Arshad H Rahmani, Yousef H Aldebasi, Sauda Srikar, Amjad A Khan, Salah M Aly

 

Natural-based products treatment is growing rapidly across the globe due to lower accessibility and side effects. Thus, different plants and products derived therefrom are used in primary treatment and they play an important role in the treatment of diseases by modifying biochemical and molecular pathways. Aloe vera, a juicy cactus species, produces gel and latex that have a therapeutic role in health issues through antioxidant, anti-tumor and anti-inflammatory activities, and also provides a viable alternative approach to the treatment of various types of diseases. This study summarizes the possible mechanism of action and the therapeutic implications of the Aloe vera plant in health, based on modulation activities and other biological activities.

 

Introduction

Traditional medicine plays an important role in the treatment of different types of diseases. Nowadays, the appeal to complementary medicine and natural products is in rapid growth across the globe, given that they are effective and cheap and have fewer side effects. Different types of medicinal plants and their constituents are used to treat diseases from ancient times. The significance of plants and their constituents in the healing of diseases has been discussed in Ayurveda, Unani and in Chinese medicine, as well as in other religious books. In Islam, plants are considered to have significant value in solving health problems, and Mohamad has recommended various herbs for curing diseases such as Nigella sativa seeds and dates. Past investigators have reported that medicinal plants and their constituents, such as Nigella sativa, dates and curcumin, have played and play an important role in disease prevention by modulation of several activities. However, only a few of the plants and their constituents have been appropriately investigated using animal models in terms of their toxicity / lethal dose and mechanism of action in preventing disease. In this regard, juicy species of Aloe Vera play an important role in healing diseases by modulating various activities. The relevant chemical constituents are vitamins, minerals, enzymes, sugars, anthraquinones, lignins, alicylic acid and saponins, and most constituents seem to have biological significance in healing diseases.

   

        

Active substances in Aloe Vera and their functions

Aloe vera contains many biologically active constituents, including vitamins, minerals, sugars, amino acids, anthraquinones, enzymes, lignans, sponins and salicylic acid. In addition, Aloe Vera contains substances for the isoprenoid pathway, such as carotenoids, steroids, terpene and phytosterols and some essential / non-essential amino acids and enzymes such as bradykinase, carboxypeptidase, cyclooxygenase and carboxypeptidase.

 

Mechanism of action in disease prevention

Aloe Vera is a useful alternative herbal plant and has a long history of use in traditional medicine to cure illness due to its ability to modulate various biological activities. Thus, several active constituents have been identified in Aloe Vera and most have therapeutic implications in disease prevention and treatment by modulation of various biological and genetic activities. The possible mechanisms of action of the Aloe Vera constituents are:
- Aloe Vera and its constituents such as aloe emodin (AE), aloin (barbaloin), anthracene and emodin are relevant to cancer prevention due to activation and inactivation of the molecular pathways associated with them.
- Also, Aloe Vera appears to function as an antioxidant by the activities of neutralizing free radicals and superoxide radicals and by anti-inflammatory activities by inhibiting the production of prostaglandin E2 from arachidonic acid and also by inhibiting various transcription factors and enzyme activities , including lipoxygenase and cyclooxygenase.
- Aloe Vera shows antimicrobial activity by breaking the cell walls of the bacteria. Previous studies have reported anti-inflammatory and antibacterial properties of the Aloe Vera gel.

 

The pharmacological effects of the Aloe Vera plant and its constituents in the healing of diseases by modulating biological activities

 

The antitumor effect

Tumor development and progression is a multi-step process, including changes at the genetic and epigenetic level. Aloe Vera and its constituents have a vital effect on tumor growth control by modulation of gene expression pathways. An important study was conducted to investigate the antitumor activity of the Aloe Vera plant against skin-induced 2-level carcinogenesis induced by 7,12-Dimethylbenz [a] anthracene (DMBA) and croton tiglium oil; the results revealed that the incidence of tumors was reduced to 50%, 60% and 40% in case of group II (DMBA + oil of DMX + croton + local application of Aloe Vera gel), III (DMBA + croton oil + oral Aloe Vera extract) and IV (DMBA + croton oil + local application of Aloe Vera gel + oral Aloe Gel Vera), respectively.

Another study has shown that Aloe Vera has lowered the lipid peroxidation level and increased antioxidant enzyme levels and the same study has shown that 50% ethanolic Aloe Vera extract has an antitumour effect by modulating lipid peroxidation and increasing the antioxidant defense system. Another experiment was carried out to evaluate the anticancer properties and modulating effects of the Aloe Vera plant and it was found that the active principles of Aloe Vera exerted a significant inhibition of the Erlich ascites carcinoma cell number (EACC) compared to the positive control, in the following order: barbaloin> aloe emodin (AE)> octapeptide> aloesin. An important study was performed on HeLa S3 uterine carcinoma cells to test the anti-proliferative and cytotoxic potential of anthracycline aloin and the results confirmed that aloine had an apparent antiproliferative effect at physiological concentrations, caused cell cycle arrest in phase S and increased apoptosis cell.

