Table 5.

Some of the antioxidant and anti-inflammatory effects of other phytochemicals of the Yucca genus reported in the literature.

Metabolite	Group	Species Where It Has Been Founded	Effect	Administrated Doses	References
					Effect	Metabolite Screening
Stigmasterol	Phytosterol	Yucca aloifolia variegata	In chondrocytes from newborn mice or human osteoarthritis treated with IL-1β, preincubation with stigmasterol decreased the expression of Matrix Metallopeptidase 3, Matrix Metallopeptidase 13, ADAMTS-4 and PGE2, this by counteracting the effect of IL-1β on the NF-κB pathway.	Cells were pre-incubated for 48 h with 20 μg/ml	[218]	[87]
			Stigmasterol treatment improved clinical severity by reducing joint destruction and decreasing the expression of TNF-α, IL-6, IL-1β, iNOS and COX-2, p65 and p38 by inhibiting the activation of p- IκBα in collagen-induced arthritic rats.	200 mg/kg orally daily for 20 days	[219]
			In rats with ischemia/reperfusion brain injury, stigmasterol treatment decreased COX-2 and p65 expressions. In addition to significantly increasing the expression of Nrf2, HO-1, SOD, CAT, and GPx.	Dosis de 20, 40 y 80 mg/kg	[220]
Phytol	Terpenes	Yucca aloifolia variegata	Phytol treatment reduced MPO activity and the concentration of TNF-α, IL-6 and COX-2. By downregulating p38 and NF-κB signaling pathways in a mouse model of arthritis induced by complete Freund’s adjuvant.	Oral administration of 50 mg/kg	[221]	[87]
			Phytol exhibits a dose-dependent anti-inflammatory effect in formalin-induced paw edema by decreasing the levels of COX-1, COX-2, NF-κB and IL-1 β.	100 mg/kg of phytol	[222]
			Phytol demonstrated a strong antioxidant effect in vitro. Eliminating hydroxyl radicals and nitric oxide and preventing the formation of TBARS	The concentration of 0.9, 1.8, 3.6, 5.4 and 7.2 ng/mL was used in the in vitro tests.	[223]
Malic acid	Dicarboxylic acid	Yucca aloifolia variegata	Malic acid decreases TNF-α levels and inhibits platelet aggregation in rats with myocardial ischemia/reperfusion injury.	Doses of 500 mg/kg and 250 mg/kg	[224]	[87]
Loliolide	Terpenes	Yucca aloifolia variegata	Loliolide was found to exert dose-dependent positive effects on the protective effects against peroxide-induced cell damage.	Cells were pretreated with 250 and 500 μM of loliode	[225]	[87]
			Loliolide treatment in LPS-stimulated RAW 264.7 macrophages decreased TNF-α and IL-6 production.	100 µM	[226]
			Loliolide treatment in LPS-stimulated RAW 264.7 macrophages downregulated IκBα and p65 in a dose-dependent manner, thereby inhibiting NF-κB nuclear translocation. In addition, it downregulates the proteins involved in the MAPK pathway (p38, ERK, and JNK), thus inhibiting MAPK phosphorylation.	15.6, 31.2, 62.5 µm/mL	[227]
α-Tocopherol	Tocopherol	Yucca aloifolia	Oral α-tocopherol supplementation maintains cellular redox status in polychlorinated biphenyl-induced toxicity in rat liver, lung, and kidney. Therefore, the activities of SOD, CAT, GPx, and glutathione reductase are maintained, and the levels of lipid peroxides, hydroxyl radicals, and hydrogen peroxides are kept low.	50 mg/kg body weight/day	[228]	[21]
			α-Tocopherol treatment significantly reduced IL-6 levels, thereby inhibiting NF-κB-mediated gene transcription in cancerous mice.	150 mg/kg per day orally for 15 consecutive days	[229]
γ-Tocotrienol	Tocotrienols	Yucca aloifolia	γ-tocotrienol an inhibits NF-κB pathaway in RAW 264.7 macrophages.	20 µM	[230]	[21]
			γ-tocotrienol treatment in TNF-α-induced inflammation in adipocytes suppressed IκB-α phosphorylation and NF-κB activation.	Cells were pretreated with 0.024, 0.24, and 2.4 μM γ-tocotrienol for 6 h.	[231]
			In rats with induced arthritis, treatment with γ-tocotrienol reduced arthritis-induced changes in the C-reactive protein, TNF-α, SOD, and GSH levels.	The rats were treated orally with 5 mg/kg body weight of γ-tocotrienol between days 21 and 45.	[232]
δ-Tocotrienol	Tocotrienols	Yucca aloifolia	δ-tocotrienol inhibits NO production and expression of IL-1β, IL-1α, IL-6, TNF-α, IL-12, iNOS, VCAM1 (Vascular cell adhesion protein 1), ICAM1, COX2, IL-1RA, TRAF1 and CD40 in mice.	Mice were fed 100 ppm tocotrienol	[233]	[21]
Succinic acid	Dicarboxylic acid	Yucca carnerosana	The injection of succinic acid in Wistar rats showed a high inhibitory capacity of LPO.	25 mg/kg intraperitoneally injected into rats	[234]	[105]
Neophytadiene	Terpenes	Yucca aloifolia variegata	Neophytadiene was treated with LPS-stimulated RAW 264.7 and pretreated in rats injected with 10 mg/kg LPS. Neophytadiene inhibited NO production and the expression of TNF-α, IL-6, and IL-10,	25, 50, 100 μM/mL in vitro 12, 25, 50 mg/kg pretreated for 7 days in vivo	[235]	[87]
Mangiferin	Xanthones	Yucca elephantipes	Mangiferin pretreatment increases GST, GPx, SOD, and CAT levels in rats with induced myocardial infarction.	100 mg/kg suspended in 2 mL dimethyl sulfoxide administered intraperitoneally for 28 days	[236]	[79]
			Mangiferin pretreatment prevented apoptosis and decreased levels of MDA, IL-1F, and IL-18 in mice subjected to cecal ligation and puncture. This is due to the inhibition of the NLRP3 inflammasome and the upregulation of Nrf2.	15 mg/kg	[237]
			Mangiferin pretreatment increases HO-1 expression and activity in sepsis-induced mice with acute lung injury. This inhibited MAPK and NF-κB signaling.	10, 30, and 100 mg/kg once daily for 7 days before cecal ligation and puncture.	[238]
Cinnamaldehyde	Terpenes	Yucca aloifolia variegata	Cinnamaldehyde increased antioxidant enzymes such as SOD, GPx, and GST.	Rats were administered orally by gavage at dose levels of 2.14, 6.96, 22.62, and 73.5 mg/kg body weight/day for a period of 10, 30, and 90 days.	[239]	[87]
			Cinnamaldehyde reduced levels of proinflammatory cytokines and increased levels of antioxidant enzymes in patients with rheumatoid arthritis. Molecular docking indicated that cinnamaldehyde interacts with the key residues of TNF-α and IL-6.	20 or 40 µM cinnamaldehyde	[240]
Nerolidol	Terpenes	Yucca elata Yucca filamentosa	Nerolidol pretreatment increases SOD, CAT, and GPx, activity by enhancing MP-activated protein kinase phosphorylation.	A significant effect started at 30 μmol/kg	[241]	[59]
			Nerolidol decreased the expression of TNF-α, IL-1β, IL-6, NF-kB, PGE-2, and COX-2 and increased the level of IL-10, IL-4, and serum, antioxidant activity in rats with arthritis induced.	Doses of 200, 400, and 800 m,g/kg were administered for 28 days.	[242]
Chrysophanol	Anthraquinone	Yucca elephantipes	Chrysophanol reduced protein expression of NF-κBp65, p-NF-κB p65, IκBα, p-IκBα, TNF-α, and IL-1β, decreased MPO and MDA levels, and increased SOD activity in mice with acute lung injury (LPS). This by regulating HMGB1/NF-κB signaling through histone deacetylase 3.	Doses of 7.5, 15 and 30 mg/kg	[243]	[79]
			Chrysophanol increased Nrf2 levels and decreased HO-1, glutamate-cysteine ligase, glutamate cysteine ligase, IKKa, IkBa, NF-kB, and ROS generation in H9C2 cells stimulated with LPS. Chrysophanol is suggested to act as an activator of Nrf2.	Cells were cultured at doses of 0, 10, 20, 40, 80, 160, and 320 uM.	[159]

