A Wonder Plant Aloe vera L. (Liliaceae): An Overview of its Folk Traditional Uses, Phytoconstituents, Biological Activities, and Cosmaceutical Applications

: Aloe vera L. (Lililaceae) bears various medicinal applications that likely date back more than a thousand years ago. The current review provides an overview of the folk traditional uses, phytochemistry, biological activities, and cosmaceutical applications of the A. vera plant to date. The data have been retrieved from different scientific databases, including PubMed-Medline, Researchgate, Google Scholar, Science Direct, Scopus, SciELO, Taylor & Francis, Web of Science, books, conference papers, Masters and Ph.D. dissertations. As per the collected data of this review, almost 40 active phytoconstituents in A. vera have been reported so far with varying concentrations. Ethnobotanical data displayed that A. vera is still used as traditional medicine among communities against more than 20 different health-related problems. The DPPH, FRAP, TAC, and ABTS assays were commonly employed where A. vera extracts showed varying antioxidant activities against reactive oxygen species (ROS). Data on the biological activities showed A. vera plant extracts with remarkable anti-inflammatory activities through the inhibition of TNF-α and prostaglandin E2 factors and also exerts anti-diabetic activity against type 1 and type 2 diabetes. As per the collected data of this review, A. vera extracts have been reported with anti-microbial activities against more than 12 bacterial and 7 fungal strains and also obstruct the uncontrollable proliferation of specific types of cancer cells like HCT-116, HepG2, HeLa, A549, and MCF-7. Conclusively, A. vera possesses wide-ranging applications in the treatment of various diseases. However, more controlled investigations and clinical trials with the elucidation of the mechanism of action activities are prerequisites in the future to substantiate the outcomes and efficacies of A. vera under different circumstances. Any toxic effects of A. vera if associated with specific extracts or compounds should be addressed for safer consumption of Aloe-based food and cosmetic products.


INTRODUCTION
Plants have a wide background in the pharmaceutical and cosmetic industries along with food fields and are very significant in the development of human civilizations [1][2][3][4].Some plants are used pliantly as folk medicine or herbal drugs since the time of the bible.Different classes of plants including bryophytes, tracheophytes, and their subclasses have been used to treat certain human diseases.It is well explained in the ethnobotanical field studies from different regions [5,6].The plants mostly used in traditional medicine belong to the tracheophyte's subclass angiosperm (94.6 %), followed by the pteridophytes (3.3 %), and gymnosperm (2 %) [7].Mosses with ~29 species are the only group with the most uses, whereas liverworts only contributed 3 species and with no available data on traditional uses of hornworts [8].
Ali et al. [7] reported the percentages of parts of plants for ethnomedicinal use including leaves (44 %), stem (12 %), roos (10.66 %), fruit bark (5.33 %), rhizome (5.33 %), stem bark (2 %), blub (3 %), shoot (1.33 %), resin (1.33 %), and come pedicle, the capsule was 0.66 %.The contribution of trees was 16 %, shrubs 11 %, and herbs 73 % (Figure 1a-b).Among all the higher plants, perennial succulent plants of the genus Aloe of the Liliaceae family are found in moderate and subtropical areas of the world.The word Aloe, which means a bitter, shining material, comes from the Arabic "Alloeh" or the Hebrew "Halal."Africa is where this plant genus first appeared [19].There are almost 200 species in the genus some of them are grown for the sticky latex that their large, meaty leaves.Aloe plants have been used as purgatives and cure for skin conditions since the time of the Bible [20]. A. vera is also called elephant's gall, burn plant, "lily of the desert" and Aloe.This plant is sometimes known as A. brobadensis having green, stilettoshaped, marginated, tapering, fleshy, spiky leaves that contain a clear viscid gel [21,22].
A. vera leaves discharged two different forms of exudates on cutting, one is a sour reddish-yellow juice found in pericyclic cells under the leaves' heavily cutinized epidermis.This "juice" has often been used in dry form as a laxative [23].Aloin, aloeemodin, and other similar chemicals give it a bitter flavor.The thin-walled, cylindrical cells in the inner center region (parenchyma) of the foliage generate the other exudate, a translucent, slick mucilage or gel [20,24].
The pharmaceutical and cosmaceutical industry most often uses the plant's latex and gel as it contains a range of organic components believed to contribute to the gel's alleged emollient, moisturizing, and are few skin conditions where A. vera is used to treat these complications. A. vera sap has healing potential [20] for cuts, burns, and eczema supposedly decreasing inflammation and relieving discomfort.However, there are still some disagreements on the benefits of A. vera sap on the healing process [1,[29][30][31].Some important reported A. vera-based food, pharmaceutical, cosmaceutical, and other products developed are shown in Figure 2.
Considering the potentials of A. vera, the present review provides a brief account of ethnobotanical uses with the range of chemical Fig. 1.A) Contribution of trees, herbs, and shrubs used as folk traditional medicine, B) Contribution of parts of plants used for ethnomedicinal purposes.Source: Ali et al. [7].cosmetic products with improved nutritional and therapeutic effects.

Data Search Approach
The data have been compiled after going through a detailed study on morphology, phytochemistry, folk traditional uses, biological activities, and cosmaceutical and food products of A. vera from different databases like Pubmed-Medline, Researchgate, Google Scholar, Science Direct, government reports, SciELO, Web of Science, Scopus, Springer Link, and Taylor & Francis, and from Masters and Ph.D. dissertations.While searching the data, specific keywords were used including ethnobotany of Aloe vera, Aloe vera morphology, Aloe vera phytochemistry, Aloe vera medicinal uses, Aloe vera biological activities, Aloe vera antioxidant activity, Aloe vera antimicrobial activity, Aloe vera antidiabetic, Aloe vera anti-inflammatory, Aloe vera cytotoxicity, and Aloe vera based cosmaceutical and food products, etc.The data for this review was collected from the articles published up to 2023 in the English language.

