The hot water extract of leaves	[75]
Anti-inflammatory	The hydro-alcohol and chloroform fractions of seeds	[89]
	Compd 54	[39]
	Compd 61	[90]
	Compd 121	[40]
	Compd 123	[43]
	Compd 124	[34]
	Compd 125	[91]
	Compd 126	[91]
Antispasmodic and anti-asthma	The aqueous extracts of seeds	[92]
	The ethanol extract of seed kernel	[93]
Antiurolithiatic and diuretic activity	The aqueous extract of bark	[92, 94]
	The aqueous extract of flowers	[92]
	The aqueous extract of leaves	[92]
	The aqueous extract of roots	[92]
	The aqueous extract of seeds	[92]
	The aqueous extract of stalks	[92]
Anthelminthic	The ethanol extracts of leaves	[95, 96]
	The aqueous extracts of leaves	[96]
Hepatoprotection	The aqueous and ethanol extracts of root and flower	[97]
Immunomodulatory	The ethanol extract of leaves	[98, 99]
	The ethanol extract of leaves	[98, 99]
	The ethanol extract of leaves	[98, 99]
Against ulcer	The 50% ethanol extract of leaves	[100]
Antidiabetic	The dehydrated powder of leaves	[101]
	The aqueous of leaves	[101–103]
	The dehydrated powder of the leaves	[101]
	The aqueous extract of the leaves	[101–103]
	The MeOH extract of the leaves	[101]
	The MeOH extract the leaves	[101, 102, 104]
	The aqueous extract of leaves	[102, 103]
	The MeOH extract of leaves	[104]
	Compd 55	[58]
	Compd 64	[58]
	Compd 66	[58]
	Compd 75	[43]
	Compd 76	[58]
	Compd 122	[58]
	Compd 160	[58]

Anti-tumour activity

In 2018, 18.1 million new cases of cancer were reported worldwide,^[105] making it one of the leading causes of global death.^[106] In recent decades, M. oleifera has been demonstrated to possess promising anti-tumour and cytotoxic activities. In 1998, two thiocarbamates, namely, niaziminin, niazimicin and a known isothiocyanate, 4-[4′-O-acetyl-α-l-rhamno-syloxy)benzyl]isothiocyanate were isolated from M. oleifera leaves. It was reported that niazimicin has no inhibitory activity, while niaziminin (IC50 = 1.3 μM) and 4-[(4′-O-acetyl-α-l-rhamno-syloxy)benzyl]isothicyanate (IC50 = 1.0 μM) were potent inhibitors of the Epstein-Barr virus. The cytotoxic and cytostatic effect of 4-[4′-O-acetyl-α-l-rhamnosyloxy)benzyl]isothiocyanate was presumed to be attributed to the interactions of the isothiocyanate group with cellular components. The activity of niaziminin is attributed to an acetoxy group at the 4′-position,^[80] as opposed to that of isothiocyanates. In 1999, it was found that the test compounds 4-α-l-rhamnosyloxybenzyl isothiocyanate (126), niazimicin (39), 3-O-6′-O-oleoyl-β-d-glucopyranosyl-β-sitosterol (145) and β-sitosterol-3-O-β-d-glucopyranoside (146), with IC50 values of 32.7, 35.3, 70.4, 70.4 μm, respectively, were capable of inhibiting the activation of Epstein–Barr virus-early antigen and showed potential as anti-tumour agents. Furthermore, an in-vivo two-stage carcinogenesis test on mouse skin indicated that niazimicin (39) is effective as an anti-tumour agent in chemical carcinogenesis.^[22]

Since the pure compounds of M. oleifera are known to exhibit anticancer activity, in 2011, a research group worked on an aqueous extract of M. oleifera pods and demonstrated that it prevents colon cancer by significantly decreasing the nuclear antigen indices of proliferating cells and suppressing the expression of inducible iNOS and COX-2.^[74] In 2012, the extracts of M. oleifera leaves were found to inhibit cell proliferation in a concentration-dependent manner (P < 0.05). When treated with M. oleifera leaves extract (200 μg/ml), the inhibition rate was as high as 80%. An alcoholic extract of M. oleifera fruit could reduce the survival rate of liver cancer HepG2 cells.^[75] The analysis of the apoptotic signals after the oral administration of M. oleifera leaf extract showed inhibition of the proliferation of human liver cancer HepG2 cells and A549 non-small-cell lung cancer cells.^[76] This study revealed that the aqueous extract of M. oleifera leaves could be used as an alternative to overcome the common problems associated with anticancer drugs, such as poor water solubility; therefore, it may be a promising therapeutic candidate drug in the treatment of certain cancers.

In 2015, the anticancer activity of the extract in colon cancer cells was reconfirmed. An in-vitro study suggested that the alcoholic extracts of the leaf and bark of M. oleifera (over 500 μg/ml) were cytotoxic to colon and breast cancer cells. It arrested the cell cycle in the G2/M phase and reduced the survival rate of HCT-8 and MDA-MB-231 cells.^[77] Although solvent cytotoxicity was not evaluated, this was the first study to evaluate the anticancer properties of M. oleifera leaves, barks and seeds and lay a research foundation for the further development of new drugs to treat breast cancer and colon cancer. The ethanolic extract of M. oleifera was demonstrated to have anti-leukaemic effects.^{[107, 108]} It should be further evaluated to determine its mechanism of action and toxicity for use as a natural anticancer drug.

