Aisha Saleem, Irum Naureen, Muhammad Naeem, Hafiza Safoora Murad, Samra Maqsood, Gulnaz Tasleem
Digestive Diseases Protection, Aloe vera extract (50%) increased cell viability of dental pulp stem cells being useful for avulsed broken teeth. This effect is attributed to polysaccharides, mainly acemannan, by inducing osteogenic-specific gene expressions, DNA synthesis, growth factor, and JAK-STAT pathway. Moreover, Aloe vera (225 mg/kg) exerted a radioprotective effect against salivary gland dysfunction in a rat model as evidenced in an increase of salivary flow rate, Periodontitis is a serious and common dental affliction in which gums are infected and become inflamed, causing tissue and bone destruction. Gingivitis is the initial phase of periodontitis and is caused by dental plaque. Significant clinical evidence has demonstrated that Aloe vera mouthwash and gel are effective in the prevention and treatment of gingivitis and periodontitis by reducing gingival index, plaque index, and probing depth and by increasing bone fill and regeneration , Aloe vera has proven to be as effective as other usual treatments such as chlorhexidine, alendronate, and chlorine dioxide, Aloe vera gel significantly reduced swelling and postoperative pain, Aloe vera gel and mineral trioxide aggregate as pulpotomy agents in primary molar teeth. The overall success rates at 3, 6, 9, and 12 months was high for patients treated with mineral trioxide aggregate, Aloe vera mouthwash alleviated radiation-induced mucositis severity in patients with head and neck cancers similarly to the reference benzydamine mouthwash, moreover, Aloe vera mouthwash has also demonstrated to be efficient in the treatment of stomatitis (mean intensity and pain) associated with radiotherapy in patients with acute myeloid leukemia and acute lymphocytic leukemia, Aloe vera (systemic as juice and topical as gel) in the treatment of oral submucous fibrosis. Clinical evidence demonstrated that Aloe vera reduced burning sensation and increased cheek flexibility, mouth opening, and tongue protrusion similar to the reference treatment hydrocortisone, hyaluronidase, and antioxidant supplements. In another study on oral submucous fibrosis, the combination of Aloe vera gel with physiotherapy was more efficient in decreasing burning sensation and increasing tongue protrusion, mouth opening, and cheek flexibility than the combination of antioxidant capsules with physiotherapy, gastroesophageal reflux disease is a common chronic digestive disease in which gastric acids move up into the esophagus. Aloe vera syrup (10 mL/day) for 4 weeks reduced the frequency of symptoms of gastroesophageal reflux diseases including heartburn, food regurgitation, dysphagia, flatulence, belching, nausea, and acid regurgitation without causing adverse effects (only one case of vertigo and another of stomach ache were reported), gastritis is an inflammation of mucous membrane layer of the stomach. Aloe vera gel protected in a Balb/c mouse model of alcohol-induced acute gastritis by increasing matrix metalloproteinase-9 inhibitory activity , the topical administration of Aloe vera 3% ointment alleviated the symptoms of diarrhea and fecal urgency in patients with acute radiation proctitis induced by radiotherapy of the pelvic area, Moreover, Aloe barbadensis extract (Innovaloe aloe vera gel powder 200X) reduced, but not significantly, the severity of gastrointestinal symptoms in patients with irritable bowel syndrome compared to a control group, revealed that Aloe polysaccharide (15 mg/kg) protected rats from 2,4,6-three nitrobenzene sulfonic acid colitis induced by increasing JAK2, p-JAK2, STAT-3, and p-STAT3 protein expression. Furthermore, Aloe vera cream applied three times daily for 6 weeks reduced chronic anal fissure pain and hemorrhaging after defection and promoted wound healing in a prospective double blind clinical trial, skin protection study the ability of Aloe vera and active compounds in wound healing. The immortalized human keratinocyte HaCaT cell line, the primary normal human epidermal keratinocytes HEKa cell line, and fibroblasts cell lines, Aloe vera up-regulated TFG?1, bFGF, and Vegf-A expression in fibroblasts and increased keratinocyte proliferation and differentiation by lysosomal membrane stability [28,29,30,31,32]. Moreover, Aloe vera solution could accelerate corneal wound closure at low concentrations (?175 ?g/mL) by increasing type IV collagen-degrading activity in a cellular model of primary cultures of corneal epithelial cells, aloe polysaccharide (20, 40, and 80 µg/mL for 24 h) could be a beneficial agent in psoriasis as evidenced in the inhibition of TNF-? levels and IL-8 and IL-12 protein expression in human keratinocyte HaCaT cell line, Application of topical Aloe vera favored wound healing in animal models with dermal incisions by reducing inflammatory cell infiltration, increasing CD4+/CD8+ ratio lymphocytes, and improving epidermal thickness and collagen deposition, in another study conducted in Indonesia with several medicinal plants, the effect of Nigella sativa oil gel and Aloe vera gel to treat diabetic ulcers was investigated. Aloe vera resulted to be more efficient in improving wound healing on alloxan-induced diabetes in Wistar rats with wounds on dorsum as evidenced by a decrease of necrotic tissue and inflammation and an improvement of re-epithelialization, furthermore, a UV-induced mice model revealed that Aloe vera gel powder increased epidermal growth factor and hyaluronan synthase and reduced matrix metalloproteinases expression (types 2, 9, and 13) , aloe sterols