RESULTS
Overall, 132 articles were studied and the required data have been retrieved and compiled, and consequently presented.The detailed review of the selected articles showed that A. vera has been long used as traditional medicine in almost 12 countries against more than 20 different disease categories (Table 1).Almost 40 different types of active phytochemicals have been reported in the extracts of A. vera so for

RESULTS
Overall, 132 articles were studied and the required data have been retrieved and compiled, and consequently presented.The detailed review of the selected articles showed that A. vera has been long used as traditional medicine in almost 12 countries against more than 20 different disease categories (Table 1).Almost 40 different types of active phytochemicals have been reported in the extracts of A. vera so for (Table 2) including phenols, flavonoids, alkaloids, tannins, saponins, etc.The total flavonoid content was estimated by the colorimetric method and the total phenol content was estimated by the folin-ciocalteu method.
Data showed that the total tannin content was mostly quantified by the vanillin-HCl method, and alkaloid content was determined with the bromocresol green method.For the antioxidant activities of A. vera extracts against reactive oxygen species, DPPH, FRAP, ABTS, and TAEC were the most widely used techniques (Table 3).It was confirmed that the phytochemicals of A. vera extract have anti-inflammatory activities by targeting/inhibiting the TNF and MMP-9 factors (Table 4).
Aloe extracts also possess anticancer activity by preventing the uncontrollable division of specific types of cancer cells like HCT-116, HepG2, HeLa, A549, and MCF-7, hence reducing the chances of blood cancer/leukaemia, liver cancer, breast and lung cancer (Table 5).The restoration of insulin level was evident for the extracts of A. vera that authenticates its potential antidiabetic activity (Table 6).Antimicrobial activity data showed that the extracts of this plant were active against 12 bacterial and 7 fungal strains (Table 7).The current review also manifested that there are a lot of Aloebased food and cosmetic products that have been commercialized with nutritional and cosmaceutical applications (Table 8).

Morphology of A. vera
The Aloe plant is comprised of leaves, short stems, roots, and flowers (Figure 3), and its morphology has been extensively studied by various authors [22][23][24]32].A. vera live for more than two years and has sukers at the base.The green, glabrous, glaucous, margin sparsely dentate leaves are sessile, erect, and linear-lanceolate with a length range from 15 -35 cm and a width range from 4 -8 cm [23,24].
Malik et al. [22] explained some physical characteristics of the fresh and dried Aloe leaves such as length, weight, width, etc.In their study, the reported lengths of the fresh and dried leaves were 43.3 and 38.5 cm, weight was 5.4 g and 5.2 g, and width was 8.2 cm, and 6.1 cm respectively.The reduction in these physical parameters of fresh and dry weight, length, and width of the leaves is due to dehydration causing the reduction of gel weight [22].The short stem had 1 -2 branches on which erect pedunculate raceme inflorescence occurs which may be 60-100 cm in length.It has ovatelanceolate and persistent bracts; 9-12 x 5-6 mm.The flower of A. vera formed on the short pedicel and the perianth is dull reddish, lobes 6, almost equalling the tube, and 2.5-3 cm long.The color of the flower ranges from reddish to pale yellow capsule of 1.5 cm [22,33].The roots are fibrous that absorb water and nutrients required for proper growth and development.Some physical parameters of A. vera roots studied [23] showed varying color, length, weight, and width.The color of the fresh roots is brown and became dark on drying.The fresh and dried root lengths reported were 35 cm, and 34 cm long, 5.4, and 5.2 cm wide with 0.5 g, and 0.4 g weight [22].

Folk Traditional Uses of A. vera
Plants have various beneficial traditional uses and different plant species are used as medicine by people of different regions according to the information they know about that particular plant [34][35][36].The traditional uses depend on the cultural and religious knowledge of the plant.The ethnobotany of A. vera (Table 1) has been extensively studied among communities of different regions where it has been used as a traditional medicine against many diseases [37][38][39][40][41][42][43][44][45].
In one study, A. vera leaves gel was used to treat the hypoglycaemic effect (condition of blood when the glucose level is lower than the normal 70 mg/dL) because the gel controls diabetes [48].The study by Siew et al. [38] in Singapore described local uses of A. vera against respiratory diseases and cancer by using its leaves as decoctions, eaten raw or in the form of juice.As per their data, it improves immunity and blood circulation and is a better remedy against acne, mouth ulcer, itching, and arthritic pain.
Asif [48] reported that A. vera is a woundhealing remedy which has been utilized against skin ulcers, gastric ulcers, mouth ulcers, psoriasis, skin injury, herpes simplex virus, and age-related problems.Mutie et al. [49] reported different uses of A. vera plant gel from Kenya, where it was used against cough, swelling of the diaphragm, peptic ulcers, malaria, and wounds.A recent study in Tanzania showed that the A. vera leaves were used to treat malaria, general stomach problems, hernia, typhoid, wounds, ringworms in humans, and new castle disease in chickens [45].Aloe latcritia, Aloe secvndiflora, and Aloe duckcri were the most frequently used species against diseases without any side effects whereas A. secundiflora was reported to cause death if taken in high doses.
As per the collected data of this review, the most commonly used parts of the A. vera plant as traditional medicine includes leaves (70 %), followed by the flowers (20 %), and roots (10 %) (Figure 4).It is found that despite of industrial use of A. vera it is also being used by people to treat almost more than ~20 different health problems.