Emerging evidence suggests that M. oleifera can be used to prevent cancers. In 2013, a study found that the crude residue aqueous extracts of M. oleifera leaves inhibited the proliferation of A549 lung cancer cells by increasing oxidative stress, DNA fragmentation and inducing cell apoptosis.^[109] Other studies report that this effect results from damage to the mitochondria caused by reactive oxygen species (ROS).^[110] The ethanol extract of M. oleifera was found to increase the activities of liver pigments Cytochrome b5 and Cytochrome P450 enzyme in phase I metabolic reactions, as well as glutathione transferase, glutathione peroxidase, glutathione reductase, catalase (CAT) in phase II, inhibiting lipid peroxidation. This finding shows the potential of the extract as a chemopreventive in chemical-induced carcinogenesis.^[79] In addition, M. oleifera can interfere with several signalling pathways. GMG-ITC (4-(α-l-rhamnopyranosyloxy)-benzyl ITC) is a potent inhibitor of the STAT5 and nuclear factor-kappa B (NF-κB) pathways and to a lesser extent, STAT1/STAT2 signalling pathways, which are involved in cancer.^[52] The aqueous extract of M. oleifera leaves shows significant inhibition in the growth of three pancreatic cancer cells, namely, Panc-1, P34 and COLO-357 and also interferes with the nuclear factor-k-gene-binding (NF-κB) signalling pathway.^[78] It increases the toxicity of cisplatin to human pancreatic cancer cells.^[111] These results collectively suggest that several disease mechanisms may be interrelated; therefore, more in-vivo studies should be designed to explore the anti-tumour mechanisms of the constituents of M. oleifera after the active compounds responsible for anticancer activity have been identified.

Antidiabetic activity

Diabetes is a group of severe and complex metabolic disorders characterized by hyperglycaemia. The global incidence of diabetes is increasing and has become a serious concern. The prevention and treatment of diabetes have, therefore, aroused extensive attention from our society and adequate measures are being taken to ease this burden.^{[112, 113]} It is estimated that the total number of adult patients afflicted with diabetes is 439 million.^[114] Up to now, antibiotics were used to treat complications caused by diabetes mellitus; however, some antibiotics, such as pentamide, have proven to be toxic to pancreatic β-cells in in-vivo studies.^[115] As a broad-spectrum antibiotic, streptozotocin induces β-cell mitochondrial vacuolization. It also induces dilatation of the endoplasmic reticulum, causes DNA-strand breaks and decreases the level of ATP in β cells. Several phytochemicals, including those from M. oleifera, have been shown to be effective in the management of diabetes, especially type 2 diabetes. The dehydrated powder of the leaves, as well as the aqueous, methanolic and ethanolic extracts (leaves, pods, seeds, stems and root barks), have significant potential as antidiabetic agents. It has been reported that the residue from the aqueous extract of M. oleifera can treat streptozotocin-induced diabetes and type 1 diabetes.^[101] A series of tests in the streptozotocin-induced diabetic mouse model indicate that the extract of M. oleifera leaves has significant antibiotic activity. It can restore the normal structure of pancreatic β-cells in adult rats with diabetes mellitus.^[116–121]

In addition to their use as antibiotics, some chemicals can induce damage to the pancreas, resulting in its inability to modulate high blood glucose levels. In alloxan-induced hyperglycaemia rats, it has been shown that the hypoglycaemic properties of M. oleifera extracts bring about a rise in the temperature and a reduction in weight loss and metabolic indices.^{[122, 123]}

Besides, M. oleifera can also reduce postprandial hyperglycaemia by inhibiting the activity of α-amylase and α-glucosidase. A kinetic study of glucose uptake in vivo reveals that an aqueous extract of M. oleifera leaves can promote the regeneration of pancreatic β-cells and reduce blood glucose levels and reduce intestinal glucose absorption, likely due to the inhibition of the activity of glucose transporters.^{[102, 103]} The compounds niazicin A, methyl-N-{4-[(α-l-rhamnopyranosyl)benzyl]}carbamate, methyl-N-{4-[(4′-O-acetyl-α-l-rhamnopyranosyl)benzyl]}carbamate, 1-O-phenyl-α-l-rhamnopyranoside and 4-[(β-d-glucopyranosyl)-(1→3)-(α-l-rhamnopyranosyl)]phenylacetonitrile extracted from M. oleifera fruit could stimulate insulin release of 15 ± 33 ng insulin/mg of protein and the most significant activity was exhibited by 1-O-phenyl-α-l-rhamnopyranoside and methyl-N-{4-[(α-l-rhamnopyranosyl)benzyl]}carbamate, which releases ~30 ng insulin/mg of protein.^[43] A study using HepG2 cells and streptozotocin-induced mouse model of diabetes reports that isolated compounds, N,N′-bis{4-[(α-l-rhamnosyloxy) benzyl]}thiourea (161), Niazirin A and S-Methyl-N-{4-[(α-rhamnosyloxy) benzyl]}thiocarbamate (64), can promote glucose consumption in insulin-resistant cells and reduce blood glucose levels in streptozotocin-induced mice.^[58]

Quinine has been extracted from many plants and there are several reports on its antidiabetic activity.^[124] A study using an alcoholic extract of M. oleifera leaves shows that the antidiabetic activity of quercetin > chlorogenic acid > moringinine and the extracts of M. oleifera leaves can restore the histological structure of the pancreas in alloxan-induced diabetic rats.^[104] However, the optimal dosage of these compounds should be determined.

Studies have also shown that low-dose aqueous extracts from M. oleifera leaves have anti-diabetic effects and can inhibit the activity of the glucose transporter and reduce the rate of glucose absorption through the intestinal membrane.^[102] In 2018, M. oleifera leaf powder was observed to reduce the absorption of glucose in the gut and skeletal muscle of diabetic mice.^[125] These results suggested that M. oleifera leaves have the potential as an antidiabetic compound either as a single or compound dosage form. However, further investigation is required before considering it as a new candidate as an antidiabetic drug.

As a rich source of phenols, proteins, vitamins and minerals, the pharmacological potential of M. oleifera has attracted considerable attention. The hypoglycaemic activity of M. oleifera has been confirmed using animal experiments. A clinical trial aimed at the Indian population showed that serum glucose and low-density lipoprotein (LDL) levels were lowered in patients with type II diabetes when the leaf powder of M. oleifera was administered.^[126] However, a larger trial with a more diverse ethnic population is warranted to substantiate these results.

