OPUNTIA FICUS-INDICA: ESCALATING FROM FARM TO PHARMACOLOGICAL ACTIONS

OPUNTIA FICUS-INDICA: ESCALATING FROM FARM TO PHARMACOLOGICAL ACTIONS

Aakriti Jain, Shivani Sharda and Anupama Sharma Avasthi *

Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India.

ABSTRACT: Medicinal plants are a reservoir of biologically active compounds with therapeutic properties, and in that context, Opuntia ficus indica and other Opuntia species are of immense importance because of their nutraceutical and pharmaceutical values along with their anti-inflammatory effects, hypoglycemic, anti-hyperlipidemic effects, anti-atherogenic and anti-spermatogenic potential. The cactus Opuntia is a xerophytic plant grown in more than thirty countries, including Mexico, South America, South Africa and India. All parts of the plant, including pear, roots, cladodes, seeds and juice, have these pharmacological properties, which have been attributed to the presence of high content of phenolic acids, flavonoids such as quercetin, kaempferol, anthocyanin and ascorbate etc., and pigments such as carotenoids, betalains, tannins etc. Other reported phytochemical components such as biopeptides, phytoalbumins, minerals such as vitamin B1, B2, B3 and Vitamin C, soluble fibers also add to the medicinal properties of Opuntia spp. presence of these bioactive has made Opuntia a high potential plant that can be investigated for commercial production and consumption as a neutraceutical. The present review provides an up-to-date report on phytochemical composition, distribution, and habitat-cultivation conditions, various pharmacological and nutraceutical properties of Opuntia. The contribution of this herb to medicinal activities has been demonstrated by numerous studies carried out in-vitro and in-vivo and it can be considered as an important medicinal plant that has enormous potential which has not yet been fully evaluated.

Keywords: Opuntia ficus indica, Nutraceutical values, Pharmaceutical properties, Anti-oxidant capacity, Agro-economical plant

INTRODUCTION: Phytopharmaceuticals have been important sources of traditional medicines as well as modern drugs. These have been harnessed since long for the prevention and cure of diverse ailments. The use of phytopharmaceutical substances to control diseases as an age-old practice has steered the drug discovery regime to identify and validate these phytopharmaceutical candidates for a safe and effective alternative approach towards creating healthy individuals.

Natural products extracted from plants especially from the Cactaceae family, have been widely used in folk medicine and in pharmaceutical and nutraceutical industries. One of the most important genuses in this family is Opuntia, with more than 200- 300 species, mainly growing wild in arid and semi-arid regions ^{1, 2}.

Opuntia ficus-indica (L.) Miller is a tree-like cactus belonging to the Cactaceae family. Although indigenous to Mexico, this plant is distributed in different parts of the world, including India. The cactus is majorly cultivated for its sweet and juicy fruit (prickly pear), having rich in nutritional benefits ² and has vast potential for commercial processing in semi-parched districts of the world for the pharmaceutical industry and nutraceutical industry due to its active nutrients and multiple properties of bioactive compounds ^3-5. This review provides a complete and updated account of various active compounds and the biological and medical benefits of wild and domesticated Opuntia spp. in chronic diseases, along with the probable mechanisms. The review aims to explore the food and functional potential of this fruit as a neutraceutical with immense health benefits to mankind.

Habitat: The cactus Opuntia (genus Opuntia, subfamily Opuntioideae, family Cactaceae) is a xerophyte representing about 200 – 300 species and is mainly growing in arid (less than 250 mm annual precipitation) and semi-arid (250 – 450 mm annual precipitation) zones. Due to their remarkable genetic variability, Opuntia plants show a high ecological adaptivity and can therefore be encountered in places of almost all climatic conditions ^{8, 11}.

Botany: The Opuntia cacti represent the most distinguishing species of succulent plants because of its shallow root system that allows rapid water uptake along with a thick, waxy cuticle that prevents unrestricted water loss and crassulacean acid metabolism (CAM), an alternative photosynthetic pathway that allows plants to uptake atmospheric carbon di oxide at night when water loss is reduced. These plants are acknowledged as supreme crops for arid regimes because they are exceptionally efficient at producing biomass under insufficient water conditions. The subfamily Opuntioideae is further classified based on short, sharp, barbed, deciduous spines called glochids ^{2, 6}. The fruit of this plant is oval or elongated berry fruit, consisting of thick fleshy skin or rind surrounding a juicy pulp having varying degrees of edibility, flavor and sweetness, which contains many hard-coated seeds. The skin and pulp colour, pulp texture, sugar content, and juice acidity of cactus fruits are directly related to the presence, intensity, and activity of nutritional and functional compounds⁷.

Production: Opuntia plants are grown in more than 30 countries on about 100 000 ha ^{2, 11, 12} among others Mexico, the Mediterranean (Egypt, Italy, Greece, Spain, Turkey), California, South America (Argentina, Brazil, Chile, Columbia, Peru), the Middle East (Israel, Jordan), North Africa (Algeria, Morocco, Tunisia), South Africa, and India ^{2, 11, 13, 14}. Commercial cultivation of Opuntia is done in Italy, Spain, Mexico, Brazil, Chile, Argentina and California. As a CAM plant, Opuntia spp. is distinguished by an increased water use efficiency of 4 - 10 mmol CO₂ per mol H₂O. Through succulence, the capacity to store high quantities of water, the plant may pull through despite extreme environmental conditions ^{2, 15}. The harvesting is done from April to August when the plant reaches a weight of 90 – 100 g and a length of 15 – 20 cm^{2 16- 18}. Opuntia plants give rise to edible stems known as pads, vegetables, cladodes, nopales, or pencas. The soft young part of the cactus stem, young cladode or “nopalitos”, is more commonly consumed as vegetable in salads, while the cactus pear fruit is consumed as a fresh fruit.

FIG. 1: OPUNTIA CLONES INTRODUCED IN INDIA FROM TEXAS, USA (1987) ¹⁴

Opuntia: Introduction in India: As shown in Fig. 1 and 2, thirty-three Opuntia clones were introduced in India in 1987 at the Nimbkar Agricultural Research Institute at Phaltan, India, through an Indo-US collaborative research program from Texas A&M University. Subsequently, five promising clones (1270, 1271, 1280, 1287, and 1308) having low water requirements were introduced at Karnal. As cactus pear can grow well with low inputs and pre-requirements and even under wasteland conditions, great potential was found for its adoption and cultivation as a commercial crop in arid regions of India such as Bikaner. It was also cultivated as four exotic varieties of cactus-pear fruiting types (1271, 1280), and vegetable type (1308 and Nopalea) in Agra. Similarly, this plant was introduced in rain-fed Bundelkhand region (Central India) as a surrogate source of forage, as a bio fence, and as a source of food for the economically weaker human and animal population settled in this ecologically poor environment ¹⁹.