Medicinal Uses of A. vera
The ancient Aloe plant has been proven to be medicinally significant by various research groups [1,2,4,[29][30][31].Manvitha and Bidya [39] reported various phytochemicals from the Aloe plant useful in medicine such as curing sunburn, tumor formation, and inflammation, maintaining cell growth and development in the body, and maintaining sugar levels in diabetic patients.According to Grace et al. [29], natural products extracted from A. vera leaves such as carbohydrates, can be applied to treat skin diseases and a liquid matrix, can be used as an effective purgative or in veterinary medicines.
Gupta and Rarawt [30] reported the effectiveness of A. vera in reducing joint pain, muscle-related tendonitis, and other injuries.Aloe juice reduces stress (oxidation stress) and biological and physical alterations in the body.Tiwari and Upadhayay [31] reported that the latex in the leaves of A. vera contains anthraquinones which stimulate bowel contraction.Particularly, emodin found in latex act as an anticancer drug for lung, prostate, and skin cancers.Asif [48] studied the sugar-controlling ability of A. vera and showed improvement in carbohydrate metabolism, anti-hyperglycemic and anti-hyperchloremia effects in diabetic patients and hence maintaining the blood sugar, body fat, and body weight.
According to Danish et al. [1], Aloe contains high water content and can be used as a body moisturizer.Moreover, it cures thermal burn, stomach ailments, sunburn, and wounds caused by radiation and helps in cell growth, and provides relief against constipation.Sayar et al. [2] reported that Aloe possesses many anti-microbial and inflammatory properties and can cure gingivitis (a mild redness, irritation, and swelling in gums) and reduces bleeding and swelling of the gums.
Farid et al. [4] reported medicinal uses of the A. vera plant due to its exceptional features.It is considered a revolutionary weapon against various diseases in medical treatments and services.Traditionally A. vera has been used to cure dermal disorders but presently, more advanced advantageous therapeutic uses of this plant in bone marrow BM-MSC (mesenchymal stem cells) transplantation has been investigated which will help in curing liver complications.
diseases and a liquid matrix, can be used as an effective purgative or in veterinary medicines.

Ethnobotany, Phytochemistry, Biological Activities and Cosmaceutical Applications of Aloe vera
Raphael et al. [33] and Kumar et al. [60] performed different tests for the analysis of the phytochemical constituents in the aqueously extracted gel from the leaf of A. vera.They reported tannins, phlorotannins, saponins, flavonoids, anthraquinones, terpenoids, steroids, and alkaloids in the extracts of A. vera.
Cardralli et al. [61] studied the Aloe marlothii and Aloe melanacatha to analyze the phytochemicals in the methanolic extracts of gel from leaves through Mass spectrophotometry.Aloeresins, Aloe resin A (843.4 g/100g), anthraquinones aloin (0.66-4.96 g/100g), and hydroyaloins were found with a major part of gallic acid and polyphenols, flavonoids and flavonols as a phytochemical constituent in the studied Aloe species.
Dharajiya et al. [56] reported phytochemicals like saponins, alkaloids, tannins, cardiac glycoside, sterols, flavanoids, and phenol in the four different types of extracts (ethyl acetate, hexane, methanol, aqueous) from the fresh leave of A. vera by using thin layer chromatography.
Usman et al. [65] also reported phytochemicals in A. vera leaves skin and gel extracted by the aqueous extraction method.They confirmed the presence of alkaloids (31.067 g/100g), saponin (10.67 g/100 g), tannins (25.66 g/100 g), glycosides (0.060 g/100 g), and minerals like phosphate and magnesium in the Aloe plant.
In a study, it has been validated that the extracts of Aloe species possess complex phytochemical components [66].Tannins, phenolics, alkaloids, flavonoids, and tri-terpenes were present in the ethanolic extract from the gel made from the leaves of A. barbadensis.The n-hexane fraction showed only phenols, alkaloids, and flavonoids.The petroleum ether showed tannins, phenolic, and flavonoids.The chloroform fraction showed tannins, phenolics, saponins, alkaloids, and flavonoids.Tanning agents, saponins, alkaloids, and flavonoids were visible in the dichloromethane fraction.Tannins, flavonoids, phenolics, saponins, alkaloids, and tri-terpenes could be seen in the acetone fraction.Additionally, tannin, phenolics, alkaloids, and flavonoids were present in the methanol fraction [66].Hamdeni et al. [17] evaluated the phytochemistry of A. vera and reported the presence of phenols, flavonoids, flavonols, and condensed tannins using various techniques.
Bendjedid et al. [67] reported phytochemicals in the leaves of A. vera by extracting the gel using ethanol as a solvent using the LC-MS method.
Overall, for the phytochemistry of A. vera, more than 40 diverse groups of chemicals have been reported with potential effects against numerous health-related disorders, however, still there is a possibility to quantify more novel groups of compounds in Aloe species using advanced analytical techniques to unveil the medicinal significance of individual compound.Some of the essential phytochemical groups reported from Aloe species are illustrated in Figure 5.

Biological Activities of A. vera
Some of the essential biological activities of A. vera extracts and chemical constituents are illustrated in Figure 6 and the details are discussed below.

Antioxidant Activity
The activity of preventing oxidation (formation of free radicals), lowers the chances of tumors and various heart diseases.Antioxidants are a group of compounds that inhibits the free radicals and lipid oxidation reactions in the body [36,77,78].A lot of studies have described the antioxidant activity of the A. vera plant [27,57,58,70,[79][80][81][82] and the details of antioxidant activity conducted globally using various methods are given in Table 3.
Vega-Gálvezv et al. [83]  Benzidia et al. [79] found that the tannins in A. vera are the major phytochemicals that can inhibit free radicals with DPPH assay using three different fractions (F1, F2, and F3) of the acetone-aqueous extracts of A. vera gel.The reported ranges of antioxidant activity were 1.9, 3.74, 5.55, and 2.8 mg/ml correspondingly.
Quispe et al. [85] evaluated the ethanolic extract of A. vera gel, peels, roots, and flowers for antioxidant activity with DPPH, ABTS, and FRAP methods.The highest antioxidant activities of peel recorded were 2.43 mM ET/g MF in the DPPH assay, 34.32 mM ET/g MF in the ABTS assay, and 3.82 mM ET/g MF in the FRAP assay.
Tariq et al. [57] validated that the extracts from A. vera gel using methanol, ethanol, n-hexane, and aqueous solvents scavenged the free radicals and

Biological Activities of A. vera
Some of the essential biological activities of A. vera extracts and chemical constituents are illustrated in Fig. 6 and the details are discussed below.