Anti-hypertension and cholesterol-lowering activity

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases. It is not only one of the leading causes of death in China but it is also prevalent worldwide.^[8]

Reports have shown that apart from reducing hypertension, M. oleifera extracts also have cholesterol-lowering effects. Thiocarbamates and isothiocyanate glycosides present in the fruit pods and seeds of M. oleifera were shown to have anti-hypertensive properties.^{[38, 81]} An in-vivo study reveals that the mustard oil glycosides of M. oleifera leaves bring about a dose-dependent hypotensive effect by inhibiting tissue contractions. This is not similar to atropine blocking the vasodilation caused by acetylcholine.^[127] However, the toxicity of these compounds has not yet been evaluated.

In high-fat mice, the crude extracts as well as the pure compounds of M. oleifera leaves can reduce cholesterol in serum, kidney and liver.^{[127, 128]} Niazinin A (37), niazinin B (38), niaziminin A + B (40+41) have been reported to have anti-hypertensive activity. These compounds inhibit the contraction of the rabbit aorta induced by K⁺ and ileal contraction induced by similar concentrations of acetylcholine (ACh) and histamine.^[82] Phytosterols from M. oleifera leaves, including β-sitosterol (147), suppress intestinal cholesterol absorption.^[82] A study published in 2002 reveals that alkaloids from M. oleifera leaves show anti-hypertensive activity, which is attributed to the presence of a calcium-channel blocker.^[83] Besides, it has been reported that the anti-hypercholesterolaemic activity in hypercholesterolemic rabbits may be owing to an increased excretion in the faeces in the form of neutral steroids.^[129]

In 2019, a study revealed that M. oleifera seeds and leaves modulated the activities of enzymes linked to hypertension and lipid metabolites in high-fat-fed rats.^[130] Further research found that the extracts inhibit the angiotensin-I-converting enzyme (ACE), acetylcholinesterase (AChE), phosphodiesterase-5 (PDE-5), arginase activities and significantly reduce NO and malondialdehyde (MDA) levels. These substances are closely related to hypertension and play an important role. The antioxidant properties of the extract and the effects of CAT, superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione (GSH), play a role in the anti-hypertensive effect. However, the appropriate dose of M. oleifera in reducing hypertension as well as the mechanism of action of these phytochemicals must be further explored.^[131]

Antibacterial and antifungal activity

Infectious diseases, mainly caused by viruses, bacteria, parasites or other pathogens, have adverse effects on health. They are highly contagious and have been the focus of public health in this century.^{[132, 133]} In 1981, the antibacterial and antifungal effects of the phytochemicals obtained from M. oleifera were reported. The study showed that 4-(α-l-rhamnosyloxy)benzylisothiocyanate isolated from M. oleifera seeds was responsible for antimicrobial activity and the minimal bactericidal concentration was reported to be 40 μmol/L for Mycobacterium phlei and 56 μmol/L for Bacillus subtilis.^[87] Subsequently, scientists began to pay attention to the biological activities of M. oleifera extract. A study in 1991 reported that the seeds and leaf extracts of M. oleifera Lam showed bactericidal effects against S. aureus and Pseudomonas aeruginosa.^[134] Then, in 2010, the filtrate of the crushed M. oleifera seeds was tested for its effect on the growth and photosystem II efficiency of the cyanobacteria, Microcystis aeruginosa. Results have shown that the filtrate obtained after pulverizing from M. oleifera seeds inhibited the growth of the bacterium.^[135] Additionally, the acetone fraction of M. oleifera leaves showed significant antibacterial activity against Klebsiella pneumoniae with a minimum inhibitory concentration of 0.78 mg/ml.^[84] Besides, in 2019, a study reported that the leaf, pulp and seed extracts of M. oleifera could inhibit certain autoimmune inflammatory diseases caused by bacteria, when used alone or in combination with conventional antibiotics.^[136]

Apart from the crude extract, niazimicine and niazirine were demonstrated to possess remarkable antibacterial properties (Vibrio species), with a phenotype compatible with virulence factors.^[137] Deoxy-niazimicine isolated from M. oleifera root bark was revealed to be active against Micrococcuspyogenes var. aureus, E. coli and Bacillus subtilis and was shown to have better antifungal activity compared with the crude extract of M. oleifera. It was tested against 14 pathogenic bacteria and six pathogenic fungi using the disc diffusion method.^{[44, 134]} Niazirin (121), marumoside A (56) and sitosterol-3-O-β-d-glucoside isolated from M. oleifera seeds were found to treat psoriasis-like lesions in vivo, by inhibiting the expression of T helper cell 17 (Th17)-relevant cytokines (IL-12/IL-23 p40, IL-17A, IL-22 and IL-23 p19). Since Th17 plays a critical role in the pathogenesis of psoriasis, these studies clearly show that M. oleifera and the isolated bioactive compounds could be potentially used as a drug to promote skin health.^[86]

In addition, Nigrospora sp. LLGLM003, an endophytic fungus of M. oleifera, has potent antifungal activity. Studies indicate that certain chemicals (griseofulvin, mellein) of Nigrospora sp. LLGLM003 were significantly active against the fungus, Botrytis cinerea, with IC50 of 6.09 μg/ml. On the whole, the four compounds isolated from the crude extract of Nigrospora sp. LLGLM003, namely, griseofulvin (1), de-chlorogriseofulvin (2), 8-dihydroramulosin (3) and mullein (4) have varying degrees of resistance to the following eight plant fungi: B. cinerea, Colletotrichum orbiculare, Fusarium oxysporum f. sp. cucumerinum, Fusarium oxysporum f. sp. melonis, Pestalotia diospyri, Pythium ultimum, Rhizoctonia solani and Sclerotinia sclerotiorum.^[85]

The active ingredients obtained from M. oleifera after extraction using different solvents vary and recent studies show that these chemical constituents have promising antibacterial and antifungal activities. However, there are a lack of clinical data and studies supporting the development of new antibacterial drugs to reduce the abuse of antibiotics by patients.

