Table 3.

An overview of the pharmacological activities of M. koenigii and its primary bioactive compounds.

Pharmacological Activities	Plant Parts	Extract	Bioactive Compounds	Model	Main Finding	Reference
In vitro studies
Antifungal	Leaves	Essential oil	−	Disc diffusion method	Essential oil extracted from M. koenigii exhibited activities with MIC in the range of 25.5 to 75 μg/mL against pathogenic fungi A. niger, F. moniliforme, P. notatum, M. mucedo, and P. funiculosum	[27]
Antibacterial	Leaves	Solvent-free microwave extraction	−	Soy agar	Minimum inhibitory concentrations (MIC) of solvent-free microwave extraction (SFME) and hydro-distilled oil from M. koenigii with values of 400 and 600 μg/mL against L. innocua SFME-essential oil at 300 μg/mL provided 92% inhibition, indicating its antibacterial potential	[37]
Antibacterial	Leaves	Methanol	Koenine, koenigine, and mahanine	Broth micro-dilution assay	Koenine, koenigine, and mahanine extracted from M. koenigii exhibited activities with MIC values of 3.12–12.5 µg/mL against bacterial strains S. aureus and K. pneumonia	[40]
Antibacterial	Leaves	Aqueous	−	Agar diffusion assay	M. koenigii-AGNPs exhibited inhibitory activity against E. coli and S. aureus, with a value of 16 mm for M. koenigii-AgNPs and 15 mm for AgNO3 solution at 100 µg/well	[18]
Antibacterial	Leaves	Essential oil	−	Microtiter assay	Essential oil extracts of M. koenigii treatment resulted in a reduction of biofilm formation in P. aeruginosa PAO1. M. koenigii essential oil may effectively control Pseudomonas biofilms in indwelling medical device	[19]
Antibacterial	Leaves	Petroleum ether, ethanol, and water	−	Colony-forming unit (CFU) assay	Ethanol extracts of M. koenigii exhibited activity half maximal inhibitory concentration ((IC50) of 400 μg/mL) against the mycobacterium smegmatis compared to petroleum ether and water extracts	[20]
Hepatoprotective	Leaves	Aqueous	−	Hep G2 cell line	M. koenigii leaves preventing alcohol-induced cellular damage	[31]
Antioxidant	Leaves	Ethanol	−	DPPH free radical scavenging assay	exhibited activities with IC50 values of 21.4–49.5 µg/mL	[21]
Antioxidant	Leaves	Aqueous	−	TBARS, CAT, SOD, and glutathione (GSH) assay	Carbazole alkaloids from M. koenigii extract exhibited activity with IC50 values of 120 μg/mL in an ethanol-induced hepatotoxicity in vitro model	[31]
Antioxidant	Leaves	Aqueous/zinc oxide nanoparticles	−	DPPH free radical scavenging assay	Zinc oxide nanoparticle-synthesized M. koenigii extract exhibited activity with an IC50 value of 36.46 μg/mL	[64]
Antioxidant	Leaves	Aqueous/zinc oxide nanoparticles	−	ABTS radical scavenging assay	Zinc oxide nanoparticle-synthesized M. koenigii extract exhibited activity with an IC50 value of 11.55 μg/mL	[64]
Antioxidant	Leaves	Aqueous/zinc oxide nanoparticles	−	Superoxide assay	Zinc oxide nanoparticle-synthesized M. koenigii extract exhibited activity with an IC50 value of 11.47 μg/mL	[64]
Antioxidant	Leaves	Aqueous/zinc oxide nanoparticles	−	H2O2 Assay	Zinc oxide nanoparticle-synthesized M. koenigii extract exhibited activity with an IC50 value of 54.06 μg/mL	[64]
Antioxidant	Leaves	Ethanoic	−	DPPH free radical scavenging assay	The ethanoic extract of M. koenigii showed an 80% scavenging activity, which was similar to the activities exhibited by the control antioxidant compound quercetin	[66]