In another study on a hepatocellular carcinoma cell line it was observed that AE induced apoptosis and was accompanied by the induction of p53 and p21 expression. Other investigators have confirmed the effectiveness of extracts derived from Aloe arborescens in the palliative thaw of patients with untreatable metastatic cancer either to improve quality of life or to extend survival time. In addition, another study has shown that emodin and AE are able to inhibit proliferation of breast cancer cells by reducing estrogen receptor (ER) alpha levels and by suppressing transcriptional activation of ER alpha. AE plays a role in inhibiting cell growth in several types of tumor cells, such as lung carcinoma, hepatoma and leukemia cell lines, and has increased specificity for neuroectodermal tumor cells.

One study has shown that activation of caspase 3, caspase 8 and caspase 9 is induced by AE and suggested that AE induces death of CH27 cells on the Bax and Fas pathways. Another major study concluded that AE-induced apoptosis in T24 cells is mediated by activation of p53, p21, Fas / APO-1, Bax and caspase 3. A study has shown that AE plays a role in inducing apoptosis by activating caspase 6 in the case of colon cancer cells in humans. Another study suggests that the decrease in expression of Cd protein kinase isoforms and protein kinase plays a critical role in AE-induced apoptosis, while another study shows that AE shows anticancerigenic activity in two colon carcinoma-DLD-1 and WiDr, and that cytotoxic mechanisms involve the induction of apoptosis.

 

Antimicrobial activity

The incidence of resistance to medication increases daily around the world and causes many health problems in terms of treatment failure. Numerous studies have shown that Aloe Vera and its constituents act as antimicrobial agents. An important study was conducted to investigate the phytochemical compounds of Aloe Vera and the antimicrobial activity of various Aloe Vera extracts, and it was found that the maximum antibacterial and antifungal activity occurred in acetone extracts compared to aqueous extracts and ethanol. In another study of the Aloe Vera plant, the serial dilution method revealed that a high concentration (1/10) inhibited the growth of gold staphylococcus, while moderate concentrations were necessary to inhibit the growth of Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi. Another study was conducted to determine the antimicrobial activity of Aloe Vera juice against Gram-positive and Gram-negative bacteria, and the results showed that the antibacterial activity of Aloe Vera juice was particularly effective against Gram-positive bacteria. An experiment was carried out to analyze the antimicrobial activities against S. aureus, S. pyogenes, P. aeruginosa and E. coli, and it was observed that the maximum antibacterial activity was in the case of the extract made with acetone, not alcohol or water. An assay was performed using isolated pathogens from dental caries and periodontal diseases; the inhibitory activities of Aloe Vera gel on some cariogenic and periodontal pathogens and an opportunistic periodontic pathogen were investigated and the results showed that S. mutans were the most sensitive species with a minimum inhibitory concentration (MIC) of 12, 5 μg / ml, whereas A. actinomycetemcomitans, P. gingivalis, and B. fragilis showed a lower sensitivity with an MIC of 25-50 μg / ml. Another study has shown that the ethanolic extract of Aloe Vera leaves showed a wider growth inhibition range of 29-30mm than the 3-4mm aqueous extract against Enterococcus bovis and Staphylococcus aureus. The antimicrobial activity of Aloe Vera juice was investigated using the agar discarding method against bacteria, fungi and yeasts, and it was observed that Aloe Vera juice showed antibacterial activity only against Gram-negative A hydrophilia and E. coli bacteria.

Other studies have confirmed that Aloe Vera juice is bacteriostatic against Staphylococcus aureus, Streptococcus pyogenes and Salmonella paratyphi. An important study focused on antimicrobial activities of various types of aloe preparations, such as fresh, preserved gel, refreshing gel and acne cream against various microorganisms; it has been observed that the fresh and preserved gel has shown maximum areas of inhibition against Bacillus subtilis and the refolding gel and acne cream against Staphylococcus aureus. An experiment was carried out to evaluate the antibacterial activity of Aloe Vera extracts such as extracts in ethanol, methanol and distilled water, and the extract in methanol showed maximum antibacterial activity among the solvent extracts.