Antiviral activity

Viral infection can pose a significant concern to public health; therefore, prevention and treatment are of utmost importance. Studies show that the ethanolic extract of M. oleifera leaves inhibited plaque formation in herpes simplex virus type 1 (HSV-1) infections and decreased the mortality of HSV-1 infected mice (250 mg/kg/dose), thus indicating its antiviral effects.^[88] The aqueous extract of M. oleifera also inhibits the hepatitis B virus, significantly decreasing the level of HBV cccDNA.^[75] The ethanolic extract of M. oleifera leaves, at a dose of 750 mg/kg/day, was effective in HSV-1 infections, significantly delayed the development of skin lesions, prolonged the mean survival times and reduced the mortality in HSV-1 infected mice.^[88] It also may have moderate inhibitory activity against plant pathogens.^[138] As a new natural medicine to prevent and treat viral diseases, it needs to be further explored.

Antioxidant activity

ROS are mainly generated by the mitochondrial electron transport chain of cells. It can play a role in the development of many diseases such as cancers,^[139] diabetes, hyperlipidaemia,^[140] cardiovascular disease,^{[140, 141]} and neurodegeneration.^[142] Previous studies report that several plant extracts can prevent or treat certain diseases, which is presumably attributed to their antioxidant activity.^{[143, 144]} Based on these findings, the antioxidant activity can be confirmed.^{[73, 145]}

In 2009, a study revealed that polyphenols of M. oleifera leaves may be responsible for its overall antioxidant potential.^[19] Subsequently, in 2010, researchers found that the root, leaf and stem bark extracts of M. oleifera had IC50 values of 8, 15 and 19 mg/ml, respectively, and indicated potent radical scavenging and antioxidant activities.^[69] In the same year, the antioxidant activity of polyphenols extracted from the leaves, stems and root barks of M. oleifera was reconfirmed, which is associated with preventing cancers.^[69]M. oleifera leaves were found to have the highest antioxidant activity in the 90% (90 : 10 ethanol : water) ethanol–ethanol gradient extract, which is an optimal gradient solvent for M. oleifera leaves.^[70]

In a study exploring erectile dysfunction in mice, it was found that the phenol components in M. oleifera leaf extracts were able to scavenge NO- and OH-free radicals and had IC50 values are 0.52 mg/ml (OH*) and 1.36 mg/ml (NO*). It couples with Fe²⁺ in a dose-dependent manner (IC50 = 0.38 mg/ml) and inhibits lipid peroxidation. Coupling with Fe²⁺ may be the polyphenols and proteins in M. oleifera leaves.^[71] Compared with the extract of velvet bean, the extract of M. oleifera seeds was found to have better antioxidant activity, was found to be an effective scavenger of OH (IC50 = 50.23 mg/ml) and DPHH-free radicals (IC50 = 50.88 mg/ml) and could inhibit Fe²⁺-induced lipid peroxidation (IC50 = 50.18 mg/ml).^[72]

The volatile oil obtained by distilling the dried leaves of M. oleifera was found to have antioxidant effects.^[146] Interestingly, different drying methods change the chemical composition of M. oleifera leaves, which results in different antioxidant and enzyme activities. The flavones and polysaccharides extracted from M. oleifera leaves were shown to have oxygen-free radical scavenging abilities using the DPPH assay.^[73] In addition to the antioxidant activity of M. oleifera leaves, the methanolic extract of M. oleifera pods exhibited increased levels of the protein, SOD, GSH and CAT and significantly decrease lipid peroxidation.^[121] Besides, the methanolic extract of M. oleifera fruit can inhibit COX-1 and COX-2 and suppress the peroxidation reaction.^[43]

Active compounds with antioxidant activity were isolated from the crude extract. Studies confirmed that 4 (α-l-rhamnosyloxy)-benzyl isothiocyanate (133) from M. oleifera seeds has a protective effect on secondary injury after spinal cord injury, by virtue of a neuroprotective antioxidant mechanism.^[147] Several reports on the antioxidant activity and immunomodulatory function of polysaccharides, including a new arabinogalactan, MOP-1, isolated from M. oleifera seeds have also been shown to have antioxidant activity, owing to their dose-dependent and significant scavenging effect on DPPH-free radicals.^[148]

Overall, the antioxidant effects of M. oleifera extracts were demonstrated using a series of studies, including (1) inhibition of linoleic acid peroxidation, (2) scavenging activity on superoxide radicals with a dose-dependent manner, (3) scavenging DPPH radical by donating hydrogen atoms, (4)inhibition peroxidation of the cell membrane^[149] and (5) inhibition of COX-1 and COX-2. Many of these mechanisms are interconnected and related to other activities or diseases, such as inflammation, asthma, tumours and immune deficiency.

Anti-inflammatory effect

Inflammation is a defense response of the body to stimuli and may be associated with cancer, metabolic syndrome and cardiovascular disease.^[150] Traditionally, M. oleifera seeds are used in water purification.^[151] In LPS-stimulated mouse macrophages, M. oleifera seeds extracts were shown to regulate the production of NO, TNF-α and IL-1β, which are indices associated with inflammatory activity.

In 2010, a study found that the compounds isolated from M. oleifera fruit inhibited NO and reduced LPS-mediated iNOS expression.^[34] Subsequently, researchers have reconfirmed the anti-inflammatory activity.^[152] In 2014, compounds 4-[(α-l-rhamnosyloxy)benzyl] isothiocyanate (126) and 4-[(4′-O-acetyl-α-l-rhamnosyloxy)benzyl)isothiocyanate (125) were revealed to have anti-inflammatory activity at the gene level. Inflammation was induced in vitro in a murine tumourous monocyte model using LPS.^[91] The hydro-alcohol and chloroform fractions were observed to have anti-inflammatory effects in the acetic acid-induced acute colitis rat model.^[89]

Aurantiamide acetate (61) and 1,3-dibenzyl urea (71) isolated from M. oleifera root could inhibit the production of TNF-α and IL-2.^[90] 4-(α-l-rhamnyloxy)-benzylerucate (glucose isosyringate; GMG) was isolated from M. oleifera seeds and hydrolysed using myrosinase at neutral pH to obtain the corresponding GMG-ITC, which controls the reduction of pro-inflammatory mediators by activating NF-κB.^[147]

Overall, these mechanisms appear to be associated with each other; therefore, they should be further explored to help comprehend the mechanism of action of the components of this traditional plant in treating skin infections.