Antioxidant Activity
The activity of preventing oxidation (formation of free radicals), lowers the chances of tumors and various heart diseases.Antioxidants are a group of compounds that inhibits the free radicals and lipid oxidation reactions in the body [36,77,78]    Martínez-Sánchez et al. [80] documented the antioxidant activity of organic extract of A. vera flowers at different maturity stages with DPPH, ABTS, and FRAP radicals scavenging assays.The obtained values of antioxidation of free radicals were 179.91 ± 8.16 mg TEA/100g, which were highest in the first immature stage of the flower and decreased as the bud opens.Kaparakou et al. [86] reported the antioxidant potency of methanol extract of A. vera leaves gel with ABTS and DPPH assays and the range of recorded activities were 1.64 to 9.21 μmol Trolox mL −1 and 0.73 to 5.14 μmol Trolox mL −1) respectively.Ojha et al. [82] validated that A. vera possesses active phytochemicals with a considerable reduction in the oxidation of compounds and a decrease in the concentration of free radical superoxide ions (42.49+ 0.92 %) and hydrogen peroxide (35.95 + 0.97 %) in male albino rate when dosed with 6 mg/kg of extraction of Aloe plant.
The data compiled in this review for the antioxidant activity of A. vera showed that overall, 9 different organic extracts from various parts of the A. vera plant were proven to have potential antioxidant activities and DPPH and FRAP methods were the commonly used methods for the evaluation of antioxidant activity of A. vera.Nevertheless, it is proposed that some biological models to evaluate the activities of A. vera extracts on lipid peroxidation and activities on different enzymes with oxidizing potentials including adenine dinucleotide phosphate oxidase (NOX), nitric oxide synthase (NOS), monoxides and nicotinic and xanthine oxidoreductase (XO) etc should be explored.

Anti-inflammatory Activity
The activity of reducing redness, swelling, and pain in living organisms is termed anti-inflammatory activity.In many studies, the phytochemicals extracted from A. vera were reported (Table 4) to be active in reducing inflammatory effects [87][88][89][90][91][92][93][94][95][96].In a study, Devaraj and Karpagam [88] tested the aqueous extract of A. vera leaf for its ability to reduce inflammation.They employed albino Wistar rats as substrates and varied extract concentrations and observed the effects of carrageenan and formaldehyde on rat paw edema to unveil the antiinflammatory efficacy of A. vera.It was confirmed that the leaf extracts at a dosage of 600 mg/kg reduce the development of edoema brought on by carrageenan and formaldehyde with no mortality and gives anti-inflammatory effects.
Vijayalakshmi et al. [90] performed MMP inhibition tests on peripheral blood mononuclear cells (PBMC) isolated from heparinized venous blood using the ficoll diatrizoate gradient centrifugation method.A. vera aqueous extract was proven to inhibit the MMP-9 in a dose-dependent manner with gelatin zymography and RT-PCR procedures.Williams et al. [87] and Huseini et al. [89] corroborated that A. vera chromones inhibit the cyclooxygenase pathway and reduce the production from arachidonic acid of prostaglandin E2 in rats with carrageenin-induced paw edema.Whereas, mice with Croton oil-induced edema show a significant decrease in inflammation due to Farzadinia et al. [91] documented the antiinflammatory effect of A. vera using it as honey milk A. vera ointment on the burning part of male albino rats.The burn was induced artificially and treated with HMA ointment containing dried Aloe gel powder, honey, and dry milk powder displayed observable anti-inflammatory effects, hence reducing edema by drying out, granulation, and closing of the wound edges, and increase in catalase activity.It also lowered the amount of collagen fiber and the hardness of the skin and increased the formation of connective tissue.
Paul et al. [93] reported the anti-inflammatory activity of A. vera gel homogenate for immune modulation of inflammatory arthritis conditions.It was validated that hypotonicity-induced (74.89 ± 1.26 %) and heat-induced (20.86 ± 0.77 %) RBC membrane lyses can be inhibited by the use of A. vera gel homogenate at a concentration of 1000 μg/ ml.The same concentration can be used for the in vitro inhibition of protein denaturation (39.35 ± 4.25 %).The effect of A. vera was also assessed in vivo, and the results showed a reduction in tissue damage thus maintaining the normal functioning of TNF-α and Cox-2 gene expressions for the immunemodulation of inflammatory arthritis condition.
Naini et al. [92] investigated the antiinflammatory activity of A. vera on experimental colitis (Inflammatory disease) in Wistar rats.Trinitrobenzenesulfonic acid (TNBS) was used for the induction of experimental colitis in rats and the extracts of A. vera were administered to the rats orally or rectally.Tumor necrosis factor, interleukin-6, and nitric oxide levels were higher in colonic tissue from rats with experimental colitis, and malondialdehyde and myeloperoxidase concentrations were also higher.A. vera treatment had a healing impact with an anti-inflammatory effect in rats.
Villarreal et al. [96] confirmed the antiinflammatory effect of A. vera with ELISA assays (enzyme-linked immunosorbent assay) and reported an increase in the expression of cytokine and IL-1β (released during immune-response) levels in human gingival fibroblasts.The A. vera gel extract was able to decrease cyclooxygenase-2, 5-lipoxygenase biosynthesis, inducible nitric oxide synthase (iNOS), and TNF-α concentration hence proving a major role in lowering inflammation.
Overall, 9 organic extracts from A. vera were used in vitro and in vivo, showing anti-inflammatory action by inhibiting enzymes and factors such as TNF-α in humans.It is further proposed that extracts from A. vera should be evaluated against more factors other than TNF-α and inflammationcausing pathways at the cellular level should be targeted to better explore the anti-inflammatory potentials of this plant.