 

Antioxidant activity

The production of free radicals is balanced by the antioxidant defense system in our body and any alteration of this balance between the generation of reactive oxygen species (ROS) and their neutralization by the defense mechanisms causes oxidative stress, which plays a role in the pathogenesis of diseases. Medicinal herbs contain different types of constituents, such as vitamins, amino acids, carbohydrates and phenolic compounds, and these compounds are active in controlling or neutralizing ROS. Previous studies have supported the role of ROS in cancer development and antioxidants in the diet and endogenous ones seem to be vital as agents that prevent cancer by neutralizing ROS. In this context, Aloe Vera with its potent antioxidant activities can be used for disease management. Aromatic Volatile Oxidative Stress (AOM) in rats was tested to study the effects of oral Aloe Vera (AGE) gel feeding and the results showed that hepatic glutathione (GSH) and AOM reduced uric acid levels were returned to normal values ​​by AGE feeding.

 

The antioxidant properties of AGE prepared in methanol (Aloe Vera gel extract in methanol or MEAG), 95% ethanol (ethanolic Aloe Vera gel or EEAG gel), hexane (HEAG), acetone (AEAG) and chloroform ( CEAG), and it was found that MEAG and AEAG had maximum free radical removal (DPPH) and superoxide radicals. In addition, a study was conducted on polysaccharide and flavonoid concentrations in 2, 3 and 4 year old Aloe Vera plants to evaluate antioxidant activities; the 3-year-old Aloe Vera extract showed the strongest free radical neutralization activity, which is significantly higher than that of butylated hydroxytoluene (BHT) and alpha-tocopherol.

 

Anti-inflammatory activity

Inflammation is the body's natural response to wounds and infections. Medicinal plants and their constituents play the role of anti-inflammatory agents without any other adverse reaction. Aloe Vera is one of the best known natural remedies that can reduce swelling / redness. An important study was conducted to evaluate the effects of different types of extract on carrageenan-induced edema in rat paw; the results showed that aqueous extracts and chloroform reduced edema in the hidden part of the paws and that the aqueous extract inhibited the production of prostaglandin E2 from arachidonic acid. Another study has been conducted on mice that have been induced with STD, a study in which anti-inflammatory activities of both Aloe Vera and gibberellin were measured, and both have been found to inhibit inflammation in a dose-response manner. A report shows that Aloe Vera extract reduced inflammation by 48% in a rat model with induced arthritic inflammation, and an in vitro colorectal human mucosa study confirmed that Aloe Vera gel inhibited prostaglandin E2 production and secretion of IL- 8.

Lupeol, a sterol present in a variety of plants including Aloe Vera, has antimicrobial, antitumor and anti-inflammatory properties.

 

Antidiabetic activity

Diabetes is a major endocrine / metabolic problem and a major problem worldwide. Several plants and constituents of these, such as ginger and ginger, have been shown to be therapeutically useful in managing diabetes problems. Aloe Vera plays an important role in the management of diabetes and associated symptoms. Studies that support the Aloe Vera efficacy have reported that the use of Aloe gel increases glucose tolerance in diabetic and normal rats, and another study concluded that Aloe contains a hypoglycemic agent that lowers blood glucose, but the exact mechanism is unknown.

 

The results of a study show that after administering for a period of 28 days 5 Aloe Vera phytosterols such as lofenol, 24-methyl-lopenol, 24-ethyl-lopenol, cyclotartanol and 24-methylenecyclaranol, the glucose level in the blood slowing down to about 64%, 28%, 47%, 51% and 55% of control levels, respectively. A key study has highlighted the significant reduction in fasting blood glucose, hepatic transaminases, plasma and tissue cholesterol, triglycerides, free fatty acids and phospholipids, and also revealed a significant improvement in insulin of plasma when AGE was administered orally at a dose of 300mg / kg. The administration of high molecular weight fractions of Aloe Vera (AHM) for 12 days, 3 times a day, together with oral hypoglycemic medications, lowered glucose levels on fasting and food and water intake in rats with induced diabetes STZ compared to rats in the control group and after administering extract of Aloe Vera juice to diabetic rats, they showed a tendency to return to normal.

 

Hepatoprotective effect

Liver diseases are a major health problem around the world. Allopathic medicines such as paracetamol and ibuprofen belong to a class of medicines called non-steroidal anti-inflammatory drugs (NSAIDs) that are used to control pain; fever and inflammation are among the main culprits in liver damage / cirrhosis. Studies have demonstrated the hepatoprotective activity of Aloe Vera against carbon tetrachloride; a study was conducted on the protective effects of fresh leaf extract of Aloe Vera in lindane-induced hepatotoxicity and genotoxicity (LD), and the results showed that pretreatment with Aloe Vera leaf extract at a concentration of 1 ml / kg body significantly reduced serum glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) elevated with 100 mg / kg body weight of LD.