Antispasmodic and anti-asthma activity

Seeds of M. oleifera have antispasmodic activity with a median effective dose of 65.6 mg/ml bath concentration, in test rats of intestinal spasm, which was induced using acetylcholine hydrochloride.^[92] It provides a scientific basis in the traditional treatment of gastrointestinal disorders.

In Ayurveda, M. oleifera has been used to treat asthma and chronic rheumatism.^[6] A study reveals that the pharmacological activity is attributed to the alkaloid, moringine (162), which relaxes the bronchioles.^[59] Additionally, results from a study in rats revealed that the anti-asthma effect of the ethanolic extract of M. oleifera seed kernel was owing to its ability to inhibit the release of histamine. Histopathological studies reveal decreased infiltration of the inflammatory cells in the lung sections.^[93] Recently, clinical studies have further confirmed the anti-asthma effect of M. oleifera and provided a scientific basis for its use in traditional Indian medicine, Ayurveda and as a pharmaceutical agent.^[153] However, owing to the small sample size of 20 patients, further trials are needed to confirm the anti-asthma activity of M. oleifera and determine its optimal dosage.

Antiurolithiatic and diuretic activity

The urinary stone disease has afflicted humankind, which is found herbs to treatment since antiquity and can persist.^{[154, 155]} In 1992, a study revealed that the extract of M. oleifera has diuretic activity at a dose of 100 mg/kg.^[92] In 2010, the antiurolithiatic activity of the aqueous extract of bark of M. oleifera 400 and 800 mg/kg) was demonstrated, which significantly decreased the size of calculi in rats.^[94] However, the antiurolithiatic activity should be more explored in other animal models or clinical trials.

Anthelminthic activity

The leaf of M. oleifera is found to have a dose-dependent anthelmintic activity, which is better than that of Vitex negundo.^[95] Furthermore, in an in-vitro study, the leaf extracts inhibited egg embryonation, egg hatching and induced mortality of L1 and L2 larvae of Haemonchus contortus, indicating the anthelminthic activity of M. oleifera.^[96] However, the biologically active ingredients failed to point out that in these studies, the research can also develop natural medicines based on this characteristic for toxicity and related pharmacokinetic tests.

Hepatoprotection

Anti-tubercular drugs can cause hepatotoxicity resulting in severe liver damages. Purportedly, in this regard, M. oleifera can reduce these side effects. Hepatotoxicity was induced by paracetamol in Albino rats in a study and the results showed that the root and flower extracts of M. oleifera had hepatoprotective effects.^[97] This effect was significantly attributed to the β-carotene (148) in the leaves of M. oleifera.^[156]

The potential hepatoprotective mechanism is likely attributed to the reduction in serum glutamic oxaloacetic transaminase, serum alkaline phosphatase, serum glutamic pyruvic transaminase levels and interference with the related signalling pathways.^[156] Using a CCl₄-induced liver fibrosis model of the rat, it was deduced that hepatoprotective activity of M. oleifera seed extracts was owing to multiple factors, including antioxidant property, anti-inflammatory activity and inhibition of the activation of hepatic stellate cells.^[157] These results suggested that M. oleifera extracts can protect the liver from chemical-induced damage in animal models; some bioactive ingredients and mechanisms have been explored. However, further studies are needed to reconfirm this activity, both in vivo and in humans.

Immunomodulatory effects

The immune system comprises the immune organs, immune cells and immune molecules. It has three functions, namely, immune defense, immune stabilization and immune surveillance. A study conducted in 2010 reports the immunosuppressive activity of M. oleifera seeds.^[158] In 2015, an alcoholic extract of M. oleifera leaves was found to regulate the immune system by affecting T lymphocytes.^[98] Subsequently, in 2016, when studying the soluble fibre of M. oleifera seeds, it was found that moringa seed-resistant protein was an effective mitogen and could enhance lymphocyte proliferation and induce giant phagocytic cells to produce NO.^[159] In the same year, the aqueous extract of M. oleifera was found to enhance the production of interferon (IFN)-γ in lymphocytes and significantly increase the proportion of CD11b⁺ and CD49b⁺ subpopulations of macrophages and spleen cells in mice infected with HSV-1.^[99] The aqueous extract of M. oleifera leaves was found to have a dose-dependent inhibitory effect on the CNS.^[160] These results suggest that M. oleifera may show potential in regulating the immune system. However, many factors affect the CNS via an extremely complex signalling pathway and an excessive involvement of signalling molecules; therefore, the exact mechanism of M. oleifera extracts in regulating the immune system needs further research.

Others

Besides the above pharmacological properties discussed in this study, other applications of M. oleifera have also been reported, such as the use of its root extract, bark extract or leaf extract in abortion (to prevent implantation) and contraception (to prevent fertilization),^[161–164] and estrogenic activity that seems to be responsible to cause abortifacient activity.^{[165, 166]} The 50% alcoholic extract of M. oleifera leaves was observed to be effective against ulcer and significantly reduced the lesion index in a test model at doses of 100 mg/kg and 150 mg/kg.^[100]

A study published in the year 2000 indicated that the isothiocyanates of M. oleifera could inhibit platelet aggregation in humans. This effect was attributed to the oxidized form of sulfur and a central chain length of 6 or 8 was found to be suitable for optimal activity. Furthermore, the isothiocyanate moiety was necessary to achieve this effect.^[167] In 2013, a study found that seeds of M. oleifera could enhance blood clotting by a mechanism similar to that of chitosan interacting with negative charges of cell membranes of erythrocytes.^[168]

Toxicity

Most literature reports that M. oleifera has almost no toxicity. This could also be likely because very few toxicity studies have been conducted to date.^[169–171] However, a study evaluated the toxicity of the aqueous extracts of M. oleifera flowers and reported that it significantly (P < 0.05) delayed the development of Biomphalaria glabrata embryos and promoted mortality in adult snails with an LC50 of 2.37 ± 0.5 mg/ml and also in Artemia salina larvae with an LC50 of 0.2 ± 0.015 mg/ml. Studies have shown that temperature affects the activity of the extract when the ultraviolet (UV) index ranges from 1 to 14, temperature ranges from 25 to 30°C, and the relative humidity is 65%. The time required for molluscicidal activity is slightly reduced (17%). The toxicity to Aspergillus salina is also reduced and the LC50 is 0.28 ± 0.01 mg/ml.^[172]