FIG. 2: TIMELINE OF OPUNTIA CLONES INTRODUCED IN INDIA

Composition and Nutritional Characteristics of Opuntia Ficus Indica: The cactus pear is an oval or elongated berry fruit (typically 100-200g), consisting of thick fleshy skin or rind (30-40 percent of total fruit weight) surrounding a juicy pulp (60-70 percent of total fruit weight), which contains many hard-coated seeds (5-10 percent of the pulp weight) ²⁰. In general, the prickly pear fruit contains approximately 85% water, 15% sugar, 0.3% ash, and less than 1% protein, as shown in Fig. 3 ^{21, 24, 25}. According to the United States Department of Agriculture and based on the amount of daily value (DV) provided in a 100 g serving, the fruit has a moderate content of essential nutrients, as shown in Fig. 4. The dietary fiber is 14% DV, and vitamin C content is 23% DV. Among minerals, magnesium has a 21% DV. The other constituents in fresh fruit pulp are carbohydrates (9.57%), fiber (3.6%), and lipids (0.51%). The nutritionally important vitamin content in 100g of fresh fruit pulp was Niacin (Vitamin B3) (Trace amounts), Riboflavin (Vitamin B2) (0.06%), Thiamine (Vitamin B1) (0.014%), Vitamin E (111–115μg) and Vitamin K1 (53μg). The mineral content in prickly pear fruit pulp was found to be as Calcium (56 mg/100g), Iron (0.30 mg/100g), Magnesium (85 mg/100g), Phosphorous (24 mg/100g), Potassium (220 mg/100g), Selenium (0.6 mg/100g), Sodium (5 mg/100g) and Zinc (0.18 mg/100g)’’ ^{21, 22}. However, the quantities and concentrations of the nutritional components of the fruit vary with the cultivation site, climate and fruit variety ^21-23. The seeds of cactus fruits contain significant amounts of proteins and lipid, the latter composed of about 75 percent linoleic acid. In fruits of different Opuntia species, seed protein content varies from 3 to 10 percent dry weight and seed lipid content varies from 6 to 13 percent dry weight ²⁰.

FIG. 3: PIE CHART REPRESENTING BASIC COMPOSITION OF OPUNTIA FICUS INDICA BASED ON AMOUNT OF DAILY VALUE PROVIDED IN 100G SERVING ACCORDING TO THE UNITED STATES DEPARTMENT OF AGRICULTURE

FIG. 4: PIE CHART REPRESENTING NUTRIENT COMPOSITION OF OPUNTIA FICUS INDICA IN mg/100g ACCORDING TO UNITED STATES DEPARTMENT OF AGRICULTURE

Pharmacological Properties of Opuntia Species: Opuntia ficus indica is used for its pharmaceutical, nutraceutical, and cosmeceutical properties in tea, jam, juice, oil, as shown in Fig. 5 and 6. It is applied as an herbal remedy for many wide ranges of health problems in different countries. For instance, in the sub-Saharan traditional medicine pharmacopeia, cactus flowers and fruits are used as anti-ulcer genic or antidiarrheal agents; flowers being also administered as an oral anti-hemorrhoid medication and cladode sap as a treatment for whooping cough. On the other hand, indigenous populations consume large amounts of either fresh or dried fruits as food. In these populations, cactus cladodes, fruits and flowers are featured for their interesting contents of antioxidants, pectin poly-saccharides and fibers ³⁴ Opuntia has high values of antioxidant compounds such as polyphenols, flavonoids, betaxanthin, and betacyanin ^{1, 26}. Hence, most parts of the cactus plant (pulp, peel, seeds, and cladode) have shown notable antioxidant activities ^{1, 27-29}. Moreover, cactus pear fruit extract has presented with activities such as anti-ulcer genic, antioxidant, anticancer, neuroprotective, hepatoprotective and anti-proliferative activities ^{2, 27, 30-33}. Prickly pear has also been used for the treatment of gastritis, hyperglycemia, arterio-sclerosis, diabetes, and prostate hypertrophy, as shown in Fig. 5 ^{35, 36}. Further sections review the various pharmacological activities of this fruit and its possible applications as a functional food with medicinal properties.

FIG. 5: VARIOUS PHARMACEUTICAL PROPERTIES OF OPUNTIA FICUS INDICA

FIG. 6: VARIOUS NUTRACEUTICAL AND COSMECEUTICAL PROPERTIES OF OPUNTIA FICUS INDICA

Anti-Oxidant Capacity: The recent advances in the knowledge of free radicals and reactive oxygen species (ROS) in biology have led to a medical revolution that promises a new age of health and disease management and the search for effective, nontoxic natural compounds with antioxidative activity has intensified in recent years. A positive correlation has been found in numerous studies between a plant-based diet and decreased risk of diseases such as cancer, neurodegenerative and cardiovascular ailments especially caused by high oxidative stress. The antioxidant action is one of many characteristics by which fruit and vegetable substances might show their beneficial health effects ^{37, 38, 44-46}. The presence of several antioxidants (ascorbic acid, carotenoids, reduced glutathione, cysteine, taurine, and flavonoids such as quercetin, kaempferol, and isorhamnetin) has been reported from fruits and vegetables of different varieties and categories of cactus prickly pear ^{37-39, 41, 47}. These characteristics are due to the ability of antioxidants to neutralize reactive oxygen species such as singlet oxygen, hydrogen peroxide or H₂O₂, or suppress the xanthine/xanthine oxidase system, all of which may lead to oxidative injury, i.e., lipid peroxidation. These have been validated by various phytochemical investigations, metabolome analysis and in-vitro and in-vivo studies ^{37, 39, 40, 42, 46-50}.

Reports and previous studies have indicated the dose-dependent protective effect of Opuntia ficus-indica fruit extract on erythrocytes against lipid oxidation induced in-vitro by ethanol ^{51, 52}. The same extract was also found to be active in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals. Phytochemical investigations of the ethanol extract revealed the presence of high number of phenolic compounds namely quercetin, (+)-dihydroquercetin, and quercetin-3-methyl ether which may be responsible for antioxidant activity. These quercetin derivated are well recognized as free radical scavengers capable of preventing neuronal cell damage caused by H₂O₂ and xanthine/xanthine oxidase ^{2, 50}. Restoration of scavenging activity in a dose-dependent manner to near normal level has also been reported in ethanol fed rats provided with prickly pear ^{51, 53}. The normalization of scavenging activity by prickly pear juice supplement could be because of the natural antioxidants, which could modify the internal imbalance between oxidant species and the antioxidant defense system ⁵¹.