Anticancer Activity
The activity of controlling the proliferation of cells or reduction of cancer-developing cells by A. vera extracts was reported by various authors  as shown in Table 5. Jose et al. [94]  Mahendiran et al. [62] reported the anticancer activity of aqueous extracts of A. vera gel against three cancerous cell lines such as cervical (HeLa), human breast adenocarcinoma (MCF-7) and epithelioma (Hep-2), and one normal human dermal fibroblast (NHDF) cell lines with MTT assay and found positive results.Karpagam et al. [97] investigated human cancer cell lines HeLa, HepG2 (liver cancer cell line), and A549 were used to test the anticancer properties of the ethanolic leaf extract of A. vera using the 3-(4, 5-dimethylthiazole-2yl)-2, 5-diphenyl tetrazolium bromide assay (human lung adenocarcinoma epithelial cell line).Their outcomes confirmed the presence of several active compounds with anticancer potential in the ethanolic leaf extract of A. vera.In another study, A. vera gel was used as a capping and reducing agent for the creation of Ag@TiO2 nanoparticles.It was also found that the nanoparticles containing A. vera gel have activity against lung cancer cell lines (A549).After being administered systemically in vitro, the Ag@TiO2 NPs produced a significant amount of reactive oxygen species (ROS), which completely suppressed the development of cancer cells [98].[99] reported that A. vera gel extract and sunlight were used to synthesize silver nanoparticles with anti-cancer activity.After 72 hours of incubation with AgNPs-AV in vitro, a rapid fall in breast cancer cells was observed.This greenly synthesized nano-formulation offers a lot of promise to be studied from a variety of angles.

Mohamed and Masry
Ahmad et al. [101] evaluated the methanolic extracts of the healing herbs Aloe castellorum and Aloe pseudorubroviolacea to reduce the human colon cancer, cell line (HCT-116).The methanolic extract of A. castellorum has more cytotoxic activity than A. pseudorubroviolacea against HCT-116, which was confirmed with the GC-MS technique.Murugesan et al. [100] developed a potent and efficient anti-carcinogenic gel material that represents a cutting-edge medicine delivery technique.The cytotoxic tests revealed that a loaded phospholipid A. vera was biocompatible and was

Antidiabetic Activity
The high sugar level in the blood of the organisms causes diabetes and different health effects and high cholesterol in the body can be controlled by the extract of the A. vera plant.A lot of studies have reported the activity of A. vera extracts against diabetes  and the details are given in Table 6.
Mohamed [102] conducted an experiment on diabetic and control rats to delineate the consequence of A. vera gel extract in the control of diabetes.Experimentation was conducted on 4 groups of forty rats, and the result showed that oral administration of A. vera gel extract can reduce serum glucose, total cholesterol, and triacylglycerols.The hypoglycemic effect of A. vera gel extract may be due to the occurrence of hypoglycemic trace elements such as Cr, Zn, and Mn which potentiate insulin action.A. vera gel extract possesses an antidiabetic effect due to an increase in serum cholesterol and tri-acylglycerols.
In another inquiry, Babu et al. [50] studied the flower and epidermis extract of A. vera that possesses amylase and alpha-glucosidase with anti-diabetic properties.The flower and gel have phytoconstituents like proteins, phytosterols, carbohydrates, and mineral components making it suitable for use as an anti-diabetic drug.Their outcomes also validated that the gel and flower of A. vera are more anti-diabetic than the epidermis of leaves.Muñiz-Ramirez et al. [103] applied different assays for the evaluation and determination of methanol extract of A. vera for the prevention of diabetes caused by AGEs (Advanced glycation end products) formation.AVM was found to be effective against the formation of AGEs as well as carbonyl protein, CML, and fructosamine.
The best results were obtained at the concentration of 5 mg/ml of AVM.AVM also worked for the inhibition of enzymes like α-amylase and α-glucosidase.Whereas thiol group content was found to be increased with the period within 4 weeks.It was found that AVM is effective against AGEs and inhibits the formation of postprandial glucose, so reducing the chances of diabetes associated with AGE.
Babu et al. [104] observed the mechanisms involved in the mitigation of streptozotocin-induced diabetes in rats by using A. vera gel extract through the proteomics approach.They validated that A. vera extract (AVE) alleviates diabetes by regulating the pathways involved in the development of diabetes.In AVE, both the components carbohydrate fraction and polypeptide fraction (CF & PPF) synergistically work to regulate the insulin fraction.Hasan and Abdulla [105] studied the gel extracted from A. vera with polysaccharide which regulates the blood sugar level.The gel was prepared by dissolving 7.5 g Aloe gel in 100 ml distilled water.

Their
outcomes confirmed that the hyperglycaemic state could be normalized by the treatment of A. vera extracts as they possess phytochemicals, minerals, and many primary metabolites that regulate blood glucose levels.
Haghani et al. [107] assessed the chemical properties of A. vera and its effects on Streptozotocininduced diabetes mellitus.A. vera can control blood glucose, recover plasma insulin, decrease oxidative stress, and stimulate the production of collagen and elastin fibers and hence leading to the healing effect of STZ-induced diabetic ulcers.A. vera inhibits oxidative stress due to its properties of inducing antioxidant enzymes and glutathione levels.Aloe vera is also capable of reducing the manufacture of inflammatory mediators, thus causing the suppression of inflammatory responses in STZinduced diabetic models.[108] evaluated the active components of A. vera, which possess hypoglycaemic and hypolipidemic activities beneficial to cure diabetes.It not only reduces the hypoglycaemic and hypolipidemic activities beneficial to cure diabetes.It not only reduces the chances of diabetes but also maintains a healthy life by reducing the adverse impact of diabetes on the liver.It was found that the oral administration of A. vera gel extracts improves blood glucose homeostasis and imparts variations in glucoselowering effects.