In 2012, a study revealed that the LC50 of the aqueous seed extract of M. oleifera was 124.0 mg/ml, when fed to carp (Cyprinus carpio) for 96 h.^[173] In 2020, an in-vitro cytotoxicity test showed that the IC50 of the methanol extract of M. oleifera leaves was >1000 μg/ml.^[174]

Studies have shown that 4(α-l-rhamnosyloxy)benzylisothiocyanate was toxic even at low dosages of 50 mg and 22 mg/kg. 4(α-l-rhamnosyloxy) phenylacetonitrile, 4-hydroxyphenylacetonitrile and 4-hydroxyphenylacetamide were mutagenic to mice at a dosage of 40 mg/kg body weight.^[175]M. oleifera seed extracts at concentrations 0.6, 0.8, 1 and 1.5 μg/μL were mutagenic to Salmonella typhimurium strains TA97, TA98, TA100 and TA102. The extract, at a concentration of 0.8 μg/μL, interfered with the plasmid migration profile.^[176]

A supra-supplementation in Sprague-Dawley rats found that M. oleifera leaf extract is toxic at 20 mg/ml; however, it did not show genotoxic results. M. oleifera leaves are genetically toxic when used as a supplement level of 3000 mg/kg body weight.^[177] Furthermore, in-vivo studies in a murine model revealed that M. oleifera seed extract was hepatotoxic and nephrotoxic as well as showed blood toxicity. The extract at a dose of 46 mg/kg can significantly alter serum aminotransferase and plasma cholesterol levels, while a dose of 70 mg/kg can alter the total bilirubin, non-protein nitrogen, blood urea and plasma protein levels.^[176]

On the other hand, the aforementioned anti-reproducibility effects of M. oleifera root extract, bark extract and leaf extract are also called reproductive toxicity. When low doses of the M. oleifera root extract (10–50 mg/kg) were administered conjointly with estradiol dipropionate (EDP), there was not much change in the uterine wet weight and the uterine histoarchitecture of immature Swiss female rats. When higher doses of the M. oleifera root extract (200–600 mg/kg) were administered conjointly with EDP, there was a successive reduction in the uterine wet weight when compared with the gain seen with EDP alone. Maximum reduction was observed at the highest dose of 600 mg/kg. Uterine histoarchitecture also revealed inhibition of the luminal epithelium at these doses.^[165] The leave extract of M. oleifera at doses of 175 mg/kg showed 100% abortifacient activity.^[161]M. oleifera is an Indian traditional contraceptive medicine. The detailed usage method is as follows: M. oleifera leaves paste is prepared and mixed with paste of fresh M. oleifera root and in equal ratio. ½ teaspoon mixture is used to prepare 1 tablet and is taken daily in empty stomach after completion of the menstrual cycle.^[163] The roots and bark extracts of M. oleifera at the doses of 200 and 400 mg/kg could prevent implantation when administered for 7 days (1–7) of pregnancy.^[165] Therefore, the usage of M. oleifera, especially at high doses such as 600 mg/kg, needs to be cautious for women who are trying to get pregnant.

Agricultural Economy and Dietary Benefit

All parts of M. oleifera can be edible and animal consume.^[178] The fact is that M. oleifera is easily cultivable, which is hardly affected by drought and introduced in China more than 100 years.^{[2–4, 179]} Nowadays, M. oleifera has been developed in food (such as cakes, biscuits, etc.), health products, agricultural products, and so on (Table 3).^{[56, 188, 221, 238]}