FIG. 7: PHYTOCHEMICAL INVESTIGATIONS REVEALED THAT OPUNTIA FICUS INDICA CONTAINS HIGH AMOUNTS OF PHENOLIC COMPOUNDS SUCH AS QUERCETIN (+) - DIHYDROQUERCETIN AND QUERCETIN- 3-METHYL ETHER WHICH ARE RESPONSIBLE FOR PROVIDING POTENT ANTIOXIDANT DEFENSE SYSTEM

Similar phytochemical investigations on the red-skinned fruits extracts reported the presence of ascorbic acid, carotenoids, betalains, taurine, flavonoids (quercetin, isorhamnetin, kaempferol, luteolin) and free radical scavenging ability ^{54, 55}. Ascorbic acid contributes up to 68% of the antioxidant activity of cactus juices ^{51, 60}. Polyphenols and betacyanin extracts of Opuntia, may play role as an electron donor to convert free radicals to more stable products, thereby scavenging the generated free radicals ^{55, 56}. Similarly, flavonol glycosides in cactus flowers extract are used as additives in food, cosmetic and pharmaceutical products for their antioxidant power ^{55, 57}. These compounds are more effective antioxidants than vitamins, since flavonoids, and phenolic compounds in general, are able to delay the pro-oxidative effects on proteins, DNA and lipids through the production of stable radicals ^{51, 61}. Opuntia ficus-indica glycoprotein did not have any cytotoxic effect and instead protected liver cells because of its scavenging activity against G/ GO-induced radical production ^{51, 62}. These results show that Opuntia ficus-indica glycoprotein shows antioxidant and cytoprotective effects in-vitro, either directly or indirectly ⁵¹.

Similar studies on Opuntia-humifusa have demonstrated the chemo preventive potential on chemical carcinogenesis in mouse skin by reducing the oxidative stress via the modulation of cutaneous lipid peroxidation, thereby enhancing the total antioxidant capacity, especially in phase II detoxifying enzyme system and partial apoptotic influence” ^{51, 58}. In other related studies in senescence-accelerated mice (SAM), the anti-oxidant activity of Opuntia ficus indica fruit was evaluated throughout the aging process. The effects on the anti-oxidant system, including thiobarbituric acid reacting substance (TBARS), glutathione (GSH), superoxide dismutase, and catalase, were studied in 7-month-old SAM-P8 after oral administration of Opuntia (1.2g/kg/day) for 30 days ^{66, 67}. The revealed that the TBARS was markedly decreased in Opuntia treated mice compared to the control group (P<0.05), while GSH content was significantly increased in Opuntia treated mice compared to the control group (P<0.0001). These findings suggested that Opuntia spp. have a functional role in increasing anti-oxidant activity in SAM, normal human beings and in-vitro cultures ⁶⁷. Studies have also been conducted in humans to test the antioxidant activity of Opuntia ficus-indica was tested. In one study 10 healthy participants consumed a diet poor in antioxidant components for 3 days followed by the addition of 300 g/ day of Opuntia ficus-indica to their meals for the period of 3 days. The blood samples showed a significant increase in antioxidant activity due to the consumption of the 300 g of Opuntia ficus-indica for 3 days which was evident to the extent of 20% in plasma and 5% in blood. The most significant result was in plasma (20%) when compared with the activity shown in the sample obtained before the intake of Opuntia ficus-indica ^{51, 59}. The body’s global antioxidant status ^{63, 64}, as well as individual antioxidant vitamins, and a number of markers of oxidative stress have also been measured in plasma and cells of healthy volunteers before (baseline) and after fifteen days during which they ingested fresh fruit pulp of Sicilian Opuntia ficus-indica (250 g twice daily), in addition to their usual diet ^{63, 65}. With respect to the baseline, a remarkable increase of plasma vitamin E and vitamin C was observed, whereas vitamin A and TEAC did not vary significantly.

Analgesic Effect: Inflammation and pain are common nonspecific manifestations of many disorders which are conventionally treated through non-steroidal anti-inflammatory drugs (NSAIDs) and opiates. However, these drugs are associated with adverse reactions like gastrointestinal disturbances, renal damage, respiratory depression, and possible dependence ^{2, 68}. In recent years, there has been an increasing interest in finding new anti-inflammatory and analgesic drugs with possibly fewer side effects from natural sources and medicinal plants. In this context, ethanolic extract of the cladodes (300 – 600 mg/kg body weight) from O. ficus-indica var. sabotenhave demonstrated almost the same analgesic effect as acetylsalicylic acid (200 mg/kg body weight) ^{2, 68} without toxic effects in mice (LD₅₀ > 2 g/kg body weight) even at high dosages. In another similar study the Opuntia elatior fruit juice was tested at varying doses for abdominal constriction caused by intra peritoneal injection of acetic acid (0.75%) and the results indicated similar analgesic effect as diclofenac sodium and tramadol even upto 6 h of intake. Study noted that the fruits of O. elatior Mill. are rich with central and peripheral analgesic properties might be due to presence of phenolic and betanin content ^{69, 70}.

Anti-inflammatory Action: Inflammatory response involves macrophages and neutrophils via several mediators that are responsible for the initiation, progression, persistence, regulation, and eventual resolution of the acute state of inflammation. In cases where this resolution does not occur, it leads to its progression into a chronic phase. Chronic inflammation is implicated in pathogenesis of many diseases like diabetes, hypertension and even cancer ². Multiple studies have advocated that, the analgesic and anti-inflammatory actions of the fruits and lyophilised cladodes of genus Opuntia. Beta-sitosterols have been ^{37, 73} identified as the active anti-inflammatory principle from these extracts. Decrease of acute inflammation by ethanolic O. ficus indica stem extracts was attributed to a lower leucocyte migration and the results were similar to other NSAID with no side effects ^{2, 68}.