are involved in this UV protection, likewise, it has been observed that Aloe vera protected against X-radiation through antioxidant mechanisms (increased antioxidant enzyme activity and GSH content and reduced ROS production and lipid peroxidation), effectiveness of Aloe vera on ulcers. Hence, the administration of Aloe vera gel twice daily for 3 months improved and accelerated wound healing as well as reduced hospitalization time [, moreover, in a randomized, triple-blind clinical trial with 80 patients hospitalized in the orthopedic ward, demonstrated that Aloe vera gel twice daily for 10 days prevented the development of pressure ulcers on the areas of hip, sacrum, and heel. Moreover, clinical trials have demonstrated that Aloe vera facilitated rapid tissue epithelialization and granulation in burns, promoted healing of cesarean wound, and accelerated wound healing of split-thickness skin graft donor sites , Furthermore, Aloe vera has been investigated in randomized, double-blind, placebo-controlled studies for its benefits to maintain healthy skin. Therefore, the daily oral intake of 40 µg of Aloe sterol (cycloartenol and lophenol) for at least 12 weeks improved skin elasticity in men under 46 years exposed to the sunlight but do not use sunscreen to protect themselves, reduced facial wrinkles in Japanese women over 40 years old by stimulating hyaluronic acid and collagen production, and increased gross elasticity, net elasticity, and biological elasticity in women aged 3059 , however, despite clinical evidence on the protective role of Aloe vera in the skin, there are clinical trials that have not yet found effectiveness of this medicinal plant, particularly in decreasing radiation-induced skin injury. Two clinical trials have been published between 2014 and 2019 in relation to this effect. Both studies found that topical administration of Aloe vera as gel or cream did not reduce the prevalence and severity of radiotherapy-induced dermatitis and skin toxicity in breast cancer patients compared to control group, acemannan increased IL-6 and IL-8 expression and NF-?B/DNA binding in human gingival fibroblast via a toll-like receptor signaling pathway. Since there is a relation between high IL-1? levels and periodontal diseases, Aloe vera 200x, a standardized Aloe vera extract which contains alin and acemannan on the activation, proliferation, and cytokine secretion of human blood T cells obtained from healthy individuals aged 1860, and they found that it decreased CD25 and CD3 expression on CD3(+) T cells. Moreover, Aloe vera 200 x exhibited concentration-dependent T cell proliferation suppression and IL-2, IFN-?, and IL-17A reduction. Moreover, the anti-inflammatory effect of Aloe vera has also been investigated in an acetaminophen-induced hepatitis (inflammatory condition of the liver) mice model. The results of this study revealed that Aloe vera (150 mg/kg) reduced hepatic MDA, IL-12, and IL-18 levels and ALT and increased GSH content, Antioxidants are compounds that prevent or slow down biomolecule oxidative damage caused by ROS through free radical scavenging, metal chelation, and enzyme regulation, antioxidant activity is related to a high content in alkaloids, glycosides, phenolic compounds, flavonoids, and saponin glycosides. Moreover, Aloe vera ethanol extract protected, particularly human microvascular endothelial cells, against hydrogen peroxide and 4-hydroxynonenal-induced toxicity by reducing ROS production and HNE-protein adducts formation, the antioxidant activity of Aloe vera and related compounds (10 µM) which possess peroxyl radical scavenging activity and reducing capacity, part from these in vitro assays, in a clinical trial with 53 healthy volunteers, the intake of Aloe vera gel extract (14 days) increased total antioxidant capacity of plasma of subjects, antimicrobial activity of Aloe vera and its main constituents. Most of these studies are in vitro and focus on the antibacterial activity. One of the most studied bacteria are Staphlococcus aureus and Pseudomonas aeruginosa. Hence, Aloe vera aqueous extract reduced growth and biofilm formation against methicillin resistant Staphylococcus aureus, moreover, this bacteria has also been inhibited by Aloe vera gel (50% and 100% concentrations), along with other oral pathogens obtained from patients with periapical and periodontal abscess including Actinobacillus actinomycetemcomitans, Clostridium bacilli, and Streptococcus mutans using disc diffusion, micro-dilution, and agar dilution methods, one of the compounds attributed to antibacterial activity against Staphylococcus aureus is aloe-emodin which acts by inhibiting biofilm development and extracellular protein production , in the case of Pseudomonas aeruginosa, Aloe vera extracts have shown to inhibit the growth of multidrug-resistant Pseudomonas aeruginosa isolated from burned patients with wounds infections at MIC50 and MIC90 values of 200?µg/mL, pseudomonas aeruginosa growth and biofilm formation inhibition has been also demonstrated for Aloe vera inner gel, this Aloe vera inner gel also inhibited other Gram-negative bacteria (Helicobacter pylori and Escherichia coli) as well as the fungus Candida albicans, moreover, in another study, Aloe vera hydroalcoholic extract showed antibacterial activity against Enterococcus faecalis, an infecting microorganism of the root canals of teeth, with inhibition zones of 13 mm (saturated) and 9.6 mm (diluted) , furthermore, concentrations up to 1 mg/mL of Aloe vera aqueous extracts could inhibit Mycobacterium tuberculosis growth, which is the pathogen Molecules