Deora and Venkatraman
Ankita et al. [106] confirmed that by taking Aloe juice, a person can maintain sugar levels in the blood due to the presence of polysaccharides that can control blood sugar and cholesterol levels.The possession of polysaccharides makes it suitable for the treatment of all diabetic situations as it exhibits hyperglycemia properties and increases the glycerin level.
Overall, in this review, the collected data on the antidiabetic activity of A. vera validated that the extracts from different parts of the Aloe plant help in controlling blood glucose and restoring insulin levels.It is believed that the isolation of novel compounds with the exploration of their antidiabetic mechanisms of action at the cellular level from A. vera extracts is a promising research mark for Aloe-based diabetes treatment.

Antimicrobial Activity
The inhibition of the growth of microbes like bacteria, fungi, viruses, etc., or prevention of the formation of microbial colonies and their destruction can be controlled by the phytochemicals obtained from the extracts of various plant species [109,110].There is a huge literature available with reported antimicrobial activities of A. vera on various pathogenic microbial strains [22,[111][112][113][114][115][116][117][118] (Table 7).
Stanley et al. [111] reported the antimicrobial activities of ethanolic, methanolic, and aqueous extracts of A. vera against Escherichia coli, Staphylococcus aureus, and Candida albican through the agar diffusion technique.Gentamycin was considered a positive and dimethyl sulfur oxide (DMSO) was considered a negative control.Of all, methanol extract was best with maximum inhibitory effects followed by ethanolic and aqueous extracts of A. vera.
Dharajiya et al. [56] reported the anti-microbial activity of Aloe gel against strains of various types of bacteria and fungi such as Bacillus cereus, Serratia marcescens, Pseudomonas aeruginosa, Aspergillus flavus, E. coli, Aspergillus oryzae, Trichoderma viride, Penicillium chrysogenum with thin layer biography method.Their outcomes showed that the A. vera gel has inhibitory effects on S. marcescens and three species of Aspergillus.
Malik et al. [22] documented methanol and ethanol extracts of A. vera with significant inhibitory actions as compared to the aqueous extracts which showed lower inhibition against A. niger and Rhizopus.Their outcomes recommended A. vera leaves extracts using ethanol and methanol solvents as better antifungal agents.
Waithaka et al. [112] revealed antimicrobial properties of the methanolic extract of leaves of A. vera, A. volkensii, and A. secundriflora.Mueller Hinton agar and potato dextrose agar for bacteria and fungi was used respectively containing S. aureus, Erwinia carotovora, Klebsiella pneumonia, E. coli, Bacillus subtilis, Candida albicans, Fusarium oxysporum.
These extracts showed positive results with various zone of inhibition on the tested strains.Gorsi et al. [113] showed that gel from Aloe barbendis leaves extracted with ethanol, methanol, and acetone inhibits the growth of bacterial strains Anju et al. [114] proclaimed that silver nanoparticles made from A. vera can be used to inhibit microbial growth.After extraction of A. vera gel naturally containing acemannan, the formation of silver nanoparticles (AgNPs) was analyzed through a spectrophotometer with 400 nm absorption.Their results showed that AgNP has anti-microbial properties against both grampositive (S. aureus) and gram-negative (E.coli, P. aeruginosa, and Enterobacter) bacteria.These activities were analyzed through the disk diffusion technique.
Ahmed et al. [116] evaluated the inhibitory effects of A. vera gel on different biological agents like bacteria, yeast, and fungi strains.For this purpose, the gel was extracted from leaves of Aloe barbadensis miller and after blending it properly powder was formed by the cold maceration method.Using the solid medium method anti-microbial activities were analyzed through nystatin and gentamycin tests for fungi and bacteria respectively.E. coli showed inhibition zones whereas S. aureus and P. aeruginosa showed resistance against A. vera gel extract.On the other hand, lower activity was observed against yeast i.e., Candida albicans.Bajalanlou and Pakbin [115] obtained the transparent gel from A. barbadensis using methanol, aqueous, dichloromethane (DSM), acetone, chloroform, n-hexane, and PET solvents and analyzed the antimicrobial activity through the disk diffusion method.The ethanol extracts displayed the overall highest inhibitory activity against Aeromonas with a 9.6 mm inhibition zone.The n-hexane extract showed the least anti-bacterial activity with 0.12 mm inhibition zones.Other extracts such as PET, chloroform, DCM, and acetone showed 0.25 to 2 mm inhibition zones whereas methanol and aqueous extracts showed 0.93 to 3.75 mm inhibition zones.Aeromonas showed resistance in PET fraction and Pseudomonas and Chryseobacterium meningospticum were resistant to the aqueous fraction of A. barbadensis.Yahya et al. [118] studied the methanol extracts of A. vera and found effective results against Helicobacter pylori which causes gastric infection in humans.
Vadiati Saberi et al. [117] evaluated the effect of A. vera gel on the growth of gram-positive and gram-negative bacteria.The acetoacetate compound extracted from the ethanol extract of the gel repressed growth of gram-positive bacteria as compared to gram-negative bacteria.
Overall, the collected data here for the antimicrobial activity of Aloe species authenticated that the Aloe extracts are effective against almost 12 bacterial and 7 fungal species.It is still believed that the elucidation of proper mechanisms of action of Aloe extracts against pathogenic microbes is a possible research line for advanced Aloe-based natural antimicrobial therapies.