Various animal experiments have validated the anti inflammatory potential of genus Opuntia. In λ-carrageenan-induced rat pleurisy, the oral administration of indica xanthin has decreased the inflammatory response ^{56, 78}. In addition, Opuntia flowers contain phenolic compounds like quercetin and isorhamnetin glycosylated derivatives, which have been reported to decrease NO production ^{56, 57}. Gastric lesions in rat animal studies were found to be reduced both by stem and fruit powders ^{37, 74, 75} Betanin and indicaxanthin present in the extracts have shown san inhibitory effect on the chlorination activity of myeloperoxidase at neutral rather than at pH 5 ^{37, 76}. In another study on the rat model of acute inflammation (pleurisy), the oral administration of indica xanthin decreases the exudate size and leukocytes recruitment in the pleural cavity, as well as the protein and mRNA expressions of PGE-2, NO, IL-1β, iNOS, and cyclooxygenase-2 (COX2) in the recruited leukocytes ^{6, 180}. In gerbils, protective effects of methanol extracts of Opuntia ficus indica given was observed against neuronal damages caused by global ischemia in the hippocampal region ^{6, 81}. Similar studies were also carried out with O. elatior extract gel on lamda carrageenan-induced rats (Rattus norvegicus L.). The first group of rats was given a gel without active ingredient (negative control), groups of 2^nd, 3^rd and 4^th rats were given gel cactus fruit extract in concentration of 5%, 10% and 15% respectively, and 5^th groups of rats were given diclofenac sodium gel (positive control). The results showed that the concentration of cactus fruit extract in proportion of 5%, 10% and 15% in the gel preparation presented different conditions on organoleptic observations and homogeneity even though there was no difference in the pH and viscosity during 14 days of storage. The results on anti-inflammatory activity test using concentration of 5%, 10%, and 15% have a protective effect against inflammation. Gel containing 10% of extract has anti-inflammatory activity which equals to 1%of sodium diclofenac activity ^{70, 82}.

In human chondrocytes cultures, Opuntia extracts have decreased the release of nitric oxide (NO), glycosaminoglycan, prostaglandin-E2 (PGE-2) and other oxygen reactive species ^{56, 77}. Similarly on human umbilical vein endothelial cells (HUVECs), non-cytotoxic micromolar concentrations of betalain (a pigment of Opuntia ficus-indica purified from fresh pulp of cactus pear) decreased the expression of cell adhesion molecules such as ICAM-1 ^{6, 73}. Betalain present in the extracts has also been acclaimed for its role in preventing degenerative disorders that specifically affect endothelial function, such as atherosclerosis, atherothrombosis, low limb ischemia, and stroke. On the murine microglial cell line (BV-2), a butanol fraction (obtained from 50% ethanol extracts of Opuntia ficus indica and hydrolysis products) has been reported to inhibit the production of NO in LPS-activated BV-2 cells via suppression of iNOS protein and mRNA expressions, inhibits the degradation of IκB-α, and displays peroxynitrite scavenging activity^{6, 79}. Combination of superoxide (O₂ ^-) and nitric oxide (NO) radicals leads to formation of cytotoxic reactive species Peroxynitrite (ONOO^-) in-vivo by endothelial cells, kupffer cells, neutrophils, and macrophages. Protonation of peroxynitrite leads to the formation of highly reactive peroxynitrous acid (ONOOH). ONOO^- is responsible for cellular damage, signal transduction, and tissue injury due to DNA strand breakage and ultimately leading to apoptotic cell death due to tyrosine nitration, lipid peroxidation, and oxidation of thiol groups etc. affecting cell metabolism. Accumulation of peroxynitrite can lead to diseases such as Alzheimer's disease, rheumatoid arthritis, cancer and inflammation of body organs. Naturally occuring ONOO^- scavengers such as ascorbic acid, y- tocopherol, flavonoids, and polyhydroxyphenols which constitute the Opuntia species are effective against ONOO^- scavenging and reducing the inflammatory response of the body ^{78, 79}.

Wound Healing Effects: Skin is the largest human organ and acts as a protective barrier between the internal organs and external environment. Wound healing is an automatic, dynamic, and cascade step of healing. Wound healing involves hemostasis phase, inflammatory phase, proliferative phase, and maturation phase. These phases are regulated by a pathological situation, metabolic disorders, and infections, or aging. Oxidative stress suppressed immune response, and inflammation can lead to chronic non-healing wounds ⁸³.

Nopal and other Opuntia spp. extracts have been in use as traditional medicine for the treatment and cure of burns, skin disorders, and wound healing and the recent studies validate their effectiveness at the molecular and cellular levels for their use in recent dermatologic preparations as ointments, creams and gels, etc. ^{83, 84} Several recent studies highlight the wound repairing and healing properties of O. ficus-indica cladode extracts by using keratinocytes stimulated by benzopyrene or TNF-α, it was also observed that O. ficus-indica cladode extracts may enhance protection the epidermal barrier and the keratinocyte function by stimulating the expression of filaggrin and loricrin, proteins present in differentiated keratinocytes and corneocytes. The barrier effect of the extract is due to an inhibition of ROS production evoked by the inflammatory agents ⁸³.

The cicatrizing properties of O. ficus-indica cladodes may entail both high molecular weight polysaccharide components such as a linear galactan polymer and a highly branched xylo-arabinan, as well as low molecular weight components such as lactic acid, D-mannitol, piscidic, eucomic, and 2-hydroxy-4-(4′-hydroxy-phenyl)- butanoic acids. These extracts could increase cell regeneration on a scratched keratinocytes monolayer, indicating that O. ficus-indica components have high anti-inflammatory and high wound healing properties ^{83, 85}. Similarly, polysaccharides extracted from cactus pear of O. ficus-indica have been reported to enhance the proliferation of fibroblasts and keratinocytes ^{83, 86}.

Similarly, cladode extracts from O. humifusa (Raf.) have also demonstrated activities that modulate the production of hyaluronic acid (HA) by increasing the expression of HA synthase in keratinocytes exhibited to UV-B treatment. Additionally, treatment using cladode extracts from O. humifusa also decreased the UV-B increased expression of hyaluronidase. Interestingly, the same protective effect on HA was observed in SKH-1 hairless mice exposed to UV-B, indicating that cladode extracts from O. humifusa have strong skin care capacities ^{83, 87}.

The efficacy of Opuntia ficus indica on wound healing was examined by measuring the tensile strength of the skin strips from the wound segments. It was found that methanolic extract of O. ficus indica stems and their n-hexane and ethyl acetate fractions showed significant wound healing activity when topically administered to rats ^{67, 88}. Hence, for topical or local applications, Opuntia hydrocolloids could be applied in wound creams (cooling cream) like Aloe vera (L.) Burm ^{2, 89-91}. Cosmetic products would profit from cladode preparations.

Summarizing the above studies, we can conclude that Opuntia spp. has the potential to enhance the wound healing process and can also be effectively used as co-treatment of skin complications due to diabetes and other pathologies characterized by a defective wound healing ⁸³.