Antioxidant	Leaves	Aqueous, alcohol, and acetone	−	DPPH free radical scavenging assay	The extracts of M. koenigii exhibited activities with an EC50 value of acetone of 4.7 µg/mL, alcohol of 4.1 µg/mL, and aqueous of 4.4 µg/mL, which were comparable to the EC50 value of 2.6 µg/mL exhibited by ascorbic acid, which was the positive control	[67]
Antioxidant	Leaves	Petroleum ether and ethyl acetate	−	Cupric-reducing antioxidant capacity	CUPRAC assays indicated the highest reducing potential in the benzene fraction, followed by petroleum ether and ethyl acetate	[68]
Antioxidant	Leaves	Benzene, ethyl acetate, acetone, methanol, and ethanol	−	DPPH free radical scavenging assay	Results showed that for 100 µg/mL, the benzene fraction extracted from M. koenigii showed 88.3% free radical scavenging activity, followed by ethyl acetate (79.5%), petrol ether (78.7%), acetone (66.1%), methanol (50.7%), and ethanol (53.0%) fractions, respectively, with the positive control being ascorbic acid (93.1%)	[69]
Antioxidant	Fruits	Aqueous	−	DPPH free radical scavenging assay	Fruit extracted from M. koenigii exhibited activities with an EC50 value of 2.6 mg/mL	[71]
Cytotoxicity	Stem bark and roots	Hexane, chloroform, and methanol	Girinimbine	MTT assay	Girinimbine was shown to significantly inhibit the proliferation of HT-29 cells with an IC50 value of 4.79 ± 0.74 μg/mL.	[85]
Cytotoxicity	Leaves	Ethanol	Murrayazoline and O-methylmurrayamine A	MTT assay	Murrayazoline and O-methylmurrayamine A exhibited activities with IC50 values of 5.7 and 17.9 mM in both HEK-293 and HaCaT cell lines, respectively	[86]
Cytotoxicity	−	−	Isolongifolene	MTT assay	Isolongifolene exhibited activities at 10 µM, showing a 90% viability in SH-SY5Y cells	[87]
Cytotoxicity	Leaves	Methanol	−	MTT assay	M. koenigii methanolic extract exhibited activities with IC50 values >400 µg/mL in the CLS-354 cell line	[96]
Cytotoxicity	Leaves	Ethanol	−	MTT assay	M. koenigii ethanolic extract exhibited activities with an IC50 value of 20 µg/mL in the mouse macrophage RAW 264.7 cell line	[20]
Cytotoxicity	Leaves	Hexane, ethyl acetate, and methanol	−	MTT assay	Three extracts of M. koenigii exhibited were very active, with values of <1 μg/mL to 2.25 μg/mL, and were thus proved to be potent cytotoxic activity agents against HeLa cancer cells	[11]
Anti-inflammatory	Stems	Methanol	Murrayakonine A, murrayanine, and O-methylmurrayamine-A	Human peripheral blood mononuclear cells	In vitro experiments showed murrayakonine A (IC50 10 µM), murrayanine (IC50 9.4 µM), and O-methylmurrayamine-A (IC50 7 µM) against TNF-α, and murrayanine (IC50 8.4 µM) and methylmurrayamine-A (IC50 8.4 µM) against IL-6, respectively	[39]
Anticancer (Colon)	Leaves	Ethanol	O-methylmurrayamine 5.7–17.9 µM	MCF-7 cells	O-methylmurrayamine A exhibited anti-colon cancer activity through downregulation of the Akt/mTOR survival pathway and activation of the intrinsic pathway of apoptosis	[86]
Anticancer (Oral)	Leaves	Methanol	Mahanine 15 μM	CLS-354 cells	Mahanine increased the expression of LC3B-II, cleaved caspase-3 proteins, and the inhibition of autophagic flux	[96]
Anticancer (Ovarian)	Stem bark	Methanol	Girinimbine 10 µM	Ovarian cancer cell line SKOV3/ SV40	Girinimbine was found to be mainly due to the induction of apoptosis and cell cycle arrest due to the inhibition of the PI3K/AKT/mTOR and Wnt/b-catenin signaling pathways	[98]