Another important study has tested the hepatoprotective activity of the Aloe Vera aqueous extract against practamol-induced hepatotoxicity in albino rats; one-day Aloe Vera extract (250 mg / kg and 500 mg / kg) reduced the aspartate transaminase (AST) and alanine transaminase (ALT) and the 500 mg / kg reduced the level of ALP in particular and restored the level of thiol in the liver.

 

Immunomodulatory effect

Aloe vera, used therapeutically, plays a vital role in the immune system, as demonstrated by macrophage viability, and is also effective in protecting against pathogens. A mouse macrophage cell line study, RAW 264.7, was designed to elucidate the effects of acemannan and was found to stimulate cytokine production in the case of macrophages, nitric oxide release, surface molecule expression, and morphological changes at the level cell. An important study was conducted to explore the effect of Aloe Vera aqueous extract on cellular and cell mediated immune parameters and it was found that Aloe Vera (400mg / kg, orally) significantly increased the secondary humoral immune response. Another study found that the suppression of pyrogalol-induced humoral and cell mediated immune response was significantly alleviated by oral treatment with Aloe Vera extract and more, the 100 mg / kg dose was found to suppress hypersensitivity reactions in a model of mouse study.

 

Anti -ulcer effect

Different factors such as food ingredients, stress, Helicobacter pylori, smoking, NSAIDs, and medicines are responsible for stomach ulcers. Aloe Vera and its constituents, including polysaccharides, anthraquinones and other valuable ingredients, can act significantly to inhibit peptic ulcers by controlling gastric secretion. An important study in supporting the anti-ulcer activity of the Aloe Vera plant revealed that the mean control group index was 50 ± 3.5, while the mean index for the Aloe Vera group was 20 ± 1.79 and the mean index for the omeprazole standard treatment group was 10 ± 1.96. Another study to support the curative activity of the Aloe Vera plant reported that treatment with sucralfate and Aloe Vera for ulcer groups reduced gastric inflammation, increased proliferation of epithelial cells, prolonged gastric glands, and reduced ulcer size.

 

Skin protection and hydration activity

Natural herbal products are effective in protecting the skin, being rich sources of antioxidants. Supplementing vitamin, mineral or essential fatty acid diet improves the condition of the skin. In this context, different plants such as Nigella sativa, turmeric and Aloe Vera are very effective for protecting the skin, being rich sources of antioxidants and vitamins, which are important for health and can also neutralize the effects of ultraviolet radiation.

The results of a key study confirmed that the Aloe Vera gel contains low molecular weight immunomodulators such as G1C2F1 that prevent ultraviolet B (UVB) -induced skin immune suppression, repairing damage to the Langherhans epidermal cells.

 

The photoprotective effect of Aloe Vera on different hair types has been investigated and it has been concluded that Aloe Vera juice was satisfactory as a photoprotective agent for all hair types, but the degree of protection varied with each type of hair. A study concluded that Aloe Vera gloves have improved skin integrity, decreased wrinkles and decreased erythema in dry skin and irritant contact dermatitis.

 

The anti-aging effect

Medicinal plants including Aloe Vera have shown significant anti-aging effects. However, the exact mechanism behind these effects is not completely understood. A previous study has shown that the anti-aging effect of Aloe Vera is linked to the production of collagen and elastin fibers, making the skin more elastic and less wrinkled.

 

Laxative effects

An important study has highlighted the relationship between increasing intestinal water content and stimulation of peristalsis, which confirms that aloe-emodin-9-antron is the main agent responsible for the cathartic effect of barbalin.

 

The role of Aloe Vera in dentistry

Medicinal plants and their constituents are used to solve dental problems due to antibacterial and healing activities. Aloe Vera is very useful in the treatment of gum disease, including gingivitis and periodontitis. A study was conducted to evaluate the effectiveness of Aloe Vera mouthwash in plaque and gingivitis (in the experimental setting), and it was observed that the mouthwash containing Aloe Vera resulted in significant reduction of plaque and gingivitis; however, the effect was weaker than that of chlorhexidine.

 

Conclusion 

Treatment based on synthetic / allopathic drugs is effective for the prevention and treatment of diseases, but such treatment is costly and also has adverse effects. The implications of natural products for disease prevention and treatment are on the rise throughout the world, especially in developing countries, due to their accessibility and reduced side effects. However, there are few studies to confirm the optimal dose and the mechanism of action of the Aloe Vera plant in preventing and treating diseases. In this situation, detailed studies are required to be carried out as soon as possible to verify the therapeutic potential, safety and mechanism of action of the Aloe Vera plant in disease management.

 

 

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