Table 3

Composition, nutritional content and value of M. oleifera edible parts

	Composition	Nutritional content	Value	Ref.
Leaves	Flavonoids, carbamates, phenols, glucosinolates, carotenoids, terpenoids, steroids, organic acids, volatile oil, alkaloids	Macronutrients:Proteins (35%), moisture (7%), fats (16%), carbohydrate (7%), fibre (23%), ash (12%)Micronutrients:Amino acids: glumatic acid (2.660% ± 0.13%), aspartic acid (2.185% ± 0.06%), leucine (2.070% ± 0.15%), arginine (1.820% ± 0.06%), alanine (1.605% ± 0.33%), phenylalanine (1.595% ± 0.06%), lysine (1.540% ± 0.14%), glycine (1.450% ± 0.11%), valine (1.345% ± 0.12%), proline (1.280% ± 0.11%), threonine (1.265% ± 0.13%), isoleucine (1.155% ± 0.03%), serine (1.060% ± 0.04%), tyrosine (0.915% ± 0.08%), histidine (0.730% ± 0.03%), hydroxylysine (0.690% ± 0.04%), methionine (0.560% ± 0.08%), tryptophan (0.510% ± 0.03%)	Human:Food: vegetable, soups, condiment, food supplement/food fortification (biscuits, yoghurt), weaning foods	[5, 128, 149, 180–190]
Leaves	Proteins, carbohydrates, amino acids, minerals	Micronutrients:Amino acids: cysteine (0.280% ± 0.04%), taurine (0.105% ± 0.02%), hydroxyproline (0.100% ± 0.01%), ornithine (0.060% ± 0.01%)Vitamins: β-carotene, VA, VB-1 (0.006%), VB-2 (0.005%), VB-3 (0.08%), VB-5, VB-6, VB-9, VB-12, VC (22%), VE (44.8%).Minerals: Na (0.67 g/kg), K (29.60 g/kg), Ca (11.00 g/kg), P (6.32 g/kg), Mg (3.73 g/kg), Fe (132.0 mg/kg), Zn (30.10 mg/kg), Cu (5.89 mg/kg), Mn (16.70 mg/kg), Se (1.570 mg/kg), Mo (0.518 mg/kg),Co (0.080 mg/kg), Si (248.0 mg/kg), B (29.10 mg/kg), V (0.136 mg/kg), Al (65.30 mg/kg), Ni (1.49 mg/kg)	Medical use: anaemia, menstrual irregularities, stomach ache, sprains, constipation and piles, arthritis, fever, sore throat, skin healing, catarrh, bronchitis, headaches, deficiency vitamin C, vaginitis, hypoglycaemic, malaria, typhoid, anti-hypertensive effect, malnutrition, lipid-lowering, arterial plaque improvement, eliminating dampness and phlegm, anti-bacteria, anti-fungi, anti-tumour, spasmolytic, anti-cardiovascular, antifertility diuretic, cholesterol-lowering, anti-ulcer, hepatoprotection, aphrodisiac, antibiotic, reducing skin erythema, snake bites, scurvy, wounds, tumours, inflammations, helminthiasis, purgative, eye and ear infections	[5, 10, 77, 82, 91, 184, 191–204]
			Livestock: fodder	[6, 50]
			Agriculture/Industry: fertilizer, bio-pesticide, biogas, moisturizer and skin conditioner, lip balm, creams, growth promoters (zeatin), domestic cleaning agent, herbal moisturizing lotion/facial toner/soap	[6, 56, 184, 205]
Flowers	Flavonoids, alkaloids, polyphenols, tannins, terpenoids (β-amyrin), steroids (β-sitosterol), saponins, trypsin inhibitors, organic acids, proteins, vitamins, amino acids, minerals	Macronutrients:Proteins, organic acids (6.42% ± 0.01%)Micronutrients:Vitamins: VC, VA.Minerals: Ca, K, calcium antioxidants (α- and γ-tocopherol)Amino acids (31%): alanine, arginine, glutamic acid, glycine, serine, threonine, valine, lysine	Human:Food: vegetable, cake, honey (flower nectar), food fortification, weaning foods	[189, 206, 207]
			Medical use: arthritis, throat, infection, trypsin inhibitor, anti-parasitic, anti-inflammatory, anti-hypertensive, diuretic, antimicrobial, antioxidant, antidiabetic, anti-hyperlipidaemic, antipyretic, hepatoprotection, anticancer, anti-ulcer, cholagogue, diuretic, antidiabetic, tonic, anti-cardiovascular, splenomegaly, anti-catarrh, antimicrobial—bacterial and viral infection, against helminths parasites, anti-neoplastic, throat infection, rheumatism, hypocholesterolaemia, anti-arthritic, cholera,	[6, 97, 182, 201, 204, 206–218]
			stimulant, aphrodisiac, abortifacient, digestive problems, hysteria, swollen lymph nodes and glands of neck, decrease serum cholesterol, phospholipid, triglycerides, cholesterol, cough remedy
			Agriculture/Industry: bio-pesticide (B. glabrata against, Aedes aegypti)	[212]
Pods	Flavonoids, carbamates, phenols, glucosinolate, tannins, steroids, carotenoids, organic acids, proteins, carbohydrates, fibres, fats, vitamins, minerals, amino acids	Macronutrients:Proteins (44%), moisture (6%), fats (8%), carbohydrate (17%), fibre (23%), ash (2%)	Human:Food: vegetable, food fortification/food supplement	[5, 180, 182, 186, 189, 219]
		Micronutrients:Amino acids: alanine, arginine, glutamic acid, glycine, serine, threonine and valine, tryptophan (0.08%), lysine (0.15%), phenylalanine (0.04%), leusin (0.65%), isoleusine (0.44%), metdionine (0.14%), valine (0.54%), threonine (0.39%), arginine (0.36%), arginine (0.11%)Vitamins: VB-1 (0.005%), VB-2 (0.007%), VB-3 (0.020%), VC (12%)Minerals: K (25.9%), P (11%), Fe (0.530%), Ca (3%), Mg (2.4%), S (13.7%), K (25.9%), S (13.7%)	Medical use: arthritis, anti-parasitic, tonify the spleen and eliminate dampness, antiviral, anti-tumour, hypotensive, hypocholesterolaemia, obesity, diarrhoea and joint pain, anti-inflammatory, antioxidant and detoxification	[38, 79, 184, 206, 211]
Seeds	Flavonoids, carbamates, phenols, glucosinolates, steroids, carotenoids, alkaloids	Macronutrients:Proteins (35%), moisture (7%), fats (16%), carbohydrates (25%), fibre (16%), ash (1%)	Human:Food: vegetable, cooking oil, functional foods/food fortification (bread), nutraceuticals	[7, 16, 180, 181, 220, 221]
Seeds	Carbohydrates, amino acids, organic acids, minerals	Micronutrients:Amino acids: glumatic acid (3.724% ± 0.18%), aspartic acid (3.059% ± 0.02%), leucine (2.898% ± 0.22%), arginine (2.548% ± 0.08%), alanine (2.247% ± 0.46%), phenylalanine (2.233% ± 0.09%), lysine (2.156% ± 0.20%), glycine (2.030% ± 0.16%), valine (1.883% ± 0.17%), threonine (1.771% ± 0.19%), isoleucine (1.617% ± 0.05%), serine (1.484% ± 0.06%), proline (1.79% ± 0.16%), tyrosine (1.281% ± 0.11%), histidine (1.022% ± 0.04%), hydroxylysine (0.966% ± 0.06%), methionine (0.784% ± 0.12%), taurine (0.147% ± 0.03%), tryptophan (0.714% ± 0.04%), cysteine (0.392% ± 0.06%), hydroxyproline (0.140% ± 0.02%), ornithine (0.084% ± 0.02%).Vitamins: VB-1 (0.005%), provitamin A (~2%), VB-2 (0.006%), VB-3 (0.02%), VC (0.45% ± 0.017%), VE (75.167% ± 0.441%), tocopherols (α-, β-, γ- and δ)	Medical use: tonify the spleen and eliminate dampness, antipyretic, anti-hypertensive, anti-inflammatory, anti-tumour, anti-cardiovascular disease, antimicrobial, antifertility, rheumatism, anticancer, antiproliferative, neuralgia, intermittent fevers, ophthalmopathy, treat arthritis, urarthritis, spasm, skin ulcer and liver fibrosis, improve the immune system, anti-asthmatic and anti-rhinitis and treatment of bronchiole relaxation and respiratory tract infections	[77, 92, 131, 157, 184, 200, 222–227]
			Livestock: fodder	[228]
Seeds	Crude fat, fibre, ash, seed oil, vitamins, proteins (lectin)	Minerals: K (75.00 mg/kg), Na (1074.09 mg/kg), P (635 mg/kg), Ca (751.67 mg/kg), Mg (45.00 mg/kg), Fe (5.20 mg/kg), Mn	Agriculture/Industry: organic fertilizer, biodiesel, biosorbent.Ben oil: perfumes, skin lotion, hairdressings, cosmetics (gentle cleansing foam/cleansing oil gel/gentle exfoliating gel, moisturizer and skin conditioner, skin lotion, dual-phase waterproof eye make-up remover), lubricant for fine machinery, water purification, honey- and sugar cane juice-clarifier, insecticidal agents	[6, 7, 14, 16, 182, 189, 229–237]