Aloe-Based Food and Cosmeceutical Products
There is extensive data available on the uses of A. vera in cosmetic items such as night creams, soaps, cleansers, shampoos, suntan creams, and lotions (Table 8).In a study, Pounikar et al. [119] prepared a cosmetic herbal hydrogel using the inner part of A. vera leaf by mixing other substances through heating.Mainly, the mixing of acacia, hydroxyl propyl methyl cellulose (HPMC), and carbopol 934 in a ratio of 1:1:2 done to make a product to increase moisture content in the skin, making skin clear by increasing transparency, and smoothness and reducing skin microbial growth.According to Estrada-Caslillon et al. [120], A. vera leaves are used in cosmetics to make shampoo, hair dye, and hair health products and are reported to be used in rituals.Rajkumar et al. [121] proclaimed the use of A. vera gel in goat meat nuggets to enhance the quality of food items in India.Different quantities of 0 %, 2.5 %, and 5 % gel were applied to nuggets before storing them in the refrigerator for 9 days.As a result, 2.5 % of A. vera gel in nuggets was said to be preferred because it does not affect the yield and does not decrease the protein content like 5 % of A. vera.It enhanced the quality of the item by improving its texture and nutritive value.
Mahmoudi et al. [122] developed yogurt by adding A. vera extract and Lactobacillus casei in cow milk and then stored it for different days like

356
Batool et al 1, 3, 5, 7, and 10 at 4 0 C. The results showed that the concentration of lactobacillus was less in yogurt with A. vera extract and did not affect the quality of yogurt when added with 2.5 % concentration rather it improved the physiochemical, microbiological, and sensory properties of yogurt.
Hendrawati et al. [123] developed an A. vera gel extract mask for improving skin quality.The composition of this A. vera mask was polyvinyl Pirolidon K30, poly vinyl chloride, methylparaben, propylparaben, BHT, and water in 7.55, 1.51, 0.10, 0.12 and 90.61 % respectively.The preferred amount of A. vera gel extract was 0.15 % for better results and was used to make the skin soft, enhance color and increase vitamin C content.
The same authors Hendrawati et al. [124] developed A. vera gel extract-based lotion by using gel from leaves.The ingredients in the lotion were heated and then melted by adding different concentrations of gel extract like 33.33 % in 50 ml, 50 % in 775 ml 66.67 % in 100 ml and 100 % in 150 ml.The best concentration with positive effects was said be 66.67 % in 100 ml.It provided a lot of therapeutic effects on the skin like reducing with montmorillonite (MMT) clay which is helpful in external detoxification and polyvinyl chloride (PVC) which is environment-friendly and provides homogeneity to the skin.This product was useful in protecting skin from UV radiation with healing properties.Moreover, it has antiseptic properties and an antiaging effect for batter and shiny skin.
In India, Mahajan et al. [129] prepared A. verabased edible film for frozen dairy products using kulfi as a modal product.A standardized file was prepared by mixing carrageenan, glycerol, and gel from A. barbadensis.The film reduced lipid oxidation, water vapor transmission, microbial growth, and antioxidant capacity with an increase in storage capacity, thickness, and density.
Haider et al. [130] studied the effects of A. vera gel coating on the shelf life and nutritional quality of strawberry fruit.They claimed that the use of 15 % A. vera gel as a coating material in strawberries prolongs post-harvest life and maintains nutritional quality for a considerable duration.
Pattnaik et al. [131] developed a mouthwash using A. vera gel which showed antiplaque and antibacterial activities.A. vera gel can also be used to prevent the deposition on teeth where bacteria can proliferate which shows its antiplaque activity for healthy teeth.
According to Otalora et al. [132], a mucilage extract from A. vera leaf is used as coating material with small capsules on pink guava using a spraydrying method.The coating with beta carotene in fruit increased the antioxidant activity and total carotenoid contents by 14 % and 36 %.The coating keeps the fruit healthy, acted as a natural colorant, and increased the content of dietary fiber.
Overall, the data reviewed here validated the applications of different Aloe-based food and cosmetics products such as cosmetic herbal hydrogel, lotion, A. vera gel extract mask, peeloff mask, mouthwash, and food products including meat nuggets, yogurt, herbal ice cream, edible coating of A. vera on fruits, khoa burfi, Kulfi, cookies, coating on pink guava.
It is believed that the consumption of Aloebased food products and the utilization of Aloebased cosmetics can be improved and increased by irritation, retaining moisture, preventing dryness, and making it clear.
Verma et al. [125] prepared herbal ice cream using A. vera and mint. A. Barbandis species was used to extract A. vera juice.The best concentration of ingredients was 10 % fat, 15 % sugar, 0.5 % stabilizer, and emulsifier, 20 % A. vera juice, and 0.5 % mint extract.After blending all ingredients, pasteurizing, homogenizing, and cooling, 10 % of A. vera juice and mint was added and then stored.The product was analyzed and total solids, acidity, protein, carbohydrates, and ash were determined showing the best chemical characteristics.The product showed good storage capacity and taste and due to A. vera juice, it increases blood circulation, and detoxification by improving the digestive system.
Another edible coating of A. vera gel was done by Kumar and Bhatnagar [126] on oranges, grapes, sweet cherries, and papaya.The gel coating increased antifungal activity and shelf life along and reduced moisture content and the appearance of brown color due to oxidation.It maintained the time of maturation of fruits by increasing storage capacity.In oranges, it caused no weight loss and increased acidity and total soluble solids.
Chaudhary et al. [127] developed Khoa Burfi by adding A. vera juice at different concentrations (5, 10, 15 and 20 %).The optimum concentration was found to be 15 % after analyzing moisture, pH, color, and texture.The pH and moisture content were increased due to A. vera juice and adhesiveness and hardness were decreased.The addition of A. vera showed improved shelf life of burfi.
Masood et al. [128] developed A. vera-based cookies where the ingredients of the cookies were wheat, butter, sugar, salt, baking soda, and water with 10, 20, and 30 % of A. vera.They found improved moisture content, crude fiber, protein content, beta carotene, and reduced fat.Other properties of the product like flavor, texture, and color were also analyzed and the product was found to be very effective for health.
Asthana et al. [3] developed a peel-off mask for skin care as a product using gel from A. Barbadensis leaves.This mask was prepared by mixing the gel adopting suitable procedures.Conversely, the study of complications associated with some specific conditions and with some specific compounds in Aloe is the possible research line for the valuation of safe utilization of Aloe-based food and cosmetic products.