Anticancer (Breast)	Leaves	Aqueous acetone	Koenimbin 4.89 μg/mL	MCF7 breast cancer stem cells	Koenimbin induced apoptosis in MCF7 cells that was mediated by cell death and regulated the mitochondrial membrane potential by downregulating Bcl2 and upregulating Bax, due to cytochrome c release from the mitochondria to the cytosol, and significantly downregulated the Wnt/β-catenin self-renewal pathway	[98]
Anticancer (Prostate)	Leaves	Aqueous acetone	Koenimbin 3.73 μg/mL	Prostate cancer stem cells	Koenimbin induced apoptosis through the intrinsic signaling pathway and suppression of the translocation of cytoplasmic NF-κB into the nucleus, in addition to displaying potential for targeting PCSCs, as affirmed by the prostasphere formation and Aldefluor assay	[99]
Anticancer	Leaves	Methanol	Mahanine 7.5 μM	Glioma HS 683 cells	Mahanine inhibited the cell migration and invasion and inhibited cell growth was simultaneous with the suppression of p-PI3K, p-AKT, and p-mTOR	[96]
Anticancer (Liver)	Leaves	Methanol	Mahanine 25 μM	HepG2, HuCCT1, and KKU-100 cells	Mahanine showed potent cytotoxicity, with increased expression levels of MITF balance between the cellular stresses	[13]
Anticancer (Cervical)	Leaves	Methanol	Mahanine 8.6 μM	HeLa (HPV-18) and SiHa (HPV-16) cell line	Mahanine and cisplatin synergistically displayed growth inhibitory activity in cervical cancer, the inhibition of STAT3 activation, cell migration, and induced apoptosis	[14]
Anticancer (Lung)	Leaves	Methanol	Mahanine 15 μM	NSCLC cancer cell line A549	Mahanine induced the impairment of mTORC2 through rictor inhibition and the destruction of NSCLC cancer cells	[22]
Anticancer (Colon)	Leaves	Methanol	Mahanine 0–30 μM	HCT116, HCT116, SW480, and Vero	Mahanine synergistically activated the two tumor suppressors PTEN and p53/p73 and can potentially be used in combination therapy with 5-FU for the treatment of colon carcinoma	[23]
Anticancer (prostate)	Leaves	Methanol	Mahanine 10 μM	PC3 and LNCaP cell line	Mahanine selectively degraded DNMT1 and DNM T3B via the ubiquitin-proteasomal pathway in a dose-dependent manner upon the inactivation of Akt signaling	[24]
Neuroprotective	Leaves	Methanol	Isolongifolene 10 µM	SH-SY5Y cells	Isolongifolene was effectively attenuated in oxidative stress, mitochondrial dysfunction, and apoptosis	[87]
Neuroprotective	Leaves	Methanol	O-methylmurrayamine A	PC12 cells	O-methylmurrayamine A possibly protects against DNA damage, apoptosis, and high levels of cell viability	[35]
In vivo studies
Antioxidant	Leaves	Aqueous	−	Male albino Wistar rat	The oral administration of an M. koenigii leaf extract resulted in a significant reduction in the level of TBARS in both the plasma (3.64 ± 0.13) and pancreas (53.40 ± 2.13) of diabetic rats	[61]
Antioxidant	Leaves	Aqueous	−	Male albino Wistar rat	The oral administration of an M. koenigii leaf extract resulted in a significant increase in the level of GSH in both the plasma (24.16 ± 1.30) and pancreas (19.52 ± 1.09) of diabetic rats	[77]
Antioxidant	Leaves	Aqueous	−	Male albino Wistar rat	The oral administration of an M. koenigii leaf extract significantly restored the activity of SOD in the pancreas (3.69 ± 0.15) of diabetic rats	[77]
Antioxidant	Leaves	Aqueous	−	Male albino Wistar rat	The oral administration of an M. koenigii leaf extract significantly restored the activity of CAT in the pancreas (12.94 ± 0.54) of diabetic rats	[77]