Anti-ulcerogenic Effects: Gastrointestinal disorders such as peptic ulcers develop due to bacterial infections such as Helicobacter pylori, acid pepsin hyper secretion, and idiopathic factors, etc. But regular use of non-steroidal anti-inflammatory drugs (NSAIDs) such as steroids, anti-coagulants, selective serotonin reuptake inhibitors (SSRIs), etc. and drugs such as proton pump inhibitors, H2 receptors, cytoprotectants, demulcents, anti cholinergics, antacids, and prostaglandin analogues are used for the treatment of ulceration, but these drugs produce several side effects such as diarrhea, abdominal pain, constipation, nausea, and headache etc. Thus, medicinal plants such as Opuntia species offer safe and effective treatment with fewer side effects due to their potent antiulcerogenic properties ^{63, 66-68}. Opuntia ficus indica (L.) Mill. Cladodes have been used to treat gastric ulcers as a part of traditional medicine regime. Anti-ulcer effects of O. ficus indica are linked with the production of mucilage, which may cover ethanol-induced gastric damage and prevent inflammation ^{62, 67, 72, 92}. Oral administration of O. ficus indica significantly inhibited gastric lesions and gastric ulcer formation in HCl ethanol or HCl aspirin-induced gastric injury. These findings indicate that O. ficus indica protects the gastric mucosa through an increased section of gastric mucins or through anti-inflammatory action ^{67, 75}. The protective effect could be attributed to the cladodes’ hydrocolloid behaving as a buffer, spreading out on the gastric mucosa, and increasing mucus production by increasing the number of secretory cells.

In a similar study, the anti-ulcer activity of O. elatior stem was evaluated by an ethanol-induced gastric ulcer in albino rats. Alcoholic extract at 100, 200 and 400 mg/kg, per oral doses significantly (P < 0.01) decreased the ulcer score, ulcer number, ulcer index, free acidity, and total acidity in the ethanol-induced ulcer model in rats. The results of the study demonstrated the antiulcer activity of stem extract of O. elatior Mill. This may be due to the presence of flavonoid, which is the cytoprotective active material for which antiulcer genic efficacy has been extensively confirmed ⁷⁰.

Hypoglycemic and Antidiabetic Effect: The intake of nopal (O. ficus-indica) in a regular diet has been reported to enhance the postprandial stimulation of glucose, insulin, glucose-dependent insulinotropic peptide (GIP) index, and the glucagon-like peptide 1 (GLP-1) index on T2DM patients after intake of a high-carbohydrate or high-soyprotein breakfast ^{83, 93}. The hypoglycemic efficacy could be increased after heating Opuntia extracts, as reported, ^{83, 94} in patients consuming broiled O. streptacantha extracts. Similarly, glycemia and glycated hemoglobin were found to be decreased to normal values in streptozotocin (STZ) induced diabetes in rats through supplementation with an extract of O. fuliginosa prickly pear ^{83, 95}. Likewise, O. humifusa stems boost blood glucose and cholesterol decrease in STZ-treated rats ^{83, 96}. In a related study, it was ^{83, 97} reported that O. streptacantha extracts do not decrease glycemia in STZ treated rats when compared to the control but do demonstrate an anti-hyperglycemic effect when used before an oral glucose tolerance test (OGTT) while the same extracts administered before an OGTT produced an anti-hyperglycemic effect compared to the control group. The O. streptacantha extracts improve glycemic control by blocking the hepatic glucose output, especially in the fasting state ^{83, 98}. The hypoglycemic mechanism summoned by Opuntia spp. ingestion could be because of dietary fibers such as pectin and mucilage, ^{83, 94} which may decrease the absorption of glucose by enhancing the viscosity of food in the gut” ^{83, 99, 100}. Many other studies have demonstrated similar results. A combination of insulin and purified extract of cactus (Opuntia fuliginosagriffiths) have been found to reduce blood glucose and glycated hemoglobin levels to normal ^{37, 101}. In this study, the oral dose of the extract (1 mg/kg body weight per day) necessary to control diabetes contrast with the high quantities of insulin required for an equivalent hypoglycemic effect. In another recent study, supplementation of diets with cactus seed oil (25mg/kg) decreased the serum glucose concentration, which is associated with a glycogen formation in the liver and skeletal muscle” ^{37, 102}.

Similar results have also been observed with O. dillenii on alloxan-induced diabetic rabbits ^{103, 104}. The use of juice from ripe fruits (5 ml/kg body weight) did not affect the plasma glucose concentrations, whereas it remarkably decreased the glucose levels resulting from oral administration of glucose (1 g/kg b.w.). This effect was not present when normoglycemic rabbits were intravenously loaded with glucose. Fruit juice expressed no effect on glucose-induced plasma insulin levels. It was believed that some compounds of the reported part of O. dillenii deprived the intestinal absorption of glucose, and others could have an insulin-like character ^{103, 104}.

Clinical studies have also reported the anti-diabetic effects of Opuntia. In one such study with 46 types 2 diabetes patients, tablets of O. dillenii crude drug (2.5 g) for four weeks consumed as four tablets each day 30 minutes before three meals remarkably improved the clinical symptoms and the glycometabolism of patients ^{103, 105}.

FIG. 8A: TYPE II DIABETES MELLITUS B. SAPONIN, THE NATURAL ANTI- DIABETIC FACTOR PRESENT IN OPUNTIA FICUS INDICA, LEADS TO HYPOGLYCEMIC EFFECT BY ACTIVATING THE GLYCOGEN SYNTHESIS, SUPPRESSION OF DISACCHARIDE ACTIVITY, REGULATING INSULIN SIGNALING, REGENERATION OF INSULIN ACTION, AND SUPPRESSION OF GLUCONEOGENESIS

Studies have also demonstrated that glucose and insulin levels in healthy fasting subjects were stable when eating cladodes; thus contributing to a positive effect to overall health in diabetes mellitus type II (non-insulin-dependent diabetes) patients. This was attributed to decreased postprandial sugar absorption. Followed by a glucose challenge test, the increase in insulin and glucose was found to be remarkably decreased. Also, the glucose and insulin plasma levels were found to be reduced. After 10 days of regular cladode consumption before meals, a remarkable decrease of the serum glucose level was observed ^{2, 106, 107}. Since these effects were not dependant on glucagon, cortisone, and human growth hormone levels, which are closely interrelated with glucose metabolism, a gastric entero hormone was marked responsible for the hypoglycemic effect as shown in Fig. 8” ^{2, 106}.

Anti-hyperlipidemic Properties and Cholesterol-Lowering Properties: Various studies have indicated that regular consumption of prickly pears from O. robusta, by patients affected with familial heterozygous hypercholesterolemia, considerably decreased the plasma levels of LDL cholesterol and the plasma and urine content of 8-epi-prostaglandin F2α, an F2 isoprostane reproduced through the peroxidation of arachidonic acid ^{83, 108}.

