Table 1.

In vitro pharmacological studies for Aloe vera.

Aloe Vera Composition	Experimental Model	Major Findings	References
Digestive Diseases Protection
Acemannan	Human deciduous pulp cells	↑ Pulp cell proliferation ↑ ALP ↑ Type I collagen ↑ BMP-2, BMP-4, vascular endothelial growth factor and dentin sialoprotein expression	[6]
Aloe polysaccharide	HT-29 cells LPS and TNF-α induced	↑ JAK2 and STAT-3 expression ↓ JAK2, p-JAK2, STAT-3 and p-STAT3 protein expression Ulcerative colitis protection	[5]
Aloe vera extract	Dental pulp stem cells from rabbits	↑ Cell viability	[4]
Skin Protection
Aloe polysaccharide	HaCaT cells	↓ TNF-α levels ↓ IL-8 and IL-12 expression levels ↓ p65 expression ↑ IkB-alpha protein expression Psoriasis protection	[49]
Aloe vera	HEKa and NFDH cells	↑ Cell viability ↑ Cell proliferation ↑ Cell migration ↑ Wound healing	[31]
Aloe vera	HaCaT cells	↓ Photodamage Membrane integrity maintenance ↑ Lysosomal stability	[32]
Aloe vera ethanolic extract	c147 cells	↑ Fibroblast migration ↑ VEGF-A gene expression ↑ Wound healing	[30]
Aloe vera gel	Mouse embryonic fibroblast cells	↑ TFGβ1 and bFGF factor expression ↑ Wound healing	[29]
Aloe vera gel	HEKa Human skin equivalent model	↑ Cell number ↑ Wound healing ↑ Keratinocyte proliferation and differentiation ↑ Cell surface expression of adhesion molecules (β1-integrin, α6-integrin, β4-integrin and E-cadhesin) ↑ Wound healing	[28]
Aloesin	HaCaT cells	↑ Cell migration ↑ Cytokines and growth factors ↑ Wound healing	[35]
Aloin	Hs 68 cells Heat stress-mediated oxidative stress	↑ GSH ↑ SOD activity ↓ Lipid peroxidation ↓ 8-OH-dG ↑ Cell viability ↓ ROS	[34]
Aloin	κβ cells	↓ IL-8 production	[63]
Emodin	THP-1 cells and HaCaT cells	↑ VEGF ↑ MCP-1 Burn wound protection	[5]
Pure Aloe vera gel	Primary cultures of corneal epithelial cells and fibroblasts	↑ Corneal epithelial cell wound closure (Aloe vera concentrations ≤ 175 μg/mL) ↑ Type IV collagen-degrading activity	[33]
Anti-Inflammatory Activity
Acemannan	Human gingival fibroblasts	↑ IL-6 and IL-8 expression ↑ NF-Κβ/DNA binding	[62]
Aloe vera extract (AVH200® Batch: 2013016)	Peripheral blood mononuclear cells	↓ CD25 and CD28 expression Suppression of T cell proliferation ↓ IL-2, IFN-γ and IL-17A secretion	[61]
Aloe-emodin sulfates/glucuronides, rhein sulfates/glucuronides, aloe-emodin and rhein	RAW 264.7 cells stimulated with LPS and mouse peritoneal excluded macrophages	↓ iNOS expression ↓ TNF-α, IL-12, and NO production ↓ MAPKs phosphorylation	[64]
Aloin	RAW 264.7 cells	↓ iNOS expression ↓ IL-1β, IL-6, tumor necrosis factor alpha and NO dose-dependently ↓ JAK1-STAT1/3 activation ↓ STAT1/3 nuclear translocation ↓ ROS production	[59]
Aloin	KB cells	↓Salivary IL-1β-induced IL-8 production ↓p38 and ERK pathway	[63]
Barbaloin/aloin	RAW 264.7 cells stimulated with LPS	↓ Phosphorylation levels of IκBα and NF-κB p65 ↓ Pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) expression ↓ ROS	[60]
Anticancer Effects
Aloe polysaccharide	BxPC-3 cells	↑ ULK1 mRNA expression ↓ BECN1 and BCL-2 mRNA expression	[77]
Aloe vera crude extract	MCF-7 cells and HeLa cells	↓ Cell viability Apoptosis induction ↓ Cyclin D1, CYP1A1 and CYP1A2 ↑ Bax and p21 expression	[68]
Aloe-emodin	Metastatic human melanoma cell lines Primary stem-like cells	↓ Cell proliferation ↑ Cell differentiation ↑ Transamidating activity of transglutaminase ↑ Dabrafenib antiproliferative activity	[85]
Aloe-emodin	TE1 cancer cells	↓ AKT and ERK phosphorylation ↓ Number cells in S phase	[76]
Aloe-emodin	MCF-7 cells Photodynamic therapy	↓ Adhesion, migration and invasion of cells cytoskeleton disorganization Apoptosis: mitochondrial and endoplasmic reticulum death pathways	[70]
Aloe-emodin	HUVECs cells Photodynamic therapy	↓ Angiogenesis and Cell Metastasis MAPK Signaling Pathway activation ↓ Adhesion, migration and invasion of cells Apoptosis: mitochondrial death pathways cytoskeleton disorganization	[79]
Aloe-emodin	SW620 and HT29 cells	↓ Cell viability ↑ Apoptosis (Upregulation of CHOP and caspase 12) ↑ ROS Upregulation of unfolded protein response proteins	[79]
Aloe-emodin	HeLa cells	↓ Cell proliferation G2/M and S phase cell cycle arrest ↑ Radiosensitivity ↑ Cyclin B and γ-H2AX expression ↑ ALP activity	[69]
