Table 3.

Potential mechanisms of efficacy for some pharmacologic properties of D. morbifera.

Activity Tested	Extract	Plant Part	Model	Major Effects	Reference
Antioxidant	Ethanol	Boughs	DPPH-radical scavenging assays	-D. morbifera extracts showed similar antioxidant capacities (82.92 ± 0.49%) to that of the vitamin C (90.11 ± 0.13%) positive control at the same concentration of 500 µg/mL	[35]
Antioxidant	Fermented	Leaves	DPPH-radical scavenging assays	-Exhibited activities with IC50 value of 65.30 µg/mL	[16]
Antioxidant	Methanol	Leaves, debarked stems, and bark	DPPH-radical scavenging assays	-Exhibited activities with RC50 values of 16.7 µg/mL for debarked stem extracts, 31.6 µg/mL for yellow leaves extract, and 37.8 µg/mL green leaf extracts	[21]
Antioxidant	Hot water and ethanol	Leaves	ABTS-radical scavenging assays	-Exhibited activities with IC50 value of 3.79 mg/mL for hot water, 3.75 mg/mL for 30% ethanol, and 3.58 mg/mL for 60% ethanol	[25]
Antioxidant	Fermented	Leaves	Hydroxyl-radical scavenging activity	-Exhibited activities with IC50 value of 57.52 µg/mL	[50]
Antioxidant	Water	Stem and leaves	Sprague–Dawley rats	-D. morbifera extracts significant enhancements in GSH, SOD, and CAT activities and a reduction in the MDA level	[30]
Antioxidant	Water	Aerial part	Sprague–Dawley rats	-D. morbifera extracts significantly decreased the hepatic MDA content and ameliorated the SOD and GSH content.	[52]
Anti-inflammatory	Aqueous	Leaves	BV-2 cells	-D. morbifera extracts effectively attenuates NO production, cell viability, and proinflammatory mediators, and subsequently suppressed the phosphorylation of both the IκB-α and NF-κB p65 subunit and MAPK signaling	[13]
Anti-inflammatory	Ethanol	Leaves	RAW264.7 macrophages	-Doses of 200 and 400 µg/mL effectively inhibited the activity of inflammatory mediators NO, TNF-α, and IL-6	[17]
Anti-inflammatory	Ethyl acetate	Leaves	BV-2 cells	-D. morbifera treatment significantly attenuated the activation of MAPKs and NF-κB, and subsequently upregulated M2 polarization of alternative anti-inflammatory markers	[20]
Anti-inflammatory	Methanol	Leaves	RAW264.7 macrophages	-D. morbifera extracts significantly and dose-dependently reduced the production of NO and PGE2 and significantly inhibited protein and mRNA expression in COX-2 and iNOS activities and could modulate NF-κB and MAPK signaling -D. morbifera extracts significantly induced Nrf2 nuclear translocation and thereby induced HO-1 expression	[26]
Anti-inflammatory	Methanol	Leaves	Ear edema mouse model	Treatment with-D. morbifera extracts triggered a protective effect against the increase in ear thickness induced by TPA Treatment with-D. morbifera reversed ear edema and epidermal hyperproliferation, and increased the number of neutrophils induced by TPA	[26]
Anti-inflammatory	Fermented	Leaves	BALB/C mice	-D. morbifera extracts at 125, 250, and 500 mg/kg reduced levels of TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-12p70, IL-13 and IFN-γ in immunized BALB/C mice	[27]
Anti-inflammatory	Water	Stem and leaves	Sprague–Dawley rats	-D. morbifera extracts administered at 25 mg/kg markedly inhibited inflammatory cytokines and TGF-β1 expression in diabetic rats	[30]
Anti-inflammatory	Water	Aerial parts	Sprague–Dawley rats	- D. morbifera extracts at 25 mg/kg showed significant anti-inflammatory effects by reducing the levels of inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and reversed IL-10 levels in a cisplatin-induced rat model	[62]
Anti-amnesic	Ethanol	Leaves	PC12 and MC-ⅨC cells	-D. morbifera extracts treatment effectively inhibited the AChE as an ACh-hydrolyzing enzyme in high glucose-induced PC12 and MC-ⅨC cells	[14]
Neuroprotective	Ethanol	Leaves	SH-SY5Y cells	-Rutin, a bioflavonoid isolated from D. morbifera, protected the higher level of intracellular Ca2+ and depleted the level of MMP, as well as subsequently decreased rotenone-induced ROS generation -Rutin prevented a decrease the levels of Bax/Bcl-2 ratio, caspase-9, and caspase-3	[63]
Neuroprotective	Ethyl acetate	Leaves	HT22 cells	-D. morbifera extracts significantly inhibited mitochondrial dysfunction and the elevation of Ca2+ levels and reversed subsequent AIF nuclear translocation in glutamate-induced HT22 mouse hippocampal neuronal cells	[64]
Neuroprotective	Ethanol	Stem	Sprague–Dawley rats	-D. morbifera administration ameliorates cognitive dysfunction via an increase in cell proliferation, neuroblast differentiation, and AChE activity in the hippocampus induced by cadmium-induced neurotoxicity	[14]
Neuroprotective	Water	Leaves	Sprague–Dawley rats	-D. morbifera extracts significantly reduced mercury levels in the hippocampus and ROS generation and reversed hippocampal activities in dimethylmercury-induced rats	[24]
Neuroprotective	Ethanol	Stems	Sprague–Dawley rats	-D. morbifera administration changes serum triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone levels in the hippocampus induced by hypothyroidism neurotoxicity	[28]
Neuroprotective	Ethanol	Leaves	C57BL/6 mice	-D. morbifera administration significantly improved D-galactose-induced reduction in microglial activation, escape latency, swimming speed, and spatial preference behavior	[65]