These lipid decreasing properties were further established on mice fed with a hypercholestero-lemic diet. When the animals were provided with a methanolic extract from O. joconostle (polyphenol enriched) seeds, they showed a significant reduction in circulating LDL cholesterol and triglyceride levels by comparison with animals fed with a placebo ^{83, 109}.

In a series of studies with Guinea pigs, it was ^{2, 111-113} shown that the reduction of blood lipids could be triggered by pectin from Opuntia. The proposed mechanism involved increased binding of bile acid, decreased lipid absorption, lower blood lipid levels, and finally weight reduction ^{2, 111, 112}. In a follow-up study, the same authors presented evidence that the low-density lipoprotein (LDL)-catabolism was found to be more important than the modulation and de novo synthesis in the liver ^{2, 113}.

Consumption of Opuntia ficus-indica dried leaves as a dietary supplement has been reported to improve some blood lipids parameters and risk factors associated with metabolic syndrome in humans too. A monocentric, randomized, placebo-controlled, double-blind study on 68 women suffering from metabolic syndrome and having a body mass index between 25 and 40 Opuntia ficus indica capsules at a dosage of 1.6g per meal reported a significant increase in HDL-C levels and a tendency toward decreased triglyceride levels. Forty-two females consuming dried leaves of Opuntia ficus-indica with no additional hypo-lipemic treatment showed a significant reduction in LDL-C, especially after day 14. At the end of the research, 39% of the women in the group administered dried Opuntia ficus-indica leaves were no longer diagnosed with metabolic syndrome. This was the case for only 8% of the placebo group ^{51, 110}.

Anti-Atherogenic Effect of Opuntia Spp.: Most antioxidants are anti-atherogenic as they neutralize the formation of ROS by vascular cells and show anti-inflammatory and anti-apoptotic properties in case of the effects of oxidized LDL on vascular cells ^{83, 115}. Comparison of the anti-atherogenic properties of Opuntia powders achieved from the cladodes of 5 different wild spp. (O. streptacantha var. cardona, tuna loca, O. hyptiacantha, and O. megacantha), medium (O. albicarpa), and domesticated (O. ficus-indica) ^{83, 116}. Specifically, the effect of cladodes was observed on oxidation of LDL evoked by murine endothelial cells (an in-vitro model mimicking the mechanism of LDL oxidation occurring in-vivo in the vascular wall). Cladode powdered and solubilized in the culture medium dose-dependently inhibited LDL oxidation and the subsequent formation of foam cells by macrophages, which suggests that Opuntia spp. could stop the early steps of atherogenesis ^{83, 116}. This inhibitory effect of Opuntia spp. entails an inhibition of NADPH oxidase (NOX2), which results in a decreased production of intracellular and extracellular superoxide anion, the main ROS involved in the LDL oxidation process as shown in Fig. 9 ^{83, 116, 117}. In similar in-vivo studies on apoE-KO mice with developed atherosclerotic lesions the supplementation of the diet with O. streptacantha or O. ficus-indica powdered cladodes (10 mg/kg for 15 weeks) demonstrated marked reduction of the development of atherosclerotic lesions ^{83, 117}. Along with the actions on lipids and lipoproteins, the consumption of the prickly pear (250g/day) has also been found to be significantly effective in reducing the platelets proteins, platelet factor 4 and beta-thromboglobulin, and ADP-induced platelet aggregation, and improves platelet sensitivity against prostacyclin and prostaglandin E1 in healthy volunteers as well as in patients with mild familial heterozygous hypercholesterolemia. Thus, it appears that prickly pears can induce at least part of its beneficial action on the cardio-vascular system by decreasing platelet activity and improving haemostatic balance ^{67, 118, 119}.

FIG. 9: A. PATHOPHYSIOLOGY OF ATHEROSCLEROSIS B. OPUNTIA FICUS INDICA ARE RICH SOURCE OF POLYPHENOLS SUCH AS PECTIN AND GLYCOPROTEIN. POLYPHENOLS INHIBIT THE MECHANISM OF ATHEROMA BY INHIBITON OF LDL AND NADPH OXIDATION. POLYPHENOLS ALSO GENERATE ANTI- INFLAMMATORY RESPONSE BY INHIBITING NUCLEAR TRANSLOCATION AND FURTHER EXPRESSION OF ICAM- 1 AND VCAM- 1 ADHESION MOLECULES

Anti-Microbial Activity: Secondary metabolites present in plant extracts have demonstrated well-established anti microbial activities. Several studies conducted have found that flavanoids may work by inhibiting the cytoplasmic membrane functioning and inhibition of DNA gyrase and b- hydroxyacyl- acyl carrier protein dehydratase activities. Terpenes and coumarins show anti microbial activity by promoting membrane disruptions and reduction in cell respiration, respectively. Tannins act on micro-organisms’ membranes as well as bind to polysaccharides or enzymes, promoting inactivation ¹²⁰. Opuntia extracts, too have demonstrated bactericidal effects against many microbes, including Campylobacter jejuni and Campylo-bacter coli, both reason of foodborne grastro-enteritis ⁵⁶ and Vibrio cholera ^{56, 120}. Various studies have been reported to corroborate the same. The antibacterial activity of methanol, ethanol, chloroform extracts of cladodes, and skin fruit extracts of Opuntia ficus indica have demonstrated great antibacterial activity against both Gram-positive and Gram-negative bacteria ^{122, 123} Antibacterial effects against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli; along with mild antifungal activity against Aspergillus niger have also been reported ^{122, 123}. The extracts of Opuntia fruits have been tested for their antibacterial and antifungal effects against Enterococcus faecium and Candida albicans with promising results ^{56, 123}. Antimicrobial activity of the peel extracts of O. elatior also demonstrated remarkable antimicrobial actions in a dose dependent manner against both bacteria (Gram-positive and Gram-negative) and fungi based on growth inhibition zone and compared with the standard drugs ^{69, 70}.

Anti-Viral Properties: Cladode extract from O. streptacantha Lem. have demonstrated antiviral properties towards DNA viruses, such as herpes, and RNA viruses, including influenza type A and human immunodeficiency virus (HIV)-1. The constituents of the extract interfered with intracellular replication of a number of DNA- and RNA-viruses such as Herpes simplex virus Type 2, Equine herpes virus, pseudorabies virus, influenza virus, respiratory syncitial disease virus. An inhibition of extra-cellular viruses was also reported. The main principle was found to be present in the outer non-cuticular tissue and attributed to a protein with unknown mechanisms of action ^{2, 124}. Both the replication of DNA and RNA viruses was inhibited ^{37, 124}.