Aloe-emodin	MG-63 cells	↑ ROS production ↓ Mitochondrial membrane potential ↑ Caspase-3, caspase-9, caspase-12 expression ↑ Cytochrome c release	[82]
Aloe-emodin	HeLa cells	↑ Mitotic death ↓ Mitotic index ↓ G2/M phase	[72]
Aloe-emodin	Breast cancer cells (MCF-7, MDA-MB-231, MDA-MB-468, BT-474, HCC-1954)	↑ Tamoxifen cytotoxicity	[71]
Aloe-emodin	MG-63 cells	↓ Cell viability ↑ Autophagy ↑ Apoptosis ↑ ROS	[83]
Aloesin	SKOV3 cells	↓ Cell viability ↓ Cell clonality ↓ Cell cycle at S-phase ↑ Apoptosis ↓ Migration and invasion cancer	[74]
Emodin	KB cells	↓ Cell proliferation ↑ Caspase-3 upregulation ↑ Bax protein levels ↓ Bcl-2 protein levels	[75]
Antidiabetic Effect
Aloe vera polysaccharides	Hamster pancreatic β-cell line HIT-T15 in response to free fatty acids	↓ Number of apoptotic β-cell death Relief of endoplasmic reticulum stress signaling	[91]
Aloe-emodin	RIN-5F cells High glucose induced toxicity	↑ Cell viability ↓ ROS generation ↓ Pro-inflammatory cytokines levels (IFN-γ, IL-1β) ↑ Anti-inflammatory cytokine levels (IL-6 and IL-10) ↓ DNA fragmentation ↓ Bax, caspase 3, Fadd, and Fas expression ↑ Bcl-2 expression	[92]
Antioxidant Properties
Aloe vera crude methanolic extracts	In vitro antioxidant methods: DPPH, metal chelating, hydrogen peroxide scavenging, reducing power and β-carotene-linoleic	Antioxidant activity	[95]
Aloe vera ethanol extracts	Cell models (HeLa, HMEC, HaCat, and HOS) hydrogen peroxide and 4-hydroxynonenal induced	↓ ROS production ↓ HNE protein adducts HMEC cells were the most sensitive	[96]
Anthraquinone derivatives Phenolic derivatives Chromones Pyrones	Peroxyl radical scavenging Reducing capacity	Antioxidant activity	[97]
Bone Protection
Aloe-emodin	ATDC5 cells	↑ Accumulation cartilage nodules ↑ Matrix proteoglycans synthesis ↑ ALP activity ↑ Chondrogenic marker genes ↑ ERKs ↑ BMP-2 protein expression	[99]
Aloin	RAW 264.7 cells	↓ RankL induced miR-21 expression ↓ Cathepsin K Osteoporosis protection	[101]
Aloin	RAW264.7 cells	↓ TRAP content ↑ F4/80 content ↓ Cathepsin K ↓ RANKL-induced NF-κB pathway ↓ DNA binding activity of NF-κB Osteoporosis protection	[100]
Cardioprotective EFFECT
Aloe emodin	Model heme protein (hemoglobin)	↓ Hemoglobin aggregation (máximum effect at 100 μM)	[106]
Antimicrobial and Prebiotic Activity
Acemannan and fructans	Lactobacillus and Bifidobacterium species Human fecal bacteria	↑ Bacterial growth (fructans) ↑ Bifidobacterium spp population ↑ Acetate concentrations	[120]
Aloe polysaccharides	H1N1 subtype Influenza A virus	↓ H1N1 subtype influenza virus replication ↓ Viral adsorption period	[117]
Aloe vera aqueous extract	Methicillin resistant Staphylococcus aureus	↓ Growth ↓ Biofilm formation	[109]
Aloe vera aqueous extracts	Drug resistant Mycobacterium tuberculosis	Inhibition zone: 60 mm (disk diffusion method) ↓ Cell growth (up to 1 mg/mL concentration) (pour plate method)	[115]
Aloe vera crude aqueous extracts	Plasmodium falciparum	Antiplasmodial activity	[95]
Aloe vera extracts	Multidrug-resistant Pseudomonas aeruginosa	Similar MIC50 and MIC90	[112]
Aloe vera gel	Actinobacillus actinomycetemcomitans Clostridium bacilli, Streptcoccus mutans and Staphlococcus aureus	Antibacterial activity against oral pathogens	[110]
Aloe vera gel	Virus herpes simplex 1	↓ HSV-1 growth	[116]
Aloe vera hydroalcoholic extract	Enterococcus facecalis	Antibacterial activity against Enterococcus faecalis	[114]
Aloe vera inner gel	Gram negative bacteria, Gram positive bacteria and Candida albicans	Antimicrobial and antibiofilm activities against Gram negative bacteria (Helicobacter pylori, Escherichia coli and Pseudomonas aeruginosa) and Candida albicans	[113]
Aloe vera mucilage	Intestinal microbiota from healthy donors	Prebiotic activity (↑ short chain fatty acids and modifications in bacterial composition)	[119]
Aloe-emodin	Staphylococcus aureus	↓ Biofilm development (initial adhesion and proliferation stages) and extracellular protein production	[111]
Other Effects
Aloe-emodin	MH7A human RA synovial fibroblast-like cells	↓ Viable cells number ↑ Apoptosis (G2/M phase arrest) Rheumatoid arthritis protection	[127]
Aloe-emodin	ARPE-19 cells	↓ VEGF secretion ↓ VEGFA and PHD-2 mRNA expression ↓ VEGFA, HIF-1α and PHD-2 protein expression	[131]