CONCLUSION
In the history of plant-based medications, A. vera has a major contribution because of its frequent use for the treatment of various diseases.It is one of the most globally utilized plants as its extracts provide therapeutic effects due to the presence of a wide variety of phytoconstituents.The phytochemicals from A. vera extracts are employed against reactive oxygen species, diabetes, cancer, inflammation, and bacterial and fungal microbes.The data presented here on A. vera could be very vital to advance the research of clinical uses and the development of Aloe-based food and medicinal products with improved nutrition and therapeutic effects.It is recommended that more controlled investigations and clinical trials are prerequisites in the future to substantiate the outcomes and efficacies of A. vera under different circumstances.Also, some complications associated with specific compounds in Aloe should be addressed for the safer consumption of Aloe-based food products and the utilization of cosmetic products.

CONFLICT OF INTEREST
The authors declared that there is no competing interests.

Fig. 1 .
Fig. 1.A) Contribution of trees, herbs, and shrubs used as folk traditional medicine, B) Contribution of parts of plants used for ethnomedicinal purposes.Source: Ali et al. [7].

Fig. 2 .
Fig. 2. Different A. vera-based food, pharmaceutical, cosmaceutical, and other products developed in the industries

Fig. 2 .
Fig. 2. Different A. vera-based food, pharmaceutical, cosmaceutical, and other products developed in the industries

Table 1 .
Folk traditional uses of A. vera reported from different regions of the world [45]aniaLeavesUsed against constipation, toothache, and skin complaints.Used to assist labor and induce abortion.Used to treat arthritis, pneumonia, gonorrhea, sleeping sickness, alleviate pain, inflammation, retarded growth of tongue, pneumonia, aid wound healing, syphilis, diseases in poultry and goats, testicular and scrotum cancer, chest pain, malaria, colds, reduce labor pain, cough, typhoid, ulcers, vomiting, swollen diaphragm, nosebleed, ringworm, skin diseases, diarrhea, anemia, backache, stomach ache, burns, gonorrhea Tanzania A. latcritia, A. secvndiflora, and A. duckcriUsed to treat malaria, general stomach in humans, new castle disease in chicken, wounds, hernia, and typhoid[45]

Ethnobotany, Phytochemistry, Biological Activities and Cosmaceutical Applications of Aloe vera
reported the effect of hydrostatic pressure on the antioxidant activity of A. vera gel ethanol extracts with DPPH (2,2′-diphenyl-steroids, protein, and phenolic compounds *LC-MS= Liquid chromatography-mass spectrophotometry, ND= Not Defined, TLC= Thin layer chromatography, FTIR= Fourier transform infrared spectrometer, HPLC= High-performance liquid chromatography, RP-HPLC= Reverse phase high-performance liquid chromatography [84] gel with a spectrophotometer.Lee et al.[84]verified the antioxidant activity of A. vera leaves in the methanol, acetonitrile, and aqueous extracts by ABTS and DPPH assays with positive results.

Table 3 .
Anti -oxidant activity of A. vera extracts reported from different regions of the world

Table 3 .
Anti-oxidant activity of A. vera extracts reported from different regions of the world activities of ethanol extract with DPPH (11.82 to 75.54 %) andFRAP (228.9 ± 39.1 µg/ mg) were recorded.The overall reported range of total antioxidant activity of different fractions of A. vera leaf was 28.77 ± 9.36 to 150.4 ± 25.8 µg EQ/ mg.Yadav et al. (2020) evaluated A. vera leaves with peel (AL-P) and A. vera without -peel (AL-WP) where the free radical scavenging activity by FRAP was 156.83 ± 0.659 and 192.66 ± 1.416 mg Fe (II)E/g DWE, DPPH was 48.12 % and 68.88 % at 1mg/mL, NO scavenging potential was 38.43 % and 54.55 % at 0.1 mg/mL, and TAC was 89.66 ± 0.577 and 108.66 ± 1.000 AAE/g DWE.

Phytochemistry, Biological Activities and Cosmaceutical Applications of Aloe vera
performed an MTT test to assess how well flavonoids derived from A. vera, Mimosa pudica, and Phyllanthus niruri inhibits the growth of the human breast carcinoma cell line (MCF-7) to evaluate their potent effects.The extracts of A. vera (IC 50 = 54.970.36 g/ml), P. niruri (IC 50 = 35.520.50g/ml), and M. pudica (IC 50 = 35.520.50 g/ml) showed the highest inhibition against the tested cells.It was proposed that the extracts could be utilized effectively to treat cancer.
[96]nother study, the in vitro anticancer activities of Calligonum comosum and A. vera extracts against HepG2 cells by MTT test, the cells' viability was evaluated[96].The cytotoxicity against HepG2 cells was individually boosted by the extracts in a time and dose-dependent manner.It was found that the extracts could, at least in part, via modulating apoptosis have anti-hepatocarcinogeniceffects.

Table 5 .
Anticancer activity of A. vera against various cancer cell lines effective against the MCF-7 cancer cell line.The outcomes demonstrated that phytosome carriers have the potential to enhance A. vera oral delivery by opening the door for its use in the treatment of cancer.Overall, for the anticancer activity of A. vera, the data reviewed here substantiated that A.

Table 6 .
Activity of A. vera plant extracts on different types of diabetes FPG= Fasting plasma glucose, ND= Not defined Ethnobotany,

Table 7 .
Antimicrobial activity of A. vera against different pathogenic microbial strains

Ethnobotany, Phytochemistry, Biological Activities and Cosmaceutical Applications of Aloe vera like
Salmonella typhi, E. coli, B. subtilis, and S. aureus.Among the tested extracts, ethanol extract was found to be more effective with 20.33 and 18.63 zone of inhibition for Bacillus and Staphylococcus, whereas, acetone extraction was found to be better than aqueous extract with 13.60 mm inhibition zone for S. typhi.

Table 8 .
Details of Aloe-based food and cosmeceutical products reported globally