Anti-spermatogenic Properties: Alarmingrate, at which the world’s population is increasing, is creating problems for all developed and undeveloped countries by creating a burden on social and economic growth. Development of ideal male contraceptive with no side effects and easy reversible options from medicinal plants such as Opuntia species, Piper, Curcuma longafistula, etc., which demonstrate remarkable anti-spermatogenic properties, can provide a solution for population control ^{2, 125}.

The defatted methanolic extract of O. dillenii Haw. has demonstrated anti-spermatogenic effects in tests on rats. According to the study, ^{2, 125,} the flavone derivatives vitexin and myricetin present in the extract were found to be the active principles behind the activity. The addition of 250 mg extract per kg body weight in a diet for 60 days led to the reasonable reduction in the weight of testis, epididymis, seminal vesicle, and ventral prostate and significant reduction of Sertoli cells, Leydig cells, and gametes. The motility of the sperms was also found to be diminished” ^{2, 125}. Similar results were obtained in another study with Opuntia elatior fruits on male mice. In this study, supplementation with 250 and 500 mg/kg ethanolic fruit extract of O. elatior resulted in significant decreases in the weight of the testis and epididymis when compared to control. Additionally, 18.12% reduction was also observed in the sperm count along with 17.82% increase in the total percentage of abnormal spermatozoa. The fertility indices with 36.08% decrease in the litter size showed the contraceptive effect of the fruit extract on mice. The weight of the testis and epididymis, total sperm count, and the percentage of the abnormal spermatozoa were returned to the normal levels after the cessation of the treatment for 30 days. The study concluded that extract from O. elatior fruit may be an effective contraceptive agent to regulate male fertility” ^{70, 126}.

Opuntia species are rich in different bioactive compounds such as phytochemicals (phenolic acids, flavonoids, carotenoids, tannins, lignans etc.), vitamins (provitamin A, C, E and K), amino acids, minerals (potassium, calcium and magnesium) and dietary fibers etc. These bioactive compounds are produced as secondary metabolites that promote toxicological and pharmaceutical effects in humans as well as animals ^{2, 20- 25}. Due to high phytochemical content, cactus pear is a valuable source of medicinal properties such as antioxidant potential, radical scavenging activity, anti-ulcerogenic benefits, anti-inflammatory, hypoglycemic effect, anti-spermatogenic effect etc. thus, being a potent source of medicinal plant and a potential nutraceutical.

Betalains: Betalains are pigments specifically from red to violet (betacyanins) and yellow to orange (betaxanthins) present in different plant parts of members of the Caryophyllales, including the cactus family ^{21, 127}. They are natural, water‐soluble nitrogen pigments, synthesized from the amino acid tyrosine, stable at 4–7 pH range and, depending on this particular, utilized as dyes for low‐acidity foods ^{1, 128}. These pigments are responsible for the gamut of the fruit color of the prickly pear fruit and add valuable constituents to its nutritional nature. The concentration of these pigments is responsible for the differences and intensity in color types of the fruit, from deep red/violet and variations of pale green to yellow-orange. The characterization of betalains in prickly pear fruits has revealed that these pigments have antioxidant properties ^{21, 129-131}. Thus, it can be stated that the prickly pear fruit is an antioxidant-rich fruit with characteristics that can potentially stop or delay cell damage in the human body. Moreover, the remarkable presence of nutrients and antioxidants in the prickly pear fruit is evidence that the consumption of the whole fruit is more beneficial from a health perspective because more potentially nutraceutical and active pharmaceutical ingredients are absorbed and utilized by our bodies.

The most remarkable feature of cactus pear fruits and flowers are the yellow (betaxanthins) and red (betacyanins) betalains, which gives the fruits and flowers its aesthetic look and more chances of pollination ¹⁰⁶. It has been reported that “fruits of cactus pear contain various betalains whose concentration depends on different species of Opunita, cultivation, environmental conditions and geographic region, etc. The various betacyanins found in Opuntia fruits include betanidin, betanin, isobetanin, isobetanidin, neobetanin, phyllocactin, and gomphrenin I” ¹⁰⁶. It has also been brought to attention that “O. streptacantha (Cardona cultivar), (Rojalisa cultivar), and O. megacantha (Naranjona cultivar) contain traces of betanidin 5-O-β-sophoroside” ¹⁰⁶.

TABLE 1: DISTRIBUTION AND CONTENTS OF BETALAINS IN THE VARIOUS PARTS OF OPUNTIA FICUS INDICA

Phenolic Compounds: Polyphenols are the class of organic molecules widely distributed in the plant kingdom. Their chemical structures are differentiated by the presence of several phenolic groups. These compounds are classified as the byproducts of plant metabolism. The keen interest in polyphenols is due to their notable antioxidant potential, which is responsible for health benefits such as the prevention of inflammation, cardiovascular dysregulation, anticancer properties, and neurodegenerative diseases, etc. ^{34, 134} Flavonoids is a major constituent of Opuntia spp. as they have anti-oxidative effects and have more efficacy and stability than the vitamins in producing stable radicals. All plant parts of Opuntia cacti have a high number of various flavonoids and phenolic compounds present. The Opunitia flower has been found to contain gallic acid and 6-isohamnetin 3-O-robinobioside as major compounds. Whereas in the case of fruit pulp, high content of isorhamnetin glycosides (50.6 mg/100g) contribute to the total phenolic content, which is 218.8 mg/100 g. fruit seeds contain high phenolic compounds such as feruloyl derivatives, sinapoyldiglucoside, and tannins. The fruit peel also has a high content of flavonoid derivatives such as kaempferol and quercetin. Overall, it was found that flowers of Opuntia were the most important source of the polyphenols and flavonoids ^{34, 135}. The total phenolic compound content in Opuntia species is dynamic and dependant on the following factors such as stages of plant, maturity, harvest, season, environment conditions, post-harvest treatments, and different species. The study has been reported in which it was found that “O. ficus-indica fruits contain 218 mg GAE/100 g FW, but the wild species O. stricta also exhibited high concentrations of these metabolites (204 mg GAE/100 g FW), followed by O. undulata, O. megacantha, O. streptacantha, and O. dinellii (164.6, 130, 120, and 117 mg/100 g FW pear, respectively)”. When compared on the basis of colour of fruits it was found reported that, “purple fruits of O. ficus indica cultivated in Italy, Spain, USA, Tunisia, and Saudi Arabia contain higher levels of phenolics (89–218.8 mg GAE/ 100 g FW) than the orange fruits (69.8 mg GAE/100 g FW). However, the Mexican cultivars, O. megacantha (orange fruits), O. streptacantha, and O. robusta (purple fruits), exhibited a similar phenolic compound concentration (120–140 mg GAE/100 g FW).” Pads of Opuntia have also been reported as source of polyphenols such as O. violacea, O. megacantha, O. atropes, and O. albicarpa contain high concentration of phenolic acids (17.8–20 mg GAE/g DW), while O. rastrera and O. undulata present the lowest values (0.39–0.95 mg GAE/g DW).