Table 5 abbreviations: MDA = Malondialdehyde, GPx = Glutathione peroxidase, CAT = Catalase, SOD = Superoxide dismutase, MAPK = Mitogen-Activated Protein Kinase, NF-κB = Nuclear transcription factor-κB, TNF-α = Tumor necrosis factor α, PGE2 = Prostaglandin E2, COX-2 = Cyclooxygenase-2, COX-1 = Cyclooxygenase-1, ROS = Reactive Oxygen, Nrf2 = Nuclear factor erythroid 2–related factor 2, IL = Interleukin, NO = Nitric oxide, ERK = Extracellular signal-regulated kinase, LPO = Lipid Peroxidation, iNOS = Inducible nitric oxide synthase, MPO = Myeloperoxidase, GSH = Glutathione, HO- 1 = Heme oxygenase 1, IKB-α = Inhibitor of nuclear factor kappa B, LPS = Lipopolysaccharide, MIP-2 = Macrophage inflammatory protein-2, IKK = IkB kinase, JNK = Jun N-terminal kinase, ICAM-1 = Intercellular adhesion molecule, GST = Glutathione-S-transferase, FGF2 = Fibroblast growth factor 2, MMP-3 = Matrix Metallopeptidase 3, MMP-13 = Matrix Metallopeptidase 13, ADAMTS- 4 = ADAM Metallopeptidase with Thrombospondin Type 1 Motif 4, TBARS = Thiobarbituric acid reactive substances, ROS = Reactive oxygen species, VCAM1 = Vascular cell adhesion protein 1.