Antioxidant	Leaves	Aqueous	−	Male albino Wistar rat	The oral administration of an M. koenigii leaf extract significantly restored the activity of GPx in the pancreas (5.86 ± 0.22) of diabetic rats	[67]
Antioxidant	Leaves	Ethanol	−	Sprague Dawley rats	For 200 and 400 µg/mL b.w, the M. koenigii extract showed 80% inhibited free radical generation and 75% restored GSH levels	[10]
Antioxidant	Leaves	Water	−	Male albino Wistar rat	Extract exhibited the potential to reduce lipid peroxidation activity in the liver (2.44 ± 0.029) and kidney (2.34 ± 0.09) in potassium dichromate-induced Wistar rats	[38]
Anti-inflammatory	Stem bark and roots	Hexane, chloroform, and methanol	Girinimbine	Adult zebrafish	Girinimbine treatment significantly suppressed the IL-1β and TNF-α levels induced by peritoneal fluid mice	[85]
Anti-inflammatory	Leaves	Ethanol	−	Sprague Dawley rats	Oral administration of an M. koenigii extract showed the reduced formation of oedema, with values of 43.28%, 59.67%, and 62.29% induced by carrageenan, histamine, and serotonin in rats	[30]
Hepatoprotective	Leaves	Hydro-ethanolic	−	Male Wistar rats	M. koenigii leaves significantly decreased CCl4 -induced hepatotoxic in a time- and dose-dependent manner	[16]
Nephroprotective	Leaves	Aqueous	−	Male Wistar rats	M. koenigii extract treatment significantly decreased the renal functional markers, like the blood urea nitrogen and creatinine level	[28]
Anti-Diabetic	Leaves	Ethanol	−	Swiss albino mice	M. koenigii possesses antidiabetic activity and has antioxidant effects on STZ-NA-induced diabetes mellitus and particularly significantly decreased the HOMA-IR index	[10]
Anticancer (Colon)	Stem bark and roots	Hexane, chloroform, and methanol	Girinimbine 1.5–100 µg/mL	Zebrafish and Male ICR mice	Girinimbine, supplementation specifically, resulted in the induction of apoptosis, the inhibition of inflammation, and a significant increase in cell numbers in the G0/G1 phase	[85]
Anticancer (Breast)	Leaves	Aqueous	−	Female BALB/c mice	M. koenigii aqueous extract has potential for cytotoxicity, anti-inflammatory, and immunomodulatory effects and delays rather than inhibits tumor formation	[12]
Neuroprotective	Leaves	Methanol	−	Male albino mice	M. koenigii is effective in attenuating memory impairment and oxidative stress and prevents abnormal oral movements	[36]
Neuroprotective	Leaves	Ethanol	−	Swiss albino mice	M. koenigii supplementation resulted in an improvement of acetylcholine (ACh) and reduction in acetylcholinesterase (AChE). In addition, a significant elevation of serum biomarkers, and decline in creatinine, total cholesterol, urea nitrogen, and glucose levels, ameliorated the hepatic and renal functions in the normal ageing process	[30]
Neuroprotective	Leaves	Ethanol	−	Male swiss albino mice	M. koenigii leaves elevated the acetylcholine level in the brain and ultimately improved memory impairment. In vitro, it showed BACE1 inhibition and was found to be a non-competitive inhibitor	[33]
Neuroprotective	Leaves	Methanol	Isolongifolene 10 mg/kg b.w.	Male albino Wistar rat	Isolongifolene effectively attenuated behavioral impairment and oxidative stress, acting as an antiaging agent	[34]
Anti-anxiety and anti-depressant	Leaves	Aqueous	−	Swiss albino mice	M. koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant-like activity and also reduced spontaneous locomotor activity	[41]