The phenolic profile in Opuntia is vast and complex, with more than 30 compounds identified in cladodes of different species, more than 20 in seeds, and 44 compounds in juices. The most common compounds present in Opuntia tissues from wild and cultivated species include kaemp-ferol, quercetin, isorhamnetin, and isorhamnetin glucoside. Kaempferol 3-O-arabinofuranoside was detected only in O. streptacantha, quercetin 3-O-rhamnosyl-(1-2)-[rhamnosyl-(1-6)]-glucoside was detected only in O. ficus-indica cladodes, and isorhamnetin-3-O-rutinoside was present in the juice and peel from O. dilleni. The rare piscidic acid and derivatives, restricted to plants exhibiting crassulacean acid metabolism and succulence, were detected in juices from O. ficus-indica. In seeds, sinapoyl-glucose, sinapoyl-diglucoside, three isomers of feruloyl-sucrose, catechin, rutin, and quercetin derivatives were detected. Taurine, an unusual sulfonic acid, was identified in Sicilian and African cultivars ⁸³.

TABLE 2: DISTRIBUTION AND CONTENTS OF PHENOLIC COMPOUNDS IN THE VARIOUS PARTS OF OPUNTIA FICUS INDICA

Amino Acids: Opuntia ficus indica has a large number of amino acids present which have been found in various phytochemical investigations. High levels of amino acids such as proline, taurine and serine have been reported in the cladodes of Opuntia. Up to 8 essential amino acids have been reported in cactus plants such as alanine, arginine, glutamin acid, lysine, tyrosine, etc. In the cladodes of Opuntia cactus, the most abudant amino acid reported is glutamine followed by leucine, lysine, valine, arginine, phenylalanine, and isoleucine. In the seeds of cactus, glutamic acid has been reported as the highest content with the percentage varying from 15.73% to 20.27%, after which comes the arginine with 4.81% to 14.61%. In contrast, the cacti fruit has two major amino acids namely proline and taurine. Thus, seeds of cacti fruit and pulp is considered a valuable source of amino acids. In the extensive study of fresh Opuntia cacti the amino acids in an alcoholic extract from fresh phyllo-clades comprised leucine, phenylalanine, valine, methionine, proline, alanine, glutamic acid, threonine, glycine, serine, lysine, cysteine, and c-aminobutyric acid, respectively. Some studies have reported the presence of amino acid patterns of Opuntia pads containing eighteen compounds. Another research study on the composition of Tunisian O. ficus-indica var. inermis protein reported content of amino acids as follows, “13.0% glutamic acid, 10.6% asparaginic acid, 8.3% leucine, 7.7% alanine, 7.0% valine, 6.5% proline, 5.9% lysine, 5.5% arginine, 5.2% isoleucine, 5.1% phenylalanine, 4.8% glycine, 4.3% threonine, 4.3% serine, 4.1% tyrosine, 2.3% histidine, 2.1% methionine, and 0.8% cysteine” ^{2, 148}.

TABLE 3: DISTRIBUTION AND CONTENTS OF PHENOLS AND FLAVONOIDS IN THE VARIOUS PARTS OF OPUNTIA FICUS INDICA

CONCLUSION AND FUTURE PERSPEC-TIVES: The Opuntia ficus indica is a reservoir of flavonoids such as kaempferol, quercetin, narcissin, dihydrokaempferol, dihydroquercetin, and erio-dictyol. Other antioxidants in prickly pear fruits include betalains, pectin, carotenes, betalains, ascorbic acid, quercetin, and quercetin derivatives. This review presented the high potential for anti-oxidant activity, anti-inflammatory actions, analgesic effects such as wound healing properties, and anti-ulcer genic effects. Opuntia spp. even has the potential for treating chronic diseases such as cardiovascular effects such as anti-hyperlipidemic properties, cholesterol-lowering properties, etc. Prickly pear has also shown hypoglycemic and anti-diabetic effects in treating diabetes mellitus. Opuntia spp. also exhibits anti-microbial properties, anti-viral properties, etc. Opuntia also has been effective in exhibiting anti-spermatogenic properties.

Opuntia ficus-indica (L.) Mill. is has the potential of being the most agro-economically important cactus crop species. There is evidence for the use of Opuntia in the human diet at least 9000 years ago or even as early as 12,000 years ago. Due to multiple uses of cactus, a cactus crop may be proven beneficial for the rehabilitation of degraded sites, including wastelands. The low cost of establishing and producing the crop, as well as its tolerance to extreme conditions, make cactus potentially suited to becoming a viable future industry in India. The Thar desert in Rajasthan, Rann of Kutch in Gujarat, southwestern parts of Haryana, Bundelkhand, and other similar rainfed areas that are prone to severe drought would be very productive in the cultivation of Opuntia species.

Opuntia spp. can be contemplated as a nutraceutical, due to their ability to prevent or delay chronic disease development and promote a better health and quality of life. More extensive research can be done to examine the bioactive compounds of Opuntia spp. and explore its pharmacological properties as a high potential nutraceutical fruit.

ACKNOWLEDGEMENT: Authors acknowledge Dr. A.K. Chauhan, Founder President, Amity University, for his continuous motivation and encouragement, and Dr. Chanderdeep Tandon, Director, Amity Institute of Biotechnology Amity University, for providing the infrastructure to carry out the investigations and Dr. Sabari Ghosal for her unrelenting support and encouragement.

AUTHOR CONTRIBUTION STATEMENT: Both authors listed have significantly contributed to the development and the writing of this article.

CONFLICTS OF INTEREST: All authors declare that there is no conflict of interest regarding the publication of this paper.

FINANCIAL SUPPORT AND SPONSORSHIP: None

ETHICAL APPROVAL: Not required.

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     Jain A, Sharda S and Avasthi AS: Opuntia ficus-indica: escalating from farm to pharmacological actions. Int J Pharm Sci & Res 2021; 12(12): 6310-40. doi: 10.13040/IJPSR.0975-8232.12(12).6310-40.

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