Table 1.

Summary of findings of safety and toxicity of M. oleifera in in vitro and in vivo studies.

Extracts	Concentration/Doses	Experimental Animal/Cell Line	Finding	Citation
In vitro studies
Aqueous leaf extract	80.0, 40.0, 20.0, 10.0, 5.0 mg/mL of M. oleifera extract	Human peripheral blood mononuclear cells (PBMCs)	Lactate dehydrogenase (LDH) released upon cell damage or lysis indicates processes that occur during apoptosis and necrosis. Thus, the number of cells corresponds to the intracellular activity of LDH. As extracts increased above 20 mg/mL, the amount of LDH was released proportionally, indicating its cytotoxicity.	[9]
Aqueous seed extract	-Aqueous seed extract: 0.78–50 μg/mL -Diluted seed extract: 6.25–400 μg/mL (only for PBMCs)	PBMCs, human pulmonary mucoepidermoid carcinoma (NCI-H292), human colon adenocarcinoma (HT-29), human larynx epidermoid carcinoma (HEp-2)	The IC50 of 144 μg/mL for PBMCs treated with diluted seed extract (used to treat drinking water) indicates that it was not cytotoxic to PBMCs and had low cytotoxic activity toward other cancer cell lines. None of the evaluations showed hemolytic activity, indicating no damage to the plasma membrane of erythrocytes.	[10]
Aqueous (AM), methanolic (MM) and petroleum ether (EM) leaf extracts	5, 25 and 62.5 µg/mL	Human embryonic kidney cells expressing SV40 large T-antigen (293 T), Henrietta Lacks cells	The 50% cytotoxic concentration (TC50) was 41.58 µg AM/mL for aqueous extract, 38.88 µg MM/mL for methanolic extract and 32.33 µg EM/mL for ether extract in the assay performed by MTT assay.	[11]
Ethanolic leaf extracts	400 to 0.02 µg/mL (serial-fold dilution)	Fibroblast cell line	The cytotoxic concentration 50 (CC50) was at 100 µg/mL as cell survival percentage decreased to 50%. The CC50 for twelve concentrations (0.02 to 50 µg/mL) was lower and safe. Two concentrations (200 µg/mL and 400 µg/mL) were above CC50 and were cytotoxic to fibroblast cells.	[12]
Ethanolic seed extract	30, 50, 66, 83 and 100 µg/mL	Human colorectal carcinoma cells (HCT-116), Normal human cell lines (HEK-293)	Non-treated groups (cancer cells MOS treatment) showed 100% cell viability, whereas cancer cells treated with MOS extract showed a significant decrease, suggesting that the treatment led to significant drop in cancer cell viability. No inhibitory action observed in HEK-293 cells (non-cancerous cells), postulating that the extract is non-cytotoxic to normal cells.	[13]
Ethanolic leaf extracts	100 to 500 μg/mL	Human cervix carcinoma cell line (Hela)	Positive control significantly reduced the cell viability to less than 25%. Extracts were considered cytotoxic when they reduced cell viability to less than 50%. Leaf extract significantly and concentration-dependently reduced the viability of Hela cells at concentrations above 260 μg/mL.	[14]
In vivo studies
Aqueous leaf extract	400, 800, 1600 and 2000 mg/kg	Rats (Male, Wistar rats)	2000 mg/kg dose showed no fatality, except decrease in body weight in a dose-dependent manner.	[15]
Aqueous seed extract	2000 mg/kg	Mice (Male, Balb/c)	No systemic toxicity, no significant changes in erythrocytes, platelets, hemoglobin and hematocrit observed.	[10]
Aqueous leaf extract	Low dose (1000 mg/mL), high dose (3000 mg/mL)	Rats (Male, Sprague Dawley)	M. oleifera shows acute toxicity at supra- supplementation levels of ≥3000 mg/kg bw.	[9]
Ethanolic leaf extracts	150 mg/mL dose every 5 min interval	White albino rats and rabbits (local breed)	Lethal dose for acute toxicity; 6616.67 mg/kg for rats and 26043.67 mg/kg for rabbits.	[16]
Aqueous-methanolic leaf extract	2000 mg/kg	Rats (Female, Wistar strain albino rats)	Increased levels of aspartate aminotransferase (AST) and total bilirubin. Decreased in alanine aminotransferase (ALT) level. Non-significant increase in hepatic index and mild distortions in liver cells via section analysis.	[17]
Crude methanol seed and leaf extracts	100, 200, 400 and 1000 mg/kg	Albino rats	No mortality at 1000 mg/kg dose. Seed extracts showed more potential in a long-term application.	[18]
Dried leaf powder	5, 50, 300 and 2000 mg/kg	Rats (Male and female, Sprague Dawley nulliparous and non-pregnant)	No adverse effect observed in clinical signs or gross pathology.	[19]