The leaves and flowers of M. oleifera can be used in soups and salads, dry seeds and roots can be ground into powder as a seasoning, as well as the pods can be edible as a vegetable.^{[3, 225, 239, 240]} The flower nectar can be make honey.^[197] Since M. oleifera leaves can be used to increase mother’s breast milk during pregnancy, which is known as mother’s best friend.^{[5, 190]} All of these provide a new option for solving the food shortage problem in underdeveloped countries.^[241]

In addition to human consumption, M. oleifera is a good source of animal feed.^{[242, 243]} Leaves,^[244] pods and seeds as animal feed can not only significantly improve the dietetic nature of roughages,^[245] but improve the milk quality and quantity,^[246] meat production, beef production, and so on.^[245]

M. oleifera seeds are used to extract oil called the ‘ben oil’, which is not easy to decay, has good aroma fixation and stability, is edible.^{[247, 248]} At present, M. oleifera seeds possess great industrial values among all parts of this plant, it can be used as biodiesel,^[249] essential oil,^[250] skin care products,^[251] and can also be used as a raw material for industrial products such as perfumes, machine lubricants and high-grade natural soaps.^{[252, 253]}

Moreover, after oil extraction, the seed cake can be used as a substitute for water treatment. M. oleifera seeds contain flocculants and antibacterial substances that purify water.^{[254, 255]} The protein lectin, which is isolated from M. oleifera seeds, is non-mutagenic, with good recoveries, and remove mental ion in contaminated water.^{[237, 256]} At the same time, it can remove 90% of cercariae from the water, which is due to the antibacterial substances contained in the seeds of M. oleifera.^{[257, 258]} Since of its low cost, low toxicity and high flocculation ability, moringa seeds are widely used in water purification.^{[259, 260, 261]}

Additionally, leaves, seeds cake can be used as fertilizer.^{[239, 262]} Studies have shown that the extract of M. oleifera leaves can promote cell division and be used as bio-pesticide,^[263] all of these achieve increasing the crop yield.^{[6, 205]}

Discussion and Conclusions

This review mainly provides a systematic summary, focusing on the botanical and traditional uses, as well as the phytochemistry, pharmacology, toxicity and agricultural economy and dietary benefit aspects of M. oleifera. This review highlights the promising biological activities of M. oleifera, including anti-inflammatory, antioxidant, anti-tumour, hepatoprotective and immunomodulatory effects, which have attracted much attention. Although some pharmacological activities are not associated with the traditional uses of the plant, they could still provide valuable clues and be further developed.

Animal experiments revealed that the toxicity of M. oleifera was limited to the liver, kidney and blood and also indicated that an overdose may result in genetic toxicity. Therefore, determining its appropriate dosage of the chemical constituents of this plant is of great significance before use and provides a basis for future clinical toxicity research. The pharmacological activity of several phytochemicals obtained from M. oleifera is summarized in this study. Studies have shown that the oil from the seeds of M. oleifera has high levels of tocopherol, which has significant antioxidant activity. It has good potential as an antidiabetic agent and provides the basis for the future development of the plant components as moringa-related foods or effective drugs that have been or are being currently developed.

To establish and compare the therapeutic activities of the phytochemicals from this plant, pharmacokinetic and pharmacodynamic studies, as well as the toxicity of isolated compounds should be evaluated using in-vivo models with appropriate controls. Studying the dosages and comparing them with reference standards may help identify and isolate effective compounds.

As recent insights into the pharmacological mechanisms of M. oleifera are limited to in-vitro bioassays of a limited number of molecules, it is essential and urgent to investigate the mechanisms of these extracts or isolates using appropriate animal models. To the best of our knowledge, few relevant data from clinical trials of M. oleifera have been reported. Most clinical trials use a relatively small sample size; therefore, insufficient data have been generated. Thus, future studies should focus on parallelly studying the pharmacological effects, mechanisms of action and clinical applications of M. oleifera. Current studies have demonstrated that M. oleifera may serve as a convenient, affordable, relatively safe and readily available source of proteins and minerals. It continues to play an important role in the daily life of people, particularly in rural and developing areas. Therefore, it is not only recommended as a source of nutrients but also as a therapeutic agent in the management and treatment of several ailments.

This review summarized the pharmacological activities and the efficacy of aqueous, hydroalcoholic and alcoholic extracts of M. oleifera in-vitro as well as in animal models. Besides, the antioxidant activity of M. oleifera is closely related to the expression of many proteins and signalling pathways. Therefore, the development of combination therapy involving M. oleifera and other drugs to enhance drug efficacy can be a breakthrough in the treatment of several diseases. Overall, M. oleifera is valuable in the food, crop and pharmaceutical industry and could result in socioeconomic benefits.

Author Contributions

R.L. retrieved the relevant literature and drafted the manuscript. Y.J. and S.L. originated the work, led the discussions, provided helpful comments and revised the manuscript. J.L. and Q.H. provided helpful comments and revised the manuscript. All authors read and approved the final version of the manuscript.

Funding

This research did not receive any funding from public, commercial or non-profit sectors.

Conflict of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.