Neuroprotective	Aqueous	Leaves	C57BL/6 mice	-D. morbifera treatment effectively improved behavioral function, and protected dopaminergic neuronal loss by restoring TH levels in the brain tissue of MPTP-induced PD mice	[13]
Neuroprotective	Ethanol	Leaves	C57BL/6 mice	-Ethanol extracts of D. morbifera significantly improved glucose tolerance status, and behavioral impairments, and significantly protects the abnormal activity of mitochondria by inhibiting phosphorylated p-JNK, p-IRS, p-Akt, and p-tau in high-fat diet-induced mice	[66]
Anti-cancer	Methanol	Leaves and debarked stems	Huh-7 cells	-D. morbifera extracts showed strong induction of p53, and p16 inhibited the activation of ERK and reduced Akt levels and the suppression of Huh-7 cell proliferation	[21]
Anti-cancer	Silver nanoparticles	Leaves	A549 and HepG2	-Silver nanoparticles synthesized from D. morbifera enhanced ROS production in both cell lines and the modification of EGFR/p38 MAPK signaling	[67]
Anti-cancer	Ethanol	Stem bark	U937 cells	-D. morbifera-induced apoptosis in U937 cells was associated with the activation of caspase-8, -9, and -3 and downregulation of anti-apoptotic IAP family proteins	[68]
Anti-cancer	Water	Aerial parts	Sprague–Dawley rats	-D. morbifera administration protects against kidney damage induced by CDDP in tumor models	[62]
Anti-diabetes	Water	Leaves	3T3-L1 cells	-D. morbiferus treatment reduced intracellular triglyceride levels and glucose uptake by lowering protein and mRNA expression levels of adipogenesis-related genes	[9]
Anti-diabetes	Water	Leaves and stem	Sprague–Dawley rats	-D. morbifera administration protected body and organ weight loss, significantly increased BUN, and significantly reduced KIM-1, SBP1, and PKM2 levels in the urinary excretions of diabetic rats	[30]
Anti-diabetes	Methanol	Leaves	Sprague–Dawley rats	-D. morbifera administration showed significant hypoglycemic activity by decreasing the total cholesterol, serum glucose, urea, triglycerides, creatinine, uric acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in streptozotocin-induced diabetic rats	[22]
Anti-diabetes	Ethanol	Leaves	C57BL/6	-D. morbifera treatment protected against high-fat diet-induced abnormal mitochondrial activity and improved p-JNK, p-IRS, p-Akt, and p-tau in high-fat diet-induced diabetic mice	[14]
Anti-diabetes	Water and ethanol	Leaves and stem	ICR mice	-D. morbifera administration maintained a high level of body weight and increased insulin secretion by reducing the glucose concentration in the blood in streptozotocin-induced diabetic mice	[31]
Hepatoprotective	Ethanol	Root, leaves and stem	HepG2 cells	-D. morbifera exhibited strong antioxidant activity, and showed hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells	[32]
Hepatoprotective	Aqueous	Leaves	Sprague–Dawley rats	-D. morbifera administration prevented ethanol-induced hepatotoxicity due to reductions of serum aspartate aminotransferase and alanine aminotransferase levels, and maintained enzymatic oxidant status, and suppressed cytochrome P-450 2E1 expression	[33]
Immunomodulatory	Fermented	Leaves	BALB/C mice	-D. morbifera administration showed an increase in spleen cells and CD8a+, CD11b, and CD3+ T-cell expression, and downregulated the IgG super-family	[27]
Immunomodulatory	Ethanol	Leaves, branch, sapling, and mixed	BALB/c mice	-D. morbifera administration significantly increased splenocyte cytokines, NO production, and LDH, and enhances innate immunity by modulator NF-κB signaling	[34]
Antimicrobial	Ethanol	Leaves	Paper disc test	With-D. morbifera extract concentrations of 40, 80, and 100 µg/mL, a 3.0 mm suggesting higher antibiotic effects against S. mutans and C. albicans	[35]
Antiplasmodial	Methanol	Stem bark	Semi-automated micro-dilution assay	-Extracts exhibited activities with IC50 values of 6.2 µg/mL and 5.3 µg/mL, against D10	[36]
Anticomplementary	Aqueous	Leaves	Classical and alternative pathway assay	-D. morbifera exhibited significant inhibitory activity against complementary system with IC50 values of 87.3 mM for (3S)-falcarinol, 15.2 mM for (3S,8S)-falcarindiol, and 39.8 mM for (3S)-diynene.	[53]
Anticomplementary	Methanol	Leaves	Classical pathway assay	-(9Z,16S)-16-hydroxy-9,17-octadecadiene-12,14-diynoic acid from D. morbifera exhibited activities with an IC50 value of 56.98 µM.	[47]
Cytotoxicity	Methanol	Leaves	MTT assay	-Extracts exhibited cytotoxic activities greater than 93% at doses of more than 100 μg/mL, and 6 to 11% at doses of less than 50 μg/mL	[35]
Cytotoxicity	Silver nanoparticles	Leaves	MTT assay	-D-AgNPs at 100 µg/mL showed potent cytotoxicity after 48 hours	[38]
Cytotoxicity	Methanol	Leaves	MTT assay	-Extracts exhibited low cytotoxicity with IC50 values exceeding 50 µg/mL, maintaining up to 80% cell viability induced by glutamate toxicity	[64]
Cytotoxicity	Aqueous	Leaves	MTT assay	-Extracts with a high concentration of D. morbifera of 500 μg/mL showed no toxic effects and maintained up to 100% cell viability induced by LPS toxicity	[13]
Toxicity	Water	Leaves	Sprague–Dawley rats	-No deaths were observed at the highest concentration tested, and the LD50 values for both extracts was above 2000 mg/kg body weight	[37]